Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis

Abstract

Background: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis.

Methods: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression.

Results: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0-25) and 25 (IQR 7-26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0-87) and 87 (IQR 0-88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177).

Conclusions: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.

Keywords: COVID-19; Intensive care unit; Mechanical ventilation; Neuromuscular blocking agent; SARS-CoV-2.

Fig. 1

Flow of patient enrolment by the censor date of October 31, 2021. MV, mechanical ventilation; NMBA, neuromuscular blocking agents

Fig. 2

Number of patients per week of intensive care unit (ICU) admission is depicted

Fig. 3

Unadjusted Kaplan–Meier event curves for in-hospital mortality from commencment of invasive mechanical ventilation to 90 days. A Before propensity score matching, 90-day ICU Kaplan-Meier curves differed between patients undergoing up to three-day NMBA therapy, within 48 hours from commencement of IMV, in comparison with those who did not (N = 1953, p < 0.001). B After propensity score matching, no difference in survival between patients undergoing NMBA therapy in comparison with those who did not was found (N = 420, due to equally sized cohorts post propensity score matching, P = 0.537). NMBA neuromuscular blocking agent, ICU intensive care unit

Fig. 4

Standard mean difference of key parameters before and after propensity score matching. *Compared with North America