FEW physiologic functions are so well guarded as the thermoneutral zone. It is kept within a narrow limit of ±0.2°C via  most sophisticated sensing/effector mechanisms. This way, optimal working conditions for the cellular machinery are preserved. During anesthesia, the thermoneutral zone widens by a factor of 10.1Therefore, protective measures to prevent heat loss, such as vasoconstriction, may be impaired, permitting redistribution of body heat from core to periphery.

Countermeasures commonly used in clinical practice include external heating by convection, conduction, and radiation. In this issue of Anesthesiology, Mizobe et al.  2approach the problem of heat loss and temperature balance during anesthesia by infusing fructose solutions to stimulate endogenous heat production. This is an innovative approach to control core body temperature via  nutrient driven endogenous mechanisms.

To be sure, manipulating endogenous heat production, particularly during the anesthetized state, calls for caution. There are few mechanisms that govern heat production when compensation for overheating is needed. The only mechanism by which we are able to decrease body heat is by sweating, which is known to be delayed during anesthesia.1,3,4Anesthesiologists are very much aware of the overheating problem during anesthesia because they sometimes are being confronted with the rare but threatening syndrome of malignant hyperthermia. This metabolic condition is a good example of how endogenous heat production can be deleterious.

Obligatory heat production, from basal metabolism and muscular exercise, is reduced by up to 25% by anesthesia.5,6Facultative heat gain from shivering and nonshivering thermogenesis are both reduced during anesthesia.1,7Mizobe et al.  demonstrate that it is possible to improve temperature balance by infusion of fructose before and during anesthesia. Is this accomplished by an increased obligatory heat production or is it due to the facultative alternatives of shivering and nonshivering thermogenesis? In conformity with what Mizobe et al.  demonstrated for fructose solutions, previous investigations have reached similar results after infusion of amino acid solutions.8,9In those studies of both awake and anesthetized adult humans, it was demonstrated that heat production caused by amino acid infusions occurred in muscle tissue.6However, responsible cellular mechanisms have not been clarified. A specific finding in previous studies that justifies caution with this approach was that heat production from 2.25 g amino acids per hour more than doubled heat production during anesthesia as compared with during the awake state.8Because recent reports have identified uncoupling proteins in skeletal muscle,10there are possibilities for an exaggerated mitochondrial heat production, such as malignant hyperthermia, from which the anesthetized individual has little chance to protect himself or herself because sweating, as stated above, is delayed as a result of the widened thermoneutral zone. In agreement with previous findings of enhanced heat production during anesthesia,8it was of great interest that heat production from the same amount of fructose was 20% higher during anesthesia as compared with during the awake state.2One wonders why. Nature has provided an interesting example. In a tetraplegic human, a defined amount of protein or amino acids result in a higher heat production than in a nontetraplegic individual.11Enhanced heat production from tetraplegics and from the unconscious anesthetized individual challenge the assumption that there might be descending inhibitory neuronal pathways permitting central nervous functions to balance metabolic rate and heat production.

So it now seems that stimulated endogenous heat production by either fructose or amino acid solutions reduces the degree of hypothermia during and after anesthesia. Although some concern has been raised with similar approaches that overheating could occur, this has not yet been reported. Another concern, raised in the late 1990s, was that the stimulated endogenous heat production during anesthesia enhances postoperative oxygen consumption.9This could have negative effects, particularly in cardiac patients with a compromised coronary circulation, but may be preferable to the shivering that may otherwise result. Indeed, previous reports on stimulated endogenous heat production during anesthesia have indicated that postoperative shivering disappears.12This may be beneficial, because postoperative shivering is relatively inefficient and may dramatically increase myocardial oxygen demands.12Shivering may also be associated with impaired quality of care, increased use of medications, and pain. It would be of interest to compare in future studies indices of oxygenation and myocardial oxygen demands in patients warmed with exogenous and endogenous methods.

Although basic mechanisms responsible for stimulated endogenous heat production during anesthesia are not well delineated, it seems to be an effective method to improve temperature balance during anesthesia and surgery. We know that improved control of perioperative temperature has definite practical benefit to important outcomes such as hospital duration of stay.12We already have effective means to do so using exogenous heating. Before this method using endogenous heating could be widely adopted, important questions remain, such as the capacity to precisely set the “furnace” during anesthesia and indeed a better understanding of the of central mechanisms responsible for this effect. Other issues of importance when comparing the two methods that will be important to address include cost effectiveness and provider compliance with regimens. Nonetheless, given the importance of perioperative temperature control, this is a promising method that deserves further evaluation.

Department of Anesthesiology and Intensive Care, Karolinska University Hospital, and Karolinska Institute, Stockholm, Sweden. sten.lindahl@karolinska.se

Sessler DI: Temperature monitoring, Anesthesia, 5th edition. Edited by R.D. Miller. New York, Churchill Livingstone, 2000, pp 1367–89R.D. Miller
New York
Churchill Livingstone
Mizobe T, Nakajima Y, Ueno H, Sessler DI: Fructose administration increases intraoperative core temperature by augmenting both metabolic rate and the vasoconstriction threshold. Anesthesiology 2006; 104:1124–30
Greger R: The formation of sweat, Comprehensive Human Physiology, 1st ed. Edited by Greger R, Winhorst U. Berlin, Springer-Verlag, pp 2219–28Greger R, Winhorst U
Boulant JA: Neural thermal reception and regulation of body temperature, Physiology and Pathophysiology of Temperature Regulation. Edited by Blatteis CM. Singapore, World Scientific, pp 94–104Blatteis CM
World Scientific
Brismar B, Hedenstierna G, Lundh R, Tokics L: Oxygen uptake, plasma catecholamines and cardiac output during neurolept-nitrous oxide and halothane anesthesias. Acta Anaesthesiol Scand 1982; 26:541–9
Sellden E, Bränström R, Brundin T: Augmented thermic effect of amino acids under general anaesthesia occurs predominantly in extra-splanchnic tissues. Clin Sci 1996; 96:431–9
Ohlsson KBE, Mohell N, Cannon B, Lindahl SGE, Nedergaard J: Thermogenesis in Brown adipocytes is inhibited by volatile anesthetic agents. Anesthesiology 1994; 81:176–83
Sellden E, Brundin T, Wahren J: Augmented thermic effect of amino acids under general anesthesia: A mechanism useful for prevention of anaesthesia-induced hypothermia. Clin Sci 1994; 86:611–8
Sellden E, Lindahl SGE: Amino acid-induced thermogenesis to prevent hypothermia during anesthesia is not associated with increased stress response. Anesth Analg 1998; 87:637–40
Hjeltnes N, Fernström M, Zierath JR, Krook A: Regulation of UCP2 and UCP3 by muscle disuse and physical activity in tetraplegic subjects. Diabetologica 1999; 42:826–30
Aksnes A-K, Brundin T, Wahren J: Metabolic, thermal and circulatory effects of intravenous infusion of amino acids in tetraplegic patients with complete spinal cord lesions. Clin Physiol 1995; 15:377–96
Sellden E, Lindahl SGE: Amino-acid induced thermogenesis reduces hypothermia during anesthesia and shortens hospital stay. Anesth Analg 1999; 89:1551–6