Lung Protective Mechanical Ventilation in Severe Acute Brain Injured Patients: A Multicenter, Randomized Clinical Trial (PROLABI)

Background: Lung protective strategies using low tidal volumes and moderate positive end expiratory pressures (PEEP) are considered best practice in critical care, but interventional trials have never been conducted in acutely brain-injured patients due to concerns about carbon dioxide control and effect of PEEP on cerebral hemodynamic. Methods: In this multicenter, open-label, controlled clinical trial 190 adult acute brain injured patients were assigned to receive either a lung-protective or a conventional ventilatory strategy. The primary outcome was a composite endpoint of death, ventilator dependency and ARDS at day 28. Neurological outcome was assessed at intensive care unit discharge by Oxford Handicap Scale and at six months by Glasgow Outcome Scale. Findings: The two study arms had similar characteristics at baseline. In the lung-protective and conventional strategy groups, using an intention-to-treat approach, the composite outcome at 28 days was 61.5% and 45.3% (RR 1.35; 95%CI 1.03-1.79; p=0.025). Mortality was 28.9% and 15.1% (RR 1.91; 95%CI 1.06-3.42; p=0.02), ventilator dependency was 42.3% and 27.9% (RR 1.52; 95%CI 1.01-2.28; p=0.039), and incidence of ARDS was 30.8% and 22.1% (RR 1.39; 95%CI 0.85-2.27; p=0.179) respectively. The trial was stopped after enrolling 190 subjects because of termination of funding. Interpretation: In acutely brain-injured patients without ARDS a lung-protective ventilatory strategy as compared to a conventional strategy did not reduce mortality, percentage of patients weaned from mechanical ventilation, incidence of ARDS and was not beneficial in terms of neurological outcomes. Due to the early termination, these preliminary results require confirmation in larger trials. Clinical trial registration available at www. Clinicaltrials: gov, ID: NCT01690819.