adult respiratory distress syndrome. case presentation a 45-year-old man develops ards after...
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Adult Respiratory Distress Syndrome
Case presentation• A 45-year-old man develops ARDS after sustaining
multiple broken bones in an automobile accident. The man weighs 70 kg. Mechanical ventilation is initiated in the AC mode with the following settings: (PEEP), 10 cm H2O; (FiO2), 70%; respiration rate, 12/min.
• The most appropriate Tidal volume at this point:A. 1000 ml
B. 420 ml
C. 500 ml
D. 560 ml
E. 700 ml
ARDS Definition
The 1994 North American-European Consensus Conference (NAECC) criteria: Onset - Acute and persistent Radiographic criteria - Bilateral pulmonary
infiltrates consistent with the presence of edema Oxygenation criteria - Impaired oxygenation
regardless of the PEEP concentration, with a Pao2/Fio2 ratio 300 torr (40 kPa) for ALI and 200 torr (27 kPa) for ARDS
Exclusion criteria - Clinical evidence of left atrial hypertension or a pulmonary-artery catheter occlusion pressure of 18 mm Hg.
Bernard GR et al., Am J Respir Crit Care Med 1994
Stratification System of Acute Lung Injury GOCA
Letter Meaning Scale Definition
G
Gas exchange
Gas exchange (to be combined with
the numeric descriptor)
0123ABCD
Pao2/Fio2 301Pao2/Fio2 200 -300Pao2/Fio2 101 – 200Pao2/Fio2 100Spontaneous breathing, no PEEPAssisted breathing, PEEP 0-5 cmH2OAssisted breathing, PEEP 6-10 cmH2OAssisted breathing, PEEP 10 cmH2O
O Organ failure
ABCD
Lung onlyLung + 1 organLung + 2 organsLung + 3 organs
C Cause123
UnknownDirect lung injuryIndirect lung injury
A Associated diseases
01
2
No coexisting disease that will cause death within 5 yrCoexisting disease that will cause death within 5 yr but not within 6 moCoexisting disease that will cause death within 6 mo
Artigas A, et al. Am J Respir Crit Care Med. 1998.
ARDS Focal Patchy Diffuse
Chest x-ray (zero PEEP)
Focal heterogeneous loss of aeration in caudal and dependent lung region
Bilateral and diffuse x-ray densities respecting lung
apices
Bilateral and diffuse hyperdensities“White lungs”
Chest CT scan (zero PEEP)
Loss of aeration
Upper lobes normally aerated despite a regional
excess of lung tissue – Lower lobes poorly or non
aerated
Lower lobes massively nonaerated – The loss of aeration involves partially
the upper lobes
Massive, diffuse and bilateral non- or poorly
aerated lung regions – No normally aerated lung
region
Response to PEEP±
PEEP <10-12 cmH2O
++++Lung recruitment curve
Open lung concept
Risk of overinflation of the aerated lung regions ++++
±
Recruitment of non aerated lung unit
Low potential for recruitment
High potential for recruitment
Rouby JJ, et al. Eur Respir J. 2003.Rouby JJ, et al. Anesthesiology. 2004.
The ARDS Lung
Early phases of ARDS Direct insult of the lungPrimary pulmonary ARDS
“Indirect” insult of the lungSecondary extrapulmonary ARDS
Pathologic changes
Lung tissue consolidation Severe intra-alveolar damage
(Edema, fibrin, collagenneutrophil aggregates, red cells)
Microvascular congestionInterstitial edemaAlveolar collapse
Less severe alveolar damage
End-expiratory lung volume EELV
Static elastance of the total respiratory system Est,rs
Static elastance of the chest wall Est,w / Static lung
elastance Est,L / /
Intra-abdominal pressure
Response to PEEP Est,rs [Est,L >> Est,w]Stretching phenomena
Est,rs [Est,L Est,w]Recruitment of previously closed alveolar
spaces
Lung recruitment ± ++++
Gattinoni L, et al. Am J Respir Crit Care Med. 1998.
The ARDS Lung
ARDS Mortality Trend
28%
2006
Crit Care Med 2009 Vol. 37, No. 5
24%
Crude 60-day mortality among Acute Respiratory Distress Syndrome (ARDS) Network patients, 1996–2005.
Baby Lung Concept
• In acute lung injury/acute respiratory distress syndrome, the normally aerated tissue has the dimensions of the lung of a 5- to 6- year-old child (300–500 g aerated tissue)
• What appears dangerous is not the VT/kg ratio but instead the VT/”baby lung” ratio.
• The practical message is straightforward: the smaller the “baby lung,” the greater is the potential for unsafe mechanical ventilation.
ARDS: Baby lungs
The amount of normally aerated tissue, measured at end-expiration, was in the order of 200–500 g in severe ARDS, i.e., roughly equivalent to the normally aerated tissue of a healthy boy of 5/6 years.
Stiff or Small?
• ARDS lung is not “stiff” at all, but small• The elasticity of the residual inflated lung is
nearly normal, as indicated by:– The specific tissue compliance:
(compliance/normally aerated tissue)• “baby lung” was a healthy anatomical
structure, located in the nondependent regions of the original lungs
Ventilating ARDS with Normal VT
Straining of the “baby lung”
Supine
Prone
Supine
The densities in the dependent lung regions are in fact due not to an increase in the amount of edema but to a loss of alveolar gases, as the result of the compressive gravitational forces, including the heart weight
Sponge Lung Concept
Superimposed Pressure Inflated 0
Alveolar Collapse(Reabsorption) 20-60 cmH2O
Small AirwayCollapse
10-20 cmH2O
Consolidation
(from Gattinoni)Lung Units at Risk for Tidal Opening & Closure
=
Opening pressure
Baby lung at end-inspirationSpectrum of Regional Opening Pressures
Elastic fibers (spring)
Collagen fibers (string).
Baby Lung and VILI
Transpulmonary Pressure
Ventilator Induced Lung Injury
Recognized Mechanisms of Airspace Injury
“Stretch”
“Shear”
Airway Trauma
End-Expiration
Tidal Forces (Transpulmonary and
Microvascular Pressures)
Extreme Stress/Strain Moderate Stress/Strain
Mechano signaling viaintegrins, cytoskeleton, ion channels
inflammatory cascade
Cellular Infiltration and Inflammation
Rupture Signaling
Marini / Gattinoni CCM 2004
Pathways to VILI
FT
min maxMead J et al. J. Appl. Physiol. 28(5):596-608 1970
L. Gattinoni, 2003
Stress distributionhomogeneous system
min maxMead J et al. J. Appl. Physiol. 28(5):596-608 1970
L. Gattinoni, 2003
Stress distributionHigh Stiffness Zone
Copyright ©2008 Canadian Medical Association or its licensorsGattinoni, L. et al. CMAJ 2008;178:1174-1176
Ventilator-induced lung injury is initiated by the application of excessive stress
NEJM 2000;342:1334-1349
NEJM 2000;342:1334-1349
ARDS
PEEP = 5 mbar
Pinsp = 40 mbar
Cytokines, complement, prostanoids, leukotrienes, O2
-
Proteases
Volutrauma
Atelectrauma
Biotrauma
Barotrauma
BiophysicalInjury
• shear• overdistention• cyclic stretch• D intrathoracic
pressure
alveolar-capillarypermeability
¯ cardiac output¯ organ perfusion
Biochemical Injury (Biotrauma)
mf
cytokines, complement,PGs, LTs, ROS,proteases
cytokines, complement,PGs, LTs, ROS,proteases
bacteriabacteria
Epithelium/interstitium
neutrophils
Distal Organ Dysfunction
MV and MODS: A Possible LinkMV and MODS: A Possible Link
Slutsky, Tremblay Am J Resp Crit Care Med. 1998;157:1721-5
DEATH
? sFasL
PRINCIPLES AND GOALS OF MECHANICAL VENTILATION IN ARDS
Healthy subjectIn normal healthy volunteers, the P/V curve explore the mechanical properties of the respiratory system
(lung + chest wall)
ARDS
RV, Residual volume; FRC, Functional residual capacity; TLC, Total lung capacity; UIP, Upper inflection point; LIP, Lower inflection point. The critical opening pressure above which most of the collapsed units open up and may be recruited - CLIN Compliance of the intermediate, linear segment of the P/V curve
Maggiore SS, et al. Eur Respir J. 2003. Rouby JJ, et al. Eur Respir J. 2003.
Respiratory Pressure/Volume (P/V) Curve
Ventilator-induced Lung Injury (VILI)
UpperDeflection point
LowerInflection point
Principles and Goals of MV in ARDS
• Appropriate oxygenation (PO2 = 55-60)• Accept hypercapnea and mild acidosis (pH~ 7.3)• Limit distending pressure=limit transpulmonary
pressure: Pplateau <28 cm H2O• Limit tidal volume: 4-6 ml/Kg• Best PEEP: 10-16 cm H2O
Preventing Overdistention and Under-Recruitment Injury
“Lung Protective” Ventilation“Lung Protective” Ventilation
VOLUME
VOLUME
PressurePressure
Limit Distending PressureLimit Distending Pressure
Add PEEPAdd PEEP
Limit VTTranspulmonary Pressure= Airway
Pressure-Pleural Pressure
4-6 mL/kg
< 28 cm H2O10-16 cm H2O
Pelosi P et al, AJRCCM 2001;164:122-130
CT at end-expiration
Lung protective ventilatory strategy
P
"safe"window
zone of overdistension
V
atelectrauma
volutrauma
LIP
UIPzone of derecruitment and atelectasis
DON’T EVEN
THINKOF PARKING
HERE
Lung Protective Ventilator Strategies
1998
53 patients
Intervention Control
TV <6 ml/KgPEEP >PFlex
TV (10-12 ml/Kg)
Lowest PEEP
28 day mortality
Intervention Control
38% 71%
ARMA Trial
861 patients
Intervention Control
TV (4-6 ml/Kg)PEEP 8.5
TV (10-12 ml/Kg)
PEEP 8.6
861 patients
Intervention Control
Pplateau <30 Pplateau <50
28 day mortality
Intervention Control
31% 40%
NIH ARDS Network trialNEJM 2000;342:1301
ARDS net mortality
Reducing from 12 to 6 ml/kg VT saved lives
NIH ARDS Network trialNEJM 2000;342:1301
Reducing from 12 to 6 ml/kg VT saved lives
Low TV
High TV
P =
Mortality 31 40 0.007
Days of free MV
12 10 0.007
Days free of organ failure
15 12 0.006
Tradeoffs with 6 ml/kg
Crs also better in the HIGH Vt group
ARDS Network: Improved Survival with Low VT
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0180160140120100806040200
Pro
po
rtio
n o
f P
atie
nts
Days after Randomization
Lower tidal volumesSurvivalDischarge
Traditional tidal valuesSurvivalDischarge
ARDS Network. N Engl J Med. 2000.
1996-9
Randomized Trials of MV in ARDS
1990s
10-16 20-26 25-32 29-38
Tidal hyperinflation during Low TV ventilation in ARDS
• 30 patients with ARDS• Ventilatory strategy (ARMA protocol)
– 6 ml/Kg IBW• BAL cytokine measurements►• CT scan on mechanical ventilation
Hyperinflated Normally aerated Poorly aerated Non-aerated
Tidal hyperinflation during low TV ventilation in ARDS
Poorly aerated Non-aerated
Hyperinflated Normally aerated
Less protected More protected
30 % of patients hyperinflated Plateau Pressure:– Protected (25.5 0.5) vs. unprotected (28.9 0.9)
Higher inflammatory cytokines in unprotected Number of ventilator-free days:– Protected (7 8) vs. unprotected (1 2)
Mortality:– Protected (30%) vs. unprotected (40%)
Limit plateau pressure to < 28
Despite the use of protective ventilatory strategy (6 ml/Kg) …..
Papazian L et al. N Engl J Med 2010;363:1107-1116
Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome
340 patientsCisatracurium besylate Placebo
# of Patients 178 162
TV 6-8 ml/Kg 6-8 ml/Kg
PEEP > 5 > 5
90 day mortality 31.6% 40.7%
p= 0.08
Papazian L et al. N Engl J Med 2010;363:1107-1116
Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome
Hazard Ratio: 0.68 (95% confidence interval [CI], 0.48 to 0.98; P = 0.04)
Possible Mechanisms by Which Neuromuscular Blocking Agents Might
Lead to improved Survival
Possible Mechanisms by Which Neuromuscular Blocking Agents Might Lead
to improved Survival
P
"safe"window
zone of overdistension
V
atelectrauma
volutrauma
LIP
UIP
zone of derecruitment and atelectasis
Optimal PEEP
The PEEP Effect
NEJM 2006;354:1839-1841
Higher vs. Lower PEEP
Recruitment
Overinflated
Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome
(EXPRESS)
ALVEOLI
Ventilation Strategy Using Low Tidal Volumes, Recruitment Maneuvers, and High Positive End-Expiratory Pressure for Acute Lung Injury and Acute
Respiratory Distress Syndrome“LOVS”
1998
53 patients
Intervention Control
TV <6 ml/KgPEEP >PFlex
TV (10-12 ml/Kg)
Lowest PEEP
28 day mortality
Intervention Control
38% 71%
50 patients 53 Patients
Intervention Control
TV 5-8 ml/Kg 9-11 ml/Kg
PEEPPflex + 2 cm
H2O>5 cm H2O
ICU Mortality 32% 53%
P= 0.04
Crit Care Med 2006. 34l 1311
385 patients 382 Patients
Intervention Control
TV 6 ml/Kg 6 ml/Kg
PEEPPlateau 28-3016±3 cm H2O
5-9 cm H2O
ICU Mortality NS
Mercat A, Richard JM, Vielle B, et al. (EXPRESS). JAMA. 2008;299:646-655
Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome
(EXPRESS)
549 patientsLow PEEP High PEEP
TV 6 ml/Kg 6 ml/Kg
PEEP 8.3 ± 3.2 13.2 ± 3.5
ICU Mortality 24.9% 27.5%
NS
N E J Med 2004. 351: 327
ALVEOLI
475 patients 508 Patients
Intervention Control
TV 6 ml/Kg 6 ml/Kg
PEEP
Pplat < 40PEEP 20 cm
H2ORM
Pplat < 30Low PEEP
ICU Mortality 36.4% 40.4%
NSMeade et al JAMA. 2008;299(6):637-645.
LOVS
Ventilation Strategy Using Low Tidal Volumes, Recruitment Maneuvers, and High Positive End-Expiratory Pressure for Acute Lung Injury and Acute
Respiratory Distress Syndrome
PEEP in ARDS
PEEP 0 PEEP 10 PEEP 15 PEEP 400%
25%
50%
75%
100%
OverinflatedNormalAtelectasis
Good
Bad
JAMA, March 3, 2010—Vol 303, No. 9
Time to Unassisted Breathing for Higher and Lower Positive End-Expiratory Pressure (PEEP) Stratified by Presence of Acute Respiratory Distress Syndrome (ARDS) at Baseline
Time to Death in Hospital for Higher and Lower Positive End-Expiratory Pressure (PEEP) Stratified by Presence of Acute
Respiratory Distress Syndrome (ARDS) at Baseline
Optimal PEEP
PEEP Table by ARDSNet
• ARDS Network, 2000: Multicenter, randomized 861 patients
Principle for FiO2 and PEEP AdjustmentFiO2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
PEEP 5 5-8 8-10 10 10-14 14 14-18 18-24
NEJM 2000; 342: 1301-1308
Rotta, J Pediatr (Rio J0 2003:79(Suppl 2):S149
Best PEEP
PV Curve
Issues with PV Curves
• Require sedation/paralysis• Difficult to identify “inflection points”• May require esophageal pressure to separate
lung from chest wall effects• Pressure volume curves of individual lung
units are not known
Optimal PEEP by Compliance• 15 normovolemic patients requiring MV for
ARF• PEEP resulting in maximum oxygen
transport and the lowest dead space fraction resulted in highest compliance
• Optimal PEEP varied from 0- to 15 cm H2O• Mixed venous PO2 increased from 0 PEEP
to the PEEP resulting in maximum oxygen transport, but then decreased at higher PEEP
• Conclusion: compliance may be used to indicated the PEEP likely to result in optimum cardiopulmonary function
Suter, N Eng J Med 1975:292:284
Concerns when using lung-protective strategy…
• Heterogeneous distribution• Hypercapnia • Auto-PEEP• Sedation and paralysis• Patient-ventilator dyssynchrony• Increased intrathoracic pressure• Maintenance of PEEP
Permissive Hypercapnia
• Low Vt (6ml/kg) to prevent over-distention• Increase respiratory rate to avoid very high level of
hypercapnia• If Respiratory rate can’t be increased further then the
PaCO2 allowed to rise • Accept PH > 7.25• Usually well tolerated • May be beneficial (shift oxygen dissociation curve to the
right)• May use bicarb infusion till the kidney is able to retain
bicarb
Permissive Hypercapnia – When would you NOT do it?
• Renal failure• High intracranial
pressures • Cardiovascular problems
Conclusion
“Lung Protective” Ventilation“Lung Protective” Ventilation
VOLUME
VOLUME
PressurePressure
Limit Distending PressureLimit Distending Pressure
Add PEEPAdd PEEP
Limit VT
4-6 mL/kg
< 28 cm H2O10-16 cm H2O
Management of refractory hypoxemia
• PEEP• Pee (diuresis)• Prone• Paralysis• Pleural evacuation (pleural
effusion drainage)• Prostacyclin (or iNO)• More PEEP/recruitment
maneuvers
What next?Prone position Inhaled nitric oxide High-frequency oscillation
ECMO
Other Ventilator Strategies
• Lung recruitment maneuvers• Prone positioning• High-frequency oscillatory ventilation
(HFOV)• ECMO
Recruitment Maneuvers
• Application of high airway pressure (35-40cmH2O) for approximately 40 seconds.
• Most common methodology– 40 cm H2O CPAP– 40 seconds
• Employed to open atelectatic alveolar units that occur with ARDS and particularly with any disconnection from ventilator
• If successful, PaO2 will increase by 20% or more.• Must use PEEP after procedure to keep recruited alveoli
open.
Effects of Recruitment Maneuvers to Promote Homogeneity within the Lung
Malhotra A. N Engl J Med 2007;357:1113-1120
Lung Recruitment
• To open the collapsed alveoli
• A sustained inflation of the lungs to higher airway pressure and volumes – Ex.: PCV, Pi = 45 cmH2O,
PEEP = 5 cmH2O, RR = 10 /min, I : E = 1:1, for 2 minutes
NEJM 2006; 354: 1775-1786
ARDSnet protocol Vs open lung protocol
• ARDSnet protocol– Tv 6 ml/kg– Plateau pressure <30– Conventional PEEP (titrate for FIO2
<0.6)
• Experimental protocol– Tv 6 ml/kg– Plateau pressure <40– Recruitment maneuvers– High PEEP (10-15)
JAMA, February 2008
JAMA, February 2008
ARDSnet protocol Vs open lung protocol
Lung Recruitment
NEJM 2006; 354: 1775-1786
Lung Recruitment
NEJM 2006; 354: 1775-1786
• Potentially recruitable (PEEP 5 15 cmH2O)– Increase in PaO2:FiO2– Decrease in PaCO2– Increase in compliance
• The effect of PEEP correlates with the percentage of potentially recruitalbe lung
• The percentage of recruitable lung correlates with the overall severity of lung injury
Lung Recruitment
Sensitivity : 71%
Specificity : 59%
NEJM 2007; 354: 1775-1786
• The percentage of potentially recruitable lung:– Extremely variable,– Strongly associated with the response to PEEP
• Not routinely recommended
Lung Recruitment
Prone Position
Prone Position
• Mechanisms to improve oxygenation:– Increase in end-
expiratory lung volume– Better ventilation-
perfusion matching– More efficient drainage
of secretions
Improved gas exchangeMore uniform alveolar
ventilationRecruitment of atelectasis
in dorsal regionsImproved postural
drainageRedistribution of perfusion
away from edematous, dependent regions
Prone Position
Prone Positioning
Prone Position
NEJM 2001;345:568-573
Prone Position
NEJM 2001;345:568-573
• Improve oxygenation in about 2/3 of all treated patients
• No improvement on survival, time on ventilation, or time in ICU
• Might be useful to treat refractory hypoxemia • Optimum timing or duration ?• Routine use is not recommended
Prone Position
High-Frequency Oscillatory Ventilation (HFOV)
HFV - the “ultimate” lung protective strategy?
Over-distended
Protected
Under-recruit
HFOV
Frequency: 180-600 breaths/min (3-10Hz)
Effect of HFOV on gas exchange in ARDS patients
AJRCCM 2002; 166:801-8
Survival difference of ARDS patients treated with HFOV or CMV
30-day: P=0.05790-day: P=0.078
AJRCCM 2002; 166:801-8
HFOV
• Complications:– Recognition of a
pneumothorax– Desiccation of secretions– Sedation and paralysis– Lack of expiratory filter
• Failed to show a mortality benefit
• Combination with other interventions ?
Chest 2007; 131:1907-1916
Acute Lung injury
• Decreased lung compliance results in high airway pressures
• Low tidal volume 6-8 ml/kg ideal body weight• Maintain IPP 30 cm H2O• PEEP to improve oxygenation
Conclusions • The only treatment that shows mortality
benefit: – lung-protective ventilation strategy– Low tidal volume (6ml/Kg), high PEEP, adequate
Pplat (<30 cmH2O)• Modalities to improve oxygenation:
– Prone position, steroid, fluid treatment, steroid, HFOV, NO
• Combining other treatments:– Antibiotics, EGDT…etc
Be Inspired
The University of Michigan