Heat Stroke

Etiology

Clinicians should determine the patient’s position along the heat-related illness continuum. Signs and symptoms of heat exhaustion may include cramping, fatigue, dizziness, nausea, vomiting, and headache. Progression to end-organ damage indicates heat injury, whereas central nervous system dysfunction distinguishes heat stroke from heat injury. Heat stroke has 2 forms: classic and exertional. Classic heat stroke typically affects older adults with chronic medical conditions, whereas exertional heat stroke affects otherwise healthy individuals who engage in strenuous exercise in hot or humid weather.[3]

Epidemiology

Estimating the public health impact of extreme heat is difficult because clinicians are not required to report heat-related illnesses. In the US, at least 3332 deaths were attributed to heat stroke from 2006 to 2010.[4] However, this number is believed to be substantially underreported. Mortality correlates with the degree of body temperature elevation, the time before cooling begins, and the number of organ systems affected.[5]

Pathophysiology

Normally, thermoregulation is an extremely efficient process, with a mere 1 °C change in core temperature for every 25 °C to 30 °C change in ambient temperature.[2] In the heat-adapted state, heat shock proteins repair cellular damage caused by hyperthermia. The body’s ability to dissipate heat through increased cardiac output, vasoconstriction within the splanchnic circulation, and sweating maintains the effective temperature range of these proteins. However, evaporative cooling becomes ineffective when environmental humidity exceeds 75%. Other methods of heat loss, including radiation, conduction, and convection, become ineffective when the ambient temperature exceeds skin temperature.[6]

Inadequate fluid replacement may subsequently cause substantial electrolyte abnormalities. Dehydration initially results in reference-range or elevated sodium levels. Severe hypernatremic dehydration may lead to hemorrhage, cerebral edema, and permanent neurologic injury. Rarely, hyponatremia occurs following excessive hypotonic fluid replacement, as seen in marathon runners and other patients with exertional heat stroke.[2] Hyperkalemia has been associated with heat stroke and may result from potassium release during muscle breakdown or from acidosis-induced movement of potassium from intracellular to extracellular fluid. Potassium is a potent vasodilator in skeletal and cardiac muscle; conversely, severe hypokalemia may cause cardiovascular instability and reduced muscle blood flow, predisposing patients to rhabdomyolysis.[1] Complications of rhabdomyolysis can range from mild hypocalcemia to acute kidney injury. Hyperkalemia and hypocalcemia together can lead to cardiac conduction abnormalities, including QT interval prolongation and ST-segment changes, and, in rare instances, fatal cardiac arrhythmias.[6] Heat stroke is also associated with a spectrum of coagulopathies, ranging from activation of the coagulation cascade and fibrinolysis to fatal hemorrhage or disseminated intravascular coagulation. Heat-induced endothelial damage is believed to promote platelet aggregation and microvascular thrombosis, resulting in consumptive coagulopathy and paradoxical bleeding when platelet consumption exceeds platelet production.[2]

History and Physical

Patients who present with heat stroke typically have vital sign abnormalities, including elevated core body temperature, sinus tachycardia, tachypnea, and a widened pulse pressure; approximately 25% are hypotensive. Other associated signs and symptoms include weakness, lethargy, nausea, vomiting, dizziness, flushing, pulmonary crackles, oliguria, excessive bleeding, and evidence of neurologic dysfunction.[1] Patients with classic heat stroke often present with hot, dry skin because of failure of the normal sweating response, known as anhidrosis. Conversely, anhidrosis is uncommon in exertional heat stroke, and prolonged sweating may continue after exercise has stopped.[6]

Evaluation

The evaluation of patients with possible heat stroke should include frequent monitoring of vital signs and rectal temperature, as well as laboratory testing with a complete blood count, comprehensive metabolic panel, prothrombin time, activated partial thromboplastin time, blood gases, serum creatine phosphokinase level, and urine myoglobin measurement. Based on clinical judgment, some patients may also benefit from toxicology screening, chest radiography, and electrocardiography.[3] Electrocardiographic findings may include ST-segment depression, QT interval prolongation, and other T-wave changes consistent with ischemia. Patients with heat stroke typically develop tachypnea and tachycardia. Arterial carbon dioxide levels often decrease to less than 20 mm Hg, and approximately 25% of patients are hypotensive.[2] Medication reconciliation is crucial when evaluating patients with suspected classic heat stroke, with particular attention to diuretics, β-blockers, and anticholinergic medications.

In classic heat stroke, respiratory alkalosis predominates, whereas exertional heat stroke may also involve concomitant lactic acidosis. Electrolyte derangements vary between the 2 forms; however, hypocalcemia, hyperphosphatemia, and hyperkalemia commonly occur in exertional heat stroke and reflect muscle breakdown. Rhabdomyolysis is more common in exertional heat stroke than in classic heat stroke, with greater elevations in creatine phosphokinase levels reported. In classic heat stroke, elevated aspartate aminotransferase and alanine aminotransferase levels are the most commonly reported laboratory abnormalities.[2] Associated kidney injury, hepatic dysfunction, and damage to other organ systems may also occur in either presentation.[1]

Treatment / Management

Management of heat stroke includes ensuring adequate airway protection, breathing, and circulation. After stabilization of the airway, breathing, and circulation, rapid cooling becomes the mainstay of treatment, with supportive care directed toward associated end-organ damage. Intubation for profound unconsciousness is rarely needed because rapid cooling often improves the Glasgow Coma Scale score.[6] Adequate rehydration is essential, although rapid correction of sodium abnormalities should be avoided. Core temperature should be continuously monitored with a rectal or esophageal probe, and active cooling should be discontinued when the temperature reaches 38 °C to 39 °C. Results from studies have not established the superiority of any single cooling method.[7] Ice-water immersion reduces core body temperature most rapidly; however, this method may be impractical in older adults because cardiac monitoring may be difficult and severe agitation may interfere with treatment.[8] Other common methods include applying ice packs to the groin and axillae and using evaporative cooling with fans and cool saline applied to the skin.(B3)

Several pharmacologic adjuncts also merit consideration in the treatment of heat stroke. Dantrolene is a skeletal muscle relaxant that reduces heat production during sustained muscle contraction and is used to treat malignant hyperthermia. However, results from studies showed that dantrolene does not improve outcomes in patients with heat stroke.[9] Results from a small study suggested that high-dose benzodiazepines may reduce shivering and oxygen consumption, providing a possible theoretical benefit. However, patients with heat stroke may already have impaired thermoregulatory responses, including shivering.[10] Therefore, routine benzodiazepine use is not recommended, although these medications may be considered for patients with agitation or shivering. Antipyretics have no role in the treatment of heat stroke and may cause hepatic toxicity.[1](A1)

Differential Diagnosis

Common differential diagnoses include polypharmacy, toxic ingestions, meningitis, sepsis, neuroleptic malignant syndrome, serotonin syndrome, and malaria. A detailed medication review can help exclude several medication-related and toxicologic causes. Except for heat cramps, muscle rigidity and clonus are not characteristic of heat stroke and may help distinguish this condition from neuroleptic malignant syndrome and serotonin syndrome. Clinicians should also obtain a detailed travel history and assess exposure to malaria-endemic regions and the malaria species prevalent in those areas. However, malaria, sepsis, and meningitis typically do not produce the same degree of core temperature elevation observed in heat stroke.

Prognosis

Mortality among patients with heat stroke varies according to the etiology. The mortality rate for exertional heat stroke is relatively low, ranging from 3% to 5%, compared with 10% to 65% for classic heat stroke.[4][5] The higher mortality associated with classic heat stroke likely reflects the greater prevalence of comorbidities and older age in this population. Results from studies showed that immediate rapid cooling was associated with no fatalities among young patients with exertional heat stroke.[4]

Complications

The effects of heat stroke may persist beyond the initial central nervous system dysfunction and involve injury to the gastrointestinal tract, kidneys, skeletal muscle, and other organ systems. Complications of heat stroke include acute respiratory distress syndrome, disseminated intravascular coagulation, acute kidney injury, hepatic injury, hypoglycemia, rhabdomyolysis, and seizures.[5] Despite normalization of core temperature with cooling, many patients continue to experience thermoregulatory abnormalities and multiorgan dysfunction. Results from studies showed that even reversible complications following heat stroke may take longer than 7 weeks to resolve.[11]