Midazolam as an intravenous induction agent in the elderly: a clinical and pharmacokinetic study

Midazolam, the first benzodiazepine derivative with water-soluble salts, was studied as an induction agent in general anesthesia for the elderly. In group 1 (n = 14), 5 or 10 mg oral diazepam was used as premedication, but in group 2 (n = 9), both oral (10 mg dixyrazin as a night-time sedative) and intramuscular (0.01 mg/kg atropine + 1 mg/kg meperidine) premedicants were used. Serum concentrations of benzodiazepines were determined using both gas-liquid chromatographic (unchanged midazolam) and radioreceptor assays (binding equivalents of benzodiazepines plus their active metabolites). In general, midazolam, 0.15 mg/kg, intravenously resulted in smooth induction of anesthesia, although the time required for induction was rather long and a sudden but transient decrease in blood pressure was found in a significant number of patients. The course of anesthesia was otherwise satisfactory. A marked amnesic effect was observed, especially when diazepam was used as premedication. The pharmacokinetic parameters based on gas-liquid chromatographic measurements were quite comparable with those in young, healthy persons published earlier. In both groups, the binding equivalents measured with radioreceptor assay (reflecting total benzodiazepine activity) were higher than the levels of unchanged midazolam determined with gas-liquid chromatography. The relatively low dose of 0.15 mg/kg of midazolam needed for anesthetic induction in the elderly indicates not pharmacokinetic, but pharmacodynamic, alterations in older patients. We conclude that midazolam is a new intravenous induction agent for use in the elderly, but careful titration of the dosage according to the response of the patient is required. Diazepam premedication prior to midazolam causes a marked anterograde amnesic effect.