Reversal of postoperative somnolence using a two-rate infusion of physostigmine.

Abstract

In order to antagonize immediate postoperative somnolence, 24 surgical patients were given a two-rate infusion of physostigmine, aiming at a constant plasma concentration in the range of 1 to 10 ng/ml. Plasma concentrations of physostigmine were determined during infusion and after infusion and the effects of physostigmine on analgesia and postoperative sedation, and its side effects were monitored throughout. On the 1st postoperative day some of the patients (n = 8) were given 5 mg physostigmine orally, after which plasma concentrations as well as effects were measured. Steady-state concentrations were generally lower than predicted. Clearance varied between 10 and 85 ml/min x kg with a mean of 40.8 +/- 21.0 ml/min x kg. Oral bioavailability was 25.3 +/- 11.1%. Physostigmine administered as an intravenous infusion antagonized immediate postoperative somnolence in 21 out of 24 patients. Effects were poorly correlated with the established steady-state concentration of physostigmine. The patients' experience of postoperative pain relief was mostly satisfactory and the side effects of physostigmine infusion were generally limited. The effects of physostigmine in the immediate postoperative period seemed dependent on the dose as well as on the time which had elapsed since administration of anticholinergic drugs. After oral physostigmine administration the following morning, the majority of patients experienced side effects such as nausea and abdominal pain. In conclusion, physostigmine given as infusion antagonizes postoperative somnolence. However, the arousal effect was considered not better than that resulting from a bolus dose of the drug, although the infusion regimen allowed a prolonged clinical effect duration.