The Effect of Physostigmine on Diazepam-induced Ventilatory Depression

Abstract

A double-blind crossover study was conducted to determine the effects of physostigmine salicylate on hyperoxic ventilatory response to CO2 (.ovrhdot.VE RCO2) and on awareness in healthy subjects previously sedated with diazepam. Diazepam 0.4 mg/kg i.v. decreased the slope of .ovrhdot.VE RCO2 from 2.41 .+-. 0.19-1.30 .+-. 0.15 l .cntdot. min-1 .cntdot. mmHg-1 (.hivin.x .+-. SEM, P < 0.001). Subsequent injection of physostigmine 2.0 mg i.v. was associated with a 0.20 .+-. 0.28 l .cntdot. min-1 .cntdot. mmHg-1 decrease in slope; this was significantly different from the 0.56 .+-. 0.22 l .cntdot. min-1 .cntdot. mmHg-1 increase in slope associated with saline placebo (P < 0.05). Level of consciousness increased more after physostigmine than after saline (P < 0.01). Despite an apparent increase in awareness resulting from physostigmine administration, the accompanying decrease in ventilatory drive may contraindicate its use in patients who previously have received diazepam.