Thermoregulatory Vasoconstriction Impairs Active Core Cooling

Background: Many clinicians now consider hypothermia indicated during neurosurgery. Active cooling often will be required to reach target temperatures < 34 degrees Celsius sufficiently rapidly and nearly always will be required if the target temperature is 32 degrees Celsius. However, the efficacy even of active cooling might be impaired by thermoregulatory vasoconstriction, which reduces cutaneous heat loss and constrains metabolic heat to the core thermal compartment. The authors therefore tested the hypothesis that the efficacy of active cooling is reduced by thermoregulatory vasoconstriction.

Methods: Patients undergoing neurosurgical procedures with hypothermia were anesthetized with either isoflurane/nitrous oxide (n = 13) or propofol/fentanyl (n = 13) anesthesia. All were cooled using a prototype forced-air cooling device until core temperature reached 32 degrees Celsius. Core temperature was measured in the distal esophagus. Vasoconstriction was evaluated using forearm minus fingertip skin-temperature gradients. The core temperature triggering a gradient of 0 degree Celsius identified the vasoconstriction threshold.

Results: In 6 of the 13 patients given isoflurane, vasoconstriction (skin-temperature gradient = 0 degree Celsius) occurred at a core temperature of 34.4 plus/minus 0.9 degree Celsius, 1.7 plus/minus 0.5 h after induction of anesthesia. Similarly, in 7 of the 13 patients given propofol, vasoconstriction occurred at a core temperature of 34.5 plus/minus 0.9 degree Celsius, 1.6 plus/minus 0.6 h after induction of anesthesia. In the remaining patients, vasodilation continued even at core temperatures of 32 degrees Celsius. Core cooling rates were comparable in each anesthetic group. However, patients in whom vasodilation was maintained cooled fastest. Patients in whom vasoconstriction occurred required nearly an hour longer to reach core temperatures of 33 degrees Celsius and 32 degrees Celsius than did those in whom vasodilation was maintained (P < 0.01).     

Upright posture reduces thermogenesis and augments core hypothermia

We recently reported that baroreceptor-mediated reflexes modulate thermoregulatory vasoconstriction during lower abdominal surgery. Accordingly, we examined the hypothesis that postural differences and the related alterations in baroreceptor loading similarly modulate the thermogenic (i.e., shivering) response to hypothermia in humans. In healthy humans (n = 7), cold saline was infused IV (30 mL/kg at 4 degrees C) for 30 min to decrease core temperature. Each participant was studied on 2 separate days, once lying supine and once sitting upright. Tympanic membrane temperature and oxygen consumption were monitored for 40 min after each saline infusion. The decrease in core temperature upon completion of the infusion in the upright posture position was 1.24 degrees C +/- 0.07 degrees C, which was significantly greater than the 1.02 degrees C +/- 0.06 degrees C seen in the supine position. The core temperature was reduced by 0.59 degrees C +/- 0.07 degrees C in the upright position but only by 0.37 degrees C +/- 0.05 degrees C in the supine position when the increase in oxygen consumption signaling thermogenic shivering occurred. Thus, the threshold temperature for thermogenesis was significantly less in the upright than the supine position. The gain of the thermogenic response did not differ significantly between the positions (363 +/- 69 mL. min(-1). degrees C(-1) for upright and 480 +/- 80 mL. min(-1). degrees C(-1) for supine). The skin temperature gradient was significantly larger in the upright than in the supine posture, suggesting that the peripheral vasoconstriction was augmented by upright posture. Plasma norepinephrine concentrations increased in response to cold saline infusion under both conditions, but the increase was significantly larger in the upright than in the supine posture. Baroreceptor unloading thus augments the peripheral vasoconstrictor and catecholamine response to core hypothermia but simultaneously reduces thermogenesis, which consequently aggravated the core temperature decrease in the upright posture. IMPLICATIONS: Upright posture attenuates the thermogenic response to core hypothermia but augments peripheral vasoconstriction. This divergent result suggests that input from the baroreceptor modifies the individual thermoregulatory efferent pathway at a site distal to the common thermoregulatory center or neural pathway.     

Halothane Selectively Inhibits Nonshivering Thermogenesis: Possible Implications for Thermoregulation during Anesthesia of Infants

Background: During halothane anesthesia, infants fail to increase oxygen consumption in response to a cold stimulus in the form of an increase in temperature gradient between body and environment. Based on recent observations with isolated brown-fat cells, it seemed feasible that this inability to respond could be due to an inhibition of nonshivering thermogenesis during halothane anesthesia.

Methods: The rate of oxygen consumption was measured in cold-acclimated hamsters and rats. The rate evoked by norepinephrine injection in hamsters at an environmental temperature of [nearly equal] 24 degrees Celsius was used as a measure of the capacity for nonshivering thermogenesis. Anesthesia was induced by 3% halothane and maintained by 1.5% halothane. One experimental series with spontaneously breathing hamsters and a second control series with spontaneously breathing rats and with rats whose lungs were mechanically ventilated were conducted.

Results: Norepinephrine injection led to a fourfold increase in the rate of oxygen consumption in control hamsters; after this response had subsided, a second injection led to a similar effect. Halothane anesthesia caused an approximately 20% decrease in resting metabolic rate (P < 0.05) and a 70% inhibition of the thermogenic response to norepinephrine (P < 0.001). The halothane concentration yielding half-maximal inhibitory effect was estimated to be less than 1.0%. After the animals had recovered from halothane anesthesia, a completely restored thermogenic response to norepinephrine was observed. The inhibitory effect of halothane also was observed in hamsters maintained at normothermia and was therefore not secondary to the slight hypothermia that otherwise developed during anesthesia. In a series of control experiments, it was confirmed that rats also showed large thermogenic responses to norepinephrine injections, and it was found that, in spontaneously breathing halothane-anesthetized rats, the thermogenic response to norepinephrine was also much inhibited. Further, in halothane-anesthetized rats whose lungs were mechanically ventilated, and where blood gases were kept at virtually normal levels, the thermogenic response to norepinephrine was found to be similarly markedly inhibited.     

Fructose administration increases intraoperative core temperature by augmenting both metabolic rate and the vasoconstriction threshold

BACKGROUND: The authors tested the hypothesis that intravenous fructose ameliorates intraoperative hypothermia both by increasing metabolic rate and the vasoconstriction threshold (triggering core temperature). METHODS: Forty patients scheduled to undergo open abdominal surgery were divided into two equal groups and randomly assigned to intravenous fructose infusion (0.5 g . kg(-1) . h(-1) for 4 h, starting 3 h before induction of anesthesia and continuing for 4 h) or an equal volume of saline. Each treatment group was subdivided: Esophageal core temperature, thermoregulatory vasoconstriction, and plasma concentrations were determined in half, and oxygen consumption was determined in the remainder. Patients were monitored for 3 h after induction of anesthesia. RESULTS: Patient characteristics, anesthetic management, and circulatory data were similar in the four groups. Mean final core temperature (3 h after induction of anesthesia) was 35.7 degrees +/- 0.4 degrees C (mean +/- SD) in the fructose group and 35.1 degrees +/- 0.4 degrees C in the saline group (P = 0.001). The vasoconstriction threshold was greater in the fructose group (36.2 degrees +/- 0.3 degrees C) than in the saline group (35.6 degrees +/- 0.3 degrees C; P < 0.001). Oxygen consumption immediately before anesthesia induction in the fructose group (214 +/- 18 ml/min) was significantly greater than in the saline group (181 +/- 8 ml/min; P < 0.001). Oxygen consumption was 4.0 l greater in the fructose patients during 3 h of anesthesia; the predicted difference in mean body temperature based only on the difference in metabolic rates was thus only 0.4 degrees C. Epinephrine, norepinephrine, and angiotensin II concentrations and plasma renin activity were similar in each treatment group. CONCLUSIONS: Preoperative fructose infusion helped to maintain normothermia by augmenting both metabolic heat production and increasing the vasoconstriction threshold.     

Fructose Administration Increases Intraoperative Core Temperature by Augmenting Both Metabolic Rate and the Vasoconstriction Threshold

Background: The authors tested the hypothesis that intravenous fructose ameliorates intraoperative hypothermia both by increasing metabolic rate and the vasoconstriction threshold (triggering core temperature).

Methods: Forty patients scheduled to undergo open abdominal surgery were divided into two equal groups and randomly assigned to intravenous fructose infusion (0.5 g [middle dot] kg-1 [middle dot] h-1 for 4 h, starting 3 h before induction of anesthesia and continuing for 4 h) or an equal volume of saline. Each treatment group was subdivided: Esophageal core temperature, thermoregulatory vasoconstriction, and plasma concentrations were determined in half, and oxygen consumption was determined in the remainder. Patients were monitored for 3 h after induction of anesthesia.

Results: Patient characteristics, anesthetic management, and circulatory data were similar in the four groups. Mean final core temperature (3 h after induction of anesthesia) was 35.7[degrees] +/- 0.4[degrees]C (mean +/- SD) in the fructose group and 35.1[degrees] +/- 0.4[degrees]C in the saline group (P = 0.001). The vasoconstriction threshold was greater in the fructose group (36.2[degrees] +/- 0.3[degrees]C) than in the saline group (35.6[degrees] +/- 0.3[degrees]C; P < 0.001). Oxygen consumption immediately before anesthesia induction in the fructose group (214 +/- 18 ml/min) was significantly greater than in the saline group (181 +/- 8 ml/min; P < 0.001). Oxygen consumption was 4.0 l greater in the fructose patients during 3 h of anesthesia; the predicted difference in mean body temperature based only on the difference in metabolic rates was thus only 0.4[degrees]C. Epinephrine, norepinephrine, and angiotensin II concentrations and plasma renin activity were similar in each treatment group.     

Increasing Mean Skin Temperature Linearly Reduces the Core- temperature Thresholds for Vasoconstriction and Shivering in Humans

Background: The contribution of mean skin temperature to the thresholds for sweating and active precapillary vasodilation has been evaluated in numerous human studies. In contrast, the contribution of skin temperature to the control of cold responses such as arteriovenous shunt vasoconstriction and shivering is less well established. Accordingly, the authors tested the hypothesis that mean skin and core temperatures are linearly related at the vasoconstriction and shivering thresholds in men. Because the relation between skin and core temperatures might vary by gender, the cutaneous contribution to thermoregulatory control also was determined in women.

Methods: In the first portion of the study, six men participated on 5 randomly ordered days, during which mean skin temperatures were maintained near 31, 34, 35, 36, and 37 degrees Celsius. Core hypothermia was induced by central venous infusion of cold lactated Ringer's solution sufficient to induce peripheral vasoconstriction and shivering. The core-temperature thresholds were then plotted against skin temperature and a linear regression fit to the values. The relative skin and core contributions to the control of each response were calculated from the slopes of the regression equations. In the second portion of the study, six women participated on three randomly ordered days, during which mean skin temperatures were maintained near 31, 35, and 37 degrees Celsius. At each designated skin temperature, core hypothermia sufficient to induce peripheral vasoconstriction and/or shivering was again induced by central venous infusion of cold lactated Ringer's solution. The cutaneous contributions to control of each response were then calculated from the skin- and core-temperature pairs at the vasoconstriction and shivering thresholds.

Results: There was a linear relation between mean skin and core temperatures at the response thresholds in the men: r = 0.90 plus/minus 0.06 for vasoconstriction and r = 0.94 plus/minus 0.07 for shivering. Skin temperature contributed 20 plus/minus 6% to vasoconstriction and 19 plus/minus 8% to shivering. Skin temperature in the women contributed to 18 plus/minus 4% to vasoconstriction and 18 plus/minus 7% to shivering, values not differing significantly from those in men. There was no apparent correlation between the cutaneous contributions to vasoconstriction and shivering in individual volunteers.     

Effect of Amino Acid Infusion on Central Thermoregulatory Control in Humans

Background: Administration of protein or amino acids enhances thermogenesis, presumably by stimulating oxidative metabolism. However, hyperthermia results even when thermoregulatory responses are intact, suggesting that amino acids also alter central thermoregulatory control. Therefore, the authors tested the hypothesis that amino acid infusion increases the thermoregulatory set point.

Methods: Nine male volunteers each participated on 4 study days in randomized order: (1) intravenous amino acids infused at 4 kJ [middle dot] kg-1 [middle dot] h-1 for 2.5 h combined with skin-surface warming, (2) amino acid infusion combined with cutaneous cooling, (3) saline infusion combined with skin-surface warming, and (4) saline infusion combined with cutaneous cooling.

Results: Amino acid infusion increased resting core temperature by 0.3 +/- 0.1[degrees]C (mean +/- SD) and oxygen consumption by 18 +/- 12%. Furthermore, amino acid infusion increased the calculated core temperature threshold (triggering core temperature at a designated mean skin temperature of 34[degrees]C) for active cutaneous vasodilation by 0.3 +/- 0.3[degrees]C, for sweating by 0.2 +/- 0.2[degrees]C, for thermoregulatory vasoconstriction by 0.3 +/- 0.3[degrees]C, and for thermogenesis by 0.4 +/- 0.5[degrees]C. Amino acid infusion did not alter the incremental response intensity (i.e., gain) of thermoregulatory defenses.     

Effect of amino acid infusion on central thermoregulatory control in humans

BACKGROUND: Administration of protein or amino acids enhances thermogenesis, presumably by stimulating oxidative metabolism. However, hyperthermia results even when thermoregulatory responses are intact, suggesting that amino acids also alter central thermoregulatory control. Therefore, the authors tested the hypothesis that amino acid infusion increases the thermoregulatory set point. METHODS: Nine male volunteers each participated on 4 study days in randomized order: (1) intravenous amino acids infused at 4 kJ x kg(-1) x h(-1) for 2.5 h combined with skin-surface warming, (2) amino acid infusion combined with cutaneous cooling, (3) saline infusion combined with skin-surface warming, and (4) saline infusion combined with cutaneous cooling. RESULTS: Amino acid infusion increased resting core temperature by 0.3 +/- 0.1 degrees C (mean +/- SD) and oxygen consumption by 18 +/- 12%. Furthermore, amino acid infusion increased the calculated core temperature threshold (triggering core temperature at a designated mean skin temperature of 34 degrees C) for active cutaneous vasodilation by 0.3 +/- 0.3 degrees C, for sweating by 0.2 +/- 0.2 degrees C, for thermoregulatory vasoconstriction by 0.3 +/- 0.3 degrees C, and for thermogenesis by 0.4 +/- 0.5 degrees C. Amino acid infusion did not alter the incremental response intensity (i.e., gain) of thermoregulatory defenses. CONCLUSIONS: Amino acid infusion increased the metabolic rate and the resting core temperature. However, amino acids also produced a synchronous increase in all major autonomic thermoregulatory defense thresholds; the increase in core temperature was identical to the set point increase, even in a cold environment with amble potential to dissipate heat. In subjects with intact thermoregulatory defenses, amino acid-induced hyperthermia seems to result from an increased set point rather than increased metabolic rate per se.     

Dexmedetomidine Does Not Alter the Sweating Threshold, But Comparably and Linearly Decreases the Vasoconstriction and Shivering Thresholds

Background: Clonidine decreases the vasoconstriction and shivering thresholds. It thus seems likely that the alpha2 agonist dexmedetomidine will also impair control of body temperature. Accordingly, the authors evaluated the dose-dependent effects of dexmedetomidine on the sweating, vasoconstriction, and shivering thresholds. They also measured the effects of dexmedetomidine on heart rate, blood pressures, and plasma catecholamine concentrations.

Methods: Nine male volunteers participated in this randomized, double-blind, cross-over protocol. The study drug was administered by computer-controlled infusion, targeting plasma dexmedetomidine concentrations of 0.0, 0.3, and 0.6 ng/ml. Each day, skin and core temperatures were increased to provoke sweating and then subsequently reduced to elicit vasoconstriction and shivering. Core-temperature thresholds were computed using established linear cutaneous contributions to control of sweating, vasoconstriction, and shivering. The dose-dependent effects of dexmedetomidine on thermoregulatory response thresholds were then determined using linear regression. Heart rate, arterial blood pressures, and plasma catecholamine concentrations were determined at baseline and at each threshold.

Results: Neither dexmedetomidine concentration increased the sweating threshold from control values. In contrast, dexmedetomidine administration reduced the vasoconstriction threshold by 1.61 +/- 0.80 [degree sign] Celsius [center dot] ng sup -1 [center dot] ml (mean +/- SD) and the shivering threshold by 2.40 +/- 0.90 [degree sign] Celsius [center dot] ng sup -1 [center dot] ml. Hemodynamic responses and catecholamine concentrations were reduced from baseline values, but they did not differ at the two tested dexmedetomidine doses.     

The thermoregulatory threshold in humans during halothane anesthesia

Although suppression of thermoregulatory mechanisms by anesthetics is generally assumed, the extent to which thermoregulation is active during general anesthesia is not known. The only thermoregulatory responses available to anesthetized, hypothermic patients are vasoconstriction and non-shivering thermogenesis. To test anesthetic effects on thermoregulation, the authors measured skin-surface temperature gradients (forearm temperature--finger-tip temperature) as an index of cutaneous vasoconstriction in unpremedicated patients anesthetized with 1% halothane and paralyzed with vecuronium during elective, donor nephrectomy. Patients were randomly assigned to undergo maximal warming (warm room, humidified respiratory gases, and warm intravenous fluids; n = 5) or standard temperature management (no special warming measures; n = 5). Skin-surface temperature gradients greater than or equal to 4 degrees C were prospectively defined as significant vasoconstriction. Normothermic patients [average minimum esophageal temperature = 36.4 +/- 0.3 degrees C (SD)] did not demonstrate significant vasoconstriction. However, each hypothermic patient displayed significant vasoconstriction at esophageal temperatures ranging from 34.0 to 34.8 degrees C (average temperature = 34.4 +/- 0.2 degrees C). These data indicate that active thermoregulation occurs during halothane anesthesia, but that it does not occur until core temperature is approximately equal to 2.5 degrees C lower than normal. In two additional hypothermic patients, increased skin-temperature gradients correlated with decreased perfusion as measured by a laser Doppler technique. Measuring skin-surface temperature gradients is a simple, non-invasive, and quantitative method of determining the thermoregulatory threshold during anesthesia.     

Meperidine Decreases the Shivering Threshold Twice as Much as the Vasoconstriction Threshold

Background: Meperidine administration is a more effective treatment for shivering than equianalgesic doses of other opioids. However, it remains unknown whether meperidine also profoundly impairs other thermoregulatory responses, such as sweating or vasoconstriction. Proportional inhibition of vasoconstriction and shivering suggests that the drug acts much like alfentanil and anesthetics but possesses greater thermoregulatory than analgesic potency. In contrast, disproportionate inhibition would imply a special antishivering mechanism. Accordingly, the authors tested the hypothesis that meperidine administration produces a far greater concentration-dependent reduction in the shivering than vasoconstriction threshold.

Methods: Nine volunteers were each studied on three days: 1) control (no opioid); 2) a target total plasma meperidine concentration of 0.6 micro gram/ml (40 mg/h); and 3) a target concentration of 1.8 micro gram/ml (120 mg/h). Each day, skin and core temperatures were increased to provoke sweating and then subsequently reduced to elicit vasoconstriction and shivering. Core-temperature thresholds (at a designated skin temperature of 34 degrees Celsius) were computed using established linear cutaneous contributions to control sweating (10%) and vasoconstriction and shivering (20%). The dose-dependent effects of unbound meperidine on thermoregulatory response thresholds was then determined using linear regression. Results are presented as means +/- SDs.

Results: The unbound meperidine fraction was [nearly equal] 35%. Meperidine administration slightly increased the sweating threshold (0.5 +/- 0.8 degrees Celsius [center dot] micro gram sup -1 [center dot] ml; r2 = 0.51 +/- 0.37) and markedly decreased the vasoconstriction threshold (-3.3 +/- 1.5 degrees Celsius [center dot] micro gram sup -1 [center dot] ml; r sup 2 = 0.92 +/- 0.08). However, meperidine reduced the shivering threshold nearly twice as much as the vasoconstriction threshold (-6.1 +/- 3.0 degrees Celsius [center dot] micro gram sup -1 [center dot] ml; r2 = 0.97 +/- 0.05; P = 0.001).     

Heat Flow and Distribution during Induction of General Anesthesia

Background: Core hypothermia after induction of general anesthesia results from an internal core-to-peripheral redistribution of body heat and a net loss of heat to the environment. However, the relative contributions of each mechanism remain unknown. The authors evaluated regional body heat content and the extent to which core hypothermia after induction of anesthesia resulted from altered heat balance and internal heat redistribution.

Methods: Six minimally clothed male volunteers in an [nearly equal] 22 degrees Celsius environment were evaluated for 2.5 control hours before induction of general anesthesia and for 3 subsequent hours. Overall heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Arm and leg tissue heat contents were determined from 19 intramuscular needle thermocouples, 10 skin temperatures, and "deep" foot temperature. To separate the effects of redistribution and net heat loss, we multiplied the change in overall heat balance by body weight and the specific heat of humans. The resulting change in mean body temperature was subtracted from the change in distal esophageal (core) temperature, leaving the core hypothermia specifically resulting from redistribution.

Results: Core temperature was nearly constant during the control period but decreased 1.6 plus/minus 0.3 degrees Celsius in the first hour of anesthesia. Redistribution contributed 81% to this initial decrease and required transfer of 46 kcal from the trunk to the extremities. During the subsequent 2 h of anesthesia, core temperature decreased an additional 1.1 plus/minus 0.3 degrees Celsius, with redistribution contributing only 43%. Thus, only 17 kcal was redistributed during the second and third hours of anesthesia. Redistribution therefore contributed 65% to the entire 2.8 plus/minus 0.5 degrees Celsius decrease in core temperature during the 3 h of anesthesia. Proximal extremity heat content decreased slightly after induction of anesthesia, but distal heat content increased markedly. The distal extremities thus contributed most to core cooling. Although the arms constituted only a fifth of extremity mass, redistribution increased arm heat content nearly as much as leg heat content. Distal extremity heat content increased [nearly equal] 40 kcal during the first hour of anesthesia and remained elevated for the duration of the study.     

The effect of meperidine on thermoregulation in mice: involvement of alpha2-adrenoceptors

Meperidine has potent antishivering properties. The underlying mechanisms are not fully elucidated, but recent investigations suggest that alpha2-adrenoceptors are likely to be involved. We performed the current study to investigate the effects of meperidine on nonshivering thermogenesis in a model of thermoregulation in mice. After injection (0.1 mL/kg intraperitoneally) of saline, meperidine (20 mg/kg), the specific alpha2-adrenoceptor antagonist atipamezole (2 mg/kg), plus saline or atipamezole plus meperidine, respectively, mice were positioned in a Plexiglas chamber. Rectal temperature and mixed expired carbon dioxide were measured after provoking thermoregulatory effects by whole body cooling. Maximum response intensity of nonshivering thermogenesis and the thermoregulatory threshold for nonshivering thermogenesis, which was defined as the temperature at which a sustained increase in expiratory carbon dioxide can be measured, were investigated. Meperidine significantly decreased the threshold of nonshivering thermogenesis (36.6 degrees C +/- 0.7 degrees C) versus saline (37.9 degrees C +/- 0.6 degrees C) and versus atipamezole plus saline (37.8 degrees C +/- 0.4 degrees C; P <0.01). This effect was abolished after administration of meperidine combined with atipamezole (37.7 degrees C +/- 0.6 degrees C; P <0.05). Meperidine did not decrease the maximum intensity of nonshivering thermogenesis. The results suggest a major role of alpha2-adrenoceptors in the inhibition of thermoregulation by meperidine in mice.     

Importance of acid-base strategy in reducing myocardial and whole body oxygen consumption during perfusion hypothermia

During induced hypothermia with cardiopulmonary bypass, acid-base management usually follows one of two strategies: the so-called ectothermic or alpha-stat strategy, in which the pH of the arterial blood increases 0.015 pH units for every degree Celsius decrease in body temperature, or the pH-stat strategy, in which pH remains 7.4 at all temperatures. It has been assumed that oxygen consumption decreases approximately equally during hypothermia with either strategy, although there are biochemical reasons to hypothesize that oxygen consumption would be better maintained with the alpha-stat strategy. We also hypothesized that venous oxygen tension would be lower with the more alkaline alpha-stat strategy than with the pH-stat acid-base strategy, because of the Bohr effect. We tested these hypotheses by placing 10 anesthetized immature domestic pigs on cardiopulmonary bypass. We measured whole body oxygen consumption and myocardial oxygen consumption. Control measurements were made at 37 degrees C. Then the animals were cooled to 27 degrees C and the measurements were repeated. The alpha-stat strategy (pH 7.554 +/- 0.020 at 27 degrees C) was used in five animals and five animals received pH-stat management (pH 7.409 +/- 0.012 at 27 degrees C). Whole body and myocardial oxygen consumption rate decreased in both groups, but more so in the alpha-stat animals than in the pH-stat animals. The unexpectedly high oxygen consumption in the pH-stat animals also resulted in a lower than expected venous oxygen tension. Thus the effect of hypothermia in reducing oxygen consumption was less pronounced with pH-stat acid-base management.     

Intraoperative phenylephrine infusion decreases the magnitude of redistribution hypothermia.

Core hypothermia during the first hour after induction of general anesthesia results largely from an internal core-to-peripheral redistribution of body heat. This redistribution results from both central inhibition of tonic thermoregulatory vasoconstriction in the arteriovenous shunt and anesthetic-induced vasodilation. We therefore tested the hypothesis that acute administration of phenylephrine, a pure alpha-adrenergic agonist, reduces the magnitude of anesthetic-induced core-to-peripheral redistribution of body heat. Patients undergoing minor oral surgery were randomly assigned to an infusion of 0.5 microgram.kg-1.min-1 phenylephrine i.v. or no treatment (control). The phenylephrine infusion was started immediately before anesthesia was induced with 2.5 mg/kg propofol i.v. Subsequently, anesthesia was maintained with sevoflurane and 60% nitrous oxide in oxygen. Calf minus toe, skin-temperature gradients < 0 degree C were considered indicative of significant arteriovenous shunt vasodilation. Ambient temperature and end-tidal concentrations of maintenance sevoflurane were comparable in each group. Although there were no significant differences in skin-temperature gradients, core temperatures in the untreated patients decreased significantly more (1.2 +/- 0.4 degrees C) than in those given phenylephrine (0.5 +/- 0.2 degree C, P < 0.001). These data suggest that maintaining precapillary vasoconstriction of blood vessels, not in the arteriovenous shunt reduces the magnitude of redistribution hypothermia. Implications: Core hypothermia immediately after induction of general anesthesia results largely from core-to-peripheral redistribution of body heat. Core temperature reduction during the first hour of anesthesia decreased less in patients given phenylephrine than in untreated controls. These data suggest that maintaining precapillary vasoconstriction possibly reduces the magnitude of redistribution hypothermia.     

Mild and Moderate Hypothermia Provide Better Protection than a Burst-suppression Dose of Thiopental against Ischemic Spinal Cord Injury in Rabbits

Background: Controversy exists over the efficacy of different methods for protecting the spinal cord against experimental ischemic injury. Therefore, the authors compared the protective effects of thiopental with those of hypothermia (35 degrees Celsius and 32 degrees Celsius) on hindlimb motor functions and histopathology after transient spinal cord ischemia.

Methods: Twenty-seven New Zealand white rabbits were assigned to one of the four groups: a thiopental-normothermia group (burst-suppression dose of thiopental; esophageal temperature = 38 degrees Celsius; n = 7), a halothane-mild hypothermia group (halothane, 1%; esophageal temperature = 35 degrees Celsius; n = 7), a halothane-moderate hypothermia group (halothane, 1%; esophageal temperature = 32 degrees Celsius; n = 6), and a halothane-normothermia group (halothane, 1%; esophageal temperature = 38 degrees Celsius; n = 7). The animals were then subjected to 20 min of spinal cord ischemia produced by occlusion of the aorta distal to the origin of left renal artery. Hindlimb motor function was observed for 48 h after reperfusion. Histopathology of the lumbar spinal cord also was examined.

Results: All animals in the halothane-mild hypothermia and halothane-moderate hypothermia groups were neurologically normal 48 h after ischemia. There was no statistical difference in the final neurologic status and histopathology between the thiopental-normothermia and halothane-normothermia groups. However, the final neurologic status and histopathology in both groups were worse than in the halothane-mild hypothermia or halothane-moderate hypothermia groups. There was a strong correlation between the final neurologic status and the numbers of normal neurons in the anterior spinal cord.     

Role of adenosine triphosphate (ATP) in trauma-induced and elective hypothermia

BACKGROUND: In trauma patients hypothermia is a frequent event. According to the literature the majority of trauma patients are presenting a core temperature of less than 34 degrees C at admission. In contrast to the benefit of hypothermia in elective surgery, clinical experience with hypothermia in trauma patients has identified hypothermia to be one major cause of severe posttraumatic complications. It was hypothetized that this diverse effect of hypothermia is related to depletion of high energy phosphates like adenosine-tri-phosphate (ATP) in trauma patients. To verify this hypothesis the relation of ATP plasma levels and hypothermia was examined in a clinical study. METHODS: Three different groups of patients were under study. The first group (group A, normothermic control group) included patients (n = 15) undergoing elective surgery of the lower limb with a mean operation time of 113 minutes. The second study group, hypothermic control (group B), comprised patients (n = 15) that were subjected to elective coronary artery bypass operation under hypothermia (31 degrees C for 48 minutes, mean total operation time being 205 minutes). The third study group (group C) included trauma patients (n = 23, mean ISS of 24.7). At the time of admission 10 patients presented a core temperature > or = 34 degrees C (group C1, mean ISS 25.2, mean TA 34.5 degrees C), 13 patients presented a TA < 34 degrees C (group C2, mean ISS 26.0, mean TA 32.9 degrees C). In both groups of surgical patients the ATP plasma level was measured preoperatively, at 2 hr, 4 hr and 24 hr postoperatively. In trauma patients this measurement was performed at admission and 24 hours later. Within the same schedule body core temperature was recorded and the clinical course was documented as well. RESULTS: Elective limb surgery in normothermic patients resulted only in a transient decrease in ATP plasma levels (preoperative: 87.8 mumol/dl, 4 hr postoperative: 52.0 mumol/dl). At 24 hours the ATP plasma level (62.6 +/- 10.0 mumol/dl) has increased towards baseline level. Elective hypothermia in patients subjected to coronary bypass also resulted only in a transient decrease in ATP plasma levels. During the operation period, including hypothermia, the ATP plasma level was comparable (50.4 mumol/dl) to group A and also returned back towards normal values at 24 hours (58.2 mumol/dl). All trauma patients revealed a significant low ATP plasma level at admission as compared to both control groups. Looking at subdivided groups the most significant drop in ATP plasma level (28.5 mumol/dl) was noted in patients presenting an initial core temperature < 34 degrees C and ISS > 30. Even 24 hours later the ATP level of this subgroup was significantly diminished despite a rise up to 44.4 mumol/dl. In contrast an only moderate drop in ATP plasma concentration (59.2 mmol/dl) was noted in the group of TA > or = 34 degrees C and ISS < 20. This group revealed almost normal values (68.3 mmol/dl) 24 hours after trauma. Beside hypothermia the metabolic state, reflected by the plasma lactate levels, significantly influenced the ATP plasma levels, as high lactate levels were paralleled by low ATP levels. Also the over all outcome was related to injury severity and hypothermia. CONCLUSION: Hypothermia in elective surgery, established by active cooling, preserves the ATP storage and maintains an aerobic metabolism, which both contribute to the beneficial effect of hypothermia in ischemia/reperfusion in cardiovascular surgery. However, in trauma patients hypothermia is caused by insufficient heat production due to utilization of ATP under anaerobic metabolic conditions. Low ATP plasma levels combined with hypothermia seem to be a predisposition for posttraumatic complications like organ failure.     

The effects of urapidil on thermoregulatory thresholds in volunteers

In a previous study we have shown that the antihypertensive drug, urapidil, stops postanesthetic shivering. One possible mechanism in the inhibition of postanesthetic shivering by urapidil may be alterations in thermoregulatory thresholds. We therefore studied the effects of urapidil on vasoconstriction and shivering thresholds during cold-induced shivering in volunteers. Seven healthy male volunteers were cooled by an infusion of saline at 4 degrees C on two study days separated by 48 h. Thermoregulatory vasoconstriction was estimated using forearm minus fingertip skin-temperature gradients, and values exceeding 0 degrees C were considered to represent significant vasoconstriction. The rectal core temperatures at the beginning of shivering and at vasoconstriction were considered the thermoregulatory thresholds. Before cooling, either 25 mg of urapidil or placebo was administered randomly and blindly to each volunteer. When shivering occurred continuously for 10 min, another 25 mg of urapidil was administered IV to completely stop shivering. Urapidil led to a decrease in core temperature at vasoconstriction and shivering threshold by 0.4 degrees C plus/minus 0.2 degrees C (P < 0.001) and 0.5 degrees C plus/minus 0.3 degrees C (P < 0.01), respectively. Oxygen consumption increased during shivering by 70% plus/minus 30% (P < 0.01) in comparison with baseline and decreased levels after shivering stopped, despite the continued low core temperature. Our investigation shows that urapidil stops postanesthetic shivering by decreasing important thermoregulatory thresholds. This means that shivering, not hypothermia, is treated, and hypothermia will need more attention in the postanesthesia care unit. IMPLICATIONS: In this study we show that the antihypertensive drug urapidil stops cold-induced shivering and decreases normal thermoregulatory responses, i.e., the thresholds for vasoconstriction and shivering, in awake volunteers.     

Meperidine and Alfentanil Do Not Reduce the Gain or Maximum Intensity of Shivering

Background: Thermoregulatory shivering can be characterized by its threshold (triggering core temperature), gain (incremental intensity increase with further core temperature deviation), and maximum intensity. Meperidine (a combined micro- and kappa-agonist) treats shivering better than equianalgesic doses of pure micro-opioid agonists. Meperidine's special antishivering action is mediated, at least in part, by a disproportionate decrease in the shivering threshold. That is, meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold, whereas alfentanil (a pure micro-agonist) decreases the vasoconstriction and shivering thresholds comparably. However, reductions in the gain or maximum shivering intensity might also contribute to the clinical efficacy of meperidine. Accordingly, we tested the hypothesis that meperidine reduces the gain and maximum intensity of shivering much more than alfentanil does.

Methods: Ten volunteers were each studied on three separate days: (1) control (no drug); (2) a target total plasma meperidine concentration of 1.2 micro gram/ml; and (3) a target plasma alfentanil concentration of 0.2 micro gram/ml. Skin temperatures were maintained near 31 [degree sign] Celsius, and core temperatures were decreased by central-venous infusion of cold lactated Ringer's solution until maximum shivering intensity was observed. Shivering was evaluated using oxygen consumption and electromyography. A sustained increase in oxygen consumption identified the shivering threshold. The gain of shivering was calculated as the slope of the oxygen consumption versus core temperature regression, and as the slope of electromyographic intensity versus core temperature regression.

Results: Meperidine and alfentanil administration significantly decreased the shivering thresholds. However, neither meperidine nor alfentanil reduced the gain of shivering, as determined by either oxygen consumption or electromyography. Opioid administration also failed to significantly decrease the maximum intensity of shivering.     

Is cerebral blood flow/metabolic mismatch during rewarming a risk factor after profound hypothermic procedures in small children?

The relation between cerebral blood flow and oxygen consumption was studied in six children during cardiac operations with profound hypothermia. A combination of topical cooling and core cooling was used to reduce the nasopharyngeal temperature to 15 degrees C. The alpha-stat principle for pH management was used. Blood flow and oxygen consumption decreased significantly with temperature. At a nasopharyngeal temperature of 15 degrees C, blood flow was reduced to 25% of the awake level, corresponding to 34% of the asleep value obtained 15-30 min after intubation. Oxygen consumption decreased to 25% of the asleep value. During stable profound hypothermia, venous saturation in the jugular bulb was at the same level as 15 min after intubation (70%). Markedly lower values were observed during topical cooling, and particularly during rewarming (down to 21%), indicating a mismatch between cerebral blood flow and oxygen consumption. The speed of rewarming correlated with the fall in venous oxygen saturation (rs = 0.82, P less than 0.05). It is suggested that periods of cerebral blood flow/metabolic mismatch during topical cooling and rewarming may explain postoperative cerebral dysfunction after deep hypothermic procedures. A moderate speed of rewarming is advocated.