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Perils of Physostigmine

Classic Anticholinergic Toxidrome

  • Hot as Hades (hyperthermia)
  • Red as a beet (cutaneous flushing)
  • Blind as a bat (mydriasis and loss of accommodation)
  • Dry as a bone (reduced sweating and secretions)
  • Mad as a hen (delirium and hallucinations)

Does this describe a patient recently treated in your emergency room?! These symptoms outline anticholinergic poisoning, a possible result of many drugs and some plants.

Anticholinergic poisoning

The peripheral manifestations of the blockade of muscarinic receptors include dilated pupils, tachycardia, elevated blood pressure, hyperthermia, warm, flushed skin, dry axilla, dry oral membranes, urinary retention, and quiet bowel. Central manifestations include agitation, delirium, hallucinations, combativeness, seizures and coma. Severe poisoning can be fatal. Depending on the agent and dose ingested, the poisoning can last for days.

Physostigmine as an antidote

An antidote that quickly reverses severe anticholinergic symptoms would be very helpful, especially to rapidly calm a violently agitated patient. An antidote is available; physostigmine reversibly inactivates acetylcholinesterase, boosting the synaptic presence of acetylcholine, and overcoming the anticholinergic agent.

However, in 2007, US poison centers reported only 209 instances of antidotal physostigmine use. Why is it not routinely used for anticholinergic poisoning? Many physicians avoid its use because they fear severe complications, including seizures, ventricular arrhythmias, bradycardia, and asystole. However, the risk is higher in patients whose EKGs also show the widened QRS characteristic of sodium channel blockade. This combination of findings anticholinergic action and widened QRS is caused most often by overdose of tricyclic antidepressants. Physostigmine should be avoided in these patients.

Physostigmine’s utility is further limited by its short duration of action compared to the anticholinergic toxin. It may last as little as 15 minutes and anticholinergic symptoms return in full force. Repeated dosing is often necessary.

When can physostigmine be used?

Consider physostigmine for severe, life-threatening central or peripheral anticholinergic symptoms (seizures, distressing hallucinations, hypertension, arrhythmias) that are not responding to standard therapy.

In selected cases, physostigmine may also be considered as a diagnostic aid for patients with coma or delirium of unclear etiology. Rapid reversal of the symptoms suggests the ingestion of an anticholinergic agent. Symptom reversal is only temporary; physostigmine should not be used continuously just to keep a patient awake.

How is physostigmine administered?

If therapeutic use of physostigmine is necessary and the EKG is free of conduction delays, a low dose of physostigmine can be administered by slow IV push under continuous cardiac monitoring. A typical adult dose would be 2 mg of physostigmine infused no faster than 1 mg per minute. Infusion must be slow to reduce the risk of serious adverse effects (seizure, arrhythmia, asystole.)

Excessive dose beyond what is necessary to counteract anticholinergic effects can lead to the opposite problem symptoms of cholinergic excess. These include gastrointestinal distress, heavy secretions, bradycardia, and muscle fasciculations and weakness. Atropine should be available at the bedside in case the patient develops iatrogenic cholinergic poisoning.

When should physostigmine be avoided?

Physostigmine is contraindicated in patients who have ingested tricyclic antidepressants or other sodium channel blocking agents. It should be used with caution in any patient with unknown ingestions or those with cardiac conduction abnormalities.

What are anticholinergic sources?

  • Atropine
  • Antihistamines
  • Motion sickness drugs
  • Cyclic antidepressants
  • Antidiarrheals
  • Antispasmodics
  • Mydriatics (eye drops)
  • Antiperkinson drugs
  • Skeletal muscle relaxants
  • Jimsonweed
  • Deadly nigthtshade
  • Jerusalem cherry
  • Some mushrooms

For more specific information on possible anticholinergic toxicity and treatment, please contact the Missouri Poison Center at 1-800-222-1222. Healthcare professionals can also call 1-888-268-4195.

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