From the Guidelines
The anticholinergic toxidrome is a potentially life-threatening condition that requires immediate supportive care, including treatment of agitation with benzodiazepines, management of hyperthermia, and consideration of physostigmine as a specific antidote in severe cases with significant central nervous system effects. The condition is caused by excessive blockade of muscarinic acetylcholine receptors, resulting in a constellation of symptoms summarized by the phrase "hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter" 1. Common causes include antihistamines, tricyclic antidepressants, antipsychotics, antiparkinsonians, and plants like jimsonweed. Patients typically present with:
- Hyperthermia
- Flushed skin
- Mydriasis (dilated pupils)
- Decreased bowel sounds
- Urinary retention
- Tachycardia
- Hypertension
- Altered mental status ranging from agitation to delirium and hallucinations
Management of anticholinergic toxidrome involves:
- Supportive care
- Activated charcoal for recent ingestions
- Physostigmine (1-2 mg IV slowly) as a specific antidote in severe cases with significant central nervous system effects, although it should be avoided in patients with cardiac conduction abnormalities or suspected tricyclic antidepressant overdose due to risk of asystole 1.
- Benzodiazepines may be used for agitation and seizures
- Cooling measures should be implemented for hyperthermia. The toxidrome occurs because anticholinergic agents block the neurotransmitter acetylcholine from binding to muscarinic receptors, disrupting parasympathetic nervous system function and causing sympathetic predominance 1.
From the FDA Drug Label
Physostigmine Salicylate Injection can reverse both central and peripheral anticholinergia. The anticholinergic syndrome has both central and peripheral signs and symptoms. Central toxic effects include anxiety, delirium, disorientation, hallucinations, hyperactivity and seizures. Severe poisoning may produce coma, medullary paralysis and death Peripheral toxicity is characterized by tachycardia, hyperpyrexia, mydriasis, vasodilation, urinary retention, diminution of gastrointestinal motility, decrease of secretion in salivary and sweat glands, and loss of secretions in the pharynx, bronchi, and nasal passages Dramatic reversal of the effects of anticholinergic symptoms can be expected in minutes after the intravenous administration of Physostigmine Salicylate Injection, if the diagnosis is correct and the patient has not suffered anoxia or other insult.
The drug Physostigmine Salicylate Injection can be used to treat anticholinergic toxidrome by reversing both central and peripheral anticholinergia. The anticholinergic syndrome is characterized by:
- Central toxic effects:
- Anxiety
- Delirium
- Disorientation
- Hallucinations
- Hyperactivity
- Seizures
- Peripheral toxicity:
- Tachycardia
- Hyperpyrexia
- Mydriasis
- Vasodilation
- Urinary retention
- Diminution of gastrointestinal motility
- Decrease of secretion in salivary and sweat glands
- Loss of secretions in the pharynx, bronchi, and nasal passages Reversal of anticholinergic symptoms can be expected in minutes after administration of Physostigmine Salicylate Injection 2.
From the Research
Anticholinergic Toxidrome Characteristics
- The anticholinergic toxidrome is characterized by both central and peripheral physical findings, including central anticholinergic syndrome and peripheral anticholinergia 3
- Central anticholinergic syndrome is characterized primarily by signs and symptoms consistent with hyperactive delirium 3
- Peripheral anticholinergia includes mydriasis and blurred vision, tremors, ataxia, fever/hyperthermia, flushed and dry skin, dry oral mucosa, decreased bowel sounds, constipation, and urinary retention, among other symptoms 3
Treatment of Anticholinergic Toxidrome
- Physostigmine is a tertiary acetylcholinesterase inhibitor that can be used to assist in the diagnosis and management of severe anticholinergic toxicity 3
- Physostigmine has been shown to be relatively safe and effective in reversing anticholinergic toxidrome 4
- Rivastigmine, a long-acting acetylcholinesterase inhibitor, is a potential alternative to physostigmine for the treatment of anticholinergic toxicity 5
- Benzodiazepines are also commonly used in the treatment of anticholinergic toxicity, particularly for patients with agitation or delirium 4, 6
Causes of Anticholinergic Toxidrome
- Anticholinergic toxidrome can be caused by a variety of substances, including medications, herbs, and plants 3, 6
- Thorn apple seeds have been identified as a cause of anticholinergic toxidrome in at least one case report 6
- Olanzapine overdose can also lead to the development of anticholinergic toxicity 3
Diagnosis and Management
- Prompt recognition of anticholinergic toxidrome is crucial for effective management and improved patient outcomes 6
- Physostigmine can be used to diagnose and treat anticholinergic toxicity, particularly in patients with severe symptoms or those who do not respond to benzodiazepines 4, 6
- It is essential to consider alternative causes of symptoms that may mimic anticholinergic toxidrome, such as viral encephalitis 7