ABSTRACT
Prone positioning is an immediately accessible, readily implementable intervention that was proposed initially as a method for improvement in gas exchange > 50 years ago. Initially implemented clinically as an empiric therapy for refractory hypoxemia, multiple clinical trials were performed on the use of prone positioning in various respiratory conditions, cumulating in the landmark PROSEVA trial, which demonstrated mortality benefit in patients with severe ARDS. After this trial and the corresponding meta-analysis, expert consensus and societal guidelines recommended the use of prone positioning for the management of severe ARDS. The ongoing COVID-19 pandemic has brought prone positioning to the forefront of medicine, including widespread implementation of prone positioning in awake, spontaneously breathing, nonintubated patients with acute hypoxemic respiratory failure. Multiple clinical trials now have been performed to investigate the safety and effectiveness of prone positioning in these patients and have enhanced our understanding of the effects of the prone position in respiratory failure. In this review, we discuss the physiologic features, clinical outcome data, practical considerations, and lingering questions of prone positioning.
ABSTRACT
The unprecedented public health burdens of coronavirus disease (COVID-19) have intensified the urgency of identifying effective, low-cost treatments that limit the need for advanced life support measures and improve clinical outcomes. However, personal protective equipment and staffing shortages, disease virulence, and infectivity have created significant barriers to traditional clinical trial practices. We present the novel design of a pragmatic, adaptive, multicenter, international, prospective randomized controlled clinical trial evaluating the safety and effectiveness of awake prone positioning in spontaneously breathing patients with COVID-19 (APPEX-19 [Awake Prone Position for Early Hypoxemia in COVID-19]). Key innovations of this trial include 1) a novel smartphone-based communication process that facilitates rapid enrollment and intervention delivery while allowing social distancing and conservation of personal protective equipment, 2) Bayesian response-adaptive randomization to allow preferential assignment to the most effective intervention and expedite trial completion compared with frequentist designs, 3) remote electronic collection of patient-reported outcomes and electronic medical record data, and 4) pragmatic prospective use of patient-reported data and data collected as part of routine clinical care. Clinical trial registered with www.clinicaltrials.gov (NCT04344587).