• Y U Adachi, K Watanabe, H Higuchi, and T Satoh.
• Department of Anesthesiology, National Defense Medical College, 3-2 Namiki Tokorozawa city, Saitama, 359-8513, Japan. grd1117@gr.ndmc.ac.jp
• J Clin Anesth. 2001 Jun 1;13(4):277-80.

Study ObjectiveTo evaluate the effect of a small dose of midazolam (10 microg kg(-1)) on induction and emergence during short-term propofol anesthesia and to investigate the effects of subsequent administration of flumazenil.DesignDouble-blinded, prospective, randomized study.SettingOperating room of a medical college hospital.Patients30 male ASA physical status I and II patients (ages 51 to 75) scheduled for minor surgery under spinal anesthesia.InterventionsPatients were randomly allocated to one of three groups: the placebo-propofol-placebo (PP) group, the midazolam-propofol-placebo (MP) group, or the midazolam-propofol-flumazenil (MF) group. After administering placebo or midazolam (10 microg kg(-1)), propofol 250 microg kg(-1) min(-1) was infused. Immediately after confirming that the patient was hypnotized, we terminated the propofol infusion and administered placebo or flumazenil (5 microg kg(-1)).MeasurementsThe dose and the times required to achieve hypnosis (the first endpoint) and to emerge from anesthesia (the second endpoint). The plasma concentration at each endpoint was determined.Main ResultsMidazolam significantly decreased the dose and time needed to achieve hypnosis [PP vs. MP, 66 +/- 14 vs. 48 +/- 15 mg, 260 +/- 55 vs. 179 +/- 44 sec, respectively (mean +/- SD)]. Thus, the plasma concentration of propofol at hypnosis was significantly lower (PP vs. MP, 3.31 +/- 0.78 vs. 2.41 +/- 0.57 microg mL(-1)). The time to emerge from anesthesia was not prolonged by midazolam, and was further shortened by administration of flumazenil (PP, MP vs. MF, 237 +/- 77, 207 +/- 71 s vs. 126 +/- 56 sec, respectively). Flumazenil also reversed the reduction in propofol concentration induced by midazolam at emergence (PP, MP, and MF, 0.54 +/- 0.17, 0.37 +/- 0.15, and 0.59 +/- 0.22 microg mL(-1), respectively).ConclusionsCoadministration of 10 microg kg(-1)midazolam decreases the dose and time required to achieve hypnosis with propofol induction without delaying emergence from anesthesia. Additional administration of flumazenil further shortens the time to emerge from midazolam-propofol anesthesia.

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