PHARMACODYNAMICS OF DOXACURIUM DURING CARDIAC-SURGERY WITH HYPOTHERMIC CARDIOPULMONARY BYPASS

Purpose: To determine the characteristics of neuromuscular block produ ced by vivo and three times the 95% effective dose (ED(95)) of doxacur ium in patients undergoing coronary artery surgery with hypothermic ca rdiopulmonary bypass. Methods: In a prospective non randomized study, ten patients received doxacurium 0.05 mg . kg(-1) (Group 1) and ten ot hers received 0.075 mg . kg(-1) (Group 2) with midazolam and sufentani l. The mechanomyographic response of the adductor pollicis muscle afte r supramaximal train-of-four (TOF) stimulation of the ulnar nerve was recorded intraoperatively and postoperatively. Additional doxacurium ( 10% of the initial dose) was administered until sternal closure whenev er the first twitch (T-1) had recovered to 25% of control. Results: Th e onset time (time to maximal T-1 depression) of doxacurium was 390 +/ - 148 sec in Group 1 and 370 +/- 74 sec in Group 2 (P = 0.71). The cli nical duration of neuromuscular block (time to 25% T-1 recovery) was 1 65 +/- 90 min in Group 1 and 258 +/- 86 min in Group 2 (P = 0.03). On arrival to recovery room the mean T-1 was 57 +/- 23% in Group 1 and 24 +/- 21% in Group 2 (P = 0.003); the mean T-4/T-1 ratio was 0.25 +/- 0 .15 for five patients of Group 1 with four responses to TOF stimulatio n and 0.10 for the only patient of Group 2 with four twitches. Conclus ion: In contrast with findings in patients without cardiac disease, th is study shows comparable onset rimes of doxacurium with doses of two and three rimes ED(95). The clinical duration of doxacurium is 60 to 1 00% longer than previously reported in noncardiac surgery.