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Hyperthermia may be associated with poisoning by amphetamines and other synthetic stimulants (cathinones, piperazines), atropine and other anticholinergic drugs, cocaine, salicylates, strychnine, 2,4-dinitrophenol, tricyclic antidepressants, and various other medications. Overdoses of serotonin reuptake inhibitors (eg, fluoxetine, paroxetine, sertraline) or their use in a patient taking an MAO inhibitor may cause agitation, hyperactivity, myoclonus, and hyperthermia (“serotonin syndrome”). Antipsychotic agents can cause rigidity and hyperthermia (neuroleptic malignant syndrome [NMS]). (See section on schizophrenia and other psychotic disorders in Chapter 25.) Malignant hyperthermia is a rare disorder associated with general anesthetic agents.

Hyperthermia is a rapidly life-threatening complication. Severe hyperthermia (temperature higher than 40–41°C) can rapidly cause brain damage and multiorgan failure, including rhabdomyolysis, acute kidney injury, and coagulopathy (see Chapter 37).


Treat hyperthermia aggressively by removing the patient’s clothing, spraying the skin with tepid water, and high-volume fanning. Alternatively, the patient can be placed in an ice water bath (not simply applying ice to selected surfaces). If external cooling is not rapidly effective, as shown by a normal rectal temperature within 30–40 minutes, or if there is significant muscle rigidity or hyperactivity, induce neuromuscular paralysis with a nondepolarizing neuromuscular blocker (eg, rocuronium, vecuronium). Once paralyzed, the patient must be intubated and mechanically ventilated and sedated. While the patient is paralyzed, the absence of visible muscular convulsive movements may give the false impression that brain seizure activity has ceased; bedside electroencephalography may be useful in recognizing continued nonconvulsive seizures.

Dantrolene (2–5 mg/kg intravenously) may be effective for hyperthermia associated with muscle rigidity that does not respond to neuromuscular blockade (ie, malignant hyperthermia). Bromocriptine, 2.5–7.5 mg orally daily, has been recommended for neuroleptic malignant syndrome. Cyproheptadine, 4 mg orally every hour for three or four doses, or chlorpromazine, 25 mg intravenously or 50 mg intramuscularly, has been used to treat serotonin syndrome.

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Van Schoor  J  et al. Dantrolene is not the answer to 2,4-dinitrophenol poisoning: more heated debate. BMJ Case Rep. 2018 Dec 19;11(1):e225323.
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