Prone positioning might reduce the need for intubation in people with severe COVID-19
Authors: W Cameron McGuire, Alex K Pearce, Atul Malhotra
Journal: The Lancet Respiratory Medicine (2021)

We applaud the recent Article in The Lancet Respiratory Medicine by Stephen Ehrmann and colleagues1Ehrmann S Li J Ibarra-Estrada M et al.Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.Lancet Respir Med. 2021; 9: 1387-1395PubMed Google Scholar regarding awake prone positioning in patients with COVID-19. Safely avoiding endotracheal intubation is important for patient wellbeing and resource allocation. The findings of this study raise important questions. Five participants withdrew consent after randomisation and were not included in the intention-to-treat analysis, which is relevant given the fragility index of 5 for the primary outcome. If both control patients avoided intubation or death and all three awake prone positioning patients were intubated or died, this result would have yielded non-significance for the primary outcome. 44 (8%) of 564 patients in the overall awake prone positioning group had a do-not-intubate order. If five awake prone positioning patients were not intubated but did not die during the study period, this could have nullified statistical significance. As the authors acknowledged, the Mexican trial results drove the positive outcome of the study. As the Mexican trial had the largest study population and effect, this trial warrants further discussion, particularly since the trial joined after a standardised protocol was implemented. Nearly 80% of the Mexican awake prone positioning patients were outside the intensive care unit, where access to endotracheal intubation was presumably restricted. Meanwhile the French and American trials had more than 80% of awake prone positioning patients in the intensive care unit. The Mexican protocol diagram shows a markedly different SpO2 threshold (SpO2 ≤80%) for intubation compared with the other trials. Presumably this protocol variation could have resulted in fewer intubations and thus statistical non-significance. We recommend use of objective intubation criteria to the extent possible, particularly in the context of an unmasked study. Remarkably, the baseline ratio of SpO2:FiO2 (135) in the Mexican awake prone positioning group was 17 points lower than the SpO2:FiO2 in any of the other trials. This SpO2:FiO2 ratio corresponds to a PaO2:FiO2 ratio of 85 if imputed linearly.2Rice TW Wheeler AP Bernard GR Hayden DL Schoenfeld DA Ware LB Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS.Chest. 2007; 132: 410-417Google Scholar Not only is this value consistent with severe acute respiratory distress syndrome (ARDS), but it is also below the intubation threshold (PaO2:FiO2 <100) of the French trial where prone positioning would have been declared a failure. Although some data suggest that prone position-induced improvements in gas exchange do not predict mortality in ARDS in ventilated patients,3Albert RK Keniston A Baboi L Ayzac L Guérin C Prone position-induced improvement in gas exchange does not predict improved survival in the acute respiratory distress syndrome.Am J Respir Crit Care Med. 2014; 189: 494-496Google Scholar it would be interesting to test prospectively if prone positioning in non-intubated patients with COVID-194Paul V Patel S Royse M Odish M Malhotra A Koenig S Proning in non-intubated (PINI) in times of COVID-19: case series and a review.J Intensive Care Med. 2020; 35: 818-824Google Scholar prevents intubation or improves mortality. Either way, we believe, based on these new data and previous prone positioning trials,5Beitler JR Shaefi S Montesi SB et al.Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis.Intensive Care Med. 2014; 40: 332-341Google Scholar that prone positioning probably protects the lung mechanically, particularly when implemented early in disease and when sustained for long periods of time each day. We declare no competing interests. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trialAwake prone positioning of patients with hypoxaemic respiratory failure due to COVID-19 reduces the incidence of treatment failure and the need for intubation without any signal of harm. These results support routine awake prone positioning of patients with COVID-19 who require support with high-flow nasal cannula. Full-Text PDF Prone positioning might reduce the need for intubation in people with severe COVID-19 – Authors' replyWe thank W Cameron McGuire and colleagues for their comments regarding our meta-trial on awake prone positioning in patients with COVID-19.1 We would like to clarify some points. Full-Text PDF