Two-stage infusion of chlormethiazole for basal sedation.

The effectiveness of chlormethiazole in providing basal sedation was studied using a two-stage infusion regimen consisting of an initial loading dose of 60 mg min-1 for 25 min (in the lateral position) followed by a maintenance constant-rate infusion of 10 mg min-1 for 60 min (in the supine position). The regimen was evaluated in five healthy young volunteers who were all moderately sedated throughout most of the infusion, lapsing into sleep when left undisturbed, yet awakened easily to obey commands. Varying periods of amnesia, corresponding with a mean chlormethiazole ethanedisulphonate blood concentration of 10.3 mg litre-1 (SD 3.8) were obtained. Light sedation occurred during the first 10 min and the last 20 min of the total infusion period, corresponding to chlormethiazole blood concentrations of 7.9 mg litre-1 (SD 1.9) and 7.4 mg litre-1 (SD 2.3) respectively. Adverse side-effects were transient nasal irritation, flushing and a coryza-like syndrome. Other side-effects of tachycardia and hypertension may be beneficial in counteracting cardiovascular depression associated with central neural blockade. A high total body clearance of chlormethiazole (mean 1.39 litre min-1, SD 0.58) was found and would contribute to the brief duration of action after termination of the infusion.