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

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Key Points

Question  Is prone positioning associated with improved outcomes among patients with COVID-19 and hypoxemia requiring supplemental oxygen but not yet receiving mechanical ventilation?

Findings  In this nonrandomized controlled trial including 501 patients with COVID-19 and hypoxemia, the odds of having a worse outcome on study day 5 based on a modified World Health Organization ordinal scale was higher among patients receiving the awake prone positioning intervention.

Meaning  This study’s findings suggest that routine recommendation for awake prone positioning among patients with COVID-19–related hypoxemia who require supplemental oxygen but not mechanical ventilation is not beneficial.

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

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Article Information

Accepted for Publication: February 26, 2022.

Published Online: April 18, 2022. doi:10.1001/jamainternmed.2022.1070

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Qian ET et al. JAMA Internal Medicine.

Corresponding Author: Edward Tang Qian, MD, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, T-1218 MCN, 1161 21st Ave S, Nashville, TN 37232-2650 (edward.t.qian@vumc.org).

Author Contributions: Drs Qian and Lindsell had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Qian and Gatto contributed equally as first authors. Drs Lindsell and Rice contributed equally as senior authors.

Concept and design: Qian, Gatto, Dear, Hiser, Buie, Kripalani, Harrell, Freundlich, Burke, Billings, Pulley, Bernard, Lindsell, Rice.

Acquisition, analysis, or interpretation of data: Qian, Amusina, Dear, Hiser, Buie, Kripalani, Harrell, Freundlich, Gao, Gong, Hennessy, Grooms, Mattingly, Bellam, Zakaria, Vasilevskis, Billings, Pulley, Lindsell, Rice.

Drafting of the manuscript: Qian, Gatto, Dear, Hiser, Buie, Zakaria, Billings, Pulley, Rice.

Critical revision of the manuscript for important intellectual content: Gatto, Amusina, Dear, Hiser, Buie, Kripalani, Harrell, Freundlich, Gao, Gong, Hennessy, Grooms, Mattingly, Bellam, Burke, Vasilevskis, Billings, Pulley, Bernard, Lindsell, Rice.

Statistical analysis: Harrell, Gao, Gong, Hennessy, Lindsell.

Obtained funding: Bernard.

Administrative, technical, or material support: Qian, Gatto, Amusina, Dear, Hiser, Buie, Freundlich, Grooms, Mattingly, Zakaria, Vasilevskis, Pulley, Bernard, Rice.

Supervision: Gatto, Dear, Hiser, Kripalani, Freundlich, Vasilevskis, Pulley, Bernard, Rice.

Other–principal investigator at one of the sites: Amusina.

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.

Funding/Support: The work was supported by grant UL1 TR002243 from the National Center for Advancing Translational Sciences (Drs Gatto and Dear, Mr Hiser, and Drs Bernard, Lindsell, and Rice); grant T32HL087738 from the National Heart, Lung, and Blood Institute (Dr Qian); grant K23HL148640 from the National Heart, Lung, and Blood Institute (Dr Freundlich); grant R01GM112871 from the National Institute of General Medical Sciences (Dr Billings); and grants to the institution from the Dolly Parton COVID-19 Research Fund (Drs Gatto and Dear, Mr Hiser, and Dr Rice).

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: A complete list of the members of the Vanderbilt Learning Healthcare System Platform Investigators appears in Supplement 3.

Disclaimer: The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.

Data Sharing Statement: See Supplement 4.

Additional Contributions: The authors are indebted to the patients and the frontline staff who endured the COVID-19 pandemic. Zameer Lodhi, BBA, MS, of Vanderbilt University provided assistance with data acquisition, and Elizabeth A. Rice, MD, SFHM, of Vanderbilt University provided coordination with clinical teams. We thank the COVID-19 charge nurses and the 8 nurse leaders and educators from Vanderbilt Medical Center East and the members of the Vanderbilt Coordinating Center, including Jill Janssen, RN, BSN; Jessica B. Collins, BA; Jenna Caserta, RN, BSN; Alesia Pruitt, BS; Jessica S. Marlin, CCRP; Krista K. Vermillion, MS, MPM; and David S. McKeel, BS. Osasumwen Osayimwen, MD, MPH, of the NorthShore University HealthSystem provided frontline care. We also acknowledge the contributions of the NorthShore University HealthSystem COVID-19 hospitalist team; the nursing staff of the NorthShore University HealthSystem; and the nursing administration at Glenbrook Hospital. The sensor work of Drs Qian, Gatto, Lindsell, and Rice was supported by Smith & Nephew, with guidance provided by Annemari Cooley, MBA, MA; Mike Pihulic, Meng; Angela Lin, MS; and Alvin Cheung, BS (all of whom were employed by Smith & Nephew). None of the contributors received additional compensation for their work.

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