Afferent Thermal Sensing

Anatomically distinct warm and cold receptors in the body periphery sense the ambient temperature. The skin contains about 10 times more cold receptors than warm receptors, acknowledging the important function of the skin in the detection of cold (Poulos, 1981). Thermosensitive receptors are also located in close proximity to the great vessels, the viscera, and the abdominal wall, as well as in the brain and in the spinal cord. Each receptor type transmits its information through an afferent-nerve–conduction pathway. Although information originates from anatomically different nerve fibers, the speed of transmission is mainly influenced by the intensity of the stimulus rather than the type of nerve fiber. It is well established that the rate of change in skin temperature alters the apparent importance of the change. Rapid changes contribute up to five times as much to the central regulatory system as slower changes with comparable intensity (Wyss et al., 1975). However, other than in patients undergoing cardiopulmonary bypass surgery (where rapid temperature changes are common), the rate of change in core temperature does not appear to substantially influence the magnitude of the provoked regulatory responses.

The thermal information from cold-sensitive receptors, which have their maximal discharge rate of impulses at a temperature between 25° and 30° C, is transmitted to the preoptic area of the hypothalamus by A-delta fibers.

Thermal information gathered from peripheral warm receptors, whose maximal discharge rate is between 45° and 50° C, is carried by unmyelinated C fibers. These C fibers also convey pain sensations, which explains why intense heat cannot be distinguished from severe pain (Pierau and Wurster, 1981; Poulos, 1981). Although most ascending thermal information travels along the spinothalamic tracts in the anterolateral spinal cord, no single spinal tract is solely responsible for conveying thermal information (Hellon, 1981).

Central Regulation

Integration of afferent thermal information takes place in the anterior hypothalamus, whereas the posterior hypothalamus controls the descending pathways to the effectors. Thermal inputs from the skin’s surface, spinal cord, and deep body tissues are integrated in the preoptic area of the anterior hypothala-mus and compared with the threshold temperatures, triggering heat gain or loss. Once the threshold has been reached, the hypothalamus then carefully orchestrates the mechanisms for heat generation and dissipation in order to maintain body temperature within the narrow limits of its set point (interthreshold range).

The preoptic area of the hypothalamus contains cold- and heat-sensitive neurons, with the latter predominating by a ratio of 4:1 (Boulant and Bignall, 1973). However, the vast majority of the neurons in this area are insensitive to temperature (Nakayama et al., 1963). This area also receives and processes nonthermic afferent information, which seems to be important in controlling the adaptive mechanisms and the behavior of the organism (Hori and Katafuchi, 1998).

Direct heat stimulation of this area results in increased discharge rates from the heat-sensitive neurons and activation of heat-loss mechanisms. Conversely, hypothalamic cold-sensitive neurons respond with increased discharge rates to direct cooling of the preoptic area of the hypothalamus (Boulant, 1974; Boulant and Demieville, 1977). Other centers involved in thermoregulation include the dorsomedial hypothalamus, periaqueductal gray matter, the nucleus raphe pallidus in the medulla oblongata, and the spinal cord, although their functions are not yet fully elucidated (Guieu and Hardy, 1970; Simon, 1974; Cabanac, 1975; Dickenson, 1977).

The contribution of the central thermoreceptors to thermal regulation under normal conditions is limited by the marked predominance of thermal input from peripheral receptors (Downey et al., 1964). These central receptors take over thermoregulation if the sensory input from peripheral sensors is disrupted (e.g., through central neuraxial anesthesia or spinal cord transection), but they are less efficient when compared with peripheral thermoreceptors (Downey et al., 1967).

The threshold temperature defines the central temperature at which a particular regulatory effector is activated (Box 6-1). When the integrated input from all sources is signaling that the interthreshold range is exceeded on either side, efferent responses are initiated from the hypothalamus to maintain normal body temperature.

The slope of the response intensity plotted against the difference between the thermal input temperature and the threshold temperature is called the gain of that response (i.e., the intensity of the response).

The difference between the lowest temperature at which warm responses are triggered and the highest temperature at which cold responses are triggered indicates the thermal sensitivity of the system. As previously stated, the interthreshold range defines the temperature range over which no regulatory responses occur (although the brain presumably detects these temperature changes). This range changes from approximately 0.4° C in the awake state to approximately 3.5° C during general anesthesia. Compared with normal body temperature (37.0° ± 0.2° C), the interthreshold range during general anesthesia expands further into the hypothermic than into the hyperthermic range. This physiologic system acts as an “all-or-none” phenomenon. The mechanism by which the body determines the absolute threshold temperatures is not known, but it appears that the thresholds are influenced by multiple factors, including plasma concentrations of sodium, calcium, thyroid hormones, tryptophan, general anesthetics, and other drugs; circadian rhythm; exercise; pyrogens; food intake; and adaptation to cold and warm environments. Central regulation is already fully functional in neonates, but it may be impaired in the premature, elderly, or critically ill patient. It is now known that regulatory responses are based on mean body temperature.

Efferent Response

Mean body temperature (MBT) is a physiologically weighted average temperature that reflects the thermoregulatory importance of various tissues, but in particular that of the central compartment. In unanesthetized humans, the MBT can be calculated as follows:

where T denotes the temperature measured in °C. Other formulas do exist (Ramanathan, 1964; Colin et al., 1971; Shanks, 1975; Puhakka et al., 1994). See the following example:

where MSK reflects the mean skin temperature (in °C), which then equals:

From that it follows:

Skin temperature is the most important parameter in triggering behavioral changes; however, in terms of impact on the thermoregulatory autonomic response, the thermal input from the skin contributes only about 20% (Cheung and Mekjavic, 1995; Lenhardt et al., 1999). The main part of this autonomic response depends on afferent information from the central core, which includes the brain (parts other than the hypothalamus), the spinal cord, and deep abdominal and thoracic tissues, with each of them contributing about 20% to the central thermoregulatory control (Jessen and Mayer, 1971; Simon, 1974; Mercer and Jessen, 1978; Jessen et al., 1984).

The thermal steady state is actively defended by the hypothalamus responding to thermal changes, that is, temperatures exceeding the interthreshold range to either side. Thus, thermal deviations from the threshold temperature initiate efferent responses that either increase metabolic heat production (shivering or nonshivering thermogenesis) and decrease environmental heat loss (active vasoconstriction and behavioral changes) or increase heat loss (active vasodilation, sweating, and behavioral maneuvers).

Efferent responses (behavioral changes, cutaneous vasoconstriction or vasodilation, nonshivering thermogenesis, shivering, and sweating) appear to be mediated according to the central interpretation of the afferent input.

The most commonly described thermoregulatory model is a set-point system in which hypothalamic integration of thermal information indicates a body temperature above or below a predetermined threshold and then triggers warm or cold defenses. This set-point model, borrowed from engineering models, provides an easy way to explain how the thermoregulatory system functions and how temperature is regulated. In this model, the body compares its actual central temperature against a set reference temperature and then balances heat loss and heat-generating mechanisms to keep the temperature at this set reference point. However, while convenient, this model may not be accurate. More recent research suggests that peripheral and central thermoreceptors are connected through several other neurons to a thermoregulatory effector cell to form a thermoeffector loop (Kobayashi, 1989). In this set-up, once the temperature reaches the range for which the particular thermosensitive neuron has its highest sensitivity, its firing rate increases significantly and—independent of a central nervous system controller—triggers a response in the thermoregulatory effector. Central body temperature in this model is then the averaged result of all the thermoeffector loop actions combined, basically making a central controller (i.e., the hypothalamus) redundant (Kobayashi, 1989; Romanovsky, 2004). Although this more recent model has received a fair amount of attention, it has not yet been widely accepted in clinical practice.

Regardless of the actual model used, if an effective thermoregulatory system is in place, behavioral responses (e.g., heating the home, looking for shelter, or putting on a jacket) to environmental temperatures outside the thermoneutral range (approximately 28° C for an unclothed adult) remain the quantitatively most important thermoregulatory effectors in humans and are far more efficient than all of the autonomic responses combined. Cutaneous vasoconstriction is the first and most consistent thermoregulatory response to hypothermia. Total digital skin blood flow can be divided into nutritional (capillaries) and thermoregulatory (arteriovenous shunts) components. Cold-mediated decreases in cutaneous blood flow are most pronounced (down to 1% of the normal blood flow seen in a thermoneutral environment) in arteriovenous shunts of the hands, feet, ears, lips, and nose (Grant and Bland, 1931; Hillman et al., 1982). These shunts are typically 100 µm in diameter, which means that one can divert 10,000 times as much blood as a capillary with a 10 µm diameter under otherwise unchanged conditions (i.e., same length and pressure gradient) (Hales, 1985).

Neuronal regulation of blood flow in cutaneous arteriovenous shunts is different in glabrous (nonhairy) and nonglabrous (hairy) skin. In glabrous skin, blood flow is controlled by norepinephrine, whereas nonglabrous arteriovenous shunt flow is controlled by the opposing actions of noradrenergic vasoconstriction and cholinergic vasodilation.

Flow changes not only in the arteriovenous shunts, but also in the far more numerous capillaries (Coffman and Cohen, 1971). The impressive decrease in cutaneous perfusion secondary to thermoregulatory vasoconstriction results in a heat-loss reduction of 50% from the hands and feet, but only of 17% from the trunk, resulting in an overall heat-loss reduction of only 25% (Sessler et al., 1991).

Voluntary muscle activity, nonshivering thermogenesis, and shivering are the efferent mechanisms that lead to heat generation.

In contrast, exposure to warmth initially results in sweating, which triggers massive precapillary vasodilation with marked increase in skin blood flow. This allows for huge amounts of heat to be transported to the skin, from where it then dissipates to the environment, mainly by evaporation because of the preconditioning by sweat.

Conduction

Conduction describes heat transfer between two surfaces in direct contact. The amount of heat transferred (C) depends on the temperature difference between the two objects in contact (T₁ − T₂), the surface area of the objects in contact (A), and the conductive heat transfer coefficient (h_k) of the materials and can be calculated as follows:

The coefficient h_k is a property of the material or interface between the two objects that determines the rate of heat transfer per unit area per unit temperature difference (W/m² • °C). During surgery, relatively little heat should be lost to the environment via conduction, because the patient is supposed to be well insulated from surrounding objects (Allen, 1987). However, conduction is also responsible for heat loss created by warming up cool intravenous fluids and irrigation solutions, which have the potential to significantly and quickly reduce body temperature. Attention should also be paid to ensure that the patient’s skin is not in contact with any metallic surfaces, because metals have a high thermal conductivity, thereby facilitating heat transfer. (In addition, contact with metallic surfaces during surgery must be avoided to prevent skin burns from electrocautery.) The physiologic factors controlling conductive heat loss are cutaneous blood flow and the thickness of the subcutaneous tissue (insulation).

Radiation

Radiant heat loss refers to transfer of heat between two objects of different temperatures that are not in contact with each other (e.g., radiation is the mechanism by which the sun warms the earth). The emitted radiation carries the energy from the warmer object to the cooler object, thereby causing the warmer object to cool and the cooler object to warm. This heat transfer occurs in the infrared light spectrum. Heat exchange by radiation depends on the difference of the fourth power of the absolute temperatures of the two objects:

where R is heat transfer by radiation (W), e is the emissivity (a material property with a value between 0 and 1), s is the Stefan Boltzmann constant (5.67 • 10⁻⁸ J/sec • m² • K⁴), A denotes the surface area of the object (m²), T_sk is the skin temperature, and T_r is the temperature of the second object (both temperature values in K).

Because the temperature differences for clinical purposes are rather small, it is acceptable to use a first-power relationship for T_sk and T_r, which then allows the calculation of radiation heat exchange as follows:

where h_r denotes the radiation coefficient, an integration of emissivity and the Stefan Boltzmann constant. Heat transfer by radiation principally depends on the temperatures of the two surfaces concerned and is unaffected by air movement or the distance between the surfaces, and it can take place even across a vacuum (Allen, 1987).

As previously stated, newborns and infants have a large surface area-to-mass ratio, thus radiant heat loss is proportionally greater the smaller the infant. In both the infant who is awake and the infant who is anesthetized, radiation is the major factor for heat loss under normal conditions. The human body is an excellent emitter of energy at wavelengths relevant to heat transfer, and the probability of photon reflection in the standard operating room is almost zero. Radiant heat loss in the operating room is therefore a function of the temperature difference between the patient’s body and the room (i.e., the floor, walls, and ceiling) and all the objects in it. Warming up the operating room (and its contents) reduces not only the temperature gradient between the patient and the environment but also radiant heat losses. However, as long as a temperature gradient exists, the patient continues to warm up the surrounding environment. At a room temperature of 22° C, about 70% of the total heat loss is a result of radiation (Hardy et al., 1941). A simple single-layer covering of the body dramatically reduces the heat loss by convection and radiation; thus, a thin shirt (e.g., a silk blouse, although it provides only negligible insulation) already results in considerably increased thermal comfort.

Convection

Convective heat loss describes the transfer of heat to moving molecules, such as air or liquids. The thin layer of air directly adjacent to the skin is warmed by conduction from the body, from which heat is then lost by convection. Changes in body posture and minute ventilation may also affect convective heat loss. In the case of an unclothed individual who is exposed to air, the rate and direction of convective heat exchange depend on airflow velocity (“wind speed”) and the temperature difference between air and the skin’s surface. The situation is more complex for a clothed individual. Convective heat transfer may be calculated as follows:

where Q is the heat exchange by convection (W), A is the sur- face area (m²), h_q is the convective heat transfer coefficient (W/m² • °C), T_sk is the mean skin temperature (°C), and T_a is the ambient temperature (°C). The convective heat exchange coefficient h_c is not a constant and depends on the rate of air movement (or fluid current), the shape of the body, and the surrounding medium (i.e., gas or liquid). Thus, convective heat loss increases in proportion to the temperature difference between the body surface and the surrounding gas (or liquid) and the square root of the flow velocity of the gas (or liquid) in contact with the patient. Convective loss is best experienced outdoors in the form of the wind chill factor.

Evaporation

Evaporative heat loss occurs through the skin and the respiratory system. Under conditions of thermal neutrality, evaporation accounts for 10% to 25% of heat loss. Physical factors governing evaporative heat loss include relative humidity of the ambient air, velocity of airflow, and lung minute ventilation. The driving force behind evaporation is the vapor pressure difference between the body surface and the environment. Evaporative losses include mainly three components: sweat (sensible water loss); insensible water loss from the skin, respiratory tract, and open surgical wounds; and evaporation of liquids applied to the skin, such as antibacterial solutions. The evaporation of water from a surface is dependent on energy that is absorbed from the surface during the transition from a liquid to a gaseous state. This energy is called the latent heat of vaporization, and in the case of sweat, it has a value of 2.5 × 10⁶ J/kg. This figure emphasizes the extraordinary power of the human sweating mechanism as a means of dissipating heat, especially considering that an adult in excellent physical condition can produce up to 2 or 3 liters of sweat per hour (Armstrong et al., 1986; Godek et al., 2008). In an environment where the air temperature is equal to or higher than the skin temperature, sweating is the only mechanism available for dissipation of heat that originates from metabolic production. In this situation, anything that limits evaporation, such as high ambient humidity or impermeable clothing, may easily lead to heat storage and a potentially fatal rise in body temperature. Evaporative heat loss can be calculated as follows:

where E is the evaporative heat loss (W); h_e is the evaporative heat transfer coefficient (W/m² • kPa); P_sk is the water vapor pressure at the skin’s surface; and P_a is the ambient water vapor pressure (both pressure values in kPa). The coefficient for evaporative heat exchange (h_e) incorporates the latent heat of vaporization of water and the paramount effect of air movement on evaporation. For practical purposes, h_e may be calculated from the following formula:

where V is the airflow velocity (m/sec). The important point to note is that evaporation is determined by the vapor pressure gradient between the exposed body surface and the ambient air and the rate of airflow across the surface (Allen, 1987).

Physiologic factors affecting evaporative losses relate to an infant’s ability to sweat and to increase the minute ventilation. Although the physical characteristics of the newborn predispose him or her to heat loss, it has been demonstrated that neonates are capable of sweating in a warm environment (Bruck, 1961). Full-term neonates begin to sweat when rectal temperature reaches 37.5° to 37.9° C and ambient temperature exceeds 35° C. Although the onset of sweat production in infants who are small for gestational age is slower than it is in full-term infants, the maximum rates of sweat production are comparable (Sulyok et al., 1973). However, premature infants with a gestational age below 30 weeks show no sweating response because the lumen of their sweat glands are not yet fully developed.

Only a small amount of heat is lost when dry, inspired respiratory gases are humidified by water evaporating from the tracheobronchial epithelium. In adults, respiratory losses account for only 5% to 10% of total heat loss during anesthesia and surgery, and total insensible losses account for approximately 25% of the total heat dissipated (Bickler and Sessler, 1990). Minute ventilation on a per-kilogram basis in infants and children is significantly higher than in adults; thus, respiratory heat loss represents about one third of the total heat loss. Obviously, respiratory heat loss increases if the patient breathes cool, dry air as opposed to warm, moisturized air (Bissonnette et al., 1989a, 1989b).

Evaporative heat loss from a large surgical incision may equal all other sources of intraoperative heat loss combined (Roe, 1971). Because of increased evaporative heat loss, hypothermia is also more likely to occur if the skin of the patient is wet or comes in contact with wet drapes.

Nonshivering Thermogenesis

Nonshivering thermogenesis is defined as an increase in metabolic heat production (above the basal metabolism) that is not associated with muscle activity. It occurs mainly through metabolism in brown fat and to a lesser degree also in skeletal muscle, liver, brain, and white fat.

Brown fat differentiates in the human fetus between 20 and 30 weeks of gestational age (Lean et al., 1986a). It comprises only 2% to 6% of the infant’s total body weight and is found in six main locations: between the scapulae, in small masses around blood vessels of the neck, in large deposits in the axillae, in medium-size masses in the mediastinum, around the internal mammary vessels, and around the adrenal glands or kidneys (Fig. 6-4A).

Brown fat is a highly specialized tissue; the brown color is secondary to the abundant content of mitochondria in the cytoplasm of its multinucleated cells. These mitochondria are densely packed with cristae and have an increased content of respiratory-chain components (Himms-Hagen, 1976). They are unique in their ability to uncouple oxidative phosphorylation, resulting in heat production instead of generating adenosine triphosphate. This uncoupling process is mediated by the presence of the uncoupling protein 1 (UCP-1, or thermogenin) that is located on the inner mitochondrial membrane (Himms-Hagen, 1976; Ricquier and Kader, 1976).

Brown fat is highly vascularized and has a rich sympathetic innervation, which appears to be primarily β-sympathetic in origin and responsible for the uncoupling of oxidative phosphorylation (Karlberg et al., 1962, 1965). In respect to nonshivering thermogenesis, mature brown fat cells mainly rely on activation by β₃-receptors. Cold stress increases sympathetic nervous system activity and norepinephrine release, which causes increased lipase activity in the brown fat tissue (Schiff et al., 1966). As a consequence, hydroxylation of triglycerides and release of free fatty acids occur. These free fatty acids act on UCP-1 and thereby increase the protein conductance across the mitochondrial membrane. In addition to norepinephrine, glucocorticoids and thyroxin have been implicated as factors that trigger nonshivering thermogenesis (Gale, 1973; Jessen, 1980b, 1980c). The heat produced by nonshivering thermogenesis is mainly a by-product of fatty acid metabolism, but to a minor degree it can also result from glucose metabolism. The activation of brown fat metabolism results in an increased proportion of the cardiac output being diverted through the brown fat. This proportion may reach as much as 25% of the cardiac output, which facilitates the direct warming of the blood.

Pharmacologic inhibition of nonshivering thermogenesis can be achieved with ganglionic and β-receptor blockade, inhalational anesthetics, and surgically by sympathectomy (Silverman et al., 1964; Stern et al., 1965; Ohlson et al., 1994). Inhibition of nonshivering thermogenesis by inhalational anesthetics starts as early as 5 minutes after turning on the vapor and starts to wean off within approximately 15 minutes after discontinuation of the inhalational anesthetic (Ohlson et al., 1994). Nonshivering thermogenesis is also inhibited in infants who have been anesthetized with fentanyl and propofol (Plattner et al., 1997).

In general, nonshivering thermogenesis seems to be quite variable in adults, but most often it does not appear to be functional or relevant (Ohlson et al., 1994; van Marken Lichtenbelt and Daanen, 2003). This assumption is supported by the fact that oxygen consumption does not increase significantly when patients exhibit thermoregulatory vasoconstriction (Mestyan et al., 1964; Dawkins and Scopes, 1965). However, it seems that adults have the potential to regenerate brown fat tissue under certain pathologic conditions, such as pheochromocytoma (secondary to high and sustained sympathetic stimulation), Chagas’ disease, hibernoma (a benign brown-fat tissue tumor), or marked cold acclimatization (Garruti and Ricquier, 1992; Lean et al., 1986b; Vybiral et al., 2000).

In contrast, premature and full-term neonates, as well as infants, are able to double their metabolic heat production during cold exposure (Mestyan et al., 1964; Dawkins and Scopes, 1965; Hey and Katz, 1969). Clinically significant nonshivering thermogenesis is possible within hours after birth and may persist up to the age of 2 years (Fig. 6-4, B) (Oya et al., 1997). Despite the fact that nonshivering thermogenesis is the main source of thermoregulatory heat production in infants, it should be kept in mind that its effect and sustainability are limited and do not compensate for the decreased ability of newborns and infants to effectively reduce heat loss through cutaneous vasoconstriction or the lack of heat production through shivering.

Core hypothermia or exposure to cold during general anesthesia with propofol and fentanyl do not trigger nonshivering thermogenesis in children; therefore, nonshivering thermogenesis seems to be nonfunctional (Plattner et al., 1997). Halothane anesthesia has been shown to block nonshivering thermogenesis in children (Ohlson et al., 1994; Dicker et al., 1995). It has been demonstrated in animal studies that pharmacologic inhibition of nonshivering thermogenesis by β-blockade also affects shivering thermogenesis (Bruck and Wunnenberg, 1965). In the animals studied, shivering did not fully compensate for the lack of heat produced by nonshivering thermogenesis. The magnitude of nonshivering thermogenesis in animals varies among species, but it appears that in newborn versus adult animals and in cold-adapted versus warm-adapted animals, the contribution of nonshivering thermogenesis to heat generation is significant (Himms-Hagen, 1976).

Shivering Thermogenesis

The precise mechanisms and factors that govern the onset of shivering and the decline of nonshivering thermogenesis are unclear. With increasing age, shivering thermogenesis takes over a more prominent role in thermoregulation. It has been shown that shivering is triggered only after all the other cold defense mechanisms, such as behavioral responses, nonshivering thermogenesis (both ineffective under anesthesia), and maximal thermoregulatory vasoconstriction, have failed to maintain body temperature within the interthreshold range (Hemingway, 1963; Hemingway and Price, 1968). Until recently, newborns and infants were considered to be unable to shiver, presumably because of the general immaturity of the musculoskeletal system on the one hand and the limited muscle mass on the other hand, which would render muscle activity ineffective in defense against cold. However, a few reports exist about shivering in neonates occurring at rectal temperatures of 35.0° to 35.3°C (Brück, 1992; Petrikovsky et al., 1997). It is debatable whether this shivering was indeed thermoregulatory in origin or whether drugs and other factors (all mothers received an intrapartum amnioinfusion) were to blame. For clinical purposes, it is probably reasonable to say that neonates do not shiver, and if they do, it is of no (or only minor) significance for thermoregulation.

For a short time and only in an otherwise healthy and young person, shivering can result in an up to a sixfold increase in metabolic heat production and oxygen consumption, but only a twofold increase is sustainable (Horvath et al., 1956; Benzinger, 1969; Ciofolo et al., 1989; Just et al., 1992; Giesbrecht et al., 1994). Oxygen consumption in elderly patients (usually the age group with the highest risk for adverse cardiac events) increases on average by approximately 130% during shivering (Bay et al., 1968).

Shivering is characterized by involuntary, irregular muscular activity usually beginning in the muscles of the upper body (commonly the masseter). Overt shivering is preceded by a generalized increase in muscle tone, and only once this muscle tone reaches a certain threshold will shivering be detectable (Guyton, 2000). The intensity of shivering is higher in central muscles than it is in peripheral muscles (Bell et al., 1992).

Shivering occurs in two different electromyographic patterns: a basal, continuous shivering with low intensity at a rate of 4 to 8 Hz and superimposed bursts of high intensity at a rate of 0.1 to 0.2 Hz. The former is associated with type 1 and the latter with type 2 muscle fibers, with the bursts creating the typical “waxing and waning” pattern in the electromyogram (Stuart et al., 1966; Haman et al., 2004).

Impulses from cold receptors impinge at the motor center for shivering in the dorsomedial part of the posterior hypothalamus, adjacent to the wall of the third ventricle. In warm conditions, this center is inhibited by impulses from the heat-sensitive area in the preoptic region of the anterior hypothalamus. However, predominantly cold impulses from the skin and the spinal cord activate the shivering center, resulting in stimulation of anterior motor neurons of the spinal cord. Initially, this leads to the described generalized increase in skeletal muscle tone throughout the body, but it does not cause the actual shivering.

In healthy patients, this rise in oxygen consumption is easily met by increased cardiac output without any signs of cardiopulmonary compromise. In patients with already limited hemodynamic, coronary, or pulmonary reserves, this increase in oxygen demand can lead to decreased mixed venous oxygen content and eventually to decreased arterial oxygen content and tissue hypoxia. An inverse correlation has been shown between intraoperative temperature and postoperative oxygen demand, as well as between different anesthetics (see “Thermoregulation and General Anesthesia,” p. 172) (Roe et al., 1966). Shivering is not only an unpleasant experience for the patient in the postoperative period; it has also been implicated in increased intracranial and intraocular pressure, wound dehiscence, and dental damage (Mahajan et al., 1987; Rosa et al., 1995; Alfonsi, 2001).

Although the incidence of postoperative shivering is inversely related to the core temperature, shivering was also found in patients who were kept strictly normothermic during isoflurane or desflurane anesthesia, indicating that a substantial fraction of shivering is nonthermoregulatory, with pain being one potential trigger (Horn et al., 1998, 1999). Inhibition of shivering with meperidine in awake, actively cooled volunteers resulted in a more than threefold higher and more than four-times prolonged core temperature afterdrop with a rewarming rate decreased by 37% when compared with the shivering control group (Giesbrecht et al., 1997).

Dietary Thermogenesis

Stimulation of energy expenditure and thermogenesis by certain nutrients (i.e., proteins and amino acids) is a well-known phenomenon (Lindahl, 2006). Despite muscle paralysis and decreased metabolism during general anesthesia, the infusion of small amounts of amino acids resulted in up to a fivefold increase in heat generation during anesthesia compared with that in adults who were awake (Sellden et al., 1994). Using pre- and intraoperative amino-acid infusions, the same researchers were able to use this advantage clinically to achieve a core temperature of 36.5° ± 0.1° C at the end of surgery, whereas the temperature dropped to 35.7° ± 0.1° C in the control group (Sellden and Lindahl, 1999). Similar findings have been reported for preoperative amino-acid infusion in patients undergoing spinal anesthesia (Kasai et al., 2003). Although effective, the exact mechanism behind this form of thermogenesis has not yet been fully elucidated. It seems that stimulation of cellular amino-acid oxidation is crucial. Furthermore, protein synthesis and breakdown in extrasplanchnic tissues that require extra synthesis of ATP, could be a contributing factor as well. Approximately half of the heat generated in association with amino-acid infusions is splanchnic in origin. Blood flow in extrasplanchnic (but not splanchnic) tissues increases significantly, reflected by a raise in cardiac output of almost 20% (Brundin and Wahren, 1994). Except for a different time course, the average whole-body thermic effect of intravenous amino-acid administration is not different from the one seen with oral protein ingestion. Fructose administration has also been shown to increase the metabolic rate by 20% in anesthetized adult surgical patients. In a study of 20 patients, Mizobe et al. (2006) noted that intravenous fructose increased the intraoperative core temperature, oxygen consumption, and the vasoconstrictive threshold (Fig. 6-5). Dietary thermogenesis has the potential to cause hyperthermia not only during general anesthesia with attenuated thermoregulation, but also in the patient who is awake (Sellden, 2002).

FIGURE 6-5 A, Core temperature measured at the distal esophagus (T_es) during surgery. Patients receiving the fructose infusion had significantly greater core temperatures than those receiving saline (*P = 0.001). B, Relationship between the forearm-minus-fingertip temperature gradient (T_forearm − T_fingertip) and distal esophageal (core) temperature (T_es). Patients assigned to fructose infusion experienced vasoconstriction (increased in the gradient) at a significantly higher core temperature than did those receiving saline infusion (P < 0.001).

(From Mizobe T, et al.: Fructose administration increases intraoperative core temperature by augmenting both metabolic rate and the vasoconstriction threshold. Anesthesiology 104:1124-1130, 2006.)

Anesthesia and Hypothermia

There is no generally accepted definition for hypothermia, but the distinction between mild (core temperature 34.0° to 35.9° C), moderate (32.0° to 33.9° C), and severe hypothermia (below 32.0° C) appears useful and reasonable for clinical purposes (Brux et al., 2005). General anesthesia reduces the threshold at which the body initiates a thermoregulatory response to cold stress (Boxes 6-3 and 6-4). Mild intraoperative hypothermia (1° to 3° C below normal) is common and results from a combination of the following events:

Hypothermia during general anesthesia has a typical profile and usually develops in three phases (Fig. 6-6):

FIGURE 6-6 This graph illustrates the three phases typical for the course of intraoperative hypothermia during general anesthesia. A represents the internal redistribution of heat; B is the thermal imbalance phase with ongoing net loss of heat to the environment; and C is the thermal steady state, which in children and infants is a rewarming phase.

(Modified from Bissonnette B: Thermoregulation and paediatric anaesthesia. Curr Opin Anaesthesia 6:537, 1993.)

Internal Redistribution

In order to understand the concept of internal redistribution, it is helpful to use the previously described division of the human body into three thermal compartments, the central, peripheral, and skin (or “shell”) compartments. The core temperature represents the central compartment temperature, which contains the vessel-rich group organs receiving approximately 75% of the cardiac output and representing about 10% of the body weight in adults and up to 22% in neonates. In an awake adult at rest, the entire central compartment accounts for approximately 66% of the body mass and extends to about 71% during general anesthesia (Deakin, 1998).

The peripheral compartment comprises the remaining part of the body mass (mainly muscles) and acts as a dynamic buffer to accommodate any changes in core temperature by thermoregulatory vasodilation or vasoconstriction. Its estimated buffer capacity of over 600 kJ allows the body to maintain core temperature constant with a minimal amount of energy expenditure for thermoregulation despite absorption or dissipation of significant amounts of heat.

The skin compartment is almost virtual and represents the barrier between the previous two compartments and the environment. After induction of anesthesia, peripheral vasodilation causes an increase in the size of the central compartment, forcing it to redistribute its heat within a larger volume. In addition, the anesthesia-induced reduction in metabolic heat generation decreases the amount of energy available to compensate for the enlargement of this compartment. The concept of internal redistribution of heat, therefore, consists primarily not of heat loss to the environment, but of a measurable decrease in core temperature and an increase in the peripheral and skin compartment temperatures because of redistribution of heat.

With induction of anesthesia, the central core temperature starts to decrease rapidly by approximately 0.5° to 1.5° C during the first 30 to 45 minutes of anesthesia (Fig. 6-7). Although this process results in reduced core temperature, the total body-heat content decreases only slightly. Heat—as the name implies—is mainly redistributed and not dissipated. This redistribution of heat accounts for 81% of the core temperature decrease in the first hour of anesthesia, whereas the remainder is the result of the anesthesia-induced reduction in metabolism and increased heat loss. For the subsequent 2 hours of anesthesia, the impact of redistribution on total heat loss decreases to approximately 43% (Matsukawa et al., 1995b). Accordingly, administration of a vasoconstrictor, such as phenylephrine, can limit the drop in core temperature caused by redistribution (Ikeda et al., 1999a).

FIGURE 6-7 The dynamic changes within the three temperature compartments of a child before induction of anesthesia, during the first hour of anesthesia, and after thermoregulatory vasoconstriction. In the awake human, temperature and size of the compartments are considered normal (A). After the first hour of anesthesia, the internal redistribution of heat results in a rapid decrease in core temperature and an increase in peripheral temperature, together causing enlargement of the central compartment and shrinkage of the peripheral compartment (B). The drop in central temperature is mainly caused by the distribution of its heat to a larger volume, and actual heat loss is minimal at this stage. C, Once thermoregulatory vasoconstriction has been initiated (after about 3 hours of anesthesia), the central compartment is shrinking in favor of the peripheral compartment. The rise in central temperature is now due to the fact that generated heat is contained in a smaller volume.

Internal redistribution results in shrinkage of the peripheral compartment and enlargement of the central compartment, which explains not only the decreased core temperature, but also the increased temperature in the peripheral and skin compartments (Fig. 6-7). This is reflected by a more than fourfold increase in the perfusion of the forearms and particularly the legs after induction of anesthesia, and a forearm-fingertip or calf-toe temperature gradient that may exceed 8° C (Matsukawa et al., 1995b).

Thermal Steady State (Plateau or Rewarming Phase)

The third stage of the hypothermic response to anesthesia consists of a thermal steady state, in which metabolic heat production equals heat dissipation to the environment, and the core temperature therefore remains constant (see Fig. 6-6). This plateau normally occurs between a core temperature of 34.5° to 35.5° C. This is only possible if the patient increases the heat production, decreases the heat loss, or both to prevent further hypothermia.

A study of adults who were anesthetized with isoflurane showed that the effect of thermoregulatory vasoconstriction reduces heat loss by a maximum of 25%, which is relatively small compared with the fall in metabolic rate and the increase in evaporative heat loss from the surgical incision (Sessler et al., 1992). Heat loss to the environment is determined mainly by the capillary blood flow in large areas of the skin that cover the limbs and the trunk. These capillaries markedly outnumber the arteriovenous shunts, but they cannot constrict as effectively as the shunts. It is possible that vasoconstriction contributes to the thermal plateau by reestablishing the temperature gradient between the central and the peripheral compartments and thereby preventing metabolic heat from being transported to the periphery, from which it would dissipate (see Fig. 6-7). The metabolic heat produced in the body core is once again confined to a smaller central compartment, allowing the core temperature to remain constant.

To reinforce this theory of compartment size, it should be noted that the use of a limb tourniquet during surgical procedures can influence the thermoregulatory response in children and adults (Bloch et al., 1992; Estebe et al., 1996). The tourniquet may induce hyperthermia, which is most likely the result of decreased effective heat loss from distal skin areas, as well as from metabolic heat constraint to the central thermal compartment. Upon release of the tourniquets, the core temperature drops quickly to levels similar to those in patients who were part of a control group without a tourniquet (Estebe et al., 1996; Sanders et al., 1996; Akata et al., 1998). Despite having a constant core temperature, total body-heat content continues to decrease, because heat loss to the environment continues.

Unlike in adults, this third phase in infants and children is a rewarming rather than a plateau (see Fig. 6-6). As mentioned, general anesthesia decreases heat production by inhibiting muscular activity and nonshivering thermogenesis and by reducing the metabolic rate. Thus, the only possible explanation for this rewarming phase must be the occurrence of marked vasoconstriction within the peripheral and central compartments that results in shrinkage of the central compartment. The amount of metabolic heat produced is then distributed within a smaller central compartment volume and results in a higher core temperature. This is associated with a simultaneous increase in oxygen consumption, carbon dioxide production, and systemic norepinephrine levels, an effect that has been observed in infants who were anesthetized with isoflurane and paralyzed with vecuronium (Bissonnette, personal observation).

In contrast to adult responses, intraoperative thermoregulatory responses in infants are effective enough to significantly increase the core temperature despite a constant ambient temperature. A clinical study in anesthetized children found a twofold increase in oxygen consumption during mild hypothermia (Ryan, 1982). Both active and passive rewarming imposes significant physiologic stress on the infant. Passive surface rewarming (with the use of warm blankets, bundling, or other measures) turns off the skin’s cold receptors. If normal core temperature is not reached or maintained with passive surface rewarming, hypothermia may result in hypoventilation or even apnea, relative anesthetic overdose (reduced minimum alveolar concentration [MAC] at lower temperatures), and metabolic acidosis. The increased oxygen demand to maintain normal core temperature in the anesthetized infant may create or exacerbate a preexisting cardiopulmonary insufficiency. The release of norepinephrine to trigger vasoconstriction may contribute to the development of acidosis and hypoxia, thereby facilitating right-to-left pulmonary shunting. Sustained pulmonary artery hypertension and right-to-left pulmonary shunting may begin a vicious cycle of hypothermia (Fig. 6-8).

FIGURE 6-8 The vicious cycle of hypothermia in neonates and infants.

(Modified from Klaus M, Faranoff A: Care of the high-risk neonate, Philadelphia, 1986, WB Saunders.)

In infants, a correlation between intraoperative hypothermia and an early increase in postoperative oxygen consumption has been demonstrated (Roe et al., 1966).

Anesthesia and Hyperthermia

Similar to hypothermia, hyperthermia triggers important physiologic thermoregulatory responses by using thresholds and gains. Similar to hypothermia, the threshold temperature represents the central temperature for which a particular regulatory effector becomes active, whereas the gain quantifies the intensity of the response (Fig. 6-9). The effector mechanisms during hyperthermia are well preserved during anesthesia (Lopez et al., 1993). The efferent-response thresholds are shifted to higher temperatures with an expansion of the interthreshold range, which corresponds to the difference between the normal central temperature and the first efferent response triggered by the hypothalamus. An interesting observation with regard to the interthreshold range resides in the difference between the shift observed for hypothermia and the shift seen for hyperthermia.

FIGURE 6-9 Thermoregulatory thresholds and gains in awake and anesthetized adults, children, and infants. The vertical height/depth of each line indicating the threshold temperature represents the maximal intensity of each effector response, whereas the slope of the lines represents the gain of the response. The temperature scale corresponds to the core temperature. The sensitivity of the thermoregulatory system is the range between the first cold response (vasoconstriction) and the first warm response (sweating) and is called interthreshold range, which is significantly expanded during anesthesia. NST, Nonshivering thermogenesis.

The poikilothermic range to the hypothermic side in the anesthetized patient may be expanded by up to 3.5° C. In contrast, clinical studies in human volunteers have demonstrated that the threshold for active vasodilation and sweating is only 1.0° to 1.4° C higher in anesthetized patients than in those who are awake (Lopez et al., 1993). This observation suggests that the human physiology responds more aggressively to the threats from hyperthermia than from hypothermia. Thus, hyperthermia seems to be a far more dangerous threat to the body than a comparable degree of hypothermia (Lopez et al., 1993).

The efferent responses during hyperthermic stress are limited to two mechanisms: active thermoregulatory vasodilation and sweating. Vasodilation triggered in response to warm stress is not simply the absence of vasoconstriction, but rather an active process mediated by sympathetic cholinergic impulses and release of vasoactive substances (e.g., vasoactive intestinal peptide [VIP], histamine) that results in increased dissipation of heat (Detry et al., 1972; Rübsamen and Hales, 1984; Kellogg et al., 1998; Bennett et al., 2003; Wilkins et al., 2004). It has been demonstrated that the effect of hyperthermia on the peripheral vasculature results in a significant increase in blood flow (Tankersley et al., 1991; Matsukawa et al., 1995b). The observation of active cutaneous vasodilation in infants under anesthesia, although difficult to quantify (skin flushing), suggests that this thermoregulatory response to hyperthermia is preserved.

Sweating represents an increase in evaporative cutaneous heat loss during episodes of heat stress. The relatively high heat of vaporization of sweat (2.5 × 10⁶ J/kg) makes sweating an extremely effective process. This allows for up to a fivefold increase in heat loss to the environment, making it proportionally more effective than all the cold-defense mechanisms combined (Fusi et al., 1989).

A study in adult volunteers showed that sweating remains functional during isoflurane anesthesia (Sessler, 1991b).

The benefits provided by induced hyperthermia (vasodilation) may be desirable during peripheral microvascular surgery, where an increase in regional blood flow is important. One of the clinical limitations of induced hyperthermia to increase cutaneous blood flow is the efficiency of the sweating mechanism. Despite active transfer of approximately 50 W of heat across the patient’s skin via convection and radiation, it was possible to demonstrate that the central temperature remains relatively constant or even decreases for exactly this reason (Sessler, 1993). Although shivering can easily double the heat production, sweating can result in the dissipation of more than 10 times the amount of normal basal heat production (Guyton, 2000).

Thermoregulation and General Anesthesia

Both intravenous and inhalational anesthetics can interfere with thermal regulation at peripheral and central receptor sites. In adults, general anesthesia has been shown to lower the thermoregulatory threshold temperature, triggering an average response to hypothermia by approximately 2.5° C, while the increases in the threshold temperature initiating a response to hyperthermia is less pronounced (approximately 1.3° C) (see Fig. 6-9) (Sessler et al., 1988a; 1988b). This anesthesia-induced expansion of the interthreshold range results in a wider temperature range over which active thermoregulatory responses are absent. Within this range, humans behave poikilothermically, with the body temperature changing passively in proportion to the difference between metabolic heat production and heat loss to the environment. Vasoconstriction and nonshivering thermogenesis are the only thermoregulatory responses available to anesthetized, paralyzed, hypothermic infants and children. Patients with mild hypothermia during surgery (e.g., a central body temperature of about 34.5° C) demonstrate profound peripheral vasoconstriction, which can easily be verified using the skin’s surface temperature gradients (e.g., forearm versus fingertip skin temperature), volume plethysmography, a laser Doppler flowmeter, or other techniques (Stuart et al., 1966; Sessler et al., 1988a, 1988b).

Thermoregulation and Inhalational Anesthetics

The maximum intensity of peripheral thermoregulatory vasoconstriction during anesthesia is similar to that in volunteers who are awake, indicating that the gain of the response is preserved, but that it is triggered at a markedly lower threshold temperature. The only exception seems to be desflurane, which lowers not only the threshold temperature for vasoconstriction but also its gain (Kurz et al., 1995b). The temperature at which vasoconstriction and nonshivering thermogenesis are triggered identifies the corresponding lower thermoregulatory threshold for the anesthetic agent at any given concentration or dose.

Halothane administration in a concentration of 1.0% in oxygen to healthy adults undergoing donor nephrectomy reduced the threshold temperature for thermoregulatory vasoconstriction to 34.4° ± 0.2° C (Sessler et al., 1988a). In infants and children who were anesthetized with 0.6% halothane combined with a caudal epidural block with bupivacaine, the threshold temperature for vasoconstriction was 35.7° C (Bissonnette and Sessler, 1992). Of note, in children with a body weight of over 30 kg, the central temperature continued to drop even after the vasoconstriction threshold temperature had been reached, whereas children and infants with a body weight below 30 kg were able to maintain or even slightly increase their central temperature. This shows that thermoregulatory defense in infants and younger children is more effective than in older children and adults.

The administration of subanesthetic concentrations of nitrous oxide (10% to 25% in a normoxic mixture) to healthy adult volunteers resulted in a significant but dose-independent reduction of shivering thermogenesis (Cheung and Mekjavic, 1995).

In a concentration of 0.6 (63%) MAC, administration of nitrous oxide resulted in a calculated reduction of the vasoconstriction threshold to 35.7° ± 0.6° C (Goto et al., 1999). Overall, nitrous oxide decreased the thermoregulatory vasoconstriction threshold less than equally potent concentrations of sevoflurane and isoflurane.

In a small study of adults anesthetized with isoflurane, the decrease in the threshold temperature for thermoregulatory vasoconstriction was found to be inversely correlated to the isoflurane concentration, with the threshold temperature decreasing by approximately 3° C per 1% increase in end-tidal isoflurane concentration (Stoen and Sessler, 1990). In a more recent study, the same group found that this dependence on dose was not linear, with isoflurane reducing the threshold temperature disproportionately at higher anesthetic concentrations (Xiong et al., 1996). In adults anesthetized with 0.7% isoflurane, the shivering-temperature threshold decreased, as did the maximum intensity of shivering. The gain of shivering increased significantly and was associated with a pattern of clonic muscular activity that was not a component of regular shivering (Ikeda et al., 1998a).

The thermoregulatory vasoconstriction-threshold temperature in infants and children anesthetized with isoflurane differs only slightly from that in adults (Bissonnette and Sessler, 1990). In pediatric patients anesthetized with 1 MAC halothane in 70% nitrous oxide, this same threshold temperature is higher (35.8° ± 0.5° C) than reported for adults (34.4° C) (Bissonnette and Sessler, 1990; Sessler et al., 1988a). In the adult study, the patients were anesthetized without nitrous oxide and the administered halothane concentration (1.3 MAC) was significantly higher than the one used in the pediatric study (1.0 MAC). In a separate study, a similar thermoregulatory threshold (35.8° ± 0.3° C) was found in pediatric patients who were anesthetized with 1 MAC of halothane in oxygen combined with a caudal epidural block with bupivacaine (Nebbia et al., 1996).

Thermoregulatory inhibition during general anesthesia with equally potent concentrations of halothane is therefore likely to affect adults and children similarly. The high surface area-to-mass ratio in infants, which allows for a rapid loss of heat to the environment, is largely offset by the high intrinsic metabolic rate. Heat loss is further reduced by the well-developed thermoregulatory vasoconstriction mechanism (Bissonnette and Sessler, 1990). Although a trend toward increased threshold temperatures was noted in smaller infants and children anesthetized with similar (age-corrected) concentrations of isoflurane, differences between groups were not statistically significant and spanned only about 0.3° C. This indicates that inhibition of thermoregulatory vasoconstriction is similar in anesthetized infants and children and relatively independent of body weight (Bissonnette and Sessler, 1990). This relatively constant degree of thermoregulatory inhibition in infants and children of different ages is in marked contrast to the age-related changes in the MAC of isoflurane. In infants 1 to 6 months of age, the MAC for isoflurane is approximately 1.5 times higher than the MAC for adults.

With regard to decreasing the threshold temperature for thermoregulatory vasoconstriction, sevoflurane was found to be similar to, although slower than, isoflurane, (Ozaki et al., 1997; Saito, 1997).

Desflurane increases the sweating threshold temperature in a concentration-dependent, linear way. The threshold temperatures for vasoconstriction and shivering at 0.8 MAC are comparable with the other volatile anesthetics, however, at 0.5 MAC, the drop in vasoconstriction threshold temperature was less pronounced. Thus, for desflurane there may be a nonlinear concentration-response relationship for cold-defense mechanisms (Annadata et al., 1995b). Desflurane also reduces the gain of thermoregulatory vasoconstriction (Kurz et al., 1995).

Enflurane is a peculiar inhalational agent with respect to its thermoregulatory effects. In healthy adult volunteers anesthetized with 1.3% enflurane (equivalent to approximately 0.77 MAC), the threshold temperature for thermoregulatory vasoconstriction was 35.1° ± 0.6° C without any patient stimulation and 35.5° ± 0.8° C during painful electrical stimulation. This result demonstrated a slight, although clinically insignificant, effect of nociception in offsetting the anesthesia-induced thermoregulatory inhibition (Washington et al., 1992). Combination with caudal or lumbar epidural blockade eliminates this effect during abdominal and peripheral surgical procedures. Thermoregulatory studies with enflurane in the pediatric population are hampered by the lack of enflurane MAC studies for this age group. In pediatric patients aged 1 to 12 years, 1.67% enflurane (equal to 1 MAC in adults, which is estimated to be equivalent to 0.75 to 1.0 MAC for the age group studied) combined with caudal bupivacaine caused a profound drop in the threshold temperature for thermoregulatory vasoconstriction (Nebbia et al., 1996). Most patients in this study failed to achieve thermoregulatory vasoconstriction despite reaching a mean core temperature of 33.9° ± 0.9° C. It was therefore concluded that the risk of hypothermia with enflurane is significantly higher when compared with the risk for isoflurane or halothane.

The effects of different inhalational anesthetics on the threshold temperature for thermoregulatory vasoconstriction are summarized in Figure 6-10. In addition, hypothermia can affect the physical characteristics of inhalational anesthetics, as well as the pharmacokinetics and pharmacodynamics of intravenous anesthetic drugs. Hypothermia reduces the MAC of inhalational agents (for isoflurane there is a linear MAC decrease of 5.1% per °C drop in core temperature) and increases their tissue solubility (Vitez et al., 1974; Eger and Johnson, 1987; Antognini, 1993; Antognini et al., 1994; Liu et al., 2001). Thus, for any inspired concentration of an inhalational anesthetic agent in a hypothermic patient, an increased amount of the agent is delivered to the tissues, when in fact the anesthetic requirements are decreased. Hypothermia also affects the pharmacokinetics of barbiturates and narcotics (Kadar et al., 1982; Koren et al., 1987).

FIGURE 6-10 Threshold temperature (in °C) for thermoregulatory vasoconstriction in adults for different concentrations of inhalational anesthetics either alone or in combination with nitrous oxide. The x-axis denotes the MAC equivalents of the different inhalational anesthetics.

(Data compiled from Sessler and Ponte, 1982; Washington et al., 1992; Annadata et al., 1995; Kurz et al., 1995b; Ozaki et al., 1995; Goto et al., 1999.)

Thermoregulation and Regional Anesthesia

During regional anesthesia, central thermoregulation remains functional, as does metabolic heat generation, thereby providing some protection against hypothermia (Hynson et al., 1991). Regional anesthesia interferes with regional thermal sensation (afferent and efferent pathways) and inhibition of thermoregulatory vasoconstriction and shivering in the anesthetized area. Increased internal redistribution of body heat followed by increased heat loss to the environment may contribute to intraoperative hypothermia. In many aspects, the factors responsible for intraoperative hypothermia during neuraxial blockade are similar to those for patients under general anesthesia: redistribution of body heat from the core to the peripheral compartment accounts for 89% of the initial drop (i.e., in the first hour) in core temperature. In the following 2 hours, redistribution contributes to 62% of the core temperature decrease (Matsukawa et al., 1995a; 1995b). The extent of this redistribution, and thus the decrease in core temperature, depend on inhibition of peripheral vasoconstriction rather than on centrally mediated effects. Neuraxial anesthesia usually affects a major part of the body mass and the decrease in core temperature can be quite pronounced. However, heat production during regional anesthesia is only minimally decreased (Hynson et al., 1991).

In contrast to patients undergoing general anesthesia, patients under central neuraxial anesthesia may fail to reach a steady state in which heat loss and heat generation are equal, because peripheral vasoconstriction is completely abolished in the area affected by neuraxial blockade. In addition, extensive regional anesthesia may alter or even block the thermal input to the hypothalamus from the anesthetized body part, with the number of dermatomes blocked being directly proportional to the inhibition of central thermoregulation (Ozaki et al., 1994; Leslie and Sessler, 1996; Frank et al., 2000). Heat loss may therefore be an ongoing issue until sympathetic function and consequently the ability for vasoconstriction have been restored. Under these circumstances, hypothermia during regional anesthesia may become even more profound than during general anesthesia. In an attempt at compensation, peripheral vessels not affected by regional anesthesia are maximally vasoconstricted, although this is often not sufficient to prevent a further drop in core temperature, particularly when the body mass affected by regional anesthesia is approximately the same or even larger than the unblocked mass.

Shivering is initiated once the patient’s core temperature reaches the shivering threshold; however, neuraxial blockade reduces the gain of shivering by more than 60%, mainly because the upper body muscles fail to compensate for lower body paralysis (Kim et al., 1998). It seems unlikely that systemic absorption of local anesthetics contributes to the thermoregulatory changes seen under regional anesthesia, because a study generating equal plasma drug concentrations without regional anesthesia failed to reproduce these thermoregulatory disturbances (Glosten et al., 1991).

Compared with general anesthesia, the use of regional anesthesia reduces the risk of hypothermia, especially during surgery with small incisions where the patient can be kept well insulated. In contrast, regional anesthesia for large surgical incisions predisposes a patient to more profound hypothermia than with general anesthesia, and recovery to normal body temperature may be prolonged (Cattaneo et al., 2000).

In adults, the changes in threshold temperatures for sweating, vasoconstriction, and shivering during spinal anesthesia and epidural anesthesia seem to be comparable and result in a twofold expansion of the interthreshold range (Ozaki et al., 1994). In adults, the combination of general anesthesia with thoracic epidural anesthesia further reduced the threshold temperature for thermoregulatory vasoconstriction and thus significantly aggravated hypothermia compared with general anesthesia alone (Joris et al., 1994). Interestingly enough, diabetic patients with autonomic neuropathy showed lower core temperatures and delayed thermoregulatory vasoconstriction during general anesthesia than diabetic patients without autonomic dysfunction (Kitamura et al., 2000).

Unlike the thermoregulatory effects of regional anesthesia in adults, the institution of a caudal block in children anesthetized with halothane does not significantly alter the threshold temperature for thermoregulatory vasoconstriction in children (35.7° C without versus 35.9° C with caudal block) (Bissonnette and Sessler, 1992). Nevertheless, temperatures during regional anesthesia should be monitored in adult and pediatric patients, because significant hypothermia is common and remains otherwise undetected and therefore also untreated. However, a survey revealed that only a third of clinicians monitors body temperature during regional anesthesia in adults (Frank et al., 1999).

Operating Room Temperature

Keeping the operating room temperature at an optimal level is crucial in the prevention of hypothermia. The major source of heat loss in the anesthetized patient is caused by radiation. As mentioned previously, radiant heat loss is a function of the temperature difference between the patient and the environment. The effectiveness of controlling ambient operating room temperature in controlling the temperature of newborns during surgery has been confirmed (Bennett et al., 1977). In adults, 21° C is reported as the critical ambient temperature for maintaining normal nasopharyngeal or esophageal temperatures (36° to 37.5° C) (Morris and Wilkey, 1970; Morris, 1971a, 1971b). Operating room temperatures of 27° and 29° C are recommended for full-term and premature newborns, respectively. It is essential that every operating room be equipped with an individual thermistor control unit so that the temperature in each operating room can be controlled independently to meet the needs of each patient.

Convective heat loss in the operating room is due to the constant air draft caused by the air conditioning system. Keeping the patient covered provides the best protection against this form of heat loss.

Evaporative heat loss from the respiratory tract accounts for only 5% to 10% of total heat loss during anesthesia. However, more important are the evaporative heat losses from open body cavities during surgery. In order to reduce this form of heat loss, the relative humidity of the operating room should be kept in the range of 40% to 60%.

Radiant Heaters

Radiant heaters are mainly used during induction of anesthesia and insertion of catheters, until the patient is prepared and draped. Prolonged use of radiant heaters may result in increased insensible water losses. The minimal manufacturer-recommended distance of the radiant heater from the skin must be respected at all times in order to avoid skin burns.

Reflecting Blankets

The use of reflective blankets in adults has produced conflicting results, and data on their use in infants and children are sparse. In adults, it has been reported that intraoperative normothermia can be maintained when the reflective blanket covers 60% or more of the patient’s body surface area (Bourke et al., 1984). One drawback of reflective blankets is the potential build-up of condensation on the inner side, which can result in wet clothes or skin, putting the patient at high risk for evaporative heat loss. With regard to heat conservation, it seems not that important what material the cover is made of; instead, it is important to cover as much of the body surface as possible (Sessler et al., 1991). The practice of covering the head with a plastic bag provides an easy, inexpensive way to significantly reduce radiant, convective, and evaporative heat losses (Fig. 6-12).

FIGURE 6-12 The head of an infant constitutes a large fraction of its body size; therefore, covering the infant’s head and as much as possible of the remaining body surface with plastic wrap can significantly reduce evaporative and convective heat loss.

Skin-Surface–Warming Devices

The use of skin-surface–warming devices in adults before the induction of anesthesia reduces the magnitude of hypothermia that results from internal redistribution of heat (Glosten et al., 1993). Aggressive skin-surface warming induces peripheral vasodilation and favorably increases the temperature of the peripheral compartment to values approaching those of the central compartment. The net result is an increased mean body temperature, and the skin-surface warming reduces the amount of energy transferred from the central to the peripheral compartment after induction of anesthesia. A variety of passive and active skin-surface warmers are available, including circulating hot-water blankets, infrared radiant heaters, and convective forced-air heaters, which blow warm air through a disposable blanket to raise the effective ambient temperature immediately surrounding the patient (Stephen et al., 1960; Vale and Lunn, 1969; Morris, 1971b; Goldblat and Miller, 1972; Sessler and Moayeri, 1990; Steele et al., 1996). A newer system that simulates water immersion using a special garment and feedback algorithms analyzed by computer to achieve a preset body temperature is available, seems to perform well, and is also safe in children (Nesher et al., 2001a, 2001b; Nesher et al., 2002). Of all these devices, convective forced-air warmers are by far the most effective, not only from a thermoregulatory perspective, but also from a cost and convenience point of view. Not only can they maintain normal body temperature, but they can also rewarm a hypothermic patient (Sessler and Moayeri, 1990; Kurz et al., 1993; Ciufo et al., 1995; Karayan et al., 1996). In patients with decreased peripheral perfusion (e.g., because of high doses of vasoconstrictors, aortic cross clamping for coarctation or abdominal aortic aneurysm repair, or severe peripheral arterial occlusive disease) the device should be used with great caution only and not for extended lengths of time to avoid skin burns, particularly in infants and neonates (Azzam and Krock, 1995; Truell et al., 2000; Siddik-Sayyid et al., 2008).

Warming Mattresses

The use of warming mattresses reduces conductive heat loss. Warming mattresses set at 40° C and covered with two layers of cotton blankets have been demonstrated to effectively conserve heat (Goudsouzian et al., 1973). This measure is mainly efficient for infants with a body surface area of less than 0.5 m². In older children and adults, only a small proportion of the skin’s surface area is in direct contact with the heating mattress, which makes these devices generally less effective to maintain normothermia.

Warming of Intravenous Fluids

Rapid infusion of chilled intravenous fluids (1° to 6° C) can be used effectively to induce hypothermia. The administration of 1 L of an ice-cold infusion in an adult is expected to decrease the core temperature by approximately 1.7° C, but values of up to 3° C are possible (Baumgardner et al., 1999; Rajek et al., 2000). Thus, intravenous fluids and blood products should be warmed before administration. It is particularly important to warm fluids in instances of rapid or massive fluid administration. In addition, attention should be paid to the length and the type of the infusion tubing, because significant heat loss of the infusion during transit from the warming device to the intravenous cannula may occur (Faries et al., 1991; Bissonnette and Paut, 2002). Even when warming the infusion to 37° C, a flow rate of more than 750 mL/hr is required to keep its temperature above 32° C at a distance of 25 cm away from the warmer when the infusion tubing is exposed to ambient air (20° C) (Faries et al., 1991). Because this flow rate is usually beyond the needs of regular pediatric cases, the length of the infusion tubing distal to the warmer should be kept as short as possible. Although a study demonstrated that conservative fluid management (1 mL/kg per hour of crystalloids warmed to 37° C) in patients aged 1 to 3 years resulted in less core hypothermia when compared with the control group who received a more aggressive fluid replacement (10 mL/kg per hour) (Ezri et al., 2003), this should not preclude pediatric patients from receiving appropriate intraoperative fluid resuscitation.

Because both the peritoneal and thoracic cavities are large heat-exchanging areas, solutions for intraoperative irrigation should always be warmed to body temperature. Although desirable from a thermoregulatory point of view, antimicrobial solutions for surgical skin preparation should not be warmed, because heat can cause chemical breakdown of the iodine solution and thereby inactivate its antimicrobial properties.

Humidified and Heated Gases

When breathing spontaneously (without an endotracheal tube or laryngeal mask airway in place), the tracheobronchial epithelium heats and moistens the inspired air, an energy-dependent process (evaporation and convection). Intubation significantly reduces the epithelial surface area that is available for warming and humidification of inspired gases. In order to minimize convective and evaporative heat losses from the respiratory tract and to minimize adverse effects on the tracheobronchial epithelium, inspiratory gases should be heated and humidified. Airway humidification in intubated patients prevents tracheal damage caused by dry inspired gases, increases tracheal mucus flow, and minimizes respiratory heat losses (Berry et al., 1973; Forbes 1974; Mercke 1975; Chalon et al., 1979b; Tollofsrud et al., 1984). Heat and humidity can be added to inspired gases either actively by evaporative or ultrasonic heated humidifiers or passively by heat and moisture exchanging filters (“artificial noses”) (Newton, 1975; Chalon et al., 1979a, 1984; Bissonnette et al., 1989a). Furthermore, there is considerable evidence that a relative humidity level of at least 50% is required to maintain normal ciliary function in the respiratory tract and to help prevent bronchospasm (Forbes, 1974; Mercke, 1975; Chalon et al., 1979a; Chan et al., 1980). More recent research, however, suggests an even higher humidity level of 75% to 100% to effectively maintain mucociliary function (Kilgour et al., 2004). Humidification to 50% (but not to 75% to 100%) is easily obtained with heat and moisture exchanging filters and should be standard for long procedures (Forbes, 1974; Mercke, 1975; Chalon et al., 1979a). In adults, heating and humidification of gases to 37° C and 100% relative humidity not only effectively helps maintain normothermia, but it also helps reverse hypothermia during general surgery (Pflug et al., 1978; Stone et al., 1981).

Because of the higher minute ventilation per kilogram of body weight in pediatric patients, airway humidification for infants is even more important and effective in helping to maintain normothermia than it is for adults (Bissonnette and Sessler, 1989a; Bissonnette et al., 1989). In newborns, heat loss during general anesthesia is significantly reduced when gases are heated and when humidified gases are used instead of dry anesthetic gases (Fonkalsrud et al., 1980). Although high- temperature humidification devices can decrease intraoperative evaporative heat loss, they may cause tracheal burns. Because there may be a large temperature gradient between the humid-ifier and the endotracheal tube, it is important to measure airway temperature as close to the patient as possible. This has the advantage of preventing heated gases from accidentally burning the trachea while providing the warmest possible inspiratory gas. In addition, intraoperative heat loss can be minimized. If these devices are used, it is recommended to heat inspiratory gases to normal body temperature only. Although heat and moisture exchanging filters are less effective than active humidifiers (especially in the first hour after induction of anesthesia), they seem to provide a reasonable, convenient, and cost-effective alternative (Bissonnette et al., 1989a).

Additional advantages of heat and moisture exchangers in small infants include the lack of risk for airway burns and overhumidification with the consequences of overhydration, and the reduced risk for breathing-circuit disconnection (Smith and Allen, 1986; Shroff and Skerman, 1988). Heat and mois-ture may falsely increase the esophageal temperature by about 0.35° C when compared with tympanic or mean body temperature (Bissonnette et al., 1989b).

All heat and moisture exchangers increase the dead space of the anesthesia tubing; however, the smallest ones have a dead space of less than 2 mL. At a fresh gas flow of 30 to 60 L/min, the increase in airway resistance is minimal, typically creating a pressure gradient of less than 2 cm H₂O. Most heat and moisture exchangers now commonly have an in-built filter for bacteria, viruses, and latex particles (Barbara et al., 2001). Copious secretions from the tracheobronchial tree may result in partial or complete obstruction of the filter and thereby severely affect ventilation (Prasad and Chen, 1990; Barnes and Normoyle, 1996; Stacey et al., 1996). The in vitro specifications of the heat and moisture exchangers given by the manufacturers do not always match the actual in vivo performance (Lemmens and Brock-Utne, 2004).

Transportation

Care in the transportation of an infant with regard to temperature management cannot be overemphasized. One short transport (e.g., to the critical care unit) can be enough to render all successful intraoperative efforts to maintain normothermia ineffective. It is therefore essential that the incubator (if available) be fully warmed before transport both to and from the operating room. Older infants and children should at least be covered with a warmed blanket for transport, and if the patient is hypothermic despite all the measures taken in the operating room, it is helpful to bring the forced-air warming blanket with the patient to the critical-care or the post-anesthesia care unit, so that the rewarming process can be continued there.