A small dose of midazolam decreases the time to achieve hypnosis without delaying emergence during short-term propofol anesthesia.
OBJECTIVE
To 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.


METHODS
Double-blinded, prospective, randomized study.


METHODS
Operating room of a medical college hospital.


METHODS
30 male ASA physical status I and II patients (ages 51 to 75) scheduled for minor surgery under spinal anesthesia.


METHODS
Patients 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)).


METHODS
The 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.


RESULTS
Midazolam 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).


CONCLUSIONS
Coadministration 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.
Adachi
Y U
YU
Department of Anesthesiology, National Defense Medical College, 3-2 Namiki Tokorozawa city, Saitama, 359-8513, Japan. grd1117@gr.ndmc.ac.jp
Watanabe
K
K
Higuchi
H
H
Satoh
T
T
D000759:Adjuvants, Anesthesia / Q000008:administration & dosage; D000368:Aged; D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005442:Flumazenil; D018757:GABA Modulators; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008874:Midazolam / Q000008:administration & dosage; D008875:Middle Aged; D015742:Propofol; D011446:Prospective Studies
D000759:Adjuvants, Anesthesia; D018686:Anesthetics, Intravenous; D018757:GABA Modulators; D005442:Flumazenil; D008874:Midazolam; D015742:Propofol