Heat illness refers to a condition caused by dysfunction of the thermoregulatory center, failure of sweat gland function, and excessive loss of water and electrolytes under conditions of hot weather, high humidity, and an airless environment. The incidence rate is estimated at 17.6–26.5 cases per 100,000 population, with high-incidence areas like Saudi Arabia reaching up to 250 cases per 100,000. Global climate change has led to increased average temperatures and a rise in the frequency, duration, and intensity of extreme heat events. Over the past decade, many regions across Europe, the Americas, and Asia have experienced extreme heat waves. Between 2000 and 2020, heat mortality among individuals aged 65 and above increased by 54%. Heatstroke, also known as sunstroke, is the primary cause of death associated with heat illness. In the United States, mortality due to heat illness during heatwaves is approximately 10 times higher than during non-heatwave periods. Among American athletes, heatstroke ranks as the third most common cause of death after spinal cord injuries and cardiac arrest.
Etiology
Heat illness occurs most frequently under conditions of high atmospheric temperature (>32°C or 89.6°F), high humidity (>60%), inadequate acclimatization to heat, prolonged exposure to or physical activity under hot conditions (e.g., work, exercise, or military training), and insufficient heat mitigation measures. In environments with high indoor temperatures and no air conditioning, certain populations, such as individuals who are obese, malnourished, elderly and frail, or those with chronic illnesses, are more prone to heat illness. Studies have shown that medical conditions like myocardial infarction or cerebrovascular accidents can increase the risk of heat illness by tenfold. Common causes of heat illness include:
- High environmental temperatures: Heat is absorbed by the human body from the surrounding environment.
- Increased heat production: Heavy physical labor, fever, hyperthyroidism, and the use of certain drugs (e.g., amphetamines) can elevate heat production.
- Impaired heat dissipation: Conditions such as high humidity, obesity, tight or poorly ventilated clothing, and calm atmospheric conditions hinder heat dissipation.
- Sweat gland dysfunction: The primary method of heat dissipation in humans is through sweating. Disorders like systemic sclerosis, extensive skin scarring, congenital anhidrosis, or the use of anticholinergic drugs and illicit drugs can inhibit sweating.
These factors can trigger or exacerbate the development of heat illness.
Pathogenesis
For healthy individuals, axillary temperature typically ranges from 36–37.4°C (96.8–99.3°F), while rectal or core temperature ranges from 36.9–37.9°C (98.4–100.2°F). The hypothalamic thermoregulatory center maintains relative thermal stability by regulating heat production and dissipation based on external environmental conditions.
Thermoregulation
Mechanisms of Thermoregulation
Heat Production
Heat is primarily generated through oxidative metabolism within the body. Physical activity and shivering also contribute to heat generation. At an ambient temperature of approximately 28°C (82.4°F), the body produces 210–252 kJ (50.4–60.48 kcal) of heat per square meter per hour in a resting state. For a person weighing 70 kg (154 lbs), basal metabolic heat production is approximately 418.7 kJ (100 kcal) per hour, which can increase body temperature by 1.1°C (2°F) in the absence of cooling mechanisms. During intense physical activity, heat production may increase 10–20 times compared to resting states, reaching approximately 2,520–3,780 kJ (604.8–907.2 kcal) per square meter per hour and accounting for 90% of total heat production.
Heat Dissipation
When body temperature rises, the autonomic nervous system induces skin vasodilation, increasing blood flow to approximately 20 times the normal level. This process, coupled with sweating, facilitates heat dissipation while also causing the loss of water and electrolytes. Heat exchange between the body and the surrounding environment occurs through the following mechanisms:
- Radiation: Accounts for approximately 60% of total heat dissipation. At ambient temperatures between 15–25°C (59–77°F), radiation is the primary method of heat loss.
- Evaporation: Accounts for approximately 25% of heat dissipation. In high-temperature environments, evaporation becomes the dominant mechanism. Each liter of sweat evaporated from the skin dissipates approximately 2,436 kJ (580 kcal) of heat. Relative humidity exceeding 75% reduces evaporation, and when humidity reaches 90–95%, evaporation ceases entirely.
- Convection: Accounts for approximately 12% of heat dissipation. The rate of heat loss depends on the temperature gradient between the skin and the environment as well as air movement.
- Conduction: Accounts for approximately 3% of heat dissipation. Heat conduction is more efficient in water than in air. Direct skin contact with water increases heat dissipation by 20–30 times compared to normal conditions.
Adaptation to High Temperatures
In hot environments, physical activity can produce 1–2 liters of sweat per hour, and in some cases, up to 4 liters per hour. Adaptation to heat requires daily exertion in hot conditions for 100 minutes over 7–14 days to achieve optimal acclimatization. Adaptations include increased cardiac output and sweat production, reduced sodium content in sweat, and enhanced thermal regulation that allows for double the heat dissipation compared to non-acclimated individuals. For example, trained marathon runners can tolerate rectal temperatures as high as 42°C (107.6°F) without adverse effects. In contrast, individuals without such adaptive and compensatory mechanisms are more susceptible to heat illness.
Effects of High-Temperature Environments on Human Systems
Heat damage primarily results from hyperthermia (body temperature >42°C), which directly injures cells. This damage includes enzyme denaturation, mitochondrial dysfunction, loss of cellular membrane stability, and disruption of aerobic metabolic pathways, ultimately leading to multiple organ dysfunction or failure.
Central Nervous System
Hyperthermia can cause rapid death of brain and spinal cord cells, resulting in secondary focal cerebral hemorrhage, edema, increased intracranial pressure, and coma. Cerebellar Purkinje cells are particularly sensitive to heat, often leading to symptoms such as dysarthria, ataxia, and dysmetria.
Cardiovascular System
Patients with heatstroke often exhibit a hyperdynamic circulatory state characterized by reduced peripheral vascular resistance, tachycardia (heart rate >180 beats per minute), elevated cardiac index, and increased central venous pressure (CVP). Prolonged high temperatures can lead to myocardial ischemia and necrosis, triggering arrhythmias and exacerbating heart failure. This in turn causes a decrease in cardiac output and reduced skin blood flow, impairing heat dissipation and creating a vicious cycle.
Respiratory System
During hyperthermia, respiratory rate and ventilation increase significantly. Prolonged hyperventilation without relief can result in respiratory alkalosis. In cases of heatstroke, endothelial damage in pulmonary vasculature may lead to acute respiratory distress syndrome (ARDS).
Water and Electrolyte Metabolism
Within the second week of heat acclimatization, total body potassium levels may decrease by more than 20% (approximately 500 mmol) due to losses from sweating, urination, and inadequate supplementation. Excessive sweating often results in significant water and sodium depletion, leading to dehydration and electrolyte imbalances.
Kidneys
Severe dehydration, cardiovascular dysfunction, and rhabdomyolysis can lead to acute kidney injury (AKI).
Gastrointestinal System
Direct thermal damage and reduced gastrointestinal blood perfusion during heat illness may cause ischemic ulcers, which increase the risk of significant gastrointestinal bleeding. Among heatstroke patients, hepatic necrosis and cholestasis of varying degrees are almost universally observed 2–3 days after onset.
Hematological System
In severe cases of heat illness, disseminated intravascular coagulation (DIC) may occur 2–3 days after onset. DIC further exacerbates dysfunction or failure in essential organs such as the heart, liver, and kidneys.
Muscles
In exertional heatstroke patients, localized hyperthermia in muscles, combined with hypoxia and metabolic acidosis, often leads to severe muscle damage, rhabdomyolysis, and elevated serum creatine kinase levels.
Pathology
Post-mortem examination of heatstroke victims reveals necrosis in cerebellar and cerebral cortical neurons, with Purkinje cell degeneration being particularly prominent. The heart shows focal myocardial hemorrhage, necrosis, and lysis, as well as hemorrhage in the epicardial, endocardial, and valvular tissues. Liver pathology includes varying degrees of hepatocyte necrosis and cholestasis. Adrenal cortical hemorrhage is also frequently observed. In cases of exertional heatstroke, pathological findings include degeneration and necrosis of muscle tissue.
Clinical Presentation
Based on different pathophysiological mechanisms and clinical manifestations, heat illnesses are typically categorized into heat cramp, heat exhaustion, and heatstroke. These conditions may develop sequentially or overlap with each other.
Heat Cramp
Following intense physical activity, heat cramp often occurs after excessive sweating and consumption of hypotonic fluids. Symptoms include headache, dizziness, and painful spasms of the limbs and abdominal muscles, which may limit movement. Abdominal pain may resemble symptoms of an acute abdomen. Symptoms generally resolve within a few minutes. Core body temperature (CBT) does not significantly increase, and there are no alterations in consciousness. Heat cramp may also represent an early manifestation of heatstroke.
Heat Exhaustion
This condition is more commonly observed in older adults, children, and patients with chronic illnesses. It results from severe heat stress, leading to excessive fluid and sodium loss and subsequent hypovolemia. Symptoms include profuse sweating, fatigue, weakness, dizziness, headache, nausea, vomiting, and muscle spasms. Tachycardia, orthostatic hypotension, or fainting may be present. CBT may rise but does not exceed 40°C, and there is no evidence of altered mental status. Laboratory findings often reveal elevated hematocrit, hypernatremia, mild azotemia, and abnormal liver function, with transaminase levels sometimes increasing to several thousand units.
Heatstroke
Heatstroke is characterized by severe hyperthermia (CBT >40°C) accompanied by altered mental status. Early damage typically affects the brain, liver, kidneys, and heart. Based on the patient's clinical context and underlying mechanisms, heatstroke is further classified into exertional heatstroke and non-exertional heatstroke. Exertional heatstroke results from excessive endogenous heat production, while non-exertional heatstroke arises from impaired thermoregulation and failed heat dissipation. According to the U.S. Centers for Disease Control and Prevention (CDC), CBT in heatstroke can spike to 41.1°C or higher within 10–15 minutes.
Exertional Heatstroke
Exertional heatstroke primarily affects young and healthy individuals after intense physical activity or labor, typically developing within a few hours. Approximately 50% of patients experience profuse sweating. Heart rate ranges from 160 to 180 beats per minute, with widened pulse pressure. Complications may include rhabdomyolysis, acute kidney injury, liver failure (liver transaminases can increase to tens of thousands of units within 24 hours), disseminated intravascular coagulation (DIC), or multi-organ dysfunction syndrome (MODS). The condition carries a high mortality rate.
Non-Exertional Heatstroke
Non-exertional heatstroke primarily affects frail older adults or postpartum women residing in poorly ventilated environments. Other high-risk groups include individuals with schizophrenia, Parkinson's disease, chronic alcoholism, hemiplegia, or paraplegia. Between 84% and 100% of patients exhibit anhidrosis, with hot, dry, and flushed skin. Rectal temperature can reach up to 46.5°C. Early symptoms may include abnormal behavior or seizure-like activity, followed by delirium, coma, and symmetric pupillary constriction. Severe cases may feature hypotension, shock, arrhythmias, heart failure, pulmonary edema, and cerebral edema. Approximately 5% of patients develop acute kidney injury, and mild to moderate DIC may occur. Death frequently ensues within 24 hours.
Laboratory Investigations
Severe cases often exhibit laboratory evidence of damage to the liver, kidneys, pancreas, and skeletal muscles. Urgent biochemical evaluations are critical for identifying organ dysfunction and include tests such as serum aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), coagulation function studies, and arterial blood gas analysis. For suspected intracranial hemorrhage or infection, brain CT and cerebrospinal fluid analysis are necessary.
Diagnosis and Differential Diagnosis
In hot summer conditions, hyperpyrexia accompanied by coma should raise strong suspicion for heatstroke. Differential diagnosis of heatstroke should consider conditions such as encephalitis, meningitis, typhoid fever, epidemic typhus, malignant malaria, thyroid storm, delirium tremens, hypothalamic hemorrhage, anticholinergic drug toxicity, and neuroleptic malignant syndrome.
Treatment
Although the types and causes of heat illnesses vary, the fundamental treatment approaches are consistent.
Cooling Therapy
Rapid cooling serves as the cornerstone of treatment and plays a decisive role in determining the prognosis of affected patients. For exertional heatstroke, the recommended timeframe for initiating cooling has been shortened from the "golden hour" to the "golden half-hour."
External Cooling
Patients are relocated to a well-ventilated, cool environment, with clothing removed and accompanied by skin and muscle massage to promote heat dissipation. For patients without circulatory collapse, the "gold standard" for rapid cooling involves cold water immersion (CWI) or ice water immersion (IWI). The body (excluding the head) is submerged as fully as possible in water at temperatures between 2.0°C and 14.0°C. Continuous agitation of the water maintains contact between cool water and the skin. Ice packs wrapped in wet towels may be placed around the head. This method reduces body temperature from 43.3°C to below 40.0°C within 20 minutes. For patients with circulatory collapse, evaporative cooling methods, such as repeated application of cold water (15°C) to the skin and use of fans or air conditioners, may be employed. Cooling measures are halted once the body temperature drops to 39°C.
Internal Cooling
For cases in which external cooling proves ineffective, techniques such as ice saline lavage through the stomach or rectum, sterile saline lavage of the peritoneal cavity, or blood dialysis can be utilized. Alternatively, chilled autologous blood may be returned to the body after extracorporeal cooling.
Pharmacological Cooling
Antipyretic agents, including salicylate-based drugs, prove ineffective in heatstroke patients and may cause harm. If rapid cooling triggers shivering, intravenous infusion of 500 ml physiological saline combined with 25–50 mg chlorpromazine is administered, alongside blood pressure monitoring.
Treatment of Complications
Coma
Intubation ensures airway patency and prevents aspiration. For patients with elevated intracranial pressure, intravenous infusion of 1–2 g/kg of mannitol over 30–60 minutes is administered. Diazepam is given intravenously for seizure management.
Fluid Resuscitation
In hypotensive patients, intravenous infusion of physiological saline or lactated Ringer's solution restores circulatory volume, with an average of 1,200 ml isotonic crystalloid solution replenished over the initial 4 hours. If needed, isoproterenol may be administered via IV drip. Vasopressors are avoided since they may impede heat dissipation through the skin.
Multi-Organ Failure
Symptomatic and supportive care is required. For instances of rhabdomyolysis, urine output should be maintained at a rate of at least 2 ml/(kg·h), with urinary pH greater than 6.5. Digoxin should be used cautiously in cases of heart failure accompanied by renal dysfunction and hyperkalemia. Persistent anuria, uremia, and hyperkalemia necessitate blood or peritoneal dialysis. Administration of H2 receptor antagonists or proton pump inhibitors assists in preventing stress ulcers and upper gastrointestinal bleeding. Patients with DIC may require transfusion of fresh frozen plasma and platelets based on clinical severity.
Monitoring
Continuous monitoring of temperature during the cooling process is undertaken to gradually reduce core body temperature to a range of 37–38°C.
Placement of a Foley catheter allows for urinary output monitoring, with a target output above 30 ml/h.
For hyperthermic patients, correction of arterial blood gas parameters is essential. At temperatures above 37°C, PaO2 decreases by 7.2%, PaCO2 increases by 4.4%, and pH drops by 0.015 for each additional degree Celsius.
Coagulation disorders may manifest within 24 hours of onset, with peak incidence occurring between 48–72 hours. Close monitoring of DIC-related laboratory parameters, such as fibrinogen levels, fibrin degradation products, prothrombin time, and platelet counts, is required.
Prognosis
The mortality rate associated with heatstroke ranges from 20% to 70%, with rates rising to 80% for patients over 50 years of age. Prognosis depends more on the cooling speed within the first 30 minutes of symptom onset than on the initial body temperature. Mortality is typically avoided when rectal temperature is reduced to below 40°C during this timeframe. Delayed cooling substantially increases mortality risk. Prognosis is further determined by the number of organ failures, with patients experiencing anuria, coma, or heart failure exhibiting higher mortality rates. Prolonged comas exceeding 6–8 hours or the onset of DIC are associated with poor outcomes. Elevated serum lactate levels may serve as prognostic indicators.
Prevention
Education campaigns on heat illness prevention should be carried out during hot summer months. Wearing loose, light-colored, breathable clothing, along with wide-brimmed hats and sunscreen, may mitigate risks during outdoor activities.
Extreme heat should prompt minimization of outdoor activities, particularly from 11:00 AM to 3:00 PM, to avoid prolonged sun exposure.
Environmental improvements should target the living conditions of vulnerable populations, including older adults, individuals with chronic illnesses, and postpartum women.
Efforts to improve working conditions in high-temperature environments should be undertaken, along with consistent consumption of hypotonic fluids (<200 mOsm/kg H2O) containing electrolytes such as potassium, magnesium, and calcium.
Patients recovering from heat illness should refrain from intense outdoor activities under direct sunlight for several weeks.