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Multicenter Study
. 2021 Jul 1;49(7):1026-1037.
doi: 10.1097/CCM.0000000000004938.

Prone Positioning and Survival in Mechanically Ventilated Patients With Coronavirus Disease 2019-Related Respiratory Failure

Kusum S Mathews  1   2 , Howard Soh  1 , Shahzad Shaefi  3 , Wei Wang  4 , Sonali Bose  1 , Steven Coca  5 , Shruti Gupta  6 , Salim S Hayek  7 , Anand Srivastava  8 , Samantha K Brenner  9   10 , Jared Radbel  11 , Adam Green  12 , Anne Sutherland  13 , Amanda Leonberg-Yoo  14 , Alexandre Shehata  15 , Edward J Schenck  16 , Samuel A P Short  17 , Miguel A Hernán  1   2   3   4   5   6   7   8   9   10   11   12   13   14   15   16   17   18   19   20 , Lili Chan  5 , David E Leaf  6 ; STOP-COVID Investigators
Affiliations
Multicenter Study

Prone Positioning and Survival in Mechanically Ventilated Patients With Coronavirus Disease 2019-Related Respiratory Failure

Kusum S Mathews et al. Crit Care Med. .

Abstract

Objectives: Therapies for patients with respiratory failure from coronavirus disease 2019 are urgently needed. Early implementation of prone positioning ventilation improves survival in patients with acute respiratory distress syndrome, but studies examining the effect of proning on survival in patients with coronavirus disease 2019 are lacking. Our objective was to estimate the effect of early proning initiation on survival in patients with coronavirus disease 2019-associated respiratory failure.

Design: Data were derived from the Study of the Treatment and Outcomes in Critically Ill Patients with coronavirus disease 2019, a multicenter cohort study of critically ill adults with coronavirus disease 2019 admitted to 68 U.S. hospitals. Using these data, we emulated a target trial of prone positioning ventilation by categorizing mechanically ventilated hypoxemic (ratio of Pao2 over the corresponding Fio2 ≤ 200 mm Hg) patients as having been initiated on proning or not within 2 days of ICU admission. We fit an inverse probability-weighted Cox model to estimate the mortality hazard ratio for early proning versus no early proning. Patients were followed until death, hospital discharge, or end of follow-up.

Setting: ICUs at 68 U.S. sites.

Patients: Critically ill adults with laboratory-confirmed coronavirus disease 2019 receiving invasive mechanical ventilation with ratio of Pao2 over the corresponding Fio2 less than or equal to 200 mm Hg.

Interventions: None.

Measurements and main results: Among 2,338 eligible patients, 702 (30.0%) were proned within the first 2 days of ICU admission. After inverse probability weighting, baseline and severity of illness characteristics were well-balanced between groups. A total of 1,017 (43.5%) of the 2,338 patients were discharged alive, 1,101 (47.1%) died, and 220 (9.4%) were still hospitalized at last follow-up. Patients proned within the first 2 days of ICU admission had a lower adjusted risk of death compared with nonproned patients (hazard ratio, 0.84; 95% CI, 0.73-0.97).

Conclusions: In-hospital mortality was lower in mechanically ventilated hypoxemic patients with coronavirus disease 2019 treated with early proning compared with patients whose treatment did not include early proning.

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Conflict of interest statement

Dr. Mathews reported receiving grants from the National Institute of Health (NIH) and the National Heart, Lung, and Blood Institute (NHLBI) during the conduct of the study and serves on the steering committee for A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE) trial, funded by Roivant/Kinevant Sciences; she received support for article research from NIH. Dr. Shaefi reported receiving grants from the NIH and the National Institute on Aging and the National Institute of General Medical Sciences; he received support for article research from NIH. Dr. Coca received funding from RenalytixAI, Relypsa, Takeda Pharmaceuticals, CHF Solutions, Bayer, Boehringer Ingelheim, Akebia, inRegen, Renal Research Institute, and XORTX Therapeutics, Inc.; he owns equities in RenalytixAI and pulseData. Dr. Gupta reported receiving grants from the NIH and is a scientific coordinator for GlaxoSmithKline’s Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor Daprodustat trial. Dr. Srivastava’s institution received funding from the NIH and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); he reported receiving funding from the NIH, NIDDK, Horizon Therapeutics PLC, AstraZeneca, Tate & Latham, and CVS Caremark. Dr. Hernán reported receiving grants from the NIH. Dr. Chan’s institution received funding from NIH and Renal Research Institute; she received funding from Gerson Lehrman Group consulting and NIH; she received support for article research from NIH. Dr. Leaf’s institution received funding from NIH, NIDDK, and NHLBI; he received funding from BioPorto. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Study cohort. ABG = arterial blood gas, COVID-19 = coronavirus disease 2019, Pao2/Fio2 = ratio of Pao2 over the corresponding Fio2.
Figure 2.
Figure 2.
Absolute standardized differences before and after applying inverse probability weighting. This figure shows the absolute standardized differences between groups for each of the 25 prespecified covariates pre and post weighting. COVID-19 = coronavirus disease 2019, Pao2/Fio2 = ratio of Pao2 over the corresponding Fio2, SOFA = Sequential Organ Failure Assessment.
Figure 3.
Figure 3.
Survival of patients initiated versus not initiated on early prone positioning ventilation within the first 2 d of ICU admission. A, Shows Kaplan-Meier survival curves for those who underwent prone positioning ventilation within first 2 ICU days versus those who did not. B, Shows the hazard ratios (HRs) for survival for proned versus nonproned patients. Sensitivity analysis # 1 used an unweighted multivariable Cox model rather than inverse probability weighting to adjust for confounding. Sensitivity analysis # 2 used a nested target trial approach to reduce the potential for immortal time bias. Sensitivity analysis # 3 excluded patients who died in the first 2 d of ICU admission as an alternative approach to reduce the potential for immortal time bias. Sensitivity analysis # 4 is similar to the primary analysis but is further adjusted for the percentage of patients at each hospital who were proned in the first 2 d of ICU admission. Sensitivity analysis #5 is similar to the primary analysis but censored patients on day 30. Sensitivity analysis #6 is similar to the sensitivity analysis #5 but assumes that individuals discharged alive before day 30 remained alive for the full 30 days. Also shown are the analyses of prespecified subgroups with the ratio of Pao2 over the corresponding Fio2 (Pao2/Fio2) less than or equal to 150 and less than or equal to 100 mm Hg.
See this image and copyright information in PMC

Comment in

References

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