The effect of physostigmine on diazepam-induced ventilatory depression: a double-blind study

The authors conducted a double-blind crossover study to determine the effects of physostigmine salicylate on hyperoxic ventilatory response to carbon dioxide (VE RCO2) and on awareness in healthy subjects previously sedated with diazepam. Diazepam 0.4 mg/kg iv decreased the slope of VE RCO2 from 2.41 +/- 0.19 to 1.30 +/- 0.15 1 . min-1 . mmHg-1 (mean +/- SEM, P less than 0.001). Subsequent injection of physostigmine 2.0 mg iv was associated with a 0.20 +/- 0.28 1 . min-1 . mmHg-1 decrease in slope; this was significantly different from the 0.56 +/- 0.22 1 . min-1 . mmHg-1 increase in slope associated with saline placebo (P less than 0.05). Level of consciousness, on the other hand, increased more after physostigmine than after saline (P less than 0.01). The authors conclude that 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.