Wet, wind, and exhaustion contribute to increased loss of body heat. Wet clothing loses 90% of its insulating value [14], rendering soaked individuals effectively nude. Exposure to rain or snow contributed greatly to the development of hypothermia in 15 of 23 incidents in hikers discussed in one review [14]. Convective heat loss because of wind may increase to more than five times baseline values, increasing with wind velocity [15]. Hikers with poor selection of clothing, campers who fail to seek appropriate shelter, or skiing in unfavorable weather can result in fatal hypothermia [15]. Victims of hypothermia display inappropriate behavior that worsens hypothermia. Up to 25% may remove their clothing and burrow, hiding under a bed or on a shelf [16]. Many quickly experience loss of coordination and then stupor or collapse. Death may occur within an hour of the onset of symptoms [15]. Immersion in water at a temperature colder than 24°C leads to extremely rapid heat loss. Core temperature drops at a rate proportional to the temperature of the water [17]. Although survival times of 1 to 2 hours have been reported for individuals immersed in water at 0°C to 10°C, death may occur within minutes.

Alcohol, phenothiazines, barbiturates, and paralytic agents frequently produce hypothermia by depressing sensory afferents, the hypothalamus, and effector responses. Alcohol impairs the perception of cold, clouds the sensorium, and acts as a direct vasodilator [18,19]. Alcoholics are also thought to be more susceptible to exposure because of a state of relative starvation, increased conductive losses from decreased subcutaneous
fat, and high levels of blood alcohol that potentially impair the metabolic response to hypothermia by decreasing blood sugar and increasing acidosis. Most sedative–hypnotic drugs, such as barbiturates and phenothiazines, cause hypothermia by inhibiting shivering and impairing voluntary control. Phenothiazines increase the threshold necessary to produce shivering and lead to hypothalamic depression [10,20]; barbiturates decrease effective shivering [21]. Paralytic agents used to suppress ventilation prevent shivering and eliminate all voluntary control mechanisms [22,23]. Unexplained hypothermia has resulted from the administration of common antibiotics, such as penicillin [24] and erythromycin [25]. Bromocriptine may cause hypothermia by altering central dopaminergic tone [26].

Diabetic ketoacidosis, hyperosmolar coma, and hypoglycemia are frequently reported causes of hypothermia [18]. In one survey, 20% of patients with blood glucose levels less than 60 mg per dL had temperatures of less than 35°C. Hypoglycemia lowers cerebral intracellular glucose concentrations and impairs hypothalamic function [27]. In acute hypoglycemia (e.g., insulin administration), hypothermia occurs due to peripheral vasodilation and sweating. At glucose concentrations less than 2.5 mmol per L, subjects fail to perceive cold environments and fail to shiver [28]. This impairment appears transient because normal regulatory mechanisms and euthermia may be restored when normal serum glucose levels are restored.

The prevalence of hypothyroidism in patients ranges from 0% to 10%. Several patients with mild hypothyroidism have been safely rewarmed to euthermia without administration of exogenous thyroid hormone. In contrast, myxedema coma, a rare presentation of hypothyroidism, is associated with subnormal temperatures in 82% of cases [29]. It has a high mortality if not treated with exogenous thyroxine. Myxedema coma occurs most frequently in middle-aged to older women, and more than 90% of cases occur in winter [29]. Severe hypothermia with temperatures less than 30°C occurs in 15% of patients [29]. Coma arises because of a cerebral thyroxine deficiency. Hypothermia then results from a combination of loss of voluntary control mechanisms, from stupor or coma, decreased calorigenesis from thyroid deficiency, and decreased shivering, presumably from impaired hypothalamic regulation [29,30].

Panhypopituitarism and adrenal insufficiency are also rare causes of hypothermia. Unless profound insufficiency exists, these conditions rarely produce significant hypothermia in the absence of some other insult to the thermoregulatory system.

Diseases such as stroke, primary and metastatic brain tumors, luetic gliosis, and sarcoidosis may produce hypothermia by direct anatomic impingement on the hypothalamus [31,32]. Metabolic derangements from carbon monoxide poisoning or thiamine deficiency (Wernicke–Korsakoff syndrome) can also produce hypothermia, by affecting the hypothalamus [33,34,35,36,37,38]. Patients with anorexia nervosa have been shown to have multiple hypothalamic abnormalities resulting in the lack of shivering and vasoconstriction and a rapid drop in core temperature when they are exposed to cold [39]. Agenesis or lipoma of the corpus callosum has been reported to cause spontaneous periodic hypothermia by an unclear mechanism [21,40]. Several patients with multiple sclerosis have experienced transient hypothermia with flares of their neuropathy, suggesting the presence of hypothalamic plaques [41]. Drugs that are active on the central nervous system, such as neuroleptics or guanabenz, have resulted in hypothermia [42].

Loss of skin and core temperature afferents, reduced body muscle mass, inability to shiver effectively, and, if mobility is compromised, inability to alter the environment make patients with spinal cord injury susceptible to thermal stress and hypothermia exposed to low ambient temperatures [43,44,45].

Skin disorders characterized by vasodilatation or increased transepithelial water loss may lead to hypothermia. Inappropriate conductive and convective heat losses in psoriasis, ichthyosis, and erythroderma have been shown to be associated with increased evaporative losses of up to 3 L per day; this computes to a potential loss of more than 1,700 kcal of heat per day [46,47]. Patients with extensive third-degree burns have been reported to have an even larger evaporative heat loss, losing up to 6 L fluid, or more than 3,400 kcal per day. When an additional cause of hypothermia is present, these patients may be in danger of severe drops in temperature. Heat loss and caloric requirements can be decreased dramatically by covering the skin with impermeable membranes to decrease evaporative losses [48,49,50].

Case reports suggest that hypothermia may occur in patients with debilitating illnesses such as Hodgkin’s disease [51]; systemic lupus erythematosus [52,53]; and severe cardiac, renal, hepatic, or septic failure. In Israel, 29% of hypothermic elderly individuals had preexistent renal failure [54]. The exact causes are unclear, but many mechanisms are likely acting in concert to produce a drop in temperature. A decrease in cardiac index from 2.8 to 1.4 L per minute results in a drop in temperature from 37°C to 35°C [55]. Temperature promptly rises when cardiac index increases. Hypothermia in hepatic failure might result from intermittent hypoglycemia. Most debilitated patients are also compromised by some degree of immobility or decreased voluntary control.

Trauma patients often are hypothermic [56,57], due to multiple insults to the thermoregulatory system, for example, loss of voluntary control in adverse environments, the presence of alcohol in up to 62% of cases in some series, and the rapid transfusion of unwarmed blood [57]. In patients with moderately elevated injury severity scores, during the first day of hospitalization, 42% experience hypothermia, with 13% having temperatures less than 32°C [56]. The presence of shock [56] and massive transfusion [57] significantly contributed to the development of hypothermia in these patients.

Increasing degrees of hypothermia result in malignant arrhythmias, depressed cardiac function, and hypotension. A decrease in cardiac conductivity and automaticity [65,66,67] and an increase in refractory period [68,69] begin during the shivering phase and progress as core temperature decreases. The electrocardiogram (ECG) in mild hypothermia may show bradycardia with prolongation of the PR, QRS, and QT intervals. Below 30°C, first-degree block is usual, and at 20°C, third-degree block may be seen [61,70]. Below 33°C, the ECG commonly shows the characteristic J-point elevation (Fig. 65.1). As temperature drops below 25°C, the J wave increases [71,72], most prominent in the mid-precordial and lateral precordial leads [73]. J waves may persist 12 to 24 hours after restoration of normal temperature [74,75].

Atrial fibrillation is common at temperatures of 34°C to 25°C, and ventricular fibrillation frequently occurs at temperatures less than 28°C. The incidence of ventricular fibrillation increases with physical stimulation of the heart and is associated with intracardiac temperature gradients of greater than 2°C [76]. Purkinje cells show marked decreases in excitability in the range of 14°C to 15°C [67], and asystole is common when core temperatures drop below 20°C. Recovery of spontaneous electrical activity after hypothermic asystole may be related to protection from the calcium paradox afforded by hypothermia [77].

Consequently, there is a gradual decrease in cardiac output. Systole may become extremely prolonged [78], greatly decreasing ejection fraction and aortic pressures. Ventricular compliance is severely reduced [79]. Output decreases to approximately 90% of normal at 30°C and may decrease rapidly at lower temperatures, with increasing bradycardia or arrhythmia. Regional blood flow is altered to preserve myocardial and cerebral perfusion [80]. Although blood pressure appears to be initially maintained by an increase in systemic vascular resistance (SVR) [81], systemic resistance decreases and hypotension is common [61] at temperatures less than 25°C. Oxygen demand usually decreases more rapidly than does cardiac output, causing mixed venous oxygen content to increase as the nonshivering phase begins.

Pulmonary mechanics and gas exchange appear to change little with hypothermia [61,82,83,84]. Although the ventilatory response to an elevation in carbon dioxide tension (PCO₂) may be blunted [82], there is no clear decrease in hypoxic drive [61]. As the increased oxygen demand and acidosis of the shivering phase decline, minute ventilation decreases. Tidal volume and respiratory rate decline at lower temperatures [20]. At 25°C, respirations may be only 3 or 4 per minute [19]; at temperatures less than 24°C, respiration may cease [59]. Apnea is presumed to be secondary to failure of respiratory drive at a brainstem level.

As blood pressure decreases during the nonshivering phase, glomerular filtration rate (GFR) may decrease by 85% [61] and renal blood flow by 75% [20], without a significant change in urine production. Maintenance of a good urine output, despite decreases in blood pressure and GFR in hypothermia, has been termed cold diuresis. This results from a defect in tubular
reabsorption. The urine may be extremely dilute, with an osmolarity of as low as 60 mOsm per L and a specific gravity of 1.002 [85]. The stimulus for this dilute diuresis may be the triggering of volume receptors as central volume increases with peripheral vasoconstriction [78], a relative insensitivity to antidiuretic hormone [75], or a direct suppression of antidiuretic hormone release [19]. Although kaliuresis and glycosuria may accompany the dilute diuresis, the net result for the patient is dehydration and a relatively hyperosmolar serum.

Hypothermic patients present with coma. Complete neurologic recovery has been described in hypothermic adults after 20 minutes of complete cardiac arrest [18] and after up to 3.5 hours of cardiopulmonary resuscitation (CPR) [85]. The mechanism by which hypothermia produces a seemingly protective effect is not well understood; it probably relates to a significant decrease in cerebral metabolism and a smaller injury by the no-reflow phenomenon [86], a mechanism whereby the brain is protected from injury until reperfusion.

Cerebral oxygen consumption decreases by approximately 55% for each 10°C decrease in temperature [87]. Cerebral blood flow decreases from 75% of normal at 30°C to only 20% of normal at 20°C [61]. The supply of nutrients and removal of wastes are adequate at these extremes given patient recovery and experimental evidence that the intracellular pH of brain tissue cooled to 20°C is unchanged even after 20 minutes of anoxia [88].

Visual [89,90] and auditory [91,92] evoked potentials demonstrate delayed latencies; latency increases as temperature decreases. The spectrum of electroencephalographic frequencies also changes with hypothermia. In healthy men cooled to 33°C by immersion, theta and beta activity increased by 17% and alpha activity decreased by 34% compared with control values [90]. Electromyography during hypothermia has been reported to be normal [93].

Hypothermia affects white blood cells (WBCs), red blood cells, platelets, and perhaps coagulation mechanisms. The WBC count in mild hypothermia remains normal to slightly elevated and drops severely at temperatures lower than 28°C [94,95]. The hematocrit usually rises in hypothermic patients at a temperature of 30°C in part due to hemoconcentration from dehydration caused by cold diuresis and in part due to splenic contraction [96]. The increase in blood viscosity in hypothermic patients appears to be due to decreased deformability of the red cell membrane [97]. After intravascular volume and euthermia have been restored, a mild anemia may last up to 6 weeks. Bone marrow aspirates obtained from these patients show erythroid hypoplasia and increased ringed sideroblasts, suggesting a maturation arrest [98]. Platelet counts drop as temperature decreases, and prolongation of the bleeding time has been noted at 20°C [94]; normal levels and function return on rewarming [99]. The decrease in platelet count is thought to be secondary to hepatic sequestration.

No clear evidence indicates that a coagulopathy is associated with hypothermia. Deep venous thrombosis (DVT) and disseminated intravascular coagulopathy (DIC) have been reported in hypothermic patients [34,100].

Ileus, pancreatitis, and hepatic dysfunction accompany hypothermia. Ileus is present at temperatures 30°C and lower. Subclinical pancreatitis appears to be common. Although patients usually lack symptoms of acute pancreatitis, more than half have amylase elevations greater than 550 Somogyi units and up to 80% of patients who die of hypothermia have evidence of pancreatitis at autopsy [101]. The relationship between alcohol use and pancreatitis in these patients is unclear. Hepatic dysfunction occurs commonly and involves synthetic and detoxification abilities [20]. Profoundly hypothermic patients in whom an acidosis develops are less able to clear lactate. Postmortem studies of patients who died from exposure-induced hypothermia have emphasized that gastric submucosal hemorrhage is common [102]. Duodenal ulceration and perforation may also be seen [103].

Hypothermia directly suppresses the release of insulin from the pancreas and increases resistance to insulin’s action in the periphery [104,105]. The blood glucose level rises in early hypothermia, due to glycogenolysis and increased corticosteroid levels, and remains elevated because of a decreased concentration and the action of insulin. Elevations in blood glucose, however, are usually mild; only 9% of patients in one series had blood glucose levels higher than 200 mg per dL. Changes in thyroid and adrenal function occur, but they are less well defined. The responses to thyroid stimulating hormone (TSH) and adrenocorticotrophic hormone appear blunted [61]. In hypothyroid patients, TSH increases in response to cold [106]. Although corticosteroid levels vary a great deal among patients, they rarely appear to be severely depressed [62,107,108]. Urinary catecholamine levels are increased threefold to sevenfold on average in hypothermic deaths compared with death due to other causes [102].

Infection is a major cause of death in hypothermic patients. Hypoperfusion increases the risk of bacterial invasion in ischemic regions of the skin and intestine. Central nervous system depression reduces the cough reflex, leaving the patient more susceptible to aspiration pneumonia. A decrease in tidal volume and minute ventilation increases the risk of atelectasis, making subsequent infection possible. Survival in hypothermia varies directly with the severity of cold-induced granulocytopenia [95,109]. Evidence from hypothermic animals with induced sepsis indicates an impaired release of PMNs from the marrow [95], as well as delayed clearance of staphylococcal [110] and Gram-negative organisms from the blood. Ineffective clearance of organisms may permit a continued low-grade bacteremia [110]. Ineffective clearance probably relates to impaired phagocytosis, migration [111], and a decrease in the half-life of circulating PMNs in hypothermia [109]. Impaired killing of bacteria by pulmonary alveolar macrophages exposed to cold in vitro has been reported and presumably increases susceptibility to pneumonia. The role of changes in antigen–antibody interactions, known to be impaired by cold in vitro, has not been clearly defined in hypothermic patients. Wound healing is delayed in patients with mild perioperative hypothermia [112]. Cytokine production may be delayed and prolonged [113]. Few human data are available regarding the activation of inflammatory mediators in hypothermia. Interleukin-6 and TNF-α are assumed to play a role in modulating an inflammatory cascade that must occur with hypothermia. Interleukin-6 concentrations fall with rewarming [114]. Thus, the hypothermic host is more susceptible to invasion by pathogens and less equipped to defend itself if invasion occurs.