Assessment of Awake Prone Positioning in Hospitalized Adults With COVID-19: A Nonrandomized Controlled Trial

Abstract

Importance: Awake prone positioning may improve hypoxemia among patients with COVID-19, but whether it is associated with improved clinical outcomes remains unknown.

Objective: To determine whether the recommendation of awake prone positioning is associated with improved outcomes among patients with COVID-19-related hypoxemia who have not received mechanical ventilation.

Design, setting, and participants: This pragmatic nonrandomized controlled trial was conducted at 2 academic medical centers (Vanderbilt University Medical Center and NorthShore University HealthSystem) during the COVID-19 pandemic. A total of 501 adult patients with COVID-19-associated hypoxemia who had not received mechanical ventilation were enrolled from May 13 to December 11, 2020.

Interventions: Patients were assigned 1:1 to receive either the practitioner-recommended awake prone positioning intervention (intervention group) or usual care (usual care group).

Main outcomes and measures: Primary outcome analyses were performed using a bayesian proportional odds model with covariate adjustment for clinical severity ranking based on the World Health Organization ordinal outcome scale, which was modified to highlight the worst level of hypoxemia on study day 5.

Results: A total of 501 patients (mean [SD] age, 61.0 [15.3] years; 284 [56.7%] were male; and most [417 (83.2%)] were self-reported non-Hispanic or non-Latinx) were included. Baseline severity was comparable between the intervention vs usual care groups, with 170 patients (65.9%) vs 162 patients (66.7%) receiving oxygen via standard low-flow nasal cannula, 71 patients (27.5%) vs 62 patients (25.5%) receiving oxygen via high-flow nasal cannula, and 16 patients (6.2%) vs 19 patients (7.8%) receiving noninvasive positive-pressure ventilation. Nursing observations estimated that patients in the intervention group spent a median of 4.2 hours (IQR, 1.8-6.7 hours) in the prone position per day compared with 0 hours (IQR, 0-0.7 hours) per day in the usual care group. On study day 5, the bayesian posterior probability of the intervention group having worse outcomes than the usual care group on the modified World Health Organization ordinal outcome scale was 0.998 (posterior median adjusted odds ratio [aOR], 1.63; 95% credibility interval [CrI], 1.16-2.31). However, on study days 14 and 28, the posterior probabilities of harm were 0.874 (aOR, 1.29; 95% CrI, 0.84-1.99) and 0.673 (aOR, 1.12; 95% CrI, 0.67-1.86), respectively. Exploratory outcomes (progression to mechanical ventilation, length of stay, and 28-day mortality) did not differ between groups.

Conclusions and relevance: In this nonrandomized controlled trial, prone positioning offered no observed clinical benefit among patients with COVID-19-associated hypoxemia who had not received mechanical ventilation. Moreover, there was substantial evidence of worsened clinical outcomes at study day 5 among patients recommended to receive the awake prone positioning intervention, suggesting potential harm.

Trial registration: ClinicalTrials.gov Identifier: NCT04359797.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Qian reported receiving grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Gatto reported receiving grants from the National Center for Advancing Translational Sciences (NCATS) during the conduct of the study. Dr Dear reported receiving grants from the NCATS during the conduct of the study. Mr Hiser reported receiving grants from the NCATS during the conduct of the study. Dr Bernard reported receiving grants from the NCATS during the conduct of the study. Dr Lindsell reported receiving grants from the NCATS during the conduct of the study; grants from the Centers for Disease Control and Prevention, the National Institutes of Health, and the US Department of Defense; fees for research services from AbbVie, bioMérieux, Endpoint Health, and Entegrion; and owning a patent for risk stratification in sepsis and septic shock (licensed to Cincinnati Children’s Hospital Medical Center) outside the submitted work. Dr Rice reported receiving grants from the NCATS during the conduct of the study and personal fees from Cumberland Pharmaceuticals, Cytovale, and Sanofi outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

aPatients who declined participation were from NorthShore University HealthSystem.

Figure 2.. Nursing Estimations of Duration of Prone Positioning

The horizontal line inside the boxes represents the median. The whiskers represent distances of 1.5 IQR higher and lower than the third and first quantiles, respectively. The dots represent outliers that are outside of this range.

Figure 3.. World Health Organization Ordinal Scale Clinical Outcomes at Study Days 5, 14, and 28

A, Differences in clinical outcomes on study day 5. B, Differences in FiO2 delivered within each applicable ordinal level by group on day 5. C, Two participants (1 from the usual care group and 1 from the prone positioning group) had missing or unknown data on study day 14. D, Data shown for study day 28 reflect 461 patients from Vanderbilt University Medical Center only. ECMO indicates extracorporeal membrane oxygenation; FiO2, fraction of inspired oxygen; HFNC, high-flow nasal cannula; MV, mechanical ventilation; NIV, noninvasive ventilation; and SNC, standard nasal cannula.