Extended Versus Standard Proning Duration for COVID-19 Associated Acute Respiratory Distress Syndrome: A Target Trial Emulation Study.

ABSTRACT

RATIONALE Prone positioning for > 16 hours in moderate-to-severe acute respiratory distress syndrome (ARDS) improves survival. However, the optimal duration of proning is unknown. OBJECTIVE: To estimate the effect of extended versus standard proning duration on patients with moderate-to-severe COVID-19 ARDS. METHODS: Data were extracted from a 5-hospital electronic medical record registry. Patients who were proned within 72 hours of mechanical ventilation were categorized as receiving extended (> 24 hours) versus standard (16-24 hours) proning based on the first proning session length. We used a target trial emulation design to estimate the effect of extended vs. standard proning on the primary outcome of 90-day mortality, and secondary outcomes of ventilator liberation and ICU discharge. Analytically we used inverse probability of treatment weighted (IPTW) Cox, or Fine and Gray regression models. RESULTS: 314 patients were included, 234 who received extended proning, and 80 who received standard duration. Extended proning patients were older, had greater comorbidity, were more often at an academic hospital, and had shorter time from admission to mechanical ventilation. After IPTW, characteristics were well balanced. Unadjusted 90-day mortality in the extended vs. standard proning groups was 39% vs 58%. In doubly-robust IPTW analyses, we found no significant effects of extended vs. standard proning duration on mortality (hazard ratio [95% CI] 0.95 [0.51-1.77]), ventilator liberation (sub-distribution hazard [sHR] 1.60, [0.97-2.64], or ICU discharge (sHR 1.31 [0.82-2.10]). CONCLUSION: Using target trial emulation, we found no significant effect of extended vs. standard proning duration on mortality, ventilator liberation, or ICU discharge. However, given the imprecision of estimates, further study is justified. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http//creativecommons.org/licenses/by-nc-nd/4.0/).