Vincent Costers, PGY-2

Intro

Summer is fast approaching, and temperatures are rising. As the heat waves roll in, heat-related illnesses will start to present to the department. Heat-related illnesses account for 600 deaths annually in the United States (3). Florida is a mecca of tourism for the world and brings in people from all walks of life from differing climates and with different levels of physical fitness. South Florida has a large migrant population of elderly from Northern states that come to visit vacation homes throughout the year as well as a rapidly growing retirement community. The global COVID pandemic has also caused a renaissance in outdoor activity as outdoor and socially distanced recreation becomes the leisure of choice for Millennials. In addition, exercise-related heat stroke is the leading cause of death in high school athletes (4). The suffocating humidity and prolonged heat of summer create a perfect recipe in Florida for heat-related illness. 

Definitions

To discuss heat-related illnesses (HRI), it is important to first define several terms when describing heat and energy transfer. The homeostatic balance of thermal energy in the body can be defined by the following equation:

Heat Storage = (Metabolic Rate – Work)– (Evaporative – Convective – Conductive – Radiative)

Where in Heat Storage (S) < 0 = Heat Loss, and (S) > = Heat Gain

Work Losses (W): Energy lost through work done to the environment, aka movement

Evaporative (E): Energy lost as water changes from liquid to a gaseous state

Convective (C): Energy transfer to adjacent moving molecules

Conductive(K): Energy transfer through contact with solid objects

Radiative (R): Energy transferred through electromagnetic radiation

Thermoregulation

The human body is always attempting to maintain homeostasis, a set point of equilibrium between interdependent elements such as pH, temperature, and osmolarity, to maintain the ideal environment for enzymatic activity and other physiologic processes. The body has developed a myriad of adaptations to regulate temperature. The preoptic anterior hypothalamus for humans is the thermostat for the body that signals the need for an increase or decrease in heat storage. The temperature this thermostat aims for under normal conditions is 37°C.  During physical activity, the work done on the environment, denominated as a negative value, leads to a rise in heat storage pushing the value of (S)>0 and body temperature above 37°C. To correct the temperature to a more physiologically favorable one, the body utilizes elements of (E, C, K, and R) from the above equation to lower body temperature. The inability of the body to compensate for increases in heat storage is the source of heat-related illness.  

The body can lose large amounts of stored thermal energy through evaporation via respiration and sweating. Every liter of fluid lost as sweat translates to 580 kcal loss of heat (5). The chest and back are the primary sources of sweat production, with the lower extremities providing only 25% of sweat lost (6). Respiration provides evaporative losses from mucous membranes and is the same mechanism that dogs utilize to the extreme as they pant. Although sweating is one of the main mechanisms for heat loss, it comes with downsides. An exercising adult sweats at a rate of 0.3-3.0L of sweat per hour, risking large fluid losses and electrolyte derangements such as hyponatremia (7,8). Another method of cooling is through convection by utilizing heat exchange in the capillaries of the skin as they encounter moving molecules in wind or water currents by vasodilation or constriction. Expansive convective heat transfer is limited by the body's need for fluid in visceral organs and is very dependent on the body's initial fluid status. Conduction can be the most effective method to cool the body but is limited by the environment one finds themselves in. For example, asphalt quickly becomes up to 72°F warmer than its surroundings under full sunlight and leads to warm microclimates (9). Heat exchange through a medium such as water happens at 25 times the rate of exchange through the air, but conductive losses generally require a behavioral adaptation to seek out improved heat transfer media. Physiologic metabolic processes continually create infrared energy, and though only a small fraction of heat loss, thermal energy is continually radiated away from the body.  Most of the compensatory mechanisms used to adjust thermal storage are controlled involuntarily through autonomic processes coordinated by the hypothalamus including sweating, vasodilation, piloerection, shivering, and brown fat thermogenesis. 

Types of Heat Illness

Heat Exhaustion: Body unable to compensate for an increase in heat storage

Heat Injury: Heat exhaustion + organ dysfunction

Classic Heat Stroke: Heat injury + T > 104°F + CNS dysfunction

Exertional Heat Stroke: Heat injury + CNS dysfunction in the setting of exercise

Heat Rash: Rash that develops during temperature dysregulation

Heat Cramps: Involuntary muscle contractions due to electrolyte dysregulation

Heat Syncope: Loss of consciousness due to fluid pooling in the periphery

Erythromyalgia: Pain in extremities due to swelling in high temperature

Uncompensated temperature rise leads to many deleterious consequences described in the various stages and forms of heat illness. As the body begins to lose control of its thermostat, the first symptoms are fatigue, nausea, vomiting, and lightheadedness as tachycardia and relative hypotension sets in. Cardiac output is no longer able to be maintained at elevated temperatures. This is known as heat exhaustion, and, like other forms of HRI, is most frequently found in the extremes of age as thermoregulation less effective.  

If heat exhaustion continues without cooling, it can lead to a heat injury. A heat injury includes organ dysfunction and can be found in elevated LFTs, Cr, Myoglobin, CK, or decreases in urine excretion. This intermediary step bridges heat exhaustion and heatstroke. Heatstroke can be divided into two phenotypes, classical and exercise-related heat stroke. 

Classical heat stroke is what is often thought of when mortality rises during a heatwave. Heatstroke, like heat injury, requires organ dysfunction but specifically needs to present with CNS involvement and a core temperature over 104°F. This usually results in a patient with altered mental status without other causes outside of body temperature. This form of heatstroke may commonly present with anhidrosis in a patient that you would otherwise expect to be sweating. Declining autonomic thermoregulatory ability makes this disease process especially devastating in elderly populations and has been described as having as high as a 60% rate of being hospitalized or found dead by EMS (10). 

  Exercise-induced heat stroke (EHS) differs from classical heatstroke in demographics and cause. EHS is most often found in young, fit athletes. The pathology of EHS is secondary to overexertion beyond the body's ability to compensate in its ability to cool. These patients usually are still sweating and do not regularly have the autonomic dysfunction of classic heat stroke leading to anhidrosis. Exercise induces this extreme hyperthermia leading to CNS dysfunction, but as the thermostat of the body is still functional, rapid return to euthermia often leads to good outcomes with a mortality rate of only 3-5%. 

  Heat rashes, syncope, and cramps are HRIs that commonly present in heat exposed individuals and are all complications of the body attempting to cool. Heat rash also known as milia rubra is caused by clogged sweat glands ineffectively trying to cool the body and becoming inflamed. Milia can be resolved by cooling and drying the skin and may show some improvement with aspirin or topical steroids. Heat syncope is a result of a fluid shift from the cardiovascular system to the capillary beds as vasodilation occurs to improve convective cooling. Adequate hydration is an excellent preventative method for heat syncope. Heat cramps are another complication of excessive evaporative cooling through sweating. Sweating causes fluid loss and, secondarily, electrolyte derangements. In combination with increased muscular exertion during exercise, calcium builds up intracellularly and leads to unwanted muscle contraction. Erythromyalgia, although less common, has also been described as a pathology in heat exposure that is due to edema in the hands and feet in an attempt to further convective cooling (11).

Physiology of Heat Stroke

The physiologic mechanism of heatstroke is very closely linked to that of SIRS in sepsis. Rising temperatures in the core lead to a breakdown of the gut lining. Epithelial barriers in the mucosa begin to break down at high temperatures and are exacerbated by blood flow away from the viscera and to the periphery leading to localized ischemia. This breakdown of the mucosa allows the permeation of endotoxins and bacterial lipopolysaccharides into the bloodstream. Similar to bacteremia sepsis, this invasion of antigens into the bloodstream starts a cytokine cascade and systemic inflammatory response. Simultaneously, high temperatures and often exertion cause muscle breakdown and an increase of circulating myoglobin that is excreted by an under-perfused renal system leading to clogging of nephrons and renal dysfunction. Renal function in coordination with a SIRS response in the setting of peripheral vasodilation and electrolyte derangements are even further complicated by the activation of coagulative processes.  

At 39°C, plasminogen and fibrinogen start to decrease in functionality. As the temperature climbs to 41.8°C, Factor VII activity declines (12). Finally, at 43°C, platelets will spontaneously aggregate irreversibly (13, 14). DIC is a common complication in heatstroke and is started by microvascular thrombosis at the site of endothelial injury causing a consumptive coagulopathy and risk for delayed hemorrhages (15, 16, 17). These changes in coagulation and widespread micro thrombosis and hemorrhages in the spleen cause disruption to immune processes, centrilobular necrosis in the liver, and acute tubular necrosis in the kidneys (18, 19, 20).  Liver failure eventually leads to disruption of enzymatic processes and glucose dysregulation due to impairment of the gluconeogenic pathway (21,22). Lactic acid builds up in the setting of ischemia, muscle breakdown, and breakdown of lactic acid metabolism by the liver resulting in metabolic acidosis often obscured by a respiratory alkalosis, especially so in EHS.

In all this chaos with loss of enzymatic function, coagulopathy, fluid dysregulation, loss of vascular tone, acidosis, and electrolyte disturbance, the CNS is affected, the hallmark of Heat Stroke. Cerebral edema sets in with microhemorrhages causing cerebellar infarcts and ultimately a loss of grey-white matter differentiation (23). This generally starts with ataxia, dysarthria, and altered mental status and progresses to obtundation and finally coma. 

Treatment Prehospital

The key to treatment in the field is early recognition. Seeing peers out in the heat with flushed faces, hyperventilation, headache, lightheadedness, or sensations of nausea, tingling, chilliness, and especially confusion should be red flags that hyperthermia occurring (24). The initial actions should be to seek shade, go indoors if possible, and start oral rehydration. 

Oral rehydration should be 1-2 liters in the first hour followed by rest and continued oral hydration for an additional 24 hours or 2 cups of fluid per pound lost in sweat. It is important to avoid overly sugary drinks for rehydration as they may delay gut absorption. A good rehydration fluid that strikes a good balance is normal Gatorade cut 50% with water.   

During outdoor athletic events, EHS should be higher on the differential. Altered mental status in an athlete in the absence of trauma is EHS until proven otherwise. The duration of hyperthermia is the primary determinant of outcome and further enforces the need for early recognition.  Before 1950 the mortality in EHS was as high as 50%, however, recent advances in recognition, education, and treatment have led to a decline in mortality to single-digit percentages (25). 

  If heat stroke is suspected change what you can about the environment; go indoors or in the shade and call EMS. Following environmental modifications, it is important to check your airway, breathing, and circulation and immediately resuscitate as the situation requires. If the patient is wearing restrictive clothing, remove those to help with heat transfer. The absolute best method for cooling is cold water immersion (26, 27). Conductive heat exchange is far and away the most efficient cooling process.  If a cold-water immersion is not feasible, then alternatives include cool water pours, icepacks to the groin/axilla, and soaked bed sheet wraps. 

When EMS arrives, continue cooling through the transition to and during transportation. EMS should not delay cooling or transportation to obtain a temperature. Large-bore IV access should become a priority to run cooled IV crystalloid. On the way to the hospital, EMS should be placing the patient on the monitor, giving NC oxygen, and giving glucose as necessary with D50 for a glucose less than 60. If the patient is not protecting their airway, first responders should obtain an airway with either a supraglottic device or endotracheal intubation if training allows. Importantly, antipyretic medications should be avoided. 

At the Hospital

             When a patient presents to the emergency department by EMS for heat stroke, do not be fooled by the temperature in a partially cooled patient. Heatstroke is a clinical diagnosis and AMS or other CNS derangement in a hyperthermic patient, even if no longer >104°F should still be treated as an acute heatstroke. On arrival, first, repeat a primary survey and ensure the patient's ABCs are intact. If an airway is required, place it. These patients will generally be tachypneic and oxygen hungry. Every degree over euthermia is associated with a 10-13% increase in oxygen demand (28). Once the primary survey is complete and any required resuscitation is addressed, cooling the patient should become the next priority. A rectal probe becomes key as it gives a reliable core temperature without delay, such as with a bladder temperature, and is not affected by resuscitative efforts such as oxygen therapy in esophageal probes. The patient should be cooled by any means available but preferably with cold water immersion. Cold packs, as well as wet sheets in conjunction with fans or water pours, can be helpful. If available, cooling catheters are also an option. A foley should still be placed and cooled crystalloid, after an initial bolus, should be given as maintenance and titrated to urine output. The patient should be on a cardiac monitor, and electrolytes and glucose should be checked at regular intervals. If the patient's mental status does not start to improve at euthermia, other diagnoses should be considered for CNS depression (29).

            Although the patient is hyperthermic, antipyretic drugs should not be used. Tylenol should be avoided as environmental hyperthermia is not equivalent to fever. Heatstroke can lead to liver failure and the need for transplant; further liver insults in an already stressed liver should be avoided. NSAIDs similarly have no role in HRI treatment and worsen kidney injury. In addition, it was found that patients who took indomethacin before an HRI had a 40% increased rate of mortality, attributable to gut hemorrhage (30). Although theoretically dantrolene would be beneficial in HRI, it has so far not been shown to improve outcomes (31). Any medication that decreases the body's ability to thermoregulate such as anticholinergics should be avoided when possible. Seizures that occur during resuscitation should be quickly dealt with using higher dose benzodiazepines as the seizure activity will start to independently raise core temperature. If cooling begins to cause shivering in the hyperthermic patient, benzodiazepines or meperidine can help in shiver suppression (32). Heat cramps can also be dampened using an infusion of magnesium. To assist in the clearance of excess myoglobin, Lasix can be used in association with fluids to improve renal blood flow. 

            Modern-day treatment of heatstroke once in the hospital leads to a survival rate of 90-95% (33). However, after leaving the emergency department patients often have a long road to recovery. Poor prognostic factors include >24hrs of coma, persistent temperature >41°C, and loss of grey-white differentiation on CT (34). Neuro deficits often dissipate with euthermia; however, 78% of heatstroke victims will have some neurologic impairments longer term (28). Luckily, these neurologic deficits usually resolve within 12-24 months. Heatstroke patients often require hemodialysis and, in some cases, will need an organ transplant.

Returning to Activity

Although every case is different, the Academy of Sports Medicine recommends the following guidelines for athletes returning to activity. 

RTP guidelines by ACSM (35)

• 7 days no exercise

• Labs and physical at 7 days

• Gradual return starting in a cooled environment over 2 weeks

• If not heat tolerant at 2-4 weeks, then lab physio testing

• If heat-tolerant after 2-4 weeks, then can return to play

Victims of classic heatstroke should work with PT and OT as neurologic deficits are common and slowly ease back into their activities of daily living as tolerated. 

Prevention 

Prevention is key in preventing HRIs. Watching the weather closely and knowing the climate when you travel can help both prepare for and avoid dangerous conditions. One measurement that can be followed is the water bulb globe temp (WGBT) more commonly known as the heat index. This measurement factors in not only the outdoor temperature but also the effects of increased humidity and the level of solar radiation. When the heat index is higher, radiation and humidity will limit the body's ability to lose heat through its normal mechanisms such as sweating. Wearing light and absorbent clothing can help to assist in cooling while constrictive or non-breathable fabrics should be avoided. Whenever possible, shade and indoor activity should be utilized when the heat index is elevated. Staying hydrated can also help in supporting the cardiovascular system to keep fluid shifts from causing syncope and injury. Although they are becoming more popular, salt tabs to assist in electrolyte balance are contraindicated in exercises where there are elevated temperatures as they cause irritation to an already irritated GI system and potentiate potassium losses through the kidneys (36). EHS is most common in the US in the first 4 days of summer training camp as athletes are not acclimatized to the heat, so training in the early morning or evening may help. A tragic, but not uncommon cause of HRI is children being left in hot cars. Education on not leaving children or pets in cars can save many lives every year. 

Adaptation 

A heatwave is defined as 3 or more days of a temperature above 90°F. Although this is a common occurrence in Florida, these events are followed by a wave of death in northern climates. The reason for this is a lack of heat acclimatization. Humans have developed many clever adaptations to adjust to climate with up and down-regulation of genes that code for heat shock proteins. Heat shock proteins (HSPs) help to allow several adaptations including more efficient vasodilation and sweating, decreased gut permeability at temperature, increased cardiovascular function, decreased metabolic rate, and better maintenance of hydration and electrolyte balance (36, 37). Upregulation of these proteins starts with exposure to heat. In the average adult, it takes 10 days of daily heat exposure to acclimate while it takes 27 days if only exposed every 3 days (38). This information can be used to help reduce HRIs by allowing gradual exposure to heat when a known heat exposure will happen. This is also why the start of training camps in the summer is a common trope for the presentation of EHS. Unfortunately, this also puts people from colder climates at risk of heatstroke as they are not adapted to handle heat stress, especially the elderly population with baseline lower autonomic regulatory and cardiovascular ability. 

Risk Factors

            There are several modifiable risk factors for HRI that may help in stratifying personal risk of injury. Obesity is one of the most common risk factors and is due to excess adipose preventing heat exchange with the environment as adipose has a 60% lower heat conductivity when compared to the viscera (39). Poor physical fitness can also be dangerous as low cardiovascular fitness can prevent the body from being able to adequately compensate for fluid shifts. Skin rashes such as widespread sunburn or a history of skin grafts can limit the ability to sweat.  Several medications also decrease the body's ability to react to heat and include anticholinergic agents, sympathomimetics, alcohols, diuretics, beta-blockers, and antidepressants.  Alcohol decreases antidiuretic hormone which leads to a decrease in fluid retention and dehydration. Finally, any chronic illness or inflammatory process can decrease thermoregulatory ability. 

Key takeaways

• Early recognition of heat illness and public education is vital to decreasing mortality and morbidity.

• Classic heat stroke presents with anhidrosis is more common in extremes of age

• Athletes with AMS in the absence of trauma are EHS until proven otherwise

• Time at hyperthermia drives outcomes and cooling should be initiated rapidly

• Coldwater immersion is the preferred method for rapid cooling

• Antipyretic medications do not help in HRI and cause harm

• Heatstroke causes multiorgan failure through a SIRS response

• Prevention through behavioral modification can prevent most HRI

• Humans can acclimatize to heat over about 2 weeks allowing resistance to HRI

• There are several modifiable factors to decrease the risk of HRI

References

Lipman, Grant S. et al: Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Heat Illness: 2019 Update. Wilderness & Environmental Medicine, Volume 30, Issue 4, S33 - S46

Auerbach, P. S., Cushing, T. A., & Harris, N. S. (2017). Chapter 12-13. In Auerbach's wilderness medicine. essay, Elsevier. 

Xu J. QuickStats: Number of heat-related deaths, by sexes national vital statistics system, United States, 1999e2010. MMWR Morb Mortal Wkly Rep. 2012;61(36):729.

Gilchrist J, Haileyesus T, Murphy M, Comstock RD, Collins C, Yard E. Heat illness among high school athletes United States, 2005e2009. MMWR Morb Mortal Wkly Rep. 2010;59(32):1009e13.

CV Gisolfi, CB Wenger: Temperature regulation during exercise: old concepts, new ideas. Exerc Sport Sci Rev. 12:339-372 1984 

ER Nadel, JW Mitchell, B Saltin, JA Stolwijk: Peripheral modifications to the central drive for sweating. J Appl Physiol. 31 (6):828-833 1971 

JF Clark: Some effects of the urban structure on heat mortality. Environ Res. 5:93-1041972 

RW Kenefick, SN Cheuvront, MN Sawka: Thermoregulatory function during the marathon. Sports Med. 37 (4–5):312-315 2007 

H Frumkin: Urban sprawl and public health. Public Health Rep. 117 (3):201-217 2002

TS Jones, Liang AP, EM Kilbourne, et al.: Morbidity and mortality associated with the July 1980 heat wave in St Louis and Kansas City, Mo. JAMA. 247 (24):3327-3331 1982

D Lipsker: Images in clinical medicine: A white hand and a red hand erythromelalgia.N Engl J Med. 363:1463 2010

SV Strother, JM Bull, SA Branham: Activation of coagulation during therapeutic whole body hyperthermia. Thromb Res. 43 (3):353-360 1986

JG White: Effects of heat on platelet structure and function. Blood. 32 (2):324-3351968

G Camus, J Poortmans, M Nys, et al.: Mild endotoxaemia and the inflammatory response induced by a marathon race. Clin Sci (Lond). 92 (4):415-422 1997

A Bouchama, F Bridey, MM Hammami, et al.: Activation of coagulation and fibrinolysis in heatstroke. Thromb Haemost. 76 (6):909-915 1996

A Bouchama, JP Knochel: Heat stroke. N Engl J Med. 346 (25):1978-1988 2002

KY Mustafa, O Omer, M Khogali, et al.: Blood coagulation and fibrinolysis in heat stroke. Br J Haematol. 61 (3):517-523 1985

Lin XJ, Li YJ, Li ZL, et al.: Pre-existing lipopolysaccharide may increase the risk of heatstroke in rats. Am J Med

N Malamud, W Haymaker, RP Custer: Heat stroke: Clinico-pathologic study of 125 fatal cases. Mil Surg. 99:397-449 1946

Chao TC, R Sinniah, JE Pakiam: Acute heat stroke deaths. Pathology. 13 (1):145-1561981

LR Leon, MD Blaha, DA DuBose: Time course of cytokine, corticosterone, and tissue injury responses in mice during heat strain recovery. J Appl Physiol. 100 (4):1400-14092006

O Szold, II Reider-Groswasser, RB Abraham, et al.: Gray-white matter discrimination: A possible marker for brain damage in heat stroke?. Eur J Radiol. 43:1-5 2002

MK Mustafa, M Khogali, K Gumaa: Respiratory pathophysiology in heat stroke. MKhogali JRS Hales Heat stoke and temperature regulation. 1983 Academic Press New York 119-127

O Appenzeller, R Atkinson: Sports medicine: fitness training injuries. Baltimore 1981

FP Ellis: Mortality from heat illness and heat-aggravated illness in the United States.Environ Res. 5:1-58 1972

DJ Casa, BP McDermott, EC Lee, et al.: Cold water immersion: The gold standard for exertional heatstroke treatment. Exerc Sport Sci Rev. 35:141-149 2007

WO Roberts: A 12-yr profile of medical injury and illness for the Twin Cities Marathon.Med Sci Sports Exerc. 32:1549-1555 2000

EF Du Bois: The basal metabolism in fever. JAMA. 77:352-355 1921

A Bouchama, JP Knochel: Heat stroke. N Engl J Med. 346:1978-1988 2002

JT Stitt: Prostaglandin E as the neural mediator of the febrile response. Yale J Biol Med. 59 (2):137-149 1986

A Bouchama, A Cafege, EB Devol, et al.: Ineffectiveness of dantrolene sodium in the treatment of heatstroke. Crit Care Med. 19 (2):176-180 1991

CI Proulx, MB Ducharme, GP Kenny: Effect of water temperature on cooling efficiency during hyperthermia in humans. J Appl Physiol.

S Shibolet, R Coll, T Gilat, E Sohar: Heatstroke: Its clinical picture and mechanism in 36 cases. Q J Med. 36:525-548 1967

M Royburt, Y Epstein, Z Solomon, J Shemer: Long-term psychological and physiological effects of heat stroke. Physiol Behav. 54:265-267 1993

LE Armstrong, DJ Casa, M Millard-Stafford, et al.: Exertional heat illness during training and competition. Med Sci Sports Exerc. 39:556-572 2007

J Gonzalez-Alonso, C Teller, SL Andersen, et al.: Influence of body temperature on the development of fatigue during prolonged exercise in the heat. J Appl Physiol (1985).86 (3):1032-1039 1999

LG Pugh, JL Corbett, RH Johnson: Rectal temperatures, weight losses, and sweat rates in marathon running. J Appl Physiol. 23 (3):347-352 1967

JT Fein, EM Haymes, ER Buskirk: Effects of daily and intermittent exposures on heat acclimation of women. Int J Biometeorol. 19 (1):41-52 1975

CB Wenger: The regulation of body temperature. GA Tanner Medical physiology. 1995Little, Brown Boston 590

Image Credits: 

https://rothmanortho.com/stories/blog/sports-related-heat-exhaustion (hiker)

https://doctorlib.info/physiology/medical/336.html (heat dispersion)

https://www.mercy.net/newsroom/2017-07-28/prepping-for-serious-student-athlete-injuries/ (immersion bath)

https://newsela.com/read/heatstroke-students/id/5513/ (football player)

About the Author

Vincent Costers is a current PGY-2 Emergency Medicine resident at USF. He completed his medical school training at USF Morsani College of medicine. He is currently working towards completing a Fellowship in the Academy of Wilderness Medicine (FAWM). He also serves as an Academic Chief and Blog Editor for the 2022-2023 academic year.