Midazolam as an Intravenous Induction Agent in the Elderly

Abstract

HOVI-WANDER M. Midazolam as an intravenous induction agent in the elderly: a clinical and pharmacokinetic study. Anesth Analg 1986;65:15-20.Midazolam, the first benzodiazepine derivative with watersoluble 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 f n = 9), both oral (10 mgdixyrazin asa night-timesedative) and intramuscular (0.01 mglkg atropine + 1 mglkg meperidine) premedicants were used. Serum concentrations of benzodiazepines were determined using both gas-liquid chromatographic (unchanged rnidazolam) and radioreceptor assays (binding equivalents of benzodiazepines plus their active metabolites). In general, midazolam, 0.15 mglkg, 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 midazolani determined with gas-liquid chromatography. The relatively low dose of 0.15 mglkg of midazolam needed for anesthetic iizduction in the elderly indicates not pharmacokinetic, but pharrnacodynamic, 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 midazolain causes a marked anterograde amnesic effect.

Recovery of postural stability following conscious sedation with midazolam in the elderly

“…It is well appreciated that aging increases the sensitivity to the sedative effects of midazolam and prolongs the duration of its action [1][2][3][4][5][6]. The increasing pharmacodynamic sensitivity due to aging has been explained by EEG data [1], the dose for disappearance of reaction to verbal commands [2], and psychometric tests [3].…”

“…The increasing pharmacodynamic sensitivity due to aging has been explained by EEG data [1], the dose for disappearance of reaction to verbal commands [2], and psychometric tests [3]. For pharmacokinetic factors, the elimination half-life was significantly prolonged and total clearance was significantly reduced [4,5], whereas no significant differences were seen in the distribution phase half-life and volume of distribution between younger and elderly patients [2,6]. In the present study, similar sedation levels were obtained in the elderly with 62% of the midazolam dosage needed for younger patients, probably because of pharmacodynamic effects.…”

“…The pharmacodynamics and pharmacokinetics of benzodiazepine in the elderly have been reported to differ from those in younger individuals [1][2][3][4][5][6]. Accordingly, excessive sedation and delayed recovery from conscious sedation can occur in the elderly.…”

Farmakokinetyczne interakcje międzylekowe w oddziale intensywnej terapii – obserwacje jednoośrodkowe i przegląd piśmiennictwa

“…Antagonism most likely involves inhibition competitive to adenosine bonds in the central nervous system (CNS) [24]. This interaction is of poor clinical relevance; however, some cases of reversal of diazepam-induced sedation following the administration of aminophylline [25], as well as the abolition of the effects of midazolam after the administration of theophylline have been reported [26].…”

Pharmacokinetic‐EEG effect relationship of midazolam in aging BN/BiRij rats

“…Also in the treatment of sleep disorders in the elderly, midazolam was reported to be effective and well-tolerated, provided that it is given in a carefully titrated, appropriate dose (Lachnit et al, 1983). Several authors emphasized the importance of titrating the dose, since dose requirement for midazolam is reduced in elderly patients (Kanto et al, 1986;Bell et al, 1987;Oldenhof et al, 1988). In a study in 800 patients in which the dose of intravenous midazolam required to produce adequate sedation prior to upper gastro-intestinal endoscopy was measured, an important decrease of approximately 75% in dose requirement from the age of 15 years to the age of 85 years was observed (Bell et al, 1987).…”