classic heat stroke, exertional heat stroke, heat-related illnesses, hyperthermia



  1. Yeo, Theresa Pluth MSN, MPH, CRNP


Heat stroke (HS) is a serious and potentially life-threatening condition defined as a core body temperature >40.6[degrees]C. Two forms of HS are recognized, classic heat stroke, usually occurring in very young or elderly persons, and exertional heat stroke, more common in physically active individuals. An elevated body temperature and neurologic dysfunction are necessary but not sufficient to diagnose HS. Associated clinical manifestations such as extreme fatigue; hot dry skin or heavy perspiration; nausea; vomiting; diarrhea; disorientation to person, place, or time; dizziness; uncoordinated movements; and reddened face are frequently observed. Potential complications related to severe HS are acute renal failure, disseminated intravascular coagulation, rhabdomyolysis, acute respiratory distress syndrome, acid-base disorders, and electrolyte disturbances. Long-term neurologic sequelae (varying degrees of irreversible brain injury) occur in approximately 20% of patients. The prognosis is optimal when HS is diagnosed early and management with cooling measures and fluid resuscitation and electrolyte replacement begins promptly. The prognosis is poorest when treatment is delayed >2 hours.


Article Content

Heat-related illness and mortality are a significant health problem in the world today. Heat stroke was first documented by the Romans in 24 BC, but it was not shown until 1946 that heat stroke could lead to multiorgan dysfunction. 1 As global warming has resulted in heat waves in climates that were previously temperate, there has been an increase in weather-related heat deaths. 2 From the observed climate record, an increase of 0.6[degrees]C has occurred in the global mean temperature. 3 Australia and New Zealand have both experienced an increase in the daily minimum temperatures. Short-term episodes of extreme heat (or cold) have had major impacts on health, as seen in the 1995 Chicago heat wave, which resulted in hundreds of fatalities. This heat wave was among the worst of the 20th century. 3


Hyperthermia is the general term for a rise in the core body temperature above the hypothalamic set point, which is the result of overwhelming the body's heat dissipating mechanisms. 4 Specifically, the ability to maintain a core temperature of 37[degrees]C in a hot environment by peripheral vasodilatation, increased blood flow to the surface of the skin, evaporation of sweat, control of inflammatory cytokines, and stimulation of heat-shock proteins is compromised.


Hyperthermia occurs along a continuum of heat-related conditions, starting with heat stress, progressing to heat exhaustion, heat stroke (HS), and culminating in multiorgan dysfunction and death in some instances. Heat stress refers to mild discomfort, cramps, physiologic strain, and possibly syncope while in a hot environment. Heat exhaustion is a more distinct clinical entity characterized by mild-to-moderate illness from water and salt depletion. The body temperature is >37[degrees]C, but <40[degrees]C. 4 HS is a systemic inflammatory response with a core temperature of >40.6[degrees]C, most often accompanied by mental status changes (anxiety, confusion, bizarre behavior, loss of coordination, hallucinations, agitation, seizures, and often, coma), and varying levels of organ dysfunction (acute renal failure, liver failure, brain injury, respiratory failure, ischemic bowel injury, pancreatitis, gastrointestinal bleeding, thrombocytopenia, and disseminated intra-vascular coagulation [DIC]). 4-6 Of the heat-related conditions along this continuum, only HS is a true medical emergency.


Current understanding of HS indicates that it is due to thermoregulatory failure in addition to an exaggerated acute-phase response and altered genetic expression of heat-shock proteins. 4 HS occurs in two forms; classic (nonexertional) heat stroke (CHS), caused by exposure to high environmental temperatures, and exertional heat stroke (EHS), due to strenuous physical exercise, usually in high environmental temperatures and/or conditions of high humidity.


Pathogenesis of Heat Stroke

Genetic polymorphisms likely determine susceptibility to heat. The genes involved regulate the activity of cytokines, coagulation proteins, and the very proteins involved in heat adaptation. The progression from heat stress to HS is due to a combination of events including: thermoregulatory failure, an exaggerated acute-phase response to heat, and alteration in the production of heat-shock proteins. 4


Consider first the process of thermoregulation. Body heat is absorbed from the environment and is generated through normal metabolism. In order to maintain a body temperature of 37[degrees]C, excess heat must be dissipated through the skin and respiratory systems. The thalamic thermoregulatory center is stimulated by a 1[degrees]C rise in the temperature of circulating blood. The delivery of heated blood in the circulation to the thalamus stimulates sweating and tachypnea. Sweat vaporizes, cooling the body. For every 1.7 mL of sweat, 1 kcal of heat energy is dissipated. 4 Therefore, via sweat production, the body can dissipate up to 600 kcal of heat energy/hr. As body heat is transferred to the environment in this fashion, dehydration and salt loss occur concurrently. Both conditions adversely affect thermoregulation in the extreme. Susceptible individuals should be cautioned to maintain adequate hydration and salt intake when exposed to heat extremes.


The acute-phase response to heat involves endothelial cells, leukocyte response, and epithelial cells. These cells protect the body against tissue injury and will promote prompt repair in the event of injury. The pathophysiologic sequence of events in HS is similar to that found in severe sepsis. The interleukins mediate the systemic inflammatory response to strenuous exercise. Interleukin-1 and 6 are primarily involved, controlling the levels of cytokines produced in response to endogenous or environmental heat. Interleukin-6 stimulates liver production of antiinflammatory acute-phase proteins that inhibit reactive oxygen and the release of proteolytic enzymes. Increased levels of cytokines, such as tissue necrosing factor alpha (TNF-[alpha]), are necessary to mediate fever, promote leukocytosis, synthesize acute-phase proteins, and prevent muscle catabolism. 4


The third event in the progression of heat stress to HS involves the production of heat-shock proteins. The production of special heat resistant proteins or stress proteins is controlled at the level of gene transcription in the DNA of the chromosomes. Heat-shock protein 72 is the primary protein that accumulates in the brain, producing a transient state of tolerance to heat stress. This mechanism protects the body from hyperthermia, arterial hypotension, and cerebral ischemia and also plays a role in heat acclimatization. 1,7 This mechanism appears only to be effective in sublethal thermal injury.


When the synthesis of heat-shock proteins is blocked or altered, as in a genetic polymorphism, at the gene transcription level or by antibodies, the cells are rendered extremely sensitive to heat stress. Therefore, some individuals may be more genetically prone to develop heat stress and HS because of their body's inability to protect itself through the production of heat-shock proteins.


A heat wave is defined as three or more consecutive days of air temperatures >32.2[degrees]C 8 Exposure to excessive heat may cause illness, as heat directly induces tissue injury, the severity of which is dependent upon the critical thermal maximum (ie, the level and duration of core heating). The critical thermal maximum in humans is a body temperature of 41.6[degrees]C to 42[degrees]C for between 45 minutes and 8 hours. At extreme body temperatures (eg, 49[degrees]-50[degrees]C), all cellular structures are destroyed and cellular necrosis occurs in <5 minutes. 4,7



According to the Centers for Disease Control and Prevention (CDC), between the years 1979 and 1999 there were 8015 deaths in the United States from excessive heat; 48% were due to weather conditions, 5% were of man-made origin (eg, boiler room, furnace, vehicle, or factory-generated extreme heat conditions), and 48% were of unspecified origin. 8 Rates for heat-related deaths increase with age. Studies in urban areas show an association between increased heat-related mortality and increases in heat as measured by either maximum temperatures or the heat index (the heat index is a mathematical formula that combines the effects of heat and humidity. See Figure 1 to calculate the heat index). 2,9,10 The associated health effects are related to temperatures above which the population is accustomed.

Figure 1 - Click to enlarge in new window

The precise incidence of HS is unknown for many reasons. First, in the United States, heat-related death is not a reportable condition in any state. 11 Second, the definition of HS varies, resulting in underreporting of HS cases. Third, many heat-related illnesses and deaths are unrecognized as such and are not reported. Therefore, the reported incidence of HS in the United States varies from 17.6 to 26.5/100,000, as compared to 22 to 250/100,000 in Saudi Arabia, where HS is relatively common. 12 The crude (unadjusted) mortality rate from HS in Saudi Arabia is 50%. 12 By contrast, the incidence of heat exhaustion in Saudi Arabia is 450 to 1800 cases per 100,000 persons. Why some cases progress to HS and others do not is unclear, but it appears that genetic polymorphisms may determine susceptibility; the likely candidate genes include those that encode cytokines, coagulation proteins, and heat-shock proteins. 4


Mortality rates for HS range from 10% to 70%, depending on the severity and age of the patient. The greatest numbers of deaths occur when treatment is delayed for >2 hours. 13


Predisposing Factors

Persons at the extremes of age in society are at greatest risk for the development of HS. Infants and small children (<15 years of age) lack sufficient body surface area to dissipate excess heat, have a lower rate of sweating, and a slower rate of acclimatization. 8,13 In contrast, the heat-regulating center in the brain, the pons, often fails to function properly in the elderly (>65 years of age). 8,13 A 2001 forensic study conducted in Australia identified predisposing factors in deaths attributed to high-environmental temperatures. 14 These factors included: lack of familiarity with environmental conditions, excessive clothing, prolonged sun exposure, use of certain drugs and medications, acute alcohol intoxication, obesity, underlying dementia, alcoholic liver disease, and (possibly) epilepsy. 14 Confirmation of dehydration was attempted via vitreous humor electrolyte analysis, but prolonged postmortem intervals and putrefaction complicated the assessment. The Australian findings were similar to those uncovered in epidemiologic investigations following the 1995 and 1999 heat waves in Chicago, which resulted in 485 and 103 heat-related deaths, respectively. 8 Drinking alcohol, participating in strenuous outdoor physical activities in hot weather, taking medications that reduce the body's ability to regulate temperature or inhibit perspiration, advanced age, inability to care for oneself, preexisting cardiac or psychiatric disease, and living alone all increased risk for heat-related death in those heat waves. 8 A comprehensive list of risk factor predisposing an individual to CHS or EHS is presented in Table 1.

Table 1 - Click to enlarge in new window Risk Factors for Heat Stroke

Drug-associated Heat Stroke

Documented reports of drugs or medications contributing to weather-related heat illnesses in the literature are scarce. Martinez, Davenport, and Saussy 15 identified drug use by toxicology screening in eight patients treated for HS during a New Orleans heat wave in 1998. The most common drug found by toxicology screening was cocaine; other drugs included diphenhydramine, tricyclic antidepressants, and phenothiazines. Six of the eight patients affected (75%) suffered rhabdomyolysis; three also developed DIC, and there were two deaths in the group (25%). 14


The lay Web site, DanceSafe (, dedicated to promoting health and safety within the rave and nightclub community), reports that >100 people have died after taking "ecstasy" (3,4 methylene-dioxymethamphetamine) at rave parties. 16 (Ecstasy, also called MDMA, Adam, XTC, Doves, or E, is a stimulant, related to mescaline and to amphetamines). These cases were not ecstasy overdoses, but rather the result of the stimulant effect of the drug causing the body's basal temperature to rise. When taken in a dance or rave setting, the risk of developing a heat-related illness worsens. Often "so-called" ecstasy tablets are laced with dextromethorphan (DXM), the cough suppressant. DXM can cause dehydration and prevent adequate sweating and has also been reported to cause hallucinations and loss of motor controls. 16


Ephedra-containing Dietary Supplements

Ephedra-containing dietary supplements have been linked to myocardial infarction, stroke, seizures, sudden death, and EHS. 17-19 A confirmed report of EHS associated with ephedra occurred in a highly trained, heat-acclimatized infantry soldier who suffered EHS near the completion of a 12-mile march. 17 He had ingested no medications other than two capsules of an ephedra-containing supplement, Xenedrine RFA-1. 17 Each capsule contained 10 mg Ma huang (ephedrine), 2.5 mg synephrine, and 100 mg caffeine. 17 The soldier suddenly collapsed, had mental status changes (disoriented to person, place, and time) and a rectal temperature of 41[degrees]C was measured. His clinical course was significant for elevated creatinine kinase levels peaking at 16,115 U/L, mild acute renal failure with a blood urea nitrogen (BUN) 24 mg/dL and creatinine 1.9 mg/dL, and an elevated liver aspartate transaminase (AST) of 46 U/L (5-40). 17 He subsequently recovered without complications. Army investigation into this case confirmed that the soldier was well acclimatized, having completed three similar marches in the month preceding this incident. He was also well-hydrated at the time of collapse, having consumed 3 L water over the 3-hour period of the march. The investigators concluded that the ephedra-containing supplement was the cause of the soldier's EHS. While the exact mechanism of ephedra-related HS and injury is not clear, it is postulated that ephedra may produce a thermogenic effect by activation of dopamine receptors and by impairing heat dissipation through peripheral vasoconstriction. 17 Hyperthermia is frequently seen with amphetamines, which are molecularly related to ephedrine.


On December 31, 2003, the FDA announced plans to ban the drug ephedra, based on evidence that it stresses the cardiovascular system, may trigger heart attacks and stroke, and is linked to irregular heartbeats. 20 Numerous sports agencies including the International Olympic Committee, the National Collegiate Athletic Association, the National Football League, and the National Basketball Association have already banned the substance in recent years, due to safety concerns about its use. 21


Two groups have independently examined the Adverse Events Reports filed with the FDA on products containing ephedrine. 22 Haller and Benowitz 18 identified 140 adverse events related to products containing ephedrine between June 1, 1997, and March 31, 1999. They concluded that 31% were definitely related temporally to the product and that another 31% were possibly related. 18 These adverse events included hypertension, palpitations, stroke, tachycardia, and seizures, of which 10 events resulted in death and 13 resulted in permanent disability.


Samenuk et al 19 assessed adverse events reported by the Food and Drug Administration (FDA) for the period between 1995 to 1997. They identified 37 adverse cardiovascular events, including 11 episodes of sudden death, 16 strokes, and 10 myocardial infarctions. 19 Neither Haller nor Samenuk found any Adverse Event Reports of EHS associated with ephedrine use during this time period. The case report by Oh and Henning appears to be the first confirmed case of an ephedra-containing supplement causing EHS. 17 The tragic case involving Baltimore Orioles pitcher Steve Bechler is complicated by the existence of multiple risk factors for EHS in addition to the presence of Xenadrine RFA-1 found on toxicology screening. Autopsy results released at a Congressional hearing on ephedra implicated morbid obesity, poor cardiovascular conditioning, fatty liver disease, untreated hypertension, and an enlarged heart as contributory factors in his EHS death in 2003. 23


Athletes: Special Risk Factors

Young athletes with sickle cell trait (SCT) may be at increased risk of heat-related illnesses and subsequent complications. 24 SCT occurs in 8% of African Americans and is considered benign in nature, conferring no increased risk of morbidity or mortality due to its presence. However, this assessment should be questioned. Several studies of recruits in the Armed Forces found a >20-fold increased risk of death in recruits with SCT, compared to recruits without SCT. 25 One case report from Dayton, OH, describes an occurrence of fatal rhabdomyolysis secondary to exertional HS in a 12-year-old athlete with SCT. 24 EHS occurred at a moderate environmental temperature of 79[degrees]F, humidity of 59%, and the calculated heat index was 80, a "Caution" condition. 10 His core temperature was only 38.5[degrees]C. The boy developed ARF, rhabdomyolysis, and DIC 6 hours after collapsing at football practice; he died 32 hours later despite heroic measures. 24 The boy was SCT positive and postmortem examination revealed no drugs of abuse, amphetamines, cocaine, or cardiovascular disease as the cause of death. The risk of EHS in African Americans with SCT is a topic meriting further molecular study.


Environmental Factors and Heatstroke

The number of heat-related deaths in athletes has risen in recent years, with 21 deaths between 1995 and 2002, compared to eight deaths between 1985 an 1994. 26,27 Recent heat waves during training camp, possible hyponatremia from excess water intake following practice, inadequate recognition and treatment of heat-illnesses, and poor medical supervision are cited as contributing factors. 26 According to the National Center for Catastrophic Sport Injury Research statistics, most heat-related deaths have occurred in players weighing >250 lbs, with many weighing >300 lbs. 27 In the 1960s through the 1980s it was rare to find a football player of such weight. 26


The Occupational Safety and Health Act of 1970 protects workers from heat-related hazards at work. 28 In 1999, 34 workers died as a result of heat stress. 29 Work becomes dangerous when the humidity reaches 60% and ambient air temperatures are >35[degrees]C. 28 Heavy work clothing, required protective equipment, and access to work and to shade are factors in the development of heat stress. Workers have a right under OSHA to know what hazards exist at their work site and how to protect themselves. OSHA also requires training in how to recognize when a coworker is experiencing a heat-related illness.


Clinical Diagnosis of Heat Stroke: Effect on Body Systems

Clinically, HS is characterized by a high body temperature (>40.6[degrees]C), altered mental status, and in CHS, hot, dry flushed skin. One-half of the cases with EHS will have persistent sweating due to excessive cate-cholamine release. 30 Early associated signs and symptoms, such as extreme fatigue, feeling faint, persistent headache, uncoordinated movements, red face, sweating or lack of perspiration, vomiting, diarrhea, and confusion may be observed. Manifestations of central nervous system (CNS) dysfunction include inappropriate behavior, impaired judgment, delirium, seizures, decreased level of consciousness (LOC), and frank coma. 31


Neurologic Dysfunction

Neurologic dysfunction is observed in both CHS and EHS. It is attributed to metabolic disturbances, metabolic encephalopathy, cerebral edema and ischemia, and possibly hypernatremic cerebral damage. 30 Hypernatremia, if severe enough, can lead to seizure activity and changes in LOC, as well as weakness and uncoordinated movements. The CNS is quite vulnerable to heat injury, particularly the cerebellum. Unfortunately, neurologic injury may not be transient. A case of central pontine myelinolysis was reported in a patient with CHS in the 1995 Chicago heat wave. 32 Using CT and MRI imaging scans, progressive cerebellar atrophy has been documented in survivors 10 weeks after the hyperthermic insult. 1 Longitudinal follow-up of survivors of near-fatal HS during the 1995 Chicago heat wave found that 24% of the survivors had no neurologic impairment, 43% had minimal impairment, and 33% had moderate to severe impairment after discharge from the hospital. 33 There is speculation that the extent of neurologic injury is related to hypernatremic cerebral damage. 1


Cardiovascular Compromise

The cardiovascular system is frequently compromised in HS. The initial response is hyperdynamic, characterized by an elevated cardiac index, decreased systemic vascular resistance, and elevated central venous pressure (CVP). 34 As EHS progresses, the cardiovascular system becomes compromised from the effects of dehydration and vasoconstriction, which limits the effectiveness of heat loss mechanisms. This constitutes the hypo-dynamic phase of EHS and is marked by a low cardiac index and increased systemic vascular resistance. The CVP may remain elevated for a time. The hypodynamic phase is poorly understood; however, heat-induced tissue injury, neurohormonal factors, and CNS reflexes appear to be involved. 34 Hypotension, tachycardia, and tachydysrhythmias (such as sinus tachycardia, atrial fibrillation, and supraventricular tachycardia) are commonly present. 1 Hypotension results from several mechanisms: shunting of blood to the periphery in an attempt to dissipate excess heat, increased production of nitric oxide, and fluid imbalance. 1,35


Hyperthermic clients may also experience thermal myocardial dysfunction, leading to dysrhythmias and/or pulmonary congestion and edema. Electrocardiogram findings associated with HS include conduction defects such as right bindle branch block, intraventricular conduction delays, prolongation of the Q-T interval, and nonspecific ST segment changes. 35 These changes tend to persist for at least 24 hours. A subpopulation of HS victims will develop reversible myocardial ischemia. 33


Acid-Base Disorders

Lactic acidosis and other acid-base disorders may occur in response to severe exertion. Lactate is normally cleared rapidly from the blood by the liver and converted to glucose. 1 In HS, the body is in hypovolemic shock, leaving skeletal muscle poorly perfused. With restoration of circulating volume, lactic acidosis may actually worsen, as reperfused ischemic skeletal muscle releases more lactate into the systemic circulation. The body compensates for the acidosis by increasing its respiratory rate, and in the process, an acute respiratory alkalosis develops. The resultant respiratory alkalosis may be a transient condition as the original lactate load is cleared or merely mask an underlying and ongoing process such as severe tissue ischemia that produces a persistent metabolic acidosis. In cases where there has been prolonged and sustained heat-induced tissue injury, and when a threshold body temperature between 42[degrees] and 43[degrees]C has been reached, the effect of extreme hyperthermia on acid-base equilibrium has not been completely delineated. 29 Research in this area is ongoing.


Bouchama and Vol 7 analyzed the acid-base disturbances of 109 HS patients in Saudi Arabia. They determined that respiratory alkalosis was independent of hypotension and hypoxemia and attributed it to the nonthermoregulatory steady state of hyperthermia. Their work suggests that a different mechanism determines acid-base balance in patients with extreme hyperthermia and that there is a threshold temperature at which this mechanism becomes operational. A threshold temperature of 41[degrees]C has been suggested for the development of lactic acidosis. Both metabolic acidosis and anion gap acidosis are due to lactic acid accumulation. In HS, both the rate of lactate production is increased, while the rate of lactate removal is decreased. In this series of 109 patients, metabolic acidosis was the predominant acid-base disturbance; the major contributors were tissue hypoxemia, hypotension, and increased metabolic rate. 7


Similarities to Septic Shock

HS and septic shock have many similarities. Due to the redistribution of blood from the splanchnic circulation to the periphery, there is a risk of gut ischemia. An ischemic gut facilitates the absorption of bacterial endotoxins, thus activating inflammatory mediators. This accounts for much of the multiple organ dysfunction seen in HS. When this occurs, continuous venovenous hemofiltration and plasma exchange may improve survival. 1 Recent research suggests that the early use of low dose dopamine may decrease splanchnic vasoconstriction, increase villi blood flow, and improve mucosal tissue oxygenation. This may avoid progression to the secondary and irreversible stage of heatstroke seen in multiorgan dysfunction. 36


Clients may develop rhabdomyolysis from the breakdown of skeletal muscle and the release of myoglobin. The presence of rhabdomyolysis makes the development of ARF more likely. Several electrolyte disturbances are associated with the breakdown of skeletal muscle. Hyperkalemia develops from cellular leakage of potassium and hyophosphatemia is related to increased glucose phosphorylation. Hyperuricemia is the result of two processes. First, increased levels of purines are released from damaged skeletal muscle; however, urinary excretion is reduced. Secondly, uric acid excretion is limited in the face of worsening lactic acidosis. 1 The end result is hyperuricemia.


Differential Diagnosis of the Client with Hyperthermia and Central Nervous System Dysfunction

The differential diagnosis of a client presenting with hyperthermia and CNS dysfunction is complex and should include consideration of the conditions found in Table 2. The history of the presenting illness is critical in selecting the appropriate clinical diagnosis and deciding the appropriate treatment course, but if these other possible diagnoses have not been entertained, the likelihood of making the correct diagnosis is low.

Table 2 - Click to enlarge in new window Differential Diagnosis of Hyperthermia and Central Nervous Dysfunction

Laboratory Evaluation

The value of the laboratory evaluation is primarily to detect end-organ damage and to exclude unlikely diagnoses. In HS, expect to find leukocytosis (from an inflammatory response), hemoconcentration and an elevated BUN and creatinine from dehydration, hyperuricemia, a decreased serum potassium initially (followed later by hyperkalemia), hyponatemia, hypocalcemia, and hypophosphatemia. The urine is typically concentrated, with elevated protein levels (from muscle breakdown), hematuria, increased specific gravity, renal tubular casts, and myoglobin (indicating acute renal damage, and, perhaps early rhabdomyolysis). An increased prothrombin time (PT) and activated partial thromboplastin time (aPTT), fibrinolysis, positive D-dimer, and thrombocytopenia provide evidence of coagulopathy and DIC. 37 Rising creatine kinase (CK) levels (normal <1000 U/L) likely indicate the development of rhabdomyolysis. Hepatic transaminases are usually elevated in HS. If both the AST and ALT levels are normal, the diagnosis of HS should be reconsidered. Arterial blood gases will likely reveal respiratory alkalosis in classic, nonexertional HS, but a respiratory alkalosis changing to a primary metabolic acidosis occurs in EHS.


Imaging studies that are necessary include a chest radiograph (to evaluate for acute respiratory distress syndrome [ARDS], aspiration, pneumonia, pulmonary edema, and to exclude other possible diagnoses), and a CT scan of the head (to assess for cerebral edema, hemorrhage, or cerebellar atrophy, and to exclude other causes of neurologic abnormalities). 13,37


A transthoracic echocardiogram is appropriate for assessing left and right ventricular function in clients exhibiting O2 desaturation and tachypnea in the setting of pulmonary edema, with lung findings such as moist bibasilar rales or elevated central venous pressure. 36


Clinical Management

An understanding of the pathophysiological changes that occur along the continuum of hyperthermia is essential to the acute and critical care advanced practice nurse's ability to provide competent, proactive care to HS clients. As scientific discovery advances, so must nursing's ability to incorporate that knowledge into clinical practice. For example, reporting temperature elevations in patient with HS has serious consequences and is an important part of nursing care. The key to survival for clients with severe HS is accurate measurement of core body temperature via rectal or tympanic probe, followed by prompt action based on that data.


Initial management of the severely ill patient with HS starts with assessment of airway, breathing, and circulation (ABCs) and correction of urgent problems, including hypoxemia, severe hyper-/hypokalemia, and acidosis. Nursing establishes the patient's baseline LOC, documents the Glasgow Coma score, and reassess the LOC on an ongoing basis. Concurrently, advanced practice nurses seek hemodynamic evidence of hypovolemia and shock (hypotension, tachycardia, bleeding) and initiate prompt fluid resuscitation with a crystalloid solution, preferably isotonic sodium chloride solution. Ringer's Lactate (RL) solution is not used, as the liver is unable to metabolize lactate effectively and using RL will worsen lactic acidosis. The total water deficit is corrected slowly, approximately one-half of the deficit is administered in the first 3 to 6 hours, with the remainder given in the next 6 to 9 hours. 13


The core body temperature is monitored using a continuous rectal or tympanic probe and central cooling is initiated in the field with the external techniques available. (No randomized clinical trials have been conducted comparing the effectiveness of the different cooling methods.) Rapid cooling is the goal; decreasing the core temperature <38.9[degrees]C within 30 minutes improves survival and minimizes end-organ damage. 1 The ideal goal is to reduce the core temperature by 0.2[degrees]C/minute. Unfortunately, tissue damage can continue to occur even after reaching this goal in approximately 25% of patients. See Table 3 for a description of cooling methods.

Table 3 - Click to enlarge in new window Cooling Methods

An indwelling urinary catheter is recommended for accurate measurement of the urine output. Osmotic diuretics, such as mannitol (Osmitrol) may be used to promote an osmotic diuresis and prevent kidney damage from myoglobin obstruction in rhabdomyolysis. Mannitol may also be used to treat acute renal failure. Arterial oxygenation is monitored by O2 saturation and periodic measurement of arterial blood gases, at least every 1 to 2 hours. A baseline 12-lead electrocardiogram (ECG) is performed with continuous rhythm strip monitoring thereafter, to observe for conduction delays or blocks that may require temporary or permanent pacing in order to maintain cardiac output. One clinical nursing pearl is to avoid shivering in persons with HS, as it promotes skeletal muscle breakdown and can actually increase body temperature. Chlorpromazine (10-50 mg IM) is used to stop shivering and minimize endogenous heat production. 38 A benzodiazepine (diazepam 5-10 mg IV, every 15-30 minutes, not to exceed 30 mg) should be available for use in the event of seizure activity or myoclonus. 13


Case reports of EHS occurring in clients with a previous history of malignant hyperthermia have been noted, suggesting a link between the conditions. 1 Dantrolene therapy is well established in the treatment of malignant hyperthermia; however, its use in HS has yielded disappointing results.


Complications of Heat Stroke

There have been reports of injury to every organ in the body from HS except the pancreas. ARF, rhabdomyolysis, lactic acidosis, DIC, neurologic insults ranging from cerebellar deficits to hemiplegia, dementia, aphasia, ataxia, seizures, and coma, and multiorgan dysfunction syndrome constitute potential complications of HS and are more commonly found in EHS than CHS. Table 4 lists additional complications of HS.

Table 4 - Click to enlarge in new window Complications of Heat Stroke

Acute Renal Failure

The incidence of ARF in EHS is approximately 30% and >50% in CHS. 33 ARF is defined as an acute decrease in the glomerular filtration rate (GFR) as evidenced by a rise in the plasma creatinine concentration to >1.5 mg/dL. Acute renal dysfunction can affect the kidney parenchyma or the renal tubules. Factors that favor the development of ARF are the presence of rhabdomyolysis, increased cytokine production, endothelial cell damage, hypokalemia, extracellular fluid depletion, endotoxin production and the development of DIC. 35 Both vasoconstrictive and vasodilatory hormones influence the pathogenesis of ARF. Levels of circulating catecholamines are affected not just by hyperthermia; the stress response of critical illness, pain, anxiety, agitation, hypovolemia, renal vascular constriction, toxins, direct heat injury, and elevated levels of cytokines all contribute to altered renal and systemic hemodynamics in EHS. 35



Rhabdomyolysis is due to the breakdown of skeletal muscle, with major crush injuries accounting for most cases. There are approximately 26,000 cases reported annually in the United States. 39 Exertional rhabdomyolysis and EHS is uncommon in women, despite their increased participation in vigorous sports. 1 The body temperature at which the thermoregulatory reflexes are stimulated is lower in women than in men. Thus, women store less heat than men for a given workload. This may be related to estrogen or a function of less bulky muscles in women.


Injured muscle leaks myoglobin, CK, and inflammatory mediators into circulation. Circulating myoglobin is filtered by kidneys, precipitating renal tubular obstruction and ARF. Rhabdomyolysis is also associated with the development of ARDS and fluid and electrolyte imbalances, such as hyperkalemia. Signs and symptoms of rhabdomyolysis include cola-colored urine, fever, malaise, nausea, emesis, confusion, agitation, and finally delirium and anuria. 39


Rhabdomyolysis becomes clinically apparent when the peak CK values exceed 10,000 U/I. 38 Treatment requires isotonic sodium chloride solution intravenous (IV) infusion (1.5 L/hr), with mannitol administration to induce an osmotic diuresis, and sodium bicarbonate to alkalinize urine ph to 6.0. Hemodialysis is usually necessary to treat the severe hyperkalemia found in persons with HS from cellular release of potassium, as well as the profound metabolic acidosis, uremia, and fluid overload. Recovery from rhabdomyolysis is possible when the condition is recognized early and aggressive treatment is initiated quickly.


Disseminated Intravascular Coagulation

Endothelial cell injury and diffuse microvascular thrombosis are prominent features of HS. 4 Coagulation abnormalities occur early in the course of HS marked by the appearance of thrombin-antithrombin III complexes, soluble fibrin monomers, and decreased levels of proteins C and S and antithrombin III. As the core temperature is normalized, fibrinolysis is inhibited but the activation of coagulation is not. (This is similar to the pattern observed in sepsis.) Therefore, patients continue to be at risk for DIC even after the goal temperature has been reached. Recombinant activated protein C is used in severe sepsis and may also reduce mortality in HS victims. 4 As the molecular mechanisms of HS are further delineated more specific therapies for the treatment of DIC may be found.


Myocardial Infarction/Injury

Myocardial involvement in EHS victims without previously diagnosed cardiovascular disease is uncommon, but may develop as the internal body temperature rises. 30,34 It has been reported in primates that at a core body temperature >40[degrees]C leakage of lipo-polysaccharide endotoxin causes pulmonary and systemic edema, as well as cardiac dysfunction. 40 Antilipopolysaccharide antibodies were protective in this setting when given to primates. Unfortunately, similar therapy is currently not available for humans. 40


Prevention of Heat Stroke

Many cases of classic and exertional HS are preventable. Prevention of classic HS requires that special attention be given to neonates and children <15 years of age and to persons over the age of 65 years in terms of adherence to published weather warnings and safety advice. 13,41,42 The National Weather Service and the CDC, in cooperation with local broadcasting companies, issue warnings regarding the air quality index and stagnant atmospheric conditions and recommendations for persons with known cardiovascular and pulmonary disease to stay indoors with air conditioning on days with poor air quality. Air conditioning is the leading protective factor against HS. 41 Other suggestions for preventing heat-related illnesses include drinking water or nonalcoholic fluids frequently; wearing lightweight, light-colored loose fitting clothing; reducing strenuous activities during the hottest times of the day; and checking on neighbors who do not have air conditioning. 42


Reduction in the incidence of EHS requires successive increments in workload in hot environments, resulting in body adaptation, or acclimatization. Acclimatization takes several weeks of training in a hot environment and involves progressive enhancement of cardiovascular performance. Through the process of acclimatization, the rennin-angiotensin-aldosterone axis is activated more readily, promoting increased salt conservation by the sweat glands and the kidneys. Increased salt conservation leads to a higher extracellular plasma volume, an improved GFR, and improved ability to resist rhabdomyolysis. 4 A word of caution: Improvement in heat-tolerance may be lost after even 6 days without exposure to heat. 43



Most patients who receive prompt and aggressive treatment recover from HS. However, recovery is poor in patients with initial CNS dysfunction, persistent hypotension, and decreased cardiac output. In-hospital mortality of 21% in CHS has been reported, with the majority of survivors recovering near normal renal, neurologic, and hematological function. 33 Approximately 20% of patients will experience varying degrees of residual brain damage (eg, altered mental status, confusion, and decreased level of consciousness), while another 33% report moderate-to-severe functional disability at discharge. The degree of functional impairment was predictive of 1-year survival. In one study, a further 28% of the functionally impaired group had died at 1-year of follow-up. 33


Case Study

K. S., a 27-year-old black male, collapsed during professional football practice in the summer of 2001 and was assumed to be suffering from HS. 44 It was the hottest day of the summer in Minnesota; the heat index at the time of his collapse was 110. He was found to be unconscious, hypertensive, and tachycardic. Upon arrival to a local emergency room, his core body temperature was measured as 43[degrees]C. He was hypotensive and bradycardiac, with an O2 saturation of 98%. The patient was externally cooled with an ice bath and packed in ice before transfer to the intensive care unit (ICU). An IV line with isotonic sodium chloride solution (1 L 0.9%) was initiated.


Review of Systems

K. S. had complained of a severe headache and vomited three times the previous evening after football practice. No neurologic symptoms were recalled by team-mates at that time.


Past Medical History

K. S. was obese, but had no known history of hypertension or cardiovascular disease.



None known at time of admission.





ICU Hospital Course

In the ICU, K. S. required acute airway management with endotracheal intubation and mechanical ventilation to improve tissue oxygenation. Vigorous efforts continued to reduce his core temperature, including the use of peritoneal ice lavage. Rhabdomyolysis with peak CK levels of 20,000 U/L developed within hours of arrival, followed closely by ARF. His serum potassium levels were dangerously high (7.0). Therefore, hemodialysis was the therapy of choice. Hemodialysis was performed twice and K. S. was clinically improving, when evidence of DIC became apparent (diffuse petechiae, splinter hemorrhages, and oozing from IV sites). Therapy with fresh frozen plasma was begun. In the midst of ongoing therapy on several levels for multiorgan failure, K. S. experienced a massive myocardial infarct with cardiogenic shock unresponsive to intraaortic balloon pump and pharmacologic intervention. Fifteen hours after his initial collapse, K. S. was pronounced dead.



K. S.'s toxicology results were negative for all chemical substances. Physicians commenting on the tragedy cited a delay in initiation of cooling as a factor in his death. They also noted that K. S. weighed 335 lbs, which had impaired efforts to lower the core temperature. The victim's family filed a wrongful death suit against the professional football organization. Nearly 2 years after the death, all but three of the alleged charges in the lawsuit were dismissed by a judge, and it seems doubtful that the case will be tried in court. 45 The Occupational Safety and Health Administration investigated the death as a workplace fatality, but no citations were issued. 29



Heat waves cause thousands of cases of heat-related illnesses each year in the United States and globally. Classic and exertional HS are the most extreme and life-threatening forms, responsible for hundreds of deaths. The youngest and oldest in society are at increased risk for the development of HS. Social isolation, poverty, lack of air conditioning, chronic illness, use of diuretics, beta-blockers, alcohol consumption, cocaine use, phenothiazines, and ephedrine are also considered risk factors for HS. The clinical signs of HS include dizziness, nausea, vomiting, change in mental status or LOC, headache, piloerection, muscle cramps, occasionally diarrhea, and unsteady gait. HS is defined as a core body temperature >40.6[degrees]C, accompanied by neurologic changes. Complications may be severe and can include seizures, acute renal failure, liver failure, cardiovascular collapse, ischemic bowel syndrome, hyper/hypokalemia, thrombocytopenia, hyper/hyponatremia, rhabdomyolysis in EHS, and multiple organ dysfunction syndrome. Treatment is aimed at rapid reduction in core temperature by external cooling methods, fluid resuscitation, and prevention of complications. The prognosis is related to the severity of the CNS injury and duration of the hyperthermia. Prevention through acclimatization and adequate fluid intake during heat waves, as well as observing weather warnings and developing neighborhood watch support groups during periods of excessive hot temperatures is strongly encouraged.




1. Grogan H, Hopkins PM. Heat stroke: implications for critical care and anesthesia. Br J Anaesth. 2002;88:700-707. [Context Link]


2. McGeehin MA, Mirabelli M. The potential impacts of climate variability and change on temperature-related morbidity and mortality in the United States. Environ Health Perspect. 2001;109(Suppl 2):185-189. [Context Link]


3. Easterling D, Meehl G, Parmesan C. Climate extremes: Observations, modeling, and impacts. Science. 2000;289:2068-2074. [Context Link]


4. Bouchama A, Knochel J. Heat stroke. N Engl J Med. 2002;346:1978-1988. [Context Link]


5. Jones-Laskowski L. Responding to summer emergencies. RN. 2000;30:35-39. [Context Link]


6. Stillwell SB (Ed). Critical care nursing reference, 3rd ed. St. Louis: Mosby; 2002:337. [Context Link]


7. Bouchama A, De Vol EB. Acid-base alterations in heatstroke. Intensive Care Med, 2001;27:680-685. [Context Link]


8. Heat-related deaths-Chicago, Illinois, 1996-2001, and United States, 1879-1999. MMWR Weekly. 2003;53:610-613. [Context Link]


9. Williams J. The heat index. The USA TODAY Weather Book. New York: Random House; 1977. Available at: Accessed 1/04/04. [Context Link]


10. Florida Division of Forestry. Calculating heat index. Available at: Accessed February 18, 2004. [Context Link]


11. Wolfe MI, Kaiser R, Naughton MP. Heat-related mortality in selected United States cities, summer 1999. Am J Forensic Med Pathol. 2001;22:352-357. [Context Link]


12. Ghaznawi HI, Ibrahim MA. Heat stroke and heat exhaustion in pilgrims performing the Haj in Saudi Arabia. Ann Saudi Med. 1987;7:323-326. [Context Link]


13. Kunihiro A, Foster J. Heat exhaustion and heat-stroke. Emedicine. April 12, 2002. Available at: Accessed December 27, 2003. [Context Link]


14. Green H, Gilbert J, James R. An analysis of factors contributing to a series of deaths caused by exposure to high environmental temperatures. Am J Forensic Med Pathol. 2001;22:196-199. [Context Link]


15. Martinez M, Davenport L, Saussy J. Drug-associated heat stroke. South Med J. 2002;95:799-802. [Context Link]


16. DanceSafe. Watch out for heat stroke. Available at: Accessed December 27, 2003. [Context Link]


17. Oh RC, Henning JS. Exertional heatstroke in an infantry soldier taking ephedra-containing dietary supplements. Mil Med. 2003;168:429-430. [Context Link]


18. Haller CA, Berkowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med. 2000;343-1833-1838. [Context Link]


19. Samenuk D, Link MS, Homoud MK, Contreras R. Adverse cardiovascular events temporally associated with Ma huang, an herbal source of ephedrine. Mayo Clin Proc. 2002;77:12-16. [Context Link]


20. Fackelman K. Ephedra: Stimulant at the center of a storm. USA Today, 12/31/03. [Context Link]


21. Mihoces G. Leagues weigh in on ephedra ban.AQUSA Today, 12/31/03. [Context Link]


22. Lindsay B. Are serious adverse cardiovascular events an unintended consequence of the Dietary Supplement Health and Education Act 0f 1994?Mayo Clin Proc. 2002;77:7-9. [Context Link]


23. Chinery R. Prepared Witness Testimony. The House Committee on Energy and Commerce. Issues Related to Ephedra-containing Dietary Supplements. Subcommittee on Oversight and Investigations, July 23, 2003. Available at: Accessed December 27, 2003. [Context Link]


24. Pretzlaff RK. Death of an adolescent athlete with sickle cell trait caused by exertional heat stroke. Pediatr Crit Care Med. 2002;3:308-310. [Context Link]


25. Drehner D, Neuhauser KM, Neuhauser TS. Death among US Air Force basic trainees. 1956 to 1996. Mil Med. 1999;164:841-847. [Context Link]


26. Kreider RB, Burke ER, Clark JF. The neurosurgeon in sport: Awareness of the risks of heat-stroke and dietary supplements. Neurosurgery. 2003;52:252-255. [Context Link]


27. Mueller F, Cantu R. National Center for Catastrophic Sport Injury Research. Annual Survey of Football Injury Research 1931-2002. February 2003. Available at: Accessed January 5, 2004. [Context Link]


28. US Department of Labor. Occupational Safety & Health Administration. Safety and health topics: Heat stress. Available at: Accessed January 4, 2004. [Context Link]


29. Fleming P. OSHA launches Stringer probe. ESPN The Magazine. Available at: Accessed January 4, 2004. [Context Link]


30. Weinmann M. Hot on the inside. Emerg Med Serv 2003;32:34. [Context Link]


31. Ayers JC, Arieff AI. Features and outcomes of classic heat stroke. Ann Med. 1999;130:613. [Context Link]


32. Macnamee T, Forsythe S, Ndokwu IM. Central pontine myelinolysis in a patient with classic heat stroke. Arch Neurol. 1997;54:935-936. [Context Link]


33. Dematte JE, O'Mara K, Bueschler J. Near-fatal heat stroke during the 1995 heat wave in Chicago. Ann Intern Med. 1998;129:173-181. [Context Link]


34. Atar S, Rozner E, Rosenfeld T. Transient cardiac dysfunction and pulmonary edema in exertional heat stroke. Mil Med. 2003;168:671-673. [Context Link]


35. Lin YF, Wang JY, Chou TC. Vasoactive mediators and renal haemodynamics in exertional heat stroke complicated by acute renal failure. QJM. 2003;96:193-201. [Context Link]


36. Eshel GM, Safar P, Stezoski W. The role of the gut in the pathogenesis of death due to hyperthermia. Am J Forensic Med Pathol. 2001;22:100-104. [Context Link]


37. Cohen R, Moelleken BR. Disorders due to physical agents. In: Tierney LM, McPhee SJ, Papadakis MA, eds. 2004 Current Medical Diagnoses & Treatment. New York: Lange; 2004:1533-1534. [Context Link]


38. Walker J, Barnes S. Heat emergencies. In: Tintinalli J, Kelen G, Stapczynski JS, eds. Emergency Medicine. New York: McGraw Hill; 2000:1235-1242. [Context Link]


39. Walls M. Orthopedic trauma. RN. 2002;65:53-56. [Context Link]


40. Gathiram P, Wells M, Raido D. Portal and systemic arterial plasma lipopolysaccharide concentrations in heat-stressed primates. Circ Shock. 1988;25:223-230. [Context Link]


41. CDC National Center for Environmental Health. Heat Stroke. Available at: Accessed December 27, 2003. [Context Link]


42. FEMA-Hazards. Backgrounder: Extreme Heat. Available at: Accessed December 27, 2003. [Context Link]


43. Prevention and treatment of heat injury. Med Lett Drugs Ther. 2003;45:58-60. [Context Link]


44. Vikings tackle Stringer dies from heat-stroke. Available at: Accessed January 4, 2004. [Context Link]


45. Viking Update Staff. Much of Stringer suit dismissed. January 30, 2003. Available at: Accessed January 4, 2004. [Context Link]