Risk Factors for Intraoperative Hypothermia during Holmium Laser Enucleation of the Prostate.

INTRODUCTION: Holmium laser enucleation of the prostate (HoLEP) is considered a size-independent gold standard for benign prostatic hyperplasia (BPH), and there is no upper limit of prostate weight that can be treated. Tissue retrieval can be time-consuming in cases of significant prostatic enlargement, which may lead to intraoperative hypothermia. As there are few studies on perioperative hypothermia in HoLEP, we conducted a retrospective study of patients who underwent HoLEP at our hospital. METHODS: The data of 147 patients who underwent HoLEP at our hospital were retrospectively collected and analyzed for the occurrence of intraoperative hypothermia (temperature <36°C); age, body mass index (BMI), anesthesia method, body temperature, total fluid infusion, operation time, and irrigation fluid were the explanatory variables. RESULTS: Intraoperative hypothermia was observed in 46 of 147 patients (31.3%). Simple logistic regression analysis showed that age (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 1.01-1.13, p = 0.021), BMI (OR: 0.84, 95% CI: 0.72-0.96, p = 0.017), spinal anesthesia (OR: 4.92, 95% CI: 1.86-14.99, p = 0.002), and surgical time (OR: 1.04, 95% CI: 1.01-1.06, p = 0.006) were predictors of hypothermia. The decrease in body temperature was more pronounced with longer-duration surgery and reached 0.58°C at 180 min. CONCLUSION: General anesthesia, instead of spinal anesthesia, is recommended in high-risk patients with advanced age or low BMI to avoid intraoperative hypothermia during HoLEP. Two-stage morcellation may be considered for large adenomas, when a prolonged operative time and hypothermia are anticipated.

Light-Emitting Diode (LED) Phototherapy versus Non-LED Phototherapy Devices for Hyperbilirubinemia in Neonates: A Systematic Review and Meta-analysis.

This review was conducted to evaluate the efficacy of light-emitting diode (LED) phototherapy as compared with the conventional phototherapy in neonates with unconjugated hyperbilirubinemia and their adverse effects. We searched the following databases right from their inception till April, 2021: MEDLINE, EMBASE, Cochrane Library, and LILACS. Randomized clinical trials (RCTs) comparing the LED phototherapy with other light sources, which enrolled newborns (term and preterm) with unconjugated hyperbilirubinemia were included. We included 21 articles in this review. The treatment with the LED light therapy had a lower failure rate as compared with the non-LED one (RR = 0.60, 95% CI: 0.39-0.94). The mean duration of phototherapy was significantly shorter in the group with the LED light source as compared with the one with the non-LED light source (mean difference [hours]: -8.07, 95% CI: -8.45 to -7.68), regardless of the type of non-LED units. However, the rate of bilirubin showed a comparable decline (mean difference [mg/dL/h]: 0.01, 95% CI: -0.00, 0.03) in both the light sources, irrespective of irradiance or distance. No studies reported primary outcomes related to the neurotoxicity effects of hyperbilirubinemia in neonates. The LED light devices caused a significantly higher risk of hypothermia. Neonates were at a lower risk of developing hyperthermia and skin rash with the LED light therapy. Our findings provide support for the use of LED light source phototherapy due to its better clinical efficacy, which is evidenced by its shorter duration and lower rate of treatment failure, as compared with the non-LED light sources. KEY POINTS: · The efficacy of phototherapy is dependent on specific characteristics of light sources of phototherapy devices.. · LED phototherapy demonstrated better efficacy with shorter duration and lower rate of treatment failure.. · Adverse effects of phototherapy devices such as hypothermia, hyperthermia, and skin rash should be monitored..

The effects of active warming on perioperative inadvertent hypothermia in patients undergoing vitreoretinal surgery under local anesthesia.

Purpose: Perioperative inadvertent hypothermia (PIH) is the decrease in core temperature below 36°C. We aimed to assess whether PIH develops in patients operated under local anesthesia (ULA) for vitreoretinal surgery in the operating room and investigate active warming efficacy. Methods: Seventy-two patients were divided into two groups: Group 1 contained unwarmed patients (n = 36), and Group 2, warmed patients (n = 36). The core temperatures, heart rate (HR), and mean arterial pressure (MAP) of the patients were measured at the beginning of surgery, after 20 min, 40 min, 1 h, at the end of the operation, and during the postoperative period. Results: PIH incidence was 44.6% in Group 1, whereas no hypothermia was observed in Group 2. Patient temperatures at 20 min (P = 0.001), 40 min (P < 0.001), 1 h (P < 0.001), the end of the operation (P < 0.001), and the postoperative period (P < 0.001) were significantly higher in Group 2 than in Group 1. Patient HRs at the end of the operation and during the postoperative period were significantly lower in Group 2 (P = 0.005) than in Group 1 (P < 0.001). The intraoperative 40th (P = 0.044) and 60th (P < 0.001) minutes, end of operation (P < 0.001), and postoperative MAP (P < 0.001) values of Group 1 were significantly higher than those of Group 2. Conclusion: PIH may develop in patients operated ULA, especially with a low ambient temperature. Actively warming may help prevent the harmful effects of PIH.

The Impact of Intraoperative Hypothermia on Blood Loss and Allogenic Blood Transfusion in Total Knee and Hip Arthroplasty: A Retrospective Study.

BACKGROUND: Total joint arthroplasty (TJA) usually leads to substantial blood loss, which may cause allogenic blood transfusion. Hypothermia occurring during operation has been reported to increase blood loss and transfusion rates in nonorthopedic cohorts. However, the relationship between intraoperative hypothermia and blood loss remains controversial in patients undergoing orthopedic surgeries. The aims of this study were to investigate the incidence of hypothermia and identify the impact of intraoperative body temperature and hypothermia on blood loss and transfusion rates in total knee and hip arthroplasty (TKA and THA, respectively). METHODS: This retrospective study enrolled 616 consecutive patients, who underwent primary unilateral TKA or THA at our institution during the period from April 2012 to July 2014. The occurrence of a temperature below 36°C during the operation was documented to identify the incidence of hypothermia. Univariate analysis was performed to find the risk factors for hypothermia. Multiple regression analysis and multivariate logistic regression analysis were employed to explore the association of intraoperative temperature and hypothermia with intraoperative blood loss and perioperative blood transfusion. RESULTS: The incidence of intraoperative hypothermia was 13.5%, 14.0%, and 13.1% in TJA, TKA, and THA, respectively. Intraoperative temperature (P = 0.045, P = 0.006) and hypothermia (P = 0.042, P < 0.001) were associated with intraoperative blood loss and perioperative transfusion in TKA. Intraoperative temperature (P = 0.002) was negatively related to the amount of blood loss, and hypothermia (P = 0.031) was the independent risk factor for transfusion in THA. CONCLUSION: Intraoperative hypothermia is associated with increased blood loss and transfusion rates in TJA. Efforts should be made to maintain normothermia during operation in these patients.

Improving the rate of surgical normothermia in gynecologic surgery.

OBJECTIVE: To increase the rate of normothermia (core temperature ≥ 36 °C) in patients undergoing gynecologic surgery. METHODS: The rate of surgical normothermia was evaluated in a single institution. A two-phase quality improvement project was undertaken; Phase 1 included the use of intra-operative room temperature regulation and intra-operative patient warming and Phase 2 included pre-operative patient warming. Clinical characteristics, median temperatures, and rate of normothermia were abstracted for patients in each phase. Cohorts were compared using chi-square and t-tests. RESULTS: The project was performed in two phases, each with a historic and intervention cohort. There were 503 patients in the historical cohort and 636 patients in the intervention cohort in phase 1; there were 291 patients in the historical cohort and 259 patients in the intervention cohort for Phase 2. Patient characteristics and anesthetic type and duration did not differ between cohorts. After intra-operative temperature regulation and patient warming in Phase 1, significantly more patients achieved normothermia (79% versus 68%, P < 0.0001). However operating room staff were more likely to rate the temperature as very hot in 40% of cases post-intervention, compared to only 2% historically. In Phase 2, after the intervention of pre-warming patients, there was no difference in achieving normothermia, 78% versus 83%, P = 0.09. Staff had no statistical difference in personal comfort with the temperature, however did feel efforts were very effective more frequently, 7.7% historic versus 32.7% post-intervention, P < 0.0001. CONCLUSIONS: Quality improvement methodology can be applied to pre- and intra-operative decision making to improve rates of surgical patient normothermia.

The Effect of a 300 mBar Increase in Barometric Pressure on Digital Microcirculation in Healthy Subjects Exposed to High Altitude: Is the Use of a Portable Hyperbaric Chamber to Treat Frostbite and/or Hypothermia in the Field Indicated? (Flow_Pulse Study).

INTRODUCTION: Hypothermia and frostbite occur when there is a significant decrease in central and peripheral body temperature in individuals exposed to cold windy conditions, often at high altitude or in a mountain environment. Portable hyperbaric chambers increase the barometric pressure and thereby the partial pressure of oxygen inside the chamber, and their use is a well-known treatment for altitude illness. This study aims to show that a portable hyperbaric chamber could also be used to treat hypothermia and frostbite in the field, when rescue or descent is impossible or delayed. METHODS: During a European research program (SOS-MAM, Flow Pulse study) measurements were taken from 27 healthy nonacclimatized voluntary subjects (21 men, 6 women, mean age 41 ± 17) at an altitude of 3800 m (Chamonix Mountain Lab, Aiguille du Midi, France) right before and immediately after spending 1 hour in a portable hyperbaric chamber at 300 mbar. We measured digital cutaneous temperature (Tcut), digital cutaneous blood flow (Fcut), digital tissue oxygenation (TcPO2), blood oxygen saturation (SpO2), heart rate, and core temperature. Air temperature inside the chamber (Tchamb) was measured throughout the whole session. RESULTS: We observed significant increases in Tchamb: 9.3°C compared with the outside temperature, Tcut: +7.5°C (±6.2°C 71%), Fcut: +58PU (±89) (+379%), TcPO2: +18 mmHg (±11.9) (304%), and SpO2: 13%. CONCLUSION: This study shows that a portable hyperbaric chamber can be used to treat frostbite and/or hypothermia in the field at altitude when descent or rescue is impossible or even simply delayed.

[The effects of crystalloid warming on maternal body temperature and fetal outcomes: a randomized controlled trial]. / Os efeitos do aquecimento de cristaloides sobre a temperatura corporal materna e nas condições fetais: ensaio clínico randômico.

BACKGROUND AND OBJECTIVES: Hypothermia occurs in about 60% of patients under anesthesia and is generally not managed properly during short lasting surgical procedures. Hypothermia is associated with adverse clinical outcomes. The current study is designed to assess the effects of crystalloid warming on maternal and fetal outcomes in patients undergoing elective cesarean section with spinal anesthesia. METHODS: In this prospective randomized controlled trial, sixty parturients scheduled for elective cesarean section with spinal anesthesia were randomly allocated to receive crystalloid at room temperature or warmed at 37°C. Spinal anesthesia was performed at L3-L4 interspace with 10mg of hyperbaric bupivacaine without adding opioids. Core temperature, shivering, and hemodynamic parameters were measured every minute until 10th minute and 5-min intervals until the end of operation. The primary outcome was maternal core temperature at the end of cesarean section. RESULTS: There was no difference for baseline tympanic temperature measurements but the difference was significant at the end of the operation (p=0.004). Core temperature was 36.8±0.5°C at baseline and decreased to 36.3±0.5°C for isothermic warmed crystalloid group and baseline tympanic core temperature was 36.9±0.4°C and decreased to 35.8±0.7°C for room temperature group at the end of the operation. Shivering was observed in 43.3% in the control group. Hemodynamic parameter changes and demographic data were not significant between groups. CONCLUSIONS: Isothermic warming crystalloid prevents the decrease in core temperature during cesarean section with spinal anesthesia in full-term parturients. Fetal Apgar scores at first and fifth minute are higher with isothermic warming.

Stress-induced hyperthermia and hypothermia.

Stress affects core body temperature (Tc). Many kinds of stress induce transient, monophasic hyperthermia, which diminishes gradually if the stressor is terminated. Stronger stressors produce a longer-lasting effect. Repeated/chronic stress induces anticipatory hyperthermia, reduces diurnal changes in Tc, or slightly increases Tc throughout the day. Animals that are exposed to chronic stress or a cold environment exhibit an enhanced hyperthermic response to a novel stress. These changes persist for several days after cessation of stress exposure. In contrast, long-lasting inescapable stress sometimes induces hypothermia. In healthy humans, psychologic stress induces slight increases in Tc, which are within the normal range of Tc or just above it. Some individuals, however, develop extremely high Tc (up to 41°C) when they are exposed to emotional events or show persistent low-grade high Tc (37-38°C) during or after chronic stress situations. In addition to the nature of the stressor itself, such stress-induced thermal responses are modulated by sex, age, ambient temperature, cage mates, past stressful experiences and cold exposure, and coping. Stress-induced hyperthermia is driven by mechanisms distinct from infectious fever, which requires inflammatory mediators. However, both stress and infection activate the dorsomedial hypothalamus-rostral medullary raphe region-sympathetic nerve axis to increase Tc.

The effects of a forced-air warming system plus electric blanket for elderly patients undergoing transurethral resection of the prostate: A randomized controlled trial.

BACKGROUND: Perioperative inadvertent hypothermia in elderly urology patients undergoing transurethral resection of the prostate (TURP) is a well-known serious complication, as it increases the risk of myocardial ischemia, blood loss, and surgical wound infection. We conducted this prospective randomized controlled trial to evaluate the combined effect of a forced-air warming system and electric blanket in elderly TURP patients. METHODS: Between January 2015 and October 2017, we recruited 443 elderly male patients undergoing elective TURP with subarachnoid blockade (SAB). These were randomly divided into 3 groups: group E (intraoperative warming using electric blankets set to 38°C; n = 128); group F (intraoperative warming using a forced-air warmer set to 38°C; n = 155) and group FE (intraoperative warming using a forced-air warmer plus electric blankets, both set to 38°C; n = 160). The primary outcome was shivering and their grades. Hemodynamic changes, esophageal temperature, recovery time, incidences of adverse effects, and patient and surgeon satisfaction were also recorded. RESULTS: Baseline characteristics showed no significant differences when compared across the 3 groups (P >.05). Compared with groups E and F, both HR and mean arterial pressure (MAP) in group FE were significantly decreased from T6 to T10 (P <.05). Compared with groups E and F, esophageal temperature in group FE increased significantly from T5 to T10 (P <.05). Compared with group E, esophageal temperature in group F was significantly increased from T5 to T10 (P <.05). Compared with groups F and FE, post-anesthesia care unit (PACU) recovery time was longer in group E, while compared with group F, PACU recovery time was shorter in group FE (P <.05). Compared to patients in groups E and F, those in group FE had a significantly lower incidence of arrhythmia and shivering (P <.05). The number of patients with shivering grades 0 to 3 was higher in group E than in other groups, while the number of patients with shivering grade 2 was significantly higher in group F than in group FE (P <.05). Patient and surgeon satisfaction scores were higher in group FE than in groups E and F (P <.05). CONCLUSIONS: Use of a forced-air warming system combined with an electric blanket was an effective method with which to retain warmth among elderly TURP patients.

Cold-Induced Thermogenesis and Inflammation-Associated Cold-Seeking Behavior Are Represented by Different Dorsomedial Hypothalamic Sites: A Three-Dimensional Functional Topography Study in Conscious Rats.

In the past, we showed that large electrolytic lesions of the dorsomedial hypothalamus (DMH) promoted hypothermia in cold-exposed restrained rats, but attenuated hypothermia in rats challenged with a high dose of bacterial lipopolysaccharide (LPS) in a thermogradient apparatus. The goal of this study was to identify the thermoeffector mechanisms and DMH representation of the two phenomena and thus to understand how the same lesion could produce two opposite effects on body temperature. We found that the permissive effect of large electrolytic DMH lesions on cold-induced hypothermia was due to suppressed thermogenesis. DMH-lesioned rats also could not develop fever autonomically: they did not increase thermogenesis in response to a low, pyrogenic dose of LPS (10 µg/kg, i.v.). In contrast, changes in thermogenesis were uninvolved in the attenuation of the hypothermic response to a high, shock-inducing dose of LPS (5000 µg/kg, i.v.); this attenuation was due to a blockade of cold-seeking behavior. To compile DMH maps for the autonomic cold defense and for the cold-seeking response to LPS, we studied rats with small thermal lesions in different parts of the DMH. Cold thermogenesis had the highest representation in the dorsal hypothalamic area. Cold seeking was represented by a site at the ventral border of the dorsomedial nucleus. Because LPS causes both fever and hypothermia, we originally thought that the DMH contained a single thermoregulatory site that worked as a fever-hypothermia switch. Instead, we have found two separate sites: one that drives thermogenesis and the other, previously unknown, that drives inflammation-associated cold seeking.SIGNIFICANCE STATEMENT Cold-seeking behavior is a life-saving response that occurs in severe systemic inflammation. We studied this behavior in rats with lesions in the dorsomedial hypothalamus (DMH) challenged with a shock-inducing dose of bacterial endotoxin. We built functional maps of the DMH and found the strongest representation of cold-seeking behavior at the ventral border of the dorsomedial nucleus. We also built maps for cold-induced thermogenesis in unanesthetized rats and found the dorsal hypothalamic area to be its main representation site. Our work identifies the neural substrate of cold-seeking behavior in systemic inflammation and expands the functional topography of the DMH, a structure that modulates autonomic, endocrine, and behavioral responses and is a potential therapeutic target in anxiety and panic disorders.

Effect of Prewarming during Induction of Anesthesia on Microvascular Reactivity in Patients Undergoing Off-Pump Coronary Artery Bypass Surgery: A Randomized Clinical Trial.

BACKGROUND: General anesthesia may induce inadvertent hypothermia and this may be related to perioperative cardiovascular complications. Microvascular reactivity, measured by the recovery slope during a vascular occlusion test, is decreased during surgery and is also related to postoperative clinical outcomes. We hypothesized that microvascular changes during surgery may be related to intraoperative hypothermia. To evaluate this, we conducted a randomized study in patients undergoing off-pump coronary artery bypass surgery, in which the effect of prewarming on microvascular reactivity was evaluated. METHODS: Patients scheduled for off-pump coronary artery bypass surgery were screened. Enrolled patients were randomized to the prewarming group to receive forced-air warming during induction of anesthesia or to the control group. Measurement of core and skin temperatures and vascular occlusion test were conducted before anesthesia induction, 1, 2, and 3 h after induction, and at the end of surgery. RESULTS: In total, 40 patients were enrolled and finished the study (n = 20 in the prewarming group and n = 20 in the control group). During the first 3 h of anesthesia, core temperature was higher in the prewarming group than the control group (p < 0.001). The number of patients developing hypothermia was lower in the prewarming group than the control group (4/20 vs. 13/20, p = 0.004). However, tissue oxygen saturation and changes in recovery slope following a vascular occlusion test at 3 h after anesthesia induction did not differ between the groups. There was no difference in clinical outcome, including perioperative transfusion, wound infection, or hospital stay, between the groups. CONCLUSIONS: Prewarming during induction of anesthesia decreased intraoperative hypothermia, but did not reduce the deterioration in microvascular reactivity in patients undergoing off-pump coronary artery bypass surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02186210.

Warming before and after epidural block before general anaesthesia for major abdominal surgery prevents perioperative hypothermia: A randomised controlled trial.

BACKGROUND: Epidural analgesia (EDA) is known to be an independent risk factor for perioperative hypothermia and its many known adverse effects. Combined general and epidural anaesthesia decreases intraoperative core temperature more rapidly than general anaesthesia alone. Hence, adequate warming procedures are needed for these patients. OBJECTIVE: We evaluated the effects of active skin-surface warming before and/or after initiation of EDA during general anaesthesia as a procedure to prevent perioperative hypothermia. DESIGN: A randomised controlled trial. SETTING: Department of Anaesthesiology in a general hospital in Germany from January 2013 until August 2014. PATIENTS: After obtaining written informed consent, we included 99 adult patients undergoing elective major abdominal surgery under combined general anaesthesia and EDA with an expected duration of surgery of at least 120 min. Patients were excluded if they were under 18 years of age, classified as American Society of Anesthesiologists' physical status 4 or higher or if patients refused EDA. INTERVENTIONS: Patients were randomly assigned to one of three groups and received either only passive insulation, 15 min of active air-forced warming after EDA and before induction of general anaesthesia, or two periods, each of 15 min, of active air-forced warming before and after EDA. Core and skin temperatures were measured at several time points throughout the study. MAIN OUTCOME MEASURES: The primary outcome measure was the incidence of hypothermia on arrival in the ICU. The secondary outcome measure was the incidence of postoperative shivering. In addition, the perioperative change in body core temperature was recorded. RESULTS: Without prewarming (n = 32), 72% of patients became hypothermic (<36°C) at the end of anaesthesia. Fifteen minutes of warming after insertion of the epidural catheter and before initiation of general anaesthesia reduced the incidence of postoperative hypothermia to 6% (n = 33). After two periods of 15 min of warming before and after insertion of the epidural catheter, no patient became hypothermic (n = 34). Prewarming in either 'warming' group prevents the initial temperature drop which was observed in the control group. CONCLUSION: Warming for 15 min before and after initiation of EDA in patients receiving combined anaesthesia is effective in preventing postoperative hypothermia. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (identifier: NCT01795482).

Effect of Preoperative Forced-Air Warming on Hypothermia in Elderly Patients Undergoing Transurethral Resection of the Prostate.

PURPOSE: Elderly patients under spinal anesthesia are vulnerable to hypothermia, leading to increased morbidity. The aim of this study was to investigate the effects of preoperative forced-air warming on perioperative hypothermia and shivering in elderly patients undergoing transurethral resection of the prostate (TURP) under spinal anesthesia. MATERIALS AND METHODS: Patients (> 65-year-old) scheduled for TURP under spinal anesthesia were randomly assigned to receive preoperative forced-air skin warming for 20 min (the pre-warmed group, n = 25) or not (control group, n = 25). Core temperatures were measured at 15-min intervals after spinal anesthesia, and intra- and post-operative shivering were also assessed. RESULTS: Incidences of intraoperative hypothermia (< 36 ºC) in the pre-warmed and control groups were not significantly different (10/25 [40%] vs. 15/24 [62.5%], P = .259). However, severities of hypothermia were significantly different (P = .019). No patient in the pre-warmed group showed moderate or profound hypothermia, whereas of patients in control group 21% and 13% did so, respectively. CONCLUSION: This study demonstrated that a brief period of preoperative forced-air warming did not completely prevent intraoperative hypothermia or shivering, but it could significantly reduce its severity in elderly male patients under spinal anesthesia.

Thiamine deficiency: a cause of profound hypotension and hypothermia after plastic surgery.

A 72-year-old woman became profoundly hypotensive and hypothermic 10 hours after undergoing a panniculectomy. She remained critically ill despite aggressive intensive care, and a diagnosis was not identified despite multiple consultations, imaging, and exploratory laparatomy. No improvement was seen until a large dose of intravenous thiamine alone was administered, dramatically restoring a normotensive and normothermic state. Although few cases of thiamine deficiency have been described in the context of plastic and reconstructive surgery, this case emphasizes the importance of considering this potentially fatal condition, which often does not manifest classically in the early postoperative period.

Fuzi-Lizhong pill compensates hypothyroid-hypothermia via ghrelin release.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzi-Lizhong pill (FLZ) is a traditional Chinese medicine for treating patients with Spleen Yang deficient syndrome. Ghrelin, a peptide with 28 amino acid residues, plays multiple roles in thermogenesis. This study aims to explore FLZ regulating ghrelin to compensate hypothermia in rats with hypothyroid and indigestion. MATERIALS AND METHODS: In litter-matched rats, hypothermia was developed with both thyroidectomy at d1 and interscapular brown adipose (IBA) removal at d42, indigestion was induced with both high fat diet and fasting-feeding cycle from d56; the littermates with hypothermia and indigestion were administrated with FLZ from d70. Adaptive thermogenesis, thyroid hormones, metabolites, ghrelin dynamics were measured at d98. RESULTS: The results showed that plasma ghrelin levels were inversely correlated with the gastric ghrelin levels and adaptive thermogenesis in rats undergone both thyroidectomy and IBA removal. Fatty diet and FLZ enhanced the increase of plasma ghrelin of hypothyroid rats. These were supported by the changes of plasma thyroid related hormones, plasma metabolites, gastric ghrelin mRNA and protein, and the effects of fatty diet or FLZ. CONCLUSIONS: Our results suggest that more ghrelin release compensate chronic hypothermia in rats with both hypothyroidism and indigestion. It could explain the mechanisms of FLZ in relieving chronic hypothermia.