The Link Between Anticholinergic Toxicity and Fever
Yes, anticholinergic toxicity can cause fever, a condition specifically referred to as hyperthermia in this clinical context. The mechanism behind this elevated body temperature is a direct result of anticholinergic agents blocking the action of acetylcholine, a key neurotransmitter. This blockage occurs at peripheral muscarinic receptors, particularly those controlling the sweat glands. Without proper nerve stimulation, the body's ability to sweat is significantly impaired, leading to a crucial loss of evaporative cooling.
Simultaneously, the central nervous system (CNS) can be affected, leading to altered mental states, agitation, and increased motor activity. This increased physical activity generates more body heat, further contributing to the hyperthermia. Compounding these issues is the potential for central temperature dysregulation, where the brain's ability to manage its own temperature is compromised. The combination of blocked heat loss, increased heat production, and central temperature control issues creates the dangerous hyperthermic state.
Other Defining Symptoms of Anticholinergic Toxicity
Fever is just one part of the wider clinical picture known as the anticholinergic toxidrome. A classic mnemonic is often used to remember the constellation of symptoms:
- Dry as a bone: Extremely dry skin and mucous membranes due to decreased glandular secretions, including sweat and saliva.
- Red as a beet: A flushed, red complexion caused by peripheral vasodilation, a compensatory mechanism to shed heat that is ultimately ineffective due to the inability to sweat.
- Blind as a bat: Significantly blurred vision and dilated pupils (mydriasis) that do not react to light, impairing the eyes' ability to focus.
- Mad as a hatter: Altered mental status, which can range from confusion and disorientation to agitation, paranoia, hallucinations, and frank delirium.
- Hot as a hare: Elevated body temperature, or hyperthermia, as discussed above.
- Full as a flask: Urinary retention resulting from the decreased muscle tone of the urinary bladder.
Other symptoms include a rapid heartbeat (tachycardia) and decreased or absent bowel sounds due to reduced gastrointestinal motility.
Common Causes of Anticholinergic Toxicity
Anticholinergic toxicity can arise from a wide variety of sources, including many common over-the-counter and prescription medications. Awareness of these agents is crucial for prevention and diagnosis.
High-Risk Medications
- Antihistamines: First-generation antihistamines like diphenhydramine (Benadryl) and doxylamine are potent anticholinergics and are frequent culprits, especially in overdoses.
- Tricyclic Antidepressants (TCAs): Older antidepressants such as amitriptyline and doxepin have significant anticholinergic effects.
- Antipsychotics: Certain antipsychotic drugs, including chlorpromazine and clozapine, can block muscarinic receptors.
- Anti-Parkinson's Agents: Medications used to treat Parkinson's disease, like benztropine and trihexyphenidyl, are specifically designed for their anticholinergic properties.
- Muscle Relaxants: Drugs such as cyclobenzaprine and orphenadrine have anticholinergic activity.
- Antispasmodics: Medications like dicyclomine, used for gastrointestinal issues, also contribute.
Other Sources
Beyond pharmaceuticals, anticholinergic toxicity can result from the ingestion of certain plants, including Jimson weed (Datura stramonium) and Deadly Nightshade (Atropa belladonna). Accidental poisoning in children, intentional overdose, or drug-drug interactions, particularly in older patients on multiple medications, can all lead to toxicity.
Differentiating Anticholinergic Toxicity from Other Conditions
Because hyperthermia and altered mental status can be caused by other conditions, differentiating anticholinergic toxicity from similar syndromes is critical for proper treatment. Below is a comparison table contrasting anticholinergic toxicity with sympathomimetic toxicity, another common drug-induced syndrome.
| Feature | Anticholinergic Toxicity (Hot as a Hare) | Sympathomimetic Toxicity (Cocaine, Amphetamines) |
|---|---|---|
| Sweating | Absent (anhidrosis) | Present (diaphoresis) |
| Skin | Hot, red, and dry | Hot, red, and moist |
| Mental State | Delirium, agitation, hallucinations | Agitation, paranoia, anxiety |
| Bowel Sounds | Decreased or absent | Hyperactive |
| Pupils | Dilated (mydriasis) | Dilated (mydriasis) |
| Urinary Retention | Common | Uncommon; may have urgency |
Treatment and Management of Anticholinergic Toxicity
Prompt medical care is essential when anticholinergic toxicity is suspected. Treatment primarily involves supportive care to manage symptoms and stabilize the patient.
- Airway, Breathing, and Circulation (ABCs): Ensuring the patient's vital functions are stable is the first priority.
- External Cooling: For hyperthermia, physical cooling measures are implemented, such as cool water mists, fans, or cooling blankets.
- Sedation: Benzodiazepines are typically used to manage agitation and increased motor activity, which can help reduce heat production.
- Activated Charcoal: In cases of recent ingestion, activated charcoal may be administered to prevent further absorption of the drug.
- Physostigmine: In severe cases, particularly with significant central nervous system effects, physostigmine—an acetylcholinesterase inhibitor—can be used as an antidote. This medication increases the level of acetylcholine to counteract the anticholinergic effects, but its use requires careful consideration and monitoring due to potential side effects. A key contraindication for physostigmine is a widened QRS complex on an electrocardiogram (ECG), which can occur with certain drug overdoses. The Utah Poison Control Center provides excellent guidance on managing such cases with physostigmine or its alternative, rivastigmine.
Conclusion
Fever is not just a coincidental symptom but a dangerous and classic sign of anticholinergic toxicity, driven by the body's impaired ability to cool itself. Caused by a wide range of common medications and plants, this condition can lead to a severe and life-threatening toxidrome involving altered mental status, dry skin, and dilated pupils. Prompt recognition and intervention are critical, differentiating it from other drug-induced syndromes like sympathomimetic toxicity, which presents with sweating. Treatment focuses on supportive measures and, in severe cases, may involve specific antidotes under careful medical supervision. If you suspect anticholinergic toxicity, seek immediate emergency medical care.
