Physostigmine is a cholinergic agent that can be administered to reverse delirium associated with anticholinergic toxicity. However, it is infrequenly used since the reports of cardiac arrest in patients with TCA overdose.

A recently published study reviewed 161 articles – involving 2299 patients – to determine the adverse effects and their frequency after the administration of physostigmine. 

Findings

Adverse effects were observed in 415 patients (18.1%)

• In patients with anticholinergic overdose: 7.7%
• In patients with non-anticholinergic agent overdose: 20.6%

Specific adverse effects

• Hypersalivation: 206 (9%) 
• Nausea/vomiting: 96 (4.2%)
• Seizure: 14 (0.61%)
• Symptomatic bradycardia: 8 (0.35%) – including 3 with bradyasystolic arrest
• Asymptomatic bradycardia: 4 (0.17%)
• Ventricular fibrillation: 1 (0.04%) patient had a history of coronary artery disease
• Cardiac arrest: 4 (0.17%)
• Death: 5 (0.22%)

Of 394 TCA overdose, adverse effects occurred in 14 patients (3.6%)

Conclusion

• Adverse effects from physostigmine occurs infrequently. 
• However, inappropriate dosing or use of physostigmine can result in cholinergic toxicity.
• For isolated anticholinergic toxicity (e.g. antihistamine overdose): physostigmine dosing: 0.5 mg (dilute in 5 – 10 mL normal saline) IV over 2 -5 minutes. May repeat every 5-10 minute to max dose total of 2 mg. (patient needs to be on cardiac monitor with atropine at bedside) 
• Therapeutic goal: reversal of delirium
• Avoid physostigmine in the presence of QRS widening (cardiac Na-channel blockade) and patients with history of underlying coronary artery disease.

References

Arens AM et al. Adverse effects of physostigmine. J Med Toxciol.  Feb 11. doi: 10.1007/s13181-019-00697-z. [Epub ahead of print] Review.