GOOD MORNING

BODY TEMPRATURE

PRESENTED BY:BRIJESH M. PATEL1ST YEAR MDSORAL AND MAXILLOFACIAL SURGERYKMSDCHVADODARA

GUIDED BY:

• DR.NAVIN SHAH• DR.RAKESH SHAH• DR.KRUTI SHAH• DR.AMIT MAHAJAN• DR.PRACHUR • DR.ANANTH• DR.DIXIT SHAH• DR.DEEPANKAR

CONTENT

• INTRODUCTION• FEVER • HYPERPYREXIA• HYPERTHERMIA• PATHOGENESIS OF FEVER• APPROACHTO THE PATIENT• ANTIPYRETIC DRUG• FEVER OF UNKNOWN ORIGIN• HYPOTHERMIA

INTRODUCTION

• Body temperature is controlled by the hypothalamus. • Neurons in both the preoptic anterior hypothalamus and the posterior

hypothalamus receive two kinds of signals: • one from peripheral nerves that transmit information from warmth/cold

receptors in the skin • and the other from the temperature of the blood bathing the region.• These two types of signals are integrated by the thermoregulatory center of

the hypothalamus to maintain normal temperature. • In a neutral temperature environment, the metabolic rate of humans

produces more heat than is necessary to maintain the core body temperature at 37°C.

• A normal body temperature is ordinarily maintained, despite environmental variations, because the hypothalamic thermoregulatory center balances the excess heat production derived from metabolic activity in muscle and the liver with heat dissipation from the skin and lungs.• According to studies of healthy individuals 18–40 years of age, the

mean oral temperature is 36.8° ± 0.4°C (98.2° ± 0.7°F), with low levels at 6 A.M. and higher levels at 4–6 P.M. • The maximum normal oral temperature is 37.2°C (98.9°F) at 6 A.M.

and 37.7°C (99.9°F) at 4 P.M.; these values define the 99th percentile for healthy individuals. • In light of these studies, an A.M. temperature of >37.2°C (>98.9°F) or

a P.M. temperature of >37.7°C (>99.9°F) would define a fever.

• In women who menstruate, the A.M. temperature is generally lower in the 2 weeks before ovulation; it then rises by ~0.6°C (1°F) with ovulation and remains at that level until menses occur. Body temperature can be elevated in the postprandial state. Pregnancy and endocrinologic dysfunction also affect body temperature.

FEVER• Fever is an elevation of body temperature that exceeds the normal daily

variation and occurs in conjunction with an increase in the hypothalamic set point (e.g., from 37°C to 39°C). • This shift of the set point from "normothermic" to febrile levels very

much resembles the resetting of the home thermostat to a higher level in order to raise the ambient temperature in a room. • Once the hypothalamic set point is raised, neurons in the vasomotor

center are activated and vasoconstriction commences. The individual first notices vasoconstriction in the hands and feet. Shunting of blood away from the periphery to the internal organs essentially decreases heat loss from the skin, and the person feels cold. • For most fevers, body temperature increases by 1°–2°C.

• Shivering, which increases heat production from the muscles, may begin at this time; however, shivering is not required if heat conservation mechanisms raise blood temperature sufficiently. Nonshivering heat production from the liver also contributes to increasing core temperature. • In humans, behavioral adjustments (e.g., putting on more clothing or

bedding) help raise body temperature by decreasing heat loss.

• The processes of heat conservation (vasoconstriction) and heat production (shivering and increased nonshivering thermogenesis) continue until the temperature of the blood bathing the hypothalamic neurons matches the new thermostat setting.• Once that point is reached, the hypothalamus maintains the

temperature at the febrile level by the same mechanisms of heat balance that function in the afebrile state.

• When the hypothalamic set point is again reset downward (in response to either a reduction in the concentration of pyrogens or the use of antipyretics), the processes of heat loss through vasodilation and sweating are initiated. Loss of heat by sweating and vasodilation continues until the blood temperature at the hypothalamic level matches the lower setting. Behavioral changes (e.g., removal of clothing) facilitate heat loss.

HYPERPYREXIA

• A fever of >41.5°C (>106.7°F) is called hyperpyrexia. This extraordinarily high fever can develop in patients with severe infections but most commonly occurs in patients with central nervous system (CNS) hemorrhages. In the preantibiotic era, fever due to a variety of infectious diseases rarely exceeded 106°F, and there has been speculation that this natural "thermal ceiling" is mediated by neuropeptides functioning as central antipyretics.

HYPOTHALAMIC FEVER

• In rare cases, the hypothalamic set point is elevated as a result of local trauma, hemorrhage, tumor, or intrinsic hypothalamic malfunction. The term hypothalamic fever is sometimes used to describe elevated temperature caused by abnormal hypothalamic function. However, most patients with hypothalamic damage have subnormal, not supranormal, body temperatures.

HYPERTHERMIA

• Although most patients with elevated body temperature have fever, there are circumstances in which elevated temperature represents not fever but hyperthermia. • Hyperthermia is characterized by an uncontrolled increase in body

temperature that exceeds the body's ability to lose heat. • The setting of the hypothalamic thermoregulatory center is

unchanged.

• In contrast to fever in infections, hyperthermia does not involve pyrogenic molecules (see "Pyrogens," below). Exogenous heat exposure and endogenous heat production are two mechanisms by which hyperthermia can result in dangerously high internal temperatures. Excessive heat production can easily cause hyperthermia despite physiologic and behavioral control of body temperature. For example, work or exercise in hot environments can produce heat faster than peripheral mechanisms can lose it

Pathogenesis of Fever

Approach to the Patient: Fever or Hyperthermia

Physical Examination• Attention must be paid to the chronology of events and to other signs and

symptoms preceding the fever. The temperature may be taken orally or rectally, but the site used should be consistent. Axillary temperatures are notoriously unreliable. Electronic devices for measuring tympanic membrane temperatures are reliable and preferred over oral temperature measurements in patients with pulmonary disease such as acute infection or asthma.

Laboratory Tests• The workup should include a complete blood count; a differential count

should be performed manually or with an instrument sensitive to the identification of eosinophils, juvenile or band forms, toxic granulations, and Döhle bodies, the last three of which are suggestive of bacterial infection. Neutropenia may be present with some viral infections.

• Measurement of circulating cytokines in patients with fever is of little use since levels of pyrogenic cytokines in the circulation often are below the detection limit of the assay or do not coincide with the fever. Although some studies have shown correlations between circulating IL 6 levels and peak febrile elevations, the most valuable measurements in patients with fever are C-reactive protein level and erythrocyte sedimentation rate. These markers of pathologic processes are particularly helpful in identifying disease in patients with small elevations in body temperature

Fever in Recipients of Anticytokine Therapy

• As of this writing, more than 750,000 patients in the United States are receiving chronic anticytokine therapy for Crohn's disease, rheumatoid arthritis, or psoriasis. Does such therapy mask infection by preventing fever? With the increasing use of anticytokines to reduce the activity of IL-1, IL-6, IL-12, and TNF, the effect of these agents on the febrile response must be considered.

• The blocking of cytokine activity has the distinct clinical drawback of lowering the level of host defenses against both routine bacterial and opportunistic infections. The opportunistic infections reported in patients given neutralizing antibodies to TNF- (infliximab or adalimumab) are similar to those reported in the HIV-1-infected population (e.g., new infection with or reactivation of Mycobacterium tuberculosis , with dissemination). A soluble receptor for TNF, etanercept, is also associated with opportunistic infections but less so than the neutralizing antibodies.

• In nearly all reported cases of infection associated with anticytokine therapy, fever is among the presenting signs. However, the extent to which the febrile response is reduced in these patients remains unknown. Fever in a patient who develops an infection during anticytokine treatment is likely to be due to the direct action of microbial products on the hypothalamic thermoregulatory center, with induction of PGE2. For example, blocking the activity of IL-1 or TNF during experimental endotoxin-induced fever in volunteers does not affect the febrile response.

Fever and Hyperthermia: Treatment

• The Decision to Treat Fever

• Most fevers are associated with self-limited infections, such as common viral diseases. The use of antipyretics is not contraindicated in these infections: there is no significant clinical evidence that antipyretics delay the resolution of viral or bacterial infections, nor is there evidence that fever facilitates recovery from infection or acts as an adjuvant to the immune system. In fact, peripheral PGE2 production is a potent immunosuppressant. In short, treatment of fever and its symptoms does no harm and does not slow the resolution of common viral and bacterial infections.

• However, in bacterial infections, withholding antipyretic therapy can be helpful in evaluating the effectiveness of a particular antibiotic therapy, particularly in the absence of cultural identification of the infecting organism. The routine use of antipyretics can mask an inadequately treated bacterial infection. Withholding antipyretics in some cases may facilitate the diagnosis of an unusual febrile disease. For example, the usual times of peak and trough temperatures may be reversed in typhoid fever and disseminated tuberculosis. Temperature-pulse dissociation (relative bradycardia) occurs in typhoid fever, brucellosis, leptospirosis, some drug-induced fevers, and factitious fever. In newborns, the elderly, patients with chronic renal failure, and patients taking glucocorticoids, fever may not be present despite infection, or core temperature may be hypothermic. Hypothermia is often observed in patients with septic shock.

• Some infections have characteristic patterns in which febrile episodes are separated by intervals of normal temperature. For example, Plasmodium vivax causes fever every third day, whereas fever occurs every fourth day with P. malariae. Other relapsing fevers are related to Borrelia infections, with days of fever followed by a several-day afebrile period and then a relapse of days of fever. In the Pel-Ebstein pattern, fever lasting 3–10 days is followed by afebrile periods of 3–10 days; this pattern can be classic for Hodgkin's disease and other lymphomas. In cyclic neutropenia, fevers occur every 21 days and accompany the neutropenia. There is no periodicity of fever in patients with familial Mediterranean fever.

• Recurrent fever is documented at some point in most autoimmune diseases and all autoinflammatory diseases. The autoinflammatory diseases include adult and juvenile Still's disease, familial Mediterranean fever, hyper-IgD syndrome, familial cold-induced autoinflammatory syndrome, neonatal-onset multisystem autoinflammatory disease, Blau syndrome, Schnitzler syndrome, Muckle-Wells syndrome, and TNF receptor–associated periodic syndrome. Besides recurrent fevers, neutrophilia and serosal inflammation characterize these diseases. The fevers associated with these illnesses are dramatically reduced by blocking of IL-1 activity. Anticytokines therefore reduce fever in autoimmune and autoinflammatory diseases. Although fevers in autoinflammatory diseases are mediated by IL-1, patients also respond to antipyretics

Mechanisms of Antipyretic Agents

• The reduction of fever by lowering of the elevated hypothalamic set point is a direct function of reducing the level of PGE2 in the thermoregulatory center. The synthesis of PGE2 depends on the constitutively expressed enzyme cyclooxygenase. The substrate for cyclooxygenase is arachidonic acid released from the cell membrane, and this release is the rate-limiting step in the synthesis of PGE2. Therefore, inhibitors of cyclooxygenase are potent antipyretics. The antipyretic potency of various drugs is directly correlated with the inhibition of brain cyclooxygenase. Acetaminophen is a poor cyclooxygenase inhibitor in peripheral tissue and lacks noteworthy anti-inflammatory activity; in the brain, however, acetaminophen is oxidized by the p450 cytochrome system, and the oxidized form inhibits cyclooxygenase activity. Moreover, in the brain, the inhibition of another enzyme, COX-3, by acetaminophen may account for the antipyretic effect of this agent. However, COX-3 is not found outside the CNS.

• Oral aspirin and acetaminophen are equally effective in reducing fever in humans. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and specific inhibitors of COX-2 are also excellent antipyretics. Chronic, high-dose therapy with antipyretics such as aspirin or any NSAID does not reduce normal core body temperature. Thus, PGE2 appears to play no role in normal thermoregulation.• As effective antipyretics, glucocorticoids act at two levels. First, similar to the

cyclooxygenase inhibitors, glucocorticoids reduce PGE2 synthesis by inhibiting the activity of phospholipase A2, which is needed to release arachidonic acid from the cell membrane. Second, glucocorticoids block the transcription of the mRNA for the pyrogenic cytokines. Limited experimental evidence indicates that ibuprofen and COX-2 inhibitors reduce IL-1-induced IL-6 production and may contribute to the antipyretic activity of NSAIDs.

Regimens for the Treatment of Fever

• The objectives in treating fever are first to reduce the elevated hypothalamic set point and second to facilitate heat loss. Reducing fever with antipyretics also reduces systemic symptoms of headache, myalgias, and arthralgias.• Oral aspirin and NSAIDs effectively reduce fever but can adversely

affect platelets and the gastrointestinal tract. Therefore, acetaminophen is preferred to all of these agents as an antipyretic. In children, acetaminophen must be used because aspirin increases the risk of Reye's syndrome. If the patient cannot take oral antipyretics, parenteral preparations of NSAIDs and rectal suppository preparations of various antipyretics can be used.

• Treatment of fever in some patients is highly recommended. Fever increases the demand for oxygen (i.e., for every increase of 1°C over 37°C, there is a 13% increase in oxygen consumption) and can aggravate preexisting cardiac, cerebrovascular, or pulmonary insufficiency. Elevated temperature can induce mental changes in patients with organic brain disease. Children with a history of febrile or nonfebrile seizure should be aggressively treated to reduce fever, although it is unclear what triggers the febrile seizure and there is no correlation between absolute temperature elevation and onset of a febrile seizure in susceptible children.• In hyperpyrexia, the use of cooling blankets facilitates the reduction of

temperature; however, cooling blankets should not be used without oral antipyretics. In hyperpyretic patients with CNS disease or trauma, reducing core temperature mitigates the ill effects of high temperature on the brain.

Treating Hyperthermia

• A high core temperature in a patient with an appropriate history (e.g., environmental heat exposure or treatment with anticholinergic or neuroleptic drugs, tricyclic antidepressants, succinylcholine, or halothane) along with appropriate clinical findings (dry skin, hallucinations, delirium, pupil dilation, muscle rigidity, and/or elevated levels of creatine phosphokinase) suggests hyperthermia. Attempts to lower the already normal hypothalamic set point are of little use. Physical cooling with sponging, fans, cooling blankets, and even ice baths should be initiated immediately in conjunction with the administration of IV fluids and appropriate pharmacologic agents (see below). If insufficient cooling is achieved by external means, internal cooling can be achieved by gastric or peritoneal lavage with iced saline. In extreme circumstances, hemodialysis or even cardiopulmonary bypass with cooling of blood may be performed.

• Malignant hyperthermia should be treated immediately with cessation of anesthesia and IV administration of dantrolene sodium. The recommended dose of dantrolene is 1–2.5 mg/kg given intravenously every 6 h for at least 24–48 h—until oral dantrolene can be administered, if needed. Procainamide should also be administered to patients with malignant hyperthermia because of the likelihood of ventricular fibrillation in this syndrome. Dantrolene at similar doses is indicated in the neuroleptic malignant syndrome and in drug-induced hyperthermia and may even be useful in the hyperthermia of the serotonin syndrome and thyrotoxicosis. The neuroleptic malignant syndrome may also be treated with bromocriptine, levodopa, amantadine, or nifedipine or by induction of muscle paralysis with curare and pancuronium. Tricyclic antidepressant overdose may be treated with physostigmine

Fever of unknown origin

• Fever of unknown origin (FUO) was defined by Petersdorf and Beeson in 1961 as (1) temperatures of >38.3°C (>101°F) on several occasions; (2) a duration of fever of >3 weeks; and (3) failure to reach a diagnosis despite 1 week of inpatient investigation. While this classification has stood for more than 30 years, Durack and Street have proposed a new system for classification of FUO: (1) classic FUO; (2) nosocomial FUO; (3) neutropenic FUO; and (4) FUO associated with HIV infection.

• Classic FUO corresponds closely to the earlier definition of FUO, differing only with regard to the prior requirement for 1 week's study in the hospital. The newer definition is broader, stipulating three outpatient visits or 3 days in the hospital without elucidation of a cause or 1 week of "intelligent and invasive" ambulatory investigation.• In nosocomial FUO, a temperature of 38.3°C (101°F) develops on

several occasions in a hospitalized patient who is receiving acute care and in whom infection was not manifest or incubating on admission. Three days of investigation, including at least 2 days' incubation of cultures, is the minimum requirement for this diagnosis

• Neutropenic FUO is defined as a temperature of 38.3°C (101°F) on several occasions in a patient whose neutrophil count is <500/L or is expected to fall to that level in 1–2 days. The diagnosis of neutropenic FUO is invoked if a specific cause is not identified after 3 days of investigation, including at least 2 days' incubation of cultures.• HIV-associated FUO is defined by a temperature of 38.3°C (101°F) on

several occasions over a period of >4 weeks for outpatients or >3 days for hospitalized patients with HIV infection. This diagnosis is invoked if appropriate investigation over 3 days, including 2 days' incubation of cultures, reveals no source.

Fever of Unknown Origin: Treatment

• The focus here is on classic FUO. Other modifiers of FUO—neutropenia, HIV infection, a nosocomial setting—all vastly affect the risk equation and dictate therapy based on the probability of various causes of fever and on the calculated risks and benefits of a guided empirical approach. The age and physical state of the patient are factors as well: the frail elderly patient may merit a trial of empirical therapy earlier than the robust young adult.

• The emphasis in patients with classic FUO is on continued observation and examination, with the avoidance of "shotgun" empirical therapy. Antibiotic therapy (even that for tuberculosis) may irrevocably alter the ability to culture fastidious bacteria or mycobacteria and delineate ultimate cause. However, vital-sign instability or neutropenia is an indication for empirical therapy with a fluoroquinolone plus piperacillin or the regimen mentioned above (see "Nosocomial FUO"), for example. Cirrhosis, asplenia, intercurrent immunosuppressive drug use, or recent exotic travel may all tip the balance toward earlier empirical anti-infective therapy. If the PPD skin test is positive or if granulomatous hepatitis or other granulomatous disease is present with anergy (and sarcoid seems unlikely), then a therapeutic trial with isoniazid and rifampin (and possibly a third drug) should be undertaken, with treatment usually continued for up to 6 weeks. A failure of the fever to respond over this period suggests an alternative diagnosis.

• The response of rheumatic fever and Still's disease to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) may be dramatic. The effects of glucocorticoids on temporal arteritis, polymyalgia rheumatica, and granulomatous hepatitis are equally dramatic. Colchicine is highly effective in preventing attacks of familial Mediterranean fever but is of little use once an attack is well under way. The ability of glucocorticoids and NSAIDs to mask fever while permitting the spread of infection dictates that their use be avoided unless infection has been largely ruled out and unless inflammatory disease is both probable and debilitating or threatening.

• When no underlying source of FUO is identified after prolonged observation (>6 months), the prognosis is generally good, however vexing the fever may be to the patient. Under such circumstances, debilitating symptoms are treated with NSAIDs, and glucocorticoids are the last resort. The initiation of empirical therapy does not mark the end of the diagnostic workup; rather, it commits the physician to continued thoughtful reexamination and evaluation. Patience, compassion, equanimity, and intellectual flexibility are indispensable attributes for the clinician in dealing successfully with FUO.

Hypothermia

• Accidental hypothermia occurs when there is an unintentional drop in the body's core temperature below 35°C (95°F). At this temperature, many of the compensatory physiologic mechanisms to conserve heat begin to fail. Primary accidental hypothermia is a result of the direct exposure of a previously healthy individual to the cold. The mortality rate is much higher for those patients who develop secondary hypothermia as a complication of a serious systemic disorder.

• Primary accidental hypothermia is geographically and seasonally pervasive. Although most cases occur in the winter months and in colder climates, it is surprisingly common in warmer regions as well. Multiple variables make individuals at the extremes of age, the elderly and neonates, particularly vulnerable to hypothermia. The elderly have diminished thermal perception and are more susceptible to immobility, malnutrition, and systemic illnesses that interfere with heat generation or conservation. Dementia, psychiatric illness, and socioeconomic factors often compound these problems by impeding adequate measures to prevent hypothermia. Neonates have high rates of heat loss because of their increased surface-to-mass ratio and their lack of effective shivering and adaptive behavioral responses. In addition, malnutrition can contribute to heat loss because of diminished subcutaneous fat and because of depleted energy stores used for thermogenesis.

• Individuals whose occupations or hobbies entail extensive exposure to cold weather are at increased risk for hypothermia. Military history is replete with hypothermic tragedies. Hunters, sailors, skiers, and climbers also are at great risk of exposure, whether it involves injury, changes in weather, or lack of preparedness.

• Ethanol causes vasodilatation (which increases heat loss), reduces thermogenesis and gluconeogenesis, and may impair judgment or lead to obtundation. Phenothiazines, barbiturates, benzodiazepines, cyclic antidepressants, and many other medications reduce centrally mediated vasoconstriction. Up to 25% of patients admitted to an intensive care unit because of drug overdose are hypothermic. Anesthetics can block the shivering responses; their effects are compounded when patients are not covered adequately in the operating or recovery rooms.

• Several types of endocrine dysfunction can lead to hypothermia. Hypothyroidism—particularly when extreme, as in myxedema coma—reduces the metabolic rate and impairs thermogenesis and behavioral responses. Adrenal insufficiency and hypopituitarism also increase susceptibility to hypothermia. Hypoglycemia, most commonly caused by insulin or oral hypoglycemic drugs, is associated with hypothermia, in part the result of neuroglycopenic effects on hypothalamic function. Increased osmolality and metabolic derangements associated with uremia, diabetic ketoacidosis, and lactic acidosis can lead to altered hypothalamic thermoregulation.• Neurologic injury from trauma, cerebrovascular accident, subarachnoid

hemorrhage, or hypothalamic lesions increases susceptibility to hypothermia. Agenesis of the corpus callosum, or Shapiro syndrome, is one cause of episodic hypothermia, characterized by profuse perspiration followed by a rapid fall in temperature. Acute spinal cord injury disrupts the autonomic pathways that lead to shivering and prevents cold-induced reflex vasoconstrictive responses.

• Hypothermia associated with sepsis is a poor prognostic sign. Hepatic failure causes decreased glycogen stores and gluconeogenesis, as well as a diminished shivering response. In acute myocardial infarction associated with low cardiac output, hypothermia may be reversed after adequate resuscitation. With extensive burns, psoriasis, erythrodermas, and other skin diseases, increased peripheral blood flow leads to excessive heat loss

Clinical presentation

Diagnosis and Stabilization• Hypothermia is confirmed by measuring the core temperature, preferably at two sites.

Rectal probes should be placed to a depth of 15 cm and not adjacent to cold feces. A simultaneous esophageal probe should be placed 24 cm below the larynx; it may read falsely high during heated inhalation therapy. Relying solely on infrared tympanic thermography is not advisable.• After a diagnosis of hypothermia is established, cardiac monitoring should be instituted,

along with attempts to limit further heat loss. If the patient is in ventricular fibrillation, one defibrillation attempt (2 J/kg) should be administered. If the rhythm does not convert, rewarm the patient to 30–32°C before repeating defibrillation attempts. Supplemental oxygenation is always warranted, since tissue oxygenation is adversely affected by the leftward shift of the oxyhemoglobin dissociation curve. Pulse oximetry may be unreliable in patients with vasoconstriction. If protective airway reflexes are absent, gentle endotracheal intubation should be performed. Adequate pre-oxygenation will prevent ventricular arrhythmias. Although cardiac pacing for hypothermic bradydysrhythmias is rarely indicated, the transthoracic technique is preferable.

• Insertion of a gastric tube prevents dilatation secondary to decreased bowel motility. Indwelling bladder catheters facilitate monitoring of cold-induced diuresis. Dehydration is commonly encountered with chronic hypothermia, and most patients benefit from a bolus of crystalloid. Normal saline is preferable to lactated Ringer's solution, as the liver in hypothermic patients inefficiently metabolizes lactate. The placement of a pulmonary artery catheter risks perforation of the less compliant pulmonary artery. Insertion of a central venous catheter into the cold right atrium should be avoided, since this can precipitate arrhythmias.• Arterial blood gases should not be corrected for temperature (Chap. 48). An

uncorrected pH of 7.42 and a PCO2 of 40 mmHg reflects appropriate alveolar ventilation and acid-base balance at any core temperature. Acid-base imbalances should be corrected gradually, since the bicarbonate buffering system is inefficient. A common error is overzealous hyperventilation in the setting of depressed CO2 production. When the PCO2 decreases 10 mmHg at 28°C, it doubles the pH increase of 0.08 that occurs at 37°C.

• The severity of anemia may be underestimated because the hematocrit increases 2% for each 1°C drop in temperature. White blood cell sequestration and bone marrow suppression are common, potentially masking an infection. Although hypokalemia is more common in chronic hypothermia, hyperkalemia also occurs; the expected electrocardiographic changes can be obscured by hypothermia. Patients with renal insufficiency, metabolic acidoses, or rhabdomyolysis are at greatest risk for electrolyte disturbances.• Coagulopathies are common because cold inhibits the enzymatic reactions

required for activation of the intrinsic cascade. In addition, thromboxane B2 production by platelets is temperature-dependent, and platelet function is impaired. The administration of platelets and fresh frozen plasma is, therefore, not effective. The prothrombin or partial thromboplastin times or INR (international normalized ratio) reported by the laboratory appear deceptively normal and contrast with the observed in vivo coagulopathy. This contradiction occurs because all coagulation tests are routinely performed at 37°C, and the enzymes are thus rewarmed.

Rewarming Strategies• The key initial decision is whether to rewarm the patient passively or actively. Passive

external rewarming simply involves covering and insulating the patient in a warm environment. With the head also covered, the rate of rewarming is usually 0.5° to 2.0°C per hour. This technique is ideal for previously healthy patients who develop acute, mild primary accidental hypothermia. The patient must have sufficient glycogen to support endogenous thermogenesis.

• The application of heat directly to the extremities of patients with chronic severe hypothermia should be avoided because it can induce peripheral vasodilatation and precipitate core temperature "afterdrop"—a response characterized by a continual decline in the core temperature after removal of the patient from the cold. Truncal heat application reduces the risk of afterdrop.

• Active rewarming is necessary under the following circumstances: core temperature < 32°C (poikilothermia), cardiovascular instability, age extremes, CNS dysfunction, hormone insufficiency, or suspicion of secondary hypothermia. Active external rewarming is best accomplished with forced-air heating blankets. Other options include radiant heat sources and hot packs. Monitoring a patient with hypothermia in a heated tub is extremely difficult. Electric blankets should be avoided because vasoconstricted skin is easily burned.

• There are numerous widely available active core rewarming options. Airway rewarming with heated humidified oxygen (40°–45°C) is a convenient option via mask or endotracheal tube. Although airway rewarming provides less heat than some other forms of active core rewarming, it eliminates respiratory heat loss and adds 1°–2°C to the overall rewarming rate. Crystalloids should be heated to 40°–42°C, but the quantity of heat provided is significant only during massive volume resuscitation. The most efficient method for heating and delivering fluid or blood is with a countercurrent in-line heat exchanger. Heated irrigation of the gastrointestinal tract or bladder transfers minimal heat because of the limited available surface area. These methods should be reserved for patients in cardiac arrest and then used in combination with all available active rewarming techniques.

• Closed thoracic lavage is far more efficient in severely hypothermic patients with cardiac arrest. The hemithoraces are irrigated through two large-bore thoracostomy tubes that are inserted into the hemithoraces. Thoracostomy tubes should not be placed in the left chest of a spontaneously perfusing patient for purposes of rewarming. Peritoneal lavage with the dialysate at 40°–45°C efficiently transfers heat when delivered through two catheters with outflow suction. Like peritoneal dialysis, standard hemodialysis is especially useful for patients with electrolyte abnormalities, rhabdomyolysis, or toxin ingestions.

• Extracorporeal blood rewarming options should be considered in severely hypothermic patients, especially those with primary accidental hypothermia. Cardiopulmonary bypass should be considered in nonperfusing patients without documented contraindications to resuscitation. Circulatory support may be the only effective option in patients with completely frozen extremities, or those with significant tissue destruction coupled with rhabdomyolysis. There is no evidence that extremely rapid rewarming improves survival in perfusing patients. The best strategy is usually a combination of passive, truncal active, and active core rewarming techniques.

Hypothermia: Treatment

• When a patient is hypothermic, target organs and the cardiovascular system respond minimally to most medications. Moreover, cumulative doses can cause toxicity during rewarming because of increased binding of drugs to proteins, and impaired metabolism and excretion. As an example, the administration of repeated doses of digoxin or insulin would be ineffective while the patient is hypothermic, and the residual drugs are potentially toxic during rewarming.

• Achieving a mean arterial pressure of at least 60 mmHg should be an early objective. If the hypotension does not respond to crystalloid/colloid infusion and rewarming, low-dose dopamine (2–5 g/kg per min) support should be considered. Perfusion of the vasoconstricted cardiovascular system may also be improved with low-dose IV nitroglycerin.

• Atrial arrhythmias should initially be monitored without intervention, as the ventricular response will be slow, and unless preexistent, most will convert spontaneously during rewarming. The role of prophylaxis and treatment of ventricular arrhythmias is problematic. Preexisting ventricular ectopy may be suppressed by hypothermia and reappear during rewarming. None of the class I agents has proved to be safe and efficacious. When available, bretylium tosylate was the class III ventricular antiarrhythmic of choice. There is no evidence that amiodarone is safe.• Initiating empirical therapy for adrenal insufficiency is usually not warranted

unless there is a history suggesting steroid dependence, hypoadrenalism, or a failure to rewarm with standard therapy. The administration of parenteral levothyroxine to euthyroid patients with hypothermia, however, is potentially hazardous. Because laboratory results can be delayed and confounded by the presence of the sick euthyroid syndrome (Chap. 335), historic clues or physical findings suggestive of hypothyroidism should be sought. When myxedema is the cause of hypothermia, the relaxation phase of the Achilles reflex is prolonged more than the contraction phase.

• Hypothermia obscures most of the symptoms and signs of infection, notably fever and leukocytosis. Shaking rigors from infection may be mistaken for shivering. Except in mild cases, extensive cultures and repeated physical examinations are essential. Unless an infectious source is identified, empirical antibiotic prophylaxis is most warranted in the elderly, neonates, and immunocompromised patients.• Preventive measures should be discussed with high-risk individuals,

such as the elderly or people whose work frequently exposes them to extreme cold. The importance of layered clothing and headgear, adequate shelter, increased caloric intake, and the avoidance of ethanol should be emphasized, along with access to rescue services.

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