Impact of awake prone positioning duration on intubation or mortality in COVID-19 patients with acute respiratory failure: secondary analysis of a randomized clinical trial

BackgroundCompared with shorter awake prone positioning (APP), prolonged APP (>= 12 h daily) reduces the intubation rate in patients with COVID-19-related acute hypoxemic respiratory failure (AHRF). However, the optimal APP duration is uncertain. In this secondary analysis, we aimed to explore whether a longer APP duration is associated with improved outcomes and to identify the optimal duration of APP.MethodsData from a multicenter randomized controlled trial involving nonintubated COVID-19 patients with AHRF were analyzed. Daily APP duration over 7 days after randomization was recorded as the primary exposure in present study. The primary outcome was the time from randomization to APP failure, which was defined as a composite of tracheal intubation or mortality within 28 days. A Cox proportional hazards regression model was employed to elucidate the associations, and the daily duration of APP was treated as time dependent.ResultsA total of 409 patients were randomized in the original trial, and 408 were enrolled in this analysis. Among these patients, 105 (25.7%) experienced APP failure. A longer daily APP duration was associated with a lower risk of APP failure, with a hazard ratio (HR) of 0.93 (95% confidence interval (CI): 0.88-0.98), and the association was significant only during the first three days after randomization. There was a nonlinear relationship between the daily APP duration and the risk of APP failure (P = 0.015 for nonlinearity). Compared with patients whose APP duration ranged from 8 to 12 h per day, patients with less than 8 h of APP per day had a greater risk of APP failure (HR 2.44, 95% CI 1.21-4.92), whereas extending APP beyond 12 h per day did not improve the outcomes further (HR 1.03, 95% CI 0.51-2.10, P = 0.932).InterpretationA longer daily APP duration was associated with a reduced risk of APP failure in COVID-19-related AHRF patients, and the optimal APP duration was 8-12 h per day.Clinical trial ClinicalTrials.gov: NCT05677984, Registered January 3, 2023. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000CST9&selectaction=Edit&uid=U0000YKY&ts=4&cx=-x0muekInterpretationA longer daily APP duration was associated with a reduced risk of APP failure in COVID-19-related AHRF patients, and the optimal APP duration was 8-12 h per day.Clinical trial ClinicalTrials.gov: NCT05677984, Registered January 3, 2023. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000CST9&selectaction=Edit&uid=U0000YKY&ts=4&cx=-x0muek