Physostigmine fails to reverse clinical, psychomotor, or EEG effects of lorazepam

Physostigmine salicylate (2.0 mg) or 0.9% NaCl (2.0 ml) was administered intravenously in a double-blind fashion to adult volunteers in an attempt to reverse the effects of a 0.05-mg/kg dose of lorazepam given intravenously 30 min earlier. No other medication affecting the central nervous system was given. No differences were observed between the two groups with regard to the frequency of amnesia, psychomotor impairment, or EEG changes during a period of 4 h. The only significant difference in the level of sedation between the two groups was observed 60 min into the study. This difference is attributed to the high incidence of nausea and vomiting that occurred at that time exclusively in one group. Time to complete recovery was the same in both groups. However, physostigmine, not saline, was associated with a high incidence of muscarinic and sympathetic stimulating effects. The results obtained indicate that at the dose used, physostigmine is of no clinical value in treating sedation induced by lorazepam.