UMEM Educational Pearls

Title: Frequency of adverse effects after administration of physostigmine

Category: Toxicology

Keywords: physostigmine, anticholinergic toxicity, adverse effects (PubMed Search)

Posted: 2/14/2019 by Hong Kim, MD
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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.