Heatstroke is a life-threatening condition in which the body temperature exceeds 40°C (104°F) because of an imbalance in heat generation and dissipation. Whereas in fever there is a physiological increase in the temperature setpoint of the body, in a heatstroke the hypothalamus setpoint remains normal. The young and elderly are at greatest risk because they do not take measures to prevent overheating (e.g., moving to a cooler environment or drinking more fluids). In addition to hot and humid weather, some drugs (e.g., vasoconstrictors, cocaine) and medical conditions (e.g., seizure, thyroid storm) can cause heatstroke. Affected individuals may present with a headache, nausea, hot skin without sweating, tender muscles, and varying degrees of neurological symptoms. Laboratory abnormalities include elevated muscle enzymes (e.g., creatine kinase) and lactic acidosis due to rhabdomyolysis. A rapid reduction of the core body temperature with fanning and ice water is essential to prevent life-threatening complications, which include renal and hepatic failure with bleeding and possible coma and death. The best way to prevent heatstroke is to drink plenty of water, refrain from strenuous exercise in hot environments, and avoid clothing or substances that interfere with heat dissipation.
- Children and the elderly are at the highest risk.
- In the US, more people die of heatstroke than of all other weather-related threats together (e.g., hurricane, floods, earthquake).
Epidemiological data refers to the US, unless otherwise specified.
- The normal physiologic response to increased body temperature is hypothalamus-mediated peripheral vasodilation (to expose blood to the cooler air) and sweating (to dissipate heat into the environment).
- In heatstroke, the hypothalamic thermoregulatory response is inadequate to maintain a normal temperature.
- Causes include:
- Increased heat production (e.g., strenuous exercise, sepsis, status epilepticus, cocaine and amphetamines, thyroid storm)
- Decreased heat dissipation (e.g., high ambient temperature or humidity, vasoconstrictor drugs, skin diseases, burns, reduced CNS response due to alcohol and sedatives)
- Reduced behavioral responsiveness (e.g., infants, the elderly, and chronically ill individuals who are unable to control their environment and water intake)
- High body temperature → protein denaturation, phospholipid and lipoprotein damage, and membrane lipid liquefaction → cell damage and loss of function (including myocardiocytes and neurons) → cardiovascular collapse → multiorgan failure and possibly death
- Hot skin, possibly absence of sweating 
- Body temperature usually > 40°C (104°F)
- Nausea, vomiting
- Tachypnea and tachycardia
- Tender, rigid, limp, or cramping muscles
- Rhabdomyolysis (a frequently encountered complication)
- Central nervous system
- Acute renal injury (∼ 30% of cases) 
- Rare features: hepatic failure, disseminated intravascular coagulation (DIC), and bleeding
- Acute respiratory distress syndrome
Heatstroke is mainly a clinical diagnosis.
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The differential diagnoses listed here are not exhaustive.
Rapid reduction of the core body temperature to 39°C (102.2°F)
- Immersion in ice water (most effective cooling modality) 
- Cooling by spraying water
- Cold IV crystalloids
- Electrolyte imbalance treatment
Antipyretics (e.g., acetaminophen and other NSAIDs), which interrupt the change in the hypothalamic setpoint caused by pyrogens in fever, are not effective in heatstroke and may even be harmful because of the risk of bleeding complications.
- Limit strenuous physical activity, alcohol intake, and use of medications and drugs that interfere with heat dissipation in hot environments.
- Ensure adequate hydration and sufficient breaks for cooling off.