The cardiovascular system plays a major role in both acclimatization and endurance training, largely resulting from an expansion of plasma volume.¹² Heart rate is lower and associated with a higher stroke volume. Other physiologic changes include earlier release of aldosterone, although acclimatized individuals generate lower plasma levels of aldosterone during exercise heat stress. Total body potassium depletion of up to 20% (500 mEq) by the second week of acclimatization can occur as a result of sweat and urine losses coupled with inadequate repletion.¹²

Although many similarities exist between thermoregulatory responses to heat and exercise, the well-conditioned athlete is not necessarily heat acclimatized. For heat and exercise-induced adaptive responses to be maintained, heat exposure needs to continue intermittently at least on 4-day intervals. Plasma volume decreases considerably within 1 week in the absence of heat stress.¹²

Pathophysiology

Predisposing Factors for Heat Illness

Elderly patients, psychiatric patients, or those with chronic diseases who are taking medications predisposing to heat illness are prone to classic heatstroke during periods of high ambient heat and humidity. Adequate fluid intake is essential. Elderly patients sometimes dress inappropriately for hot weather; heat loss is maximized by light, loose-fitting garments.

Exertional heatstroke is most likely to occur in young, healthy people involved in strenuous physical activity, especially if they have not acclimatized to environmental factors that overwhelm heat-dissipating mechanisms. Fluid intake is the most critical variable. Dehydration can be minimized by education on work-rest cycles and fluid consumption and through provision of cool, pleasantly flavored fluids.

The goal is to maximize voluntary fluid intake and gastric emptying so that fluid can rapidly enter the small intestine, where it is absorbed. Gastric emptying is accelerated to 25 mL/min by large fluid volumes (500-600 mL) and cool temperatures (10-15.8° C). High osmolality inhibits gastric emptying; osmolality of less than 200 mOsm/L is optimal. Most commercially available electrolyte solutions contain excessive sugar. Hydration can be monitored by measurement of body weight before and after training or athletic competition. An athlete with a loss of 2 or 3% body weight (1.5-2 L in a 70-kg man) should drink extra fluid and be permitted to compete only when body weight is within 0.5 to 1 kg (1 or 2 pounds) of the starting weight on the previous day. A weight loss of 5 or 6% represents a moderately severe deficit and usually is associated with intense thirst, scanty urine, tachycardia, and increase in rectal temperature of approximately 2° C. Such athletes should be restricted to light workouts after hydration until they return to normal weight. A loss of 7% or more of body weight represents severe water depletion; participation in sports should not be permitted until the athlete is examined by a physician. Wrestlers frequently fast, restrict food and fluid intake, and exercise vigorously wearing vapor-impermeable clothing to lose weight quickly so that they can compete in a lower weight class.¹³

The administration of salt tablets during strenuous exercise can cause delayed gastric emptying, osmotic fluid shifts into the gut, gastric mucosal damage, and hypernatremic dehydration. A 6-g sodium diet is sufficient for successful adaptation for work in the heat, with sweat losses averaging 7 L/day. Excessively high salt intake in relation to salt losses in sweat during initial heat exposure can impair acclimatization because of inhibition of aldosterone secretion. Excessive salt ingestion can also exacerbate potassium depletion.

Evaporative cooling can be lost when clothing inhibits air convection and evaporation. Loose-fitting clothing or ventilated fishnet jerseys allow efficient evaporation. Light-colored clothing reflects rather than absorbs light. Water evaporated from clothing is much less efficient for body cooling than is water evaporated from the skin.14,15

The body’s heat dissipation mechanisms are analogous to the cooling system of an automobile (Fig. 141-1). Coolant (blood) is circulated by a pump (heart) from the hot inner core to a radiator (skin surface cooled by the evaporation of sweat). Temperature is sensed by a thermostat (CNS), which alters coolant flow by a system of pipes, valves, and reservoirs (vasculature). Failure of any of these components can result in overheating.

Figure 141-1 Predisposing factors for heat illness: an automotive analogy.

Effective circulation requires both an intact pump and adequate coolant levels. Individuals with cardiac disease or those taking beta-adrenergic blocking agents or calcium channel blockers may be unable to increase their cardiac output sufficiently to produce the necessary peripheral vasodilation to dissipate heat. Dehydration caused by gastroenteritis, diuretics, or inadequate fluid intake predisposes to heat illness. Individuals working in the heat seldom voluntarily drink as much fluid as they lose and replace only approximately two thirds of net water loss (“voluntary dehydration”). Dehydration alone increases body temperature at rest by increasing the work of the sodium-potassium adenosine triphosphatase pump, which accounts for 25 to 45% of basal metabolic rate. This is particularly true in cases of hypernatremic dehydration. The pipes and valves of the coolant system may be abnormal in diabetic or elderly patients with extensive atherosclerosis.

Radiator function depends on the skin and sweat glands. Occlusive, vapor-impermeable clothing hinders evaporative and convective cooling. Anticholinergic medications and some drugs of abuse interfere with sweating and produce heat illness.¹¹ Various skin diseases, including miliaria (prickly heat rash), extensive burns, scleroderma, ectodermal dysplasia, and cystic fibrosis, are risk factors. Anhidrosis can be secondary to either central or peripheral nervous system disorders as well.

Increased heat production causing heat illness most often accompanies exercise in hot, humid environments. Athletes and military recruits are commonly affected. When heat and humidity are extreme, exertion is not necessary to produce heat-related problems. Several indices help objectify heat strain. The indices can be divided into two categories: heat scales that are based on meteorologic parameters only and heat scales that combine environmental and physiologic parameters.¹⁶

The wet bulb globe temperature heat index is an excellent meteorologic measure of environmental heat stress (Box 141-1). It includes the effects of temperature, humidity, and radiant thermal energy from the sun. When climatic conditions exceed 25° C wet bulb, even healthy people are at high risk if they choose to exercise. Above 28° C, exercise and strenuous work should be avoided or limited to extremely short periods.¹⁷

BOX 141-1 Wet Bulb Globe Temperature

T_n “Natural” wet bulb temperature; the temperature achieved by a thermometer covered with a moistened white wick and left exposed to the ambient environment

T_g Globe temperature; the temperature inside a blackened hollow copper sphere exposed to the ambient environment

T_a Ambient temperature

These measurements can be done manually or automatically calculated with the help of computer algorithms.

WBGT, wet bulb globe temperature.

The heat strain index is widely accepted as an example of an index that includes environmental and physiologic factors. There are several variations and modified heat strain indices in existence, with varying ease of use and accuracy (Fig. 141-2).¹⁶

Figure 141-2 National Weather Service Heat Index Chart.
Key:
extreme danger
danger

Before the advent of air conditioning, mortality increased threefold to fivefold in nursing homes and threefold in the general population during heat waves. Mortality in geriatric patients correlates with average weekly peak air temperature. Most deaths in the 2003 European heat wave occurred in elderly patients. Microclimates conducive to heat illness are produced in the interiors of automobiles, tanks, and tents in the sun as well as in engine rooms, hot tubs, and saunas.⁴ Children are more susceptible to heat stressors because the higher surface area–to–mass ratios allow increased absorption of heat. They also have lower sweat rates per gland.¹⁸

Endogenous factors, such as hyperthyroidism and pheochromocytoma, can also drastically increase heat production. An overdose of sympathomimetics or stimulants, such as amphetamines, cocaine, and phencyclidine, can cause fatal hyperpyrexia. High ambient temperature is associated with a significant increase in mortality from cocaine overdose. Many younger patients who die of hyperthermia test positive for cocaine.¹⁹ Heatstroke can occur with delirium resulting from ethanol withdrawal.²⁰ There are also reports of heatstroke occurring in well-trained military soldiers or athletes who ingest dietary supplements containing ephedrine or the ergogenic aid creatine.^21,22

Certain patients undergoing general anesthesia rapidly experience severe hyperthermia, muscle rigidity, and acidosis. This syndrome, termed malignant hyperthermia, is the result of a genetically determined instability of skeletal muscle sarcoplasmic reticulum that allows inappropriate intracellular calcium release. Dantrolene, which lowers myoplasmic calcium, is effective in the prevention and treatment of this syndrome.²³

Malignant hyperthermia is rarely seen in outpatient settings, but a clinically similar entity, neuroleptic malignant syndrome, is often encountered. This syndrome is induced by antipsychotic medications and is characterized by muscle rigidity, severe dyskinesia or akinesia, hyperthermia, tachycardia, dyspnea, dysphagia, and urinary incontinence. Although the lead-pipe rigidity and hyperthermia are reminiscent of malignant hyperthermia, the putative mechanism is different. Dopamine receptor blockade in the corpus striatum caused by butyrophenones and similar agents produces severe muscle spasticity and dystonia, leading to overproduction of heat. Some antipsychotics also cause suppression of thirst recognition. Other miscellaneous risk factors include obesity.²⁴ Individuals with a history of heatstroke, with or without an inherent aberration that predisposed them to the initial episode, are at increased risk for a recurrence.

Fever versus Hyperthermia

It is both diagnostically and therapeutically important to identify patients suffering from a febrile response rather than heat illness. For many years, fever was attributed to pyrogens released by bacteria or viruses (exogenous pyrogens) or to cells undergoing autolysis after phagocytic activity (endogenous pyrogens).²⁵ These circulating pyrogens would directly affect the thermoregulatory control center. It now appears that fever is the result of triggering by pyrogens of pathways involving cytokine receptors or other signals to reset the thermal set point in the preoptic area of the anterior hypothalamus to a new level above 37° C.²⁵

Once this temperature is established, the thermoregulatory center uses all available heat-regulatory servomechanisms to maintain the new temperature. Thus a patient with fever in an environment previously believed to be thermally comfortable begins to feel cold and chooses a warmer environment. This behavioral drive is coordinated with the autonomic mechanisms, such as shivering, to increase body temperature to the new set point. In most circumstances, temperature elevation is not a significant problem, and therapy is directed at the underlying disease state. Fever does not cause primary pathologic or physiologic damage to humans and does not require primary emphasis in the therapeutic regimen, which is directed at the underlying disease state. If temperature-related physiologic changes, such as febrile seizures and tachycardia, compromise a patient with marginal cardiac reserve, temperature must be artificially regulated.

Because fever is the product of a molecular interaction that establishes a new physiologic thermal set point, therapeutic attempts to lower temperature are opposed by body mechanisms that attempt to maintain the new set point. Thus attempts at whole-body cooling produce violent shivering and discomfort.²⁶ The use of agents to block the causative molecular interaction is the most clinically effective approach. Antipyretics block the action of the pyrogen at hypothalamic receptor sites through inhibition of prostaglandin synthesis.²⁷ These antipyretics are not effective against and should not be used to control environmental hyperthermia.

Minor Heat Illness

Heat Cramps

Physiology

Heat cramps are brief, intermittent, and often severe muscle cramps occurring typically in muscles that are fatigued by heavy work. Heat cramps appear to be related to a salt deficiency. Heat cramps occur most commonly during the first days of work in a hot environment and develop in persons who produce large amounts of thermal sweat and subsequently drink copious amounts of hypotonic fluid.²⁸

Clinical Factors

Athletes, roofers, steel workers, coal miners, field workers, and boiler operators are among the most common victims of heat cramps. Heat cramps tend to occur after exercise when the victim stops working and is relaxing (Box 141-2). In this respect, they differ from the cramps experienced by athletes during exercise, which tend to last for several minutes, are relieved by massage, and resolve spontaneously.

BOX 141-2 Heat Cramps

Essentials of Diagnosis

Cramps of most worked muscles

Usually occur after exertion

Copious sweating during exertion

Copious hypotonic fluid replacement during exertion

Hyperventilation not present in cool environment

Heat cramps are occasionally confused with hyperventilation tetany, which can occur during heat exhaustion. Hyperventilation tetany can be distinguished by the presence of carpopedal spasm and paresthesias in the distal extremities and perioral area. Heat cramps accompanied by systemic symptoms may be part of salt depletion heat exhaustion. Heat cramp victims exhibit hyponatremia, hypochloremia, and low serum sodium and chloride levels. Rhabdomyolysis or resultant renal damage is not present with isolated heat cramps.

Heat Exhaustion

Physiology

Heat exhaustion (heat prostration) is a clinical syndrome characterized by volume depletion that occurs under conditions of heat stress. Two types of heat exhaustion are classically described: water depletion and salt depletion.

Water depletion heat exhaustion results from inadequate fluid replacement by individuals working in a hot environment, usually laborers, athletes, military personnel, and incapacitated individuals without free access to water. Those working in the heat seldom drink as much as they lose and replace only approximately two thirds of net water loss. This voluntary dehydration results in progressive hypovolemia. Left untreated, water depletion heat exhaustion will progress to heatstroke.

Salt depletion heat exhaustion takes longer to develop than the water depletion form. It occurs when large volumes of thermal sweat are replaced by water with too little salt. It differs from heat cramps in that systemic symptoms occur. This syndrome is characterized by hyponatremia, hypochloremia, and low urinary sodium and chloride concentrations. Symptoms are similar to those seen in water depletion heat exhaustion; body temperature usually remains nearly normal.

Clinical Features

The symptoms and signs associated with both types of heat exhaustion are variable and nonspecific and include weakness, fatigue, frontal headache, impaired judgment, vertigo, nausea and vomiting, and occasionally muscle cramps (Box 141-3). Orthostatic dizziness and syncope can occur. Sweating persists and may be profuse. The core temperature is only moderately elevated, usually below 40° C, and signs of severe CNS dysfunction are not present.

BOX 141-3 Heat Exhaustion

Diagnosis

Vague malaise, fatigue, headache

Core temperature often normal; if elevated, below 40° C (104° F)

Mental function essentially intact; no coma or seizures

Tachycardia, orthostatic hypotension, clinical dehydration (may occur)

Other major illness ruled out

If in doubt, treat as heatstroke

Mild heat exhaustion and full-blown heatstroke represent extremes of the spectrum of heat illness, and intermediate cases may prove difficult to differentiate. Nevertheless, heat exhaustion should not be diagnosed in the presence of major CNS dysfunction (seizures and coma) or severe hyperthermia (40.5° C). If uncertainty exists, measurement of hepatic transaminases may prove helpful. Elevations to several thousand units can be seen in patients with heat exhaustion or in healthy runners after a marathon, whereas in patients with heatstroke, such levels are usually in the tens of thousands after 24 hours.30,31

Management

Pure forms of either type of heat exhaustion are rare, and most cases of heat exhaustion involve mixed salt and water depletion. Heat exhaustion is primarily a volume depletion problem, and rapid recovery generally follows fluid administration. Decisions regarding the type of fluid and electrolyte replacements should be based on serum electrolyte measurements and the estimation of hydration status by clinical and laboratory parameters.

Patients with significant volume depletion or electrolyte abnormalities require intravenous fluids. If the patient is orthostatic, normal saline should be administered until the patient is hemodynamically stable. Free water deficits should be replaced slowly during 48 hours to avoid a decrease of serum osmolality more than 2 mOsm/hr. Overly rapid correction of hypernatremia is associated with seizures caused by cerebral edema.

Disposition

Young, otherwise healthy patients who do not have significant laboratory abnormalities and who respond rapidly to hydration do not require hospitalization. These patients can be discharged with instructions to drink plenty of fluids and to avoid heat stress for 24 to 48 hours. Older patients, particularly those with cardiovascular disease or other predisposing factors described in Figure 141-4, require more cautious inpatient fluid and electrolyte replacement and frequent reassessment (Box 141-4).

BOX 141-4 Heat Exhaustion

Treatment

Rest

Cool environment

Assess volume status (orthostatic changes, blood urea nitrogen level, hematocrit, serum sodium concentration)

Fluid replacement: normal saline to replete volume if the patient is orthostatic; replace free water deficits slowly to avoid cerebral edema

Healthy young patients are usually treated as outpatients; consider admission if the patient is elderly, has significant electrolyte abnormalities, or would be at risk for recurrence if discharged

Figure 141-4 Pathogenesis of hemorrhage. FSP, fibrin split products.

Heatstroke

In the previously discussed forms of heat illness, although the body temperature rises, homeostatic thermoregulatory mechanisms remain intact. Heatstroke is the catastrophic life-threatening emergency that occurs when these mechanisms fail. This failure results in elevation of body temperature to extreme levels, usually higher than 40.5° C (105° F), producing multisystem tissue damage and organ dysfunction.

Physiology

As heatstroke develops, energy will be insufficient to sustain thermoregulatory mechanisms, resulting in dramatic increases in core temperature and the clinical manifestations of heatstroke.³² An exact temperature at which cellular damage begins to occur in an individual patient varies. Credible reports exist of full recovery despite rectal temperatures of 44.4 to 46.5° C.³³ Damage is a function not only of temperature but also of the exposure time.³⁴ The resultant damage to tissues is a function of a complex interaction of body temperature, exposure time, workload, tissue perfusion, and individual factors, which vary markedly.

Neurologic dysfunction is a hallmark of heatstroke, and cerebral edema is common. Other pathologic changes include petechiae in the walls of the third and fourth ventricles and marked cerebellar Purkinje cell damage.³⁵ Interestingly, the hypothalamus, the predominant site of central thermoregulatory control, is usually not damaged.

Heat stress creates tremendous demands on the cardiovascular system, and patients who succumb to heatstroke show signs of circulatory failure. Although such pathologic changes are common, cardiac damage alone is not lethal.

Prolonged heat stress produces impressive increases in skin blood flow (peripheral vasodilation) and a reduction of the thermal gradient between the core and the skin (Fig. 141-5). Functional hypovolemia is avoided by compensatory vasoconstriction of the splanchnic and renal vasculature. The resulting splanchnic and renal ischemia may explain the nausea, vomiting, and diarrhea observed in runners after a marathon. Hepatic damage is such a consistent feature of heatstroke that its absence should cast doubt on the diagnosis. This is manifested pathologically by centrilobular necrosis with extensive cholestasis.

Figure 141-5 Human infrared image. Note that the palms and the face are substantially warmer than the rest of the body. (From Auerbach PS: Wilderness Medicine, 5th ed. Philadelphia, Mosby/Elsevier, 2007.)

If severe heat stress continues, compensatory splanchnic vasoconstriction will eventually fail. Failure to perfuse the skin with heated blood from the core results in a dramatically increased rate of heat storage. This produces elevated intracranial pressure, which in combination with a reduction in mean arterial pressure caused by failure of compensatory splanchnic vasoconstriction, conspires to produce a decrease in cerebral blood flow. This results in the major CNS dysfunction characteristic of heatstroke.

Clinical Features

Heatstroke versus Heat Exhaustion

The onset of heatstroke is sudden, and the patient’s level of consciousness is altered.³⁵ Prodromal symptoms lasting minutes to hours occur in approximately 20% of cases. These are nonspecific and may include weakness, dizziness, nausea, vomiting, anorexia, frontal headache, confusion, drowsiness, disorientation, muscle twitching, ataxia and signs of cerebellar dysfunction, and psychiatric symptoms ranging from anxiety and irritability to psychosis.^36,37

These prodromal symptoms are reminiscent of the description of heat exhaustion. Heat exhaustion, particularly the water depletion variety, can progress to heatstroke if it is untreated. These two syndromes should be considered extremes on a spectrum of responses to heat stress. Heatstroke occurs when the thermoregulatory responses are overwhelmed and fail. If the patient is evaluated as this is occurring, differentiation between heat exhaustion and heatstroke is difficult. If heatstroke cannot be excluded, efforts to cool the patient should begin immediately.

The usual manifestations of heatstroke include hyperpyrexia above 40.5° C, profound CNS dysfunction, and hot skin (Box 141-5). Persistent sweating can be observed in patients with rectal temperatures of 41.5 to 42.4° C with heatstroke. In one large series of exertional heatstroke victims, sweating persisted in 50% of cases.³⁸ Therefore, the cessation of sweating is not the cause of heatstroke, and continued sweating does not preclude the diagnosis.

BOX 141-5 Heatstroke

Diagnosis

Exposure to heat stress, endogenous or exogenous

Signs of severe central nervous system dysfunction (coma, seizures, delirium)

Core temperature usually above 40.5° C (105° F), but may be lower

Hot skin common, and sweating may persist

Marked elevation of hepatic transaminases

Although in heatstroke the core temperature is elevated above 40.5° C, significant cooling may occur in the out-of-hospital phase, and the first temperature obtained in the emergency department (ED) may not represent the original maximum core temperature.

Classic Heatstroke versus Exertional Heatstroke

The two forms of heatstroke have significantly different presentations and manifestations: classic (epidemic) heatstroke (CHS) and exertional heatstroke (EHS) (Table 141-1).

Table 141-1

Usual Characteristics of Heatstroke

EXERTIONAL	CLASSIC
Healthy	Predisposing factors or medications
Younger	Older
Exercise	Sedentary
Sporadic	Heat wave occurrence
Diaphoresis	Anhidrosis
Hypoglycemia	Normoglycemia
DIC	Mild coagulopathy
Rhabdomyolysis	Mild CK elevation
Acute renal failure	Oliguria
Marked lactic acidosis	Mild acidosis
Hypocalcemia	Normocalcemia

CK, creatine kinase; DIC, disseminated intravascular coagulation.

CHS occurs during periods of sustained high ambient temperatures and humidity, such as during summer heat waves. Victims are often elderly and poor and live in underventilated dwellings without air conditioning. Debilitated patients who have limited access to oral fluids may develop water depletion heat exhaustion, which progresses to heatstroke if it is untreated. Victims of CHS commonly suffer from chronic diseases, alcoholism, or schizophrenia, which predisposes to heat illness. Such patients are often prescribed medications (e.g., diuretics, antihypertensives, neuroleptics, and anticholinergics) that impair the ability to tolerate heat stress. Sweating ceases in the majority of CHS patients. Factors such as advanced age, hypotension, altered coagulation status, and the necessity for endotracheal intubation on arrival at the ED predict a poor outcome despite successful cooling measures.³⁹ In contrast, patients with EHS are usually young and healthy individuals whose heat-dispelling mechanisms are overwhelmed by endogenous heat production. Athletes and military recruits are typical victims.^40–42 Rhabdomyolysis and acute renal failure, rarely seen in patients with CHS, are common in patients with EHS.⁴³ Sweating is present in half the cases of EHS. Hypoglycemia may occur as the result of increased glucose metabolism and hepatic damage, resulting in impaired gluconeogenesis. Coagulopathy is common. Hyponatremia with serum sodium levels of less than 130 mmol/L has been detected in summer hikers in the Grand Canyon; many present with neurologic symptoms or seizures.⁴¹ Signs of profound CNS dysfunction dominate the early course of heatstroke. Delirium or coma is characteristic, but virtually any neurologic abnormality, including bizarre behavior, opisthotonos, hallucinations, decerebrate rigidity, oculogyric crisis, and cerebellar dysfunction, can be seen.³⁸ Convulsions occur in up to 75% of patients and can be precipitated by therapeutic cooling maneuvers. Profound muscle rigidity with tonic contractions, coarse tremor, and dystonic movements can mimic seizures. Pupils may be fixed and dilated, and the electroencephalogram may be isoelectric. All these changes are potentially reversible, although permanent damage, including cerebellar deficits, hemiplegia, dementia, and personality changes, is common in severe cases. Patients with heatstroke usually have hyperdynamic cardiovascular systems with low peripheral vascular resistance, tachycardia (up to 180 beats/min), and elevated cardiac index.⁹ Elevation of cardiac troponin I is not uncommon with CHS; however, it is rarer in EHS.^44,45 The central venous pressure (CVP) is usually elevated. The combination of elevated CVP with right-sided cardiac dilation suggests right-sided heart failure, which is also seen after shock or sepsis.⁴⁶ These changes are expected because skin blood vessels dilate to dissipate heat; however, this low peripheral vascular resistance has persisted in patients after reduction of body temperature to nearly normal.

Respiratory alkalosis is a physiologic response to active or passive heating and may be severe enough to produce tetany. Although most patients with CHS have respiratory alkalosis, those with EHS usually have a relatively pure lactic acidosis. Lactic acidosis is associated with a poor prognosis in cases of CHS but not necessarily in cases of EHS. Both CHS and EHS cause the hemoglobin-oxygen dissociation curve to shift to the right. An increase in the temperature denatures the bond between oxygen and hemoglobin, decreasing the concentration of oxyhemoglobin. Aberrations in coagulation are common in patients with severe heatstroke, and their presence is a poor prognostic sign.⁴⁷ Abnormal hemostasis is manifested clinically by purpura, conjunctival hemorrhage, melena, bloody diarrhea, hemoptysis, hematuria, myocardial bleeding, or hemorrhage into the CNS.⁴⁸

Hepatic damage is so consistently featured in heatstroke that its absence should cast doubt on the diagnosis. Hepatic injury is evidenced by markedly elevated levels of hepatic aminotransferases (serum aspartate transaminase and alanine transaminase).⁴⁷ Jaundice typically appears 24 to 72 hours after the onset of severe heatstroke and gradually recedes if the victim survives. Survivors generally have no permanent impairment of liver function. Hypoglycemia with a serum glucose level of less than 65 mg/dL is common in cases of EHS. Renal damage is common. The initial urine specimen, usually obtained by catheterization, is a scanty, brownish, turbid fluid resembling machine oil. Microscopic examination reveals proteinuria with abundant granular casts and red blood cells. Acute oliguric renal failure complicates 25 to 30% of EHS cases and 5% of CHS cases. Glomerular filtration rate, renal plasma flow, urine flow, and sodium excretion diminish markedly during exercise. Heavy physical exertion in hot climates produces acidic and maximally concentrated urine, which can result in acute oliguric renal failure in combination with hypotension and myoglobinuria.²⁸ Cocaine use is also associated with rhabdomyolysis and hyperthermia.⁴⁹ Diarrhea, probably caused by intense splanchnic vasoconstriction, is commonly seen. Cooling aggravates the diarrhea, creating an unpleasant treatment problem. Pancreatitis is described with elevated serum amylase and lipase levels.

Diagnostic Strategies

Thermometry

Unfortunately, most standard measurements of body temperature vary significantly from the actual core temperature. Oral thermometry is affected by mouth breathing and is a poor approximation of the core. Rectal thermometry is less variable but responds to changes in core temperature slowly. Thermistors that are inserted 15 cm into the rectum offer continuous monitoring of temperature and less variability. Although rectal measurements are slower to respond to changes in core temperature than tympanic temperature readings, rectal measurements are not biased by head skin temperature. An esophageal thermistor positioned adjacent to the heart is another option.

Placement of a tympanic temperature sensor directly on the tympanic membrane is difficult and is not used clinically. Commercially available infrared thermometers do not physically contact the tympanic membrane and are unreliable in detection of hyperthermia.⁵⁰ Only after the initial assessment and cooling have begun is the differential diagnosis relevant. When a history of collapse under conditions of heat stress is present, rapid improvement in mental status and blood pressure with cooling eliminates alternative diagnoses. If, however, the temperature does not respond and the patient does not recover neurologically, other causes of fever and coma should be considered (Box 141-6).

The history may be helpful; shaking chills suggest fever with an altered hypothalamic set point rather than heat illness. Meningitis and encephalitis can masquerade as heatstroke. In patients with heatstroke, the spinal fluid should be crystal clear, with occasional lymphocytic pleocytosis and elevated protein levels. Cerebral falciparum malaria, which presents a clinical picture of high fever and encephalitis, is seen in tropical areas where heat illness can also occur.

In patients with thyroid storm, the clinical symptoms resemble those of heatstroke. It should be suspected if the thyroid gland is enlarged or nodular, but a normal thyroid gland does not exclude the diagnosis. Thyroid function test results are elevated, but these are not available on an emergency basis. Fortunately, thyroid storm is rare, and some critical aspects of treatment, such as rapid cooling, coincide with those for heatstroke.

Drug-induced heat illness is an important consideration, particularly anticholinergic poisoning. Differentiation may be difficult because both heatstroke and anticholinergic poisoning produce hyperpyrexia, hot and dry skin, tachycardia, and abnormal mental status. Constricted pupils are present in many heatstroke patients.⁵¹ Mydriasis should be present in patients with anticholinergic poisoning, and its absence argues strongly against this diagnosis. Typhoid fever, typhus, delirium tremens, and hypothalamic hemorrhage all produce a symptom complex similar to that of heatstroke.

Malignant hyperthermia and neuroleptic malignant syndrome are characterized by lead-pipe rigidity. The serotonin syndrome can also mimic heatstroke because of the elevated body temperature tremors and CNS alterations that occur. Serotonin syndrome is classically a triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities secondary to increased CNS serotonergic activity. A history of recent exposure to illicit or therapeutic medication is an important clue.

Hepatic transaminase elevations may be diagnostically helpful. In most febrile states that include altered mental status or coma, these enzymes will be normal or minimally elevated, although they are usually dramatically elevated early in the course of heatstroke.

Management

It does not take long either to boil an egg or to cook neurons.

David Hamilton ⁵²

Cooling

Immediate cooling is the cornerstone of treatment. Mortality correlates with the temperature and the number of dysfunctional organ systems, with an increased risk of death if patients present with anuria, coma, or cardiovascular failure.⁵³ Patients who present to the hospital with heat stroke have high mortality rates ranging from 21 to 63%,^4,54 and mortality increases significantly when cooling is delayed.^34,55 Cooling efforts take precedence over any time-consuming search for the cause. In the out-of-hospital setting, cooling should be initiated after removal of the patient from the hot environment. When the patient arrives at the hospital, clothes should be removed, a thermistor probe should be inserted, and the temperature should be continuously monitored.

The ideal method of evaporative cooling uses a body cooling unit on which the patient lies suspended on a net surface while being sprayed with atomized 15° C water from above and below.⁵⁶ Air warmed to 45 to 48° C is blown over the skin surface at 3 m/min. The unit, not widely available, maximizes evaporative cooling by maintaining cutaneous vasodilation and avoiding heat generation caused by shivering.

Less complex equipment can also be used to maximize evaporative cooling, which is the most widely used cooling method. The combination of atomized tepid water at 40° C from a spray bottle and standing fans cools at rates comparable to both body cooling unit and immersion.⁵⁷ Other evaporative techniques, including the use of downdraft from a helicopter, can be applied successfully.⁵⁸ Immersion in ice water results in a rapid reduction of core temperature to below 39° C within 10 to 40 minutes but complicates the resuscitation.⁵⁵ Vigorous skin massage to maintain cutaneous circulation has been advocated, but there is no objective evidence that this is efficacious. When the body temperature reaches 39° C, cooling measures should be discontinued to avoid hypothermic overshoot. Continuous monitoring is necessary to maintain the core temperature at 37 to 38° C.

Military studies of EHS patients treated with ice water immersion have reported no fatalities or permanent sequelae.⁴⁰ A mortality rate of 14% was reported in a study of 28 patients with CHS treated by immersion.⁵¹ Immersion is technically difficult in the ED. Vasoconstriction from ice water immersion may be beneficial to hypotensive patients and may be better than evaporative cooling for victims in shock who have poor peripheral circulation.⁵⁹

Cooling modalities other than evaporation and immersion should be considered adjunctive treatments (Box 141-7). Application of ice packs to high heat transfer areas (neck, groin, and axillae) is commonly used. Cooling blankets may be a useful adjunct but will not produce rapid cooling if they are used exclusively. Peritoneal dialysis with cold fluids, although successful in a canine model, is invasive. Cold-irrigant gastric or rectal lavage will not provide significant heat exchange if it is used as the primary cooling modality.

Resuscitation

Aspiration and seizures are common in patients with heatstroke, and airway control is essential.⁶⁰ Hypoxemia may occur because of aspiration, pneumonitis and pulmonary infarction, hemorrhage, or edema. Metabolic demands are high, and normal pulmonary ventilation may be inadequate in this setting.

Circulatory fluid requirements are modest in some cases, averaging 1200 mL of isotonic crystalloid solution in the first 4 hours. Pulmonary edema occurs in patients with heatstroke and can be exacerbated by overzealous fluid administration. The use of a CVP catheter to monitor fluid resuscitation may be deceptive. Most patients have a hyperdynamic circulation with high cardiac index, low peripheral vascular resistance, and elevated CVP as a result of right-sided heart failure. These patients may require only modest intravenous fluids because cooling produces vasoconstriction and increases blood pressure.⁶¹ Nevertheless, crystalloid resuscitation is essential.

Hypotension is common in patients with heatstroke and is usually caused by peripheral vasodilation resulting in high-output cardiac failure in addition to dehydration.⁹ Blood pressure usually rises with cooling. If this does not occur, or if the patient monitored invasively has a low CVP, a fluid challenge of 250 to 500 mL of 0.9% saline should be given rapidly while blood pressure, pulse, and urine output are monitored. If the blood pressure rises, more fluids are given with careful monitoring of the CVP. Aggressive fluid replacement is continued until the blood pressure reaches 90/60 mm Hg or the CVP exceeds 12 mL H₂O. On occasion, patients exhibit hypodynamic responses with low cardiac index, elevated CVP, and hypotension. These patients may be cyanotic, whereas patients with hyperdynamic circulation are initially pink. This clinical observation can be helpful in identifying patients who may respond to catecholamines.

A variety of tachyarrhythmias commonly occur during heatstroke. These usually resolve with cooling, and electrical cardioversion should be avoided until the myocardium is cooled. The use of alpha-adrenergic agents such as norepinephrine is not recommended because they promote vasoconstriction without improving cardiac output or perfusion, decrease cutaneous heat exchange, and may enhance ischemic renal and hepatic damage. Atropine and other anticholinergic drugs that inhibit sweating should be avoided.

Because the pathophysiologic processes of heatstroke and fever differ, antipyretics are not indicated and may be harmful. Salicylates, particularly in large doses, can worsen hyperthermia by uncoupling oxidative phosphorylation and aggravate coagulopathies. Large doses of acetaminophen can result in further hepatic damage. The efficacy of dantrolene is not established.⁶² If rhabdomyolysis is present, maintenance of urinary output of at least 2 mL/kg/hr is required.⁶³ Urinary alkalinization higher than 6.5 should be considered early in patients with acidemia, dehydration, or underlying renal disease. After volume repletion, administration of mannitol may be considered to increase intravascular volume and to increase glomerular filtration rate. Mannitol should not be used in an oliguric patient.⁶⁴ Persistent anuria, uremia, or hyperkalemia is an indication for consideration of hemodialysis.

Hematologic evaluation should include arterial blood gas determination; complete blood cell count and platelet counts; electrolyte values and blood urea nitrogen, glucose, creatinine, aspartate transaminase, alanine transaminase, lactate dehydrogenase, creatine kinase, uric and lactic acid, and calcium levels; prothrombin and partial thromboplastin times; international normalized ratio; and fibrin degradation products and hepatic enzymes. Serum cardiac troponin I levels should be obtained. Acidosis is common, especially in patients with EHS. Lactate levels are usually elevated; this may persist or even worsen with improved extremity perfusion.⁵³

Cooling modalities that drastically lower skin temperature may induce violent shivering; this increases metabolic heat production and may impede cooling. Intravenous benzodiazepines are the treatment of choice for shivering. Neuroleptics, like chlorpromazine, have anticholinergic properties that can interfere with sweating and cause hypotension or, rarely, precipitate seizures; therefore, they should be avoided. Many patients are extremely agitated during the initial cooling period. Short-acting benzodiazepines can be used for sedation and to control seizures. Barbiturates are less desirable for treatment of seizures because metabolism is altered by hepatic dysfunction.

Coagulopathies can occur during the first day of illness but are more common on the second and third days. Initial treatment after cooling should include replacement therapy with fresh frozen plasma and platelets.⁴⁸ The clinician should monitor the laboratory signs of disseminated intravascular coagulation (hypofibrinogenemia, elevated fibrin split products, prolonged prothrombin time, and thrombocytopenia).⁴⁸ The bleeding diathesis in patients with heatstroke may be the result of fibrinolysis. Although α-aminocaproic acid can impede fibrinolysis, administration of this compound is associated with rhabdomyolysis, and its use is not recommended in patients with heatstroke.

Key Concepts

Antipyretics are ineffective and should not be used to control environmental hyperthermia.