Prone positioning of patients with moderate hypoxaemia due to covid-19: multicentre pragmatic randomised trial (COVID-PRONE).

OBJECTIVES: To assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients admitted to hospital with covid-19. DESIGN: Multicentre pragmatic randomised clinical trial. SETTING: 15 hospitals in Canada and the United States from May 2020 until May 2021. PARTICIPANTS: Eligible patients had a laboratory confirmed or a clinically highly suspected diagnosis of covid-19, needed supplemental oxygen (up to 50% fraction of inspired oxygen), and were able to independently lie prone with verbal instruction. Of the 570 patients who were assessed for eligibility, 257 were randomised and 248 were included in the analysis. INTERVENTION: Patients were randomised 1:1 to prone positioning (that is, instructing a patient to lie on their stomach while they are in bed) or standard of care (that is, no instruction to adopt prone position). MAIN OUTCOME MEASURES: The primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as needing at least 60% fraction of inspired oxygen for at least 24 hours. Secondary outcomes included the change in the ratio of oxygen saturation to fraction of inspired oxygen. RESULTS: The trial was stopped early on the basis of futility for the pre-specified primary outcome. The median time from hospital admission until randomisation was 1 day, the median age of patients was 56 (interquartile range 45-65) years, 89 (36%) patients were female, and 222 (90%) were receiving oxygen via nasal prongs at the time of randomisation. The median time spent prone in the first 72 hours was 6 (1.5-12.8) hours in total for the prone arm compared with 0 (0-2) hours in the control arm. The risk of the primary outcome was similar between the prone group (18 (14%) events) and the standard care group (17 (14%) events) (odds ratio 0.92, 95% confidence interval 0.44 to 1.92). The change in the ratio of oxygen saturation to fraction of inspired oxygen after 72 hours was similar for patients randomised to prone positioning and standard of care. CONCLUSION: Among non-critically ill patients with hypoxaemia who were admitted to hospital with covid-19, a multifaceted intervention to increase prone positioning did not improve outcomes. However, wide confidence intervals preclude definitively ruling out benefit or harm. Adherence to prone positioning was poor, despite multiple efforts to increase it. Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning. STUDY REGISTRATION: ClinicalTrials.gov NCT04383613.

Exertional hypoxia in patients without resting hypoxia is an early predictor of moderate to severe COVID-19.

The importance of exertional hypoxia without resting hypoxia in COVID-19 is unknown and may help objectively identify high-risk patients. Interventions may be initiated earlier with sufficient lead-time between development of exertional hypoxia and other outcome measures. We performed a retrospective study of adult patients hospitalized with COVID-19 from March 1, 2020 to October 30, 2020 in an integrated academic medical system in the Chicagoland area. We analyzed patients who had daily exertional oximetry measurements taken. We defined exertional hypoxia as SpO2 < 90% with ambulation. We excluded patients who had first exertional oximetry measurements or first exertional hypoxia after the use of oxygen therapies. We determined the association of exertional hypoxia without resting hypoxia with the eventual need for nasal cannula or advanced oxygen therapies (defined as high flow nasal cannula, Bi-PAP, ventilator, or extracorporeal membrane oxygenation). We also calculated the time between development of exertional hypoxia and the need for oxygen therapies. Of 531 patients included, 132 (24.9%) had exertional hypoxia. Presence of exertional hypoxia was strongly associated with eventual use of nasal cannula (OR 4.8, 95% CI 2.8-8.4) and advanced oxygen therapy (IRR 7.7, 95% CI 3.4-17.5). Exertional hypoxia preceded nasal cannula use by a median 12.5 h [IQR 3.25, 29.25] and advanced oxygenation by 54 h [IQR 25, 82]. Exertional hypoxia without resting hypoxia may serve as an early, non-invasive physiologic marker for the likelihood of developing moderate to severe COVID-19. It may help clinicians triage patients and initiate earlier interventions.