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Opioid-Induced Respiratory Failure (OIRD) Are There Early Warning Signs? Robert J Farney MD Clinical Professor of Medicine University of Utah School of Medicine [email protected] Parcka Parleys 18 Aug 2020

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Page 1: Parcka Parleys - University of Utah

Opioid-Induced Respiratory Failure (OIRD) Are There Early Warning Signs

Robert J Farney MDClinical Professor of Medicine

University of Utah School of Medicine

robertjfarneygmailcom

Parcka Parleys18 Aug 2020

Drug Overdose Deaths in the United States 1999-2016 H Hedegaard NCHS Data Brief No 294 December 2017

Fentanyl

OxycodoneHydrocodoneHydromorphone

Main Teaching Points1 Opioids suppress all aspects of respiration including drive

(RR and VT) and pattern

2 Respiratory effects occur mainly during sleep or non-awake states

3 Sub-population with enhanced sensitivity and without known risk factors

4 Quantified ataxic breathing patterns can aid early recognition of opioid induced respiratory depression (OIRD)

Sleep-disordered breathing in stable methadone programme patients a pilot study

H Teichtahl Addiction 200196395-403

5 minutes

35 year old female Chronic fatigue and poor sleepStaging

Stage 4Stage 3Stage 2Stage 1

REMAwake

Movement Time

6 AM5 AM4 AM3 AM2 AM1 AM12 AM11 PM

SaO2

90

100

70

Hydrocodone 2nd dose

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Tracheal sound

Airflow

Thorax

Abdomen

Oximetry

600 seconds

Recurrent extremely prolonged obstructive ldquohypopneasrdquo only during NREM sleep

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Reversal of prolonged obstructive ldquohypopneardquo during NREM sleep

Airflow

Thorax

Abdomen

Oximetry

Inspiratory airflow flattening

60 seconds

Inspiratory airflow flattening

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

77 7679 89

Oximetry

Abdomen

Thorax

Airflow

NREM SLEEP REM SLEEP

CPAP = 16 cm H2O

300 seconds

CENTRAL APNEAS during NREM sleep Unresponsive to nasal CPAP

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Airflow

Thorax

Abdomen

Oximetry

Tracheal sound

300 secondsAtaxic breathing and severe hypoxia during NREM

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Camille Biot (19 Dec 1850)

Presenter
Presentation Notes
Camille Biot 19 Dec 1850 -

Contribution a lrsquoegravetude de phegravenomegravenerespiratoire de Cheyne-Stokes

MC Biot Lyon Megraved 1876 23 517-528 561-567

ldquoBiotrsquosrdquo breathing in a 16 year old male with tuberculous meningitis

Opioid Non-Opioid pAtaxic Breathing 70 5 lt0001

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

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Page 2: Parcka Parleys - University of Utah

Drug Overdose Deaths in the United States 1999-2016 H Hedegaard NCHS Data Brief No 294 December 2017

Fentanyl

OxycodoneHydrocodoneHydromorphone

Main Teaching Points1 Opioids suppress all aspects of respiration including drive

(RR and VT) and pattern

2 Respiratory effects occur mainly during sleep or non-awake states

3 Sub-population with enhanced sensitivity and without known risk factors

4 Quantified ataxic breathing patterns can aid early recognition of opioid induced respiratory depression (OIRD)

Sleep-disordered breathing in stable methadone programme patients a pilot study

H Teichtahl Addiction 200196395-403

5 minutes

35 year old female Chronic fatigue and poor sleepStaging

Stage 4Stage 3Stage 2Stage 1

REMAwake

Movement Time

6 AM5 AM4 AM3 AM2 AM1 AM12 AM11 PM

SaO2

90

100

70

Hydrocodone 2nd dose

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Tracheal sound

Airflow

Thorax

Abdomen

Oximetry

600 seconds

Recurrent extremely prolonged obstructive ldquohypopneasrdquo only during NREM sleep

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Reversal of prolonged obstructive ldquohypopneardquo during NREM sleep

Airflow

Thorax

Abdomen

Oximetry

Inspiratory airflow flattening

60 seconds

Inspiratory airflow flattening

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

77 7679 89

Oximetry

Abdomen

Thorax

Airflow

NREM SLEEP REM SLEEP

CPAP = 16 cm H2O

300 seconds

CENTRAL APNEAS during NREM sleep Unresponsive to nasal CPAP

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Airflow

Thorax

Abdomen

Oximetry

Tracheal sound

300 secondsAtaxic breathing and severe hypoxia during NREM

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Camille Biot (19 Dec 1850)

Presenter
Presentation Notes
Camille Biot 19 Dec 1850 -

Contribution a lrsquoegravetude de phegravenomegravenerespiratoire de Cheyne-Stokes

MC Biot Lyon Megraved 1876 23 517-528 561-567

ldquoBiotrsquosrdquo breathing in a 16 year old male with tuberculous meningitis

Opioid Non-Opioid pAtaxic Breathing 70 5 lt0001

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

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Page 3: Parcka Parleys - University of Utah

Main Teaching Points1 Opioids suppress all aspects of respiration including drive

(RR and VT) and pattern

2 Respiratory effects occur mainly during sleep or non-awake states

3 Sub-population with enhanced sensitivity and without known risk factors

4 Quantified ataxic breathing patterns can aid early recognition of opioid induced respiratory depression (OIRD)

Sleep-disordered breathing in stable methadone programme patients a pilot study

H Teichtahl Addiction 200196395-403

5 minutes

35 year old female Chronic fatigue and poor sleepStaging

Stage 4Stage 3Stage 2Stage 1

REMAwake

Movement Time

6 AM5 AM4 AM3 AM2 AM1 AM12 AM11 PM

SaO2

90

100

70

Hydrocodone 2nd dose

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Tracheal sound

Airflow

Thorax

Abdomen

Oximetry

600 seconds

Recurrent extremely prolonged obstructive ldquohypopneasrdquo only during NREM sleep

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Reversal of prolonged obstructive ldquohypopneardquo during NREM sleep

Airflow

Thorax

Abdomen

Oximetry

Inspiratory airflow flattening

60 seconds

Inspiratory airflow flattening

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

77 7679 89

Oximetry

Abdomen

Thorax

Airflow

NREM SLEEP REM SLEEP

CPAP = 16 cm H2O

300 seconds

CENTRAL APNEAS during NREM sleep Unresponsive to nasal CPAP

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Airflow

Thorax

Abdomen

Oximetry

Tracheal sound

300 secondsAtaxic breathing and severe hypoxia during NREM

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Camille Biot (19 Dec 1850)

Presenter
Presentation Notes
Camille Biot 19 Dec 1850 -

Contribution a lrsquoegravetude de phegravenomegravenerespiratoire de Cheyne-Stokes

MC Biot Lyon Megraved 1876 23 517-528 561-567

ldquoBiotrsquosrdquo breathing in a 16 year old male with tuberculous meningitis

Opioid Non-Opioid pAtaxic Breathing 70 5 lt0001

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
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  • Slide Number 6
  • Slide Number 7
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  • Slide Number 70
Page 4: Parcka Parleys - University of Utah

Sleep-disordered breathing in stable methadone programme patients a pilot study

H Teichtahl Addiction 200196395-403

5 minutes

35 year old female Chronic fatigue and poor sleepStaging

Stage 4Stage 3Stage 2Stage 1

REMAwake

Movement Time

6 AM5 AM4 AM3 AM2 AM1 AM12 AM11 PM

SaO2

90

100

70

Hydrocodone 2nd dose

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Tracheal sound

Airflow

Thorax

Abdomen

Oximetry

600 seconds

Recurrent extremely prolonged obstructive ldquohypopneasrdquo only during NREM sleep

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Reversal of prolonged obstructive ldquohypopneardquo during NREM sleep

Airflow

Thorax

Abdomen

Oximetry

Inspiratory airflow flattening

60 seconds

Inspiratory airflow flattening

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

77 7679 89

Oximetry

Abdomen

Thorax

Airflow

NREM SLEEP REM SLEEP

CPAP = 16 cm H2O

300 seconds

CENTRAL APNEAS during NREM sleep Unresponsive to nasal CPAP

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Airflow

Thorax

Abdomen

Oximetry

Tracheal sound

300 secondsAtaxic breathing and severe hypoxia during NREM

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Camille Biot (19 Dec 1850)

Presenter
Presentation Notes
Camille Biot 19 Dec 1850 -

Contribution a lrsquoegravetude de phegravenomegravenerespiratoire de Cheyne-Stokes

MC Biot Lyon Megraved 1876 23 517-528 561-567

ldquoBiotrsquosrdquo breathing in a 16 year old male with tuberculous meningitis

Opioid Non-Opioid pAtaxic Breathing 70 5 lt0001

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
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  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
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  • Slide Number 30
  • Slide Number 31
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  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
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  • Slide Number 38
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  • Slide Number 41
  • Slide Number 42
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  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
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  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
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  • Slide Number 55
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  • Slide Number 70
Page 5: Parcka Parleys - University of Utah

35 year old female Chronic fatigue and poor sleepStaging

Stage 4Stage 3Stage 2Stage 1

REMAwake

Movement Time

6 AM5 AM4 AM3 AM2 AM1 AM12 AM11 PM

SaO2

90

100

70

Hydrocodone 2nd dose

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Tracheal sound

Airflow

Thorax

Abdomen

Oximetry

600 seconds

Recurrent extremely prolonged obstructive ldquohypopneasrdquo only during NREM sleep

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Reversal of prolonged obstructive ldquohypopneardquo during NREM sleep

Airflow

Thorax

Abdomen

Oximetry

Inspiratory airflow flattening

60 seconds

Inspiratory airflow flattening

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

77 7679 89

Oximetry

Abdomen

Thorax

Airflow

NREM SLEEP REM SLEEP

CPAP = 16 cm H2O

300 seconds

CENTRAL APNEAS during NREM sleep Unresponsive to nasal CPAP

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Airflow

Thorax

Abdomen

Oximetry

Tracheal sound

300 secondsAtaxic breathing and severe hypoxia during NREM

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Camille Biot (19 Dec 1850)

Presenter
Presentation Notes
Camille Biot 19 Dec 1850 -

Contribution a lrsquoegravetude de phegravenomegravenerespiratoire de Cheyne-Stokes

MC Biot Lyon Megraved 1876 23 517-528 561-567

ldquoBiotrsquosrdquo breathing in a 16 year old male with tuberculous meningitis

Opioid Non-Opioid pAtaxic Breathing 70 5 lt0001

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
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  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
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Page 6: Parcka Parleys - University of Utah

Tracheal sound

Airflow

Thorax

Abdomen

Oximetry

600 seconds

Recurrent extremely prolonged obstructive ldquohypopneasrdquo only during NREM sleep

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Reversal of prolonged obstructive ldquohypopneardquo during NREM sleep

Airflow

Thorax

Abdomen

Oximetry

Inspiratory airflow flattening

60 seconds

Inspiratory airflow flattening

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

77 7679 89

Oximetry

Abdomen

Thorax

Airflow

NREM SLEEP REM SLEEP

CPAP = 16 cm H2O

300 seconds

CENTRAL APNEAS during NREM sleep Unresponsive to nasal CPAP

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Airflow

Thorax

Abdomen

Oximetry

Tracheal sound

300 secondsAtaxic breathing and severe hypoxia during NREM

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Camille Biot (19 Dec 1850)

Presenter
Presentation Notes
Camille Biot 19 Dec 1850 -

Contribution a lrsquoegravetude de phegravenomegravenerespiratoire de Cheyne-Stokes

MC Biot Lyon Megraved 1876 23 517-528 561-567

ldquoBiotrsquosrdquo breathing in a 16 year old male with tuberculous meningitis

Opioid Non-Opioid pAtaxic Breathing 70 5 lt0001

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
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  • Slide Number 61
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  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 7: Parcka Parleys - University of Utah

Reversal of prolonged obstructive ldquohypopneardquo during NREM sleep

Airflow

Thorax

Abdomen

Oximetry

Inspiratory airflow flattening

60 seconds

Inspiratory airflow flattening

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

77 7679 89

Oximetry

Abdomen

Thorax

Airflow

NREM SLEEP REM SLEEP

CPAP = 16 cm H2O

300 seconds

CENTRAL APNEAS during NREM sleep Unresponsive to nasal CPAP

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Airflow

Thorax

Abdomen

Oximetry

Tracheal sound

300 secondsAtaxic breathing and severe hypoxia during NREM

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Camille Biot (19 Dec 1850)

Presenter
Presentation Notes
Camille Biot 19 Dec 1850 -

Contribution a lrsquoegravetude de phegravenomegravenerespiratoire de Cheyne-Stokes

MC Biot Lyon Megraved 1876 23 517-528 561-567

ldquoBiotrsquosrdquo breathing in a 16 year old male with tuberculous meningitis

Opioid Non-Opioid pAtaxic Breathing 70 5 lt0001

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 8: Parcka Parleys - University of Utah

Oximetry

Abdomen

Thorax

Airflow

NREM SLEEP REM SLEEP

CPAP = 16 cm H2O

300 seconds

CENTRAL APNEAS during NREM sleep Unresponsive to nasal CPAP

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Airflow

Thorax

Abdomen

Oximetry

Tracheal sound

300 secondsAtaxic breathing and severe hypoxia during NREM

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Camille Biot (19 Dec 1850)

Presenter
Presentation Notes
Camille Biot 19 Dec 1850 -

Contribution a lrsquoegravetude de phegravenomegravenerespiratoire de Cheyne-Stokes

MC Biot Lyon Megraved 1876 23 517-528 561-567

ldquoBiotrsquosrdquo breathing in a 16 year old male with tuberculous meningitis

Opioid Non-Opioid pAtaxic Breathing 70 5 lt0001

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
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  • Slide Number 41
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  • Slide Number 50
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Page 9: Parcka Parleys - University of Utah

Airflow

Thorax

Abdomen

Oximetry

Tracheal sound

300 secondsAtaxic breathing and severe hypoxia during NREM

Sleep-Disordered Breathing Associated with Long-term Opioid Therapy

RJ Farney Walker JM Cloward TV Rhondeau S Chest 2003123632-639

Camille Biot (19 Dec 1850)

Presenter
Presentation Notes
Camille Biot 19 Dec 1850 -

Contribution a lrsquoegravetude de phegravenomegravenerespiratoire de Cheyne-Stokes

MC Biot Lyon Megraved 1876 23 517-528 561-567

ldquoBiotrsquosrdquo breathing in a 16 year old male with tuberculous meningitis

Opioid Non-Opioid pAtaxic Breathing 70 5 lt0001

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
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  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
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  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
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  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
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  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 10: Parcka Parleys - University of Utah

Camille Biot (19 Dec 1850)

Presenter
Presentation Notes
Camille Biot 19 Dec 1850 -

Contribution a lrsquoegravetude de phegravenomegravenerespiratoire de Cheyne-Stokes

MC Biot Lyon Megraved 1876 23 517-528 561-567

ldquoBiotrsquosrdquo breathing in a 16 year old male with tuberculous meningitis

Opioid Non-Opioid pAtaxic Breathing 70 5 lt0001

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
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  • Slide Number 70
Page 11: Parcka Parleys - University of Utah

Contribution a lrsquoegravetude de phegravenomegravenerespiratoire de Cheyne-Stokes

MC Biot Lyon Megraved 1876 23 517-528 561-567

ldquoBiotrsquosrdquo breathing in a 16 year old male with tuberculous meningitis

Opioid Non-Opioid pAtaxic Breathing 70 5 lt0001

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
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  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
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  • Slide Number 69
  • Slide Number 70
Page 12: Parcka Parleys - University of Utah

Opioid Non-Opioid pAtaxic Breathing 70 5 lt0001

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
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  • Slide Number 70
Page 13: Parcka Parleys - University of Utah

32 yo female morphine dose equivalent 375 mg BMI 22 kgm2

32 yo female no opioids BMI 23 kgm2

120 seconds Stage 2 NREM

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
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  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 14: Parcka Parleys - University of Utah

Opioid Effects on RespirationPathophysiologic

Opioids can suppress all aspects of respiration Drive and Pattern

ClinicalCentral apneas

Obstructive apneasHypopneas

Ataxic breathing BradypneaHypoxemia

PhysiologicBreathing frequencyTidal Volume

and Pattern Chemoresponsiveness to CO2 and O2

Upper airway patencyChest amp abdominal wall compliance

Arousal response

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
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Page 15: Parcka Parleys - University of Utah

All commercially available narcotics are μ-opioid receptor agonists and reduce neuronal activity of

both pain and respiratory neurons

Mu-opioid receptors are widely distributed throughout the central and peripheral nervous systems

cortex brain stem and carotid body

Opioid Effects on RespirationPhysiologic

Key targets preBoumltzinger complex in ventral-lateral medulla amp Koumllliker-Fuse pontine neurons

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
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  • Slide Number 35
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  • Slide Number 46
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  • Slide Number 48
  • Slide Number 49
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  • Slide Number 51
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  • Slide Number 53
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  • Slide Number 56
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Page 16: Parcka Parleys - University of Utah

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Holy Grail

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 17: Parcka Parleys - University of Utah

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 18: Parcka Parleys - University of Utah

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

Presenter
Presentation Notes
Bilateral but not unilateral SP-SAP lesions profoundly affected breathing We measured respiratory period and inspiratory amplitude from unrestrained awake adult rats Bilaterally SP-SAP injected rats with near-complete bilateral destruction of preBotC NK1R neurons (see below) exhibited a transformation in breathing pattern 4ndash5 days after injection going from a eupneic to a severely ataxic pattern in room air (preBotCndash n = 10 Fig 2) 13The respiratory period of uninjected (control) rats was 053 plusmn 0001 s (n = 10) and normalized peak inspiratory amplitude (Ipeak) was 100 plusmn 0006 (n = 3) with occasional sniffing (period 018 plusmn 0001 s) and sighing (Figs 2 and 3) Ataxia in preBotCndash rats was characterized by shortened respiratory periods (029 plusmn 001 s n = 8 p lt 00001) and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with (prolonged) periods of apnea or very low amplitude inspiration (Ipeak = 085 plusmn 0004 n = 3 p lt 0001 Figs 2 and 3) 13PreBotCndash rats had pathological responses to changes in inspired gases In response to 100 O2 control rats had an increased period (06 plusmn 0002 s n = 9 p lt 0001) and an increased Ipeak (13 plusmn 0008 n = 3 p lt 00001 Figs 2 and 3) PreBotCndash rats responded with a marked (further) depression of breathing with a small decrease (~3) in period (028 plusmn 0002 s n = 4 p lt 005) and a decrease in Ipeak (07 plusmn 0006 n = 3 p lt 00001) due primarily to the loss of normal amplitude events (Fig 3) Two rats developed fatal apneas The depressive effects of 100 O2 in ataxic animals are in contrast to its normalizing effects in humans with Cheynendash Stokes breathing which has a vaguely similar respiratory phenotype this suggests a different etiology for preBotCndash rats In control rats 5 CO2 and 95 O2 caused a significantly decreased (~25) period (04 plusmn 0001 s p lt 00001) and increased Ipeak (18 plusmn 0009 n = 3 p lt 00001) compared to response when breathing room air (Figs 2 and 3) PreBotCndash rats in contrast showed a smaller (~14) decrease in respiratory period from breathing room air (025 plusmn 0001 s n = 5 p lt 00001) with an increase in Ipeak (11 plusmn 0007 p lt 00001) due primarily to the appearance of a number of higher amplitude respiratory events among continued low- amplitude inspiration (Fig 3) In response to severe hypoxia (44 O2956 N2) control and injected rats up to four days after injection showed shortened (~34) periods (035 plusmn 0001 s n = 7 p lt 00001) and increased amplitude these rats tolerated this challenge for at least 15 minutes (n = 16 data not shown) PreBotCndash rats (n = 8) had a brief increase in frequency and amplitude followed within 2ndash7 minutes by apneas of increasing and eventually fatal duration 1313Five days after injection however preBotCndash rats had a profile typical of respiratory depression giving rise to CO2 retention and consequent acidosis (pH 726 plusmn 007 PCO2 564 plusmn 37 mm Hg PO2 765 plusmn 55 mm Hg n = 2 T = 368 plusmn 01degC n = 14) 13131313

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
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  • Slide Number 33
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  • Slide Number 35
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  • Slide Number 46
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  • Slide Number 50
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  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
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Page 19: Parcka Parleys - University of Utah

Normal breathing requires preBoumltzinger complex neurokinin-1 receptor-expressing neurons

PA Gray Nat Neurosci 20014(9)927-930

1 Rats with bilateral but not unilateral destruction of NK1R neurons developed severe ataxic breathing pattern 4-5 days after injection

2 Ataxic patterns characterized by shortened respiratory periods and an irregular sequence of inspiratory efforts of near normal amplitude interspersed with prolonged apneas or very low amplitude inspiration

3 Arterial blood gas profile showed respiratory depression pH 726 PaCO2 56 mmHg and PaO2 77 mmHg

4 Compared to control rats that showed increased respiratory rate and increased inspiratory amplitude for gt 15 minutes to severe hypoxia (44 O2956 N2) injected rats developed apneas of increasing and eventually fatal duration

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 20: Parcka Parleys - University of Utah

High RR

Low RR

Sleep Awake

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 21: Parcka Parleys - University of Utah

PreBoumltzinger Complex Neurokinin-1REceptor-Expressing Neurons Mediate Opioid-Induced Respiratory Depression

G Montandon J of Neuroscience 201131(4)1292-1301

Opioids at the PreBoumltzinger complex depress breathing and cause persistent apnea

Presenter
Presentation Notes
DAMGO is a u opioid agonist aCSF artificial CSF Moving-time average of respiratory rate diaphragm and genioglossus EMG1313ldquoWe then demonstrated that opioids at the preBoumltC at sufficient concentration (DAMGO 200 1113088μM) can cause complete cessation of breathing (Fig 1D) Such respiratory arrest was identified as complete cessation of diaphragm and tongue (genioglossus) muscle activities (mean latency for complete suppression of genioglossus and diaphragm activities was 35 plusmn1113095 13 and 38 plusmn 14 min respectively n 1113091 3) Cessation of breathing was reversed with artificial ventilation and perfusion of naloxone (100 μM) into the preBoumltC in 240 plusmn 31 minrdquo13

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
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  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
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  • Slide Number 70
Page 22: Parcka Parleys - University of Utah

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
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  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
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  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 23: Parcka Parleys - University of Utah

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 24: Parcka Parleys - University of Utah

Definition of Opioid Induced Respiratory DepressionPrimary Clinical Measurements

1Respiratory Rate (lt 8-10 bpm)

2Oximetry (SpO2 lt 90-92)

3End-Tidal CO2 (ETCO2 gt 50 mmHg)

4Mental Status (Sedated)

How do you assess these parameters in a sleeping patient on oxygen

Presenter
Presentation Notes
RR is not reliable Oximetry not useful when oxygen Rx Capnography not widely available and temperamental Mental status not meaningful when patient is asleep at night

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 25: Parcka Parleys - University of Utah

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 26: Parcka Parleys - University of Utah

Why is the Respiratory Rate unreliable for detection opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 27: Parcka Parleys - University of Utah

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 10min

4 minutes

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
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  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 28: Parcka Parleys - University of Utah

PTAF

Thermistor

Thorax

Abdomen

Oximetry

Severe Ataxic Breathing Pattern Secondary to Opioids

60 seconds

RR = 7min

4 minutes

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 29: Parcka Parleys - University of Utah

Why is the Respiratory Rate unreliable for detection of opioid induced respiratory depression

1 RR obtained by physical examination is notoriously inaccurate (eg poor technique patient arousal)

2 Most technologies are not validated for detecting slow respiratory rates

3 Automated methods are insensitive to respiratory patterns (eg apneas) resulting in inaccurate RR

4 RR does not equate to adequate ventilation

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 30: Parcka Parleys - University of Utah

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 31: Parcka Parleys - University of Utah

Opioids suppress multiple components of respiration that can be measured and respiratory depression probably precedes acute cardiorespiratory arrest

So what are the problems What could possibly go wrong

1 How should we monitor patients2 How should respiratory depression be defined3 Does any measurement or set of observations predict

the onset of respiratory depression4 Are there warning signs that actually predict

cardiorespiratory arrest

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 32: Parcka Parleys - University of Utah

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

41 year old female (BMI 367 kgm2) underwent right hip arthroplasty

Post-Operative Day 30800 Alert 010 pain

1100 Asleep but easily arousable 010 pain

Epidural bupivacaine and fentanyl continued

1200 Found unresponsive ldquoKussmall respirationrdquoRR 18minRapid breathing (RR 20-30 breaths)Apnea (20-40 seconds)

Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 33: Parcka Parleys - University of Utah

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

66 year old male (BMI 363 kgm2) underwent right hip arthroplasty

Post-Operative Day 20900 AlertOriented RR 20min

Oxygen discontinued

1345 Oximetry on room air SpO2 86Nasal oxygen resumed SpO2 98

Post-Operative Day 30630 ldquoChecked by Orthopedic servicerdquo

0700 Seen by nurses and orthopedic physiciansldquoHe was sleepingrdquo and not disturbedRR 14min HR 120min BP 10550 mmHg

0725 Found unresponsive Resuscitation efforts unsuccessful

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
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  • Slide Number 8
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Page 34: Parcka Parleys - University of Utah

Three Sudden Postoperative Respiratory Arrests Associated with Epidural Opioids in Patients with Sleep Apnea

AM Ostermeier Anesth Analg 199785452-460

47 year old male (BMI 275 kgm2) underwent ventral hernia repair

Post-Operative Day 20600 ldquoSlight unimportant changes in vital signsrdquo since 1200 (MN)

ldquoNo painrdquoRR 14min BP 11050 HR 78 bpm

Continuous epidural bupivacaine and fentanyl without dose activation by the patient

0700 Found ldquobreathless with cool skin and cyanotic He was asystolic and advanced cardiac life support was givenrdquo

ldquoDied laterrdquo

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
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Page 35: Parcka Parleys - University of Utah

Cardiopulmonary Arrest

Risk Factors + Opioids

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
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  • Slide Number 69
  • Slide Number 70
Page 36: Parcka Parleys - University of Utah

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Cardiopulmonary Arrest

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

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  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
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  • Slide Number 6
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Page 37: Parcka Parleys - University of Utah

Risk Factors + Opioids

Respiratory Depression

RRVT

Ataxia

Hypoxia

Hypoventilation

Hypercapnic acidosis

Cardiopulmonary Arrest

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
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Page 38: Parcka Parleys - University of Utah

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Severe Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

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  • Slide Number 2
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Page 39: Parcka Parleys - University of Utah

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

Moderate Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
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  • Slide Number 70
Page 40: Parcka Parleys - University of Utah

Airflow (Thermistor)

Airflow (PTAF)

Thorax

Abdomen

SpO2

300 s

Sleep disordered breathing in patients receiving therapy with buprenorphinenaloxone

RJ Farney Eur Respir J 2013 42394-403

Mild Sleep ApneaHypopnea with ataxia (Biotrsquos Respiration)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
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Page 41: Parcka Parleys - University of Utah

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

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Page 42: Parcka Parleys - University of Utah

Effect-site target controlled infusions of low dose Propofol and escalating doses of Remifentanil administered to 26 normal volunteers

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
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Page 43: Parcka Parleys - University of Utah

1 Stabilization

0 10 up to 20

2 Monitoring 4 Ventilation Prompting Protocol

30 35 36

5 Quiet 6 OAAS

Time (min)

Protocol at each target effect site concentration pair

Aim 1 Aim 2

Classify Airway Events

Randomized nurse or computer prompts first

Possible repeated computer prompts

3 OAAS BP

NIBP

If no airway events proceed to next drug step

7 RB

Change Drug

Drug Equal

1 Steady state drug reached2 Subject not talking or perturbed3 No intervention4 At least 30 breaths

Observer Assessment of Alertness Score (1-5)The quick brown fox jumps over the lazy dogSpeech Facial Expression Eyes

Take a deep breath

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

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Page 44: Parcka Parleys - University of Utah

Adaptive Servoventilation (ASV) in Patients with Sleep Disordered Breathing Associated with Chronic Opioid Medications for Non-Malignant Pain

RJ Farney J Clin Sleep Med 20084(4)311-319

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

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  • Slide Number 3
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Page 45: Parcka Parleys - University of Utah

Jules Henri Poincareacute29 Apr 1854 ndash 17 Jul 1912

Father of Chaos Theory

Presenter
Presentation Notes
Jules henri Poincare 29 Apr 1854-17 Jul 1912

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
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Page 46: Parcka Parleys - University of Utah

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
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Page 47: Parcka Parleys - University of Utah

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560 560

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
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  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
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  • Slide Number 44
  • Slide Number 45
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  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
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  • Slide Number 56
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Page 48: Parcka Parleys - University of Utah

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 49: Parcka Parleys - University of Utah

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

560

POINCAREacute PLOT OF RR INTERVALS

360

Acceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 50: Parcka Parleys - University of Utah

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

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Page 51: Parcka Parleys - University of Utah

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

360 760

Deceleration

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
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Page 52: Parcka Parleys - University of Utah

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
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Page 53: Parcka Parleys - University of Utah

0

100

200

300

400

500

600

700

800

900

1000

0 100 200 300 400 500 600 700 800 9001000RR-First (ms)

RR-Second (ms)

POINCAREacute PLOT OF RR INTERVALS

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
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  • Slide Number 32
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  • Slide Number 34
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  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
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  • Slide Number 44
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  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
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  • Slide Number 70
Page 54: Parcka Parleys - University of Utah

Do Existing Measures of Poincaregrave Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
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  • Slide Number 65
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  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 55: Parcka Parleys - University of Utah

Do Existing Measures of Poincareacute Plot Geometry Reflect Nonlinear Features of Heart Rate Variability

M Brennan IEEE Transactions on Biomedical Engineering 2001481342-1347

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
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  • Slide Number 50
  • Slide Number 51
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  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
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  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 56: Parcka Parleys - University of Utah

Factor change in Tidal Volume

Interbreath Interval at t = i + 1 (sec)

Poincareacute Plot

Interbreath Interval at t = i (sec)

An automated algorithm incorporating Poincareacute analysis can quantify the severity of opioid-induced ataxic breathing

SC Ermer RJ Farney L M Brewer et al Anesthesia amp Analgesia In Press 2019

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
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  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
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  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 57: Parcka Parleys - University of Utah

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 0

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 58: Parcka Parleys - University of Utah

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 1

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 59: Parcka Parleys - University of Utah

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 2

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 60: Parcka Parleys - University of Utah

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 3

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 61: Parcka Parleys - University of Utah

1

15

25

3+

2

0 20 40 60

20

40

60

Factor change in Tidal Volume

Interbreath Interval at t = i (sec)

Poincareacute Plot

Ataxia Score 4

RIP Flow

Interbreath Interval at t = i + 1 (sec)

PTAF

Air Flow Waveform

Chest BlueAbdomen Red

(minutes)

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 62: Parcka Parleys - University of Utah

Subject 23 gradually going off the cliff

OAAS 5OAAS 5 OAAS 5 OAAS 4OAAS 5 OAAS 5 OAAS 5 OAAS 4

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 63: Parcka Parleys - University of Utah

Subject 4 suddenly going off the cliff

OAAS 2 OAAS 4 OAAS 2 OAAS 4

OAAS 4OAAS 5

OAAS 2 OAAS 4 OAAS 2 OAAS 4 OAAS 4OAAS 5

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
  • Slide Number 7
  • Slide Number 8
  • Slide Number 9
  • Slide Number 10
  • Slide Number 11
  • Slide Number 12
  • Slide Number 13
  • Slide Number 14
  • Slide Number 15
  • Slide Number 16
  • Slide Number 17
  • Slide Number 18
  • Slide Number 19
  • Slide Number 20
  • Slide Number 21
  • Slide Number 22
  • Slide Number 23
  • Slide Number 24
  • Slide Number 25
  • Slide Number 26
  • Slide Number 27
  • Slide Number 28
  • Slide Number 29
  • Slide Number 30
  • Slide Number 31
  • Slide Number 32
  • Slide Number 33
  • Slide Number 34
  • Slide Number 35
  • Slide Number 36
  • Slide Number 37
  • Slide Number 38
  • Slide Number 39
  • Slide Number 40
  • Slide Number 41
  • Slide Number 42
  • Slide Number 43
  • Slide Number 44
  • Slide Number 45
  • Slide Number 46
  • Slide Number 47
  • Slide Number 48
  • Slide Number 49
  • Slide Number 50
  • Slide Number 51
  • Slide Number 52
  • Slide Number 53
  • Slide Number 54
  • Slide Number 55
  • Slide Number 56
  • Slide Number 57
  • Slide Number 58
  • Slide Number 59
  • Slide Number 60
  • Slide Number 61
  • Slide Number 62
  • Slide Number 63
  • Slide Number 64
  • Slide Number 65
  • Slide Number 66
  • Slide Number 67
  • Slide Number 68
  • Slide Number 69
  • Slide Number 70
Page 64: Parcka Parleys - University of Utah

Fact

or c

hang

e in

Tid

al V

olum

e

Animated Poincareacute Plot of Progresssively Severe

Ataxic Breathing

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

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Page 65: Parcka Parleys - University of Utah

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min714

(N = 21)

239

48

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

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Page 66: Parcka Parleys - University of Utah

143 95

48 14348

333

48

143

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 8-10min

0 1 2 3 4

714

ATAXIA SCORE

(N = 21)

239

48

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
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Page 67: Parcka Parleys - University of Utah

2828 2883

28

222

114 56

278

2828

56

28

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 5-7min

0 1 2 3 4ATAXIA SCORE

(N = 36)

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

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Page 68: Parcka Parleys - University of Utah

22 2 4 28 2

24 4

12 20 624

60

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate 0-4min

0 1 2 3 4ATAXIA SCORE

(N = 50)

21143

35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
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Page 69: Parcka Parleys - University of Utah

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35771

143

71

0

10

20

30

40

50

60

70

OAAS 0 OAAS 1 OAAS 2 OAAS 3 OAAS 4 OAAS 5

Respiratory Rate gt 10min

0 1 2 3 4ATAXIA SCORE

(N = 14)

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
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Page 70: Parcka Parleys - University of Utah

CONCLUSIONS

1 Threshold values (ie RR SpO2 ETCO2) may be useful in defining the state of respiratory depression but evidence is lacking that any reliably predict cardiorespiratory arrest

2 Erratic breathing is an important physiologic consequence of opioid induced respiratory depression and can be quantified for clinical applications and further research

3 Patterns of erratic breathing could provide early evidence for impending life threatening critical respiratory events

  • Slide Number 1
  • Slide Number 2
  • Slide Number 3
  • Slide Number 4
  • Slide Number 5
  • Slide Number 6
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