Comparative evaluation of intravenous agents for rapid sequence induction--thiopental, ketamine, and midazolam

The pharmacologic effects of ketamine, midazolam, and a midazolam-ketamine combination were compared with thiopental for rapid induction of general anesthesia. Thiopental, 4 mg/kg, 1.5 mg/kg ketamine, 0.3 mg/kg midazolam, or 0.15 mg/kg midazolam, and 0.75 mg/kg ketamine, were administered intravenously in a randomized fashion to 80 patients undergoing emergency surgery. Adequacy of induction, hemodynamic changes, and postoperative effects were assessed during and after a standardized induction-maintenance anesthetic technique. Midazolam had the slowest onset (15-60 s) and longest duration of action. During induction, thiopental decreased mean arterial pressure (MAP) by 11%, ketamine increased MAP by 10%, while neither midazolam nor the midazolam-ketamine combination significantly changed MAP. Heart rate (HR) increased during induction in all groups; however, the increase was significantly less in the combination group. After intubation, MAP and HR increased to the same extent in all four groups. Significantly more patients who received ketamine for induction were disoriented during emergence. Midazolam most effectively produced anxiolysis and antegrade amnesia. Significantly more patients who received thiopental felt depressed postoperatively, and 95% required parenteral opiate analgesics in the recovery room. Dreaming was highest after ketamine (55%) and lowest after midazolam (0%) and the combination (5%). Thus, midazolam effectively attenuated both the cardiostimulatory responses and unpleasant emergence reactions associated with ketamine. The author concludes that both midazolam and the midazolam-ketamine combination are safe and effective induction agents for emergency surgery, which may offer an advantage over thiopental in situations where hemodynamic stability is crucial. Furthermore, midazolam effectively attenuates the side effects of ketamine.