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

Mauri, T.; Foti, G.; Fornari, C.; Grasselli, G.; Pinciroli, R.; Lovisari, F.; Tubiolo, D.; Volta, C. A.; Spadaro, S.; Rona, R.; Rondelli, E.; Navalesi, P.; Garofalo, E.; Knafelj, R.; Gorjup, V.; Colombo, R.; Cortegiani, A.; Zhou, J. -X.; D'Andrea, R.; Calamai, I.; Gonzalez, A. V.; Roca, O.; Grieco, D. L.; Jovaisa, T.; Bampalis, D.; Becher, T.; Battaglini, D.; Ge, H.; Luz, M.; Constantin, J. -M.; Ranieri, M.; Guerin, C.; Mancebo, J.; Pelosi, P.; Fumagalli, R.; Brochard, L.; Pesenti, A.; Papoff, A.; Di Fenza, R.; Gianni, S.; Spinelli, E.; Lissoni, A.; Abbruzzese, C.; Bronco, A.; Villa, S.; Russotto, V.; Iachi, A.; Ball, L.; Patroniti, N.; Spina, R.; Giuntini, R.; Peruzzi, S.; Menga, L. S.; Fossali, T.; Castelli, A.; Ottolina, D.; Garcia-De-Acilu, M.; Santafe, M.; Schadler, D.; Weiler, N.; Carvajal, E. R.; Calvo, C. P.; Neou, E.; Wang, Y. -M.; Zhou, Y. -M.; Longhini, F.; Bruni, A.; Leonardi, M.; Gregoretti, C.; Ippolito, M.; Milazzo, Z.; Querci, L.; Ranieri, S.; Insom, G.; Berden, J.; Noc, M.; Mikuz, U.; Arzenton, M.; Lazzeri, M.; Villa, A.; Barreto, B. B.; Rios, M. N. O.; Gusmao-Flores, D.; Phull, M.; Barnes, T.; Musarat, H.; Conti, S.

doi:10.1016/j.chest.2020.10.079

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