Neuromuscular blocking agents in critically-ill COVID-19 patients requiring mechanical ventilation

ABSTRACT

RATIONALE. Neuromuscular blocking agents (NMBA) are used in patients with moderate to severe acute respiratory distress syndrome. NMBA have also been used in COVID-19 patients who required mechanical ventilation (MV), but their benefit-to-risk ratio remains uncertain.METHODS. We investigated the effects associated with the use of NMBA in COVID-19 patients who required MV from January 1, 2020 to October 31, 2020 in 153 hospitals across 6 continents, comprising the COVID-19 Critical Care Consortium. Cox proportional hazards analysis was conducted to study the impact of NMBA on 28-day intensive care unit (ICU) mortality. Hospital/ICU lengths of stay were appraised. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTS. 1227 patients were eligible for analysis, among those 598 (48.7%) received NMBA for 2 days or longer, with a median time from ICU admission to commencement of NMBA therapy of 0 day (IQR 0-1 days). The median duration of NMBA therapy was 2 days (N=789, IQR 1-5). In comparison with standard of care, treatment with NMBA was more frequent in obese (31% vs. 39%, P = 0.03) and diabetic patients (2% vs. 8%, P <0.01) and less frequent in patients with hypertension (52% vs. 46%, P =0.04) or cardiac diseases (21% vs. 14%, P =0.003). Upon commencement of MV, patients who underwent NMBA therapy vs those who did not presented a PaO2/FiO2 of 136.1±69.2 vs. 162.7 ±125.8 (p<0.01), required more often ECMO (10% vs 5.2%, p <0.01) and prone position (25.1% vs 6.2%, p <0.01). Unadjusted 28-day all-cause mortality was similar (58.2% vs. 62.4%, P =0.134) between patients without or with NMBA therapy, respectively, but length of MV (3 days [2-5] vs. 6 [3-12] P <0.01) and ICU stay (8 days [4-14] vs. 13 [7-19] P <0.01) were prolonged. After PS matching, NMBA therapy was strongly associated with 28-day ICU mortality (adjusted HR 3.18, 95% CI 2.65-3.81, P <0.01). CONCLUSION. Use of NMBA in COVID-19 patients requiring MV is associated with increased 28-day mortality, delayed discontinuation of MV and prolonged ICU stay.