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 C sufficiently rapidly and nearly always will be required if the target temperature is 32 degrees C. 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 C. 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 C identified the vasoconstriction threshold. RESULTS: In 6 of the 13 patients given isoflurane, vasoconstriction (skin-temperature gradient = 0 degrees C) occurred at a core temperature of 34.4 +/- 0.9 degree C, 1.7 +/- 0.58 h after induction of anesthesia. Similarly, in 7 of the 13 patients given propofol, vasoconstriction occurred at a core temperature of 34.5 +/- 0.9 degree C, 1.6 +/- 0.6 h after induction of anesthesia. In the remaining patients, vasodilation continued even at core temperatures of 32 degrees C. 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 C and 32 degrees C than did those in whom vasodilation was maintained (P < 0.01). CONCLUSIONS: Vasoconstriction did not produce a full core temperature "plateau," because of the extreme microenvironment provided by forced-air cooling. However, it markedly decreased the rate at which hypothermia developed. The approximately 1-h delay in reaching core temperatures of 33 degrees C and 32 degrees C could be clinically important, depending on the target temperature and the time required to reach critical portions of the operation.     

Postanesthetic vasoconstriction slows peripheral-to-core transfer of cutaneous heat, thereby isolating the core thermal compartment

Forced-air warming during anesthesia increases core temperature comparably with and without thermoregulatory vasoconstriction. In contrast, postoperative forced-air warming may be no more effective than passive insulation. Nonthermoregulatory anesthesia-induced vasodilation may thus influence heat transfer. We compared postanesthetic core rewarming rates in volunteers given cotton blankets or forced air. Additionally, we compared increases in peripheral and core heat contents in the postanesthetic period with data previously acquired during anesthesia to determine how much vasomotion alters intercompartmental heat transfer. Six men were anesthetized and cooled passively until their core temperatures reached 34 degrees C. Anesthesia was then discontinued, and shivering was prevented by giving meperidine. On one day, the volunteers were covered with warmed blankets for 2 h; on the other, volunteers were warmed with forced air. Peripheral tissue heat contents were determined from intramuscular and skin thermocouples. Predicted changes in core temperature were calculated assuming that increases in body heat content were evenly distributed. Predicted changes were thus those that would be expected if vasomotor activity did not impair peripheral-to-core transfer of applied heat. These results were compared with those obtained previously in a similar study of anesthetized volunteers. Body heat content increased 159 +/- 35 kcal (mean +/- SD) more during forced-air than during blanket warming (P < 0.001). Both peripheral and core temperatures increased significantly faster during active warming: 3.3 +/- 0.7 degrees C and 1.1 +/- 0.4 degrees C, respectively. Nonetheless, predicted core temperature increase during forced-air warming exceeded the actual temperature increase by 0.8 +/- 0.3 degree C (P < 0.001). Vasoconstriction thus isolated core tissues from heat applied to the periphery, with the result that core heat content increased 32 +/- 12 kcal less than expected after 2 h of forced-air warming (P < 0.001). In contrast, predicted and actual core temperatures differed only slightly in the anesthetized volunteers previously studied. In contrast to four previous studies, our results indicate that forced-air warming increases core temperature faster than warm blankets. Postanesthetic vasoconstriction nonetheless impeded peripheral-to-core heat transfer, with the result that core temperatures in the two groups differed less than might be expected based on systemic heat balance estimates. Implications: Comparing intercompartmental heat flow in our previous and current studies suggests that anesthetic-induced vasodilation influences intercompartmental heat transfer and distribution of body heat more than thermoregulatory shunt vasomotion.     

Epidural anesthesia impairs both central and peripheral thermoregulatory control during general anesthesia

BACKGROUND: The authors tested the hypotheses that: (1) the vasoconstriction threshold during combined epidural/general anesthesia is less than that during general anesthesia alone; and (2) after vasoconstriction, core cooling rates during combined epidural/general anesthesia are greater than those during general anesthesia alone. Vasoconstriction thresholds and heat balance were evaluated under controlled circumstances in volunteers, whereas the clinical importance of intraoperative thermoregulatory vasoconstriction was evaluated in patients. METHODS: Five volunteers were each evaluated twice. On one of the randomly ordered days, epidural anesthesia (approximately T9 dermatomal level) was induced and maintained with 2-chloroprocaine. On both study days, general anesthesia was induced and maintained with isoflurane (0.7% end-tidal concentration), and core hypothermia was induced by surface cooling and continued for at least 1 h after fingertip vasoconstriction was observed. Patients undergoing colorectal surgery were randomly assigned to combined epidural/enflurane anesthesia (n = 13) or enflurane alone (n = 13). In appropriate patients, epidural anesthesia was maintained by an infusion of bupivacaine. The core temperature that triggered fingertip vasoconstriction identified the threshold. RESULTS: In the volunteers, the vasoconstriction threshold was 36.0 +/- 0.2 degrees C during isoflurane anesthesia alone, but significantly less, 35.1 +/- 0.7 degrees C, during combined epidural/isoflurane anesthesia. Cutaneous heat loss and the rates of core cooling were similar 30 min before vasoconstriction with and without epidural anesthesia. In the 30 min after vasoconstriction, heat loss decreased 33 +/- 13 W when the volunteers were given isoflurane alone, but only 8 +/- 16 W during combined epidural/isoflurane anesthesia. Similarly, the core cooling rates in the 30 min after vasoconstriction were significantly greater during combined epidural/isoflurane anesthesia (0.8 +/- 0.2 degrees C/h) than during isoflurane alone (0.2 +/- 0.1 degrees C/h). In the patients, end-tidal enflurane concentrations were slightly, but significantly, less in the patients given combined epidural/enflurane anesthesia (0.6 +/- 0.2% vs. 0.8 +/- 0.2%). Nonetheless, the vasoconstriction threshold was 34.5 +/- 0.6 degrees C in the epidural/enflurane group, which was significantly less than that in the other patients, 35.6 +/- 0.8 degrees C. When the study ended after 3 h of anesthesia, patients given combined epidural/enflurane anesthesia were 1.2 degrees C more hypothermic than those given general anesthesia alone. The rate of core cooling during the last hour of the study was 0.4 +/- 0.2 degrees C/h during combined epidural/enflurane anesthesia, but only 0.1 +/- 0.3 degrees C/h during enflurane alone. CONCLUSIONS: These data indicate that epidural anesthesia reduces the vasoconstriction threshold during general anesthesia. Furthermore, the markedly reduced rate of core cooling during general anesthesia alone illustrates the importance of leg vasoconstriction in maintaining core temperature.     

Leg temperature and heat content in humans during immersion hypothermia and rewarming

Core temperature afterdrop following cold water immersion has previously been shown to be greater during treadmill exercise than shivering (J. Appl. Physiol. 1987; 63:2375-9). To test the hypothesis that this results from increased transfer of heat from the core to exercising muscles, we quantified the changes in leg temperature and heat content during cooling and exercise/shivering protocols. Upper and lower leg muscle temperatures were measured at multiple depths in five thin healthy male subjects immersed in 8 degrees C water until core temperatures reached 32.8-34.9 degrees C. In these thin subjects there was a significant but small difference between exercise and shivering afterdrop (approximately 0.2 degrees C), and total leg heat content was unchanged during this period with both protocols. Subsequent heat gain was similar in both treatments but, in the lower leg, was greater during exercise than shivering, suggesting that shivering is less effective than exercise in increasing lower leg heat content.     

Heat stroke: opioid-mediated mechanisms

In our previous study in guinea pigs, intensive and prolonged intraperitoneal heating (IPH) caused heat stroke characterized by high mortality and accompanied by two paradoxical phenomena: ear skin vasoconstriction at a high body temperature (Tb) (hyperthermia-induced vasoconstriction) and a post-IPH Tb fall at an ambient temperature (Ta) below thermoneutrality (hyperthermia-induced hypothermia). In this study, we tested the hypothesis that the mechanisms of the two phenomena involve endogenous opioid agonists. Experiments were conducted in 24 unanesthetized, lightly restrained guinea pigs, each chronically implanted with an intraperitoneal thermode and intrahypothalamic thermocouple. The thermoregulatory effects of a wide-spectrum opioid-receptor antagonist, naltrexone (NTX; 50 or 0 mumol/kg sc), were studied in IPH-induced heat stroke and under normal conditions. IPH was accomplished by perfusing (50 ml/min; 80 min) water (45 degrees C) through the thermode. Ta was maintained at approximately 24 degrees C. Skin vasodilation occurred at the onset of IPH but later changed to vasoconstriction despite high Tb and continuing IPH. IPH-induced hyperthermia (1.8 +/- 0.1 degrees C) was followed by a post-IPH Tb fall (-5.1 +/- 0.7 degree C; calculated for the survivors only). The 48-h mortality rate was 50%. NTX prevented the hyperthermia-induced vasoconstriction and attenuated the hyperthermia-induced hypothermia (-1.8 +/- 0.4 degree C). None of the NTX-treated animals died. The effects of NTX on Tb regulation under normal conditions were minor. These results indicate that the phenomena of both hyperthermia-induced vasoconstriction and hyperthermia-induced hypothermia are opioid dependent. The latter is speculated to reflect opioid-mediated inhibition of metabolism; the former is thought to result from opioid-induced hemodynamic alterations. Because both phenomena did not occur in the NTX-treated survivors, the skin vasoconstriction at high Tb and the posthyperthermia Tb fall may be viewed as markers of the severity of heat stroke. It is suggested that opioid antagonists may have therapeutic potential in heat-induced disorders.     

Dobutamine infusion modifies thermoregulation during general anesthesia

A redistribution of body heat from core to peripheral tissues causes a rapid decrease in core temperature. The present study tested whether a dobutamine infusion would facilitate redistribution and induce a further decrease in core temperature. Volunteers were randomly assigned to the control group (n = 8) and the experimental group (n = 8). They were anesthetized with isoflurane at an end-tidal concentration of near 1.2% for 120 min. In the experimental group, dobutamine was infused at a rate of 4 micrograms.kg-1.min-1. Core temperature, skin temperature, tissue temperature, and laser-Doppler perfusion index were measured. Leg heat content was calculated by morphometric data and observed temperatures. The decrease in leg heat content was larger in the control group than in the experimental group 30 min after anesthetic induction (P < 0.05). In contrast, the core temperature decreased further in the dobutamine group than in the control group 40 min after induction (P < 0.05). Dobutamine induced further hypothermia, presumably by facilitating heat transfer and by increasing cutaneous heat loss. Hypothermia will be increased when using dobutamine for anesthesia.     

PCL reconstruction. In vitro biomechanical comparison of ''isometric'' versus single and double-bundled ''anatomic'' grafts

The analgesic tramadol inhibits the neuronal reuptake of norepinephrine and 5-hydroxytryptamine, facilitates 5-hydroxytryptamine release, and activates mu-opioid receptors. Each of these actions is likely to influence thermoregulatory control. We therefore tested the hypothesis that tramadol inhibits thermoregulatory control. Eight volunteers were evaluated on four study days, on which they received no drugs, tramadol 125 mg, tramadol 250 mg, and tramadol 250 mg with naloxone, respectively. Skin and core temperatures were gradually increased until sweating was observed and then decreased until vasoconstriction and shivering were detected. The core temperature triggering each response defined its threshold. Tramadol decreased the sweating threshold by -1.03 +/- 0.67 degrees C microgram-1.mL (r2 = 0.90 +/- 0.12). Tramadol also decreased the vasoconstriction threshold by -3.0 +/- 4.0 degrees C microgram-1.mL (r2 = 0.94 +/- 0.98) and the shivering threshold by -4.2 +/- 4.0 degrees C microgram-1.mL(r2 = 0.98 +/- 0.98). The sweating to vasoconstriction interthreshold range nearly doubled from 0.3 +/- 0.4 degree C to 0.7 +/- 0.6 degree C during the administration of large-dose tramadol (P = 0.04). The addition of naloxone only partially reversed the thermoregulatory effects of tramadol. The thermoregulatory effects of tramadol thus most resemble those of midazolam, another drug that slightly decreases the thresholds triggering all three major autonomic thermoregulatory defenses. In this respect, both drugs reduce the "setpoint" rather than produce a generalized impairment of thermoregulatory control. Nonetheless, tramadol nearly doubled the interthreshold range at a concentration near 200 ng/mL. This indicates that tramadol slightly decreases the precision of thermoregulatory control in addition to reducing the setpoint. IMPLICATIONS: The authors evaluated the effects of the analgesic tramadol on the three major thermoregulatory responses: sweating, vasoconstriction, and shivering. Tramadol had only slight thermoregulatory effects. Its use is thus unlikely to provoke hypothermia or to facilitate fever.     

Inhibition of shivering increases core temperature afterdrop and attenuates rewarming in hypothermic humans

During severe hypothermia, shivering is absent. To simulate severe hypothermia, shivering in eight mildly hypothermic subjects was inhibited with meperidine (1.5 mg/kg). Subjects were cooled twice (meperidine and control trials) in 8 degrees C water to a core temperature of 35.9 +/- 0.5 (SD) degrees C, dried, and then placed in sleeping bags. Meperidine caused a 3.2-fold increase in core temperature afterdrop (1.1 +/- 0.6 vs. 0.4 +/- 0.2 degree C), a 4.3-fold increase in afterdrop duration (89.4 +/- 31.4 vs. 20.9 +/- 5.7 min), and a 37% decrease in rewarming rate (1.2 +/- 0.5 vs. 1.9 +/- 0.9 degrees C/h). Meperidine inhibited overt shivering. Oxygen consumption, minute ventilation, and heart rate decreased after meperidine injection but subsequently returned toward preinjection values after 45 min postimmersion. This was likely due to the increased thermoregulatory drive with the greater afterdrop and the short half-life of meperidine. These results demonstrate the effectiveness of shivering heat production in attenuating the postcooling afterdrop of core temperature and potentiating core rewarming. The meperidine protocol may be valuable for comparing the efficacy of various hypothermia rewarming methods in the absence of shivering.     

Alfentanil slightly increases the sweating threshold and markedly reduces the vasoconstriction and shivering thresholds

BACKGROUND: Hypothermia is common in surgical patients and victims of major trauma; it also results from environmental exposure and drug abuse. In most cases, hypothermia results largely from drug-induced inhibition of normal thermoregulatory control. Although opioids are given to a variety of patients, the thermoregulatory effects of opioids in humans remain unknown. Accordingly, the hypothesis that opioid administration impairs thermoregulatory control was tested. METHODS: Eight volunteers were studied, each on 3 days: (1) a target total plasma alfentanil concentration of 100 ng/ml, (2) control (no drug), and (3) a target alfentanil concentration of 300 ng/ml. Each day, skin and core temperatures were increased sufficiently to provoke sweating. Temperatures subsequently were reduced to elicit peripheral vasoconstriction and shivering. Mathematical compensations were made for changes in skin temperature using the established linear cutaneous contributions to control of sweating (10%) and to vasoconstriction and shivering (20%). From the calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C) and unbound plasma alfentanil concentrations, the individual concentration-response relationship was determined. The concentration-response relationship for all the volunteers was determined similarly using total alfentanil concentrations. RESULTS: In terms of unbound concentration, alfentanil increased the sweating threshold (slope = 0.021 +/- 0.016 degrees C.ng-1.ml; r2 = 0.92 +/- 0.06). Alfentanil also significantly decreased the vasoconstriction (slope = -0.075 +/- 0.067 degrees C.ng-1.ml; r2 = 0.92 +/- 0.07) and shivering thresholds (slope = -0.063 +/- -0.037 degrees C.ng-1.ml; r2 = 0.98 +/- 0.04). In terms of total alfentanil concentration (degrees C.ng-1.ml), the sweating threshold increased according to the equation: threshold (degrees C) = 0.0014[alfentanil] + 37.2 (r2 = 0.33). In contrast, alfentanil produced a linear decrease in the core temperature, triggering vasoconstriction: threshold (degrees C) = -0.0049[alfentanil] + 36.7 (r2 = 0.64). Similarly, alfentanil linearly decreased the shivering threshold: threshold (degrees C) = -0.0057[alfentanil] + 35.9 (r2 = 0.70). CONCLUSIONS: The observed pattern of thermoregulatory impairment is similar to that produced by most general anesthetics: a slight increase in the sweating threshold and a substantial, linear decrease in the vasoconstriction and shivering thresholds.     

Eucapnic hypoxia lowers human cold thermoregulatory response thresholds and accelerates core cooling

Hypoxia lowers the basic thermoregulatory responses of animals and humans. In cold-exposed animals, hypoxia increases core temperature (Tco) cooling rate and suppresses shivering thermogenesis. In humans, the experimental effects of hypoxia on thermoregulation are equivocal. Also, the effect of hypoxia has not been separated from that of hypocapnia consequent to hypoxic hyperventilation. To determine the isolated effects of hypoxia on warm and cold thermoregulatory responses and core cooling during mild cold stress, we examined the Tco thresholds for sweating, vasoconstriction, and shivering as well as the core cooling rates of eight subjects immersed in 28 degrees C water under eucapnic conditions. On 2 separate days, subjects exercised on an underwater cycle ergometer to elevate Tco above the sweating threshold. They then rested and cooled until they shivered vigorously. Subjects inspired humidified room air during the control trial. For the eucapnic hypoxia trial, they inspired 12% O2-balance N2 with CO2 added to maintain eucapnia. Eucapnic hypoxia lowered the Tco thresholds for vasoconstriction and shivering by 0.14 and 0.19 degrees C, respectively, and increased core cooling rate by 33% (1.83 vs. 1.38 degrees C/h). These results demonstrate that eucapnic hypoxia enhances the core cooling rate in humans during mild cold stress. This may be attributed in part to a delay in the onset of vasoconstriction and shivering as well as increased respiratory heat loss during hypoxic hyperventilation.     

Interventional radiologic procedures in postoperative complications after liver transplantation

Because deliberate hypothermia is becoming commonly used during neurosurgery, this study was performed to investigate the effects of a progressive reduction of body core temperature (T) on whole body oxygenation variables in patients undergoing elective intracranial surgery. In 13 patients (Hypothermic Group), T was reduced to 32.0 degrees C using convective-based surface cooling. In six patients (Control Group), T was maintained at 35.5 degrees C during the entire study period. The cardiac index (CI) was determined with a pulmonary artery catheter by thermodilution. Whole body oxygen delivery (DO2) was calculated from CI and arterial oxygen content. Whole body oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (EE) were determined by ventilation gas analysis (indirect calorimetry). Mixed venous oxygen tension at 50% saturated hemoglobin (P50), and whole body oxygen extraction ratio (O2ER) were calculated. Repeated-measures analysis of variance and the Mann-Whitney test were used for statistical analysis. Data are expressed as means +/- SD. VO2 (from 100 +/- 13 to 77 +/- 11 ml.min-1.m-2), VCO2 (from 75 +/- 7 to 57 +/- 7 ml.min-1. m-2), EE (from 667 +/- 67 to 509 +/- 66 kcal.d-1.m-2), P50 (from 23.8 +/- 1.7 to 20 +/- 0.9 mm Hg), and O2ER (from 0.29 +/- 0.05 to 0.22 +/- 0.03%) decreased significantly in the Hypothermic Group between 35.5 and 32.0 degrees C (p < 0.05). None of these variables changed in the Control Group and at 32.0 degrees C VO2, VCO2, EE, P50, and O2ER were significantly lower in the Hypothermic Group than in the Control Group. DO2 remained unchanged in both groups. We conclude that progressive hypothermia in anesthetized patients reduces metabolic rate but does not change DO2. The significant decrease in O2ER may partly be related to a leftward shift of the oxyhemoglobin dissociation curve, as evidenced by the decrease in P50.     

Effect of brain, body, and magnet bore temperatures on energy metabolism during global cerebral ischemia and reperfusion monitored by magnetic resonance spectroscopy in rats

To record brain temperature for comparison with rectal and temporalis muscle temperatures in preliminary studies before MR spectroscopy experiments, a thermistor was inserted into the basal ganglia in eight anesthetized, ventilated, and physiologically monitored rats. The rats were placed in an MR spectrometer and subjected to 60 min of global cerebral ischemia and 2 h of reperfusion without radiofrequency (RF) pulsing. Body temperature was maintained at 37.5-38.0 degrees C (normothermia) or 36.5-37.0 degrees C (mild hypothermia). Brain temperature during ischemia, which dropped to 31.9 +/- 0.3 (hypothermia) and 33.6 +/- 0.5 degrees C (normothermia), correlated with temporalis muscle temperature (r2 = 0.92) but not with body or magnet bore temperature measurements. Ischemia reduced brain temperature approximately 1.7 degrees C in rats subjected to mild hypothermia (1 degree reduction of body temperature). Parallel MR spectroscopy experiments showed no significant difference in energy metabolites between normothermic and hypothermic rats during ischemia. However, the metabolic recovery was more extensive 20-60 min after the onset of reperfusion in hypothermic rats, although not thereafter (P < 0.05). Mild hypothermia speeds metabolic recovery temporarily during reperfusion but does not retard energy failure during global ischemia in rats.     

Thermoregulatory and metabolic responses following cardiac surgery

The thermoregulatory responses in 13 haemodynamically stable patients were evaluated over a 7-h period following coronary artery bypass graft surgery. Cutaneous vasoconstriction was defined by a forearm-to-fingertip skin temperature gradient (delta Tskin) > or = 4 degrees C and muscular hyperactivity was assessed by integrating the electromyographic signals (iEMG). Blood gases and lactate were measured in arterial, mixed venous and femoral venous blood. After arrival in ICU, we observed: (1) mild central hypothermia (Tc = 34.8 +/- 0.6 degrees C) and elevated peripheral vascular resistance in all the patients; (2) delta Tskin > or = 4 degrees C in 11 of 13 patients that persisted until a median Tc of 37.1 degrees C was achieved; (3) a transient increase in iEMG (+ 18%) was accompanied by an increase in total body O2 uptake (+ 28%); (4) elevated muscle O2 extraction rate (56 +/- 18% after 3 h) and lactate release. These data suggest that residual hypothermia in sedated patients after cardiac surgery elicits appropriate thermoregulatory responses that are associated with transient O2 supply/uptake mismatch within skeletal muscles.     

Effects of Shan-dou-gen (Euchresta formosana) on metabolic, respiratory and vasomotor activities as well as body temperature in rats

The effects of the Chinese herb Shan-dou-gen, Euchresta formosana, on metabolic, respiratory and vasomotor activities as well as body temperature were assessed in conscious rats at various ambient temperatures. Systemic administration of Shan-dou-gen produced a dose-dependent hypothermia in rats at room temperature (22 degrees C) and below. The hypothermia in response to Shan-dou-gen was brought about by both cutaneous vasodilatation and decreased metabolic heat production. There were no changes in respiratory evaporative heat loss. However, in the heat (30 degrees C), administration of Shan-dou-gen produced no changes in rectal temperature or other thermoregulatory variables. Furthermore, the hypothermia induced by Shan-dou-gen was greatly antagonized by pretreatment of animals with 5,6-dihydroxytryptamine (predominantly a depletor of central serotonin nerve fiber), but not with 6-hydroxydopamine (a relative depletor of central catecholamine nerve fiber). It appears that the hypothermic effects of Shan-dou-gen may be mediated through serotonin release within the brain.     

Decision making: the context of nurse prescribing

BACKGROUND: Alterations in body temperature result from changes in tissue heat content. Heat flow is a complex function of vasomotor status and core, peripheral, and ambient temperatures. Consequently it is difficult to quantify specific mechanisms responsible for observed changes in body heat distribution. Therefore the authors developed two mathematical models that independently express regional tissue heat production and the motion of heat through tissues in terms of measurable quantities. METHODS: The equilibrium model expresses the effective regional heat transfer coefficient in terms of cutaneous heat flux, skin temperature, and temperature at the center of the extremity. It applies at steady states and provides a ratio of the heat transfer coefficients before and after an intervention. In contrast, the heat flow model provides a time-dependent estimate of the heat transfer coefficient in terms of ambient temperature, skin temperature, and temperature at the center of the extremity. RESULTS: Each model was applied to data acquired in a previous evaluation of heat balance during anesthesia induction. The relation between the ratio of steady state regional heat transfer coefficients calculated using each model was linear. The effective heat transfer coefficient for the forehead (a core site) decreased approximately 20% after induction of anesthesia. In contrast, heat transfer coefficients in the six tested extremity sites more than doubled. CONCLUSIONS: Effective heat transfer coefficients can be used to evaluate the thermal effects of various clinical interventions, such as induction of regional anesthesia or administration of vasodilating drugs. The heat transfer coefficient for the forehead presumably decreased because general anesthesia reduces brain perfusion. In contrast, increased heat transfer coefficients in the extremity sites indicate that thermoregulatory and anesthetic-induced vasodilation more than doubles the core-to-peripheral flow of heat. This flow of heat causes redistribution hypothermia, which is usually the major cause of core hypothermia during anesthesia.     

Infusion of hot crystalloid during operative burn wound debridement

BACKGROUND: Hypothermia exacerbates coagulopathy and is thus a potentially devastating morbidity during operative debridement of burn wounds. Current techniques for maintaining body temperature include warming intravenous fluids at 38 degrees C. The purpose of this study was to assess the safety of infusing saline heated to 55-60 degrees C. METHODS: Using a modified fluid warmer, saline heated to 60 degrees C was infused through central venous access in eight adult patients undergoing debridement of burn wounds. The temperature of the saline actually entering the patient was measured by a thermocouple attached at the connection to the central line catheter. RESULTS: The actual infusate temperature was 54.0 +/- 1.2 degrees C. Over the first hour, 1,100 mL of hot saline was given, thus delivering 17.6 kcal more heat than fluid warmed to the traditional 38 degrees C. Core temperature measured via esophageal and Foley catheters had an insignificant trend toward increase during the operative procedure. There was no evidence of intravascular hemolysis or coagulopathy. CONCLUSION: This pilot study suggests that infusion of hot crystalloids given via central venous access is safe and may be an acceptable adjuvant in attenuating hypothermia during operative procedures.     

Desflurane reduces the febrile response to administration of interleukin-2

BACKGROUND: Intraoperative fever is relatively rare considering how often pyrogenic causes are likely to be present and how common fever is postoperatively. This low incidence suggests that general anesthesia per se inhibits the normal response to pyrogenic stimulation. The authors therefore tested the hypothesis that desflurane-induced anesthesia produces a dose-dependent inhibition of the febrile response. METHODS: Eight volunteers were studied, each on 3 study days. Each was given an intravenous injection of 50,000 IU/ kg of interleukin-2 (elapsed time, 0 h), followed 2 h later by 100,000 IU/kg. One hour after the second dose, the volunteers were assigned randomly to three doses of desflurane to induce anesthesia: (1) 0.0 minimum alveolar concentration (MAC; control), (2) 0.6 MAC, and (3) 1.0 MAC. Anesthesia continued for 5 h. Core temperatures were recorded from the tympanic membrane. Thermoregulatory vasoconstriction was evaluated using forearm-minus-fingertip skin temperature gradients; shivering was evaluated with electromyography. Integrated and peak temperatures during anesthesia were compared with repeated-measures analysis of variance and Scheffé's F tests. RESULTS: Values are presented as mean +/- SD. Desflurane reduced the integrated (area under the curve) febrile response to pyrogen, from 7.7 +/- 2.0 degrees C x h on the control day to 2.1 +/- 2.3 degrees C x h during 0.6 MAC and to -1.4 +/- 3.1 degrees C x h during 1.0 MAC desflurane-induced anesthesia. Peak core temperature (elapsed time, 5-8 h) decreased in a dose-dependent fashion: 38.6 +/- 0.5 degrees C on the control day, 37.7 +/- 0.7 degrees C during 0.6 MAC and 37.2 +/- 1.0 degrees C during 1.0 MAC desflurane anesthesia. Rising core temperature was always associated with fingertip vasoconstriction and often with shivering. CONCLUSIONS: Desflurane-induced anesthesia produced a dose-dependent decrease in integrated and peak core temperatures after administration of pyrogen, with 1.0 MAC essentially obliterating fever. Anesthetic-induced inhibition of the pyrogenic response is therefore one reason that fever is an inconsistent clinical response to inflammation during surgery.     

Selective deimination of vimentin in calcium ionophore-induced apoptosis of mouse peritoneal macrophages

Amino acid infusions during general anesthesia induce thermogenesis and prevent postoperative hypothermia. The effects of increased heat production during anesthesia on postoperative nitrogen balance have not been examined. Therefore, we studied the effect of perioperative amino acid infusions on postoperative nitrogen excretion in 24 patients scheduled for hysterectomy. Seven volunteers not subjected to anesthesia or surgery were used as awake controls. During isoflurane anesthesia, 8 patients received acetated Ringer's solution, and 16 patients received an IV amino acid mixture, 240 kJ/h, before and during anesthesia. Rectal temperature and energy expenditure were measured. The urinary nitrogen content was calculated from urea, creatinine, and urate the day before surgery and for 4 days postoperatively. Diets were recorded. In anesthetized control patients, postoperative nitrogen excretion was less than preoperative levels. Those patients also experienced the largest decrease in core body temperature during anesthesia (1.7+/-0.1 degrees C). All had postoperative shivering. In the amino acid-treated patients, the temperature decrease during anesthesia was less pronounced (1.0+/-0.1 degrees C; P < 0.001) and postoperative shivering disappeared. In addition, the nitrogen excretion was unchanged postoperatively, perhaps indicating an increase in protein turnover known to generate heat. In conclusion, the increase in heat production induced by amino acids reduced hypothermia, abolished shivering, and attenuated/normalized the postoperative nitrogen saving that occurred in patients who did not receive amino acids. IMPLICATIONS: We compared nitrogen excretion before and after surgery in patients who received a saline or amino acid infusion during isoflurane anesthesia. The increase in heat production induced by amino acids reduced hypothermia, abolished shivering, and attenuated/normalized the postoperative nitrogen saving that occurred in patients who did not receive amino acids.     

Quantitative changes in periplasmic proteins of the macronucleus-specific bacterium Holospora obtusa in the infection process of the ciliate Paramecium caudatum

PURPOSE: This study was conducted to test the hypothesis that clonidine produces a dose-dependent increase in the sweating threshold and dose-dependent decreases in vasoconstriction and shivering thresholds. METHODS: Six healthy subjects (two female) were studied on four days after taking clonidine in oral doses of either 0 (control), 3, 6 or 9 micrograms.kg-1. The order followed a balanced design in a double-blind fashion. Oesophageal temperature and mean skin temperature (from 12 sites) were measured. Subjects were seated in 37 degrees C water which was gradually warmed until sweating occurred (sweat rate increased above 50 g.m-2.h-1). The water was then cooled gradually until thresholds for vasoconstriction (onset of sustained decrease in fingertip blood flow) and shivering (sustained elevation in metabolism) were determined. Thresholds were then referred to as the core temperature, adjusted to a designated mean skin temperature of 33 degrees C. RESULTS: High dose clonidine similarly decreased the adjusted core temperature thresholds for vasoconstriction by 1.16 +/- 0.30 degrees C and for shivering by 1.63 +/- 0.23 degrees C (P < 0.01). The dose response effects were linear for both cold responses with vasoconstriction and shivering thresholds decreasing by 0.13 +/- 0.05 and 0.19 +/- 0.09 degree C.microgram-1 respectively (P < 0.0001). The sweating threshold was unaffected by clonidine, however the interthreshold range between sweating and vasoconstriction thresholds increased from control (0.19 +/- 0.48 degree C) to high dose clonidine (1.31 +/- 0.54 degrees C). CONCLUSION: The decreases in core temperature thresholds for cold responses and increased interthreshold range are consistent with the effects of several anaesthetic agents and opioids and is indicative of central thermoregulatory inhibition.     

Malignant melanoma in Europe: changes in mortality rates (1970-90) in European Community countries

We measured metabolic rates (mL O2 h-1, converted to kcal d-1), deep body temperatures (degree C), and skin temperatures (degree C) and calculated whole-animal thermal conductances (mL O2 g-1 h-1 degree C-1) of five 3-yr-old harbor seals (Phoca vitulina concolor) at air temperatures between -20 degrees and 35 degrees C. The mean thermal neutral zone of these seals extended from a lower critical temperature of -12.9 degrees +/- 1.6 degrees C (SD) to an upper critical temperature of 28.6 degrees +/- 1.7 degrees C. Hyperthermia was observed at an ambient air temperature of 35 degrees C. Mean standard metabolic rate was 1,553.6 +/- 168.2 kcal d-1, about 1.2 times the value expected for adult animals of similar body mass (mean mass = 49.2 +/- 7.5 kg). Mean deep body temperature increased from 37.5 degrees +/- 0.30 degrees C at an ambient temperature of 30 degrees C and reached 39.3 degrees +/- 0.33 degrees C at an ambient temperature of 35 degrees C. Skin temperature decreased with decreasing ambient temperature but remained well above ambient temperature. Mean whole-animal thermal conductance decreased from an ambient temperature of 35 degrees C until it reached a minimum value of 0.007 mL O2 g-1 h-1 degree C-1 at -4.0 degrees C; it then increased with a further decrease in ambient temperature. In comparison to the thermal limits of the same seals during their first year of life, the results indicate a broadening of the thermal neutral zone with age: an 11 degrees C decrease in the lower critical temperature and a 3.5 degrees C increase in the upper critical temperature. These findings suggest that warm ambient air temperatures should not pose any particular thermoregulatory problems for larger and older harbor seals, even beyond the limits of their current annual distribution.