Body temperature regulation is complex and requires a balance between heat production
and dissipation. Hyperthermia occurs when metabolic heat production exceeds heat dissipation.
Many exogenously administered xenobiotics are capable of altering the body's ability
to maintain a constant temperature. For example, agents with anticholinergic activity
may contribute to hyperthermia by eliminating sweating and evaporation [
[1]
]. Because both recognition and treatment vary with the cause of hyperthermia, it is
important for clinicians to understand the various presentations and treatments of
toxin-induced hyperthermic syndromes.To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.
Content published before 2002 is available via pay-per-view purchase only.
Subscribe:
Subscribe to Clinics in Laboratory MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Oxybutynin-induced heatstroke in an elderly patient.Ann Pharmacother. 1996; 30: 144-147
- Towards a molecular understanding of adaptive thermogenesis.Nature. 2000; 404: 652-660
- Skin blood flow in adult human thermoregulation: how it works, when it does not, and why.Mayo Clin Proc. 2003; 78: 603-612
- Heat acclimation—mechanisms of adaptation to exercise in the heat.Int J Sports Med. 1998; 19: S154-S156
- Perioperative shivering: physiology and pharmacology.Anesthesiology. 2002; 96: 467-484
- Presence of alpha-1 adrenoreceptors on thermosensitive neurons in the medial preoptico-anterior hypothalamic area in rats.Neuropharmacology. 2002; 42: 697-705
- Further evidence for a physiological role for hypothalamic dopamine in thermoregulation in the rat.J Physiol. 1980; 300: 7-17
- CNS regulation of thermogenesis.Crit Rev Neurobiol. 1994; 8: 1-10
- Sympathoadrenal system and regulation of thermogenesis.Am J Physiol. 1984; 247: E181-E189
- Mitochondrial targets of drug toxicity.Annu Rev Pharmacol Toxicol. 2000; 40: 353-388
- The uncoupling proteins, a review.Eur J Endocrinol. 1998; 139: 1-9
- Thermogenic mechanisms in brown fat.Physiol Rev. 1984; 64: 1-64
- Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression.FEBS Lett. 1997; 408: 39-42
- Cold-induced changes in the energy coupling and the UCP3 level in rodent skeletal muscles.Biochim Biophys Acta. 2001; 1505: 271-279
- Evidence of UCP1-independent regulation of norepinephrine-induced thermogenesis in brown fat.Am J Physiol Endocrinol Metab. 2000; 279: E314-E322
- Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta 3-adrenergic agonists, and leptin.J Biol Chem. 1997; 272: 24129-24132
- Effects of thyroid hormone on norepinephrine signaling in brown adipose tissue. I. Beta 1- and beta 2-adrenergic receptors and cyclic adenosine 3′,5′–monophosphate generation.Endocrinology. 1995; 136: 3267-3276
- Thyroxine 5′-deiodination mediates norepinephrine-induced lipogenesis in dispersed brown adipocytes.Endocrinology. 1998; 139: 571-578
- Thyroid hormone control of thermogenesis and energy balance.Thyroid. 1995; 5: 481-492
- Thyroid hormone and other regulators of uncoupling proteins.Int J Obes Relat Metab Disord. 1999; 23: S56-S59
- Severe hyperthermia secondary to intravenous drug abuse.Am J Emerg Med. 1984; 2: 373
- Rhabdomyolysis and shock after intravenous amphetamine administration.Ann Intern Med. 1977; 86: 381-387
- Amphetamine intoxication with coagulopathy, hyperthermia, and reversible renal failure. A syndrome resembling heatstroke.Ann Intern Med. 1970; 73: 81-85
- MDMA induced hyperthermia: report of a fatality and review of current therapy.Intensive Care Med. 1996; 22: 995-996
- Serotonin toxicity with therapeutic doses of dexamphetamine and venlafaxine.Med J Aust. 2002; 176: 240-241
- Serotonin syndrome.Neurology. 1995; 45: 219-223
- Convulsive ergotism: epidemics of the serotonin syndrome?.Lancet Neurol. 2003; 2: 429-434
- Ergotism: the satan loosed in Salem?.Science. 1976; 192: 21-26
- Fatal toxic encephalitis occurring during iproniazid therapy in pulmonary tuberculosis.Ann Intern Med. 1955; 42: 417-424
- The Libby Zion case. One step forward or two steps backward?.N Engl J Med. 1988; 318: 771-775
- Serotonin syndrome. A clinical update.Crit Care Clin. 1997; 13: 763-783
- The serotonin syndrome.Am J Psychiatry. 1991; 148: 705-713
- Serotonin syndrome and drug combinations: focus on MAOI and RIMA.Eur Arch Psychiatry Clin Neurosci. 1997; 247: 113-119
- An exploratory approach to the serotonin syndrome: an update of clinical phenomenology and revised diagnostic criteria.Med Hypotheses. 2000; 55: 218-224
- Pathology of deaths associated with “ecstasy” and “eve” misuse.J Clin Pathol. 1996; 49: 149-153
- The health effects of ecstasy: a literature review.Drug Alcohol Rev. 2002; 21: 53-63
- Serotonin syndrome. Presentation of 2 cases and review of the literature.Medicine. 2000; 79: 201-209
- Isolated venlafaxine-induced serotonin syndrome.J Emerg Med. 1997; 15: 491-493
- The serotonin syndrome.Am J Psychiatry. 1992; 149: 1410-1411
- The serotonin syndrome associated with paroxetine, an over-the-counter cold remedy, and vascular disease.Am J Emerg Med. 1994; 12: 642-644
- Toxicity secondary to meperidine in patients on monoamine oxidase inhibitors: a case report and critical review.J Clin Psychopharmacol. 1981; 1: 319-321
- L-dopa induced “serotonin syndrome” in a parkinsonian patient on bromocriptine.J Clin Psychopharmacol. 1986; 6: 194-195
- Serotonin syndrome with tramadol and citalopram.Am J Psychiatry. 2004; 161: 1129
- Serotonin syndrome produced by a combination of fluoxetine and lithium.Am J Psychiatry. 1993; 150: 1565
- Small changes in ambient temperature cause large changes in 3,4-methylenedioxymethamphetamine (MDMA)–induced serotonin neurotoxicity and core body temperature in the rat.J Neurosci. 1998; 18: 5086-5094
- Low environmental temperatures or pharmacologic agents that produce hypothermia decrease methamphetamine neurotoxicity in mice.Brain Res. 1994; 658: 33-38
- Elevated environmental temperature and methamphetamine neurotoxicity.Environ Res. 2003; 92: 48-53
- Effects of 3,4-methylenedioxymethamphetamine on autonomic thermoregulatory responses of the rat.Pharmacol Biochem Behav. 1991; 38: 339-344
- Ambient temperature and mortality from unintentional cocaine overdose.JAMA. 1998; 279: 1795-1800
- Strenuous exercise aggravates MDMA-induced skeletal muscle damage in mice.Toxicology. 2005; 206: 349-358
- The effect of exercise and limitation of movement on amphetamine toxicity.J Pharmacol Exp Ther. 1963; 145: 47-51
- The role of mitochondrial uncoupling in 3,4-methylenedioxymethamphetamine mediated skeletal muscle hyperthermia and rhabdomyolysis.J Pharmacol Exp Ther. 2005; 313: 629-639
- Toxicity and deaths from 3,4-methylenedioxymethamphetamine (“ecstasy”).Lancet. 1992; 340: 384-387
- Attenuation of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)–induced rhabdomyolysis with alpha1- plus beta3-adrenoreceptor antagonists.Br J Pharmacol. 2004; 142: 667-670
- The distribution of 3,4-methylenedioxymethamphetamine “Ecstasy”–induced c-fos expression in rat brain.Neuroscience. 1999; 92: 1011-1023
- Diazepam and chlormethiazole attenuate the development of hyperthermia in an animal model of the serotonin syndrome.Neurochem Int. 2003; 43: 155-164
- Risperidone counteracts lethality in an animal model of the serotonin syndrome.Psychopharmacology (Berl). 2000; 150: 9-14
- Extracellular serotonin, dopamine and glutamate levels are elevated in the hypothalamus in a serotonin syndrome animal model induced by tranylcypromine and fluoxetine.Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28: 633-640
- Abnormal CSF monoamine metabolism in serotonin syndrome.J Clin Psychopharmacol. 2003; 23: 528-531
- Abnormal monoamine metabolism in cerebrospinal fluid in a case of serotonin syndrome.J Clin Psychopharmacol. 2000; 20: 107-108
- Influences of the corticotropic axis and sympathetic activity on neurochemical consequences of 3,4-methylenedioxymethamphetamine (MDMA) administration in Fischer 344 rats.Eur J Neurosci. 2002; 16: 607-618
- Hypothalamic-pituitary-thyroid axis and sympathetic nervous system involvement in hyperthermia induced by 3,4-methylenedioxymethamphetamine (Ecstasy).J Pharmacol Exp Ther. 2003; 305: 159-166
- UCP3 and thyroid hormone involvement in methamphetamine-induced hyperthermia.Biochem Pharmacol. 2004; 68: 1339-1343
- Sympatho-adrenal involvement in methamphetamine-induced hyperthermia through skeletal muscle hypermetabolism.Eur J Pharmacol. 1998; 363: 107-112
- Carvedilol reverses hyperthermia and attenuates rhabdomyolysis induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in an animal model.Crit Care Med. 2005; 33: 1311-1316
- Plasma concentrations of 5-HT, 5-HIAA, norepinephrine, epinephrine and dopamine in ecstasy users.Neuro Endocrinol Lett. 2002; 23: 259-261
- Cutaneous vasoconstriction contributes to hyperthermia induced by 3,4-methylenedioxymethamphetamine (ecstasy) in conscious rabbits.J Neurosci. 2001; 21: 8648-8654
- Mechanism of cocaine-induced hyperthermia in humans.Ann Intern Med. 2002; 136: 785-791
- Alpha1-adrenergic stimulation potentiates the thermogenic action of beta3-adrenoreceptor–generated cAMP in brown fat cells.J Biol Chem. 1997; 272: 32847-32856
- The role of the sympathetic nervous system and uncoupling proteins in the thermogenesis induced by 3,4-methylenedioxymethamphetamine.J Mol Med. 2004; 82: 787-799
- Uncoupling the agony from ecstasy.Nature. 2003; 426: 403-404
- Potent serotonin (5-HT)(2A) receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome.Brain Res. 2001; 890: 23-31
- The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) to rats.Br J Pharmacol. 2002; 135: 170-180
- Role of 5-HT(2) receptors in the tryptamine-induced 5-HT syndrome in rats.Behav Pharmacol. 2002; 13: 313-318
- Clozapine reverses hyperthermia and sympathetically mediated cutaneous vasoconstriction induced by 3,4-methylenedioxymethamphetamine (ecstasy) in rabbits and rats.J Neurosci. 2003; 23: 6385-6391
- Dantrolene use in 3,4-methylenedioxymethamphetamine (ecstasy)–mediated hyperthermia.Anesthesiology. 2004; 101 ([author reply: 264]): 263
- An overdose of ecstasy. A role for dantrolene.Anaesthesia. 1992; 47: 686-687
- Exertional heat stroke induced by amphetamine analogues. Does dantrolene have a place?.Anaesthesia. 1993; 48: 1057-1060
- Ecstasy intoxication: appreciation of complications and the role of dantrolene.Anaesthesia. 1993; 48: 542-543
- Treatment of the serotonin syndrome with cyproheptadine.J Emerg Med. 1998; 16: 615-619
- Treatment of the serotonin syndrome with cyproheptadine.N Engl J Med. 1994; 331: 1021-1022
- The serotonin syndrome and its treatment.J Psychopharmacol. 1999; 13: 100-109
- Effects of psychoactive drugs on plasma catecholamines during stress in rats.Neuropharmacology. 1984; 23: 1105-1108
- The effect of extracorporeal cooling on amphetamine toxicity.Arch Int Pharmacodyn Ther. 1966; 159: 189-195
- Heat stroke: a review of cooling methods.Sports Med. 2004; 34: 501-511
- Hypothermia attenuates circulatory shock and cerebral ischemia in experimental heatstroke.Shock. 2003; 19: 388-393
- Recognition, assessment and management of neuroleptic malignant syndrome.S D J Med. 2000; 53: 395-400
- Neuroleptic malignant syndrome and atypical antipsychotic drugs.J Clin Psychiatry. 2004; 65: 464-470
- The neuroleptic malignant syndrome: a logical approach to the patient with temperature and rigidity.Postgrad Med J. 1998; 74: 72-76
- The neuroleptic malignant and serotonin syndromes.Emerg Med Clin North Am. 2000; 18: 317-325
- Neuroleptic malignant syndrome.Med Clin North Am. 1993; 77: 185-202
- Facilitating prompt diagnosis and treatment of the neuroleptic malignant syndrome.Clin Pharmacol Ther. 1991; 50: 580-586
- A prospective analysis of 24 episodes of neuroleptic malignant syndrome.Am J Psychiatry. 1989; 146: 717-725
- Mutism and hyperthermia in a patient treated with neuroleptics.Med J Aust. 1973; 2: 228-229
- Progression of symptoms in neuroleptic malignant syndrome.J Nerv Ment Dis. 1994; 182: 168-173
- Serum iron and neuroleptic malignant syndrome.Lancet. 1991; 338: 149-151
- Metoclopramide-induced neuroleptic malignant syndrome.Arch Intern Med. 1987; 147: 1495-1497
- Prochlorperazine-induced neuroleptic malignant syndrome.J Emerg Med. 1996; 14: 727-729
- Neuroleptic malignant syndrome due to promethazine.South Med J. 1999; 92: 1017-1018
- Neuroleptic malignant syndrome. When levodopa withdrawal is the cause.Postgrad Med. 1991; 89 (180): 175-178
- Neuroleptic malignant syndrome: guidelines for treatment and reinstitution of neuroleptics.South Med J. 1988; 81: 888-891
- Neuroleptic malignant syndrome: a pathogenetic role for dopamine receptor blockade?.Neurology. 1981; 31: 132-137
- Sympathoadrenal hyperactivity and the etiology of neuroleptic malignant syndrome.Am J Psychiatry. 1999; 156: 169-180
- Cerebrospinal fluid monoamine metabolism in a case of neuroleptic malignant syndrome improved by electroconvulsive therapy.Biol Psychiatry. 1996; 39: 383-384
- Sympathoadrenomedullary hyperactivity in the neuroleptic malignant syndrome: a case report.Am J Psychiatry. 1981; 138: 1115-1116
- Sympathoadrenomedullary activity in the neuroleptic malignant syndrome.Biol Psychiatry. 1992; 32: 334-343
- Prospective evaluation of circulatory levels of catecholamines and serotonin in neuroleptic malignant syndrome.Acta Psychiatr Scand. 2000; 102: 226-230
- Bromocriptine treatment of neuroleptic malignant syndrome.J Clin Psychiatry. 1987; 48: 69-73
- Successful treatment of neuroleptic malignant syndrome with bromocriptine.South Med J. 1986; 79: 1567-1571
- Neuroleptic malignant syndrome: successful treatment with bromocriptine.Biol Psychiatry. 1985; 20: 680-684
- Dantrolene—a new therapeutic approach to the neuroleptic malignant syndrome.Acta Neurol Scand Suppl. 1984; 100: 193-198
- Drug treatment of the neuroleptic malignant syndrome.Psychopharmacol Bull. 1991; 27: 381-384
- The treatment of neuroleptic malignant syndrome. Are dantrolene and bromocriptine useful adjuncts to supportive care?.Br J Psychiatry. 1991; 159: 709-712
- Neuroleptic malignant syndrome, bromocriptine, and anticholinergic drugs.J Clin Psychiatry. 1988; 49: 283-284
- Management of suspected neuroleptic malignant syndrome.Can J Psychiatry. 1995; 40: 545-550
- Chlorpromazine-induced neuroleptic malignant syndrome and its response to diazepam.Biol Psychiatry. 1983; 18: 1441-1446
- Diazepam-responsive neuroleptic malignant syndrome: a diagnostic subtype?.Am J Psychiatry. 1997; 154: 882
- Treatment of a mild form of neuroleptic malignant syndrome with oral diazepam.Acta Psychiatr Scand. 1988; 78: 396-398
- Efficacy of methylprednisolone pulse therapy on neuroleptic malignant syndrome in Parkinson's disease.J Neurol Neurosurg Psychiatry. 2003; 74: 574-576
- Twenty neuroleptic rechallenges after neuroleptic malignant syndrome in 15 patients.J Clin Psychiatry. 1989; 50: 295-298
- Anaesthetic deaths in a family.Lancet. 1960; 2: 45
- Malignant hyperthermia.Lancet. 1998; 9134: 1131-1136
- Malignant hyperthermia and central core disease: disorders of Ca2+ release channels.Am J Med. 1998; 104: 470-486
- Malignant hyperthermia: advances in clinical management and diagnosis.Br J Anaesth. 2000; 85: 118-128
- Adverse effects of neuromuscular blockers and their antagonists.Drug Saf. 1998; 18: 99-116
- Malignant hyperthermia and apparent heat stroke.JAMA. 2001; 286: 168-169
- Evidence for susceptibility to malignant hyperthermia in patients with exercise-induced rhabdomyolysis.Anesthesiology. 2001; 94: 95-100
- Malignant hyperthermia.Pediatr Clin North Am. 1994; 41: 221-237
- The role of sympathetic activity in initiating malignant hyperthermia.Acta Anaesthesiol Scand. 1990; 34: 677-682
- Plasma levels of norepinephrine and epinephrine during malignant hyperthermia in susceptible pigs.J Chromatogr. 1985; 344: 71-80
- Porcine malignant hyperthermia. III. Adrenergic blockade.Br J Anaesth. 1976; 48: 831-838
- Porcine malignant hyperthermia. VI. The effects of bilateral adrenalectomy and pretreatment with bretylium on the halothane-induced response.Br J Anaesth. 1978; 50: 241-246
- Norepinephrine does not potentiate porcine malignant hyperthermia.Anesth Analg. 1996; 82: 790-795
- Increase of serotonin in plasma during onset of halothane-induced malignant hyperthermia in pigs.Eur J Pharmacol. 1992; 220: 91-94
- Pharmacodynamic effects of serotonin (5-HT) receptor ligands in pigs: stimulation of 5-HT2 receptors induces malignant hyperthermia.Naunyn Schmiedebergs Arch Pharmacol. 1990; 341: 483-493
- Induction of malignant hyperthermia in susceptible swine by 3,4-methylenedioxymethamphetamine (“ecstasy”).Anesthesiology. 2003; 99: 1132-1136
- Effects of a 5HT(2) receptor agonist on anaesthetized pigs susceptible to malignant hyperthermia.Br J Anaesth. 2003; 91: 281-284
- Lack of prophylactic or therapeutic efficacy of 5-HT2A receptor antagonists in halothane-induced porcine malignant hyperthermia.Naunyn Schmiedebergs Arch Pharmacol. 1994; 350: 365-374
- Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity.Drugs. 1986; 32: 130-168
- Dantrolene sodium can increase or attenuate activity of skeletal muscle ryanodine receptor calcium release channel: clinical implications.Anesthesiology. 1996; 84: 1368-1379
- Genetics and pathogenesis of malignant hyperthermia.Muscle Nerve. 2000; 23: 4-17
- Clinical effects of intravenously administered dantrolene.Mayo Clin Proc. 1995; 70: 241-246
Article info
Footnotes
Portions of this article were previously published in Holstege CP, Rusyniak DE: Medical Toxicology. 89:6, Med Clin North Am, 2005; with permission.
Identification
Copyright
© 2006 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
