Hyperthermia

Hyperthermia, commonly referred to as overheating, is a condition in which the body temperature rises above its normal range due to a failure of thermoregulation. In this state, the body generates or absorbs more heat than it can dissipate, resulting in a potentially dangerous elevation in core temperature. When temperature increases become extreme, hyperthermia constitutes a medical emergency that requires urgent intervention to prevent long-term disability or death. Globally, it is estimated that hundreds of thousands of deaths occur each year as a result of hyperthermia. The condition most frequently develops from heat stroke or adverse drug reactions, although trauma-related disruptions in brain temperature control may also contribute.

Definition and Classification

Hyperthermia is defined in humans as a body temperature that rises significantly above normal without any change in the thermoregulatory set point. Unlike fever, which results from a controlled upward shift in the body’s set point, hyperthermia represents an uncontrolled elevation due to external or internal heat load. Normal human temperature fluctuates during the day and may be higher in the late afternoon, but hyperthermia requires a marked increase from the expected physiological level.
Elevations in temperature range from mild to severe. Body temperatures exceeding approximately 40°C are considered dangerous and may quickly lead to organ damage. The opposite condition, hypothermia, occurs when body temperature falls below that required for normal metabolism.

Signs and Symptoms

Hyperthermia often begins with heat exhaustion, heat stress or heat prostration. Early symptoms include excessive sweating, rapid breathing and a fast but weak pulse. As the condition progresses to heat stroke, the skin may become hot and dry because vasodilation increases heat loss while perspiration decreases.
Individuals with neurological disease-related hyperthermia may experience anhidrosis, cardiovascular instability and confusion or delirium. Additional symptoms include dehydration, nausea, vomiting, headache and low blood pressure, which may lead to dizziness or fainting, particularly when standing. Severe heat stroke may cause marked confusion, agitation, tachycardia and tachypnoea. A drop in blood pressure may lead to pale or blue-tinged skin. In young children, seizures are relatively common. Without prompt treatment, hyperthermia may progress to multi-organ failure, unconsciousness and death.

Causes and Mechanisms

Heat stroke represents the most serious form of hyperthermia and arises when thermoregulation is overwhelmed by excessive metabolic heat production, physical exertion or extreme environmental conditions. In severe cases, core temperatures may exceed 41°C. Heat stroke may occur without exertion, known as classical heat stroke, or may be exertional, which is commonly associated with strenuous physical activity in hot, humid environments.
Heat loss normally depends on evaporation through sweating and heat dissipation via vasodilation. When humidity is high, evaporative cooling becomes inefficient, and factors such as dehydration, inadequate water intake, alcohol consumption and lack of ventilation or air conditioning may worsen heat retention.
At high temperatures, enzymatic activity in metabolic pathways becomes disrupted. Essential enzymes may denature, reducing the efficiency of biochemical reactions and affecting high-demand organs such as the brain and heart. Loss of fluid and electrolytes can produce heat cramps, characterised by painful muscle spasms lasting several minutes. These cramps typically occur in heavily used muscles after vigorous exertion.

Situational Hyperthermia

Situational or non-exertional hyperthermia occurs without significant physical activity and commonly affects the very young and the elderly. In older individuals, reduced cardiovascular, renal and respiratory function may limit thermoregulation. Medications such as anticholinergic drugs, antihistamines and diuretics may further diminish sweating and vasodilation.
During heat waves, mortality rates rise sharply. The 1995 Chicago heatwave resulted in more than 700 documented deaths, with the highest risk observed in individuals confined to bed or living alone. Access to air conditioning and transportation significantly reduced risk. Many heat-related deaths may be underreported due to misclassification as cardiac or cerebrovascular events.

Drug-Induced Hyperthermia

Multiple therapeutic and recreational drugs can precipitate hyperthermia. Psychotropic medications, including selective serotonin reuptake inhibitors, monoamine oxidase inhibitors and tricyclic antidepressants, may trigger serotonin syndrome, a condition sometimes associated with tremor, agitation and hyperthermia. Neuroleptic malignant syndrome, a reaction to neuroleptic agents, may present with lead-pipe rigidity and severely elevated temperature.
Recreational substances such as amphetamines, cocaine, LSD, phencyclidine, dextromethorphan and MDMA can significantly increase metabolic heat production. Rarely, exposure to certain anaesthetic agents may cause malignant hyperthermia, a genetically mediated, potentially fatal reaction characterised by rapid temperature escalation.
Drugs that impair parasympathetic activity, particularly muscarinic antagonists, may lead to mild hyperthermic episodes by reducing the body’s ability to cool. Agents that uncouple oxidative phosphorylation, such as 2,4-dinitrophenol once used for weight loss, can produce dangerous rises in temperature.

Occupational and Environmental Factors

Individuals working in hazardous environments, such as industrial settings, emergency response, firefighting and military operations, often rely on personal protective equipment (PPE) for safety. PPE may include hazmat suits, body armour and bomb disposal suits, which create microclimates that impede heat dissipation by increasing thermal resistance and reducing vapour permeability. Combined with physical exertion, high ambient temperatures and direct sunlight, PPE substantially increases the risk of heat stress. During the Ebola outbreak in West Africa, healthcare workers could remain in protective suits for only short periods due to the risk of heat stroke.

Other Medical Causes

Certain medical disorders contribute to hyperthermia. Conditions such as thyrotoxicosis and adrenal tumours like phaeochromocytoma increase metabolic heat production. Damage to the hypothalamus from traumatic brain injury, brain haemorrhage, status epilepticus or other neurological insults may disrupt central thermoregulation, leading to uncontrolled temperature elevation.

Pathophysiology

Hyperthermia reflects an uncontrolled rise in body temperature above the thermoregulatory set point, with the normal temperature range remaining unchanged. In contrast, fever involves a regulated increase in the set point itself. As temperature rises in hyperthermia, cellular proteins and enzymes begin to lose stability, compromising metabolic functions across multiple organ systems. The cardiovascular system initially compensates through increased heart rate and vasodilation, but persistent stress may lead to circulatory collapse.