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Ventilatory Management of ARDS: What Have We
Learned and What Questions are Unanswered!
ByBob Kacmarek
Massachusetts General Hospital,Harvard Medical School,Boston, Massachusetts
Mechanical Ventilation
Biochemical Injury
Biophysical Injury
Distal Organs Affected MSOF
Slutsky, Tremblay AJRCCM 1998;157:1721
Hickling ICM 1990; 16:216• 50 ARDS patients• Mortality: actual 16%, predicted 40%• SIMV, volume targeted• PIP < 40 cmH2O
• VT as low as 5 mL/kg
• PaCO2 averaged about 60 mmHg
• PEEP 9 + 6 cmH2O, FIO2 < 0.60
Randomizied Controlled Trials LPVS
MortalityAmato* Steward Brochard Brower NIH*(C) 71% 48.3% 37.9% 46% 40%(T) 38% 46.3% 46.6% 50% 31%
*P < 0.002, P = 0.0054
Amato et al (To Be Submitted)
• Original data from :• Amato et al NEJM 1998;338:347• Stewart et al NEJM 1998;338:355• Brochard et al AJRCCM
1998;158:1831• Brower et al CCM 1999;27:1492
• Pooled and analyzed for the effect of VT, plateau pressure, and PEEP on Outcome (n=331)
6050403020100
1.1
1.0
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DAYS AFTER ENTRY
BROCHARD & BROWER & STEWART & AMATO
P < 0.0001
n = 341CU
MM
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IVA
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PPLAT > 33
PPLAT < 23
23 2727 33
( Adjusted for APACHE & pH & PEEP )
15 20 25 30 35 40 450
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PLATEAU PRESSURES (cmH2O)
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BROCHARD & BROWER & STEWART & AMATO
Mortality vs Day 1 Plateau PressureMortality vs Day 1 Plateau PressureNIH Trial of 6 vs 12 ml/kg Tidal NIH Trial of 6 vs 12 ml/kg Tidal
VolumeVolume
ARDSnet
• 6 mL/kg reduces mortality vs 12 mL/kg• Use rapid rates, avoid auto-PEEP (<
35/minute)• PPLAT < 30 cmH2O, mortality reduced
regardless of VT?
• Lower the PPLAT, better the outcome
Optimal Ventilatory Strategy in ARDS: What is Still Unclear
• Mode of Ventilation• Method of Setting PEEP• PEEP Level• Need for Lung Recruitment• High Frequency Ventilation• Prone Positioning• Liquid Ventilation
Grasso Anes 2002; 96:795• 22 pt’s ARDS, VT 6 ml/Kg• RM-40 cm H2O, CPAP 40 sec• Responders > 50% P/F with RM• N=11 non-responders P/F 20 3%• N=11 responders P/F 175 23%
Grasso Anes 2002; 96:795(P< 0.01) Respond Nonrespond
Est 24.2 2.9 28.4 2.2Estw 5.6 0.08 10.4 1.8CO 2 1% 31 2%MAP2 1% 19 3%MV days 1 0.3 7 1
No Difference pul vs extra-pul ARDS
Lapinsky ICM 1999;25:1297
Lung Recruitment
• Useful in ARDS?• Perform early in ARDS• Works better in extra pulmonary than
primary ARDS?• More difficult the stiffer the chest wall• Start with low pressure increase as tolerated
and needed
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UNIVARIATE
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PEEP (cmH2O)
MORTALITY ACROSS PEEP LEVELS ( 6 TILES )( Amato & Stewart & Brochard & Brower )
P = 0.001
n = 331
Setting PEEP• PEEP/FIO2 algorithm either stated or
unstated• Increasing PEEP trial Oxygenation
Lung Mechanics Cardiovascular Stability
• Pressure – Volume Curve (Pflex)• Decelerating PEEP TrialAll applied following a lung recruitment
maneuver
Takeuchi Anes 2002;97:682• 3 approaches to setting PEEP in ARDS• N=7 sheep lavage injury in each group• Injury, RMs to restore P/F• Group 1 PEEP PCL + 2• Group 2 PEEP PMCEX
• Group 3 PEEP based on PaO2 at FIO2 0.5• Target PaO2 60-100 mmHg
Takeuchi Anes 2002;97:682
Takeuchi Anes 2002;97:682
1st RM 1st PEEP 2nd PEEP PEEP 50 26 24 PO2 432 + 90 82 + 10 89 + 16 PCO2 63 + 10 56 + 7 52 + 8 PH 7.29 + 0.11 7.32 + 0.06 7.34 + 0.10 Number 7 2 7
3rd PEEP 4th PEEP 5th PEEP 6th PEEP
22 20 18 16 103 + 22 110 + 19 98 + 14 111+14
46 + 9 45 + 11 45 + 7 48+5 7.33 + 0.08 7.36 + 0.12 7.39 + 0.09 7.34+0.03
7 7 7 3
Khalad Sedeek (preliminary data)
2nd RM 60 min PEEP 50 20/18 PO2 448 + 68 108+22 PCO2 55 + 12 47 + 10 PH 7.33 + 0.13 7.36 + 0.07 Number 7 4/3
120 min 180 min 240 min 20/18 20/18 20/18
115+14 103+31 105+26 42 + 8 39 + 6 42 + 8
7.38 + 0.10 7.41 + 0.06 7.39 + 0.08 4/3 4/3 4/3
Khalad Sedeek (preliminary data)
Karim Kamal (Preliminary Data)
• 20 med/surg ICU pts with ALI/ARDS• All met AECC definition of ALI at BL• P/F<300; PEEP >8cm H20• 1.2 days MV; Age 41.5+14.0 years• Up to 3 RM (40 cm H20 CPAP, 40 sec)• Decelerating PEEP trial• RM after optimal PEEP,followed for 4 hr
FIO2 0.54 1.00 1.00 0.375* 0.375* 0.375*PEEP 11.9 11.9 20 9.1 9.1 9.1
Karim Kamal (Preliminary Data)
*
*#
* * *
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BL PRE RM POST RM PEEP 1 HR 4 HR
P/F
Karim Kamal (Preliminary Data)
Karim Kamal (Preliminary Data)• % Increase in P/F ratio
– BL vs Post RM (100% O2) – 220%
• All pts > 50% increase• 13 pts > 100%
– Pre RM (100% O2) vs Post RM – 148.5%
• All >20% increase• 8 > 50% increase
• Almost all patients maintained PO2 for four hour period
• Assessment of Low tidal Volume and elevated End-expiratory volume to Obviate Lung Injury
• RCT of:
6 ml/kg IBW vs 6ml/kg IBW + PEEP
• PEEP set by PEEP/Fi02 scale
ARDS Network - ALVEOLI Trial
ALVEOLI:ALVEOLI: PaO2 = 55-80 mmHg or SpO2 = 88-95%
Control
PEEP 5 5 8 8 10 12 14 16 -18 20-24
FiO2 .3 .4 .4 .5 .5-.7 .7 .7-.9 .9 1.0
Higher PEEP
PEEP 12 14 14 16 16 18 20 22 24
FiO2 .3 .3 .4 .4 .5 .5 .5-.8 .8-.9 1.0
ARDSnet AlveoliAt Entry
PEEP Low HighAge 48+1 54+1 P<0.0003PaO2/FIO2 149+4 137+4 P=0.056
ALVEOLI - Mortality Before Hospital ALVEOLI - Mortality Before Hospital DischargeDischarge
Low PEEP High PEEP
Adjusted p= 0.44
27.6 24.9
Low PEEP High PEEP
25.1 27.2
Unadjustedp=0.56
French High PEEP TrialCanadian LOVS Trial
• High vs low PEEP by algorithm• Recruitment maneuvers• Pressure ventilation• PIP to 40 cmH2O in high PEEP group• Over 300 enrolled, will continue to
enroll to 900
HFO MOAT2• Multicenter RCT, N=74 each group• Based on 95% CI that HFO was comparable
to CMV but not >10 % worse then CMV and not > 20% difference in adverse outcomes
• Computer randomizied at each site(Max diff of two patients with OI>40 between HFO and CMV groups
• Intention to treat analysisDerdek AJRCCM 2002;166:801
Conclusion
• No significant differences in mortality, morbidity, hemodynamics, oxygenation failure, ventilation failure, barotrauma or mucus plugging between groups.
• HFO equivalent to CMV in managing ARDS.
Derdek AJRCCM 2002:166:801
HFO vs CMV• RCT - adult ARDS• Mortality Difference
• 38% HFO• 52% CMV
• VT 10.2 ml/kg IBW• Mode PCV , PIP 37+8 cmH2ODerdek AJRCCM 2002;166:801
Gattinoni NEJM 2001; 345:568
Prone Positioning• Cannot be dismissed based on this single
study• Length of time prone 7 + 4.8 hours/day• Ventilatory strategy
VT 10.3 + 2.8 mL/kg
PEEP 9.6 + 30 cmH2O
Rate 17.2 + 5.1/min
Gattinoni NEJM 2001:345;568
Mortality
Low PLV
6-month 30.3%
CMV
21.5%
High PLV
24.8%
28-day 26.3% 15.0%19.1%
Overall
25.4%
19.9%
n=99 n=107 n=105 n=311
(26) (20) (16) (62)
(30) (26) (23) (79)
Mortality Comparison
TrialVentilation
Strategy28-Day
Mortality
15.0%
19.7%ARDSnet "low stretch" arm
age < 65 yrs(n=350)
PLV-007CMV arm
age < 65 yrs(n=107)
TV 6ml/kg/IBWPEEP 9 cmH20EIP 28 cmH20
TV 9 ml/kg/IBWPEEP 14 cmH20EIP 28 cmH20
Management of ARDSSummary
• 6 mL/kg reduces mortality vs 12 mL/kg• Use rapid rates, avoid auto-PEEP (<
35/minute)• PPLAT < 30 cmH2O, mortality reduced
regardless of VT?
• Lower the PPLAT, better the outcome
Management of ARDSSummary
• Lung Recruitment of Benefit?????• Perform early in ARDS - Yes• Works better in extra pulmonary than
primary ARDS?• More difficult the stiffer the chest wall• Start with low pressure increase as tolerated
and needed
Management of ARDSSummary
• Method to Set PEEP???, But Should be Sufficient to Avoid Derecruitment
• HFO as Good as CMV, but Better??? Must Demonstrate Superiority to ARDSNet
• Prone Position Improves PO2, but Effect on Mortality Unclear, Need More Clinical Trials
• PLV -Unlikely To See More Clinical Trials• Need to Add Standard Ventilator Settings to
AECC definition of ARDS for Clinical Trials?
Thank You