Retrospective Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Crit Care Med. Sep 9, 2025; 14(3): 101327
Published online Sep 9, 2025. doi: 10.5492/wjccm.v14.i3.101327
Impact of proning with and without inhaled pulmonary vasodilators and neuromuscular blocking agents in COVID acute respiratory distress syndrome
Matthew Cabrera, Sarika Bharil, Meghan Chin, Seife Yohannes, Paul Clark
Matthew Cabrera, Sarika Bharil, Meghan Chin, Department of Critical Care Medicine, Georgetown University School of Medicine, Washington, DC 20007, United States
Seife Yohannes, Paul Clark, Department of Critical Care, MedStar Washington Hospital Center, Washington, DC 20010, United States
Author contributions: Cabrera M wrote the original draft; Cabrera M, Bharil S and Chin M designed the study, were responsible for developing the methodology and participated in the formal analysis and investigation; Cabrera M, Bharil S, Chin M, Yohannes S, and Clark P participated in the review and editing; all of the authors read and approved the final version of the manuscript to be published.
Institutional review board statement: This study was approved by the Georgetown University-Medstar Health Institutional Review Board (No. STUDY00002769). It was determined exempt due to the low risk of harm of this research to its participants.
Informed consent statement: Signed informed consent was exempt by our Institutional Review Board given the data collected was retrospective chart review and all patients were de-identified during data collection.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Matthew Cabrera, MD, Researcher, Department of Critical Care Medicine, Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC 20007, United States. mpc125@georgetown.edu
Received: September 10, 2024
Revised: February 3, 2025
Accepted: February 25, 2025
Published online: September 9, 2025
Processing time: 310 Days and 15.7 Hours
Abstract
BACKGROUND

A major cause of mortality in the coronavirus disease 2019 (COVID-19) pandemic was acute respiratory distress syndrome (ARDS). Currently, moderate to severe ARDS induced by COVID-19 (COVID ARDS) and other viral and non-viral etiologies are treated by traditional ARDS protocols that recommend 12-16 hours of prone position ventilation (PPV) with neuromuscular blocking agents (NMBA) and a trial of inhaled vasodilators (IVd) if oxygenation does not improve. However, debate on the efficacy of adjuncts to PPV and low tidal volume ventilation persists and evidence about the benefits of IVd/NMBA in COVID ARDS is sparse. In our multi-center retrospective review, we evaluated the impact of PPV, IVd, and NMBA on outcomes and lung mechanics in COVID ARDS patients with moderate to severe ARDS.

AIM

To evaluate the impact of PPV used alone or in combination with pulmonary IVd and/or NMBA in mechanically ventilated patients with moderate to severe ARDS during the COVID-19 pandemic.

METHODS

A retrospective study at two tertiary academic medical centers compared outcomes between COVID ARDS patients receiving PPV and patients in the supine position. PPV patients were divided based on concurrent use of ARDS adjunct therapies resulting in four subgroups: (1) PPV alone; (2) PPV and IVd; (3) PPV and NMBA; and (4) PPV, IVd, and NMBA. Primary outcomes were hospital and intensive care unit (ICU) length of stay (LOS), mortality, and venovenous extracorporeal membrane oxygenation (VV-ECMO) status. Secondary outcomes included changes in lung mechanics at 24-hour intervals for 7 days.

RESULTS

Total 114 patients were included in this study. Baseline respiratory parameters and Sequential Organ Failure Assessment scores were significantly worse in the PPV group. ICU LOS and LOS were significantly longer for patients who were proned, but no mortality benefit or difference in VV-ECMO status was found. Among the subgroups, no difference in primary outcomes were found. In the secondary analysis, PPV was associated with a significant improvement in arterial oxygen partial pressure (PaO2)/fractional inspired oxygen (FiO2) (P/F) ratio from day 1 to day 4 (P < 0.05) and higher driving pressures day 5 to day 7 (P < 0.05). The combination of PPV and IVd together resulted in improvements in P/F ratio from day 1 to day 7 and plateau pressure on day 4 and day 6 (P < 0.05). PPV with NMBA was not associated with improvements in any of the secondary outcomes. The use of all three rescue therapies together resulted in improvements in lung compliance on day 2 (P < 0.05) but no other improvements.

CONCLUSION

In mechanically ventilated patients diagnosed with moderate to severe COVID ARDS, PPV and PPV with the addition of IVd produced a significant and sustained increase in P/F ratio. The combination of PPV, IVd and NMBA improved compliance however this did not reach significance. Mortality and LOS did not improve with adjunct therapies. Further research is warranted to determine the efficacy of these therapies alone and in combination in the treatment of COVID ARDS.

Keywords: Acute respiratory distress syndrome; COVID; Prone position ventilation; Neuromuscular blocking agents; Pulmonary vasodilators; Mechanical ventilation; Plateau pressure; Driving pressure; Peak end expiratory pressure

Core Tip: In this retrospective study at two tertiary academic medical centers during the initial coronavirus disease 2019 surge, we examine trends in ventilator mechanics and outcomes of 114 acute respiratory distress syndrome (ARDS) patients receiving three adjunct therapies (prone positioning, neuromuscular blockade and inhaled vasodilations). We found a significant improvement in arterial oxygen partial pressure/fractional inspired oxygen ratio with the addition of inhaled vasodilators while proning and in lung compliance with the addition of continuous neuromuscular blockade among others. Our groups were not large enough to detect a difference in mortality or length of stay. However, this study provides a large amount of data and multi-day trends to further our understanding of the physiologic response to multiple adjunct therapies for ARDS in combination.