Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial

Abstract

Importance: The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain.

Objective: To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy.

Design, setting, and participants: Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS.

Interventions: An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning.

Main outcomes and measures: The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality.

Results: A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, -1.1; 95% CI, -2.1 to -0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality.

Conclusions and relevance: In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients.

Trial registration: clinicaltrials.gov Identifier: NCT01374022.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. All authors received grant support from Program to Support Institutional Development of Universal System (PROADI) from the Brazilian Ministry of Health to conduct the study. Dr Amato also received grants from Timpel S. A. and Medtronic. No other disclosures are reported.

Figures

Figure 1.. Flow of Patients in the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial

ARDS indicates acute respiratory distress syndrome; Fio2, fraction of inspired oxygen; MAP, mean arterial pressure; Pao2, partial pressure of arterial oxygen; PEEP, positive end-expiratory pressure. aPatients could have more than 1 reason for exclusion.

Figure 2.. 28-Day Mortality in the Lung Recruitment Maneuver With Titrated PEEP Group vs the Low-PEEP Group

PEEP indicates positive end-expiratory pressure.

Figure 3.. Effects of the Lung Recruitment Maneuver With Titrated PEEP vs the Low-PEEP Group on Mortality According to Subgroups

The size of data markers is proportional to the inverse of variance. Protocol modification indicates the modification in the experimental group strategy after the 556th patient, with decreases in the pressures and duration of the recruitment maneuver. ARDS indicates acute respiratory distress syndrome; Fio2,fraction of inspired oxygen; Pao2, partial pressure of arterial oxygen; PEEP, positive end-expiratory pressure.