Ventilatory Management of ARDS: What Have We Learned and What Questions are Unanswered

1. Ventilatory Management of ARDS: What Have We Learned and What Questions are Unanswered! By Bob Kacmarek Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

3. 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

4. Randomizied Controlled Trials LPVS Mortality Amato* 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

6. 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)

9. Mortality vs Day 1 Plateau PressureNIH Trial of 6 vs 12 ml/kg Tidal Volume

11. 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

12. 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

15. 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%

16. Grasso Anes 2002; 96:795 (P< 0.01) Respond Nonrespond Est 24.2 ? 2.9 28.4 ? 2.2 Estw 5.6 ? 0.08 10.4 ? 1.8 CO 2 ? 1% 31 ? 2% MAP 2 ? 1% 19 ? 3% MV days 1 ? 0.3 7 ? 1 No Difference pul vs extra-pul ARDS

17. Lapinsky ICM 1999;25:1297

18. 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

25. Setting PEEP PEEP/FIO2 algorithm either stated or unstated Increasing PEEP trial Oxygenation Lung Mechanics Cardiovascular Stability Pressure – Volume Curve (Pflex) Decelerating PEEP Trial All applied following a lung recruitment maneuver

27. Takeuchi Anes 2002;97:682

28. Takeuchi Anes 2002;97:682

29. Khalad Sedeek (preliminary data)

31. 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

32. 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 ±3.0 ±3.0 ±4.7 ±4.7 ±4.7Karim Kamal (Preliminary Data)

33. Karim Kamal (Preliminary Data)

34. 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

35. 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

36. 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

37. ARDSnet AlveoliAt Entry PEEP Low High Age 48+1 54+1 P<0.0003 PaO2/FIO2 149+4 137+4 P=0.056

38. ALVEOLI - Mortality Before Hospital Discharge

39. 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

40. 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 analysis Derdek AJRCCM 2002;166:801

41. 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

42. HFO vs CMV RCT - adult ARDS Mortality Difference • 38% HFO • 52% CMV VT 10.2 ml/kg IBW Mode PCV , PIP 37+8 cmH2O Derdek AJRCCM 2002;166:801

43. Gattinoni NEJM 2001; 345:568

44. 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

46. Mortality

47. Mortality Comparison Trial

48. 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

49. 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

50. 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?

51. Thank You