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

Miguel Ibarra-Estrada, Jie Li, Ivan Pavlov, Yonatan Perez, Oriol Roca, Elsa Tavernier, Bairbre McNicholas, David Vines, Miguel Marín-Rosales, Alexandra Vargas-Obieta, Roxana García-Salcido, Sara A Aguirre-Díaz, José A López-Pulgarín, Quetzalcóatl Chávez-Peña, Julio C Mijangos-Méndez, Guadalupe Aguirre-Avalos, Stephan Ehrmann, John G Laffey, Miguel Ibarra-Estrada, Jie Li, Ivan Pavlov, Yonatan Perez, Oriol Roca, Elsa Tavernier, Bairbre McNicholas, David Vines, Miguel Marín-Rosales, Alexandra Vargas-Obieta, Roxana García-Salcido, Sara A Aguirre-Díaz, José A López-Pulgarín, Quetzalcóatl Chávez-Peña, Julio C Mijangos-Méndez, Guadalupe Aguirre-Avalos, Stephan Ehrmann, John G Laffey

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Trial registration: This study was retrospectively registered in ClinicalTrials.gov at July 20, 2021. Identification number NCT04477655. https://ichgcp.net/clinical-trials-registry/NCT04477655?term=PRO-CARF&draw=2&rank=1.

Keywords: Acute hypoxemic respiratory failure; Awake prone positioning; COVID-19; Intubation.

Conflict of interest statement

JL discloses research funding from Fisher & Paykel Healthcare Ltd, Aerogen Ltd, and Rice Foundation, and speaker fees from American Association for Respiratory Care, Aerogen Ltd, Heyer Ltd, and Fisher & Paykel Healthcare Ltd. IP discloses a research grant and speaker fees from Fisher & Paykel Healthcare Ltd. YP discloses research support from Fisher & Paykel Healthcare Ltd. OR discloses a research grant from Hamilton Medical and speaker fees from Hamilton Medical, Ambu and Aerogen Ltd, and non-financial research support from Timpel and Masimo Corporation. His institution received fees for consultancy from Hamilton Medical. DV discloses research funding from Teleflex Medical, Inc. and Rice Foundation, and speaker fees from Theravance Biopharma. SE discloses consultancies from Aerogen Ltd, research support from Aerogen Ltd, Fisher & Paykel Healthcare Ltd, Hamilton medical, travel reimbursements from Aerogen Ltd and Fisher & Paykel Healthcare Ltd. JGL discloses consulting fees from Baxter Healthcare and Glaxosmithkline. All other authors have no conflict of interest to disclose.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart of participants. HFNC, high-flow nasal cannula; RT-PCR, reverse-transcription polymerase chain reaction; APP, awake prone positioning; ITT, intention to treat
Fig. 2
Fig. 2
Physiological response to awake prone positioning according to subgroups of treatment success and failure. a RR decreased by 1.5 breaths/min in patients with treatment failure vs 3.7 breaths/min in patients with treatment success after the first APP session. b SpO2/FiO2 ratio increased by 12 in patients with treatment failure vs 18 in patients with treatment success after the first APP session. c ROX index increased by 0.7 in patients with treatment failure vs 2.3 in patients with treatment success after the first APP session. d LUS score decreased 2.4 points in patients with treatment success, while patients with treatment failure had no change after 3 days. RR, respiratory rate; APP, awake prone positioning; LUS, lung ultrasound score
Fig. 3
Fig. 3
Variables with the highest areas under the curve for prediction of treatment success at day 28 (alive without intubation) in the APP group. a Respiratory rate at enrollment. b ROX index after the first APP session. c Mean daily duration of APP at 3 days. d Decrease in LUS score at 3 days. APP, awake prone positioning; LUS, lung ultrasound; AUC, area under the curve
Fig. 4
Fig. 4
Mean daily duration of APP at the first 3 days. a Time on awake prone positioning in patients with silent and dyspneic hypoxemia. b Proportion of patients with treatment success rate according to mean daily duration of APP at 3 days. c Linear correlation between adjusted probability of failure (according to respiratory rate, SpO2/FIO2, lung ultrasound score, silent hypoxemia, and D-dimer) and mean daily duration of APP at 3 days (r = 0.70, P < 0.001) (APP, awake prone positioning)
Fig. 5
Fig. 5
Kaplan–Meier plots of the cumulative incidence of treatment success (a) and death (b) (APP, awake prone positioning)

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