Chapter 88. Thermoregulation and Perioperative Hypothermia

1. Adults thermoregulate with their environment by cutaneous vasomotor adjustments, sweating, shivering, and environmental behavioral adaptation (dressing appropriately, modifying environmental temperature).

2. Neonates do not shiver but can generate heat via nonshivering thermogenesis.

3. Heat loss occurs via sweating and cutaneous vasodilation. Heat conservation results from cutaneous vasoconstriction and behavioral adaptation.

4. Although not precisely defined, core temperature reflects mean temperature of the well-perfused organs (eg, brain, heart, kidney, and lungs).

5. Hypothermia that develops during general anesthesia typically follows a predictable pattern: (1) an initial rapid decrease in core temperature of between 0.5°C and 1.5°C during the first hour after induction, believed to be the result of internal redistribution of heat; (2) a more gradual linear decline in core temperature, usually lasting 2 to 3 hours, that results from cutaneous heat loss exceeding metabolic heat production (typically 0.5°C/h to 1°C/h); and (3) a plateau phase when core temperature stabilizes after 3 to 4 hours that results from the thermoregulatory balance of continual heat production and loss.

6. Following redistribution-mediated decreases in temperature, body heat loss occurs via radiation (60% of heat loss) and convection (30%), with less than 10% occurring via evaporation, and a negligible amount via conduction.

7. Postanesthesia shivering is most likely mediated via a normal thermoregulatory response to hypothermia.

8. Hypothermia during regional anesthesia is caused by the depression of regional thermal afferent input and efferent responses, such as vasoconstriction and shivering, loss of heat to the operating room environment, and redistribution of heat within the body.

9. Hypothermia during anesthesia may be prevented or treated by prewarming, the control of ambient temperature, skin insulation, warm intravenous solutions, heating and humidifying inspired gases, the application of a forced-air convective heating system, and the use of new-generation circulating-water convective heating systems.

10. There is an abundance of experimental evidence for the neuroprotective effects of hypothermia; clinical applications include deep hypothermic circulatory arrest for cardiac surgery, patients having suffered from witnessed cardiac arrest from ventricular fibrillation, and possibly perinatal asphyxia.

Hypothermia is a common perioperative occurrence resulting in a number of clinical consequences that range in significance from mild to serious (Table 88-1).1 With normal body temperature being 37°C, and taking into account a 1°C diurnal variation with an additional variation of 0.5°C in females depending on the menstrual cycle, perioperative hypothermia can be defined as a core temperature of less than 36°C.2 As with other mammals, humans require a nearly constant internal body temperature to maintain optimal homeostatic function. Significant deviation in this internal temperature can result in alterations in numerous metabolic and physiologic functions that, if not reversed, may contribute to significant morbidity and eventually mortality. The human body has evolved a sophisticated thermoregulatory control system by which to maintain core temperature (usually to within 0.2°C of its ideal target temperature). Anesthetics profoundly affect these control mechanisms, and when coupled with adverse environmental conditions (such as a cool operating room) and other heat-losing perioperative events, the risk of developing hypothermia easily becomes apparent. An understanding of both normal and anesthetic-modulated thermoregulation is essential for the prevention and management of perioperative hypothermia.

The body produces heat as a direct result of its metabolic activities. The major organs, and in particular the brain, generate the greatest proportion of this heat. In addition, muscle can significantly contribute to this, but usually only during relatively brief periods of intense use.3,4 Thermal energy within the body is distributed between central (core) and peripheral compartments. The core compartment consists of the trunk (including the major organs) and the head. The skin (including superficial tissues of the trunk) as well as the arms and legs represent the peripheral compartment.5 Temperature in this peripheral compartment is usually 2°C to 4°C lower than the core—a gradient that becomes highly relevant when anesthesia is induced and vasodilation occurs.3,5

Just as defining terms for what comprises normothermia and hypothermia is important, choosing an appropriate site for monitoring is equally so. Wide discrepancies exist between different body sites and for different operative situations.6,7 The skin is a peripheral temperature monitoring site and correlates poorly to core temperature.8 Core temperature, a term widely used by anesthesiologists, is somewhat nebulously defined, but is generally accepted to reflect mean temperature of the well-perfused organs (ie, brain, heart, kidney, and lungs). Acceptable sites for measurement of core temperature include the tympanic membrane, nasopharynx, esophagus, and bladder.

Similar to many other physiologic systems, the thermoregulatory system has at least 3 major components: (1) sensory receptors (an afferent limb), (2) a central integrator or controller, and (3) an effector organ system (an efferent limb). The sensory receptors provide information from thermosensitive sites in the skin and other body structures (spinal cord and viscera) to a central controller that then integrates this information and compares it with a standard reference or set-point (Fig. 88-1).2,9 The skin, deep tissues (viscera), spinal cord, hypothalamus, and other brain structures each contribute approximately 20% of the input to the autonomic thermoregulatory control center. On the basis of the difference between the afferent input and the target set-point, the controller provides information to effector systems that then initiate changes to regulate heat production or loss.

There is general agreement that the anterior hypothalamus is the central controller for body temperature, comparing the afferent input with the central set-point, and instituting an appropriate autonomic neural response. Investigations by neuroanatomists and neurophysiologists have greatly increased understanding of how the 3 components of the thermoregulatory system function to maintain a thermal balance; details concerning these experimental studies are the subject of numerous books and review articles.2,5,10-15

An important concept to consider in the control of temperature is the inter-threshold range. This is defined as the range between which thermoregulatory responses to cold versus those for warmth are activated. That is, if body temperature is in this range, no autonomic thermoregulatory defenses are triggered. In the normal adult, this range is typically 0.2°C but may be wider in the elderly.9,16

Anesthesia significantly widens the inter-threshold range to as much as 4°C.17-20 With a range this wide, it becomes easy to understand that under anesthesia, body temperature is greatly influenced by the surrounding environment and trends toward equilibrating with ambient temperature, thus defining the anesthetized patient as poikilothermic. Thermoregulatory responses are diminished in the elderly and may also be attenuated in persons with poor general health. An impairment of the skin sympathetic nerve traffic responses to thermal challenge has been demonstrated in the elderly.21 This impairment of thermoregulation and vasoconstrictor response has been seen even in mild thermal (cold) challenges.22 In contrast to the elderly, premature infants appear to have an intact central thermoregulatory control.

Normal Thermoregulatory Efferent Responses

In normal, unanesthetized humans, behavioral regulation (dressing appropriately and/or modifying environmental temperature) is one of the most important mechanisms contributing to heat regulation. After this behavioral adjustment is made, humans further regulate heat exchange with their environment by balancing several thermoregulatory effects: (1) cutaneous vasomotor tone adjustments (vasodilation, vasoconstriction), (2) sweating, (3) shivering, and (4) nonshivering thermogenesis.

In hypothermic situations where the hypothalamus activates heat conservation and production mechanisms, thermoregulatory vasoconstriction occurs via the activation of arteriovenous shunts in the periphery.23 Arteriovenous shunts (approximately 100 μm in diameter, roughly 10 times the size of a capillary) are located primarily in the fingers, toes, and nose. Cutaneous vasoconstriction can reduce heat loss by modulating convection and radiation from the skin surface. Shunt vasoconstriction initially halves the heat loss from the fingers and toes via a reduction of peripheral blood flow. This ultimately leads to a gradual cooling of the arms and legs.24 These shunts are controlled by centrally mediated α-adrenergic receptors in response to the release of norepinephrine from presynaptic adrenergic nerve terminals.25 In addition to the centrally mediated vasoconstriction, there is also a component of nonadrenergic vasoconstriction that can occur in response to local cooling.26

Cutaneous vasoconstriction is usually the first and most consistent thermoregulatory response to hypothermia. This vasoconstriction raises thermal insulation provided by the skin and can decrease whole body heat loss by 25% to 50%.27,28 If heat loss continues and core temperature continues to fall, shivering, with its metabolically driven increases in heat production, is initiated.

The shivering response is the primary mechanism activated to increase heat production when hypothermic conditions persist in the presence of thermoregulatory constriction; it is dependent on central neuronal coordination and normal neuromuscular function. Shivering is initiated only after the failure of maximal vasoconstriction, nonshivering thermogenesis (in neonates), and behavioral adjustments have proven to be inadequate to maintain target body temperature (see Fig. 88-1). Shivering is an energy-inefficient means of heat production and can cause a 2- to 3-fold increase in whole-body oxygen consumption.29 Cardiac output is directly dependent on metabolic rate. As a result, patients who shiver have a higher cardiac index and heart rate during maximal muscular activity.30 This metabolic effect of shivering on oxygen consumption depends on its intensity and the affected muscle mass.31 The actual increase reported in the literature has been widely variable (from as low as 7% to >700%), depending on the clinical situation, selected sample, and measuring technique.32 More often, it is considered in the 200% to 400% range.4,8

Intermediate between the efferent vasoconstrictive and shivering thermoregulatory responses to cold is nonshivering thermogenesis. This response, occurring in both normal and premature infants, increases metabolic heat production without inducing any mechanical work.33 Brown adipose tissue is an important site of nonshivering heat production in the neonate. The brown fat is rich in mitochondria (which gives it its brownish macroscopic hue) and is distributed over the neck, back, viscera, and great vessels. The metabolism of brown fat is initiated by β3-adrenergic effects on terminal nerves within it.34 Although the exact mechanism of heat production is not clearly understood, it is thought that it is either related to an uncoupling of oxidative phosphorylation within the mitochondria in the presence of fatty acids or results from lipolysis-lipogenesis coupled with ATP utilization.2 It is generally agreed that nonshivering thermogenesis does not occur in adult humans.35

Under static conditions, heat produced by the body's metabolic process must eventually be dissipated to the environment. Close to 95% of this heat traverses the skin, with the remainder occurring via the respiratory tract. As a result, factors that modulate heat loss must involve the skin itself, either directly via sweating or indirectly via modifying cutaneous blood flow. Sweating is the most effective method of heat loss. Evaporation of sweat is an energy-absorbing process. In a dry environment, sweating alone can easily dissipate the heat generated at basal levels. Furthermore, an increase in temperature of 0.5°C can produce a 7-fold increase in sweat rate and body conductivity.10,36,37 Sweating is mediated by cholinergic sympathetic fibers and can be nearly abolished by even small doses of atropine—something to consider in the perioperative state. Vasodilation is important for the transfer of heat from the core to the periphery. Sweating and vasodilation responses work synchronously to counter any increases in core temperature, with vasodilation increasing cutaneous blood flow and heat delivery for the evaporative sweating heat loss mechanism.38

Hypothermia is a well-studied complication in anesthetized patients with numerous studies having documented its incidence and severity.39-42 Hypothermia that develops during general anesthesia typically follows a predictable pattern. Following an initial rapid decrease in core temperature (0.5°C-1.5°C) during the first hour after anesthesia induction, a more gradual linear decline in core temperature, usually lasting 2 to 3 hours, occurs. A plateau in temperature, resulting from an equilibrium in heat loss and production, is then seen, usually after 3 to 4 hours.41,43 This pattern is described in Figure 88-2. The rapid temperature decline phase is believed to be the result of internal redistribution of heat.44 The linear second phase of the hypothermia curve is characterized by continual cutaneous heat loss that exceeds metabolic heat production (typically 0.5°C/h-1°C/h; Fig. 88-3).45

Most of the heat is lost through the skin, with radiation and convection resulting in most of the loss—far greater than losses from evaporation or conduction (Fig. 88-4).2 About 90% of heat loss in the operating room (OR) is through the skin, with radiation and convection playing a more dominant role than evaporation or conduction.2 Radiation accounts for the largest source of heat loss (representing ∼60% of heat loss) and depends on the difference in temperature between the patient and the environment. The next significant source of heat loss is convection (leading to 30% of the heat loss), which is influenced by the temperature gradient between the body and the surrounding fluid or air. Evaporation can vary depending on the patient's current volume status and room humidity. Finally, conductive heat loss depends on the temperature difference between surfaces and any material that is in direct contact with them.46

In the unanesthetized patient, tonic thermoregulatory vasoconstriction maintains a significant core to peripheral temperature gradient. Induction of general anesthesia causes vasodilation, which results in redistribution of heat from the warm core to the relatively cool periphery. The result is a markedly decreased core temperature, but mean (ie, the weighted average) body temperature and heat content remain unchanged (Fig. 88-5).44 Although internal redistribution of heat is the major reason core body temperature decreases shortly after the induction of general anesthesia, several other factors continue to exert an affect on the patient's thermoregulatory balance. These factors include (1) decreased metabolic heat production under general anesthesia, (2) heat loss from the patient to the environment, and (3) the effects of anesthetic agents on thermoregulatory thresholds. Induction of anesthesia decreases metabolic heat production by approximately 20% by limiting muscular activity, reducing the metabolic rate, and diminishing the work of breathing.47,48 Evaporation of surgical skin-preparation solutions,49 anesthetic-induced vasodilation and impairment of central thermoregulatory control,44,50 and cold operating room temperatures all increase cutaneous heat loss, although not enough to be the major cause of this initial hypothermia seen during surgery.

Behavioral regulation is not relevant during general anesthesia, and shivering is frequently prevented because of muscle relaxants. Therefore, vasoconstriction is the principal thermoregulatory response available to anesthetized, paralyzed, hypothermic adult patients. However, this response is profoundly affected by anesthetics. Clinically relevant doses of general anesthetics decrease the activation threshold (the temperature triggering a response) for hypothermia by 2°C to 4°C.41,50,51 Interestingly, activation thresholds for responses to hyperthermia are also affected, but to a lesser degree than those for hypothermia.3 The result is an increase in the inter-threshold range, with core temperature changes passively determined by redistribution of heat within the body combined with environmental heat loss.

The exact central temperature that triggers thermoregulatory vasoconstriction is both anesthetic agent and dose dependent, and may vary depending on the age of the patient and the intensity of surgical stimulation. Patients who become sufficiently hypothermic during surgery eventually reach the vasoconstriction threshold and trigger the response. Once triggered, the actual gain and maximum intensity of the thermoregulatory response remains near normal.52-54 In summary, markedly altered thermoregulatory thresholds with preserved gain and maximal intensities characterize the effect of general anesthetics on the thermoregulatory system.55

Regional Anesthesia and Thermoregulation

Regional anesthesia (in the form of spinal and epidural anesthesia) impairs thermoregulation via inhibition of both thermal afferents and efferents. As the usual thermoregulatory efferent responses are neuronally mediated, it is no surprise that central neuroaxial blockade would interfere with these responses (sweating, vasoconstriction, and shivering). Compounding these efferent abnormalities, blockade of thermoregulatory afferents results in the hypothalamic control centers incorrectly interpreting peripheral temperature to be normal (or high).56,57 This explains the development of the warming sensation that patients report following the injection of neuroaxial local anesthetics.58 Regional anesthesia affects the inter-threshold range, increasing it by 3 to 4 times its normal value. With the impairment in thermoregulatory efferents, the warm sensation reported by patients, and the general lack of temperature monitoring in the awake patient, hypothermia is common and frequently goes undetected in the patient undergoing regional anesthesia.

Traditionally, hypothermia during regional anesthesia was believed to primarily result from increased heat loss to the environment secondary to sympathetic blockade-induced vasodilation. However, Hynson et al59 investigated the importance of different etiologic factors in causing hypothermia during epidural blockade. In healthy, nonpregnant, normal volunteers, core and skin temperature, heat loss, and oxygen consumption were measured before and after epidural blockade to an approximate T4 level was induced. They found that during epidural anesthesia, skin temperature increased, core temperature decreased, and heat loss to the environment increased only slightly. Most subjects shivered during the epidural block, so heat production actually increased somewhat during the study. These data suggest that heat loss to the environment cannot account for the fall in core temperature seen during regional anesthesia. Indeed, the authors concluded that redistribution of heat within the body is the primary factor responsible for the development of central hypothermia during epidural blockade. A subsequent study by Glosten et al confirmed this hypothesis.60

In summary, during regional anesthesia hypothermia occurs because (1) regional anesthetics depress regional thermal afferent input and efferent responses, such as vasoconstriction and shivering; (2) patients lose some heat to the operating room environment; but most importantly, (3) redistribution of heat within the body occurs.61,62 Interestingly, rewarming from hypothermia can be accelerated in the patient with residual spinal anesthesia (if using active heating modalities) due to the relatively vasodilated state of the patient (Fig. 88-6).63

Hypothermia during regional anesthesia is often accompanied by shivering with an incidence of up to 70% being reported.64 There is some variability in clinical studies being able to demonstrate a consistent relationship between core temperature and shivering during major regional anesthesia raising the question of whether this response is thermoregulatory or of some other etiology. As a result, shivering that occurs with regional anesthesia can often be prevented if normothermia is maintained, although this is not always the case.65 Cutaneous warming of patients for 2 hours prior to inducing epidural anesthesia can help in preventing hypothermia and reduces shivering.60 The same pharmacologic therapies used to treat shivering in patients recovering from general anesthesia can also be used in regional anesthesia patients.

Interestingly, the tremor seen in pregnant patients undergoing regional anesthesia may have a different nonthermoregulatory etiology. A number of studies have shown an increased incidence of shivering in pregnant patients when cold solutions are injected epidurally.66,67 This response is not seen in nonpregnant volunteers or patients, suggesting that thermosensitive tissue within the spinal canal contributes to the shivering observed with epidural anesthesia in parturients.64

Postanesthesia Shivering

In the anesthetized patient, it is unusual to reach temperatures where shivering is induced. However, in the postanesthetic period, shivering is common and has been reported to occur in up to 40% of patients.68,69 This common perioperative problem is both uncomfortable to the patient and problematic for the caregiver, but more importantly it may also increase perioperative morbidity. In addition to cold sensations that accompany shivering, postanesthesia tremor can itself lead to an increase in perioperative pain by stretching within surgical incisions. It can also lead to increases in intracranial and intraocular pressure in addition to its increases in metabolic demand.29,70-72

The etiology of this troublesome perioperative occurrence has been considerably debated.15 General agreement suggests that the most likely explanation for this postanesthetic tremor relates to an abrupt change in anesthetic-induced thermoregulatory inhibition, thus increasing the threshold for shivering toward normal. That is, the residual low body temperature (resulting from the dysregulation of thermoregulation by anesthetic state itself) seen upon discontinuing of anesthesia is usually well below the near-normal threshold to activate thermoregulatory shivering.73,74

Despite this normal thermoregulatory response to intraoperative heat loss, there are alternative explanations for postanesthetic shivering that may partly explain some unusual observations. For example, postanesthesia shivering does not universally occur in the markedly hypothermic patient,75 and shivering frequently occurs in normothermic postanesthetic patients.73 As a result, there may be some other mitigating factors that influence whether or not a patient shivers after anesthesia. It has been suggested that surgery itself, due to the stress response or associated pain, can contribute to postoperative tremor.76 For example, the surgical stress itself may abnormally increase the thermoregulatory set-point.77 There is also evidence that residual volatile anesthetics (isoflurane) may cause a nonthermoregulatory shivering pattern.59,78 The exact mechanism by which anesthesia may interact directly in causing the shivering pattern is not known. However, this tremor pattern that is observed at low concentrations of isoflurane (0.2%-0.4%) is very similar to the electromyographic (EMG) pattern that is seen after spinal cord transection, suggesting that the isoflurane may cause some inhibition of spinal cord reflexes resulting in this troublesome tremor.79

Postanesthetic shivering can be prevented in most patients by maintaining normothermia. Skin-surface warming may be effective therapy.80 Pharmacologic treatments include meperidine (25 mg intravenously [IV]),80-82 clonidine (75 μg IV),82,83 and ketanserin (10 mg IV).84-86 Most recently, dexmedetomidine has also been used.81,87,88 The exact mechanism(s) by which these drugs abolish shivering is not completely understood, but the antishivering action is thought to involve the κ receptors on the spinal cord and μ receptors on the hypothalamus. Unique among opioids, meperidine decreases the shivering threshold significantly more (twice as much) than the vasoconstriction threshold.89 It is thought that meperidine reduces the vasoconstriction threshold through its μ effect in the hypothalamus, and the shivering threshold is reduced by both its hypothalamic μ effect and its κ activity at level of the spinal cord.90,91 Another possible explanation is via the activation of α2b adrenoreceptors.92

α2-Adrenoceptor agonists have been shown to have anesthetic and analgesic sparing effects. Dexmedetomidine, an α2-agonist with an 8 times higher affinity compared to clonidine, has been demonstrated to reduce both the vasoconstriction and shivering thresholds.87 As postoperative surgical pain can promote nonthermoregulatory shivering, dexmedetomidine, with its analgesic sparing effect, may also play another role in decreasing incidence of postoperative shivering.93 Tramadol and nefopam have also been used to treat postoperative shivering.92

Perioperative hypothermia is associated with a number of adverse consequences (see Table 88-1). Although the mechanisms linking hypothermia to these events are known for some, it is unclear for others. For example, although myocardial ischemia is a serious postoperative problem, and postoperative shivering can adversely affect oxygen consumption (increasing it by 200%-400%),4,8 there are few actual data linking shivering to the occurrence of ischemic events.16,23,27 Despite this, there is a strong link in high-risk patients between mild postoperative hypothermia (1°C-3°C) and overall adverse myocardial outcomes.27 The mechanism by which this hypothermia leads to these adverse events is not clear, however. Potential mechanisms for the adverse myocardial events (other than shivering) includes cold-induced hypertension.29 In addition, the increase in circulating catecholamines accompanying this hypertension can augment cardiac irritability and lead to ventricular arrhythmias.28

Although long considered to be a factor in increasing perioperative blood loss, the effects of mild hypothermia in studies designed to examine blood loss and transfusion have produced variable results. Schmied et al showed that just 1.6°C of hypothermia increased blood loss by 30%, which in this study of hip surgery, amounted to 500 mL.94 Overall, the data suggest that there is an increase in both blood loss and transfusion requirements,94 although there are certainly other studies discounting this association.95 The surgical setting itself likely plays a role. For example, cardiac surgery, with a hemostatic system already stressed by the bleeding perturbations of cardiopulmonary bypass, may increase the risk of hypothermia-mediated hemostatic abnormalities. Boodhwani et al recently reported significantly increased bleeding in patients randomized to hypothermia (vs normothermia) during cardiopulmonary bypass.96 This bleeding tendency was also seen in a trial of intraoperative hypothermia during intracranial aneurysm clipping.97 Despite some conflicting results, there are clearly effects of hypothermia on platelet function and clotting factor function, as well as fibrinolytic activity. For example, Valeri et al demonstrated that platelet function can be impaired by mild degrees of perioperative hypothermia.98 This has subsequently been demonstrated by others to be potentially related to a defect in the release of thromboxane-A2.99-101 The effects of hypothermia on in vivo clotting factor function is not clear (due to most laboratory tests being performed at 37°C), although most in vitro clotting tests, if performed at hypothermic temperatures, will show some impairment. There are few data outlining the effects of hypothermia on the fibrinolytic response. Paradoxically, one can theorize that fibrinolysis may actually be inhibited by mild hypothermia (thus decreasing bleeding) because of the temperature-related impairment of the enzyme responsible for the conversion of plasminogen to plasmin, which is fundamental to the fibrinolytic process.

Infection is one of the most serious consequences of hypothermia. Trials investigating warming interventions to treat postoperative hypothermia have been successful in reducing postoperative wound infection. A pivotal trial by Kurz et al investigated 200 patients undergoing gastrointestinal (colorectal) surgery, assigning them to either conventional treatment (hypothermia group) or additional warming (normothermia group).102 The normothermia group had significantly fewer wound infections (6%) compared to the hypothermia group (19%) and also had evidence for improved wound healing and shorter hospitalization.102 The mechanisms behind these adverse affects of hypothermia on perioperative wound infection and healing are likely related to the vasoconstriction induced by the thermoregulatory responses41,103 that lead to decreased subcutaneous oxygen tension (tissue hypoxia),104 as well as direct hypothermia-mediated impairments in immune function.105-108 In addition to the direct immune function impairment, the reduced oxygen tension in subcutaneous tissues also impairs wound healing. Duration of hospitalization, although clearly made worse by postoperative wound infection, has also been shown to be prolonged in hypothermic patients irrespective of the occurrence of any infection.102 The mechanism behind this noninfection-related prolongation of hospitalization is not clear but is certainly consistent with evidence of impaired wound healing or potential metabolic disturbances such as protein wasting.109

Although the best evidence linking hypothermia to perioperative infection was seen in colorectal surgery, similar effects on infection risk have also been outlined in relatively clean surgery. A retrospective study analyzed infection in pediatric cardiothoracic surgery patients subjected to deep hypothermia, finding that the most significant risk factor for operative site infection was deep hypothermia. In spinal surgery, a recent study demonstrated that brief periods of mild hypothermia are not related to an increased rate of complications, but wound infection risk may be increased with longer periods of hypothermia.110 A study by Melling et al111 examined the impact of preoperative systemic and local surgical site warming on infection rates in clean operations (breast, hernia, or varicose vein procedures). A total of 416 patients were followed for 6 weeks postoperatively. Infections were found in 19 out of 139 control (unwarmed) patients presumed to have a higher risk of perioperative hypothermia. In comparison, only 5 of the 138 local warming patients and 8 of the 139 systemically warmed group developed infections. These statistically significant results stress the importance of preventing perioperative hypothermia, even in relatively clean surgery.

Although not necessarily a complication of hypothermia, there are several pharmacokinetic and pharmacodynamic effects of hypothermia that are relevant to anesthesia. For example, hypothermia has a significant impact on the duration of action of muscle relaxants. This is thought principally to be related to a pharmacokinetic effect (as opposed to a pharmacodynamic effect), although there is some evidence for a direct hypothermia effect on skeletal muscle responsiveness.112-114 Another direct pharmacodynamic effect of hypothermia is its impact on minimal alveolar concentration (MAC). There is approximately a 5% reduction in MAC per degree in core body temperature.115 This can be seen most dramatically in the cardiac surgical patient undergoing hypothermic circulatory arrest where, as the temperature drops to more moderate to severe ranges (20°C), significant changes (slowing) can be seen in the EEG, with the bispectral index significantly decreasing consistent with a significant reduction in the requirement of inhaled or intravenous anesthetics.116 The principal hypothermic effects on intravenous anesthetics relate to changes in their pharmacokinetic profile with alterations in clearance from central and peripheral compartments. Some of these pharmacokinetic and pharmacodynamic effects may partly explain the prolonged recovery profiles in hypothermic patients in the postanesthesia period.117

Relatively minor (in terms of serious consequences) complications of hypothermia include thermal discomfort118 as well as mild hypothermia-induced hypokalemia.119,120 Finally, monitoring the hypothermic patient can be a problem at times because shivering may lead to artifacts in electrocardiogram monitoring, as well as vasoconstriction-induced reductions in cutaneous blood flow that may impair pulse oximetry measurements.121

A number of strategies have been used to prevent and treat hypothermia. These are summarized in Table 88-2. Most therapies target the linear phase of the hypothermic curve where heat is lost cutaneously. As a result, these modalities attempt to either minimize this cutaneous heat loss or to deliver heat via skin-mediated mechanisms. However, as redistribution from the core to the periphery results in the initial and sharpest drop in temperature, minimizing the redistributive decrease in temperature can also be addressed.

Prewarming the patient prior to induction of either general or regional anesthesia has been successful,60,122 but due to logistical and other time constraints, this is not as frequently practiced as it could be. It works through reducing the core-peripheral temperature gradient and in doing so, increasing the overall body heat content. As a result of the reduced core-peripheral temperature gradient, there are fewer redistributive-mediated decreases in temperature occurring with a much-reduced anesthetic vasodilation. The overall effectiveness of prewarming has been investigated in a study of spinal surgery under general anesthesia. Patients were prewarmed for 60 minutes at 38°C, which resulted in an attenuated decrease in core temperature and a reduction in perioperative hypothermia. In another study of total hip arthroplasty, a small subset of patients demonstrated that preanesthetic warming for at least 90 minutes reduced the incidence of hypothermia and subsequent postoperative shivering.122 An additional study reported that 2 hours of prewarming before an epidural increased skin temperature and also prevented hypothermia during initiation of the epidural.60

Increasing ambient operating room temperature has also been shown to be an effective method of preventing heat loss in surgical patients, made most effective if the operating room temperature is increased to at least 24°C. This modality also relies on reducing the gradient between the body and the ambient environment decreasing the heat that is lost across this gradient. However, this temperature is generally considered to be too warm for the comfort of others in the operating room.11 Relying solely on this modality will not be effective in maintaining normothermia.

Insulation of the skin has been demonstrated to reduce heat loss by approximately 30% mainly by reducing radiation losses.1 Blankets, however, work principally via the insulating layer of air trapped between the skin and the external environment such that regardless of whether blankets are heated or not, they are equally effective at preventing further heat loss. Despite the thermal comfort they provide to patients by providing a perception of warmth, they do little to actively warm patients. A study by Sessler and Schroeder compared patients who were covered with either unwarmed or warmed blankets for 60 minutes. In addition, the use of a single or 3 blankets was also studied.123 The results showed that the use of a single blanket, either warmed or unwarmed, reduced heat loss by 33 ± 5%, and the use of 3 warmed or unwarmed blankets had an additional 18 ± 6% reduction in heat loss. Compared to unwarmed blankets, the benefit of using warm blankets was found to be brief (dissipating within 10 minutes).

Heat loss is directly proportional to surface area. As a result, no skin surface is either more or less likely to lose heat. The head, for example, frequently thought to lose more heat than other parts of the body, does not lose any more heat than one would predict its 10% surface to do.1 Radiant heaters have also been used to reduce surface heat loss and actively warm patients, but they have little benefit with the exception of situations where significant skin contact is limited, such as in the neonate.

Heating and humidification of inspired gases address the less than 10% of metabolic heat that can be lost from the respiratory tract.124 Although heating and humidifying inspired gases can prevent all of this heat loss, it has a negligible effect on improving core temperature.45 Inspired gases can be passively warmed and humidified by artificial devices to a similar degree to that induced by the nasopharynx. Although these types of devices are good at maintaining humidity and minimizing heat loss, such devices cannot deliver significant heat energy.124,125 However, they do have other advantages including reducing the drying of pulmonary secretions.

Heated mattresses that usually circulate warmed water (up to 42°C) have not been demonstrated to be effective in the prevention or treatment of hypothermia. When placed under the patient, they make poor contact with the body surface and therefore cannot provide significant conductive transfer of heat. In addition, very little heat is lost via the posterior body surface because of the relatively good insulation provided by foam that is usually integrated into operating table surfaces. It is the anterior surface of the body that loses 90% of the body heat.45 In addition, these devices have significant limitations related to safety. Due to body pressure points (with subsequent poor circulation) being unable to dissipate heat, they can increase the risks of localized burns to the skin.45 Other non–water-heated mattresses would be expected to have similar limitations and subsequent poor efficiency.

Forced-air convective warming systems are one of the most effective active warming systems.126,127 These systems work via 2 principal mechanisms. They first reduce radiant heat loss (by increasing the temperature of the surfaces surrounding the patient), and they also increase heat gain via convection. Lennon et al studied the efficiency of a forced-air heating system compared to covering patients only with cotton blankets warmed to 37°C.128 With activation of the forced-air convective warming system, patients were warmer at all measured time intervals. Numerous other studies have evaluated forced-air systems and found them to maintain normothermia, even during prolonged and extensive procedures.45,118,119 As this modality of warming has grown in acceptance and wide-scale use, multiple devices have emerged on the market. Although the various systems differ somewhat in their capabilities, in the hypothermic patient, all convective forced-air warming systems provide excellent warming.129

Despite the failure of conventional heated water mattresses to efficiently warm patients via conduction, a new generation of circulating-water conductive heating systems are now available (such as the Kimberly Clark Patient Warming System, Kimberly Clark, Roswell, GA; and Allon MTRE 3365, MTRE Advanced Technologies, Akiva, Israel). These devices differ from their predecessors by using markedly improved skin contact that optimizes conduction of heat through the skin. These devices have been particularly studied in cardiac surgery, both in on- and off-pump procedures, and have considerable efficiency.118,120,130,131 They have significant advantages by heating the posterior body, which is otherwise not accessible in the supine patient. In addition, in surgery where there is large skin exposure (such as cardiac surgery) where forced-air warmers have limited skin surface contact, these devices excel.

When rapid infusion of large volumes of either cold IV fluids or blood products is required, significant hypothermia can result. For example, 1 unit of refrigerated blood, or 1 L of room-temperature crystalloid can decrease core temperature in adults by approximately 0.25°C.132 Fluid warmers are effective methods to warm both blood products and other IV fluids prior to administration. Although fluid warming can reduce the degree of hypothermia, it cannot add any significant heat to patients. Warming skin preparation solutions and irrigation fluids can also help prevent evaporative heat loss.

Intravascular warming utilizing invasive intravascular catheters has also been applied to both warm patients and, in an opposite thermodynamic fashion, intentionally cool patients. These systems are less widely available. They are also limited by the technical need for large-bore (up to 14 Fr or more) vascular cannulation, with all its associated risks.133-135 Their role in perioperative hypothermia treatment has not been directly examined. The CoolGardTM catheter heat exchange system (Alsius Corp, Irving, CA) is a multilumen central venous catheter that contains inflatable balloons that allow for the closed-loop recirculation of fluid that can be heated (or cooled). It is relatively new and can be used in conjunction with standard warming methods, although it is more frequently used to cool patients (such as after cardiac arrest). A case report demonstrated its effectiveness in warming a patient with severe hypothermia (27.9°C) to a temperature of 37.5°C within 12 hours.136 A retrospective study examining 11 critically injured patients using the system demonstrated feasibility in warming in acute care settings.137 Its safety and efficacy have not specifically been examined in the perioperative setting. Indeed, there is a case report of 2 catheter-related thromboses, so it is important to be cognizant of this possibility and to follow the manufacturer's recommended maximum period of use for each catheter.138

Although much of the previous discussion outlined the spectrum of disadvantages of perioperative hypothermia, providing extensive reasons why it should at all costs be avoided, there are situations where, without its use, catastrophic consequences would result. This is no more apparent than the setting of the ischemic brain. A classic example of this is when deep hypothermia is used to protect the brain during circulatory arrest for surgery on the aorta139,140 or cerebral aneurysms.141 In these situations, the circulation to the brain and the rest of the body organs can be stopped for up to an hour with few (if any) significant long-term effects. This period of "suspended animation" makes possible lifesaving procedures that would have otherwise been impossible. This is not dissimilar to some of the anecdotal reports of accidental near-drowning whereby cold-water immersion and the ensuing hypothermia that followed allowed for dramatic survival despite long periods without oxygen.142

Although these extremes of temperature are clearly protective in that type of surgery, lesser degrees of hypothermia in other settings, such as cardiac surgery, are less obviously protective121,143-145 and are also tightly linked to optimizing how rewarming is performed.146 Interestingly, cardiac surgery is rather unique in its consideration of temperature. In addition to its use of hypothermic benefits, it is also a setting that has had little evaluation and description of hypothermic complications. Indeed, most of the studies outlining the adverse effects of hypothermia in the perioperative patient have not been performed in the setting of cardiac surgery. Therefore, extrapolating all the potential adverse effects to cardiac surgical patients would be erroneous. However, common sense dictates that some of the effects of temperature (possibly the effects of wound healing, infection, and coagulopathy) would also apply to the cardiac surgery patient.

The salutary effects of hypothermia on the brain are due to the numerous enzymatic and metabolic pathways modulated by temperature. In addition to depressing cerebral metabolism (∼6%-7% decline per degree Celsius),147 its other putative neuroprotective effects of hypothermia are likely mediated by nonmetabolic pathways. In the ischemic brain, moderate hypothermia blocks the release of glutamate,148 reduces calcium influx,149 hastens recovery of protein synthesis,150 diminishes membrane-bound protein kinase C activity,151 can slow the time of onset of depolarization,152 suppresses nitric oxide synthase activity,153 and reduces the formation of reactive oxygen species.154 Protection from hypothermia likely results from a summation of all these mechanisms. Although experimental demonstrations of the neuroprotective benefits of hypothermia have been well characterized for decades,155-158 it is only recently that clinical examples of its benefits have been described.97,159-161

Outside the surgical setting, hypothermia has been evaluated as a direct neuroprotective strategy. In patients suffering from cardiac arrest, 2 large, well-controlled trials demonstrated that comatose survivors of out-of-hospital cardiac arrest significantly benefit from prolonged (>24-h) periods of postarrest induced hypothermia. Bernard et al studied 77 patients following witnessed cardiac arrest who, within 2 hours of return of spontaneous circulation, had their core body temperature reduced to 33°C for 12 hours.159 Both the numbers of surviving patients as well as those having either minimal or moderate disability were significantly greater in the hypothermic group. In a similar larger multicenter trial of 275 patients, induced hypothermia (32°C-34°C) for a period of 24 hours was associated with an increased number of patients with favorable neurologic outcomes, as well as a significant reduction in 6-month mortality.160

Subsequent to these 2 studies, guidelines have been instituted that have recommended the use of therapeutic hypothermia after cardiac arrest as part of an overall resuscitation strategy.162 Although there were few adverse affects reported in these studies, there were some interesting trends that emerged that support some of the perioperative hypothermia studies highlighting the complications of hypothermia. For example, in the large multicenter trial,160 there were trends toward an increase in bleeding as well as pneumonia and sepsis, although the study was not sufficiently powered to look at these complications. In general, however, for the nonsurgical patient suffering cardiac arrest, the weight of the evidence suggests that there is a significant advantage to the induction of a period of postcardiac arrest hypothermia.

Mid to moderate hypothermia has also been investigated as a neuroprotective strategy in the setting of neonatal hypoxic-ischemic encephalopathy.163 Although hypothermia had been demonstrated to be protective against brain injury in animal models of asphyxia, only recently has this been demonstrated in 2 well-conducted, randomized trials. The first trial evaluated 238 infants who presented with perinatal asphyxia; hypothermia (33.5°C) was instituted within 6 hours of birth and was maintained for 72 hours followed by slow rewarming. Neurodevelopmental outcomes were assessed at 18 to 22 months of age. Whole-body hypothermia was shown to reduce the combined end point of death or moderate/severe disability compared to conventional therapy (maintaining these patients at a normothermic temperature). Importantly, the hypothermia did not increase severe disability in the survivors, a clinical situation that would be clearly disadvantageous.

A second study was the TOBY (Total Body Hypothermia for Neonatal Encephalopathy) trial. It was a multicenter, randomized trial that also examined term infants suffering from asphyxial encephalopathy. In this study, 325 infants were randomized to either cooling for 72 hours or to controls that did not receive cooling.164 Although there was no significant difference in the primary outcome, the combined rates of death or severe disability, the assessment of survivors at 18 months showed a reliable improvement in neurologic outcomes. It is not known whether this improvement could be preserved in the long term. Studies continue in this field.

Considerable caution and balance should always be used when using these clinical applications of hypothermia. Extrapolating these 2 beneficial situations (cardiac arrest and possibly neonatal asphyxia) to other surgical settings of potential brain injury has, as yet, no foundation. Although there is a wealth of beneficial experimental studies outlining both the mechanisms and the degree to which hypothermia can protect the brain, other clinical applications apart from those discussed above are lacking. For example, hypothermia has been explored in patients undergoing cerebral aneurysm clipping, clearly a setting where the brain is at risk of ischemia. However, in a trial of 1001 patients by Todd et al,97 there was no benefit to the use of mild degrees (33°C) of hypothermia induced intraoperatively using convective forced-air devices for cooling. Again, some cautious findings were also identified, including a higher incidence of bacteremia in the hypothermic group.

Overall, one's enthusiasm for doing everything to reduce hypothermia must be tempered with the realization that there are likely situations where hypothermia can have a benefit. As in many areas of medicine, there is clearly no right or wrong answer, only a balance of risk versus benefit.

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