ventilatory management of ards kacmarek

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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.8

.7

.6

.5

.4

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DAYS AFTER ENTRY

BROCHARD & BROWER & STEWART & AMATO

P < 0.0001

n = 341CU

MM

UL

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SU

RV

IVA

L

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)

REL

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RIS

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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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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)

*

*#

* * *

0

50

100

150

200

250

300

350

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