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.     

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.     

The thermoregulatory threshold in humans during nitrous oxide-fentanyl anesthesia

Narcotics and nitrous oxide (N2O) inhibit thermoregulatory responses in animals. The extent to which N2O/fentanyl anesthesia lowers the thermoregulatory threshold in humans was tested by measuring peripheral cutaneous vasoconstriction using skin-surface temperature gradients (forearm temperature-fingertip temperature) and the laser Doppler perfusion index. Fifteen unpremedicated patients were anesthetized with N2O (70%) and fentanyl (10 micrograms/kg iv bolus followed by 4 micrograms.kg-1.h-1 infusion) during elective, donor nephrectomy. Patients were randomly assigned to undergo additional warming (humidified respiratory gases, warmed intravenous fluids, and a heating blanket over the legs; n = 5) or standard temperature management (no special warming measures; n = 10). Significant vasoconstriction was prospectively defined as a skin-surface temperature gradient between forearm surface and finger-tip surface greater than or equal to 4 degrees C, and the thermoregulatory threshold was defined as the esophageal temperature at which such vasoconstriction occurred. Vasoconstriction did not occur in the patients who received additional warming and thus remained nearly normothermic [average minimum esophageal temperature = 35.8 +/- 0.4 degrees C (SD)] but did in six hypothermic patients at a mean esophageal temperature of 34.2 +/- 0.5 degrees C. Four hypothermic patients developed a passive thermal steady state without becoming sufficiently cold to trigger vasoconstriction. Thus, active thermoregulation occurs during N2O/fentanyl anesthesia but does not occur until core temperatures are approximately 2.5 degrees C lower than normal. The thermoregulatory threshold during N2O/fentanyl anesthesia is similar to that previously determined during halothane (34.4 +/- 0.2 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)     

Thermoregulatory vasoconstriction decreases cutaneous heat loss

To determine the extent to which thermoregulatory vasoconstriction decreases heat loss to the environment, we measured regional heat flux, average skin temperature, and tympanic membrane temperature before and after thermoregulatory vasoconstriction in five minimally clothed volunteers maintained in a 30.8 +/- 0.1 degrees C environment. Thermoregulatory vasoconstriction was induced by central venous infusion of cooled fluid. Peripheral cutaneous blood flow was evaluated with venous-occlusion volume plethysmography and skin-surface temperature gradients. Laser Doppler flowmetry was used to measure vasoconstriction in centrally located skin. This model mimics the common clinical situation in which patients in a warm environment are centrally cooled by administration of cold intravenous fluids or by lavage of internal cavities with cold fluids. Tympanic membrane temperature decreased 1.5 +/- 0.3 degrees C in the first 15 min after the cold fluid infusion was started and remained approximately 1 degrees C below control values during the rest of the study. Average skin-surface temperature decreased slowly to approximately 0.7 degrees C below control. Flow in capillaries of centrally distributed skin, determined with laser Doppler flowmetry, decreased only approximately 40%. Total heat flux, and flux from the arms and legs decreased approximately 25% (15.5 +/- 0.3 W). Heat loss from the trunk and head decreased only 17%, whereas, loss from the hands and feet (10.5% of the body surface area) decreased approximately 50%. All measured values decreased significantly following vasoconstriction (P less than 0.01). Therefore, thermoregulatory vasoconstriction in a thermoneutral environment appears to decrease cutaneous loss of metabolic heat approximately 25%.     

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.     

Amino acid-induced thermogenesis reduces hypothermia during anesthesia and shortens hospital stay

Amino acid infusion during general anesthesia induces thermogenesis and prevents postoperative hypothermia and shivering. We propose that amino acid prevention of hypothermia during anesthesia shortens the hospital stay. Core temperatures and pulmonary oxygen uptake were measured in 45 patients, receiving an IV amino acid mixture, 126 mL/h, before and/or during isoflurane anesthesia and 30 control patients receiving acetated Ringer's solution. At awakening, mean core temperature was 36.5 degrees+/-0.1 degrees C in the amino acid group and 35.7 degrees+/-0.1 degrees C (P < 0.001) in the controls. Energy expenditure increased by 54%+/-9% from baseline in amino acid patients in whom shivering was uncommon, but only by 5%+/-4% (P < 0.001) in control patients, of whom the majority developed postoperative shivering. The estimated difference in hospital stay between the two groups was 2.7 days (CI 95%: 1.3-4.0). Multiple regression analysis showed that the variables best predicting hospitalization were duration of surgery, amino acid treatment, and awakening temperatures. Duration of surgery was similar in the two groups and core temperatures at awakening were a result of amino acid infusion, which indicates that amino acid infusion during anesthesia and surgery was the most important factor for the shorter hospitalization. IMPLICATIONS: Amino acid infusion during general anesthesia induces thermogenesis and prevents postoperative hypothermia and shivering. Multiple regression analysis indicated that this resulted in a shorter hospital stay.     

Efficacy of Two Methods for Reducing Postbypass Afterdrop

Background: Afterdrop, defined as the precipitous reduction in core temperature after cardiopulmonary bypass, results from redistribution of body heat to inadequately warmed peripheral tissues. The authors tested two methods of ameliorating afterdrop: (1) forced-air warming of peripheral tissues and (2) nitroprusside-induced vasodilation.

Methods: Patients were cooled during cardiopulmonary bypass to approximately 32[degrees]C and subsequently rewarmed to a nasopharyngeal temperature near 37[degrees]C and a rectal temperature near 36[degrees]C. Patients in the forced-air protocol (n = 20) were assigned randomly to forced-air warming or passive insulation on the legs. Active heating started with rewarming while undergoing bypass and was continued for the remainder of surgery. Patients in the nitroprusside protocol (n = 30) were assigned randomly to either a control group or sodium nitroprusside administration. Pump flow during rewarming was maintained at 2.5 l [middle dot] m-2 [middle dot] min-1 in the control patients and at 3.0 l [middle dot] m-2 [middle dot] min-1 in those assigned to sodium nitroprusside. Sodium nitroprusside was titrated to maintain a mean arterial pressure near 60 mmHg. In all cases, a nasopharyngeal probe evaluated core (trunk and head) temperature and heat content. Peripheral compartment (arm and leg) temperature and heat content were estimated using fourth-order regressions and integration over volume from 18 intramuscular needle thermocouples, nine skin temperatures, and "deep" hand and foot temperature.

Results: In patients warmed with forced air, peripheral tissue temperature was higher at the end of warming and remained higher until the end of surgery. The core temperature afterdrop was reduced from 1.2 +/- 0.2[degrees]C to 0.5 +/- 0.2[degrees]C by forced-air warming. The duration of afterdrop also was reduced, from 50 +/- 11 to 27 +/- 14 min. In the nitroprusside group, a rectal temperature of 36[degrees]C was reached after 30 +/- 7 min of rewarming. This was only slightly faster than the 40 +/- 13 min necessary in the control group. The afterdrop was 0.8 +/- 0.3[degrees]C with nitroprusside and lasted 34 +/- 10 min which was similar to the 1.1 +/- 0.3[degrees]C afterdrop that lasted 44 +/- 13 min in the control group.     

Nefopam, a Nonsedative Benzoxazocine Analgesic, Selectively Reduces the Shivering Threshold in Unanesthetized Subjects

Background: The analgesic nefopam does not compromise ventilation, is minimally sedating, and is effective as a treatment for postoperative shivering. The authors evaluated the effects of nefopam on the major thermoregulatory responses in humans: sweating, vasoconstriction, and shivering.

Methods: Nine volunteers were studied on three randomly assigned days: (1) control (saline), (2) nefopam at a target plasma concentration of 35 ng/ml (low dose), and (3) nefopam at a target concentration of 70 ng/ml (high dose, approximately 20 mg total). Each day, skin and core temperatures were increased to provoke sweating and then reduced to elicit peripheral vasoconstriction and shivering. The authors determined the thresholds (triggering core temperature at a designated skin temperature of 34[degrees]C) by mathematically compensating for changes in skin temperature using the established linear cutaneous contributions to control of each response.

Results: Nefopam did not significantly modify the slopes for sweating (0.0 +/- 4.9[degrees]C [middle dot] [mu]g-1 [middle dot] ml; r2 = 0.73 +/- 0.32) or vasoconstriction (-3.6 +/- 5.0[degrees]C [middle dot] [mu]g-1 [middle dot] ml; r2 = -0.47 +/- 0.41). In contrast, nefopam significantly reduced the slope of shivering (-16.8 +/- 9.3[degrees]C [middle dot] [mu]g-1 [middle dot] ml; r2 = 0.92 +/- 0.06). Therefore, high-dose nefopam reduced the shivering threshold by 0.9 +/- 0.4[degrees]C (P < 0.001) without any discernible effect on the sweating or vasoconstriction thresholds.     

Dietary-induced thermogenesis and perioperative thermoregulation

After the ingestion or infusion of nutrients, there is an increase in energy expenditure which has been referred to as dietary or nutrient-induced thermogenesis. This thermogenesis induced by protein or amino acids is well known to be largest and most prolonged. According to these physiological backgrounds, preoperative amino acid infusion was reported to prevent postoperative hypothermia during general anesthesia and spinal anesthesia. Also, perioperative amino acid infusion is reported to improve the outcome of the patients undergoing off-pump CABG. Amino acid infusion was observed to shift upward the threshold core temperature for thermoregulatory vasoconstriction as well as to increase energy expenditure. Fructose also prevents perioperative hypothermia during surgery by the same mechanisms.     

Amino acid infusion induces thermogenesis and reduces blood loss during hip arthroplasty under spinal anesthesia

The thermic effect of amino acids is augmented under general anesthesia and counteracts hypothermia. Mild hypothermia may increase surgical bleeding. We studied whether amino acids also induce thermogenesis under spinal anesthesia and whether this endogenous heat production reduces bleeding during hip arthroplasty. Rectal temperature, oxygen uptake, and perioperative bleeding were measured in 22 patients receiving an IV amino acid mixture (Vamin 18), 240 kJ/h) for 1 h before and then during spinal anesthesia and in 24 control patients receiving acetated Ringer's solution. Blood loss was calculated after surgery by weighing the swabs and the content of the suction tubes after subtraction of the saline used. After surgery, the closed drains were weighed after 24 h. In the amino acid group, the preanesthesia temperature increased by 0.4 degrees C +/- 0.2 degrees C (P < 0.01) and was unchanged in controls. At end of surgery, core temperature had decreased by 0.9 degrees C +/- 0.4 degrees C in controls and by 0.4 degrees C +/- 0.3 degrees C in the amino acid patients (P < 0.01). Oxygen uptake increased by 26 +/- 7 mL/min, or 16% +/- 5% (P < 0.05), from baseline in the amino acid patients, whereas it was unchanged in the controls. Blood loss during surgery was significantly larger in the control patients (702 +/- 344 mL) than in the amino acid patients (516 +/- 272 mL) (P < 0.05). After surgery, there were no significant differences in shed blood volume. In conclusion, amino acid infusion also induced a thermogenic response under spinal anesthesia. In addition, the prevention of temperature decrease during spinal anesthesia seemed to have a positive effect on intraoperative blood loss. IMPLICATIONS: Infusion of a balanced mixture of amino acids during spinal anesthesia prevented core body temperature decrease. Bleeding was also less pronounced.     

Elevated Thermostatic Setpoint in Postoperative Patients

Background: The mechanism and clinical relevance of increased core temperature (Tc) after surgery are poorly understood. Because fever is used as a diagnostic sign of infection, it is important to recognize what constitutes the normal postoperative thermoregulatory response. In the current study the authors tested the hypothesis that a regulated increase in Tc setpoint occurs after surgery.

Methods: The authors prospectively studied 271 patients in the first 24 h after a variety of vascular, abdominal, and thoracic surgical procedures. Tc measured in the urinary bladder, skin-surface temperatures, thermoregulatory responses (vasoconstriction and shivering), and total leukocyte counts were assessed. In a subset of 34 patients, plasma concentrations of tumor necrosis factor, interleukin (IL)-6, and IL-8 were measured before and after surgery.

Results: In the early postoperative period, the maximum increase in Tc above the preoperative baseline averaged 1.4 +/- 0.8[degrees]C (2.5 +/- 1.4[degrees]F), with the Tc peak occurring 11.1 +/- 5.8 h after surgery. Fifty percent of patients had a maximum Tc greater than or equal to 38.0[degrees]C (100.4[degrees]F) and 25% had a maximum Tc greater than or equal to 38.5[degrees]C (101.3[degrees]F). The progressive postoperative increase in Tc was clearly associated with cutaneous vasoconstriction and shivering, indicating a regulated elevation in Tc setpoint. The elevated Tc was associated with an increased IL-6 response but not with leukocytosis. Maximum postoperative Tc was positively correlated with duration and extent of the surgical procedure.     

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.     

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).     

Atropine prevents midazolam-induced core hypothermia in elderly patients.

STUDY OBJECTIVE: To test the hypothesis that core temperature is well preserved when atropine and midazolam are combined. DESIGN: Randomized, blinded study. SETTING: Department of Anesthesia, Yamanashi Medical University. PATIENTS: 40 elderly, ASA physical status I and II patients (aged more than 60 years). INTERVENTIONS: Patients were randomly assigned (n = 10 per group) to premedication with: 1) saline control; 2) midazolam 0.05 mg/kg; 3) atropine 0.01 mg/kg; and 4) midazolam 0.05 mg/kg combined with atropine 0.01 mg/kg. All premedication was given on the ward at approximately 8:30 am, approximately 30 minutes before induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Core temperatures were measured at the right tympanic membrane. Mean skin temperature was calculated as 0.3 x (T(chest) + T(arm)) + 0.2 x (T(thigh) + T(calf)). Fingertip perfusion was evaluated using forearm minus fingertip and calf minus toe, skin-surface temperature gradients. Temperatures were evaluated at the time of premedication and 30 minutes later, just before induction of anesthesia. Core temperature remained nearly constant in the control patients (0.1 +/- 0.2 degrees C; mean +/- SD), whereas it decreased significantly in the patients given midazolam alone (-0.3 +/- 0.1 degrees C). Atropine alone increased core temperature (0.3 +/- 0.2 degrees C), although the increase was not statistically significant. The combination of midazolam and atropine attenuated the hypothermia induced by midazolam alone (0.0 +/- 0.2 degrees C). Initial skin-temperature gradients exceeded 0 degrees C in all groups, indicating that the patients were vasoconstricted. The gradients were unchanged by premedication with saline or atropine. Midazolam significantly decreased the gradient (-1.8 +/- 1.1 degrees C), as did the combination of midazolam and atropine (-1.4 +/- 0.9 degrees C). CONCLUSIONS: The thermoregulatory effects of benzodiazepine receptor agonist and cholinergic inhibitors oppose each other, and the combination leaves core temperature unchanged.     

Perioperative amino acid infusion improves recovery and shortens the duration of hospitalization after off-pump coronary artery bypass grafting

Perioperative amino acid infusion helps maintain core temperature and improves patient outcomes after gynecologic and orthopedic surgery. In the present study we prospectively determined the effect of amino acid infusion on esophageal core temperature and postoperative outcomes during off-pump coronary artery bypass grafting (CABG). One-hundred-eighty consecutive patients undergoing primary elective or urgent off-pump CABG were randomly divided into two groups: the i.v. amino acid infusion group (4 kJ kg(-1) h(-1) starting 2 h before surgery) and the saline infusion group (similar period and volume of saline infusion). The esophageal core temperature at the end of surgery was 35.6 (35.3-35.8) degrees C [mean (95% confidence interval)] in the saline infusion group and 36.1 degrees C (35.9-36.3) degrees C in the amino acid infusion group (P = 0.01). Kaplan-Meier analysis demonstrated that patients given amino acids required a significantly shorter duration of postoperative mechanical ventilation than patients given saline [median (95% confidence interval), 3.0 (2.5-3.9) vs 4.5 (3.8-5.8) h; P = 0.01]. Furthermore, intensive care unit stay [20 (19.5-38.4) vs 44 (21-45) h; P = 0.001] and days until fit for discharge from hospital [10 (9-11) vs 12 (11-13) days; P = 0.004] were significantly shorter in patients given amino acid. Perioperative amino acid infusion in patients undergoing off-pump CABG effectively minimizes intraoperative hypothermia and improves postoperative recovery.     

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.     

Core Cooling by Central Venous Infusion of Ice-cold (4°C and 20°C) Fluid: Isolation of Core and Peripheral Thermal Compartments

Background: Central venous infusion of cold fluid may be a useful method of inducing therapeutic hypothermia. The aim of this study was to quantify systemic heat balance and regional distribution of body heat during and after central infusion of cold fluid.

Methods: The authors studied nine volunteers, each on two separate days. Anesthesia was maintained with use of isoflurane, and on each day 40 ml/kg saline was infused centrally over 30 min. On one day, the fluid was 20[degrees]C and on the other it was 4[degrees]C. By use of a tympanic membrane probe core (trunk and head) temperature and heat content were evaluated. Peripheral compartment (arm and leg) temperature and heat content were estimated with use of fourth-order regressions and integration over volume from 18 intramuscular thermocouples, nine skin temperatures, and "deep" hand and foot temperature. Oxygen consumption and cutaneous heat flux estimated systemic heat balance.

Results: After 30-min infusion of 4[degrees]C or 20[degrees]C fluid, core temperature decreased 2.5 +/- 0.4[degrees]C and 1.4 +/- 0.2[degrees]C, respectively. This reduction in core temperature was 0.8[degrees]C and 0.4[degrees]C more than would be expected if the change in body heat content were distributed in proportion to body mass. Reduced core temperature resulted from three factors: (1) 10-20% because cutaneous heat loss exceeded metabolic heat production; (2) 50-55% from the systemic effects of the cold fluid per se; and (3) approximately 30% because the reduction in core heat content remained partially constrained to core tissues. The postinfusion period was associated with a rapid and spontaneous recovery of core temperature. This increase in core temperature was not associated with a peripheral-to-core redistribution of body heat because core temperature remained warmer than peripheral tissues even at the end of the infusion. Instead, it resulted from constraint of metabolic heat to the core thermal compartment.     

Negative pressure rewarming vs. forced air warming in hypothermic postanesthetic volunteers

We compared changes in core temperature and systemic heat balance with a new negative pressure/warming device (Vital Heat(R) ) that uses negative pressure combined with heat to facilitate warming in vasoconstricted postoperative patients to those resulting from passive insulation or forced air. Seven healthy volunteers were anesthetized and cooled to a tympanic membrane temperature near 34 degrees C. Anesthesia was discontinued and shivering was prevented by using meperidine. The vasoconstricted volunteers were rewarmed for 2 h using three randomly assigned methods: 1) Vital Heat plus cotton blanket; 2) one layer of cotton blanket; 3) forced-air warming. Thermal flux was recorded from 15 skin-surface sites; metabolic heat production was estimated from total body oxygen consumption. Metabolic heat production remained constant throughout the study. Systemic heat loss remained constant during warming with cotton blankets but decreased significantly during the other treatments. Systemic heat balance increased significantly more with forced air (140 +/- 21 kcal) than with Vital Heat (66 +/- 19 kcal) or cotton blankets (47 +/- 18 kcal). Core temperature increased no faster with Vital Heat warming (1.3 +/- 0.4 degrees C) than with a cotton blanket (1.2 +/- 0.4 degrees C). In contrast, core temperature increased more rapidly with forced air warming (2.6 +/- 0.6 degrees C). In this study we show that calories from a negative pressure rewarming device are largely constrained to the forearm and that heat does not flow to the core thermal compartment.     

Thermogenic effect of amino acids not demonstrated in heart surgery with cardiopulmonary bypass

BACKGROUND: In abdominal surgery and in healthy volunteers, amino acids increased thermogenesis. In this double-blind study we investigated if a similar effect would ensue in heart surgery and accelerate the rewarming process postoperatively. METHODS: Thirty-four patients undergoing coronary artery bypass grafting or aortic valve replacement were randomized into two groups, and received either 500 ml of amino acids or Ringer's solution intravenously during 4 h. The infusion was started approximately 30 min before the end of a cardiopulmonary bypass (CPB), performed at a temperature of 34 degrees C with rewarming to 36-37 degrees C. The lowest pulmonary artery (PA) temperature after the CPB and the time interval until the temperature reached 37 degrees C were recorded. Oxygen uptake was calculated from cardiac output (thermodilution) and the pulmonary av-difference of oxygen after induction of anaesthesia, at the end of surgery, and 1 and 2 h after the CPB. RESULTS: Demographic data, medication including beta-blockers, CPB data and case mix were similar. The lowest temperature after the CPB was 35.9 +/- 0.1 degrees C in the amino acid group and 35.6 +/- 0.2 degrees C in the control group, and the increase per hour was 0.6 +/- 0.1 degrees C and 0.6 +/- 0.0 degrees C, respectively, with no differences between the groups. During the infusion, oxygen uptake was higher in the amino acid group, 115 +/- 4 ml m(-2), than in the controls, 102 +/- 3 ml m(-2) (P < 0.05). No adverse effects of the infusions were noted. CONCLUSION: The lack of a thermal effect of the amino acids in the heart surgery was most probably due to the temperature gradients between the different body compartments, and also may have been due to the use of beta-blockers.     

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.