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Meta-Analysis
. 2022 Dec 7:379:e071966.
doi: 10.1136/bmj-2022-071966.

Efficacy of awake prone positioning in patients with covid-19 related hypoxemic respiratory failure: systematic review and meta-analysis of randomized trials

Jason Weatherald  1   2   3   4 , Ken Kuljit S Parhar  5   6   7   4 , Zainab Al Duhailib  8 , Derek K Chu  9   10   11 , Anders Granholm  12 , Kevin Solverson  2   6 , Kimberley Lewis  13 , Morten Hylander Møller  12 , Mohammed Alshahrani  14 , Emilie Belley-Cote  13   15 , Nicole Loroff  16 , Edward T Qian  17 , Cheryl L Gatto  18   19 , Todd W Rice  17 , Dan Niven  6   7 , Henry T Stelfox  6   7 , Kirsten Fiest  6   7 , Deborah Cook  10   11   13 , Yaseen M Arabi  20   21   22 , Waleed Alhazzani  10   11   13   23
Affiliations
Meta-Analysis

Efficacy of awake prone positioning in patients with covid-19 related hypoxemic respiratory failure: systematic review and meta-analysis of randomized trials

Jason Weatherald et al. BMJ. .

Abstract

Objective: To determine the efficacy and safety of awake prone positioning versus usual care in non-intubated adults with hypoxemic respiratory failure due to covid-19.

Design: Systematic review with frequentist and bayesian meta-analyses.

Study eligibility: Randomized trials comparing awake prone positioning versus usual care in adults with covid-19 related hypoxemic respiratory failure. Information sources were Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to 4 March 2022.

Data extraction and synthesis: Two reviewers independently extracted data and assessed risk of bias. Random effects meta-analyses were performed for the primary and secondary outcomes. Bayesian meta-analyses were performed for endotracheal intubation and mortality outcomes. GRADE certainty of evidence was assessed for outcomes.

Main outcome measures: The primary outcome was endotracheal intubation. Secondary outcomes were mortality, ventilator-free days, intensive care unit (ICU) and hospital length of stay, escalation of oxygen modality, change in oxygenation and respiratory rate, and adverse events.

Results: 17 trials (2931 patients) met the eligibility criteria. 12 trials were at low risk of bias, three had some concerns, and two were at high risk. Awake prone positioning reduced the risk of endotracheal intubation compared with usual care (crude average 24.2% v 29.8%, relative risk 0.83, 95% confidence interval 0.73 to 0.94; high certainty). This translates to 55 fewer intubations per 1000 patients (95% confidence interval 87 to 19 fewer intubations). Awake prone positioning did not significantly affect secondary outcomes, including mortality (15.6% v 17.2%, relative risk 0.90, 0.76 to 1.07; high certainty), ventilator-free days (mean difference 0.97 days, 95% confidence interval -0.5 to 3.4; low certainty), ICU length of stay (-2.1 days, -4.5 to 0.4; low certainty), hospital length of stay (-0.09 days, -0.69 to 0.51; moderate certainty), and escalation of oxygen modality (21.4% v 23.0%, relative risk 1.04, 0.74 to 1.44; low certainty). Adverse events related to awake prone positioning were uncommon. Bayesian meta-analysis showed a high probability of benefit with awake prone positioning for endotracheal intubation (non-informative prior, mean relative risk 0.83, 95% credible interval 0.70 to 0.97; posterior probability for relative risk <0.95=96%) but lower probability for mortality (0.90, 0.73 to 1.13; <0.95=68%).

Conclusions: Awake prone positioning compared with usual care reduces the risk of endotracheal intubation in adults with hypoxemic respiratory failure due to covid-19 but probably has little to no effect on mortality or other outcomes.

Systematic review registration: PROSPERO CRD42022314856.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Canadian Institutes of Health Research and University of Calgary Cumming School of Medicine Clinical Research Fund; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Summary of trial identification for review and meta-analysis. *Twelve articles representing 17 separate trials were identified. One article was a prospective meta-analysis of six individual randomized trials
Fig 2
Fig 2
Forest plots for awake prone positioning compared with usual care for intubation and mortality in adults with hypoxemic respiratory failure due to covid-19. Six trials assessed intubation at 28 days (six Ehrmann trials), two trials assessed intubation at any time during hospital admission (Johnson, Fralick), three trials assessed intubation at 30 days (Alhazzani, Rosén, Harris), one trial assessed intubation at 14 days (Rampon), and two trials did not specify (Jayakumar, Hashemian). Two trials had no intubation events in both arms and were not included in this analysis (Taylor, Kharat). The quasi-randomized trial (Qian) was not included in this analysis. Six trials assessed mortality at 28 days (five Ehrmann trials, Harris), two trials assessed in-hospital mortality (Johnson, Fralick), two trials assessed mortality during intensive care unit admission (Jayakumar, Hashemian), one trial assessed mortality at 14 days (Rampon), one trial assessed mortality at 30 days (Rosén), and one trial assessed mortality at 60 days (Alhazzani). Three trials had no mortality events in both arms and were not included in this analysis (Ehrmann (Ireland), Taylor, Kharat). The quasi-randomized trial (Qian) was not included in this analysis. APP=awake prone positioning
Fig 3
Fig 3
Forest plot for subgroup analysis of awake prone positioning compared with usual care for endotracheal intubation in patients with hypoxemic respiratory failure due to covid-19 according to duration of awake prone positioning. Two trials had no intubation events in both arms (Taylor, Kharat) and four trials that did not report the median duration of prone positioning (Jayakumar, Hashemian, Rampon, Harris) were excluded from this analysis. APP=awake prone positioning
Fig 4
Fig 4
Forest plot for subgroup analysis of awake prone positioning compared with usual care for endotracheal intubation in patients with hypoxemic respiratory failure due to covid-19 according to median baseline oxygen saturation to fraction of inspired oxygen (SpO2:FiO2). Two trials had no intubation events in both arms (Taylor, Kharat) and three trials did not report the baseline SpO2:FiO2 (Johnson, Hashemian, Qian) and were excluded from this analysis. One trial reported baseline arterial oxygen tension to fraction of inspired oxygen (PaO2:FiO2), which was converted to SpO2:FiO2. APP=awake prone positioning
Fig 5
Fig 5
Forest plot for subgroup analysis of awake prone positioning compared with usual care for endotracheal intubation in patients with hypoxemic respiratory failure due to covid-19 according to baseline mode of oxygen delivery. Two trials had no intubation events in both arms (Taylor, Kharat) and were excluded from this analysis. One trial reported outcomes separately according to baseline mode of oxygen delivery (Alhazanni). APP=awake prone positioning; NIV=non-invasive ventilation
Fig 6
Fig 6
Forest plot for subgroup analysis of awake prone positioning compared with usual care for endotracheal intubation in patients with hypoxemic respiratory failure due to covid-19 according to location in hospital. Two trials had no intubation events in both arms (Taylor, Kharat) and were excluded from this analysis. APP=awake prone positioning; ICU=intensive care unit
Fig 7
Fig 7
Forest plot for subgroup analysis of awake prone positioning compared with usual care for endotracheal intubation in patients with hypoxemic respiratory failure due to covid-19 according to country status (low or middle income and high income). Two trials had no intubation events in both arms (Taylor, Kharat) and were excluded from this analysis. Trials were classified as low or middle income countries or high income countries based on the Organisation for Economic Co-operation and Development in 2021. APP=awake prone positioning; HIC=high income countries; LMIC=low or middle income countries
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Comment in

  • Awake prone positioning and covid-19.
    Verma AA, Razak F, Munshi L, Fralick M. Verma AA, et al. BMJ. 2022 Dec 7;379:o2888. doi: 10.1136/bmj.o2888. BMJ. 2022. PMID: 36740852 No abstract available.

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