Clinical Care in Extreme Environments: High Pressure, Immersion, Drowning, Hypo- and Hyperthermia

Acute Effects of Immersion

The upright posture of humans results in gravitational effects on the venous blood pool, which tends to be distributed into the lower half of the body. Because water and blood have almost the same density, immersion in water causes immediate redistribution of blood from the legs and splanchnic bed into the heart and pulmonary circulation. This causes a reduction in lung volumes, a rise in central venous and pulmonary vascular pressures, and an increase in ventricular and stroke volumes. These effects are accentuated in cold versus warm water due to peripheral vasoconstriction.

Prolonged Immersion and Rescue

Because of atrial stretch, there is an increase in B-type natriuretic protein (BNP) secretion. In conjunction with the increase in cardiac output this induces a diuresis. Prolonged immersion, such as may occur during loss at sea, can result in severe hypovolemia due to lack of fluid intake and prolonged diuresis. Indeed, some marine accident survivors have died during extraction from the water in the vertical position. It is therefore recommended that victims who have spent significant time in the water be kept in the horizontal position during rescue ( Fig. 75.1 ).

Immersion Pulmonary Edema

Pulmonary vascular pressures that are elevated due to immersion are increased even further during exercise, particularly in cold water. Drinking water prior to immersion can activate the osmopressor response and further augment central translocation of venous blood. Blood centralization then raises pulmonary vascular pressures, which in susceptible individuals can be sufficiently elevated to induce acute pulmonary edema. This condition is referred to as immersion pulmonary edema (IPE) or swimming-induced pulmonary edema (SIPE). Individuals with cardiovascular pathology, such as hypertension, left ventricular hypertrophy, cardiac valve disease, and cardiomyopathy are particularly susceptible because of their preexisting elevation of left atrial pressure. However, healthy individuals can also experience SIPE, particularly during heavy exercise in the water. SIPE has been reported during a long swim in approximately 1.5% of triathletes, 3% to 5% of US Navy special forces trainees, and up to 60% of Israel Defense Force recruits. SIPE tends to recur in some individuals and has been linked to higher than normal pulmonary artery (PA) and PA wedge pressures.

The condition usually resolves within a few hours after removal from the water (which immediately reduces intravascular pressure within the pulmonary vessels) and administration of first aid O ₂ . Nebulized β _2- adrenergic agents may be helpful to treat bronchospasm and accelerate water reabsorption from alveoli. Although resolution within a few hours is the norm, SIPE-induced death has been reported.

Definition

A definition of drowning was proposed and adopted in 2002 by the World Health Organization as follows: Drowning is the process of experiencing respiratory impairment from submersion/immersion in liquid . This definition was modified slightly by a consensus of international investigators on guidelines for the uniform reporting of data from drowning studies (Utstein style), which has subsequently been updated. A recent publication has reviewed 14 drowning publications based on this reporting convention.

Evolution of the drowning syndrome in a patient depends on the extent of aspiration of fluid into the airways, leading to hypoxemia and cardiac arrest, which can evolve to progressive and irreversible neurologic damage. Death at any time as a result of drowning is described as fatal drowning . When the process of drowning is interrupted, it is referred to as nonfatal drowning . Any submersion incident without respiratory impairment should be considered a water rescue and not a drowning. Other terms such as “near drowning” or “dry” or “wet drowning” or similar distinctions should not be used, in order to standardize appropriate reporting of outcomes.

Prevalence

The number of accidental drownings in the world exceeds 500,000 persons per year, causing over 370,000 deaths. Undoubtedly these numbers are underestimates due to additional unaccounted cases such as the thousands of victims each year from floods, tsunamis, and asylum seekers seeking to flee by sea. Approximately 20% of people who die from drowning are children younger than 15 years of age. From 2005 to 2014, there was an average of nearly 3900 fatal unintentional drownings per year in the United States. It is estimated that 4000 children receive emergency department care for nonfatal submersion injuries. At least 50% of drowning victims treated in hospital emergency departments require inpatient care. Nonfatal drowning can lead to severe brain damage and long-term disability.

These statistics show that drowning is a significant public health issue, surpassing the number of annual traffic accident deaths. However, multiple agencies at a national level follow and attempt to regulate traffic, whereas drowning has not elicited appropriate attention.

Pathophysiology

After submersion in water when a person cannot maintain a clear airway, water is voluntarily expelled from the nose and mouth and breath-holding is initiated. This usually cannot last more than one minute, because involuntarily inspiratory efforts produce swallowing attempts, water inhalation, and cough. Laryngospasm may occur for some time but will cease during progressive brain hypoxia.

Continued water aspiration leads to hypoxia, loss of consciousness, and deterioration of cardiac function. The hypoxic cardiac insult can rapidly progress through tachycardia, followed by bradycardia, pulseless electrical activity (PEA), and finally asystole. Irreversible damage to the heart and the brain usually occurs within a few minutes. In exceptional but rare circumstances, such as drowning in ice water, cardiac and brain cooling can provide extended hypothermic protection and afford possibility of reversible resuscitation after prolonged submersion times, although systematic reviews have failed to find a correlation between water temperature and survival. Drowning in cold water may also be accompanied by several unique aspects related to gasp response, autonomic effects, hemodynamic changes, and hypothermia (see later).

Water aspiration induces pulmonary edema with impairment of pulmonary gas exchange, in part due to surfactant dilution and dysfunction. Although conventional wisdom is that fresh and salt water drowning differ due to osmotically driven fluid exchange across the alveolar-capillary membrane with resulting changes in electrolyte concentrations, animal studies and clinical case reports have not supported differences in clinical course. A study of hemodynamics and pulmonary mechanics in anesthetized dogs using tracheal instillation of 20 mL/kg of fluid with various sodium chloride (NaCl) concentrations (sterile water, 0.225%, 0.45%, 0.9%, 2%, and 3% NaCl) and anoxic controls failed to find any differences among the groups. This is supported by recent clinical series, where outcomes of drownings were similar in fresh and salt water.

Rescue and Resuscitation

Enhanced local surveillance by lifeguards has been shown to be highly effective in early rescue and improved outcomes from drowning: the majority of rescued victims in areas of effective surveillance do not need medical attention and only 6% of all rescued persons require emergency medical admission and very few require cardiopulmonary resuscitation (CPR).

Safe rescue techniques comprise reaching the victim with a pole, a rope, or other buoyant life-saving device, avoiding rescuer entanglement with the victim. American Heart Association resuscitation guidelines recommend that rescuers should remove drowning victims from the water by the fastest means available and should begin resuscitation as quickly as possible. Since cardiac arrest is caused by progressive hypoxia, any attempt to institute CPR must include ventilatory maneuvers to attempt to refill the alveoli with air or oxygen. For drowning victims who present in cardiac arrest, a shockable rhythm is predictive of survival, but one series reported that most drowning victims in arrest have asystole or PEA.

Rescuers should provide CPR, particularly rescue breathing, as soon as an unresponsive submersion victim is removed from the water. Mouth-to-mouth ventilation in the water may be helpful when administered by a trained rescuer, but chest compressions are difficult to perform in water and are often ineffective. Maneuvers to relieve foreign-body airway obstruction are not recommended. It is reasonable for the lone healthcare provider to give 5 cycles (about 2 minutes) of CPR before leaving the victim to activate the emergency medical service (EMS) system. Victims with obvious clinical signs of injury, alcohol intoxication, or a history of diving into shallow water are at higher risk of spinal cord injury, and thus stabilization of the cervical and thoracic spine for such individuals may be considered, although spinal cord injury among drowning victims is uncommon. Often the victim has swallowed variable volumes of water and can vomit early during rescue-breathing; in patients with spontaneous circulation, the lateral position is therefore recommended to minimize the risk of aspiration.

The clinical presentation of the drowning victim is variable and stratifying risk based on clinical presentation may be useful for initial triage ( Table 75.1 ). American Heart Association guidelines recommend that all victims of drowning who require any form of resuscitation (including rescue breathing alone) should be transported to the hospital for evaluation and monitoring, even if they appear to be alert and demonstrate effective cardiorespiratory function at the scene.

Hospital Care

The sequence of resuscitation efforts after emergency department admission includes securing a definitive airway, improving oxygenation, reestablishing circulation, insertion of a gastric tube, and rewarming. Previous medical history should be addressed, since trauma, cardiac arrhythmias, or seizures may have precipitated the near-drowning episode. Toxicology evaluation for alcohol or drug intoxication may be helpful to establish causes of impaired consciousness and treatment.

If the patient is unstable, intensive care unit (ICU) admission may be required for observation and weaning from mechanical ventilation, which can usually be accomplished using traditional algorithms. Bronchodilator support may be useful to treat bronchoconstriction and accelerate water clearance from alveoli, but glucocorticoids have not been shown to be effective.

Bronchoscopy might be required for pulmonary toilet or aspiration of solid materials, and secondary pneumonia can occur. It has been reported that aspiration of swimming pool water rarely results in pneumonia whereas it is more common in salt water aspiration and most common after polluted water aspiration; however other studies have found no relationship between the type of water and development of pneumonia.

In a small number of patients admitted to the ICU, pulmonary function can deteriorate beyond the ability of conventional mechanical ventilation to maintain adequate gas exchange. In such cases, administration of surfactant substitutes and nitric oxide has been tried. Case series of extracorporeal membrane oxygenation (ECMO) have also been published. Initiation of such measures is best determined on the basis of individual patient requirements. It has been recommended that ECMO should be considered earlier in the course of therapy (e.g., when arterial pH < 7.2, PCO ₂ > 60 mm Hg, SaO ₂ < 85%) before progressive respiratory failure leads to cardiovascular collapse.

Outcome of Drowning

If a person is rescued the outcome will depend on submersion duration, EMS response times, volume of water aspirated and its effects, the skill of the providers, and the availability of support systems. Outcomes of 1831 cases of drowning are shown in Table 75.1 . In a series of 336 drowning-related cardiac arrests, EMS resuscitation was attempted on 154, of whom 27% survived to hospital arrival and 8% survived to hospital discharge. Only 6% were found in a shockable rhythm.

Prevention

Increasing documentation and international interest from institutions supported by coastal and fluvial societies and advocacy groups have demonstrated the value of prevention in drowning. Use of life vests in the water and instructions teaching swimming and/or floating, as well as Dutch, Brazilian, South African, and Australian lifeguard experiences have shown that 85% of drowning cases can be prevented by public education, supervision, and public preparedness. The recent multiple tragedies of refugees drowning at sea have re-sensitized medical groups to renew efforts to prevent drowning.

Physiology of Hypothermia

Hypothermia is defined by a low core body temperature (generally less than 35°C, with more conservative perioperative thresholds of 36°C ). Thresholds for further categorical breakdown into mild, moderate, and severe hypothermia are not consistent within the literature, and vary depending on context (e.g., trauma, immersion/environmental, therapeutic indication). Extremes of age, sepsis, burns, trauma, some endocrine disturbances, intoxication, exertional fatigue, or malnutrition can place patients at higher risk for developing both hypothermia and complications thereof, with a high degree of variability even among healthy individuals.

On a molecular and cellular level, decreased temperature decreases the speed of chemical and enzymatic reactions, influences intracellular signaling cascades, and alters cellular structure ; the overall metabolic rate is suppressed to varying degrees for different tissues. As such, cold exposure and hypothermia impact each tissue or organ system differently. The microvasculature of the skin and peripheral tissues manifests a rapid vasoconstrictive sympathetic response to either superficial cold exposure or decreased core body temperature. This response reduces skin blood flow and attenuates cutaneous heat flux, while shifting blood volume to the central compartment. The high surface to volume ratio of the extremities can result in profound decreases in peripheral tissue temperatures with maintenance of the core body temperature.

Superficial peripheral cooling impacts muscle and nerve function, which can impair a victim’s capability for self-rescue or preservation in the case of accidental hypothermia, and has implications for monitoring in clinical settings (see the section on “Clinical Considerations”). Muscle function declines due to impaired release and diffusion of calcium and acetylcholine, and changes in elastic components. Furthermore, as peripheral cooling progresses and the more superficial muscle fibers become impaired, fatigue occurs more quickly in muscle fibers left to bear the load. Peripheral cooling also impairs nerve conduction velocities and amplitudes, further impacting physical performance. As a final comment on peripheral cooling, accidental hypothermia or improper therapeutic cooling with ice packs or conductive cooling devices can lead to cold injury or frostbite of peripheral tissues (fingers, toes, nose, ears are most susceptible). Treatment is conservative in mild to moderate cases, through protection from mechanical injury, slow rewarming, and consideration of nerve blocks or improving oxygenation when possible. However, tissue salvage in severe injury may also require early therapy with thrombolytics or iloprost.

The cardiovascular system is impacted in a number of ways. Peripheral sympathetic vasoconstriction leads to increased systemic vascular resistance and blood pressure, as well as increased central venous pressure due to redistribution of blood volume to the central compartment. Shivering increases metabolic requirements; in combination with increased sympathetic tone this leads to increased cardiac output, tachycardia, and a propensity for atrial arrhythmias in mild hypothermia. With more severe hypothermia (<32°C), cardiac conduction delays develop, including J waves (positive deflection at the QRS-ST junction) signaling abnormal early ventricular repolarization (Osborn waves, Fig. 75.2 ), and decreased spontaneous polarization of pacemaker cells, resulting in bradycardia. The likelihood of cardiac arrest increases with cooling below 32°C, with very high risk at 28° to 24°C or below ; gentle handling and maintaining horizontal positioning in hypothermic patients can minimize the likelihood of arrhythmia or cardiovascular collapse.

Decreased cerebral metabolism in hypothermia is useful as the basis of neuroprotection for a variety of therapeutic indications and in accidental hypothermia complicated by hypoxia (particularly if cooling occurs before the onset of hypoxia); however, neurologic and respiratory function also decline with increasing severity of hypothermia. Impaired judgment progresses to hallucinations, delirium, and decreased consciousness as body temperature falls; loss of consciousness is common below 28°C. Reflexes, pupillary reactivity, and electroencephalographic (EEG) activity decline and become absent with progressive hypothermia, precluding neurologic assessment. From a respiratory standpoint, neurologic impairment can necessitate intervention for airway protection, and with severe hypothermia respiration can even cease. Although decreased metabolic requirements afford some tolerance to hypoxia and decreased ventilation (tidal volume, respiratory rate, and compliance decrease), sensitivity to hypercapnia is diminished, leading to hypoventilation and acidosis, which can exacerbate electrolyte abnormalities and other physiologic changes.

Renal and hepatic impairment have a variety of implications. Hepatic impairment decreases clearance of lactate and other metabolic byproducts and metabolism of some medications (see the section on “Clinical Considerations”). Renal blood flow is increased in mild hypothermia, due to increased blood volume in the central compartment. Increased renal blood flow in combination with decreased antidiuretic hormone activity results in diuresis. However, as hypothermia progresses, renal blood flow and glomerular filtration rate both decrease, although diuresis may persist due to inhibition of tubular water reabsorption. Additionally, edema that develops in damaged peripheral tissues can exacerbate depletion of circulating blood volume. Respiratory, renal, and endocrine changes result in electrolyte imbalances in both mild and moderate/severe hypothermia. Hypokalemia and hyperglycemia can be present in mild hypothermia, whereas acidosis, increased sodium excretion, and hyperkalemia manifest with progressive cooling. Hyperglycemia results from decreased insulin sensitivity and secretion, requiring intensive insulin therapy and frequent monitoring of blood glucose levels. Distal tubular transport of sodium is impaired, which also affects acid-base regulation. Finally, the threshold for cardiac toxicity from hyperkalemia diminishes with progressive hypothermia. Therapies and medications that increase serum potassium levels (blood transfusion, succinylcholine administration) should be carefully considered in these patients.

Because of increased gas solubility with decreased temperature, arterial partial pressure of oxygen (PaO ₂ ) and arterial partial pressure of carbon dioxide (PaCO ₂ ) decrease and pH increases. Samples corrected to patient body temperature will appear to be alkalotic and hypercarbic, whereas samples left uncorrected at 37°C will correspond to normal reference ranges for these values in the absence of physiologic changes. As such, results should be interpreted in the context of whether temperature correction was or was not performed. As discussed in hypothermia, impaired ventilation and a higher ventilatory threshold for hypercapnia result in hypoventilation, which generally tracks with the reduction in metabolic rate. However, since pH increases and increased carbon dioxide (CO ₂ ) solubility decreases PaCO ₂ with decreasing temperature, cerebral blood flow is generally also decreased in proportion to reduced metabolic rate in hypothermia. Clinically, a strategy that has been investigated in hypothermic cardiac surgical patients is correction for known changes in PaCO ₂ solubility (known as pH-stat blood gas management, as opposed to alpha-stat management where hypocarbia and alkalosis are permitted), with the theoretical advantage of increasing cerebral blood flow. Some benefit has been shown in pediatric, but not in adult populations, where there is concern for increased cerebral embolic risk.

Hematologic changes observed in hypothermia are secondary to changes in blood volume, microvascular tone, and coagulation factor function. Contraction of the blood volume due to diuresis (possibly combined with dehydration due to environmental exposure or exertion) increases blood viscosity. In combination with increased viscosity, vasomotor abnormalities in the microcirculation lead to sludging, stasis, and hypoperfusion. Impaired circulation prevents tissue oxygenation, but also clearance of metabolic byproducts, which accumulate in peripheral tissues. Leukocyte and platelet counts fall with severe hypothermia and platelet activation and coagulation factor enzymatic function are highly sensitive to pH and temperature. This can result in a coagulopathic state with progressive hypothermia, but may also be partially offset by simultaneous inhibition of anticoagulant factors, depending on relative concentrations.

Clinical Considerations

In general, hypothermia may impair drug absorption in the bowel. Both core and peripheral cooling, even to a mild degree (∼34°C), can have a clinically significant impact on the recovery from, or twitch response to, neuromuscular blockade. This is explained by both impaired neuromuscular function and pharmacokinetic changes (increased plasma concentration) with decreased temperature. The minimum alveolar concentration (MAC) for volatile anesthetics decreases with hypothermia. With profound cooling (∼20°C), anesthesia may no longer be needed to prevent movement, although the precise temperature at which EEG silence is achieved is somewhat lower and demonstrates individual variability. Plasma concentrations of some intravenous anesthetics increase because of reduced compartmental clearance; the clearance of CYP450-metabolized drugs (including propofol and ketamine) is also reduced in proportion to the decrease in body temperature. As a result, reduced infusion rates will achieve similar levels of sedation. In parallel, general anesthetic and some sedative medications have an impact on thermoregulation (both vasoconstriction and shivering thresholds are reduced by up to ∼2° to 4°C or more), and can contribute to hypothermia.

There are also considerations for monitoring hypothermic patients, the most obvious being the measurement of temperature itself. Even in thermoneutral conditions there is very high variability in skin temperature at different sites, an effect which is attenuated but persistent for common core temperature measurement locations ( Fig. 75.3 ). In hypothermia, changes in blood flow distribution exaggerate these temperature variations among site differences. Similarly, rewarming methods can have dynamic effects on temperatures in different tissue compartments (see Treatment of Hypothermia). Apart from the rational yet clinically variable application, the recommendation is “if one’s interest lies with the temperature of a specific body tissue, then measure temperature from that site, or a valid surrogate.” The guiding principles for measurement of core body temperature are to measure temperature in a location (1) where there is good tissue perfusion, which promotes thermal equilibration with other body sites; (2) that is insulated from the external environment or peripheral tissues, which may be cooled to a greater degree than core tissues; and (3) that is as adjacent as possible to the organ of interest (i.e., the tympanic membrane or nasopharynx for the brain). Blood temperature can be an excellent surrogate for core temperature, with PA blood temperature often cited as a gold standard. However, this invasive method may also suffer some inaccuracy in the setting of acute mixing of fluids administered via central venous catheters or adjacent placement of invasive warming devices. Esophageal temperature is often used to represent blood temperature due to its proximity to the central circulation.

The response time for pulse oximetry is limited or the signal may fail altogether in conditions of local hypoperfusion, as occurs with peripheral vasoconstriction in hypothermia. Although there have been advances in device algorithms, pulse oximetry often does not give a reliable reading from the digits in even mild hypothermia, with relatively preserved performance for ear or forehead sensors. Similarly, concerns for exaggerated or prolonged neuromuscular blockade can be complicated by the fact that local or body cooling decreases nerve stimulation (mechanomyography) twitch tensions, even in the absence of paralytic medications.

There are important differences between accidental hypothermia due to environmental exposure and induced hypothermia in controlled, clinical situations such as therapeutic hypothermia for neuroprotection or during cardiac surgery. The most obvious difference is that the mechanism of cooling may vary—environmental exposure results in cooling across the skin and body surface, through radiation, evaporation, convection, or conduction from cold air, water, or contact surface (with the exception of drowning, where aspiration and swallowing of cold fluid can impart some degree of “internal cooling”). In contrast, in addition to surface cooling, clinical hypothermia may be induced and maintained by more efficient, evenly distributed, and precisely controlled invasive methods, such as intravascular catheters, cold fluid infusion, or cardiopulmonary bypass. Second, clinical support throughout the period of cooling, hypothermia, and rewarming can mitigate some of the major physiologic perturbations that would otherwise limit hypothermia tolerance or resuscitation and allow cooling to temperatures not tolerated outside of the clinical setting. Death is not uncommon in accidental hypothermia with body temperatures of 24° to 28°C, and the lowest documented temperatures from which resuscitation has occurred for accidental hypothermia are ∼13°C ; on the other hand, recovery from induced hypothermia to 10°C and lower has been reported. Finally, accidental hypothermia is often complicated by immersion or drowning, prolonged fasting and/or hypovolemia, extreme exertion or exhaustion, trauma, or a variety of other clinically relevant conditions.

Treatment of Hypothermia

Supportive care for the previously mentioned physiologic perturbations should be provided, and hypothermic patients should be protected from further heat loss with insulation and/or a vapor barrier, and they should be transferred to a controlled clinical setting when available. Intrinsic thermoregulatory responses should be addressed, including the vasoconstrictive sympathetic response in the skin and shivering in the muscles (primarily truncal muscles), which can both be stimulated by skin or core cooling. Shivering effectively provides heat at the expense of increased metabolic requirements that cannot be indefinitely maintained. Similarly, after provision of caloric supplementation to support increased metabolic requirements, and taking steps to prevent a further drop in temperature, exercise is recommended to augment rewarming in the case of mild accidental hypothermia where neurologic function is intact. Physiologically, shivering is blunted by exertional fatigue (termed thermoregulatory fatigue), hypoglycemia, and paradoxically, shivering is markedly attenuated and eventually stops as core temperatures continue to fall (<∼31°C). It may be undesirable in some clinical situations, and can be treated with a number of interventions, pharmacologic and otherwise.

The vasoconstrictive sympathetic response protects from heat loss during cold exposure, but also impairs effectiveness of transcutaneous warming. On application of external heat, local vasodilation does occur despite continued core hypothermia. Cutaneous warming can be applied using large heat packs (primarily in prehospital settings), or with forced air or circulating water devices when more advanced care is available. Radiant or resistive heating devices are less commonly used. Limitations to all of these methods include the potential for tissue damage from heat application (and therefore their maximum safe set temperature), and their reliance on effective peripheral circulation to distribute heat from the periphery to the core. Regarding the latter point, cutaneous warming is significantly more effective when applied to areas of skin with optimal blood flow; that is, in nondependent areas that are not compressed by body weight.

As mentioned, cutaneous warming demonstrates improved heat transfer efficiency with peripheral vasodilation. General anesthesia and some sedative medications can also affect peripheral vasodilation, which can exacerbate cooling in the context of exposure to cold environments, but in the context of cutaneous rewarming can similarly increase the effectiveness of warming, if vasodilation is not already maximal. On the other hand, vasodilation also makes simultaneous cooling across exposed skin possible, even with warming devices covering other locations. Efforts should be made to cover or warm as much exposed skin as possible in patients under anesthesia (and those sedated using vasodilating agents) to prevent this inefficiency.

Administered fluids should be warmed, which is of increasing importance with administration of large volumes such as in severe diuresis, dehydration, or traumatic blood loss. However, administration of warmed fluids rarely actively warms patients to any important extent because of the small amounts given relative to the heat distribution volume in most patients, and because it is unsafe to heat fluids much above normal body temperature. Similarly, airway heating and humidification can result in environmental heat loss. Provision of heated, humidified oxygen can prevent further heat loss, but its capacity for heat exchange is limited and it should only be used in conjunction with other warming methods.

A number of invasive warming methods have been used, including heat exchange through intravascular warming catheters; hemodialysis circuits; and peritoneal, gastric, bladder, or pleural lavage. Increasing invasiveness generally also predisposes to potential for complications; primarily it should be kept in mind that some of these methods can negatively impact the circulation (i.e., impaired preload, bleeding) and precipitate circulatory collapse in at-risk patients. In general, all of these rewarming methods rely on the circulation for heat equilibration, and prolonged CPR may be logistically difficult or have limited effectiveness. Therefore, in the case of arrested, severely compromised, or at-risk circulation, an increasing number of centers report and recommend the use of extracorporeal life support (ECLS) for both circulatory support and controlled rewarming in patients with profound hypothermia (typically core temperature < 30°C). As expected, these methods are not without pitfalls, but they can make resuscitation possible in extreme cases. Rewarming for these methods is relatively rapid, and is primarily limited by standard guidelines for (1) temperature gradients between blood return and patient blood of greater than 10°C, to avoid outgassing and generation of gaseous emboli when blood is returned to the patient; and (2) an upper threshold of 37°C for outlet blood temperature to avoid cerebral hyperthermia.

Finally, it is worth reviewing issues that present in the setting of hypothermia that may complicate the rewarming process. The most important are the concepts of rescue arrest and afterdrop. Hypothermic patients are likely to be hypovolemic and to suffer from acidosis and electrolyte abnormalities, and are predisposed to significant cardiac arrhythmias. As such, changes in posture that impact preload, or significant vasodilation that may occur on initiation of cutaneous rewarming can contribute to cardiovascular collapse. Peripheral vasodilation or improvement in tissue hypoperfusion can also allow accumulated metabolic byproducts to enter the circulation and exacerbate acidosis. Afterdrop refers to the phenomenon of continued core cooling even after rewarming has been initiated, due to continued loss of heat from the core to the cool periphery. In general, as rewarming progresses, clinical and laboratory parameters must be followed closely to avoid overcorrection, particularly in the case of pH or temperature-dependent phenomenon such as insulin sensitivity.

Hypothermia Outcome

Outcome after treatment of hypothermia is highly dependent on whether there has been coincidental trauma, cardiac arrest, significant hypoxia, or advanced age, all of which adversely affect prognosis. On the other hand, resuscitation from hypothermia with intact cardiac activity (core temperature typically > 28°C) has low mortality. Of a series of 1028 children admitted to hospital with accidental hypothermia, 91.5% survived. In a study of 572 adults with accidental hypothermia (core temperature ≤ 32°C), 83% of patients younger than 75 survived to hospital discharge.

Physiology of Hyperthermia

Optimal physiologic and biochemical homeostasis requires regulation of body temperature within a narrow range, typically 36.7°C to 37.5°C. Heat is generated by metabolism, which can vary several-fold from resting during sleep to heavy exercise. Internally generated heat is dissipated through the skin by conduction, radiation, convection, and evaporation of sweat. In an environment where ambient temperature is greater than skin temperature (typically around 33°C), heat is gained from the environment, allowing only sweating as a mechanism for maintenance of normal body temperature. Adaptation to hot environments (acclimatization) can occur over days or weeks. Mechanisms of acclimatization include increased blood volume and body water, lower body temperature, enhanced skin vasodilatation and sweating, and production of a more dilute sweat.

When core temperature increases, the normal adaptive response is cutaneous vasodilatation and initiation of sweating. There is redistribution of cardiac output to the skin, with concomitant reduction in splanchnic and renal blood flow, which can lead to gut, liver, and kidney ischemia. Dehydration and the resulting hypovolemia attenuate the increase in skin blood flow and accentuate splanchnic vasoconstriction. With continued hyperthermia, a nitric oxide-mediated mechanism causes vasodilatation in the splanchnic bed, which can precipitate hypotension and shock, and possibly gastrointestinal ischemia-reperfusion injury.

Heat-induced cell damage occurs at temperatures beyond a threshold that is species-specific. In humans, the critical temperature is between 41.6°C and 42°C sustained for 0.75 to 8 hours. The major mechanism for body injury from high temperature is damage to macromolecules, including lipids, DNA, and proteins. Temperature increases can cause oxidative stress, protein unfolding, entanglement, and aggregation. Uncoupling of oxidative phosphorylation and a reduction in mitochondrial number lead to a decrease in adenosine triphosphate (ATP) levels. In parallel with physiologic adaptive mechanisms, there is a cellular stress response (CSR), which is triggered by accumulation of damaged macromolecules. The CSR consists of altered gene expression that initiates the production of a series of heat shock proteins (HSPs) that falls into seven categories. The major HSP group consists of what are referred to as ‘‘molecular chaperones.’’ These chaperone proteins recognize unfolded proteins and either refold them into their normal functional state or direct them into degradation pathways. Another group of HSPs is proteolytic, which clear irreversibly damaged proteins. A third group facilitates DNA and ribonucleic acid (RNA) damage. A fourth group consists of enzymes that facilitate re-establishment of metabolic pathways after heat stress. A fifth group includes regulatory proteins. The sixth category comprises proteins involved in sustaining cellular structures such as the cytoskeleton. The final category consists of proteins that facilitate transport, detoxification, and membrane-modulation.

Clinical Scenarios

Definitions. Heat exhaustion is a mild form of heat illness that is notable for inadequate cardiac output accompanied by elevated body temperature, dehydration, and hot, dry skin. Symptoms include fatigue, dizziness, nausea and vomiting, headache, and hypotension. Heat exhaustion occurs in hot environments, often precipitated by exercise. It can also be precipitated by some medications such as diuretics and inadequate water intake, often in older adults. Body temperature in heat exhaustion is usually between 37°C and 40°C. Heat injury is more severe than heat exhaustion and after some hours may include some organ and tissue damage. If patients with heat injury are not rapidly cooled the condition may worsen to heat stroke , which is life-threatening. Heat stroke is commonly classified as exertional or classic . Exertional heat stroke usually occurs in young healthy individuals who are exercising in hot environments, often presenting with collapse. Classic heat stroke usually occurs in very young or older individuals exposed to a hot environment without strenuous physical activity.

Manifestations of heat stroke include hot dry skin, weakness, anorexia, dizziness, syncope, nausea and vomiting, headache, and confusion. Neurologic manifestations in heat stroke include mental status changes, delirium, coma, and convulsions, but there is often a lucid interval during which the patient may have normal mental status despite severe temperature elevation.

Body temperature in heat stroke is generally in the range of 40°C to 44°C, although temperatures extending from mild elevation to above normal to 47°C have been reported. Differentiating heat stroke from exercise-related heat exhaustion requires assessment of body temperature. Sensors placed on or close to sites on the exterior of the body (e.g., axillary, oral, tympanic, and skin) are not valid during or after intense exercise in the heat. The only adequate measurement sites in this setting are from sensors in the rectum or via radio telemetry from pre-ingested thermistor capsules.

Metabolic acidosis occurs in the majority of cases of severe heat stroke, especially in exertional heat stroke, often accompanied by respiratory alkalosis. Rhabdomyolysis, hyperkalemia, and disseminated intravascular coagulation are common. Renal failure commonly occurs in exertional heat stroke, but not classic heat stroke. Hyperglycemia and hypophosphatemia are common in classic heat stroke, whereas biochemical features in exertional heat stroke include hyperphosphatemia, hypocalcemia, and hypoglycemia.

The differential diagnosis of heat stroke includes status epilepticus, stroke, and drug use (including recreational drugs, antidepressants, antihistamines, and antiparkinsonian drugs). Another life-threatening condition that can be confused with heat stroke is exercise-associated hyponatremia (EAH). This condition, which occurs during prolonged exercise, has manifestations similar to heat shock: lightheadedness, nausea, headache, vomiting, altered mental status, and collapse but often without hyperthermia. When these signs and symptoms occur during prolonged exercise it is essential to exclude EAH as its treatment requires correction of serum sodium. When hyperthermia occurs in the perioperative environment, possible diagnoses include malignant hyperthermia (MH), neuroleptic malignant syndrome (NMS), thyroid storm, and serotonin syndrome. Assessment of MH is described in Chapter 35 . NMS is manifested by muscle rigidity, fever, mental disturbances such as delirium and abnormal metabolic changes in patients treated with classic triggering agents such as antipsychotic drugs (e.g., phenothiazines, butyrophenones, lithium), metoclopramide, antidepressants, and some anticonvulsants. In addition to fever, manifestations of serotonin syndrome include clonus, agitation, tremor, muscle rigidity, and hyperreflexia in patients taking serotonergic medication.

Treatment of Hyperthermia

As in the treatment of hypothermia, supportive care to correct physiologic derangements and potential complications is as vital as rapid correction of the core temperature. Fluid management is a primary consideration in virtually any hyperthermic patient, with the degree of perturbation dependent on the heat source, duration of exposure, and amount of sweating. Electrolyte depletion from sweating may also be profound, and hypercalcemia, hyper- or hypokalemia, hypophosphatemia, or hyper/hypoglycemia may require correction in hyperthermic patients.

The underlying cause of hyperthermia determines therapeutic options, and also impacts the effectiveness of selected cooling methods. Cooling in any hyperthermic patient should be expeditious to limit further organ damage, but ongoing excessive metabolic heat generation must also be addressed for cooling to be effective.

Fever induced by immunologic reaction may be responsive to antipyretics or antiinflammatory medications, and discontinuation of a fever-inducing medication or toxin is an obvious first step. Seizures or shivering can contribute significantly to hyperthermia, and a number of therapeutic options exist. In these conditions, pharmacologic treatments may be combined with cooling, depending on the degree of hyperthermia. Treatment of MH is described in Chapter 35 . NMS is treated by discontinuation of suspected triggering drugs and supportive care. Pharmacotherapy may include dantrolene, bromocriptine, and amantadine. Treatment of serotonin syndrome also includes discontinuation of triggering agents, supportive care, and administration of a 5-HT _2A antagonist such as cyproheptadine, and possibly benzodiazepines. For heat stroke there is no recommended pharmacologic treatment (due to concerns for hepatic toxicity). Nonsteroidal antiinflammatory drugs (NSAIDs) and aspirin are ineffective, and acetaminophen is contraindicated (see earlier). Dantrolene is ineffective in heat stroke.

Heat exhaustion usually responds to simple methods of cooling such as moving to an air-conditioned space, removal of excessive clothing, and application of cloths soaked in cool water. Hyperthermia in heat stroke is managed by institution of cooling as quickly as possible, combined with supportive treatment. The target to which cooling should be pursued is not well-supported by evidence, but many studies have used a target of less than 39°C rectal temperature. Ice water immersion and evaporative cooling are among the most effective noninvasive cooling methods, but they are not always logistically feasible, including in clinical settings where there are concerns for infection or significantly compromised integrity of the skin (e.g., dressings, burns, line sites). Ice packs (with a skin barrier to avoid direct contact and risk of tissue injury) can be applied to central areas with good blood flow, such as the groin, axillae, neck, and torso. All of these methods require ongoing refreshment of the cold source to maintain an effective temperature gradient, and attention to the skin at the site of application to avoid cold injury to tissue is critical. Adhesive cold-water circulating devices are contained, provide continuous refreshment of the temperature gradient, and may be equipped with thresholds and alarms to provide some margin of safety from cold injury. But, as in the case of cutaneous warming, adhesive pads require large areas of intact skin with good blood flow for effective use. These transcutaneous cooling methods all depend on cutaneous vasodilation for effective heat transfer from the core. But with cutaneous cooling, local vasoconstriction and shivering can be induced if temperatures are sufficiently low. Inhibition of shivering or vasoconstrictive responses, as previously discussed, may be used to offset these effects.

Effective but increasingly invasive cooling methods include bladder, gastric, or colonic irrigation with cold saline, intravascular cooling catheters, and administration of cold intravenous fluids. Immersion in ice water is safe and effective in young individuals suffering from exertional heat stroke; however, in classic heat stroke it is poorly tolerated and may be associated with increased morbidity and mortality. As in the case of hypothermia treatment, the effectiveness of cold intravenous fluids is limited by concerns for overexpansion of intravascular volume, although the temperature gradient that can be achieved is larger than that for warmed fluids for treatment of hypothermia; cold fluids can be near 4°C, as opposed to warm fluids, which must be near 37°C to avoid local hyperthermia. For patients requiring ECLS (or ECMO), some degree of cooling can be achieved passively due to blood volume flowing through external circuit components. It is noteworthy that while it is common for extracorporeal support circuits to be equipped with heat exchangers to warm the blood, some lack the ability to provide monitored active cooling (as opposed to cardiopulmonary bypass circuits, in which cooling capability is a standard feature). If cooling is a therapeutic goal, this should be considered at the time of circuit choice if there are multiple options available.

After cooling and successful resolution of hyperthermia, clinicians must continue to be vigilant for (1) hypothermia due to aggressive cooling or a dysregulated thermoregulatory response; (2) recurrent hyperthermia; and (3) the development and secondary effects of organ injury that occurred when body temperature was elevated. Short- and/or long-term lung, kidney, liver, cardiovascular, and neurologic injuries have all been described after heat stroke.

Hyperthermia Outcome

After cooling, sequelae can include ongoing encephalopathy, seizures, liver failure, renal failure, and adult respiratory distress syndrome (ARDS). Recurrent fever is common during recovery, does not respond to aspirin or NSAIDs, and may further exacerbate brain injury. Acetaminophen is sometimes prescribed but has been associated with liver failure and is contraindicated.

Mortality in exertional heat stroke is reported as 3% to 5%. As many as 60% of patients with classic heat stroke die before reaching the hospital, thus it is difficult to determine the true mortality. Of those who are admitted to an ICU, in-hospital mortality is 10% to 65%, however there is also 10% to 28% mortality at one and two years after treatment. Persistent neurologic manifestations including ataxia, dysarthria, and problems with coordination occur in a high percentage of patients and are associated with imaging abnormalities such as cerebellar atrophy.