05. Drug-Induced Hyperthermia

Definition

  • Temperature >38.3° related to a medication ingestion. Usually not clinically significant unless >39.5°.
  • Fever vs. hyperthermia:
    • Fever: increased hypothalamic set point.
    • Hyperthermia: imbalance of heat generation (typically increased muscle activity) and heat dissipation (e.g., impaired sweating).

Differential Diagnosis

Syndrome

Agents

Signs/Symptoms

Management

Adrenergic hyperthermia

Cocaine, amphetamines, MDMA, thyroxine, alcohol or benzodiazepine withdrawal, hallucinogens.

Agitation, autonomic instability, diaphoresis.

Note if dehydrated, sweating may be impaired.

Immediate cooling.

Benzodiazepines, supportive care.

Consider sedation, intubation and paralysis if refractory.

Anticholinergic hyperthermia

Atropine, scopolamine, antihistamines, antispasmodics, TCAs.

AMS, tachycardia, tremor, absence of sweat.

Immediate cooling, intravenous fluids.

Sedative-hypnotics, consider physostigmine for mod/severe cases. Check ECG to ensure QRS interval normal. (Contraindicated in TCA OD with widened QRS.)

Neuroleptic malignant syndrome (dopaminergic)

Antipsychotics, withdrawal from Parkinson’s meds, metoclopramide, compazine.

“Lead pipe” rigidity, AMS.

Possible role for bromocriptine and dantrolene (see dantrolene below), and amantadine.

Serotonin syndrome

MAOI, SSRI, TCA, MDMA, meperidine, lithium.

Tremor, clonus (especially lower extremity), rigidity, hyperreflexia, AMS (all usually within minutes to hours), dilated pupils, flushing, diarrhea, coma.

Benzodiazepines.

May consider cyproheptadine or chlorpromazine (can also precipitate anticholinergic symptoms).

Malignant hyperthermia

Volatile anesthetics (halothane, isoflurane), +/- succinylcholine.

Severe rigidity (especially of masseter muscles), hypercarbia, tachycardia.

Dantrolene.

Uncoupling of oxidative phosphorylation

Salicylates, dinitrophenol, pentachlorophenol.

Agitation, tachycardia.

Urine alkalinization or dialysis for salicylates.

Evaluation

  • Monitor for common consequences including encephalopathy, seizures, DIC, rhabdomyolysis (with consequent hyperkalemia and renal insufficiency), hepatic failure.
  • Rule out infection/fever.
  • Take careful ingestion history, although management is similar for most types of hyperthermia (below).

Management

  • Recognize early, as aggressive cooling may prevent multisystem organ failure and death.
  • Hold potentially offending medications!
  • It may be difficult initially to determine the cause of hyperthermia, but treatment is generally the same and mostly supportive, with the exception of specific medications available for certain syndromes.
  • Moderate hyperthermia: initiate cooling if temperature >39° with water mist and fans.
  • Severe hyperthermia: if refractory, rapidly worsening, or temperature >41°, have a low threshold for intubation and paralysis, which stops muscular activity and can be lifesaving (NM paralysis may not be effective in patients with malignant hyperthermia).
  • Benzodiazepines to decrease adrenergic activity.
  • The role of ice packs, cooling blankets, and iced gastric or peritoneal lavage is controversial. Cooling blanket may be effective for mild hyperthermia. Ice packs may be effective for moderate to severe hyperthermia but must cover a large surface area (not just armpits and groin) otherwise increased heat generation from induced shivering may outweigh conductive heat losses.
  • Stop cooling if temperature stabilizes below 38°.
  • Usually no role for antipyretics, as the mechanism (lowering body temperature set point) is ineffective in toxin-mediated hyperthermia.
  • Careful monitoring of liver and renal function and CK with supportive care.
  • Dantrolene: primarily indicated for malignant hyperthermia caused by volatile anesthetics. There is some evidence that it may be useful for treating hyperthermia and rhabdomyolysis caused by drug-induced muscular hyperactivity not controlled by usual methods and paralysis.

Key Points

  • Initiation of aggressive cooling can be lifesaving.
  • Consider intubation and paralysis in refractory, rapidly worsening, or life-threatening hyperthermia >41°.

 

Eyer F, Zilker T. Bench-to-bedside review: mechanisms and management of hyperthermia due to toxicity. Crit Care 2007; 11(6): 236-244.

McAllen K, Schwartz D. Adverse drug reactions resulting in hyperthermia in the intensive care unit. Crit Care Med 2010; 38(6 suppl): S244-S252.

Musselman ME, Saely S. Diagnosis and treatment of drug-induced hyperthermia. Am J Health Syst Pharm. 2013 Jan 1;70(1):34-42.