Impact of proning with and without inhaled pulmonary vasodilators and neuromuscular blocking agents in COVID acute respiratory distress syndrome.

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.