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

Prone positioning for ⩾16 hours in moderate-to-severe acute respiratory distress syndrome (ARDS) improves survival. However, the optimal duration of proning is unknown. To estimate the effect of extended versus standard proning duration on patients with moderate-to-severe coronavirus disease (COVID-19) ARDS. Data were extracted from a five-hospital electronic medical record registry. Patients who were proned within 72 hours of mechanical ventilation were categorized as receiving extended (⩾24 h) versus standard (16-24 h) proning based on the first proning session length. We used a target trial emulation design to estimate the effect of extended versus standard proning on the primary outcome of 90-day mortality and secondary outcomes of ventilator liberation and intensive care unit (ICU) discharge. Analytically, we used inverse probability of treatment weighted (IPTW) Cox or Fine-Gray regression models. A total of 314 patients were included; 234 received extended proning, and 80 received standard-duration proning. Patients who received extended proning 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 versus standard proning groups was 39% versus 58%. In doubly robust IPTW analyses, we found no significant effects of extended versus standard proning duration on mortality (hazard ratio [95% confidence interval], 0.95 [0.51-1.77]), ventilator liberation (subdistribution hazard, 1.60 [0.97-2.64], or ICU discharge (subdistribution hazard, 1.31 [0.82-2.10]). Using target trial emulation, we found no significant effect of extended versus standard proning duration on mortality, ventilator liberation, or ICU discharge. However, given the imprecision of estimates, further study is justified.