THE EFFECT OF ONDANSETRON ON ATRACURIUM-INDUCED NEUROMUSCULAR BLOCKADE

Study Objective: To determine whether treatment with ondansetron, a ne w antiemetic drug, affects nondepolarizing neuromuscular blockade. Des ign: Randomized, double-blind, prospective study. Setting: Operating r oom at a university medical center. Patients: 30 ASA physical status I and II patients scheduled for elective surgery. Interventions: After the induction of anesthesia with midazolam 2 to 4 mg/kg, sodium thiope ntal 6 to 8 mg/kg, and fentanyl 4 to 8 mug/kg, the ulnar nerve was sti mulated at the wrist through subcutaneous needle electrodes at a frequ ency of 0.15 Hz. The response to stimulation was measured and recorded with a force-displacement transducer applied to the thumb. Patients w ere randomized to one of three treatment groups. A steady baseline to ulnar nerve stimulation with nitrous oxide-oxygen-opioid-thiopental an esthesia was established. The first study group (Group 1) received a p lacebo, the second group (Group 2) received 8 mg of ondansetron, and t he third group (Group 3) received 16 mg of ondansetron as an intraveno us infusion over 5 minutes. Patients were then given incremental doses of atracurium 0.05 mg/kg at 3-minute intervals to establish approxima tely 95% twitch inhibition so as to construct a dose-response curve. A n atracurium infusion was then begun to maintain a constant degree of neuromuscular blockade. At the end of surgery, patients were allowed t o recover spontaneously, or pharmacologic antagonism of residual neuro muscular blockade was achieved with neostigmine 0.05 mg/kg and glycopy rrolate 0.01 mg/kg. Mechanomyographic response to train-of-four stimul i (2 Hz for 2 seconds) every 20 seconds was monitored during the atrac urium infusion and recovery from neuromuscular blockade. Measurements and Main Results: Log dose-response curves were determined for the stu dy groups and compared using analysis of variance (ANOVA). The 50%, 75 %, and 95% effective doses (ED50, ED75, and ED95) were calculated from the equation describing the log dose-response. Maintenance infusion r ates were determined, and the neostigmine-accelerated recovery index o f 25% to 75% was measured for each group. The results were compared us ing ANOVA. There were no significant differences among the treatment g roups with respect to maintenance infusion rate (7.8 +/- 1.8 mug/kg/mi n for Group 1, 7.7 +/- 2.5 mug/kg/min for Group 2, and 7.3 +/- 2.3 mug /kg/min for Group 3) or neostigmine-accelerated recovery interval of 2 5% to 75% (4.5 +/- 2.3 minutes, 4.4 +/- 3.1 minutes, 6.6 +/- 3.9 minut es in Groups 1, 2, and 3, respectively). The log dose-response data fo r Groups 1, 2, and 3 did not differ significantly (p = 0.068), and the calculated ED95 in each treatment group demonstrated no dose-related change (0.254 +/- 0.022, 0.279 +/- 0.033, and 0.240 +/- 0.022 for Grou ps 1, 2, and 3, respectively). Conclusions: Ondansetron is an antiemet ic drug that can be used in the perioperative period without concern f or potentiation Of nondepolarizing neuromuscular blockade, change in a tracurium maintenance dose, or change in rate Of neostigmine-induced r ecovery from neuromuscular blockade with atracurium.