Heat stroke in children

INTRODUCTION — The manifestations, evaluation, and management of heat stroke in children will be reviewed here. Other forms of heat illness in children and hyperthermia in the adult patient are discussed separately. (See "Heat illness (other than heat stroke) in children" and "Severe nonexertional hyperthermia (classic heat stroke) in adults" and "Malignant hyperthermia: Diagnosis and management of acute crisis".)

DEFINITIONS

Hyperthermia — Hyperthermia is a physiologic process defined as elevation of core body temperature above the normal diurnal range of 36 to 37.5°C (96.8 to 99.5°F) due to failure of the body's innate thermoregulation. Heat-related illnesses are various clinical manifestations of hyperthermia caused by excessive environmental heat exposure. They range from minor syndromes (table 1) to life-threatening processes (table 2). While there are many manifestations of heat-related illnesses, all heat-related illnesses result from excessive heat stress caused by an increased environmental heat burden, an inability of the body to dissipate endogenous heat, or a combination of these two factors. Heat stroke is the most severe heat-related illness and can rapidly lead to death without prompt treatment.

In contrast to hyperthermia, fever is the body's response to infection or inflammation; it is induced by cytokine activation, regulated at the level of the hypothalamus, and is a normal host response.

Heat stroke — Heat stroke occurs in patients with environmental heat exposure and is defined as a core body temperature ≥40 to 40.5^oC (104 to 105°F) accompanied by central nervous system (CNS) dysfunction [1]. While anhidrosis (lack of sweating) is frequently present, especially with classic heat stroke, this is not an absolute diagnostic criterion [1,2]. This condition represents a failure of the body's ability to maintain thermoregulatory homeostasis. Heat stroke is further classified as follows:

●Classic (nonexertional) heat stroke – Classic heat stroke arises from environmental exposure to heat and is more common in younger children who are unable to escape from hot environments and those with underlying chronic medical conditions that impair thermoregulation (table 3).

●Exertional heat stroke – Exertional heat stroke generally occurs in young, otherwise healthy individuals who engage in heavy exercise during periods of high ambient temperature and humidity. Typical patients are athletes, especially football players [3], and military personnel [4,5].

EPIDEMIOLOGY — Heat-related deaths occur with regularity in the United States. Between 2004 and 2018, an average of 702 heat-related deaths occurred annually [6]. The highest rates of death from heat-related illness are in the older adult population and in adult patients with comorbid disease [7-11], but young children are also at risk [6]. For example, infants and young children, who cannot operate car door locks or who are restrained in car seats, may suffer morbidity or mortality when left unattended in vehicles, as temperatures inside a closed vehicle rapidly rise to dangerous levels even when ambient temperature is only moderately high [12-15].

Among teenage athletes, heat illness is the third major cause of death behind traumatic and cardiac causes [16-18]. The highest rate of nonfatal heat illness in United States high school athletes is found among American football players, who account for 4.5 episodes of heat illness and limitation of athletic activity per 100,000 athlete exposures [19]. American football is also the leading activity associated with an emergency department evaluation for heat illness in United States patients ≤19 years of age [20,21]. Approximately two-thirds of these episodes occur in August, and increased body mass index (ie, being overweight or obese) appears to pose a significant risk. Prescription amphetamines for attention deficit hyperactivity disorder (ADHD) and dietary supplements including creatine may also contribute to subclinical dehydration and heat stroke in selected athletes [22].

In the United States, the estimated annual incidence of heat-related emergency department (ED) visits for heat stroke and other heat-related conditions has ranged from 18 to 32 ED visits per 100,000 persons over 10 years with the highest incidence occurring in 2018, the last year of the study [23]. Children 0 to 17 years old accounted for over 12 percent of total visits during this period. Furthermore, in Japan, increased incidence of ambulance transports for heat stroke was associated with daily maximum temperature or wet bulb globe temperature, with the highest incidence in adults ≥ 65 years, followed by children 7 to 17 years old and lowest in adults 18 to 64 years [24].

PATHOPHYSIOLOGY — Body temperature is maintained within a narrow range by balancing heat load with heat dissipation. The body's heat load results from both metabolic processes and absorption of heat from the environment [25]. As core temperature rises, the preoptic nucleus of the anterior hypothalamus stimulates efferent fibers of the autonomic nervous system to produce sweating and cutaneous vasodilation to allow for reduction of body heat.

Evaporation is the principal mechanism of heat loss in a hot environment, but this becomes ineffective above a relative humidity of 75 percent [26]. The other major methods of heat dissipation; radiation (emission of infrared electromagnetic energy), conduction (direct transfer of heat to an adjacent, cooler object), and convection (direct transfer of heat to convective air currents) cannot efficiently transfer heat when environmental temperature exceeds skin temperature (typically 35°C or 95°F).

Temperature elevation is accompanied by an increase in oxygen consumption and metabolic rate, resulting in hyperpnea and tachycardia [4]. Above 42°C (108°F), oxidative phosphorylation becomes uncoupled and a variety of enzymes cease to function. Hepatocytes, vascular endothelium, and neural tissue are most sensitive to these effects, but all organs may be involved. As a result, patients with these elevated temperatures are at risk of multiorgan failure.

The critical thermal maximum (CTM) is defined as the degree of elevated body temperature and duration of heat exposure that can be tolerated before cell damage occurs [27]. Children sustain serious heat-related injury when the CTM is exceeded. Human thermal maximum is estimated as a core body temperature of 42°C (107.6°F) lasting between 45 minutes and 8 hours.

Physiologic heat stress causes cell injury through several proposed mechanisms:

●Production of acute-phase reactants (eg, cytokines) that initiate an inflammatory cascade [1,28]

●Direct injury to cells with denaturation of proteins [29]

●Direct injury to the vascular endothelium resulting in impaired microcirculation and disseminated intravascular coagulation [30,31]

●Intestinal ischemia and increased permeability followed by endotoxemia [29]

These pathophysiologic changes result in a systemic inflammatory response that causes multiple organ dysfunction and injury [1]. The cascade of acute-phase reactants is countered, to some degree, by the production of heat shock proteins, which confer protection by preventing unfolding of denatured proteins and by impeding cytokine production [28].

In addition to the height of ambient temperature and humidity levels, much of the risk for heat illness in children is attributable to general anatomic and physiologic characteristics [32-34]:

●Heat production – Children produce more metabolic heat per kilogram of body weight because they have a higher basal metabolic rate than adults [32].

●Body surface area – Younger children have a higher surface area to mass ratio, resulting in a greater rate of heat absorption in hot environments [34]. However, body composition (especially an increase in body fat) and lack of fitness are likely more important contributors to susceptibility to heat illness in older children and adolescents [34].

●Blood circulation – Children have a smaller absolute blood volume, which limits the potential of blood-borne heat transfer from the body core to the body surface, where this heat can be dissipated [35]. In addition, children have a lower cardiac output at a given metabolic rate than adults, further limiting heat dissipation during exercise [32].

●Sweat production – Children have a lower rate of sweating than adults as a result of a lower sweat rate per gland and begin sweating at a higher body temperature [32,36,37].

●Fluid replenishment – If not appropriately supervised, children are more likely to inadequately replenish fluid losses during prolonged exercise [33,34,38,39].

●Acclimatization – Physiologic changes that result in increased heat tolerance include increased rate of sweating, a lower temperature threshold for sweating, reduced electrolyte losses in sweat, lower heart rate, increased aldosterone production with decreased urinary sodium, and lower core and skin temperatures [40,41]. Children achieve these adaptations to a hot environment more slowly than adults and typically require 10 to 14 days to achieve adequate acclimatization [32,34].

Medical conditions that may increase the susceptibility to heat illness in specific individuals are provided in the table (table 3).

CLINICAL FEATURES — The diagnostic criteria for patients with heat stroke are elevated core temperature (≥40 to 40.5° C [104 to 105° F]) and central nervous system (CNS) abnormalities following environmental heat exposure. However, because of the inherent variability in thermometry, the ability for acclimatized individuals (eg, conditioned athletes) to tolerate temperatures that exceed this threshold, and the potential of cooling between the time of injury and temperature measurement, CNS dysfunction, rather than a temperature cutoff, should be the main diagnostic criterion to identify patients with heat stroke [42].

There is some overlap of symptoms between heat exhaustion and heat stroke (table 2). While the distinction between heat exhaustion and heat stroke is sometimes unclear, children with elevated body temperature and CNS abnormalities should be treated as victims of heat stroke, given the significant morbidity and mortality associated with this condition. (See "Heat illness (other than heat stroke) in children", section on 'Heat exhaustion'.)

CNS symptoms may be subtle or deceptive and can be manifested as impaired judgment or inappropriate behavior. However, children commonly present with more significant neurologic symptoms such as seizures, delirium, hallucinations, ataxia, dysarthria, or coma.

Other typical clinical manifestations include tachycardia and tachypnea. The skin may be flushed and warm or diaphoretic. Vomiting and diarrhea are also common. In addition, those patients with coagulopathy may demonstrate purpura, hemoptysis, hematemesis, melena, or hematochezia.

DIAGNOSTIC EVALUATION

Core body temperature and clinical findings — The diagnosis of heat stroke is based upon a careful history and physical examination (table 2). Core body temperature should be determined in all patients and, ideally, monitored continuously. Rectal temperature is the most commonly obtained core temperature measurement, although esophageal, central venous, pulmonary artery, or bladder probe temperature are potential alternatives. Oral, axillary, or tympanic membrane temperatures are unreliable for diagnosis and managing heat illness [32].

The differential diagnosis of hyperthermia should be considered in each patient. The context in which symptoms develop usually suggests the etiology (eg, evidence of environmental heat stress in patients with heat stroke, serotonin syndrome in patients receiving serotonergic agents, or sepsis among children with an infectious prodrome). (See 'Differential diagnosis' below.)

Laboratory findings — Patients with heat stroke have abnormal laboratory findings, reflecting the systemic inflammatory response and end-organ damage resulting from heat stress. Laboratory studies should include:

●Rapid blood glucose to identify hypoglycemia [43]

●Blood gas determination (venous or arterial) to evaluate for the presence and severity of metabolic acidosis (especially in patients with exertional heat stroke) and respiratory alkalosis [44]

●Complete blood count, prothrombin time, partial thromboplastin time, and international normalized ratio to detect anemia and disseminated intravascular coagulation [30,31,43]

●Serum electrolytes to check for increased or decreased sodium and potassium levels [43]

●Liver enzymes (aspartate aminotransferase and alanine aminotransferase) to assess for liver injury

●Blood urea nitrogen and/or serum creatinine to identify prerenal azotemia or renal failure resulting from myoglobinuria

●Serum creatine kinase, ionized or total calcium, and phosphate to detect rhabdomyolysis and associated hypocalcemia and hyperphosphatemia

●Urine rapid dipstick and microscopic urinalysis to diagnose myoglobinuria, which should be suspected in a patient who has a brown urine supernatant that tests positive for hemoglobin, but does not have increased red blood cells seen on microscopic analysis (see "Rhabdomyolysis: Clinical manifestations and diagnosis" and "Clinical features and diagnosis of heme pigment-induced acute kidney injury")

●Toxicologic screening for drugs of abuse or prescribed medications in those patients for whom an illicit drug or medication side effect is suspected

Ancillary studies — Additional studies may be indicated based on the patient's clinical presentation and response to treatment:

●Chest radiograph – A chest radiograph helps identify pulmonary edema in patients who develop persistent high-output cardiac insufficiency and is useful in patients for whom pulmonary aspiration is a concern.

●Electrocardiogram – An electrocardiogram should be obtained in patients with electrolyte abnormalities (eg, hyperkalemia, hypokalemia, hypocalcemia) and/or rhabdomyolysis.

●Computed tomography – A computed tomography scan of the head should be obtained if a child has persistently altered mental status despite cooling or shows signs of increased intracranial pressure suggestive of cerebral edema or intracranial hemorrhage. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)

DIFFERENTIAL DIAGNOSIS — Other medical conditions may coexist with or mimic heat stroke in children:

●Sepsis – Sepsis, especially in association with meningitis, can cause high fever and abnormal mental status. However, in most instances, the height of the fever does not exceed 41°C (105.8°F). Furthermore, a focus for infection (eg, pneumonia, cellulitis, meningitis) or an infectious prodrome (eg, upper respiratory infection, gastrointestinal complaints) is frequently present. (See "Sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis".)

●Central nervous system conditions – Central nervous system (CNS) pathology can result in an elevated body temperature and alteration in mental status. This can occur from acute or chronic injury isolated to the hypothalamus (eg, CNS infection, cerebrovascular accident, hemorrhage). However, traumatic brain injury involving any part of the brain can cause neurogenic fever [45]. In addition, congenital anomalies of the brain may cause temperature dysregulation, including hyperthermia. In all of these conditions, the CNS abnormality precedes temperature elevation.

●Status epilepticus – Status epilepticus from any cause can result in hyperthermia. The most common cause of status epilepticus in young children is prolonged febrile seizures or underlying epilepsy. Rhabdomyolysis is a common comorbidity. Clinical features may be indistinguishable from heat stroke. (See "Clinical features and complications of status epilepticus in children" and "Clinical features and evaluation of febrile seizures".)

●Toxic overdose – Drug-related causes of seizures and hyperthermia (eg, overdose of cocaine, methamphetamine, amphetamine, MDMA [ecstasy], salicylates, anticholinergic agents) are important considerations in the hyperthermic child. Therapeutic levels of prescribed amphetamines or anticholinergic agents may also impair thermoregulation. In addition, salicylate intoxication also causes uncoupling of oxidative phosphorylation resulting in hyperthermia and multiple organ failure. A history of drug exposure, an elevated salicylate level, or a positive toxicology screen for drugs of abuse is typically present. (See "Cocaine: Acute intoxication" and "MDMA (ecstasy) intoxication" and "Methamphetamine: Acute intoxication" and "Anticholinergic poisoning" and "Salicylate (aspirin) poisoning: Clinical manifestations and evaluation".)

●Serotonin syndrome – Hyperthermia commonly occurs in patients with serotonin syndrome, a potentially life-threatening condition associated with increased serotonergic activity in the CNS. Although classically described as the triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities, serotonin syndrome is actually a spectrum of clinical findings ranging from benign to lethal. The recognition that the patient has been exposed to a serotonergic drug is essential to the diagnosis. (See "Serotonin syndrome (serotonin toxicity)".)

●Hemorrhagic shock and encephalopathy syndrome – Hemorrhagic shock and encephalopathy syndrome is a rare condition associated with hyperpyrexia, altered mental status, shock, disseminated intravascular coagulopathy, diarrhea, renal insufficiency, and liver failure, primarily in previously healthy infants under one year of age [46-48]. Although the etiology is unknown, this syndrome is very similar to heat stroke and is treated with supportive care and rapid cooling.

●Neuroleptic malignant syndrome – Neuroleptic malignant syndrome (NMS) is an idiosyncratic reaction to antipsychotic agents. In addition to hyperthermia, NMS is also characterized by "lead pipe" muscle rigidity, altered mental status, choreoathetosis, tremors, and evidence of autonomic dysfunction, such as diaphoresis, labile blood pressure, and arrhythmias. The history of antipsychotic drug exposure is a key component of the diagnosis. (See "Neuroleptic malignant syndrome".)

●Thyroid storm – Although most commonly seen in adults, children can manifest symptoms of thyroid storm including tachycardia, heart failure, and hyperpyrexia (temperature elevation up to 41.1°C [106°F]). Agitation, delirium, psychosis, stupor, or coma is usually associated with the diagnosis. Although thyroid storm can develop in patients with long-standing untreated hyperthyroidism, it is more often precipitated by an acute event such as thyroid or nonthyroidal surgery, trauma, infection, or an acute iodine load. (See "Thyroid storm".)

●Malignant hyperthermia – Malignant hyperthermia is a rare genetic disorder that manifests following exposure to certain agents, most commonly succinylcholine and halothane. Other potent inhalational anesthetics (eg, sevoflurane, desflurane, isoflurane) can also cause malignant hyperthermia. The onset of malignant hyperthermia is usually within one hour of the administration of general anesthesia but, rarely, may be delayed up to 10 hours after induction. (See "Malignant hyperthermia: Diagnosis and management of acute crisis".)

PREHOSPITAL CARE — We suggest that children with heat stroke undergo prehospital treatment with either cold-water immersion (if equipment and trained personnel are immediately available for initiation of this technique), tarp-assisted cooling [49], or evaporative external cooling [50,51] while ensuring expeditious transport to definitive care.

In general, children who have a loss of consciousness with exertion in warm weather should be treated as patients with heat stroke, even when environmental conditions seem mild. However, the diagnosis of heat-related illness can be challenging in the prehospital environment. Core temperature measurement is generally not performed, and some cooling may have occurred prior to the arrival of prehospital personnel, which may make the skin cool or cold to touch. Thus, the rescuer should maintain a high index of suspicion for heat stroke [52]. Because significant cooling can occur during transport, the prehospital provider should relay the concern for heat-related illness to clinicians at the hospital.

Patients with severe heat-related illness require removal from the source of heat stress. Rapid cooling must be initiated because the risk of morbidity and mortality increases with prolonged duration of hyperthermia [5,53]. Interventions include the removal of clothing and external cooling techniques.

The choice of cooling modality should be dictated by the maximum cooling rate that can be achieved by the resources available [54]. While evidence suggests that cold-water immersion is the most effective method for rapidly cooling adolescent and adult patients, evidence is lacking regarding the best method of prehospital cooling in prepubertal children [55,56]. The procedure for prehospital cold-water immersion is described separately. (See "Exertional heat illness in adolescents and adults: Management and prevention", section on 'Rapid cooling'.)

Because of the large surface area to body mass for convective heat loss, evaporative cooling can rapidly lower body temperature in infants and prepubertal children [57]. Evaporative cooling may be accomplished in the field by spraying patients with water or saline and fanning these patients, either manually or with ambulance fans or air conditioners. Application of ice packs to the neck, axilla, and groin and administration of room-temperature intravenous (IV) normal saline may complement evaporative cooling efforts. Regardless of modality, however, cooling measures should be initiated immediately in order to minimize the duration of hyperthermia and should be started prior to, or simultaneously with, activation of emergency medical services. Aggressive cooling methods should continue en route to the hospital. (See 'Rapid cooling' below.)

Prehospital management for healthy adolescents and adults with exertional heat illness is discussed in detail separately. (See "Exertional heat illness in adolescents and adults: Management and prevention", section on 'Prehospital assessment and initial interventions'.)

HOSPITAL MANAGEMENT

Stabilization — In addition to the careful assessment and support of airway, breathing, and circulation, the clinician should anticipate and aggressively manage hyperthermia, dehydration, rhabdomyolysis, disseminated intravascular coagulation, high-output cardiac insufficiency, renal failure, and hepatic failure [58,59]. (See 'Rapid cooling' below and 'Treatment of end-organ dysfunction' below.)

Initial stabilization should focus on the following:

●Airway and breathing – Children with heat stroke frequently require basic or advanced airway management to maintain oxygenation and ventilation because of central nervous system (CNS) effects (eg, coma, seizures). (See "Basic airway management in children" and "Technique of emergency endotracheal intubation in children".)

●Circulation – All patients with heat stroke need circulatory access, ideally with two large-bore intravenous (IV) catheters or a central venous catheter. Initial therapy, however, can begin with a single peripheral catheter of any gauge or an intraosseous needle.

Fluid resuscitation depends on the type of heat stroke and should replenish intravascular volume while avoiding fluid overload. Children with classic (nonexertional) heat stroke tend to be only mildly to moderately hypovolemic, while those with exertional heat stroke may be moderately to severely hypovolemic. Thus, an initial rapid IV infusion of 20 to 40 mL/kg of isotonic crystalloid (eg, normal saline) may be adequate fluid resuscitation for a patient with classic heat stroke, while a child with exertional heat stroke may require 60 mL/kg or more of normal saline. Infusion of room-temperature fluids assists with other methods of rapid cooling. (See "Hypovolemic shock in children in resource-abundant settings: Initial evaluation and management".)

Patients with shock who are unresponsive or minimally responsive to fluid resuscitation should undergo central venous pressure monitoring to guide additional therapy. Children with heat stroke may have decreased cardiac contractility and systemic vascular resistance as a byproduct of heat stress and require initiation of vasopressor therapy (eg, norepinephrine or epinephrine) to maintain adequate tissue perfusion. (See "Shock in children in resource-abundant settings: Initial management", section on 'Clinical and physiologic targets'.)

●Disability – Altered mental status typically resolves once oxygenation, adequate tissue perfusion, and normothermia are achieved. Seizures should be treated with benzodiazepines (eg, lorazepam 0.1 mg/kg IV).

Rapid cooling — Children with heat stroke require aggressive treatment because the extent of end-organ damage and mortality is related to the duration of hyperthermia [43,60]. For children receiving treatment for heat stroke in the hospital, we suggest evaporative cooling rather than cold-water immersion. Evaporative cooling is preferred for hospital treatment of heat stroke in children because it does not interfere with efforts to maintain monitoring and ongoing resuscitation in unstable patients and can achieve rapid cooling [57].

Evaporative cooling is achieved by spraying patients with tepid water (to minimize shivering) while fanning with high-flow fans to maximize air circulation. Cooling rates approaching 0.15°C (0.27°F) per minute have been achieved in adults [43]. Both spray bottles and fans are usually available from hospital housekeeping services. Suspension of the patient on a mesh hammock during treatment enhances air circulation and may increase the rate of cooling.

Use of a cooling blanket; application of ice packs to the neck, axilla, and groin; and/or administration of room-temperature IV normal saline may complement evaporative cooling efforts and may be especially efficacious for rapidly lowering body temperature in infants based upon experience with total-body cooling of young infants after cardiac arrest [61]. Use of cooling blankets or ice packs is often associated with shivering, which may require suppression with benzodiazepines or other measures. (See 'Suppression of shivering' below.)

Decreases in core body temperature as measured by rectal temperature generally lag behind the actual drop in core temperature at the hypothalamus [62]. For this reason, cooling measures are generally stopped in pediatric heat stroke victims once the core temperature reaches approximately 38°C (100.4°F) to prevent overshoot hypothermia [58,59]. The amount of time required to reach this endpoint depends on the patient's initial temperature and the mode of cooling.

For patients who fail rapid cooling by evaporative cooling or cold-water immersion, invasive measures such as cardiac bypass or insertion of intravascular cooling catheters have well-established efficacy for rapid cooling but require time to deploy and are associated with significant risk [63-65].

Cold-water immersion is associated with significant discomfort, shivering, agitation, and combativeness. It is not clearly more efficacious for rapid hospital-based cooling in the pediatric population, although there are no trials of hospital-based cooling methods in children [57]. When evaporative cooling is not available, cold immersion is suggested.

The use of ice water immersion for adolescents and adults with exertional heat stroke is discussed separately. (See "Exertional heat illness in adolescents and adults: Management and prevention".)

Suppression of shivering — We suggest that patients with heat stroke receive IV benzodiazepines (eg, midazolam or lorazepam) to prevent or to treat shivering during cooling measures, especially if a cooling blanket or ice packs are being used. Suppression of shivering helps prevent increased endogenous heat production. Benzodiazepines have the added benefit of treating or preventing seizures (see 'Stabilization' above). If shivering is persistent and interfering with cooling, then rapid sequence intubation followed by mechanical ventilation under sedation with neuromuscular blockade may be necessary.

Other medications commonly used for postoperative shivering in adults, such as meperidine, clonidine, or dexmedetomidine, have significant adverse side effects and should be avoided in children with heat stroke; meperidine metabolites can lower the threshold for seizures, and both clonidine and dexmedetomidine may cause bradycardia or hypotension. (See "Intensive care unit management of the intubated post-cardiac arrest adult patient", section on 'Adverse effects'.)

Treatment of end-organ dysfunction — After stabilization and rapid cooling, the child with heat stroke remains at high risk for multiple organ failure, metabolic abnormalities, and disorders of coagulation. The clinician should carefully evaluate for the following abnormalities and treat accordingly:

●Rhabdomyolysis with hyperkalemia, hypocalcemia, and hyperphosphatemia (see "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)")

●Disseminated intravascular coagulation (see "Disseminated intravascular coagulation in infants and children", section on 'Management')

●Acute kidney injury (see "Prevention and management of acute kidney injury (acute renal failure) in children")

●Hyponatremic dehydration (see "Treatment of hypovolemia (dehydration) in children in resource-abundant settings", section on 'Therapy according to serum sodium')

●Cardiogenic shock with low systemic vascular resistance (see "Shock in children in resource-abundant settings: Initial management", section on 'Clinical and physiologic targets')

●Cardiogenic and noncardiogenic pulmonary edema (see "Noncardiogenic pulmonary edema", section on 'Permeability pulmonary edema due to ARDS')

●Liver failure – Treatment is supportive; rarely, liver transplantation has been necessary in teenagers with heat stroke-associated liver failure [66-69] (see "Acute liver failure in children: Management, complications, and outcomes")

●Cerebral edema (see "Elevated intracranial pressure (ICP) in children: Management", section on 'Ongoing Management' and "Elevated intracranial pressure (ICP) in children: Management", section on 'Treatment of elevated ICP')

Ineffective therapies — Antipyretic medications (eg, acetaminophen, ibuprofen) are ineffective for the treatment of hyperthermia in heat stroke victims and should not be used because they may exacerbate liver injury (acetaminophen) or cause kidney injury or gastrointestinal bleeding (ibuprofen).

Isopropyl alcohol baths may lead to dermal absorption with toxicity in children and are contraindicated [70,71].

Dantrolene, a nonspecific skeletal muscle relaxant that acts by blocking the release of calcium from the sarcoplasmic reticulum, is used for the treatment of malignant hyperthermia and had been proposed as a treatment for hyperthermia from heat stroke. Although initial evidence suggested that dantrolene shortened cooling times in adults with heat stroke, additional small trials have not identified a consistent benefit [72-74]. Thus, dantrolene is not routinely used. Some experts advocate the use of dantrolene in patients who are not responsive or are poorly responsive to initial cooling efforts [74].

Disposition — All children with heat stroke should be admitted to a pediatric critical care unit setting in order to maintain appropriate monitoring and to treat ongoing and delayed end-organ dysfunction. (See 'Treatment of end-organ dysfunction' above.)

If there is no pediatric critical care coverage at the admitting hospital, the child should be resuscitated and promptly transferred to an appropriate institution, if possible.

Prognosis — The prognosis in children with heat stroke is poorly characterized. Extrapolation from studies in adults suggests that morbidity or mortality are directly related to duration and degree of hyperthermia [75]. Thus, heat stroke must be treated aggressively. In addition, prognosis depends upon the patient population and type of heat stroke:

●Mortality – Mortality of up to 63 percent has been reported in older adults with classic heat stroke. In contrast, mortality is much lower (eg, 1 to 15 percent) in adolescents and young adults with exertional heat stroke [43]. (See "Severe nonexertional hyperthermia (classic heat stroke) in adults".)

●Neurologic abnormalities – Permanent neurologic damage is more commonly seen in patients with core temperatures >42°C (107.6°F) and consists of spasticity, ataxia, dysarthria, poor coordination, impaired memory, and behavioral changes [58]. Patients recovering from rapidly treated exertional or classic heat stroke with core body temperatures below this level may manifest some of these neurologic findings but typically recover fully [76,77].

RECOVERY — The clinician should anticipate some degree of heat intolerance in all children who recover from heat stroke. Heat intolerance refers to a disorder in temperature homeostasis that is seen in heat stroke victims and that places them at greater risk for repeated heat illness. Children and their families/primary caregivers should be counseled to avoid heat exposure until repeat evaluation establishes that they have fully recovered and a period of acclimatization has occurred [78-80]. Patients with severe heat stroke may have ongoing impaired physiologic response to exertion in hot environments [80].

Children with exertional heat illness should only return to practice and competition when their temperature homeostasis is reestablished, generally after a minimum of one week of rest, full recovery from the initial insult based on repeat physical examination and laboratory testing (as needed to ensure all previously identified laboratory abnormalities have resolved), and a period of acclimatization [78,79]. Once these conditions are met, the child should gradually return to physical activity over two to four weeks [76]. The decision to return to play must be individualized, taking into consideration predisposing conditions for heat illness (eg, age, obesity).

PREVENTION — Heat stroke and heat-related deaths in young children may be prevented by education of caregivers regarding the high risk of leaving infants and young children unattended in cars [12,13]. Key components of guidance include reinforcing the vulnerability of infants and young children to heat stress, the rapidity with which temperature may rise in a locked car (even when ambient temperature is only moderately high), and the importance of keeping cars locked when not in use.

Heat illness and heat stroke in athletes are also potentially preventable. Key components of a successful strategy include [81] (see "Heat illness (other than heat stroke) in children", section on 'Prevention of heat illness' and "Exertional heat illness in adolescents and adults: Management and prevention", section on 'Prevention of exertional heat illness'):

●Age-appropriate periods of acclimatization

●Nonparticipation in athletic activities when ill

●Emphasis on proper hydration before, during, and after organized sports activities

●Awareness of ambient temperatures with limitation of activities when heat poses a significant risk (table 4)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heat illness in children" and "Society guideline links: Exertional heat illness".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Heat stroke (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Heat stroke is defined as a core body temperature ≥40 to 40.5^oC (104 to 105^oF) accompanied by central nervous system (CNS) dysfunction. Heat stroke is further classified as (see 'Heat stroke' above):

•Classic (nonexertional) heat stroke – Classic heat stroke arises from environmental exposure to heat and is more common in younger children who are unable to escape from hot environments and those with underlying chronic medical conditions that impair thermoregulation (table 3).

•Exertional heat stroke – Exertional heat stroke generally occurs in young, otherwise healthy individuals who engage in heavy exercise during periods of high ambient temperature and humidity. Typical patients are athletes, especially football players, and military personnel.

●Clinical features and diagnostic evaluation – Clinical features of heat stroke are provided in the table (table 2). Core body temperature, such as rectal temperature, should be determined in all patients with possible heat stroke. (See 'Core body temperature and clinical findings' above.)

Children with heat stroke commonly have abnormal laboratory findings, reflecting end-organ damage caused by heat stress. These patients warrant ancillary studies, as described above. (See 'Laboratory findings' above and 'Ancillary studies' above.)

●Diagnosis – Elevated core body temperature and CNS dysfunction as well as exclusion of other causes of hyperthermia (eg, status epilepticus, drug overdose, serotonin syndrome) establish the diagnosis of heat stroke. While the distinction between heat exhaustion and heat stroke is sometimes unclear, all children with elevated body temperature and CNS abnormalities should be treated for heat stroke. (See 'Diagnostic evaluation' above and 'Differential diagnosis' above.)

●Rapid cooling – Children with heat stroke require aggressive and rapid cooling because the extent of end-organ damage and mortality is related to the duration of hyperthermia (see 'Rapid cooling' above):

•Prehospital cooling – We suggest prehospital treatment with either cold-water immersion (if equipment and trained personnel are immediately available for initiation of this technique), tarp-assisted cooling, or evaporative external cooling. Prehospital cooling measures should be initiated prior to, or simultaneously with, activation of emergency medical services (Grade 2C). (See 'Prehospital care' above.)

•Hospital cooling – For hospital treatment of children with heat stroke, we suggest rapid cooling in the hospital using evaporative external cooling rather than cold-water immersion (Grade 2C). Placing the child on a cooling blanket; application of ice packs to the neck, axilla, and groin; and administration of room-temperature intravenous (IV) normal saline complement evaporative cooling efforts. Cooling measures should be stopped in pediatric heat stroke victims once the core temperature reaches 38°C (100.4°F) to prevent overshoot hypothermia. (See 'Rapid cooling' above.)

For children undergoing rapid cooling for heat stroke, we suggest benzodiazepines (eg, midazolam 0.05 to 0.1 mg/kg IV) to prevent shivering during cooling measures (Grade 2C). Other medications commonly used for postoperative shivering in adults, such as meperidine, clonidine, or dexmedetomidine, have significant adverse side effects and should be avoided. (See 'Suppression of shivering' above.)

●Stabilization – Simultaneously with rapid cooling, children with heat stroke frequently require basic and/or advanced airway management to maintain oxygenation and ventilation because of coma and/or seizures. (See 'Stabilization' above.)

Fluid resuscitation should seek to replenish intravascular volume while avoiding fluid overload. All patients should receive an initial rapid infusion of 20 to 40 mL/kg of room temperature, isotonic crystalloid (eg, normal saline). Patients with shock unresponsive or minimally responsive to fluid resuscitation should receive continuous infusion of a vasopressor (eg, norepinephrine or epinephrine). (See 'Stabilization' above.)

●Supportive care of end-organ dysfunction – The clinician should anticipate and aggressively manage:

•Rhabdomyolysis with hyperkalemia, hypocalcemia, and hyperphosphatemia (see "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)")

•Disseminated intravascular coagulation (see "Disseminated intravascular coagulation in infants and children", section on 'Management')

•Acute kidney injury (see "Prevention and management of acute kidney injury (acute renal failure) in children")

•Hyponatremic dehydration (see "Treatment of hypovolemia (dehydration) in children in resource-abundant settings", section on 'Therapy according to serum sodium')

•Cardiogenic shock with low systemic vascular resistance (see "Shock in children in resource-abundant settings: Initial management", section on 'Clinical and physiologic targets')

•Cardiogenic and noncardiogenic pulmonary edema (see "Noncardiogenic pulmonary edema", section on 'Permeability pulmonary edema due to ARDS')

•Liver failure (see "Acute liver failure in children: Management, complications, and outcomes")

•Cerebral edema (see "Elevated intracranial pressure (ICP) in children: Management")

●Recovery – Children who have recovered from heat stroke are at a greater risk for repeated heat illness. They should avoid heat exposure until follow-up medical evaluation determines that temperature homeostasis has returned to normal. (See 'Recovery' above.)