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Istvan Seri MD, PhD, HonDSidra Center of Excellence in NeonatologySidra Medical and Research Center

Weill-Cornell Medical College-Qatar, Doha, Qatar

Comprehensive Hemodynamic Monitoring in Neonates

IPOKRaTES Foundation – Clinical Course

Neonatal Hemodynamic Course - Singapore

Istvan Seri, MD, PhD, HonD has disclosed the following financial

relationships. Any real or apparent conflicts of interest related to the

content of this presentation have been resolved.

Affiliation / Financial Interest Organization

Educational Grant to support the

Neonatal Hemodynamics Club,

2013, 2014

Covidien Inc.; Mansfield, MA

Co-editorship of “Cardiology and

Neonatal Hemodynamics”; Book Royalty

Elsevier, Inc.; Philadelphia, PA

Disclosure Statement

Organ BF Distribution:

Vital OBF - O2 DeliveryNIRS – Cerebral rSO2

Doppler - US

BP = CO x SVR

Monitoring:

Blood pressure

measurements

Monitoring:

• Calculated (BP/CO);• Laser-Doppler;• Visible-light;

• NIRS

Monitoring:• Echocardiography;

• Impedance EC;• Pressure wave-form analysis;

• MRI

Systemic

Blood PressureDependent Variable

Systemic ResistanceIndependent variable

(Vasopressors, Lusitropes)

Systemic FlowIndependent variable

(Inotropes)

Organ BF Distribution:

Non-vital OBF - O2 Delivery

NIRS – Renal, intestinal, muscle rSO2

Doppler - US

O2 Delivery

O2 Demand

When blood flow regulation

exhausted:

1. ↑ Capillary recruitment (Visible light; Dark-field imaging)

2. ↑↑↑↑ O2 extraction (NIRS)

3. ↓↓↓↓ brain function (aEEG)

DEVELOPMENTAL HEMODYNAMICSBLOOD PRESSURE, BLOOD FLOW, BLOOD FLOW DISTRIBUTION, VASCULAR RESISTANCE

Soleymani et al, Expert Rev. Med. Devices 9, 501–511; 2012

↔

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1. Conventional assessment

a) Blood pressure, heart rate, O2 saturation

b) Indirect clinical & lab signs of CV function (Uv, CRT, ∆TC-P, BD, serum lactate)

2. Systemic and organ blood flow using

a) Echocardiography (LVO, RVO, SVC flow, PAP, EF, SF, MPI, VTI, PI, RI, etc)

b) Dilution techniques, direct & modified Fick methods, intra-arterial ultrasound probes, arterialpressure waveform analysis, electrical impedance cardiography, electrical cardiometry

c) NIRS, Laser Doppler, side-stream dark field imaging technology* (microvascular blood flow)

3. O2 delivery and consumption in tissues

a) Continuous wave differential or SR NIRS for CBF (∆CBV, absolute CBF, CFOE, TOI^)

b) SR NIRS for cerebral, renal intestinal and muscle oxygenation ([rSO2])

c) Visible light technology (buccal, other mucosal or skin blood flow)

4. Functional assessment (aEEG for brain activity)

5. MRI

6. Data collection requires use of real-time data acquisition systems

Assessment of cardiovascular function, organ perfusion, O2 delivery

and brain function in neonates at the bedside

Soleymani et al; Exp Rev Med Devices 2012; 9:501–511

Hypotheses:

1. Comprehensive hemodynamic monitoring aids in the

a. timely diagnosis

b. pathophysiology-targeted treatment of neonatal shock

2. Diagnosis and pathophysiology-targeted treatment of

neonatal shock especially in its early, compensated phase will

improve clinically relevant, short- and long-term outcomes

Comprehensive Hemodynamic Monitoring in Neonates

Comprehensive Hemodynamic Monitoring

Real-time, Comprehensive Monitoring and Data

Acquisition

1. In addition to conventional parameters (SpO2,HR, BP, RR,

TCOM), continuous assessment of changes in systemic blood

flow (EV, US) and vital and non-vital organ blood flow

(NIRS, US) and peripheral perfusion (Laser Doppler) and

brain function (aEEG)

2. More data needed to establish

• Pathophysiologic and clinical relevance of neonatal shock

• Hemodynamic effectiveness of treatment

• Clinical relevance of hemodynamic effectiveness of treatment

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Sadaf Soleymani, MS

Hemodynamic Monitoring and Data Acquisition System

Patient Monitoring System #1

Computer

Data Acquisition System

Camera

Impedance Electrical Cardiometry

Modules for Modules for HR, BP, SPO2, RR, TCOM

Near Infrared Spectroscopy(NIRS)

Patient Monitoring System #2

(for additional channels)

aEEG

Laser Doppler (Peripheral BF)

0

100

200

300

400

500

600

700

800

900

LVO-ev LVO-echo

ᴏ

ᴏᴏ

Cardiac Output (m

L/m

in)

Continuous Non-Invasive Cardiac Output Measurements in

Neonates by Electrical Velocimetry (EV) - Comparison with

Echocardiography

EV’s Error percentage (EP) = 43.6%

ECHO’s precision = 30%

True precision of EV = 31.6%

115 paired measurements in 20 healthy term neonates on postnatal days #1 and 2

True PrecisionEV = √ [(EP)2 – (precisionecho)2]

Noori et al, Arch Dis Child Fetal-Neonatal Ed, 2012 Hot Topics, Washington, DC -

2013

ICON (Cardiac Output)

Continuous Web-Based Data Collection

Usual NICU Set-up

•EMR data charted hourly

•Data from Servers not getting to Viewer Workstations

•Data from additional devices not connected to monitors and do not reach collection workstations

Solution

•To record data continuously from patient monitosr and bedside equipment

•Continuous data recording can be accomplished in any number of beds

•Needs a DataBase

Execution

•Ensure system meets hospital standards

•Create a VM for DBase

•Viewer workstations with receiver software for HL7 data from Philips servers

•Bridges used for devices that are not connected to Philips server

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Philips MP70: Numeric: HR, BP, SPO2, TCOM, RRWaveform: ECG wave, BP wave

ICON: Cardiac Output (CO)

INVOS:Regional O2(rSO2)

Ventilators: (AVEA/ Servo-i)

CPC Virtual ServerCPC Virtual Server

CHLA NICCU Data Flow: Bernoulli System

Patient Monitor (MP70)Patient Monitor (MP70)

Bernoulli Multi Port BridgeBernoulli Multi Port Bridge

Bedside MonitorsBedside Monitors

Comprehensive Hemodynamic Monitoring

Examples

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Dopamine2 mcg/kg/min

0.9% SalineBolus (15 min)

Mechanisms of Action of Vasoactive Medications: VolumeEffect of saline bolus in a 1-day old 36-week’s gestation neonate

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Hemodynamic Parameters and Cerebral and Renal Regional

Tissue Oxygenation in a Very Preterm Infant during Postnatal Day

#1

Steady increase in CrSO2 despite no change or decreases in SPO2 (CO and pCO2 and continuously monitored)

(GA=26 weeks; BW=976 g) HR

SPaO2

RrSO2

CrSO2

MBP RR

Hemodynamic Effects of Positioning in Neonates

Neonates without congenital cardiac defects admitted to the NICU are eligible for enrollment.

Heart rate, stroke volume (SV) and cardiac output (CO) are monitored

continuously by electrical cardiometry (Aesculon, San Diego, CA).

Skin blood flow is continuously assessed on the forehead or foot using Laser Doppler technology (PeriFlux 5000, Ardmore, PA).

Statistical analysis: Wilcoxon matched-pairs signed-ranks test.

→ →

10min 10min 10min

Ma et al; AAP Meeting, Orlando, FL 2013

5010

015

020

0

beat

s/m

inut

e

Heart Rate

supine prone back to supine

p<0.01 p<0.01

.51

1.5

22.

5

ml/k

g

Stroke Volume

supine prone back to supineN = 30 N = 30

Outlier

Maximum (within 1.5x IQR)

Upper Quartile

Median

Lower Quartile

Minimum (within 1.5x IQR)

Outlier

Box and whisker plot

Neonatal Hemodynamic Monitoring:

Hemodynamic Effects of Positioning in Neonates

Ma et al; AAP Meeting, Orlando, FL 2013

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p<0.01 p<0.01

0.5

11.

5

perf

usio

n un

it

Skin Blood Flow Index

supine prone back to supine

p<0.01 p<0.05

.1.2

.3.4

.5m

mH

g / m

l / k

g

Calculated SVR Index

supine prone back to supine

N=21

N = 30 N = 21

p=0.09

p=0.08

2040

6080

100

mm

Hg

Blood Pressure

supine prone back to supineSBP DBP MBP

N=21

p<0.01 p<0.01

100

150

200

250

300

ml/k

g/m

in

Cardiac Output

supine prone back to supineN = 30 N = 21

Ma et al; AAP Meeting, Orlando, FL 2013

Hemodynamic Effects of Positioning in Neonates

Conclusion

Short term prone positioning is associated with significant

changes in cardiovascular function

1. Decreased stroke volume and cardiac output

2. Decreased skin blood flow

3. Increased calculated vascular resistance

4. However, it’s unclear why HR does not increase to compensate for

the decreased CO and BP (DBP) increases at the same time.

Neonatal Hemodynamic Monitoring:

Hemodynamic Effects of Positioning in Neonates

Ma et al; AAP Meeting, Orlando, FL 2013

Cerebral and renal regional O2 saturations during arterial desaturation

episodes in ≤3-day old ELBW infants (n=7)

Duration of Desaturations: 8±±±±3 minutes

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Renal and Cerebral rSO2 vs. SPO2 % Change

0,0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

0 0,2 0,4 0,6 0,8

rSO

2Change

SPO2 change

Renal

Cerebral SPO2 = 20.5% ±13.6

CrSO2=24.2% ±15.8

RrSO2=41.0% ±19.8*

* = p<0.05

Soleymani et al. PAS, 2012

Gestational Age 25.9 ±1.7 weeks

Birth Weight 899 ±152 g

Duration of Desaturations 8 ±3 minutes

Results

While the decreases in SPO2 and CrSO2 were similar (20.5 vs. 24.2%), the decrease in RrSO2 was close to twice that of CrSO2 (41.0 vs. 24.2%)

Conclusion

In response to decreases in SPO2, blood flow decreases in the kidneys while cerebral blood flow is likely maintained

Cerebral and renal regional O2 saturation during arterial desaturation

episodes in ELBW neonates during the first postnatal days

Soleymani et al. PAS, 2012

MR-COMPATIBLE INCUBATOR, VENTILATOR AND

MONITORING SYSTEM

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Fore- and Hindbrain Blood Flow

Response to Changes in O2 or CO2

Delivery in Adults and Neonates

Simultaneous MRI - NIRS

• Perfusion and blood flow changes assessed by MRI using BOLD signal and phase contrast method, respectively.

• Changes in tissue perfusion assessed by NIRS

IPoKRATES -Rio 2013

Phases of Neonatal Shock

Compensated phase

Heart rate; Urine output; No change in blood pressure;

Blood flow distributed to vital organs (brain, heart, adrenal glands) at the

expense of non-vital organ perfusion

Uncompensated phase

Heart rate; Urine output; Blood pressure

Blood flow in all organs, tissue hypoperfusion and acidemia develop

Irreversible phase

Irreversible cellular damage

Phases of Neonatal Shock

Compensated phase

Heart rate; Urine output; No change in blood pressure;

Blood flow distributed to vital organs (brain, heart, adrenal glands) at the

expense of non-vital organ perfusion

Uncompensated phase

Heart rate; Urine output; Blood pressure

Blood flow in all organs, tissue hypoperfusion and acidemia develop

Irreversible phase

Irreversible cellular damage

During compensated phase of shock when BP is maintained in the

normal range, organ blood flow is determined by organ assignment:

1. Vessels in vital organs (brain, heart, adrenal glands) vasodilate when

perfusion pressure falls

2. Vessels in non-vital organs vasoconstrict when perfusion pressure falls

Thus, if patient is stressed but not hypotensive, cerebral blood flow

is maintained

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1. What is the explanation for the documented

decrease in CBF in normotensive very preterm

neonates during the first postnatal day?

2. Why do very preterm neonates mostly

develop P/IVH during the second or third

postnatal day?

Questions

Pathophysiology of Brain Injury in Very Preterm

Neonates

1. Proposed mechanisms of brain injury during transition

a. Developmental regulation of vital organ assignment of

forebrain (answer to Question #1)

b. Hypoperfusion-reperfusion cycle (answer to Question #2)

2. Pathophysiology-targeted prevention and treatment

approaches

Hernandez MJ et al. CBF, effects of nerves and neurotransmitters. Heistad DD, Marcus ML (Ed). Elsevier; 1982; p. 359–66

Normoxia

Hypoxia

Changes in fore- and hindbrain vascular resistance in response

to hypoxia in beagle pups

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*

Postnatal Age (h)

Decreased CBF in ELBW neonates immediately after delivery

Cerebral tissue O2

saturation (CrSO2)-NIRS:

CrSO2 is directly related to CBF if SpO2 and metabolic rate are comparable and stable, respectively.

(Lemmers et al – shown with permission)

<28 weeks 28-29 weeks 30-31 weeks

CrS

O2(%

)

Cerebral Fractional O2 Extraction (CFOE) by

NIRS:

CFOE is inversely related to CBF as long as metabolic rate and SPsO2 are unchanged.

(Kissack et al. J Cereb B Flow Metab; 2005; 25:545)

CFOE

Postnatal days

↓↓↓↓ FiO2

NIRS

Simultaneous Use of MRI - NIRS

↓↓↓↓ FiO2

MRI

Hindbrain-NIRS

Functional

Activity

Functional

Activity

Borzage et al; Preliminary data, 2012

Neonate

Adult

↓↓↓↓FiO2

FiO2 = 0.12

HYPOXIC CHALLENGE IN ADULT AND NEONATAL FOREBRAIN

NIRS

Forebrain

Borzage et al; Preliminary data, 2012

Neonate

Adult

BOLD –MRI

Fore-an

d Hindbrain

↓↓↓↓FiO2

FiO2 = 0.12

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Blood Flow Changes in Adult Fore- and Hindbrain during CO2

Challenge by Phase Contrast MRI

-1

0

1

2

3

1 2 3 4 5 6 7 8

∆Flow [ml/s]

Forebrain Flow Hindbrain Flow

Carbon Dioxide

P<0.05 vs baseline

Time (minutes)= Carotid and basilar arteries

= Vertebral and basilar arteries Borzage et al; Preliminary data, 2013

INVESTIGATORS

CHLA-USC faculty International Collaborations

Philipe Friedlich, MD, MEpi, MBA Barna Vasarhelyi, PhD

Shahab Noori, MD Tivadar Tulassay, MD, DSciRowena Cayabyab, MD Lola Stavroudis, MDMac Ebrahimi, MD Anita Aperia, MDPierre Wong, MD Ann-Christine Eklof, PhDBijan Siassi, MD Alejandro Bertorello, MDRangasamy Ramanathan, MD Gianni Celsi, MD

Frank van BelPetra LemmersFlora Wong

CHLA-USC fellows/residents National Collaborations

Shazia Bohmbal, MD Michael Wider, PhD (Somanetics)Bonnie Tam, MD Sandra L Drake, PhD (Somanetics)Amin Addie, MD Erin A Booth, PhD (Somanetics)Karine Barzaghyen, MD Jackie Evans, MD

Soraya Abbasi, MD

CHLA-USC PhD students Jeffrey Gerdes, MDMatt Borzage Barbara Ballermann, MDSadaf Soliemani Steven R Gullans, PhD

Barry Brenner

International FellowsRaul Nachar, MD, Valerio Romano, MD

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COMPREHENSIVE HEMODYNAMIC MONITORING

QUESTIONS?