Neural circuits of long-term thermoregulatory adaptations to cold temperatures and metabolic demands.

The mammalian brain controls heat generation and heat loss mechanisms that regulate body temperature and energy metabolism. Thermoeffectors include brown adipose tissue, cutaneous blood flow and skeletal muscle, and metabolic energy sources include white adipose tissue. Neural and metabolic pathways modulating the activity and functional plasticity of these mechanisms contribute not only to the optimization of function during acute challenges, such as ambient temperature changes, infection and stress, but also to longitudinal adaptations to environmental and internal changes. Exposure of humans to repeated and seasonal cold ambient conditions leads to adaptations in thermoeffectors such as habituation of cutaneous vasoconstriction and shivering. In animals that undergo hibernation and torpor, neurally regulated metabolic and thermoregulatory adaptations enable survival during periods of significant reduction in metabolic rate. In addition, changes in diet can activate accessory neural pathways that alter thermoeffector activity. This knowledge may be harnessed for therapeutic purposes, including treatments for obesity and improved means of therapeutic hypothermia.

Preventing hypothermia in pediatric neurosurgery in Africa-A randomized controlled non-inferiority trial of insulation versus active warming.

PURPOSE: The objective of this study was to compare the efficacy of a low-cost heat-preserving method in preventing intraoperative hypothermia with that of forced-air warming in a resource-limited setting. METHODS: In this randomized controlled non-inferiority trial, we recruited children younger than 12 years scheduled for cranial neurosurgery in a large East-African hospital. Patients were block-randomized by age to intraoperative warming measures using Hibler's method (intervention) or warm air (comparator). Hibler's group patients were circumferentially wrapped in transparent plastic sheeting (providing a vapor-trap) over a layer of cotton blankets, then laid on an insulating foam mattress. Warm air group patients were treated with forced-air convection via an underlying Snuggle Warm™ Pediatric Full Body mattress. Allocated warming measures were initiated in the operating theatre and discontinued upon anesthesia emergence. Perioperative temperatures were measured using noninvasive forehead probes (SpotOn™). The primary outcome was incidence of hypothermia (core temperature < 36.0° for longer than 5 min). Our null hypothesis was that Hibler's method is inferior in efficacy to the warm air method by a margin exceeding 20%. Among secondary outcomes were duration of hypothermia as proportion of surgical duration, incidence of postoperative shivering and rescue measure requirements. RESULTS: We analyzed data for 77 participants (Hibler's = 38; warm air = 39). There was no significant difference between the Hibler's and warm air arms of the study in the primary outcome of incidence of hypothermia (59.0% vs. 60.5% respectively; OR 1.07; 95% CI 0.43-2.65; p = .890). However, the risk difference (1.55%; 95% CI -0.20 to -0.24) exceeded the 0.2 margin and non-inferiority could not be declared. There was considerable need for rescue measures in both groups (71.1 0% vs. 69.2%; OR 1.09; 95% CI 0.41-2.90; p = .861). There was no statistically significant difference between groups for any prespecified secondary outcome. CONCLUSION: Although perioperative core temperatures were not significantly different, we could not declare an inexpensive heat-preserving method non-inferior to warm air convection in preventing intraoperative hypothermia in children undergoing anesthesia for cranial neurosurgery in a resource-limited setting. The extensive need for rescue measures may have masked important differences. TRIAL REGISTRATION: US National Institutes of Health Clinicaltrials.gov database (ID no. NCT02975817).

A century of exercise physiology: concepts that ignited the study of human thermoregulation. Part 4: evolution, thermal adaptation and unsupported theories of thermoregulation.

This review is the final contribution to a four-part, historical series on human exercise physiology in thermally stressful conditions. The series opened with reminders of the principles governing heat exchange and an overview of our contemporary understanding of thermoregulation (Part 1). We then reviewed the development of physiological measurements (Part 2) used to reveal the autonomic processes at work during heat and cold stresses. Next, we re-examined thermal-stress tolerance and intolerance, and critiqued the indices of thermal stress and strain (Part 3). Herein, we describe the evolutionary steps that endowed humans with a unique potential to tolerate endurance activity in the heat, and we examine how those attributes can be enhanced during thermal adaptation. The first of our ancestors to qualify as an athlete was Homo erectus, who were hairless, sweating specialists with eccrine sweat glands covering almost their entire body surface. Homo sapiens were skilful behavioural thermoregulators, which preserved their resource-wasteful, autonomic thermoeffectors (shivering and sweating) for more stressful encounters. Following emigration, they regularly experienced heat and cold stress, to which they acclimatised and developed less powerful (habituated) effector responses when those stresses were re-encountered. We critique hypotheses that linked thermoregulatory differences to ancestry. By exploring short-term heat and cold acclimation, we reveal sweat hypersecretion and powerful shivering to be protective, transitional stages en route to more complete thermal adaptation (habituation). To conclude this historical series, we examine some of the concepts and hypotheses of thermoregulation during exercise that did not withstand the tests of time.

Impact of intraoperative hypothermia on the recovery period of anesthesia in elderly patients undergoing abdominal surgery.

BACKGROUND: This study aimed to investigate the impact of intraoperative hypothermia on the recovery period of anesthesia in elderly patients undergoing abdominal surgery. METHODS: A prospective observational study was conducted based on inclusion and exclusion criteria. A total of 384 elderly patients undergoing abdominal surgery under general anesthesia were enrolled in a grade A tertiary hospital in Chengdu, Sichuan Province from October 2021 and October 2022. After anesthesia induction, inflatable warming blankets were routinely used for active heat preservation, and nasopharyngeal temperature was monitored to observe the occurrence of intraoperative hypothermia. Patients were divided into hypothermia group and nonhypothermia group according to whether hypothermia occurred during the operation. Anesthesia recovery time and the incidence of adverse events or unwanted events during anesthesia recovery between the two groups were compared. RESULTS: The numbers (percentage) of 384 patients who underwent abdominal surgery developed intraoperative hypothermia occurred in 240 (62.5%) patients, all of whom had mild hypothermia. There were statistically significant differences between mild hypothermia after active warming and nonhypothermia in the occurrence of shivering (χ2 = 5.197, P = 0.023) and anesthesia recovery time (Z = -2.269, P = 0.02) in elderly patients undergoing abdominal surgery during anesthesia recovery, and there were no statistically significant differences in hypoxemia, nausea or vomiting, hypertension, hypokalemia, hypocalcemia, analgesic drug use,postoperative wound infection or postoperative hospitalization days. CONCLUSIONS: The incidence of intraoperative mild hypothermia after active warming was high in elderly patients who underwent abdominal surgery. Mild hypothermia increased the incidence of shivering and prolonged anesthesia recovery time in elderly patients undergoing abdominal surgery.

The Effect of Warmed Serum on Shivering and Recovery Period of Patients Under General and Spinal Anesthesia: A Randomized Clinical Trial.

PURPOSE: Postoperative hypothermia followed by shivering is a common phenomenon in patients undergoing surgery under anesthesia, and should be prevented and treated in postoperative patient care units. This study was conducted to investigate the effect of warmed serum injection on postoperative shivering and recovery period of patients operated under general and spinal anesthesia. DESIGN: In this clinical trial, patients to be operated on under general and spinal anesthesia were randomly assigned into two groups of test and control. In the test group, patients received warmed intravenous fluids and blood products. All patients were monitored to record vital signs, incidences of hypothermia and shivering, and recovery period. METHODS: The collected data were analyzed with repeated measures analysis of variance to detect significant differences between groups and significant changes within groups over time. FINDINGS: The incidence of nausea, vomiting, and shivering in the intervention and control groups was (4.7%, 42%), (2.8%, 16.8%), and (6.6%, 43%), respectively. Patients in the intervention group had higher body temperature than the control group (<0.001). Also, patients under spinal anesthesia had higher body temperature than patients under general anesthesia (<0.001). Blood pressure reduction was also significantly higher in the control group than in the intervention group. The patients who received warm intravenous serum, and especially those who had received spinal anesthesia spent less time in the recovery room (<0.001). CONCLUSIONS: The use of warmed intravenous serum increased the patients' core temperature, reduced their postoperative shivering, and shortened their recovery period. Considering the potential risks associated with hypothermia, using such methods for hypothermia prevention can be highly effective in preventing shivering and prolongation of the recovery period and other potential complications. Anesthesia specialists and technicians are therefore encouraged to use this method as a preventive measure.

The Effect of Clonidine Premedication on Hemodynamic Changes Following Tracheal Intubation and Co2 Gas Insufflation and Postoperative Shivering In Patients Undergoing Laparoscopic Cholecystectomy; a Randomized Clinical Trial.

BACKGROUND: Laparoscopic cholecystectomy is a proper treatment for cholecystitis but the Carbon dioxide gas which is used in surgery stimulates the sympathetic system and causes hemodynamic changes and postoperative shivering in patients undergoing operations. This study was conducted to evaluate the effects of clonidine on reducing hemodynamic changes during tracheal intubation and Carbon dioxide gas insufflation and postoperative shivering in patients undergoing laparoscopic cholecystectomy. MATERIAL AND METHODS: This prospective, randomized, triple-blind clinical trial was conducted on 60 patients between the 18-70 years-old age group, who were candidates of laparoscopic cholecystectomy surgery. The patients randomized into two groups (30 patients received 150 µg oral clonidine) and 30 patients received 100 mg oral Vitamin C). Heart rate and mean arterial pressure of patients were recorded before anesthesia, before and after laryngoscopy, before and after Carbon dioxide gas insufflation. Data were analyzed using Chi-2, student t-test, and analysis of variance by repeated measure considering at a significant level less than 0.05. RESULTS: The findings of this study showed that both heart rate and mean arterial pressure in clonidine group after tracheal intubation and Carbon dioxide gas insufflation were lower than patients in the placebo group, but there was not any statistically significant difference between the two groups (p>0.05) and also postoperative shivering was not different in groups. There was no significant statistical difference in postoperative shivering between the two groups (p>0.05). CONCLUSION: Using 150 µg oral clonidine as a cheap and affordable premedication in patients undergoing laparoscopic cholecystectomy improves hemodynamic stability during operation.

The Effect of Granisetron, Ondansetron, and Meperidine in Preventing Postoperative Shivering: Controlled Clinical Trial.

BACKGROUND: Recently, use of HT35 receptor antagonists to prevent postoperative shivering has attracted a great deal of attention. This study was conducted with the aim of investigating the effectiveness of granisetron as an HT35 antagonist when compared with ondansetron and meperidine in preventing postoperative shivering. MATERIAL AND METHODS: In this triple blind random clinical trial study, 90 patients 18-50 years of age with ASA Class I and II undergoing general anesthesia were randomly assigned into one of the three drug groups: O (4-mg ondansetron), G (40 µg/kg of granisetron), and P (25 mg meperidine), immediately before induction of anesthesia. After anesthesia induction, at the end of the surgery, after the entrance and after leaving the recovery state, central temperature, peripheral temperature, heart rate, systolic blood pressure, diastolic blood pressure, and shivering were measured and documented. Two-tailed P < 0.05 was considered significant. RESULTS: In the meperidine, ondansetron, and granisetron groups, 4 (13.3%), 3 (10%), and 10 (33.3%) of patients experienced shivering during recovery, where the difference between the ondansetron and granisetron groups was significant (p-value=0.02). The variations in the mean arterial pressure during the investigation stages only in the ondansetron group were not significant (p>0.05). At the beginning of recovery, the reduction of peripheral temperature significantly was lower in the ondansetron group (p<0.05), while reduction of the central temperature was significantly (p<0.05) higher in the granisetron group. By the end of the recovery, the variations in the peripheral temperature across the three groups were consistent with the changes at the beginning of recovery, but variations of the central temperature across the three groups was not significantly diverse. CONCLUSION: Granisetron was not found to be much effective in preventing postoperative shivering. Ondansetron and meperidine were equally effective in preventing postoperative shivering. Ondansetron also causes less hemodynamic changes compared to other drugs, while granisetron is more effective in terms of preventing nausea and vomiting.

Modulation of cold-induced shivering activity by intermittent and continuous voluntary suppression.

This investigation assessed the physiological effects of voluntary suppression of shivering thermogenesis in response to whole body cooling. Eleven healthy volunteers underwent passive air cooling (10°C), across three visits: NO_SUP, where participants allowed their body to freely regulate against the cold; FULL_SUP, where participants constantly suppressed shivering; INT_SUP, where participants intermittently suppressed shivering (5 min phases), interspersed with 5 min free regulation. Shivering was assessed via electromyography (EMG), mechanomyography (MMG), and whole body oxygen uptake (V̇o2), whereas body temperature and heat exchange were assessed via skin temperature, rectal temperature, and heat flux sensors. A 29% increase was observed in shivering onset time in the FULL_SUP trial compared with NO_SUP (P = 0.032). Assessing shivering intensity, EMG activity decreased by 29% (P = 0.034), MMG activity decreased by 35% (P = 0.031), whereas no difference was observed in V̇o2 (P = 0.091) in the FULL_SUP trial compared with NO_SUP. Partitioning the no-suppression and suppression phases of the INT_SUP trial, acute voluntary suppression significantly decreased V̇o2 (P = 0.001), EMG (P < 0.001), and MMG (P = 0.012) activity compared with the no-suppression phases. Shivering activity was restored in the no-suppression phases, equivalent to that in the NO_SUP trial (P > 0.3). No difference was observed in thermal metrics between conditions up to 60 min (P > 0.4). Humans can both constantly and periodically suppress shivering activity, leading to a delay in shivering onset and a reduction in shivering intensity. Following suppression, regular shivering is resumed.

The Effect of Prophylactic Steroids on Shivering in Adults Undergoing Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Shivering is common following anesthesia and surgery. Corticosteroids (steroids) have been tried to reduce the risk of shivering, but the evidence in favor of their use is uncertain. The primary objective of this review was to evaluate the effect of steroids on the risk of perioperative (intra- and postoperative) shivering versus controls (placebo and active controls). Additional objectives were to assess the risk of severity of shivering, patient satisfaction with shivering prophylaxis, quality of recovery (QoR), and the risk of steroid-related adverse effects. METHODS: PubMed, Embase, Cochrane Central Registry of Trials, Google Scholar, and preprint servers were searched from inception until November 30, 2022. Randomized controlled trials (RCTs) published in the English language were retrieved, provided they reported on shivering either as a primary or secondary outcome following steroid prophylaxis in adult patients undergoing surgery under spinal or general anesthesia. RESULTS: A total of 3148 patients from 25 RCTs were included in the final analysis. The steroids used in the studies were either dexamethasone or hydrocortisone. Dexamethasone was administered intravenously or intrathecally, while hydrocortisone was administered intravenously. Prophylactic administration of steroids reduced the risk of overall shivering (risk ratio [RR], 0.65 [95% confidence interval {CI}, 0.52-0.82]; P = .0002; I2 = 77%) as well as the risk of moderate to severe shivering (RR, 0.49 [95% CI, 0.34-0.71]; P = .0002; I2 = 61%) in comparison to controls. Administration of intravenous dexamethasone (RR, 0.67 [95% CI, 0.52-0.87]; P = .002; I2 = 78%) and hydrocortisone (RR, 0.51 [95% CI, 0.32-0.80]; P = .003; I2 = 58%) were effective in shivering prophylaxis. For intrathecal dexamethasone (RR, 0.84 [95% CI, 0.34-2.08]; P = .7; I2 = 56%), the null hypothesis of no subgroup difference was not rejected ( P = .47), preventing definitive conclusions about the efficacy of this route of administration. The prediction intervals for both overall shivering risk (0.24-1.70) and risk of severity of shivering (0.23-1.0) precluded generalization of results in future studies. Meta-regression analysis was used to further explore heterogeneity. Factors like the dose and timing of administration of steroids or the type of anesthesia were not found to be significant. Patient satisfaction and QoR were higher in the dexamethasone groups versus placebo. No increased risk of adverse events of steroids was noted versus placebo or controls. CONCLUSIONS: Prophylactic steroid administration may be beneficial in reducing the risk of perioperative shivering. However, the quality of evidence in favor of steroids is very low. Further well-designed studies are needed for establishing generalization.

Effect of early oral carbohydrate intake after elective Cesarean delivery on maternal body temperature and satisfaction: a randomized controlled trial.

PURPOSE: Although the Enhanced Recovery After Cesarean Delivery (ERAC) consensus statement provides recommendations for early postoperative drinking and eating, evidence from high-quality clinical research directly addressing parturients is sparse. Our objective was to assess if early oral carbohydrate intake after elective Cesarean delivery improves maternal recovery. METHODS: In this randomized controlled trial, we enrolled parturients undergoing elective Cesarean delivery under spinal anesthesia with tympanic membrane temperatures ≤ 36.5 °C immediately upon arrival at the postanesthesia care unit. Parturients were randomized to either 100 mL of oral complex carbohydrate intake (group CC) or 10 mL of water (group C). The primary outcome was maternal tympanic membrane temperature. Other outcomes included maternal thermal comfort score, degree of shivering, satisfaction, degree of thirst and hunger, and gastric emptying assessed by ultrasonography. RESULTS: We included 90 participants in the final analysis. The mean (standard deviation [SD]) maternal body temperature at 120 min after ingestion was 36.7 (0.3) °C in group CC and 36.6 (0.3) °C in group C (difference in means, 0.14 °C; 95% confidence interval, 0.02 to 0.26; P = 0.02). Furthermore, using repeated measure models, the linear trends of temperature changes over time between groups CC and C were significantly different (P = 0.04). The thermal comfort scores at 120 min after ingestion were higher in group CC than in group C (P = 0.02), and the linear trends of shivering score changes over time between groups CC and C also were different (P = 0.003). The mean (SD) visual analogue scale scores for maternal satisfaction were 84 (13) mm in group CC and 47 (20) mm in group C (P < 0.001). Nevertheless, at 90 and 120 min after ingestion, there were no differences between the two groups in the number of participants with a gastric antrum cross-sectional area > 10.3 cm2. CONCLUSIONS: Early oral carbohydrate intake after Cesarean delivery helped to restore maternal body temperature postoperatively and improve maternal satisfaction. Nevertheless, the clinical importance of these finding is unclear, given that most of the differences were small. In addition, there was no delay in maternal gastric emptying after consumption of a complex carbohydrate beverage in the early post-Cesarean period. STUDY REGISTRATION: www.chictr.org.cn (ChiCTR2000031085); first submitted 13 November 2022.

RéSUMé: OBJECTIF: Bien que la déclaration de consensus sur la Récupération améliorée après un accouchement par césarienne (ERAC/RAAC) fournisse des recommandations pour l'ingestion postopératoire précoce de liquides et d'aliments, les données probantes issues de recherches cliniques de haute qualité portant directement sur les personnes parturientes sont rares. Notre objectif était d'évaluer si l'ingestion précoce de glucides par voie orale après une césarienne programmée améliorait la récupération maternelle. MéTHODE: Dans cette étude randomisée contrôlée, nous avons recruté des personnes parturientes bénéficiant d'une césarienne programmée sous rachianesthésie avec une température tympanique ≤ 36,5 °C immédiatement après leur arrivée en salle de réveil. Les personnes parturientes ont été randomisées à recevoir soit 100 mL de glucides complexes par voie orale (groupe GC) ou 10 mL d'eau (groupe C). Le critère d'évaluation principal était la température tympanique maternelle. Les autres critères d'évaluation comprenaient, chez la mère, le score de confort thermique, le degré de frissons, la satisfaction, le degré de soif et de faim, et la vidange gastrique évaluée par échographie. RéSULTATS: Nous avons inclus 90 personnes dans l'analyse finale. La température corporelle maternelle moyenne (écart type [ET]) à 120 minutes après l'ingestion était de 36,7 (0,3) °C dans le groupe GC et de 36,6 (0,3) °C dans le groupe C (différence dans les moyennes, 0,14 °C; intervalle de confiance à 95 %, 0,02 à 0,26; P = 0,02). De plus, à l'aide de modèles à mesures répétées, les tendances linéaires des changements de température au fil du temps entre les groupes GC et C étaient significativement différentes (P = 0,04). Les scores de confort thermique à 120 minutes après l'ingestion étaient plus élevés dans le groupe GC que dans le groupe C (P = 0,02), et les tendances linéaires des changements de score de frissons au fil du temps entre les groupes GC et C étaient également différentes (P = 0,003). Les scores moyens (ET) de l'échelle visuelle analogique concernant la satisfaction maternelle étaient de 84 (13) mm dans le groupe GC et de 47 (20) mm dans le groupe C (P < 0,001). Néanmoins, à 90 et 120 minutes après l'ingestion, il n'y avait aucune différence entre les deux groupes dans le nombre de personnes présentant une section transversale de l'antre gastrique > 10,3 cm2. CONCLUSION: L'ingestion précoce de glucides par voie orale après un accouchement par césarienne a aidé à rétablir la température corporelle maternelle postopératoire et à améliorer la satisfaction maternelle. Néanmoins, l'importance clinique de ces résultats n'est pas claire, étant donné que la plupart des différences étaient faibles. De plus, il n'y avait pas de retard dans la vidange gastrique maternelle après la consommation d'une boisson glucidique complexe au début de la période post-césarienne. ENREGISTREMENT DE L'éTUDE: www.chictr.org.cn (ChiCTR2000031085); soumis pour la première fois le 13 novembre 2022.

Incidence of postoperative hypothermia and shivering and risk factors in patients undergoing malignant tumor surgery: a retrospective study.

BACKGROUND: Perioperative hypothermia and shivering are common and can cause adverse outcomes. The aim of this study was to investigate the incidence of postoperative hypothermia and shivering and their risk factors in patients undergoing malignant tumor surgery. METHODS: This retrospective study collected data from patients with American Society of Anesthesiologists physical status (ASA) I or II who underwent scheduled surgery from November 2020 to March 2021 at Fudan University Shanghai Cancer Center. Each patient's core body temperature was measured at three time points: time point 1 (arrival at the postanesthesia care unit (PACU)), time point 2 (after 30-min care in the PACU), and time point 3 (at discharge from the PACU). At time point 1, if the patient's body temperature was below 36 ℃, we provided an active forced-air warmer. At time point 2, if it was still below 36 ℃, the forced-air warmer was still applied until the patient was discharged from the PACU. If it reached 36 ℃, the forced-air warmer would be switched off. Univariate and multivariate logistic regression combined with stepwise methods and linear regression were used to explore risk factors for postoperative hypothermia and shivering. RESULTS: The numbers (percentage) of 202 patients who developed postoperative hypothermia at the different time points were 52 (25.7%), 37 (18.3%) and 28 (13.9%). Eight patients (4.0%) experienced shivering. Multivariate logistic regression showed that high weight (OR = 0.923, 95% CI: 0.884 to 0.964, P = 0.0003) and low estimated blood loss (OR = 0.252, 95% CI: 0.115 to 0.550, P = 0.0005) were protective factors against hypothermia, while long surgical duration (OR = 3.339, 95% CI: 1.675 to 6.655, P = 0.0006) was an independent risk factor for hypothermia at time point 1. There was no risk factor associated with the occurrence of shivering (P > 0.05). There was a significant difference between the hypothermia and normothermia groups in the median length of stay in the PACU (59.0 vs. 49.0 min, P = 0.0123). CONCLUSIONS: Postoperative hypothermia occurred frequently. Weight, estimated blood loss and surgical duration were significantly associated with hypothermia on arrival at the PACU.

Minimizing Shivering During Targeted Normothermia: Comparison Between Novel Transnasal and Surface Temperature-Modulating Devices.

BACKGROUND: Shivering is a common adverse effect of achieving and maintaining normothermia in neurocritical care patients. We compared the burden of shivering and shivering-related interventions between a novel transnasal temperature-modulating device (tnTMD) and surface cooling temperature-modulating devices (sTMDs) during the first 24 h of targeted normothermia in mechanically ventilated febrile neurocritical care patients. METHODS: This is a case-control study controlling for factors that impact shiver burden: age, sex, body surface area. All patients underwent transnasal cooling (CoolStat, KeyTech, Inc.) as part of an ongoing multicenter clinical trial (NCT03360656). Patients undergoing treatment with sTMDs were selected from consecutively treated patients during the same time period. Data collected included the following: core body temperature (every 2 h), bedside shivering assessment scale (BSAS) score (every 2 h), and administration of antishivering medication for a BSAS score > 1. Time to normothermia (≤ 37.5 °C), as well as temperature burden > 37.5 °C (°C × h), were compared between groups using Student's t-test for mean differences. The proportion of patients requiring interventions, as well as the number of interventions per patient, was compared using the χ2 test. Significance was determined based on a p value < 0.05. RESULTS: There were 10 tnTMD patients and 30 sTMD patients included in the analysis (mean age: 62 ± 4, 30% women, body surface area = 1.97 ± 0.25). There were no differences between groups in temperature at cooling initiation (tnTMD: 38.5 ± 0.2 °C vs. sTMD: 38.7 ± 0.5 °C, p = 0.3), time to ≤ 37.5 °C (tnTMD: 1.8 ± 1.5 h vs. sTMD: 2.9 ± 1.4 h, p = 0.1), or temperature burden > 37.5 (tnTMD: - 0.4 ± 1.13 °C × h vs. sTMD median [IQR]: - 0.57 ± 0.58 °C × h, p = 0.67). The number of tnTMD patients who received pharmacologic shivering interventions was lower than the number of controls (20 vs. 67%, p = 0.01). tnTMD patients also had fewer shivering interventions per patient (0 [range: 0-3] vs. 4 [range: 0-23], p < 0.001). CONCLUSIONS: A transnasal cooling approach achieved similar time to normothermia and temperature burden with less shivering than surface cooling. This approach may be a feasible option to consider for mechanically ventilated febrile neurocritical care patients.

A meta-analysis of randomized controlled trials: efficiency and safety of ondansetron in preventing post-anesthesia shivering during cesarean section.

OBJECTIVE: Although ondansetron was considered to prevent post-anesthesia shivering during cesarean section, its efficiency remained controversial. Our review was conducted to estimate the efficiency and safety of ondansetron in preventing post-anesthesia shivering during cesarean section. METHODS: The literature were searched from their inception to October 2020 without restriction of language. All randomized controlled trials investigating the efficacy of ondansetron versus placebo in preventing shivering during cesarean section under neuraxial anesthesia were included. The meta-analysis was conducted using Stata software. RESULTS: Eleven randomized controlled studies with a total of 748 individuals were finally included in our meta-analysis. Our results manifested that intravenous ondansetron compared with intravenous placebo significantly reduced the incidence of post-anesthesia shivering (PAS) (RR 0.53, 95% CI 0.14-0.68). Subgroup analysis according to doses of ondansetron indicated that the efficacy of 4 mg doses of ondansetron (RR 0.37, 95% CI 0.21-0.64) is equivalent to that of 8 mg doses of ondansetron (RR 0.61, 95% CI 0.47-0.81) in preventing PAS. In addition, the intravenous ondansetron led to a lower incidence of hypotension than intravenous placebo (OR 0.47, 95% CI 0.32-0.70). We could not demonstrate differences in the incidence of bradycardia between intravenous ondansetron and intravenous placebo. CONCLUSION: Our results found that intravenous ondansetron was effective in preventing shivering during cesarean section under neuraxial anesthesia, and had an advantage in reducing the incidence of hypotension compared with intravenous placebo.

The hyperthermic response to intra-preoptic area administration of agmatine in male rats.

Agmatine is an endogenous biogenic amine that exerts various effects on the central nervous system. The hypothalamic preoptic area (POA, thermoregulatory command center) has high agmatine immunoreactivity. In this study, in conscious and anesthetized male rats, agmatine microinjection into the POA induced hyperthermic responses associated with increased heat production and locomotor activity. Intra-POA administration of agmatine increased the locomotor activity, the brown adipose tissue temperature and rectum temperature, and induced shivering as demonstrated by increased neck muscle electromyographic activity. However, intra-POA administration of agmatine almost had no impact on the tail temperature of anesthetized rats. Furthermore, there were regional differences in the response to agmatine in the POA. The most effective sites for the microinjection of agmatine to elicit hyperthermic responses were localized in the medial preoptic area (MPA). Agmatine microinjection into the median preoptic nucleus (MnPO) and lateral preoptic nucleus (LPO) had a minimal effect on the mean core temperature. Analysis of the in vitro discharge activity of POA neurons in brain slices when perfused with agmatine showed that agmatine inhibited most warm-sensitive but not temperature-insensitive neurons in the MPA. However, regardless of thermosensitivity, the majority of MnPO and LPO neurons were not responsive to agmatine. The results demonstrated that agmatine injection into the POA of male rats, especially the MPA, induced hyperthermic responses, which may be associated with increased BAT thermogenesis, shivering and locomotor activity by inhibiting warm-sensitive neurons.

Droperidol lowers the shivering threshold in rabbits.

PURPOSE: 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. METHODS: 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 5 mg/kg droperidol bolus followed by continuous infusion at 5 mg/kg/h, those in the low-dose group received a 0.5 mg/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. RESULTS: 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. CONCLUSIONS: 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.

Evaluation of Postoperative Warming Care Protocol for Thermal Comfort and Temperature Management Immediately After Surgery: Nonrandomized Controlled Trial.

PURPOSE: This study aimed to determine the effects of a warming care protocol (WCM) on temperature control and thermal comfort perception in hypothermia following major abdominal surgery. DESIGN: A prospective nonrandomized controlled trial. METHODS: A total of 54 patients undergoing major abdominal surgery were assigned to receive routine care (control group, 27 patients) or the WCM (intervention group, 27 patients). The body temperature (core and peripheral) was measured, and physical symptoms were monitored every hour for 4 hours after arriving at the ward and then every 4 hours for up to 12 hours. FINDINGS: The temperature gap, calculated as the difference between the core and skin temperatures, was similar between the control and intervention groups at the end of surgery. However, the temperature gap in the intervention group decreased within 3 hours after arrival at the ward and remained lower than that in the control group. The visual analog scale score for postoperative thermal discomfort was significantly lower in the intervention group than in the control group, indicating achievement of higher comfort with the warming intervention. CONCLUSIONS: Patients were warmed using active warming methods under the WCM, which in turn increased the thermal comfort perception with the body temperature. Postoperative patients often require warming care for thermal comfort, which may be improved by proper observation and management within 1 to 2 hours postoperatively. Our results indicate that nurses could effectively warm the patient to maintain normal body temperature following surgery not only to improve thermal comfort, but also to prevent shivering and possibly various postoperative complications.

Combined Forced Air Warming and Warm Intravenous Fluid Strategy for Perioperative Hypothermia in Cesarean Delivery: A Systematic Review and Meta-Analysis.

PURPOSE: Evaluate the effect of a combined forced-air warming (FAW) and warm intravenous fluid (IVF) modality on maternal and neonatal outcomes in cesarean delivery under neuraxial anesthesia. DESIGN: Systematic Review and Meta-analysis. METHODS: An extensive search was conducted using PubMed, Cochrane Library, MEDLINE, CINAHL, Google Scholar, and other grey literature. Only randomized controlled trials examining the combined modality on maternal temperatures were included. Risk ratio (RR), mean difference (MD), and standardized mean difference (SMD) were used to estimate outcomes with suitable effect models. Quality of evidence was assessed using the Risk of Bias and GRADE system. FINDINGS: Nine trials involving 595 patients were included. Combined strategy showed a smaller change in maternal temperature from baseline by 0.42°C (MD, -0.42; 95% CI, -0.62 to -0.22; P < .0001), higher temperature on PACU arrival (MD, 0.46; 95% CI, 0.11-0.82; P = .01), 15 minutes (MD, 0.43; 95% CI, 0.19-0.67; P = .0004) and 30 minutes after surgery (MD, 0.38; 95% CI, 0.12-0.64; P = .005). Combined strategy also reduced the incidence of hypothermia (RR, 0.55; 95% CI, 0.31-0.95; P = .03), and shivering (RR, 0.40; 95% CI, 0.28-0.58; P < .00001) with improvement in maternal comfort score (SMD; 0.38; 95% CI, 0.08-0.69; P = .01). However, there were no differences in clinical indicators of adverse neonatal outcomes. Lack of participants blinding, and substantial heterogeneity were limitations of this review. CONCLUSION: The use of combined FAW and warm IVF is an effective strategy in mitigating perioperative hypothermia in cesarean delivery under neuraxial anesthesia.

The Effect of Remimazolam Compared to Sevoflurane on Postoperative Shivering in Patients Undergoing Laparoscopic Gynecologic Surgery under General Anesthesia: A Prospective Randomized Controlled Trial.

Background and objectives: Anesthesia maintenance agents affect the incidence of postoperative shivering (PS) after general anesthesia. This study compared the effects of remimazolam with sevoflurane on PS in patients undergoing laparoscopic gynecologic surgery under general anesthesia. Materials and methods: Seventy-four patients were allocated into one of two groups. In anesthesia maintenance, group S received sevoflurane and remifentanil, and group R received remimazolam and remifentanil. Results: The incidence and severity of postoperative shivering, mean arterial pressure (MAP), heart rate (HR), core body temperature, and the association of PS with hypothermia, MAP, or HR in the post-anesthesia care unit (PACU) were measured. Group R had significantly lower rates of perioperative hypothermia (58.8 vs. 27.8%, p = 0.009) and postoperative shivering (41.2 vs. 19.4%, p = 0.047). The severity of PS was also lower in group R than in group S (p = 0.034). Core body temperature was significantly higher in group R than in group S from 10 min after induction (p = 0.047) to the PACU (p = 0.009). MAP and HR were significantly higher in group R than in group S from 20 min after induction (p = 0.047) to the PACU (p = 0.009). In group S, the correlation between the severity of PS and the incidence of hypothermia (φc = 0.414, p = 0.121) was moderate but not significant. In group R, the correlation between PS severity and hypothermia (φc = 0.418, p = 0.043) was moderate and significant. Conclusions: Remimazolam showed better results than sevoflurane in anesthesia maintenance regarding hypothermia and PS.

Effects of a short-term cold exposure on circulating microRNAs and metabolic parameters in healthy adult subjects.

This discovery study investigated in healthy subjects whether a short-term cold exposure may alter circulating microRNAs and metabolic parameters and if co-expression networks between these factors could be identified. This open randomized crossover (cold vs no cold exposure) study with blind end- point evaluation was conducted at 1 center with 10 healthy adult male volunteers. Wearing a cooling vest perfused at 14°C for 2 h reduced the local skin temperature without triggering shivering, increased norepinephrine and blood pressure while decreasing copeptin, C-peptide and heart rate. Circulating microRNAs measured before and after wearing the cooling vest twice (4 time points) identified 196 mature microRNAs with excellent reproducibility over 72 h. Significant correlations of microRNA expression with copeptin, norepinephrine and C-peptide were found. A co-expression-based microRNA-microRNA network, as well as microRNA pairs displaying differential correlation as a function of temperature were also detected. This study demonstrates that circulating miRNAs are differentially expressed and coregulated upon cold exposure in humans, supporting their use as predictive and dynamic biomarkers of cardio-metabolic disorders.

Thermogenic responses to different clamped skin temperatures in cold-exposed men and women.

Despite many decades of research examining thermoregulatory responses under varying cold stresses in humans, very little is known about the variability in metabolic heat production and shivering activity. Here, we used a novel closed-loop mean skin temperature clamping technique with a liquid-conditioned suit to isolate the effects of mean skin temperature on the subjective evaluation of thermal sensation, heat production, shivering responses, and oxidative fuel selection in young, lean, and healthy men (n = 12) and women (n = 12). Our results showed a skin temperature-dependent increase in metabolic heat production (5.2 ± 1.2 kJ/min, 5.9 ± 1.5 kJ/min, and 7.0 ± 1.8 kJ/min with skin temperature maintained at 31 ± 0.1°C, 29 ± 0.2°C, and 27 ± 0.1°C, respectively; P < 0.0001) and shivering intensity in both men and women [0.6 ± 0.1% maximal voluntary contraction (MVC), 1.1 ± 0.4% MVC, and 2.5 ± 0.7% MVC, respectively; P < 0.0001], including sex-dependent differences in heat production at all three temperatures (P < 0.005). Even when controlling for lean body mass and fat mass, sex differences persisted (P = 0.048 and P = 0.004, respectively), whereas controlling for differences in body surface area eliminated these differences. Interestingly, there were no sex differences in the cold-induced change in thermogenesis. Despite clamping skin temperature, there was tremendous variability in the rate of heat production and shivering intensity. Collectively this data suggests that many of the interindividual differences in thermogenesis and shivering may be explained by differences in morphology and body composition.