Prone Positioning of Nonintubated Patients With Coronavirus Disease 2019—A Systematic Review and Meta-Analysis

  1. Mallikarjuna Ponnapa Reddy
  2. Ashwin Subramaniam
  3. Afsana Afroz
  4. Baki Billah
  5. Zheng Jie Lim
  6. Alexandr Zubarev
  7. Gabriel Blecher
  8. Ravindranath Tiruvoipati
  9. Kollengode Ramanathan
  10. Suei Nee Wong
  11. Daniel Brodie
  12. Eddy Fan
  13. Kiran Shekar

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Abstract

Several studies have reported prone positioning of nonintubated patients with coronavirus diseases 2019–related hypoxemic respiratory failure. This systematic review and meta-analysis evaluated the impact of prone positioning on oxygenation and clinical outcomes.

DESIGN AND SETTING:

We searched PubMed, Embase, and the coronavirus diseases 2019 living systematic review from December 1, 2019, to November 9, 2020.

SUBJECTS AND INTERVENTION:

Studies reporting prone positioning in hypoxemic, nonintubated adult patients with coronavirus diseases 2019 were included.

MEASUREMENTS AND MAIN RESULTS:

Data on prone positioning location (ICU vs non-ICU), prone positioning dose (total minutes/d), frequency (sessions/d), respiratory supports during prone positioning, relative changes in oxygenation variables (peripheral oxygen saturation, Pao2, and ratio of Pao2 to the Fio2), respiratory rate pre and post prone positioning, intubation rate, and mortality were extracted. Twenty-five observational studies reporting prone positioning in 758 patients were included. There was substantial heterogeneity in prone positioning location, dose and frequency, and respiratory supports provided. Significant improvements were seen in ratio of Pao 2 to the Fio 2 (mean difference, 39; 95% CI, 25–54), Pao 2 (mean difference, 20 mm Hg; 95% CI, 14–25), and peripheral oxygen saturation (mean difference, 4.74%; 95% CI, 3–6%). Respiratory rate decreased post prone positioning (mean difference, –3.2 breaths/min; 95% CI, –4.6 to –1.9). Intubation and mortality rates were 24% (95% CI, 17–32%) and 13% (95% CI, 6–19%), respectively. There was no difference in intubation rate in those receiving prone positioning within and outside ICU (32% [69/214] vs 33% [107/320]; p = 0.84). No major adverse events were recorded in small subset of studies that reported them.

CONCLUSIONS:

Despite the significant variability in frequency and duration of prone positioning and respiratory supports applied, prone positioning was associated with improvement in oxygenation variables without any reported serious adverse events. The results are limited by a lack of controls and adjustments for confounders. Whether this improvement in oxygenation results in meaningful patient-centered outcomes such as reduced intubation or mortality rates requires testing in well-designed randomized clinical trials.

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  1. Version published to 10.1097/ccm.0000000000005086
  2. ScreenIT

    SciScore for 10.1101/2020.10.12.20211748: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search strategy, Information Sources and Study Selection: Two authors (MR and AZ) independently searched on PubMed, Embase, Cochrane, Scopus and the COVID-19 living systematic review from December 1st, 2019 to July 23rd, 2020.
    Cochrane
    suggested: (Cochrane Library, RRID:SCR_013000)
    COVID-19 living systematic review has a daily-updated list of pre-print and published articles relating to COVID-19 obtained from PubMed, EMBASE, medRxiv and bioRxiv.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    bioRxiv
    suggested: (bioRxiv, RRID:SCR_003933)
    Data Analysis: Statistical analyses were performed using the statistical software package Stata-Version 16 (Statacorp, USA).
    Statacorp
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Given these limitations, the population that clearly stands to benefit from PP could not be clearly defined. Although all patients demonstrated improved oxygenation, the patients with PaO2/FiO2 ratio of ≤150 demonstrated a greater improvement. The reasons may possibly be that patients with more severe hypoxaemia had a greater degree of pulmonary vascular dysregulation and ventilation: those with perfusion mismatch to start with and benefited more with PP. However, such an interpretation is speculative and not much inference can be drawn from these data as an improved oxygenation with PP depends on several factors such as timing, duration, underlying pathophysiology and other respiratory supports used. For example, the duration of and frequency of prone ventilation were quite variable with some studies reporting a combination of lateral positioning and PP. Such variability is a concern when it comes to feasibility and generalisability of PP outside of centres that have some experience in PP of awake patients. In addition, there was significant heterogeneity in oxygen therapies provided prior to and during PP. For example, 69% of the patients were receiving NIV and 12.6% were receiving oxygen via nasal cannula. These two populations can be drastically different and may represent different stages of disease evolution. This is likely to have a significant bearing on adjunctive use of PP as essentially the outcomes depend on the success of combinations of these therapies. It shoul...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2020.10.12.20211748v1 on medRxiv