Soluble thrombomodulin ameliorates aberrant hemostasis after rewarming in a rat accidental hypothermia model.

BACKGROUND: Accidental hypothermia (AH) sometimes leads to coagulation disorder, especially in severe AH. We previously demonstrated that intrasplenic platelet activation caused aberrant hemostasis and thrombus formation after rewarming in a murine AH model. However, no study has focused on the appropriate management of platelets causing coagulation activation after rewarming of AH. We investigated whether or not recombinant soluble thrombomodulin (rTM) can suppress thrombosis formation after rewarming using a rat AH model. METHODS: Wistar rats were exposed to an ambient temperature of -20 °C under general anesthesia until their rectal temperature decreased to 26 °C. The Hypo group rats (n = 5) were immediately euthanized, while the Hypo/Re group (n = 5) and rTM group rats (n = 5), which were administered rTM (1 mg/kg) via the tail vein, were rewarmed until the rectal temperature returned to 34 °C and then euthanized 6 h later. Tissue and blood samples were collected from all rats for histopathological and coagulation analyses at euthanasia. RESULTS: There was no significant change in the D-dimer level in the Hypo group rats, while the D-dimer level was significantly elevated at 6 h after rewarming in the Hypo/Re group rats (P = 0.015), and histopathology detected both fibrin and platelets in the renal glomerulus. However, the rTM group rats did not show any elevation of the D-dimer levels at 6 h after rewarming, and no fibrin was noted on histopathology. CONCLUSIONS: rTM may be useful as an appropriate anticoagulant in cases of aberrant hemostasis after rewarming of AH.

Central GABAA receptor mediates taurine-induced hypothermia and possibly reduces food intake in thermo-neutral chicks and regulates plasma metabolites in heat-exposed chicks.

The aim of this study was to examine the central action of taurine on body temperature and food intake in neonatal chicks under control thermoneutral temperature (CT) and high ambient temperature (HT). Intracerebroventricular injection of taurine caused dose-dependent hypothermia and reduced food intake under CT. The mRNA expression of the GABAA receptors, GABAAR-α1 and GABAAR-γ, but not that of GABABR, significantly decreased in the diencephalon after central injection of taurine. Subsequently, we found that picrotoxin, a GABAAR antagonist, attenuated taurine-induced hypothermia. Central taurine significantly decreased the brain concentrations of 3-methoxy-4-hydroxyphenylglycol, a major metabolite of norepinephrine; however, the concentrations of serotonin, dopamine, and the epinephrine metabolites, 3,4-hydroxyindoleacetic acid and homovanillic acid, were unchanged. Although hypothermia was not observed under HT after central injection of taurine, plasma glucose and uric acid levels were higher, and plasma sodium and calcium levels were lower, than those in chicks under CT. In conclusion, brain taurine may play a role in regulating body temperature and food intake in chicks through GABAAR. The changes in plasma metabolites under heat stress suggest that brain taurine may play an important role in maintaining homeostasis in chicks.

Successful mild brain hypothermia therapy followed by targeted temperature management for pediatric hemorrhagic shock and encephalopathy syndrome.

OBJECTIVE: Hemorrhagic shock and encephalopathy syndrome (HSES) is the most severe form of acute encephalopathy that progresses rapidly, often resulting in death or severe neurological sequelae. We report the case of a 4-year-old girl with HSES with shock and impaired consciousness. PATIENT AND METHODS: Blood test results showed hypercytokinemia, and the 4-year-old patient was immediately admitted to the intensive care unit. Within 4 h of symptom onset, she received mild brain hypothermia therapy with a target body temperature of 35°C. Methylprednisolone pulse, high dose immunoglobulin, and large doses of circulatory drugs were administered. RESULTS: After 72 h of brain hypothermia therapy, targeted temperature management with a target body temperature between 36°C and 37°C was continued for 96 h. The patient was diagnosed with HSES based on acute encephalopathy with shock, hypercytokinemia, low platelet count, coagulation disorder, renal damage, and intestinal bleeding. Magnetic resonance imaging results revealed no signs of any specific acute encephalopathy. She was discharged without neurological sequelae 28 days after symptom onset. CONCLUSIONS: Mild brain hypothermia therapy initiated in the early stages followed by targeted temperature management may be an effective way to improve neurological outcomes in children suffering from HSES.

Fibroblast Growth Factor-21, Leptin, and Adiponectin Responses to Acute Cold-Induced Brown Adipose Tissue Activation.

BACKGROUND: Adipocyte-derived hormones play a role in insulin sensitivity and energy homeostasis. However, the relationship between circulating fibroblast growth factor 21 (FGF21), adipocytokines and cold-induced supraclavicular brown adipose tissue (sBAT) activation is underexplored. OBJECTIVE: Our study aimed to investigate the relationships between cold-induced sBAT activity and plasma FGF21 and adipocytokines levels in healthy adults. DESIGN: Nineteen healthy participants underwent energy expenditure (EE) and supraclavicular infrared thermography (IRT) within a whole-body calorimeter at baseline and at 2 hours post-cold exposure. 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scans were performed post-cold exposure. PET sBAT mean standardized uptake value (SUV mean), MR supraclavicular fat fraction (sFF), anterior supraclavicular maximum temperature (Tscv max) and EE change (%) after cold exposure were used to quantify sBAT activity. MAIN OUTCOME MEASURES: Plasma FGF21, leptin, adiponectin, and tumor necrosis factor alpha (TNFα) at baseline and 2 hours post-cold exposure. Body composition at baseline by dual-energy x-ray absorptiometry (DXA). RESULTS: Plasma FGF21 and adiponectin levels were significantly reduced after cold exposure in BAT-positive subjects but not in BAT-negative subjects. Leptin concentration was significantly reduced in both BAT-positive and BAT-negative participants after cold exposure. Adiponectin concentration at baseline was positively strongly associated with sBAT PET SUV mean (coefficient, 3269; P = 0.01) and IRT Tscv max (coefficient, 6801; P  = 0.03), and inversely correlated with MR sFF (coefficient, -404; P  = 0.02) after cold exposure in BAT-positive subjects but not in BAT-negative subjects. CONCLUSION: Higher adiponectin concentrations at baseline indicate a greater cold-induced sBAT activity, which may be a novel predictor for sBAT activity in healthy BAT-positive adults. HIGHLIGHTS: A higher adiponectin concentration at baseline was associated with higher cold-induced supraclavicular BAT PET SUV mean and IRT Tscv max, and lower MR supraclavicular FF. Adiponectin levels maybe a novel predictor for cold-induced sBAT activity.

Impact of acute ethanol exposure on body temperatures in aged, adult and adolescent male rats.

The mean population age of the United States continues to increase, and data suggest that by the year 2060 the population of people over the age of 65 will more than double, providing a potentially massive strain on health care systems. Research demonstrates individuals 65 and older continue to consume ethanol, often at high levels. However, preclinical animal models are still being developed to understand how ethanol might interact with the aged population. The current experiments investigated differential body temperature responses in aged rats compared to adult rats and adolescent rats. Aged (19 months of age), adult (70 days of age), or adolescent (30 days of age) male Sprague Dawley rats were administered 1.0 g/kg, 2.0 g/kg, or 3.0 g/kg ethanol, intraperitoneally (i.p.), in a balanced Latin square design. Prior to ethanol administration, a core body temperature via an anal probe was obtained, and then repeatedly determined every 60 min following ethanol exposure for a total of 360 min. In addition, a blood sample was obtained from a tail nick 60, 180, and 300 min following the ethanol injection to investigate the relationship of ethanol levels and body temperature in the same animals. Aged rats had significantly greater reductions in body temperature compared to either adult or adolescent rats following both the 2.0 g/kg and 3.0 g/kg ethanol injection. Additionally, adolescent rats cleared ethanol significantly faster than aged or adult animals. These experiments suggest body temperature regulation in aged rats might be more sensitive to acute ethanol compared to adult rats or adolescent rats. Future studies are needed to identify the neurobiological effects underlying the differential sensitivity in aged rats to ethanol.

Risk factors and diagnostic markers of bacteremia in Stevens-Johnson syndrome and toxic epidermal necrolysis: A cohort study of 176 patients.

BACKGROUND: Sepsis is the main cause of death in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). OBJECTIVES: Our aim was to identify admission risk factors predictive of bacteremia and the accompanying clinical or biochemical markers associated with positive blood cultures. METHODS: A retrospective cohort study over a 14-year period (2003-2016) was performed. RESULTS: The study included 176 patients with SJS (n = 59), SJS-TEN overlap (n = 51), and TEN (n = 66). During hospitalization, bacteremia developed in 52 patients (29.5%), who experienced poorer outcomes, including higher intensive care unit admission (P < .0005), longer length of stay (P < .0005), and higher mortality (P < .0005). There were 112 episodes of bacteremia, and isolates included Acinetobacter baumannii (27.7%, n = 31) and Staphylococcus aureus (21.4%, n = 24). On multivariate analysis, clinical factors present at admission that were predictive of bacteremia included hemoglobin ≤10 g/dL (odds ratio [OR] 2.4, confidence interval [CI] 2.2-2.6), existing cardiovascular disease (OR 2.10, CI 2.0-2.3), and body surface area involvement ≥10% (OR 14.3, CI 13.4-15.2). The Bacteremia Risk Score was constructed with good calibration. Hypothermia (P = .03) and procalcitonin ≥1 µg/L (P = .02) concurrent with blood culture sampling were predictive of blood culture positivity. LIMITATIONS: This is a retrospective study performed in a reference center. CONCLUSION: Hemoglobin ≤10 g/dL, cardiovascular disease, and body surface area involvement ≥10% on admission were risk factors for bacteremia. Hypothermia and elevated procalcitonin are useful markers for the timely detection of bacteremia.

Mitochondrial-Derived Peptide MOTS-c Increases Adipose Thermogenic Activation to Promote Cold Adaptation.

Cold exposure stress causes hypothermia, cognitive impairment, liver injury, and cardiovascular diseases, thereby increasing morbidity and mortality. Paradoxically, cold acclimation is believed to confer metabolic improvement to allow individuals to adapt to cold, harsh conditions and to protect them from cold stress-induced diseases. However, the therapeutic strategy to enhance cold acclimation remains less studied. Here, we demonstrate that the mitochondrial-derived peptide MOTS-c efficiently promotes cold adaptation. Following cold exposure, the improvement of adipose non-shivering thermogenesis facilitated cold adaptation. MOTS-c, a newly identified peptide, is secreted by mitochondria. In this study, we observed that the level of MOTS-c in serum decreased after cold stress. MOTS-c treatment enhanced cold tolerance and reduced lipid trafficking to the liver. In addition, MOTS-c dramatically upregulated brown adipose tissue (BAT) thermogenic gene expression and increased white fat "browning". This effect might have been mediated by MOTS-c-activated phosphorylation of the ERK signaling pathway. The inhibition of ERK signaling disturbed the up-regulatory effect of MOTS-c on thermogenesis. In summary, our results indicate that MOTS-c treatment is a potential therapeutic strategy for defending against cold stress by increasing the adipose thermogenesis via the ERK pathway.

Postmortem diagnosis of fatal hypothermia/hyperthermia by spectrochemical analysis of plasma.

Postmortem diagnosis of extreme-weather-related deaths is a challenging forensic task. Here, we present a state-of-the-art study that employed attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy in combination with Chemometrics for postmortem diagnosis of fatal hypothermia/hyperthermia by biochemical investigation of plasma in rats. The results of principal component analysis (PCA) and spectral analysis revealed that plasma samples from the fatal hypothermia, fatal hyperthermia, and control groups, are substantially different from each other based on the spectral variations associated with the lipid, carbohydrate and nucleic acid components. Two partial least squares-discriminant analysis (PLS-DA) classification models (hypothermia-nonhypothermia and hyperthermia-nonhyperthermia binary models) with a 100% accuracy rate were constructed. Subsequently, internal cross-validation was performed to assess the robustness of these two models, which resulted in 98.1 and 100% accuracy. Ultimately, classification predictions of 42 unknown plasma samples were performed by these two models, and both models achieved 100% accuracy. Additionally, our results demonstrated that hemolysis and postmortem hypothermic/hyperthermic effects did not weaken the prediction ability of these two classification models. In summary, this work demonstrates ATR-FTIR spectroscopy's great potential for postmortem diagnosis of fatal hypothermia/hyperthermia.

Cut-off values of serum potassium and core temperature at hospital admission for extracorporeal rewarming of avalanche victims in cardiac arrest: A retrospective multi-centre study.

AIM: Evidence of existing guidelines for the on-site triage of avalanche victims is limited and adherence suboptimal. This study attempted to find reliable cut-off values for the identification of hypothermic avalanche victims with reversible out-of-hospital cardiac arrest (OHCA) at hospital admission. This may enable hospitals to allocate extracorporeal life support (ECLS) resources more appropriately while increasing the proportion of survivors among rewarmed victims. METHODS: All avalanche victims with OHCA admitted to seven centres in Europe capable of ECLS from 1995 to 2016 were included. Optimal cut-off values, for parameters identified by logistic regression, were determined by means of bootstrapping and exact binomial distribution and served to calculate sensitivity, rate of overtriage, positive and negative predictive values, and receiver operating curves. RESULTS: In total, 103 avalanche victims with OHCA were included. Of the 103 patients 61 (58%) were rewarmed by ECLS. Six (10%) of the rewarmed patients survived whilst 55 (90%) died. We obtained optimal cut-off values of 7 mmol/L for serum potassium and 30 °C for core temperature. CONCLUSION: For in-hospital triage of avalanche victims admitted with OHCA, serum potassium accurately predicts survival. The combination of the cut-offs 7 mmol/L for serum potassium and 30 °C for core temperature achieved the lowest overtriage rate (47%) and the highest positive predictive value (19%), with a sensitivity of 100% for survivors. The presence of vital signs at extrication is strongly associated with survival. For further optimisation of in-hospital triage, larger datasets are needed to include additional parameters.

Biomarkers of Cerebral Damage in Fatal Hypothermia: Preliminary Results.

The identification of hypothermia as the cause of death remains challenging in forensic pathology because of unspecific radiological, morphological, and biochemical results. Hyperemia, edema, and petechial hemorrhages within the cerebral parenchyma were described in cases of death by hypothermia. On the other hand, the effect of low temperatures in the brain has been speculated to cause local injuries on a cellular level with potential occurrences of necrosis and inflammation. In the study herein described, endocan, alkaline phosphatase, neuron-specific enolase, S100 protein subunit B, glial fibrillary acidic protein, and C-reactive protein were measured in postmortem serum from femoral blood and cerebrospinal fluid in a series of hypothermia fatalities and control cases. The combination of data collected failed to identify a specific biochemical profile for death by hypothermia in postmortem serum and/or the cerebrospinal fluid, thus suggesting that an alternative panel of brain damage biomarkers indicative of diffuse hypoxic brain injury needs to be defined in hypothermia fatalities.

Programming of the Adult HPA Axis After Neonatal Separation and Environmental Stress in Male and Female Rats.

Maternal separation, hypoxia, and hypothermia are common stressors in the premature neonate. Using our rat model of human prematurity, we evaluated sexual dimorphisms in the long-term effects of these neonatal stressors on behavior of the hypothalamic-pituitary-adrenal (HPA) axis in adult rats. Neonatal rats were exposed daily on postnatal days 2 to 6 to maternal separation with normoxia, with hypoxia allowing spontaneous hypothermia, with hypothermia per se, and with hypoxia while maintaining isothermia with external heat. The major findings were that (a) prior maternal-neonatal separation during the first week of postnatal life attenuated the plasma ACTH and corticosterone response to restraint stress in adult male but not female rats, (b) prior neonatal hypothermia augmented the plasma ACTH and corticosterone response to restraint stress in adult male rats, but not female rats, and (c) changes in hypothalamic, pituitary, and adrenal mRNA expression did not account for most of these HPA axis effects. Most of the programming effects on adult HPA axis was attributed to prior maternal-neonatal separation alone (with normoxia) because the addition of hypoxia with spontaneous hypothermia, hypothermia per se, and hypoxia while preventing hypothermia during maternal-neonatal separation had minimal effects on the HPA axis. These results may inform strategies to prevent sexually dimorphic sequelae of neonatal stress including those due to medical interventions.

Effect of hypothermia treatment on gentamicin pharmacokinetics in neonates with hypoxic-ischaemic encephalopathy: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Hypothermia is the current standard therapy for asphyxiated neonates with hypoxic-ischaemic encephalopathy (HIE). Gentamicin is used for the empirical treatment of early-onset neonatal sepsis. We investigated the influence of hypothermia treatment on gentamicin pharmacokinetics and suggested the appropriate dosing recommendations for gentamicin in neonates with HIE receiving hypothermia treatment. METHODS: We searched studies published until February 2017 in MEDLINE using PubMed, EMBASE and the Cochrane Library. Three independent reviewers screened the literature and extracted data from each study. All of the studies that reported the blood concentrations or pharmacokinetic parameters of gentamicin in hypothermic neonates with HIE were included in this review. Articles were excluded if they were not original research. RESULT AND DISCUSSION: A total of 8 observational studies met the inclusion criteria. Meta-analyses were performed in which the mean difference of gentamicin for the trough concentration and clearance between hypothermic and normothermic neonates were 0.81 mg/L (95% confidence interval [-0.07, 1.69]) and -0.21 mL/kg/min (95% confidence interval [-0.31, -0.12]), respectively. The factors affecting gentamicin clearance in hypothermic neonates with HIE were gestational age, birthweight and serum creatinine. WHAT IS NEW AND CONCLUSION: Gentamicin clearance is decreased in neonates with HIE receiving hypothermia treatment compared to those not receiving hypothermia treatment. Modified gentamicin dosing regimens are required to avoid potential toxicity related to higher concentrations during hypothermia treatment.

Hypothermia outcome prediction after extracorporeal life support for hypothermic cardiac arrest patients: The HOPE score.

AIMS: Currently, the decision to initiate extracorporeal life support for patients who suffer cardiac arrest due to accidental hypothermia is essentially based on serum potassium level. Our goal was to build a prediction score in order to determine the probability of survival following rewarming of hypothermic arrested patients based on several covariates available at admission. METHODS: We included consecutive hypothermic arrested patients who underwent rewarming with extracorporeal life support. The sample comprised 237 patients identified through the literature from 18 studies, and 49 additional patients obtained from hospital data collection. We considered nine potential predictors of survival: age; sex; core temperature; serum potassium level; mechanism of hypothermia; cardiac rhythm at admission; witnessed cardiac arrest, rewarming method and cardiopulmonary resuscitation duration prior to the initiation of extracorporeal life support. The primary outcome parameter was survival to hospital discharge. RESULTS: Overall, 106 of the 286 included patients survived (37%; 95% CI: 32-43%), most (84%) with a good neurological outcome. The final score included the following variables: age, sex, core temperature at admission, serum potassium level, mechanism of cooling, and cardiopulmonary resuscitation duration. The corresponding area under the receiver operating characteristic curve was 0.895 (95% CI: 0.859-0.931) compared to 0.774 (95% CI: 0.720-0.828) when based on serum potassium level alone. CONCLUSIONS: In this large retrospective study we found that our score was superior to dichotomous triage based on serum potassium level in assessing which hypothermic patients in cardiac arrest would benefit from extracorporeal life support. External validation of our findings is required.

NLX-112, a highly selective 5-HT1A receptor agonist: Effects on body temperature and plasma corticosterone levels in rats.

NLX-112 (a.k.a. F13640 or befiradol), exhibits nanomolar affinity, exceptional selectivity and high agonist efficacy at 5-hydroxytryptamine 5-HT1A receptors. It possesses marked activity in a variety of animal models of depression, pain and L-DOPA-induced dyskinesia. However, its influence on translational biomarkers of central 5-HT1A receptor activation has not been previously described. Here, we report on the activity, in rats, of NLX-112 to increase plasma corticosterone levels and produce hypothermia, two responses which are also elicited by 5-HT1A receptor agonists in humans. NLX-112 elicited dose-dependent hypothermia (minimal effective dose, MED: 0.31mg/kg p.o.) and also increased plasma corticosterone both by oral and intraperitoneal routes (MED: 0.63mg/kg in both cases). The increase in corticosterone induced by NLX-112 (0.63mg/kg p.o.) was abolished by co-administration of the selective 5-HT1A receptor antagonist, WAY100635. Additionally, NLX-112 also dose-dependently induced flat body posture, forepaw treading and lower lip retraction (MEDs 0.31-0.63mg/kg p.o.). The doses of NLX-112 which induce hypothermia or corticosterone release were similar to those inducing serotonergic behaviors but greater than those reported previously in models of therapeutic-like activity (range 0.04 to 0.16mg/kg). Overall, the present study provides information for clinical dose estimations of NLX-112 and suggests that therapeutic effects may occur at doses below those at which biomarker responses are observed.

Insulin sensitivity, leptin, adiponectin, resistin, and testosterone in adult male and female rats after maternal-neonatal separation and environmental stress.

Care of premature infants often requires parental and caregiver separation, particularly during hypoxic and hypothermic episodes. We have established a neonatal rat model of human prematurity involving maternal-neonatal separation and hypoxia with spontaneous hypothermia prevented by external heat. Adults previously exposed to these neonatal stressors show a sex difference in the insulin and glucose response to arginine stimulation suggesting a state of insulin resistance. The current study used this cohort of adult rats to evaluate insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)], plasma adipokines (reflecting insulin resistance states), and testosterone. The major findings were that daily maternal-neonatal separation led to an increase in body weight and HOMA-IR in adult male and female rats and increased plasma leptin in adult male rats only; neither prior neonatal hypoxia (without or with body temperature control) nor neonatal hypothermia altered subsequent adult HOMA-IR or plasma adiponectin. Adult male-female differences in plasma leptin were lost with prior exposure to neonatal hypoxia or hypothermia; male-female differences in resistin were lost in the adults that were exposed to hypoxia and spontaneous hypothermia as neonates. Exposure of neonates to daily hypoxia without spontaneous hypothermia led to a decrease in plasma testosterone in adult male rats. We conclude that neonatal stressors result in subsequent adult sex-dependent increases in insulin resistance and adipokines and that our rat model of prematurity with hypoxia without hypothermia alters adult testosterone dynamics.

The biomarkers neuron-specific enolase and S100b measured the day following admission for severe accidental hypothermia have high predictive values for poor outcome.

AIM: The aim of the present study was to assess the ability of the biomarkers neuron-specific enolase (NSE) and S100 calcium-binding protein b (S100b) to predict mortality and poor neurologic outcome after 30days in patients admitted with severe accidental hypothermia. METHODS: Consecutive patients with severe accidental hypothermia, defined as a core temperature <32°C, were included. Patients were treated with active rewarming and/or extracorporeal life support (ECLS) using extra corporeal circulation (ECC) and/or extra corporeal membrane oxygenation (ECMO). The day following admission blood was analyzed for NSE and S100b. Follow-up was conducted after 30days and poor neurologic outcome was defined as a Cerebral Performance Category (CPC) score of 3-5. The predictive value of NSE and S100b was assessed as the area under the receiver-operating characteristics curve (AUC). RESULTS: A total of 34 patients were admitted with a diagnosis of severe accidental hypothermia and 29 (85%) were resuscitated from cardiac arrest. ECLS was initiated in 27 (79%) of patients. The day following admission three (9%) patients had died and one (3%) patient was awake, and accordingly, NSE and S100b were analyzed in 30 unconscious and/or sedated patients. NSE and S100b achieved AUCs of 0.93 and 0.88, respectively, for prediction of 30day mortality and AUCs of 0.88 and 0.87, respectively, for prediction of poor neurologic outcome. CONCLUSIONS: In patients remaining unconscious the day following admission for severe accidental hypothermia, the biomarkers NSE and S100b appear to be solid predictors of mortality and poor neurologic outcome after 30days.

The impact of hypothermia on serum potassium concentration: A systematic review.

BACKGROUND: Blood potassium is the main prognostic biomarker used for triage in hypothermic cardiac arrest. The aim of this review was to assess the impact of hypothermia on blood potassium levels and compare the underlying pathophysiological theories. METHODS: The Medline electronic database was searched via PubMed for articles published from January 1970 to December 2016. The search strategy included studies related to hypothermia and potassium levels. The relevant literature on clinical studies and experimental studies was reviewed by the authors. RESULTS: Among the 50 studies included in the review, 39 (78%) reported a decrease in blood potassium levels upon hypothermia onset. Hypothermic hypokalaemia is linked to an intracellular shift rather than an actual net loss. The intracellular shift is caused by a variety of factors such as enhanced functioning of Na+K+ATPase, beta-adrenergic stimulation, pH and membrane stabilisation in deep hypothermia. In contrast, hypothermia can act as an aggravating factor in severe trauma with hyperkalaemia being an indicator of an irreversible state of cell death. An increase in the blood potassium level during hypothermia may result from a lack of enzyme functioning at cold temperatures and blocked active transport. CONCLUSION: Hypothermia causes an initial decrease of potassium levels; however, the final stage of hypothermic cardiac arrest can induce hyperkalaemia due to cell lysis and final depolarisation. Better understanding the physiopathology of potassium levels during accidental hypothermia could be critically important to better select patients who could benefit from aggressive resuscitation therapy such as extracorporeal cardiopulmonary resuscitation.

Hemodialysis-refractory metformin-associated lactate acidosis with hypoglycemia, hypothermia, and bradycardia in a diabetic patient with belated diagnosis and chronic kidney disease
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Metformin is a first-line oral antidiabetic therapy for patients with type 2 diabetes mellitus. Metformin-associated lactate acidosis (MALA) is a well-known, life-threatening, but rare side effect of metformin therapy. Chronic kidney disease (CKD) patients have a much greater risk of MALA. We report the case of a severe refractory MALA despite hemodialysis (HD) treatment, associated with hypoglycemia, hypothermia, and bradycardia in a neglected and thus untimely-recognized CKD patient with type 2 diabetes mellitus. Despite the recent rehabilitation of metformin as a treatment of choice for type 2 diabetes mellitus, the drug should be prescribed with caution as it can be associated with life-threatening refractory acidosis, particularly in CKD patients. Moreover, HD treatment could occasionally be ineffective, resulting in a fatal outcome.
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Equations for O2 and CO2 solubilities in saline and plasma: combining temperature and density dependences.

Solubilities of respiratory gasses in water, saline, and plasma decrease with rising temperatures and solute concentrations. Henry's Law, C = α·P, states that the equilibrium concentration of a dissolved gas is solubility times partial pressure. Solubilities in the water of a solution depend on temperature and the content of other solutes. Blood temperatures may differ more than 20°C between skin and heart, and an erythrocyte will undergo that range as blood circulates. The concentrations of O2 and CO2 are the driving forces for diffusion, exchanges, and for reactions. We provide an equation for O2 and CO2 solubilities, α, that allows for continuous changes in temperature, T, and solution density, ρ, in dynamically changing states:[Formula: see text]This two-exponential expression with a density scalar γ, and a density exponent ß, accounts for solubility changes due to density changes of an aqueous solution. It fits experimental data on solubilities in water, saline, and plasma over temperatures from 20 to 40°C, and for plasma densities, ρsol up to 1.020 g/ml with ~0.3% error. The amounts of additional bound O2 (to Hb) and CO2 (bicarbonate and carbamino) depend on the concentrations in the local water space and the reaction parameters. During exercise, solubility changes are large; both ρsol and T change rapidly with spatial position and with time. In exercise hemoconcentration plasma, ρsol exceeds 1.02, whereas T may range over 20°C. The six parameters for O2 and the six for CO2 are constants, so solubilities are calculable continuously as T and ρsol change.NEW & NOTEWORTHY Solubilities for oxygen and carbon dioxide are dependent on the density of the solution, on temperature, and on the partial pressure. We provide a brief equation suitable for hand calculators or mathematical modeling, accounting for these factors over a wide range of temperatures and solution densities for use in rapidly changing conditions, such as extreme exercise or osmotic transients, with better than 0.5% accuracy.

Glial fibrillary acidic protein plasma levels are correlated with degree of hypothermia during cardiopulmonary bypass in congenital heart disease surgery.

Objectives: Improved congenital heart defect (CHD) operations have reduced operative mortality to 3%. The major concern is now long-term neurological outcomes. We measured plasma glial fibrillary acidic protein (GFAP), an early marker of brain injury, during different phases of cardiopulmonary bypass (CPB), to correlate the increase of GFAP to clinical parameters or specific operative phases. Methods: We performed a prospective, single-centre, observational study in children undergoing cardiac operations. We studied 69 children with CHD and biventricular heart physiology: 26 had tetralogy of Fallot; 17 transposition of the great arteries; and 26 ventricular/atrial septal defects with or without associated arch defects. GFAP levels were measured by ELISA at different stages of CPB. We recorded clinical and surgical parameters and applied multivariable and logistic regressions to assess which parameters were independent predictors of variations in plasma GFAP. Results: GFAP increased during CPB and peaked at the end of rewarming. Multivariable regression showed degree of hypothermia as the only significant independent predictor of GFAP increase, adjusted for age, prematurity, type of CHD, cyanosis, aortic cross-clamp time, haemodilution, neurological risk time interval and rewarming rate. Temperature nadir and neurological risk time interval were significant independent predictors of a GFAP value > 0.46 ng/ml. Conclusions: Hypothermia degree during CPB is correlated with GFAP plasma increase in children with biventricular heart defects undergoing surgical repair. Rewarming is the most critical CPB phase for GFAP increase. The implication of high plasma GFAP is still under evaluation. Follow-up studies are ongoing to assess the reliability of GFAP as a marker of brain injury and/or as a predictor of neurodevelopmental abnormalities.