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Conflicting takes on prone positioning in COVID-19 hospitalised patients

Two recent studies offer conflicting data about the proper use of prone positioning – a belly-down approach to improve respiration – in hospitalised, non-intubated patients with COVID-19.

One study, which was non-randomised, suggested that the intervention is useless and may actually be harmful. The other, a randomised controlled trial, linked proning to a reduced risk of intubation but not to a mortality benefit.

What should clinicians do?

Considering the evidence available about non-intubated patients, “it is unclear which patients will benefit, how long they need to be proned, and if proning masks disease progression delaying further interventions”, said Dr Peter Sottile of the University of Colorado Anschutz Medical Campus in Aurora, co-author of a commentary accompanying the first study, which was published in JAMA Internal Medicine.

Dr Miguel Ángel Ibarra Estrada of the University of Guadalajara in Mexico, the lead author of the second study, said that “awake prone positioning is an effective measure, as this is a no-cost and safe procedure”.

The non-randomised, controlled study by Dr Edward Tang Qian of Vanderbilt University Medical Center in Nashville, and colleagues, tracked 501 patients with COVID-19 and hypoxia who were not on mechanical ventilation (mean age 61, 56.7% male). Of those, 258 underwent prone positioning and were found to be more likely to have worse outcomes than the usual-care group at 5 days and to show no signs of clinical improvement.

However, the commentary noted the relatively short amount of time that patients spent in the prone position (mean of 4.2 hours), along with other limitations.

“Concerns related to study design weaken the strength of [the] conclusions,” Sottile and co-authors wrote.

Ibarra Estrada and colleagues randomly assigned 216 patients with COVID-19 and hypoxia to prone positioning and 214 to standard care. All patients were receiving oxygen through high-flow nasal cannula. (The study by Qian and co-authors included patients who received oxygen in various ways other than mechanical ventilation.)

The intubation rate was lower in the proned patients compared with those who had standard care (30% vs 43%, respectively), and there was no statistically significant difference in mortality (33% vs 37%), Ibarra Estrada reported.

Based on the statistical trend, “there is a high probability” the mortality difference would have been significant if recruitment had continued, he said, noting that the study was stopped because proning showed a clear benefit.

The team linked treatment failure to less daily time proned (i.e., less than 7.7 hours), higher respiratory rate at enrolment, and decrease in respiratory rate less than 3 bpm after the first session of proning.

Proning caused back pain in 7.4% of patients and dislodged intravenous lines in 6.5%. “Tolerance of patients is frequently limited due to pain, anxiety, body habitus, comorbidities, etc.,” which can limit the amount of time that patients can be proned, Ibarra Estrada said.

He said the study was the largest randomised controlled trial of proning in non-intubated patients with COVID-19 and was included in a recent meta-analysis that found that awake proning reduced the need for intubation among patients receiving advanced respiratory support.

Sottile told MedPage Today it was clear that “intubated patients with moderate to severe acute respiratory distress syndrome should be considered for prone positioning unless contra-indications to proning exist”.

But the situation is murky for non-intubated patients, he added. “It is still unclear if awake prone positioning improves mortality in patients with acute hypoxic respiratory failure, such as COVID. It remains unclear if the improvement in oxygenation masks the progression of lung injury and delays potentially life-saving interventions such as intubation and mechanical ventilation with low tidal volume ventilation or actually improves the disease progression.”

Study 1 details

Assessment of awake prone positioning in hospitalised adults with COVID-19: A non-randomised controlled trial

Edward Tang Qian, Cheryl Gatto, Olga Amusina, et al.

Published in JAMA Internal Medicine on 18 April 2022

Key Points

Question Is prone positioning associated with improved outcomes among patients with COVID-19 and hypoxaemia requiring supplemental oxygen but not yet receiving mechanical ventilation?
Findings In this non-randomised 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 (WHO) 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 hypoxaemia who require supplemental oxygen but not mechanical ventilation is not beneficial.


Awake prone positioning may improve hypoxaemia among patients with COVID-19, but whether it is associated with improved clinical outcomes remains unknown.

To determine whether the recommendation of awake prone positioning is associated with improved outcomes among patients with COVID-19–related hypoxaemia who have not received mechanical ventilation.

Design, Setting, and Participants
This pragmatic non-randomised controlled trial was conducted at 2 academic medical centres (Vanderbilt University Medical Center and NorthShore University HealthSystem) during the COVID-19 pandemic. A total of 501 adult patients with COVID-19–associated hypoxaemia who had not received mechanical ventilation were enrolled from May 13 to December 11, 2020.

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 hypoxaemia on study day 5.

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 non-randomised controlled trial, prone positioning offered no observed clinical benefit among patients with COVID-19–associated hypoxaemia 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.

Study 2 details

Prone positioning in awake patients with COVID-19-associated respiratory failure: The Procarf Trial

Ibarra-estrada, Miguel; Vargas-Obieta, Alexandra; Marin-Rosales, Miguel; Aguirre-Díaz, Sara; García-Salcido, Roxana; López-Pulgarín, Jose; Chavez-Peña, Quetzalcoatl; Mijangos-Méndez, Julio; Aguirre-Avalos, Guadalupe.

Published in Critical Care Journal on 22 January 2022

Awake prone positioning (APP) has been increasingly used in patients with acute respiratory failure due to COVID-19; however, most data supporting this therapy are observational/retrospective. The aim of this trial was to compare the outcomes in COVID-19 patients managed with APP versus standard care (SC).

Randomised controlled superiority trial, which included patients with COVID-19 and requirement of oxygen through high-flow nasal cannula (HFNC). Patients were randomised to remain in APP as long as possible or SC while HFNC therapy was needed. The primary outcome was intubation rate; treatment failure, defined as intubation or death without intubation, and mortality were secondary, with a follow-up to 28 days. Baseline characteristics, physiological response to APP, factors associated to failure, and adverse events were also analysed.

We enrolled 216 patients to APP and 214 to SC. Baseline characteristics were similar. Intubation rate was 30% in APP and 43% in SC patients (RR 0.70; 95% CI 0.54-0.90, p=0.006); mortality was 33% and 37%, respectively (RR 0.89; 95% CI 0.69-1.15, p=0.37). At multivariate analysis, the factors associated to an increased risk of failure were respiratory rate at enrolment (p=< 0.001), SpO2/FiO2 at enrolment (p=< 0.001), absence of silent hypoxaemia (p=0.01), lung ultrasound score at enrolment (p=< 0.001) and D-dimer at hospital admission (p=< 0.001). Mean daily duration of APP was 9.4 h (5.6-12.9), with a median of 6 days (3.7-9.0). At ROC curve analysis, the best predictors of treatment failure were a daily duration of APP < 7.7h (AUROC 0.96, p=< 0.001), respiratory rate at enrolment ≥25 bpm (AUROC 0.93, p=< 0.001), D-dimer >1.4 mg/dL (AUROC 0.82, p=< 0.001), and a decrease in respiratory rate < 3 bpm after the first session of APP (AUROC 0.79, p=< 0.001). The most common adverse events were back pain in 16 (7.4%) patients and intravascular lines dislodgement in 14 (6.5%).

We found APP is associated with a reduced risk of intubation, with no difference in mortality. As a safe and effective procedure, we suggest APP should be encouraged to all COVID-19 patients requiring oxygen support with HFNC, aiming for the longest daily duration as possible, with closer monitoring of patients with predictive factors of failure.


Critical Care Journal article – Prone positioning in awake patients with COVID-19-associated respiratory failure: The PROCARF Trial (Open access)


JAMA Internal Medicine article – Assessment of awake prone positioning in hospitalised adults with COVID-19: A non-randomised controlled trial (Open access)

See more from MedicalBrief archives:


Proning: Some acute ventilator patients have permanent nerve damage


COVID-19: Intensive Care Society issues new guidelines on ‘proning’


Groote Schuur doctors on benefits of high-flow nasal oxygen — Spotlight report




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