Yes, Does Atropine Toxicity Cause Fever? Understanding the Anticholinergic Mechanism

October 11, 2025 •

4 min read

In cases of overdose, atropine toxicity is well-documented to cause a significant rise in body temperature, a condition often referred to as 'atropine fever'. This potentially dangerous side effect confirms that, yes, atropine toxicity causes fever, primarily by inhibiting the body's natural cooling process.

Quick Summary

Atropine toxicity causes hyperthermia (fever) by blocking sweat gland function, impairing the body's ability to regulate temperature. This is a key feature of the anticholinergic toxidrome, which also includes dry skin, dilated pupils, and altered mental status. Children are particularly susceptible to this effect.

Key Points

Inhibition of Sweating: Atropine toxicity causes fever by inhibiting the sweat glands, which prevents the body from cooling itself effectively.
Anticholinergic Toxidrome: The resulting hyperthermia is a key feature of the anticholinergic toxidrome, along with dry skin, dilated pupils, and altered mental status.
High-Risk Groups: Infants and small children are more susceptible to atropine-induced fever due to their less-developed thermoregulatory systems.
Treatment Approach: The treatment for atropine fever involves supportive care and external cooling measures, as antipyretics are ineffective.
Antidote Use: In cases of severe CNS toxicity, physostigmine, a cholinesterase inhibitor, may be used to reverse the central effects of atropine.
Dose-Dependent Effect: The severity of the fever and other symptoms of atropine toxicity is generally dose-dependent.

The Anticholinergic Toxidrome: 'Hot as a Hare'

Atropine is a potent anticholinergic agent, meaning it blocks the action of the neurotransmitter acetylcholine at muscarinic receptors. When toxic levels of atropine accumulate in the body, they produce a characteristic set of signs and symptoms known as the anticholinergic toxidrome. A common mnemonic for remembering these symptoms is "red as a beet, dry as a bone, blind as a bat, mad as a hatter, and hot as a hare". The "hot as a hare" component directly refers to the fever, or hyperthermia, that results from atropine toxicity.

This fever can range from a mild temperature elevation to a dangerously high body temperature, or hyperpyrexia, especially in infants and small children. The mechanism is a direct result of atropine's primary pharmacological action. While atropine is used therapeutically to reduce salivary, bronchial, and other secretions, an overdose extends this effect to block sweating across the entire body.

The Mechanism of Atropine-Induced Hyperthermia

The human body primarily regulates its temperature through sweating. When core body temperature rises, the central nervous system stimulates sweat glands to produce sweat, which cools the body as it evaporates. The nerve fibers that innervate sweat glands are sympathetic but use acetylcholine as their neurotransmitter, making them sensitive to anticholinergic drugs like atropine.

In a case of atropine toxicity:

Acetylcholine blockade: High levels of atropine competitively block muscarinic receptors on sweat glands, preventing the glands from receiving the signal to sweat.
Anhidrosis: This leads to a complete or near-complete cessation of sweating, a condition known as anhidrosis.
Impaired thermoregulation: With the body's primary cooling mechanism disabled, heat cannot be dissipated effectively.
Hyperthermia: This heat retention causes the core body temperature to rise, resulting in the characteristic fever of anticholinergic poisoning.

The risk of developing significant hyperthermia is especially high in warm environments or during physical exercise, as these conditions naturally increase the demand for thermoregulation through sweating. Infants and young children are particularly vulnerable because they have less-developed thermoregulatory systems and a higher body surface area to mass ratio.

Signs and Symptoms of Anticholinergic Toxicity

While fever is a hallmark of atropine toxicity, it typically occurs alongside a constellation of other signs. These can vary in severity depending on the dose.

Peripheral effects:
- Skin: Flushed, hot, and dry skin due to anhidrosis and vasodilation, especially in the "blush" area.
- Eyes: Markedly dilated pupils (mydriasis) that are poorly responsive to light, and blurred vision due to the paralysis of accommodation.
- Mouth: Extreme dryness of the mouth and mucous membranes.
- Cardiovascular: A rapid heartbeat (tachycardia).
- Gastrointestinal: Decreased bowel sounds and constipation.
- Urinary: Urinary retention.
Central nervous system effects (CNS):
- Mental status: Restlessness, irritability, disorientation, confusion, delirium, and hallucinations.
- Movement: Weakness, giddiness, and muscular incoordination.
- Severe cases: Can progress to seizures, respiratory depression, coma, and circulatory collapse.

Comparison of Atropine-Induced Fever and Infectious Fever


Feature	Atropine-Induced Fever	Infectious Fever
Cause	Inhibition of sweat glands (anticholinergic effect)	Pyrogens released by infectious agents, causing a change in the hypothalamic set point
Associated Symptoms	Flushed, hot, DRY skin; dilated pupils; altered mental status; tachycardia; urinary retention	Potentially diaphoretic (sweating); other signs of infection (e.g., cough, chills)
Onset	Can be rapid, particularly after overdose	Generally more gradual, though can be acute in some conditions
Response to Antipyretics	Poor response, as the underlying mechanism is not addressed	Often responsive to antipyretics like acetaminophen or NSAIDs
Treatment Focus	Cooling measures and supportive care; physostigmine for CNS effects	Treating the underlying infection with antibiotics or antivirals; fever reduction is secondary

Treatment and Management

Management of atropine toxicity requires prompt recognition of the anticholinergic toxidrome. Since fever is a primary concern, especially in vulnerable populations, cooling is a critical intervention.

Supportive Care: The patient's airways, breathing, and circulation (ABCs) must be stabilized. Continuous monitoring of vital signs is essential.
External Cooling: Physical cooling methods are employed to reduce the patient's body temperature. These include applying ice bags, using hypothermia blankets, or alcohol sponges. Unlike fever from infection, antipyretics are not effective because they do not address the root cause of the heat retention.
Antidotal Therapy: For severe anticholinergic syndrome, particularly with significant central nervous system (CNS) effects like agitated delirium, the cholinesterase inhibitor physostigmine can be administered. Physostigmine increases acetylcholine levels, helping to reverse both CNS and peripheral anticholinergic effects, but it must be used with caution and careful monitoring.
Other measures: Catheterization may be necessary for urinary retention. Benzodiazepines can be used to control severe excitement and convulsions, but CNS depressants should be used carefully.

Conclusion

In summary, does atropine toxicity cause fever? The answer is an unequivocal yes. Through its anticholinergic action, atropine blocks the body's ability to sweat, leading to heat retention and potentially dangerous hyperthermia. This is a crucial component of the anticholinergic toxidrome, easily remembered by the mnemonic "hot as a hare." Recognition of this symptom, along with other classic signs like dry skin, dilated pupils, and confusion, is critical for prompt diagnosis and effective treatment. Management focuses on supportive care, external cooling, and in severe cases, the use of the antidote physostigmine. For more in-depth medical information on atropine overdose and its management, a resource like the National Institutes of Health (NIH) is recommended(https://www.rxlist.com/atropen-drug.htm).

Frequently Asked Questions

Atropine is an anticholinergic drug that blocks the muscarinic receptors on sweat glands. This inhibition prevents the glands from producing sweat, which is the body's main mechanism for heat dissipation. The resulting heat retention causes the body temperature to rise, leading to fever.

Yes, infants and small children are more susceptible to atropine-induced hyperthermia. This is because their thermoregulatory systems are not fully developed, and they have a higher body surface area-to-mass ratio, making them less efficient at regulating temperature.

The classic mnemonic for anticholinergic toxicity is 'hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter.' Each phrase corresponds to a specific set of symptoms, with 'hot as a hare' referencing the fever.

Treatment involves supportive care, such as ensuring the patient's airway is clear, and aggressive external cooling measures. This can include ice packs, hypothermia blankets, and alcohol sponges. Antipyretic medications are not effective because they do not address the cause of the heat retention.

Yes, even ophthalmic atropine (eye drops) can be absorbed systemically and cause toxicity, including fever, particularly if high doses are used or if administered to children. The medication can enter the bloodstream through the conjunctiva and the lacrimal drainage system.

Physostigmine is an antidote that can be used to treat severe central nervous system (CNS) effects, such as delirium and coma, caused by atropine toxicity. It works by inhibiting acetylcholinesterase, thereby increasing acetylcholine levels to counteract the atropine overdose.

No, atropine fever is not caused by an infection. The fever is a direct result of the drug's pharmacological effect on sweat glands. This is a critical distinction for medical professionals, as misdiagnosing it as an infectious fever would lead to inappropriate treatment.

Besides fever, atropine toxicity can cause flushed, warm, dry skin. This is due to both vasodilation in the skin (especially the face) and the complete lack of sweating.