PEEP titration increases mortality in patients with ARDS compared with standard low PEEP

Clinical Question

As compared with a conventional low PEEP strategy, does PEEP titration using lung recruitment maneuvers improve outcomes in patients with acute respiratory distress syndrome?

Bottom Line

In patients with moderate to severe acute respiratory distress syndrome (ARDS), using lung recruitment maneuvers to titrate positive end-expiratory pressure (PEEP) to best respiratory compliance resulted in increased deaths and higher risk of pneumothorax and barotrauma as compared with the standard low PEEP strategy. (LOE = 1b)

Reference

Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial Investigators, Cavalcanti AB, Suzumura EA, et al. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome. JAMA 2017;318(14):1335-1345.  [PMID:28973363]

Study Design

Randomized controlled trial (nonblinded)

Funding

Government

Allocation

Concealed

Setting

Inpatient (ICU only)

Synopsis

The purpose of lung recruitment maneuvers and PEEP titration in patients with ARDS is to open areas of collapsed small airways and alveoli and keep them open, thus potentially reducing ventilator-induced lung injury. This study, conducted at 120 intensive care units in 9 countries, compared a strategy of lung recruitment and PEEP titration using stepwise increases in PEEP with a conventional low-PEEP strategy for patients with moderate to severe ARDS. Patients in the experimental group (n = 501) underwent a lung recruitment maneuver with gradually increasing PEEP levels up to 35 to 45 cm H2O, followed by a decrease in PEEP to a level of best static lung compliance. The optimal PEEP was the PEEP associated with the best compliance plus 2 cm H2O. Following recruitment and PEEP titration, patients were ventilated in volume-assist control mode at that optimal PEEP level. The control group (n = 512) received a standard low-PEEP strategy without lung recruitment maneuvers. The 2 groups were similar at baseline. Two-thirds of the patients had septic shock and approximately 60% had ARDS of pulmonary origin. Mean PEEP and plateau pressure values, as well as mean PaO2/FiO2 ratios, were higher in the experimental group. The modified intention-to-treat analysis included all randomized patients, except 3 from the control group who were lost to follow-up. Overall, the experimental group had a greater number of deaths at 28 days with a number needed to treat to harm of 17 (55% vs 49%; adjusted hazard ratio 1.22; 95% CI 1.04 - 1.45; P = .02) and a higher 6-month all-cause mortality (65% vs 60%; hazard ratio 1.18, 95% CI 1.01 - 1.38; P = .04). Pneumothorax requiring drainage, barotrauma, death due to barotrauma, and the need for vasopressors were all significantly increased in the experimental group. There were no differences detected between the 2 groups in the presence of refractory hypoxemia or severe acidosis or in deaths due to either of these conditions.

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