Question 1

List the possible causes, and outline your principles of management of hyperthermia in the Intensive Care patient.

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College Answer

•    Causes of hyperthermia (? specific temperature definition: eg. Core temperature > 38 °C) include: infection (bacteria, virus etc), inflammatory response (burns, pancreatitis etc), exertion (status epilepticus, posturing, delirium), auto-immune conditions (arthritis, inflammatory bowel disease), endocrine disorders (eg. hyperthyroidism/thyroid storm), malignancy (esp. haematological), drug associated (eg. overdose with cocaine, salicylates; withdrawal states eg. from alcohol, opiates; and occasionally drug fever) and unusual but requiring specific therapy: malignant hyperthermia (MH) and neuroleptic malignant syndrome (NMS). 

•    Principles of management include: treatment of underlying cause, and consideration of whether specific temperature lowering therapy is required. Obvious specific therapies
include antimicrobial therapy, chemotherapy (including corticosteroids). MH requires urgent removal of exposure to triggering agent, dantrolene (eg. 2.4 mg/kg IV and repeat according to protocol), aggressive cooling and fluid resuscitation. NMS requires removal of
responsible drugs (eg. phenothiazines, butyrophenones), symptomatic treatment and consideration of other specific therapies (eg. dantrolene, bromocriptine etc).

•    Mild to moderate elevations of temperature are generally not thought to be harmful.
Lowering of temperature (independent of the cause) may be beneficial in some circumstances (eg. for comfort), and may be indicated to avoid potential harm in other circumstances (eg. stroke, head injury, hypoxic injury). Aggressive management of temperature should be undertaken if temperature exceeds 39°C in children under 3 (increased risk of seizures) or 41°C in others (concern regarding long term effects on brain, rhabdomyolysis etc). Methods used may be simple (paracetamol, aspirin) or more complex (sponging through to ice packs and cooling blankets).


As one of the readers (Sarah, you know who you are) had correctly pointed out, in their answer, the college examiner failed to distinguish between hyperthermia and fever, which are distinct entities. To borrow a turn of phrase from Still (1979), fever is a regulated increase in body temperature associated with an increased hypothalamic temperature setpoint and thermopreferendum (the behavioural preference for an environmental temperature), whereas in hyperthermia the body temperature is elevated above this preferred temperature. As such causes of elevated body temperature shoud be classified in terms of whether the temperature is elevated because of the body's thermoregulatory mechanisms, or in spite of them.  

However, for the purpose of answering questions on this topic, the trainees were not expected to discriminate between hypothermia and fever. In fact judging by the college answer, they really meant "fever" all along, as their answer has no mention of (for example) being in a fire as a cause of hyperthermia.   Paul Marik's excellent article on fever remains a definitive resource for the person trying to generate a broad range of differentials for fever specifically.

Firstly, the definition and measurement of fever. Marik suggests that the measurement of mixed venous blood with a PA catheter is the gold standard (in the face of all those heretics who think hypothalamic temperature is more important). The upper threshold for temperature is defined by the Society of Critical Care Medicine as 38.3°C

In summary, any process which releases IL-1, IL-6 and TNF-α will cause a fever. The process could be infectious or non-infectious.

Marik's article has a series of excellent (and extremely long) tables regarding the various differential causes of fever.

Highlights from these tables include the following:

  • Vascular causes
    • MI
    • PE
    • SAH
    • Gut ischaemia
    • DVT
  • Infectious causes
    • Systemic sepsis
    • Line-related
    • Acalculous cholecystitis
  • Neoplastic causes
    • Tumour-related pyrexia
    • "Drug fever"
    • Neuroleptic-malignant syndrome
    • Serotonin syndrome
    • Drug withdrawal (alcohol)
  • Idiopathic/inflammatory
    • Malignant hyperthermia
    • Rhabdomyolysis
    • Pancreatitis
    • Gout
  • Autoimmune/allergic
    • Vasculitis
    • Anaphylaxis
    • Transfusion reaction
    • Transplant rejection
    • IV contrast reaction
  • Inflammatory causes

The answer for the management of a fever could be approached in a systematic manner.

  • Treat underlying cause:
    • Antibiotics for sepsis
    • Steroids for inflammatory/autoimmune states
    • Benzodiazepines for withdrawal
    • Dantrolene/bromocryptine/cyproheptadine
  • Treat the temperature:
    • One would wish to keep it under 41°C to prevent rhabdomyolysis, seizures and brain damage
    • Various cooling techniques are discussed elsewhere; in brief:
    • Ice bags, cold water sponges
    • Cooling blankets and vests
    • Cold IV fluids
    • Paracetamol/NSAIDs
    • Extracorporeal cooling


Marik, Paul E. "Fever in the ICU." Chest Journal 117.3 (2000): 855-869.


O'Grady, Naomi P., et al. "Practice guidelines for evaluating new fever in critically ill adult patients." Clinical infectious diseases 26.5 (1998): 1042-1059.