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Cold-induced heat production preceding shivering.

Individual changes in heat production and body temperature were studied in response to cold exposure, prior to shivering. The subjects ten women (seven men) were of normal weight, had a mean age of 23 (SD 3) years and average BMI 22.2 (SD 1.6) Kg/m2. They were lying supine under thermoneutral conditions for 30 min and were subsequently exposed to air of 15 degrees C until shivering occurred. Heat production was measured with a ventilated hood. Body composition was measured with underwater weighing and 2H dilution. Body temperatures were measured with thermistors. Heat production during cold exposure prior to shivering increased and reached a plateau. Skin temperature decreased and did not reach a plateau during the test period. The non-shivering interval (NSI) ranged from 20 to 148 min, was not related to body composition and was not significantly different between women (81 (sd 15) min) and men (84 (sd 34) min). NSI was negatively related to skin temperature (r2 0.44, P=0.004), and skin temperature was related to heat production (r2 0.39, P=0.007). In conclusion, subjects with a relatively large heat production during cold exposure maintained a relatively high skin temperature but showed a short NSI, independent of differences in body composition.

Adult↗

Contribution of extradural temperature to shivering during extradural anaesthesia.

Thirty patients having postpartum tubal ligation under extradural anaesthesia were studied. All received bupivacaine at 4 degrees C initially and the incidence of shivering (47%), and the extradural temperatures measured with a small thermistor threaded into the extradural catheter, were recorded. To eight patients in whom the resultant shivering was marked, further bupivacaine warmed to 41 degrees C was injected. In four of these patients, shivering was stopped. The results suggest that thermosensitive tissue within the spinal canal contributes to the shivering observed in association with extradural anaesthesia.

Adult↗

IV clonidine for post-extradural shivering in parturients: a preliminary study.

We have studied the efficacy of i.v. clonidine to suppress post-extradural shivering in parturients. Forty healthy parturients who received extradural block for labour (n = 20) or for Caesarean section (n = 20) and who required treatment for shivering after delivery were allocated randomly to two groups. Group I received i.v. clonidine 30 micrograms diluted in saline to a total volume of 5 ml (therapeutic solution). This bolus was repeated every 5 min if the initial therapy produced no improvement, up to a maximum dose of 90 micrograms. Group II received saline 5 ml (placebo solution), repeated every 5 min if the initial bolus produced no improvement, up to a maximum of three boluses. After 15 min of observation, patients in group I received the placebo solution and those in group II received the study solution. All patients who received clonidine improved, and 75% ceased to shiver within 5 min after only one dose of clonidine 30 micrograms. In contrast, none of the patients treated with saline improved. When patients in the placebo group received clonidine, improvement occurred. Arterial pressure, heart rate, core and peripheral temperature and oxygen saturation did not differ significantly between and within the groups before and after administration of clonidine. We conclude that a small dose of i.v. clonidine may be useful to suppress post-extradural shivering in parturients.

Anesthesia Recovery Period↗

The effects of prostaglandin E1 on intraoperative temperature changes and the incidence of postoperative shivering during deliberate mild hypothermia for neurosurgical procedures.

UNLABELLED: We investigated the effects of i.v. prostaglandin E1 (PGE1) on intraoperative changes of core temperature and the incidence of postoperative shivering in neurosurgical patients undergoing deliberate mild hypothermia. Eighty-three patients were randomly assigned to one of three groups: patients in the control group did not receive PGE1, whereas patients in the PG20 group and PG50 group received PGE1 at a dose of 0.02 and 0.05 microg x kg(-1) x min(-1), respectively. The administration of PGE1 was started just after the induction of anesthesia and continued until the end of anesthesia. Anesthesia was maintained with nitrous oxide in oxygen, sevoflurane, and fentanyl. After the induction of anesthesia, patients were cooled using a water blanket and a convective device blanket. Tympanic membrane temperature was maintained at 34.5 degrees C. During surgical wound closure, patients were rewarmed. Intraoperative changes in tympanic membrane and skin temperatures and the incidence of postoperative shivering were compared among groups. Demographic and intraoperative variables were similar among groups. There were no significant differences in tympanic temperatures among groups at each point during the operation. Skin temperature 30 min after rewarming and just after tracheal extubation was significantly lower in the PG20 group than in the PG50 group. Postoperative shivering was more frequent in the PG20 group (43%) than in the control (13%) and PG50 (17%) groups. These results suggest that the intraoperative administration of PGE1 does not affect changes in core temperature during deliberate mild hypothermia and that PGE1 at a dose of 0.02 microg x kg(-1) x min(-1) may increase the occurrence of postoperative shivering. IMPLICATIONS: Deliberate mild hypothermia has been proposed as a means of providing cerebral protection during neurosurgical procedures. Vasodilating drugs may be used during deliberate mild hypothermia to maintain peripheral circulation and to enhance the cooling and rewarming rate. In the present study, however, we found no benefit from i.v. prostaglandin E1 administration during deliberate mild hypothermia in neurosurgical patients.

Alprostadil↗

Ondansetron given before induction of anesthesia reduces shivering after general anesthesia.

UNLABELLED: The neurotransmitter pathways involved in the mechanism of postanesthetic shivering (PAS) are poorly understood. Meperidine, clonidine, and physostigmine are all effective treatments, indicating that opioid, alpha(2)-adrenergic, and anticholinergic systems are probably involved. We investigated the effect of ondansetron, a 5-HT(3) antagonist used to treat postoperative nausea and vomiting, on intraoperative core and peripheral temperatures and PAS. Eighty-two patients (age, 18-60 yr) undergoing orthopedic, general, or urological surgery were randomized into three groups in this double-blinded, placebo-controlled, study: Group O4 (n = 27) received ondansetron 4 mg IV, Group O8 (n = 27) received ondansetron 8 mg IV, and Group C (n = 28) received saline IV immediately before the anesthetic induction. Core (tympanic) and fingertip temperature (dorsum of middle finger) were recorded. Anesthesia was induced with IV fentanyl 1 microg/kg and propofol 2.0-2.5 mg/kg and maintained with 1 minimum alveolar anesthetic concentration isoflurane in 70% nitrous oxide/oxygen. The occurrence of shivering was documented clinically during recovery by nursing staff, who were unaware of the group assignment. PAS occurred in 16 of 28 (57%) patients in Group C, compared with 9 of 27 (33%) in Group O4 (P = 0.13) and 4 of 27 (15%) patients in Group O8 (P = 0.003). Within each group, core temperature decreased and peripheral temperature increased significantly, but there were no significant differences among the groups at any time interval. We conclude that ondansetron 8 mg IV given during the induction of anesthesia prevents PAS without affecting the core-to-peripheral redistribution of heat during general anesthesia. This suggests that serotonergic pathways have a role in the regulation of PAS. IMPLICATIONS: In a randomized, double-blinded, placebo-controlled, clinical study, ondansetron 8 mg IV, given just before the induction, reduced the incidence of postanesthetic shivering compared with saline. The anticipated core-to-peripheral redistribution of body temperature during general anesthesia was not affected. This implies that ondansetron probably acts by a central inhibitory mechanism, and that 5-hydroxytryptaminergic pathways have a role in regulating postanesthetic shivering.

Adult↗

Spontaneous post-anesthetic tremor does not resemble thermoregulatory shivering.

Spontaneous post-anesthetic tremor that resembles shivering is common during recovery from anesthesia. Risks to postoperative patients include an increase in metabolic rate of up to 400%, hypoxemia, wound dehiscence, dental damage, and disruption of delicate surgical repairs. The etiology of spontaneous post-anesthetic tremor is most commonly attributed to normal thermoregulatory shivering in response to intraoperative hypothermia. However, the mechanism of this tremor remains unknown, hampering prevention and treatment. The present study was designed to determine whether mechanisms other than thermoregulation contribute to the tremor. The electromyograms (EMGs) of eight muscles were observed in nine women during recovery from isoflurane anesthesia. Signals from each muscle were compared to those of pathologic clonus induced by plantar flexion in unanesthetized patients with spinal cord transections and to those of cold-induced shivering in normal, unanesthetized subjects. Two distinct EMG patterns were identified: 1) regular, bursting signals of 5-7 Hz similar to those produced by pathologic clonus in patients with spinal cord transections; and 2) tonic, irregular signals of 5-15 Hz which had poorly defined bursts that did not demonstrate the synchronous 4-8-cycle/min waxing and waning pattern typical of normal shivering. EMG activity occurred most often at expired isoflurane concentrations of 0.1-0.19%, and was not related to rectal temperature. During the later part of recovery when isoflurane concentrations were less than or equal to 0.1%, hypothermic patients frequently demonstrated no clinical or EMG evidence of muscular activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Naloxone, meperidine, and shivering.

BACKGROUND: Meperidine, which binds both mu and kappa opioid receptors, is reportedly more effective in treating shivering than are equianalgesic doses of morphine (a nearly pure mu-receptor agonist). Furthermore, butorphanol, a kappa-receptor agonist/antagonist, treats shivering better than does fentanyl, which mostly binds mu receptors. These data indicate that much of meperidine's special antishivering activity may be mediated by its kappa activity. Accordingly, the authors tested the hypothesis that the antishivering activity of meperidine will be minimally impaired by low-dose naloxone (blocking most mu-receptors), but largely prevented by high-dose naloxone (blocking all mu and most kappa receptors). METHODS: Twelve volunteers each participated on 2 days. On both days, shivering was induced by central venous infusion of cold fluid. Twenty minutes later, six volunteers were given a placebo infusion of saline on one day, or an infusion of 0.5 microgram.kg-1.min-1 naloxone hydrochloride ("low-dose," designed to block mu receptors) on the other. The second group of six volunteers was given a saline bolus and infusion on one day, or a bolus of 11.5 micrograms/kg naloxone hydrochloride followed by an infusion of naloxone at 5 micrograms.kg-1.min-1 ("high-dose," designed to block both mu and kappa receptors) on the other day. The infusions were continued for the duration of the study. The order of the treatment days (saline vs. naloxone) was randomly assigned, and the study was double blinded. Fifteen minutes after the test infusion was started, all 12 volunteers were given an intravenous bolus of 1 mg/kg meperidine hydrochloride. Pupillary diameter and light reflex amplitude were used to quantify opioid-receptor agonist activity; shivering intensity was evaluated using oxygen consumption. RESULTS: Administration of naloxone alone did not alter oxygen consumption, pupil size, or the pupillary light reflex. No pupillary constriction was detected in either group when naloxone and meperidine were combined; in contrast, meperidine alone decreased pupil size and amplitude of the light reflex 30%. The meperidine bolus decreased oxygen consumption nearly to control values when the volunteers were given saline placebo. Combined administration of meperidine and low-dose naloxone also significantly reduced oxygen consumption, but the reduction and the duration of the reduction was less than during saline. When the volunteers were given high-dose naloxone, meperidine only slightly reduced oxygen consumption, and the values rapidly returned to premeperidine levels. CONCLUSIONS: These data indicate that the antishivering property of meperidine is not fully mediated by mu-receptors. Although meperidine has well-known nonopioid actions, stimulation of kappa receptors seems a likely alternative explanation for much of the drug's antishivering action.

Adult↗

Facial warming increases the threshold for shivering.

A decrease of 1-2 degrees C core temperature provides protection against cerebral ischemia. However, shivering usually prevents reduction in core temperature in unanesthetized patients. Therefore, it was tested whether facial and airway heating increases the shivering threshold and enables core cooling in unanesthetized patients. Nine trials were performed on seven healthy male volunteers. Each subject was positioned supine on a circulating-water mattress (8-15 degrees C) with a convective-air coverlet (15-18 degrees C) extending from the neck to the feet. A dynamic study protocol governed by individualized physiological responses was used. Focal facial (and airway) warming was employed to suppress involuntary motor activity (muscle tensing, shivering) and, thereby, enabling noninvasive cooling to lower the core temperature. The following parameters were monitored: 1) heart rate, 2) blood pressure, 3) core temperature (tympanic, axilla, and rectal), 4) cutaneous temperatures, and 5) a subjective shiver index (scale 1-10). In three, electromyograms and infrared thermographs were also obtained. Upon cooling without facial and airway warming, involuntary motor activity increased until it was widespread. This vigorous motor activity prevented any significant lowering of core temperature or caused it to slightly increase. Subsequently, in all subjects, within seconds after the application of facial focal warming, motor activity was suppressed almost completely, and within minutes core temperatures significantly decreased. Preliminary studies described here indicate that focal facial warming applied during active whole body cooling to initiate mild hypothermia might minimize the need to pharmacologically suppress involuntary motor activity. Such a procedure might be useful for initiating as soon as possible (such as during emergency transport), cerebral mild hypothermia in order to maximize protection and thus improve outcome in neurologically injured patients (head trauma, stroke).

Adult↗

Physostigmine for the prevention of postanaesthetic shivering following general anaesthesia - a placebo-controlled comparison with nefopam.

Physostigmine was studied for its efficacy in the prevention of postanaesthetic shivering compared to nefopam and placebo. We studied 89 patients undergoing abdominal and urological surgery. The study was randomised and double-blind, the patients received physostigmine 2 mg (n = 31), nefopam 10 mg (n = 30) or saline (n = 28). Haemodynamic parameters and temperature were measured at induction of anaesthesia (T0), and 5 min (T1), 15 min (T2), 30 min (T3) and 60 min (T4) after reaching the postanaesthetic care unit (PACU). Significantly less shivering occurred following administration of physostigmine and nefopam (9.7 and 3.3%) compared to placebo (53.6%). The degree of shivering was also significantly reduced following physostigmine and nefopam (p < 0.01). Extubation time, haemodynamic parameters and tympanic temperature were found to be similar in all groups. Aldrete score, duration of PACU stay and postoperative analgesic requirements did not differ between the groups. Only nefopam significantly (p < 0.01) reduced postoperative nausea and vomiting. Physostigmine is a safe alternative to nefopam, significantly reducing the incidence and severity of postanaesthetic shivering without affecting postanaesthetic recovery.

Adult↗

Effect of injury on shivering thermogenesis in the rat.

1. Shivering in response to changes in ambient or core temperature has been measured in control rats and rats injured by bilateral hind-limb ischaemia, both with and without fur.2. Removal of the fur increased the threshold ambient temperature for the onset of shivering.3. This threshold was lower than in uninjured controls during the latter half of a 4 hr period of bilateral hind-limb ischaemia in rats with or without fur.4. The threshold was also lower than in uninjured controls after the period of bilateral hind-limb ischaemia but was not significantly different from that during the period of ischaemia.5. The alterations in threshold were not accompanied by any significant changes in the slope of the regression line relating intensity of shivering and ambient temperature.6. When the core temperature fell after limb ischaemia to levels which provoked shivering in uninjured controls, no shivering was seen in the injured rats.7. These results are interpreted as further evidence for the lowering of the ;set-point' for thermogenesis after injury in the rat and are discussed in relation to the changes in body temperature after injury in that species.

Animals↗

Catecholaminergic alpha-receptors and shivering in the rat.

1. A rise or a fall in systemic blood pressure brought about by the I.V. infusion of peripherally acting drugs (adenosine, noradrenaline or methoxamine) inhibited shivering in the cold-exposed rat. 2. Since the injection of commonly used doses of noradrenaline (0.05-0.10 mumole) into a lateral cerebral ventricle of a rat was usually accompanied by a rise in blood pressure special precautious were required to determine whether noradrenaline had a specific central effect on shivering. 3. Small doses of noradrenaline (0.02-0.03 mumole) or clonidine (0.01 mumole) which had no effect on blood pressure when injected into a lateral cerebral ventricle still inhibited shivering in the cold-exposed rat and this effect was prevented by phentolamine. 4. It is concluded that noradrenaline can inhibit the cold sensor-shivering pathway in its central course by an action on alpha-receptors.

Adenosine↗

Fuel selection during intense shivering in humans: EMG pattern reflects carbohydrate oxidation.

The thermogenic response of humans depends critically on the coordination of muscle fibre recruitment and oxidative fuel metabolism. The primary goal of this study was to determine whether the electromyographic (EMG) pattern of muscle recruitment could provide metabolic information on oxidative fuel selection during high-intensity shivering. EMG activity (of 8 large muscles) and fuel metabolism were monitored simultaneously in non-acclimatized adult men during high-intensity shivering. Even though acute cold exposure elicited similar changes in metabolic rate among subjects, lipid and carbohydrate use was very different. Depending on the subject, the cold-induced increase in carbohydrate (CHO) oxidation ranged between 2- and 8-fold, with CHO accounting for 33-78% of total heat production, and lipids for 14-60%. This high variability in fuel selection was primarily explained by differences in 'burst shivering' rate, indicating that the recruitment of type II fibres plays a key role in orchestrating fuel selection. This study is the first to show that the pattern of muscle recruitment can provide quantitative information on energy metabolism. Future work should focus on the study of shivering bursts that may provide essential clues on what limits human survival in the cold.

Adult↗

Shivering and nonshivering thermogenic responses of rats subjected to different patterns of heat acclimation.

Male Wistar rats were divided into five groups: a control group kept at an ambient temperature of 24 degrees C for 14 days, and four heat-acclimated groups (two groups subjected to a constant ambient temperature of 33 degrees C for 4 days or 14 days (HC-14) immediately preceding the measurement; and another two groups subjected to an ambient temperature of 33 degrees C for about 5 h once a day for 4 days, or 14 days (HI-14) just prior to the measurement). After the completion of the schedule, the rats were placed in a temperature-controlled chamber. Hypothalamic (Thy) and interscapular brown adipose tissue (TBAT) temperatures, oxygen consumption (VO2), and shivering activity were measured during a gradual fall in temperature of a water jacket surrounding the chamber (TW) from 30 to 10 degrees C at a constant rate of 0.18 degree C/min. During the fall in TW, VO2 and TBAT increased significantly and shivering was induced without associate changes in Thy in all groups. TW at the onset of a rise in metabolic heat production (onset of cold-induced thermogenesis) coincided with that at the onset of a rise in TBAT (onset of BAT thermogenesis), but was significantly higher than that at the onset of shivering. In HC-14 and HI-14 rats, TWS at the onset of cold-induced thermogenesis and BAT thermogenesis were significantly higher than those in control rats, whereas TWS at the onset of shivering were not different from those in control rats. The onset of cold-induced thermogenesis did not change after the 4-day heat exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

Electrical stimulation of the posterior and ventromedial hypothalamic nuclei causes specific activation of shivering and nonshivering thermogenesis.

Experiments were designed to determine in the same animal whether electrical stimulation of the posterior hypothalamus and ventromedial hypothalamic nucleus could specifically evoke shivering and nonshivering (brown adipose tissue) thermogenesis, respectively, in anesthetized, normothermic rats. Urethane-anesthetized, male Long-Evans rats, kept at 37 degrees C, had colonic (Tc), gastrocnemius muscle (Tm), intrascapular brown adipose tissue (TIBAT), and tail (Tt) temperatures measured via thermistor probes, and electromyogram activity (differential multiunit activity from bipolar recording electrodes within gastrocnemius muscle) recorded, before and after unilateral electrical stimulation (monophasic 0.5-ms pulses of 200 microA at 50 Hz for 30 s) of the posterior hypothalamus and ventromedial hypothalamic nucleus (via stereotaxically implanted concentric stimulating electrodes). Each rat showed shivering (increased electromyogram activity) following posterior hypothalamic stimulation, which caused an immediate rise in Tm values with no change in TIBAT or Tt values. Electrical stimulation of the ventromedial hypothalamic nucleus of the same animals elicited no shivering activity, but significant increases in TIBAT values occurred with no change in Tm or Tt values. Results confirm that stimulation of the posterior and ventromedial hypothalamic nuclei in rodents specifically activates shivering and nonshivering (brown adipose tissue) effector mechanisms, respectively, to raise core temperature.

Adipose Tissue, Brown↗

Shivering and nonshivering thermogenic responses of cold-exposed rats to hypothalamic warming.

The concurrent neural control of two thermoregulatory responses, shivering thermogenesis (ST) and nonshivering thermogenesis (NST), was investigated in chronically implanted cold-exposed rats. The effects of heating the preoptic/anterior hypothalamus (POAH) on shivering and on the rate of oxygen consumption (Vo2) were measured in these unanesthetized animals. With ambient temperature maintained constant (at some value between 10 and 16 degrees C), warming the hypothalamus 2-3 degrees C resulted in a significant decrease in Vo2 (Psmaller than 0.001) and an increase in shivering (Psmaller than .01), these responses being reversed on cessation of hypothalamic warming. These results are consistent with the proposal that, in the cold-exposed animal, elevated POAH temperatures directly inhibit NST even though shivering may increase (possibly as a compensation for the decrease in nonshivering heat production). They also rule out the possibility that, in the rat, signals from cutaneous and hypothalamic thermoreceptors are integrated in an indentical manner by the neural controllers for ST and NST.

Animals↗

Brainstem control of shivering in the cat. I. Inhibition.

Regions containing heat gain tonic inhibitory areas in mesencephalon and upper pons were studied using topical microinjection of a local anesthetic. This inhibition was compared in the mesencephalic decerebrated and intact animals. In mesencephalic animals that failed to shiver, bilateral injections of procaine into the ventromedial pontine tegmental areas released some heat gain responses and in intact anesthetized cats injections in the same regions increased intensity of shivering. These effects on inhibitory areas are reversible and can be repeated in the same preparation several times. Permanent effects were obtained by electrolytic lesions or by the local microinjections of 1% osmic acid. In summary, it is shown, by means of microinjection of local anesthetic, that a tonic inhibitory area located in the ventromedial pontine reticular formation completely inhibits shivering in the mesencephalic decerebrate preparation and partially inhibits shivering in the intact anesthetized preparation.

Animals↗

Lateral distribution of hypothalamic signals controlling thermoregulatory vasomotor activity and shivering in rats.

The present study explored the laterality of central nervous thermoregulatory control in anesthetized rats by measuring paw skin vasomotor activity and cold-induced shivering in hind leg muscles during unilateral preoptic area and anterior hypothalamus (POAH) warming and electrical stimulation or during unilateral thermal stimulation of abdominal skin. Unilateral POAH warming produced vasodilation on both sides of the body, but vasodilation on the ipsilateral side always either occurred at a lower threshold hypothalamic temperature or was stronger than on the contralateral side. In a cold environment (5 degrees C), shivering was suppressed simultaneously in both hind legs when one side of the POAH was warmed, and shivering reappeared simultaneously on both sides when POAH warming stopped. These results suggest that different thermoregulatory effectors are regulated in a different way by each side of the POAH. Unilateral thermal stimulation of the abdominal skin, on the other hand, affected vasomotor activity and shivering equally on both sides of the body, as previously reported for its influence on salivary secretion. Skin thermal signals from both sides of the body therefore seem to converge before they act on different thermoregulatory effector systems.

Abdomen↗

Fever: exchange of shivering by nonshivering pyrogenesis in cold-acclimated guinea pigs.

The pyrogenic response of adult, unanesthetized guinea pigs to 2 mug/kg iv of Salmonella enteritidis endotoxin was measured at 27 and 7 degrees C ambient temperatures, both before and after an 8-wk exposure to 7 degrees C. There were no significant differences between the onset, maximum height, and total duration of the fevers produced before and after cold acclimation in both thermal environments. However, in 27 degrees C, before cold acclimation, fever production was associated with vigorous shivering activity; two temperature maxima typically developed. After cold acclimation, visible shivering was not detectable during pyrogenesis; moreover, only a single maximum occurred, culminating during the interval between the two rises previously. In 7 degrees C, shivering occurred in both the non-cold- and cold-acclimated endotoxin-treated guinea pigs, but the increase in oxygen consumption was significantly greater in the latter. These results indicated, therefore, that nonshivering (NST) replaces shivering thermogenesis (ST) in a thermoneutral, while ST is added onto NST in a cold, environment in cold-acclimated guinea pigs in supplying the necessary heat for fever production, and that these effects involve alterations in the character of the febrile course.

Adipose Tissue, Brown↗