STUDY OBJECTIVE: To compare the hemodynamics, efficacy, safety, and postoperative recovery of patients following the use of either midazolam plus propofol or placebo plus propofol for induction and maintenance of general anesthesia for outpatient surgical procedures of less than two hours' duration. DESIGN: Prospective, parallel, randomized, double-blind, placebo-controlled, multicenter study. SETTING:Ten outpatient surgery centers. PATIENTS: 203 ASA physical status I, II, and III patients undergoing various outpatient surgical procedures. INTERVENTIONS: Patients were randomly assigned to one of the two treatment groups. For induction of anesthesia, Group 1 received midazolam (0.077 +/- 0.0021 mg/kg) via slow intravenous (IV) push plus continuous infusion propofol (provided in a concentration of 5 mg/ml), and Group 2 received placebo plus full-concentration (10 mg/ml) propofol. Thereafter, Group 1 received half-concentration propofol and Group 2 received full-concentration propofol via continuous infusion for maintenance of anesthesia. Investigators administered doses of study medication in a blinded fashion as required to achieve the desired clinical effect. Drugs used to maintain anesthesia were restricted to study drug, short-acting opioids, and nitrous oxide. Succinylcholine chloride or vecuronium were used to facilitate intubation of study patients. MEASUREMENTS AND MAIN RESULTS: There were no statistically significant differences between the midazolam/propofol and placebo/propofol groups with respect to the mean (SE) decrease in mean arterial pressure from pre-dose to time of intubation or from time of intubation to initiation of surgery; the mean (SE) time required from initiation of study medication to completion of intubation [6.7 (0.23) minutes vs. 7.0 (0.26) minutes, respectively]; or the mean (SE) amount of propofol required to induce and maintain anesthesia [6.03 (0.329) mg/kg vs. 9.71 (0.489) mg/kg, respectively]. There was no significant difference between the two treatment groups in the time to recovery following the completion of surgery (as assessed by Aldrete Post Anesthesia Recovery Score). Most patients (approximately 79%) in both groups rated the quality of the anesthetic regimen as excellent; however, as assessed by patient questionnaires, fewer patients in the midazolam/ propofol group were able to recall the events surrounding their surgical procedure as compared with patients in the placebo/ propofol group (89.2% vs. 77.9%; p = 0.022). There were no differences between the two groups with respect to the frequency or severity of adverse events. CONCLUSIONS: Concomitantly administered midazolam and reduction-concentration propofol did not exacerbate the well-described hypotensive effects of full-strength propofol during induction of anesthesia. The time to intubation was equivalent with the combination of midazolam/propofol as compared with propofol alone. Recovery from the two regimens was not significantly different. However, reduced recall of perioperative events was observed more often in the midazolam/propofol regimen compared with propofol alone.
RCT Entities:
STUDY OBJECTIVE: To compare the hemodynamics, efficacy, safety, and postoperative recovery of patients following the use of either midazolam plus propofol or placebo plus propofol for induction and maintenance of general anesthesia for outpatient surgical procedures of less than two hours' duration. DESIGN: Prospective, parallel, randomized, double-blind, placebo-controlled, multicenter study. SETTING: Ten outpatient surgery centers. PATIENTS: 203 ASA physical status I, II, and III patients undergoing various outpatient surgical procedures. INTERVENTIONS:Patients were randomly assigned to one of the two treatment groups. For induction of anesthesia, Group 1 received midazolam (0.077 +/- 0.0021 mg/kg) via slow intravenous (IV) push plus continuous infusion propofol (provided in a concentration of 5 mg/ml), and Group 2 received placebo plus full-concentration (10 mg/ml) propofol. Thereafter, Group 1 received half-concentration propofol and Group 2 received full-concentration propofol via continuous infusion for maintenance of anesthesia. Investigators administered doses of study medication in a blinded fashion as required to achieve the desired clinical effect. Drugs used to maintain anesthesia were restricted to study drug, short-acting opioids, and nitrous oxide. Succinylcholine chloride or vecuronium were used to facilitate intubation of study patients. MEASUREMENTS AND MAIN RESULTS: There were no statistically significant differences between the midazolam/propofol and placebo/propofol groups with respect to the mean (SE) decrease in mean arterial pressure from pre-dose to time of intubation or from time of intubation to initiation of surgery; the mean (SE) time required from initiation of study medication to completion of intubation [6.7 (0.23) minutes vs. 7.0 (0.26) minutes, respectively]; or the mean (SE) amount of propofol required to induce and maintain anesthesia [6.03 (0.329) mg/kg vs. 9.71 (0.489) mg/kg, respectively]. There was no significant difference between the two treatment groups in the time to recovery following the completion of surgery (as assessed by Aldrete Post Anesthesia Recovery Score). Most patients (approximately 79%) in both groups rated the quality of the anesthetic regimen as excellent; however, as assessed by patient questionnaires, fewer patients in the midazolam/ propofol group were able to recall the events surrounding their surgical procedure as compared with patients in the placebo/ propofol group (89.2% vs. 77.9%; p = 0.022). There were no differences between the two groups with respect to the frequency or severity of adverse events. CONCLUSIONS: Concomitantly administered midazolam and reduction-concentration propofol did not exacerbate the well-described hypotensive effects of full-strength propofol during induction of anesthesia. The time to intubation was equivalent with the combination of midazolam/propofol as compared with propofol alone. Recovery from the two regimens was not significantly different. However, reduced recall of perioperative events was observed more often in the midazolam/propofol regimen compared with propofol alone.