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Postoperative shivering in children: a review on pharmacologic prevention and treatment.

Postoperative shivering consists of muscular tremor and rigidity. It is often associated with body heat loss, although hypothermia alone does not fully explain the occurrence of shivering. Shivering is self-limiting, never becomes chronic, and is rarely associated with major morbidity. However, it affects the comfort of the patients, and may sometimes lead to more serious complications. The efficacy of a great variety of pharmacologic interventions to prevent shivering and to treat established symptoms has been tested in randomized controlled trials. These can be gathered systematically; recommendations on prevention and treatment can then be based on the strongest evidence. Unfortunately all these trials have been performed in adults. Thus, recommendations for the control of postoperative shivering in children have to be extrapolated from adult data. In adults, a systematic review strongly suggests that simple measurements are efficacious for both prevention and treatment. For prevention, extrapolation of these adult data indicates that three children have to receive intravenous clonidine 1.5 micro g/kg during anesthesia for one not to shiver, when they would have done so had they not received clonidine. For this degree of efficacy, the expected incidence of shivering (baseline risk) has to be high (approximately 50%). For treatment, extrapolation from adult data indicates that less than two children need to receive intravenous meperidine (pethidine) 0.35 mg/kg, or clonidine 1.5 micro g/kg for one to stop shivering five minutes after drug administration, when they would not have done so had they not received one of these drugs. Since the treatment of established shivering is efficacious, simple, inexpensive, and relatively safe, and since prevention is only efficacious if the baseline risk is very high, we recommend the 'wait and see' strategy.

Adrenergic alpha-Agonists↗

Postanaesthetic shivering. Epidemiology, pathophysiology and approaches to prevention and management.

Postanaesthetic shivering is one of the leading causes of discomfort for patients recovering from general anesthesia. During EMG records, the distinguishing factor from shivering in fully awake patients is the existence of clonus similar to that recorded in patients with spinal cord transection. They coexist with the classic waxing and waning signals associated with cutaneous vasoconstriction (thermoregulatory shivering). The causes responsible for their appearance primarily include hypothermia, which sets in due to thermoregulation inhibition by anesthetics. However, we also note the existence of shivering associated with cutaneous vasodilatation (non-thermoregulatory shivering) one of the origins of which is postoperative pain. Apart from the discomfort and aggravated pain, postanaesthetic shivering raises metabolic demand proportionally to the solicited muscle mass and the patient's cardiac capacities. No link has been demonstrated between their occurrence and an increase in cardiac morbidity but it is preferable to avoid postanaesthetic shivering since it is oxygen draining. Prevention mainly entails preventing hypothermia by actively rewarming the patient. Postoperative skin surface rewarming is a way of obtaining the threshold shivering temperature while raising the skin temperature and improving the patient's comfort. However, it is less efficient than certain drugs such as meperidine, nefopam or tramadol, which act by reducing the shivering threshold temperature.

Anesthesia↗

Effects of extremity wraps to control drug-induced shivering: a pilot study.

Efficacy of a nursing intervention to control amphotericin B-induced, febrile shivering was tested in 40 hospitalized adult patients with cancer. Extremity wraps were used to modify the rate of heat loss from skin to prevent shivering stimulus. Duration of shivering and amount of meperidine required for shivering suppression were compared between treatment and control groups. Total shivering duration was shorter in the treatment group than in the control, p less than .005. Less meperidine was administered to the treatment group than to controls but differences were not statistically significant. The fact that nurses differ in their propensity to use a narcotic to treat shivering may make use of meperidine a poor measure of the intervention's efficacy. Shivering was found to significantly affect myocardial oxygen consumption (MVO2) among subjects who shivered. MVO2, as reflected in the rate pressure product, was found to be significantly higher during shivering (p less than .0001) than at pre- or postshivering periods.

Adult↗

Peripheral nervous system of shiverer mutant mice: developmental change of myelin components and immunohistochemical demonstration of the absence of MBP and presence of P2 protein.

Peripheral nerves of the shiverer mouse, which are characterized by the absence of major dense lines and myelin basic proteins in CNS myelin, were analyzed. From subcellular fractionation of sciatic nerves, it was found from the SDS-polyacrylamide gel electrophoresis that the Pl and Pr proteins equivalent to myelin basic protein of CNS and PM protein were missing in the shiverer in both P2A and P3A fractions in which PNS myelin is recovered. No extra bands were observed in any other fractions of the shiverer in place of the absence of the proteins. The activities of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) of P2A and P3A fractions were high, but that of the P3X fraction which floated over 0.32 M sucrose was the highest among the fractions examined in both the shiverer and the control. Developmental analysis of the protein profiles revealed that PO, Pl, Pr and PM proteins increased rapidly from the sixth day postnatally up to the twentieth day after birth in the control. No differences were observed between the shiverer and the control as for PO protein, but Pl, Pr and PM proteins were absent in the shiverer throughout the development. The CNPase activity of total homogenate of sciatic nerve fibers at birth in the control showed high activity comparable to that of the adult value, but there was no significant difference in activity between the control and the shiverer at any stage of development. Immunohistochemical reaction using peroxidase anti-peroxidase method showed that the myelin from the shiverer did not react with the MBP antiserum, while that of the control reacted positively. On the contrary, the myelin from both shiverer and the control reacted positively against P2 antibody.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗

Prevalences and clinical signs of polysaccharide storage myopathy and shivers in Belgian draft horses.

OBJECTIVE: To determine prevalences of polysaccharide storage myopathy (PSSM) and shivers in Belgian Draft Horses (BDHs) and determine whether there was an association between these 2 conditions. DESIGN: Prospective cohort study. ANIMALS: 103 BDHs > 1 year old. PROCEDURE: Owners were questioned regarding clinical signs of PSSM, shivers, and hindquarter weakness, defined as poor hindquarter muscling and lack of propulsion. Blood samples were collected for determination of serum creatine kinase and aspartate transferase activities and serum selenium and vitamin E concentrations. A biopsy sample from the gluteus medius muscle was submitted for histologic, histochemical, and biochemical analysis. A diagnosis of PSSM was made if abnormal amylase-resistant polysaccharide inclusions were seen histologically. RESULTS: 37 (36%) horses had PSSM and 19 (18%) had shivers, but only 6 (6%) had both PSSM and shivers, whereas 31 (30%) had PSSM alone, 13 (13%) had shivers alone, and 53 (51%) had neither, and a significant association between PSSM and shivers was not detected. Hindquarter weakness was found in 30 horses. Only 13 of 37 (35%) horses with PSSM and 11 of 19 (58%) horses with shivers had hindquarter weakness. Serum creatine kinase and aspartate transferase activities and serum selenium and vitamin E concentrations were not significantly different between horses with and without PSSM or between horses with and without shivers. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that PSSM and shivers are common but unrelated disorders in BDHs.

Animals↗

Alteration of shivering threshold in cold- and warm-adapted guinea pigs following intrahypothalamic injections of noradrenaline and of an adrenergic alpha-receptor blocking agent.

The role of adrenergic receptors in the central thermoregulatory pathways controlling the shivering activity has been studied in groups of cold-adapted (CA), warm-adapted (WA) and newborn (NB) guinea pigs, which show quantitative differences in shivering threshold. In the CA and NB animals, which normally start to shiver at lower mean body temperature levels than the WA controls, microinjection of noradrenaline (1 mug in 1 mul) into the noradrenaline-sensitive area of the anterior hypothalamus elicited shivering at higher body temperatures at which normally only WA animals start to shiver. Similar injections into the hypothalamus of WA animals did not induce any further shift of the shivering threshold. Microinjections of the alpha-receptor blocking agent phentolamine into the same brain area shifted the shivering threshold in all groups of animals to lower body temperatures, the shift being proportional to the injected dose of phentolamine. The CA and NB animals required higher doses of phentolamine to produce a change in shivering threshold. It is concluded that adrenergic alpha receptors are involved in the central thermoregulatory mechanisms which adjust the thresholds for the thermoregulatory reactions.

Adaptation, Physiological↗

Intravenous meperidine for control of shivering during caesarean section under epidural anaesthesia.

To determine the efficacy of meperidine in controlling shivering during epidural anaesthesia for Caesarean section, forty-six parturients were studied. After delivery of the infant, shivering patients received either a single dose of intravenous meperidine 50 mg, or saline in a randomized double-blind fashion. Shivering was classified on a scale of 0 to 3 (grade 0 = none, grade 3 = severe shivering that was distressing to the patient and interfered with monitoring). Shivering and other variables were recorded at epidural placement, skin incision, delivery, and 2, 5, 15, 30 and 60 minutes following injection. Administration of meperidine resulted in a significant decrease in both the overall incidence of shivering (87 to 35 per cent, p less than 0.01) and severity of shivering (grade 3:57 to 0 per cent, p less than 0.01), compared with saline (incidence: 87 to 83 per cent, grade 3:57 per cent, no change). This effect was apparent within two minutes of drug injection and persisted throughout the study period. There were no differences in vital signs, oxygen saturation or temperature between groups. The incidence of nausea was similar, although patients receiving meperidine were more drowsy at two and five minutes following injection (p less than 0.01) compared with patients in the saline group. There were no differences in level of consciousness at the later intervals. The mechanism of action of meperidine on shivering remains to be elucidated.

Adult↗

Magnesium sulphate only slightly reduces the shivering threshold in humans.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗

Late intraoperative clonidine administration prevents postanesthetic shivering after total intravenous or volatile anesthesia.

Postoperative administration of clonidine is an effective treatment for shivering. However, the ability of this drug to stop postanesthetic shivering when administered intraoperatively remains controversial. Furthermore, the relative efficacy of clonidine during isoflurane and propofol anesthesia remains unknown. We therefore evaluated the incidence of postanesthetic shivering in patients given clonidine during nitrous oxide/isoflurane or propofol anesthesia. Because clonidine is an analgesic, we also evaluated postoperative pain and analgesic requirements. We studied 60 patients undergoing elective ear or nose surgery. General anesthesia was induced with 2.0 mg/kg propofol, 1.5 micrograms/kg fentanyl, and 0.1 mg/kg vecuronium. General anesthesia was maintained with isoflurane and 70% nitrous oxide in one group of patients; in the other, a continuous infusion of propofol (8 mg.kg-1.h-1) was administered (without nitrous oxide). Five minutes before tracheal extubation, patients in each group were randomly assigned to receive saline, placebo, or 3 micrograms/kg clonidine intravenously. Postanesthetic shivering was evaluated by a blind investigator. Postoperative pain was assessed using a visual analog scale. Postoperative shivering was observed in 53% of the patients given isoflurane without clonidine and in 13% of the patients given propofol without clonidine. No patient given clonidine shivered. Clonidine administration significantly reduced postoperative pain. The incidence of postanesthetic shivering was significantly less after propofol anesthesia than after isoflurane/nitrous oxide anesthesia. However, a late intraoperative bolus administration of 3 micrograms/kg clonidine prevents postoperative shivering in patients given either type of anesthesia.

Adult↗

Dexamethasone decreases the incidence of shivering after cardiac surgery: a randomized, double-blind, placebo-controlled study.

UNLABELLED: Shivering after cardiac surgery is common, and may be a result of intraoperative hypothermia. Another possible etiology is fever and chills secondary to activation of the inflammatory response and release of cytokines by cardiopulmonary bypass. Dexamethasone decreases the gradient between core and skin temperature and modifies the inflammatory response. The goal of this study was to determine whether dexamethasone can reduce the incidence of shivering. Two hundred thirty-six patients scheduled for elective coronary and/or valvular surgery were randomly assigned to receive either dexamethasone 0.6 mg/kg or placebo after the induction of anesthesia. All patients received standard monitoring and anesthetic management. After arrival in the intensive care unit (ICU), nurses unaware of the treatment groups recorded visible shivering, as well as skin and pulmonary artery temperatures. Analysis of shivering rates was performed by using chi2 tests and logistic regression analysis. Compared with placebo, dexamethasone decreased the incidence of shivering (33.0% vs 13.1%; P = 0.001). It was an independent predictor of reduced incidence of shivering and was also associated with a higher skin temperature on ICU admission and a lower central temperature in the early postoperative period. IMPLICATIONS: Dexamethasone is effective in decreasing the incidence of shivering. The effectiveness of dexamethasone is independent of temperature and duration of cardiopulmonary bypass. Shivering after cardiac surgery may be part of the febrile response that occurs after release of cytokines during cardiopulmonary bypass.

Anti-Inflammatory Agents↗

Clonidine comparably decreases the thermoregulatory thresholds for vasoconstriction and shivering in humans.

BACKGROUND: Clonidine stops postoperative shivering, but its underlying mechanism of action is unknown. Clonidine may impair central control of thermoregulation or act on peripheral receptors. Accordingly, the authors tested the hypothesis that clonidine reduces both the vasoconstriction and shivering thresholds, a pattern consistent with central thermoregulatory impairment. METHODS: Seven healthy volunteers participated in the study. Thermoregulatory vasoconstriction was evaluated using forearm minus fingertip, skin-temperature gradients; values exceeding 4 degrees C were considered to be significant vasoconstriction. Systemic oxygen consumption (VO2) was measured with a canopy system. In addition, shivering was qualitatively evaluated using a simple scale, graduated from 0 (no shivering) to 2 (intense shivering). The tympanic membrane temperatures triggering significant vasoconstriction and grade 1 shivering were considered to be the thresholds for the two thermoregulatory responses. Measurements were performed after a 10-min steady state period and during cooling by central venous infusion of Ringer's lactate solution at 4 degrees C. Each subject was evaluated at two sessions, separated by at least 48 h. They were randomly and blindly assigned to received either an intravenous bolus of 75 micrograms clonidine or a placebo before cooling. When the shivering score equaled 2, 75 micrograms clonidine was injected intravenously, and repeated if necessary, to completely stop shivering.

Adult↗

Propofol linearly reduces the vasoconstriction and shivering thresholds.

BACKGROUND: Skin temperature is best kept constant when determining response thresholds because both skin and core temperatures contribute to thermoregulatory control. In practice, however, it is difficult to evaluate both warm and cold thresholds while maintaining constant cutaneous temperature. A recent study shows that vasoconstriction and shivering thresholds are a linear function of skin and core temperatures, with skin contributing 20 +/- 6% and 19 +/- 8%, respectively. (Skin temperature has long been known to contribute approximately 10% to the control of sweating). Using these relations, we were able to experimentally manipulate both skin and core temperatures, subsequently compensate for the changes in skin temperature, and finally report the results in terms of calculated core-temperature thresholds at a single-designated skin temperature. METHODS: Five volunteers were each studied on 4 days: (1) control; (2) a target blood propofol concentration of 2 micrograms/ml; (3) a target concentration of 4 micrograms/ml; and (4) a target concentration of 8 micrograms/ml. On each day, we increased skin and core temperatures sufficiently to provoke sweating. Skin and core temperatures were subsequently reduced to elicit peripheral vasoconstriction and shivering. We mathematically compensated for changes in skin temperature by using the established linear cutaneous contributions to the control of sweating (10%) and to vasoconstriction and shivering (20%). From these calculated core-temperature thresholds (at a designated skin temperature of 35.7 degrees C), the propofol concentration-response curves for the sweating, vasoconstriction, and shivering thresholds were analyzed using linear regression. We validated this new method by comparing the concentration-dependent effects of propofol with those obtained previously with an established model. RESULTS: The concentration-response slopes for sweating and vasoconstriction were virtually identical to those reported previously. Propofol significantly decreased the core temperature triggering vasoconstriction (slope = -0.6 +/- 0.1 degrees C.micrograms-1.ml-1; r2 = 0.98 +/- 0.02) and shivering (slope = -0.7 +/- 0.1 degrees C.micrograms -1.ml-1; r2 = 0.95 +/- 0.05). In contrast, increasing the blood propofol concentration increased the sweating threshold only slightly (slope = 0.1 +/- 0.1 degrees C.micrograms -1.ml-1; r2 = 0.46 +/- 0.39). CONCLUSIONS: Advantages of this new model include its being nearly noninvasive and requiring relatively little core-temperature manipulation. Propofol only slightly alters the sweating threshold, but markedly reduces the vasoconstriction and shivering thresholds. Reductions in the shivering and vasoconstriction thresholds are similar; that is, the vasoconstriction-to-shivering range increases only slightly during anesthesia.

Adult↗

Isoflurane produces marked and nonlinear decreases in the vasoconstriction and shivering thresholds.

BACKGROUND: Desflurane decreases the vasoconstriction and shivering thresholds disproportionately at high anesthetic concentrations. This result contrasts with the authors' previous report that isoflurane decreases the vasoconstriction threshold linearly. It is surprising that the basic shape of the concentration-response curve should differ with these two otherwise similar anesthetics. Therefore, the hypothesis that isoflurane produces a nonlinear reduction in the vasoconstriction threshold was tested. Because the effect of isoflurane on shivering remains unknown, the extent to which isoflurane reduces the shivering threshold also was determined. METHODS: Eight men volunteered to be studied on four randomly ordered days: (1) a target end-tidal isoflurane concentration of 0.55%, (2) a target concentration of 0.7%, (3) control (no anesthesia) and a target end-tidal concentration of 0.85%, and (4) a target end-tidal concentration of 1.0%. Volunteers were surface-cooled until peripheral vasoconstriction and shivering were observed. We arithmetically compensated for changes in skin temperature using the established linear cutaneous contributions to control for each response. From the calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C), the concentration-response relation was determined. RESULTS: Isoflurane administration produced a dose-dependent reduction in the vasoconstriction and shivering thresholds, decreasing each approximately 4.6 degrees C at an end-tidal concentration of 1%. Residual analysis indicated that the vasoconstriction and shivering thresholds were decreased in a nonlinear fashion during isoflurane administration. The vasoconstriction-to-shivering range was 1.5 +/- 0.8 degree C without isoflurane, and did not change significantly during isoflurane administration. CONCLUSIONS: The vasoconstriction-to-shivering range remained unchanged by isoflurane administration. In this regard, the effects of isoflurane are similar to those of desflurane, propofol, and alfentanil. The current data differ from the authors' previous report, in that the dose-dependence for vasoconstriction was nonlinear, with isoflurane reducing the threshold disproportionately at higher anesthetic concentrations. Differing dose-dependence in the two studies may result either because the current study's volunteers were not exposed to surgical stimulation and were given less isoflurane, or because of design limitations in the previous protocol.

Adult↗

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 microgram/ml (40 mg/h); and 3) a target concentration of 1.8 micrograms/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 C) 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 approximately 35%. Meperidine administration slightly increased the sweating threshold (0.5 +/- 0.8 degree C.microgram-1.ml; r2 = 0.51 +/- 0.37) and markedly decreased the vasoconstriction threshold (-3.3 +/- 1.5 degrees C.microgram-1.ml; r2 = 0.92 +/- 0.08). However, meperidine reduced the shivering threshold nearly twice as much as the vasoconstriction threshold (-6.1 +/- 3.0 degrees C.microgram-1.ml; r2 = 0.97 +/- 0.05; P = 0.001). CONCLUSIONS: The special antishivering efficacy of meperidine results at least in part from an uncharacteristically large reduction in the shivering threshold rather than from exaggerated generalized thermoregulatory inhibition. This pattern of thermoregulatory impairment differs from that produced by alfentanil, clonidine, propofol, and the volatile anesthetics, all which reduce the vasoconstriction and shivering thresholds comparably.

Alfentanil↗

Physostigmine prevents postanesthetic shivering as does meperidine or clonidine.

BACKGROUND: Postanesthetic shivering develops in as many as one half of patients recovering from isoflurane anesthesia. Cholinergic stimulation of the hypothalamic-pituitary-adrenal axis and adrenal medulla by physostigmine enhances secretion of arginine vasopressin, epinephrine, and norepinephrine. Because the hypothalamus is the dominant thermoregulatory controller in mammals, and these neurotransmitters may be involved in body temperature control, physostigmine administration may influence the incidence of shivering. Accordingly, the authors tested the hypothesis that physostigmine administration inhibits postanesthetic shivering. Its efficacy was compared with that of saline (negative control) and meperidine and clonidine (positive controls). METHODS: Sixty patients having surgery of the ear or nose were tested. General anesthesia was induced with 2 mg/kg propofol, 0.1 mg/kg vecuronium, and 1.5 microg/kg fentanyl and maintained with isoflurane (1.5 +/- 0.4%) in 70% nitrous oxide. At the end of surgery, the patients were randomly assigned to receive an intravenous bolus of 0.04 mg/kg physostigmine, isotonic saline, 0.5 mg/kg meperidine, or 1.5 microg/kg clonidine. Heart rate, mean arterial blood pressure, oxygen saturation, visual analog pain score, temperature, and postanesthetic shivering were measured during recovery. RESULTS: Postanesthetic shivering occurred in 6 of 15 (40%) patients given saline. In contrast, postanesthetic shivering was significantly reduced in physostigmine-treated patients (1 of 15, or 7%) and was absent in patients given clonidine or meperidine. CONCLUSIONS: Physostigmine inhibited shivering as well as did two established treatments, meperidine and clonidine. These data suggest that cholinergic systems contribute to the genesis and control of postanesthetic shivering.

Adult↗

Relative contribution of skin and core temperatures to vasoconstriction and shivering thresholds during isoflurane anesthesia.

BACKGROUND: Thermoregulatory control is based on both skin and core temperatures. Skin temperature contributes approximately 20% to control of vasoconstriction and shivering in unanesthetized humans. However, this value has been used to arithmetically compensate for the cutaneous contribution to thermoregulatory control during anesthesia--although there was little basis for assuming that the relation was unchanged by anesthesia. It even remains unknown whether the relation between skin and core temperatures remains linear during anesthesia. We therefore tested the hypothesis that mean skin temperature contributes approximately 20% to control of vasoconstriction and shivering, and that the contribution is linear during general anesthesia. METHODS: Eight healthy male volunteers each participated on 3 separate days. On each day, they were anesthetized with 0.6 minimum alveolar concentrations of isoflurane. They then were assigned in random order to a mean skin temperature of 29, 31.5, or 34 degrees C. Their cores were subsequently cooled by central-venous administration of fluid at approximately 3 degrees C until vasoconstriction and shivering were detected. The relation between skin and core temperatures at the threshold for each response in each volunteer was determined by linear regression. The proportionality constant was then determined from the slope of this regression. These values were compared with those reported previously in similar but unanesthetized subjects. RESULTS: There was a linear relation between mean skin and core temperatures at the vasoconstriction and shivering thresholds in each volunteer: r2 = 0.98+/-0.02 for vasoconstriction, and 0.96+/-0.04 for shivering. The cutaneous contribution to thermoregulatory control, however, differed among the volunteers and was not necessarily the same for vasoconstriction and shivering in individual subjects. Overall, skin temperature contributed 21+/-8% to vasoconstriction, and 18+/-10% to shivering. These values did not differ significantly from those identified previously in unanesthetized volunteers: 20+/-6% and 19+/-8%, respectively. CONCLUSIONS: The results in anesthetized volunteers were virtually identical to those reported previously in unanesthetized subjects. In both cases, the cutaneous contribution to control of vasoconstriction and shivering was linear and near 20%. These data indicate that a proportionality constant of approximately 20% can be used to compensate for experimentally induced skin-temperature manipulations in anesthetized as well as unanesthetized subjects.

Adult↗

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. microg-1. ml; r2 = 0.73 +/- 0.32) or vasoconstriction (-3.6 +/- 5.0 degrees C. microg-1. ml; r2 = -0.47 +/- 0.41). In contrast, nefopam significantly reduced the slope of shivering (-16.8 +/- 9.3 degrees C. microg-1. 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. CONCLUSIONS: Most drugs with thermoregulatory actions-including anesthetics, sedatives, and opioids-synchronously reduce the vasoconstriction and shivering thresholds. However, nefopam reduced only the shivering threshold. This pattern has not previously been reported for a centrally acting drug. That pharmacologic modulations of vasoconstriction and shivering can be separated is of clinical and physiologic interest.

Adult↗

The space blanket and shivering during extradural analgesia in labour.

The incidence of shivering in women during epidural analgesia in labour is up to 33%, and may be highly distressing. Its mechanism is unclear, but the most widely held theory is that it is thermogenic. Pharmacological suppression may adversely effect the foetus or induce maternal hypothermia, and although physical remedies such as direct heat application are effective, they are also expensive and cumbersome. We recently found that the space blanket, a simple aluminised metallic foil, used pre-emptively, reduces shivering after general anaesthesia. We investigated the effect of the space blanket on the incidence and intensity of shivering, axilliary skin temperature, and subjective perception of cold during epidural analgesia for labour in 50 women over a four-hour time frame. Patients were randomised into group 1, who were wrapped in a space blanket immediately after commencement of epidural analgesia with bupivacaine, and group 2 (matched controls). Shivering was defined as visible tremor of the head, neck, trunk or limbs as observed by the attending midwives. Twenty-nine percent of group 1 and 35% of group 2 shivered (not significant), but a reduction in shivering intensity was observed in group 1 (P < 0.05). There was no significant difference in skin temperatures in either group, and no significant temperature change within the groups. Both groups had similar thermal comfort scores throughout the study, which correlated poorly with the presence of shivering. We conclude that there is no benefit in application of the space blanket to reduce epidural-analgesia related shivering in labour, which may indicate a non-thermogenic mechanism for this phenomenon.

Adult↗