Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.

BACKGROUND Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients. METHODS We randomly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen. RESULTS Mean (+/-SD) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group (P=0.50). CONCLUSIONS These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used.

[1]  G Saumon,et al.  High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. , 1988, The American review of respiratory disease.

[2]  J. Laaban,et al.  [Heart-lung interactions]. , 2003, Revue des maladies respiratoires.

[3]  B Efron,et al.  Statistical Data Analysis in the Computer Age , 1991, Science.

[4]  J. Whitsett,et al.  Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. , 1999, American journal of respiratory and critical care medicine.

[5]  Arthur S Slutsky,et al.  Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome , 2002, Critical care medicine.

[6]  D. Schoenfeld,et al.  Meta-analysis of acute lung injury and acute respiratory distress syndrome trials. , 2002, American journal of respiratory and critical care medicine.

[7]  F. Jardin PEEP and ventricular function , 2005, Intensive Care Medicine.

[8]  G. Bernard,et al.  Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome , 2002, Critical care medicine.

[9]  M. Matthay,et al.  Elevated pulmonary edema fluid concentrations of soluble intercellular adhesion molecule-1 in patients with acute lung injury: biological and clinical significance. , 1999, Chest.

[10]  W. Knaus,et al.  The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. , 1991, Chest.

[11]  Laurence L. George,et al.  The Statistical Analysis of Failure Time Data , 2003, Technometrics.

[12]  Salvador Benito,et al.  Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. , 2002, JAMA.

[13]  G. Rubenfeld,et al.  Lung-protective ventilation strategies in acute lung injury , 2003, Critical care medicine.

[14]  Douglas Hayden,et al.  Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end-expiratory pressure* , 2003, Critical care medicine.

[15]  R. Hubmayr,et al.  Mechanisms of recruitment in oleic acid-injured lungs. , 2001, Journal of applied physiology.

[16]  W. Wolfe,et al.  Oxygen toxicity. , 1975, Annual review of medicine.

[17]  J. Mead,et al.  Stress distribution in lungs: a model of pulmonary elasticity. , 1970, Journal of applied physiology.

[18]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .

[19]  M. Tobin Principles and Practice of Mechanical Ventilation , 1994 .

[20]  R. Albert,et al.  Extra-alveolar vessel fluid filtration coefficients in excised and in situ canine lobes. , 1985, Journal of applied physiology.

[21]  F Lemaire,et al.  Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS. , 1998, American journal of respiratory and critical care medicine.

[22]  K. Peevy,et al.  Mechanisms of ventilator-induced lung injury. , 1993, Critical care medicine.

[23]  F. Lemaire,et al.  Principles and practice of mechanical ventilation , 1995, Intensive Care Medicine.

[24]  G. Bernard,et al.  Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Ibuprofen in Sepsis Study Group. , 1999, Critical care medicine.

[25]  D A Schoenfeld,et al.  A Simple Algorithm for Designing Group Sequential Clinical Trials , 2001, Biometrics.

[26]  Arthur S Slutsky,et al.  Tidal ventilation at low airway pressures can augment lung injury. , 1994, American journal of respiratory and critical care medicine.

[27]  P. Dorinsky,et al.  Diagnosis and therapy of acute respiratory distress syndrome in adults: an international survey. , 1996, Journal of critical care.

[28]  B. Rippe,et al.  Increased microvascular permeability in dog lungs due to high peak airway pressures. , 1984, Journal of applied physiology: respiratory, environmental and exercise physiology.

[29]  J. Sznajder,et al.  Adverse effects of large tidal volume and low PEEP in canine acid aspiration. , 1991, The American review of respiratory disease.

[30]  Arthur S Slutsky,et al.  Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. , 1999, JAMA.

[31]  D. Dreyfuss,et al.  Ventilator-induced lung injury: lessons from experimental studies. , 1998, American journal of respiratory and critical care medicine.

[32]  C. Carvalho,et al.  Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. , 1998, The New England journal of medicine.

[33]  P. Parsons,et al.  Clinicians' approaches to mechanical ventilation in acute lung injury and ARDS. , 2001, Chest.

[34]  J. Cameron,et al.  The beneficial and harmful effects of positive end expiratory pressure. , 1978, Surgery, gynecology & obstetrics.

[35]  L. Brochard,et al.  Titration of tidal volume and induced hypercapnia in acute respiratory distress syndrome. , 1995, American journal of respiratory and critical care medicine.

[36]  D. Schoenfeld,et al.  Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. , 2000, The New England journal of medicine.

[37]  A. Anzueto,et al.  Aerosolized Surfactant in Adults with Sepsis-Induced Acute Respiratory Distress Syndrome , 1996 .

[38]  M. Pinsky,et al.  The hemodynamic consequences of mechanical ventilation: an evolving story , 1997, Intensive Care Medicine.

[39]  Michael R. Pinsky Heart–lung interactions , 1998 .

[40]  M. Takeya,et al.  Histopathologic pulmonary changes from mechanical ventilation at high peak airway pressures. , 1991, The American review of respiratory disease.