A dose-ranging study of midazolam for postoperative sedation of patients: A randomized, double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the dose range, efficacy, and safety of midazolam for induction of sedation of mechanically ventilated postoperative patients in the intensive care unit. DESIGN: A randomized, double-blind, placebo-controlled study. SETTING: Thirteen intensive care units in Japan. PATIENTS: We included 98 patients undergoing general surgery who were ASA physical status I-III. The following inclusion criteria were applied to the patients after surgery: under mechanical ventilation, sedation level 2 or 3 on the Ramsay Sedation Scale, and any pain level but 4 on the Pybus and Torda Pain Scale. MEASUREMENTS AND RESULTS: Of the 98 patients initially enrolled in the study, 95 patients received one of the study medications: placebo (n = 24), 0.015 mg/kg midazolam (n = 21), 0.03 mg/kg midazolam (n = 26), or 0.06 mg/kg midazolam (n = 24). Level of sedation was assessed by using the Ramsay Sedation Scale before and 10 mins after medication. The proportions of patients with sedation level 4 or deeper after medication were 4.3%, 14.3%, 52.0%, and 90.9% in the placebo and the midazolam 0.015 mg/kg, 0.03 mg/kg, and 0.06 mg/kg groups, respectively. Safety was assessed by routine monitoring of body functions and monitoring for adverse events. Although midazolam dose-dependently reduced mean systolic arterial pressure, the changes in this variable were small; only one or two patients in each treatment group had decreases in systolic arterial pressure of >20%. No clear dose dependency was found for changes in other body functions measured in the intensive care unit. CONCLUSION: The proportion of patients who achieved a satisfactory level of sedation increased with an increasing dose of midazolam. Intravenous bolus injection of midazolam also dose-dependently reduced mean systolic arterial pressure. This study indicated that, balancing sedative efficacy and safety, from 0.03 to 0.06 mg/kg of midazolam provides relatively safe sedation in postoperative patients.