A 50 year old man presents with agitation and delirium.  He has sinus tachycardia to 120bpm but his vital signs are otherwise within normal ranges. He answers some questions, but is disoriented, illogical and rambling.  He is picking at “ants” crawling on his skin.  On physical exam you find bilaterally dilated pupils and his skin is warm, dry, and flushed.  The patient’s medical record describes a past history of abuse of doxylamine-containing cough medicines, and hydroxyzine is one of his current medications. The patient denies any recent intentional or unintentional overdoses. You begin a full AMS work up, but highly suspect this is an anticholinergic overdose.   Should you give physostigmine?

Physostigmine is a short-acting acetylcholinesterase inhibitor, which increases synaptic concentrations of acetylcholine and can overcome the postsynaptic receptor blockade produced by anticholinergic agents. It has activity in both the central and peripheral nervous system, and thus may effectively reverse the peripheral and central anticholinergic toxic syndromes.

Due to the relative rarity of anticholinergic causes of delirium, and the potential side effects of bradycardia, dysrythmia, convulsion and bronchospasm, physostigmine is not indicated in undifferentiated coma or delirium.

Using physostigmine diagnostically with the proper precautions is likely safe, and may avoid unecessary CT scans and LPs when anticholinergic delirium is highly probable. Physostigmine has been successfully given as a diagnostic tool without any significant complications in a small series of ED patients suspected of having anticholinergic delirium.

As a treatment for known anticholinergic delirium, physostigmine has been shown in a retrospective study to be more effective, with fewer complications and shorter hospital stays than treatment with benzodiazepines.

Physostigmine should be given in and initial IV infusion of 1-2mg over a minimum of 5 minutes, with faster infusions more likely to have cardiac side effects.  Improvement of anticholinergic symptoms including normalization of mental status should occur in minutes. Repeat doses of 0.5mg may be given every 10-15minutes until full reversal is achieved.  Though it has a half life of 16 minutes, the duration of action for physostigmine is significantly longer.  Additional repeat doses may be given if the patient has symptomatic relapse.

Patients should be placed on telemetry monitoring before administering physostigmine.  A pretreatment ECG is required.  Prolonged QRS (especially relevant in potential TCA overdose), prolonged QTc, bradycardia, and asthma or significant pulmonary disease should be considered contraindications to physostigmine.  Airway equipment and atropine should be available at the bedside when administering physostigmine given the potential risk of cholinergic toxicity.

 1)      Burns MJ, Linden CH, Graudins A, Brown RM, Fletcher KE.  A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning.. Ann Emerg Med. 2000 Apr;35(4):374-81.

 2)      Howland MA. Antidotes in Depth (A12): Physostigmine Salicylate. In: Hoffman RS, Nelson LS, Goldfrank LR, Howland MA, Lewin NA, Flomenbaum NE, eds. Goldfrank’s Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011.

 3)      Schneir AB, Offerman SR, Ly BT, Davis JM, Baldwin RT, Williams SR, Clark RF. Complications of diagnostic physostigmine administration to emergency department patients. Ann Emerg Med. 2003 Jul;42(1):14-9.