Acacetin suppresses the electrocardiographic and arrhythmic manifestations of the J wave syndromes.

BACKGROUND: J wave syndromes (JWS), including Brugada (BrS) and early repolarization syndromes (ERS), are associated with increased risk for life-threatening ventricular arrhythmias. Pharmacologic approaches to therapy are currently very limited. Here, we evaluate the effects of the natural flavone acacetin. METHODS: The effects of acacetin on action potential (AP) morphology and transient outward current (Ito) were first studied in isolated canine RV epicardial myocytes using whole-cell patch clamp techniques. Acacetin's effects on transmembrane APs, unipolar electrograms and transmural ECGs were then studied in isolated coronary-perfused canine RV and LV wedge preparations as well as in whole-heart, Langendorff-perfused preparations from which we recorded a 12 lead ECG and unipolar electrograms. Using floating glass microelectrodes we also recorded transmembrane APs from the RVOT of the whole-heart model. The Ito agonist NS5806, sodium channel blocker ajmaline, calcium channel blocker verapamil or hypothermia (32°C) were used to pharmacologically mimic the genetic defects and conditions associated with JWS, thus eliciting prominent J waves and provoking VT/VF. RESULTS: Acacetin (5-10 µM) reduced Ito density, AP notch and J wave area and totally suppressed the electrocardiographic and arrhythmic manifestation of both BrS and ERS, regardless of the experimental model used. In wedge and whole-heart models of JWS, increasing Ito with NS5806, decreasing INa or ICa (with ajmaline or verapamil) or hypothermia all resulted in accentuation of epicardial AP notch and ECG J waves, resulting in characteristic BrS and ERS phenotypes. Phase 2-reentrant extrasystoles originating from the RVOT triggered VT/VF. The J waves in leads V1 and V2 were never associated with a delay of RVOT activation and always coincided with the appearance of the AP notch recorded from RVOT epicardium. All repolarization defects giving rise to VT/VF in the BrS and ERS models were reversed by acacetin, resulting in total suppression of VT/VF. CONCLUSIONS: We present experimental models of BrS and ERS capable of recapitulating all of the ECG and arrhythmic manifestations of the JWS. Our findings provide definitive support for the repolarization but not the depolarization hypothesis proposed to underlie BrS and point to acacetin as a promising new pharmacologic treatment for JWS.

Comparison of the Protective Effect of Salvia officinalis and Rosmarinus officinalis Infusions Against Hepatic Damage Induced by Hypotermic-Ischemia in Wistar Rats.

We aimed to evaluate, in this study, the effect of Rosmarinus officinalis L. and Salvia officinalis L. in the amelioration of liver hypothermic conservation in male wistar rats. Livers from each rat were collected and preserved for 24 h at 4 °C in a Krebs solution with or without increasing doses of sage or rosemary infusions (25, 50, and 100 mg/mL). Liver hypothermic conservation induced a decrease in the activity of superoxide dismutase, catalase, and glutathione peroxidase and a significant increase in lipid peroxidation. S. officinalis L. infusion at 25 mg/mL normalized this oxidative disturbance but appears toxic at 50 and 100 mg/mL due to the presence of large amount of pyrogallol which contribute to the cytoplasmic alteration of hepatocytes. The addition of different doses of R. officinalis L. infusion induced an increase in catalase and glutathione peroxidase activities and a decrease in lipid peroxidation with an amelioration of cellular architecture. In conclusion, increasing doses of R. officinalis L. infusion protect against hepatic hypotermic-ischemia while S. officinalis L. infusion could have an hepatoprotective role when administrated at lower dose.

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.

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.

Cryogenic role of central endogenous hydrogen sulfide in the rat model of endotoxic shock.

Thermoregulatory responses to lipopolysaccharide (LPS) are affected by modulators that increase (propyretic) or decrease (cryogenic) body temperature (Tb). We tested the hypothesis that central hydrogen sulfide (H2S) acts as a thermoregulatory modulator and that H2S production in the anteroventral preoptic region of the hypothalamus (AVPO) is increased during hypothermia and decreased during fever induced by bacterial lipopolysaccharide (LPS, 2.5mg/kg i.p.) in rats kept at an ambient temperature of 25°C. Deep Tb was recorded before and after pharmacological inhibition of the enzyme cystathionine ß-synthase (CBS - responsible for H2S endogenous production in the brain) combined or not with LPS administration. To further investigate the mechanisms responsible for these thermoregulatory adjustments, we also measured prostaglandin D2 (PGD2) production in the AVPO. LPS caused typical hypothermia followed by fever. Levels of AVPO H2S were significantly increased during hypothermia when compared to both euthermic and febrile rats. Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS inhibitor; 100 pmol) neither affected Tb nor basal PGD2 production during euthermia. In LPS-treated rats, AOA caused increased Tb values during hypothermia, along with enhanced PGD2 production. We conclude that the gaseous messenger H2S modulates hypothermia during endotoxic shock, acting as a cryogenic molecule.

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).

Dexmedetomidine reduces cranial temperature in hypothermic neonatal rats.

BACKGROUND: The α2-adrenergic agonist dexmedetomidine (DEX) is increasingly used for prolonged sedation of critically ill neonates, but there are currently no data evaluating possible consequences of prolonged neonatal DEX exposure. We evaluated the pharmacokinetics and histological consequences of neonatal DEX exposure. METHODS: DEX was administered (s.c.) to naive (uninjured) neonatal Lewis rats to provide acute (25 µg/kg, ×1) or prolonged (25 µg/kg three times daily, ×2 or ×4 d) exposure. Therapeutic hypothermia was simulated using a water-cooled blanket. Cranial temperatures were measured using an infrared thermometer. DEX concentrations were measured by LC-MS in plasma and homogenized brainstem tissue for pharmacokinetic analysis. Cortex, cerebellum, and brainstem were evaluated for evidence of inflammation or injury. RESULTS: Prolonged neonatal DEX exposure was not associated with renal or brain pathology or indices of gliosis, macrophage activation, or apoptosis in either hypothermic or control rats. Plasma and brain DEX concentrations were tightly correlated. DEX peaked within 15 min in brain and reduced cranial temperature from 32 to 30 °C within 30 min after injection in cooled rats. CONCLUSION: Prolonged DEX treatment in neonatal rats was not associated with abnormal brain histology. These data provide reassuring preliminary results for using DEX with therapeutic hypothermia to treat near-term brain injury.

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.

[Restoration of respiratory function of an organism after cold oppressions without warming].

In experiments on rats studied influence of intravenous introduction NazdTA on respiratory function of rats after the full termination of breath at deep hypothermia. It is shown that such method without warming application it is possible to lower on 1.5-2.0 degrees C a temperature threshold of approach full a cold paralysis of respiratory function of an organism. It confirms the hypothesis put forward earlier about an important role of infringement of balance of ions of calcium in cytoplasm of cells in development of a pathology of an organism at deep hypothermia. The received results can be used at resuscitation of victims accidental hypothermia.

Wilderness Medical Society practice guidelines for the out-of-hospital evaluation and treatment of accidental hypothermia: 2014 update.

To provide guidance to clinicians, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the out-of-hospital evaluation and treatment of victims of accidental hypothermia. The guidelines present the main diagnostic and therapeutic modalities and provide recommendations for the management of hypothermic patients. The panel graded the recommendations based on the quality of supporting evidence and the balance between benefits and risks/burdens according the criteria published by the American College of Chest Physicians. The guidelines also provide suggested general approaches to the evaluation and treatment of accidental hypothermia that incorporate specific recommendations. This is an updated version of the original Wilderness Medical Society Practice Guidelines for the Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia published in Wilderness & Environmental Medicine 2014;25(4):425-445.

Electrocardiogram artifact caused by rigors mimicking narrow complex tachycardia: a case report.

BACKGROUND: The electrocardiogram (ECG) is useful in the diagnosis of cardiac and non-cardiac conditions. Rigors due to shivering can cause electrocardiogram artifacts mimicking various cardiac rhythm abnormalities. CASE PRESENTATION: We describe an 80-year-old Sri Lankan man with an abnormal electrocardiogram mimicking narrow complex tachycardia during the immediate post-operative period. Electrocardiogram changes caused by muscle tremor during rigors could mimic a narrow complex tachycardia. CONCLUSIONS: Identification of muscle tremor as a cause of electrocardiogram artifact can avoid unnecessary pharmacological and non-pharmacological intervention to prevent arrhythmias.

[Experimental evaluation of actoprotective activity of nitrogen-containing heterocyclic compounds derivatives in extreme conditions].

In experiments on nonlinear male mice the ability of new derivatives of nitrogen-containing heterocyclic compounds to increase the physical working capacity in conditions of hyperthermia, hypothermia and acute normobaric hypoxia and hypercapnia has been investigated. It is established, that pyridine derivative IBHF-11 has more expressed positive action in the said conditions. It provided increase of the working capacity of animals at all kinds of extreme influence, and the value of positive action was comparable, and in conditions of acute normobaric hypoxia and hypercapnia exceeded those at the reference products bemitil and bromantan.

Comparison of thermoregulatory devices used during anesthesia of C57BL/6 mice and correlations between body temperature and physiologic parameters.

General anesthesia affects several body systems, including thermoregulation. Decreased body temperature during anesthesia has potential negative effects, including delayed recovery to consciousness. Thermoregulatory support devices are used to maintain temperature in anesthetized rodents. We analyzed 2 novel thermoregulatory devices, thermogenic gel packs and reflective foils, to compare their effectiveness in maintaining temperatures with that of a standard circulating-warm-water blanket (CWWB) in C57BL/6 mice. Mice were grouped randomly: control (no thermal support), reflective foil, gel pack, gel pack plus reflective foil, CWWB on medium setting, CWWB on high setting, and CWWB on high setting plus reflective foil. Mice were anesthetized with isoflurane for 30 min, and temperature and heart and respiratory rates were monitored. Results indicated that the temperatures of mice with reflective foil only (start temperature, 36.2 ± 0.38 °C; end temperature, 28.8 ± 0.78 °C) did not differ significantly from those of control mice; however, the inclusion of foil heightened thermogenic properties when combined with other devices. Thermogenic gel packs and CWWB on high setting, both with and without reflective foil, caused significant temperature increases (that is, 1.6 °C to 4.4 °C) in mice. CWWB on medium setting (blanket temperature, 37.5 °C) maintained mice at temperatures within 1 °C of the 36.1 °C baseline. Strong correlations existed between temperature, heart and respiratory rates, and recovery time to consciousness. This information provides guidance regarding the use of thermoregulatory devices in anesthetized rodents and demonstrates the effect of maintaining a consistent core temperature on physiologic parameters.

Differential drug-drug interactions of the synthetic Cannabinoids JWH-018 and JWH-073: implications for drug abuse liability and pain therapy.

Marijuana substitutes often contain blends of multiple psychoactive synthetic cannabinoids (SCBs), including the prevalent SCBs (1-pentyl-1H-indole-3-yl)-1-naphthalenyl-methanone (JWH-018) and (1-butyl-1H-indole-3-yl)-1-naphthalenyl-methanone (JWH-073). Because SCBs are frequently used in combinations, we hypothesized that coadministering multiple SCBs induces synergistic drug-drug interactions. Drug-drug interactions between JWH-018 and JWH-073 were investigated in vivo for Δ(9)-tetrahydrocannabinol (Δ(9)-THC)-like discriminative stimulus effects, analgesia, task disruption, and hypothermia. Combinations (JWH-018:JWH-073) of these drugs were administered to mice in assays of Δ(9)-THC discrimination, tail-immersion, and food-maintained responding, and rectal temperatures were measured. Synergism occurred in the Δ(9)-THC discrimination assay for two constant dose ratio combinations (1:3 and 1:1). A 1:1 and 2:3 dose ratio induced additivity and synergy, respectively, in the tail-immersion assay. Both 1:1 and 2:3 dose ratios were additive for hypothermia, whereas a 1:3 dose ratio induced subadditive suppression of food-maintained responding. In vitro drug-drug interactions were assessed using competition receptor-binding assays employing mouse brain homogenates and cannabinoid 1 receptor (CB1R)-mediated inhibition of adenylyl cyclase activity in Neuro2A wild-type cells. Interestingly, synergy occurred in the competition receptor-binding assay for two dose ratios (1:5 and 1:10), but not in the adenylyl cyclase activity assay (1:5). Altogether, these data indicate that drug-drug interactions between JWH-018 and JWH-073 are effect- and ratio-dependent and may increase the relative potency of marijuana substitutes for subjective Δ(9)-THC-like effects. Combinations may improve the therapeutic profile of cannabinoids, considering that analgesia but not hypothermia or task disruption was potentiated. Importantly, synergy in the competition receptor-binding assay suggests multiple CB1R-SCB binding sites.

Oily nanosuspension for long-acting intramuscular delivery of curcumin didecanoate prodrug: preparation, characterization and in vivo evaluation.

The objective of this study was to prepare the nanocrystals of curcumin didecanoate (CurDD) by wet ball milling and to investigate the comparative pharmacokinetics of oily nano- and micro-suspensions after intramuscular (i.m.) administration to rats. Upon optimizing the wet ball milling parameters, CurDD nanocrystals were produced with median particle size of ~500 nm and the freeze-dried nanocrystals were readily dispersed in peanut oil to form stable nanosuspensions. Although the nanosuspension appeared to exhibit slower clearance from the injection site after i.m. injection, compared to microsuspension (~5 µm), a significantly higher maximum plasma curcumin concentration (69.0 ng/ml) was observed for the former than that for the latter (18.5 ng/ml). In addition, the nanosuspension provided significant higher plasma curcumin concentrations and brain CurDD contents for at least 15 days than the microsuspension, except for the initial times. A single i.m. injection of nanosuspension appeared to achieve reversal effect on reserpine-induced hypothermia for at least 13 days. This study demonstrates that CurDD nanosuspension may act as a long-acting i.m. injectable for sustained delivery of curcumin, potentially applicable to elicit a long-lasting antidepressant effect.

Regulatory mechanism of body temperature in the central nervous system during the maintenance phase of hibernation in Syrian hamsters: involvement of ß-endorphin.

We have shown previously that intracerebroventricular (icv) injection of naloxone (a non-selective opioid receptor antagonist) or naloxonazine (a selective µ1-opioid receptor antagonist) at the maintenance phase of hibernation arouses Syrian hamsters from hibernation. This study was designed to clarify the role of ß-endorphin (an endogenous µ-opioid receptor ligand) on regulation of body temperature (T(b)) during the maintenance phase of hibernation. The number of c-Fos-positive cells and ß-endorphin-like immunoreactivity increased in the arcuate nucleus (ARC) after hibernation onset. In contrast, endomorphin-1 (an endogenous µ-opioid receptor ligand)-like immunoreactivity observed on the anterior hypothalamus decreased after hibernation onset. In addition, hibernation was interrupted by icv injection of anti-ß-endorphin antiserum at the maintenance phase of hibernation. The mRNA expression level of proopiomelanocortin (a precursor of ß-endorphin) on ARC did not change throughout the hibernation phase. However, the mRNA expression level of prohormone convertase-1 increased after hibernation onset. [D-Ala2,N-MePhe4,Gly-ol5] enkephalin (DAMGO, a selective µ-opioid receptor agonist) microinjection into the dorsomedial hypothalamus (DMH) elicited the most marked T(b) decrease than other sites such as the preoptic area (PO), anterior hypothalamus (AH), lateral hypothalamus (LH), ventromedial hypothalamus and posterior hypothalamus (PH). However, microinjected DAMGO into the medial septum indicated negligible changes in T(b). These results suggest that ß-endorphin which synthesizes in ARC neurons regulates T(b) during the maintenance phase of hibernation by activating µ-opioid receptors in PO, AH, VMH, DMH and PH.

Moderate temperature alterations affect Gram-negative immune signalling in ex vivo whole blood.

BACKGROUND: Alterations in body temperature may influence immune system function and consequently affect the risk of infection and inflammatory diseases. Lipopolysaccharide (LPS) from gram-negative bacteria induces production of inflammatory cytokines after ligand binding to Toll-like receptor 4 (TLR4) on immune cells (especially monocytes/ macrophages). Our aim was to explore how clinically relevant hypo- and hyperthermia affect this signalling in an ex vivo whole blood model, and investigate if the cytokine response was correlated with monocyte TLR4 expression level. METHODS: Blood from 11 healthy volunteers was incubated with LPS 10 ng/ml for 6 h at 33, 37 or 40°C. The concentrations of selected pro-inflammatory (tumour necrosis factor-α (TNF-α) and interleukin (IL)-1ß) and anti-inflammatory (IL-10) cytokines were measured in plasma, and the surface expression of TLR4 was quantified on CD14 + monocytes. RESULTS: Monocyte TLR4 expression and plasma IL-1ß were inversely related to temperature. The TNF-α production was unaffected by hypothermia but increased significantly during hyperthermia, whereas plasma IL-10 was significantly reduced during both hypo- and hyperthermic incubation. No correlation was found between TLR4 expression and cytokine concentrations. During hypothermia, the TNF-α/IL-10 and IL-1ß/IL-10 ratios increased seven and nine times, respectively. Hyperthermia increased the TNF-α/IL-10 ratio, but to a lesser extent (doubling), whereas the IL-1ß/IL-10 ratio remained unchanged. CONCLUSION: Hypothermia significantly changed the cytokine ratios in the pro-inflammatory direction. In comparison, the effect of hyperthermia was sparse, with a modest increase in the TNF-α/IL-10 ratio only. No association was found between LPS-stimulated cytokine production and TLR4 expression on CD14 + monocytes.

[Accidental hypothermia]. / Hipotermia accidental.

Accidental hypothermia is an infrequent and under-diagnosed pathology, which causes fatalities every year. Its management requires thermometers to measure core temperature. An esophageal probe may be used in a hospital situation, although in moderate hypothermia victims epitympanic measurement is sufficient. Initial management involves advance life support and body rewarming. Vigorous movements can trigger arrhythmia which does not use to respond to medication or defibrillation until the body reaches 30°C. External, passive rewarming is the method of choice for mild hypothermia and a supplementary method for moderate or severe hypothermia. Active external rewarming is indicated for moderate or severe hypothermia or mild hypothermia that has not responded to passive rewarming. Active internal rewarming is indicated for hemodynamically stable patients suffering moderate or severe hypothermia. Patients with severe hypothermia, cardiac arrest or with a potassium level below 12 mmol/l may require cardiopulmonary bypass treatment.