Diazepam tolerance: effect of age, regular sedation, and alcohol.

doi:10.1136/bmj.289.6441.351

Br Med J (Clin Res Ed) 1984;289:351-353 (11 August), doi:10.1136/bmj.289.6441.351

Diazepam tolerance: effect of age, regular sedation, and alcohol.

P J Cook, R Flanagan, I M James

The dose of intravenous diazepam required for sedation was estimatedin a series of 78 patients aged 17-85 years given the drug fordental and endoscopic procedures. Multiple regression analysisshowed a significant correlation (r = 0.71; p less than 0.001)between dose and age, body weight, the taking of regular sedation,and the taking of more than 40 g alcohol daily, but there wereno differences in the doses required between men and women,smokers and non-smokers, inpatients and outpatients, or dentaland endoscopy patients. Patients aged 80 required an averagedose of 10 mg and patients aged 20 an average dose of 30 mg,and the dose required was much higher in those receiving regularsedation or having a high alcohol intake. Plasma total and freediazepam concentrations were measured in the second half ofthe series of patients (n = 37). Plasma concentrations requiredfor sedation fell twofold to threefold between the ages of 20and 80 and were significantly higher in those taking regularsedation or alcohol. Differences in the acute response to diazepamappeared to be due to differences in the sensitivity of thecentral nervous system (pharmacodynamic tolerance) rather thanto differences in pharmacokinetic factors.

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