Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: a systematic review and meta-analysis

Importance
The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19.


Objective
To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19.


Design, Setting, and Participants
Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021.


Intervention
Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195).


Main Outcomes and Measures
The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events.


Results
Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, -6.37% [95% CI, -15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, -1.15% [95% CI, -9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group.


Conclusions and Relevance
In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit.


Trial Registration
ClinicalTrials.gov Identifier: NCT04350723.

Effect of Awake Prone Positioning on Endotracheal Intubation in Patients With COVID-19 and Acute Respiratory Failure: A Randomized Clinical Trial.

Background Prone positioning in non-intubated spontaneously breathing patients is becoming widely applied in practice alongside noninvasive respiratory support. This systematic review and meta-analysis evaluates the effect, timing, and populations that might benefit from awake proning regarding oxygenation, mortality, and tracheal intubation compared with supine position in hypoxaemic acute respiratory failure. Methods We conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, CINAHL, and BMJ Best Practice until August 2021 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD42021250322). Studies included comprise least-wise 20 adult patients with hypoxaemic respiratory failure secondary to acute respiratory distress syndrome or coronavirus disease (COVID-19). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and study quality was assessed using the Newcastle–Ottawa Scale and the Cochrane risk-of-bias tool. Results Fourteen studies fulfilled the selection criteria and 2352 patients were included; of those patients, 99% (n=2332/2352) had COVID-19. Amongst 1041 (44%) patients who were placed in the prone position, 1021 were SARS-CoV-2 positive. The meta-analysis revealed significant improvement in the PaO2/FiO2 ratio (mean difference –23.10; 95% confidence interval [CI]: –34.80 to 11.39; P=0.0001; I2=26%) after prone positioning. In patients with COVID-19, lower mortality was found in the group placed in the prone position (150/771 prone vs 391/1457 supine; odds ratio [OR] 0.51; 95% CI: 0.32–0.80; P=0.003; I2=48%), but the tracheal intubation rate was unchanged (284/824 prone vs 616/1271 supine; OR 0.72; 95% CI: 0.43–1.22; P=0.220; I2=75%). Overall proning was tolerated for a median of 4 h (inter-quartile range: 2–16). Conclusions Prone positioning can improve oxygenation amongst non-intubated patients with acute hypoxaemic respiratory failure when applied for at least 4 h over repeated daily episodes. Awake proning appears safe, but the effect on tracheal intubation rate and survival remains uncertain.

Prone positioning for non-intubated spontaneously breathing patients with acute hypoxaemic respiratory failure: a systematic review and meta-analysis.

BackgroundProne positioning in non-intubated spontaneously breathing patients is becoming widely applied in practice alongside noninvasive respiratory support. This systematic review and meta-analysis evaluates the effect, timing, and populations that might benefit from awake proning regarding oxygenation, mortality, and tracheal intubation compared with supine position in hypoxaemic acute respiratory failure.MethodsWe conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, CINAHL, and BMJ Best Practice until August 2021 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD42021250322). Studies included comprise least-wise 20 adult patients with hypoxaemic respiratory failure secondary to acute respiratory distress syndrome or coronavirus disease (COVID-19). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and study quality was assessed using the Newcastle–Ottawa Scale and the Cochrane risk-of-bias tool.ResultsFourteen studies fulfilled the selection criteria and 2352 patients were included; of those patients, 99% (n=2332/2352) had COVID-19. Amongst 1041 (44%) patients who were placed in the prone position, 1021 were SARS-CoV-2 positive. The meta-analysis revealed significant improvement in the PaO2/FiO2 ratio (mean difference –23.10; 95% confidence interval [CI]: –34.80 to 11.39; P=0.0001; I2=26%) after prone positioning. In patients with COVID-19, lower mortality was found in the group placed in the prone position (150/771 prone vs 391/1457 supine; odds ratio [OR] 0.51; 95% CI: 0.32–0.80; P=0.003; I2=48%), but the tracheal intubation rate was unchanged (284/824 prone vs 616/1271 supine; OR 0.72; 95% CI: 0.43–1.22; P=0.220; I2=75%). Overall proning was tolerated for a median of 4 h (inter-quartile range: 2–16).ConclusionsProne positioning can improve oxygenation amongst non-intubated patients with acute hypoxaemic respiratory failure when applied for at least 4 h over repeated daily episodes. Awake proning appears safe, but the effect on tracheal intubation rate and survival remains uncertain. 

http://www.bjanaesthesia.org/article/S0007091221006395/pdf

Prone positioning for non-intubated spontaneously breathing patients with acute hypoxaemic respiratory failure: a systematic review and meta-analysis

Awake prone positioning (APP) improves oxygenation in coronavirus disease (COVID-19) patients and, when successful, may decrease the risk of intubation. However, factors associated with APP success remain unknown. In this secondary analysis, we aimed to assess whether APP can reduce intubation rate in patients with COVID-19 and to focus on the factors associated with success.In this multicenter randomized controlled trial, conducted in three high-acuity units, we randomly assigned patients with COVID-19-induced acute hypoxemic respiratory failure (AHRF) requiring high-flow nasal cannula (HFNC) oxygen to APP or standard care. Primary outcome was intubation rate at 28 days. Multivariate analyses were performed to identify the predictors associated to treatment success (survival without intubation).Among 430 patients randomized, 216 were assigned to APP and 214 to standard care. The APP group had a lower intubation rate (30% vs 43%, relative risk [RR] 0.70; CI95 0.54-0.90, P = 0.006) and shorter hospital length of stay (11 interquartile range [IQR, 9-14] vs 13 [IQR, 10-17] days, P = 0.001). A respiratory rate ≤ 25 bpm at enrollment, an increase in ROX index > 1.25 after first APP session, APP duration > 8 h/day, and a decrease in lung ultrasound score ≥ 2 within the first 3 days were significantly associated with treatment success for APP.In patients with COVID-19-induced AHRF treated by HFNC, APP reduced intubation rate and improved treatment success. A longer APP duration is associated with APP success, while the increase in ROX index and decrease in lung ultrasound score after APP can also help identify patients most likely to benefit.This study was retrospectively registered in ClinicalTrials.gov at July 20, 2021. Identification number NCT04477655. https://clinicaltrials.gov/ct2/show/NCT04477655?term=PRO-CARF&draw=2&rank=1. 

/pdf/factors-for-success-of-awake-prone-positioning-in-patients-1v2ipvt9.pdf

Factors for success of awake prone positioning in patients with COVID-19-induced acute hypoxemic respiratory failure: analysis of a randomized controlled trial

Background: The effect of awake prone positioning on intubation rates is not established. The aim of this trial was to investigate if a protocol for awake prone positioning reduces the rate of endo ...

/pdf/awake-prone-positioning-in-patients-with-hypoxemic-8j6nt7enqh.pdf

Ludvig Eby

Papers

Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.