Physostigmine in coma due to drug overdose

Twelve patients with coma due to drug overdose were treated with physostigmine salicylate in a double-blind, placebo-controlled crossover trial. Three of the 9 patients who had taken drugs without anticholinergic action (methyprylon, barbiturates, ethchlorvynol, benzodiazepines) and 2 of 3 who had taken drugs with anticholinergic action (amitriptyline) showed dramatic decrease of depth of coma after physostigmine. Among patients with non-anticholinergic overdose, in 10 min physostigmine induced an increase in mean arterial pressure from a mean of 80.3 mm Hg to 103.8 mm Hg (p < 0.05) and in heart rate from a mean of 87.9 beats/min to 98.3 beats/min (p < 0.001). When given to patients with anticholinergic drug intoxication, physostigmine induced a fall in mean arterial pressure from a mean of 105.4 mm Hg to 96.1 mm Hg (p < 0.01) and in heart rate from a mean of 104 beats/min to 91.3 beats/min (p < 0.10). Physostigmine induced dilation of pupils in all patients with non-anticholinergic overdose and in none with anticholinergic overdose (p < 0.01). The effects of physostigmine in non-anticholinergic overdose appear to be due to a nonspecific action on the central nervous system. Physostigmine may also be of value in the differential diagnosis of coma. Its routine use in the treatment of drug-induced coma is not recommended except in anticholinergic drug overdose unless standard measures fail and artificial mechanical ventilation cannot be provided to patients with severe drug-induced respiratory depression.