(1204) Comparison of Fixed Dosing Versus Train-of-Four Titration of Cisatracurium in COVID-19 ARDS Patients

Introduction: Early neuromuscular blockade with cisatracurium has been associated with improved outcomes in moderate-severe acute respiratory distress syndrome (ARDS). Previous studies have demonstrated increased drug utilization without benefits in oxygenation using fixed dose cisatracurium compared to train-of-four (TOF) titration. The objective of this study was to compare a novel, lower fixed dose cisatracurium protocol to TOF titration evaluating the impact on PaO2:FiO2 ratio (P/F).

Methods: We conducted a single-center retrospective cohort study comparing fixed dose cisatracurium to TOF titration. We included patients aged 18-89 treated for COVID-19 ARDS with a baseline P/F≤200 who received a cisatracurium infusion for greater than or equal to 12h. The primary outcome was change in P/F at 48h from baseline. Secondary outcomes included change in P/F at 24h and 7 days, need for mechanical ventilation at day 28, and cisatracurium utilization. The primary outcome, change in P/F ratio at 48 hours, was analyzed using a linear regression model. We adjusted for baseline and treatment characteristics including age, body mass index, net volume status, baseline SOFA, administration of inhaled epoprostenol, use of prone positioning, and diagnosis of a thrombotic complication during hospitalization.

Results: Analyses included 125 patients (fixed dose=65, TOF=60). Severe ARDS was common with a baseline median P/F of 73.7 vs 79.5, p=0.133. The change in P/F at 48h was larger in the TOF cohort in the adjusted analysis (24.9 vs 70.8, p< 0.005). There was no difference in need for mechanical ventilation at day 28 between groups. The rate and total cumulative dose of cisatracurium were higher in the fixed dose cohort (5 vs 3 mcg/kg/min, p< 0.001; 1034 vs 612 mg, p< 0.001) despite similar infusion durations (44.1h vs 48.5h, p=0.642).

Conclusions: Patients in the TOF cisatracurium cohort had improved P/F at 48h compared to the fixed dose cohort, while also using only 60% of the cumulative dose. Future directions should include analysis of the implications of increased cisatracurium exposure on patient outcomes.