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.     

Effect of amino acid solutions on intraoperative hypothermia and postoperative shivering. Comparison of two anesthetic regimens

BACKGROUND: Intraoperative hypothermia is a major adverse effect of general anesthesia. The different anesthetics may influence thermoregulation differently. Proteins or amino acids have been postulated to stimulate heat production. The purpose of this study is to compare the effects of intraoperative administration of amino acid solutions on intraoperative hypothermia and postoperative shivering in two different anesthetic regimens. METHODS: Forty ASA I-III craniotomy patients were assigned to four groups of 10 patients in a randomized prospective study, as follows: ISO - isoflurane-based anesthesia; PRO - propofol-based anesthesia; ISO + AA - Isoflurane-based anesthesia with supplementation of amino acid infusion; PRO + AA - Isoflurane-based anesthesia with supplementation of amino acid infusion. Hemodynamic parameters, esophageal temperature and postoperative shivering scores were recorded. RESULTS: Core temperatures were higher during emergence in amino acid-treated propofol group, compared with the other groups. The core temperature decreased significantly in three groups throughout the operation, except the in amino acid-treated propofol group. The shivering intensity was less in the amino acid-treated groups. CONCLUSION: The anesthetic method may influence the thermic effect of amino acids under general anesthesia. Propofol anesthesia has more thermogenic effect than isoflurane when combined with amino acid solutions.     

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.     

Preoperative infusion of amino acids prevents postoperative hypothermia

Intraoperative infusion of amino acids has been found to stimulate energy expenditure and thereby prevent anaesthesia-induced hypothermia. Rectal temperature and respiratory gas exchange were measured in 24 female patients before and after isoflurane anaesthesia. Sixteen patients had an amino acid mixture of 240 kJ h-1, infused over 1-2 h before anaesthesia and eight control patients received saline. We compared the results with data from six female volunteers treated with amino acids; they were not premedicated or anaesthetized. In lorazepam premedicated patients, amino acids increased the pre-anaesthesia temperature by 0.3 degrees C h-1, twice that observed in the volunteers. At awakening after anaesthesia, energy expenditure increased to 50-60% above baseline in the amino acid treated patients, while in the control patients, receiving saline, no increase occurred, despite vigorous shivering. Amino acid infusion prevented hypothermia by increasing heat accumulation and causing delayed stimulation of heat production. The heat accumulation response to amino acid infusion was increased after premedication with lorazepam.      

Effect of amino acid infusion for prevention of intraoperative hypothermia during laparotomy

BACKGROUND: Amino acid infusion prevents intraoperative hypothermia. The purpose of this study is to examine the effect of amino acid infusion on intraoperative core temperature of patients during laparotomy. METHODS: Forty-two patients (duration of surgery of 180 min or more) and 32 patients (duration of surgery less than 180 min) scheduled for open gastrectomy under sevoflurane anesthesia combined with epidural anesthesia were randomly allocated to receive either amino acid solution (A group) or electrolyte solution (S group) intravenously. Each solution was started at anesthesia induction. The levels of tympanic temperature were recorded after induction, during surgery and at extubation. RESULTS: Patients in each of the two groups (A group vs. S group) were comparable with their characteristics and anesthetic management. Amino acid infusion prevented intraoperative hypothermia for cases of 180 min or more. The number of patients with temperature of less than 35.5 degrees C in A group was less those that in S group for cases shorter than 180 min. CONCLUSIONS: Amino acid infusion has more preventive effect on intraoperative hypothermia than electrolyte solution.     

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.     

Intraoperative clonidine administration to neurosurgical patients

The goals of this two-part study were to determine the dose of clonidine to prevent postoperative shivering after mild hypothermia and to evaluate the effect of clonidine on recovery from anesthesia in patients undergoing surgery for intracranial lesions. We enrolled 48 patients undergoing elective supratentorial neurosurgical procedures into one of two studies. In study 1 (n=14) we determined the ED50 of clonidine to prevent postoperative shivering after mild hypothermia (35 degrees C) using Dixon's up-and-down method. Clonidine dose for the first study patient was 3 microg/kg. The dose was then adjusted in 1-microg/kg increments for the following patients. Shivering was assessed for 1 h postoperatively. Study 2 (n=34) was a prospective, randomized, double-blind, placebo controlled study to evaluate the effect of 3 microg/kg clonidine on recovery from anesthesia. At the beginning of dural closure, patients randomly received a 15-min infusion of either clonidine or normal saline. Recovery variables were studied for 2 h after the end of anesthesia. The ED50 of clonidine to prevent shivering was 1.1 +/- 1.5 microg/kg in neurosurgical patients whose target core temperature was 35 degrees C at the end of surgery. Compared with saline, 3 microg/kg of clonidine administered to neurosurgical patients 1 h before the end of anesthesia did not delay emergence from anesthesia nor did it have clinically significant sedative or hemodynamic effects. Our results imply that clonidine may be used in neurosurgical patients to prevent postoperative shivering after mild hypothermia.     

Age-related thermoregulatory differences in a warm operating room environment (approximately 26 degrees C)

Inadvertent hypothermia occurs frequently at typical ambient operating room (OR) temperatures, especially in elderly patients receiving general anesthesia. The aims of the current study were to 1) determine the incidence and magnitude of core hypothermia in an unusually warm OR environment, and 2) to assess age-related differences in perioperative thermoregulatory responses under these circumstances. Forty patients receiving general anesthesia for orthopedic surgical procedures (20 younger patients, 20-40 yr old) and (20 older patients, 60-75 yr old) were enrolled. Mean ambient temperature in the ORs was 25.8 degrees +/- 0.2 degrees C. Core temperature, vasoconstriction, and shivering were compared in the younger and older age groups. Mean core temperature on admission to the postanesthesia care unit was not significantly different in the younger (36.7 degrees +/- 0.1 degrees C) and older (36.4 degrees +/- 0.1 degrees C) age groups. Only 10% of patients (n = 4, 1 younger, 3 older) were admitted with a core temperature <36.0 degrees C. Only 2% of patients (n = 1, older group) had a core temperature <35.5 degrees C. This very mild degree of hypothermia was associated with postoperative vasoconstriction in 80% of the younger and 55% of the older patients (P = 0.18). Postoperative shivering occurred in 40% of the younger patients and in 10% of the older patients (P = 0.06). In summary, an ambient OR temperature near 26 degrees C (79 degrees F) is effective in preventing core hypothermia during general anesthesia regardless of patient age. Even very mild postoperative hypothermia may initiate thermoregulatory responses. Implications: By increasing ambient temperature in the operating room to 26 degrees C (79 degrees F), the incidence of core hypothermia can be dramatically reduced in both younger and older patients.     

Thermal balance and tremor patterns during epidural anesthesia

Five healthy, nonpregnant volunteers were studied before and after induction of lumbar epidural anesthesia to determine the cause of central hypothermia during epidural anesthesia. Cutaneous heat loss was measured from 10 area-weighted sites using thermal flux transducers. Oxygen consumption was measured and converted to heat production in watts (W). After a 2-h control period at approximately 20 degrees C, epidural anesthesia was induced by injection of 30-50 ml 3% chloroprocaine. Additional boluses were given to extend the sensory blockade to at least the T5 dermatome. Tremor during epidural anesthesia was compared with normal shivering induced by rapid central venous infusion of approximately 4 l iced saline in six unanesthetized volunteers. Average skin temperature and cutaneous heat loss decreased during the control period, while tympanic membrane temperature remained stable. During the 1st h of epidural blockade, tympanic membrane temperature decreased 1.1 +/- 0.3 degrees C, and average skin temperature increased 0.9 +/- 0.5 degrees C. Cutaneous heat loss increased 16 +/- 6% (15 +/- 5 W), but metabolic heat production increased even more (and was associated with a shivering-like tremor). Tremor during epidural anesthesia and shivering induced by iced saline infusion had similar synchronous waxing-and-waning patterns. No abnormal EMG patterns were detected during epidural anesthesia. We conclude that central hypothermia during the 1st h of epidural anesthesia does not result from heat loss to the environment in excess of metabolic heat production, but results primarily from redistribution of body heat from central to peripheral tissues. Analysis of the tremor patterns suggests that oscillations recorded during epidural anesthesia in nonpregnant individuals is normal thermoregulatory shivering. Shivering occurred sooner and was more intense during iced saline infusion than during epidural anesthesia, despite comparable central hypothermia. The low intensity of shivering during epidural anesthesia, and in some individuals the delay in onset, may result from blockade of afferent cutaneous cold signals.     

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.     

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.     

Chronic treatment with antipsychotics enhances intraoperative core hypothermia

Antipsychotics can induce hypothermia, but intraoperative temperature regulation in schizophrenic patients taking antipsychotics remains unclear. We investigated intraoperative temperature regulation and postoperative shivering in chronic schizophrenic patients receiving antipsychotics. We studied 30 schizophrenic patients and 30 control patients who underwent orthopedic surgery. Tympanic membrane temperatures (35.7 degrees C +/- 0.5 degrees C, 35.6 degrees C +/- 0.5 degrees C, 35.6 degrees C +/- 0.4 degrees C, 35.5 degrees C +/- 0.4 degrees C, 35.4 degrees C +/- 0.5 degrees C, and 35.4 degrees C +/- 0.3 degrees C) 15, 30, 45, 60, 75, and 90 min, respectively, after induction in schizophrenic patients were significantly (P < 0.001) lower than those (36.5 degrees C +/- 0.5 degrees C, 36.4 degrees C +/- 0.5 degrees C, 36.3 degrees C +/- 0.4 degrees C, 36.2 degrees C +/- 0.5 degrees C, 36.2 degrees C +/- 0.4 degrees C, and 36.1 degrees C +/- 0.4 degrees C) in control patients. Mean skin temperatures (31.1 degrees C +/- 0.4 degrees C [P = 0.008], 31.1 degrees C +/- 0.3 degrees C [P = 0.007], and 31.1 degrees C +/- 0.2 degrees C [P = 0.006]) 60, 75, and 90 min, respectively, after induction in schizophrenic patients were significantly lower than those (31.5 degrees C +/- 0.3 degrees C, 31.5 degrees C +/- 0.3 degrees C, and 31.5 degrees C +/- 0.3 degrees C) in control patients. Four of 30 schizophrenic patients and 7 of 30 control patients developed postanesthesia shivering. There were no significant differences within 1 h after tracheal extubation in tympanic membrane temperatures between patients who shivered and those who did not shiver. In conclusion, chronic schizophrenic patients were more hypothermic during anesthesia. The incidence of postanesthesia shivering was not significantly increased. IMPLICATIONS: Antipsychotics inhibit autonomic thermoregulation. This is caused by decreased heat production, increased heat loss, and impaired central action at the hypothalamus. Thus, schizophrenic patients receiving antipsychotics may have impaired intraoperative temperature regulation.     

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.     

Effect of intraoperative amino acids with or without glucose infusion on body temperature,insulin, and blood glucose levels in patients undergoing laparoscopic colectomy: A preliminary report

ObjectiveAmino acid administration helps to prevent intraoperative hypothermia but may enhance thermogenesis when combined with glucose infusion. The aim of this study was to examine the effect of intraoperative amino acid administration, with or without glucose infusion, on temperature regulation during laparoscopic colectomy.MethodsTwenty-one patients whose physical status was classified I or II by the American Society of Anesthesiologists, and who were undergoing elective laparoscopic colectomy were enrolled. The exclusion criteria were a history of diabetes and/or obesity, preoperative high levels of C-reactive protein, high blood glucose and/or body temperature after anesthesia induction, and surgical time >500 minutes. Each patient received an acetate ringer solution and was randomly assigned to one of three groups. Group A patients were given only amino acids. Group AG patients were given amino acids and glucose. Group C patients were given neither amino acids nor glucose. Tympanic membrane temperatures and blood glucose and insulin levels were measured intraoperatively.ResultsIntraoperative amino acid infusion significantly increased body temperature during surgery as compared with either Group AG or C. The blood glucose levels in Group AG were significantly higher than those in Groups A and C. However, there were no significant differences between Groups A and C. Two hours after anesthesia induction, serum insulin levels in Groups A and AG significantly increased compared with Group C. No significant differences in the postoperative complications or patient hospitalization lengths were detected between the groups.ConclusionIntraoperative amino acid infusion without glucose administration maintains body temperature more effectively than combined amino acid and glucose infusion in patients undergoing laparoscopic colectomy, despite unaltered intraoperative insulin levels.     

Preoperative combined with intraoperative skin-surface warming avoids hypothermia caused by general anesthesia and surgery

STUDY OBJECTIVES: To evaluate the effects of intraoperative skin-surface warming with and without 1 hour of preoperative warming, in preventing intraoperative hypothermia, and postoperative hypothermia, and shivering, and in offering good conditions to early tracheal extubation. DESIGN: Prospective, randomized, blind study. SETTING: Teaching hospital. PATIENTS: 30 ASA physical status I and II female patients scheduled for elective abdominal surgery. INTERVENTIONS: Patients received standard general anesthesia. In 10 patients, no special precautions were taken to avoid hypothermia. Ten patients were submitted to preoperative and intraoperative active warming. Ten patients were only warmed intraoperatively. MEASUREMENTS AND MAIN RESULTS: Temperatures were recorded at 15-minute intervals. The patients who were warmed preoperatively and intraoperatively had core temperatures significantly more elevated than the other patients during the first two hours of anesthesia. All patients warmed intraoperatively were normothermic only at the end of the surgery. The majority of the patients warmed preoperatively and intraoperatively or intraoperatively only were extubated early, and none had shivering. In contrast, five unwarmed patients shivered. CONCLUSIONS: One hour of preoperative warning combined with intraoperative skin-surface warming, not simply intraoperative warming alone, avoided hypothermia caused by general anesthesia during the first two hours of surgery. Both methods prevented postoperative hypothermia and shivering and offered good conditions for early tracheal extubation.     

Active warming during cesarean delivery.

We tested the hypothesis that 15 min of forced-air prewarming, combined with intraoperative warming, prevents hypothermia and shivering in patients undergoing elective cesarean delivery. We simultaneously tested the hypothesis that maintaining maternal normothermia increases newborn temperature, umbilical vein pH, and Apgar scores. Thirty patients undergoing elective cesarean delivery were randomly assigned to forced-air warming or to passive insulation. Warming started 15 min before the induction of epidural anesthesia. Core temperature was measured at the tympanic membrane, and shivering was graded by visual inspection. Patients evaluated their thermal sensation with visual analog scales. Rectal temperature and umbilical pH were measured in the infants after birth. Results were compared with unpaired, two-tailed Student's t-tests and chi(2) tests. Core temperatures after 2 h of anesthesia were greater in the actively warmed (37.1 degrees C +/- 0.4 degrees C) than in the unwarmed (36.0 degrees C +/- 0.5 degrees C; P < 0.01) patients. Shivering was observed in 2 of 15 warmed and 9 of 15 unwarmed mothers (P < 0.05). Babies of warmed mothers had significantly greater core temperatures (37.1 degrees C +/- 0.5 degrees C vs 36.2 degrees C +/- 0.6 degrees C) and umbilical vein pH (7.32 +/- 0.07 vs 7.24 +/- 0.07). IMPLICATIONS: Perioperative forced-air warming of women undergoing cesarean delivery with epidural anesthesia prevents maternal and fetal hypothermia, reduces maternal shivering, and improves umbilical vein pH.     

Physiologic responses to mild perianesthetic hypothermia in humans

To evaluate physiologic responses to mild perianesthetic hypothermia, we measured tympanic membrane and skin-surface temperatures, peripheral vasoconstriction, thermal comfort, and muscular activity in nine healthy male volunteers. Each volunteer participated on three separate days: 1) normothermic isoflurane anesthesia; 2) hypothermic isoflurane anesthesia (1.5 degrees C decrease in central temperature); and 3) hypothermia alone (1.5 degrees C decrease in central temperature) induced by iced saline infusion. Involuntary postanesthetic muscular activity was considered thermoregulatory when preceded by central hypothermia and peripheral cutaneous vasoconstriction. Tremor was considered normal shivering when electromyographic patterns matched those produced by cold exposure in unanesthetized individuals. During postanesthetic recovery, central temperatures in hypothermic volunteers increased rapidly when residual end-tidal isoflurane concentrations were less than or equal to 0.3% but remained 0.5 degree C less than control values throughout 2 h of recovery. All volunteers were vasodilated during isoflurane administration. Peripheral vasoconstriction occurred only during recovery from hypothermic anesthesia, at end-tidal isoflurane concentrations of less than approximately 0.4%. Spontaneous tremor was always preceded by central hypothermia and peripheral vasoconstriction, indicating that muscular activity was thermoregulatory. Maximum tremor intensity during recovery from hypothermic anesthesia occurred when residual end-tidal isoflurane concentrations were less than or equal to 0.4%. Three patterns of postanesthetic muscular activity were identified. The first was a tonic stiffening that occurred in some normothermic and hypothermic volunteers when end-tidal isoflurane concentrations were approximately 0.4-0.2%. This activity appeared to be largely a direct, non-temperature-dependent effect of isoflurane anesthesia. In conjunction with lower residual anesthetic concentrations, stiffening was followed by a synchronous, tonic waxing-and-waning pattern and spontaneous electromyographic clonus, both of which were thermoregulatory. Tonic waxing-and-waning was by far the most common pattern and resembled that produced by cold-induced shivering in unanesthetized volunteers; it appears to be thermoregulatory shivering triggered by hypothermia. Spontaneous clonus resembled flexion-induced clonus and pathologic clonus and did not occur during hypothermia alone; it may represent abnormal shivering or an anesthetic-induced modification of normal shivering. We conclude that among the three patterns of muscular activity, only the synchronous, tonic waxing-and-waning pattern can be attributed to normal thermoregulatory shivering.     

Postoperative ventilatory and circulatory effects of extended rewarming during cardiopulmonary bypass

Postoperative effects of extended rewarming (ECR) after hypothermic cardiopulmonary bypass (CPB) were studied. All (n = 28) patients were rewarmed to a nasopharyngeal temperature exceeding 38 degrees C before terminating CPB. In 12 patients (control group) the rectal temperature (Tre) was 33.8 +/- 1.7 degrees C (mean +/- sd) at termination of CPB. In sixteen patients (ECR group) rewarming during CPB was continued to a Tre of 36.8 +/- 0.5 degrees C. Postoperative body temperatures, heat content, shivering, oxygen uptake, CO2 production and haemodynamic variables were measured. ECR reduced the heat gain required to complete core rewarming to 665 +/- 260 kJ, compared with 1037 +/- 374 kJ in the control group (p less than 0.01). The incidence of shivering was reduced (p less than 0.05) as well as shivering intensity and duration. In seven non-shivering ECR group patients this coincided with significantly reduced metabolic and ventilatory demands but these improvements were not valid for the group as a whole. The required ventilation temporarily during postoperative rewarming in both groups increased to 250 per cent of the basal need. Extending CPB rewarming (to at least 36 degrees C Tre) was inefficient when used as the sole measure to reduce the untoward effects of residual hypothermia during recovery after cardiac surgery with hypothermic CPB.     

Doxapram only slightly reduces the shivering threshold in healthy volunteers

We determined the effects of doxapram on the major autonomic thermoregulatory responses in humans. Nine healthy volunteers were studied on 2 days: control and doxapram (IV infusion to a plasma concentration of 2.4 +/- 0.8, 2.5 +/- 0.9, and 2.6 +/- 1.1 microg/mL at the sweating, vasoconstriction, and shivering thresholds, respectively). Each day, skin and core temperatures were increased to provoke sweating, then reduced to elicit peripheral vasoconstriction and shivering. We determined the sweating, vasoconstriction, and shivering thresholds with compensation for changes in skin temperature. Data were analyzed with paired t-tests and presented as mean +/- sd; P < 0.05 was considered statistically significant. Doxapram did not change the sweating (control: 37.5 degrees +/- 0.4 degrees C, doxapram: 37.3 degrees +/- 0.4 degrees C; P = 0.290) or the vasoconstriction threshold (36.8 degrees +/- 0.7 degrees C versus 36.4 degrees +/- 0.5 degrees C; P = 0.110). However, it significantly reduced the shivering threshold from 36.2 degrees +/- 0.5 degrees C to 35.7 degrees +/- 0.7 degrees C (P = 0.012). No sedation or symptoms of panic were observed on either study day. The observed reduction in the shivering threshold explains the drug's efficacy for treatment of postoperative shivering; however, a reduction of only 0.5 degrees C is unlikely to markedly facilitate induction of therapeutic hypothermia as a sole drug.     

Buspirone and meperidine synergistically reduce the shivering threshold.

Mild hypothermia (i.e., 34 degrees C) may prove therapeutic for patients with stroke, but it usually provokes shivering. We tested the hypothesis that the combination of buspirone (a serotonin 1A partial agonist) and meperidine synergistically reduces the shivering threshold (triggering tympanic membrane temperature) to at least 34 degrees C while producing little sedation or respiratory depression. Eight volunteers each participated on four randomly-assigned days: 1) large-dose oral buspirone (60 mg); 2) large-dose IV meperidine (target plasma concentration of 0.8 microg/mL); 3) the combination of buspirone (30 mg) and meperidine (0.4 microg/mL); and 4) a control day without drugs. Core hypothermia was induced by infusion of lactated Ringer's solution at 4 degrees C. The control shivering threshold was 35.7 degrees C +/- 0.2 degrees C. The threshold was 35.0 degrees C +/- 0.8 degrees C during large-dose buspirone and 33.4 degrees C +/- 0.3 degrees C during large-dose meperidine. The threshold during the combination of the two drugs was 33.4 degrees C +/- 0.7 degrees C. There was minimal sedation on the buspirone and combination days and mild sedation on the large-dose meperidine day. End-tidal PCO2 increased approximately 10 mm Hg with meperidine alone. Buspirone alone slightly reduced the shivering threshold. The combination of small-dose buspirone and small-dose meperidine acted synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. IMPLICATIONS: Mild hypothermia may be an effective treatment for acute stroke, but it usually triggers shivering, which could be harmful. Our results indicate that the combination of small-dose buspirone and small-dose meperidine acts synergistically to reduce the shivering threshold while causing little sedation or respiratory toxicity. This combination may facilitate the induction of therapeutic hypothermia in stroke victims.