Prehospital Care

In the prehospital setting, focus primarily on removing the patient from the current environment to prevent further decreases in core temperature. Studies have shown that oral temperatures are sufficiently accurate for field use⁴¹; however, infrared tympanic thermometers may not be reliable in the prehospital setting.⁴² Handle these patients with special care and anticipate the presence of an irritable myocardium because aggressive measures can inadvertently trigger cardiac dysrhythmias. Hypovolemia and a large temperature gradient often exist between the periphery and the core in a hypothermic patient.⁶ Avoid aggressive field management and prolonged transport times.^43,44 After removing the patient’s wet clothing, wrap the patient in dry blankets or sleeping bags. “Field rewarming” is a misnomer because adding significant heat to a hypothermic patient in the field is extremely difficult. Studies have shown that for mild hypothermia, resistive heating (e.g., warming blankets) can be used safely in the prehospital setting. Resistive heating augments thermal comfort, increases core temperature by approximately 0.8°C/hr (33.4°F/hr), and reduces patient pain and anxiety during transport.⁴⁵ In one study, resistive heating more than doubled the rewarming rate when compared with passive insulation and did not produce an afterdrop.⁴⁶ With longer transport times, use active rewarming methods limited to heated inhalation and truncal heat application. Place insulated hot water bottles near the patient’s axilla or groin. The Res-Q-Air device (CF Electronics, Inc., Commack, NY) is lightweight and portable and delivers heated humidified air or oxygen at temperatures ranging from 42°C to 44°C (107.6°F to 111.2°F) and down to ambient conditions of −20°C (−4°F). In more remote settings, another option is to use a modified forced-air warming system in the field. The Portable Rigid Forced-Air Cover is heated with a Bair Hugger heater/blower (Augustine Medical, Inc., Eden Prairie, MN). It covers the patient’s trunk and thighs and can adapt to various transport vehicle power sources.⁶

Immobilize patients with potential traumatic injuries to the spine or extremities before transport. Pay continuous attention to airway maintenance. Initiate fluid resuscitation with intravenous (IV) crystalloid, preferably 5% dextrose in normal saline (D₅NS). Alternatively, give warmed oral glucose-containing drinks to a patient who is awake and alert. Most hypothermic patients are dehydrated because fluid intake is reduced and cold causes diuresis. Avoid using lactated Ringer’s solution because it can theoretically decrease the metabolism of lactate by cold-induced hepatic dysfunction. If possible, use warmed IV fluids because they are generally well tolerated.47,48 If available, use a flameless heater, which is currently being used by military medical units and provides an easy and expedient means of warming fluids in the prehospital setting.⁴⁹

Intubate unresponsive patients, but recognize that there is no universal agreement on when to intubate a hypothermic patient who has detectable vital signs. Pulse oximetry is not usually helpful because vasoconstriction limits blood flow to the periphery and readings may be inaccurate or not possible. Some authors suggest that pulseless victims with core temperatures below 32°C (<89.6°F) should be transported with continuous CPR.⁴⁷ Other authors believe that it is unnecessary to perform CPR on a patient who has any perfusing cardiac rhythm because it may precipitate ventricular fibrillation.⁵⁰ There is no universally accepted standard for intubation or CPR in hypothermic patients with detectable vital signs.⁵¹

Definitive prehospital determination of cardiac activity requires a cardiac monitor. Cardiac arrest is a common misdiagnosis because peripheral pulses are difficult to palpate when extreme bradycardia is present along with peripheral vasoconstriction. Some authors report that asystole is a more common rhythm than ventricular fibrillation. In the field, differentiating ventricular fibrillation from asystole may be impractical.

Transport cold, stiff, cyanotic patients with fixed and dilated pupils because the treatment dictum for prehospital personnel remains, “No one is dead until warm and dead.” A succinct summary of the prehospital care of a hypothermic patient is rescue, examine, insulate, and transport.⁶

ED Management

There are no universally established standards of care regarding the use of specific techniques for rewarming a hypothermic patient or cooling a hyperthermic patient. This chapter describes all potentially useful modalities. Many are not applicable for general use in the ED, whereas others are safe, beneficial, and easily accomplished in the general ED setting. Some invasive procedures, however, such as cardiopulmonary bypass and irrigation of the peritoneal or thoracic cavity, may be overly aggressive or of anecdotal or theoretical benefit only. Exactly when to institute any given intervention is best determined by the resources available, the initial scenario, and clinical judgement individualized for each patient.

Treatment priorities in the ED setting are to prevent further decreases in core body temperature; establish a steady, safe rewarming rate; maintain stability of the cardiopulmonary system; and provide sufficient physiologic support. Adjust the rate of rewarming and the techniques used according to the degree of hypothermia and the severity of the patient’s clinical condition (Table 65-2). Anticipate and prevent complications.

In a pulseless, apneic patient, initiate CPR and continue until the core temperature is above 34°C (>93.2°F). Profound hypothermia results in coma, hyporeflexia, fixed and dilated pupils, severe bradycardia, and often an unobtainable blood pressure. With severe hypothermia, a pulse might not be palpable and measurement of blood pressure might require the use of a Doppler device. If available, use ultrasound to detect the presence of cardiac wall motion. Follow the heart rate and rhythm with electrocardiographic monitoring. In patients who have anything more than minimal impairment, perform arterial blood gas analysis frequently to determine oxygenation, ventilation, and acid-base status. If feasible, establish large-bore IV lines. Avoid central lines if possible because insertion of such lines may exacerbate the myocardial irritation. Give maintenance IV fluids. Warm all IV fluids to 40°C to 42°C (104°F to 107.6°F), but be aware that the usual volumes administered will not contribute significant heat calories. With long standard IV tubing, the heated IV fluids may actually cool to room temperature before entering the patient’s IV site.

With a mild to moderate reduction in core temperature, the level of mentation correlates with the severity of the AH, associated illnesses, or both. Noteworthy exceptions are alcoholics and diabetics, who can be in a coma at higher core temperatures because of concomitant hypoglycemia. Perform bedside glucose measurements on patients when they arrive in the ED. A high correlation exists between alcohol consumption and the development of hypothermia, especially in colder climates.¹ A review of 68 cases of hypothermic deaths in Jefferson County, Alabama, found that a significant number of cases involved middle-aged men who had consumed alcohol.³ In the 22 cases of AH reviewed by Fitzgerald,⁵² all but 2 patients were alcoholics. The serum glucose level was less than 50 mg/dL in 41% (nine patients). This study noted glycosuria in two patients, even when low serum glucose values were evident, and described a renal tubular glycosuria in patients with AH. Such glycosuria may worsen or cause hypoglycemia. Glycosuria in AH is no guarantee of an adequate serum glucose concentration. This supports the routine use of supplemental IV glucose unless a normal serum glucose value can be quickly ensured. Consider administering IV thiamine (100 mg) and a trial dose of 0.4 to 2 mg of IV naloxone (Narcan) in a comatose patient. Although failure to rewarm spontaneously has been noted in victims with hypothyroidism and other endocrine deficiencies, reserve the use of thyroid hormones and corticosteroids for patients with suspected thyroid and adrenal insufficiency, respectively.

The thermoregulatory vasoconstriction caused by hypothermia significantly decreases subcutaneous oxygen tension.²¹ Good correlation exists between the incidence of wound infection and subcutaneous oxygen tension. As core temperatures decrease from 41°C to 26°C (105.8°F to 78.8°F), neutrophil function is significantly impaired.²¹ In animal models, hypothermia appears to decrease leukocyte sequestration within the brain parenchyma, thus offering some resistance to meningitis.⁵³ Although antibiotics are not routinely indicated for victims of uncomplicated mild hypothermia, some authors advocate the routine empirical initiation of broad-spectrum antibiotic therapy on admission of severely hypothermic patients. In this setting, detection and treatment of the underlying cause, such as infection, may be more critical than treatment of the hypothermia.¹

Passive External Rewarming

The cornerstone of the effectiveness of passive external rewarming relies on the body’s ability to restore normal body temperature through its own mechanisms for heat production. Stop further heat loss with insulation and manipulation of the environment. Give warm fluids containing glucose to patients who are fully alert. For patients with mild AH, remove wet clothing and then provide passive external rewarming with blankets. The technique is simple, but the patient must be capable of generating enough body heat for this method to be successful. Give warmed IV fluids to counteract the cold-induced diuresis. Internal heat generation is required for rewarming, and this effect will be relatively slow. In an otherwise stable patient, aggressive intervention with drugs and invasive monitoring might be more harmful than beneficial. Patients who cannot shiver, those who are hypotensive, or those who are intoxicated or malnourished may not have this capability. Survival rates with passive external rewarming have ranged from 55% to 100%.56–59

For patients in the moderate or severe category of hypothermia, a more aggressive approach may be warranted. The options available are active external rewarming and active core rewarming. Active core rewarming techniques can be further divided into less invasive and more invasive techniques. The aggressiveness of therapy depends more on the patient’s underlying health, hemodynamic status, and response to initial therapy than on the initial temperature.

Active External Rewarming

The application of heat to the skin of a hypothermic patient has been termed active external rewarming.

Active Core Rewarming

There is evidence that active core rewarming may decrease mortality from severe hypothermic exposure when compared with other techniques. In the face of circulatory failure, often the best chance of survival is treatment with extracorporeal circulation (ECC) and warming of the blood.⁷² Several methods have been described, including the use of warm humidified air through an endotracheal tube or mask, peritoneal lavage, gastric or bladder lavage with warm fluid, thoracic tube lavage, cardiopulmonary bypass, AVR, peripheral vascular extracorporeal warming, hemodialysis, and thoracotomy with mediastinal lavage. These techniques transfer heat actively to the body core and achieve varying rewarming rates. The specific techniques and some of the advantages and disadvantages for each procedure follow.

Cardiac Arrest

Cardiac arrest secondary to AH requires immediate treatment for the best chance of a successful outcome. Rapid rewarming and restoration of cardiac rhythm are essential for patients in cardiopulmonary arrest and can best be achieved with a combination of passive and multiple active core rewarming techniques. Because of numerous cases of survival from hypothermic cardiac arrest with prolonged external cardiac compression,5,41,99 thoracotomy is not mandatory. Thoracotomy does offer some theoretical advantages, however, such as increased cardiac output with open-chest massage,⁹⁰ direct observation of cardiac activity, and direct warming of cardiac tissue with thoracic cavity lavage of warm fluid. Cardiopulmonary bypass is an effective technique for rapid rewarming. Blunt trauma and head trauma victims were previously not ideal candidates for cardiac bypass because of the anticoagulation requirement, but some authors have advocated this technique with heparin-bonded tubing even in the setting of known traumatic injury.⁵ A review of outcomes after hypothermic cardiac arrest from one institution found that the average time from thoracotomy to the development of a perfusing rhythm was 38 minutes (range, 10 to 90 minutes).⁵ The optimal rate of cardiac compressions in hypothermic patients is not known. Because of decreased oxygen consumption by vital organs, the rate required in hypothermic cardiac arrest is less than that recommended for normothermic cardiac arrest. Cardiac compressions should be initiated at half the normal rate in profoundly hypothermic patients. Guidelines developed by the American Heart Association and the Wilderness Medical Society recommend that CPR be initiated in patients with AH unless any of the following conditions exist: a “do-not-resuscitate” status is documented and verified, obvious lethal injuries are present, chest wall depression is impossible, no signs of life are present, or rescuers are endangered by delays in evacuation and altered triage conditions.⁶

The duration of CPR depends on the time required to raise the core temperature to a level at which defibrillation should be successful (i.e., >30°C [>86°F]). Previously, it was recommended that patients not receive a set of three countershocks until a core temperature above 30°C (>86°F) could be attained. There have been reports of successful defibrillation in patients with profound hypothermia with core temperatures of 25.6°C (78.1°F).⁸⁶ The decision to terminate resuscitative efforts remains a clinical one, but there are certain poor prognostic factors. Certainly, survival is unlikely in patients who persist in asystole or go from ventricular fibrillation to asystole as they are warmed past 32°C (>89.6°F). Prognostic markers for patients with severe hypothermia and cardiac arrest have been proposed as contraindications to ED thoracotomy and cardiac bypass by some authors.⁵ Such markers include potassium levels elevated to above 10 mmol/L (mEq/L) and pH levels below 6.5. Nonetheless, there are reports of survival in patients with higher potassium levels and a pH as low as 6.29.⁹² The decision to continue resuscitative efforts should not be based solely on specific laboratory values or the initial core temperature.

Isolated reports of survival of hypothermic patients with prolonged CPR make extended efforts to resuscitate such patients reasonable. Children may be the best candidates for heroic measures.⁵⁰ Under ideal conditions, hypothermic cardiac arrest patients may reasonably be admitted to an intensive care unit for a 4- to 5-hour trial of rewarming with CPR in progress. Manual CPR should be replaced by mechanical methods if the equipment is available. The oxygen-powered “thumper” has been successful during prolonged hypothermic resuscitation. Absence of responsiveness to treatment, in conjunction with a highly elevated potassium level, is an indication for termination of resuscitative efforts.

Airway Management

Maintain a secure functioning airway for hypothermic patients, just as in any critically ill patient. With mild hypothermia, deliver heated, humidified oxygen by face mask. Recognize that a hypothermic patient can be combative and uncooperative and may require arm restraints if a mask is used. Intubate patients with decreased sensorium who cannot reliably maintain their airway or hypothermic patients who may be hypoxic. Endotracheal intubation may be performed safely without the added risk of ventricular dysrhythmias.¹⁵ The technique for endotracheal intubation depends on the specific circumstances and the expertise of the operator. Once an endotracheal tube has been placed and secured, use it to provide warm humidified oxygen. There is no evidence that tracheal intubation is detrimental in severely hypothermic patients, and it should be considered if indicated for ventilation, oxygenation, or airway protection.

Acid-Base Disturbances

Acid-base disturbances are variable and can lead to metabolic acidosis from carbon dioxide retention and to lactic acidosis or metabolic alkalosis from decreased carbon dioxide production or hyperventilation. Interpretation of arterial blood gases in a hypothermic patient has been the cause of some confusion. Previously, it was suggested that all blood gases be corrected for temperature with correlation factors. With a decrease in temperature of 1°C (33.8°F), pH rises 0.015, carbon dioxide pressure (Pco₂) drops by 4.4%, and oxygen pressure (Po₂) drops 7.2% relative to values that would be obtained with blood analyzed under normal conditions. Despite the conversion guide, optimal or normal values in hypothermia have not been well documented.³² Other recent literature supports the use of uncorrected arterial blood gas values to guide therapy with bicarbonate or hyperventilation.³⁰ This approach appears appropriate to support optimal enzymatic function. Gradual correction of acid-base imbalance will allow increased efficiency of the bicarbonate buffering system as the body warms. Arterial pH did not correlate with patient death in the Multicenter Hypothermia Study and should not be used as a prognostic guide to resuscitation.⁸⁴

Coagulopathies

Abnormal clotting occurs frequently in hypothermic patients, probably because cold inhibits the enzymatic coagulation cascade.100–102 Hypothermia-induced coagulopathy does not result from excessive clot lysis, but rather from impaired clot formation.^16,21 Platelet function is also impaired during hypothermia because production of thromboxane B₂ is inhibited. Hypothermia-induced platelet aggregation with or without neutrophil involvement has been associated with neurologic dysfunction in patients undergoing surgical procedures.⁹¹ Hypercoagulability with a risk for thromboembolism may also occur, but the importance of cold-induced coagulopathy mainly involves patients with coincidental trauma. Such victims often have bleeding that is difficult to control. Replace appropriate clotting factors and use warm blood to limit further blood loss and worsening of the hypothermia.

Trauma and Hypothermia

Mortality is increased in trauma patients with temperatures below 32°C (<89.6°F). It is not clear whether this increased mortality is actually a result of the hypothermia or whether the hypothermia is merely an indicator of severe injury and response to a massive transfusion of cold fluid.21,103 Patients with severe trauma are prone to hypothermia because their injuries often expose them to environmental heat loss. Concurrent alcohol intoxication may add to the heat loss as a result of its vasodilatory effects on cutaneous vasculature and the prolonged cold exposure secondary to altered mental status. Victims of severe injury also lose heat because of exposure during resuscitation and rapid administration of cold fluids.

It is unknown to what degree correcting the hypothermia improves outcome. Nevertheless, devices to rapidly infuse warm fluids such as the Level 1 fluid warmer (Level 1 Technologies, Rockland, MA) and the Thermostat 900 (Arrow International, Reading, PA) are frequently used to warm large-volume fluid transfusions. Use of these devices seems reasonable to prevent the hypothermia associated with massive transfusions (see Chapter 28). Their use for hypothermia not associated with severe trauma is limited by the relatively low fluid requirements of patients with environmental exposure. Another Thermostat device (Aquarius Medical Corp., Phoenix, AZ) is used to accelerate recovery from hypothermia by mechanically distending blood vessels in the hand, thereby increasing transfer of exogenous heat to the body core. One article found that this particular rewarming device was not very effective in accelerating rewarming in hypothermic surgical patients after general anethesia.¹⁰⁴

Mild Heat Illness

Heat cramps and heat exhaustion are induced by a hot environment.¹⁴⁴ The body’s heat dissipation mechanisms are generally able to keep up with heat production and absorption in these disorders. Symptoms are largely due to the mechanisms used by the body to dissipate heat, and body temperatures remain at or near normal. Rapid cooling techniques are not required, and supportive care and hydration in a cool environment are usually adequate therapy.

Heat cramps are intensely painful but generally benign involuntary skeletal muscle spasms. The pain most often occurs in the calf, hamstring, or quadriceps muscles but may also involve the arms and back. The cramps may be severe and prolonged but only rarely lead to rhabdomyolysis. Heat cramps occur after strenuous exercise or heavy labor in a hot environment. Heat cramps were previously thought to be the result of dehydration associated with significant loss of sodium chloride, but some clinical observations have proved that heat cramps can occur at rest or during exercise under any environmental conditions.¹⁴⁵ Rest in a cool environment plus vigorous oral fluid replacement with isotonic solutions is usually adequate therapy, but in some cases IV saline is required.¹⁴⁵ The benefits of oral rehydration over IV hydration directly relate to oropharyngeal stimulation, which influences the release of antidiuretic hormone (arginine vasopressin), cutaneous vasodilation, thirst sensation, and mean arterial pressure.¹⁴⁶ A common mistake is to rely on thirst to indicate dehydration. The pain of severe cramping may be resistant to narcotics in the absence of adequate fluid replacement.

Heat exhaustion, commonly referred to as heat syncope, is a poorly defined syndrome with nonspecific symptoms that occur after heat exposure.¹⁴⁷ Many have suggested replacing the current terminology of heat exhaustion with the term exercise-associated collapse.¹⁴⁸ Malaise, flulike symptoms, orthostasis, dehydration, nausea, headache, and collapse may all occur. Previously it was believed that heat exhaustion is the result of dehydration-induced heat retention that is not severe enough to cause heatstroke.¹⁴⁹ There is modern evidence that postural hypotension developing after exercise is the result of exercise-induced changes in blood pressure regulation. These changes involve recalibration of the arterial baroreflex to lower pressures after exercise, impaired sympathetic vascular regulation, and H₁ and H₂ receptor–mediated vasodilation.¹⁴⁹ When compared with the more severe heat disorder of heatstroke, mental status is normal and body temperature is normal or mildly elevated with heat exhaustion. There does not appear to be any thermoregulatory failure in persons with heat exhaustion. Rehydration, rest, and supportive care in a cool environment are adequate therapy for heat exhaustion.^144,145,148 Some authors advocate cooling and placing the patient either in the supine position with the legs elevated or seated with the head between the knees to decrease skin blood flow and increase venous blood flow to the heart.¹⁴⁹ Recovery is usually evident within a few minutes to hours. Occasionally, heat exhaustion is accompanied by heat cramps, thus presenting a confusing scenario if the diagnosis is not suspected. Rapid cooling techniques, IV hydration, and advanced therapies are not usually required, but patients should be observed for progression to heatstroke because heat exhaustion and heatstroke are a continuum of one disease process.^146,149

MH

MH is a pharmacogenetic disease attributable to a medication that triggers a life-threatening, hypermetabolic syndrome.¹⁶⁷ It results from a rare inherited autosomal dominant abnormality in the skeletal muscle membrane and has an incidence of 1 in 50,000 in adults.¹³⁹ In response to certain stresses or drugs (Box 65-1), patients with this disorder sustain a potentially lethal hypermetabolic reaction with massive efflux of calcium from the skeletal muscle sarcoplasmic reticulum. This results in contraction of the sarcomeres, skeletal muscle rigidity, increased skeletal muscle metabolism, elevated serum creatine kinase levels, heat production, and finally, systemic hyperthermia.^168,169 Hyperthermia is a late development and occurs after rigidity has been present for some time and the body’s normal heat dissipation mechanisms are overwhelmed. The earliest signs of MH are increased carbon dioxide production, muscle rigidity, and tachycardia.¹⁷⁰ Cardiac output and cutaneous blood flow also increase to maximize the heat loss. Diagnosis of MH is based on the clinical triad of (1) exposure to an agent or stress known to trigger the condition, (2) skeletal muscle rigidity, and (3) hyperthermia.

MH is usually encountered in the operating room while patients are undergoing general anesthesia, particularly with halogenated inhalational agents and depolarizing muscle relaxants. Heat production in anesthetized patients can be profound with as much as a fivefold increase in oxygen consumption.¹⁶⁹ Cases of MH may be encountered anywhere that general anesthetics or neuromuscular blocking agents are used.^169,170 A massive increase in creatine kinase is a strong indicator of an MH reaction.¹⁶⁷

As with heatstroke, treatment of MH requires rapid cooling and supportive care for the sequelae described previously. Unlike heatstroke, MH requires specific pharmacologic therapy to stop excessive heat production by skeletal muscle. Dantrolene sodium induces muscle relaxation in patients with MH by blocking release of calcium from the muscle cell sarcoplasmic reticulum.¹⁷¹ In all cases of MH, the inciting stimulus (see Table 65-4) should be discontinued immediately and dantrolene therapy administered. A dantrolene bolus of 2.5 mg/kg should started and repeated at 5-min intervals until normalization of the hypermetabolic state is achieved and all MH symptoms disappear.¹⁷¹ Procainamide has been used successfully when dantrolene is unavailable.¹⁷¹

It has been suggested that dantrolene administration speeds cooling of heatstroke victims by reducing skeletal muscle heat production.¹⁷¹ A randomized, controlled trial of the use of dantrolene for heatstroke found no difference between the treatment and placebo groups in terms of cooling time, complications, or length of stay.¹⁷² In 2005 a metaanalysis concluded that there was no role for the use of dantrolene in the management of heatstroke.¹⁷³ Currently, dantrolene administration is best reserved for patients with clinical muscle rigidity or suspected MH. Routine use of this drug in heatstroke patients is not recommended.¹⁷³ New and promising treatments of MH are being investigated. Researchers have discovered mutations in the gene coding for the ryanodine receptor calcium release channel (RyRI) in families with MH, which may be the functional basis for MH. Some studies have examined the effects of MH mutations on the sensitivity of the RyRI to drugs and endogenous channel effectors, including Ca²⁺ and calmodulin.¹⁷⁴

NMS

First described in the late 1960s, NMS is characterized by hyperthermia, muscle rigidity, altered level of consciousness, and autonomic instability.¹⁷⁵ Mortality from NMS is estimated to be 20% in patients in whom the condition develops.^175,176 This idiosyncratic disorder follows the therapeutic use of neuroleptic drugs, including phenothiazines, butyrophenones, thioxanthenes, lithium, and tricyclic antidepressants. The reaction is triggered by blockade of dopaminergic receptors and results in skeletal muscle spasticity, which generates excessive heat and impairs hypothalamic thermoregulation and heat dissipation.¹⁷⁶ Muscle rigidity, described as “lead pipe” rigidity in its most severe form,¹⁷⁶ can be manifested as oculogyric crisis, dyskinesia, akinesia, dysphagia, dysarthria, or opisthotonos. NMS occurs in 0.2% of patients who take neuroleptic agents either chronically or acutely. Haloperidol and depot fluphenazine appear to be the most commonly offending agents.¹⁷⁵ Temperatures can exceed 42°C (107.6°F). The initial agitation often progresses to stupor and coma. Catatonia and mutism may also be present. Autonomic instability is manifested as tachycardia, labile blood pressure, sweating, and incontinence. Ventilations are impaired by the chest wall rigidity.

This syndrome is more likely to occur at the initiation of or after an increase in neuroleptic dosage. Researchers suggest that NMS typically occurs over a period of several days (average in patients taking neuroleptic agents). It may also occur if the use of antiparkinsonian drugs is suddenly discontinued.176–179 NMS resembles MH but usually lasts longer (5 to 10 days) after use of the inciting drug is discontinued. The syndrome may be misinterpreted as worsening of an underlying psychiatric disorder, drug intoxication (e.g., cocaine and amphetamines), a severe dystonic reaction, tetanus, or a variety of CNS infections. In addition to agents with increased dopaminergic blocking activity, other risk factors for NMS include dehydration, previous history of dystonia, catatonia, agitation, and iron deficiency.¹⁷⁵ The mortality rate is high, and respiratory failure, renal failure, cardiovascular collapse, or thromboembolic disease usually causes death.¹⁸⁰

Treatment of severe NMS (i.e., hypotension, hyperthermia, marked rigidity) closely follows that of MH, except that therapy must be maintained for several days until the symptoms resolve. Therapy for NMS involves discontinuation of the triggering agent; rapid cooling; benzodiazepines; a combination of a central dopamine agonist, bromocriptine, or levodopa; dantrolene; and supportive treatment of the ensuing organ failure.¹⁷⁹ Although the effects are not immediate, pharmaceutical therapy is directed at overriding the dopaminergic blockade caused by the offending neuroleptic agent or the dopamine depletion resulting from the cessation of antiparkinsonian medications. There are reports of successful treatment of NMS with subcutaneous apomorphine monotherapy or high-dose lorazepam and diazepam.^180,181 As with MH, dantrolene (2.5 mg/kg) can be given to treat NMS-induced muscle rigidity.¹⁷ The beneficial response stems not only from effects at the sarcoplasmic reticulum of skeletal muscle but also from central dopamine metabolism of calcium in the CNS. Bromocriptine, a central dopamine agonist, is reported to be efficacious in treating NMS at doses of 2.5 to 10 mg three times a day.¹⁸¹ Although both these agents have been noted to reduce the duration of hyperthermia, there have been mixed results with the use of bromocriptine and dantrolene.^178,181

A more recently described disorder often confused with NMS is serotonin syndrome.¹⁸² This syndrome involves the newer antidepressants fluoxetine, paroxetine, citalopram, fluvoxamine, venlafaxine, and sertraline,¹⁸² which are selective serotonin reuptake inhibitors. These drugs can adversely react with other stronger serotonin receptor agents such as monoamine oxidase inhibitors and nonselective serotonin reuptake inhibitors (clomipramine and tricyclic antidepressants) to induce a clinical picture similar to that of NMS, only milder. Serotonin syndrome classically occurs when two or more drugs that interfere with serotonin metabolism act synergistically on the 5-HT_1A receptor and lead to overstimulation.^178,182 Drugs that act at any of the other serotonin receptors are not likely to produce the syndrome.¹⁸² The range of symptoms varies from mild gastrointestinal upset, insomnia, and agitation to more severe symptoms that include muscle spasms, seizures, ataxia, rhabdomyolysis, and autonomic instability. Treatment is primarily supportive in milder cases and consists of prompt recognition and withdrawal of the offending agent. Most cases resolve spontaneously within 24 hours. For the most severe cases, aggressive intensive care unit management is warranted to prevent renal failure and death. The drug cyproheptadine (Periactin) has shown promise in managing the agitation often seen in severe cases.^178,182 Cyproheptadine is an antihistamine with antiserotonergic properties. There has been limited success with benzodiazepines and β-blockers in these patients to treat agitation.¹⁸² In cases in which serotonin syndrome and NMS cannot be differentiated, benzodiazepines represent the safest therapeutic option.¹⁷⁸ Further study of the newer antipsychotic drugs, such as ziprasidone, a powerful 5-HT_1A receptor blocker, may delineate other possible benefits.¹⁸²

Hyperthermia and Psychostimulant Overdose

As mentioned previously, the recognized incidence of hyperthermia induced by sympathomimetic psychostimulant drugs of abuse is on the rise. The offending agents most commonly described are cocaine, phencyclidine, amphetamine, and amphetamine derivatives such as 3,4-methylenedioxy-N-methamphetamine (MDMA) (“ecstasy”) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA) (“Eve”).183,184 A number of studies have looked specifically at the club drug MDMA and its impairment of heat dissipation.^183,184 Animal studies in rats suggest that MDMA-induced hyperthermia results not from MDMA-induced release of 5-HT but from increased release of dopamine acting at D₁ receptors, thus suggesting a future role for the use of dopamine antagonists in clinical treatment.¹⁸⁵

Hyperthermia is a common feature of these potentially severe to lethal poisonings with sympathomimetic psychostimulant drugs and may be the primary cause of fatality or MDMA-induced neurotoxicity.¹⁸⁴ Because of the nonlinear pharmacokinetics of MDMA and γ-hydroxybutyrate, it is difficult to estimate a dose-response relationship.¹⁸⁴ Some have applied a pathophysiologic model of exertional heatstroke or NMS to profound cocaine intoxication.¹⁸⁵ In addition to profound hyperthermia (>42°C [>107.6°F]), acute rhabdomyolysis, disseminated intravascular coagulation, psychiatric and cognitive dysfunction, renal failure, coma, seizures, and death have been described in these patients.^186–189 As demonstrated by Roberts and associates,¹⁸⁸ even a patient with a core temperature of 45.5°C (114°F) because of acute cocaine intoxication may survive with aggressive cooling methods. Treatment requires prompt recognition, maintenance of adequate hydration, rapid cooling, and the aggressive use of sedatives or paralyzing agents (or both) to control agitation. Importantly, the longer that psychostimulant-overdosed patients remain hyperthermic, the higher their morbidity and mortality rates. Agitation and seizures must be chemically controlled because they lead to continued generation of heat and muscle injury. Therefore, liberal doses of benzodiazepines are recommended.¹⁸⁸ Some have advocated the use of bromocriptine and dantrolene as for MH and NMS, but their efficacy in the setting of drug-associated hyperthermia remains controversial.^189,190

Hemorrhagic Shock and Encephalopathy Syndrome

The condition of hemorrhagic shock and encephalopathy syndrome in children (mainly infants, but some older children also) resembles heatstroke in adults. The full-blown syndrome includes hyperthermia, coagulopathy, encephalopathy, and renal and hepatic dysfunction.¹⁹¹ Although there may be an association with concurrent viral illness, the condition generally follows an elevation in temperature, which may be triggered by “bundling” of a child with a low-grade fever. Therapy is largely supportive and includes volume replacement with rapid cooling of the hyperthermic child while sources of bacterial infection are sought and treated.

General Considerations

Heatstroke mortality is proportional to the magnitude and duration of thermal stress measured in degree-minutes.¹⁹² Delay in cooling may be the single most important factor leading to death or residual disability in those who survive.¹⁴⁴ In addition, advanced age and underlying disease states are significant contributing factors.^{144,145,151,152}

Many exertional heatstroke victims are volume-depleted and may exhibit hypotension. Initial stabilization with cooled (room-temperature) IV fluids and correction of electrolyte abnormalities are valuable in hypotensive patients. Traditional sources recommend a rate of 1200 mL over the first 4 hours.¹⁹³ Others advise a 2-L bolus over the first hour, with an additional 1 L/hr for the following 3 hours.¹⁹⁴ Seraj and coworkers challenged this more aggressive recommendation.¹⁹⁵ In their study of pilgrims who suffered heatstroke, 65% had normal or above normal central venous pressure (CVP) on arrival. These authors found that an average of 1 L of saline was sufficient to normalize CVP during the cooling period in their patients, who had a mean age of 55 years (range, 31 to 80 years). In older patients, fluid resuscitation should be monitored carefully to avoid pulmonary edema. Regarding antipyretics, there is no indication for either salicylates or acetaminophen in the setting of heatstroke because their efficacy depends on a normally functioning hypothalamus. Overzealous use of acetaminophen could potentiate hepatic damage, and salicylates may promote bleeding tendencies.¹⁹⁶ A study comparing acetaminophen and physical cooling methods found that in patients treated with antipyretics only, mean body temperature increased by 0.2°C (32.4°F) on average.¹⁹⁷

Given that rapid cooling is accepted as the cornerstone of effective heatstroke therapy, the clinician must choose which cooling technique to use. Studies in animal models are based on the assumption that the fastest cooling technique is the best. In clinical patient care, other factors also influence the choice of technique. Patient access, monitoring, safety, ease of use, availability, and speed are all considerations.¹⁹⁸ A technique that may not be the most rapid but allows easy patient access and is readily available may be preferable to more cumbersome (albeit more rapid once established) cooling techniques in some clinical settings.

The cooling rates achieved in various human and animal studies of heatstroke are summarized in Table 65-5.^199–213 The advantages and disadvantages of various cooling techniques are outlined in Table 65-6.

In addition to the cooling procedures outlined, it is imperative that the clinician institute the judicious use of sedation, muscle paralysis, or both to control agitation, suppress shivering, reduce energy expenditure, and make the patient receptive to sometimes unpleasant therapies.²¹⁴ In general, IV benzodiazepines are the easiest and safest first-line drugs used for sedation.

Indications for Rapid Cooling

Rapid cooling should be instituted as soon as the diagnosis of heatstroke (rectal temperature >40°C [104°F], altered mental status, history of heat stress or exposure) is made. Rapid cooling is also indicated for the treatment of MH and NMS but should be instituted concurrently with discontinuation of the triggering agent or drug and administration of dantrolene. Because studies show that the degree of organ damage correlates with the degree and duration of temperature elevation above 40°C (>104°F), a reasonable clinical goal is to reduce the temperature to below 40°C (<104°F) within 30 minutes to an hour after the start of therapy.145,214

Contraindications to Rapid Cooling

Rapid cooling is never contraindicated in patients with heatstroke. Immersion cooling is relatively contraindicated when cardiac monitoring of an unstable patient is required or when limited personnel make constant patient supervision impossible. Iced gastric lavage is contraindicated in patients with depressed airway reflexes unless the airway is protected by endotracheal intubation. Gastric lavage is also contraindicated by conditions that preclude placement of an orogastric or nasogastric tube. Cold peritoneal lavage is relatively contraindicated when multiple previous abdominal surgeries make placement of a lavage catheter risky.

Evaporative Cooling

Evaporating water is thermodynamically a much more effective cooling medium than melting ice, given an appropriate water-vapor gradient. Evaporating 1 g of water requires 540 kcal. Melting 1 g of ice requires only 80 kcal. In theory, evaporative cooling should be approximately seven times more efficient than ice packing. In practice, evaporative cooling is more efficient. In separate human studies, Wyndham and colleagues and Weiner and Khogali found that evaporative cooling rates were substantially greater than cooling rates with water immersion at 14.4°C (57.9°F).200,202 Studies in primate models demonstrated faster cooling rates with evaporative cooling as an adjunct to ice bag placement.²¹⁵ Methods using convection and evaporation were more effective than those involving conduction for the treatment of hyperthermia. In clinical practice, ice water immersion or ice packing causes heat loss by conduction and heat consumption by the phase change of melting ice. In healthy volunteers, evaporative cooling techniques (e.g., facial fanning) were associated with decreased thermal sensation and improved thermal comfort.²¹⁶

Despite the continued enthusiasm of some clinicians for ice water immersion, evaporative cooling has been an effective noninvasive cooling technique in human studies.214,217 To maximize evaporative cooling rates, several factors must be optimized. Airflow rates must be high and therefore large fans are required. The air must be warm but not humid because evaporation is decreased at lower temperatures. The entire body surface must be exposed to airflow and continuously moistened with water. Ideally, the patient is suspended in a mesh sling to expose the back to airflow and moisture. Finally, the temperature of the water used to moisten the skin must be tepid (15°C [59°F]). Warm forced air is essential for effective evaporation. It maintains good peripheral perfusion and prevents shivering by warming the skin.²¹⁷ If the water is ice cold, evaporation will be slowed. Conversely, if it is hot, conductive heat gain may occur. Studies conducted in heat-stressed laying hens demonstrated superior cooling rates with ventral cooling regimes over dorsal cooling.²¹⁸

Weiner and Khogali constructed a sophisticated “body cooling unit” (BCU) to maximize evaporative cooling.²⁰⁰ Patients in the BCU are suspended in a mesh net. High airflow rates (30 m/min) at a temperature of 45°C (113°F) are maintained both anterior and posterior to the mesh net. Atomized water at 15°C (59°F) is continuously sprayed on all body surfaces. For EDs without access to a BCU,²¹⁹ temporary units can be set up with shower sprays and fans, provided that the ambient temperature in the ED is relatively cool. An alternative less expensive, portable device developed at King Saud University involves covering the patient with a gauze sheet soaked in water at 20°C (68°F) while two fans direct room air over the patient.²²⁰ Cooling rates obtained with this device (0.087°C/min [32.2°F/min]) were nearly double the cooling rates achieved with the original BCU developed by Weiner and Khogali.²⁰⁰

The realities of clinical practice make these conditions hard to reproduce. Half the body surface, the back, will usually be unavailable for evaporative cooling. Airflow rates and temperatures are usually limited by the ambient temperature in the treatment facility and by the size and power of the fan available. These realities are reflected by the slower cooling rates achieved with evaporative cooling in a clinical setting.

Immersion Cooling

It would seem obvious that the fastest way to cool a heatstroke patient would be immersion in ice water. In a case series of exertional heatstroke patients, iced water immersion cooled patients to lower than 39°C (<102.2°F) within 19.2 minutes.²¹⁴ A recent study found that cold water immersion for 9 minutes in a 2.0°C circulated water bath until a rectal temperature of 38.6°C was achieved avoided any risk associated with overcooling.²²³ Some contemporary sources recommend ice water immersion as the cooling technique of choice for heatstroke.^214,224 Plattner and associates demonstrated cooling rates with ice water immersion that were six times faster than rates seen with forced air or circulating water.²²⁵

Costrini reported no fatalities in 252 consecutive young marine recruits with exertional heatstroke who were treated by ice water immersion within 20 minutes of diagnosis.²⁰⁶ He regarded ice water immersion as superior to other conventional methods described in the literature in reducing mortality rates.

In clinical trials, cold water immersion remains one of the fastest noninvasive cooling techniques available (see Table 65-5). Cold water immersion takes advantage of the high-conductance property of water, which is 25 times that of air.²²⁴ When an adequate evaporative cooling system is not available, immersion may be the cooling technique of choice. Several factors are important in maximizing the rate of immersion cooling. Conductive heat loss depends on cutaneous blood flow to maintain a heat gradient from skin to water. Theoretically, contact with ice water causes skin and subcutaneous vasoconstriction, which blocks heat exchange and turns these structures into insulators.²²⁶ Intense cutaneous vasoconstriction will impede conductive heat loss. Mekjavic and coworkers reported that motion sickness actually potentiates core cooling during immersion by attenuating the vasoconstrictor response to skin and core cooling, thereby augmenting heat loss and the magnitude of the decrease in deep body temperature.²²⁷ Careful monitoring is required because this may predispose patients to hypothermia.

Researchers have suggested that ice water immersion may be superior to cold water immersion because of the establishment of a steeper thermal gradient between the skin and the environment.²²⁶ A study comparing the cooling capacity of ice water immersion (5.2°C [41.4°F]), tepid water immersion (14°C [57.2°F]), and passive cooling in experienced distance runners with body temperatures of 39.3°C to 39.6°C (102.7°F to 103.3°F) found comparable cooling rates with ice water and cold water immersion. Both techniques were superior to passive cooling techniques.²²⁶ The optimal water temperature for cooling human heatstroke patients has not been defined. Aggressive skin cooling may stimulate shivering and peripheral vasoconstriction, thus hindering cooling efficacy. Investigators suggest the inclusion of skin massage as a crucial component of immersion cooling techniques.²²⁸

Regardless of the water temperature, it is clear that increasing surface area increases conductive heat loss. Maximizing the body’s surface area in contact with water will increase cooling rates with immersion cooling. In clinical practice, this means that complete immersion of the trunk and extremities will cool the patient faster than partial immersion of the trunk (back only) with the extremities extended out of the bath.

Whole-Body Ice Packing

Packing a heatstroke victim in ice may enhance conductive heat loss without the attendant logistic problems caused by water immersion (Figs. 65-7 and 65-8). Constant attendance, as required for skin moistening with evaporative cooling and as described for immersion cooling, may not be necessary with ice packing. Kielblock and associates demonstrated in a human study of mild, exercise-induced hyperthermia that whole-body ice packing cooled just as fast as evaporative cooling did (see Table 65-5).²⁰¹

Strategic Ice Packs

Noakes suggested that strategic placement of ice packs over areas of the body where large blood vessels run close to the skin may be an effective cooling technique.²³⁰ Cooling in these areas occurs despite cutaneous vasoconstriction because of direct conductive heat loss from blood within the vessel and across the vessel wall, subcutaneous tissue, and skin to ice. The most common areas used for strategic ice packing are the anterior aspect of the neck (carotid and jugular vessels), the axilla (axillary artery and vein), and the groin (femoral vessels). There have been numerous reports of successful cooling using ice packs as primary or adjunctive therapy (see Table 65-5).^230,231 In addition, application of ice packs, though easier to perform than immersion or total-body ice packing, limits the conductive cooling offered by the latter two procedures. A study in pigtail monkeys demonstrated that a combination of strategic ice packs with evaporative cooling results in faster cooling than either technique alone, although the relative increase achieved by adding ice packs to evaporative cooling was small.²³²

In unconscious patients or in awake patients who can tolerate ice packs without excessive shivering, this technique could be added to evaporative cooling. Kielblock and associates found that the combination of strategic ice packs and evaporative cooling yielded higher cooling rates than did either method individually (0.036°C/min versus 0.027°C/min and 0.034°C/min).²⁰¹ The clinical value of strategic ice packs alone or in combination with other techniques remains to be determined. Anecdotally, during the Chicago heat wave of 1995, the majority of heatstroke patients who went to EDs survived after being effectively cooled with the evaporation method accompanied by strategic placement of ice packs.²³³

External versus Core Cooling

All the external cooling techniques described previously are noninvasive and involve heat loss by evaporation or conduction across the skin as the primary cooling mechanism. With each of these techniques, central temperature will continue to drop even after the technique is discontinued and the skin is dried. This is due to a delay in establishment of an equilibrium between the cold skin and the core. The amount of “core afterdrop” can exceed 2°C (>35.6°F).217,219,234 For this reason, cooling is discontinued when the core temperature reaches 39°C (102.2°F).

Because the sites of significant cell damage with heatstroke are centrally located (e.g., liver, kidney, heart), central cooling techniques are theoretically preferable to external techniques. Core cooling techniques studied in both animal and human models include iced gastric lavage, intravascular cooling, bladder lavage, and peritoneal lavage.208–210,212,235,236 Central venous cooling is effective in rapidly decreasing core temperatures.²³⁵ Studies conducted in healthy volunteers have demonstrated that reductions in core temperature vary according to the temperature of the infused fluid. Subjects receiving 30-minute infusions of fluid at 4°C (39.2°F) experienced decreases in core temperature of 2.5°C ± 0.4°C (36.5°F ± 32.7°F). Subjects receiving 30-minute infusions of fluid at 20°C (68°F) experienced decreases of 1.4°C (±0.2°C [34.5°F ± 32.4°F]).²³⁵ Clinical trials investigating this method showed that cooling via the respiratory tract had no significant impact on temperature changes when used exclusively but did demonstrate effectiveness as an adjunctive measure to other external cooling techniques.²²⁴ Cool air (10°C [50°F]) was administered via a hood or mask. Cooling via the respiratory tract has been studied in animals but not investigated clinically.^237–239 Central cooling techniques are necessarily more invasive than external techniques and have the potential for more significant complications.

Cold Gastric Lavage

The stomach lies in close proximity to the liver, great vessels, kidneys, and heart. The gastric mucosa is not subject to the intense vasoconstriction observed on exposure of the skin to ice water.²⁰⁸ For these reasons, lavage of the stomach might be expected to be an effective central cooling method. Studies of cold gastric lavage in a canine model produced cooling rates five times greater than in controls exposed to ambient air at room temperature (0.15°C/min versus 0.03°C/min).²⁰⁹ Human heatstroke victims have been cooled successfully with gastric lavage, but only in combination with external techniques.²¹⁰ Cold gastric lavage seems to be best suited for use in patients with severe hyperthermia who are cooled at a slow rate with external techniques alone. The presence of an endotracheal tube and passage of a large-bore gastric tube make rapid lavage without aspiration possible. This technique should be reserved for patients whose airway is protected by endotracheal intubation and who do not have a contraindication to gastric tube placement.

Cold Peritoneal Lavage

The surface area and blood flow of the peritoneum greatly exceed those of the stomach. Peritoneal lavage is expected to exchange heat much faster than possible with gastric lavage. Peritoneal lavage achieves some of the fastest cooling rates ever reported in large animal or human studies (see Table 65-5). A case report of cooling via cold peritoneal lavage for hyperthermia after the ingestion of ecstasy demonstrated rapid cooling.²³⁶ As with gastric lavage, this central cooling technique offers the advantage of directly cooling the core organs that are most susceptible to thermal damage. Unlike gastric lavage, endotracheal intubation is not required. Peritoneal lavage is used extensively to treat hyperthermia under various conditions and typically decreases core temperatures 5°C/hr to 10°C/hr (41°F/hr to 50°F/hr).^210,236

Peritoneal lavage is a more invasive cooling technique. Because heat exchange is more efficient across the peritoneum, smaller volumes of fluid can be used. Surgical placement of the lavage catheter is necessary. This cooling technique is relatively contraindicated by conditions that preclude placement of a lavage catheter (e.g., multiple abdominal surgical scars).

Peritoneal lavage is the most rapid central cooling technique. It can theoretically be combined with other techniques to speed cooling of heatstroke patients with refractory hyperthermia. As the most invasive cooling technique, it requires time, proper equipment, and surgical expertise to institute. Its use is probably best suited to situations in which heatstroke patients are not responding to external cooling and adequate equipment and personnel are readily available.²¹⁷

Other Cooling Techniques

“Rewarming” techniques are used to minimize ongoing heat loss via the respiratory tract in hypothermic patients.⁷² Although high-frequency jet ventilation (HFJV) achieves core cooling in critically ill patients,²³⁷ efforts to use the respiratory tract to cool heatstroke victims have been unsuccessful. In a canine model of heatstroke, HFJV was shown to be a relatively ineffective cooling technique.²³⁸ Heat loss by convection (air transfer) is relatively inefficient when compared with the conductive heat loss mechanism used by other cooling techniques. The use of dry, hot air to maximize evaporative heat loss from the lungs might cause respiratory complications.²³¹

In human trials, ice water lavage of the bladder (300 mL of iced Ringer’s solution every 10 minutes) provided only minimal cooling at rates of 0.8°C/hr (±0.3°C/hr [33.4°F/hr ± 32.5°F/hr]).²⁰¹ Iced water lavage of the rectum would theoretically provide faster cooling rates secondary to the increased surface area and better perfusion, but it has not been investigated in human trials.

Hemodialysis or partial cardiopulmonary bypass could theoretically be used to cool heatstroke patients. Before the availability of dantrolene in 1979, partial cardiopulmonary bypass was one of the treatments of MH.¹⁷³ Drawbacks include the need for technical expertise and preparation time for the procedure. A recent case report described successful treatment of a heatstroke patient with multiple-organ failure refractory to conventional cooling techniques with cold hemodialysis initially at 30°C (86°F) and later at 35°C (95°F), followed by continuous hemodiafiltration with cold dialysate (35°C [95°F]) at a high flow rate of 18,000 mL/hr. Within 3 hours of starting this particular technique, the patient’s body temperature was below 38°C (<100.4°F).²³⁹

Cyclic lung lavage with cold perfluorochemicals is currently under investigation in animal models. Benefits include rapid cooling rates of 0.5°C/min (32.9°F/min) and minimally invasive nature in already mechanically ventilated subjects.213,240

Intravascular cooling catheters have demonstrated efficiency as cooling devices. They circulate temperature-controlled sterile saline placed in the bladder or inferior vena cava. Although these devices have not been used in heatstroke patients, studies have found the cooling catheters to be very effective for neurologic conditions in both human and animal models.241,242 Another promising cooling technique involves the use of a hypothermic retrograde jugular vein flush (HRJVF) for heatstroke. HRJVF has been studied only in animal models thus far. This technique involves the infusion of 4°C (39.2°F) isotonic sodium chloride solution through the external jugular vein (1.7 mL/100 g of body weight over a 5-minute period). Use of HRJVF was found to increase survival rates during heatstroke by attenuating cerebral oxidative stress, tissue ischemia or injury, systemic inflammation, and activated coagulation.²⁴³

Pharmacologic agents have demonstrated merit as adjunctive agents in the management of hyperthermia. There are anecdotal reports of enhanced reduction in temperature with IV ketorolac. Cienki and colleagues demonstrated enhanced decreases in temperature with the administration of ketorolac, 30 mg intravenously.²⁴⁴ All patients received standard hyperthermia treatment (e.g., ice packs, iced lavage, circulating air). Patients were randomized to receive ketorolac versus saline. In the group receiving ketorolac, the average rectal temperature after 90 minutes was two times lower than in those receiving placebo saline (3.7°C versus 1.6°C [38.7°F versus 34.9°F]).