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.

Effects of different forced-air warming systems on the core temperature of patients: a manikin and multi-center clinical study.

BACKGROUND: The use of forced-air warming (FAW) blankets is widely recognized for preventing shivering and hypothermia in patients under general anesthesia. Various types of products are currently available for hospitals, and we have conducted a preliminary evaluation of insulation equipment based on expert opinions and initial parameters. However, we lack real-world experiments and accurate clinical data to validate these parameters and the accuracy of our decision-making results. This study aims to confirm the effectiveness of different FAW systems by assessing the thermal protection and operational characteristics of the equipment in both experimental and clinical settings, thereby enhancing our evaluation database. METHODS: In the manikin test, we conducted six tests including heat distribution and heating rate, heater outlet temperature stability, etc. In the clinical study, patients were randomly assigned to four groups [Group A (Bair Hugger Therapy, 3 M, St. Paul, MN, USA; 63500); Group B (EQUATOR® level I, Smith Medical ASD, MN, USA; Snuggle Warm, SW-2013); Group C (Jiang Men Da Cheng Medical Devices Co., Ltd, China; IOB-006); and Group D (Shang Hai Nest Tech Medical Materials Co., Ltd, China; BH-017)], with each group comprising 30 individuals. At the start of anesthesia induction, the FAW blanket was activated and set to 43 °C until the completion of surgery. The primary endpoint was the average core body temperature during surgery. Secondary endpoints included hemodynamic and surgical variables, adverse events, and recovery metrics. RESULTS: In the manikin test, the observed results of the experimental parameters (heat distribution, air pressure difference, and hole observation test) for Group A are superior to those of the other groups. In the clinical study, although the mean perioperative core body temperature remained above 36 °C across all groups [Group A: 36.31 ± 0.04; Group B: 36.26 ± 0.06; Group C: 36.17 ± 0.03; Group D: 36.25 ± 0.05], patients in Group A maintained higher temperatures compared to the other groups (p < 0.001). CONCLUSIONS: Among patients undergoing laparoscopic radical resection of colorectal cancer with general anesthesia, all four FAW systems effectively prevented perioperative hypothermia. However, the system in Group A minimized heat loss more effectively than the others, providing superior thermal protection. TRIAL REGISTRATION: ChiCTR2200065394, 03/11/2022.

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.

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.

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.

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.

Clinical efficacy of short-term prewarming in elderly and adult patients: A prospective observational study.

Background: Short-term prewarming effectively reduces intraoperative hypothermia in adult patients. However, few data exist regarding its efficacy in elderly patients. Elderly people have a reduced ability to regulate their body temperature, which affects the efficacy of prewarming. This study aimed to compare the clinical efficacy of short-term pre-warming in elderly patients with that in adult patients. Methods: We enrolled 25 adult (20-50 years) and 25 elderly (> 65 years) patients scheduled for ureteroscopic stone surgery under general anaesthesia. All patients received preanaesthetic forced-air warming for 20 min. The core temperature was measured using an infrared tympanic thermometer during awakening and nasopharyngeal thermistors during anaesthesia. Incidence and severity of intraoperative hypothermia (< 36°C) was compared. Postoperative shivering and number of patients requiring active warming in the post-anaesthesia care unit were also assessed. Results: Intraoperative hypothermia was more frequent in elderly than in adult patients (58.3% vs. 12.0%; relative risk 2.6; 95% confidence interval 1.5 to 4.6; effect size h = 1.010; p = 0.001). The severity of intraoperative hypothermia showed a significant intergroup difference (p = 0.002). Postoperative shivering was more frequent in elderly than in adult patients (33.3% vs. 8.0%, p = 0.037). A greater number of elderly patients in the post-anaesthesia care unit required active warming (33.3% vs. 8.0%, p = 0.037). Conclusions: The effects of short-term prewarming on the prevention of hypothermia and maintenance of perioperative normothermia are not the same in the elderly and adult patients.

Independent and combined impact of hypoxia and acute inorganic nitrate ingestion on thermoregulatory responses to the cold.

PURPOSE: This study assessed the impact of normobaric hypoxia and acute nitrate ingestion on shivering thermogenesis, cutaneous vascular control, and thermometrics in response to cold stress. METHOD: Eleven male volunteers underwent passive cooling at 10 °C air temperature across four conditions: (1) normoxia with placebo ingestion, (2) hypoxia (0.130 FiO2) with placebo ingestion, (3) normoxia with 13 mmol nitrate ingestion, and (4) hypoxia with nitrate ingestion. Physiological metrics were assessed as a rate of change over 45 min to determine heat loss, and at the point of shivering onset to determine the thermogenic thermoeffector threshold. RESULT: Independently, hypoxia expedited shivering onset time (p = 0.05) due to a faster cooling rate as opposed to a change in central thermoeffector thresholds. Specifically, compared to normoxia, hypoxia increased skin blood flow (p = 0.02), leading to an increased core-cooling rate (p = 0.04) and delta change in rectal temperature (p = 0.03) over 45 min, yet the same rectal temperature at shivering onset (p = 0.9). Independently, nitrate ingestion delayed shivering onset time (p = 0.01), mediated by a change in central thermoeffector thresholds, independent of changes in peripheral heat exchange. Specifically, compared to placebo ingestion, no difference was observed in skin blood flow (p = 0.5), core-cooling rate (p = 0.5), or delta change in rectal temperature (p = 0.7) over 45 min, while nitrate reduced rectal temperature at shivering onset (p = 0.04). No interaction was observed between hypoxia and nitrate ingestion. CONCLUSION: These data improve our understanding of how hypoxia and nitric oxide modulate cold thermoregulation.

Autonomic effects induced by pharmacological activation and inhibition of Raphe Pallidus neurons in anaesthetized adult pigs.

The Raphe Pallidus (RPa) is a region of the brainstem that was shown to modulate the sympathetic outflow to many tissues and organs involved in thermoregulation and energy expenditure. In rodents, the pharmacological activation of RPa neurons was shown to increase the activity of the brown adipose tissue, heart rate, and expired CO2 , whereas their inhibition was shown to induce cutaneous vasodilation and a state of hypothermia that, when prolonged, leads to a state resembling torpor referred to as synthetic torpor. If translatable to humans, this synthetic torpor-inducing procedure would be advantageous in many clinical settings. A first step to explore such translatability, has been to verify whether the neurons within the RPa play the same role described for rodents in a larger mammal such as the pig. In the present study, we show that the physiological responses inducible by the pharmacological stimulation of RPa neurons are very similar to those observed in rodents. Injection of the GABAA agonist GABAzine in the RPa induced an increase in heart rate (from 99 to 174 bpm), systolic (from 87 to 170 mm Hg) and diastolic (from 51 to 98 mm Hg) arterial pressure, and end-tidal CO2 (from 49 to 62 mm Hg). All these changes were reversed by the injection in the same area of the GABAA agonist muscimol. These results support the possibility for RPa neurons to be a key target in the research for a safe and effective procedure for the induction of synthetic torpor in humans.

Multiorgan contribution to non-shivering and shivering thermogenesis and vascular responses during gradual cold exposure in humans.

PURPOSE: Human brown adipose tissue (BAT) is known to be a significant thermoeffector in non-shivering thermogenesis (NST), albeit with individual variations in the BAT activity. We hypothesized that humans with less BAT would have more contribution from the skeletal muscle (SM) to NST or earlier shivering onset and greater vasoconstriction to compensate for less BAT-mediated thermogenesis. METHODS: Eighteen males participated in this study. Their BAT activity and detectable volume were investigated. A gradual cold exposure was conducted for inducing NST at 18.6 °C and initiating shivering at 11.6 °C. The energy expenditure, electromyograph of the pectoralis major, skin blood flow, and rectal (Tre) and skin temperatures were evaluated. RESULTS: BAT volume significantly correlated with the change in metabolic heat production during mild cold phase relative to baseline (NST; r = 0.562, P < 0.05), but not with shivering initiation phase (NST+ ST). SM mass correlated with baseline metabolic heat production (Mbase; r = 0.839, P < 0.01) but not with NST or NST + ST. A positive correlation was noted between BAT volume and Tre at the end of the 18.6 °C exposure period (r = 0.586, P < 0.05), which positively correlated with shivering onset time (r = 0.553, P < 0.05). The skin blood flow, mean skin temperature, and forearm and finger skin temperature difference at the end of the 18.6 °C exposure period did not correlate with NST or BAT volume. CONCLUSION: BAT volume positively correlated with NST. Notably, lower Tre in individuals with less BAT volume induced earlier shivering onset for offsetting the less NST. Whereas, no correlation between metabolic and vasomotor responses was observed.

Effect of intrathecal lipophilic opioids on the incidence of shivering in women undergoing cesarean delivery after spinal anesthesia: a systematic review and bayesian network meta- analysis of randomized controlled trials.

BACKGROUND: Shivering is a common side effect in women having cesarean delivery (CD) under spinal anesthesia, which can be bothersome to the patient, and it can also interfere with perioperative monitoring. In several studies, the intrathecal (IT) addition of a lipophilic opioid to local anesthetics has been shown to decrease the incidence of shivering. OBJECTIVE: We performed this network meta-analysis to evaluate the effects of intrathecal lipophilic opioids in preventing the incidence of shivering in patients undergoing CD. METHODS: This review was planned according to the PRISMA for Network Meta-Analysis (PRISMA-NMA) guidelines. An English literature search of multiple electronic databases was conducted. We included randomized controlled trials (RCTs) that reported on the incidence of shivering, with study groups receiving either IT fentanyl, sufentanil, or meperidine in women undergoing CD under spinal anesthesia. Quality of the studies was assessed using the modified Oxford scoring system. Using random-effects modeling, dichotomous data were extracted and summarized using odds ratio (OR) with a 95% credible interval (CrI). Statistical analysis was conducted using R studio version 1.0.153 - Inc. RESULTS: Twenty-one studies consisting of 1433 patients (Control group: 590 patients in twenty-one studies; Fentanyl group:199 patients in seven studies; Sufentanil group: 156 patients in five studies; Meperidine group: 488 patients in ten studies) met the inclusion criteria for this systematic review investigating the effect of intrathecal lipophilic opioids in preventing the incidence of shivering in women undergoing cesarean delivery under spinal anesthesia. Methodological validity scores ranged from 3 to 7. The Bayesian mixed network estimate showed the incidence of shivering was significantly lower with IT fentanyl (pooled odds ratio (OR): 0.13; 95% credible interval (CrI): 0.04 to 0.35; P = 0.0004) and IT meperidine (OR: 0.12; 95% CrI: 0.05 to 0.29; P < 0.00001), but not with IT sufentanil (OR: 0.37; 95% CrI: 0.11 to 1.22; P = 0.23). The IT fentanyl group had a significantly lower incidence of intraoperative discomfort [Risk Ratio (RR): 0.19; 95% CI: 0.10-0.35; P < 0.00001], the IT sufentanil group had a significantly higher incidence of pruritus (RR: 6.18; 95% CI: 1.18-32.46; P = 0.03) The IT meperidine group had a significantly lower incidence of intraoperative discomfort (2.7% vs. 13.6%; RR: 0.22; 95% CI: 0.09-0.55; P = 0.001), but there was a significant increase in nausea and vomiting (IT meperidine group vs. Control group: 42.7% vs. 19.4%; RR: 2.56; 95% CI: 1.14-5.75; P = 0.02). Meta-regression analysis based on the opioid dose and quality of the study did not impact the final inference of our result. CONCLUSION: IT fentanyl significantly decreased the incidence of shivering in women undergoing CD under spinal anesthesia without increasing maternal adverse events, confirming that routine use in this patient population is a good choice. IT sufentanil did not decrease the incidence of shivering. IT meperidine decreased the incidence and severity of shivering, but its use was also associated with significant nausea and vomiting.

Safety of intraoperative hypothermia for patients: meta-analyses of randomized controlled trials and observational studies.

BACKGROUND: Previous studies have shown that intraoperative hypothermia was associated with higher risks of clinical adverse events, but we found otherwise from recent evidences. This study aims to synthesize the existing evidence evaluating safety of intraoperative hypothermia. METHODS: Articles, reviews, ongoing trials and grey literatures were retrieved from PubMed, The Cochrane Library, Clinical Trails and CNKI (a Chinese national database) till February 2nd, 2019. Both randomized controlled trials and observational studies compared incidences of all sorts of intra- and post-operative consequences between hypothermia and normothermia were included. Researches comparing different warming systems were excluded. We also examined risks of hypothermia using lowered standards (35.5 °C and 35 °C) from a Chinese trial (ChiCTR-IPR-17011099). RESULTS: A total of 9 RCT studies and 11 observational studies were included. RCT-synthesized results showed that intraoperative hypothermia was associated with higher risks of bleeding (MD = 131.90, 95%CI: 117.42, 146.38), surgical site infection (RD = 0.14, 95%CI: 0.06, 0.21) and shivering (RD = 0.32, 95%CI: 0.06, 0.58) but with no significant differences in duration of surgery, hospital stay or mortality. Observational study-synthesized evidences showed that intraoperative hypothermia did not result in higher risks in any of these adverse events. Results didn't change even if the standard of hypothermia was lowered by 0.5-1.0 °C. CONCLUSIONS: The study indicates that the synthesized risks resulted by intra-operative hypothermia might be overestimated and the eligibility of 36 °C to define hypothermia is not sensitive enough. Given body-temperature protection has not been popularized in China, it is still critical to normalize the hypothermia prevention at this stage.

Energy Expenditure and Shivering Severity During Targeted Temperature Management at 36°C After Cardiac Arrest: A Case Series.

Patients undergoing targeted temperature management (TTM) after cardiac arrest are at risk for shivering, which increases energy expenditure (EE) and may attenuate TTM benefits. This article reports patterns of EE for patients with and without shivering who received TTM at 36°C after cardiac arrest. Based on 96 case assessments, there were 14 occasions when more than one 15-minute interval period was required to appropriately modify the Bedside Shivering Assessment Scale (BSAS) score. Investigators noted that although higher EE was related to higher BSAS scores, there may be opportunities for earlier detection of shivering.

Effectiveness of Magnesium in Preventing Shivering in Surgical Patients: A Systematic Review and Meta-analysis.

BACKGROUND: Clinical trials regarding the antishivering effect of perioperative magnesium have produced inconsistent results. We conducted a systematic review and meta-analysis with Trial Sequential Analysis to evaluate the effect of perioperative magnesium on prevention of shivering. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and 2 registry sites for randomized clinical trials that compared the administration of magnesium to a placebo or no treatment in patients undergoing surgeries. The primary outcome of this meta-analysis was the incidence of shivering. The incidence of shivering was combined as a risk ratio with 95% CI using a random-effect model. The effect of the route of administration was evaluated in a subgroup analysis, and Trial Sequential Analysis with a risk of type 1 error of 5% and power of 90% was performed. The quality of each included trial was evaluated, and the quality of evidence was assessed using the Grading of Recommendation Assessment, Development, and Evaluation approach. We also assessed adverse events. RESULTS: Sixty-four trials and 4303 patients (2300 and 2003 patients in magnesium and control groups, respectively) were included. The overall incidence of shivering was 9.9% in the magnesium group and 23.0% in the control group (risk ratio, 0.42; 95% CI, 0.33-0.52). Subgroup analysis revealed that the incidence of shivering was lower with IV (risk ratio, 0.29; 95% CI, 0.29-0.54; Grading of Recommendation Assessment, Development, and Evaluation, moderate), epidural (risk ratio, 0.24; 95% CI, 0.13-0.43; Grading of Recommendation Assessment, Development, and Evaluation, low), and intrathecal administration (risk ratio, 0.64; 95% CI, 0.43-0.96; Grading of Recommendation Assessment, Development, and Evaluation, moderate). Only trials with low risk of bias were included for Trial Sequential Analysis. The Z-cumulative curve for IV magnesium crossed the Trial Sequential Analysis monitoring boundary for benefit even though only 34.9% of the target sample size had been reached. The Z-cumulative curve for epidural or intrathecal administration did not cross the Trial Sequential Analysis monitoring boundary for benefit. No increase in adverse events was reported. CONCLUSIONS: Perioperative IV administration of magnesium effectively reduced shivering and Trial Sequential Analysis suggested that no more trials are required to confirm that IV magnesium effectively reduces shivering.

Efficacy of forced-air warming and warmed intravenous fluid for prevention of hypothermia and shivering during caesarean delivery under spinal anaesthesia: A randomised controlled trial.

BACKGROUND: Peri-operative hypothermia and shivering are frequent events in patients during caesarean delivery under spinal anaesthesia. OBJECTIVE: We assessed the efficacy of combined pre-anaesthetic forced-air warming in combination with warmed intravenous fluid infusion for preventing hypothermia and shivering during caesarean delivery under spinal anaesthesia. DESIGN: A randomised controlled study. SETTING: A tertiary care teaching hospital from July 2017 to April 2018. PATIENTS: A total of 50 pregnant women, American Society of Anaesthesiologists physical status 2, aged 20 to 45 years, scheduled for caesarean delivery under spinal anaesthesia. INTERVENTION: Patients were enrolled and randomised into two groups: an active warming group (n = 25), which received combined pre-anaesthetic whole body forced-air warming for 15 min and prewarmed intravenous fluids, and a control group, which received no active warming or warmed fluids (C group; n = 25). Spinal anaesthesia was induced with 10 mg bupivacaine containing fentanyl (10 µg). MAIN OUTCOME MEASURES: Tympanic membrane temperature and shivering severity were measured at baseline and every 10 min during surgery, and then every 10 min for 1 h postoperatively. Neonatal outcomes (tympanic membrane temperature at birth, umbilical venous blood pH, Apgar score) were also recorded. RESULTS: The incidences of peri-operative hypothermia (0 vs. 48%, P < 0.001) and shivering (22 vs. 52%, P = 0.031) were significantly lower in the active warming than in the C group. The maximum temperature change was also significantly lower in the active warming than in the C group. Maternal thermal comfort scores were higher in the active warming than in the C group. Neonatal parameters were not significantly different between the groups. CONCLUSION: The combination of pre-anaesthetic forced-air warming and warmed intravenous fluid infusions appears to be effective for preventing hypothermia and shivering during caesarean delivery under spinal anaesthesia. TRIAL REGISTRATION: This trial was registered with Clinical Trials.gov (identifier: NCT03256786).

Preoperative Warming Versus no Preoperative Warming for Maintenance of Normothermia in Women Receiving Intrathecal Morphine for Cesarean Delivery: A Single-Blinded, Randomized Controlled Trial.

BACKGROUND: Rates of hypothermia for women undergoing spinal anesthesia for cesarean delivery are high and prevention is desirable. This trial compared the effectiveness of preoperative warming versus usual care among women receiving intrathecal morphine, which is thought to exacerbate perioperative heat loss. METHODS: A prospective, single-blinded, randomized controlled trial compared 20 minutes of forced air warming (plus intravenous fluid warming) versus no active preoperative warming (plus intravenous fluid warming) in 50 healthy American Society of Anesthesiologists graded II women receiving intrathecal morphine as part of spinal anesthesia for elective cesarean delivery. The primary outcome of maternal temperature change was assessed via aural canal and bladder temperature measurements at regular intervals. Secondary outcomes included maternal thermal comfort, shivering, mean arterial pressure, agreement between aural temperature, and neonatal outcomes (axillary temperature at birth, Apgar scores, breastfeeding, and skin-to-skin contact). The intention-to-treat population was analyzed with descriptive statistics, general linear model analysis, linear mixed-model analysis, χ test of independence, Mann-Whitney, and Bland-Altman analysis. Full ethical approval was obtained, and the study was registered on the Australia and New Zealand Clinical Trials Registry (Trial No: 367160, registered at http://www.ANZCTR.org.au/). RESULTS: Intention-to-treat analysis (n = 50) revealed no significant difference in aural temperature change from baseline to the end of the procedure between groups: F (1, 47) = 1.2, P = .28. There were no other statistically significant differences between groups in any of the secondary outcomes. CONCLUSIONS: A short period of preoperative warming is not effective in preventing intraoperative temperature decline for women receiving intrathecal morphine. A combination of preoperative and intraoperative warming modalities may be required for this population.

Comparative study between Dexmedetomidine and Ondansteron for prevention of post spinal shivering. A randomized controlled trial.

BACKGROUND: Regional anesthesia could affect the homeostatic system functions resulting frequently in perioperative hypothermia and consequently shivering. The objective of this trial was to evaluate the efficacy of dexmedetomidine and ondansetron to reduce the incidence and severity of shivering after intrathecal blocks. METHODS: This randomized placebo-controlled trial included 120 patients allocated equally in three groups. All patients were anesthetized by standard intrathecal blocks for surgical procedure at lower half of the body and received one of the study drugs intravenously (IV) according to the group assignments. Group S patients (placebo) were administered saline, Group O (ondansetron) were given 8 mg ondansetron, and Group D (dexmedetomidine) were given 1 µg/kg of dexmedetomidine. Shivering incidence and scores, sedation scores, core body temperature, hemodynamic variables, and incidence of complications (nausea, vomiting, hypotension, bradycardia, over-sedation, and desaturation) were recorded. RESULTS: The incidence and 95% confidence interval (95% CI) of shivering in group S 57.5% (42.18-72.82%) was significantly higher than that of both group O 17.5% (5.73-29.27%), P < 0.001 and group D 27.5% (13.66-41.34%), P = 0.012. However, the difference in the incidence of shivering between group O and group D was comparable, P = 0.425. The sedation scores were significantly higher in group D than those of both group S and group O, P < 0.001. Sedation scores between group S and group O were comparable, P = 0.19. Incidences of adverse effects were comparable between the three groups. CONCLUSION: Prophylactic administrations of dexmedetomidine or ondansetron efficiently decrease the incidence and severity of shivering after spinal anesthesia as compared to placebo without significant difference between their efficacies when compared to each other. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR) under trial number (PACTR201710002706318). 18-10-2017. 'retrospectively registered'.

Evidence of viscerally-mediated cold-defence thermoeffector responses in man.

KEY POINTS: Visceral thermoreceptors that modify thermoregulatory responses are widely accepted in animal but not human thermoregulation models. Recently, we have provided evidence of viscerally-mediated sweating alterations in humans during exercise brought about by warm and cool fluid ingestion. In the present study, we characterize the modification of shivering and whole-body thermal sensation during cold stress following the administration of a graded thermal stimuli delivered to the stomach via fluid ingestion at 52, 37, 22 and 7°C. Despite no differences in core and skin temperature, fluid ingestion at 52°C rapidly decreased shivering and sensations of cold compared to 37°C, whereas fluid ingestion at 22 and 7°C led to equivalent increases in these responses. Warm and cold fluid ingestion independently modifies cold defence thermoeffector responses, supporting the presence of visceral thermoreceptors in humans. However, the cold-defence thermoeffector response patterns differed from previously identified hot-defence thermoeffectors. ABSTRACT: Sudomotor activity is modified by both warm and cold fluid ingestion during heat stress, independently of differences in core and skin temperatures, suggesting independent viscerally-mediated modification of thermoeffectors. The present study aimed to determine whether visceral thermoreceptors modify shivering responses to cold stress. Ten males (mean ± SD: age 27 ± 5 years; height 1.73 ± 0.06 m, weight 78.4 ± 10.7 kg) underwent whole-body cooling via a water perfusion suit at 5°C, on four occasions, to induce a steady-state shivering response, at which point two aliquots of 1.5 ml kg-1 (SML) and 3.0 ml kg-1 (LRG), separated by 20 min, of water at 7, 22, 37 or 52°C were ingested. Rectal, mean skin and mean body temperature (Tb ), electromyographic activity (EMG), metabolic rate (M) and whole-body thermal sensation on a visual analogue scale (WBTS) ranging from 0 mm (very cold) to 200 mm (very hot) were all measured throughout. Tb was not different between all fluid temperatures following SML fluid ingestion (7°C: 35.7 ± 0.5°C; 22°C: 35.6 ± 0.5°C; 37°C: 35.5 ± 0.4°C; 52°C: 35.5 ± 0.4°C; P = 0.27) or LRG fluid ingestion (7°C: 35.3 ± 0.6°C; 22°C: 35.3 ± 0.5°C; 37°C: 35.2 ± 0.5°C; 52°C: 35.3 ± 0.5°C; P = 0.99). With SML fluid ingestion, greater metabolic rates and cooler thermal sensations were observed with ingestion at 7°C (M: 179 ± 55 W, WBTS: 29 ± 21 mm) compared to 52°C (M: 164 ± 34 W, WBTS: 51 ± 28 mm; all P < 0.05). With LRG ingestion, compared to shivering and thermal sensations with ingestion at 37°C (M: 215 ± 47 W, EMG: 3.9 ± 2.5% MVC, WBTS: 33 ± 2 mm), values were different (all P < 0.05) following ingestion at 7°C (M: 269 ± 77 W, EMG: 5.5 ± 0.9% MVC, WBTS: 14 ± 12 mm), 22°C (M: 270 ± 86 W, EMG: 5.6 ± 1.0% MVC, WBTS: 18 ± 19 mm) and 52°C (M: 179 ± 34 W, EMG: 3.3 ± 2.1% MVC, WBTS: 53 ± 28 mm). In conclusion, fluid ingestion at 52°C decreased shivering and the sensation of coolness, whereas fluid ingestion at 22 and 7°C increased shivering and sensations of coolness to similar levels, independently of core and skin temperature.

Pilot Feasibility Study of Therapeutic Hypothermia for Moderate to Severe Acute Respiratory Distress Syndrome.

OBJECTIVES: Prior studies suggest hypothermia may be beneficial in acute respiratory distress syndrome, but cooling causes shivering and increases metabolism. The objective of this study was to assess the feasibility of performing a randomized clinical trial of hypothermia in patients with acute respiratory distress syndrome receiving treatment with neuromuscular blockade because they cannot shiver. DESIGN: Retrospective study and pilot, prospective, open-label, feasibility study. SETTING: Medical ICU. PATIENTS: Retrospective review of 58 patients with acute respiratory distress syndrome based on Berlin criteria and PaO2/FIO2 less than 150 who received neuromuscular blockade. Prospective hypothermia treatment in eight acute respiratory distress syndrome patients with PaO2/FIO2 less than 150 receiving neuromuscular blockade. INTERVENTION: Cooling to 34-36°C for 48 hours. MEASUREMENTS AND MAIN RESULTS: Core temperature, hemodynamics, serum glucose and electrolytes, and P/F were sequentially measured, and medians (interquartile ranges) presented, 28-day ventilator-free days, and hospital mortality were calculated in historical controls and eight cooled patients. Average patient core temperature was 36.7°C (36-37.3°C), and fever occurred during neuromuscular blockade in 30 of 58 retrospective patients. In the prospectively cooled patients, core temperature reached target range less than or equal to 4 hours of initiating cooling, remained less than 36°C for 92% of the 48 hours cooling period without adverse events, and was lower than the controls (34.35°C [34-34.8°C]; p < 0.0001). Compared with historical controls, the cooled patients tended to have lower hospital mortality (75% vs 53.4%; p = 0.26), more ventilator-free days (9 [0-21.5] vs 0 [0-12]; p = 0.16), and higher day 3 P/F (255 [160-270] vs 171 [120-214]; p = 0.024). CONCLUSIONS: Neuromuscular blockade alone does not cause hypothermia but allowed acute respiratory distress syndrome patients to be effectively cooled. Results support conducting a randomized clinical trial of hypothermia in acute respiratory distress syndrome and the feasibility of studying acute respiratory distress syndrome patients receiving neuromuscular blockade.