Hyperthermia is a core (oesophageal, tympanic) temperature above 40.5°C. Hyperthermia may be an extreme form of pyrogen-induced fever associated with infection, inflammation, neoplasia or CVA

Heat stroke

Heat Stoke is a life-threatening illness characterised by:

  • Core temperature > 40°
  • CNS dysfunction (delirium, convulsions, coma)

Pathophysiology of Heat Stroke

  • Cellular oxidative phosphorylation becomes uncoupled at temperatures >42°C
  • Cellular damage is directly proportional to the temp and exposure time
  • Compensatory mechanisms for heat dissipation fail
  • Dehydration increases the sodium/potassium pump activity and increases metabolic rate
  • Complications may arise in multiple organ systems

At risk - very young and elderly, obese and those undertaking unaccustomed or prolonged muscular activity, grand mal fitting, athletes, marathon runners and armed forces recruits. 

Predisposing factors include:

  • Alcohol use/withdrawal
  • Cardiac disease
  • Conditions which cause or aggravate sodium/water loss (gastroenteritis, cystic fibrosis)
  • Drugs:
    • Anticholinergics - atropine, lithium, TCAs, phenothiazines
    • B-blockers
    • Disrupted thermoregulation - LSD, phenothiazines
    • Disrupted oxidative phosphorylation - salicylates, lithium
    • Muscle activity - PCP, amphetamines, cocaine
    • Malignant hyperthermia - anaesthetic agents, succinylcholine
    • Neuroleptic malignant syndrome - neuroleptics
    • Serotonin syndrome - SSRIs
    • Dehydration (diuretics)

Clinical features Heat Stroke


  • Oedema and petechial haemorrhages cause focal and generalised damage


  • Skeletal muscles show widespread degeneration of fibres
  • Rhabdomyolysis releases myoglobin, K+, CPK and purines (which are metabolised into uric acid) into the circulation


  • Non cardiogenic pulmonary oedema


  • Oliguric acute renal failure due to renal ischaemia, muscle breakdown products, DIC, hyperuricaemia and hypovolaemia
  • Renal failure occurs in up to 35%


  • DIC (poor prognosis), thrombocytopaenia, leukocytosis
  • Thermal injury to endothelium releases thromboplastins which result in intravascular thrombosis and secondary fibrinolysis


  • Metabolic acidosis, respiratory alkalosis, hypoglycaemia, hyper- or hypokalaemia

Poor Prognostic Factors in Heat Stroke

  • Core temperature >41.1°C
  • AST >1000 IU in first 24 hours
  • Hypotension not responsive to cooling and fluid replacement
  • Renal failure or hyperkalaemia

Malignant hyperthermia

Rare, autosomal dominant, drug-induced myopathy associated with a Ca++ transfer defect in patients receiving volatile anaesthetics, muscle relaxants, antidepressants, alcohol or Ecstasy. Heat production is increased by muscle catabolism, spasm and peripheral vasoconstriction.

The neuroleptic malignant syndrome

A drug induced hyperthermic syndrome secondary to antipsychotics - especially dopamine antagonists such as haloperidol, thioridazine and chlorpromazine. It is associated with muscle rigidity, extra pyramidal signs, dyskinesia, impaired consciousness and autonomic dysfunction and continues for 1-2 weeks.

Features NMS

  • Sweating may or may not be present - hot dry skin was previously thought to be a feature of heat stroke but patients with heat stroke may still be sweating
  • Skin surface may be cool due to peripheral vasoconstriction
  • Tachycardia and hypotension. Arrhythmias. Hypotension results from a combination of hypovolaemia, peripheral vasodilation and cardiac dysfunction
  • Tachypnoea is a universal finding in heat stroke
  • Confusion, delirium and seizures
  • Dilated pupils, oculogyric crises
  • Coma with decerebrate posturing
  • Cerebellar dysfunction
  • Salt water depletion
  • Rhabdomyolysis
  • Disseminated intravascular coagulation. Purpura, conjunctival haemorrhages, melaena, haematocrit
  • Heart failure with ST depression and T wave flattening

Laboratory Investigations

  • Hypo - K+, PO4--, Ca++
  • Hyper - K+ if rhabdomyolysis
  • Renal impairment
  • Urate - often elevated (? role in development of ARF)
  • Glucose - elevated in up to 70% of cases
  • LFTs Hi AST, LDH more likely in heat stroke than exhaustion
  • LDH >1000 in hepatic/renal/myocardial damage
  • CK  usually > 10,000  (can be as low as 1,000)
  • WBC up to 30-40,000
  • Clotting-usually abnormal. DIC may be present
  • ABG - respiratory alkalosis, metabolic acidosis
  • Serum/urinary myoglobin - may be elevated
  • ECG - Conduction abnormal, ST -T changes
  • CXR - ? aspiration. May be signs of pulmonary oedema but significant fluid replacement may be required.

Management of hyperthermia

Mortality from heat stroke approaches 80% if prompt, effective treatment is not undertaken

  • Secure the airway and give high flow oxygen. Shivering and vasoconstriction may occur during rapid cooling and increase oxygen consumption and heat production
  • Rapid cooling should be instituted for patients with temperatures >41°C. (Outcome depends on the height and duration of temperature elevation)
  • Clothing should be removed and patients nursed in a cool environment
  • Use surface cooling with a fan, tepid sponging, wet sheets, ice packs or a cool bath.
  • Do not give antipyretics such as aspirin (risk DIC) or paracetamol (ineffective)
  • Correct hypoglycaemia with dextrose 10%
  • Active cooling measures should be stopped when temperature is <38.5°C
  • Supportive treatment includes fluid replacement and seizure control.
    • Control fits with benzodiazepines.
    • Saline or 0.45% saline/5% dextrose may be used (depending on U&Es,  clinical assessment and haematocrit)
    • Up to 4L may be required over 6-12 hours but avoid over-rapid infusion, which may cause pulmonary/cerebral oedema. Monitor CVP
  • Pressor agents may be indicated for hypotension but alpha adrenergic agents (noradrenaline, Adrenaline) should be avoided since they impair heat dissipation by causing vasoconstriction. Consider low dose dopamine (2.5mcg/kg/min)
  • Insert a urinary catheter. If myoglobinuria is present aim for urine output >50ml/h and consider bicarbonate and/or mannitol. If using bicarbonate 1-2mEq/Kg boluses should be given to maintain urinary pH>6
  • Phenothiazines may be used to reduce temperature and prevent shivering (not in neuroleptic malignant syndrome)
  • Muscle relaxants with non depolarising agents should be used if the patient is ventilated/resistant to external cooling
  • For malignant hyperthermia the offending drug should be stopped and dantrolene 1mg/kg given i.v. every 5 minutes to a maximum dose of 10mg/kg
  • Mechanical ventilation with a high FiO2 and treatment of hyperkalaemia are required
  • The neuroleptic malignant syndrome is treated by stopping the offending drug, giving dantrolene, as above, and dopamine agonists (e.g. L-dopa or bromocriptine)
  • Coagulopathy should be treated with FFP and platelets

Differential Diagnosis of Heat Stroke

  • Meningitis / Encephalitis
  • Intracranial haemorrhage
  • Thyrotoxic crisis
  • Drug induced hyperthermic syndromes
  • Delirium tremens
  • Malaria

Content by Dr Jon Dallimore, Dr Íomhar O' Sullivan 10/02/04. Reviewed by Dr ÍOS 10/02/05. Reviewed by Dr IOS 25/04/2007. Last review Dr ÍOS 21/06/21.