Hyperthermia, Heat Injury, and Heatstroke

Hyperthermia, Heat Injury, and Heatstroke

By: Stacy Chow, MD, and Michael S. Tripp, MD
Chest Infections and Disaster Response Network
October 19, 2023

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Hyperthermia is an elevation in core body temperature above the normal diurnal range of 36 °C to 37.5 °C. It differs from fever, as the body’s thermoregulatory set point remains unaltered, with elevation in body temperature occurring in an uncontrolled fashion due to exogenous heat exposure or endogenous heat production. In contrast, fever occurs when either endogenous or exogenous pyrogens induce elevation in the body’s thermoregulatory set point.

This difference in pathophysiology explains the lack of improvement or resolution of hyperthermia with antipyretic administration. When the degree of hyperthermia is such that the body’s natural ability to balance heat load with dissipation is disrupted, central nervous system dysfunction may result. This potentially fatal condition is known as heatstroke. There are two recognized types of heatstroke, nonexertional or classic and exertional.

Individuals who experience nonexertional heatstroke are typically older and have underlying chronic medical conditions that result in some impairment of thermoregulatory control. In contrast, exertional heatstroke typically affects younger otherwise healthy individuals who engage in relatively heavy exercise in settings with high ambient temperature and humidity. Classic examples are athletes and military recruits undergoing conditioning for sports or basic training.

In these cases, underlying thermoregulatory mechanisms are intact but overwhelmed by environmental thermal conditions and increase in endogenous heat production. Notably, exertional heatstroke can occur even within the first 60 minutes of exertion and in environments with relatively modest ambient temperatures. Lack of patient heat adaption is also a risk factor for developing exertional heatstroke.

The pathophysiology of the organ damage associated with heatstroke is due to direct cellular toxicity of temperatures above 42 °C. With drastic increases in temperature comes deterioration of cell function secondary to cessation of mitochondrial activity, alterations in chemical bonds integral to enzymatic reactions, and induction of cell membrane instability. A systemic inflammatory response syndrome-like inflammatory response occurs and can progress to vasoplegic shock.

Clinical presentation

Clinical presentation varies by organ systems. Direct thermal toxicity to the brain and spinal cord can result in cell death, cerebral edema, and focal hemorrhage. Patients may exhibit altered mental status, generalized weakness, lethargy, seizures, agitation, delirium, or coma. Cerebellar symptoms such as ataxia, dysmetria, and dysarthria may be present, as the Purkinje cells of the cerebellum are particularly sensitive to the effects of increased temperature.

Cardiovascular findings may include hypotension and progression to distributive shock with high cardiac output and low vascular resistance due to vasodilation and dehydration. Cardiogenic shock can occur from temperature-induced myocardial injury and necrosis with subsequent cardiac depression and, ultimately, failure.

Pulmonary findings include noncardiogenic pulmonary edema and progress to ARDS due to direct thermal injury to the endothelium of the pulmonary vasculature. Patients may be tachypneic from increased oxygen demands and underlying metabolic acidosis.

Acute liver injury or failure may develop due to ischemia as blood gets preferentially shunted from the splanchnic circulation to skin and muscles. Ischemia may also precipitate ulcerations that result in frank bleeding. Presence of liver failure may indicate associated toxic ingestion such as stimulants or acetaminophen.

Acute kidney injury with or without rhabdomyolysis is commonly seen. Hypoglycemia is common in patients with combined liver and kidney injuries. With nonexertional heatstroke, the incidence of acute renal failure occurs, on average, in about 5% of patients as a result of dehydration. In comparison, in exertional heatstroke, the rate rises up to 35% of cases.

Heat injury affects the hematologic system in several ways. Leukocytosis may be noted secondary to catecholamine release and hemoconcentration. Coagulopathy may occur either due to the direct compromise of platelets and coagulation factor functions by hyperthermia, decrease in coagulation factor synthesis due to liver injury, decrease in platelet and megakaryocyte counts, or impacts on platelet aggregation. Disseminated intravascular coagulation is a notable complication, as it is present in most cases of fatal heatstroke and is associated with more severe dysfunction of other organ systems. It is thought to be due to the activation of the clotting cascade by vascular endothelial damage and generalized cell necrosis.

Diagnostic work-up

Diagnostic work-up begins with assessment of core temperature via the rectum, bladder, or esophagus. A comprehensive set of labs should be obtained to include complete blood cell count, comprehensive metabolic panel, magnesium, phosphorus, coagulation profile, D-dimer, arterial or venous blood gas, lactate, creatine kinase, urinalysis, urine drug screen, thyroid panel, acetaminophen and salicylate levels, random cortisol, troponin, and pro-brain natriuretic peptide level.

Chest radiograph is helpful to assess for signs of pulmonary involvement and to exclude complications like aspiration. An electrocardiogram should be completed to assess dysrhythmias, conduction disturbances, myocardial ischemia, or overt infarction. Point-of-care ultrasound is a beneficial tool to examine volume status, determine volume responsiveness, and evaluate for pulmonary edema. Advanced neuroimaging to include head CT scan or brain MRI may be considered depending on the given patient’s clinical presentation.

Management and treatment

Heatstroke management focuses upon controlling the patient’s core body temperature, with the goal of lowering the core body temperature to 38 °C as rapidly as possible with continuous monitoring. All active cooling measures should be stopped once temperature reaches 38 °C to 39 °C to prevent overshooting and inducing iatrogenic hypothermia.

A multimodal cooling strategy should be implemented with both internal and surface cooling approaches. Internal cooling is achieved via instillation of refrigerated crystalloid. Each liter of chilled crystalloid can reduce body temperature by roughly 1 °C. For surface cooling, it is important to first remember to remove all clothing from patients. Immersive ice baths are helpful, with an estimated cooling rate of about 0.2 °C per minute. Evaporative cooling is an alternative method to consider if an immersive ice bath is not available. This may be accomplished by spraying the patient with lukewarm water while a fan is directed at them.

Additional therapies include placing a cooling blanket underneath the patient and applying ice packs to junctional areas with increased heat exchange capacity, such as the neck, axillae, and groin. It is prudent to avoid the use of antipyretic agents, as the underlying mechanism does not involve a change in the hypothalamic set point and may increase risk of iatrogenic injury to the liver and renal system.

Ensuring adequate patient sedation is another important management principle. Agitation must be avoided, as this physical activity increases heat generation and risk of rhabdomyolysis. Potential medication options include benzodiazepines (muscle relaxation, antiseizure effects), opioids, ketamine, propofol (antiseizure effects), and dexmedetomidine.

Shivering suppression is another important objective, as shivering can impair temperature management and should be intentionally controlled during the acute cooling phase. Potential medication options include benzodiazepines, dexmedetomidine, fentanyl, ketamine, and IV magnesium. Neuromuscular blocking agents can be considered in patients who are intubated.

Patients should also be continuously assessed for indications for intubation, such as severe rigidity interfering with temperature control, status epilepticus, any inability to protect their own airway, or worsening respiratory failure. Intubation may also be needed in situations where the cause of heatstroke is unclear, and the patient is too agitated or combative to undergo needed diagnostic studies.

Overall morbidity and mortality are directly related to the peak temperature reached and total time spent at elevated temperatures. There is evidence that suggests delaying treatment by just 2 hours can result in increased mortality up to 70%. This highlights the urgency in swiftly recognizing and aggressively treating heatstroke. Within older populations, mortality from heatstroke exceeds 50% in patients who present with organ dysfunction.

Lastly, preventative measures should be highlighted often and implemented for those at risk. This includes increasing patient awareness about risk factors for and signs of symptoms of heatstroke. Counseling should be provided to modify activities when in severe heat and/or humid environments, ensure adequate hydration during waking hours, and wear clothing that allows for ventilation and evaporative cooling. Patients should be specifically reminded to change their clothing if saturated with sweat, as this impairs evaporative cooling.

In summary, hyperthermia is a condition with a potentially high degree of morbidity and mortality. While it shares features and complications with other conditions associated with systemic inflammation, it has unique and critical aspects of management that must be considered to ensure proper management.

References

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