Shivering Threshold Research Articles

Droperidol lowers the shivering threshold in rabbits.

Perioperative shivering is common and can occur as a result of hypothermia or changes in the threshold of thermoregulation. Droperidol usage for anesthesia is currently limited to its sedative and antiemetic effects. We investigated the effects of high and low doses of droperidol on the shivering threshold in rabbits. Forty-two male Japanese white rabbits were anesthetized with isoflurane and randomly assigned to the control, high-dose, or low-dose group. Rabbits in the high-dose group received a 5mg/kg droperidol bolus followed by continuous infusion at 5mg/kg/h, those in the low-dose group received a 0.5mg/kg droperidol bolus, and those in the control group received the same volume of saline as the high-dose group. Body temperature was reduced at a rate of 2-3°C/h, and the shivering threshold was defined as the subject's core temperature (°C) at the onset of shivering. The shivering thresholds in the control, high-dose, and low-dose groups were 38.1°C ± 1.1°C, 36.7°C ± 1.2°C, and 36.9°C ± 1.0°C, respectively. The shivering thresholds were significantly lower in the high-dose and low-dose groups than in the control group (P < 0.01). The thresholds were comparable between the high-dose and low-dose groups. Droperidol in high and low doses effectively reduced the shivering threshold in rabbits. Droperidol has been used in low doses as an antiemetic. Low doses of droperidol can reduce the incidence of shivering perioperatively and during the induction of therapeutic hypothermia.

Short-Term Cooling Increases Plasma ANGPTL3 and ANGPTL8 in Young Healthy Lean Men but Not in Middle-Aged Men with Overweight and Prediabetes.

Angiopoietin-like proteins (ANGPTLs) regulate triglyceride (TG)-rich lipoprotein distribution via inhibiting TG hydrolysis by lipoprotein lipase in metabolic tissues. Brown adipose tissue combusts TG-derived fatty acids to enhance thermogenesis during cold exposure. It has been shown that cold exposure regulates ANGPTL4, but its effects on ANGPTL3 and ANGPTL8 in humans have not been elucidated. We therefore investigated the effect of short-term cooling on plasma ANGPTL3 and ANGPTL8, besides ANGPTL4. Twenty-four young, healthy, lean men and 20 middle-aged men with overweight and prediabetes were subjected to 2 h of mild cooling just above their individual shivering threshold. Before and after short-term cooling, plasma ANGPTL3, ANGPTL4, and ANGPTL8 were determined by ELISA. In young, healthy, lean men, short-term cooling increased plasma ANGPTL3 (+16%, p < 0.05), ANGPTL4 (+15%, p < 0.05), and ANGPTL8 levels (+28%, p < 0.001). In middle-aged men with overweight and prediabetes, short-term cooling only significantly increased plasma ANGPTL4 levels (+15%, p < 0.05), but not ANGPTL3 (230 ± 9 vs. 251 ± 13 ng/mL, p = 0.051) or ANGPTL8 (2.2 ± 0.5 vs. 2.3 ± 0.5 μg/mL, p = 0.46). We show that short-term cooling increases plasma ANGPTL4 levels in men, regardless of age and metabolic status, but only overtly increases ANGPTL3 and ANGPTL8 levels in young, healthy, lean men.

Continuous surface EMG power reflects the metabolic cost of shivering during targeted temperature management after cardiac arrest

AimShivering may interfere with targeted temperature management (TTM) after cardiac arrest, contributing to secondary brain injury. Early identification of shivering is challenging with existing tools. We hypothesized that shivering detected by continuous surface sEMG monitoring would be validated with calorimetry and detected earlier than by intermittent clinical observation. MethodsThis prospective observational study enrolled a convenience sample of comatose adult cardiac arrest patients treated with TTM at 33 °C. Clinical shivering was monitored hourly using the Bedside Shivering Assessment Scale (BSAS) by bedside nurses who administered intermittent neuromuscular blockade (NMB) when BSAS ≥ 1. The research team monitored independently for shivering with BSAS every 15 min during continuous blinded monitoring of oxygen consumption (VO2) via indirect calorimetry and sEMG power during the maintenance phase of TTM. A sustained 20% increase in the 5-min rolling average of VO2 above baseline identified the Gold Standard shivering threshold (VO2-20). ResultsAmong 18 patients, clinical shivering was detected 23 times in 14 patients. Hierarchical models to predict a shiver event determined by the VO2-20 for sEMG power and BSAS revealed an AUC for sEMG power of 0.92 (95%CI = 0.88–0.95), and 0.90 (CI = 0.87–0.94) for BSAS. The optimal threshold of sEMG to predict VO2-20 was 32 decibels (dB), and this was exceeded 38 (29–56) min before nurse-detected shivering. ConclusionsShivering was detected by sEMG power earlier than by clinical assessment with BSAS, with similar accuracy compared to the indirect calorimetry gold standard. Continuous sEMG monitoring appears useful for clinical assessment and research for shivering during TTM.

The Effects of Blood Glucose Concentration on the Shivering Threshold in Rabbits

Hyperglycemia is common in critically ill and surgical patients, as are core temperature disturbances. The effect of hyperglycemia on thermoregulatory defenses remains unknown. We determined the effect of blood glucose concentration on the shivering threshold in rabbits. Twenty-seven rabbits lightly anesthetized with isoflurane were randomly assigned to infusions of (1) saline, (2) insulin titrated to produce blood glucose concentrations 60 to 100 mg/dL, or (3) 50% dextrose titrated to produce blood glucose concentrations 200 to 300 mg/dL. Core temperature was reduced at a rate of 2 to 3°C/h by perfusing water at 10°C through a plastic tube positioned in the colon. Cooling continued until shivering was observed by an investigator blinded to treatment or until esophageal (core) temperature reached 34°C. Core temperatures at the onset of shivering defined the threshold. All analyses were conducted using SAS version 9.3 (SAS Institute Inc., Cary, NC). Rabbits given saline shivered at 37.2 ± 0.5°C (mean ± SD). Rabbits given insulin shivered at 36.3 ± 1.1°C. Rabbits given dextrose shivered at 38.0 ± 0.6°C. The shivering threshold increased as a function of blood glucose concentration: shivering threshold (°C) = 0.009 [blood glucose concentration (mg/dL)] + 35.6, r = 0.53. The shivering threshold thus increased approximately 1°C for each 100 mg/dL increase in blood glucose concentration. Hyperglycemia increases the threshold for shivering, whereas hypoglycemia lowers the threshold on rabbits.

Nefopam and meperidine are infra-additive on the shivering threshold in humans.

Induction of therapeutic hypothermia is often complicated by shivering. Nefopam, a nonsedative benzoxazocine analgesic, reduces the shivering threshold (triggering core temperature) with minimal side effects. Consequently, nefopam is an attractive drug for inducing therapeutic hypothermia. However, nefopam alone is insufficient and thus needs to be combined with another drug. Meperidine also reduces the shivering threshold. We therefore determined whether the combination of nefopam and meperidine is additive, infra-additive, or synergistic on the shivering threshold. Ten volunteers were each studied on 4 randomly assigned days. In random order, they were given the following treatments: (1) control, no drug; (2) nefopam to a target concentration of 0.1 μg/mL; (3) meperidine to a target concentration of 0.1 μg/mL; and (4) both nefopam and meperidine at target concentrations of 0.1 μg/mL each. Lactated Ringer's solution at 4°C was infused to decrease core temperature while mean skin temperature was kept near 30.5°C. The core temperature that increased oxygen consumption >25% defined the shivering threshold. Nefopam reduced the shivering thresholds by 0.7°C ± 0.3°C compared with no drug. Meperidine reduced the shivering thresholds by 0.4°C ± 0.3°C compared with no drug. When combined, the shivering threshold decreased by only 0.6°C ± 0.4°C, which was about half what would have been expected based on the individual effects of each drug (P < 0.001). The effect of combined nefopam and meperidine on the shivering threshold was thus infra-additive. The combination of nefopam and meperidine should be avoided for induction of therapeutic hypothermia. Better options would be combinations of drugs that are at least additive or even synergistic.

Shivering: scores and protocols

Shivering is both an anticipated consequence and, potentially, a major adverse effect of therapeutic hypothermia. Even mild hypothermia can elicit a vigorous thermoregulatory defense to maintain body temperature at the hypothalamic set point. In healthy humans, peripheral vasoconstriction is triggered at 36.5°C and shivering at 35.5°C. Temperature thresholds for vasoconstriction and shivering are often higher than normal in brain-injured patients; therefore, these thermoregulatory defenses may occur more vigorously and at higher temperatures in these individuals. Control of shivering is essential for effective cooling, as shivering fights the cooling process, makes attaining target temperature difficult, is extremely uncomfortable, and can trigger massive increases in systemic and cerebral energy consumption and metabolic demand. The first step in treatment is adequate tools to recognize shivering. The Bedside Shivering Assessment Scale is a simple, validated four-point scale that enables repeated quantification of shivering at the bedside. Therapy for shivering should ideally stop or suppress the central thermoregulatory reflex rather than just uncoupling this response from skeletal muscle contraction, as the latter approach does not mitigate the ongoing cerebral and systemic stress response. Analgo-sedation with opioids, α2-receptor agonists, or propofol is almost always effective as a last resort to prevent shivering. However, nonpharmacological strategies as first-line interventions for shivering minimize the risk of excessive sedation, which can make neurological examination difficult and increase the risk of complications. The Columbia Anti Shivering protocol has been developed with these strategies in mind, and we base our approach on prospectively collected cooling data on 213 patients who underwent 1,388 patient-days of temperature modulation. Eighty-nine patients underwent hypothermia and 124 patients underwent induced normothermia. In 18% of patients and 33% of the total patient-days, only none-sedating baseline interventions were needed. The first agent used was most commonly dexmeditomidine half the time, followed by opiates and increased doses of propofol. Younger patients, men, and lower body surface area were factors associated with increased number of anti-shivering interventions. As noted by this protocol, a significant proportion of patients undergoing temperature modulation can be effectively treated for shivering without oversedation and paralysis. Patients at higher risk for needing more interventions are younger men with decreased body surface area.

Mechanisms of Modulation of Thermoregulatory Reactions during Cooling in Hypertensive Rats by the Sympathetic Nervous System

Susceptibility of thermoregulatory responses to cold to blockage of α(1)- and β-adrenoreceptors differs in health and hypertension. α(1)-Adrenoceptor blockade reduces vessel reactivity during cooling and vessel reaction to cold becomes similar to that in intact normotensive rats. Changes in the structure of metabolic response to cold in favor of non-shivering thermogenesis typical of hypertensive animals becomes even more pronounced under conditions of α(1)-adrenoceptor blockade due to inhibition of cold shivering. Blockage of β-adrenoceptors does not affect parameters of vascular response to cooling. In hypertensive rats, in contrast to normotensive animals, β-adrenoceptor blockade during cooling increased temperature thresholds for total metabolic reaction and shivering. The maximum shivering intensity also increased, which partially compensated inhibition of non-shivering thermogenesis. In the whole organism, blockade of one type of adrenoceptors during cooling leads to intensification of compensatory mechanisms realized through adrenoceptors of the other type. In hypertensive rats, compensatory capacities of thermogenic processes controlled by α(1)- and β-adrenoceptors are impaired in comparison with normotensive animals under conditions of inhibition of both shivering and non-shivering thermogenesis.

The Effects of Nefopam on the Gain and Maximum Intensity of Shivering in Healthy Volunteers

Mild hypothermia has been shown to improve neurologic outcome after cardiac arrest. Nefopam, a centrally acting, nonsedative analgesic, decreases the threshold of shivering, but not vasoconstriction, and thus might be a suitable drug for induction of therapeutic hypothermia. However, not only the threshold but also the gain and maximum intensity of shivering define the thermoregulatory properties of a drug and thus are clinically important. Therefore, we evaluated the gain and maximum intensity of shivering at 2 different doses of nefopam and placebo. Seven healthy volunteers were randomly assigned to 3 study days: (1) control (saline), (2) small-dose nefopam (50 ng/mL), and (3) large-dose nefopam (100 ng/mL). On all study days volunteers were cooled using central venous infusion of cold IV fluid while mean skin temperature was maintained at 31 degrees C. Core temperature was recorded at the tympanic membrane. Threshold, gain, and maximum intensity of shivering were evaluated using oxygen consumption. Both 50 and 100 ng/mL nefopam significantly reduced the shivering threshold as well as the gain of shivering: shivering threshold: 35.6 degrees C + or - 0.2 degrees C (control); 35.2 degrees C + or - 0.3 degrees C (small dose); 34.9 degrees C + or - 0.5 degrees C (large dose), P = 0.004; gain of shivering: 597 + or - 235 mL x min(-1) x degrees C(-1) (control); 438 + or - 178 mL x min(-1) x degrees C(-1) (small dose); 301 + or - 134 mL x min(-1) x degrees C(-1) (large dose), P = 0.028. Maximum intensity of shivering did not differ among the 3 treatments. Nefopam significantly reduced the gain of shivering. This reduction, in combination with a reduced shivering threshold, will allow clinicians to cool patients even further when therapeutic hypothermia is indicated.

Nefopam and Alfentanil Additively Reduce the Shivering Threshold in Humans whereas Nefopam and Clonidine Do Not

Induction of therapeutic hypothermia is often complicated by shivering. Nefopam reduces the shivering threshold with minimal side effects. Consequently, nefopam is an attractive component for induction of therapeutic hypothermia. However, nefopam alone is insufficient; it will thus need to be combined with another drug. Clonidine and alfentanil each reduce the shivering threshold. This study, therefore, tested the hypothesis that nefopam, combined either with clonidine or alfentanil, synergistically reduces the shivering threshold. For each combination, ten volunteers were studied on 4 days. Combination 1: (1) control (no drug); (2) nefopam (100 ng/ml); (3) clonidine (2.5 microg/kg); and (4) nefopam plus clonidine (100 ng/ml and 2.5 microg/kg, respectively). Combination 2: (1) control (no drug); (2) nefopam (100 ng/ml); (3) alfentanil (150 ng/ml); and (4) nefopam plus alfentanil (100 ng/ml and 150 ng/ml, respectively). Lactated Ringer's solution (approximately 4 degrees C) was infused to decrease core temperature. Mean skin temperature was maintained at 31 degrees C. The core temperature that increased oxygen consumption to more than 25% of baseline identified the shivering threshold. With nefopam and clonidine, the shivering thresholds were significantly lower than on the control day. The shivering threshold decreased significantly less than would be expected on the basis of the individual effects of each drug (P = 0.034). In contrast, the interaction between nefopam and alfentanil on shivering was additive, meaning that the combination reduced the shivering threshold as much as would be expected by the individual effect of each drug. Nefopam and alfentanil additively reduce the shivering threshold, but nefopam and clonidine do not.

Suppression of Shivering during Hypothermia Using a Novel Drug Combination in Healthy Volunteers

Hypothermia may be beneficial in stroke victims; however, it provokes vigorous shivering. Buspirone and dexmedetomidine each linearly reduce the shivering threshold with minimal sedation and no respiratory depression. This study tested the hypotheses that the combination of buspirone and dexmedetomidine would (1) synergistically reduce the shivering threshold, (2) synergistically reduce the gain and maximum intensity of shivering, and (3) produce sufficient inhibition to permit cooling to 34 degrees C without excessive hypotension or sedation. Eight healthy men were randomly assigned on 4 days to (1) no drug, (2) buspirone (60 mg orally), (3) dexmedetomidine (intravenous infusion to target plasma concentration of 0.6 ng/ml), or (4) combination of buspirone and dexmedetomidine at same doses. Lactated Ringer's solution (approximately 3 degrees C) was infused intravenously to decrease tympanic membrane temperature by 1.5 degrees C/h. Shivering threshold was defined as an increase in oxygen consumption greater than 20%. Sedation was evaluated using the Observer's Assessment of Sedation/Alertness scale. Mean arterial pressure and heart rate were slightly lower on dexmedetomidine and combination days. Likewise, the level of sedation was statistically different on these 2 days but clinically unimportant. Buspirone reduced the shivering threshold from 36.6 degrees C +/- 0.4 degrees C to 35.9 degrees C +/- 0.4 degrees C, dexmedetomidine reduced it to 34.7 degrees C +/- 0.5 degrees C, and the combination to 34.1 +/- 0.4 degrees C. The interaction effect of 0.04 degrees C was not significant. The gain of shivering and maximum shivering intensity were similar on each day. The combination of buspirone and dexmedetomidine additively reduced the shivering threshold. Thus, supplementing dexmedetomidine with buspirone blocks shivering and causes only minimal sedation.

The Shivering Threshold in Rabbits with JM-1232(−), a New Benzodiazepine Receptor Agonist

JM-1232(-) is a novel isoindoline derivative which shows sedative and hypnotic activities through the benzodiazepine site of gamma-aminobutyric acid type A (GABAA) receptors. Typical doses of midazolam, another GABAA receptor agonist, slightly reduce the shivering threshold in humans. We thus determined the extent to which JM-1232(-) decreases the shivering threshold. Eighteen rabbits, lightly anesthetized with isoflurane 0.2 minimum alveolar anesthetic concentration (MAC), were randomly assigned to infusions of 1) saline (control), 2) 0.01 mg x kg(-1) x min(-1) JM-1232(-), or 3) 0.1 mg x kg(-1) x min(-1) JM-1232(-). Body temperature was reduced at a rate of 2-3 degrees C/h by perfusing water at 10 degrees C though a U-shaped plastic tube positioned in the colon. Cooling continued until shivering was observed by an investigator blinded to treatment, or until core temperature reached 34 degrees C. Core temperatures were recorded from the distal esophagus, and core temperature at the onset of shivering defined the threshold. Data were analyzed by one-way analysis of variance with Student-Newman-Keuls tests. Results are presented as means +/- SD; P < 0.05 was considered statistically significant. The rabbits given a saline infusion shivered at 36.5 +/- 0.3 degrees C. Five of the six rabbits given JM-1232(-) at a rate of 0.01 mg x kg(-1) x min(-1) shivered at 35.7 +/- 0.8 degrees C, and one of these rabbits failed to shiver at 34.0 degrees C. None of the rabbits given JM-1232(-) at a rate of 0.1 mg x kg(-1) x min(-1) shivered before reaching the 34.0 degrees C cutoff temperature. A low dose of JM-1232(-) reduced the shivering threshold in rabbits approximately 0.8 degrees C which is similar to the effects in humans given premedication doses of midazolam. In contrast, a 10-fold larger dose reduced the threshold more than 2.5 degrees C. This is a substantial decrement and might facilitate induction of therapeutic hypothermia.

Isovolaemic haemodilution decreases the shivering threshold in rabbits

The inhibition of thermoregulatory control by anaesthesia is manifested by reduced vasoconstriction and shivering thresholds. As intraoperative bleeding can result in haemodynamic changes, including vasoconstriction, we investigated the effect of experimental bleeding on the shivering threshold in rabbits. Twenty-four rabbits were randomly assigned to one of three treatment strategies: (1) no blood removal (control), (2) 5 mL kg(-1) isovolaemic blood removal and (3) 10 mL kg(-1) isovolaemic blood removal. After tracheal intubation under isoflurane anaesthesia, anaesthesia was maintained with 50% nitrous oxide in oxygen. The removed blood volume was replaced with the same volume of warm hydroxyethyl starch colloid solution. Oesophageal temperature was measured as a core temperature at 1-min intervals. After blood removal, the animal's body was cooled at a rate of 2-3 degrees C h(-1) by perfusing water at 10 degrees C through a U-shaped thermode positioned in the colon. Hypothermic shivering was evaluated by visual inspection, and the core temperature at which shivering was triggered was identified as the thermoregulatory threshold for this response. Just before the cooling, the body temperature of the animals was around 38.6 degrees C in all of the three groups. The shivering threshold in the control group was 37.2 +/- 0.2 degrees C (mean +/- SD). The shivering thresholds in the 5 mL kg(-1) (36.9 degrees +/- 0.3 degrees C) and 10 mL kg(-1) (36.5 degrees +/- 0.5 degrees C) blood removal groups were significantly lower and in proportion with the volume of blood removed than that in the control group. Isovolaemic haemodilution decreased the shivering threshold in rabbits in proportion with the volume of blood removed.

Lower-Body Warming Mimics the Normal Epidural-Induced Reduction in the Shivering Threshold

Neuraxial anesthesia reduces the shivering threshold approximately 0.6 degrees C. This effect might be mediated by an apparent (as opposed to actual) increase in lower body temperature. Accordingly, sufficient lower body warming should result in thermoregulatory inhibition comparable to that exerted by epidural anesthesia. We tested the hypothesis that increasing leg skin temperature to 38 degrees C mimics the normal approximately 0.6 degrees C reduction in the shivering threshold during epidural anesthesia. Shivering threshold during internal body cooling was determined in nine female volunteers on two separate days: one unanesthetized control day, and one day with a T10-11 epidural block. On each study day, lower body skin temperature was maintained near 38 degrees C and upper body skin temperature near 33 degrees C. We assessed equivalency of the shivering thresholds on the control and epidural days using the two one-sided tests method. The thresholds on the control (35.8 degrees C +/- 0.5 degrees C; mean +/- sd) and epidural (35.8 degrees C +/- 0.5 degrees C) days were shown to be equivalent because the 95% CI for the difference in means, 0.0 (-0.4, 0.4), was within our prespecified limits of -0.6 degrees C to +0.6 degrees C (P < 0.025 for both one-sided equivalency tests). Lower body warming mimics the normal epidural-induced reduction in the shivering threshold. Our results support a mechanism based on increased apparent lower body skin temperature during neuraxial anesthesia.

Meperidine and skin surface warming additively reduce the shivering threshold: a volunteer study

IntroductionMild therapeutic hypothermia has been shown to improve outcome for patients after cardiac arrest and may be beneficial for ischaemic stroke and myocardial ischaemia patients. However, in the awake patient, even a small decrease of core temperature provokes vigorous autonomic reactions–vasoconstriction and shivering–which both inhibit efficient core cooling. Meperidine and skin warming each linearly lower vasoconstriction and shivering thresholds. We tested whether a combination of skin warming and a medium dose of meperidine additively would reduce the shivering threshold to below 34°C without producing significant sedation or respiratory depression.MethodsEight healthy volunteers participated on four study days: (1) control, (2) skin warming (with forced air and warming mattress), (3) meperidine (target plasma level: 0.9 μg/ml), and (4) skin warming plus meperidine (target plasma level: 0.9 μg/ml). Volunteers were cooled with 4°C cold Ringer lactate infused over a central venous catheter (rate ≈ 2.4°C/hour core temperature drop). Shivering threshold was identified by an increase of oxygen consumption (+20% of baseline). Sedation was assessed with the Observer's Assessment of Alertness/Sedation scale.ResultsControl shivering threshold was 35.5°C ± 0.2°C. Skin warming reduced the shivering threshold to 34.9°C ± 0.5°C (p = 0.01). Meperidine reduced the shivering threshold to 34.2°C ± 0.3°C (p < 0.01). The combination of meperidine and skin warming reduced the shivering threshold to 33.8°C ± 0.2°C (p < 0.01). There were no synergistic or antagonistic effects of meperidine and skin warming (p = 0.59). Only very mild sedation occurred on meperidine days.ConclusionA combination of meperidine and skin surface warming reduced the shivering threshold to 33.8°C ± 0.2°C via an additive interaction and produced only very mild sedation and no respiratory toxicity.

Hot flashes: behavioral treatments, mechanisms, and relation to sleep

Hot flashes are the most common symptom of the climacteric and occur in about 75% of perimenopausal and postmenopausal women in Western societies. Although hot flashes accompany the withdrawal of estrogen at menopause, the decline in estrogen levels is not sufficient to explain their occurrence. Elevated sympathetic activation acting through central alpha(2)-adrenergic receptors contributes to the initiation of hot flashes, possibly by narrowing the thermoneutral zone in symptomatic women. Hot flashes are then triggered by small elevations in core body temperature acting within this narrowed zone. A relaxation-based method, paced respiration, has been shown in 3 controlled investigations to significantly reduce objectively measured hot flash occurrence by about 50% with no adverse effects. In 6 studies of physical exercise, however, investigators did not find positive effects on hot flashes, possibly because exercise raises core body temperature, thereby triggering hot flashes. Although many epidemiologic studies have found increased reports of sleep disturbance during the menopausal transition, recent laboratory investigations have not found this effect, nor have they found that hot flashes produce disturbed sleep. Therefore, sleep complaints in women at midlife should not routinely be attributed to hot flashes or to menopause.

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.

Magnesium sulphate only slightly reduces the shivering threshold in humans

Hypothermia may be an effective treatment for stroke or acute myocardial infarction; however, it provokes vigorous shivering, which causes potentially dangerous haemodynamic responses and prevents further hypothermia. Magnesium is an attractive anti-shivering agent because it is used for treatment of postoperative shivering and provides protection against ischaemic injury in animal models. We tested the hypothesis that magnesium reduces the threshold (triggering core temperature) and gain of shivering without substantial sedation or muscle weakness. We studied nine healthy male volunteers (18-40 yr) on two randomly assigned treatment days: (1) control and (2) magnesium (80 mg kg(-1) followed by infusion at 2 g h(-1)). Lactated Ringer's solution (4 degrees C) was infused via a central venous catheter over a period of approximately 2 h to decrease tympanic membrane temperature by approximately 1.5 degrees C h(-1). A significant and persistent increase in oxygen consumption identified the threshold. The gain of shivering was determined by the slope of oxygen consumption vs core temperature regression. Sedation was evaluated using a verbal rating score (VRS) from 0 to 10 and bispectral index (BIS) of the EEG. Peripheral muscle strength was evaluated using dynamometry and spirometry. Data were analysed using repeated measures anova; P<0.05 was statistically significant. Magnesium reduced the shivering threshold (36.3 [SD 0.4] degrees C vs 36.6 [0.3] degrees C, P = 0.040). It did not affect the gain of shivering (control, 437 [289] ml min(-1) degrees C(-1); magnesium, 573 [370] ml min(-1) degrees C(-1); P=0.344). The magnesium bolus did not produce significant sedation or appreciably reduce muscle strength. Magnesium significantly reduced the shivering threshold. However, in view of the modest absolute reduction, this finding is considered to be clinically unimportant for induction of therapeutic hypothermia.

Dexmedetomidine and Meperidine Additively Reduce the Shivering Threshold

Dexmedetomidine and Meperidine Additively Reduce the Shivering Threshold

Room C, 10/17/2000 9: 00 AM - 11: 00 AM (PS) Buspirone and Meperidine Synergistically Reduce the Shivering Threshold

<b>Room C, 10/17/2000 9: 00 AM - 11: 00 AM (PS) Buspirone and Meperidine Synergistically Reduce the Shivering Threshold</b>

The effect of dynamic exercise on resting cold thermoregulatory responses measured during water immersion

The purpose of this study was to evaluate the effect of exercise on the subsequent post-exercise thresholds for vasoconstriction and shivering measured during water immersion. On 2 separate days, seven subjects (six males and one female) were immersed in water (37.5 degrees C) that was subsequently cooled at a constant rate of approximately 6.5 degrees C x h(-1) until the thresholds for vasoconstriction and shivering were clearly established. Water temperature was then increased to 37.5 degrees C. Subjects remained immersed for approximately 20 min, after which they exited the water, were towel-dried and sat in room air (22 degrees C) until both esophageal temperature and mean skin temperature (Tsk) returned to near-baseline values. Subjects then either performed 15 min of cycle ergometry (at 65% maximal oxygen consumption) followed by 30 min of recovery (Exercise), or remained seated with no exercise for 45 min (Control). Subjects were then cooled again. The core temperature thresholds for both vasoconstriction and shivering increased significantly by 0.2 degrees C Post-Exercise (P < 0.05). Because the Tsk at the onset of vasoconstriction and shivering was different during Pre- and Post-Exercise Cooling, we compensated mathematically for changes in skin temperatures using the established linear cutaneous contribution of skin to the control of vasoconstriction and shivering (20%). The calculated core temperature threshold (at a designated skin temperature of 32.0 degrees C) for vasoconstriction increased significantly from 37.1 (0.3) degrees C to 37.5 ( 0.3) degrees C post-exercise (P < 0.05). Likewise, the shivering threshold increased from 36.2 (0.3) degrees C to 36.5 (0.3) degrees C post-exercise (P < 0.05). In contrast to the post-exercise increase in cold thermal response thresholds, sequential measurements demonstrated a time-dependent similarity in the Pre- and Post-Control thresholds for vasoconstriction and shivering. These data indicate that exercise has a prolonged effect on the post-exercise thresholds for both cold thermoregulatory responses.