ARDSに対する人工呼吸療法

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1 特集人工臓器と救急集中治療 ARDS Shingo ICHIBA 1. はじめに acute respirator y distress syndrome, ARDS 2. ARDSの病態について ARDS 1967 Ashbaugh 1) ARDS ARDS 3. 定義 ARDS 1994 American-European Consensus Conference 2) PaO2 FIO2 P/F ratio 200 mmhg 著者連絡先 sichiba@bme.ous.ac.jp 18 mmhg acute lung injury, ALI P/F ratio 300 mmhg ARDS 4. 疫学 ARDS 100, / 65 Barnard 3) ARDS 9 16 multiple organ failure, MOF ICU 4) ALI ARDS MOF ARDS 5. 病態生理 ARDS primar y secondar y Primar y Secondary 2 / /

2 ARDS 5) 1) 浸出期 1 free radical ARDS TNF- IL-1, 6, 8 vasoconstriction 2) 器質化期 Type 3) 線維化期 Type 6. 機械的人工呼吸 (mechanical ventilation, MV)の功罪 ARDS ARDS MOF MV MV ventilator induced lung injury VILI VILI biochemical biophysical injur y Biophysical injury barotrauma 6) Tsuno 30 cmh2o barotrauma 7) 150 cmh2o 1 30 ml/kg transpulmonary pressure volutrauma atelectrauma 8) Gattinoni ARDS CT ARDS baby lung model 9) volutrauma 10) atelectrauma MV humoral mediator biotrauma 11) Imai apoptosis 12) ARDS MOF 7. Lung protective ventilation strategy (LPVS) ( 肺保護戦略に基づく人工呼吸管理 ) ARDS 3 FIO

3 13) LPVS VILI Amato 14) LPVS RCT ARDS Network ARDSnet 15) 1 6 ml/kg predicted body weight, PBW 12 ml/kg PBW 2008 Surviving Sepsis Campaign Sepsis ALI/ARDS tidal volume of 6 ml/kg PBW Grade 1B moderate quality of evidence, strong recommendation 16) 1 30 cmh2o PEEP VILI LPVS 17),18) open-lung strategy PEEP 19),20) 1 ph 7.2 permissive hypercapnia 21) LPVS CO2 22) 23) CO2 vasoactive Komori PaCO2 PaCO2 150 mmhg 24) hypercapnia ARDS high frequency oscillatory ventilation, HFOV 1 10 HFOV ml/kg volutrauma 25) 2 RCT ARDS ARDS LPVS 1 6 ml/ kg PBW PEEP 8. 人工肺の関与 ARDS? Bernard 3) Roentgen X iron lung Swan-Ganz ARDS 1970 extracorporeal life support ECLS 26) 3 severe ARDS 20 27) ARDS ECLS 表 1 ECLS pre-p/f ratio pre-paco2 3 extracorporeal membrane oxygenation ECMO veno-ar terial bypass VAB veno-venous bypass VVB VVB low frquency positive pressure ventilation with extracorporeal CO2 removal

4 表 1 Landmark research papers of extracorporeal life support for severe ARDS Author/ country (Reference No) Zapol WM/ USA 26 Gattinoni L/ Italy 31 Morris AH/ USA 32 Lewandowski K/Germany Hemmila MR/ USA 33 Bein T/ Germany Peek GJ/UK Publication year (reference) Method of research 1979 Prospective randomized controlled trial 1986 Uncontrolled study 1994 Prospective randomized controlled trial 1997 Prospective uncontrolled trial 2004 Uncontrolled study 2006 Uncontrolled study Publishing soon Prospective randomized controlled trial Type of ECLS VAB ECMO LFPPV- ECCO2R LFPPV- ECCO2R VVB ECMO VVB or VAB ECMO AVCO2R VVB ECMO Entry criteria Fast entry: At FIO2 1.0 and PEEP 5, PaO2 50 for 2 h Slow entry: At FIO2 0.6 and PEEP 5, PaO2 50, QS/QT 0.3 for 12 h Fast entry: At FIO2 1.0 and PEEP 5, PaO2 50 for 2 h Slow entry: At FIO2 0.6 and PEEP 5, PaO2 50, QS/QT 0.3, CTstat 30 ml/ cmh2o for 12h Fast entry: At FIO2 1.0 and PEEP 5, PaO2 50 for 2 h Slow entry: At FIO2 0.6 and PEEP 5, PaO2 50, QS/QT 0.3 for 12 h Fast entry: At PEEP 10, P/F ratio 50 for 2 h Slow entry: At PEEP 10, P/F ratio 150, Q S/QT 0.3, EVLW 15 ml/kg, CTstat 30 ml/cmh2o for 12 h Failure to algorithm for treatment of severe ARDS: At FIO2 1.0, PaO2 100, A-aDO2 600, or QS/QT 0.3 Failure of advanced treatment: At FIO2 1.0, PaO2 55 and/or hypercapnic acidosis with hemodynamic instability for 2 h, or tendency toward deterioration Severe but potentially reversible respiratory failure, Murray score 2.5 or uncompensated hypercapnea with ph 7.2 Mean Mean ECLS pre-p/f pre-paco2 cases ratio mmhg (survived) Survival rate (%) 9.5% 48.8% 33.3% 55.1% 51.8% 41.1% ECMO was favourable PaO2/FIO2 ratio: P/F ratio, A-aDO2: alveolar-arterial gradient, CTstat: thracopulmonary compliance, ECLS: extracorporeal life support, EVLW: extravascular lung water, QS/QT: intrapulmonary right-to-left shunt. Peek, personal communication. LFPPV-ECCO2R ar terio-venous CO2 removal AVCO2R pumpless extracorporeal inter ventional lung assist ila Novalung GmbH, Hechingen, Germany 9. 歴史的な流れ 1972 Hill ECMO 28) 24 4 ARDS 75 VAB ECMO Hill ECMO ECMO randomized controlled trial RCT US National Institute of Health NIH FIO2 50 ECMO fast entr y: FIO2 100 PEEP 5 cmh2o PaO2 50 mmhg 2 slow entry: FIO2 60, PEEP 5 cmh2o PaO2 50 mmhg 12 shunt fraction 30 VAB ECMO

5 randomize 9 26) VAB Kolobow VAB VVB ARDS 29) ECMO 9 Kolla ECMO 100 ECMO 7 LPVS 30) RCT ECMO Gattinoni CO2 LFPPV-ECCO2R 1970 NIH ECMO ) LFPPV-ECCO2R PEEP cmh2o, 3 5 /min, peak airway pressure cmh2o Tidal volume VT LPVS open lung apneic oxygenation Morris LFPPV-ECCO2R RCT 32) Gattinoni 1970 US ECMO trial 40 3 ECCO2R CO ml/kg PBW volutrauma Ppeak 45.4 cmh2o barotrauma 1.76 l/day LFPPV-ECCO2R pressure controlled inverse ratio ventilation PCIRV LPVS LFPPV- ECCO2R Gattinoni 31) 2 RCT ECLS Bar tlett ECMO 33) VVB ECMO full support 34) severe ARDS 35) Lewandowski ARDS VVB ECMO ARDS 75 36) Bar tlett 33) 1989 Extracorporeal Life Support Organization ELSO ECMO Center 図 1 37) ECMO conventional ventilation poly-methyl pentene PMP 38) ECMO ECMO ECMO specialist

6 図 1 Extracorporeal Life Support Organization International Registry as of July 2007 Cumulative Survival of Adult Respiratory Cases. Hemmila learning curve 33) ECMO GGH National Health Service NHS ECMO RCT conventional ventilator support vs extracorporeal membrane oxygenation for severe adult respiratory failure CESAR trial 39) ECMO 表 1 ARDS randomize ECMO ECMO GGH ECMO conventionai conventional treatment center ECMO was favorable 40) 10. 人工肺の挑戦 severe ARDS ECMO ELSO registry report ECMO 1,373 oxygenator failure 19.7 surgical site/cannulation site/gastrointerstinal GI bleeding 40.5 dialysis/hemofiltration/ continuous arteriovenous hemofiltration CAVH required 47.5 Inotropes on ECLS 59.7 cardiac arr ythmia 20 hyper glycemia glucose culture proven infection ) ECMO 40.5 ARDS LPVS 1 PEEP ARDS LPVS ECMO quality of life QOL ila ECMO CO2 LPVS LFPPV-ECCO2R Bein ECMO severe ARDS ila

7 図 2 Clinical algorithm for the treatment of ARDS using extracorporeal lung support Permission by Dr Thomas Bein, University Hospital Regensburg 24 FIO2 1 ph PaCO2 41) 41.1 ECMO severe ARDS ELSO 42) 43) 1 2 l/min P/F ratio 70 VVB ECMO 43) 11. 結語 ARDS magic bullet ARDS Bein ARDS LPVS 43) ECMO ila 図 2 文献 1) Ashbaugh DG, Bigelow DB, Petty TL, et al: Acute respiratory distress in adults. Lancet 29: , ) Bernard GR, Artigas A, Brigham KL, et al: The American- European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coodination. Am J Respir Crit Care Med 149: , ) Bernard GR: Acute respirator y distress syndrome: a historical perspective. Am J Respir Crit Care Med 172: , ) ICU 10: , ) Ware LB, Matthay MA: The acute respirator y distress syndrome. N Eng J Med 342: , ) Kumar A, Pontoppidan H, Falke KJ, et al: Pulmonar y barotrauma during mechanical ventilation. Crit Care Med 1: 181-6, ) Tsuno K, Prato P, Kolobow T: Acute lung injur y from mechanical ventilation at moderately high airway pressures. J Appl Physiol 69: , ) Muscedere JG, Mullen JB, Gan K, et al: Tidal ventilation at low airway pressure can augment lung injury. Am J Respir Crit Care Med 149: , ) Gattinoni L, Pesenti A: The concept of baby lung. Intensive Care Med 31: , ) Dreyfus D, Soler P, Basset G, et al: High inflation pressure pulmonar y edema: respective ef fects of high air way pressure, high tidal volume, and positive end-expiratory pressure. AmRev Respir Dis 137: ,

8 11) Tremblay LN, Slutsky AS: Ventilator-induced injury: from barotraumas to biotrauma. Proc Assoc Am Physicians 110: 482-8, ) Imai Y, Parodo J, Perrol M, et al: Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute reapiratory distress syndrome. JAMA 289: , ) Lachman B: Open up the lung and keep the lung open. Intensive Care Med 18: , ) Amato MB, Barbas CS, Medeiros DM, et al: Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 338: , ) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respirator y distress syndrome. The Acute Respirator y Distress Syndrome Network. N Eng J Med 342: , ) Dellinger RP, Levy MM, Carlet JM, et al: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: Crit Care Med 36: , ) ALI/ARDS ARDS ) VI 55. ARDS 18: 667-8, ) Meade MO, Cook JD, Guyatt G, et al: Ventilation strategy using low tidal volumes, recruit maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome. JAMA 299: , ) Gattinoni L, Caironi P: Refining ventilatory treatment for acute lung injury and acute respiratory distress syndrome. JAMA 299: 691-3, ) Hickling KG, Walsh J, Henderson S: Low mortality rate in adult respirator y distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: a prospective study. Crit Care Med 22: , ) Sinclair SE, Kregenow DA, Lamm WJE: Hypercapnic acidosis is protective in an in vivo model of ventilatorinduced lung injury. Am J Respir Crit Care Med 166: 403-8, ) Lang JD, Figueroa M, Sanders D: Hypercapnea via reduced rate and tidal volume contributes to lipopolysaccharideinduced lung injur y. Am J Respir Crit Care Med 171: , ) Komori M, Takada K, Tomizawa Y, et al: Permissive range of hypercapnia for improved peripheral microcirculation and cardiac output in rabbits. Crit Care Med 35: , ) Chan KPW, Stewar t TE, Mehta S: High-frequency oscillatory ventilation for adult patients with ARDS. Chest 131: , ) Zapol WM, Snider MT, Hill JD, et al: Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study. JAMA 242: , ) ECMO , ) Hill JD, O Brien TG, Murray JJ, et al: Prolonged extracorporeal oxygenation for acute post-traumatic respiratory failure (shock-lung syndrome). Use of the Bramson membrane lung. N Eng J Med 286: , ) Kolobow T, Spragg R, Pierce J: Massive pulmonar y infarction during total cardiopulmonar y bypass in unanesthetized spontaneously breathing lambs. Int J Artif Organs 4: 76-81, ) Kolla S, Awad SS, Rich PB: Extracorporeal life support for 100 adult patients with severe respiratory failure. Ann Surg 226: , ) Gattinoni L, Pesenti A, Masheroni D, et al: Low-frequency positive pressure ventilation with extracorporeal CO2 removal in severe acute respiratory failure. JAMA 256: 881-6, ) Morris AH, Wallace CJ, Menlove RL, et al: Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO 2 removal for adult respirator y distress syndrome. Am J Respir Crit Care Med 149: , ) Hemmila MR, Rowe SA, Boules TN, et al: Extracorporeal life support for severe acute respiratory distress syndrome in adults. Ann Surg 240: , ) Ichiba S, Peek GJ, Sosnowski AW, et al: Modifying a venovenous ECMO circuit to reduce recirculation. Ann Thorac Surg 69: 298, ) Peek GJ, Moore HM, Moore N, et al: Extracorporeal membrane oxygenation for adult respiratory failure. Chest 112: , ) Lewandowski K, Rossaint R, Pappert D, et al: High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation. Intensive Care Med 23: , ) Extracorporeal Life Support Organization International Registry, July ) Nishinaka T, Tatsumi E, Ohnishi H, et al: Up to 151 days of continuous animal perfusion with trivial heparin infusion by the application of a long-term durable antithrombogenic coating to a combination of a seal-less centrifugal pump and a diffusion membrane oxygenator. J Artif Organs 10: 240-4, ) Peek GJ, Clemens F, Elbourne D: CESAR: conventional ventilator support vs extracorporeal membrane oxygenation for severe adult respiratory failure. BMC Health Serv Res 6: 163, ) Giles J Peek: Personal communication 41) Bein T, Weber F, Phillip A, et al: A new pumpless extracorporeal inter ventional lung assist in critical hypoxemia/hypercapnia. Crit Care Med 34: , ) Thomas Bein: Personal communication 43) Bein T: Recent advances in extracorporeal lung assist. International Journal of Intensive Care. Autum 19-22,

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1 65 ARDS 2 3 ARMA by ARDS Network 1 12ml/kg 6ml/kg RCT ARDS 4 Low Tidal Volume Amato Stewart Brochard Brower ARMA Lower Higher Lower Higher Lower Higher Lower Higher Lower Higher N 29 24 60 60 58 58 26