DOUBLE-BLIND, RANDOMIZED, MULTICENTER STUDY OF DOXACURIUM VS PANCURONIUM IN INTENSIVE-CARE UNIT PATIENTS WHO REQUIRE NEUROMUSCULAR-BLOCKINGAGENTS

Objective: To compare the neuromuscular-blocking and hemodynamic effec ts of doxacurium vs. pancuronium administered by intermittent bolus to intensive care unit (ICU) patients who required neuromuscular block t o facilitate mechanical ventilation for greater than or equal to 24 hr s. Design: A multicenter, prospective, double-blind, randomized study comparing doxacurium, a new benzylisoquinolone neuromuscular-blocking agent, with pancuronium. Setting: ICUs of three tertiary care hospital s. Patients: Forty critically ill patients (29 male, 11 female) with a n average age of 52.5 yrs (range 19 to 80). Interventions: With approv al of our Institutional Review Boards and after obtaining informed con sent, 40 critically ill patients were entered into the study. Historie s and the results of physical examinations were recorded, laboratory d ata 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 bol us injection with continuous measurement of vital signs every minute f or 15 mins. We measured the degree of neuromuscular blockade using a p eripheral-nerve stimulator to measure the Train-of-Four count. Patient s were rebolused (doxacurium dose of 0.025 mg/kg, pancuronium dose of 0.05 mg/kg) based on clinical criteria, which were substantiated by me asurement 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 us ing repeated measures analysis of variance, Fisher's exact test, and t wo sample t-tests, when appropriate. Spearman's rank-correlation coeff icients were calculated to assess the relationship of onset time and r ecovery time with all baseline laboratory values and the APACHE II sco res. A p < .05 was used to establish statistical significance. Measure ments and Main Results: There were no differences between the two grou ps with respect to age, gender, or APACHE II scores. There were no dif ferences between groups in terms of adverse experiences, nor with resp ect to time of onset of block, number of doses, or the duration of neu romuscular 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) with out any differences noted after doxacurium (107 +/- 21 vs. 109 +/- 21 beats/min, respectively). Furthermore, once neuromuscular block was di scontinued, the pancuronium group had a more prolonged and variable re covery time (279 +/- 229 mins) compared with the doxacurium group (138 +/- 46 mins, p < .05). Conclusions: In critically ill patients requir ing neuromuscular block for > 24 hrs, doxacurium was well tolerated wi thout evidence of tachycardia and with a relatively prompt recovery pr ofile.