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• W2912793993 abstract "Drugs can cause dysregulation of the hypothalamic–pituitary–adrenal axis which can result in a rise in core temperature. This type of hyperthermia is unresponsive to antipyretics and can be complicated by rhabdomyolysis, multi-organ failure and disseminated intravascular coagulationOrganic causes of fever such as infection must be ruled out. Syndromes associated with drug-induced fever include neuroleptic malignant syndrome and anticholinergic, sympathomimetic and serotonin toxicityThe class of offending drugs, as well as the temporal relationship to starting or stopping them, assists in differentiating between neuroleptic malignant syndrome and serotonin toxicityImmediate inpatient management is needed. The mainstay of management is stopping the drug, and supportive care often in the intensive care unitKeywords: fever, hyperthermia, muscle rigidity, rhabdomyolysisIntroductionDrugs that alter the neurotransmitters noradrenaline (norepinephrine), dopamine and serotonin can affect thermoregulation by the hypothalamic–pituitary– adrenal axis.1,2 In drug-induced hyperthermia the core temperature is at least 38.3 °C.3 Hyperthermia can be complicated by peripheral factors such as increased heat production (e.g. with 3,4-methylenedioxymethamphetamine (MDMA/ ecstasy) and other sympathomimetics) and decreased heat loss (e.g. with anticholinergic drugs). Excessive heat production can result in life-threatening complications such as rhabdomyolysis and secondary hyperkalaemia, metabolic acidosis, multi-organ failure and disseminated intravascular coagulation.1The most commonly used drugs that affect thermoregulation include antipsychotic drugs, serotonergic drugs (especially when taken in combination), sympathomimetic drugs, anaesthetics and drugs with anticholinergic properties (Table 1).Table 1Drugs commonly known to cause hyperthermia and associated muscle rigidityDrug-induced syndromeAssociated drugsNeuroleptic malignant syndromeAntipsychotics (haloperidol, olanzapine), some antiemetics (metoclopramide), withdrawal of antiparkinson drugsSerotonin toxicitySerotonin reuptake inhibitors, monoamine oxidase inhibitors, dextrometorphan, tramadol, tapentadol, linezolid, St John’s wort (toxicity most often occurs when the drugs are used in combination)Anticholinergic toxicityAntispasmodics, anticholinergic drugs, plant alkaloids (such as belladonna, Brugmansia) and mushrooms (e.g. Amanita)Sympathomimetic syndromePhenthylamines, e.g. amphetamines, methamphetamines (MDMA), cocaine, monoamine oxidase inhibitorsMalignant hyperthermiaVolatile anaesthetics and depolarising muscle relaxants, e.g. suxamethoniumUncoupling of oxidative phosphorylationSalicylates in overdose, dinitrophenolOpen in a separate windowNon-drug-induced causes of hyperthermiaThere are numerous causes of complicated hyperthermia that are not due to drug exposure (Table 2). Non-drug causes should always be considered and excluded. Lethal catatonia (which can develop over weeks), central nervous system lesions or infections, and tetanus can all cause hyperthermia associated with muscle rigidity. The diagnosis is based on the history and clinical picture.Table 2Non-drug causes of hyperthermia and muscle rigidityNon-drug-induced causesAssociated featuresSevere catatoniaSevere rigidity accompanied by psychosis, severe affective disorder, stuporHeat strokeExtreme dehydration, exercise or stress in hot, humid environments particularly in patients taking diureticsCentral nervous system infectionGeneral malaise, neurological deterioration, meningeal irritationTetanusTrismus, muscle spasm starting from the neck down, profuse sweating, spasticity intensified by stimuliThyrotoxicosisTachycardia, tremor and hypertensionPhaeochromocytomaTachycardia, hypertension and tremor, diaphoresis, agitationOpen in a separate windowThyrotoxicosis and phaeochromocytoma should be considered in the differential diagnosis of hyperthermia. However, they are rarely associated with muscle rigidity." @default.
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• W2912793993 title "The hot patient: acute drug-induced hyperthermia" @default.
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