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A Randomized Controlled Trial

Maureen O. Meade, MD, MSc; Deborah J. Cook, MD, MSc; Gordon H. Guyatt, MD, MSc; Arthur S. Slutsky, MD; Yaseen M. Arabi, MD; D. James Cooper, MD; Andrew R. Davies, MD; Lori E. Hand, RRT, CCRA; Qi Zhou, PhD; Lehana Thabane, PhD; Peggy Austin, CCRA; Stephen Lapinsky, MD; Alan Baxter, MD; James Russell, MD; Yoanna Skrobik, MD; Juan J. Ronco, MD; Thomas E. Stewart, MD; for the Lung Open Ventilation Study Investigators

JAMA. 2008;299(6):637-645.

Context  Low-tidal-volume ventilation reduces mortality in critically ill patients with acute lung injury and acute respiratory distress syndrome. Instituting additional strategies to open collapsed lung tissue may further reduce mortality.

Objective  To compare an established low-tidal-volume ventilation strategy with an experimental strategy based on the original "open-lung approach," combining low tidal volume, lung recruitment maneuvers, and high positive-end–expiratory pressure.

Design and Setting  Randomized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada, Australia, and Saudi Arabia.

Patients  Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250.

Interventions  The control strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau airway pressures not exceeding 30 cm H₂O, and conventional levels of positive end-expiratory pressure (n = 508). The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau pressures not exceeding 40 cm H₂O, recruitment maneuvers, and higher positive end-expiratory pressures (n = 475).

Main Outcome Measure  All-cause hospital mortality.

Results  Eighty-five percent of the 983 study patients met criteria for acute respiratory distress syndrome at enrollment. Tidal volumes remained similar in the 2 groups, and mean positive end-expiratory pressures were 14.6 (SD, 3.4) cm H₂O in the experimental group vs 9.8 (SD, 2.7) cm H₂O among controls during the first 72 hours (P < .001). All-cause hospital mortality rates were 36.4% and 40.4%, respectively (relative risk [RR], 0.90; 95% confidence interval [CI], 0.77-1.05; P = .19). Barotrauma rates were 11.2% and 9.1% (RR, 1.21; 95% CI, 0.83-1.75; P = .33). The experimental group had lower rates of refractory hypoxemia (4.6% vs 10.2%; RR, 0.54; 95% CI, 0.34-0.86; P = .01), death with refractory hypoxemia (4.2% vs 8.9%; RR, 0.56; 95% CI, 0.34-0.93; P = .03), and previously defined eligible use of rescue therapies (5.1% vs 9.3%; RR, 0.61; 95% CI, 0.38-0.99; P = .045).

Conclusions  For patients with acute lung injury and acute respiratory distress syndrome, a multifaceted protocolized ventilation strategy designed to recruit and open the lung resulted in no significant difference in all-cause hospital mortality or barotrauma compared with an established low-tidal-volume protocolized ventilation strategy. This "open-lung" strategy did appear to improve secondary end points related to hypoxemia and use of rescue therapies.

Trial Registration  clinicaltrials.gov Identifier: NCT00182195

Author Affiliations: McMaster University, Hamilton, Ontario, Canada (Drs Meade, Cook, Guyatt, Zhou, and Thabane and Mss Hand and Austin); University of Toronto, Toronto, Ontario, Canada (Drs Slutsky, Lapinsky, and Stewart); King Saud Bin Abdulaziz University, Riyadh, Saudi Arabia (Dr Arabi); Monash University, Melbourne, Australia (Drs Cooper and Davies); Ottawa University, Ottawa, Ontario, Canada (Dr Baxter); University of British Columbia, Vancouver, British Columbia, Canada (Drs Russell and Ronco); and University of Montreal, Montreal, Quebec, Canada (Dr Skrobik).

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