Hyperthermia and Heat-Related Illness

As summer gets closer, so does the risk for heat injury. In this post we will review heat injury, as well discuss some of the misconceptions in regards to hyperthermia and other classic heat related illnesses.

First off, it needs to be understood that hyperthermia does not equal fever. Fever is a desired change in homeostatic baseline core body temperature as a means of defense against infection, and body temperature rises because the hypothalamus wants it to. In contrast, hyperthermia is an undesired net gain of heat which causes an increase in body temperature in spite of the hypothalamic set point. In essence, heat gained > heat lost.

Heat transfer occurs by four primary mechanisms:

  1. Evaporation: heat liberation by liquid changing into a vapor (sweating)
  2. Radiation: heat transfer from a warm object into the surrounding environment (solar warmed rock in cool air)
  3. Conduction: heat transfer from a warm object by direct contact with a cooler object (warm hand on a metal chair)
  4. Convection: moving current removes radiated heat from the area adjacent to the body (this is prevented by a wet suit or a down jacket that keeps the radiated warmth next to the body)

Heat accumulation has both internal and external components. Routine metabolism generates heat through exothermic reactions leading to approximately enough heat to increase body temperature by 1.1°C per hour. Intense exercise can increase this metabolic heat production up to 20x. Heat can also be gained from the environment through the heat transfer mechanisms discussed above. Normally, the body deals with this heat accumulation through sweating (evaporation) and vasodilation of the skin vasculature (radiation). Heat can also be dissipated through respiration, although this in minimal in comparison to dogs which can lose a good deal of heat through panting.

The environment can play a large role in our ability to lose heat. As humidity reaches 100%, sweat evaporation is impaired as there is no "room" in the air for the vaporized sweat molecules. Also, once the ambient temperature reaches 35°C, the temperature gradient begins to favor heat retention, and as it increases, can lead to heat gain.

As body temperature rises, more blood is shunted to the periphery in attempts to dissipate the excess heat. This is done so at the expense of core perfusion. The first organ to suffer hypo-perfusion is the mesentery, which leads to loss of microvilli in the gut and endothelial compromise. Endotoxins, normally contained in the intestines, are able to cross into the blood. Intracellular toxins from muscle breakdown also release into the bloodstream. This toxemia leads to a massive systemic inflammatory response (SIRS). There is also some degree of direct thermal injury, but this only occurs at extremely high temperatures (>42°C). Temperatures of this magnitude can cause intracellular protein deformation and mitochondrial dysfunction, as well as apoptosis and cell death. Eventually, if the process is not halted and reversed, multi-organ injury occurs, and ultimately death.

There are several factors that help to assess the risk for heat injury. These should always be considered, especially when any activity is scheduled, from sporting events, to military training, to expeditions. These risk factors can be broken down into four categories:

  1. Individual factors: Overall fitness, BMI, chronic medical conditions, and hydration status both pre and during exertion all play a big role. Medications that interfere with the response to heat, such as those that prevent increases in heart rate (B-Blockers, Calcium Channel Blockers, etc.), decrease intravascular volume (diuretics), reduce vasodilatation (nicotine), or increase metabolic production (caffeine, SSRIs, amphetamines, cocaine, etc.) all predispose to heat injury. Deficiencies in the ability to sweat (ichthyosis, scars) can also play a role. The biggest risk factor for developing heat injury is previous history of heat injury, and should be taken seriously when considering medical clearance for a particular event.
  2. Activity: Metabolic Thermal Production = Intensity + Duration. Simply put, higher exertion levels for longer periods of time leads to increased heat production, which will need to be dissipated.
  3. Environment: Several environmental factors come into play when assessing heat transfer. Ambient temperature, solar radiation, humidity, and wind speed can all affect the heat transfer mechanisms and lead to a significant decrease in the ability to dissipate heat. Wet bulb globe temperature (WBGT) takes all of these factors into play and can give a baseline risk assessment for development of heat injury.
  4. Clothing and Equipment: This comes into play in sports like football where pads and helmets, or military personnel required to wear full coverage uniforms with heavy flak, can significantly inhibit heat loss mechanisms.

Taking all of these factors into account can help to both predict and mitigate the risk of significant heat injury.

Acclimation can help to reduce the likelihood of heat injury, however it is a process. General recommendations are to exercise in a hot environment, 90 minutes per day for 14 days. Acclimation leads to several changes in the physiological response to heat stress, including cardiovascular, metabolic, and biochemical protective factors. Cardiovascular affects include earlier heart rate response and lower upper exertion heart rate, preservation of cardiac output despite peripheral vasodilation, and better heat-loss mechanisms. Sweating starts sooner, with a significantly lower concentration of sodium in the sweat which helps to maintain electrolyte and fluid balances. In response to the heat stress during acclimation, heat shock proteins (HSP) are developed. There are multiple types of HSP that fulfill separate roles, but the basic function of protective HSP is to stabilize the intracellular environment to maintain protein conformation and function, and to help break down deformed and rebuild proteins required for intracellular processes and mitochondrial functions. All of these changes lead to better performance in hot environments as well as decreased risk of developing heat injury. 

here are several conditions that have be classically termed "heat related illness". 

  1. Heat rash (miliaria rubra): pruritic, vesiculo-pustular rash generally in areas covered by clothing. This results from clogging and subsequent inflammation of sweats glads. Prevention consists of wearing wicking clothing and keeping the skin clear of pore-clogging dust/dirt. It generally resolves spontaneously, but topical anti-itch therapies may help with symptoms.
  2. Heat edema: dependent swelling of the distal extremities that occurs during prolonged exercise, primarily due to peripheral vasodilation and increased hydrostatic pressures leading to vascular leak. Rings and other constrictive items should be removed, however there is no other necessary therapy. The edema resolves once exertion ceases and with elevating the extremities.
  3. Heat cramps: muscle spams that can occur in single muscles or in multiple large muscle groups. There are several theories on the pathophysiology, including hypovolemia from dehydration, electrolyte abnormalities, or fatigue at the neuromuscular junction, however nothing has panned out in the literature. The cramps tend to improve with rest, stretching, hydration, and electrolytes, but will occasionally persist and require cessation of activity. 
  4. Heat syncope: brief loss of consciousness with rapid return to baseline associated with exertional activity. This usually occurs just after an athlete finishes their activity, with a sudden loss of pumping action from the leg muscles that leads to orthostatic pooling in the lower extremities leading to a drop in right atrial pre-load. This induces a reflex skeletal muscle vasodilation and decrease in cardiac output (Barcroft/Edholm reflex) and vasogenic syncope. Evaluation of other cases of syncope should be investigated, however the majority of finish line collapses can be attributed to this reflex. Treatment consist of placing the patient supine with their lower extremities elevated. Very rarely are IV fluids indicated, and no further therapies are required. If there is a delay in return to baseline or any other situation that points to a more complicated process, further evaluation and treatment is warranted. 
  5. Heat exhaustion: generalized fatigue, nausea, and cramping related to exertion. This may be due to a combination of dehydration, electrolyte imbalance, and caloric depletion from prolonged effort. Rest, repleting calories, oral hydration, electrolyte replacement, and passive cooling with close monitoring for worsening symptoms if indicated. There is some thought that heat exertion will progress to heat stroke if not recognized and treated.

There is some controversy regarding the so called "heat associated illnesses", as they require neither hyperthermia nor a hot environment to occur. All have been documented in normothermia and in cooler temperatures, leading to a call to reclassify and rename them as exertional or exercise associated illnesses as opposed to heat related. This would prevent early dismissal of the possibility of these etiologies in moderate temperatures or in the absence of elevated body temperature, and better indicate the pathology in the name. 

True heat injury is referred to as Heat Stroke. Three things are required for the diagnosis of heat stroke: 1) Hyperthermia >40°C, 2) CNS manifestations, and 3) prolonged exposure to heat or exertion. There are two types of heat stroke: Classic and Exertional. Classic heat stroke occurs with prolonged exposure to high ambient temperatures in the absence of significant exertion. It generally occurs in those limited abilities to dissipate heat or change their environment in order to prevent heat gain, such as the young, the old, and the bed bound. Exertional heat stroke occurs in the setting of prolonged intense exercise, and is more likely in hot temperatures but can occur in cooler temperatures if other factors are present. 

Recognition of heat stroke and early institution of treatment is directly related to outcome. Morbidity and mortality is directly related to the duration and magnitude of the heat stress. If hypotension occurs, mortality increases 3x from 10% to over 30%. After assessing the ABCs, the next step is to stop heat gain and start active cooling. Moving the patient off of hot rocks or asphalt and into the shade will prevent further heat gain by conduction and radiation. There are several active cooling methods, however the best by far is submersion in an ice bath. If an ice bath is not available, a cold stream or lake is an option, with care taken to prevent the patient from completely submersing. Other less optimal options include misting with spray bottles while fanning the patient to help with evaporative and conductive heat loss, or cold packs in the groin, axillae, and neck to cool the large, superficial vasculature. There was also a small study published in 2014 about placing cold packs on the cheeks, palms and soles which showed better cooling rates than the traditional placement sites. Ice packs are always preferable to chemical cold packs, if available. 

It is important to assess for other causes of altered mental status (AMS). Although hyperthermia and CNS manifestations are required for the diagnosis of heat stroke, not all hyperthermia and AMS is heat stroke. A study monitoring core temperatures in marathoners showed several asymptomatic runners with core temperatures >40°C, and two >41°C without symptoms of heat illness. Hypoglycemia and exercise associated hyponatremia (EAH) should be ruled out with blood glucose and sodium levels, if possible. Dehydration, rhabdomyolysis, and acute renal failure with uremia can occur. If altitude is a factor, high altitude cerebral edema should be considered. Metabolic (thyrotoxicosis) or toxicologic hyperthermia (silicates, serotonin syndrome, neuroleptic malignant syndrome) are also possibilities. Make sure to keep a broad differential while instituting cooling mechanisms. 

Transport to a critical care capable facility should take place as soon as possible. IV hydration should be performed with caution unless EAH has been ruled out with sodium testing, however resuscitation should be initiated in the setting of hypotension to prevent further hypo-perfusion and organ damage. Cooling should be continued in hospital until <39°C. Evaluation for end organ injury and intensive supportive care are required. There is no role for antipyretics in heat stroke, as the hypothalamic set point is already at baseline, and NSAIDs and acetaminophen (paracetamol) can worsen organ injury. 

In summary, heat stroke is the only true heat injury, and must be recognized and treated early. Submersion is the best form of cooling, however other methods should be used if submersion is not available. Emergent transfer to definitive care is imperative. The other "heat related illnesses" are actually exertion related conditions, and can generally be treated in the austere environment without the need for evacuation depending on the circumstances. 

References:

  1. Lipman GS, Eifling KP, Ellis MA et al. Wilderness Medicine Society practice guidelines for the preventions and treatment of heat related illness: 2014 update. JWildEnMed; 2013;25(4):S55-65.
  2. Auerbach, P. (2011). Wilderness Medicine (6th ed., pp.215-239). Mosby.
  3. Noakes TD. A modern classification of the exercise-related heat illnesses. JSciMedSport; 2008 Jan;11(1):33-9.

Title image obtained from: Maynard, P. (2014, Jan 21). Tempted to complain about the cold and the snow? Just be glad you're not part of one of these blisteringly hot event. [Warning: Graphic images]. Retrieved May 10, 2015, from http://darkroom.baltimoresun.com/2014/01/tempted-to-complain-about-the-cold-and-the-snow-just-be-glad-youre-not-part-of-one-of-these-blisteringly-hot-events-warning-graphic-images/#15