Double-blind, randomized, multicenter study of doxacurium vs. pancuronium in intensive care unit patients who require neuromuscular-blocking agents

Objective: To compare the neuromuscular-blocking and hemodynamic effects of doxacurium vs. pancuronium administered by intermittent bolus to intensive care unit (ICU) patients who required neuromuscular block to facilitate mechanical ventilation for ≥24 hrs. Design: A multicenter, prospective, double-blind, randomized study comparing doxacurium, a new benzylisoquinolone neuromuscular-blocking agent, with pancuronium. Setting: ICUs of three tertiary care hospitals. Patients: Forty critically ill patients (29 male, 11 female) with an average age of 52.5 yrs (range 19 to 80). Interventions: With approval of our Institutional Review Boards and after obtaining informed consent, 40 critically ill patients were entered into the study. Histories and the results of physical examinations were recorded, laboratory data were collected, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated during the 8 hrs before the start of the study medication. Patients received either doxacurium (initial dose of 0.04 mg/kg) or pancuronium (initial dose of 0.07 mg/kg) by bolus injection with continuous measurement of vital signs every minute for 15 mins. We measured the degree of neuromuscular blockade using a peripheral-nerve stimulator to measure the Train-of-Four count. Patients were rebolused (doxacurium dose of 0.025 mg/kg, pancuronium dose of 0.05 mg/kg) based on clinical criteria, which were substantiated by measurement of the Train-of-Four count. The neuromuscular-blocking drugs were stopped when the patient no longer required paralysis or after 5 days of therapy, whichever came first. Group comparisons were made using repeated measures analysis of variance, Fisher's exact test, and two sample t-tests, when appropriate. Spearman's rank-correlation coefficients were calculated to assess the relationship of onset time and recovery time with all baseline laboratory values and the APACHE II scores. Ap < .05 was used to establish statistical significance. Measurements and Main Results: There were no differences between the two groups with respect to age, gender, or APACHE II scores. There were no differences between groups in terms of adverse experiences, nor with respect to time of onset of block, number of doses, or the duration of neuromuscular blockade (2.6 vs. 2.2 days for doxacurium vs. pancuronium, respectively). There was a statistically significant increase in heart rate after the initial dose of pancuronium (120 ± 23 vs. 109 ± 22 beats/min postinjection vs. preinjection, respectively; p < .05) without any differences noted after doxacurium (107 ± 21 vs. 109 ± 21 beats/min, respectively). Furthermore, once neuromuscular block was discontinued, the pancuronium group had a more prolonged and variable recovery time (279 ± 229 mins) compared with the doxacurium group (138 ± 46 mins, p < .05). Conclusions: In critically ill patients requiring neuromuscular block for >24 hrs, doxacurium was well tolerated without evidence of tachycardia and with a relatively prompt recovery profile.