Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS: The PROTECTION Pilot Randomized Clinical Trial

Background: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. Research Question: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study Design and Methods: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. Results: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, –7%; 95% CI, –18% to 4%; P =. 015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P =. 852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P =. 337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P =. 300) for the sigh vs no-sigh group. Interpretation: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk. Trial Registry: ClinicalTrials.gov; No.: NCT03201263; URL: www.clinicaltrials.gov