Sample records for hypothermia induced

  1. Role of neurotensin in radiation-induced hypothermia in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kandasamy, S.B.; Hunt, W.A.; Harris, A.H.

    1991-05-01

    The role of neurotensin in radiation-induced hypothermia was examined. Intracerebroventricular (ICV) administration of neurotensin produced dose-dependent hypothermia. Histamine appears to mediate neurotensin-induced hypothermia because the mast cell stabilizer disodium cromoglycate and antihistamines blocked the hypothermic effects of neurotensin. An ICV pretreatment with neurotensin antibody attenuated neurotensin-induced hypothermia, but did not attenuate radiation-induced hypothermia, suggesting that radiation-induced hypothermia was not mediated by neurotensin.

  2. Experience with prolonged induced hypothermia in severe head injury

    PubMed Central

    Bernard, Stephen A; MacC Jones, Bruce; Buist, Michael

    1999-01-01

    Background: Recent prospective controlled trials of induced moderate hypothermia (32⌓34°C) for relatively short periods (24⌓48 h) in patients with severe head injury have suggested improvement in intracranial pressure control and outcome. It is possible that increased benefit might be achieved if hypothermia was maintained for more periods longer than 48 h, but there is little in the literature on the effects of prolonged moderate hypothermia in adults with severe head injury. We used moderate induced hypothermia (30⌓33°C) in 43 patients with severe head injury for prolonged periods (mean 8 days, range 2⌓19 days). Results: Although nosocomial pneumonia (defined in this study as both new chest radiograph changes and culture of a respiratory pathogen from tracheal aspirate) was quite common (45%), death from sepsis was rare (5%). Other findings included hypokalaemia on induction of hypothermia and a decreasing total white cell and platelet count over 10 days. There were no major cardiac arrhythmias. There was a satisfactory neurological outcome in 20 out of 43 patients (47%). Conclusion: Moderate hypothermia may be induced for more prolonged periods, and is a relatively safe and feasible therapeutic option in the treatment of selected patients with severe traumatic brain injury. Thus, further prospective controlled trials using induced hypothermia for longer periods than 48 h are warranted. PMID:11056742

  3. Induced Hypothermia Does Not Harm Hemodynamics after Polytrauma: A Porcine Model

    PubMed Central

    Mommsen, Philipp; Pfeifer, Roman; Mohr, Juliane; Ruchholtz, Steffen; Flohé, Sascha; Fröhlich, Matthias; Keibl, Claudia; Seekamp, Andreas; Witte, Ingo

    2015-01-01

    Background. The deterioration of hemodynamics instantly endangers the patients' life after polytrauma. As accidental hypothermia frequently occurs in polytrauma, therapeutic hypothermia still displays an ambivalent role as the impact on the cardiopulmonary function is not yet fully understood. Methods. We have previously established a porcine polytrauma model including blunt chest trauma, penetrating abdominal trauma, and hemorrhagic shock. Therapeutic hypothermia (34°C) was induced for 3 hours. We documented cardiovascular parameters and basic respiratory parameters. Pigs were euthanized after 15.5 hours. Results. Our polytrauma porcine model displayed sufficient trauma impact. Resuscitation showed adequate restoration of hemodynamics. Induced hypothermia had neither harmful nor major positive effects on the animals' hemodynamics. Though heart rate significantly decreased and mixed venous oxygen saturation significantly increased during therapeutic hypothermia. Mean arterial blood pressure, central venous pressure, pulmonary arterial pressure, and wedge pressure showed no significant differences comparing normothermic trauma and hypothermic trauma pigs during hypothermia. Conclusions. Induced hypothermia after polytrauma is feasible. No major harmful effects on hemodynamics were observed. Therapeutic hypothermia revealed hints for tissue protective impact. But the chosen length for therapeutic hypothermia was too short. Nevertheless, therapeutic hypothermia might be a useful tool for intensive care after polytrauma. Future studies should extend therapeutic hypothermia. PMID:26170533

  4. Inducing Therapeutic Hypothermia in Cardiac Arrest Caused by Lightning Strike.

    PubMed

    Scantling, Dane; Frank, Brian; Pontell, Mathew E; Medinilla, Sandra

    2016-09-01

    Only limited clinical scenarios are grounds for induction of therapeutic hypothermia. Its use in traumatic cardiac arrests, including those from lightning strikes, is not well studied. Nonshockable cardiac arrest rhythms have only recently been included in resuscitation guidelines. We report a case of full neurological recovery with therapeutic hypothermia after a lightning-induced pulseless electrical activity cardiac arrest in an 18-year-old woman. We also review the important pathophysiology of lightning-induced cardiac arrest and neurologic sequelae, elaborate upon the mechanism of therapeutic hypothermia, and add case-based evidence in favor of the use of targeted temperature management in lightning-induced cardiac arrest. Copyright © 2016 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  5. Alpha-lipoic acid protects mitochondrial enzymes and attenuates lipopolysaccharide-induced hypothermia in mice

    EPA Science Inventory

    Abstract: Hypothermia is a key symptom of sepsis and the mechanism(s) leading to hypothermia during sepsis is largely unknown. To investigate a potential mechanism and find an effective treatment for hypothermia in sepsis, we induced hypothermia in mice by lipopolysaccharide (LP...

  6. Hypothermia can reverse hepatic oxidative stress damage induced by hypoxia in rats.

    PubMed

    Garnacho-Castaño, Manuel Vicente; Alva, Norma; Sánchez-Nuño, Sergio; Bardallo, Raquel G; Palomeque, Jesús; Carbonell, Teresa

    2016-12-01

    Our previous findings demonstrated that hypothermia enhances the reduction potential in the liver and helps to maintain the plasmatic antioxidant pool. Here, we aimed to elucidate if hypothermia protects against hypoxia-induced oxidative stress damage in rat liver. Several hepatic markers of oxidative stress were compared in three groups of animals (n = 8 in each group): control normothermic group ventilated with room air and two groups under extreme hypoxia (breathing 10 % O 2 ), one kept at normothermia (HN) (37 °C) and the other under deep hypothermia (HH) (central body temperature of 21-22 °C). Hypoxia in normothermia significantly increased the levels of hepatic nitric oxide, inducible nitric oxide synthase expression, protein oxidation, Carbonilated proteins, advanced oxidation protein products, 4-hydroxynonenal (HNE) protein adducts, and lipid peroxidation when compared to the control group (p < 0.05). However, when hypoxia was induced under hypothermia, results from the oxidative stress biomarker analyses did not differ significantly from those found in the control group. Indeed, 4-HNE protein adduct amounts were significantly lower in the HH versus HN group (p < 0.05). Therefore, hypothermia can mitigate hypoxia-induced oxidative stress damage in rat liver. These effects could help clarify the mechanisms of action of therapeutic hypothermia.

  7. FGF21 is dispensable for hypothermia induced by fasting in mice.

    PubMed

    Oishi, Katsutaka; Sakamoto, Katsuhiko; Konishi, Morichika; Murata, Yusuke; Itoh, Nobuyuki; Sei, Hiroyoshi

    2010-01-01

    Fibroblast growth factor 21 (FGF21) is a key metabolic regulator that is induced by peroxisome proliferator-activated receptor alpha (PPARalpha) activation in response to fasting. We recently reported that bezafibrate, a pan-agonist of PPARs, decreases body temperature late at night through hypothalamic neuropeptide Y (NPY) activation and others have shown that mice overexpressing FGF21 are prone to torpor. We examined whether FGF21 is essential for fasting-induced hypothermia using FGF21 knockout (KO) mice. Acute fasting decreased body temperature late at night accompanied by the induction of hepatic FGF21 and hypothalamic NPY expression in wild-type mice. A deficiency of FGF21 affected neither fasting-induced hypothermia nor hypothalamic NPY induction. Fasting enhanced locomotor activity in both genotypes. On the other hand, a deficiency of FGF21 significantly attenuated chronic hypothermia and hypoactivity induced by a ketogenic diet (KD). Our findings suggest that FGF21 is not essential for the hypothermia that is associated with the early stages of fasting, although it might be involved in the adaptive response of body temperature to chronic starvation.

  8. Neuroprotective Effects of Drug-Induced Therapeutic Hypothermia in Central Nervous System Diseases.

    PubMed

    Ma, Junwei; Wang, Yibin; Wang, Zhong; Li, Haiying; Wang, Zhimin; Chen, Gang

    2017-01-01

    This review article focuses on the neuroprotective effect of drug-induced hypothermia in cerebrovascular diseases and discusses its related side effects. A systematic literature search was performed using Pubmed and Embase electronic databases for a retrospective analysis. Experimental studies have shown that drug-induced hypothermia alleviates brain damage and plays a neuroprotective role, thereby reducing mortality and ameliorating neurological deficits. Therefore, drug-induced hypothermia has an important research value and is worth further consideration in the clinical setting. However, drug-induced hypothermia is also associated with side effects, such as ventricular tachycardia, ventricular fibrillation, suppressed immune function, infection, electrolyte imbalance, glucose metabolism disorders, and skeletal muscle tremor. Existing drugs with cooling effects belong to the following categories: (1) dopamine receptor agonists; (2) cannabis; (3) opioid receptors; (4) vanilloid receptors; (5) vasopressins (potent neurotensin receptor agonists); (6) thyroid drugs; (7) adenosine drugs; and (8) purine drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Method for inducing hypothermia

    DOEpatents

    Becker, Lance B.; Hoek, Terry Vanden; Kasza, Kenneth E.

    2003-04-15

    Systems for phase-change particulate slurry cooling equipment and methods to induce hypothermia in a patient through internal and external cooling are provided. Subcutaneous, intravascular, intraperitoneal, gastrointestinal, and lung methods of cooling are carried out using saline ice slurries or other phase-change slurries compatible with human tissue. Perfluorocarbon slurries or other slurry types compatible with human tissue are used for pulmonary cooling. And traditional external cooling methods are improved by utilizing phase-change slurry materials in cooling caps and torso blankets.

  10. Method for inducing hypothermia

    DOEpatents

    Becker, Lance B [Chicago, IL; Hoek, Terry Vanden [Chicago, IL; Kasza, Kenneth E [Palos Park, IL

    2008-09-09

    Systems for phase-change particulate slurry cooling equipment and methods to induce hypothermia in a patient through internal and external cooling are provided. Subcutaneous, intravascular, intraperitoneal, gastrointestinal, and lung methods of cooling are carried out using saline ice slurries or other phase-change slurries compatible with human tissue. Perfluorocarbon slurries or other slurry types compatible with human tissue are used for pulmonary cooling. And traditional external cooling methods are improved by utilizing phase-change slurry materials in cooling caps and torso blankets.

  11. Method for inducing hypothermia

    DOEpatents

    Becker, Lance B.; Hoek, Terry Vanden; Kasza, Kenneth E.

    2005-11-08

    Systems for phase-change particulate slurry cooling equipment and methods to induce hypothermia in a patient through internal and external cooling are provided. Subcutaneous, intravascular, intraperitoneal, gastrointestinal, and lung methods of cooling are carried out using saline ice slurries or other phase-change slurries compatible with human tissue. Perfluorocarbon slurries or other slurry types compatible with human tissue are used for pulmonary cooling. And traditional external cooling methods are improved by utilizing phase-change slurry materials in cooling caps and torso blankets.

  12. Coagulopathy induced by acidosis, hypothermia and hypocalcaemia in severe bleeding.

    PubMed

    De Robertis, E; Kozek-Langenecker, S A; Tufano, R; Romano, G M; Piazza, O; Zito Marinosci, G

    2015-01-01

    Acidosis, hypothermia and hypocalcaemia are determinants for morbidity and mortality during massive hemorrhages. However, precise pathological mechanisms of these environmental factors and their potential additive or synergistic anticoagulant and/or antiplatelet effects are not fully elucidated and are at least in part controversial. Best available evidences from experimental trials indicate that acidosis and hypothermia progressively impair platelet aggregability and clot formation. Considering the cell-based model of coagulation physiology, hypothermia predominantly prolongs the initiation phase, while acidosis prolongs the propagation phase of thrombin generation. Acidosis increases fibrinogen breakdown while hypothermia impairs its synthesis. Acidosis and hypothermia have additive effects. The effect of hypocalcaemia on coagulopathy is less investigated but it appears that below the cut-off of 0.9 mmol/L, several enzymatic steps in the plasmatic coagulation system are blocked while above that cut-off effects remain without clinical sequalae. The impact of environmental factor on hemostasis is underestimated in clinical practice due to our current practice of using routine coagulation laboratory tests such as partial thromboplastin time or prothrombin time, which are performed at standardized test temperature, after pH correction, and upon recalcification. Temperature-adjustments are feasible in viscoelastic point-of-care tests such as thrombelastography and thromboelastometry which may permit quantification of hypothermia-induced coagulopathy. Rewarming hypothermic bleeding patients is highly recommended because it improves patient outcome. Despite the absence of high-quality evidence, calcium supplementation is clinical routine in bleeding management. Buffer administration may not reverse acidosis-induced coagulopathy but may be essential for the efficacy of coagulation factor concentrates such as recombinant activated factor VII.

  13. Differential Expression of Ethanol-Induced Hypothermia in Adolescent and Adult Rats Induced by Pretest Familiarization to the Handling/Injection Procedure

    PubMed Central

    Ristuccia, Robert C.; Hernandez, Michael; Wilmouth, Carrie E.; Spear, Linda P.

    2007-01-01

    Background Previous work examining ethanol’s autonomic effects has found contrasting patterns of age-related differences in ethanol-induced hypothermia between adolescent and adult rats. Most studies have found adolescents to be less sensitive than adults to this effect, although other work has indicated that adolescents may be more sensitive than adults under certain testing conditions. To test the hypothesis that adolescents show more ethanol hypothermia than adults when the amount of disruption induced by the test procedures is low, but less hypothermia when the experimental perturbation is greater, the present study examined the consequences of manipulating the amount of perturbation at the time of testing on ethanol-induced hypothermia in adolescent and adult rats. Methods The amount of test disruption was manipulated by administering ethanol through a chronically indwelling gastric cannula (low perturbation) versus via intragastric intubation (higher perturbation) in Experiment 1 or by either familiarizing animals to the handling and injection procedure for several days pretest or leaving them unmanipulated before testing in Experiment 2. Results The results showed that the handling manipulation, but not the use of gastric cannulae, altered the expression of ethanol-induced hypothermia differentially across age. When using a familiarization protocol sufficient to reduce the corticosterone response to the handling and injection procedure associated with testing, adolescents showed greater hypothermia than adults. In contrast, the opposite pattern of age differences in hypothermia was evident in animals that were not manipulated before the test day. Surprisingly, however, this difference across testing circumstances was driven by a marked reduction in hypothermia among adults who had been handled before testing, with handling having relatively little impact on ethanol hypothermia among adolescents. Conclusions Observed differences between adolescents and

  14. Differential expression of ethanol-induced hypothermia in adolescent and adult rats induced by pretest familiarization to the handling/injection procedure.

    PubMed

    Ristuccia, Robert C; Hernandez, Michael; Wilmouth, Carrie E; Spear, Linda P

    2007-04-01

    Previous work examining ethanol's autonomic effects has found contrasting patterns of age-related differences in ethanol-induced hypothermia between adolescent and adult rats. Most studies have found adolescents to be less sensitive than adults to this effect, although other work has indicated that adolescents may be more sensitive than adults under certain testing conditions. To test the hypothesis that adolescents show more ethanol hypothermia than adults when the amount of disruption induced by the test procedures is low, but less hypothermia when the experimental perturbation is greater, the present study examined the consequences of manipulating the amount of perturbation at the time of testing on ethanol-induced hypothermia in adolescent and adult rats. The amount of test disruption was manipulated by administering ethanol through a chronically indwelling gastric cannula (low perturbation) versus via intragastric intubation (higher perturbation) in Experiment 1 or by either familiarizing animals to the handling and injection procedure for several days pretest or leaving them unmanipulated before testing in Experiment 2. The results showed that the handling manipulation, but not the use of gastric cannulae, altered the expression of ethanol-induced hypothermia differentially across age. When using a familiarization protocol sufficient to reduce the corticosterone response to the handling and injection procedure associated with testing, adolescents showed greater hypothermia than adults. In contrast, the opposite pattern of age differences in hypothermia was evident in animals that were not manipulated before the test day. Surprisingly, however, this difference across testing circumstances was driven by a marked reduction in hypothermia among adults who had been handled before testing, with handling having relatively little impact on ethanol hypothermia among adolescents. Observed differences between adolescents and adults in the autonomic consequences of

  15. The thermoregulatory mechanism of melatonin-induced hypothermia in chicken.

    PubMed

    Rozenboim, I; Miara, L; Wolfenson, D

    1998-01-01

    The involvement of melatonin (Mel) in body temperature (Tb) regulation was studied in White Leghorn layers. In experiment 1, 35 hens were injected intraperitoneally with seven doses of Mel (0, 5, 10, 20, 40, 80, or 160 mg Mel/kg body wt) dissolved in ethanol. Within 1 h, Mel had caused a dose-dependent reduction in Tb. To eliminate a possible vehicle effect, 0, 80, and 160 mg/kg body wt Mel dissolved in N-methyl-2-pyrrolidone (NMP) was injected. NMP had no effect on Tb, with Mel again causing a dose-dependent hypothermia. In experiment 2 (n = 30), Mel injected before exposure of layers to heat reduced Tb and prevented heat-induced hyperthermia. Injection after heat stress had begun did not prevent hyperthermia. Under cold stress, Mel induced hypothermia, which was not observed in controls. In experiment 3 (n = 12), Mel injection reduced Tb and increased metatarsal and comb temperatures (but not feathered-skin temperature), respiratory rate, and evaporative water loss. Heart rate rose and then declined, and blood pressure increased 1 h after Mel injection. Heat production rose slightly during the first hour, then decreased in parallel to the Tb decline. We conclude that pharmacological doses of Mel induce hypothermia in hens by increasing nonevaporative skin heat losses and slightly increasing respiratory evaporation.

  16. Under-humidification and over-humidification during moderate induced hypothermia with usual devices.

    PubMed

    Lellouche, François; Qader, Siham; Taille, Solenne; Lyazidi, Aissam; Brochard, Laurent

    2006-07-01

    In mechanically ventilated patients with induced hypothermia, the efficacy of heat and moisture exchangers and heated humidifiers to adequately humidify the airway is poorly known. The aim of the study was to assess the efficacy of different humidification devices during moderate hypothermia. Prospective, cross-over randomized study. Medical Intensive Care Unit in a University Hospital. Nine adult patients hospitalized after cardiac arrest in whom moderate hypothermia was induced (33 degrees C for 24[Symbol: see text]h). Patients were ventilated at admission (period designated "normothermia") with a heat and moisture exchanger, and were randomly ventilated during hypothermia with a heat and moisture exchanger, a heated humidifier, and an active heat and moisture exchanger. Core temperature, inspired and expired gas absolute and relative humidity were measured. Each system demonstrated limitations in its ability to humidify gases in the specific situation of hypothermia. Performances of heat and moisture exchangers were closely correlated to core temperature (r (2)[Symbol: see text]=[Symbol: see text]0.84). During hypothermia, heat and moisture exchangers led to major under-humidification, with absolute humidity below 25[Symbol: see text]mgH(2)O/l. The active heat and moisture exchanger slightly improved humidification. Heated humidifiers were mostly adequate but led to over-humidification in some patients, with inspiratory absolute humidity higher than maximal water content at 33 degrees C with a positive balance between inspiratory and expiratory water content. These results suggest that in the case of moderate hypothermia, heat and moisture exchangers should be used cautiously and that heated humidifiers may lead to over-humidification with the currently recommended settings.

  17. Induced hypothermia reduces the hepatic inflammatory response in a swine multiple trauma model.

    PubMed

    Fröhlich, Matthias; Hildebrand, Frank; Weuster, Matthias; Mommsen, Philipp; Mohr, Juliane; Witte, Ingo; Raeven, Pierre; Ruchholtz, Steffen; Flohé, Sascha; van Griensven, Martijn; Pape, Hans-Christoph; Pfeifer, Roman

    2014-06-01

    Mild therapeutic hypothermia following trauma has been introduced in several studies to reduce the posttraumatic inflammation and organ injury. In this study, we analyzed the effects of induced mild hypothermia (34°C) on the inflammation of the shock organs liver and kidney. In a porcine model of multiple trauma including blunt chest trauma, liver laceration, and hemorrhagic shock followed by fluid resuscitation, the influence of induced hypothermia on hepatic and renal damage and organ-specific inflammation were evaluated. A total of 40 pigs were randomly assigned to four groups, which were sham (anesthesia only) or trauma groups receiving either hypothermia or normothermia. The parameters analyzed were laboratory parameters (aspartate transaminase [AST], lactate dehydrogenase, urea, creatinine) as well as hepatic and renal cytokine expression determined by real-time polymerase chain reaction (interleukin 6 [IL-6], IL-8). Blinded analysis of histologic changes in the liver and kidney was performed. Fifteen and a half hours following combined trauma, hepatic cytokine expression and liver damage were significantly increased in animals with normothermia compared with the respective sham group. Hypothermia, however, resulted in a fivefold reduced hepatic expression of IL-8 (mean ± SE, 2.4 ± 1.3; p = 0.01) when compared with the normothermic trauma group (IL-8, 12.8 ± 4.7). Accordingly, granulocyte infiltration and a histologic, semiquantitative score for liver injury were significantly higher in the normothermic trauma group. Serum AST levels raised significantly after trauma and normothermia compared with the respective sham group, while AST levels showed no difference from the sham groups in the hypothermic trauma group. In contrast, neither trauma nor hypothermia influenced the expression of IL-6 and IL-8 and tissue injury in the kidney. Therapeutic hypothermia seems to attenuate the hepatic inflammatory response and the associated liver injury after severe

  18. Helium-cold induced hypothermia in the white rat.

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Jacobs, M.

    1973-01-01

    Hypothermia was induced in white rats by exposing them to low ambient temperatures (about 0 C) and a gaseous atmosphere of 80% helium and 20% oxygen (helox). Biological survival, in which revival from hypothermia to normothermia is achieved, and clinical survival, in which one or more functional attributes are monitored in the hypothermic animal until it dies, are examined. The helium-cold method appears to produce a hypothermic state in the rat quite similar to that resulting from such techniques as ice water immersion or hypercapnia + hypoxia. There is a direct relationship between body weight and percent survival. Despite the fact that they require a longer period to become hypothermic, the heavier animals are better able to survive.

  19. Hypothermia induced by adenosine 5'-monophosphate attenuates injury in an L-arginine-induced acute pancreatitis rat model.

    PubMed

    Wang, Yunlong; Guo, Weiting; Li, Yuan; Pan, Xinting; Lv, Wenshan; Cui, Lingling; Li, Changgui; Wang, Yangang; Yan, Shengli; Zhang, Jidong; Liu, Bin

    2014-04-01

    This study sought to investigate the effects of hypothermia induced by adenosine 5'-monophosphate (5'-AMP) on L-arginine (L-Arg)-induced acute pancreatitis in rats. The rats were divided into four groups: the control group, the acute pancreatitis group, the 5'-AMP pretreatment group, and the 5'-AMP posttreatment group. Rats in all groups, except for the control group, received two injections of 2.5 g/kg body weight (intraperitoneally) L-Arg, with an interval of 1 h between the injections. Subsequently, the rats were observed to assess whether hypothermia induced by 5'-AMP could effectively inhibit inflammation associated with L-Arg-induced acute pancreatitis in rats. Hypothermia induced by 5'-AMP produced protective effects in our acute pancreatitis model. These effects exhibited the following manifestations: (i) a significant reduction in rat mortality rates; (ii) a significant decrease in the occurrence of pancreatic edema; (iii) significant reductions in serum amylase (P < 0.001), interleukin-6 (P < 0.001), interleukin-1β (P < 0.001) and tumor necrosis factor-α (P < 0.001); (iv) the significant inhibition of nuclear factor-κB (NF-κB) activation in rats that were pre- and posttreated with 5'-AMP compared with rats that were only injected with L-Arg; and (v) significant decreases in the occurrence of pancreatic interstitial edema, inflammatory cell infiltration, hemorrhage, and acinar cell necrosis. Hypothermia induced by 5'-AMP could inhibit the acute inflammatory reaction and NF-κB activation associated with acute pancreatitis. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  20. The effects of mild hypothermia on thiopental-induced electroencephalogram burst suppression.

    PubMed

    Kim, J H; Kim, S H; Yoo, S K; Kim, J Y; Nam, Y T

    1998-07-01

    Thiopental intravenous injections before temporary clipping and mild hypothermia have protective effects in the setting of cerebral ischemia, and are used clinically in some centers. However, it is not known whether mild hypothermia affects thiopental-induced electroencephalogram (EEG) burst suppression. In this study, the authors compared the onset and duration of EEG suppression by thiopental in normothermic (n=10) and mildly hypothermic (n=10) patients undergoing cerebral aneurysm surgery. Spectral analysis was used to compare the prethiopentonal continuous EEG patterns in normothermic and mild hypothermic patients. The patients' body temperatures were controlled by a circulating water mattress and intravenous fluids (normothermia = 36.4+/-0.1 degrees C, mild hypothermia = 33.3+/-0.1 degrees C). Immediately before temporary clipping, thiopental sodium (5 mg/kg) was administered intravenously. Onset time (the amount of time from thiopental injection to the first complete EEG suppression), duration of suppression (the amount of time from the first complete EEG suppression to recovery on continuous EEG from burst suppression), and maximum duration of isoelectric EEG (the longest time interval between two bursts during burst suppression) were measured. Onset time was shortened (25.8+/-1.4 versus 43.5+/-5.6 seconds), and duration of suppression (531.0+/-56.6 versus 165.0+/-16.9 seconds) and the maximum duration of isoelectric EEG (47.7+/-5.8 versus 22.8+/-2.0 seconds) were prolonged in the patients with mild hypothermia. In two normothermic patients, the standard dose of thiopental did not produce burst suppression, but only a mild decrease in spectral edge frequency. The authors concluded that the effects of mild hypothermia on thiopental-induced EEG suppression are not simply additive, but synergistic.

  1. Induced hypothermia does not impair coagulation system in a swine multiple trauma model.

    PubMed

    Mohr, Juliane; Ruchholtz, Steffen; Hildebrand, Frank; Flohé, Sascha; Frink, Michael; Witte, Ingo; Weuster, Matthias; Fröhlich, Matthias; van Griensven, Martijn; Keibl, Claudia; Mommsen, Philipp

    2013-04-01

    Accidental hypothermia, acidosis, and coagulopathy represent the lethal triad in severely injured patients. Therapeutic hypothermia however is commonly used in transplantations, cardiac and neurosurgical surgery, or after cardiac arrest. However, the effects of therapeutic hypothermia on the coagulation system following multiple trauma need to be elucidated. In a porcine model of multiple trauma including blunt chest injury, liver laceration, and hemorrhagic shock followed by fluid resuscitation, the influence of therapeutic hypothermia on coagulation was evaluated. A total of 40 pigs were randomly assigned to sham (only anesthesia) or trauma groups receiving either hypothermia or normothermia. Each group consisted of 10 pigs. Analyzed parameters were cell count (red blood cells, platelets), pH, prothrombin time (PT), fibrinogen concentration, and analysis with ROTEM and Multiplate. Trauma and consecutive fluid resuscitation resulted in impaired coagulation parameters (cell count, pH, PT, fibrinogen, ROTEM, and platelet function). During hypothermia, coagulation parameters measured at 37°C, such as PT, fibrinogen, thrombelastometry measurements, and platelet function, showed no significant differences between normothermic and hypothermic animals in both trauma groups. Additional analyses of thrombelastometry at 34°C during hypothermia showed significant differences for clotting time and clot formation time but not for maximum clot firmness. We were not able to detect macroscopic or petechial bleeding in both trauma groups. Based on the results of the present study we suggest that mild hypothermia can be safely performed after stabilization following major trauma. Mild hypothermia has effects on the coagulation system but does not aggravate trauma-induced coagulopathy in our model. Before hypothermic treatment can be performed in the clinical setting, additional experiments with prolonged and deeper hypothermia to exclude detrimental effects are required.

  2. Cold Shock Induced Protein RBM3 but Not Mild Hypothermia Protects Human SH-SY5Y Neuroblastoma Cells From MPP+-Induced Neurotoxicity.

    PubMed

    Yang, Hai-Jie; Shi, Xiang; Ju, Fei; Hao, Bei-Ning; Ma, Shuang-Ping; Wang, Lei; Cheng, Bin-Feng; Wang, Mian

    2018-01-01

    The cold shock protein RBM3 can mediate mild hypothermia-related protection in neurodegeneration such as Alzheimer's disease. However, it remains unclear whether RBM3 and mild hypothermia provide same protection in model of Parkinson's disease (PD), the second most common neurodegenerative disorder. In this study, human SH-SY5Y neuroblastoma cells subjected to insult by 1-methyl-4-phenylpyridinium (MPP + ) served as an in-vitro model of PD. Mild hypothermia (32°C) aggravated MPP + -induced apoptosis, which was boosted when RBM3 was silenced by siRNA. In contrast, overexpression of RBM3 significantly reduced this apoptosis. MPP + treatment downregulated the expression of RBM3 both endogenously and exogenously and suppressed its induction by mild hypothermia (32°C). In conclusion, our data suggest that cold shock protein RBM3 provides neuroprotection in a cell model of PD, suggesting that RBM3 induction may be a suitable strategy for PD therapy. However, mild hypothermia exacerbates MPP + -induced apoptosis even that RBM3 could be synthesized during mild hypothermia.

  3. Physiological responses to hypothermia.

    PubMed

    Wood, Thomas; Thoresen, Marianne

    2015-04-01

    Therapeutic hypothermia is the only treatment currently recommended for moderate or severe encephalopathy of hypoxic‒ischaemic origin in term neonates. Though the effects of hypothermia on human physiology have been explored for many decades, much of the data comes from animal or adult studies; the latter originally after accidental hypothermia, followed by application of controlled hypothermia after cardiac arrest or trauma, or during cardiopulmonary bypass. Though this work is informative, the effects of hypothermia on neonatal physiology after perinatal asphyxia must be considered in the context of a prolonged hypoxic insult that has already induced a number of significant physiological sequelae. This article reviews the effects of therapeutic hypothermia on respiratory, cardiovascular, and metabolic parameters, including glycaemic control and feeding requirements. The potential pitfalls of blood‒gas analysis and overtreatment of physiological changes in cardiovascular parameters are also discussed. Finally, the effects of hypothermia on drug metabolism are covered, focusing on how the pharmacokinetics, pharmacodynamics, and dosing requirements of drugs frequently used in neonatal intensive care may change during therapeutic hypothermia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Accidental Hypothermia,

    DTIC Science & Technology

    1988-03-03

    on risk factors.329,538,539,303,93 Safe experimental investigations of hypothermia in hurman volunteers terminate cooling at 350C. This precludes...clinical experiments and surgically induced hypothermia. 423 a195 ,19 3 13 ,202 ,543 ,19 7 ,84 ,175 ,227 ,10 1,443 yward measured his own esophageal...the periphery and core. L9 For example, hypothermic patients experience major afterdrops when frostbitten extremities are thawed prematurely

  5. Mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury by improving lysosomal function and autophagic flux.

    PubMed

    Zhou, Tianen; Liang, Lian; Liang, Yanran; Yu, Tao; Zeng, Chaotao; Jiang, Longyuan

    2017-09-15

    Mild hypothermia has been proven to be useful to treat brain ischemia/reperfusion injury. However, the underlying mechanisms have not yet been fully elucidated. The present study was undertaken to determine whether mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion(OGD/R)-induced injury via improving lysosomal function and autophagic flux. The results showed that OGD/R induced the occurrence of autophagy, while the acidic environment inside the lysosomes was altered. The autophagic flux assay with RFP-GFP tf-LC3 was impeded in hippocampal neurons after OGD/R. Mild hypothermia recovered the lysosomal acidic fluorescence and the lysosomal marker protein expression of LAMP2, which decreased after OGD/R.Furthermore, we found that mild hypothermia up-regulated autophagic flux and promoted the fusion of autophagosomes and lysosomes in hippocampal neurons following OGD/R injury, but could be reversed by treatment with chloroquine, which acts as a lysosome inhibitor. We also found that mild hypothermia improved mitochondrial autophagy in hippocampal neurons following OGD/R injury. Finally,we found that chloroquine blocked the protective effects of mild hypothermia against OGD/R-induced cell death and injury. Taken together, the present study indicates that mild hypothermia protects hippocampal neurons against OGD/R-induced injury by improving lysosomal function and autophagic flux. Copyright © 2017. Published by Elsevier Inc.

  6. Effect of hypothermia on doxorubicin-induced cardiac myoblast signaling and cell death.

    PubMed

    L'Ecuyer, Thomas J; Aggarwal, Sanjeev; Zhang, Jiang Ping; Van der Heide, Richard S

    2012-01-01

    Anthracyclines (AC) are useful chemotherapeutic agents whose principal limitation is cardiac toxicity, which may progress to heart failure, transplantation or even death. We have shown that this toxicity involves oxidative stress-induced activation of the DNA damage pathway. Hypothermia has been shown to be protective against other diseases involving oxidative stress but has not been studied in models of AC toxicity. In the current experiments, H9C2 cardiac myoblasts were treated with varying concentrations of the AC doxorubicin (DOX) during normothermia (37°C) or mild hypothermia (35°C). Total cell death was assayed using trypan blue exclusion and apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine-biotin nick end labeling (TUNEL) staining. Oxidative stress was assayed using the fluorescent indicator 2'7'-dichlorofluorescein diacetate. DNA damage pathway activation was assayed by immunostaining for H2AX and p53. Mitochondrial membrane potential was assayed by JC-1 staining. At all concentrations of DOX examined (1, 2.5 and 5 μM), hypothermia reduced oxidative stress, activation of H2AX and p53, loss of mitochondrial membrane potential and total and apoptotic cell death (P=.001-.03 for each observation). The reduction of oxidative stress-induced activation of the DNA damage pathway and consequent cell death by mild hypothermia supports a possible protective role to reduce the clinical impact of DOX-induced cardiac toxicity. Such an approach may allow expanded use of these effective chemotherapeutic agents to increase cancer cure rates. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. 5'- Adenosine monophosphate induced hypothermia reduces early stage myocardial ischemia/reperfusion injury in a mouse model.

    PubMed

    Tao, Zhenyin; Zhao, Zhaoyang; Lee, Cheng Chi

    2011-08-15

    Early intervention using hypothermia treatment has been shown to reduce early inflammation, apoptosis and infarct size in animal models of cardiac ischemia/reperfusion. We have shown that 5'-adenosine monophosphate (5'-AMP) can induce a reversible deep hypothermia in mammals. We hypothesize that 5'-AMP-induced hypothermia (AIH) may reduce ischemic/reperfusion damage following myocardial infarct. C57BL/6J male mice were subjected to myocardial ischemia by ligating the left anterior descending coronary artery (LAD) followed by reperfusion. Compared to euthermic controls, mice given AIH treatment exhibited significant inhibition of neutrophil infiltration and a reduction in matrix metallopeptidase 9 (MMP-9) expressions in the infarcted myocardium. A decrease in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive nuclei in the left ventricle myocardium were also observed. The overall infarct size of the heart was significantly smaller in AIH treated mice. Myocardial ischemia in mice given 5'-AMP without hypothermia had similar ischemia/reperfusion injuries as the euthermic control. Thus, the AIH cardio-protective effects were primarily hypothermia based.

  8. Assessing the role of the medial preoptic area in ethanol-induced hypothermia.

    PubMed

    Westerman, Ashley T; Roma, Peter G; Price, Rebecca C; Dominguez, Juan M

    2010-05-07

    Administration of ethanol produces hypothermia. The preoptic area/anterior hypothalamus (POA/AH) contains warm- and cold-sensitive neurons that are important for temperature regulation. The present study evaluated the effect of ethanol on Fos immunoreactivity (Fos-ir) in the medial preoptic area (MPOA) and the effect of lesions to the MPOA on ethanol-induced hypothermia. Rats receiving 1.5-g/kg ethanol showed an increase in Fos-ir in the MPOA. However, lesions to the MPOA did not affect core body temperature. These findings indicate that ethanol increases neural activity in the MPOA, but this increased activity does not influence ethanol-induced changes in core body temperature. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  9. Effects of hypothermia and cerebral ischemia on cold-inducible RNA-binding protein mRNA expression in rat brain.

    PubMed

    Liu, Aijun; Zhang, Zhiwen; Li, Anmin; Xue, Jinghui

    2010-08-06

    CIRP (cold-inducible RNA-binding protein) mRNA is highly expressed in hypothermic conditions in mammalian cells, and the relationship between CIRP and neuroprotection for cerebral ischemia under hypothermia has been focused upon. At present, however, the expression characteristics of CIRP under hypothermia and cerebral ischemia in vivo are not clearly elucidated. In this study, CIRP mRNA expression in various regions of rat brain was examined by reverse transcriptase polymerase chain reaction (RT-PCR). CIRP expression levels were found to be similar in the hippocampus and cortex. Real-time quantitative PCR analysis revealed increasing CIRP mRNA expression in the cortex during the 24-h observation period following treatment with hypothermia or cerebral ischemia, with a greater increase in the hypothermia group. When cerebral ischemia was induced following hypothermia, CIRP mRNA expression in the cortex again showed a significant increasing tendency, but ischemia delayed the appearance of this increase. To reveal the relationship between CIRP and energy metabolism in the rat brain, lactate and pyruvate concentrations in the cortex of the rats treated with hypothermia, ischemia and ischemia after hypothermia were determined by spectrophotometric assay, and levels of phosphofructokinas-1 (PFK-1), the major regulatory enzyme of the glycolytic pathway, in the rat cortex in the three groups was also analyzed by Western blot. Using linear correlation, lactate and pyruvate concentrations, and PFK-1 levels, were each analyzed in the three groups in association with CIRP mRNA expression levels. The analysis did not reveal any correlation between the three metabolic parameters and CIRP mRNA expression induced by hypothermia, suggesting that while playing a role in neuroprotection under hypothermia, CIRP does not affect cerebral energy metabolism. Copyright 2010. Published by Elsevier B.V.

  10. [Hypothermia for intracranial hypertension].

    PubMed

    Bruder, N; Velly, L; Codaccioni, J-L

    2009-04-01

    There is a large body of experimental evidence showing benefits of deliberate mild hypothermia (33-35 degrees C) on the injured brain as well as an improvement of neurological outcome after cardiac arrest in humans. However, the clinical evidence of any benefit of hypothermia following stroke, brain trauma and neonatal asphyxia is still lacking. Controversial results have been published in patients with brain trauma or neonatal asphyxia. Hypothermia can reduce the elevation of intracranial pressure, through mechanisms not completely understood. Hypothermia-induced hypocapnia should have a role on the reduction of intracranial pressure. The temperature target is unknown but no additional benefit was found below 34 degrees C. The duration of deliberate hypothermia for the treatment of elevated intracranial pressure might be at least 48 hours, and the subsequent rewarming period must be very slow to prevent adverse effects.

  11. 5'-adenosine monophosphate-induced hypothermia attenuates brain ischemia/reperfusion injury in a rat model by inhibiting the inflammatory response.

    PubMed

    Miao, Yi-Feng; Wu, Hui; Yang, Shao-Feng; Dai, Jiong; Qiu, Yong-Ming; Tao, Zhen-Yi; Zhang, Xiao-Hua

    2015-01-01

    Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5'-adenosine monophosphate (5'-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5'-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5'-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia.

  12. Neuroprotective effects of hypothermia on synaptic actin cytoskeletal changes induced by perinatal asphyxia.

    PubMed

    Muñiz, Javier; Romero, Juan; Holubiec, Mariana; Barreto, George; González, Janneth; Saint-Martin, Madeleine; Blanco, Eduardo; Carlos Cavicchia, Juan; Castilla, Rocío; Capani, Francisco

    2014-05-14

    Cerebral hypoxia-ischemia damages synaptic proteins, resulting in cytoskeletal alterations, protein aggregation and neuronal death. In the previous works, we have shown neuronal and synaptic changes in rat neostriatum subjected to hypoxia that leads to ubi-protein accumulation. Recently, we also showed that, changes in F-actin organization could be related to early alterations induced by hypoxia in the Central Nervous System. However, little is known about effective treatment to diminish the damage. The main aim of this work is to study the effects of birth hypothermia on the actin cytoskeleton of neostriatal post-synaptic densities (PSD) in 60 days olds rats by immunohistochemistry, photooxidation and western blot. We used 2 different protocols of hypothermia: (a) intrahypoxic hypothermia at 15°C and (b) post-hypoxia hypothermia at 32°C. Consistent with previous data at 30 days, staining with phalloidin-Alexa(488) followed by confocal microscopy analysis showed an increase of F-actin fluorescent staining in the neostriatum of hypoxic animals. Correlative photooxidation electron microscopy confirmed these observations showing an increment in the number of mushroom-shaped F-actin staining spines in neostriatal excitatory synapses in rats subjected to hypoxia. In addition, western blot revealed β-actin increase in PSDs in hypoxic animals. The optic relative density measurement showed a significant difference between controls and hypoxic animals. When hypoxia was induced under hypothermic conditions, the changes observed in actin cytoskeleton were blocked. Post-hypoxic hypothermia showed similar answer but actin cytoskeleton modifications were not totally reverted as we observed at 15°C. These data suggest that the decrease of the body temperature decreases the actin modifications in dendritic spines preventing the neuronal death. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Involvement of α₂-adrenoceptors, imidazoline, and endothelin-A receptors in the effect of agmatine on morphine and oxycodone-induced hypothermia in mice.

    PubMed

    Bhalla, Shaifali; Andurkar, Shridhar V; Gulati, Anil

    2013-10-01

    Potentiation of opioid analgesia by endothelin-A (ET(A)) receptor antagonist, BMS182874, and imidazoline receptor/α₂-adrenoceptor agonists such as clonidine and agmatine are well known. It is also known that agmatine blocks morphine hyperthermia in rats. However, the effect of agmatine on morphine or oxycodone hypothermia in mice is unknown. The present study was carried out to study the role of α₂-adrenoceptors, imidazoline, and ET(A) receptors in morphine and oxycodone hypothermia in mice. Body temperature was determined over 6 h in male Swiss Webster mice treated with morphine, oxycodone, agmatine, and combination of agmatine with morphine or oxycodone. Yohimbine, idazoxan, and BMS182874 were used to determine involvement of α₂-adrenoceptors, imidazoline, and ET(A) receptors, respectively. Morphine and oxycodone produced significant hypothermia that was not affected by α₂-adrenoceptor antagonist yohimbine, imidazoline receptor/α₂ adrenoceptor antagonist idazoxan, or ET(A) receptor antagonist, BMS182874. Agmatine did not produce hypothermia; however, it blocked oxycodone but not morphine-induced hypothermia. Agmatine-induced blockade of oxycodone hypothermia was inhibited by idazoxan and yohimbine. The blockade by idazoxan was more pronounced compared with yohimbine. Combined administration of BMS182874 and agmatine did not produce changes in body temperature in mice. However, when BMS182874 was administered along with agmatine and oxycodone, it blocked agmatine-induced reversal of oxycodone hypothermia. This is the first report demonstrating that agmatine does not affect morphine hypothermia in mice, but reverses oxycodone hypothermia. Imidazoline receptors and α₂-adrenoceptors are involved in agmatine-induced reversal of oxycodone hypothermia. Our findings also suggest that ET(A) receptors may be involved in blockade of oxycodone hypothermia by agmatine. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de

  14. THE MUSCARINIC ANTAGONIST SCOPOLAMINE ATTENUATES CHLORPYRIFOS INDUCED HYPOTHERMIA IN THE DEVELOPING RAT.

    EPA Science Inventory

    Chlorpyrifos (CHP), an anticholinesterase organophosphate (OP) pesticide, induces acute hypothermia in adult and developing rats. Previously we demonstrated that thermoregulation in preweanling pups is markedly more sensitive to the neurotoxic effects of CHP than in adults. The c...

  15. Role of Neurotensin in Radiation-Induced Hypothermia in Rats

    DTIC Science & Technology

    1991-01-01

    radiation-in- appears to mediate neurotensin-induced hylothemnia becaus duced hypothermia and to elucidate the mechanisms in- th mas cell stabilizer...of neurotensin an- tibody alone had no effect on body temperature. An ICV administration of the mast cell stabilizer disodium cromo- 30 3 120glycate...David Kopf Instruments. No. 320) A single cannula was in- pear to be centrally mediated (4. 5). H- stamine has been serteil aseptically into the

  16. Cellular Mechanism Underlying Hypothermia-Induced VT/VF in the Setting of Early Repolarization and the Protective Effect of Quinidine, Cilostazol and Milrinone

    PubMed Central

    Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V.; Antzelevitch, Charles

    2014-01-01

    Background Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome (ERS) and examines the effectiveness of quinidine, cilostazol and milrinone to prevent hypothermia-induced arrhythmias. Method and Results Transmembrane action potentials (AP) were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left-ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3–10 µM) and verapamil (1µM) was used to pharmacologically model the genetic mutations responsible for ERS. Acetylcholine (3µM) was used to simulate increased parasympathetic tone, which is known to promote ER. In control, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J wave area on the ECG and accentuated epicardial AP notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial AP notch, leading to loss of the AP dome at some sites but not others, thus creating the substrate for development of phase-2-reentry and VT/VF. Addition of the Ito antagonist quinidine (5 µM) or the phosphodiesterase III inhibitors cilostazol (10 µM) or milrinone (5 µM), diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Conclusions Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase-2-reentry. Quinidine, cilostazol and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities. PMID:24429494

  17. Hypothalamic control of pituitary and adrenal hormones during hypothermia.

    PubMed

    Okuda, C; Miyazaki, M; Kuriyama, K

    1986-01-01

    In order to investigate neuroendocrinological mechanisms of hypothermia, we determined the changes in plasma concentrations of corticosterone (CS), prolactin (PRL), and thyrotropin (TSH), and their correlations with alterations in hypothalamic dopamine (DA) and thyrotropin releasing hormone (TRH), in rats restrained and immersed in a water bath at various temperatures. A graded decrease of body temperature induced a progressive increase in the plasma level of CS, whereas that of PRL showed a drastic decrease. The plasma level of TSH also showed an increase during mild hypothermia (about 35 degrees C), but this increase was not evident during profound hypothermia (below 24 degrees C). The changes in these hormones were readily reversed by rewarming animals. Although DA content in the hypothalamus was not affected, its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), showed an increase following the decrease of body temperature. Pretreatment of the animals with sulpiride, a D2-antagonist, prevented the hypothermia-induced inhibition of PRL release. Hypothalamic TRH was significantly decreased during mild hypothermia, and it returned to control levels after rewarming. These results suggest that the decrease in plasma PRL induced by hypothermia may be associated with the activation of hypothalamic DA neurons, whereas the increase in plasma TSH during mild hypothermia seems to be caused by the increased release of TRH in the hypothalamus.

  18. Cellular mechanism underlying hypothermia-induced ventricular tachycardia/ventricular fibrillation in the setting of early repolarization and the protective effect of quinidine, cilostazol, and milrinone.

    PubMed

    Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V; Antzelevitch, Charles

    2014-02-01

    Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome and examines the effectiveness of quinidine, cilostazol, and milrinone to prevent hypothermia-induced arrhythmias. Transmembrane action potentials were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3-10 μmol/L) and verapamil (1 μmol/L) was used to pharmacologically model the genetic mutations responsible for ER syndrome. Acetylcholine (3 μmol/L) was used to simulate increased parasympathetic tone, which is known to promote ER. In controls, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J-wave area on the ECG and accentuated epicardial action potential notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial action potential notch, leading to loss of the action potential dome at some sites but not others, thus creating the substrate for development of phase 2 reentry and VT/VF. Addition of the transient outward current antagonist quinidine (5 μmol/L) or the phosphodiesterase III inhibitors cilostazol (10 μmol/L) or milrinone (5 μmol/L) diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase 2 reentry. Quinidine, cilostazol, and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities.

  19. mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia

    PubMed Central

    Yang, Guo-Shuai; Zhou, Xiao-Yan; An, Xue-Fang; Liu, Xuan-Jun; Zhang, Yan-Jun; Yu, Dan

    2018-01-01

    Stroke is considered an underlying etiology of the development of seizures. Stroke leads to glucose and oxygen deficiency in neurons, resulting in brain dysfunction and injury. Mild hypothermia is a therapeutic strategy to inhibit stroke-induced seizures, which may be associated with the regulation of energy metabolism of the brain. Mammalian target of rapamycin (mTOR) signaling and solute carrier family 2, facilitated glucose transporter member (GLUT)-1 are critical for energy metabolism. Furthermore, mTOR overactivation and GLUT-1 deficiency are associated with genetically acquired seizures. It has been hypothesized that mTOR and GLUT-1 may additionally be involved in seizures elicited by stroke. The present study established global cerebral ischemia (GCI) models of rats. Convulsive seizure behaviors frequently occurred during the first and the second days following GCI, which were accompanied with seizure discharge reflected in the EEG monitor. Expression of phosphor (p)-mTOR and GLUT-1 were upregulated in the cerebral cortex and hippocampus, as evidenced by immunohistochemistry and western blot analyses. Mild hypothermia and/or rapamycin (mTOR inhibitor) treatments reduced the number of epileptic attacks, seizure severity scores and seizure discharges, thereby alleviating seizures induced by GCI. Mild hypothermia and/or rapamycin treatments reduced phosphorylation levels of mTOR and the downstream effecter p70S6 in neurons, and the amount of GLUT-1 in the cytomembrane of neurons. The present study revealed that mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia. The role of GLUT-1 in stroke-elicited seizures appears to be different from the role in seizures induced by other reasons. Further studies are necessary in order to elucidate the exact function of GLUT-1 in stroke-elicited seizures. PMID:29484389

  20. [Accidental hypothermia].

    PubMed

    Soteras Martínez, Iñigo; Subirats Bayego, Enric; Reisten, Oliver

    2011-07-09

    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. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  1. The Human Burst Suppression Electroencephalogram of Deep Hypothermia

    PubMed Central

    Kumaraswamy, Vishakhadatta M.; Akeju, Seun Oluwaseun; Pierce, Eric; Cash, Sydney S.; Kilbride, Ronan; Brown, Emery N.; Purdon, Patrick L.

    2015-01-01

    Objective Deep hypothermia induces ‘burst suppression’ (BS), an electroencephalogram pattern with low-voltage ‘suppressions’ alternating with high-voltage ‘bursts’. Current understanding of BS comes mainly from anesthesia studies, while hypothermia-induced BS has received little study. We set out to investigate the electroencephalogram changes induced by cooling the human brain through increasing depths of BS through isoelectricity. Methods We recorded scalp electroencephalograms from eleven patients undergoing deep hypothermia during cardiac surgery with complete circulatory arrest, and analyzed these using methods of spectral analysis. Results Within patients, the depth of BS systematically depends on the depth of hypothermia, though responses vary between patients except at temperature extremes. With decreasing temperature, burst lengths increase, and burst amplitudes and lengths decrease, while the spectral content of bursts remains constant. Conclusions These findings support an existing theoretical model in which the common mechanism of burst suppression across diverse etiologies is the cyclical diffuse depletion of metabolic resources, and suggest the new hypothesis of local micro-network dropout to explain decreasing burst amplitudes at lower temperatures. Significance These results pave the way for accurate noninvasive tracking of brain metabolic state during surgical procedures under deep hypothermia, and suggest new testable predictions about the network mechanisms underlying burst suppression. PMID:25649968

  2. The human burst suppression electroencephalogram of deep hypothermia.

    PubMed

    Westover, M Brandon; Ching, Shinung; Kumaraswamy, Vishakhadatta M; Akeju, Seun Oluwaseun; Pierce, Eric; Cash, Sydney S; Kilbride, Ronan; Brown, Emery N; Purdon, Patrick L

    2015-10-01

    Deep hypothermia induces 'burst suppression' (BS), an electroencephalogram pattern with low-voltage 'suppressions' alternating with high-voltage 'bursts'. Current understanding of BS comes mainly from anesthesia studies, while hypothermia-induced BS has received little study. We set out to investigate the electroencephalogram changes induced by cooling the human brain through increasing depths of BS through isoelectricity. We recorded scalp electroencephalograms from eleven patients undergoing deep hypothermia during cardiac surgery with complete circulatory arrest, and analyzed these using methods of spectral analysis. Within patients, the depth of BS systematically depends on the depth of hypothermia, though responses vary between patients except at temperature extremes. With decreasing temperature, burst lengths increase, and burst amplitudes and lengths decrease, while the spectral content of bursts remains constant. These findings support an existing theoretical model in which the common mechanism of burst suppression across diverse etiologies is the cyclical diffuse depletion of metabolic resources, and suggest the new hypothesis of local micro-network dropout to explain decreasing burst amplitudes at lower temperatures. These results pave the way for accurate noninvasive tracking of brain metabolic state during surgical procedures under deep hypothermia, and suggest new testable predictions about the network mechanisms underlying burst suppression. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Hypothermia Inhibits Endothelium-Independent Vascular Contractility via Rho-kinase Inhibition

    PubMed Central

    Chung, Yoon Hee; Oh, Keon Woong; Kim, Sung Tae; Park, Eon Sub; Je, Hyun Dong; Yoon, Hyuk-Jun; Sohn, Uy Dong; Jeong, Ji Hoon; La, Hyen-Oh

    2018-01-01

    The present study was undertaken to investigate the influence of hypothermia on endothelium-independent vascular smooth muscle contractility and to determine the mechanism underlying the relaxation. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Hypothermia significantly inhibited fluoride-, thromboxane A2-, phenylephrine-, and phorbol ester-induced vascular contractions regardless of endothelial nitric oxide synthesis, suggesting that another pathway had a direct effect on vascular smooth muscle. Hypothermia significantly inhibited the fluoride-induced increase in pMYPT1 level and phorbol ester-induced increase in pERK1/2 level, suggesting inhibition of Rho-kinase and MEK activity and subsequent phosphorylation of MYPT1 and ERK1/2. These results suggest that the relaxing effect of moderate hypothermia on agonist-induced vascular contraction regardless of endothelial function involves inhibition of Rho-kinase and MEK activities. PMID:28208012

  4. [Role of oxotremorine in arginine vasopressin-induced hypothermia and its effects on behavioral thermoregulatory response in rats].

    PubMed

    Shen, Zi-Ling; Yang, Yong-Lu; Sun, Bing; Tang, Yu; Wang, Nian

    2012-03-01

    To investigate the role of oxotremorine in arginine vasopressin (AVP)-induced hypothermia and its effects on the behavioral thermoregulatory response. Core temperature (Tc), brown adipose tissue (BAT) temperature and motor activities were monitored in undisturbed female SD rats using radiotelemetry. The behavioral thermoregulatory response was monitored in rats using radiotelemetric temperature gradient apparatus. Effect of AVP (10 microg/kg) and oxotremorine (0.25 mg/kg) on Tc, motor activities, BAT temperature (T(BAT)), grooming activities and the behavioral thermoregulatory response were observed in rats. Administration of AVP and oxotremorine caused a significant drop in Tc, T(BAT), and an increases in grooming activities, respectively. The hypothermic responses were accompanied with a preference for cooler ambient temperature. Oxotremorine augmented the reduction of Tc, T(BAT), and the elevation of grooming activities resulting from AVP, and lasting a longer time. Administration of oxotremorine followed immediately by AVP injection in rats was also shown to induce a preference for cooler ambient temperature, but there was no significant difference compared with AVP. AVP-induced hypothermia was related with the set point temperature reduction, inhibiton of BAT thermogenesis and an increases in grooming activities. Oxotremorine could participate in peripheral AVP-induced hypothermia by affecting BAT thermogenesis and behavioral thermoregulation.

  5. Hypothermia as an Adjunct Therapy to Vesicant-induced Skin Injury

    PubMed Central

    Sawyer, Thomas W; Nelson, Peggy

    2008-01-01

    Objective: The notion that cooling vesicant-exposed tissue may ameliorate or prevent resultant injury is not a novel concept. During both World Wars, studies were conducted that investigated this potential mode of therapy with sulfur mustard and seemed to conclude that there might be merit in pursuing this research direction. However, it does not appear that these studies were followed up vigorously, and the literature that describes this work is not readily accessible. In this report, we compare the toxicities of lewisite and sulfur mustard in vitro and in vivo and also provide an overview of historical and recent work on the effect of temperature on the toxicity of these vesicating chemical warfare agents.Methods: Tissue culture and animal studies were utilized to examine the effects of hypothermia on vesicant-induced toxicity. Results: Cytotoxicity was either significantly delayed (lewisite) or prevented (sulfur mustard) when cultures were maintained at 25°C. However, the effects of hypothermia on sulfur mustard–induced cell death were reversible when the cells were returned to 37°C. Despite these in vitro results, animal studies demonstrated that the therapeutic cooling of both mustard sulfur–exposed and lewisite-exposed skin resulted in dramatic and permanent protection against injury. Cooling also increased the therapeutic window in which drugs were effective against vesicant agents in tissue culture and lewisite-induced skin injury. Conclusions: The simple and noninvasive application of cooling measures may not only provide significant therapeutic relief to vesicant-exposed skin but also increase the therapeutic window in which medical countermeasures against vesicant agents are useful. PMID:18516227

  6. 5-HT1a activation in PO/AH area induces therapeutic hypothermia in a rat model of intracerebral hemorrhage

    PubMed Central

    Liang, Tan; Chen, Qianwei; Li, Qiang; Li, Rongwei; Tang, Jun; Hu, Rong; Zhong, Jun; Ge, Hongfei; Liu, Xin; Hua, Feng

    2017-01-01

    Therapeutic hypothermia is widely applied as a neuroprotective measure on intracerebral hemorrhage (ICH). However, several clinical trials regarding physical hypothermia encountered successive failures because of its side-effects in recent years. Increasing evidences indicate that chemical hypothermia that targets hypothalamic 5-HT1a has potential to down-regulate temperature set point without major side-effects. Thus, this study examined the efficacy and safety of 5-HT1a stimulation in PO/AH area for treating ICH rats. First, the relationship between head temperature and clinical outcomes was investigated in ICH patients and rat models, respectively. Second, the expression and distribution of 5-HT1a receptor in PO/AH area was explored by using whole-cell patch and confocal microscopy. In the meantime, the whole-cell patch was subsequently applied to investigate the involvement of 5-HT1a receptors in temperature regulation. Third, we compared the efficacy between traditional PH and 5-HT1a activation-induced hypothermia for ICH rats. Our data showed that more severe perihematomal edema (PHE) and neurological deficits was associated with increased head temperature following ICH. 5-HT1a receptor was located on warm-sensitive neurons in PO/AH area and 8-OH-DPAT (5-HT1a receptor agonist) significantly enhanced the firing rate of warm-sensitive neurons. 8-OH-DPAT treatment provided a steadier reduction in brain temperature without a withdrawal rebound, which also exhibited a superior neuroprotective effect on ICH-induced neurological dysfunction, white matter injury and BBB damage compared with physical hypothermia. These findings suggest that chemical hypothermia targeting 5-HT1a receptor in PO/AH area could act as a novel therapeutic manner against ICH, which may provide a breakthrough for therapeutic hypothermia. PMID:29088731

  7. The effect of amino acid infusion on anesthesia-induced hypothermia in muscle atrophy model rats.

    PubMed

    Kanazawa, Masahiro; Ando, Satoko; Tsuda, Michio; Suzuki, Toshiyasu

    2010-01-01

    An infusion of amino acids stimulates heat production in skeletal muscle and then attenuates the anesthesia-induced hypothermia. However, in a clinical setting, some patients have atrophic skeletal muscle caused by various factors. The present study was therefore conducted to investigate the effect of amino acids on the anesthesia-induced hypothermia in the state of muscle atrophy. As the muscle atrophy model, Sprague-Dawley rats were subjected to hindlimb immobilization for 2 wk. Normal rats and atrophy model rats were randomly assigned to one of the two treatment groups: saline or amino acids (n=8 for each group). Test solutions were administered intravenously to the rats under sevoflurane anesthesia for 180 min, and the rectal temperature was measured. Plasma samples were collected for measurement of insulin, blood glucose, and free amino acids. The rectal temperature was significantly higher in the normal-amino acid group than in the muscle atrophy-amino acid group from 75 to 180 min. The plasma insulin level was significantly higher in the rats given amino acids than in the rats given saline in both normal and model groups. In the rats given amino acids, plasma total free amino acid concentration was higher in the model group than in the normal group. These results indicate that skeletal muscle plays an important role in changes in body temperature during anesthesia and the effect of amino acids on anesthesia-induced hypothermia decreases in the muscle atrophy state. In addition, intravenous amino acids administration during anesthesia induces an increase in the plasma insulin level.

  8. Hypothermia for preventing chemotherapy-induced neuropathy - a pilot study on safety and tolerability in healthy controls.

    PubMed

    Bandla, Aishwarya; Sundar, Raghav; Liao, Lun-De; Sze Hui Tan, Stacey; Lee, Soo-Chin; Thakor, Nitish V; Wilder-Smith, Einar P V

    2016-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of several chemotherapeutic agents, often leading to treatment discontinuation. Up to 20% of patients treated with weekly paclitaxel experience severe CIPN and no effective treatment has been established so far. The mechanisms of CIPN damage are unclear, but are directly dose-related. We had earlier demonstrated, in rats, the influence of hypothermia in reducing nerve blood flow. Here, we hypothesize that continuous flow limb hypothermia during chemotherapy reduces the incidence and severity of CIPN, by limiting deliverance of the neurotoxic drug to the peripheral nerves. In this study, prior to assessing the effect of hypothermia in preventing CIPN in cancer subjects undergoing paclitaxel chemotherapy, we assess the safety and tolerable temperatures for limb hypothermia in healthy human subjects. In 15 healthy human subjects, hypothermia was administered as continuous flow cooling, unilaterally, via a thermoregulator setup covering the digits up to the elbow/knee, along with continuous skin temperature monitoring. Thermoregulator coolant temperatures between 25 °C and 20 °C were tested for tolerability, based on a carefully designed temperature regulation protocol, and maintained for three hours mimicking the duration of chemotherapy. Tolerability was evaluated using various safety and tolerability scores to monitor the subjects. At the end of the cooling session the healthy subjects presented without significant adverse effects, the main being brief mild skin erythema and transient numbness. Coolant temperatures as low as 22 °C were well tolerated continuously over three hours. Our results confirm the safety and tolerability of continuous flow limb hypothermia in healthy subjects. Further studies will use 22 °C thermoregulator temperature to investigate hypothermia in preventing CIPN in breast cancer patients receiving adjuvant weekly paclitaxel. This pilot study

  9. 2-Iminobiotin Superimposed on Hypothermia Protects Human Neuronal Cells from Hypoxia-Induced Cell Damage: An in Vitro Study.

    PubMed

    Zitta, Karina; Peeters-Scholte, Cacha; Sommer, Lena; Gruenewald, Matthias; Hummitzsch, Lars; Parczany, Kerstin; Steinfath, Markus; Albrecht, Martin

    2017-01-01

    Perinatal asphyxia represents one of the major causes of neonatal morbidity and mortality. Hypothermia is currently the only established treatment for hypoxic-ischemic encephalopathy (HIE), but additional pharmacological strategies are being explored to further reduce the damage after perinatal asphyxia. The aim of this study was to evaluate whether 2-iminobiotin (2-IB) superimposed on hypothermia has the potential to attenuate hypoxia-induced injury of neuronal cells. In vitro hypoxia was induced for 7 h in neuronal IMR-32 cell cultures. Afterwards, all cultures were subjected to 25 h of hypothermia (33.5°C), and incubated with vehicle or 2-IB (10, 30, 50, 100, and 300 ng/ml). Cell morphology was evaluated by brightfield microscopy. Cell damage was analyzed by LDH assays. Production of reactive oxygen species (ROS) was measured using fluorometric assays. Western blotting for PARP, Caspase-3, and the phosphorylated forms of akt and erk1/2 was conducted. To evaluate early apoptotic events and signaling, cell protein was isolated 4 h post-hypoxia and human apoptosis proteome profiler arrays were performed. Twenty-five hour after the hypoxic insult, clear morphological signs of cell damage were visible and significant LDH release as well as ROS production were observed even under hypothermic conditions. Post-hypoxic application of 2-IB (10 and 30 ng/ml) reduced the hypoxia-induced LDH release but not ROS production. Phosphorylation of erk1/2 was significantly increased after hypoxia, while phosphorylation of akt, protein expression of Caspase-3 and cleavage of PARP were only slightly increased. Addition of 2-IB did not affect any of the investigated proteins. Apoptosis proteome profiler arrays performed with cellular protein obtained 4 h after hypoxia revealed that post-hypoxic application of 2-IB resulted in a ≥ 25% down regulation of 10/35 apoptosis-related proteins: Bad, Bax, Bcl-2, cleaved Caspase-3, TRAILR1, TRAILR2, PON2, p21, p27, and phospho Rad17. In

  10. Facts and Fiction: The Impact of Hypothermia on Molecular Mechanisms following Major Challenge

    PubMed Central

    Frink, Michael; Flohé, Sascha; van Griensven, Martijn; Mommsen, Philipp; Hildebrand, Frank

    2012-01-01

    Numerous multiple trauma and surgical patients suffer from accidental hypothermia. While induced hypothermia is commonly used in elective cardiac surgery due to its protective effects, accidental hypothermia is associated with increased posttraumatic complications and even mortality in severely injured patients. This paper focuses on protective molecular mechanisms of hypothermia on apoptosis and the posttraumatic immune response. Although information regarding severe trauma is limited, there is evidence that induced hypothermia may have beneficial effects on the posttraumatic immune response as well as apoptosis in animal studies and certain clinical situations. However, more profound knowledge of mechanisms is necessary before randomized clinical trials in trauma patients can be initiated. PMID:22481864

  11. The Molecular Mechanism and Neuroprotective Effect of Dihydrocapsaicin-Induced Mild Hypothermia After Cardiopulmonary Resuscitation in Rats.

    PubMed

    Zhong, Xiaopeng; Wang, Xiujuan; Fei, Fei; Zhang, ManCui; Ding, Po; Zhang, Shiwu

    2018-06-01

    To investigate the molecular mechanism of dihydrocapsaicin (DHC)-induced mild hypothermia in rats, and to compare its protective effect on the central nervous system with that of a conventional method of inducing hypothermia, 24 healthy male Sprague Dawley rats were randomly divided into four groups based on the following conditions: control group, cardiopulmonary resuscitation (CPR) group, body surface cooling group, and DHC group. Tracheal clipping was used to mimic asphyxia arrest. Rats were assessed for their neurological deficit scores. After sacrifice, immunohistochemical staining was used to examine caspase-3 expression in the cerebral cortex and TRPV1 (transient receptor potential vanilloid subfamily, member 1) expression in the hypothalamus. Terminal TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining was used to evaluate cell apoptosis in the cerebral cortex. Furthermore, intracellular Ca 2+ concentration in the hypothalamus and arginine vasopressin (AVP) concentration in ventral septal tissues were also detected in these four groups. Results of our study showed that neurological deficit scores in the DHC group were significantly higher than those in the CPR and body surface cooling groups (p < 0.05). Caspase-3 expression in the cerebral cortex of control group rats was significantly lower than that in other three groups (p < 0.05). Hypothalamic TRPV1 expression, hypothalamic intracellular Ca 2+ concentration, and AVP concentration in the ventral septum in the DHC group were significantly higher than that in the other three groups (p < 0.05). Within these three groups, there were significantly fewer apoptotic cells in the DHC and body surface cooling group rats than in the CPR group rats (p < 0.05). DHC has the neuroprotective effect. DHC induced mild hypothermia and reduces apoptosis through a mechanism whereby DHC activates TRPV1 on hypothalamic cells to cause a large Ca 2+ influx, which alters corresponding physiological

  12. Therapeutic Effects of Pharmacologically Induced Hypothermia against Traumatic Brain Injury in Mice

    PubMed Central

    Lee, Jin Hwan; Wei, Ling; Gu, Xiaohuan; Wei, Zheng; Dix, Thomas A.

    2014-01-01

    Abstract Preclinical and clinical studies have shown therapeutic potential of mild-to-moderate hypothermia for treatments of stroke and traumatic brain injury (TBI). Physical cooling in humans, however, is usually slow, cumbersome, and necessitates sedation that prevents early application in clinical settings and causes several side effects. Our recent study showed that pharmacologically induced hypothermia (PIH) using a novel neurotensin receptor 1 (NTR1) agonist, HPI-201 (also known as ABS-201), is efficient and effective in inducing therapeutic hypothermia and protecting the brain from ischemic and hemorrhagic stroke in mice. The present investigation tested another second-generation NTR1 agonist, HPI-363, for its hypothermic and protective effect against TBI. Adult male mice were subjected to controlled cortical impact (CCI) (velocity=3 m/sec, depth=1.0 mm, contact time=150 msec) to the exposed cortex. Intraperitoneal administration of HPI-363 (0.3 mg/kg) reduced body temperature by 3–5°C within 30–60 min without triggering a shivering defensive reaction. An additional two injections sustained the hypothermic effect in conscious mice for up to 6 h. This PIH treatment was initiated 15, 60, or 120 min after the onset of TBI, and significantly reduced the contusion volume measured 3 days after TBI. HPI-363 attenuated caspase-3 activation, Bax expression, and TUNEL-positive cells in the pericontusion region. In blood–brain barrier assessments, HPI-363 ameliorated extravasation of Evans blue dye and immunoglobulin G, attenuated the MMP-9 expression, and decreased the number of microglia cells in the post-TBI brain. HPI-363 decreased the mRNA expression of tumor necrosis factor-α and interleukin-1β (IL-1β), but increased IL-6 and IL-10 levels. Compared with TBI control mice, HPI-363 treatments improved sensorimotor functional recovery after TBI. These findings suggest that the second generation NTR-1 agonists, such as HPI-363, are efficient

  13. Platelet Dynamics during Natural and Pharmacologically Induced Torpor and Forced Hypothermia

    PubMed Central

    de Vrij, Edwin L.; Vogelaar, Pieter C.; Goris, Maaike; Houwertjes, Martin C.; Herwig, Annika; Dugbartey, George J.; Boerema, Ate S.; Strijkstra, Arjen M.; Bouma, Hjalmar R.; Henning, Robert H.

    2014-01-01

    Hibernation is an energy-conserving behavior in winter characterized by two phases: torpor and arousal. During torpor, markedly reduced metabolic activity results in inactivity and decreased body temperature. Arousal periods intersperse the torpor bouts and feature increased metabolism and euthermic body temperature. Alterations in physiological parameters, such as suppression of hemostasis, are thought to allow hibernators to survive periods of torpor and arousal without organ injury. While the state of torpor is potentially procoagulant, due to low blood flow, increased viscosity, immobility, hypoxia, and low body temperature, organ injury due to thromboembolism is absent. To investigate platelet dynamics during hibernation, we measured platelet count and function during and after natural torpor, pharmacologically induced torpor and forced hypothermia. Splenectomies were performed to unravel potential storage sites of platelets during torpor. Here we show that decreasing body temperature drives thrombocytopenia during torpor in hamster with maintained functionality of circulating platelets. Interestingly, hamster platelets during torpor do not express P-selectin, but expression is induced by treatment with ADP. Platelet count rapidly restores during arousal and rewarming. Platelet dynamics in hibernation are not affected by splenectomy before or during torpor. Reversible thrombocytopenia was also induced by forced hypothermia in both hibernating (hamster) and non-hibernating (rat and mouse) species without changing platelet function. Pharmacological torpor induced by injection of 5′-AMP in mice did not induce thrombocytopenia, possibly because 5′-AMP inhibits platelet function. The rapidness of changes in the numbers of circulating platelets, as well as marginal changes in immature platelet fractions upon arousal, strongly suggest that storage-and-release underlies the reversible thrombocytopenia during natural torpor. Possibly, margination of platelets

  14. Mechanisms underlying hypothermia-induced cardiac contractile dysfunction.

    PubMed

    Han, Young-Soo; Tveita, Torkjel; Prakash, Y S; Sieck, Gary C

    2010-03-01

    Rewarming patients after profound hypothermia may result in acute heart failure and high mortality (50-80%). However, the underlying pathophysiological mechanisms are largely unknown. We characterized cardiac contractile function in the temperature range of 15-30 degrees C by measuring the intracellular Ca(2+) concentration ([Ca(2+)](i)) and twitch force in intact left ventricular rat papillary muscles. Muscle preparations were loaded with fura-2 AM and electrically stimulated during cooling at 15 degrees C for 1.5 h before being rewarmed to the baseline temperature of 30 degrees C. After hypothermia/rewarming, peak twitch force decreased by 30-40%, but [Ca(2+)](i) was not significantly altered. In addition, we assessed the maximal Ca(2+)-activated force (F(max)) and Ca(2+) sensitivity of force in skinned papillary muscle fibers. F(max) was decreased by approximately 30%, whereas the pCa required for 50% of F(max) was reduced by approximately 0.14. In rewarmed papillary muscle, both total cardiac troponin I (cTnI) phosphorylation and PKA-mediated cTnI phosphorylation at Ser23/24 were significantly increased compared with controls. We conclude that after hypothermia/rewarming, myocardial contractility is significantly reduced, as evidenced by reduced twitch force and F(max). The reduced myocardial contractility is attributed to decreased Ca(2+) sensitivity of force rather than [Ca(2+)](i) itself, resulting from increased cTnI phosphorylation.

  15. [Hypothermia and cerebral protection after head trauma. Influence of blood gases modifications].

    PubMed

    Odri, A; Geeraerts, T; Vigué, B

    2009-04-01

    The usefulness of therapeutic hypothermia is highly debated after traumatic brain injury. A neuroprotective effect has been demonstrated only in experimental studies: decrease in cerebral metabolism, restoration of ATP level, better control of cerebral edema and cellular effects. Despite negative multicenter clinical studies, therapeutic hypothermia is still used to a better control of intracranial pressure. However, important issues need to be clarified, particularly the level and duration of hypothermia, the depth and modalities of sedation. A clear understanding of blood gases variations induced by hypothermia is needed to understand the cerebral perfusion and oxygenation changes. It is essential to recognize and to use hypothermia-induced physiological hypocapnia and alkalosis under strict control of cerebral oxygen balance (jugular venous saturation or tissue PO(2)) and also to take into account the increased affinity of hemoglobin for oxygen. Management of post-traumatic intracranial hypertension using hypothermia, directed by intracranial pressure level, and consequently for long duration, is potentially beneficial but needs further clarification.

  16. Monosodium glutamate-induced arcuate nucleus damage affects both natural torpor and 2DG-induced torpor-like hypothermia in Siberian hamsters.

    PubMed

    Pelz, Kimberly M; Routman, David; Driscoll, Joseph R; Kriegsfeld, Lance J; Dark, John

    2008-01-01

    Siberian hamsters (Phodopus sungorus) have the ability to express daily torpor and decrease their body temperature to approximately 15 degrees C, providing a significant savings in energy expenditure. Daily torpor in hamsters is cued by winterlike photoperiods and occurs coincident with the annual nadirs in body fat reserves and chronic leptin concentrations. To better understand the neural mechanisms underlying torpor, Siberian hamster pups were postnatally treated with saline or MSG to ablate arcuate nucleus neurons that likely possess leptin receptors. Body temperature was studied telemetrically in cold-acclimated (10 degrees C) male and female hamsters moved to a winterlike photoperiod (10:14-h light-dark cycle) (experiments 1 and 2) or that remained in a summerlike photoperiod (14:10-h light-dark cycle) (experiment 3). In experiment 1, even though other photoperiodic responses persisted, MSG-induced arcuate nucleus ablations prevented the photoperiod-dependent torpor observed in saline-treated Siberian hamsters. MSG-treated hamsters tended to possess greater fat reserves. To determine whether reductions in body fat would increase frequency of photoperiod-induced torpor after MSG treatment, hamsters underwent 2 wk of food restriction (70% of ad libitum) in experiment 2. Although food restriction did increase the frequency of torpor in both MSG- and saline-treated hamsters, it failed to normalize the proportion of MSG-treated hamsters undergoing photoperiod-dependent torpor. In experiment 3, postnatal MSG treatments reduced the proportion of hamsters entering 2DG-induced torpor-like hypothermia by approximately 50% compared with saline-treated hamsters (38 vs. 72%). In those MSG-treated hamsters that did become hypothermic, their minimum temperature during hypothermia was significantly greater than comparable saline-treated hamsters. We conclude that 1) arcuate nucleus mechanisms mediate photoperiod-induced torpor, 2) food-restriction-induced torpor may also be

  17. Oxotremorine-induced hypothermia as a method for evaluating long-term neuronal changes following poisoning by cholinesterase inhibitors in rats.

    PubMed

    Grauer, E; Levy, A

    2007-12-05

    Severe poisoning by inhibitors of cholinesterase (ChE) enzymes is often associated with prolonged central or peripheral neuronal damage. Oxotremorine is a cholinergic agonist known to induce acute hypothermia. Central and peripheral cholinergic signaling is involved in the induction of hypothermia as well as in its recovery. These processes were used in the present study to reveal prolonged neuronal abnormalities in poisoned rats, using oxotremorine with and without concomitant administration of the peripheral muscarinic antagonist methyl scopolamine. In non-poisoned naïve rats, the hypothermic effect of oxotremorine appeared faster while its recovery was delayed following co-administration of methyl scopolamine, suggesting predominantly peripheral processes in counteracting the hypothermia. One month after exposure to approximately 1LD(50) of the carbamates aldicarb and oxamyl, the hypothermic effect of oxotremorine was similar to that found in saline-treated control group. However, the effect of methyl scopolamine on the recovery process was significantly diminished, indicating that the impaired cholinergic mechanisms were predominantly peripheral. In contrast, 1 month following organophosphate (OP) poisoning by the nerve agents sarin and VX, oxotremorine-induced hypothermia was reduced, indicating mainly impaired central cholinergic mechanisms. The development of severe convulsions during nerve agent poisoning may explain the central neuronal damage in OP-poisoned rats, displayed as reduced hypothermia. As convulsions were not part of the poisoning symptoms with the carbamates tested, their long-term damage was displayed at the recovery stage. This method might be used as a relatively simple means for detecting differential long-term central and peripheral cholinergic injuries, long after toxicity signs have receded.

  18. Hypothermia in bleeding trauma: a friend or a foe?

    PubMed Central

    2009-01-01

    The induction of hypothermia for cellular protection is well established in several clinical settings. Its role in trauma patients, however, is controversial. This review discusses the benefits and complications of induced hypothermia--emphasizing the current state of knowledge and potential applications in bleeding patients. Extensive pre-clinical data suggest that in advanced stages of shock, rapid cooling can protect cells during ischemia and reperfusion, decrease organ damage, and improve survival. Yet hypothermia is a double edged sword; unless carefully managed, its induction can be associated with a number of complications. Appropriate patient selection requires a thorough understanding of the pre-clinical literature. Clinicians must also appreciate the enormous influence that temperature modulation exerts on various cellular mechanisms. This manuscript aims to provide a balanced view of the published literature on this topic. While many of the advantageous molecular and physiological effects of induced hypothermia have been outlined in animal models, rigorous clinical investigations are needed to translate these promising findings into clinical practice. PMID:20030810

  19. Unintended Perioperative Hypothermia

    PubMed Central

    Hart, Stuart R.; Bordes, Brianne; Hart, Jennifer; Corsino, Daniel; Harmon, Donald

    2011-01-01

    Background Hypothermia, defined as a core body temperature less than 36°C (96.8°F), is a relatively common occurrence in the unwarmed surgical patient. A mild degree of perioperative hypothermia can be associated with significant morbidity and mortality. A threefold increase in the frequency of surgical site infections is reported in colorectal surgery patients who experience perioperative hypothermia. As part of the Surgical Care Improvement Project, guidelines aim to decrease the incidence of this complication. Methods We review the physiology of temperature regulation, mechanisms of hypothermia, effects of anesthetics on thermoregulation, and consequences of hypothermia and summarize recent recommendations for maintaining perioperative normothermia. Results Evidence suggests that prewarming for a minimum of 30 minutes may reduce the risk of subsequent hypothermia. Conclusions Monitoring of body temperature and avoidance of unintended perioperative hypothermia through active and passive warming measures are the keys to preventing its complications. PMID:21960760

  20. Brain Perfusion In Asphyxiated Newborns Treated with Therapeutic Hypothermia

    PubMed Central

    Wintermark, Pia; Hansen, Anne; Gregas, Matthew C.; Soul, Janet; Labrecque, Michelle; Robertson, Richard L.; Warfield, Simon K.

    2012-01-01

    Background and Purpose Induced hypothermia is thought to work partly by mitigating reperfusion injury in asphyxiated term newborns. The purpose of this study is to assess brain perfusion in the first week of life in these newborns. Patients and Methods In this prospective cohort study, magnetic resonance imaging (MRI) and perfusion imaging by arterial spin labeling (ASL-PI) was used to assess brain perfusion in these newborns. We measured regional cerebral blood flow values on 1–2 MRIs obtained during the first week of life and compared them to values obtained in control term newborns. The same or later MRI scans were obtained to define the extent of brain injury. Results Eighteen asphyxiated and four control term newborns were enrolled; eleven asphyxiated newborns were treated with hypothermia. Those developing brain injury despite being treated with induced hypothermia usually displayed hypoperfusion on day of life (DOL) 1, and then hyperperfusion on DOL 2–3 in brain areas subsequently exhibiting injury. Asphyxiated newborns not treated with hypothermia who developed brain injury also displayed hyperperfusion on DOL 1–6 in brain areas displaying injury. Conclusions Our data show that ASL-PI may be useful for identifying asphyxiated newborns at risk of developing brain injury, whether or not hypothermia is administered. Since hypothermia for 72 hours may not prevent brain injury when hyperperfusion is found early in the course of neonatal hypoxic-ischemic encephalopathy, such newborns may be candidates for adjustments in their hypothermia therapy or for adjunctive neuroprotective therapies. PMID:21979494

  1. Hypothermia-induced increase of oligodendrocyte precursor cells: Possible involvement of plasmalemmal voltage-dependent anion channel 1.

    PubMed

    Imada, Shinya; Yamamoto, Masahiro; Tanaka, Kayoko; Seiwa, Chika; Watanabe, Kenji; Kamei, Yoshimasa; Kozuma, Shiro; Taketani, Yuji; Asou, Hiroaki

    2010-12-01

    Hypothermia is believed to suppress cell proliferation by inducing apoptosis/necrosis and phase-specific/nonspecific cell cycle arrest, which are, directly or indirectly, related to a reduced energy supply. Intriguingly, hypothermia is known to improve neurological recovery of animals and humans exposed to focal brain hypoxic-ischemic injury. The underlying mechanism of the neuroprotective effect of hypothermia is unclear, although the prevention of neural cell apoptosis is thought to play a role. Herein we demonstrate that in vitro cell culture of oligodendrocyte precursor cells (OPCs) under conditions of mild hypothermia (31.5°C) results in an increase in cell number relative to cells cultured under normothermic conditions (37°C). Cell cycle analysis, immunoblotting of cyclins, TUNEL assay, and immunocytochemistry of OPC differentiation markers suggest that hypothermia shifts the balance between proliferation and apoptosis/differentiation toward proliferation. A combination of transcriptome analysis, pharmacological intervention, and immunoaffinity-based assays suggests a possible involvement of the Gα13-Rho GTPase Cdc42-ERK1/2 signaling cascade and voltage-dependent anion channel 1 (VDAC1), which associate or dissociate with Gα13 protein at 37°C and 31.5°C, respectively. Immunoelectron microscopy revealed the presence of VDAC1 in the plasma membrane of OPCs. Furthermore, the exogenous addition of impermeable VDAC1 inhibitors enhanced proliferation of OPCs at 37°C. These results may contribute to the elucidation of the mechanism of hypothermic neuroprotection as well as the possible novel role of plasmalemmal VDAC1. Copyright © 2010 Wiley-Liss, Inc.

  2. Hypothermia.

    PubMed

    Turk, Elisabeth E

    2010-06-01

    Hypothermia refers to a situation where there is a drop in body core temperature below 35 degrees C. It is a potentially fatal condition. In forensic medicine and pathology, cases of hypothermia often pose a special challenge to experts because of their complex nature, and the often absent or nonspecific nature of morphological findings. The scene of the incident may raise suspicions of a crime initially, due to phenomena such as terminal burrowing behavior and paradoxical undressing. An element of hypothermia often contributes to the cause of death in drug- and alcohol-related fatalities, in the homeless, in immersion deaths, in accidents and in cases of abuse or neglect, making the condition extremely relevant to forensic medical specialists. The aim of this review is to give an overview of the pathophysiological aspects of hypothermia and to illustrate different aspects relevant to forensic medical casework.

  3. Hypothermia for Neuroprotection in Convulsive Status Epilepticus.

    PubMed

    Legriel, Stephane; Lemiale, Virginie; Schenck, Maleka; Chelly, Jonathan; Laurent, Virginie; Daviaud, Fabrice; Srairi, Mohamed; Hamdi, Aicha; Geri, Guillaume; Rossignol, Thomas; Hilly-Ginoux, Julia; Boisramé-Helms, Julie; Louart, Benjamin; Malissin, Isabelle; Mongardon, Nicolas; Planquette, Benjamin; Thirion, Marina; Merceron, Sybille; Canet, Emmanuel; Pico, Fernando; Tran-Dinh, Yves-Roger; Bedos, Jean-Pierre; Azoulay, Elie; Resche-Rigon, Matthieu; Cariou, Alain

    2016-12-22

    Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus. In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90. A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval [CI], 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group. In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).

  4. Can Induced Hypothermia Be Assured During Brain MRI in Neonates with Hypoxic-Ischemic Encephalopathy?

    PubMed Central

    Wintermark, Pia; Labrecque, Michelle; Warfield, Simon. K.; DeHart, Stephanie; Hansen, Anne

    2012-01-01

    Until now, brain magnetic resonance imaging (MRIs) in asphyxiated neonates receiving therapeutic hypothermia have been performed after treatment is complete. However, there is increasing interest in early brain MRI while hypothermia is still being provided, in order to rapidly understand the degree of brain injury and possibly refine neuroprotective strategies. This study was designed to assess whether therapeutic hypothermia can be maintained while performing a brain MRI. Twenty MRI scans were obtained in twelve asphyxiated neonates while they were treated with hypothermia. Median difference between esophageal temperature on NICU departure and return was 0.1°C (range: −0.8 to 0.8°C). In conclusion, therapeutic hypothermia can be safely and reproducibly maintained during a brain MRI. Hypothermia treatment should not prevent obtaining an early brain MRI if clinically indicated. PMID:20737144

  5. [Hypothermia].

    PubMed

    García Iriarte, Antxon; Sáenz Mendía, Raquel; Marín Fernández, Blanca

    2010-01-01

    A deep understanding about the causes and situations which predispose a patient to hypothermia can prevent its progression and the emergence of complications which present life-threatening risks and can lead to irreversible organ deterioration. The distinct degrees of hypothermia require a diagnosis and a distinct therapeutic treatment which share common pillars based on: the need to employ general measures which counterarrest the deterioration of those organs caused by heat loss; and the use of internal or external reheating methods which vary due to the degree of hypothermia and the hemodynamic stability of the patient. In moderate or severe cases, a nurse's role, as one who collaborates in patient treatment, requires paying special attention to strict monitoring of vital constants, neurological, metabolic and cardio-respiratory signs, as well as collaborating in various therapeutic procedures. As a nursing diagnosis, hypothermia refers to those situations in which a nurse's professional competence capacitates he/she to carry out actions which resolve that prejudicial situation a patient faces.

  6. EARLY VERSUS LATE MRI IN ASPHYXIATED NEWBORNS TREATED WITH HYPOTHERMIA

    PubMed Central

    Wintermark, Pia; Hansen, Anne; Soul, Janet; Labrecque, Michelle; Robertson, Richard L.; Warfield, Simon K.

    2012-01-01

    Objective The purposes of this feasibility study are to assess: (1) the potential utility of early brain magnetic resonance imaging (MRI) in asphyxiated newborns treated with hypothermia; (2) whether early MRI predicts later brain injury observed in these newborns after hypothermia is completed; and (3) whether early MRI indicators of brain injury in these newborns represent reversible changes. Patients and Methods All consecutive asphyxiated term newborns meeting the criteria for therapeutic hypothermia were enrolled prospectively. Each of them underwent 1–2 “early” MRI scans while receiving hypothermia, on day of life (DOL) 1 and DOL 2–3, and also 1–2 “late” MRI scans on DOL 8–13 and at 1 month of age. Results Thirty-seven MRI scans were obtained in twelve asphyxiated neonates treated with induced hypothermia. Four newborns did develop MRI evidence of brain injury, already visible on early MRI scans. The remaining eight newborns did not develop significant MRI evidence of brain injury on any of the MRI scans. In addition, two patients displayed unexpected findings on early MRIs, leading to early termination of hypothermia treatment. Conclusions MRI scans obtained on DOL 2–3 during hypothermia seem to predict later brain injuries in asphyxiated newborns in this feasibility study. Brain injuries identified during this early time appear to represent irreversible changes. Early MRI scans might also be useful to demonstrate unexpected findings not related to hypoxic-ischemic encephalopathy, which could potentially be exacerbated by induced hypothermia. Additional studies with larger numbers of patients will be useful to more definitively confirm these results. PMID:20688865

  7. Increased ethanol preference and serotonin 1A receptor-dependent attenuation of ethanol-induced hypothermia in PACAP-deficient mice.

    PubMed

    Tanaka, Kazuhiro; Kunishige-Yamamoto, Akiko; Hashimoto, Hitoshi; Shintani, Norihito; Hayata, Atsuko; Baba, Akemichi

    2010-01-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient mice display remarkable behavioral changes including increased novelty-seeking behavior and reduced hypothermia induced by either serotonin (5-HT)(1A) receptor agonists or ethanol. Because 5-HT(1A) receptors have been implicated in the development of alcohol dependence, we have examined ethanol preference in PACAP-deficient mice using a two-bottle choice and a conditioned place preference test, as well as additive effects of ethanol and 5-HT(1A) receptor agents on hypothermia. PACAP-deficient mice showed an increased preference towards ethanol compared with wild-type mice. However, they showed no preference for the ethanol compartment after conditioning and neither preference nor aversion to sucrose or quinine. The 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) restored the attenuated hypothermic response to ethanol in the mutants to similar levels in wild-type mice, with no effect in wild-types. In contrast, the 5-HT(1A) receptor antagonist WAY-100635 attenuated the ethanol-induced hypothermia in wild-type mice, with no effect in the mutants. These results demonstrate increased ethanol preference in PACAP-deficient mice that may be mediated by 5-HT(1A) receptor-dependent attenuation of ethanol-induced central inhibition. Copyright 2009 Elsevier Inc. All rights reserved.

  8. Future Directions for Hypothermia following Severe Traumatic Brian Injury.

    PubMed

    Chiu, Annie W; Hinson, Holly E

    2017-12-01

    Traumatic brain injury (TBI) is a serious health care problem on both individual and public health levels. As a major cause of death and disability in the United States, it is associated with a significant economic and public health burden. Although the evidence to support the use of induced hypothermia on neurologic outcome after cardiac arrest is well established, its use in treating TBI remains controversial. Hypothermia has the potential to mitigate some of the destructive processes that occur as part of secondary brain injury after TBI. Hypothermia can be helpful in lowering intracranial pressure, for example, but its influence on functional outcome is unclear. There is insufficient evidence to support the broad use of prophylactic hypothermia for neuroprotection after TBI. Investigators are beginning to more carefully select patients for temperature modulating therapies, in a more personalized approach. Examples include targeting immunomodulation and scaling hypothermia to achieve metabolic targets. This review will summarize the clinical evidence for the use of hypothermia to limit secondary brain injury following acute TBI. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. A cool approach to reducing electrode-induced trauma: Localized therapeutic hypothermia conserves residual hearing in cochlear implantation.

    PubMed

    Tamames, Ilmar; King, Curtis; Bas, Esperanza; Dietrich, W Dalton; Telischi, Fred; Rajguru, Suhrud M

    2016-09-01

    The trauma caused during cochlear implant insertion can lead to cell death and a loss of residual hair cells in the cochlea. Various therapeutic approaches have been studied to prevent cochlear implant-induced residual hearing loss with limited success. In the present study, we show the efficacy of mild to moderate therapeutic hypothermia of 4 to 6 °C applied to the cochlea in reducing residual hearing loss associated with the electrode insertion trauma. Rats were randomly distributed in three groups: control contralateral cochleae, normothermic implanted cochleae and hypothermic implanted cochleae. Localized hypothermia was delivered to the middle turn of the cochlea for 20 min before and after implantation using a custom-designed probe perfused with cooled fluorocarbon. Auditory brainstem responses (ABRs) were recorded to assess the hearing function prior to and post-cochlear implantation at various time points up to 30 days. At the conclusion of the trials, inner ears were harvested for histology and cell count. The approach was extended to cadaver temporal bones to study the potential surgical approach and efficacy of our device. In this case, the hypothermia probe was placed next to the round window niche via the facial recess or a myringotomy. A significant loss of residual hearing was observed in the normothermic implant group. Comparatively, the residual hearing in the cochleae receiving therapeutic hypothermia was significantly conserved. Histology confirmed a significant loss of outer hair cells in normothermic cochleae receiving the surgical trauma when compared to the hypothermia treated group. In human temporal bones, a controlled and effective cooling of the cochlea was achieved using our approach. Collectively, these results suggest that therapeutic hypothermia during cochlear implantation may reduce traumatic effects of electrode insertion and improve conservation of residual hearing. Copyright © 2016 The Authors. Published by Elsevier B.V. All

  10. Hypothermia-induced acute kidney injury in a diabetic patient with nephropathy and neuropathy.

    PubMed

    Yamada, Shunsuke; Shimomura, Yukiko; Ohsaki, Masato; Fujisaki, Akiko; Tsuruya, Kazuhiko; Iida, Mitsuo

    2010-01-01

    Hypothermia is a life-threatening medical condition defined as an unintentional fall in body temperature below 35 degrees C. Exposure to cold environment stimulates the thermoregulatory system to maintain the body temperature within the physiological range. Patients with malnutrition and/or diabetes mellitus are at high risk for accidental hypothermia, and acute kidney injury, which is mainly caused by pre-renal factors, occurs in relation to hypothermia. However, acute exacerbation of pre-existing chronic kidney disease has been rarely reported. Here, we present a patient with diabetes mellitus and malnutrition who developed two separate episodes of hypothermia followed by acute exacerbation of chronic kidney disease.

  11. A new microcontroller supervised thermoelectric renal hypothermia system.

    PubMed

    Işik, Hakan

    2005-10-01

    In the present study, a thermoelectric system controlled by a microcontroller is developed to induce renal hypothermia. Temperature value was managed by 8-byte microcontroller, PIC16F877, and was programmed using microcontroller MPASM package. In order to ensure hypothermia in the kidney 1-4 modules and sensors perceiving temperature of the area can be selected. Temperature values are arranged proportionately for the selected area and the determined temperature values can be monitored from an Liquid Crystal Display (LCD) screen. The temperature range of the system is between -50 and +50 degrees C. Renal hypothermia system was tried under in vivo conditions on the kidney of a dog.

  12. Inducible nitric oxide synthase during the late phase of sepsis is associated with hypothermia and immune cell migration.

    PubMed

    Takatani, Yudai; Ono, Kenji; Suzuki, Hiromi; Inaba, Masato; Sawada, Makoto; Matsuda, Naoyuki

    2018-02-14

    Hypothermia is a significant sign of sepsis, which is associated with poor prognosis, but few mechanisms underlying the regulation of hypothermia are known. Inducible nitric oxide synthase (iNOS) is a key inflammatory mediator of sepsis. However, the therapeutic benefit of iNOS inhibition in sepsis is still controversial, and requires elucidation in an accurate model system. In this study, wild-type (WT) mice showed temperature drops in a biphasic manner at the early and late phase of sepsis, and all mice died within 48 h of sepsis. In contrast, iNOS-knockout (KO) mice never showed the second temperature drop and exhibited improved mortality. Plasma nitric oxide (NO) levels of WT mice increased in the late phase of sepsis and correlated to hypothermia. The results indicate that iNOS-derived NO during the late phase of sepsis caused vasodilation-induced hypothermia and a lethal hypodynamic state. The expression of the iNOS mRNA was high in the lung of WT mice with sepsis, which reflects the pathology of acute respiratory distress syndrome (ARDS). We obtained the results in a modified keyhole-type cecal ligation and puncture model of septic shock induced by minimally invasive surgery. In this accurate and reproducible model system, we transplanted the bone marrow cells of GFP transgenic mice into WT and iNOS-KO mice, and evaluated the role of increased pulmonary iNOS expression in cell migration during the late phase of sepsis. We also investigated the quantity and type of bone marrow-derived cells (BMDCs) in the lung. The number of BMDCs in the lung of iNOS-KO mice was less than that in the lung of WT mice. The major BMDCs populations were CD11b-positive, iNOS-negative cells in WT mice, and Gr-1-positive cells in iNOS-KO mice that expressed iNOS. These results suggest that sustained hypothermia may be a beneficial guide for future iNOS-targeted therapy of sepsis, and that iNOS modulated the migratory efficiency and cell type of BMDCs in septic ARDS.

  13. The effectiveness of low-dose desmopressin in improving hypothermia-induced impairment of primary haemostasis under influence of aspirin - a randomized controlled trial.

    PubMed

    Tsui, Pui Yee; Cheung, Chi Wai; Lee, Yvonne; Leung, Susan Wai Sum; Ng, Kwok Fu Jacobus

    2015-05-28

    Mild hypothermia (34-35 °C) increases perioperative blood loss. Our previous studies showed that desmopressin could have in vitro beneficial effects on hypothermia-induced primary haemostasis impairment. In this study, we investigate the in vitro effects of desmopressin on hypothermia-induced primary haemostasis impairment under the influence of aspirin in healthy volunteers. Sixty healthy volunteers were randomly allocated to taking aspirin 100 mg or placebo for three days. On the sixth day blood samples were taken before and after the injection of desmopressin (1.5 microgram or 5 microgram) or normal saline subcutaneously. Measurements including Platelet Function Analyzer (PFA-100®) closure times, plasma von Willebrand Factor antigen, haemoglobin and platelet levels were made at 32 °C and 37 °C respectively. Collagen/epinephrine closure time (EPICT) was significantly prolonged by 21.13 % (95 %CI 2.34-39.74 %, p = 0.021) in aspirin group at 37 °C. While hypothermia alone prolonged both collagen/adenosine diphosphate (ADPCT) and EPICT by 17.63 % (95 %CI 13.5-20.85 %, p < 0.001) and 8.0 % (95 %CI 6.38-10.04 %, p = 0.024) respectively, addition of aspirin only further prolonged EPICT by 19.9 % (95 %CI 3.32-36.49 %, p = 0.013). In aspirin group, desmopressin 1.5 microgram and 5 microgram significantly reduced ADPCT to below baseline levels at 37 °C (p = 0.025 and <0.001 respectively), whereas reduction in EPICT was seen with desmopressin 5 microgram (p =0.008). The effect was less pronounced at 32 °C, with a significant reduction in EPICT obtained with a dosage of 5 microgram only (p = 0.011). It was shown that aspirin could further potentiate the hypothermia-induced closure time prolongations. Low dose desmopressin (1.5 microgram) reduced PFA-100® closure times towards baseline. A higher dosage (5 microgram) further reduced the closure times below baseline. Therefore low dose desmopressin (1.5 microgram) might have the potential to

  14. The role of multiple dopamine receptors in apomorphine and N-n-propylnorapomorphine-induced climbing and hypothermia.

    PubMed

    Moore, N A; Axton, M S

    1990-03-20

    Apomorphine and N-n-propylnorapomorphine (NPA) were compared for their ability to induce stereotyped cage climbing and hypothermia in mice. Climbing behavior was produced by similar doses of apomorphine and NPA (0.625-2.5 mg/kg s.c.), whereas NPA was 43 times more potent than apomorphine in inducing a hypothermic response. SKF38393 caused a shift to the left in the dose-response curve for NPA-induced climbing, the ED50 changing from 0.98 to 0.014 mg/kg. SKF38393 had no effect on apomorphine-induced climbing behaviour. The climbing response produced by apomorphine was antagonised by both D-1 and D-2 antagonists. Climbing behaviour induced by NPA (2.5 mg/kg) could be antagonised by SCH23390 but not by clebopride, however climbing behaviour induced by a low dose of NPA (0.06 mg/kg) plus SKF38393 could be blocked by both D-1 and D-2 receptor antagonists. The hypothermic responses produced by either apomorphine or NPA could only be reversed by the selective D-2 antagonist, clebopride. These results demonstrate that dopamine agonist-induced stereotyped cage climbing requires both D-1 and D-2 receptor stimulation, whereas the hypothermic response is D-2-mediated. The results also show that it is possible to assess the relative activity of a dopamine agonist at D-1 or D-2 receptors in vivo by comparing the ability of the compound to induce hypothermia and climbing behaviour.

  15. Neuroprotective assessment of prolonged local hypothermia post contusive spinal cord injury in rodent model.

    PubMed

    Teh, Daniel Boon Loong; Chua, Soo Min; Prasad, Ankshita; Kakkos, Ioannis; Jiang, Wenxuan; Yue, Mu; Liu, Xiaogang; All, Angelo Homayoun

    2018-03-01

    Although general hypothermia is recognized as a clinically applicable neuroprotective intervention, acute moderate local hypothermia post contusive spinal cord injury (SCI) is being considered a more effective approach. Previously, we have investigated the feasibility and safety of inducing prolonged local hypothermia in the central nervous system of a rodent model. Here, we aimed to verify the efficacy and neuroprotective effects of 5 and 8 hours of local moderate hypothermia (30±0.5°C) induced 2 hours after moderate thoracic contusive SCI in rats. Rats were induced with moderate SCI (12.5 mm) at its T8 section. Local hypothermia (30±0.5°C) was induced 2 hours after injury induction with an M-shaped copper tube with flow of cold water (12°C), from the T6 to the T10 region. Experiment groups were divided into 5-hour and 8-hour hypothermia treatment groups, respectively, whereas the normothermia control group underwent no hypothermia treatment. The neuroprotective effects were assessed through objective weekly somatosensory evoked potential (SSEP) and motor behavior (basso, beattie and bresnahan Basso, Beattie and Bresnahan (BBB) scoring) monitoring. Histology on spinal cord was performed until at the end of day 56. All authors declared no conflict of interest. This work was supported by the Singapore Institute for Neurotechnology Seed Fund (R-175-000-121-733), National University of Singapore, Ministry of Education, Tier 1 (R-172-000-414-112.). Our results show significant SSEP amplitudes recovery in local hypothermia groups starting from day 14 post-injury onward for the 8-hour treatment group, which persisted up to days 28 and 42, whereas the 5-hour group showed significant improvement only at day 42. The functional improvement plateaued after day 42 as compared with control group of SCI with normothermia. This was supported by both 5-hour and 8-hour improvement in locomotion as measured by BBB scores. Local hypothermia also observed insignificant changes

  16. Detrimental effect of hypothermia during acute normovolaemic haemodilution in anaesthetized cats

    NASA Astrophysics Data System (ADS)

    Talwar, A.; Fahim, Mohammad

    Haemodynamic responses to hypothermia were studied at normal haematocrit and following the induction of acute normovolaemic haemodilution. Experiments were performed on 20 cats anaesthetized with a mixture of chloralose and urethane in two groups. In one group (n=10) the effects of hypothermia on various haemodynamic variables were studied at normal haematocrit (41.0+/-1.7%) and in the second group of cats (n=10) the effects of hypothermia on various haemodynamic variables were studied after the induction of acute normovolaemic haemodilution (14.0+/-1.0%). The haemodynamic variables left ventricular pressure, left ventricular contractility, arterial blood pressure, heart rate and right atrial pressure were recorded on a polygraph. Cardiac output was measured using a cardiac output computer. In both groups hypothermia was induced by surface cooling with the help of ice. Cardiovascular variables were recorded at each 1° C fall in body temperature. Hypothermia produced a significant (P<0.05) drop in heart rate, cardiac output, arterial blood pressure and left ventricular contractility in both groups. However, the percentage decrease in these variables in response to hypothermia was significantly (P<0.05) higher in cats with low haematocrit than in those with normal haematocrit. The severity of hypothermia - induced cardiovascular effects is evident from the drastic decrease in heart rate, cardiac output, arterial blood pressure and myocardial contractility in cats with low haematocrit, indicating a higher risk of circulatory failure under anaemic conditions at low temperatures.

  17. [Regulated hypothermia after cardiac arrest. A glimpse into the future].

    PubMed

    Schneider, A; Popp, E; Böttiger, B W

    2006-12-01

    The introduction of therapeutic mild hypothermia after cardiac arrest allows the neuronal damage caused by global cerebral ischemia to be advantageously influenced for the first time. Currently, hypothermia is induced by external or internal cooling of the patient (forced hypothermia). However, this results in activation of counter-regulation mechanisms which could be possible risk factors for the patient. The aim of this article is to give a review of possible, but at present only experimental, methods which could allow the body temperature set point to be decreased pharmacologically (regulated hypothermia). Various classes of substances will be discussed based on their effect on thermoregulation and their performance in animal experiments on cerebral ischemia.

  18. Hypothermia and Alzheimer's disease neuropathogenic pathways.

    PubMed

    Whittington, R A; Papon, M-A; Chouinard, F; Planel, E

    2010-12-01

    Alzheimer's disease (AD) remains a major health problem, and accounts for 50 to 60% of all cases of dementia. The two histopathological hallmarks of AD are senile plaques, composed of the β-amyloid peptide (Aβ), and intraneuronal neurofibrillary tangles composed of abnormally hyperphosphorylated tau protein. Only a small proportion of AD is due to mutations in the genome of patients, the large majority of cases being of late onset and sporadic in origin. The relative contribution of genetics and environment to the sporadic cases is unclear, but they are accepted to be of multifactorial origin. This means that genetic and environmental factors can interact together to induce or accelerate the disease. Among environmental factors, studies suggest that hypothermia may contribute to the development and exacerbation AD. Here, we review the preclinical data involving hypothermia with tau and Aβ, as well as clinical evidence implicating hypothermia in the development of AD.

  19. Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist.

    PubMed

    Fosgerau, Keld; Weber, Uno J; Gotfredsen, Jacob W; Jayatissa, Magdalena; Buus, Carsten; Kristensen, Niels B; Vestergaard, Mogens; Teschendorf, Peter; Schneider, Andreas; Hansen, Philip; Raunsø, Jakob; Køber, Lars; Torp-Pedersen, Christian; Videbaek, Charlotte

    2010-10-09

    The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion. Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours. Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia.

  20. [Preoperative fluid management contributes to the prevention of intraoperative hypothermia].

    PubMed

    Yatabe, Tomoaki; Yokoyama, Masataka

    2011-07-01

    Intraoperative hypothermia causes several unfavorable events such as surgical site infection and cardiovascular events. Therefore, during anesthesia, temperature is routinely regulated, mainly by using external heating devices. Recently, oral amino acid intake and intravenous amino acid or fructose infusion have been reported to prevent intraoperative hypothermia during general and regional anesthesia. Diet (nutrient)-induced thermogenesis is considered to help prevent intraoperative hypothermia. Since the Enhanced Recovery After Surgery (ERAS) protocol has been introduced, it has been used in perioperative management in many hospitals. Prevention of intraoperative hypothermia is included in this protocol. According to the protocol, anesthesiologists play an important role in both intraoperative and perioperative management. Management of optimal body temperature by preoperative fluid management alone may be difficult. To this end, preoperative fluid management and nutrient management strategies such as preoperative oral fluid intake and carbohydrate loading have the potential to contribute to the prevention of intraoperative hypothermia.

  1. Local cerebral hypothermia induced by selective infusion of cold lactated ringer's: a feasibility study in rhesus monkeys.

    PubMed

    Wang, Bincheng; Wu, Di; Dornbos Iii, David; Shi, Jingfei; Ma, Yanhui; Zhang, Mo; Liu, Yumei; Chen, Jian; Ding, Yuchuan; Luo, Yinghao; Ji, Xunming

    2016-06-01

    Hypothermia has shown promise as a neuroprotective strategy for stroke. The use of whole body hypothermia has limited clinical utility due to many severe side effects. Selective brain cooling, or local brain hypothermia, has been previously proposed as an alternative treatment strategy. This study investigated the safety, feasibility, and efficacy of selective brain hypothermia induced by local infusion of ice-cold lactated Ringer's solution in rhesus monkeys. Eight male rhesus monkeys were used in this study. Brain temperature in the territory supplied by middle cerebral artery (MCA) was reduced by infusing 100 mL of ice-cold (0 °C) lactated Ringer's solution over 20 min via a micro-catheter placed in the proximal MCA (n = 4). Vital signs and the temperature of the brain and rectum were monitored before and after infusion. Transcranial Doppler, Magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) were used to evaluate cerebral blood flow, cerebrovascular reactivity (CVR), cerebral edema, and vasospasm. Another cohort of rhesus monkeys (n = 4) were used as systemic cooling controls. Oxygen saturation, blood pressure, heart rate, and hematologic analysis of the two groups remained within the normal range after infusion. Mild cerebral hypothermia (<35 °C) was achieved in 10 min (0.3 °C/min) and was maintained for 20 min in local cortex and striatum following local infusion. The average lowest cerebral temperature in the locally cooled animals was 33.9 ± 0.3 °C in the striatum following 20-min infusion. This was not observed in animals cooled by systemic infusion. The decreases in the rectal temperature for local and systemic infusion were 0.5 ± 0.2 °C and 0.5 ± 0.3 °C, respectively. Selective brain cooling did not cause any cerebral edema as determined by MRI or vasospasm in the perfused vessel based on DSA. Selective cerebral hypothermia did not significantly alter CVR. Local infusion of ice-cold lactated Ringer

  2. An unusual autopsy case of lethal hypothermia exacerbated by body lice-induced severe anemia.

    PubMed

    Nara, Akina; Nagai, Hisashi; Yamaguchi, Rutsuko; Makino, Yohsuke; Chiba, Fumiko; Yoshida, Ken-ichi; Yajima, Daisuke; Iwase, Hirotaro

    2016-05-01

    Pediculus humanus humanus (known as body lice) are commonly found in the folds of clothes, and can cause skin disorders when they feed on human blood, resulting in an itching sensation. Body lice are known as vectors of infectious diseases, including typhus, recurrent fever, and trench fever. An infestation with blood-sucking body lice induces severe cutaneous pruritus, and this skin disorder is known as "vagabond's disease." A body lice infestation is sometimes complicated with iron deficiency anemia. In the present case, a man in his late 70s died of lethal hypothermia in the outdoors during the winter season. The case history and autopsy findings revealed that the cause of the lethal hypothermia was iron deficiency anemia, which was associated with a prolonged infestation of blood-sucking body lice. Also, he had vagabond's disease because the skin on his body was abnormal and highly pigmented. This is an unusual autopsy case since the body lice contributed to the cause of the death.

  3. Functional laser speckle imaging of cerebral blood flow under hypothermia

    NASA Astrophysics Data System (ADS)

    Li, Minheng; Miao, Peng; Zhu, Yisheng; Tong, Shanbao

    2011-08-01

    Hypothermia can unintentionally occur in daily life, e.g., in cardiovascular surgery or applied as therapeutics in the neurosciences critical care unit. So far, the temperature-induced spatiotemporal responses of the neural function have not been fully understood. In this study, we investigated the functional change in cerebral blood flow (CBF), accompanied with neuronal activation, by laser speckle imaging (LSI) during hypothermia. Laser speckle images from Sprague-Dawley rats (n = 8, male) were acquired under normothermia (37°C) and moderate hypothermia (32°C). For each animal, 10 trials of electrical hindpaw stimulation were delivered under both temperatures. Using registered laser speckle contrast analysis and temporal clustering analysis (TCA), we found a delayed response peak and a prolonged response window under hypothermia. Hypothermia also decreased the activation area and the amplitude of the peak CBF. The combination of LSI and TCA is a high-resolution functional imaging method to investigate the spatiotemporal neurovascular coupling in both normal and pathological brain functions.

  4. Hypothermia blocks beta-catenin degradation after focal ischemia in rats.

    PubMed

    Zhang, Hanfeng; Ren, Chuancheng; Gao, Xuwen; Takahashi, Tetsuya; Sapolsky, Robert M; Steinberg, Gary K; Zhao, Heng

    2008-03-10

    Dephosphorylated and activated glycogen synthase kinase (GSK) 3beta hyperphosphorylates beta-catenin, leading to its ubiquitin-proteosome-mediated degradation. beta-catenin-knockdown increases while beta-catenin overexpression prevents neuronal death in vitro; in addition, protein levels of beta-catenin are reduced in the brain of Alzheimer's patients. However, whether beta-catenin degradation is involved in stroke-induced brain injury is unknown. Here we studied activities of GSK 3beta and beta-catenin, and the protective effect of moderate hypothermia (30 degrees C) on these activities after focal ischemia in rats. The results of Western blot showed that GSK 3beta was dephosphorylated at 5 and 24 h after stroke in the normothermic (37 degrees C) brain; hypothermia augmented GSK 3beta dephosphorylation. Because hypothermia reduces infarction, these results contradict with previous studies showing that GSK 3beta dephosphorylation worsens neuronal death. Nevertheless, hypothermia blocked degradation of total GSK 3beta protein. Corresponding to GSK 3beta activity in normothermic rats, beta-catenin phosphorylation transiently increased at 5 h in both the ischemic penumbra and core, and the total protein level of beta-catenin degraded after normothermic stroke. Hypothermia did not inhibit beta-catenin phosphorylation, but it blocked beta-catenin degradation in the ischemic penumbra. In conclusion, moderate hypothermia can stabilize beta-catenin, which may contribute to the protective effect of moderate hypothermia.

  5. Hypothermia during migraine attacks.

    PubMed

    Porta-Etessam, Jesús; Cuadrado, María L; Rodríguez-Gómez, Octavio; Valencia, Cristina; García-Ptacek, Sara

    2010-11-01

    Episodic spontaneous hypothermia is an infrequent disorder. Here, the case of a patient with migraine who experienced hypothermia during her migraine attacks is presented. The authors propose that larger clinical series should be studied to evaluate the occurrence of hypothermia in migraine, as well as the possible influence of some preventive regimens in this setting.

  6. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial

    PubMed Central

    Clifton, Guy L; Valadka, Alex; Zygun, David; Coffey, Christopher S; Drever, Pamala; Fourwinds, Sierra; Janis, L Scott; Wilde, Elizabeth; Taylor, Pauline; Harshman, Kathy; Conley, Adam; Puccio, Ava; Levin, Harvey S; McCauley, Stephen R; Bucholz, Richard D; Smith, Kenneth R; Schmidt, John H; Scott, James N; Yonas, Howard; Okonkwo, David O

    2013-01-01

    Summary Background The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury. We aimed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury. Methods The National Acute Brain Injury Study: Hypothermia II (NABIS: H II) was a randomised, multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada. Patients with non-penetrating brain injury who were 16–45 years old and were not responsive to instructions were randomly assigned (1:1) by a random number generator to hypothermia or normothermia. Patients randomly assigned to hypothermia were cooled to 35°C until their trauma assessment was completed. Patients who had none of a second set of exclusion criteria were either cooled to 33°C for 48 h and then gradually rewarmed or treated at normothermia, depending upon their initial treatment assignment. Investigators who assessed the outcome measures were masked to treatment allocation. The primary outcome was the Glasgow outcome scale score at 6 months. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, NCT00178711. Findings Enrolment occurred from December, 2005, to June, 2009, when the trial was terminated for futility. Follow-up was from June, 2006, to December, 2009. 232 patients were initially randomised a mean of 1·6 h (SD 0·5) after injury: 119 to hypothermia and 113 to normothermia. 97 patients (52 in the hypothermia group and 45 in the normothermia group) did not meet any of the second set of exclusion criteria. The mean time to 35°C for the 52 patients in the hypothermia group was 2·6 h (SD 1·2) and to 33°C was 4·4 h (1·5). Outcome was poor (severe disability, vegetative state, or death) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group (relative

  7. Hypothermia and Rewarming Induce Gene Expression and Multiplication of Cells in Healthy Rat Prostate Tissue

    PubMed Central

    Kaija, Helena; Pakanen, Lasse; Kortelainen, Marja-Leena; Porvari, Katja

    2015-01-01

    Prostate cancer has been extensively studied, but cellular stress responses in healthy prostate tissue are rarely investigated. Hypothermia is known to cause alterations in mRNA and protein expressions and stability. The aim of this study was to use normal rat prostate as a model in order to find out consequences of cold exposure and rewarming on the expressions of genes which are either members or functionally/structurally related to erythroblastic leukemia viral oncogene B (ErbB) signaling pathway. Relative mRNA expressions of amphiregulin (AMR), cyclin D1 (CyD1), cyclin-dependent kinase inhibitor 1A (p21), transmembrane form of the prostatic acid phosphatase (PAcP), thrombomodulin (TM) and heat shock transcription factor 1 (HSF1) in rat ventral prostate were quantified in mild (2 or 4.5 h at room temperature) and severe (2 or 4.5 h at +10°C) hypothermia and in rewarming after cold exposure (2 h at +10°C followed by 2 h at room temperature or 3 h at +28°C). AMR protein level, apoptotic Bcl-2 associated X protein to B-cell CLL/lymphoma 2 (Bax/Bcl-2) mRNA ratio and proliferative index Ki-67 were determined. 4.5-h mild hypothermia, 2-h severe hypothermia and rewarming increased expression of all these genes. Elevated proliferation index Ki-67 could be seen in 2-h severe hypothermia, and the proliferation index had its highest value in longer rewarming with totally recovered normal body temperature. Pro-apoptotic tendency could be seen in 2-h mild hypothermia while anti-apoptosis was predominant in 4.5-h mild hypothermia and in shorter rewarming with only partly recovered body temperature. Hypothermia and following rewarming promote the proliferation of cells in healthy rat prostate tissue possibly via ErbB signaling pathway. PMID:25996932

  8. Cooling the injured brain: how does moderate hypothermia influence the pathophysiology of traumatic brain injury.

    PubMed

    Sahuquillo, Juan; Vilalta, Anna

    2007-01-01

    Neither any neuroprotective drug has been shown to be beneficial in improving the outcome of severe traumatic brain injury (TBI) nor has any prophylactically-induced moderate hypothermia shown any beneficial effect on outcome in severe TBI, despite the optimism generated by preclinical studies. This contrasts with the paradox that hypothermia still is the most powerful neuroprotective method in experimental models because of its ability to influence the multiple biochemical cascades that are set in motion after TBI. The aim of this short review is to highlight the most recent developments concerning the pathophysiology of severe TBI, to review new data on thermoregulation and induced hypothermia, the regulation of core and brain temperature in mammals and the multiplicity of effects of hypothermia in the pathophysiology of TBI. Many experimental studies in the last decade have again confirmed that moderate hypothermia confers protection against ischemic and non-ischemic brain hypoxia, traumatic brain injury, anoxic injury following resuscitation after cardiac arrest and other neurological insults. Many posttraumatic adverse events that occur in the injured brain at a cellular and molecular level are highly temperature-sensitive and are thus a good target for induced hypothermia. The basic mechanisms through which hypothermia protects the brain are clearly multifactorial and include at least the following: reduction in brain metabolic rate, effects on cerebral blood flow, reduction of the critical threshold for oxygen delivery, blockade of excitotoxic mechanisms, calcium antagonism, preservation of protein synthesis, reduction of brain thermopooling, a decrease in edema formation, modulation of the inflammatory response, neuroprotection of the white matter and modulation of apoptotic cell death. The new developments discussed in this review indicate that, by targeting many of the abnormal neurochemical cascades initiated after TBI, induced hypothermia may modulate

  9. Deep hypothermia therapy attenuates LPS-induced microglia neuroinflammation via the STAT3 pathway.

    PubMed

    Tong, G; Krauss, A; Mochner, J; Wollersheim, S; Soltani, P; Berger, F; Schmitt, K R L

    2017-09-01

    Deep hypothermia therapy (HT) is a standard method for neuroprotection during complex pediatric cardiac surgery involving extracorporeal circulation and deep hypothermic cardiac arrest. The procedure, however, can provoke systemic inflammatory response syndrome (SIRS), one of the most severe side effects associated with pediatric cardiac surgery. To date, the cellular inflammatory mechanisms induced by deep HT remain to be elucidated. Therefore, we investigated the effects of deep HT (17°C) and rewarming on the inflammatory response in lipopolysaccharide (LPS) stimulated BV-2 murine microglia. Additionally, we also investigated the application of Stattic, a signal transducer and activator of transcription 3 (STAT3) activation inhibitor, as an alternative to physical cooling to attenuate the LPS-induced inflammatory response. Deep HT had no cytotoxic effect but attenuated microglia migration. IκBα degradation was delayed by deep HT resulting in the attenuation of pNF-κB p65 migration into the nucleus and significant decreases in pro-inflammatory IL-6, TNF-α, and MCP-1 expressions and secretions, as well as decreased anti-inflammatory IL-10 and SOCS3 expressions. Additionally, pStat3 was significantly down regulated under deep hypothermic conditions, also corresponding with the significant reduction in IL-6 and TNF-α expressions. Similar to the effects of HT, the application of Stattic under normothermic conditions resulted in significantly reduced IL-6 and TNF-α expressions. Moreover, attenuation of the inflammatory response resulted in decreased apoptosis in a direct co-culture of microglia and neurons. HT reduces the inflammatory response in LPS-stimulated BV-2 microglial cells, alluding to a possible mechanism of therapeutic hypothermia-induced neuroprotection. In the future, attenuating the phospho-STAT3 pathway may lead to the development of a neuroprotectant with greater clinical efficacy. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights

  10. History of accidental hypothermia.

    PubMed

    Guly, Henry

    2011-01-01

    Death from exposure to cold has been recognised for thousands of years but hypothermia as a clinical condition was not generally recognised until the mid-20th century and then only in extreme conditions such as immersion in cold water or snow. In the UK, hypothermia in less extreme conditions was not generally recognised until the 1960s. Recognition of hypothermia required the temperature to be measured and this did not become a clinical tool until the late 1800s and it was not used routinely until the early 1900s. Although John Hunter and James Curry did some physiological experiments in the 1700s, detailed physiological experiments were not done until the early 20th century and the use of therapeutic hypothermia for malignancy and in anaesthesia in the 1930s and 1940s provided more impetus for investigating the physiology of hypothermia in humans and familiarising the medical profession with measuring core temperatures. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Hypothermia--it's more than a toy.

    PubMed

    Pestel, Gunther J; Kurz, Andrea

    2005-04-01

    Perioperative hypothermia triples the incidence of adverse myocardial outcomes in high-risk patients; it significantly increases blood loss and augments allogeneic transfusion requirements. Even mild hypothermia increases the incidence of surgical wound infection following colon resection and therefore the duration of hospitalization. Hypothermia adversely affects antibody- and cell-mediated immune defenses, as well as the oxygen availability in the peripheral wound tissues. Mild perioperative hypothermia changes the kinetics and action of various anesthetic and paralyzing agents, increases thermal discomfort, and is associated with delayed postanesthetic recovery. On the other hand however, therapeutic hypothermia may be an interesting approach in various settings. Lowering core temperature to 32-34 degrees C may reduce cell injury by suppressing excitotoxins and oxygen radicals, stabilizing cell membranes, and reducing the number of abnormal electrical depolarizations. Evidence in animals indicates that even mild hypothermia provides substantial protection against cerebral ischemia and myocardial infarction. Mild hypothermia has been shown to improve outcome after cardiac arrest in humans. Randomized trials are in progress to evaluate the potential benefits of mild hypothermia during aneurysm clipping and after stroke or acute myocardial infarction. This article reviews recent publications in the field of accidental as well as therapeutic hypothermia, and tries to assess what evidence is available at the present time.

  12. Hypothermia protects against oxygen-glucose deprivation-induced neuronal injury by down-regulating the reverse transport of glutamate by astrocytes as mediated by neurons.

    PubMed

    Wang, D; Zhao, Y; Zhang, Y; Zhang, T; Shang, X; Wang, J; Liu, Y; Kong, Q; Sun, B; Mu, L; Liu, X; Wang, G; Li, H

    2013-05-01

    Glutamate is the major mediator of excitotoxic neuronal death following cerebral ischemia. Under severe ischemic conditions, glutamate transporters can functionally reverse to release glutamate, thereby inducing further neuronal injury. Hypothermia has been shown to protect neurons from brain ischemia. However, the mechanism(s) involved remain unclear. Therefore, the aim of this study was to investigate the mechanism(s) mediating glutamate release during brain ischemia-reperfusion injury under hypothermic conditions. Neuron/astrocyte co-cultures were exposed to oxygen-glucose deprivation (OGD) at various temperatures for 2h, and cell viability was assayed 12h after reoxygenation. PI and MAP-2 staining demonstrated that hypothermia significantly decreased neuronal injury. Furthermore, [(3)H]-glutamate uptake assays showed that hypothermia protected rat primary cortical cultures against OGD reoxygenation-induced injury. Protein levels of the astrocytic glutamate transporter, GLT-1, which is primarily responsible for the clearance of extracellular glutamate, were also found to be reduced in a temperature-dependent manner. In contrast, expression of GLT-1 in astrocyte-enriched cultures was found to significantly increase following the addition of neuron-conditioned medium maintained at 37 °C, and to a lesser extent with neuron-conditioned medium at 33 °C. In conclusion, the neuroprotective effects of hypothermia against brain ischemia-reperfusion injury involve down-regulation of astrocytic GLT-1, which mediates the reverse transport of glutamate. Moreover, this process may be regulated by molecules secreted by stressed neurons. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Hypothermia increases interleukin-6 and interleukin-10 in juvenile endotoxemic mice.

    PubMed

    Stewart, Corrine R; Landseadel, Jessica P; Gurka, Matthew J; Fairchild, Karen D

    2010-01-01

    To develop a juvenile mouse model to establish effects of in vivo hypothermia on expression of the inflammation-modulating cytokines tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-10. Although induced hypothermia is neuroprotective in some patients, the mechanisms of protection are not well understood and concerns remain over potential detrimental effects, particularly in the setting of infection. We previously showed that in vitro hypothermia increases production of tumor necrosis factor-alpha and interleukin-1beta in lipopolysaccharide-treated monocytes. : Laboratory investigation. Research laboratory. Juvenile (4-wk) male C57BL/6 mice. : Mice were given chlorpromazine to suspend thermoregulation and lipopolysaccharide to stimulate cytokine production. Core temperature was maintained at 32 degrees C or 37 degrees C for 6 hrs by adjusting environmental temperature. In separate experiments, lipopolysaccharide-treated mice were kept in a cooling chamber without chlorpromazine treatment. Plasma and organs were collected for cytokine quantitation. Chlorpromazine-treated hypothermic mice had 2.3-fold and 1.8-fold higher plasma interleukin-6 and interleukin-10 levels at 6 hrs compared with identically treated normothermic mice (p < .05), whereas plasma tumor necrosis factor-alpha and interleukin-1beta were not significantly different at 2 hrs or 6 hrs. Liver tumor necrosis factor-alpha and interleukin-6 were significantly higher in hypothermic vs. normothermic mice, but lung and brain cytokines were not different. Lipopolysaccharide-treated mice kept in a cooling chamber without chlorpromazine treatment developed varying degrees of hypothermia with associated increases in plasma interleukin-6 and interleukin-10. A nonspecific marker of stress (plasma corticosterone) was not affected by hypothermia in lipopolysaccharide-treated mice. Further studies are necessary to determine the mechanism and physiologic consequences of augmented systemic

  14. Therapeutic hypothermia as a bridge to transplantation in patients with fulminant hepatic failure

    PubMed Central

    Castillo, Luis; Bugedo, Guillermo; Rovegno, Max

    2015-01-01

    The most important topics in fulminant hepatic failure are cerebral edema and intracranial hypertension. Among all therapeutic options, systemic induced hypothermia to 33 - 34ºC has been reported to reduce the high pressure and increase the time during which patients can tolerate a graft. This review discusses the indications and adverse effects of hypothermia. PMID:25909316

  15. Kv7 (KCNQ) channel openers induce hypothermia in the mouse.

    PubMed

    Kristensen, Line V; Sandager-Nielsen, Karin; Hansen, Henrik H

    2011-01-20

    Kv7 channels, encoded by corresponding kcnq genes, are expressed both centrally and peripherally where they serve to dampen neuronal activity. While Kv7 channel openers have shown efficacy in neurological and neuropsychiatric disease models, the impact of Kv7 channel activation on physiological endpoint markers have not been addressed in detail. In this study we assessed the effect of a range of Kv7 channel openers with different affinity for neuronal Kv7.2-5 channel subunits on body temperature regulation in mice. Female NMRI mice were acutely exposed to vehicle (10% Tween-80, i.p.), retigabine (3-30 mg/kg, i.p., pan-Kv7 channel opener), (S)BMS-204352 (60-240 mg/kg, i.p., Kv7.4/5 channel-preferring opener), ICA-27243 (1-10mg/kg, i.p., Kv7.2/3 channel-preferring opener), or S-(1) (10-60 mg/kg, i.p., Kv7.2/3 channel-preferring opener), and rectal body temperature was measured 15-120 min post-injection. Retigabine (>10mg/kg), ICA-27243 (≥ 10 mg/kg), and S-(1) (≥ 30 mg/kg) dose-dependently lowered rectal body temperature with maximal doses of each Kv7 channel opener inducing a marked drop (>4°C) in rectal temperature. The Kv7 channel openers showed differential temporal pharmacodynamics, which likely reflects their different pharmacokinetic profiles. Pretreatment with the pan-Kv7 channel blocker XE-991 (1.0mg/kg, i.p.) completely reversed the hypothermic effect of the pan-Kv7 opener, retigabine (15 mg/kg), whereas ICA-27243-induced hypothermia (10mg/kg) could only be partially prevented by XE-991. Because ICA-27743 and S-(1) are Kv7.2/3 channel subunit-preferring compounds, this suggests that the Kv7.2/3 channel isoform is the predominant substrate for Kv7 channel opener-evoked hypothermia. These data indicate the physiological relevance of Kv7 channel function on body temperature regulation which may potentially reside from central inhibitory Kv7 channel activity. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Acetaminophen (Paracetamol) Induces Hypothermia During Acute Cold Stress.

    PubMed

    Foster, Josh; Mauger, Alexis R; Govus, Andrew; Hewson, David; Taylor, Lee

    2017-11-01

    Acetaminophen is an over-the-counter drug used to treat pain and fever, but it has also been shown to reduce core temperature (T c ) in the absence of fever. However, this side effect is not well examined in humans, and it is unknown if the hypothermic response to acetaminophen is exacerbated with cold exposure. To address this question, we mapped the thermoregulatory responses to acetaminophen and placebo administration during exposure to acute cold (10 °C) and thermal neutrality (25 °C). Nine healthy Caucasian males (aged 20-24 years) participated in the experiment. In a double-blind, randomised, repeated measures design, participants were passively exposed to a thermo-neutral or cold environment for 120 min, with administration of 20 mg/kg lean body mass acetaminophen or a placebo 5 min prior to exposure. T c , skin temperature (T sk ), heart rate, and thermal sensation were measured every 10 min, and mean arterial pressure was recorded every 30 min. Data were analysed using linear mixed effects models. Differences in thermal sensation were analysed using a cumulative link mixed model. Acetaminophen had no effect on T c in a thermo-neutral environment, but significantly reduced T c during cold exposure, compared with a placebo. T c was lower in the acetaminophen compared with the placebo condition at each 10-min interval from 80 to 120 min into the trial (all p < 0.05). On average, T c decreased by 0.42 ± 0.13 °C from baseline after 120 min of cold exposure (range 0.16-0.57 °C), whereas there was no change in the placebo group (0.01 ± 0.1 °C). T sk , heart rate, thermal sensation, and mean arterial pressure were not different between conditions (p > 0.05). This preliminary trial suggests that acetaminophen-induced hypothermia is exacerbated during cold stress. Larger scale trials seem warranted to determine if acetaminophen administration is associated with an increased risk of accidental hypothermia, particularly in vulnerable

  17. Enhanced dispersion of repolarization explains increased arrhythmogenesis in severe versus therapeutic hypothermia.

    PubMed

    Piktel, Joseph S; Jeyaraj, Darwin; Said, Tamer H; Rosenbaum, David S; Wilson, Lance D

    2011-02-01

    Hypothermia is proarrhythmic, and, as the use of therapeutic hypothermia (TH) increases, it is critically important to understand the electrophysiological effects of hypothermia on cardiac myocytes and arrhythmia substrates. We tested the hypothesis that hypothermia-enhanced transmural dispersion of repolarization (DOR) is a mechanism of arrhythmogenesis in hypothermia. In addition, we investigated whether the degree of hypothermia, the rate of temperature change, and cooling versus rewarming would alter hypothermia-induced arrhythmia substrates. Optical action potentials were recorded from cells spanning the transmural wall of canine left ventricular wedge preparations at baseline (36°C), during cooling and during rewarming. Electrophysiological parameters were examined while varying the depth of hypothermia. On cooling to 26°C, DOR increased from 26±4 ms to 93±18 ms (P=0.021); conduction velocity decreased from 35±5 cm/s to 22±5 cm/s (P=0.010). On rewarming to 36°C, DOR remained prolonged, whereas conduction velocity returned to baseline. Conduction block and reentry was observed in all severe hypothermia preparations. Ventricular fibrillation/ventricular tachycardia was seen more during rewarming (4/5) versus cooling (2/6). In TH (n=7), cooling to 32°C mildly increased DOR (31±6 to 50±9, P=0.012), with return to baseline on rewarming and was associated with decreased arrhythmia susceptibility. Increased rate of cooling did not further enhance DOR or arrhythmogenesis. Hypothermia amplifies DOR and is a mechanism for arrhythmogenesis. DOR is directly dependent on the depth of cooling and rewarming. This provides insight into the clinical observation of a low incidence of arrhythmias in TH and has implications for protocols for the clinical application of TH.

  18. [Assessment of therapeutic passive hypothermia in newborns with hypoxic-ischemic encephalopathy that need interhospital transport].

    PubMed

    Fuentes-Ruiz, José A; Lagares-Franco, Carolina; Rodríguez-Molina, Óscar; Cordero-Cañas, Enrique; Benavente-Fernández, Isabel

    2015-04-01

    Induced hypothermia for the first hours of life in a newborn is an effective treatment to reduce mortality and serious effects in neonates that had suffered a hypoxia episode. This method needs an universal attendance independently of the place of birth being usually necessary a transfer to the reference hospital. To analyze the efficacy of the newborn with hypoxic-ischemic encephalopathy transfer in passive hypothermia. Descriptive study of series of cases with retrospective character of newborn from Cadiz's province that need induced hypothermia. 46 newborn were included in the study: 33 of them (71.74%) needed being transfer by the Critical Patients Transport service (CPT group), the rest (28.26%) were born into the reference hospital. Both groups are similar in age gestational at birth, sex, weight and hypoxic-ischemic encephalopathy degree. It analyzed variables related to hypothermia therapy and in addition in CPT group transfer specific variables. At discharge, it does not exist significant differences between groups in the efficiency-consequence of neuroprotection therapy with hypothermia (p = 0.159). It does not find complications derived from the interhospital move. Neonatal inter-hospital transfer in passive therapeutic hypothermia is effective, safe and necessary for the therapy compliance. It is required reach an agreement between the attendance and the reference service, setting up guides for the support and suitable range of temperature.

  19. Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chan, Ming-Huan; Institute of Neuroscience, National Changchi University, Taipei, Taiwan; Chung, Shiang-Sheng

    Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-D-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDAmore » receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. -- Highlights: ► Toluene induces impairments in Rotarod test and novel object recognition test. ► Toluene lowers rectal temperature and ICSS thresholds in mice. ► Sarcosine reverses toluene-induced changes in motor, memory and body temperature. ► Sarcosine pretreatment does not affect toluene-induced

  20. [Prevention of adriamycin-induced alopecia by scalp hypothermia with a deep-frozen Duncool-Cap].

    PubMed

    Konishi, Y; Kuroki, T

    1988-11-01

    In order to prevent Adriamycin (ADM)-induced alopecia, scalp hypothermia with a Duncool-Cap frozen in a freezer at -70 degrees C was carried out. Of the 18 patients studied, one patient given total ADM doses of 240 mg developed alopecia of moderate degree, and another patient treated with ADM at a dose level of 50 mg developed mild alopecia. Alopecia could be almost completely prevented in 10 of the 11 patients given total ADM doses of 100 mg or less, and in 6 of the 7 patients given total doses of 200 mg or more.

  1. Therapeutic Hypothermia for Neuroprotection

    PubMed Central

    Karnatovskaia, Lioudmila V.; Wartenberg, Katja E.

    2014-01-01

    The earliest recorded application of therapeutic hypothermia in medicine spans about 5000 years; however, its use has become widespread since 2002, following the demonstration of both safety and efficacy of regimens requiring only a mild (32°C-35°C) degree of cooling after cardiac arrest. We review the mechanisms by which hypothermia confers neuroprotection as well as its physiological effects by body system and its associated risks. With regard to clinical applications, we present evidence on the role of hypothermia in traumatic brain injury, intracranial pressure elevation, stroke, subarachnoid hemorrhage, spinal cord injury, hepatic encephalopathy, and neonatal peripartum encephalopathy. Based on the current knowledge and areas undergoing or in need of further exploration, we feel that therapeutic hypothermia holds promise in the treatment of patients with various forms of neurologic injury; however, additional quality studies are needed before its true role is fully known. PMID:24982721

  2. Possible involvement of opioid receptors in moclobemide-induced hypothermia in mice.

    PubMed

    Ginawi, O T

    2003-09-01

    Effect of moclobemide, a selective monoamine oxidase-type A enzyme inhibitor, was investigated on the body temperature of male mice. Moclobemide (15-30 mg kg(-1), i.p.) produced significant reductions of body temperature in both normal and yeast-induced hyperthermic male mice. The hypothermic effect of moclobemide was moderate and short-lasting. Moclobemide-induced hypothermia was not antagonized by previous administration of prazosin (10 and 20 mg kg(-1), s.c.), propranolol (5, 10, and 20 mg kg(-1), s.c.), haloperidol (2 and 10 mg kg(-1), s.c.), atropine (10 and 20 mg kg(-1), s.c.), mepyramine (25 and 50 mg kg(-1), s.c.), or methysergide (0.5, 1, and 2 mg kg(-1), s.c.). Pretreatment with the opioid antagonist naloxone (10 mg kg(-1), s.c.), however, was able to reverse the hypothermic effect of moclobemide (30 mg kg(-1), i.p.) in both normal and yeast-induced hyperthermic mice. The present results indicate a possible role for central opioid receptors in the hypothermic effect of moclobemide. Also, a peripheral component for this effect of moclobemide at the mitochondria of peripheral tissues is suspected. The peripheral tissue mitochondria could be considered a common target for moclobemide and opioids actions on body temperature.

  3. Cannabidiol fails to reverse hypothermia or locomotor suppression induced by Δ(9) -tetrahydrocannabinol in Sprague-Dawley rats.

    PubMed

    Taffe, Michael A; Creehan, Kevin M; Vandewater, Sophia A

    2015-04-01

    Growing evidence shows cannabidiol (CBD) modulates some of the effects of Δ(9) -tetrahydrocannabinol (THC). CBD is a constituent of some strains of recreational cannabis but its content is highly variable. High CBD strains may have less memory-impairing effects than low-CBD strains and CBD can reverse behavioural effects of THC in monkeys. CBD/THC interactions in rodents are more complicated as CBD can attenuate or exacerbate the effects of THC. This study was undertaken to determine if CBD could reverse hypothermia or hypolocomotor effects caused by THC in rats. Male Sprague-Dawley rats were prepared with radiotelemetry devices and then given doses of THC (10-30 mg·kg(-1) , i.p.) with or without CBD. Experiments determined the effect of simultaneous or 30 min pretreatment with CBD in a 1:1 ratio with THC, as well as the effect of CBD in a 3:1 ratio. Additional experiments determined the effects of pretreatment with the cannabinoid CB1 receptor antagonist SR141716 (rimonabant). CBD did not attentuate THC-induced hypothermia or hypolocomotion but instead exaggerated these effects in some conditions. The antagonist SR141716 blocked hypolocomotor effects of THC for the first hour after injection and the hypothermia for 6 h; thus validating the pharmacological model. There is no evidence from this study that elevated CBD content in cannabis could provide protection from the physiological effects of THC, in rats. © 2014 The British Pharmacological Society.

  4. Adrenocortical response in rats subjected to a stress of restraint by immobilization whether accompanied by hypothermia or not

    NASA Technical Reports Server (NTRS)

    Buchel, L.; Prioux-Guyonneau, M.; Libian, L.

    1980-01-01

    The restraint associated with hypothermia which increases the adrenal activity in rats was investigated. In rats with nomothermia or light hypothermia, the plasma and adrenal corticosterone levels increase at least threefold whatever the duration of restraint. Their return to normal values depends on the duration of the restraint. Exposure to cold produces in free rats a light hypothermia with an increase of the plasma and adrenal corticosterone levels, and in restraint animals an important hypothermia which does not potentiate the stimulation of adrenocortical activity induced by the restraint alone.

  5. Possible long-acting risperidone-induced hypothermia precipitating phenytoin toxicity in an elderly patient.

    PubMed

    Brandon Bookstaver, P; Miller, A D

    2011-06-01

    Thermodysregulation, including hypothermia, is recognized as a potential adverse effect secondary to atypical antipsychotics. We report the first known case of hypothermia possibly associated with long-acting risperidone depot injection, precipitating further adverse events secondary to supratherapeutic phenytoin concentrations. A 75-year-old African-American female presented as a transfer from an outpatient psychiatric center with hypothermia (35·1 °C), bradycardia, altered mental status and a series of witnessed tonic-clonic seizures. The patient was discovered to be profoundly neutropenic (absolute neutrophil count = 266 × 10(9) /L) and a corrected phenytoin concentration was 147·708 μm. During the 3 months preceding admission, phenytoin dosing was stable and consecutive therapeutic concentrations were documented. The only recent change in medication regimen was a switch from oral risperidone to the long-acting injectable formulation. Upon discontinuation of the risperidone and phenytoin, the patient's mental status and laboratory abnormalities returned to baseline. The patient did not experience additional seizure activity. This unintentional significant drop in core body temperature may have resulted in altered metabolism of phenytoin leading to supratherapeutic concentrations and subsequent tonic-clonic seizures, bradycardia and neutropenia. Low core body temperatures can alter the pharmacokinetic profiles of hepatically metabolized medications, prompting careful patient assessment especially in those receiving medications with a narrow-therapeutic index. Hypothermia should be recognized as a potential adverse event with the long-acting injectable formulation of risperidone. © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

  6. Hypothermia broadens the therapeutic time window of mesenchymal stem cell transplantation for severe neonatal hypoxic ischemic encephalopathy.

    PubMed

    Ahn, So Yoon; Chang, Yun Sil; Sung, Dong Kyung; Sung, Se In; Park, Won Soon

    2018-05-16

    Recently, we have demonstrated that concurrent hypothermia and mesenchymal stem cells (MSCs) transplantation synergistically improved severe neonatal hypoxic ischemic encephalopathy (HIE). The current study was designed to determine whether hypothermia could extend the therapeutic time window of MSC transplantation for severe neonatal HIE. To induce HIE, newborn rat pups were exposed to 8% oxygen for 2 h following unilateral carotid artery ligation on postnatal day (P) 7. After approving severe HIE involving >50% of the ipsilateral hemisphere volume, hypothermia (32 °C) for 2 days was started. MSCs were transplanted 2 days after HIE modeling. Follow-up brain MRI, sensorimotor function tests, assessment of inflammatory cytokines in the cerebrospinal fluid (CSF), and histological evaluation of peri-infarction area were performed. HIE induced progressively increasing brain infarction area over time, increased cell death, reactive gliosis and brain inflammation, and impaired sensorimotor function. All these damages observed in severe HIE showed better, robust improvement with a combination treatment of hypothermia and delayed MSC transplantation than with either stand-alone therapy. Hypothermia itself did not significantly reduce brain injury, but broadened the therapeutic time window of MSC transplantation for severe newborn HIE.

  7. Hypothermia

    MedlinePlus

    Cold weather can affect your body in different ways. You can get frostbite, which is an injury to the ... Anyone who spends much time outdoors in cold weather can get hypothermia. You can also get it ...

  8. Mild hypothermia alleviates brain oedema and blood-brain barrier disruption by attenuating tight junction and adherens junction breakdown in a swine model of cardiopulmonary resuscitation

    PubMed Central

    Li, Jiebin; Li, Chunsheng; Yuan, Wei; Wu, Junyuan; Li, Jie; Li, Zhenhua; Zhao, Yongzhen

    2017-01-01

    Mild hypothermia improves survival and neurological recovery after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). However, the mechanism underlying this phenomenon is not fully elucidated. The aim of this study was to determine whether mild hypothermia alleviates early blood–brain barrier (BBB) disruption. We investigated the effects of mild hypothermia on neurologic outcome, survival rate, brain water content, BBB permeability and changes in tight junctions (TJs) and adherens junctions (AJs) after CA and CPR. Pigs were subjected to 8 min of untreated ventricular fibrillation followed by CPR. Mild hypothermia (33°C) was intravascularly induced and maintained at this temperature for 12 h, followed by active rewarming. Mild hypothermia significantly reduced cortical water content, decreased BBB permeability and attenuated TJ ultrastructural and basement membrane breakdown in brain cortical microvessels. Mild hypothermia also attenuated the CPR-induced decreases in TJ (occludin, claudin-5, ZO-1) and AJ (VE-cadherin) protein and mRNA expression. Furthermore, mild hypothermia decreased the CA- and CPR-induced increases in matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression and increased angiogenin-1 (Ang-1) expression. Our findings suggest that mild hypothermia attenuates the CA- and resuscitation-induced early brain oedema and BBB disruption, and this improvement might be at least partially associated with attenuation of the breakdown of TJ and AJ, suppression of MMP-9 and VEGF expression, and upregulation of Ang-1 expression. PMID:28355299

  9. Induction, maintenance, and reversal of therapeutic hypothermia with an esophageal heat transfer device.

    PubMed

    Kulstad, Erik; Metzger, Anja K; Courtney, D Mark; Rees, Jennifer; Shanley, Patrick; Matsuura, Timothy; McKnite, Scott; Lurie, Keith

    2013-11-01

    To evaluate a novel esophageal heat transfer device for use in inducing, maintaining, and reversing hypothermia. We hypothesized that this device could successfully induce, maintain (within a 1 °C range of goal temperature), and reverse, mild therapeutic hypothermia in a large animal model over a 30-h treatment protocol. Five female Yorkshire swine, weighing a mean of 65 kg (range 61-70) kg each, were anesthetized with inhalational isoflurane via endotracheal intubation and instrumented. The esophageal device was connected to an external chiller and then placed into the esophagus and connected to wall suction. Reduction to goal temperature was achieved by setting the chiller to cooling mode, and a 24h cooling protocol was completed before rewarming and recovering the animals. Histopathologic analysis was scheduled for 3-14 days after protocol completion. Average baseline temperature for the 5 animals was 38.6 °C (range 38.1-39.2 °C). All swine were cooled successfully, with average rate of temperature decrease of 1.3 °C/h (range 1.1-1.9) °C/h. Standard deviation from goal temperature averaged 0.2 °C throughout the steady-state maintenance phase, and no treatment for shivering was necessary during the protocol. Histopathology of esophageal tissue showed no adverse effects from the device. A new esophageal heat transfer device successfully and safely induced, maintained, and reversed therapeutic hypothermia in large swine. Goal temperature was maintained within a narrow range, and thermogenic shivering did not occur. These findings suggest a useful new modality to induce therapeutic hypothermia. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  10. Cannabidiol fails to reverse hypothermia or locomotor suppression induced by Ù9-tetrahydrocannabinol in Sprague-Dawley rats

    PubMed Central

    Taffe, Michael A; Creehan, Kevin M; Vandewater, Sophia A

    2015-01-01

    Background and Purpose Growing evidence shows cannabidiol (CBD) modulates some of the effects of Δ9-tetrahydrocannabinol (THC). CBD is a constituent of some strains of recreational cannabis but its content is highly variable. High CBD strains may have less memory-impairing effects than low-CBD strains and CBD can reverse behavioural effects of THC in monkeys. CBD/THC interactions in rodents are more complicated as CBD can attenuate or exacerbate the effects of THC. This study was undertaken to determine if CBD could reverse hypothermia or hypolocomotor effects caused by THC in rats. Experimental Approaches Male Sprague-Dawley rats were prepared with radiotelemetry devices and then given doses of THC (10–30 mg·kg−1, i.p.) with or without CBD. Experiments determined the effect of simultaneous or 30 min pretreatment with CBD in a 1:1 ratio with THC, as well as the effect of CBD in a 3:1 ratio. Additional experiments determined the effects of pretreatment with the cannabinoid CB1 receptor antagonist SR141716 (rimonabant). Key Results CBD did not attentuate THC-induced hypothermia or hypolocomotion but instead exaggerated these effects in some conditions. The antagonist SR141716 blocked hypolocomotor effects of THC for the first hour after injection and the hypothermia for 6 h; thus validating the pharmacological model. Conclusions and Implications There is no evidence from this study that elevated CBD content in cannabis could provide protection from the physiological effects of THC, in rats. PMID:25425111

  11. Transient Receptor Potential Channel Opening Releases Endogenous Acetylcholine, which Contributes to Endothelium-Dependent Relaxation Induced by Mild Hypothermia in Spontaneously Hypertensive Rat but Not Wistar-Kyoto Rat Arteries.

    PubMed

    Zou, Q; Leung, S W S; Vanhoutte, P M

    2015-08-01

    Mild hypothermia causes endothelium-dependent relaxations, which are reduced by the muscarinic receptor antagonist atropine. The present study investigated whether endothelial endogenous acetylcholine contributes to these relaxations. Aortic rings of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were contracted with prostaglandin F2 α and exposed to progressive mild hypothermia (from 37 to 31°C). Hypothermia induced endothelium-dependent, Nω-nitro-l-arginine methyl ester-sensitive relaxations, which were reduced by atropine, but not by mecamylamine, in SHR but not in WKY rat aortae. The responses in SHR aortae were also reduced by acetylcholinesterase (the enzyme responsible for acetylcholine degradation), bromoacetylcholine (inhibitor of acetylcholine synthesis), hemicholinium-3 (inhibitor of choline uptake), and vesamicol (inhibitor of acetylcholine release). The mild hypothermia-induced relaxations in both SHR and WKY rat aortae were inhibited by AMTB [N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide; the transient receptor potential (TRP) M8 inhibitor]; only those in SHR aortae were inhibited by HC-067047 [2-methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide; TRPV4 antagonist] while those in WKY rat aortae were reduced by HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; TRPA1 antagonist]. The endothelial uptake of extracellular choline and release of cyclic guanosine monophosphate was enhanced by mild hypothermia and inhibited by HC-067047 in SHR but not in WKY rat aortae. Compared with WKY rats, the SHR preparations expressed similar levels of acetylcholinesterase and choline acetyltransferase, but a lesser amount of vesicular acetylcholine transporter, located mainly in the endothelium. Thus, mild hypothermia causes nitric oxide-dependent relaxations by opening TRPA1 channels in WKY rat aortae

  12. Synergistic neuroprotective therapies with hypothermia

    PubMed Central

    Cilio, Maria Roberta; Ferriero, Donna M.

    2010-01-01

    summary Neuroprotection is a major health care priority, given the enormous burden of human suffering and financial cost caused by perinatal brain damage. With the advent of hypothermia as therapy for term hypoxic–ischemic encephalopathy, there is hope for repair and protection of the brain after a profound neonatal insult. However, it is clear from the published clinical trials and animal studies that hypothermia alone will not provide complete protection or stimulate the repair that is necessary for normal neurodevelopmental outcome. This review critically discusses drugs used to treat seizures after hypoxia–ischemia in the neonate with attention to evidence of possible synergies for therapy. In addition, other agents such as xenon, N-acetylcysteine, erythropoietin, melatonin and cannabinoids are discussed as future potential therapeutic agents that might augment protection from hypothermia. Finally, compounds that might damage the developing brain or counteract the neuroprotective effects of hypothermia are discussed. PMID:20207600

  13. Paradoxical undressing associated with subarachnoid hemorrhage in a non-hypothermia case?

    PubMed

    Descloux, Emilienne; Ducrot, Kewin; Scarpelli, Maria Pia; Lobrinus, Alexander; Palmiere, Cristian

    2017-09-01

    Paradoxical undressing is a phenomenon characterizing some fatal hypothermia cases. The victims, despite low environmental temperatures, paradoxically remove their clothes due to a sudden feeling of warmth. In this report, we describe a case of suspected paradoxical undressing in a non-hypothermia case. The victim, a 51-year-old Caucasian man, was found dead wearing only sneakers and socks. All other clothing was found in his car. Postmortem investigations allowed the hypothesis of hypothermia to be ruled out and revealed the presence of a ruptured cerebral aneurysm that caused a subarachnoid hemorrhage, the latter responsible for the death. The absence of any elements suggesting a voluntary undressing or any third party's DNA profile or involvement along with the possibility that the subarachnoid hemorrhage might have determined a hypothalamic injury, somehow rendered conceivable the hypothesis of an inappropriate feeling of warmth due to hemorrhage-induced dysregulation of the hypothalamic temperature-regulating centers.

  14. The Effect of Intraoperative Hypothermia on Shoulder Arthroplasty.

    PubMed

    Jildeh, Toufic R; Okoroha, Kelechi R; Marshall, Nathan E; Amato, Chad; Trafton, Hunter; Muh, Stephanie J; Kolowich, Patricia

    2018-05-16

    Limited evidence is available regarding the correlation between intraoperative hypothermia and perioperative complications in shoulder arthroplasty. The purpose of this study was to determine the incidence of intraoperative hypothermia in patients treated with shoulder arthroplasty and its effect on perioperative complications. A retrospective chart review was performed on 657 consecutive patients who underwent shoulder arthroplasty at a single institution between August 2013 and June 2016. Demographic data, surgery-specific data, postoperative complications, length of stay, and 30-day read-mission were recorded. Patients were classified as hypothermic if their mean intraoperative temperature was less than 36°C. Statistical analyses with univariate and multivariate logistic regression were performed to evaluate the association of intraoperative hypothermia with perioperative complications. The incidence of intraoperative hypothermia in shoulder arthroplasty was 52.7%. Increasing age (P=.002), lower body mass index (P=.006), interscalene anesthetic (P=.004), and lower white blood cell count (P<.001) demonstrated increased association with hypothermia. Longer operating room times and increased estimated blood loss were not found to be associated with intraoperative hypothermia. Hypothermia demonstrated no significant association with surgical site infections nor any other perioperative complications. Patients undergoing shoulder arthroplasty showed a high incidence of intraoperative hypothermia. Lower body mass index, increasing age, interscalene anesthetic, and lower white blood cell count were associated with an increased incidence of hypothermia. Contrary to previous studies, intraoperative hypothermia was not found to contribute to perioperative complications in shoulder arthroplasty. [Orthopedics. 201x; xx(x):xx-xx.]. Copyright 2018, SLACK Incorporated.

  15. Effect of enhanced geomagnetic activity on hypothermia and mortality in rats

    NASA Astrophysics Data System (ADS)

    Bureau, Y. R. J.; Persinger, M. A.; Parker, G. H.

    1996-12-01

    The hypothesis was investigated that variability in the severity of limbic seizure-induced hypothermia in rats was affected by ambient geomagnetic activity. Data were obtained in support of this hypothesis. The depth of the hypothermia was significantly ( P < 0.001) reduced if the ambient geomagnetic activity exceeded 35 nT to 40 nT. Mortality during the subsequent 5 days was increased when the geomagnetic activity was > 20 nT. The magnitude of the effect was comparable to the difference between exposure to light or to darkness during the 20 h after the induction of limbic seizures.

  16. A preliminary study on determining the time window of hypothermia cerebral protection in rat cortex by laser speckle flowmetry

    NASA Astrophysics Data System (ADS)

    Wang, Wenjia; Li, Qiang; Zeng, Shaoqun; Luo, Qingming; Li, Pengcheng

    2007-02-01

    Laser speckle imaging technique was used to characterize the spatiotemporal changes in cerebral blood flow (CBF) in rat cortex induced by the local ultraprofound hypothermia(0°C) with the duration time of 1 min, 2 min, 5 min, 7 min and 10 min. The experimental results showed significant difference of the spatiotemporal characteristics of changes in CBF between short term and long term of ultraprofound hypothermia. For the short duration of ultraprofound hypothermia (1 min, 2 min and 5 min), the hypothermia cause the CBF decrease firstly, and then the CBF increase rapidly when the temperature is recovered to 37°C, exceeding the baseline level and lasting 10+/-3 min, finally return to the baseline. This trend of changes in CBF is similar in the regions of artery, vein and parenchyma, but with different amplitude. For the duration time of 7 min, the changes in CBF also exhibit the similar decrease induced by ultraprofound hypothermia and the rapid increase induced by the temperature recovering, however the increase does not show the overshoot, but only reach around 75% of the baseline level. For the duration of 10 min of ultraprofound hypothermia, the CBF does not increase rapidly when the temperature is recovered to 37°C, but remains at the low level of CBF for 12+/-2 min, and then increases gradually at artery sites, or increases rapidly and then decrease slightly later at the vein and parenchyma sites. Similar as the case in the duration time of 7 min, the final CBF only recovers to about 75% of the baseline level. The experimental results suggest that the CBF can not recover to the baseline after a long duration of ultraprofound hypothermia longer than 7 min.

  17. Halting Hypothermia: Cold Can Be Dangerous

    MedlinePlus

    ... who spends much time outdoors in very cold weather can get hypothermia. But hypothermia can happen anywhere— ... just outside and not just in bitter winter weather. It can strike when temperatures are cool—for ...

  18. A Novel Method for Inducing Therapeutic Hypothermia in a Swine Model of Blast-Induced Traumatic Brain Injury with Associated Hemorrhagic Shock

    DTIC Science & Technology

    2012-05-01

    injury (TBI) remains a significant cause of mortality and morbidity in military and civilian life . The use of therapeutic hypothermia in the...of hypothermia using the lungs as a heat exchanger. Using an inhalant of perfluorocarbon (PFC) mist and heliox, evaporative cooling is achieved...animals has been built and bench tested. The device consists of a ventilator capable of delivering cooled respiratory gases and aerosol PFC into the

  19. Incidence of postoperative hypothermia and the relationship to clinical variables.

    PubMed

    Burns, Shari M; Piotrowski, Kathy; Caraffa, Guy; Wojnakowski, Mary

    2010-10-01

    A prospective, quantitative, correlational study was conducted to determine the incidence of postoperative hypothermia and the relationship of hypothermia to numerous clinical variables previously studied. The study reflects the researchers' interest in updating previous data regarding the incidence of hypothermia. Although hypothermia remains a significant clinical concern, interventions aimed at minimizing hypothermia have evolved over the past 20 years, thus prompting new interest in determining the extent to which hypothermia exists in today's PACU patients. A convenience sample of 287 adult, nonemergency patients scheduled for surgery were included in the study. Hypothermia (temperature <36°C) was demonstrated in only 4% of the sample (N = 287). Because of the low incidence of hypothermia, correlation statistics were not performed. The study provides a foundation for future research regarding this important clinical phenomenon while offering evidence supporting efforts to avoid hypothermia in today's surgical patients. Copyright © 2010 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

  20. Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia.

    PubMed

    Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling; Lai, Ted Weita

    2017-01-01

    Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8-24 h, whereas the late phase of BBB disruption begins 48-58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison

  1. Brief Rewarming Blunts Hypothermia-Induced Alterations in Sensation, Motor Drive and Cognition

    PubMed Central

    Brazaitis, Marius; Paulauskas, Henrikas; Skurvydas, Albertas; Budde, Henning; Daniuseviciute, Laura; Eimantas, Nerijus

    2016-01-01

    hypothermia-induced alterations in neural drive transmission (4.3 ± 0.5 vs. 3.4 ± 0.8 mV H-reflex and 4.9 ± 0.2 vs. 4.4 ± 0.4 mV V-wave, P < 0.05), which increased central fatigue during a 2-min maximum load (P < 0.05). Furthermore, only in brief warm water rewarming cerebral alterations were restored to the control level and it was indicated by shortened reaction times (P < 0.05). Conclusions: Brief rewarming in warm water rather than the same duration rewarming in thermoneutral environment blunted the hypothermia-induced alterations for sensation, motor drive, and cognition, despite the fact that rectal and deep muscle temperature remained lowered. PMID:27990123

  2. Feasibility and cardiac safety of inhaled xenon in combination with therapeutic hypothermia following out-of-hospital cardiac arrest.

    PubMed

    Arola, Olli J; Laitio, Ruut M; Roine, Risto O; Grönlund, Juha; Saraste, Antti; Pietilä, Mikko; Airaksinen, Juhani; Perttilä, Juha; Scheinin, Harry; Olkkola, Klaus T; Maze, Mervyn; Laitio, Timo T

    2013-09-01

    Preclinical studies reveal the neuroprotective properties of xenon, especially when combined with hypothermia. The purpose of this study was to investigate the feasibility and cardiac safety of inhaled xenon treatment combined with therapeutic hypothermia in out-of-hospital cardiac arrest patients. An open controlled and randomized single-centre clinical drug trial (clinicaltrials.gov NCT00879892). A multipurpose ICU in university hospital. Thirty-six adult out-of-hospital cardiac arrest patients (18-80 years old) with ventricular fibrillation or pulseless ventricular tachycardia as initial cardiac rhythm. Patients were randomly assigned to receive either mild therapeutic hypothermia treatment with target temperature of 33°C (mild therapeutic hypothermia group, n=18) alone or in combination with xenon by inhalation, to achieve a target concentration of at least 40% (Xenon+mild therapeutic hypothermia group, n=18) for 24 hours. Thirty-three patients were evaluable (mild therapeutic hypothermia group, n=17; Xenon+mild therapeutic hypothermia group, n=16). Patients were treated and monitored according to the Utstein protocol. The release of troponin-T was determined at arrival to hospital and at 24, 48, and 72 hours after out-of-hospital cardiac arrest. The median end-tidal xenon concentration was 47% and duration of the xenon inhalation was 25.5 hours. The frequency of serious adverse events, including inhospital mortality, status epilepticus, and acute kidney injury, was similar in both groups and there were no unexpected serious adverse reactions to xenon during hospital stay. In addition, xenon did not induce significant conduction, repolarization, or rhythm abnormalities. Median dose of norepinephrine during hypothermia was lower in xenon-treated patients (mild therapeutic hypothermia group=5.30 mg vs Xenon+mild therapeutic hypothermia group=2.95 mg, p=0.06). Heart rate was significantly lower in Xenon+mild therapeutic hypothermia patients during hypothermia

  3. Hypothermia and targeted temperature management in cats and dogs.

    PubMed

    Brodeur, Andrea; Wright, Annie; Cortes, Yonaira

    2017-03-01

    To review current knowledge surrounding the effects, treatment, and prognosis of hypothermia in people, dogs, and cats, as well as the application of therapeutic hypothermia in clinical medicine. Hypothermia may be a primary or secondary condition, and may be due to environmental exposure, illness, medications, anesthesia, or trauma. Hypothermia has been applied therapeutically in human medicine for a variety of conditions, including postcardiac arrest. In veterinary medicine, the technique has been applied in cardiac surgeries requiring bypass and in a patient with intractable seizures. Hypothermia can be diagnosed based on presenting temperature or clinical signs, and appropriate diagnosis may require nontraditional thermometers. Rewarming is the primary treatment for accidental hypothermia, with intensity ranging from passive surface rewarming to extracorporeal rewarming. The goal is to return the core temperature to a level that restores normal physiologic function of all body processes. Other supportive therapies such as intravenous fluids are typically indicated, and if cardiopulmonary arrest is present, prolonged resuscitation may be required. In cases of secondary hypothermia, reversal of the underlying cause is important. There are few prognostic indicators in human and veterinary patients with hypothermia. Even the most severely affected individuals, including those presenting in cardiopulmonary arrest, have potential for complete recovery with appropriate therapy. Therapeutic hypothermia has been shown to improve outcome in people following cardiac arrest. Further studies are needed to examine this application in veterinary medicine, as well as appropriate therapy and prognosis for cases of spontaneous hypothermia. © Veterinary Emergency and Critical Care Society 2017.

  4. Effects of prior aversive experience upon retrograde amnesia induced by hypothermia.

    PubMed

    Jensen, R A; Riccio, D C; Gehres, L

    1975-08-01

    Two experiments examined the extent to which retrograde amnesia (RA) is attenuated by prior learning experiences. In Experiment 1, rats initially received either passive avoidance training in a step-through apparatus, exposure to the apparatus, or noncontingent footshock. When training on a second but different passive avoidance task was followed by hypothermia treatment, RA was obtained only in the latter two groups. In Experiment 2, one-way active avoidance training, yoked noncontingent shocks, or apparatus exposure constituted the initial experience. Subsequent step-down passive avoidance training and amnestic treatment resulted in memory loss for the prior apparatus exposure group, but not for either of the preshocked conditions. These experiments demonstrate that certain types of prior aversive experience can substantially modify the magnitude of RA, and, in conjunction with other familiarization studies, emphasize a paradox for interpretations of RA based solely upon CNS disruption. The possibility that hypothermia treatment serves as an important contextual or encoding cue necessary for memory retrieval was considered. It was suggested that prior experience may block RA by enabling rats to differentiate training and treatment conditions.

  5. Cellular mechanisms of desynchronizing effects of hypothermia in an in vitro epilepsy model.

    PubMed

    Motamedi, Gholam K; Gonzalez-Sulser, Alfredo; Dzakpasu, Rhonda; Vicini, Stefano

    2012-01-01

    Hypothermia can terminate epileptiform discharges in vitro and in vivo epilepsy models. Hypothermia is becoming a standard treatment for brain injury in infants with perinatal hypoxic ischemic encephalopathy, and it is gaining ground as a potential treatment in patients with drug resistant epilepsy. However, the exact mechanism of action of cooling the brain tissue is unclear. We have studied the 4-aminopyridine model of epilepsy in mice using single- and dual-patch clamp and perforated multi-electrode array recordings from the hippocampus and cortex. Cooling consistently terminated 4-aminopyridine induced epileptiform-like discharges in hippocampal neurons and increased input resistance that was not mimicked by transient receptor potential channel antagonists. Dual-patch clamp recordings showed significant synchrony between distant CA1 and CA3 pyramidal neurons, but less so between the pyramidal neurons and interneurons. In CA1 and CA3 neurons, hypothermia blocked rhythmic action potential discharges and disrupted their synchrony; however, in interneurons, hypothermia blocked rhythmic discharges without abolishing action potentials. In parallel, multi-electrode array recordings showed that synchronized discharges were disrupted by hypothermia, whereas multi-unit activity was unaffected. The differential effect of cooling on transmitting or secreting γ-aminobutyric acid interneurons might disrupt normal network synchrony, aborting the epileptiform discharges. Moreover, the persistence of action potential firing in interneurons would have additional antiepileptic effects through tonic γ-aminobutyric acid release.

  6. Hypothermia in mouse is caused by adenosine A1 and A3 receptor agonists and AMP via three distinct mechanisms.

    PubMed

    Carlin, Jesse Lea; Jain, Shalini; Gizewski, Elizabeth; Wan, Tina C; Tosh, Dilip K; Xiao, Cuiying; Auchampach, John A; Jacobson, Kenneth A; Gavrilova, Oksana; Reitman, Marc L

    2017-03-01

    Small mammals have the ability to enter torpor, a hypothermic, hypometabolic state, allowing impressive energy conservation. Administration of adenosine or adenosine 5'-monophosphate (AMP) can trigger a hypothermic, torpor-like state. We investigated the mechanisms for hypothermia using telemetric monitoring of body temperature in wild type and receptor knock out (Adora1 -/- , Adora3 -/- ) mice. Confirming prior data, stimulation of the A 3 adenosine receptor (AR) induced hypothermia via peripheral mast cell degranulation, histamine release, and activation of central histamine H 1 receptors. In contrast, A 1 AR agonists and AMP both acted centrally to cause hypothermia. Commonly used, selective A 1 AR agonists, including N 6 -cyclopentyladenosine (CPA), N 6 -cyclohexyladenosine (CHA), and MRS5474, caused hypothermia via both A 1 AR and A 3 AR when given intraperitoneally. Intracerebroventricular dosing, low peripheral doses of Cl-ENBA [(±)-5'-chloro-5'-deoxy-N 6 -endo-norbornyladenosine], or using Adora3 -/- mice allowed selective stimulation of A 1 AR. AMP-stimulated hypothermia can occur independently of A 1 AR, A 3 AR, and mast cells. A 1 AR and A 3 AR agonists and AMP cause regulated hypothermia that was characterized by a drop in total energy expenditure, physical inactivity, and preference for cooler environmental temperatures, indicating a reduced body temperature set point. Neither A 1 AR nor A 3 AR was required for fasting-induced torpor. A 1 AR and A 3 AR agonists and AMP trigger regulated hypothermia via three distinct mechanisms. Published by Elsevier Ltd.

  7. Ghrelin-induced hypothermia: A Physiological basis but no clinical risk

    PubMed Central

    Wiedmer, Petra; Strasser, Florian; Horvath, Tamas L.; Blum, David; DiMarchi, Richard; Lutz, Thomas; Schürmann, Annette; Joost, Hans-Georg; Tschöp, Matthias H.; Tong, Jenny

    2011-01-01

    Ghrelin increases food intake and decreases energy expenditure, promoting a positive energy balance. We observed a single case of serious hypothermia during sustained ghrelin treatment in a male subject, suggesting that ghrelin may play a role in the regulation of body temperature. We therefore investigated the effect of ghrelin treatment on body temperature in rodents and humans under controlled conditions. Intriguingly, we could demonstrate ghrelin binding in axon terminals of the medial preoptic area of the hypothalamus located in the vicinity of cold-sensitive neurons. This localization of ghrelin receptors provides a potential anatomical basis for the regulation of body temperature by ghrelin. However, our follow-up studies also indicated that neither a chronic i.c.v. application of ghrelin in rats, nor a single s.c. injection under cold exposure in mice resulted in a relevant decrease in body core temperature. In addition, a four-hour intravenous ghrelin infusion did not decrease body surface temperature in healthy humans. We concluded that while there is a theoretical molecular basis for ghrelin to modify body temperature in mammals, its magnitude is irrelevant under physiologic circumstances. Hypothermia is not likely to represent a serious risk associated with this agent and pathway. PMID:21513721

  8. Hypothermia after cardiac arrest: expanding the therapeutic scope.

    PubMed

    Bernard, Stephen

    2009-07-01

    Therapeutic hypothermia for 12 to 24 hrs following resuscitation from out-of-hospital cardiac arrest is now recommended by the American Heart Association for the treatment of neurological injury when the initial cardiac rhythm is ventricular fibrillation. However, the role of therapeutic hypothermia is uncertain when the initial cardiac rhythm is asystole or pulseless electrical activity, or when the cardiac arrest is primarily due to a noncardiac cause, such as asphyxia or drug overdose. Given that survival rate in these latter conditions is very low, it is unlikely that clinical trials will be undertaken to test the efficacy of therapeutic hypothermia in this setting because of the very large sample size that would be required to detect a significant difference in outcomes. Therefore, in patients with anoxic brain injury after nonventricular fibrillation cardiac arrest, clinicians will need to balance the possible benefit of therapeutic hypothermia with the possible side effects of this therapy. Given that the side effects of therapeutic hypothermia are generally easily managed in the critical care setting, and there is benefit for anoxic brain injury demonstrated in laboratory studies, consideration may be given to treat comatose post-cardiac arrest patients with therapeutic hypothermia in this setting. Because the induction of therapeutic hypothermia has become more feasible with the development of simple intravenous cooling techniques and specialized equipment for improved temperature control in the critical care unit, it is expected that therapeutic hypothermia will become more widely used in the management of anoxic neurological injury whatever the presenting cardiac rhythm.

  9. Neonatal hypothermia in low-resource settings.

    PubMed

    Mullany, Luke C

    2010-12-01

    Hypothermia among newborns is considered an important contributor to neonatal morbidity and mortality in low-resource settings. However, in these settings only limited progress has been made towards understanding the risk of mortality after hypothermia, describing how this relationship is dependent on both the degree or severity of exposure and the gestational age and weight status of the baby, and implementing interventions to mitigate both exposure and the associated risk of poor outcomes. Given the centrality of averting neonatal mortality to achieving global milestones towards reductions in child mortality by 2015, recent years have seen substantial resources and efforts implemented to improve understanding of global epidemiology of neonatal health. In this article, a summary of the burden, consequences, and risk factors of neonatal hypothermia in low-resources settings is presented, with a particular focus on community-based data. Context-appropriate interventions for reducing hypothermia exposure and the role of these interventions in reducing global neonatal mortality burden are explored. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Therapeutic hypothermia: applications in pediatric cardiac arrest.

    PubMed

    Kochanek, Patrick M; Fink, Ericka L; Bell, Michael J; Bayir, Hülya; Clark, Robert S B

    2009-03-01

    There is a rich history for the use of therapeutic hypothermia after cardiac arrest in neonatology and pediatrics. Laboratory reports date back to 1824 in experimental perinatal asphyxia. Similarly, clinical reports in pediatric cold water drowning victims represented key initiating work in the field. The application of therapeutic hypothermia in pediatric drowning victims represented some of the seminal clinical use of this modality in modern neurointensive care. Uncontrolled application (too deep and too long) and unique facets of asphyxial cardiac arrest in children (a very difficult insult to affect any benefit) likely combined to result in abandonment of therapeutic hypothermia in the mid to late 1980s. Important studies in perinatal medicine have built upon the landmark clinical trials in adults, and are once again bringing therapeutic hypothermia into standard care for pediatrics. Although more work is needed, particularly in the use of mild therapeutic hypothermia in children, there is a strong possibility that this important therapy will ultimately have broad applications after cardiac arrest and central nervous system (CNS) insults in the pediatric arena.

  11. Hypometabolism and hypothermia in the rat model of endotoxic shock: independence of circulatory hypoxia

    PubMed Central

    Corrigan, Joshua J; Fonseca, Monique T; Flatow, Elizabeth A; Lewis, Kevin; Steiner, Alexandre A

    2014-01-01

    We tested the hypothesis that development of hypothermia instead of fever in endotoxic shock is consequential to hypoxia. Endotoxic shock was induced by bacterial lipopolysaccharide (LPS, 500 μg kg−1 i.v.) in rats at an ambient temperature of 22°C. A β3-adrenergic agonist known to activate metabolic heat production, CL316,243, was employed to evaluate whether thermogenic capacity could be impaired by the fall in oxygen delivery () during endotoxic shock. This possibility was rejected as CL316,243 (0.15 mg kg−1 i.v.) evoked similar rises in oxygen consumption () in the presence and absence of endotoxic shock. Next, to investigate whether a less severe form of circulatory hypoxia could be triggering hypothermia, the circulating volume of LPS-injected rats was expanded using 6% hetastarch with the intention of improving tissue perfusion and alleviating hypoxia. This intervention attenuated not only the fall in arterial pressure induced by LPS, but also the associated falls in and body temperature. These effects, however, occurred independently of hypoxia, as they were not accompanied by any detectable changes in NAD+/NADH ratios. Further experimentation revealed that even the earliest drops in cardiac output and during endotoxic shock did not precede the reduction in that brings about hypothermia. In fact, and fell in such a synchrony that the / ratio remained unaffected. Only when hypothermia was prevented by exposure to a warm environment (30°C) did an imbalance in the / ratio become evident, and such an imbalance was associated with reductions in the renal and hypothalamic NAD+/NADH ratios. In conclusion, hypometabolism and hypothermia in endotoxic shock are not consequential to hypoxia but serve as a pre-emptive strategy to avoid hypoxia in this model. PMID:24951620

  12. Impact of hypothermia in the rural, pediatric trauma patient.

    PubMed

    Waibel, Brett H; Durham, Chris A; Newell, Mark A; Schlitzkus, Lisa L; Sagraves, Scott G; Rotondo, Michael F

    2010-03-01

    Hypothermia is an independent predictor of mortality in adult trauma studies. However, the impact of hypothermia on the pediatric trauma population has not been described. The purpose of this study is to evaluate hypothermia as a cofactor to mortality, complications, and among survivors, hospital length of stay parameters in the pediatric trauma population. Retrospective review of a prospectively collected database (National Trauma Registry of the American College of Surgeons) over a 5-yr period (July 2002 to June 2007). A rural, level I trauma center. One thousand six hundred twenty-nine pediatric patients admitted with a traumatic injury. None. Multivariate regression models were used to evaluate the association of hypothermia with mortality, infectious complications, organ dysfunction, and among survivors, hospital length of stay parameters. Of 1,629 pediatric trauma patients admitted, 182 (11.1%) patients were hypothermic (temperature below 36 degrees C) on admission. Hypothermia had an adjusted odds ratio (AOR) of 2.41 (95% confidence interval [CI], 1.12-5.22, p = .025) for mortality. After controlling for covariates, hypothermia had associations with developing pneumonia (AOR, 0.185, 95% CI, 0.040-0.853; p = .031) and a bleeding diathesis (AOR, 3.14, 95% CI, 1.04-9.44; p = .042). The median days in the hospital, intensive care unit (ICU), and ventilator were longer in the hypothermic cohort; however, after controlling for covariates, hypothermia was not associated with differences in hospital days, ICU days, or ventilator days. Hypothermia is a common problem at admission among pediatric trauma patients. Hypothermia is associated with an increase in the odds of death and the development of a bleeding diathesis, while having decreased odds for developing pneumonia. While the length of stay indicators were longer in the hypothermic cohort among survivors, no significant association was noted with hypothermia for hospital, ICU, or ventilator days after

  13. Hypothermia for Intracranial Hypertension after Traumatic Brain Injury.

    PubMed

    Andrews, Peter J D; Sinclair, H Louise; Rodriguez, Aryelly; Harris, Bridget A; Battison, Claire G; Rhodes, Jonathan K J; Murray, Gordon D

    2015-12-17

    In patients with traumatic brain injury, hypothermia can reduce intracranial hypertension. The benefit of hypothermia on functional outcome is unclear. We randomly assigned adults with an intracranial pressure of more than 20 mm Hg despite stage 1 treatments (including mechanical ventilation and sedation management) to standard care (control group) or hypothermia (32 to 35°C) plus standard care. In the control group, stage 2 treatments (e.g., osmotherapy) were added as needed to control intracranial pressure. In the hypothermia group, stage 2 treatments were added only if hypothermia failed to control intracranial pressure. In both groups, stage 3 treatments (barbiturates and decompressive craniectomy) were used if all stage 2 treatments failed to control intracranial pressure. The primary outcome was the score on the Extended Glasgow Outcome Scale (GOS-E; range, 1 to 8, with lower scores indicating a worse functional outcome) at 6 months. The treatment effect was estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common odds ratio (with an odds ratio <1.0 favoring hypothermia). We enrolled 387 patients at 47 centers in 18 countries from November 2009 through October 2014, at which time recruitment was suspended owing to safety concerns. Stage 3 treatments were required to control intracranial pressure in 54% of the patients in the control group and in 44% of the patients in the hypothermia group. The adjusted common odds ratio for the GOS-E score was 1.53 (95% confidence interval, 1.02 to 2.30; P=0.04), indicating a worse outcome in the hypothermia group than in the control group. A favorable outcome (GOS-E score of 5 to 8, indicating moderate disability or good recovery) occurred in 26% of the patients in the hypothermia group and in 37% of the patients in the control group (P=0.03). In patients with an intracranial pressure of more than 20 mm Hg after traumatic brain injury, therapeutic hypothermia plus

  14. Mild perioperative hypothermia and the risk of wound infection.

    PubMed

    Flores-Maldonado, A; Medina-Escobedo, C E; Ríos-Rodríguez, H M; Fernández-Domínguez, R

    2001-01-01

    Bacterial destruction caused by free radicals, which are synthesized by neutrophils in the presence of oxygen, depends on adequate tissue perfusion. Mild perioperative hypothermia causes vasoconstriction, reducing nutrient and oxygen supply to wounds and increasing frequency of surgical wound infection. However, the causal role of hypothermia in surgical wound infection is the subject of controversy. The present work proposes the hypothesis that mild perioperative hypothermia is associated with infection of the surgical wound. A prospective cohort of 290 surgical patients was studied in a second-level hospital; 261 (90%) of the patients concluded the follow-up. The relationship of hypothermia and of other confounding factors, such as diabetes mellitus, antibiotic treatment, and wound drains with infection outcome was evaluated. One physician, blinded to patient hypothermia, gathered the data. Surgical wound infection was defined as the surgeon's diagnosis with positive culture. Twenty subjects (7.6%) showed infection of surgical wound; 18 (11.5%) of 156 hypothermics and two (2%) 105 normothermics (p = 0.004). Hypothermia proved to be a significant independent risk of infection with relative risk of 6.3 (p = 0.01). Mild perioperative hypothermia is associated with infection of the surgical wound and its prevention is therefore justified.

  15. Hypothermia for the treatment of ischemic and hemorrhagic stroke.

    PubMed

    Linares, Guillermo; Mayer, Stephan A

    2009-07-01

    Hypothermia is considered nature's "gold standard" for neuroprotection, and its efficacy for improving outcome in patients with hypoxic-ischemic brain injury as a result of cardiac arrest is well-established. Hypothermia reduces brain edema and intracranial pressure in patients with traumatic brain injury. By contrast, only a few small pilot studies have evaluated hypothermia as a treatment for acute ischemic stroke, and no controlled trials of hypothermia for hemorrhagic stroke have been performed. Logistic challenges present an important barrier to the widespread application of hypothermia for stroke, most importantly the need for high-quality critical care to start immediately in the emergency department. Rapid induction of hypothermia within 3 to 6 hrs of onset has been hampered by slow cooling rates, but is feasible. Delayed cooling for the treatment of cytotoxic brain edema does not provide definitive or lasting treatment for intracranial mass effect, and should not be used as an alternative to hemicraniectomy. Sustained fever control is feasible in patients with intracerebral and subarachnoid hemorrhage, but has yet to be tested in a phase III study. Important observations from studies investigating the use of hypothermia for stroke to date include the necessity for proactive antishivering therapy for successful cooling, the importance of slow controlled rewarming to avoid rebound brain edema, and the high risk for infectious and cardiovascular complications in this patient population. More research is clearly needed to bring us closer to the successful application of hypothermia in the treatment for stroke.

  16. Quantification of Induced Hypothermia from Aseptic Scrub Applications during Rodent Surgery Preparation

    PubMed Central

    Skorupski, Anna M; Zhang, Jingyi; Ferguson, Danielle; Lawrence, Frank

    2017-01-01

    Laboratory mice (Mus musculus) are prone to develop hypothermia during anesthesia for surgery, thus potentially impeding anesthetic recovery, wound healing, and future health. The core body temperatures of isoflurane-anesthetized mice are influenced by the choice of supplemental heat sources; however, the contribution of various surgical scrubs on the body temperatures of mice under gas anesthesia has not been assessed. We sought to quantify the effect of using alcohol (70% isopropyl alcohol [IPA]) compared with saline to rinse away surgical scrub on the progression of hypothermia in anesthetized mice (n = 47). IPA, room-temperature saline, or warmed saline (37 °C) was combined with povidone–iodine and then assessed for effects on core (rectal) and surface (infrared) temperatures. Agents were applied to a 2×2-cm shaved abdominal area of mice maintained on a water-recirculating blanket (at 38 °C) under isoflurane anesthesia (1.5% to 2.0% at 0.6 L/min) for 30 min. Although all scrub regimens significantly decreased body temperature at the time of application, treatments that included povidone–iodine led to the coldest core temperatures, which persisted while mice were anesthetized. Compared with room-temperature saline and when combined with povidone–iodine, warming of saline did not ameliorate heat loss. IPA alone demonstrated the most dramatic cooling of both surface and core readings at application but generated an unanticipated warming (rebound) phase during which body temperatures equilibrated with those of controls within minutes of application. Although alcohol is inappropriate as a stand-alone agent for surgical skin preparation, IPA is a viable alternative to saline-based rinses in this context, and its use should be encouraged within institutional guidance for rodent surgical procedures without concern for prolonged hypothermia in mice. PMID:28903829

  17. Nitric oxide system alteration at spinal cord as a result of perinatal asphyxia is involved in behavioral disabilities: hypothermia as preventive treatment.

    PubMed

    Dorfman, Verónica Berta; Rey-Funes, Manuel; Bayona, Julio César; López, Ester María; Coirini, Héctor; Loidl, César Fabián

    2009-04-01

    Perinatal asphyxia (PA) is able to induce sequelae such as spinal spasticity. Previously, we demonstrated hypothermia as a neuroprotective treatment against cell degeneration triggered by increased nitric oxide (NO) release. Because spinal motoneurons are implicated in spasticity, our aim was to analyze the involvement of NO system at cervical and lumbar motoneurons after PA as well as the application of hypothermia as treatment. PA was performed by immersion of both uterine horns containing full-term fetuses in a water bath at 37 degrees C for 19 or 20 min (PA19 or PA20) or at 15 degrees C for 20 min (hypothermia during PA-HYP). Some randomly chosen PA20 rats were immediately exposed for 5 min over grain ice (hypothermia after PA-HPA). Full-term vaginally delivered rats were used as control (CTL). We analyzed NO synthase (NOS) activity, expression and localization by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reactivity, inducible and neuronal NOS (iNOS and nNOS) by immunohistochemistry, and protein nitrotyrosilation state. We observed an increased NOS activity at cervical spinal cord of 60-day-old PA20 rats, with increased NADPH-d, iNOS, and nitrotyrosine expression in cervical motoneurons and increased NADPH-d in neurons of layer X. Lumbar neurons were not altered. Hypothermia was able to maintain CTL values. Also, we observed decreased forelimb motor potency in the PA20 group, which could be attributed to changes at cervical motoneurons. This study shows that PA can induce spasticity produced by alterations in the NO system of the cervical spinal cord. Moreover, this situation can be prevented by perinatal hypothermia.

  18. [Death in a rainwater tank--unusual death by hypothermia].

    PubMed

    Doberentz, Elke; Madea, Burkhard

    2013-01-01

    Death due to hypothermia is often accidental and associated with alcohol intoxication, diseases or previous trauma. A very rare phenomenon is suicidal hypothermia. A 74-year-old depressive woman was found dead in a rain barrel with her head above the water level in February at an outdoor temperature of 0 degrees C. Forensic autopsy did not reveal any findings typical of drowning. Likewise, there was no morphological evidence of hypothermia, but this cannot be expected in immersion hypothermia with a very short agony. Unusual situations at scene always require comprehensive police investigations and medicolegal examinations.

  19. Hypoxic-Ischemic Encephalopathy-Associated Liver Fatty Degeneration and the Effects of Therapeutic Hypothermia in Newborn Piglets.

    PubMed

    Kubo, Hiroyuki; Shimono, Ryuichi; Nakamura, Shinji; Koyano, Kosuke; Jinnai, Wataru; Yamato, Satoshi; Yasuda, Saneyuki; Nakamura, Makoto; Tanaka, Aya; Fujii, Takayuki; Kanenishi, Kenji; Chiba, Yoichi; Miki, Takanori; Kusaka, Takashi; Ueno, Masaki

    2017-01-01

    Although liver can be injured under the hypoxic-ischemic encephalopathy (HIE) condition, there is currently no histopathological evidence. Therapeutic hypothermia is used to protect the brain; however, the therapeutic potential for concomitant liver injury is unknown. This study aimed to histopathologically prove HIE-associated liver injury and to investigate the influence of therapeutic hypothermia in a newborn piglet HIE model. Eighteen newborn piglets were divided into 3 groups: control (n = 4), HIE (n = 8), and therapeutic hypothermia (n = 6) groups. The hypoxic insult was induced by decreasing the fraction of inspiratory oxygen from 21 to 2-4% over 40 min while monitoring cerebral blood volume and cerebral hemoglobin oxygen saturation. For therapeutic hypothermia, whole-body cooling at 33-34°C was administered for 24 h after the hypoxic insult. We hematologically and histopathologically investigated the liver injury in all groups. Alanine transaminase and lactate dehydrogenase levels in the HIE group were significantly elevated compared with those in the control group. Micro-lipid droplet accumulation in the periportal zone, but not in the perivenous zone, was significantly greater in the HIE group than in the control group and significantly smaller in the therapeutic hypothermia group than in the HIE group. We demonstrated that micro-lipid droplet accumulation in the cytoplasm of hepatocytes in the periportal zone occurs under the HIE condition and that this accumulation is suppressed by therapeutic hypothermia. © 2016 S. Karger AG, Basel.

  20. Fast therapeutic hypothermia prevents post-cardiac arrest syndrome through cyclophilin D-mediated mitochondrial permeability transition inhibition.

    PubMed

    Jahandiez, Vincent; Cour, Martin; Bochaton, Thomas; Abrial, Maryline; Loufouat, Joseph; Gharib, Abdallah; Varennes, Annie; Ovize, Michel; Argaud, Laurent

    2017-07-01

    The opening of the mitochondrial permeability transition pore (PTP), which is regulated by the matrix protein cyclophilin D (CypD), plays a key role in the pathophysiology of post-cardiac arrest (CA) syndrome. We hypothesized that therapeutic hypothermia could prevent post-CA syndrome through a CypD-mediated PTP inhibition in both heart and brain. In addition, we investigated whether specific pharmacological PTP inhibition would confer additive protection to cooling. Adult male New Zealand White rabbits underwent 15 min of CA followed by 120 min of reperfusion. Five groups (n = 10-15/group) were studied: control group (CA only), hypothermia group (HT, hypothermia at 32-34 °C induced by external cooling at reperfusion), NIM group (injection at reperfusion of 2.5 mg/kg NIM811, a specific CypD inhibitor), HT + NIM, and sham group. The following measurements were taken: hemodynamics, echocardiography, and cellular damage markers (including S100β protein and troponin Ic). Oxidative phosphorylation and PTP opening were assessed on mitochondria isolated from both brain and heart. Acetylation of CypD was measured by immunoprecipitation in both the cerebral cortex and myocardium. Hypothermia and NIM811 significantly prevented cardiovascular dysfunction, pupillary areflexia, and early tissue damage. Hypothermia and NIM811 preserved oxidative phosphorylation, limited PTP opening in both brain and heart mitochondria and prevented increase in CypD acetylation in brain. There were no additive beneficial effects in the combination of NIM811 and therapeutic hypothermia. In conclusion, therapeutic hypothermia limited post-CA syndrome by preventing mitochondrial permeability transition mainly through a CypD-dependent mechanism.

  1. Hypothermia therapy for newborns with hypoxic ischemic encephalopathy.

    PubMed

    Silveira, Rita C; Procianoy, Renato S

    2015-01-01

    Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 °C for selective head cooling and 33.5 °C for total body cooling. Temperatures lower than 32 °C are less neuroprotective, and temperatures below 30 °C are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6h after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 h, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate hypoxic-ischemic encephalopathy. Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and hypoxic-ischemic encephalopathy. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  2. Incidence and seasonality of hypothermia among newborns in southern Nepal.

    PubMed

    Mullany, Luke C; Katz, Joanne; Khatry, Subarna K; Leclerq, Steven C; Darmstadt, Gary L; Tielsch, James M

    2010-01-01

    To quantify incidence, age distribution, and seasonality of neonatal hypothermia among a large population cohort. Longitudinal cohort study. Sarlahi, Nepal. A total of 23 240 newborns born between September 2, 2002, and February 1, 2006. Main Exposures Community-based workers recorded axillary temperature on days 1 through 4, 6, 8, 10, 12, 14, 21, and 28 (213 636 total measurements). Regression smoothing was used to describe axillary temperature patterns during the newborn period. Hypothermia incidence in the first day, week, and month were estimated using standard cutoffs. Ambient temperatures allowed comparison of mild hypothermia (36.0 degrees C to <36.5 degrees C) and moderate or severe hypothermia (<36.0 degrees C) incidence over mean ambient temperature quintiles. Measurements lower than 36.5 degrees C were observed in 21 459 babies (92.3%); half (48.6%) had moderate or severe hypothermia, and risk peaked in the first 24 to 72 hours of life. Risk of moderate or severe hypothermia increased by 41.3% (95% confidence interval, 40.0%-42.7%) for every 5 degrees C decrease in average ambient temperature. Relative to the highest quintile, risk was 4.03 (95% confidence interval, 3.77-4.30) times higher among babies exposed to the lowest quintile of average ambient temperature. In the hot season, one-fifth of the babies (18.2%) were observed below the moderate hypothermia cutoff. Mild or moderate hypothermia was nearly universal, with substantially higher risk in the cold season. However, incidence in the hot season was also high; thus, year-round thermal care promotion is required. Research on community, household, and caretaker practices associated with hypothermia can guide behavioral interventions to reduce risk.

  3. Spontaneous periodic hypothermia and hyperhidrosis: a possibly novel cerebral neurotransmitter disorder.

    PubMed

    Rodrigues Masruha, Marcelo; Lin, Jaime; Arita, Juliana Harumi; De Castro Neto, Eduardo Ferreira; Scerni, Débora Amado; Cavalheiro, Esper Abrão; Mazzacoratti, Maria Da Graça Naffah; Vilanova, Luiz Celso Pereira

    2011-04-01

    Spontaneous periodic episodes of hypothermia still defy medical knowledge. In 1969, Shapiro et al. described the first two cases of spontaneous periodic hypothermia associated with agenesis of the corpus callosum. Recently, Dundar et al. reported a case of spontaneous periodic hypothermia and hyperhidrosis without corpus callosum agenesis, suggesting that the periodic episodes of hypothermia might be of epileptiform origin. Here we describe two paediatric patients with spontaneous periodic hypothermia without corpus callosum agenesis and demonstrate, to our knowledge for the first time, altered levels of neurotransmitter metabolites within the cerebrospinal fluid. © The Authors. Journal compilation © Mac Keith Press 2010.

  4. Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone Severe Sepsis Study Group.

    PubMed

    Clemmer, T P; Fisher, C J; Bone, R C; Slotman, G J; Metz, C A; Thomas, F O

    1992-10-01

    To evaluate the consequences of clinical hypothermia associated with sepsis syndrome and septic shock. Analysis of data from a multi-institutional, randomized, placebo-controlled, prospective study with predetermined end-point analysis of development of shock, recovery from shock, hospital length of stay, and death. Multi-institutional medical and surgical ICUs. Patients meeting predetermined criteria for severe sepsis syndrome. Appropriate sepsis and shock care with 50% of patients receiving methylprednisolone and 50% receiving placebo. The occurrence rate of hypothermia (< 35.5 degrees C) is 9% in this population. When compared with febrile patients, hypothermic patients had a higher frequency of central nervous system dysfunction (88% vs. 60%), increased serum bilirubin concentration (35% vs. 15%), prolonged prothrombin times (50% vs. 23%), shock (94% vs. 61%), failure to recover from shock (66% vs. 26%), and death (62% vs. 26%). The hypothermic patients were also more likely to be classified as having a rapidly or ultimately fatal disease upon study admission. This prospective study confirms that hypothermia associated with sepsis syndrome has a significant relationship to outcome manifest by increased frequency of shock and death from shock. This finding is in sharp contrast to the protective effects of induced hypothermia in septic animals and perhaps man.

  5. A clinical audit cycle of post-operative hypothermia in dogs.

    PubMed

    Rose, N; Kwong, G P S; Pang, D S J

    2016-09-01

    Use of clinical audits to assess and improve perioperative hypothermia management in client-owned dogs. Two clinical audits were performed. In Audit 1 data were collected to determine the incidence and duration of perioperative hypothermia (defined as rectal temperatures <37·0°C). The results from Audit 1 were used to reach consensus on changes to be implemented to improve temperature management, including re-defining hypothermia as rectal temperature <37·5°C. Audit 2 was performed after 1 month with changes in place. Audit 1 revealed a high incidence of post-operative hypothermia (88·0%) and prolonged time periods (7·5 hours) to reach normothermia. Consensus changes were to use a forced air warmer on all dogs and measure rectal temperatures hourly post-operatively until temperature ≥37·5°C. After 1 month with the implemented changes, Audit 2 identified a significant reduction in the time to achieve a rectal temperature of ≥37·5°C, with 75% of dogs achieving this goal by 3·5 hours. The incidence of hypothermia at tracheal extubation remained high in Audit 2 (97·3% with a rectal temperature <37·5°C). Post-operative hypothermia was improved through simple changes in practice, showing that clinical audit is a useful tool for monitoring post-operative hypothermia and improving patient care. Overall management of perioperative hypothermia could be further improved with earlier intervention. © 2016 British Small Animal Veterinary Association.

  6. Mild hypothermia alters midazolam pharmacokinetics in normal healthy volunteers.

    PubMed

    Hostler, David; Zhou, Jiangquan; Tortorici, Michael A; Bies, Robert R; Rittenberger, Jon C; Empey, Philip E; Kochanek, Patrick M; Callaway, Clifton W; Poloyac, Samuel M

    2010-05-01

    The clinical use of therapeutic hypothermia has been rapidly expanding due to evidence of neuroprotection. However, the effect of hypothermia on specific pathways of drug elimination in humans is relatively unknown. To gain insight into the potential effects of hypothermia on drug metabolism and disposition, we evaluated the pharmacokinetics of midazolam as a probe for CYP3A4/5 activity during mild hypothermia in human volunteers. A second objective of this work was to determine whether benzodiazepines and magnesium administered intravenously would facilitate the induction of hypothermia. Subjects were enrolled in a randomized crossover study, which included two mild hypothermia groups (4 degrees C saline infusions and 4 degrees C saline + magnesium) and two normothermia groups (37 degrees C saline infusions and 37 degrees C saline + magnesium). The lowest temperatures achieved in the 4 degrees C saline + magnesium and 4 degrees C saline infusions were 35.4 +/- 0.4 and 35.8 +/- 0.3 degrees C, respectively. A significant decrease in the formation clearance of the major metabolite 1'-hydroxymidazolam was observed during the 4 degrees C saline + magnesium compared with that in the 37 degrees C saline group (p < 0.05). Population pharmacokinetic modeling identified a significant relationship between temperature and clearance and intercompartmental clearance for midazolam. This model predicted that midazolam clearance decreases 11.1% for each degree Celsius reduction in core temperature from 36.5 degrees C. Midazolam with magnesium facilitated the induction of hypothermia, but shivering was minimally suppressed. These data provided proof of concept that even mild and short-duration changes in body temperature significantly affect midazolam metabolism. Future studies in patients who receive lower levels and a longer duration of hypothermia are warranted.

  7. [Prevention of perioperative hypothermia].

    PubMed

    Horn, Ernst-Peter; Torossian, Alexander

    2010-03-01

    Inadvertent perioperative hypothermia impairs postoperative outcome in surgical patients due to ischemic myocardial events, wound infections and coagulation disorders. Body core temperature should be assessed 1-2h preoperatively and continuously during surgery. To prevent hypothermia patients and nursing clinical staff should be teached and trained. Preoperatively surgical patients should always be prewarmed by using convective warming devices and active warming should be continued in surgeries longer than 1 hour. Warming of IV fluids is effective if infusion rates are above 1l/h. Core temperature should be measured in the recovery room and active warming should be started when patients are hypothermic or if they feel cold. Georg Thieme Verlag Stuttgart * New York.

  8. A microarray analysis of the effects of moderate hypothermia and rewarming on gene expression by human hepatocytes (HepG2).

    PubMed

    Sonna, Larry A; Kuhlmeier, Matthew M; Khatri, Purvesh; Chen, Dechang; Lilly, Craig M

    2010-09-01

    The gene expression changes produced by moderate hypothermia are not fully known, but appear to differ in important ways from those produced by heat shock. We examined the gene expression changes produced by moderate hypothermia and tested the hypothesis that rewarming after hypothermia approximates a heat-shock response. Six sets of human HepG2 hepatocytes were subjected to moderate hypothermia (31 degrees C for 16 h), a conventional in vitro heat shock (43 degrees C for 30 min) or control conditions (37 degrees C), then harvested immediately or allowed to recover for 3 h at 37 degrees C. Expression analysis was performed with Affymetrix U133A gene chips, using analysis of variance-based techniques. Moderate hypothermia led to distinct time-dependent expression changes, as did heat shock. Hypothermia initially caused statistically significant, greater than or equal to twofold changes in expression (relative to controls) of 409 sequences (143 increased and 266 decreased), whereas heat shock affected 71 (35 increased and 36 decreased). After 3 h of recovery, 192 sequences (83 increased, 109 decreased) were affected by hypothermia and 231 (146 increased, 85 decreased) by heat shock. Expression of many heat shock proteins was decreased by hypothermia but significantly increased after rewarming. A comparison of sequences affected by thermal stress without regard to the magnitude of change revealed that the overlap between heat and cold stress was greater after 3 h of recovery than immediately following thermal stress. Thus, while some overlap occurs (particularly after rewarming), moderate hypothermia produces extensive, time-dependent gene expression changes in HepG2 cells that differ in important ways from those induced by heat shock.

  9. Handling Hypothermia.

    ERIC Educational Resources Information Center

    Saho, S. Bamba

    1996-01-01

    Presents a unit on the body's response to hypothermia. Includes activities in which students measure the amount of heat absorbed by a white piece of cloth and a black piece of the same material, use cooperative-learning techniques to design a graphic organizer that explains metabolic responses to cold stress, and study the effect of temperature on…

  10. The feasibility of inducing mild therapeutic hypothermia after cardiac resuscitation using iced saline infusion via an intraosseous needle.

    PubMed

    Mader, Timothy J; Walterscheid, Joshua K; Kellogg, Adam R; Lodding, Cynthia C

    2010-01-01

    This study was done, using a swine model of prolonged ventricular fibrillation out-of-hospital cardiac arrest, to determine the feasibility of inducing therapeutic hypothermia after successful resuscitation by giving an intraosseous infusion of iced saline. This study was IACUC approved. Liter bags of normal saline, after being refrigerated for at least 24h, were placed in an ice filled cooler. Female Yorkshire swine weighing between 27 and 35 kg were sedated and instrumented under general anesthesia. A temperature probe was inserted 10 cm into the esophagus. Ventricular fibrillation was electrically induced and allowed to continue untreated for 10 min. Animals were randomized to one of two resuscitation schemes for the primary study (N=53). One group had central intravenous access for drug delivery and the other had an intraosseous needle inserted into the proximal tibia for drug administration. Animals in which spontaneous circulation was restored were immediately cooled, for this secondary study, by means of a rapid, pump-assisted infusion of 1L of iced saline either through the intraosseous needle (n=8), the central access (n=6), or a peripheral intravenous catheter (n=7) in a systematic, non-randomized fashion. Room, animal, and saline temperatures were recorded at initiation and upon completion of infusion. The data were analyzed descriptively using Stata SE v8.1 for Macintosh. The baseline characteristics of all three groups were mathematically the same. The average ambient room temperature during the experimental sessions was 25.5 degrees C (SD=1.3 degrees C). There were no statistically significant differences between the three groups with regard to saline temperature, rate of infusion, or decrease in core body temperature. The decrease in core temperature for the intraosseous group was 2.8 degrees C (95% CI=1.8, 3.8) over the infusion period. Mild therapeutic hypothermia can be effectively induced in swine after successful resuscitation of prolonged

  11. Childhood outcomes after hypothermia for neonatal encephalopathy.

    PubMed

    Shankaran, Seetha; Pappas, Athina; McDonald, Scott A; Vohr, Betty R; Hintz, Susan R; Yolton, Kimberly; Gustafson, Kathryn E; Leach, Theresa M; Green, Charles; Bara, Rebecca; Petrie Huitema, Carolyn M; Ehrenkranz, Richard A; Tyson, Jon E; Das, Abhik; Hammond, Jane; Peralta-Carcelen, Myriam; Evans, Patricia W; Heyne, Roy J; Wilson-Costello, Deanne E; Vaucher, Yvonne E; Bauer, Charles R; Dusick, Anna M; Adams-Chapman, Ira; Goldstein, Ricki F; Guillet, Ronnie; Papile, Lu-Ann; Higgins, Rosemary D

    2012-05-31

    We previously reported early results of a randomized trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy showing a significant reduction in the rate of death or moderate or severe disability at 18 to 22 months of age. Long-term outcomes are now available. In the original trial, we assigned infants with moderate or severe encephalopathy to usual care (the control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (the hypothermia group). We evaluated cognitive, attention and executive, and visuospatial function; neurologic outcomes; and physical and psychosocial health among participants at 6 to 7 years of age. The primary outcome of the present analyses was death or an IQ score below 70. Of the 208 trial participants, primary outcome data were available for 190. Of the 97 children in the hypothermia group and the 93 children in the control group, death or an IQ score below 70 occurred in 46 (47%) and 58 (62%), respectively (P=0.06); death occurred in 27 (28%) and 41 (44%) (P=0.04); and death or severe disability occurred in 38 (41%) and 53 (60%) (P=0.03). Other outcome data were available for the 122 surviving children, 70 in the hypothermia group and 52 in the control group. Moderate or severe disability occurred in 24 of 69 children (35%) and 19 of 50 children (38%), respectively (P=0.87). Attention-executive dysfunction occurred in 4% and 13%, respectively, of children receiving hypothermia and those receiving usual care (P=0.19), and visuospatial dysfunction occurred in 4% and 3% (P=0.80). The rate of the combined end point of death or an IQ score of less than 70 at 6 to 7 years of age was lower among children undergoing whole-body hypothermia than among those undergoing usual care, but the differences were not significant. However, hypothermia resulted in lower death rates and did not increase rates of severe disability among survivors. (Funded by the National Institutes of

  12. Hemodialysis as a treatment of severe accidental hypothermia.

    PubMed

    Caluwé, Rogier; Vanholder, Raymond; Dhondt, Annemieke

    2010-03-01

    We describe a case of severe accidental hypothermia (core body temperature 23.2 degrees C) successfully treated with hemodialysis in a diabetic patient with preexisting renal insufficiency. Consensus exists about cardiopulmonary bypass as the treatment of choice in cases of severe accidental hypothermia with cardiac arrest. Prospective randomized controlled trials comparing the different rewarming modalities for hemodynamically stable patients with hypothermia, however, are lacking. In our opinion, the choice of a rewarming technique should be patient tailored, knowing that hemodialysis is an efficient, minimally invasive, and readily available technique with the advantage of providing electrolyte support.

  13. Myocardial correlates of helium-cold induction and maintenance of hypothermia.

    NASA Technical Reports Server (NTRS)

    Anderson, G. L.; Prewitt, R., Jr.; Musacchia, X. J.

    1971-01-01

    Hypothermia was induced in the golden hamster Mesocricetus auratus, using the helium-cold method. The first group of hamsters was sacrificed immediately after induction to rectal temperature 7 C, a second group was sacrificed after being maintained at a body temperature of 7 C for 18-24 hr, and a third group consisted of unexposed controls. The hearts were excised and the ventricles analyzed for hypoxic damage, glycogen, and catecholamines. In the short-term hypothermic animals, resting tension was increased while peak isometric tension, generated tension after 10 min of anoxic exposure, glycogen, and catecholamines were all reduced. All of the functional parameters recovered in the long-term hypothermic group, while glycogen and catecholamines showed a trend toward recovery. It is concluded that myocardial hypoxia develops during induction into hypothermia when using the helium-cold method. This effect is reversible and hypoxic damage does not increase as the hypothermic exposure is prolonged.

  14. Short- and Long-Term Outcomes in Very Low Birth Weight Infants with Admission Hypothermia.

    PubMed

    Chang, Hung-Yang; Sung, Yi-Hsiang; Wang, Shwu-Meei; Lung, Hou-Ling; Chang, Jui-Hsing; Hsu, Chyong-Hsin; Jim, Wai-Tim; Lee, Ching-Hsiao; Hung, Hsiao-Fang

    2015-01-01

    Neonatal hypothermia remains a common problem and is related to elevated morbidities and mortality. However, the long-term neurodevelopmental effects of admission hypothermia are still unknown. This study attempted to determine the short-term and long-term consequences of admission hypothermia in VLBW preterm infants. This retrospective study measured the incidence and compared the outcomes of admission hypothermia in very low birth weight (VLBW) preterm infants in a tertiary-level neonatal intensive care unit. Infants were divided into the following groups: normothermia (36.5-37.5°C), mild hypothermia (36.0-36.4°C), moderate hypothermia (32.0-35.9°C), and severe hypothermia (< 32°C). We compared the distribution, demographic variables, short-term outcomes, and neurodevelopmental outcomes at 24 months of corrected age among groups. We studied 341 infants: 79 with normothermia, 100 with mild hypothermia, 162 with moderate hypothermia, and 0 with severe hypothermia. Patients in the moderate hypothermia group had significantly lower gestational ages (28.1 wk vs. 29.7 wk, P < .02) and smaller birth weight (1004 g vs. 1187 g, P < .001) compared to patients in the normothermia group. Compared to normothermic infants, moderately hypothermic infants had significantly higher incidences of 1-min Apgar score < 7 (63.6% vs. 31.6%, P < .001), respiratory distress syndrome (RDS) (58.0% vs. 39.2%, P = .006), and mortality (18.5% vs. 5.1%, P = .005). Moderate hypothermia did not affect neurodevelopmental outcomes at 2 years' corrected age. Mild hypothermia had no effect on short-term or long-term outcomes. Admission hypothermia was common in VLBW infants and correlated inversely with birth weight and gestational age. Although moderate hypothermia was associated with higher RDS and mortality rates, it may play a limited role among multifactorial causes of neurodevelopmental impairment.

  15. Hypothermia augments neuroprotective activity of mesenchymal stem cells for neonatal hypoxic-ischemic encephalopathy.

    PubMed

    Park, Won Soon; Sung, Se In; Ahn, So Yoon; Yoo, Hye Soo; Sung, Dong Kyung; Im, Geun Ho; Choi, Soo Jin; Chang, Yun Sil

    2015-01-01

    Though hypothermia is the only clinically available treatment for neonatal hypoxic-ischemic encephalopathy (HIE), it is not completely effective in severe cases. We hypothesized that combined treatment with hypothermia and transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) would synergistically attenuate severe HIE compared to stand-alone therapy. To induce hypoxia-ischemia (HI), male Sprague-Dawley rats were subjected to 8% oxygen for 120 min after unilateral carotid artery ligation on postnatal day (P) 7. After confirmation of severe HIE involving >50% of the ipsilateral hemisphere volume as determined by diffusion-weighted brain magnetic resonance imaging (MRI) within 2 h after HI, intraventricular MSC transplantation (1 × 105 cells) and/or hypothermia with target temperature at 32°C for 24 h were administered 6 h after induction of HI. Follow-up brain MRI at P12 and P42, sensorimotor function tests at P40-42, evaluation of cytokines in the cerebrospinal fluid (CSF) at P42, and histologic analysis of peri-infarct tissues at P42 were performed. Severe HI resulted in progressively increased brain infarction over time as assessed by serial MRI, increased number of cells positive for terminal deoxynucleotidyl transferase nick-end labeling, microgliosis and astrocytosis, increased CSF cytokine levels, and impaired function in behavioral tests such as rotarod and cylinder tests. All of the abnormalities observed in severe HIE showed greater improvement after combined treatment with hypothermia and MSC transplantation than with either therapy alone. Overall, these findings suggest that combined treatment with hypothermia and human UCB-derived MSC transplantation might be a novel therapeutic modality to improve the prognosis of severe HIE, an intractable disease that currently has no effective treatment.

  16. Susceptibility of ascending dopamine projections to 6-hydroxydopamine in rats: effect of hypothermia.

    PubMed

    Grant, R J; Clarke, P B S

    2002-01-01

    The aims of this study were to determine (1) whether mesolimbic and nigrostriatal DA cell bodies degenerate to different extents after 6-hydroxydopamine (6-OHDA) is administered into their respective terminal fields and (2) whether hypothermia, associated with sodium pentobarbital anesthesia, protects DA neurons from the toxic effects of 6-OHDA. To address these questions, 6-OHDA or vehicle was infused into either the ventral or dorsal striatum or into the medial forebrain bundle, under conditions of brain normothermia or hypothermia. Two weeks post-surgery, tyrosine hydroxylase-positive cell bodies were counted in the ventral tegmental area (VTA) and substantia nigra. In addition, autoradiographic labeling of tyrosine hydroxylase protein and dopamine transporter was quantified in dopamine terminal fields and cell body areas. Overall, DA cell bodies in the VTA were substantially less susceptible than those in the substantia nigra to depletion of dopaminergic markers. Hypothermia provided two types of neuroprotection. The first occurred when 6-OHDA was administered into the dorsal striatum, and was associated with a 30-50% increase in residual dopaminergic markers in the lateral portion of the VTA. The second neuroprotective effect of hypothermia occurred when 6-OHDA was given into the medial forebrain bundle. This was associated with a 200-300% increase in residual dopaminergic markers in the mesolimbic and nigrostriatal terminal fields; no significant protection occurred in the cell body regions.Collectively, these findings show that (1) the dopaminergic somata in the substantia nigra are more susceptible than those in the VTA to 6-OHDA-induced denervation, and (2) hypothermia can provide anatomically selective neuroprotection within the substantia nigra-VTA cell population. The continued survival of mesolimbic dopamine cell bodies after a 6-OHDA lesion may have functional implications relating to drugs of abuse, as somatodendritic release of dopamine in the VTA

  17. Hand-touch method for detection of neonatal hypothermia in Nepal.

    PubMed

    Tuitui, Roshani Laxmi; Suwal, Satya Narayan; Shrestha, Sarala

    2011-06-01

    Neonatal hypothermia is the fourth leading causes of neonatal death in Nepal. Thus, it is the caregivers' responsibility to identify the hypothermia by using valid and less time consuming method like hand-touch method. Therefore, we examined the diagnostic validity of hand-touch method against low-reading mercury (LRM) thermometer for detecting neonatal hypothermia. We assessed neonate's temperature first by hand-touch method, then by LRM thermometer and tympanic thermometer among 100 full-term neonates, delivered within 24 h in Maternity Ward of Tribhuvan University Teaching Hospital, Nepal. We used World Health Organization (1997) criteria for classification of neonatal hypothermia. The sensitivity and specificity of the hand-touch method for detection of neonatal hypothermia were 95.6% and 70.1% against LRM thermometer and 76.6% and 83% against the tympanic thermometer, respectively. Touching method is practical and therefore has a good diagnostic validity; it can be introduced in essential newborn care package after giving adequate training to caregivers.

  18. Xenon and hypothermia combine to provide neuroprotection from neonatal asphyxia.

    PubMed

    Ma, Daqing; Hossain, Mahmuda; Chow, Andre; Arshad, Mubarik; Battson, Renee M; Sanders, Robert D; Mehmet, Huseyin; Edwards, A David; Franks, Nicholas P; Maze, Mervyn

    2005-08-01

    Perinatal asphyxia can result in neuronal injury with long-term neurological and behavioral consequences. Although hypothermia may provide some modest benefit, the intervention itself can produce adverse consequences. We have investigated whether xenon, an antagonist of the N-methyl-D-aspartate subtype of the glutamate receptor, can enhance the neuroprotection provided by mild hypothermia. Cultured neurons injured by oxygen-glucose deprivation were protected by combinations of interventions of xenon and hypothermia that, when administered alone, were not efficacious. A combination of xenon and hypothermia administered 4 hours after hypoxic-ischemic injury in neonatal rats provided synergistic neuroprotection assessed by morphological criteria, by hemispheric weight, and by functional neurological studies up to 30 days after the injury. The protective mechanism of the combination, in both in vitro and in vivo models, involved an antiapoptotic action. If applied to humans, these data suggest that low (subanesthetic) concentrations of xenon in combination with mild hypothermia may provide a safe and effective therapy for perinatal asphyxia.

  19. ThermoSpots to detect hypothermia in children with severe acute malnutrition.

    PubMed

    Mole, Thomas B; Kennedy, Neil; Ndoya, Noel; Emond, Alan

    2012-01-01

    Hypothermia is a risk factor for increased mortality in children with severe acute malnutrition (SAM). Yet frequent temperature measurement remains unfeasible in under-resourced units in developing countries. ThermoSpot is a continuous temperature monitoring sticker designed originally for neonates. When applied to skin, its liquid crystals are designed to turn black with hypothermia and remain green with normothermia. To (i) estimate the diagnostic accuracy of ThermoSpots for detecting WHO-defined hypothermia (core temperature <35.5°C or peripheral temperature <35.0°C) in children with SAM and (ii) determine their acceptability amongst mothers. Children with SAM in a malnutrition unit in Malawi were enrolled during March-July 2010. The sensitivity and specificity of ThermoSpots were calculated by comparing the device colour against 'gold standard' rectal temperatures taken on admission and follow up peripheral temperatures taken until discharge. Guardians completed a questionnaire to assess acceptability. Hypothermia was uncommon amongst the 162 children enrolled. ThermoSpot successfully detected the one rectal temperature and two peripheral temperatures recorded that met the WHO definition of hypothermia. Overall, 3/846 (0.35%) temperature measurements were in the WHO-defined hypothermia range. Interpreting the brown transition colour (between black and green) as hypothermia improved sensitivities. For milder hypothermia definitions, sensitivities declined (<35.4°C, 50.0%; <35.9°C, 39.2%). Specificity was consistently above 94%. From questionnaires, 40/43 (93%) mothers reported they were 90-100% happy with the device overall. Free-text answers revealed themes of "Skin Rashes", "User-satisfaction" and "Empowerment". Although hypothermia was uncommon in this study, ThermoSpots successfully detected these episodes in malnourished children and were acceptable to mothers. Research in settings where hypothermia is common is needed to determine performance with

  20. Post-traumatic seizure susceptibility is attenuated by hypothermia therapy

    PubMed Central

    Atkins, Coleen M.; Truettner, Jessie S.; Lotocki, George; Sanchez-Molano, Juliana; Kang, Yuan; Alonso, Ofelia F.; Sick, Thomas J.; Dietrich, W. Dalton; Bramlett, Helen M.

    2010-01-01

    Traumatic brain injury (TBI) is a major risk factor for the subsequent development of epilepsy. Currently, chronic seizures after brain injury are often poorly controlled by available anti-epileptic drugs. Hypothermia treatment, a modest reduction in brain temperature, reduces inflammation, activates pro-survival signaling pathways, and improves cognitive outcome after TBI. Given the well-known effect of therapeutic hypothermia to ameliorate pathological changes in the brain after TBI, we hypothesized that hypothermia therapy may attenuate the development of post-traumatic epilepsy and some of the pathomechanisms that underlie seizure formation. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury, and then were maintained at normothermic or moderate hypothermic temperatures for 4 hr. At 12 weeks after recovery, seizure susceptibility was assessed by challenging the animals with pentylenetetrazole (PTZ), a GABAA receptor antagonist. PTZ elicited a significant increase in seizure frequency in TBI normothermic animals as compared to sham surgery animals and this was significantly reduced in TBI hypothermic animals. Early hypothermia treatment did not rescue chronic dentate hilar neuronal loss, nor did it improve loss of doublecortin-labeled cells in the dentate gyrus post-seizure. However, mossy fiber sprouting was significantly attenuated by hypothermia therapy. These findings demonstrate that reductions in seizure susceptibility after TBI are improved with post-traumatic hypothermia and provide a new therapeutic avenue for the treatment of post-traumatic epilepsy. PMID:21044182

  1. Therapeutic hypothermia in patients following traumatic brain injury: a systematic review.

    PubMed

    Dunkley, Steven; McLeod, Anne

    2017-05-01

    The efficacy of therapeutic hypothermia in adult patients with traumatic brain injury is not fully understood. The historical use of therapeutic hypothermia at extreme temperatures was associated with severe complications and led to it being discredited. Positive results from animal studies using milder temperatures led to renewed interest. However, recent studies have not convincingly demonstrated the beneficial effects of therapeutic hypothermia in practice. This review aims to answer the question: in adults with a severe traumatic brain injury (TBI), does the use of therapeutic hypothermia compared with normothermia affect neurological outcome? Systematic review. Four major electronic databases were searched, and a hand search was undertaken using selected key search terms. Inclusion and exclusion criteria were applied. The studies were appraised using a systematic approach, and four themes addressing the research question were identified and critically evaluated. A total of eight peer-reviewed studies were found, and the results show there is some evidence that therapeutic hypothermia may be effective in improving neurological outcome in adult patients with traumatic brain injury. However, the majority of the trials report conflicting results. Therapeutic hypothermia is reported to be effective at lowering intracranial pressure; however, its efficacy in improving neurological outcome is not fully demonstrated. This review suggests that therapeutic hypothermia had increased benefits in patients with haematoma-type injuries as opposed to those with diffuse injury and contusions. It also suggests that cooling should recommence if rebound intracranial hypertension is observed. Although the data indicates a trend towards better neurological outcome and reduced mortality rates, higher quality multi-centred randomized controlled trials are required before therapeutic hypothermia is implemented as a standard adjuvant therapy for treating traumatic brain injury

  2. Acute brain injury and therapeutic hypothermia in the PICU: A rehabilitation perspective

    PubMed Central

    Fink, Ericka L.; Beers, Sue R.; Russell, Mary Louise; Bell, Michael J.

    2011-01-01

    Acquired brain injury from traumatic brain injury, cardiac arrest (CA), stroke, and central nervous system infection is a leading cause of morbidity and mortality in the pediatric population and admission to inpatient rehabilitation. Therapeutic hypothermia is the only intervention shown to have efficacy from bench to bedside in improving neurological outcome after birth asphyxia and adult arrhythmia-induced CA, thought to be due to its multiple mechanisms of action. Research to determine if therapeutic hypothermia should be applied to other causes of brain injury and how to best apply it is underway in children and adults. Changes in clinical practice in the hospitalized brain-injured child may have effects on rehabilitation referral practices, goals and strategies of therapies offered, and may increase the degree of complex medical problems seen in children referred to inpatient rehabilitation. PMID:21791822

  3. The association between hypothermia, prehospital cooling, and mortality in burn victims.

    PubMed

    Singer, Adam J; Taira, Breena R; Thode, Henry C; McCormack, Jane E; Shapiro, Mark; Aydin, Ani; Lee, Christopher

    2010-04-01

    Hypothermia is associated with increased morbidity and mortality in trauma victims. The prognostic value of hypothermia on emergency department (ED) presentation in burn victims is not well known. The objective of this study was to determine the incidence of hypothermia in burn victims and its association with mortality and hospital length of stay (LOS). The study also examined the potential causative role of prehospital cooling in hypothermic burn patients. This was a retrospective review of a county trauma registry. The county was both suburban and rural, with a population of 1.5 million and with one burn center. Burn patients between 1994 and 2007 who met trauma registry criteria were included. Demographic and clinical data including prehospital cooling, burn size and depth, and presence of inhalation injury were collected. Hypothermia was defined as a core body temperature of less than or equal to 35 degrees C. Data analysis consisted of univariate associations between patient characteristics and hypothermia. There were 1,215 burn patients from 1994 to 2007. Mean age (+/-standard deviation [+/-SD]) was 29 (+/-24) years, 67% were male, 248 (26.7%) had full-thickness burns, and 24 (2.6%) had inhalation injury. Only 17 (1.8%) had a burn larger than 70% total body surface area (TBSA). A total of 929 (76%) patients had an initial ED temperature recorded. Only 15/929 (1.6%) burn patients had hypothermia on arrival, and all were mild (lowest temperature was 32.6 degrees C). There was no association between sex, year, and presence of inhalation injury with hypothermia. Hypothermic patients were older (44 years vs. 29 years, p = 0.01), and median Injury Severity Score (ISS) was higher (25 vs. 4, p = 0.002) than for nonhypothermic patients. Hypothermia was present in 6/17 (35%) patients with a TBSA of 70% or greater and in 8/869 (0.9%) patients with a TBSA of <70% (p < 0.001). Mortality was higher in hypothermic patients (60% vs. 3%, p < 0.001). None of the hypothermic

  4. Spontaneous hypothermia on intensive care unit admission is a predictor of unfavorable neurological outcome in patients after resuscitation: an observational cohort study.

    PubMed

    den Hartog, Alexander W; de Pont, Anne-Cornélie J M; Robillard, Laure B M; Binnekade, Jan M; Schultz, Marcus J; Horn, Janneke

    2010-01-01

    A large number of patients resuscitated for primary cardiac arrest arrive in the intensive care unit (ICU) with a body temperature < 35.0 degrees C. The aim of this observational cohort study was to determine the association between ICU admission temperature and neurological outcome in this patient group. Demographics and parameters influencing neurological outcome were retrieved from the charts of all patients resuscitated for primary cardiac arrest and treated with induced mild hypothermia in our ICU from January 2006 until January 2008. Patients were divided into two groups according to their body temperature on ICU admission: a hypothermia group (< 35.0 degrees C) and a non-hypothermia group (>or=35.0 degrees C). Neurological outcome after six months was assessed by means of the Glasgow Outcome Score (GOS), with GOS 1 to 3 defined as unfavorable and GOS 4 to 5 as favorable. A logistic regression model was used to analyze the influence of the different parameters on neurological outcome. The data of 105 consecutive patients resuscitated for primary cardiac arrest and treated with induced mild hypothermia were analyzed. Median ICU admission temperature was 35.1 degrees C (interquartile range (IQR) 34.3 to 35.7). After six months, 61% of the patients had an unfavorable outcome (59% died and 2% were severely disabled), whereas 39% had a favorable outcome (moderate disability or good recovery). Among patients with spontaneous hypothermia on ICU admission, the percentage with unfavorable outcome was higher (69% versus 50%, P = 0.05). Logistic regression showed that age, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores and spontaneous hypothermia on ICU admission all had an increased odds ratio (OR) for an unfavorable outcome after six months. Spontaneous hypothermia had the strongest association with unfavorable outcome (OR 2.6, 95% CI (confidence interval) 1.1 to 5.9), which became even stronger after

  5. Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia.

    PubMed

    Shellhaas, Renée A; Ng, Chee M; Dillon, Christina H; Barks, John D E; Bhatt-Mehta, Varsha

    2013-02-01

    Phenobarbital is the first-line treatment for neonatal seizures. Many neonates with hypoxic ischemic encephalopathy are treated with therapeutic hypothermia, and about 40% have clinical seizures. Little is known about the pharmacokinetics of phenobarbital in infants with hypoxic ischemic encephalopathy who undergo therapeutic hypothermia. The objective of this study was to determine the effect of therapeutic hypothermia on phenobarbital pharmacokinetics, taking into account maturational changes. Level 3 neonatal ICU. Infants with hypoxic ischemic encephalopathy and suspected seizures, all treated with phenobarbital. Some of these infants also received treatment with therapeutic hypothermia. None. A retrospective cohort study of 39 infants with hypoxic ischemic encephalopathy treated with phenobarbital (20 were treated with therapeutic hypothermia and 19 were not). Data on phenobarbital plasma concentrations were collected in 39 subjects with hypoxic ischemic encephalopathy with or without therapeutic hypothermia. Using nonlinear mixed-effects modeling, population pharmacokinetics of phenobarbital were developed with a total of 164 plasma concentrations. A one-compartment model best described the pharmacokinetics. The clearance of phenobarbital was linearly related to body weight and matured with increasing age with a maturation half-life of 22.1 days. Therapeutic hypothermia did not influence the pharmacokinetic parameters of phenobarbital. Therapeutic hypothermia does not influence the clearance of phenobarbital after accounting for weight and age. Standard phenobarbital dosing is appropriate for the initial treatment of seizures in neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia.

  6. Bradycardia and Hypothermia Complicating Azithromycin Treatment.

    PubMed

    Benn, Kerri; Salman, Sam; Page-Sharp, Madhu; Davis, Timothy M E; Buttery, Jim P

    2017-08-11

    BACKGROUND Azithromycin is a macrolide antibiotic widely used to treat respiratory, urogenital, and other infections. Gastrointestinal upset, headache, and dizziness are common adverse effects, and prolongation of the rate-corrected electrocardiographic QT interval and malignant arrhythmias have been reported. There are rare reports of bradycardia and hypothermia but not in the same patient. CASE REPORT A 4-year-old boy given intravenous azithromycin as part of treatment for febrile neutropenia complicating leukemia chemotherapy developed hypothermia (rectal temperature 35.2°C) and bradycardia (65 beats/minute) after the second dose, which resolved over several days post-treatment, consistent with persistence of high tissue azithromycin concentrations relative to those in plasma. A sigmoid Emax pharmacokinetic/pharmacodynamic model suggested a maximal azithromycin-associated reduction in heart rate of 23 beats/minute. Monitoring for these potential adverse effects should facilitate appropriate supportive care in similar cases. CONCLUSIONS Recommended azithromycin doses can cause at least moderate bradycardia and hypothermia in vulnerable pediatric patients, adverse effects that should prompt appropriate monitoring and which may take many days to resolve.

  7. Mild hypothermia attenuates changes in respiratory system mechanics and modifies cytokine concentration in bronchoalveolar lavage fluid during low lung volume ventilation.

    PubMed

    Dostál, P; Senkeřík, M; Pařízková, R; Bareš, D; Zivný, P; Zivná, H; Cerný, V

    2010-01-01

    Hypothermia was shown to attenuate ventilator-induced lung injury due to large tidal volumes. It is unclear if the protective effect of hypothermia is maintained under less injurious mechanical ventilation in animals without previous lung injury. Tracheostomized rats were randomly allocated to non-ventilated group (group C) or ventilated groups of normothermia (group N) and mild hypothermia (group H). After two hours of mechanical ventilation with inspiratory fraction of oxygen 1.0, respiratory rate 60 min(-1), tidal volume 10 ml x kg(-1), positive end-expiratory pressure (PEEP) 2 cm H2O or immediately after tracheostomy in non-ventilated animals inspiratory pressures were recorded, rats were sacrificed, pressure-volume (PV) curve of respiratory system constructed, bronchoalveolar lavage (BAL) fluid and aortic blood samples obtained. Group N animals exhibited a higher rise in peak inspiratory pressures in comparison to group H animals. Shift of the PV curve to right, higher total protein and interleukin-6 levels in BAL fluid were observed in normothermia animals in comparison with hypothermia animals and non-ventilated controls. Tumor necrosis factor-alpha was lower in the hypothermia group in comparison with normothermia and non-ventilated groups. Mild hypothermia attenuated changes in respiratory system mechanics and modified cytokine concentration in bronchoalveolar lavage fluid during low lung volume ventilation in animals without previous lung injury.

  8. Risk of mortality associated with neonatal hypothermia in southern Nepal.

    PubMed

    Mullany, Luke C; Katz, Joanne; Khatry, Subarna K; LeClerq, Steven C; Darmstadt, Gary L; Tielsch, James M

    2010-07-01

    To quantify the neonatal mortality/hypothermia relationship and develop evidence-based cutoffs for global definitions of neonatal hypothermia. Cohort study. Field workers recorded neonatal axillary temperature at home and recorded vital status at 28 days. Rural Nepal. Twenty-three thousand two hundred forty infants in Sarlahi, Nepal. Hypothermia. Mortality risk was estimated using binomial regression models. Infants were classified using (1) World Health Organization (WHO) cutoffs for mild, moderate, and severe hypothermia; (2) quarter-degree intervals from 32.0 degrees C to 36.5 degrees C; and (3) continuous temperatures. Estimates were adjusted for age, ambient temperature, and other potential confounders. Mortality increased among mild (relative risk [RR], 1.70; 95% confidence interval [CI], 1.23-2.35]), moderate (RR, 4.66; 95% CI, 3.47-6.24]), and severe (RR, 23.36; 95% CI, 4.31-126.70]) hypothermia cases. Within the WHO's moderate classification, risk relative to normothermic infants ranged from 2 to 30 times. Adjusted mortality risk increased 80% (95% CI, 63%-100%) for each degree decrease, was strongly associated with temperatures below 35.0 degrees C (RR, 6.11; 95% CI, 3.98-9.38), and was substantially higher among preterm infants (RR, 12.02; 95% CI, 6.23-23.18]) compared with full-term infants (RR, 3.12; 95% CI, 1.75-5.57). Relative risk was highest in the first 7 days, but remained elevated through 28 days. A new hypothermia classification system should be considered by the WHO for global guidelines. We recommend that grade 1 be equivalent to the current mild category (36.0 degrees C), restricting and splitting the moderate category into grades 2 (35.0 degrees C-36.0 degrees C) and 3 (34.0 degrees C-35.0 degrees C), and expanding severe hypothermia to less than 34.0 degrees C (grade 4). Reducing hypothermia may dramatically decrease the global neonatal mortality burden.

  9. Mild Hypothermia Attenuates Mitochondrial Oxidative Stress by Protecting Respiratory Enzymes and Upregulating MnSOD in a Pig Model of Cardiac Arrest

    PubMed Central

    Gong, Ping; Li, Chun-Sheng; Hua, Rong; Zhao, Hong; Tang, Zi-Ren; Mei, Xue; Zhang, Ming-Yue; Cui, Juan

    2012-01-01

    Mild hypothermia is the only effective treatment confirmed clinically to improve neurological outcomes for comatose patients with cardiac arrest. However, the underlying mechanism is not fully elucidated. In this study, our aim was to determine the effect of mild hypothermia on mitochondrial oxidative stress in the cerebral cortex. We intravascularly induced mild hypothermia (33°C), maintained this temperature for 12 h, and actively rewarmed in the inbred Chinese Wuzhishan minipigs successfully resuscitated after 8 min of untreated ventricular fibrillation. Cerebral samples were collected at 24 and 72 h following return of spontaneous circulation (ROSC). We found that mitochondrial malondialdehyde and protein carbonyl levels were significantly increased in the cerebral cortex in normothermic pigs even at 24 h after ROSC, whereas mild hypothermia attenuated this increase. Moreover, mild hypothermia attenuated the decrease in Complex I and Complex III (i.e., major sites of reactive oxygen species production) activities of the mitochondrial respiratory chain and increased antioxidant enzyme manganese superoxide dismutase (MnSOD) activity. This increase in MnSOD activity was consistent with the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and protein expressions, and with the increase of Nrf2 nuclear translocation in normothermic pigs at 24 and 72 h following ROSC, whereas mild hypothermia enhanced these tendencies. Thus, our findings indicate that mild hypothermia attenuates mitochondrial oxidative stress in the cerebral cortex, which may be associated with reduced impairment of mitochondrial respiratory chain enzymes, and enhancement of MnSOD activity and expression via Nrf2 activation. PMID:22532848

  10. Therapeutic hypothermia and pressure ulcer risk in critically ill intensive care patients: A retrospective study.

    PubMed

    Ahtiala, Maarit; Laitio, Ruut; Soppi, Esa

    2018-06-01

    To examine the role of therapeutic hypothermia in pressure ulcer development in critically ill patients. Retrospective study in a mixed intensive care unit over 2010-2013. The incidences of pressure ulcers among patients treated with therapeutic hypothermia (n = 148) and the non-hypothermia patient population (n = 6197) were compared. Patients treated with hypothermia developed more pressure ulcers (25.0%) than the non-hypothermia group 6.3% (p < 0.001). More patients in the hypothermia group were rated as the high pressure ulcer risk group, as defined by the modified Jackson/Cubbin (mJ/C) risk score ≤29 than the rest of the patients. Among the therapeutic hypothermia patients more pressure ulcers tended to emerge in the lower risk group (mJ/C score ≥30) (p = 0.056). Intensive care mortality was higher in the hypothermia (24.3%) than the non-hypothermia group (9.3%, p < 0.0001). Patients treated with therapeutic hypothermia should be considered at high risk for pressure ulcer development and should be managed accordingly. The hypothermia may not as such increase the risk for pressure ulcers, but combined with the severity of the underlying illness, may be more likely. The pressure ulcer risk in this patient group cannot be reliably assessed by the Jackson/Cubbin risk scale. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. The anti-influenza drug oseltamivir evokes hypothermia in mice through dopamine D2 receptor activation via central actions.

    PubMed

    Fukushima, Akihiro; Fukui, Arisa; Takemura, Yuki; Maeda, Yasuhiro; Ono, Hideki

    2018-01-01

    Oseltamivir has a hypothermic effect in mice when injected intraperitoneally (i.p.) and intracerebroventricularly (i.c.v.). Here we show that the hypothermia evoked by i.c.v.-oseltamivir is inhibited by non-selective dopamine receptor antagonists (sulpiride and haloperidol) and the D 2 -selective antagonist L-741,626, but not by D 1 /D 5 -selective and D 3 -selective antagonists (SCH-23390 and SB-277011-A, respectively). The hypothermic effect of i.p.-administered oseltamivir was not inhibited by sulpiride, haloperidol, L-741,626 and SCH-23390. In addition, neither sulpiride, haloperidol nor SCH-23390 blocked hypothermia evoked by i.c.v.-administered oseltamivir carboxylate (a hydrolyzed metabolite of oseltamivir). These results suggest that oseltamivir in the brain induces hypothermia through activation of dopamine D 2 receptors. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  12. Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury

    PubMed Central

    Gao, Xiao-Ya; Huang, Jian-Ou; Hu, Ya-Fang; Gu, Yong; Zhu, Shu-Zhen; Huang, Kai-Bin; Chen, Jin-Yu; Pan, Su-Yue

    2014-01-01

    Co-treatment of neuroprotective reagents may improve the therapeutic efficacy of hypothermia in protecting neurons during ischemic stroke. This study aimed to find promising drugs that enhance the neuroprotective effect of mild hypothermia (MH). 26 candidate drugs were selected based on different targets. Primary cultured cortical neurons were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) to induce neuronal damage, followed by either single treatment (a drug or MH) or a combination of a drug and MH. Results showed that, compared with single treatment, combination of MH with brain derived neurotrophic factor, glibenclamide, dizocilpine, human urinary kallidinogenase or neuroglobin displayed higher proportion of neuronal cell viability. The latter three drugs also caused less apoptosis rate in combined treatment. Furthermore, co-treatment of those three drugs and MH decreased the level of reactive oxygen species (ROS) and intracellular calcium accumulation, as well as stabilized mitochondrial membrane potential (MMP), indicating the combined neuroprotective effects are probably via inhibiting mitochondrial apoptosis pathway. Taken together, the study suggests that combined treatment with hypothermia and certain neuroprotective reagents provide a better protection against OGD/R-induced neuronal injury. PMID:25404538

  13. Heat and cold acclimation in helium-cold hypothermia in the hamster.

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.

    1972-01-01

    A study was made of the effects of acclimation of hamsters to high (34-35 C) and low (4-5 C) temperatures for periods up to 6 weeks on the induction of hypothermia in hamsters. Hypothermia was achieved by exposing hamsters to a helox mixture of 80% helium and 20% oxygen at 0 C. Hypothermic induction was most rapid (2-3 hr) in heat-acclimated hamsters and slowest (6-12 hr) in cold-acclimated hamsters. The induction period was intermediate (5-8 hr) in room temperature nonacclimated animals (controls). Survival time in hypothermia was relatable to previous temperature acclimations. The hypothesis that thermogenesis in cold-acclimated hamsters would accentuate resistance to induction of hypothermia was substantiated.

  14. A knowledge translation collaborative to improve the use of therapeutic hypothermia in post-cardiac arrest patients: protocol for a stepped wedge randomized trial.

    PubMed

    Dainty, Katie N; Scales, Damon C; Brooks, Steve C; Needham, Dale M; Dorian, Paul; Ferguson, Niall; Rubenfeld, Gordon; Wax, Randy; Zwarenstein, Merrick; Thorpe, Kevin; Morrison, Laurie J

    2011-01-14

    Advances in resuscitation science have dramatically improved survival rates following cardiac arrest. However, about 60% of adults that regain spontaneous circulation die before leaving the hospital. Recently it has been shown that inducing hypothermia in cardiac arrest survivors immediately following their arrival in hospital can dramatically improve both overall survival and neurological outcomes. Despite the strong evidence for its efficacy and the apparent simplicity of this intervention, recent surveys show that therapeutic hypothermia is delivered inconsistently, incompletely, and often with delay. This study will evaluate a multi-faceted knowledge translation strategy designed to increase the utilization rate of induced hypothermia in survivors of cardiac arrest across a network of 37 hospitals in Southwestern Ontario, Canada. The study is designed as a stepped wedge randomized trial lasting two years. Individual hospitals will be randomly assigned to four different wedges that will receive the active knowledge translation strategy according to a sequential rollout over a number of time periods. By the end of the study, all hospitals will have received the intervention. The primary aim is to measure the effectiveness of a multifaceted knowledge translation plan involving education, reminders, and audit-feedback for improving the use of induced hypothermia in survivors of cardiac arrest presenting to the emergency department. The primary outcome is the proportion of eligible OHCA patients that are cooled to a body temperature of 32 to 34°C within six hours of arrival in the hospital. Secondary outcomes will include process of care measures and clinical outcomes. Inducing hypothermia in cardiac arrest survivors immediately following their arrival to hospital has been shown to dramatically improve both overall survival and neurological outcomes. However, this lifesaving treatment is frequently not applied in practice. If this trial is positive, our results

  15. Chronic hypothermia following tuberculous meningitis.

    PubMed Central

    Dick, D J; Sanders, G L; Saunders, M; Rawlins, M D

    1981-01-01

    A patient who developed chronic hypothermia following tuberculous meningitis is described. A central defect of thermoregulation was discovered, probably due to a discrete vascular lesion in the anterior hypothalmus. PMID:6785394

  16. Effects of accidental hypothermia on posttraumatic complications and outcome in multiple trauma patients.

    PubMed

    Mommsen, P; Andruszkow, H; Frömke, C; Zeckey, C; Wagner, U; van Griensven, M; Frink, M; Krettek, C; Hildebrand, F

    2013-01-01

    Accidental hypothermia seems to predispose multiple trauma patients to the development of posttraumatic complications, such as Systemic Inflammatory Response Syndrome (SIRS), sepsis, Multiple Organ Dysfunction Syndrome (MODS), and increased mortality. However, the role of accidental hypothermia as an independent prognostic factor is controversially discussed. The aim of the present study was to evaluate the incidence of accidental hypothermia in multiple trauma patients and its effects on the development of posttraumatic complications and mortality. Inclusion criteria for patients in this retrospective study (2005-2009) were an Injury Severity Score (ISS) ≥16, age ≥16 years, admission to our Level I trauma centre within 6h after the accident. Accidental hypothermia was defined as body temperature less than 35°C measured within 2 h after admission, but always before first surgical procedure in the operation theatre. The association between accidental hypothermia and the development of posttraumatic complications as well as mortality was investigated. Statistical analysis was performed with χ(2)-test, Student's t-test, ANOVA and logistic regression. Statistical significance was considered at p<0.05. 310 multiple trauma patients were enrolled in the present study. Patients' mean age was 41.9 (SD 17.5) years, the mean injury severity score was 29.7 (SD 10.2). The overall incidence of accidental hypothermia was 36.8%. The overall incidence of posttraumatic complications was 77.4% (SIRS), 42.9% (sepsis) and 7.4% (MODS), respectively. No association was shown between accidental hypothermia and the development of posttraumatic complications. Overall, 8.7% died during the posttraumatic course. Despite an increased mortality rate in hypothermic patients, hypothermia failed to be an independent risk factor for mortality in multivariate analysis. Accidental hypothermia is very common in multiply injured patients. However, it could be assumed that the increase of

  17. Brain injury following trial of hypothermia for neonatal hypoxic–ischaemic encephalopathy

    PubMed Central

    Shankaran, Seetha; Barnes, Patrick D; Hintz, Susan R; Laptook, Abbott R; Zaterka-Baxter, Kristin M; McDonald, Scott A; Ehrenkranz, Richard A; Walsh, Michele C; Tyson, Jon E; Donovan, Edward F; Goldberg, Ronald N; Bara, Rebecca; Das, Abhik; Finer, Neil N; Sanchez, Pablo J; Poindexter, Brenda B; Van Meurs, Krisa P; Carlo, Waldemar A; Stoll, Barbara J; Duara, Shahnaz; Guillet, Ronnie; Higgins, Rosemary D

    2013-01-01

    Objective The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic–ischaemic encephalopathy treated with hypothermia. Design and patients Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18–22 months of age. Results Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability. Conclusions Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18–22 months following hypothermia for neonatal encephalopathy. PMID:23080477

  18. Additional risk factors for lethal hypothermia.

    PubMed

    Bright, Fiona; Gilbert, John D; Winskog, Calle; Byard, Roger W

    2013-08-01

    An 86-year-old woman was found dead lying on her back on the floor of an unkempt kitchen. She had last been seen four days before. Her dress was pulled up and she was not wearing underpants. The house was noted to be in "disarray" with papers covering most surfaces and the floor. Rubbish was piled up against one of the doors. At autopsy the major findings were of a fractured left neck of femur, fresh pressure areas over her right buttock, Wischnewski spots of the stomach and foci of pancreatic necrosis, in keeping with hypothermia. No significant underlying organic diseases were identified and there was no other evidence of trauma. Death was due to hypothermia complicating immobility from a fractured neck of femur. This case confirms the vulnerability of frail, elderly and socially-isolated individuals to death from hypothermia if a significant illness or injury occurs. Additional risk factors for hypothermia are also illustrated in this case that involve inadequate housing construction with absent insulation and window double glazing. The approach to hypothermic deaths should, therefore, include checking for these features as well as measuring room and environmental temperatures, evaluating the type and quality of heating and the nature of the floor and its coverings, Given the ageing population in many Western countries, increasing social isolation of the elderly, cost of fuel and electricity, and lack of energy efficient housing, this type of death may become an increasingly witnessed occurrence during the colder months of the year. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  19. Fasting triggers hypothermia, and ambient temperature modulates its depth in Japanese quail Coturnix japonica.

    PubMed

    Ben-Hamo, Miriam; Pinshow, Berry; McCue, Marshall D; McWilliams, Scott R; Bauchinger, Ulf

    2010-05-01

    We tested three hypotheses regarding the cues that elicit facultative hypothermia in Japanese quail (Coturnix japonica): H(1)) Ambient temperature (T(a)), alone, influences the onset and depth of hypothermia; H(2)) Fasting, alone, influences the onset and depth of hypothermia; H(3)) T(a) acts synergistically with fasting to shape the use of hypothermia. Eight quail were maintained within their thermoneutral zone (TNZ) at 32.6+/-0.2 degrees C, and eight below their lower critical temperature (T(lc)) at 12.7+/-3.0 degrees C. All quail entered hypothermia upon food deprivation, even quail kept within their TNZ. Body temperature (T(b)) decreased more (38.36+/-0.53 degrees C vs. 39.57+/-0.57 degrees C), body mass (m(b)) loss was greater (21.0+/-7.20 g vs.12.8+/-2.62g), and the energy saved by using hypothermia was greater (25.18-45.01% vs. 7.98-28.06%) in low the T(a) treatment than in TNZ treatment. Interestingly, the depth of hypothermia was positively correlated with m(b) loss in the low T(a) treatment, but not in TNZ treatment. Our data support H(3), that both thermoregulatory costs and body energy reserves are proximate cues for entry into hypothermia in quail. This outcome is not surprising below the T(lc). However, the quail kept at their TNZ also responded to food deprivation by entering hypothermia with no apparent dependence on m(b) loss. Therefore inputs, other than thermoregulatory costs and body condition, must serve as cues to enter hypothermia. Consequently, we address the role that tissue sparing may play in the physiological 'decision' to employ hypothermia. Copyright 2009 Elsevier Inc. All rights reserved.

  20. Neonatal hypothermia and associated risk factors among newborns of southern Nepal.

    PubMed

    Mullany, Luke C; Katz, Joanne; Khatry, Subarna K; LeClerq, Steven C; Darmstadt, Gary L; Tielsch, James M

    2010-07-08

    Neonatal hypothermia is associated with an increased mortality risk for 28 days. There are few community-based data on specific risk factors for neonatal hypothermia. Estimates of association between neonatal hypothermia in the community and risk factors are needed to guide the design of interventions to reduce exposure. A cohort of 23,240 babies in rural southern Nepal was visited at home by field workers who measured axillary temperatures for 28 days (213,316 temperature measurements). The cumulative incidence of hypothermia (defined as < 35.0 degrees C based on an analysis of the hypothermia-mortality risk relationship) was examined for any association with infant characteristics, care practices and parental, household, socioeconomic and demographic factors. Estimates were adjusted for age and ambient temperature. Ten percent of the babies (n = 2342) were observed with temperatures of < 35.0 degrees C. Adjusted prevalence ratios (Adj PR) were increased among those who weighed < 2000 g [Adj PR = 4.32 (3.73, 5.00)] or < 1500 g [Adj PR = 11.63 (8.10, 16.70)] compared to those of normal weight (> 2500 g). Risk varied inversely along the entire weight spectrum: for every 100 g decrement hypothermia risk increased by 7.4%, 13.5% and 31.3%% for babies between 3000 g and 2500 g, 2500 g and 2000 g and < 2000 g, respectively. Preterm babies (< 34 weeks), females, those who had been first breastfed after 24 h and those with hypothermic mothers were at an increased risk. In the hot season the risk disparity between smaller and larger babies increased. Hypothermia was not associated with delayed bathing, hat wearing, room warming or skin-to-skin contact: they may have been practiced reactively and thereby obscured any potential benefit. In addition to season in which the babies were born, weight is an important risk factor for hypothermia. Smaller babies are at higher relative risk of hypothermia during the warm period and do not receive the protective seasonal benefit

  1. Mechanisms of Hypothermia, Delayed Hyperthermia and Fever Following CNS Injury

    EPA Science Inventory

    Central nervous system (CNS) damage is often associated with robust body temperature changes, such as hypothermia and delayed hyperthermia. Hypothermia is one of the most common body temperature changes to CNS insults in rodents and is often associated with improved outcome. Alth...

  2. Mild intraoperative hypothermia during surgery for intracranial aneurysm.

    PubMed

    Todd, Michael M; Hindman, Bradley J; Clarke, William R; Torner, James C

    2005-01-13

    Surgery for intracranial aneurysm often results in postoperative neurologic deficits. We conducted a randomized trial at 30 centers to determine whether intraoperative cooling during open craniotomy would improve the outcome among patients with acute aneurysmal subarachnoid hemorrhage. A total of 1001 patients with a preoperative World Federation of Neurological Surgeons score of I, II, or III ("good-grade patients"), who had had a subarachnoid hemorrhage no more than 14 days before planned surgical aneurysm clipping, were randomly assigned to intraoperative hypothermia (target temperature, 33 degrees C, with the use of surface cooling techniques) or normothermia (target temperature, 36.5 degrees C). Patients were followed closely postoperatively and examined approximately 90 days after surgery, at which time a Glasgow Outcome Score was assigned. There were no significant differences between the group assigned to intraoperative hypothermia and the group assigned to normothermia in the duration of stay in the intensive care unit, the total length of hospitalization, the rates of death at follow-up (6 percent in both groups), or the destination at discharge (home or another hospital, among surviving patients). At the final follow-up, 329 of 499 patients in the hypothermia group had a Glasgow Outcome Score of 1 (good outcome), as compared with 314 of 501 patients in the normothermia group (66 percent vs. 63 percent; odds ratio, 1.14; 95 percent confidence interval, 0.88 to 1.48; P=0.32). Postoperative bacteremia was more common in the hypothermia group than in the normothermia group (5 percent vs. 3 percent, P=0.05). Intraoperative hypothermia did not improve the neurologic outcome after craniotomy among good-grade patients with aneurysmal subarachnoid hemorrhage. Copyright 2005 Massachusetts Medical Society.

  3. Hypothermia is a frequent sign of severe hypoglycaemia in patients with diabetes.

    PubMed

    Tran, C; Gariani, K; Herrmann, F R; Juan, L; Philippe, J; Rutschmann, O T; Vischer, U M

    2012-10-01

    Hypothermia is a recognized complication of severe hypoglycaemia, but its prevalence and characteristics are poorly studied. For this reason, this study aimed to evaluate hypothermia in severely hypoglycaemic patients. A retrospective chart review was performed including all patients discharged between 2007 and 2010 from the Emergency Department of the Geneva University Hospital with a diagnosis of severe hypoglycaemia. Hypothermia was identified in 30 (23.4%) out of 128 patients with severe hypoglycaemia. Its incidence was not affected by age, type of diabetes, season or time of day (day/night). Using linear regression, the lowest recorded temperature was associated with the Glasgow coma scale (GCS) score (r2 = 13.8%, P < 0.0001) and inversely associated with the leukocyte count (r2 = 13.1%, P = 0.001). Hypothermia is a frequent sign of severe hypoglycaemia in patients with diabetes. The associations between hypothermia and the GCS score and the leukocyte count suggest that it is a marker of hypoglycaemia severity and/or duration. Hypothermia may represent an important compensatory mechanism in severe hypoglycaemia, reflecting a decrease in energy demand during glucose deprivation. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  4. Reversible inactivation and excitation of nucleus raphe magnus can modulate tail blood flow of male Wistar rats in response to hypothermia.

    PubMed

    Malakouti, Seyed Mansour; Kourosh Arami, Masoomeh; Sarihi, Abdorahman; Hajizadeh, Sohrab; Behzadi, Gila; Shahidi, Siamak; Komaki, Alireza; Heshmatian, Behnam; Vahabian, Mehrangiz

    2008-10-01

    The nucleus raphe magnus (NRM) is involved in thermoregulatory processing. There is a correlation between changes in the firing rates of the cells in the NRM and the application of the peripheral thermal stimulus. we examined the effect of reversible inactivation and excitation of NRM on mechanisms involved in tail blood flow (TBF) regulation in hypothermia. Hypothermia was induced in Male Wistar rats and cannula was implanted above the NRM. To evaluate the effect of nucleus inactivation on TBF, the amount of TBF was measured by Laser Doppler in hypothermic rats, before and after lidocaine microinjection into NRM. TBF was also measured after glutamate microinjection to assess the effect of nucleus excitation in hypothermic rats. Results indicated that after dropping TBF by hypothermia, microinjection of lidocaine into NRM significantly decreased TBF from 54.43 +- 5.7 to 46.81 +- 3.4, whereas glutamate microinjection caused a significant increase from 44.194 +- 0.6 to 98 +- 10.0 CONCLUSION: These data suggest that NRM have thermoregulatory effect in response to hypothermia.

  5. [Transitory hypothermia as early prognostic factor in term newborns with intrauterine growth retardation].

    PubMed

    Lazić-Mitrović, Tanja; Djukić, Milan; Cutura, Nedjo; Andjelić, Spaso; Curković, Aleksandar; Soldo, Vesna; Radlović, Nedeljko

    2010-01-01

    According to numerous researches, transitory hypothermia is a part of the neonatological energetic triangle and represents a significant prognostic factor within morbidity and mortality in newborns with intrauterine growth retardation (IUGR), that are, due to their characteristics, more inclined to transitory hypothermia. The aim of the study was an analysis of frequency of transitory hypothermia in term newborns with IUGR, as well as an analysis of frequency of the most frequent pathological conditions typical of IUGR newborns depending on the presence of transitory hypothermia after birth (hypoglycaemia, perinatal asphyxia, hyperbilirubinaemia and hypocalcaemia). The study included 143 term newborns with IUGR treated at the Neonatology Ward of the Gynaecology-Obstetrics Clinic "Narodni front", Belgrade. The newborns were divided into two groups: the one with registered transitory hypothermia--the observed group, and the one without transitory hypothermia--the control group. The data analysis included the analysis of the frequency of transitory hypothermia depending on gestation and body mass, as well as the analysis of pathological conditions (perinatal asphyxia, hypoglycaemia, hypocalcaemia, hyperbilirubinaemia) depending on the presence of hypothermia. The analysis was done by statistical tests of analytic and descriptive statistics. In morbidity structure dominate hypothermia (65.03%), hypoglycaemia (43.36%), perinatal asphyxia (37.76%), hyperbilirubinaemia (30.77%), hypocalcaemia (25.17%). There were 93 newborns in the observed group, and 50 in the control one. Mean value of the measured body temperature was 35.9 degrees C. 20 newborns (32.26%) had moderate hypothermia, and 73 newborns (67.74%) had mild hypothermia. In the observed group, average gestation was 39.0 weeks, and 39.6 (p < 0.01) in the control group. Average body mass at birth in the whole group was 2339 g: 2214 g in the observed and 2571 g in the control group. The frequency of hypoglycaemia in

  6. The geography of hypothermia in the United States: An analysis of mortality, morbidity, thresholds, and messaging

    NASA Astrophysics Data System (ADS)

    Spencer, Jeremy M.

    Hypothermia within the United States has seldom been studied from a geographic perspective. This dissertation assessed the following aspects of hypothermia: 1) A cataloging of Internet web pages containing hypothermia-related guidance, with a summary of the information contained within. The summarized hypothermia information was assessed for scientific validity through an extensive assessment of the peer-reviewed medical literature; 2) the spatio-temporal distribution of hypothermia deaths in U.S. Combined Statistical areas for the years 1979-2004, and their association with National Weather Service windchill advisory and warning thresholds; 3) the spatio-temporal distribution of hypothermia morbidity in the State of New York from 1991-1992 to 2005-2006 and its association with Spatial Synoptic Classification weather types. The results indicate that web-based hypothermia information has generally poor content not supported by the scientific literature, and there are many prominent omissions of well-established hypothermia information. A total of 9,185 hypothermia fatalities attributable to cold exposure occurred in 89 metro areas from 1979 to 2004. The southeastern US had the greatest vulnerability to hypothermia, with high rates of deaths occurring at higher temperatures than northern states. Median windchill temperature associated with deaths was generally latitudinal, with southern deaths occurring at higher temperatures. For all regions, hypothermia deaths occurred at temperatures considerably higher than windchill advisory criteria. Hypothermia morbidity within New York State was associated with long-lasting polar weather types. There are a number of findings common to these three papers. Information about hypothermia tends to be under-communicated (no central location for wind chill alerts, unsupported statements on many websites). Hypothermia deaths and hospitalizations increase when locally cold and long-lasting weather types occur, which fits in with what

  7. THERAPEUTIC HYPOTHERMIA DECREASES PHENYTOIN ELIMINATION IN CHILDREN WITH TRAUMATIC BRAIN INJURY

    PubMed Central

    Empey, Philip E.; Velez de Mendizabal, Nieves; Bell, Michael J.; Bies, Robert R.; Anderson, Kacey B.; Kochanek, Patrick M.; Adelson, P. David; Poloyac, Samuel M.

    2013-01-01

    Objective Preclinical and clinical studies have suggested that therapeutic hypothermia, while decreasing neurological injury, may also lead to drug toxicity that may limit its benefit. Cooling decreases cytochrome p450(CYP)-mediated drug metabolism and limited clinical data suggest that drug levels are elevated. Fosphenytoin is metabolized by CYP2C, has a narrow therapeutic range, and is a commonly used antiepileptic medication. The objective of the study was to evaluate the impact of therapeutic hypothermia on phenytoin levels and pharmacokinetics in children with severe TBI. Design Pharmacokinetic analysis of subjects participating in a multicenter randomized Phase III study of therapeutic hypothermia for severe TBI. Setting Intensive care unit at the Children’s Hospital of Pittsburgh Patients Nineteen children with severe TBI. Interventions None Measurements and Main Results A total of 121 total and 114 free phenytoin levels were evaluated retrospectively in 10 hypothermia- and 9 normothermia-treated children who were randomized to 48h of cooling to 32–33°C followed by slow rewarming or controlled normothermia. Drug dosing, body temperatures, and demographics were collected during cooling, rewarming, and post-treatment periods(8 days). A trend towards elevated free phenytoin levels in the hypothermia group(p=0.051) to a median of 2.2 mg/L during rewarming was observed and was not explained by dosing differences. Nonlinear mixed effects modeling incorporating both free and total levels demonstrated that therapeutic hypothermia specifically decreased the time-variant component of the maximum velocity of phenytoin metabolism(Vmax) 4.6-fold(11.6 to 2.53 mg/h) and reduced the overall Vmax by ~50%. Simulations showed that the increased risk for drug toxicity extends many days beyond the end of the cooling period. Conclusions Therapeutic hypothermia significantly reduces phenytoin elimination in children with severe TBI leading to increased drug levels for an

  8. No association between intraoperative hypothermia or supplemental protective drug and neurologic outcomes in patients undergoing temporary clipping during cerebral aneurysm surgery: findings from the Intraoperative Hypothermia for Aneurysm Surgery Trial.

    PubMed

    Hindman, Bradley J; Bayman, Emine O; Pfisterer, Wolfgang K; Torner, James C; Todd, Michael M

    2010-01-01

    Although hypothermia and barbiturates improve neurologic outcomes in animal temporary focal ischemia models, the clinical efficacy of these interventions during temporary occlusion of the cerebral vasculature during intracranial aneurysm surgery (temporary clipping) is not established. A post hoc analysis of patients from the Intraoperative Hypothermia for Aneurysm Surgery Trial who underwent temporary clipping was performed. Univariate and multivariate logistic regression methods were used to test for associations between hypothermia, supplemental protective drug, and short- (24-h) and long-term (3-month) neurologic outcomes. An odds ratio more than 1 denotes better outcome. Patients undergoing temporary clipping (n = 441) were assigned to intraoperative hypothermia (33.3 degrees +/- 0.8 degrees C, n = 208) or normothermia (36.7 degrees +/- 0.5 degrees C, n = 233), with 178 patients also receiving supplemental protective drug (thiopental or etomidate) during temporary clipping. Three months after surgery, 278 patients (63%) had good outcome (Glasgow Outcome Score = 1). Neither hypothermia (P = 0.847; odds ratio = 1.043, 95% CI = 0.678-1.606) nor supplemental protective drug (P = 0.835; odds ratio = 1.048, 95% CI = 0.674-1.631) were associated with 3-month Glasgow Outcome Score. The effect of supplemental protective drug did not significantly vary with temperature. The effects of hypothermia and protective drug did not significantly vary with temporary clip duration. Similar findings were made for 24-h neurologic status and 3-month Neuropsychological Composite Score. In the Intraoperative Hypothermia for Aneurysm Surgery Trial, neither systemic hypothermia nor supplemental protective drug affected short- or long-term neurologic outcomes of patients undergoing temporary clipping.

  9. Perioperative hypothermia (33 degrees C) does not increase the occurrence of cardiovascular events in patients undergoing cerebral aneurysm surgery: findings from the Intraoperative Hypothermia for Aneurysm Surgery Trial.

    PubMed

    Nguyen, Hoang P; Zaroff, Jonathan G; Bayman, Emine O; Gelb, Adrian W; Todd, Michael M; Hindman, Bradley J

    2010-08-01

    Perioperative hypothermia has been reported to increase the occurrence of cardiovascular complications. By increasing the activity of sympathetic nervous system, perioperative hypothermia also has the potential to increase cardiac injury and dysfunction associated with subarachnoid hemorrhage. The Intraoperative Hypothermia for Aneurysm Surgery Trial randomized patients undergoing cerebral aneurysm surgery to intraoperative hypothermia (n = 499, 33.3 degrees +/- 0.8 degrees C) or normothermia (n = 501, 36.7 degrees +/- 0.5 degrees C). Cardiovascular events (hypotension, arrhythmias, vasopressor use, myocardial infarction, and others) were prospectively followed until 3-month follow-up and were compared in hypothermic and normothermic patients. A subset of 62 patients (hypothermia, n = 33; normothermia, n = 29) also had preoperative and postoperative (within 24 h) measurement of cardiac troponin-I and echocardiography to explore the association between perioperative hypothermia and subarachnoid hemorrhage-associated myocardial injury and left ventricular function. There was no difference between hypothermic and normothermic patients in the occurrence of any single cardiovascular event or in composite cardiovascular events. There was no difference in mortality (6%) between groups, and there was only a single primary cardiovascular death (normothermia). There was no difference between hypothermic and normothermic patients in postoperative versus preoperative left ventricular regional wall motion or ejection fraction. Compared with preoperative values, hypothermic patients had no postoperative increase in cardiac troponin-I (median change 0.00 microg/l), whereas normothermic patients had a small postoperative increase (median change + 0.01 microg/l, P = 0.038). In patients undergoing cerebral aneurysm surgery, perioperative hypothermia was not associated with an increased occurrence of cardiovascular events.

  10. Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: Effect on Spreading Depolarizations

    DTIC Science & Technology

    2017-10-01

    AWARD NUMBER: W81XWH-16-C-0161 TITLE: Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: Effect on Spreading Depolarizations...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-16-C-0161 Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: Effect on Spreading...in a sub-study of the HOPES trial to assess the effects of hypothermia on the pathologic mechanism of spreading depolarizations (SD). HOPES is a

  11. Persisting mild hypothermia suppresses hypoxia-inducible factor-1alpha protein synthesis and hypoxia-inducible factor-1-mediated gene expression.

    PubMed

    Tanaka, Tomoharu; Wakamatsu, Takuhiko; Daijo, Hiroki; Oda, Seiko; Kai, Shinichi; Adachi, Takehiko; Kizaka-Kondoh, Shinae; Fukuda, Kazuhiko; Hirota, Kiichi

    2010-03-01

    The transcription factor hypoxia-inducible factor-1 (HIF-1) plays an essential role in regulating gene expression in response to hypoxia-ischemia. Ischemia causes the tissue not only to be hypoxic but also to be hypothermic because of the hypoperfusion under certain circumstances. On the other hand, the induced hypothermia is one of the most common therapeutic modalities to extend tolerance to hypoxia. Although hypoxia elicits a variety of cellular and systemic responses at different organizational levels in the body, little is known about how hypoxia-induced responses are affected by low temperature. We examined the influence of mild hypothermic conditions (28-32 degrees C) on HIF-1 in both in vitro and in vivo settings. In vitro experiments adopting cultured cells elucidated that hypoxia-induced HIF-1 activation was resistant to 4-h exposure to the low temperature. In contrast, exposure to the low temperature as long as 24 h suppressed HIF-1 activation and the subsequent upregulation of HIF-1 target genes such as VEGF or GLUT-1. HIF-1alpha protein stability in the cell was not affected by hypothermic treatment. Furthermore, intracellular ATP content was reduced under 1% O(2) conditions but was not largely affected by hypothermic treatment. The evidence indicates that reduction of oxygen consumption is not largely involved in suppression of HIF-1. In addition, we demonstrated that HIF-1 DNA-binding activity and HIF-1-dependent gene expressions induced under 10% O(2) atmosphere in mouse brain were not influenced by treatment under 3-h hypothermic temperature but were inhibited under 5-h treatment. On the other hand, we indicated that warming ischemic legs of mice for 24 h preserved HIF-1 activity. In this report we describe for the first time that persisting low temperature significantly reduced HIF-1alpha neosynthesis under hypoxic conditions, leading to a decrease in gene expression for adaptation to hypoxia in both in vitro and in vivo settings.

  12. The small chill: mild hypothermia for cardioprotection?

    PubMed

    Tissier, Renaud; Chenoune, Mourad; Ghaleh, Bijan; Cohen, Michael V; Downey, James M; Berdeaux, Alain

    2010-12-01

    Reducing the heart's temperature by 2-5°C is a potent cardioprotective treatment in animal models of coronary artery occlusion. The anti-infarct benefit depends upon the target temperature and the time at which cooling is instituted. Protection primarily results from cooling during the ischaemic period, whereas cooling during reperfusion or beyond offers little protection. In animal studies, protection is proportional to both the depth and duration of cooling. An optimal cooling protocol must appreciably shorten the normothermic ischaemic time to effectively salvage myocardium. Patients presenting with acute myocardial infarction could be candidates for mild hypothermia since the current door-to-balloon time is typically 90 min. But they would have to be cooled quickly shortly after their arrival. Several strategies have been proposed for ultra-fast cooling, but most like liquid ventilation and pericardial perfusion are too invasive. More feasible strategies might include cutaneous cooling, peritoneal lavage with cold solutions, and endovascular cooling with intravenous thermodes. This last option has been investigated clinically, but the results have been disappointing possibly because the devices lacked capacity to cool the patient quickly or cooling was not implemented soon enough. The mechanism of hypothermia's protection has been assumed to be energy conservation. However, whereas deep hypothermia clearly preserves ATP, mild hypothermia has only a modest effect on ATP depletion during ischaemia. Some evidence suggests that intracellular signalling pathways might be responsible for the protection. It is unknown how cooling could trigger these pathways, but, if true, then it might be possible to duplicate cooling's protection pharmacologically.

  13. Human touch to detect hypothermia in neonates in Indian slum dwellings.

    PubMed

    Agarwal, Siddharth; Sethi, Vani; Srivastava, Karishma; Jha, Prabhat; Baqui, Abdullah H

    2010-07-01

    To assess the validity of human touch (HT) method to measure hypothermia compared against axillary digital thermometry (ADT) and study association of hypothermia with poor suckle and underweight status in newborns and environmental temperature in 11 slums of Indore city, India. Field supervisors of slum-based health volunteers measured body temperature of 152 newborns by HT and ADT, observed suckling and weighed newborns. Underweight status was determined using WHO growth standards. Hypothermia prevalence (axillary temperature <36.5 degrees C) was 30.9%. Prevalence varied by season but insignificantly. Hypothermia was insignificantly associated with poor suckle (31% vs 19.7%, p=0.21) and undernutrition (33.3% vs 25.3%, p=0.4). HT had moderate diagnostic accuracy when compared with ADT (kappa: 0.38, sensitivity: 74.5%, specificity: 68.5%). HT emerged simpler and programmatically feasible. There is a need to examine whether trained and supervised community-based health workers and mothers can use HT accurately to identify and manage hypothermia and other simple signs of newborn illness using minimal algorithm at home and more confidently refer such newborns to proximal facilities linked to the program to ensure prompt management of illness.

  14. Therapeutic dormancy to delay postsurgical glioma recurrence: the past, present and promise of focal hypothermia.

    PubMed

    Wion, Didier

    2017-07-01

    Surgery precedes both radiotherapy and chemotherapy as the first-line therapy for glioma. However, despite multimodal treatment, most glioma patients die from local recurrence in the resection margin. Glioma surgery is inherently lesional, and the response of brain tissue to surgery includes hemostasis, angiogenesis, reactive gliosis and inflammation. Unfortunately, these processes are also associated with tumorigenic side-effects. An increasing amount of evidence indicates that the response to a surgery-related brain injury is hijacked by residual glioma cells and participates in the local regeneration of tumor tissues at the resection margin. Inducing therapeutic hypothermia in the brain has long been used to treat the secondary damage, such as neuroinflammation and edema, that are caused by accidental traumatic brain injuries. There is compelling evidence to suggest that inducing therapeutic hypothermia at the resection margin would delay the local recurrence of glioma by (i) limiting cell proliferation, (ii) disrupting the pathological connection between inflammation and glioma recurrence, and (iii) limiting the consequences of the functional heterogeneity and complexity inherent to the tumor ecosystem. While the global whole-body cooling methods that are currently used to treat stroke in clinical practice may not adequately treat the resection margin, the future lies in implantable focal microcooling devices similar to those under development for the treatment of epilepsy. Preclinical and clinical strategies to evaluate focal hypothermia must be implemented to prevent glioma recurrence in the resection margin. Placing the resection margin in a state of hibernation may potentially provide such a long-awaited therapeutic breakthrough.

  15. Postoperative fatal hypothermia in hydranencephaly with pre-operative hypothermia and a nerve palsy: a case report and review of the literature.

    PubMed

    Musara, A; Kalangu, K K N

    2010-01-01

    Hydranencephaly is a rare condition characterised by complete or near complete absence of the cerebral hemispheres within relatively normal sized meninges and skull, the resulting cavity being filled with cerebrospinal fluid. The following is a case report of a five month old hydranencephalic child with right upper motor facial nerve palsy who presented with signs of hydrocephalus who developed intractable hypothermia rapidly post ventriculo-peritoneal shunt insertion and demised. Her preoperative condition was associated with hypothermia.

  16. OUTCOMES in CHILDHOOD FOLLOWING THERAPEUTIC HYPOTHERMIA for NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE)

    PubMed Central

    Natarajan, Girija; Pappas, Athina; Shankaran, Seetha

    2017-01-01

    In this chapter we review the childhood outcomes of neonates with birth depression and/or hypoxic-ischemic encephalopathy. The outcomes of these children prior to the era of hypothermia for neuroprotection will first be summarized, followed by discussion of results from randomized controlled trials of therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy. The predictors of outcome in childhood following neonatal HIE using clinical and imaging biomarkers following hypothermia therapy will be described. PMID:27863707

  17. Effect of a pharmacologically induced decrease in core temperature in rats resuscitated from cardiac arrest.

    PubMed

    Katz, Laurence M; Frank, Jonathan E; Glickman, Lawrence T; McGwin, Gerald; Lambert, Brice H; Gordon, Christopher J

    2015-07-01

    Hypothermia is recommended by international guidelines for treatment of unconscious survivors of cardiac arrest to improve neurologic outcomes. However, temperature management is often underutilized because it may be difficult to implement. The present study evaluated the efficacy of pharmacologically induced hypothermia on survival and neurological outcome in rats resuscitated from cardiac arrest. Cardiac arrest was induced for 10 min in 120 rats. Sixty-one rats were resuscitated and randomized to normothermia, physical cooling or pharmacological hypothermia 5 min after resuscitation. Pharmacological hypothermia rats received a combination of ethanol, vasopressin and lidocaine (HBN-1). Physical hypothermia rats were cooled with intravenous iced saline and cooling pads. Rats in the pharmacological hypothermia group received HBN-1 at ambient temperature (20 °C). Normothermic rats were maintained at 37.3 ± 0.2 °C. HBN-1 (p < 0.0001) shortened the time (85 ± 71 min) to target temperature (33.5 °C) versus physical hypothermia (247 ± 142 min). The duration of hypothermia was 17.0 ± 6.8h in the HBN-1 group and 17.3 ± 7.5h in the physical hypothermia group (p = 0.918). Survival (p = 0.034), neurological deficit scores (p < 0.0001) and Morris Water Maze performance after resuscitation (p = 0.041) was improved in the HBN-1 versus the normothermic group. HBN-1 improved survival and early neurological outcome compared to the physical hypothermia group while there was no significant difference in performance in the Morris water maze. HBN-1 induced rapid and prolonged hypothermia improved survival with good neurological outcomes after cardiac arrest suggesting that pharmacologically induced regulated hypothermia may provide a practical alternative to physical cooling. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Accidental hypothermia in Poland – estimation of prevalence, diagnostic methods and treatment.

    PubMed

    Kosiński, Sylweriusz; Darocha, Tomasz; Gałązkowski, Robert; Drwiła, Rafał

    2015-02-06

    The incidence of hypothermia is difficult to evaluate, and the data concerning the morbidity and mortality rates do not seem to fully represent the problem. The aim of the study was to estimate the actual prevalence of accidental hypothermia in Poland, as well as the methods of diagnosis and management procedures used in emergency rooms (ERs). A specially designed questionnaire, consisting of 14 questions, was mailed to all the 223 emergency rooms (ER) in Poland. The questions concerned the incidence, methods of diagnosis and risk factors, as well as the rewarming methods used and available measurement instruments. The analysis involved data from 42 ERs providing emergency healthcare for the population of 5,305,000. The prevalence of accidental hypothermia may have been 5.05 cases per 100.000 residents per year. Among the 268 cases listed 25% were diagnosed with codes T68, T69 or X31, and in 75% hypothermia was neither included nor assigned a code in the final diagnosis. The most frequent cause of hypothermia was exposure to cold air alongside ethanol abuse (68%). Peripheral temperature was measured in 57%, core temperature measurement was taken in 29% of the patients. Peripheral temperature was measured most often at the axilla, while core temperature measurement was predominantly taken rectally. Mild hypothermia was diagnosed in 75.5% of the patients, moderate (32-28°C) in 16.5%, while severe hypothermia (less than 28°C) in 8% of the cases. Cardiopulmonary resuscitation was carried out in 7.5% of the patients. The treatment involved mainly warmed intravenous fluids (83.5%) and active external rewarming measures (70%). In no case was extracorporeal rewarming put to use. The actual incidence of accidental hypothermia in Polish emergency departments may exceed up to four times the official data. Core temperature is taken only in one third of the patients, the treatment of hypothermic patients is rarely conducted in intensive care wards and extracorporeal rewarming

  19. Osborn waves in severe accidental hypothermia secondary to prolonged immobilization and malnutrition.

    PubMed

    Rotondi, Francesco; Manganelli, Fiore; Candelmo, Fiore; Marino, Luciano; Di Lorenzo, Emilio; Alfano, Ferdinando; Stanco, Giovanni; Rosato, Giuseppe

    2010-07-01

    We report the case of a 77-year-old man, in whom accidental hypothermia was secondary to prolonged immobilization and malnutrition. The electrocardiogram showed typical Osborn waves, which disappeared with the rewarming of the patient. The diagnosis of hypothermia is easy in patients with a history of prolonged exposure to a cold environment but accidental hypothermia may also occur as a consequence of prolonged immobilization and malnutrition. ECG analysis is very important for a correct and fast diagnosis.

  20. Systemic hypothermia for the treatment of acute cervical spinal cord injury in sports.

    PubMed

    Dietrich, William Dalton; Cappuccino, Andrew; Cappuccino, Helen

    2011-01-01

    Spinal cord injury is a devastating condition that affects approximately 12,000 patients each year in the United States. Major causes for spinal cord injury include motor vehicle accidents, sports-related injuries, and direct trauma. Moderate hypothermia has gained attention as a potential therapy due to recent experimental and clinical studies and the use of modest systemic hypothermia (MSH) in high profile case of spinal cord injury in a National Football League (NFL) player. In experimental models of spinal cord injury, moderate hypothermia has been shown to improve functional recovery and reduce overall structural damage. In a recent Phase I clinical trial, systemic hypothermia has been shown to be safe and provide some encouraging results in terms of functional recovery. This review will summarize recent preclinical data, as well as clinical findings that support the continued investigations for the use of hypothermia in severe cervical spinal cord injury.

  1. Mechanisms responsible for decreased glomerular filtration in hibernation and hypothermia

    NASA Technical Reports Server (NTRS)

    Tempel, G. E.; Musacchia, X. J.; Jones, S. B.

    1977-01-01

    Measurements of blood pressure, heart rate, red blood cell and plasma volumes, and relative distribution of cardiac output were made on hibernating and hypothermic adult male and female golden hamsters weighing 120-140 g to study the mechanisms underlying the elimination or marked depression of renal function in hibernation and hypothermia. The results suggest that the elimination or marked depression in renal function reported in hibernation and hypothermia may partly be explained by alterations in cardiovascular system function. Renal perfusion pressure which decreases nearly 60% in both hibernation and hypothermia and a decrease in plasma volume of roughly 35% in the hypothermic animal might both be expected to markedly alter glomerular function.

  2. Therapeutic Hypothermia Reduces Oxidative Damage and Alters Antioxidant Defenses after Cardiac Arrest

    PubMed Central

    Hackenhaar, Fernanda S.; Medeiros, Tássia M.; Heemann, Fernanda M.; Behling, Camile S.; Putti, Jordana S.; Mahl, Camila D.; Verona, Cleber; da Silva, Ana Carolina A.; Guerra, Maria C.; Gonçalves, Carlos A. S.; Oliveira, Vanessa M.; Riveiro, Diego F. M.; Vieira, Silvia R. R.

    2017-01-01

    After cardiac arrest, organ damage consequent to ischemia-reperfusion has been attributed to oxidative stress. Mild therapeutic hypothermia has been applied to reduce this damage, and it may reduce oxidative damage as well. This study aimed to compare oxidative damage and antioxidant defenses in patients treated with controlled normothermia versus mild therapeutic hypothermia during postcardiac arrest syndrome. The sample consisted of 31 patients under controlled normothermia (36°C) and 11 patients treated with 24 h mild therapeutic hypothermia (33°C), victims of in- or out-of-hospital cardiac arrest. Parameters were assessed at 6, 12, 36, and 72 h after cardiac arrest in the central venous blood samples. Hypothermic and normothermic patients had similar S100B levels, a biomarker of brain injury. Xanthine oxidase activity is similar between hypothermic and normothermic patients; however, it decreases posthypothermia treatment. Xanthine oxidase activity is positively correlated with lactate and S100B and inversely correlated with pH, calcium, and sodium levels. Hypothermia reduces malondialdehyde and protein carbonyl levels, markers of oxidative damage. Concomitantly, hypothermia increases the activity of erythrocyte antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione S-transferase while decreasing the activity of serum paraoxonase-1. These findings suggest that mild therapeutic hypothermia reduces oxidative damage and alters antioxidant defenses in postcardiac arrest patients. PMID:28553435

  3. Therapeutic hypothermia attenuates tissue damage and cytokine expression after traumatic brain injury by inhibiting necroptosis in the rat.

    PubMed

    Liu, Tao; Zhao, Dong-xu; Cui, Hua; Chen, Lei; Bao, Ying-hui; Wang, Yong; Jiang, Ji-yao

    2016-04-15

    Necroptosis has been shown as an alternative form of cell death in many diseases, but the detailed mechanisms of the neuron loss after traumatic brain injury (TBI) in rodents remain unclear. To investigate whether necroptosis is induced after TBI and gets involved in the neuroprotecton of therapeutic hypothermia on the TBI, we observed the pathological and biochemical change of the necroptosis in the fluid percussion brain injury (FPI) model of the rats. We found that receptor-interacting protein (RIP) 1 and 3, and mixed lineage kinase domain-like protein (MLKL), the critical downstream mediators of necroptosis recently identified in vivo, as well as HMGB1 and the pro-inflammation cytokines TNF-α, IL-6 and IL-18, were increased at an early phase (6 h) in cortex after TBI. Posttraumatic hypothermia (33 °C) led to the decreases in the necroptosis regulators, inflammatory factors and brain tissue damage in rats compared with normothermia-treated TBI animals. Immunohistochemistry studies showed that posttraumatic hypothermia also decreased the necroptosis-associated proteins staining in injured cortex and hippocampal CA1. Therefore, we conclude that the RIP1/RIP3-MLKL-mediated necroptosis occurs after experimental TBI and therapeutic hypothermia may protect the injured central nervous system from tissue damage and the inflammatory responses by targeting the necroptosis signaling after TBI.

  4. Outcomes in childhood following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE).

    PubMed

    Natarajan, Girija; Pappas, Athina; Shankaran, Seetha

    2016-12-01

    In this article, we review the childhood outcomes of neonates with birth depression and/or hypoxic-ischemic encephalopathy. The outcomes of these children prior to the era of hypothermia for neuroprotection will first be summarized, followed by discussion of results from randomized controlled trials of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy. The predictors of outcome in childhood following neonatal HIE using clinical and imaging biomarkers following hypothermia therapy will be described. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Occurrence of hypothermia in a prehospital setting, southern Sweden.

    PubMed

    Kornfält, Jonas; Johansson, Anders

    2010-04-01

    Severe accidental hypothermia mainly affects victims of outdoor accidents. However, hypothermia can also occur in non-traumatized indoor patients. The aim of this study was to examine the occurrence of hypothermia obtained at the scene of the rescue in patients classified as priority 1 cases during two three-month periods in southern Sweden. This prospective, clinical cohort study was performed in a prehospital setting, southern Sweden. Ninety-four patients were included during two three-month periods. According to where the patients were found they were split into two groups, outdoor or indoor and then separated into three categories; general medicine-, trauma- and intoxicated patients. The environment temperature was measured on arrival according to the location where the rescue occurred and core temperatures (tympanic membrane) of patients were measured in connection with the monitoring in the ambulance before departure and at the time of arrival to the emergency room at the hospital. This study demonstrated that the only group that shows body core temperature below 36 degrees C, was the outdoor intoxication-group during the winter-period (35.7+/-1.3 degrees C). We conclude that intoxicated patients are at higher risk for hypothermia than minor trauma patients. Copyright 2009 Elsevier Ltd. All rights reserved.

  6. The global burden of neonatal hypothermia: systematic review of a major challenge for newborn survival

    PubMed Central

    2013-01-01

    Background To provide evidence on the global epidemiological situation of neonatal hypothermia and to provide recommendations for future policy and research directions. Methods Using PubMed as our principal electronic reference library, we searched studies for prevalence and risk factor data on neonatal hypothermia in resource-limited environments globally. Studies specifying study location, setting (hospital or community based), sample size, case definition of body temperature for hypothermia, temperature measurement method, and point estimates for hypothermia prevalence were eligible for inclusion. Results Hypothermia is common in infants born at hospitals (prevalence range, 32% to 85%) and homes (prevalence range, 11% to 92%), even in tropical environments. The lack of thermal protection is still an underappreciated major challenge for newborn survival in developing countries. Although hypothermia is rarely a direct cause of death, it contributes to a substantial proportion of neonatal mortality globally, mostly as a comorbidity of severe neonatal infections, preterm birth, and asphyxia. Thresholds for the definition of hypothermia vary, and data on its prevalence in neonates is scarce, particularly on a community level in Africa. Conclusions A standardized approach to the collection and analysis of hypothermia data in existing newborn programs and studies is needed to inform policy and program planners on optimal thermal protection interventions. Thermoprotective behavior changes such as skin-to-skin care or the use of appropriate devices have not yet been scaled up globally. The introduction of simple hypothermia prevention messages and interventions into evidence-based, cost-effective packages for maternal and newborn care has promising potential to decrease the heavy global burden of newborn deaths attributable to severe infections, prematurity, and asphyxia. Because preventing and treating newborn hypothermia in health institutions and communities is

  7. Cytokine changes in newborns with therapeutic hypothermia after hypoxic ischemic encephalopathy.

    PubMed

    Moon, C J; Youn, Y A; Yum, S K; Sung, I K

    2016-12-01

    This study aimed to examine changes in cytokines according to therapeutic hypothermia (TH) for newborn hypoxic ischemic encephalopathy (HIE). We studied 20 neonates who were admitted with a diagnosis of HIE in the neonatal intensive care unit. Cytokine concentration assay was carried out for neonates (n=12) who received TH and neonates (n=8) who were not treated with hypothermia by collecting blood sample at 12, 48 and 120 h after birth. At 48 h after birth, interleukin (IL)-6 in the normothermia group was higher than that in the hypothermia group (P=0.010). At 48 h after birth, IL-10 was higher in the hypothermia group than in the normothermia group (P=0.038). This study confirmed that TH performs a role in the prevention of inflammatory process by way of maintaining proinflammatory cytokine IL-6 at low levels and anti-inflammatory cytokines IL-10 at high levels.

  8. Hypothermia and associated outcomes in seriously injured trauma patients in a predominantly sub-tropical climate.

    PubMed

    Aitken, L M; Hendrikz, J K; Dulhunty, J M; Rudd, M J

    2009-02-01

    This study aimed to determine factors linked to hypothermia (<35 degrees C) in Queensland trauma patients. The relationship of hypothermia with mortality, admission to intensive care and hospital length of stay was also explored. A retrospective analysis of data from the Queensland Trauma Registry was undertaken, and included all patients admitted to hospital for > or =24h during 2003 and 2004 with an injury severity score (ISS)>15. Demographic, injury, environmental, care and clinical status factors were considered. A total of 2182 patients were included; 124 (5.7%) had hypothermia on admission to the definitive care hospital, while a further 156 (7.1%) developed hypothermia during hospitalisation. Factors associated with hypothermia on admission included winter, direct admission to a definitive care hospital, an ISS> or =40, a Glasgow Coma Scale of 3 or ventilated and sedated, and hypotension on admission. Hypothermia on admission to the definitive care hospital was an independent predictor of mortality (odds ratio [OR]=4.05; 95% confidence interval [CI] 2.26-7.24) and hospital length of stay (incidence rate ratio [IRR]=1.22; 95% CI 1.03-1.43). Hypothermia during definitive care hospitalisation was independently associated with mortality (OR=2.52; 95% CI 1.52-4.17), intensive care admission (OR=1.73; 95% CI 1.20-2.93) and hospital length of stay (IRR=1.18; 95% CI 1.02-1.36). Trauma patients in a predominantly sub-tropical climate are at risk of accidental and endogenous hypothermia, with associated higher mortality and care requirements. Prevention of hypothermia is important for all severely injured patients.

  9. Hypothermia in Uremic Dogs and Cats.

    PubMed

    Kabatchnick, E; Langston, C; Olson, B; Lamb, K E

    2016-09-01

    The prevalence of uremic hypothermia (UH) and the effects of improving uremia on body temperature have not been determined in veterinary patients. To determine the prevalence of UH and correlations between uremia and body temperature in patients undergoing intermittent hemodialysis (IHD). Uremic dogs (n = 122) and cats (n = 79) treated by IHD at the Bobst Hospital of the Animal Medical Center from 1997 to 2013. Retrospective review of medical records. The prevalence of hypothermia was 38% in azotemic cats and 20.5% in azotemic dogs. Statistically significant temperature differences were observed between uremic and nonuremic dogs (nonuremic: mean, 100.8°F; range, 91.2-109.5°F; uremic: mean, 99.9°F; range, 95.6-103.8°F; P < .0001) and cats (nonuremic: mean, 100.6°F; range, 94.0-103.8°F; uremic: mean, 99.3°F; range, 92.3-103.4°F; P < .0001). In dog dialysis patients, significant models included (1) timing (pre-dialysis versus post-dialysis) with weight class (small [P < .0001], medium [P = .016], and large breed [P = .033] dogs), (2) timing with serum creatinine concentration (P = .021), and (3) timing with BUN concentration (P < .0001). In cat dialysis patients, there was a significant interaction between timing and weight as a categorical variable (<5 kg and ≥5 kg). Uremic hypothermia appears to be a clinical phenomenon that occurs in cats and dogs. Uremic patients are hypothermic compared to ill nonuremic patients and body temperatures increase when uremia is corrected with IHD in dogs and in cats >5 kg. In cats, UH seems to be a more prevalent phenomenon driven by uremia. Uremic hypothermia does occur in dogs, but body weight is a more important predictor of body temperature. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  10. Transpulmonary hypothermia: a novel method of rapid brain cooling through augmented heat extraction from the lungs.

    PubMed

    Kumar, Matthew M; Goldberg, Andrew D; Kashiouris, Markos; Keenan, Lawrence R; Rabinstein, Alejandro A; Afessa, Bekele; Johnson, Larry D; Atkinson, John L D; Nayagam, Vedha

    2014-10-01

    Delay in instituting neuroprotective measures after cardiac arrest increases death and decreases neuronal recovery. Current hypothermia methods are slow, ineffective, unreliable, or highly invasive. We report the feasibility of rapid hypothermia induction in swine through augmented heat extraction from the lungs. Twenty-four domestic crossbred pigs (weight, 50-55kg) were ventilated with room air. Intraparenchymal brain temperature and core temperatures from pulmonary artery, lower esophagus, bladder, rectum, nasopharynx, and tympanum were recorded. In eight animals, ventilation was switched to cooled helium-oxygen mixture (heliox) and perfluorocarbon (PFC) aerosol and continued for 90min or until target brain temperature of 32°C was reached. Eight animals received body-surface cooling with water-circulating blankets; eight control animals continued to be ventilated with room air. Brain and core temperatures declined rapidly with cooled heliox-PFC ventilation. The brain reached target temperature within the study period (mean [SD], 66 [7.6]min) in only the transpulmonary cooling group. Cardiopulmonary functions and poststudy histopathological examination of the lungs were normal. Transpulmonary cooling is novel, rapid, minimally invasive, and an effective technique to induce therapeutic hypothermia. High thermal conductivity of helium and vaporization of PFC produces rapid cooling of alveolar gases. The thinness and large surface area of alveolar membrane facilitate rapid cooling of the pulmonary circulation. Because of differences in thermogenesis, blood flow, insulation, and exposure to the external environment, the brain cools at a different rate than other organs. Transpulmonary hypothermia was significantly faster than body surface cooling in reaching target brain temperature. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Therapeutic Hypothermia: Critical Review of the Molecular Mechanisms of Action

    PubMed Central

    González-Ibarra, Fernando Pavel; Varon, Joseph; López-Meza, Elmer G.

    2010-01-01

    Therapeutic hypothermia (TH) is nowadays one of the most important methods of neuroprotection. The events that occur after an episode of ischemia are multiple and hypothermia can affect the various steps of this cascade. The mechanisms of action of TH are varied and the possible explanation for the benefits of this therapy is probably the multiple mechanisms of action blocking the cascade of ischemia on many levels. TH can affect many metabolic pathways, reactions of inflammation, apoptosis processes, and promote neuronal integrity. To know the mechanisms of action of TH will allow a better understanding about the indications for this therapy and the possibility of searching for other therapies when used in conjunction with hypothermia will provide a therapeutic synergistic effect. PMID:21331282

  12. Mild hypothermia increases pulmonary anti-inflammatory response during protective mechanical ventilation in a piglet model of acute lung injury.

    PubMed

    Cruces, Pablo; Erranz, Benjamín; Donoso, Alejandro; Carvajal, Cristóbal; Salomón, Tatiana; Torres, María Fernanda; Díaz, Franco

    2013-11-01

    The effects of mild hypothermia (HT) on acute lung injury (ALI) are unknown in species with metabolic rate similar to that of humans, receiving protective mechanical ventilation (MV). We hypothesized that mild hypothermia would attenuate pulmonary and systemic inflammatory responses in piglets with ALI managed with a protective MV. Acute lung injury (ALI) was induced with surfactant deactivation in 38 piglets. The animals were then ventilated with low tidal volume, moderate positive end-expiratory pressure (PEEP), and permissive hypercapnia throughout the experiment. Subjects were randomized to HT (33.5°C) or normothermia (37°C) groups over 4 h. Plasma and tissue cytokines, tissue apoptosis, lung mechanics, pulmonary vascular permeability, hemodynamic, and coagulation were evaluated. Lung interleukin-10 concentrations were higher in subjects that underwent HT after ALI induction than in those that maintained normothermia. No difference was found in other systemic and tissue cytokines. HT did not induce lung or kidney tissue apoptosis or influence lung mechanics or markers of pulmonary vascular permeability. Heart rate, cardiac output, oxygen uptake, and delivery were significantly lower in subjects that underwent HT, but no difference in arterial lactate, central venous oxygen saturation, and coagulation test was observed. Mild hypothermia induced a local anti-inflammatory response in the lungs, without affecting lung function or coagulation, in this piglet model of ALI. The HT group had lower cardiac output without signs of global dysoxia, suggesting an adaptation to the decrease in oxygen uptake and delivery. Studies are needed to determine the therapeutic role of HT in ALI. © 2013 John Wiley & Sons Ltd.

  13. Temperature control during therapeutic hypothermia for newborn encephalopathy using different Blanketrol devices.

    PubMed

    Laptook, Abbot R; Kilbride, Howard; Shepherd, Edward; McDonald, Scott A; Shankaran, Seetha; Truog, William; Das, Abhik; Higgins, Rosemary D

    2014-12-01

    Therapeutic hypothermia improves the survival and neurodevelopmental outcome of infants with newborn encephalopathy of a hypoxic-ischemic origin. The NICHD Neonatal Research Network (NRN) Whole Body Cooling trial used the Cincinnati Sub-Zero Blanketrol II to achieve therapeutic hypothermia. The Blanketrol III is now available and provides additional cooling modes that may result in better temperature control. This report is a retrospective comparison of infants undergoing hypothermia using two different cooling modes of the Blanketrol device. Infants from the NRN trial were cooled with the Blanketrol II using the Automatic control mode (B2 cohort) and were compared with infants from two new NRN centers that adopted the NRN protocol and used the Blanketrol III in a gradient mode (B3 cohort). The primary outcome was the percent time the esophageal temperature stayed between 33°C and 34°C (target 33.5°C) during maintenance of hypothermia. Cohorts had similar birth weight, gestational age, and level of encephalopathy at the initiation of therapy. Baseline esophageal temperature differed between groups (36.6°C ± 1.0°C for B2 vs. 33.9°C ± 1.2°C for B3, p<0.0001) reflecting the practice of passive cooling during transport prior to initiation of active device cooling in the B3 cohort. This difference prevented comparison of temperatures during induction of hypothermia. During maintenance of hypothermia the mean and standard deviation of the percent time between 33°C and 34°C was similar for B2 compared to B3 cohorts (94.8% ± 0.1% vs. 95.8% ± 0.1%, respectively). Both the automatic and gradient control modes of the Blanketrol devices appear comparable in maintaining esophageal temperature within the target range during maintenance of therapeutic hypothermia.

  14. Temperature Control During Therapeutic Hypothermia for Newborn Encephalopathy Using Different Blanketrol Devices

    PubMed Central

    Kilbride, Howard; Shepherd, Edward; McDonald, Scott A.; Shankaran, Seetha; Truog, William; Das, Abhik; Higgins, Rosemary D.

    2014-01-01

    Therapeutic hypothermia improves the survival and neurodevelopmental outcome of infants with newborn encephalopathy of a hypoxic-ischemic origin. The NICHD Neonatal Research Network (NRN) Whole Body Cooling trial used the Cincinnati Sub-Zero Blanketrol II to achieve therapeutic hypothermia. The Blanketrol III is now available and provides additional cooling modes that may result in better temperature control. This report is a retrospective comparison of infants undergoing hypothermia using two different cooling modes of the Blanketrol device. Infants from the NRN trial were cooled with the Blanketrol II using the Automatic control mode (B2 cohort) and were compared with infants from two new NRN centers that adopted the NRN protocol and used the Blanketrol III in a gradient mode (B3 cohort). The primary outcome was the percent time the esophageal temperature stayed between 33°C and 34°C (target 33.5°C) during maintenance of hypothermia. Cohorts had similar birth weight, gestational age, and level of encephalopathy at the initiation of therapy. Baseline esophageal temperature differed between groups (36.6°C±1.0°C for B2 vs. 33.9°C±1.2°C for B3, p<0.0001) reflecting the practice of passive cooling during transport prior to initiation of active device cooling in the B3 cohort. This difference prevented comparison of temperatures during induction of hypothermia. During maintenance of hypothermia the mean and standard deviation of the percent time between 33°C and 34°C was similar for B2 compared to B3 cohorts (94.8%±0.1% vs. 95.8%±0.1%, respectively). Both the automatic and gradient control modes of the Blanketrol devices appear comparable in maintaining esophageal temperature within the target range during maintenance of therapeutic hypothermia. PMID:25285767

  15. Nocturnal hypothermia impairs flight ability in birds: a cost of being cool

    PubMed Central

    Carr, Jennie M.; Lima, Steven L.

    2013-01-01

    Many birds use regulated drops in night-time body temperature (Tb) to conserve energy critical to winter survival. However, a significant degree of hypothermia may limit a bird's ability to respond to predatory attack. Despite this likely energy–predation trade-off, the behavioural costs of avian hypothermia have yet to be examined. We thus monitored the nocturnal hypothermia of mourning doves (Zenaida macroura) in a laboratory setting in response to food deprivation. Nocturnal flight tests were used to quantify the flight ability of hypothermic doves. Many hypothermic doves (39% of tests) could not fly while carrying a small weight, but could do so after quickly warming up to typical daytime Tb. Doves that were unable to fly during their first test were more hypothermic than those that could fly, with average Tb reductions of 5.3°C and 3.3°C, respectively, but there was no overall indication of a threshold Tb reduction beyond which doves were consistently incapable of flight. These results suggest that energy-saving hypothermia interferes with avian antipredator behaviour via a reduction in flight ability, likely leading to a trade-off between energy-saving hypothermia and the risk of predation. PMID:24107528

  16. Delayed treatment with hypothermia protects against the no-reflow phenomenon despite failure to reduce infarct size.

    PubMed

    Hale, Sharon L; Herring, Michael J; Kloner, Robert A

    2013-01-04

    Many studies have shown that when hypothermia is started after coronary artery reperfusion (CAR), it is ineffective at reducing necrosis. However, some suggest that hypothermia may preferentially reduce no-reflow. Our aim was to test the effects of hypothermia on no-reflow when initiated close to reperfusion and 30 minutes after reperfusion, times not associated with a protective effect on myocardial infarct size. Rabbits received 30 minutes coronary artery occlusion/3 hours CAR. In protocol 1, hearts were treated for 1 hour with topical hypothermia (myocardial temperature ≈32°C) initiated at 5 minutes before or 5 minutes after CAR, and the results were compared with a normothermic group. In protocol 2, hypothermia was delayed until 30 minutes after CAR and control hearts remained normothermic. In protocol 1, risk zones were similar and infarct size was not significantly reduced by hypothermia initiated close to CAR. However, the no-reflow defect was significantly reduced by 43% (5 minutes before CAR) and 38% (5 minutes after CAR) in hypothermic compared with normothermic hearts (P=0.004, ANOVA, P=ns between the 2 treated groups). In protocol 2, risk zones and infarct sizes were similar, but delayed hypothermia significantly reduced no-reflow in hypothermic hearts by 30% (55±6% of the necrotic region in hypothermia group versus 79±6% with normothermia, P=0.008). These studies suggest that treatment with hypothermia reduces no-reflow even when initiated too late to reduce infarct size and that the microvasculature is especially receptive to the protective properties of hypothermia and confirm that microvascular damage is in large part a form of true reperfusion injury.

  17. Sex-specific effects of N-acetylcysteine in neonatal rats treated with hypothermia after severe hypoxia-ischemia.

    PubMed

    Nie, Xingju; Lowe, Danielle W; Rollins, Laura Grace; Bentzley, Jessica; Fraser, Jamie L; Martin, Renee; Singh, Inderjit; Jenkins, Dorothea

    2016-07-01

    Approximately half of moderate to severely hypoxic-ischemic (HI) newborns do not respond to hypothermia, the only proven neuroprotective treatment. N-acetylcysteine (NAC), an antioxidant and glutathione precursor, shows promise for neuroprotection in combination with hypothermia, mitigating post-HI neuroinflammation due to oxidative stress. As mechanisms of HI injury and cell death differ in males and females, sex differences must be considered in translational research of neuroprotection. We assessed the potential toxicity and efficacy of NAC in combination with hypothermia, in male and female neonatal rats after severe HI injury. NAC 50mg/kg/d administered 1h after initiation of hypothermia significantly decreased iNOS expression and caspase 3 activation in the injured hemisphere versus hypothermia alone. However, only females treated with hypothermia +NAC 50mg/kg showed improvement in short-term infarct volumes compared with saline treated animals. Hypothermia alone had no effect in this severe model. When NAC was continued for 6 weeks, significant improvement in long-term neuromotor outcomes over hypothermia treatment alone was observed, controlling for sex. Antioxidants may provide insufficient neuroprotection after HI for neonatal males in the short term, while long-term therapy may benefit both sexes. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  18. Therapeutic Hypothermia in Spinal Cord Injury: The Status of Its Use and Open Questions.

    PubMed

    Wang, Jiaqiong; Pearse, Damien D

    2015-07-24

    Spinal cord injury (SCI) is a major health problem and is associated with a diversity of neurological symptoms. Pathophysiologically, dysfunction after SCI results from the culmination of tissue damage produced both by the primary insult and a range of secondary injury mechanisms. The application of hypothermia has been demonstrated to be neuroprotective after SCI in both experimental and human studies. The myriad of protective mechanisms of hypothermia include the slowing down of metabolism, decreasing free radical generation, inhibiting excitotoxicity and apoptosis, ameliorating inflammation, preserving the blood spinal cord barrier, inhibiting astrogliosis, promoting angiogenesis, as well as decreasing axonal damage and encouraging neurogenesis. Hypothermia has also been combined with other interventions, such as antioxidants, anesthetics, alkalinization and cell transplantation for additional benefit. Although a large body of work has reported on the effectiveness of hypothermia as a neuroprotective approach after SCI and its application has been translated to the clinic, a number of questions still remain regarding its use, including the identification of hypothermia's therapeutic window, optimal duration and the most appropriate rewarming rate. In addition, it is necessary to investigate the neuroprotective effect of combining therapeutic hypothermia with other treatment strategies for putative synergies, particularly those involving neurorepair.

  19. Altered circulating leukocytes and their chemokines in a clinical trial of therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy*.

    PubMed

    Jenkins, Dorothea D; Lee, Timothy; Chiuzan, Cody; Perkel, Jessica K; Rollins, Laura Grace; Wagner, Carol L; Katikaneni, Lakshmi P; Bass, W Thomas; Kaufman, David A; Horgan, Michael J; Laungani, Sheela; Givelichian, Laurence M; Sankaran, Koravangatta; Yager, Jerome Y; Martin, Renee

    2013-10-01

    To determine systemic hypothermia's effect on circulating immune cells and their corresponding chemokines after hypoxic ischemic encephalopathy in neonates. In our randomized, controlled, multicenter trial of systemic hypothermia in neonatal hypoxic ischemic encephalopathy, we measured total and leukocyte subset and serum chemokine levels over time in both hypothermia and normothermia groups, as primary outcomes for safety. Neonatal ICUs participating in a Neurological Disorders and Stroke sponsored clinical trial of therapeutic hypothermia. Sixty-five neonates with moderate to severe hypoxic ischemic encephalopathy within 6 hours after birth. Patients were randomized to normothermia of 37°C or systemic hypothermia of 33°C for 48 hours. Complete and differential leukocyte counts and serum chemokines were measured every 12 hours for 72 hours. The hypothermia group had significantly lower median circulating total WBC and leukocyte subclasses than the normothermia group before rewarming, with a nadir at 36 hours. Only the absolute neutrophil count rebounded after rewarming in the hypothermia group. Chemokines, monocyte chemotactic protein-1 and interleukin-8, which mediate leukocyte chemotaxis as well as bone marrow suppression, were negatively correlated with their target leukocytes in the hypothermia group, suggesting active chemokine and leukocyte modulation by hypothermia. Relative leukopenia at 60-72 hours correlated with an adverse outcome in the hypothermia group. Our data are consistent with chemokine-associated systemic immunosuppression with hypothermia treatment. In hypothermic neonates, persistence of lower leukocyte counts after rewarming is observed in infants with more severe CNS injury.

  20. Serum procalcitonin, C-reactive protein and white blood cell levels following hypothermia after cardiac arrest: a retrospective cohort study.

    PubMed

    Schuetz, Philipp; Affolter, Barbara; Hunziker, Sabina; Winterhalder, Clemens; Fischer, Michael; Balestra, Gianmarco M; Hunziker, Patrick; Marsch, Stephan

    2010-04-01

    The aim of this study was to investigate time course of procalcitonin (PCT), C-reactive protein (CRP) and white blood cell (WBC) levels in patients with therapeutic hypothermia after cardiac arrest. We retrospectively assessed laboratory and clinical data in a consecutive cohort of patients admitted to the medical intensive-care-unit of the University Hospital in Basel, Switzerland, in whom therapeutic hypothermia was induced because of cardiac arrest between December 2007 and January 2009. Infection was considered based on microbiological evidence (restricted definition) and/or clinical evidence of infection with prescription of antibiotics (extended definition). From 34 included patients, 25 had respiratory tract infection based on the clinical judgment and in 18 microbiological cultures turned positive (restricted definition). PCT concentrations were highest on the first day after hypothermia and showed a steady decrease until day 7 without differences in patients with and without presumed infection. CRP concentrations increased to a peak level at days 3-4 followed by a steady decrease; CRP concentrations were higher in patients with clinical diagnosis of infection on day 4 (P = 0.02); and in patients with evidence of bacterial growth in cultures on days 4 and 5 (P = 0.01 and P = 0.006). WBC remained unchanged after hypothermia without differences between patients with and without infection. High initial values of PCT and high peak levels after 3-4 days of CRP were found in patients with induction of hypothermia after cardiac arrest. This increase was unspecific and mirrors rather an inflammatory reaction than true underlying infection, limiting the diagnostic potential for early antibiotic stewardship in these patients.

  1. Neurotensin analog selective for hypothermia over antinociception and exhibiting atypical neuroleptic-like properties.

    PubMed

    Boules, M; McMahon, B; Warrington, L; Stewart, J; Jackson, J; Fauq, A; McCormick, D; Richelson, E

    2001-11-16

    Neurotensin (NT) is a tridecapeptide neurotransmitter in the central nervous system. It has been implicated in the therapeutic effects of neuroleptics. Central activity of NT can only be demonstrated by direct injection into the brain, since it is readily degraded by peptidases in the periphery. We have developed many NT(8-13) analogs that are resistant to peptidase degradation and can cross the blood-brain barrier (BBB). In this study, we report on one of these analogs, NT77L. NT77L induced hypothermia (ED(50)=6.5 mg/kg, i.p.) but induced analgesia only at the highest dose examined (20 mg/kg, i.p.). Like the atypical neuroleptic clozapine, NT77L blocked the climbing behavior in rats induced by the dopamine agonist apomorphine (600 microg/kg) with an ED(50) of 5.6 mg/kg (i.p.), without affecting the licking and the sniffing behaviors. By itself NT77L did not cause catalepsy, but it moderately reversed haloperidol-induced catalepsy with an ED(50) of 6.0 mg/kg (i.p.). Haloperidol alone did not lower body temperature, but it potentiated the body temperature lowering effect of NT77L. In studies using in vivo microdialysis NT77L showed similar effects on dopamine turnover to those of clozapine, and significantly different from those of haloperidol in the striatum. In the prefrontal cortex, NT77L significantly increased serotonergic transmission as evidenced by increased 5-hydroxyindole acetic acid:5-hydroxytryptamine (5-HIAA:5-HT) ratio. Thus, NT77L selectively caused hypothermia, over antinociception, while exhibiting atypical neuroleptic-like effects.

  2. Induced hypothermia for infants with hypoxic- ischemic encephalopathy using a servo-controlled fan: an exploratory pilot study.

    PubMed

    Horn, Alan; Thompson, Clare; Woods, David; Nel, Alida; Bekker, Adrie; Rhoda, Natasha; Pieper, Clarissa

    2009-06-01

    Several trials suggest that hypothermia is beneficial in selected infants with hypoxic-ischemic encephalopathy. However, the cooling methods used required repeated interventions and were either expensive or reported significant temperature variation. The objective of this pilot study was to describe the use, efficacy, and physiologic impact of an inexpensive servo-controlled cooling fan blowing room-temperature air. A servo-controlled fan was manufactured and used to cool 10 infants with hypoxic-ischemic encephalopathy to a rectal temperature of 33 degrees C to 34 degrees C. The infants were sedated with phenobarbital, but clonidine was administered to some infants if shivering or discomfort occurred. A servo-controlled radiant warmer was used simultaneously with the fan to prevent overcooling. The settings used on the fan and radiant warmer differed slightly between some infants as the technique evolved. A rectal temperature of 34 degrees C was achieved in a median time of 58 minutes. Overcooling did not occur, and the mean temperature during cooling was 33.6 degrees C +/- 0.2 degrees C. Inspired oxygen requirements increased in 6 infants, and 5 infants required inotropic support during cooling, but this was progressively reduced after 1 to 2 days. Dehydration did not occur. Five infants shivered when faster fan speeds were used, but 4 of the 5 infants had hypomagnesemia. Shivering was controlled with clonidine in 4 infants, but 1 infant required morphine. Servo-controlled fan cooling with room-temperature air, combined with servo-controlled radiant warming, was an effective, simple, and safe method of inducing and maintaining rectal temperatures of 33 degrees C to 34 degrees C in sedated infants with hypoxic-ischemic encephalopathy. After induction of hypothermia, a low fan speed facilitated accurate temperature control, and warmer-controlled rewarming at 0.2 degrees C increments every 30 minutes resulted in more appropriate rewarming than when 0.5 degrees C

  3. Localized hypothermia aggravates bleeding in the collagenase model of intracerebral hemorrhage.

    PubMed

    John, Roseleen F; Williamson, Michael R; Dietrich, Kristen; Colbourne, Frederick

    2015-03-01

    Animal studies testing whether therapeutic hypothermia is neuroprotective after intracerebral hemorrhage (ICH) have been inconclusive. In rodents, ICH is often produced in the striatum by infusing collagenase, which causes prolonged hemorrhaging from multiple vessels. Our previous data shows that this bleeding (hematoma) is worsened by systemic hypothermia given soon after collagenase infusion. In this study we hypothesized that localized brain hypothermia would also aggravate bleeding in this model (0.2 U of collagenase in 1.2 μL of saline). We also evaluated cooling after intrastriatal thrombin infusion (1 U in 30 μL of saline)-a simplified model of ICH thought to cause bleeding. Focal hypothermia was achieved by flushing cold water through an implanted cooling device attached to the skull underneath the temporalis muscle of adult rats. Previous work and data at this time shows this method cools the striatum to ∼33°C, whereas the body remains normothermic. In comparison to normothermic groups, cooling significantly worsened bleeding when instituted at 6 hours (∼94 vs. 42 μL, p=0.018) and 12 hours (79 vs. 61 μL, p=0.042) post-ICH (24-hour survival), but not after a 24-hour delay (36-hour survival). Rats were cooled until euthanasia when hematoma size was determined by a hemoglobin-based spectrophotometry assay. Cooling did not influence cerebral blood volume after just saline or thrombin infusion. The latter is explained by the fact that thrombin did not cause bleeding beyond that caused by saline infusion. In summary, local hypothermia significantly aggravates bleeding many hours after collagenase infusion suggesting that bleeding may have confounded earlier studies with hypothermia. Furthermore, these findings serve as a cautionary note on using cooling even many hours after cerebral bleeding.

  4. Short Duration Combined Mild Hypothermia Improves Resuscitation Outcomes in a Porcine Model of Prolonged Cardiac Arrest

    PubMed Central

    Yu, Tao; Yang, Zhengfei; Li, Heng; Ding, Youde; Huang, Zitong

    2015-01-01

    Objective. In this study, our aim was to investigate the effects of combined hypothermia with short duration maintenance on the resuscitation outcomes in a porcine model of ventricular fibrillation (VF). Methods. Fourteen porcine models were electrically induced with VF and untreated for 11 mins. All animals were successfully resuscitated manually and then randomized into two groups: combined mild hypothermia (CH group) and normothermia group (NT group). A combined hypothermia of ice cold saline infusion and surface cooling was implemented in the animals of the CH group and maintained for 4 hours. The survival outcomes and neurological function were evaluated every 24 hours until a maximum of 96 hours. Neuron apoptosis in hippocampus was analyzed. Results. There were no significant differences in baseline physiologies and primary resuscitation outcomes between both groups. Obvious improvements of cardiac output were observed in the CH group at 120, 180, and 240 mins following resuscitation. The animals demonstrated better survival at 96 hours in the CH group when compared to the NT group. In comparison with the NT group, favorable neurological functions were observed in the CH group. Conclusion. Short duration combined cooling initiated after resuscitation improves survival and neurological outcomes in a porcine model of prolonged VF. PMID:26558261

  5. Dopamine treatment attenuates acute kidney injury in a rat model of deep hypothermia and rewarming - The role of renal H2S-producing enzymes.

    PubMed

    Dugbartey, George J; Talaei, Fatemeh; Houwertjes, Martin C; Goris, Maaike; Epema, Anne H; Bouma, Hjalmar R; Henning, Robert H

    2015-12-15

    Hypothermia and rewarming produces organ injury through the production of reactive oxygen species. We previously found that dopamine prevents hypothermia and rewarming-induced apoptosis in cultured cells through increased expression of the H2S-producing enzyme cystathionine β-Synthase (CBS). Here, we investigate whether dopamine protects the kidney in deep body cooling and explore the role of H2S-producing enzymes in an in vivo rat model of deep hypothermia and rewarming. In anesthetized Wistar rats, body temperature was decreased to 15°C for 3h, followed by rewarming for 1h. Rats (n≥5 per group) were treated throughout the procedure with vehicle or dopamine infusion, and in the presence or absence of a non-specific inhibitor of H2S-producing enzymes, amino-oxyacetic acid (AOAA). Kidney damage and renal expression of three H2S-producing enzymes (CBS, CSE and 3-MST) was quantified and serum H2S level measured. Hypothermia and rewarming induced renal damage, evidenced by increased serum creatinine, renal reactive oxygen species production, KIM-1 expression and influx of immune cells, which was accompanied by substantially lowered renal expression of CBS, CSE, and 3-MST and lowered serum H2S levels. Infusion of dopamine fully attenuated renal damage and maintained expression of H2S-producing enzymes, while normalizing serum H2S. AOAA further decreased the expression of H2S-producing enzymes and serum H2S level, and aggravated renal damage. Hence, dopamine preserves renal integrity during deep hypothermia and rewarming likely by maintaining the expression of renal H2S-producing enzymes and serum H2S. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Unexpectedly high incidence of hypothermia before induction of anesthesia in elective surgical patients.

    PubMed

    Wetz, Anna J; Perl, Thorsten; Brandes, Ivo F; Harden, Markus; Bauer, Martin; Bräuer, Anselm

    2016-11-01

    Perioperative hypothermia is a frequently observed phenomenon of general anesthesia and is associated with adverse patient outcome. Recently, a significant influence of core temperature before induction of anesthesia has been reported. However, there are still little existing data on core temperature before induction of anesthesia and no data regarding potential risk factors for developing preoperative hypothermia. The purpose of this investigation was to estimate the incidence of hypothermia before anesthesia and to determine if certain factors predict its incidence. Data from 7 prospective studies investigating core temperature previously initiated at our department were analyzed. Patients undergoing a variety of elective surgical procedures were included. Core temperature was measured before induction of anesthesia with an oral (314 patients), infrared tympanic (143 patients), or tympanic contact thermometer (36 patients). Available potential predictors included American Society of Anesthesiologists status, sex, age, weight, height, body mass index, adipose ratio, and lean body weight. Association with preoperative hypothermia was assessed separately for each predictor using logistic regression. Independent predictors were identified using multivariable logistic regression. A total of 493 patients were included in the study. Hypothermia was found in 105 patients (21.3%; 95% confidence interval, 17.8%-25.2%). The median core temperature was 36.3°C (25th-75th percentiles, 36.0°C-36.7°C). Two independent factors for preoperative hypothermia were identified: male sex and age (>52years). As a consequence of the high incidence of hypothermia before anesthesia, measuring core temperature should be mandatory 60 to 120minutes before induction to identify and provide adequate treatment to hypothermic patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Hypothermia is associated with improved outcomes in a porcine model of hemorrhagic shock.

    PubMed

    George, Mark E; Mulier, Kristine E; Beilman, Greg J

    2010-03-01

    : Hypothermia after trauma is, in current medical practice, both avoided and aggressively treated. However, the effects of environmental hypothermia during early resuscitation after hemorrhagic shock have been only poorly characterized. : The objective of our study was to compare normothermia versus mild and severe levels of hypothermia in a porcine model of hemorrhagic shock. In a prospective survival study, we anesthetized 19 juvenile male pigs (Yorkshire-Landrace, 15-25 kg) and caused them to hemorrhage until their systolic blood pressure was 45 mm Hg to 55 mm Hg for a duration of 45 minutes. Then, we randomized them into three groups (all of which underwent an 8-hour limited resuscitation period) as follows: normothermic (39 degrees C), mildly hypothermic (36 degrees C), and severely hypothermic (33 degrees C). We used ice packs to achieve surface cooling that mimicked environmental hypothermia. After 8 hours, we rewarmed the pigs and fully resuscitated them for 16 hours. We extubated the survivors and observed them for an additional 24 hours, before killing them. : Surface cooling resulted in significant reduction in core body temperature. The mortality rate was significantly higher in the normothermic group (60%) than in the two hypothermic groups combined (7%) (p = 0.015) or in the severely hypothermic group (0%) (p = 0.023). Hypothermic animals had significantly lower levels of creatinine kinase, lactate dehydrogenase, and lactate in addition to a lower base deficit after shock. However, severely hypothermic animals required greater volumes of colloid infusion and whole blood transfusion to maintain our target systolic blood pressure and hemoglobin levels when compared with normothermic animals. We saw a strong trend toward decreased oxygen consumption with hypothermia. : In our porcine model, we found that simulating mild and severe levels of environmental hypothermia during early resuscitation after hemorrhage was associated with a significantly decreased

  8. Adding 5 h delayed xenon to delayed hypothermia treatment improves long-term function in neonatal rats surviving to adulthood.

    PubMed

    Liu, Xun; Dingley, John; Scull-Brown, Emma; Thoresen, Marianne

    2015-06-01

    We previously reported that combining immediate hypothermia with immediate or 2 h delayed inhalation of an inert gas, xenon, gave additive neuroprotection in rats after a hypoxic-ischemic insult, compared to hypothermia alone. Defining the therapeutic time window for this new combined intervention is crucial in clinical practice when immediate treatment is not always feasible. The aim of this study is to investigate whether combined hypothermia and xenon still provide neuroprotection in rats after a 5 h delay for both hypothermia and xenon. Seven-day-old Wistar rat pups underwent a unilateral hypoxic-ischemic insult. Pups received 5 h of treatment starting 5 h after the insult randomized between normothermia, hypothermia, or hypothermia with 50% xenon. Surviving pups were tested for fine motor function through weeks 8-10 before being euthanized at week 11. Their hemispheric and hippocampal areas were assessed. Both delayed hypothermia-xenon and hypothermia-only treated groups had significantly less brain tissue loss than those which underwent normothermia. The functional performance after 1 wk and adulthood was significantly better after hypothermia-xenon treatment as compared to the hypothermia-only or normothermia groups. Adding 50% xenon to 5 h delayed hypothermia significantly improved functional outcome as compared to delayed hypothermia alone despite similar reductions in brain area.

  9. Hypothermia is associated with poor outcome in pediatric trauma patients.

    PubMed

    Sundberg, Jennifer; Estrada, Cristina; Jenkins, Cathy; Ray, Jacqueline; Abramo, Thomas

    2011-11-01

    The objective of the study was to determine if hypothermia in pediatric trauma patients is associated with increased mortality. We reviewed the charts of level 1 trauma patients aged 3 months to 17 years who presented between September 2006 and March 2008. We analyzed data for patients with temperatures recorded within 30 minutes of arrival to the pediatric emergency department. Logistic regression models were used to test for associations of hypothermia with death while adjusting for mode of transport, season of year, and presence of intracranial pathology as documented by an abnormal head computed tomographic scan. Of the 226 level 1 trauma patients presenting during the study period, 190 met inclusion criteria. Twenty-one patients (11%) died. The odds ratio (OR) of a hypothermic patient dying was 9.2 times that of a normothermic patient when adjusting for seasonal variation (95% confidence interval [CI], 3.2-26.2; P < 0.0001). The OR of a hypothermic patient dying was 8.7 times that of a normothermic patient when adjusting for mode of transport (ground vs air) (95% CI, 3.1-24.6; P < 0.0001). Although it did not reach statistical significance, there was a trend toward an association between hypothermia and the presence of traumatic brain injury as evidenced by an abnormal head computed tomographic scan (OR = 2.4; 95% CI, 0.9-6.0; P = .07). Hypothermia is a risk factor for increased mortality in pediatric trauma patients. This pilot study warrants a more detailed, multicenter analysis to assess the impact of hypothermia in the pediatric trauma patient. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Hypothermia postpones DNA damage repair in irradiated cells and protects against cell killing.

    PubMed

    Baird, Brandon J; Dickey, Jennifer S; Nakamura, Asako J; Redon, Christophe E; Parekh, Palak; Griko, Yuri V; Aziz, Khaled; Georgakilas, Alexandros G; Bonner, William M; Martin, Olga A

    2011-06-03

    Hibernation is an established strategy used by some homeothermic organisms to survive cold environments. In true hibernation, the core body temperature of an animal may drop to below 0°C and metabolic activity almost cease. The phenomenon of hibernation in humans is receiving renewed interest since several cases of victims exhibiting core body temperatures as low as 13.7°C have been revived with minimal lasting deficits. In addition, local cooling during radiotherapy has resulted in normal tissue protection. The experiments described in this paper were prompted by the results of a very limited pilot study, which showed a suppressed DNA repair response of mouse lymphocytes collected from animals subjected to 7-Gy total body irradiation under hypothermic (13°C) conditions, compared to normothermic controls. Here we report that human BJ-hTERT cells exhibited a pronounced radioprotective effect on clonogenic survival when cooled to 13°C during and 12h after irradiation. Mild hypothermia at 20 and 30°C also resulted in some radioprotection. The neutral comet assay revealed an apparent lack on double strand break (DSB) rejoining at 13°C. Extension of the mouse lymphocyte study to ex vivo-irradiated human lymphocytes confirmed lower levels of induced phosphorylated H2AX (γ-H2AX) and persistence of the lesions at hypothermia compared to the normal temperature. Parallel studies of radiation-induced oxidatively clustered DNA lesions (OCDLs) revealed partial repair at 13°C compared to the rapid repair at 37°C. For both γ-H2AX foci and OCDLs, the return of lymphocytes to 37°C resulted in the resumption of normal repair kinetics. These results, as well as observations made by others and reviewed in this study, have implications for understanding the radiobiology and protective mechanisms underlying hypothermia and potential opportunities for exploitation in terms of protecting normal tissues against radiation. 2011. Published by Elsevier B.V.

  11. The Cold Blooded Killer: Hypothermia.

    ERIC Educational Resources Information Center

    Keller, Rosanne

    Part of a series of home literacy readers with conversational text and sketches, this booklet depicts the subarctic Alaskan environment where cold makes extreme demands on body metabolism. Body temperature must be maintained above 80F (26.7C). A condition of too little body-heat is termed hypo- ('deficit') thermia ('heat'). Hypothermia is the…

  12. A new microcontroller-based human brain hypothermia system.

    PubMed

    Kapidere, Metin; Ahiska, Raşit; Güler, Inan

    2005-10-01

    Many studies show that artificial hypothermia of brain in conditions of anesthesia with the rectal temperature lowered down to 33 degrees C produces pronounced prophylactic effect protecting the brain from anoxia. Out of the methods employed now in clinical practice for reducing the oxygen consumption by the cerebral tissue, the most efficacious is craniocerebral hypothermia (CCH). It is finding even more extensive application in cardiovascular surgery, neurosurgery, neurorenimatology and many other fields of medical practice. In this study, a microcontroller-based designed human brain hypothermia system (HBHS) is designed and constructed. The system is intended for cooling and heating the brain. HBHS consists of a thermoelectric hypothermic helmet, a control and a power unit. Helmet temperature is controlled by 8-bit PIC16F877 microcontroller which is programmed using MPLAB editor. Temperature is converted to 10-bit digital and is controlled automatically by the preset values which have been already entered in the microcontroller. Calibration is controlled and the working range is tested. Temperature of helmet is controlled between -5 and +46 degrees C by microcontroller, with the accuracy of +/-0.5 degrees C.

  13. The practice of therapeutic hypothermia after cardiac arrest in France: a national survey.

    PubMed

    Orban, Jean-Christophe; Cattet, Florian; Lefrant, Jean-Yves; Leone, Marc; Jaber, Samir; Constantin, Jean-Michel; Allaouchiche, Bernard; Ichai, Carole

    2012-01-01

    Cardiac arrest is a major health concern worldwide accounting for 375,000 cases per year in Europe with a survival rate of <10%. Therapeutic hypothermia has been shown to improve patients' neurological outcome and is recommended by scientific societies. Despite these guidelines, different surveys report a heterogeneous application of this treatment. The aim of the present study was to evaluate the clinical practice of therapeutic hypothermia in cardiac arrest patients. This self-declarative web based survey was proposed to all registered French adult intensive care units (ICUs) (n=357). Paediatrics and neurosurgery ICUs were excluded. The different questions addressed the structure, the practical modalities of therapeutic hypothermia and the use of prognostic factors in patients admitted after cardiac arrest. One hundred and thirty-two out of 357 ICUs (37%) answered the questionnaire. Adherence to recommendations regarding the targeted temperature and hypothermia duration were 98% and 94% respectively. Both guidelines were followed in 92% ICUs. During therapeutic hypothermia, sedative drugs were given in 99% ICUs, mostly midazolam (77%) and sufentanil (59%). Neuromuscular blocking agents (NMBA) were used in 97% ICUs, mainly cisatracurium (77%). Numerous prognostic factors were used after cardiac arrest such as clinical factors (95%), biomarkers (53%), electroencephalography (78%) and evoked potentials (35%). In France, adherence to recommendations for therapeutic hypothermia after cardiac arrest is higher than those previously reported in other countries. Numerous prognostic factors are widely used even if their reliability remains controversial.

  14. Armanni-Ebstein phenomenon and hypothermia.

    PubMed

    Zhou, Chong; Byard, Roger W

    2011-03-20

    Retrospective review was undertaken of 46 cases of lethal hypothermia for the presence of subnuclear vacuolization of renal tubular epithelial cells. Fifteen of the 46 cases (33%) had renal tubular vacuolization typical of the Armanni-Ebstein phenomenon. The age range was 30-87 years (average 59 years) with a male to female ratio of 6:9. Nine of the 15 cases with Armanni-Ebstein changes (60%) had a history of diabetes mellitus, and in seven of these vitreous humour biochemical analyses were performed, all of which revealed diabetic ketoacidosis (vitreous glucose levels = 32.9-85.3 mmol/L; β-hydroxybutyrate = 7.4-20 mmol/L). This study has confirmed the association between hypothermia and renal tubular epithelial vacuolization, but in addition raises the prospect that this may be contributed to in some cases by underlying diabetic ketoacidosis. Hypothermic deaths should, therefore, raise the possibility of diabetes mellitus and initiate postmortem biochemical measurement of vitreous humor glucose and β-hydroxybutyrate levels. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  15. The characterization of oxotremorine-induced hypothermic response in the rat.

    PubMed

    Ryan, P M; Kelly, J P; Chambers, P L; Leonard, B E

    1996-11-01

    Oxotremorine is a muscarinic receptor agonist that induces a variety of physiological and behavioural effects including hypothermia in mice. These effects are antagonized dose-dependently by classical anticholinergic compounds such as atropine. Although the oxotremorine-induced hypothermic response has been demonstrated in mice, few studies of the effects of this muscarinic agonist have been made in the rat. The following studies were made in male Sprague Dawley rats: 1. an investigation of the dose-response relationship between oxotremorine and hypothermia; 2. an examination of the effect of housing on the oxotremorine-induced hypothermic response, and 3, an investigation of the acute administration of various doses of atropine sulphate on the hypothermia caused by oxotremorine. The results indicate that the dose-response relationship between oxotremorine and the antagonism of hypothermia is similar in rat as it is in mice. The results also showed that this effect did not occur in group-housed animals.

  16. Moderate hypothermia technique for chronic implantation of a total artificial heart in calves.

    PubMed

    Karimov, Jamshid H; Grady, Patrick; Sinkewich, Martin; Sunagawa, Gengo; Dessoffy, Raymond; Byram, Nicole; Moazami, Nader; Fukamachi, Kiyotaka

    2017-06-01

    The benefit of whole-body hypothermia in preventing ischemic injury during cardiac surgical operations is well documented. However, application of hypothermia during in vivo total artificial heart implantation has not become widespread because of limited understanding of the proper techniques and restrictions implied by constitutional and physiological characteristics specific to each animal model. Similarly, the literature on hypothermic set-up in total artificial heart implantation has also been limited. Herein we present our experience using hypothermia in bovine models implanted with the Cleveland Clinic continuous-flow total artificial heart.

  17. Effect of wet-cold weather transportation conditions on thermoregulation and the development of accidental hypothermia in pullets under tropical conditions

    NASA Astrophysics Data System (ADS)

    Minka, Ndazo S.; Ayo, Joseph O.

    2016-03-01

    The present study examines onboard thermal microclimatic conditions and thermoregulation of pullets exposed to accidental hypothermia during wet-cold weather transportation conditions, and the effect of rewarming on colonic temperature (CT) of the birds immediately after transportation. A total of 2200 pullets were transportation for 5 h in two separate vehicles during the nighttime. The last 3 h of the transportation period was characterized by heavy rainfall. During the precipitation period, each vehicle was covered one fourth way from the top-roof with a tarpaulin. The onboard thermal conditions inside the vehicles during transportation, which comprised ambient temperature and relative humidity were recorded, while humidity ratio and specific enthalpy were calculated. The CT of the birds was recorded before and after transportation. During transportation, onboard thermal heterogeneity was observed inside the vehicles with higher ( p < 0.05) values in the front and center, and lower values recorded at the air inlets at the sides and rear planes. The CT values recorded in birds at the front and center planes were between 42.2 and 42.5 °C, indicative of mild hypothermia; while lower CT values between 28 and 38 °C were recorded at the sides and rear planes, indicative of mild to severe hypothermia. Several hours of gradual rewarming returned the CT to normal range. The result, for the first time, demonstrated the occurrence of accidental hypothermia in transported pullets under tropical conditions and a successful rewarming outcome. In conclusion, transportation of pullets during wet weather at onboard temperature of 18-20 °C induced hypothermia on birds located at the air inlets, which recovered fully after several hours of gradual rewarming.

  18. Technical Note: System for evaluating local hypothermia as a radioprotector of the rectum in a small animal model.

    PubMed

    Hrycushko, Brian A; Bing, Chenchen; Futch, Cecil; Wodzak, Michelle; Stojadinovic, Strahinja; Medin, Paul M; Chopra, Rajiv

    2017-08-01

    The protective effects of induced or even accidental hypothermia on the human body are widespread with several medical uses currently under active research. In vitro experiments using human cell lines have shown hypothermia provides a radioprotective effect that becomes more pronounced at large, single-fraction doses common to stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) treatments. This work describes the development of a system to evaluate local hypothermia for a radioprotective effect of the rat rectum during a large dose of radiation relevant to prostate SBRT. This includes the evaluation of a 3D-printed small animal rectal cooling device and the integration with a small animal irradiator. A 3-cm long, dual-lumen rectal temperature control apparatus (RTCA) was designed in SOLIDWORKS CAD for 3D printing. The RTCA was capable of recirculating flow in a device small enough for insertion into the rat rectum, with a metal support rod for strength as well as visibility during radiation treatment planning. The outer walls of the RTCA comprised of thin heat shrink plastic, achieving efficient heat transfer into adjacent tissues. Following leak-proof testing, fiber optic temperature probes were used to evaluate the temperature over time when placed adjacent to the cooling device within the rat rectum. MRI thermometry characterized the relative temperature distribution in concentric ROIs surrounding the probe. Integration with an image-guided small animal irradiator and associated treatment planning system included evaluation for imaging artifacts and effect of brass tubing on dose calculation. The rectal temperature adjacent to the cooling device decreased from body temperature to 15°C within 10-20 min from device insertion and was maintained at 15 ± 3°C during active cooling for the evaluated time of one hour. MR thermometry revealed a steep temperature gradient with increasing distance from the cooling device with the desired

  19. Partners' ambivalence towards cardiac arrest and hypothermia treatment: a qualitative study.

    PubMed

    Holm, Marianne S; Norekvål, Tone M; Fålun, Nina; Gjengedal, Eva

    2012-01-01

    The purpose of this study was to examine the experiences of partners of patients who had cardiac arrest and subsequent hypothermia treatment in an intensive care unit (ICU). Nine in-depth interviews were conducted 5 months to 1 year after hospitalization. The participants were partners of patients who had survived cardiac arrest and had undergone hypothermia treatment without serious brain damage. All the interviews were analysed using Giorgi's phenomenological method. Six main themes emerged from the analysis: (1) terrified by witnessing the cardiac arrest; (2) ambivalence towards the ICU room and the cold body; (3) need for honest and realistic information; (4) anticipating the awakening; (5) social network as support and burden; and (6) the frightening homecoming. The essential structure of the partners' experiences of loved ones' cardiac arrest and hypothermia treatment was characterized by ambivalence; they experienced both fear and relief. There may be a relationship between experiences before entering the ICU and reactions during hypothermia treatment and afterwards. Some partners experienced a feeling of guilt after the resuscitation event, and especially during the awakening phase. After discharge, the partners described feeling anxiety. Nurses play a pivotal role in providing partners with information and in nurturing hope and feelings of security. Partners need to fully understand the reason for hypothermia treatment to enable them to accept the cold body as part of a life-saving process. We recommend follow-up after discharge. This may increase the partners' sense of security and control. © 2012 The Authors. Nursing in Critical Care © 2012 British Association of Critical Care Nurses.

  20. Preoperative carbohydrate-rich beverage reduces hypothermia during general anesthesia in rats.

    PubMed

    Yatabe, Tomoaki; Kawano, Takashi; Yamashita, Koichi; Yokoyama, Masataka

    2011-08-01

    Intraoperative hypothermia is associated with several unfavorable events; therefore, it is important to prevent the development of hypothermia. Amino acid consumption and/or infusion have been reported to prevent hypothermia. We hypothesized that preoperative carbohydrate-rich beverage (Arginaid Water™) loading can reduce intraoperative hypothermia in rats under general anesthesia. We divided 18 rats into 3 groups (group A, 8 mL/kg of saline; group B, 8 mL/kg of a carbohydrate-rich beverage; and group C, 21 mL/kg of the carbohydrate-rich beverage). The rats were administered each beverage at the above mentioned doses via an oral gastric tube 30 min before the induction of anesthesia. During the 2-h general anesthesia, rectal temperature was measured at 20-min intervals. Serum ketone body concentration was measured at 0 and 120 min. The baseline temperature was not significantly different among the groups. At the end of the experiment, group A showed a significantly greater decrease in temperature from the baseline (5.4 ± 0.8°C) than group B (3.9 ± 0.7°C, P = 0.01) and group C (3.8 ± 0.8°C, P = 0.01). The temperatures in groups B and C were not significantly different. There was no significant change in the serum ketone body concentration from the baseline at the end of the experiment in group A. However, the serum ketone body concentrations in group B and group C were significantly decreased from the baseline. Preoperative carbohydrate loading reduces hypothermia in rats under general anesthesia.

  1. Randomized controlled trial of moderate hypothermia versus deep hypothermia anesthesia on brain injury during Stanford A aortic dissection surgery.

    PubMed

    Sun, Xufang; Yang, Hua; Li, Xinyu; Wang, Yue; Zhang, Chuncheng; Song, Zhimin; Pan, Zhenxiang

    2018-01-01

    This study aimed to compare the effects of moderate versus deep hypothermia anesthesia for Stanford A aortic dissection surgery on brain injury. A total of 82 patients who would undergo Stanford A aortic dissection surgery were randomized into two groups: moderate hypothermia group (MH, n = 40, nasopharyngeal temperature 25 °C, and rectal temperature 28 °C) and deep hypothermia group (DH, n = 42, nasopharyngeal temperature 20 °C, and rectal temperature 25 °C). Different vascular replacement techniques including aortic root replacement, Bentall, and Wheat were used. The intraoperative and postoperative indicators of these patients were recorded. There were no differences in intraoperative and postoperative measures between MH and DH groups. The concentrations of neuron-specific enolase and S-100β increased with operation time, and were significantly lower in MH group than those in the DH group (P < 0.05). The occurrence rates of complications including chenosis, postoperative agitation, and neurological complications in MH group were significantly lower than in DH group. The recovery time, postoperative tube, and ICU intubation stay were significantly shorter in MH group than those in DH group (P < 0.05). There were no significant differences revealed in hospital stay and death rate. MH exhibited better cerebral protective effects, less complications, and shorter tube time than DH in surgery for Stanford A aortic dissection.

  2. Regulation of Therapeutic Hypothermia on Inflammatory Cytokines, Microglia Polarization, Migration and Functional Recovery after Ischemic Stroke in Mice

    PubMed Central

    Lee, Jin Hwan; Wei, Zheng Z; Cao, Wenyuan; Won, Soonmi; Gu, Xiaohuan; Winter, Megan; Dix, Thomas A.; Wei, Ling; Yu, Shan Ping

    2016-01-01

    Stroke is a leading threat to human life and health in the US and around the globe, while very few effective treatments are available for stroke patients. Preclinical and clinical studies have shown that therapeutic hypothermia (TH) is a potential treatment for stroke. Using novel neurotensin receptor 1 (NTR1) agonists, we have demonstrated pharmacologically induced hypothermia and protective effects against brain damages after ischemic stroke, hemorrhage stroke, and traumatic brain injury (TBI) in rodent models. To further characterize the mechanism of TH-induced brain protection, we examined the effect of TH (at ±33°C for 6 hrs) induced by the NTR1 agonist HPI-201 or physical (ice/cold air) cooling on inflammatory responses after ischemic stroke in mice and oxygen glucose deprivation (OGD) in cortical neuronal cultures. Seven days after focal cortical ischemia, microglia activation in the penumbra reached a peak level, which was significantly attenuated by TH treatments commenced 30 min after stroke. The TH treatment decreased the expression of M1 type reactive factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-12, IL-23, and inducible nitric oxide synthase (iNOS) measured by RT-PCR and Western blot analyses. Meanwhile, TH treatments increased the expression of M2 type reactive factors including IL-10, Fizz1, Ym1, and arginase-1. In the ischemic brain and in cortical neuronal/BV2 microglia cultures subjected to OGD, TH attenuated the expression of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α), two key chemokines in the regulation of microglia activation and infiltration. Consistently, physical cooling during OGD significantly decreased microglia migration 16 hrs after OGD. Finally, TH improved functional recovery at 1, 3, and 7 days after stroke. This study reveals the first evidence for hypothermia mediated regulation on inflammatory factor expression, microglia polarization

  3. Peripheral kappa-opioid agonist, ICI 204448, evokes hypothermia in cold-exposed rats.

    PubMed

    Rawls, Scott M; Ding, Zhe; Gray, Alex M; Cowan, Alan

    2005-05-01

    ICI 204448, a selective kappa-opioid agonist with limited CNS access, can be used to discriminate central and peripheral opioid actions on physiological systems such as pain and thermoregulation. Therefore, we investigated the effect of ICI 204448 (2.5, 5, and 10 mg/kg, s.c.) on male Sprague-Dawley rats exposed to ambient temperatures of 5, 20, or 32 degrees C. ICI 204448 did not alter the body temperature of rats maintained at 20 or 32 degrees C. However, 5 and 10 mg/kg of ICI 204448 evoked significant hypothermia in rats exposed to 5 degrees C. The i.c.v. administration of nor-BNI, a kappa-opioid antagonist, did not affect the hypothermia produced by the systemic injection of ICI 204448. Thus, an involvement of brain kappa-opioid receptors in ICI 204448-evoked hypothermia is unlikely. The present data demonstrate for the first time that ICI 204448 produces hypothermia in cold-exposed rats and suggest that the role of peripheral kappa-opioid receptors in thermoregulation becomes more significant at cold ambient temperatures. Copyright (c) 2005 S. Karger AG, Basel.

  4. Does therapeutic hypothermia reduce acute kidney injury among term neonates with perinatal asphyxia?--a randomized controlled trial.

    PubMed

    Tanigasalam, Vasanthan; Bhat, Vishnu; Adhisivam, Bethou; Sridhar, M G

    2016-01-01

    The objective of this study is to evaluate whether therapeutic hypothermia reduces the incidence of acute kidney injury (AKI) among term neonates perinatal asphyxia. This randomized controlled trial conducted in a tertiary care teaching hospital, south India included 120 term neonates with perinatal asphyxia who were randomized to receive either therapeutic hypothermia or standard supportive care. Renal parameters of neonates in both the groups were monitored and AKI was ascertained as per Acute Kidney Injury Network criteria. The incidence of AKI was less in therapeutic hypothermia group compared to standard treatment group (32% versus 60%, p < 0.05). The incidence of Stages 1, 2, and 3 AKI was 22%, 5%, and 5% in therapeutic hypothermia group compared with 52%, 5%, and 3%, respectively, in the standard treatment group. The mortality was less in therapeutic hypothermia group compared with the standard treatment group (26% versus 50%, p < 0.05). Therapeutic hypothermia reduces the incidence and severity of AKI among term neonates with perinatal asphyxia.

  5. Hypothermia as a cause of coagulopathy during hepatectomy.

    PubMed

    Lau, Albert Wai-Cheung; Chen, Chia-Chen; Wu, Rick Sai-Chuen; Poon, Kin-Shing

    2010-06-01

    We report a 27-year-old hemostatically competent female scheduled for partial hepatectomy. During the operation, she experienced an accidental inferior vena cava tear and suffered acute blood loss. After fluid resuscitation and blood transfusion, she developed hypothermia, with a temperature of 33.8 degrees C, and severe coagulopathy with activated clotting time exceeding 1500 seconds measured using the Hemochron Response system (ITC, Edison, NJ, USA). Despite sufficient blood transfusion and correction of her electrolyte imbalance, the poor hemostasis persisted. After per-forming peritoneal lavage with warm saline, her condition dramatically improved and her hypothermia and severe coagulopathy were reversed. 2010 Taiwan Society of Anesthesiologists. Published by Elsevier B.V. All rights reserved.

  6. The big chill: accidental hypothermia.

    PubMed

    Davis, Robert Allan

    2012-01-01

    A potential cause of such emergent issues as cardiac arrhythmias, hypotension, and fluid and electrolyte shifts, accidental hypothermia can be deadly, is common among trauma patients, and is often difficult to recognize. The author discusses predisposing conditions, the classic presentation, and the effects on normal thermoregulatory processes; explains how to conduct a systems assessment of the hypothermic patient; and describes crucial management strategies.

  7. Effect of wet-cold weather transportation conditions on thermoregulation and the development of accidental hypothermia in pullets under tropical conditions.

    PubMed

    Minka, Ndazo S; Ayo, Joseph O

    2016-03-01

    The present study examines onboard thermal microclimatic conditions and thermoregulation of pullets exposed to accidental hypothermia during wet-cold weather transportation conditions, and the effect of rewarming on colonic temperature (CT) of the birds immediately after transportation. A total of 2200 pullets were transportation for 5 h in two separate vehicles during the nighttime. The last 3 h of the transportation period was characterized by heavy rainfall. During the precipitation period, each vehicle was covered one fourth way from the top-roof with a tarpaulin. The onboard thermal conditions inside the vehicles during transportation, which comprised ambient temperature and relative humidity were recorded, while humidity ratio and specific enthalpy were calculated. The CT of the birds was recorded before and after transportation. During transportation, onboard thermal heterogeneity was observed inside the vehicles with higher (p < 0.05) values in the front and center, and lower values recorded at the air inlets at the sides and rear planes. The CT values recorded in birds at the front and center planes were between 42.2 and 42.5 °C, indicative of mild hypothermia; while lower CT values between 28 and 38 °C were recorded at the sides and rear planes, indicative of mild to severe hypothermia. Several hours of gradual rewarming returned the CT to normal range. The result, for the first time, demonstrated the occurrence of accidental hypothermia in transported pullets under tropical conditions and a successful rewarming outcome. In conclusion, transportation of pullets during wet weather at onboard temperature of 18-20 °C induced hypothermia on birds located at the air inlets, which recovered fully after several hours of gradual rewarming.

  8. Perioperative hypothermia and incidence of surgical wound infection: a bibliographic study

    PubMed Central

    da Silva, Aline Batista; Peniche, Aparecida de Cassia Giani

    2014-01-01

    The purpose of this review article was to understand and analyze the scientific production related to the occurrence of perioperative hypothermia and the incidence of infection on the surgical site. For this purpose, a search was conducted in the databases LILACS, MEDLINE, PubMed, CINAHL and Cochrane, using the health science descriptors DECS, from 2004 to 2009. A total of 91 articles were found. After eliminating duplicate items and using selection criteria for inclusion, six manuscripts remained for analysis. The studies were classified as retrospective, prospective, case studies, and clinical trials. After analysis, the majority of studies showed that hypothermia must be prevented during the perioperative period to reduce complications in the healing process of the surgical incision. Therefore, unadverted hypothermia directly influences in surgical site healing, increasing the incidence of infection in the surgical wound. PMID:25628208

  9. Immunohistochemistry of catecholamines in the hypothalamic-pituitary-adrenal system with special regard to fatal hypothermia and hyperthermia.

    PubMed

    Ishikawa, Takaki; Yoshida, Chiemi; Michiue, Tomomi; Perdekamp, Markus Grosse; Pollak, Stefan; Maeda, Hitoshi

    2010-05-01

    Catecholamines are involved in various stress responses. Previous studies have suggested applicability of the postmortem blood levels to investigations of physical stress responses or toxic/hyperthermic neuronal dysfunction during death process. The present study investigated cellular immunopositivity for adrenaline (Adr), noradrenaline (Nad) and dopamine (DA) in the hypothalamus, adenohypophysis and adrenal medulla with special regard to fatal hypothermia (cold exposure) and hyperthermia (heat stroke) to examine forensic pathological significance. Medicolegal autopsy cases (n=290, within 3 days postmortem) were examined. The proportions of catecholamine (Adr, Nad and DA)-positive cells (% positivity) in each tissue were quantitatively estimated using immunostaining. Hyperthermia cases (n=12) showed a lower neuronal DA-immunopositivity in the hypothalamus than hypothermia cases (n=20), while Nad- and DA-immunopositivities in the adrenal medulla were higher for hyperthermia than for hypothermia. Rates of Nad-immunopositivity in the adrenal medulla were very low for hypothermia. No such difference between hypothermia and hyperthermia was seen in the adenohypophysis. In hypothermia cases, cellular Nad-immunopositivity in the adrenal medulla correlated with the Nad level in cerebrospinal fluid (r=0.591, p<0.01). These observations suggest a characteristic immunohistochemical pattern of systemic stress response to fatal hypothermia and hyperthermia, involving the hypothalamus and adrenal medulla. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Optimal Control of Inspired Perfluorocarbon Temperature for Ultrafast Hypothermia Induction by Total Liquid Ventilation in an Adult Patient Model.

    PubMed

    Nadeau, Mathieu; Sage, Michael; Kohlhauer, Matthias; Mousseau, Julien; Vandamme, Jonathan; Fortin-Pellerin, Etienne; Praud, Jean-Paul; Tissier, Renaud; Walti, Herve; Micheau, Philippe

    2017-12-01

    Recent preclinical studies have shown that therapeutic hypothermia induced in less than 30 min by total liquid ventilation (TLV) strongly improves the survival rate after cardiac arrest. When the lung is ventilated with a breathable perfluorocarbon liquid, the inspired perfluorocarbon allows us to control efficiently the cooling process of the organs. While TLV can rapidly cool animals, the cooling speed in humans remains unknown. The objective is to predict the efficiency and safety of ultrafast cooling by TLV in adult humans. It is based on a previously published thermal model of ovines in TLV and the design of a direct optimal controller to compute the inspired perfluorocarbon temperature profile. The experimental results in an adult sheep are presented. The thermal model of sheep is subsequently projected to a human model to simulate the optimal hypothermia induction and its sensitivity to physiological parameter uncertainties. The results in the sheep showed that the computed inspired perfluorocarbon temperature command can avoid arterial temperature undershoot. The projection to humans revealed that mild hypothermia should be ultrafast (reached in fewer than 3 min (-72 °C/h) for the brain and 20 min (-10 °C/h) for the entire body). The projection to human model allows concluding that therapeutic hypothermia induction by TLV can be ultrafast and safe. This study is the first to simulate ultrafast cooling by TLV in a human model and is a strong motivation to translate TLV to humans to improve the quality of life of postcardiac arrest patients.

  11. The Role of Transmural Repolarization Gradient in the Inversion of Cardiac Electric Field: Model Study of ECG in Hypothermia.

    PubMed

    Arteyeva, Natalia V; Azarov, Jan E

    2017-01-01

    The changes in ventricular repolarization gradients lead to significant alterations of the electrocardiographic body surface T waves up to the T wave inversion. However, the contribution of a specific gradient remains to be elucidated. The objective of the present investigation was to study the role of the transmural repolarization gradient in the inversion of the body surface T wave with a mathematical model of the hypothermia-induced changes of ventricular repolarization. By means of mathematical simulation, we set the hypothermic action potential duration (APD) distribution on the rabbit ventricular epicardium as it was previously experimentally documented. Then the parameters of the body surface potential distribution were tested with the introduction of different scenarios of the endocardial and epicardial APD behavior in hypothermia resulting in the unchanged, reversed or enlarged transmural repolarization gradient. The reversal of epicardial repolarization gradients (apicobasal, anterior-posterior and interventricular) caused the inversion of the T waves regardless of the direction of the transmural repolarization gradient. However, the most realistic body surface potentials were obtained when the endocardial APDs were not changed under hypothermia while the epicardial APDs prolonged. This produced the reversed and increased transmural repolarization gradient in absolute magnitude. The body surface potentials simulated under the unchanged transmural gradient were reduced in comparison to those simulated under the reversed transmural gradient. The simulations demonstrated that the transmural repolarization gradient did not play a crucial role in the cardiac electric field inversion under hypothermia, but its magnitude and direction contribute to the T wave amplitude. © 2016 Wiley Periodicals, Inc.

  12. Hypothermia and rapid rewarming is associated with worse outcome following traumatic brain injury.

    PubMed

    Thompson, Hilaire J; Kirkness, Catherine J; Mitchell, Pamela H

    2010-01-01

    The purpose of the present study was to determine (1) the prevalence and degree of hypothermia in patients on emergency department admission and (2) the effect of hypothermia and rate of rewarming on patient outcomes. Secondary data analysis was conducted on patients admitted to a level I trauma center following severe traumatic brain injury (n = 147). Patients were grouped according to temperature on admission according to hypothermia status and rate of rewarming (rapid or slow). Regression analyses were performed. Hypothermic patients were more likely to have lower postresuscitation Glasgow Coma Scale scores and a higher initial injury severity score. Hypothermia on admission was correlated with longer intensive care unit stays, a lower Glasgow Coma Scale score at discharge, higher mortality rate, and lower Glasgow outcome score-extended scores up to 6 months postinjury (P < .05). When controlling for other factors, rewarming rates more than 0.25°C/h were associated with lower Glasgow Coma Scale scores at discharge, longer intensive care unit length of stay, and higher mortality rate than patients rewarmed more slowly although these did not reach statistical significance. Hypothermia on admission is correlated with worse outcomes in brain-injured patients. Patients with traumatic brain injury who are rapidly rewarmed may be more likely to have worse outcomes. Trauma protocols may need to be reexamined to include controlled rewarming at rates 0.25°C/h or less.

  13. Deep hypothermia-enhanced autophagy protects PC12 cells against oxygen glucose deprivation via a mitochondrial pathway.

    PubMed

    Tang, Dang; Wang, Cheng; Gao, Yongjun; Pu, Jun; Long, Jiang; Xu, Wei

    2016-10-06

    Deep hypothermia is known for its organ-preservation properties, which is introduced into surgical operations on the brain and heart, providing both safety in stopping circulation as well as an attractive bloodless operative field. However, the molecular mechanisms have not been clearly identified. This study was undertaken to determine the influence of deep hypothermia on neural apoptosis and the potential mechanism of these effects in PC12 cells following oxygen-glucose deprivation. Deep hypothermia (18°C) was given to PC12 cells while the model of oxygen-glucose deprivation (OGD) induction for 1h. After 24h of reperfusion, the results showed that deep hypothermia decreased the neural apoptosis, and significantly suppressed overexpression of Bax, CytC, Caspase 3, Caspase 9 and cleaved PARP-1, and inhibited the reduction of Bcl-2 expression. While deep hypothermia increased the LC3II/LC3I and Beclin 1, an autophagy marker, which can be inhibited by 3-methyladenine (3-MA), indicating that deep hypothermia-enhanced autophagy ameliorated apoptotic cell death in PC12 cells subjected to OGD. Based on these findings we propose that deep hypothermia protects against neural apoptosis after the induction of OGD by attenuating the mitochondrial apoptosis pathway, moreover, the mechanism of these antiapoptosis effects is related to the enhancement of autophagy, which autophagy might provide a means of neuroprotection against OGD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. [Prolonged therapeutic hypothermia after pericardial effusion drain surgery].

    PubMed

    Román Fernández, A; López Álvarez, A; Barreiro Canosa, J L; Varela García, O; Fossati Puertas, S; Pereira Tamayo, J Á

    2014-01-01

    Therapeutic hypothermia is an effective treatment for neurological protection after out-of-hospital cardiac arrest, and may also be beneficial for in-hospital cardiac arrest. Its use is limited in post-surgical patients due to the risk of specific complications, particularly bleeding. There are significant differences among previous publications regarding the time to reach the target temperature and the duration of therapy, so the optimal strategy is not yet established. We present the case of a patient who suffered a perioperative cardiac arrest related to a pericardial tamponade, and who underwent therapeutic hypothermia for 48h. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  15. Therapeutic hypothermia in the prevention of hypoxic-ischaemic encephalopathy: new categories to be enrolled.

    PubMed

    Gancia, Paolo; Pomero, Giulia

    2012-10-01

    Therapeutic hypothermia is now the standard of care for brain injury control in term infants with perinatal hypoxic ischemic encephalopathy (HIE). Accumulated evidence shows a reduction in mortality and long-term neurodevelopmental disability at 12-24 months of age, with more favourable effects in the less severe forms of HIE. Only few trials recruited newborns <36 weeks gestational age, or mild-to-moderate encephalopathy with base deficit (BD) <16. The new categories of patients to be enrolled should include (late) preterm infants, neonates with unexpected postnatal collapse, and newborns with stroke. Preterm HIE: Therapeutic hypothermia shows a good safety profile in clinical studies, and no adverse effects were noted in the preterm fetal animal model. Recently, it has been shown that mild hypothermia in preterm newborns with necrotizing enterocolitis (NEC) and multiple organ dysfunction syndrome (MODS) does not increase mortality, bleeding, infection, or need for inotropes in cooled newborns. A pilot study (NCT00620711) is currently recruiting newborns of > 32 but < 36 weeks gestation with standard criteria for HIE. Postnatal Collapse: The postnatal collapse (PNC) is a rare (0.03-0.5/1000 live births) but life-threatening hypoxic-ischemic event. No clinical trials of therapeutic hypothermia have specifically addressed to PNC. Nevertheless, a beneficial effect of brain cooling is expectable, and it has been proposed to include in brain hypothermia trials the infants with PNC fulfilling the entry criteria for HIE. Stroke: Perinatal arterial ischemic stroke is the most common cause of cerebral palsy (CP) in term and near-term newborn. In a systematic review and meta-analysis of animal studies of focal cerebral ischemia, hypothermia reduced the infarct size by 44%. No specific neuroprotective interventions are available for the management of acute perinatal stroke. Hypothermia may decrease seizures in newborns with encephalopathy and a focal infarct, potentially

  16. Quality-Improvement Effort to Reduce Hypothermia Among High-Risk Infants on a Mother-Infant Unit.

    PubMed

    Andrews, Christine; Whatley, Colleen; Smith, Meaghan; Brayton, Emily Caron; Simone, Suzanne; Holmes, Alison Volpe

    2018-02-14

    Neonatal hypothermia is common in low birth weight (LBW) (<2500 g) and late-preterm infants (LPIs) (34 0/7-36 6/7 weeks' gestation). It can be a contributory factor for newborn admission to a NICU, resulting in maternal-infant separation and increased resource use. Our objective was to study the efficacy of a quality-improvement bundle of hypothermia preventive measures for LPIs and/or LBW infants in a mother-infant unit. We conducted plan-do-study-act (PDSA) cycles aimed at decreasing environmental hypothermia for LPIs and/or LBW infants in a mother-infant unit with no other indications for NICU-level care. Interventions included using warm towels after delivery, a risk identification card, an occlusive hat, delayed timing of first bath, submersion instead of sponge-bathing, and conducting all assessments under a radiant warmer during the initial hours of life. We implemented these interventions in 3 PDSA cycles and followed hypothermia rates by using statistical process control methods. The baseline mean monthly hypothermia rate among mother-infant unit LPIs and/or LBW infants was 29.8%. Postintervention, the rate fell to 13.3% (-16.5%; P = .002). This decrease occurred in a stepwise fashion in conjunction with the PDSA cycles. In the final, full-intervention period, the rate was 10.0% (-19.8%; P = .0003). A special-cause signal shift was observed in this final period. Targeted interventions can significantly reduce hypothermia in otherwise healthy LPIs and/or LBW newborns and allow them to safely remain in a mother-infant unit. If applied broadly, such preventive practices could decrease preventable hypothermia in high-risk populations. Copyright © 2018 by the American Academy of Pediatrics.

  17. Short-duration hypothermia after ischemic stroke prevents delayed intracranial pressure rise.

    PubMed

    Murtha, L A; McLeod, D D; McCann, S K; Pepperall, D; Chung, S; Levi, C R; Calford, M B; Spratt, N J

    2014-07-01

    Intracranial pressure elevation, peaking three to seven post-stroke is well recognized following large strokes. Data following small-moderate stroke are limited. Therapeutic hypothermia improves outcome after cardiac arrest, is strongly neuroprotective in experimental stroke, and is under clinical trial in stroke. Hypothermia lowers elevated intracranial pressure; however, rebound intracranial pressure elevation and neurological deterioration may occur during rewarming. (1) Intracranial pressure increases 24 h after moderate and small strokes. (2) Short-duration hypothermia-rewarming, instituted before intracranial pressure elevation, prevents this 24 h intracranial pressure elevation. Long-Evans rats with two hour middle cerebral artery occlusion or outbred Wistar rats with three hour middle cerebral artery occlusion had intracranial pressure measured at baseline and 24 h. Wistars were randomized to 2·5 h hypothermia (32·5°C) or normothermia, commencing 1 h after stroke. In Long-Evans rats (n = 5), intracranial pressure increased from 10·9 ± 4·6 mmHg at baseline to 32·4 ± 11·4 mmHg at 24 h, infarct volume was 84·3 ± 15·9 mm(3) . In normothermic Wistars (n = 10), intracranial pressure increased from 6·7 ± 2·3 mmHg to 31·6 ± 9·3 mmHg, infarct volume was 31·3 ± 18·4 mm(3) . In hypothermia-treated Wistars (n = 10), 24 h intracranial pressure did not increase (7·0 ± 2·8 mmHg, P < 0·001 vs. normothermia), and infarct volume was smaller (15·4 ± 11·8 mm(3) , P < 0·05). We saw major intracranial pressure elevation 24 h after stroke in two rat strains, even after small strokes. Short-duration hypothermia prevented the intracranial pressure rise, an effect sustained for at least 18 h after rewarming. The findings have potentially important implications for design of future clinical trials. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke

  18. Avoiding hypothermia, an intervention to prevent morbidity and mortality from pneumonia in young children.

    PubMed

    Pio, Antonio; Kirkwood, Betty R; Gove, Sandy

    2010-02-01

    Observations and experiments in animals and human beings grant plausibility to the hypothesis that hypothermia is a risk factor for pneumonia. Exposure of body to cold stress causes alterations in the systemic and local defenses against respiratory infections, favoring the infection by inhalation of pathogens normally present in the oropharynx. Neonates and young infants with hypothermia have an increased risk of death; however, there is no strong demonstration that hypothermia leads to pneumonia in these children. Studies that properly addressed the problem of confounding variables have shown an association between cold weather and pneumonia incidence. Probably the strongest evidence that supports the plausibility of the hypothesis is provided by the controlled comparison between patients with traumatic brain injury treated with hypothermia and those treated under normal body temperature. The association between exposure to cold and pneumonia is strong enough to warrant further research focused in young children in developing countries.

  19. Hypothermia reduces VEGF-165 expression, but not osteogenic differentiation of human adipose stem cells under hypoxia

    PubMed Central

    Bakker, Astrid D.; Hogervorst, Jolanda M. A.; Nolte, Peter A.; Klein-Nulend, Jenneke

    2017-01-01

    Cryotherapy is successfully used in the clinic to reduce pain and inflammation after musculoskeletal damage, and might prevent secondary tissue damage under the prevalent hypoxic conditions. Whether cryotherapy reduces mesenchymal stem cell (MSC) number and differentiation under hypoxic conditions, causing impaired callus formation is unknown. We aimed to determine whether hypothermia modulates proliferation, apoptosis, nitric oxide production, VEGF gene and protein expression, and osteogenic/chondrogenic differentiation of human MSCs under hypoxia. Human adipose MSCs were cultured under hypoxia (37°C, 1% O2), hypothermia and hypoxia (30°C, 1% O2), or control conditions (37°C, 20% O2). Total DNA, protein, nitric oxide production, alkaline phosphatase activity, gene expression, and VEGF protein concentration were measured up to day 8. Hypoxia enhanced KI67 expression at day 4. The combination of hypothermia and hypoxia further enhanced KI67 gene expression compared to hypoxia alone, but was unable to prevent the 1.2-fold reduction in DNA amount caused by hypoxia at day 4. Addition of hypothermia to hypoxic cells did not alter the effect of hypoxia alone on BAX-to-BCL-2 ratio, alkaline phosphatase activity, gene expression of SOX9, COL1, or osteocalcin, or nitric oxide production. Hypothermia decreased the stimulating effect of hypoxia on VEGF-165 gene expression by 6-fold at day 4 and by 2-fold at day 8. Hypothermia also decreased VEGF protein expression under hypoxia by 2.9-fold at day 8. In conclusion, hypothermia decreased VEGF-165 gene and protein expression, but did not affect differentiation, or apoptosis of MSCs cultured under hypoxia. These in vitro results implicate that hypothermia treatment in vivo, applied to alleviate pain and inflammation, is not likely to harm early stages of callus formation. PMID:28166273

  20. Optimal Protective Hypothermia in Arrested Mammalian Hearts

    PubMed Central

    Villet, Outi M.; Ge, Ming; Sekhar, Laigam N.; Corson, Marshall A.; Tylee, Tracy S.; Fan, Lu-Ping; Yao, Lin; Zhu, Chun; Olson, Aaron K.; Buroker, Norman E.; Xu, Cheng-Su; Anderson, David L.; Soh, Yong-Kian; Wang, Elise; Chen, Shi-Han; Portman, Michael A.

    2015-01-01

    Many therapeutic hypothermia recommendations have been reported, but the information supporting them is sparse, and reveals a need for the data of target therapeutic hypothermia (TTH) from well-controlled experiments. The core temperature ≤35°C is considered as hypothermia, and 29°C is a cooling injury threshold in pig heart in vivo. Thus, an optimal protective hypothermia (OPH) should be in the range 29–35°C. This study was conducted with a pig cardiopulmonary bypass preparation to decrease the core temperature to 29–35°C range at 20 minutes before and 60 minutes during heart arrest. The left ventricular (LV) developed pressure, maximum of the first derivative of LV (dP/dtmax), cardiac power, heart rate, cardiac output, and myocardial velocity (Vmax) were recorded continuously via an LV pressure catheter and an aortic flow probe. At 20 minutes of off-pump during reperfusion after 60 minutes arrest, 17 hypothermic hearts showed that the recovery of Vmax and dP/dtmax established sigmoid curves that consisted of two plateaus: a good recovery plateau at 29–30.5°C, the function recovered to baseline level (BL) (Vmax=118.4%±3.9% of BL, LV dP/dtmax=120.7%±3.1% of BL, n=6); another poor recovery plateau at 34–35°C (Vmax=60.2%±2.8% of BL, LV dP/dtmax=28.0%±5.9% of BL, p<0.05, n=6; ), which are similar to the four normothermia arrest (37°C) hearts (Vmax=55.9%±4.8% of BL, LV dP/dtmax=24.5%±2.1% of BL, n=4). The 32–32.5°C arrest hearts showed moderate recovery (n=5). A point of inflection (around 30.5–31°C) existed at the edge of a good recovery plateau followed by a steep slope. The point presented an OPH that should be the TTH. The results are concordant with data in the mammalian hearts, suggesting that the TTH should be initiated to cool core temperature at 31°C. PMID:25514569

  1. Effects of Cannabidiol and Hypothermia on Short-Term Brain Damage in New-Born Piglets after Acute Hypoxia-Ischemia

    PubMed Central

    Lafuente, Hector; Pazos, Maria R.; Alvarez, Antonia; Mohammed, Nagat; Santos, Martín; Arizti, Maialen; Alvarez, Francisco J.; Martinez-Orgado, Jose A.

    2016-01-01

    Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration. Six hours after treatment, brains were processed to quantify the number of damaged neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate) and excitotoxicity (glutamate/Nacetyl-aspartate). Western blot studies were performed to quantify protein nitrosylation (oxidative stress), content of caspase-3 (apoptosis) and TNFα (inflammation). Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone. The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult. PMID:27462203

  2. Perioperative Hypothermia: Incidence and Prevention

    DTIC Science & Technology

    1990-01-01

    airways warm and moist by heating fluids within the respiratory passages. If this does not occur, the respiratory passages will dry up and become...during hypothermia and corrected for temperatures, the results will show 11 hypoxemia and alkalosis . Wong concludes that both the alkalosis and...basal heat production of the body. Prevention of this respiratory heat loss has been proven by this study as well as others to significantly reduce

  3. The importance of cavity roosting and hypothermia to the energy balance of the winter acclimatized Carolina chickadee

    NASA Astrophysics Data System (ADS)

    Mayer, L.; Lustick, S.; Battersby, B.

    1982-09-01

    Noctural hypothermia and cavity roosting account for a significant reduction in energy expenditure in winter acclimatized Carolina chickadees. As much as 10‡C hypothermia amounted to a 33.0% reduction in metabolic requirements. Noctural hypothermia combined with a reduction in radiative and convective heat loss due to cavity roosting accounted for as much as a 50% savings in energy expenditure.

  4. Is it time to stop chilling? Induced therapeutic hypothermia doesn't appear to have the prehospital effect we thought it did.

    PubMed

    Bledsoe, Bryan E

    2015-02-01

    The evidence is quite clear that ITH in the prehospital setting is of dubious benefit. But what is the harm in continuing the practice? Well, prehospital ITH most likely takes away from more beneficial therapies such as high-quality CPR, rapid defibrillation, recognition of ST-segment elevation myocardial infarction (STEMI), and similar essential treatments. Several studies have shown prehospital ITH, in many cases, delays hospital transport. When the initial studies of ITH were released, I was immediately on the ITH bandwagon. Interestingly, the American Heart Association (AHA) has never recommended prehospital ITH. Even the position paper on ITH by the National Association of EMS Physicians (NAEMSP) was cautious, saying, "A lack of evidence on induced hypothermia in the prehospital setting currently precludes recommending this treatment modality as standard of care for all emergency medical services (EMS) patients resuscitated from cardiac arrest. A systematic review of ITH recently published states, "In cardiac arrest, the initiation of therapeutic hypothermia in the out-of-hospital environment has not been shown to improve neurologic outcomes, although studies to date have been limited. We now know that caution Fxercised by the AHA and preMSP was appropriate. One medmy mentors in residency and ays said, "Never be the first- Univtor to prescribe a new drug or of Mlast doctor to prescribe an old is th" Lik" many things in EMS, EMS tms something that was put in Practe with good intent but lim- scientific evidence. We now P ITH is probably not a good ice and it is time to abandon it. However, we should still carry chilled IV fluids for hyperthermia, excited delirium and to main- tainormothermia in patients in cardiac arrest where transport times are long.

  5. Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects

    PubMed Central

    Darwazeh, Rami; Yan, Yi

    2013-01-01

    Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study. PMID:25206579

  6. Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects.

    PubMed

    Darwazeh, Rami; Yan, Yi

    2013-10-05

    Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study.

  7. Effects of hypothermia on pharmacokinetics and pharmacodynamics: a systematic review of preclinical and clinical studies.

    PubMed

    van den Broek, Marcel P H; Groenendaal, Floris; Egberts, Antoine C G; Rademaker, Carin M A

    2010-05-01

    Examples of clinical applications of therapeutic hypothermia in modern clinical medicine include traumatic cardiac arrest, ischaemic stroke and, more recently, acute perinatal asphyxia in neonates. The exact mechanism of (neuro)protection by hypothermia is unknown. Since most enzymatic processes exhibit temperature dependency, it can be expected that therapeutic hypothermia may cause alterations in both pharmacokinetic and pharmacodynamic parameters, which could result in an increased risk of drug toxicity or therapy failure. Generalizable knowledge about the effect of therapeutic hypothermia on pharmacokinetics and pharmacodynamics could lead to more appropriate dosing and thereby prediction of clinical effects. This article reviews the evidence on the influence of therapeutic hypothermia on individual pharmacokinetic and pharmacodynamic parameters. A literature search was conducted within the PubMed, Embase and Cochrane databases from January 1965 to September 2008, comparing pharmacokinetic and/or pharmacodynamic parameters in hypothermia and normothermia regarding preclinical (animal) and clinical (human) studies. During hypothermia, pharmacokinetic parameters alter, resulting in drug and metabolite accumulation in the plasma for the majority of drugs. Impaired clearance is the most striking effect. Based on impaired clearance, dosages should be decreased considerably, especially for drugs with a low therapeutic index. Hypothetically, high-clearance compounds are affected more than low-clearance compounds because of the additional effect of impaired hepatic blood flow. The volume of distribution also changes, which may lead to therapy failure when it increases and could lead to toxicity when it decreases. The pH-partitioning hypothesis could contribute to the changes in the volumes of distribution for weak bases and acids, depending on their acid dissociation constants and acid-base status. Pharmacodynamic parameters may also alter, depending on the hypothermic

  8. The incidence and significance of accidental hypothermia in major trauma--a prospective observational study.

    PubMed

    Ireland, Sharyn; Endacott, Ruth; Cameron, Peter; Fitzgerald, Mark; Paul, Eldho

    2011-03-01

    Serious sequelae have been associated with injured patients who are hypothermic (<35°C) including coagulopathy, acidosis, decreased myocardial contractility and risk of mortality. Establish the incidence of accidental hypothermia in major trauma patients and identify causative factors. Prospective identification and subsequent review of 732 medical records of major trauma patients presenting to an Adult Major Trauma Centre was undertaken between January and December 2008. Multivariate analysis was performed using logistic regression. Significant and clinically relevant variables from univariate analysis were entered into multivariate models to evaluate determinants for hypothermia and for death. Goodness of fit was determined with the use of the Hosmer-Lemeshow statistic. Overall mortality was 9.15%. The incidence of hypothermia was 13.25%. The mortality of patients with hypothermia was 29.9% with a threefold independent risk of death: OR (CI 95%) 3.44 (1.48-7.99), P = 0.04. Independent determinants for hypothermia were pre-hospital intubation: OR (CI 95%) 5.18 (2.77-9.71), P < 0.001, Injury Severity Score (ISS): 1.04 (1.01-1.06), P = 0.01, Arrival Systolic Blood Pressure (ASBP) < 100 mm Hg: 3.04 (1.24-7.44), P = 0.02, and winter time: 1.84 (1.06-3.21), P = 0.03. Of the 87 hypothermic patients who had repeat temperatures recorded in the Emergency Department, 77 (88.51%) patients had a temperature greater than the recorded arrival temperature. There was no change in recorded temperature for four (4.60%) patients, whereas six (6.90%) patients were colder at Emergency Department discharge. Seriously injured patients with accidental hypothermia have a higher mortality independent of measured risk factors. For patients with multiple injuries a coordinated effort by paramedics, nurses and doctors is required to focus efforts toward early resolution of hypothermia aiming to achieve a temperature >35 °C. Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All

  9. Accidental hypothermia and death from cold in urban areas

    NASA Astrophysics Data System (ADS)

    Tanaka, Masatoshi; Tokudome, Shogo

    1991-12-01

    Hypothermia is considered a sericus problem in big cities. In order to clarify factors contributing to urban hypothermia and death from cold which will continue to be an issue in cities in the future, we analyzed autopsy reports recorded in the Tokyo Medical Examiner's Office from 1974 to 1983. In a total of 18346 autopsy reports 157 deaths had been diagnosed as due to exposure to cold. Of these cases, the greatest number were males in their forties and fifties, and most of these were inebriated and/or homeless. Eighty-four perent of urban hypothermia cases occurred when the outdoor temperature was below 5°C, and 50% of deaths from cold occurred when the outdoor temperature was between 0° and 5°C. There were no incidences of death from cold when the minimum outdoor temperature had remained above 16°C. Seventy-four percent of deaths from cold occurred during the winter months of December, January and February, and most of the remaining deaths occurred in March and November. There were no deaths from cold from June to August. More than half of all deaths from cold occurred from 3.00 a.m. to 9.00 a.m., with the peak occurring at 5.00 a.m. A blood alcohol concentration of over 2.5 mg/ml had often been found in those in their forties and fifties who had died from hypothermia, and autopsy had often revealed disorders of the liver, digestive system, and circulatory system. Chronic lesions of the liver, probably due to alcoholism, were found in many cases; few cases showed no evidence of alcoholism and these were significantly different from the former group.

  10. Mild hypothermia for treatment of diffuse axonal injury: a quantitative analysis of diffusion tensor imaging

    PubMed Central

    Jing, Guojie; Yao, Xiaoteng; Li, Yiyi; Xie, Yituan; Li, Wang#x2019;an; Liu, Kejun; Jing, Yingchao; Li, Baisheng; Lv, Yifan; Ma, Baoxin

    2014-01-01

    Fractional anisotropy values in diffusion tensor imaging can quantitatively reflect the consistency of nerve fibers after brain damage, where higher values generally indicate less damage to nerve fibers. Therefore, we hypothesized that diffusion tensor imaging could be used to evaluate the effect of mild hypothermia on diffuse axonal injury. A total of 102 patients with diffuse axonal injury were randomly divided into two groups: normothermic and mild hypothermic treatment groups. Patient's modified Rankin scale scores 2 months after mild hypothermia were significantly lower than those for the normothermia group. The difference in average fractional anisotropy value for each region of interest before and after mild hypothermia was 1.32-1.36 times higher than the value in the normothermia group. Quantitative assessment of diffusion tensor imaging indicates that mild hypothermia therapy may be beneficial for patients with diffuse axonal injury. PMID:25206800

  11. Optimization of brain metabolism using metabolic-targeted therapeutic hypothermia can reduce mortality from traumatic brain injury.

    PubMed

    Feng, Jin-Zhou; Wang, Wen-Yuan; Zeng, Jun; Zhou, Zhi-Yuan; Peng, Jin; Yang, Hao; Deng, Peng-Chi; Li, Shi-Jun; Lu, Charles D; Jiang, Hua

    2017-08-01

    Therapeutic hypothermia is widely used to treat traumatic brain injuries (TBIs). However, determining the best hypothermia therapy strategy remains a challenge. We hypothesized that reducing the metabolic rate, rather than reaching a fixed body temperature, would be an appropriate target because optimizing metabolic conditions especially the brain metabolic environment may enhance neurologic protection. A pilot single-blind randomized controlled trial was designed to test this hypothesis, and a nested metabolomics study was conducted to explore the mechanics thereof. Severe TBI patients (Glasgow Coma Scale score, 3-8) were randomly divided into the metabolic-targeted hypothermia treatment (MTHT) group, 50% to 60% rest metabolic ratio as the hypothermia therapy target, and the body temperature-targeted hypothermia treatment (BTHT) control group, hypothermia therapy target of 32°C to 35°C body temperature. Brain and circulatory metabolic pool blood samples were collected at baseline and on days 1, 3, and 7 during the hypothermia treatment, which were selected randomly from a subgroup of MTHT and BTHT groups. The primary outcome was mortality. Using H nuclear magnetic resonance technology, we tracked and located the disturbances of metabolic networks. Eighty-eight severe TBI patients were recruited and analyzed from December 2013 to December 2014, 44 each were assigned in the MTHT and BTHT groups (median age, 42 years; 69.32% men; mean Glasgow Coma Scale score, 6.17 ± 1.02). The mortality was significantly lower in the MTHT than the BTHT group (15.91% vs. 34.09%; p = 0.049). From these, eight cases of MTHT and six cases from BTHT group were enrolled for metabolomics analysis, which showed a significant difference between the brain and circulatory metabolic patterns in MTHT group on day 7 based on the model parameters and scores plots. Finally, metabolites representing potential neuroprotective monitoring parameters for hypothermia treatment were identified through

  12. Therapeutic mild hypothermia improves early outcomes in rats subjected to severe sepsis.

    PubMed

    Ding, Wu; Shen, Yuehong; Li, Qiang; Jiang, Shouyin; Shen, Huahao

    2018-04-15

    Therapeutic hypothermia has shown beneficial effects in sepsis. This study focused on its mechanism. Sixteen male Sprague-Dawley rats underwent cecal ligation and perforation and subsequently were treated with either hypothermia (HT; body temperature cooled and maintained at 34 °C by ice pad for 10 h; n = 8) or normothermia (NT; n = 8). Three additional rats underwent sham surgery. The body temperatures of the sham-operated and NT groups were maintained at 38 °C with a thermal pad. After the hypothermia treatment, the HT rats were rewarmed for 2 h. The groups were compared for circulating cytokines (IL-6, IL-10), lactate, high mobility group box-1 protein (HMGB1), and lung and intestinal lesions. Animals were observed for 24 h. Compared with the sham-operated group, the 2 sepsis group rats had significantly higher circulating IL-6, HMGB1, and lactate levels, and tissue injury. In the HT rats, the levels of IL-6, HMGB1, and lactate, the lung wet-to-dry ratio, and lung and intestinal damage were significantly lower than that of the NT group. Circulating IL-10 levels increased significantly after 12 h in the sepsis groups compared with sham animals, while that of the NT and HT groups were comparable. The survival rates of the NT and HT rats were also comparable. Therapeutic hypothermia in a rat model of sepsis was associated with lower levels of circulating IL-6 and HMGB1, and less capillary leakage and tissue edema. These results suggest that mild hypothermia has potential as a therapy in sepsis. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Early Imaging and Adverse Neurodevelopmental Outcome in Asphyxiated Newborns Treated With Hypothermia.

    PubMed

    Al Amrani, Fatema; Kwan, Saskia; Gilbert, Guillaume; Saint-Martin, Christine; Shevell, Michael; Wintermark, Pia

    2017-08-01

    Brain injury can be identified as early as day two of life in asphyxiated newborns treated with hypothermia, when using diffusion magnetic resonance imaging (MRI). However, it remains unclear whether these diffusion changes can predict future neurodevelopment. This study aimed to determine whether abnormal early diffusion changes in newborns treated with hypothermia are associated with adverse neurodevelopmental outcome at age two years. Asphyxiated newborns treated with hypothermia were enrolled prospectively. They underwent magnetic resonance imaging (MRI) at specific time points over the first month of life, including diffusion-weighted imaging and diffusion-tensor imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in different regions of interest. Adverse neurodevelopmental outcome was defined as cerebral palsy, global developmental delay, and/or seizure disorder around age two years. ADC and FA values were compared between the newborns developing or not developing adverse outcome. Twenty-nine asphyxiated newborns treated with hypothermia were included. Among the newborns developing adverse outcome, ADC values were significantly decreased on days two to three of life and increased around day ten of life in the thalamus, posterior limb of the internal capsule, and the lentiform nucleus. FA values decreased in the same regions around day 30 of life. These newborns also had increased ADC around day ten of life and around day 30 of life, and decreased FA around day 30 of life in the anterior and posterior white matter. Diffusion changes that were evident as early as day two of life, when the asphyxiated newborns were still treated with hypothermia, were associated with later abnormal neurodevelopmental outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Episodic spontaneous hypothermia: a periodic childhood syndrome.

    PubMed

    Ruiz, Cynthia; Gener, Blanca; Garaizar, Carmen; Prats, José M

    2003-04-01

    Episodic spontaneous hypothermia is an infrequent disorder, with unknown pathogenic mechanisms. A systemic cause or underlying brain lesion has not been found for the disease. We report four new patients, 3-9 years old, with episodic hypothermia lower than 35 degrees C, marked facial pallor, and absent shivering. The episodes could last a few hours or four days, and recurred once a week or every 2-3 months. Two patients also demonstrated bradycardia, mild hypertension, and somnolence during the events; in one of them, profuse sweating was also a feature, and all four presented with either headache, a periodic childhood syndrome, or both (recurrent abdominal pain, cyclic vomiting, or vertigo). Three patients reported a family history of migraine. Neurologic examination, endocrine function, and imaging studies were normal. Migraine prophylactic therapy was of moderate efficacy. Spontaneous resolution was observed in one patient. The clinical characteristics of the syndrome allow for its inclusion as a childhood periodic syndrome related to migraine.

  15. Changes in the PQRST intervals and heart rate variability associated with rewarming in two newborns undergoing hypothermia therapy.

    PubMed

    Lasky, Robert E; Parikh, Nehal A; Williams, Amber L; Padhye, Nikhil S; Shankaran, Seetha

    2009-01-01

    Little is known about the effects of hypothermia therapy and subsequent rewarming on the PQRST intervals and heart rate variability (HRV) in term newborns with hypoxic-ischemic encephalopathy (HIE). This study describes the changes in the PQRST intervals and HRV during rewarming to normal core body temperature of 2 newborns with HIE after hypothermia therapy. Within 6 h after birth, 2 newborns with HIE were cooled to a core body temperature of 33.5 degrees C for 72 h using a cooling blanket, followed by gradual rewarming (0.5 degrees C per hour) until the body temperature reached 36.5 degrees C. Custom instrumentation recorded the electrocardiogram from the leads used for clinical monitoring of vital signs. Generalized linear mixed models were calculated to estimate temperature-related changes in PQRST intervals and HRV. For every 1 degrees C increase in body temperature, the heart rate increased by 9.2 bpm (95% CI 6.8-11.6), the QTc interval decreased by 21.6 ms (95% CI 17.3-25.9), and low and high frequency HRV decreased by 0.480 dB (95% CI 0.052-0.907) and 0.938 dB (95% CI 0.460-1.416), respectively. Hypothermia-induced changes in the electrocardiogram should be monitored carefully in future studies. Copyright 2009 S. Karger AG, Basel.

  16. [Neuroprotection with hypothermia in the newborn with hypoxic-ischaemic encephalopathy. Standard guidelines for its clinical application].

    PubMed

    Blanco, D; García-Alix, A; Valverde, E; Tenorio, V; Vento, M; Cabañas, F

    2011-11-01

    Standardisation of hypothermia as a treatment for perinatal hypoxic-ischaemic encephalopathy is supported by current scientific evidence. The following document was prepared by the authors on request of the Spanish Society of Neonatology and is intended to be a guide for the proper implementation of this therapy. We discuss the difficulties that may arise when moving from the strict framework of clinical trials to clinical daily care: early recognition of clinical encephalopathy, inclusion and exclusion criteria, hypothermia during transport, type of hypothermia (selective head or systemic cooling) and side effects of therapy. The availability of hypothermia therapy has changed the prognosis of children with hypoxic-ischaemic encephalopathy and our choices of therapeutic support. In this sense, it is especially important to be aware of the changes in the predictive value of the neurological examination and the electroencephalographic recording in cooled infants. In order to improve neuroprotection with hypothermia we need earlier recognition of to recognise earlier the infants that may benefit from cooling. Biomarkers of brain injury could help us in the selection of these patients. Every single infant treated with hypothermia must be included in a follow up program in order to assess neurodevelopmental outcome. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  17. Preferential cephalic redistribution of left ventricular cardiac output during therapeutic hypothermia for perinatal hypoxic-ischemic encephalopathy

    PubMed Central

    Hochwald, Ori; Jabr, Mohammed; Osiovich, Horacio; Miller, Steven P.; McNamara, Patrick J.; Lavoie, Pascal M.

    2015-01-01

    Objective To determine the relationship between left ventricular cardiac output (LVCO), superior vena cava (SVC) flow, and brain injury during whole-body therapeutic hypothermia. Study design Sixteen newborns with moderate or severe hypoxic-ischemic encephalopathy were studied using echocardiography during and immediately after therapeutic hypothermia. Measures were also compared with 12 healthy newborns of similar postnatal age. Newborns undergoing therapeutic hypothermia also had a cerebral magnetic resonance imaging as part of routine clinical care on postnatal day 3–4. Results LVCO was markedly reduced (mean+/−SD: 126+/−38 mL/kg/min) during therapeutic hypothermia, whereas SVC flow was maintained within expected normal values (88+/− 27 mL/kg/min) such that it represented 70% of the LVCO. The reduction in LVCO during therapeutic hypothermia was mainly accounted by a reduction in heart rate (99 +/− 13 BPM versus 123 +/− 17 BPM; p<0.001) compared to immediately post-warming, in the context of myocardial dysfunction. Neonates with documented brain injury on MRI showed higher SVC flow pre-rewarming, compared to newborns without brain injury (p=0.013). Conclusion Newborns with perinatal hypoxic-ischemic encephalopathy showed a preferential systemic-to cerebral redistribution of cardiac blood flow during whole-body therapeutic hypothermia, which may reflect a lack of cerebral vascular adaptation in newborns with more severe brain injury. PMID:24582011

  18. Preferential cephalic redistribution of left ventricular cardiac output during therapeutic hypothermia for perinatal hypoxic-ischemic encephalopathy.

    PubMed

    Hochwald, Ori; Jabr, Mohammad; Osiovich, Horacio; Miller, Steven P; McNamara, Patrick J; Lavoie, Pascal M

    2014-05-01

    To determine the relationship between left ventricular cardiac output (LVCO), superior vena cava (SVC) flow, and brain injury during whole-body therapeutic hypothermia. Sixteen newborns with moderate or severe hypoxic-ischemic encephalopathy were studied using echocardiography during and immediately after therapeutic hypothermia. Measures were also compared with 12 healthy newborns of similar postnatal age. Newborns undergoing therapeutic hypothermia also had cerebral magnetic resonance imaging as part of routine clinical care on postnatal day 3-4. LVCO was markedly reduced (mean ± SD 126 ± 38 mL/kg/min) during therapeutic hypothermia, whereas SVC flow was maintained within expected normal values (88 ± 27 mL/kg/min) such that SVC flow represented 70% of the LVCO. The reduction in LVCO during therapeutic hypothermia was mainly accounted by a reduction in heart rate (99 ± 13 vs 123 ± 17 beats/min; P < .001) compared with immediately postwarming in the context of myocardial dysfunction. Neonates with brain injury on magnetic resonance imaging had higher SVC flow prerewarming, compared with newborns without brain injury (P = .013). Newborns with perinatal hypoxic-ischemic encephalopathy showed a preferential systemic-to-cerebral redistribution of cardiac blood flow during whole-body therapeutic hypothermia, which may reflect a lack of cerebral vascular adaptation in newborns with more severe brain injury. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Nitrous oxide causes a regulated hypothermia: rats select a cooler ambient temperature while becoming hypothermic.

    PubMed

    Ramsay, Douglas S; Seaman, Jana; Kaiyala, Karl J

    2011-04-18

    An initial administration of 60% nitrous oxide (N(2)O) evokes hypothermia in rats and if the administration continues for more than 1-2h, acute tolerance typically develops such that the initial reduction in core temperature (Tc) reverses and Tc recovers toward control values. Calorimeter studies at normal ambient temperature indicate that hypothermia results from a transient reduction in heat production (HP) combined with an elevation in heat loss. Acute tolerance develops primarily due to progressive increases in HP. Our aim was to determine whether rats provided a choice of ambient temperatures would behaviorally facilitate or oppose N(2)O-induced hypothermia. A gas-tight thermally-graded alleyway (range, 6.7-37.0°C) enabled male Long-Evans rats (n=12) to select a preferred ambient temperature during a 5-hour steady-state administration of 60% N(2)O and a separate paired control gas exposure (order counterbalanced). Tc was measured telemetrically from a sensor surgically implanted into the peritoneal cavity >7days before testing. Internal LED lighting maintained the accustomed day:night cycle (light cycle 0700-1900h) during sessions lasting 45.5h. Rats entered the temperature gradient at 1100h, and the 5-h N(2)O or control gas period did not start until 23h later to provide a long habituation/training period. Food and water were provided ad libitum at the center of the alleyway. The maximum decrease of mean Tc during N(2)O administration occurred at 0.9h and was -2.05±0.25°C; this differed significantly (p<0.0001) from the corresponding Tc change at 0.9h during control gas administration (0.01±0.14°C). The maximum decrease of the mean selected ambient temperature during N(2)O administration occurred at 0.7h and was -13.58±1.61°C; this differed significantly (p<0.0001) from the corresponding mean change in the selected ambient temperature at 0.7h during control gas administration (0.30±1.49°C). N(2)O appears to induce a regulated hypothermia because the

  20. Nitrous Oxide Causes a Regulated Hypothermia: Rats Select a Cooler Ambient Temperature While Becoming Hypothermic

    PubMed Central

    Ramsay, Douglas S.; Seaman, Jana; Kaiyala, Karl J.

    2011-01-01

    An initial administration of 60% nitrous oxide (N2O) evokes hypothermia in rats and if the administration continues for more than 1 – 2 hours, acute tolerance typically develops such that the initial reduction in core temperature (Tc) reverses and Tc recovers toward control values. Calorimeter studies at normal ambient temperature indicate that hypothermia results from a transient reduction in heat production (HP) combined with an elevation in heat loss. Acute tolerance develops primarily due to progressive increases in HP. Our aim was to determine whether rats provided a choice of ambient temperatures would behaviorally facilitate or oppose N2O -induced hypothermia. A gas-tight thermally-graded alleyway (range, 6.7 – 37.0°C) enabled male Long-Evans rats (n=12) to select a preferred ambient temperature during a 5-hour steady-state administration of 60% N2O and a separate paired control gas exposure (order counterbalanced). Tc was measured telemetrically from a sensor surgically implanted into the peritoneal cavity > 7 days before testing. Internal LED lighting maintained the accustomed day:night cycle (light cycle 0700 – 1900 h) during sessions lasting 45.5 hours. Rats entered the temperature gradient at 1100 h, and the 5-h N2O or control gas period did not start until 23 hours later to provide a long habituation / training period. Food and water were provided ad libitum at the center of the alleyway. The maximum decrease of mean Tc during N2O administration occurred at 0.9 h and was −2.05 ± 0.25°C; this differed significantly (p<0.0001) from the corresponding Tc change at 0.9 h during control gas administration (0.01 ± 0.14°C). The maximum decrease of mean selected ambient temperature during N2O administration occurred at 0.7 h and was −13.58 ± 1.61°C; this differed significantly (p < 0.0001) from the corresponding mean change in selected ambient temperature at 0.7 h during control gas administration (0.30 ± 1.49°C). N2O appears to induce a

  1. Lack of effect of moderate hypothermia on brain tissue oxygenation after acute intracranial hypertension in pigs.

    PubMed

    Bao, Ying-Hui; Liang, Yu-Min; Gao, Guo-Yi; Jiang, Ji-Yao

    2010-02-01

    In this study, we explored the effect of moderate hypothermia on brain tissue oxygenation following acute intracranial hypertension in micropigs. Twenty healthy juvenile micropigs weighting 4-6 kg were randomized into two groups: a normothermia group (n = 10) and a moderate hypothermia group (n = 10). The animals were intravenously anesthetized with propofol (4 mg/kg), an endotracheal tube was inserted, and mechanical ventilation was begun. Autologous arterial blood was injected into the left frontal lobe to establish acute intracerebral hematoma and intracranial hypertension (intracranial pressure [ICP] >40 mm Hg) in all animals. Cooling was initiated at 30 min after injection of the blood, and was achieved via the use of an ice bath and ice packs. In the hypothermia group, the brain temperature decreased to 33-34 degrees C. Brain temperature was maintained at 37 +/- 0.3 degrees C in the normothermia group. The ICP, cerebral perfusion pressure (CPP), brain tissue oxygen pressure (P(br)O(2)), brain tissue carbon dioxide pressure (P(br)CO(2)), and brain tissue pH value (pH(br)) were continuously monitored for 3 h in all animals. Compared to normothermia group, ICP values significantly decreased and CPP markedly improved in the hypothermia group (p < 0.05). Further, pH(br) also markedly increased and P(br)CO(2) decreased significantly in the hypothermia group (p < 0.05). However, P(br)O(2) did not statistically significantly improve in the hypothermia group (p > 0.05). In sum, moderate hypothermia significantly decreased ICP, reduced P(br)CO(2), and increased pH(br) values, but did not improve cerebral oxygenation following acute intracranial hypertension.

  2. [Effect of local hypothermia on H- and M-responses after spinal cord contusion in dogs].

    PubMed

    Iafarova, G G; Tumakaev, R F; Khazieva, A R; Baltina, T V

    2014-01-01

    In this study we investigated a motor-neuronal functional state based on H- and M-responses from m. quadratus plantae in dogs before and after experimental spinal cord contusion with and without following local intraoperative hypothermia. H- and M-responses from m. quadratus plantae were recorded during stimulation of the tibial nerve and results were compared between the groups. Our results demonstrate that local hypothermia applied after spinal cord contusion reduces amplitude of both M- and H-responses and also H(max)/M(max) ratio that may indicate depression of motorneurons excitability. After spinal cord contusion without following hypothermia the excitability of the spinal motorneurons during post-traumatic period, in opposite, was significantly increased. These results support a conclusion that intraoperative hypothermia after spinal cord contusion can delay development of functional excitability of the motoneurons and protect from further changes in H- and M-responses.

  3. Therapeutic hypothermia after cardiac arrest: outcome predictors

    PubMed Central

    Leão, Rodrigo Nazário; Ávila, Paulo; Cavaco, Raquel; Germano, Nuno; Bento, Luís

    2015-01-01

    Objective The determination of coma patient prognosis after cardiac arrest has clinical, ethical and social implications. Neurological examination, imaging and biochemical markers are helpful tools accepted as reliable in predicting recovery. With the advent of therapeutic hypothermia, these data need to be reconfirmed. In this study, we attempted to determine the validity of different markers, which can be used in the detection of patients with poor prognosis under hypothermia. Methods Data from adult patients admitted to our intensive care unit for a hypothermia protocol after cardiac arrest were recorded prospectively to generate a descriptive and analytical study analyzing the relationship between clinical, neurophysiological, imaging and biochemical parameters with 6-month outcomes defined according to the Cerebral Performance Categories scale (good 1-2, poor 3-5). Neuron-specific enolase was collected at 72 hours. Imaging and neurophysiologic exams were carried out in the 24 hours after the rewarming period. Results Sixty-seven patients were included in the study, of which 12 had good neurological outcomes. Ventricular fibrillation and electroencephalographic theta activity were associated with increased likelihood of survival and improved neurological outcomes. Patients who had more rapid cooling (mean time of 163 versus 312 minutes), hypoxic-ischemic brain injury on magnetic resonance imaging or neuron-specific enolase > 58ng/mL had poor neurological outcomes (p < 0.05). Conclusion Hypoxic-ischemic brain injury on magnetic resonance imaging and neuron-specific enolase were strong predictors of poor neurological outcomes. Although there is the belief that early achievement of target temperature improves neurological prognoses, in our study, there were increased mortality and worse neurological outcomes with earlier target-temperature achievement. PMID:26761469

  4. Serum cytokines in a clinical trial of hypothermia for neonatal hypoxic-ischemic encephalopathy.

    PubMed

    Jenkins, Dorothea D; Rollins, Laura Grace; Perkel, Jessica K; Wagner, Carol L; Katikaneni, Lakshmi P; Bass, W Thomas; Kaufman, David A; Horgan, Michael J; Languani, Sheela; Givelichian, Lawrence; Sankaran, Koravangattu; Yager, Jerome Y; Martin, Renee H

    2012-10-01

    Inflammatory cytokines may mediate hypoxic-ischemic (HI) injury and offer insights into the severity of injury and the timing of recovery. In our randomized, multicenter trial of hypothermia, we analyzed the temporal relationship of serum cytokine levels in neonates with hypoxic-ischemic encephalopathy (HIE) with neurodevelopmental outcome at 12 months. Serum cytokines were measured every 12 hours for 4 days in 28 hypothermic (H) and 22 normothermic (N) neonates with HIE. Monocyte chemotactic protein-1 (MCP-1) and interleukins (IL)-6, IL-8, and IL-10 were significantly higher in the H group. Elevated IL-6 and MCP-1 within 9 hours after birth and low macrophage inflammatory protein 1a (MIP-1a) at 60 to 70 hours of age were associated with death or severely abnormal neurodevelopment at 12 months of age. However, IL-6, IL-8, and MCP-1 showed a biphasic pattern in the H group, with early and delayed peaks. In H neonates with better outcomes, uniform down modulation of IL-6, IL-8, and IL-10 from their peak levels at 24 hours to their nadir at 36 hours was observed. Modulation of serum cytokines after HI injury may be another mechanism of improved outcomes in neonates treated with induced hypothermia.

  5. Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

    PubMed

    Moler, Frank W; Silverstein, Faye S; Holubkov, Richard; Slomine, Beth S; Christensen, James R; Nadkarni, Vinay M; Meert, Kathleen L; Clark, Amy E; Browning, Brittan; Pemberton, Victoria L; Page, Kent; Shankaran, Seetha; Hutchison, Jamie S; Newth, Christopher J L; Bennett, Kimberly S; Berger, John T; Topjian, Alexis; Pineda, Jose A; Koch, Joshua D; Schleien, Charles L; Dalton, Heidi J; Ofori-Amanfo, George; Goodman, Denise M; Fink, Ericka L; McQuillen, Patrick; Zimmerman, Jerry J; Thomas, Neal J; van der Jagt, Elise W; Porter, Melissa B; Meyer, Michael T; Harrison, Rick; Pham, Nga; Schwarz, Adam J; Nowak, Jeffrey E; Alten, Jeffrey; Wheeler, Derek S; Bhalala, Utpal S; Lidsky, Karen; Lloyd, Eric; Mathur, Mudit; Shah, Samir; Wu, Theodore; Theodorou, Andreas A; Sanders, Ronald C; Dean, J Michael

    2015-05-14

    Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by

  6. Interventions for treating inadvertent postoperative hypothermia.

    PubMed

    Warttig, Sheryl; Alderson, Phil; Campbell, Gillian; Smith, Andrew F

    2014-11-20

    Inadvertent postoperative hypothermia (a drop in core body temperature to below 36°C) occurs as an effect of surgery when anaesthetic drugs and exposure of the skin for long periods of time during surgery result in interference with normal temperature regulation. Once hypothermia has occurred, it is important that patients are rewarmed promptly to minimise potential complications. Several different interventions are available for rewarming patients. To estimate the effectiveness of treating inadvertent perioperative hypothermia through postoperative interventions to decrease heat loss and apply passive and active warming systems in adult patients who have undergone surgery. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 2), MEDLINE (Ovid SP) (1956 to 21 February 2014), EMBASE (Ovid SP) (1982 to 21 February 2014), the Institute for Scientific Information (ISI) Web of Science (1950 to 21 February 2014) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EBSCO host (1980 to 21 February 2014), as well as reference lists of articles. We also searched www.controlled-trials.com and www.clincialtrials.gov. Randomized controlled trials of postoperative warming interventions aiming to reverse hypothermia compared with control or with each other. Three review authors identified studies for inclusion in this review. One review author extracted data and completed risk of bias assessments; two review authors checked the details. Meta-analysis was conducted when appropriate by using standard methodological procedures as expected by The Cochrane Collaboration. We included 11 trials with 699 participants. Ten trials provided data for analysis. Trials varied in the numbers and types of participants included and in the types of surgery performed. Most trials were at high or unclear risk of bias because of inappropriate or unclear randomization procedures, and because blinding of assessors and participants generally was

  7. Study on Control of Brain Temperature for Brain Hypothermia Treatment

    NASA Astrophysics Data System (ADS)

    Gaohua, Lu; Wakamatsu, Hidetoshi

    The brain hypothermia treatment is an attractive therapy for the neurologist because of its neuroprotection in hypoxic-ischemic encephalopathy patients. The present paper deals with the possibility of controlling the brain and other viscera in different temperatures from the viewpoint of system control. It is theoretically attempted to realize the special brain hypothermia treatment to cool only the head but to warm the body by using the simple apparatus such as the cooling cap, muffler and warming blanket. For this purpose, a biothermal system concerning the temperature difference between the brain and the other thoracico-abdominal viscus is synthesized from the biothermal model of hypothermic patient. The output controllability and the asymptotic stability of the system are examined on the basis of its structure. Then, the maximum temperature difference to be realized is shown dependent on the temperature range of the apparatus and also on the maximum gain determined from the coefficient matrices A, B and C of the biothermal system. Its theoretical analysis shows the realization of difference of about 2.5°C, if there is absolutely no constraint of the temperatures of the cooling cap, muffler and blanket. It is, however, physically unavailable. Those are shown by simulation example of the optimal brain temperature regulation using a standard adult database. It is thus concluded that the surface cooling and warming apparatus do no make it possible to realize the special brain hypothermia treatment, because the brain temperature cannot be cooled lower than those of other viscera in an appropriate temperature environment. This study shows that the ever-proposed good method of clinical treatment is in principle impossible in the actual brain hypothermia treatment.

  8. Vaginal delivery to reduce the risk of hypothermia to newborn

    NASA Astrophysics Data System (ADS)

    Zulala, Nuli Nuryanti; Sitaresmi, Mei Neni; Sulistyaningsih

    2017-08-01

    The prevalence of hypothermia in the world is in the range of 8.5% to 52%, while in Indonesia it is around 47%. Hypothermia has caused 6.3% of neonatal deaths. The method in the process of giving birth determines the way to take care of the newborn. This study aims to observe the effect of the method of delivery on the hypothermia in newborn. This research has obtained an approval from the Ethics Committee of Aisyiyah University, Yogyakarta. This prospective cohort study was conducted to 74 newborns in November 2016. The research subjects were divided into the group of Caesarian section (n = 28) and the group of vaginal delivery (n = 46). Axillary temperature was measured using a digital thermometer at 1st minute, 30th minute, 60th minute, 6th hour, 12th hour and 24th hour. The average temperature difference between the caesarian section group and vaginal delivery group at the 1st minute was at 36°C vs. 36.4° C, at 30th minute at 35.7°C vs. 36.5°C, at 60th minute at 36°C vs. 36.5°C), at 6th hour at 36.2 °C vs. 36.6°C), 12th hour at 36.4°C vs. 36.7°C, and at 24th hour at 36.7°C vs. 36.8°C. The results of the study showed that vaginal delivery could reduce the risk of hypothermia by 1.5 times compared to caesarian section (ρ-value 0.004 CI 95% 1.154 to 1.880)

  9. ACUTE BEHAVIORAL TOXICITY OF SULFOLANE: INFLUENCE OF HYPOTHERMIA

    EPA Science Inventory

    Sulfolane is a solvent which produces hypothermia and decreased oxygen consumption following acute exposure. In the present experiment, the author investigated effects of sulfolane on a behavioral measure of toxicity at ambient temperatures which would either prevent or facilitat...

  10. Hypothermia-induced dystonia and abnormal cerebellar activity in a mouse model with a single disease-mutation in the sodium-potassium pump

    PubMed Central

    Isaksen, Toke Jost; Vedovato, Natascia; Vitenzon, Ariel; Gadsby, David C.; Khodakhah, Kamran

    2017-01-01

    Mutations in the neuron-specific α3 isoform of the Na+/K+-ATPase are found in patients suffering from Rapid onset Dystonia Parkinsonism and Alternating Hemiplegia of Childhood, two closely related movement disorders. We show that mice harboring a heterozygous hot spot disease mutation, D801Y (α3+/D801Y), suffer abrupt hypothermia-induced dystonia identified by electromyographic recordings. Single-neuron in vivo recordings in awake α3+/D801Y mice revealed irregular firing of Purkinje cells and their synaptic targets, the deep cerebellar nuclei neurons, which was further exacerbated during dystonia and evolved into abnormal high-frequency burst-like firing. Biophysically, we show that the D-to-Y mutation abolished pump-mediated Na+/K+ exchange, but allowed the pumps to bind Na+ and become phosphorylated. These findings implicate aberrant cerebellar activity in α3 isoform-related dystonia and add to the functional understanding of the scarce and severe mutations in the α3 isoform Na+/K+-ATPase. PMID:28472154

  11. Accidental hypothermia in a healthy quadriplegic patient.

    PubMed

    Altus, P; Hickman, J W; Nord, H J

    1985-03-01

    An otherwise healthy 28-year-old quadriplegic patient was admitted to the hospital with a core temperature of 76 degrees F secondary to accidental hypothermia. Her neurologic disability was detrimental to thermoregulation by decreasing her ability to shiver actively and to vasoconstrict. The relationship between shivering and thermoregulation is discussed.

  12. SU-C-213-07: Fabrication and Testing of a 3D-Printed Small Animal Rectal Cooling Device to Evaluate Local Hypothermia as a Radioprotector During Prostate SBRT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hrycushko, B; Chopra, R; Futch, C

    Purpose: The protective effects of induced or even accidental hypothermia on the human body are widespread with several medical uses currently under active research. In vitro experiments using human cell lines have shown hypothermia provides a radioprotective effect that becomes more pronounced at large, single-fraction doses common to SBRT treatments. Relevant to prostate SBRT, this work details the fabrication and testing of a 3D-printed cooling device to facilitate the investigation of the radioprotective effect of local hypothermia on the rat rectum. Methods: A 3cm long, two-channel rectal cooling device was designed in SOLIDWORKS CAD for 3D printing. The water intakemore » nozzle is connected to a 1mm diameter brass pipe from which water flows and circulates back around to the exit nozzle. Both nozzles are connected by plastic tubing to a water chiller pump. Following leak-proof testing, fiber optic temperature probes were used to evaluate the temperature over time when placed adjacent to the cooling device within a rat rectum. MRI thermometry characterized the relative temperature distribution in concentric ROIs surrounding the probe. CBCT images from a small-animal irradiator were evaluated for imaging artifacts which could affect Monte Carlo dose calculations during treatment planning. Results: The rectal temperature adjacent to the cooling device decreased from body temperature (37°C) to 15°C in 10–20 minutes from device insertion. Rectal temperature was maintained at 15±3°C during active cooling. MRI thermometry tests revealed a steep temperature gradient with increasing distance from the cooling device, with the desired temperature range maintained within the surrounding few millimeters. Conclusion: A 3D printed rectal cooling device was fabricated for the purpose of inducing local hypothermia in rat rectums. Rectal cooling capabilities were characterized in-vivo to facilitate an investigation of the radioprotective effect of hypothermia for late

  13. Prehospital therapeutic hypothermia after cardiac arrest: a systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Diao, Mengyuan; Huang, Fenglou; Guan, Jun; Zhang, Zhe; Xiao, Yan; Shan, Yi; Lin, Zhaofen; Ding, Liangcai

    2013-08-01

    Therapeutic hypothermia has been recommended for the treatment of cardiac arrest patients who remain comatose after the return of spontaneous circulation. However, the optimal time to initiate therapeutic hypothermia remains unclear. The objective of the present study is to assess the effectiveness and safety of prehospital therapeutic hypothermia after cardiac arrest. Databases such as MEDLINE, Embase, and Cochrane Library were searched from their establishment date to May of 2012 to retrieve randomized control trials on prehospital therapeutic hypothermia after cardiac arrest. Thereafter, the studies retrieved were screened based on predefined inclusion and exclusion criteria. Data were extracted and the quality of the included studies was evaluated. A meta-analysis was performed by using the Cochrane Collaboration Review Manager 5.1.6 software. Five studies involving 633 cases were included, among which 314 cases were assigned to the treatment group and the other 319 cases to the control group. The meta-analysis indicated that prehospital therapeutic hypothermia after cardiac arrest produced significant differences in temperature on hospital admission compared with in-hospital therapeutic hypothermia or normothermia (patient data; mean difference=-0.95; 95% confidence interval -1.15 to -0.75; I(2)=0%). However, no significant differences were observed in the survival to the hospital discharge, favorable neurological outcome at hospital discharge, and rearrest. The risk of bias was low; however, the quality of the evidence was very low. This review demonstrates that prehospital therapeutic hypothermia after cardiac arrest can decrease temperature on hospital admission. On the other hand, regarding the survival to hospital discharge, favorable neurological outcome at hospital discharge, and rearrest, our meta-analysis and review produces non-significant results. Using the Grading of Recommendations, Assessment, Development and Evaluation methodology, we conclude

  14. Milrinone ameliorates cardiac mechanical dysfunction after hypothermia in an intact rat model.

    PubMed

    Dietrichs, Erik Sveberg; Kondratiev, Timofei; Tveita, Torkjel

    2014-12-01

    Rewarming from hypothermia is often complicated by cardiac dysfunction, characterized by substantial reduction in stroke volume. Previously we have reported that inotropic agents, working via cardiac β-receptor agonism may exert serious side effects when applied to treat cardiac contractile dysfunction during rewarming. In this study we tested whether Milrinone, a phosphodiesterase III inhibitor, is able to ameliorate such dysfunction when given during rewarming. A rat model designed for circulatory studies during experimental hypothermia with cooling to a core temperature of 15°C, stable hypothermia at this temperature for 3h and subsequent rewarming was used, with a total of 3 groups: (1) a normothermic group receiving Milrinone, (2) a hypothermic group receiving Milrinone the last hour of hypothermia and during rewarming, and (3) a hypothermic saline control group. Hemodynamic function was monitored using a conductance catheter introduced to the left ventricle. After rewarming from 15°C, stroke volume and cardiac output returned to within baseline values in Milrinone treated animals, while these variables were significantly reduced in saline controls. Milrinone ameliorated cardiac dysfunction during rewarming from 15°C. The present results suggest that at low core temperatures and during rewarming from such temperatures, pharmacologic efforts to support cardiovascular function is better achieved by substances preventing cyclic AMP breakdown rather than increasing its formation via β-receptor stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. ERK phosphorylation plays an important role in the protection afforded by hypothermia against renal ischemia-reperfusion injury.

    PubMed

    Choi, Dae Eun; Jeong, Jin Young; Choi, Hyunsu; Chang, Yoon Kyung; Ahn, Moon Sang; Ham, Young Rok; Na, Ki Ryang; Lee, Kang Wook

    2017-02-01

    Although hypothermia attenuates the renal injury induced by ischemia-reperfusion, the detailed molecular pathway(s) involved remains unknown. ERK phosphorylation is known to protect against ischemia-reperfusion injury. Also, it has been reported that hypothermia may induce ERK phosphorylation in the heart and brain. We evaluated the role played by ERK in hypothermic protection against renal ischemia-reperfusion injury. C57Bl/6 mice were divided into the following groups: sham-operated (cold, 32°C) vs normal temperature (37°C); ischemia-reperfusion mice (32°C vs 37°C); and PD98059- or vehicle-treated ischemia-reperfusion mice (32°C). Kidneys were harvested 10 and 27 minutes after induction of renal ischemia and 24 hours after ischemia-reperfusion injury. Functional and molecular markers of kidney injury were evaluated. To explore the molecular mechanism involved the expression levels of renal HIF-1 and associated proteins were evaluated. The blood urea nitrogen (BUN) and serum creatinine (s-Cr) levels and the histologic renal injury scores were significantly lower in 32°C ischemia-reperfusion than 37°C ischemia-reperfusion kidneys (all P values < .05). The expression levels of Bax and caspase-3 and the extent of TUNEL and 8-OHdG cell positivity decreased, whereas the renal Bcl-2 level increased, in 32°C ischemia-reperfusion compared to 37°C ischemia-reperfusion mice. The extent of renal ERK phosphorylation was significantly higher in ischemia-reperfusion than sham-operated kidneys. Also, ERK phosphorylation was significantly increased in the kidneys of 32°C compared to 37°C ischemia-reperfusion mice. PD98059 treatment of 32°C ischemia-reperfusion mice significantly decreased the renal HIF-1 level (P < .05) and increased the BUN, s-Cr, renal Bax, and caspase-3 expression levels; the tissue injury score; and the proportions of TUNEL- and 8-OHdG-positive cells. PD98059 also increased the renal Bcl-2 level in such mice. Hypothermia attenuates the renal

  16. Heat Capacity, Body Temperature, and Hypothermia

    NASA Astrophysics Data System (ADS)

    Kimbrough, Doris R.

    1998-01-01

    Even when air and water are at the same temperature, water will "feel" distinctly colder to us. This difference is due to the much higher heat capacity of water than of air. Offered here is an interesting life science application of water's high heat capacity and its serious implications for the maintenance of body temperature and the prevention of hypothermia in warm-blooded animals.

  17. Use of plastic bags to prevent hypothermia at birth in preterm infants--do they work at lower gestations?

    PubMed

    Ibrahim, C P H; Yoxall, C W

    2009-02-01

    Hypothermia at birth is strongly associated with mortality and morbidity in preterm infants. Occlusive wrapping of preterm infants during resuscitation, including polythene bags have been shown to prevent hypothermia. To evaluate the effectiveness of the introduction of polythene bags at resuscitation of infants born below 30 weeks gestation in a large tertiary neonatal centre. Retrospective audit of admission temperatures of all infants born below 30 weeks gestation for two years before and two years after the introduction of polythene bags. Hypothermia was defined as admission axillary temperature < 36 degrees C. A total of 334 eligible infants were born during the study period. Two hundred and fifty-three (75.8%) had admission temperatures recorded. The incidence of hypothermia fell from 25% to 16%(p = 0.098) for the whole group since the introduction of polythene bags. The main reduction in hypothermia was seen in infants born above 28 weeks gestation (19.4% vs. 3.9%, p = 0.017). There was no significant effect in infants born between 28 weeks and 30 weeks (29.3% vs. 24.8%, p = 0.58). Polythene bags are effective in reducing the incidence of hypothermia at admission in infants born below 30 weeks gestation. The benefit in infants born below 28 weeks gestation was only marginal. This is in contrast to previously published studies. This may be related to the comparatively low incidence of hypothermia at the study centre even prior to introduction of polythene bags.

  18. Randomized trial of plastic bags to prevent term neonatal hypothermia in a resource-poor setting.

    PubMed

    Belsches, Theodore C; Tilly, Alyssa E; Miller, Tonya R; Kambeyanda, Rohan H; Leadford, Alicia; Manasyan, Albert; Chomba, Elwyn; Ramani, Manimaran; Ambalavanan, Namasivayam; Carlo, Waldemar A

    2013-09-01

    Term infants in resource-poor settings frequently develop hypothermia during the first hours after birth. Plastic bags or wraps are a low-cost intervention for the prevention of hypothermia in preterm and low birth weight infants that may also be effective in term infants. Our objective was to test the hypothesis that placement of term neonates in plastic bags at birth reduces hypothermia at 1 hour after birth in a resource-poor hospital. This parallel-group randomized controlled trial was conducted at University Teaching Hospital, the tertiary referral center in Zambia. Inborn neonates with both a gestational age ≥37 weeks and a birth weight ≥2500 g were randomized 1:1 to either a standard thermoregulation protocol or to a standard thermoregulation protocol with placement of the torso and lower extremities inside a plastic bag within 10 minutes after birth. The primary outcome was hypothermia (<36.5°C axillary temperature) at 1 hour after birth. Neonates randomized to plastic bag (n = 135) or to standard thermoregulation care (n = 136) had similar baseline characteristics (birth weight, gestational age, gender, and baseline temperature). Neonates in the plastic bag group had a lower rate of hypothermia (60% vs 73%, risk ratio 0.76, confidence interval 0.60-0.96, P = .026) and a higher axillary temperature (36.4 ± 0.5°C vs 36.2 ± 0.7°C, P < .001) at 1 hour after birth compared with infants receiving standard care. Placement in a plastic bag at birth reduced the incidence of hypothermia at 1 hour after birth in term neonates born in a resource-poor setting, but most neonates remained hypothermic.

  19. Expression of Hsp27 and Hsp70 and vacuolization in the pituitary glands in cases of fatal hypothermia.

    PubMed

    Doberentz, Elke; Markwerth, Philipp; Wagner, Rebecca; Madea, Burkhard

    2017-09-01

    Hypothermia causes systemic cellular stress. The pituitary gland is an endocrine gland and plays an important role in thermoregulation. When the core body temperature drops, the pituitary gland is activated by stimulation of hypothalamic hormones. In this study, we investigated morphological alterations of the pituitary gland in cases of fatal hypothermia. Several morphological alterations of the anterior lobe of the pituitary gland, such as hemorrhage, vacuolization, and hyperemia, have been previously described in fatal hypothermia. However, the diagnostic value of these findings is controversial. We compared 11 cases of fatal hypothermia with 10 cases lacking antemortem hypothermic influences. In the presence of thermal cellular stress, the expression of heat shock proteins increases to protect cellular structures. Therefore, we immunohistochemically analyzed Hsp27 and Hsp70. Hsp27 expression was detected in 27.3% of the cases of fatal hypothermia and in 10.0% of the control cases, whereas Hsp70 expression was not detected in any case. Additionally, Sudan staining was performed to quantify fatty degeneration. A positive reaction was found in 45.5% of the study group and in 10.0% of the control group. This indicates that fatty degeneration might be a valuable marker when other macroscopic signs of hypothermia are absent.

  20. [Analysis of biochemical markers in serum of guinea pigs after death caused by hypothermia].

    PubMed

    Li, Shi-ying; Deng, Kai-fei; Shao, Yu; Li, Zheng-dong; Qin, Zhi-qiang; Chen, Yi-jiu; Huang, Ping

    2014-08-01

    To explore the changes and rules of biochemical markers in serum of guinea pigs after death caused by hypothermia and to provide references for fatal hypothermia diagnosis by serum biochemical markers. Twenty guinea pigs were randomly divided into experimental group and control group. The guinea pigs in the experimental group were kept at -30 °C until death, while the ones in control group were decapitated after same survival intervals at 25 °C. The serum was extracted from the whole blood of right ventricular immediately. Subsequently, a series of serum biochemical markers were analyzed by auto bio-chemical analyzer. The levels of glucose, uric acid, creatinine and urea nitrogen in the experimental group were significantly higher than those in control group, respectively (P<0.05). Compared with the control group, the levels of total protein and albumin were significantly lower in the experimental group (P<0.05). There were no significantly differences of the levels of other markers such as serum enzymes and ions observed between the two groups. There are characteristic changes of some specific serum biochemical markers in fatal hypothermia, which may be potentially useful for auxiliary diagnosis of fatal hypothermia.

  1. Demographics and clinical characteristics of episodic hypothermia in multiple sclerosis.

    PubMed

    Toledano, Michel; Weinshenker, Brian G; Kaufmann, Timothy J; Parisi, Joseph E; Paz Soldán, M Mateo

    2018-03-01

    Episodic hypothermia (EH) can occur in multiple sclerosis (MS). The putative mechanism is impairment of thermoregulation due to a presumed demyelinating hypothalamic lesion. To describe a cohort of patients with MS, who developed EH. Patients were identified through review of the Mayo Clinic electronic medical record (1996 to July 2015). Search terms were [multiple sclerosis] or [MS] within the diagnoses field and [hypothermia] within any field. We reviewed records for accuracy of diagnoses and abstracted relevant data. Magnetic resonance imaging (MRI) was reviewed for presence of hypothalamic lesions. Of 156 patients, 34 had concurrent MS and hypothermia. Thirty-two (94%) had progressive disease at EH onset. Median MS duration was 19.9 years, and median expanded disability status scale (EDSS) was 8.0. Most patients presented with alterations in consciousness. Infection was suspected as the precipitating factor in 19 (56%), but clinically/laboratory supported in only 9 (28%). MRI lesions were evident within the hypothalamus in only 4 (14%). EH occurs predominantly in patients with advanced secondary progressive MS. The major manifestation is altered consciousness. Infection is often suspected as causal, but infrequently confirmed. Although commonly implicated, hypothalamic lesions were rarely evident on MRI and were absent in two post-mortem evaluations.

  2. Detection and management of hypothermia at a large outdoor endurance event in the United kingdom.

    PubMed

    Bhangu, Aneel; Parmar, Rinesh

    2010-06-01

    Optimum detection of hypothermia in athletes during outdoor exposure events remains controversial. The aims of this study were firstly to assess whether temperature readings affected competitor discharge from the treatment station and secondly to assess agreement between oral and tympanic thermometer measurements. All competitors treated for symptomatic hypothermia at an outdoor endurance event in the United Kingdom during January 2009 were included. Temperature readings were taken using oral (Digitemp digital oral thermometer) and tympanic (Braun Thermoscan IRT 4520 ExacTemp) thermometers, with a temperature <35 degrees C classifying hypothermia. From 4700 competitors, 64 (1.4%) were treated for symptomatic hypothermia. Of these, 92% were male, the mean age was 26 years, and the mean treatment time was 25 minutes. There was no severe/life-threatening hypothermia, and no competitors required transport to a hospital for hypothermia. At discharge, 19% of competitors were still classed as hypothermic in the oral group and 28% in the tympanic group, despite competitors only being discharged when no longer symptomatic. Oral readings at discharge were significantly lower than tympanic readings (33.8 degrees C [95% CI, 33.2 degrees C to 34.5 degrees C] vs 35.0 degrees C [95% CI, 34.6 degrees C to 35.3 degrees C], respectively, P = .003). The use of thermometers had a limited role in discharging competitors at this event, who were apparently safely discharged when no longer symptomatic. Treating clinicians and the thermometers did not always agree on whether a patient was hypothermic or not. Oral and tympanic thermometers had poor agreement. Routine thermometer readings at future events may be unnecessary, although screening competitors of concern will remain useful. Copyright (c) 2010 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  3. Prediction of the outcome in cardiac arrest patients undergoing hypothermia using EEG wavelet entropy.

    PubMed

    Moshirvaziri, Hana; Ramezan-Arab, Nima; Asgari, Shadnaz

    2016-08-01

    Cardiac arrest (CA) is the leading cause of death in the United States. Induction of hypothermia has been found to improve the functional recovery of CA patients after resuscitation. However, there is no clear guideline for the clinicians yet to determine the prognosis of the CA when patients are treated with hypothermia. The present work aimed at the development of a prognostic marker for the CA patients undergoing hypothermia. A quantitative measure of the complexity of Electroencephalogram (EEG) signals, called wavelet sub-band entropy, was employed to predict the patients' outcomes. We hypothesized that the EEG signals of the patients who survived would demonstrate more complexity and consequently higher values of wavelet sub-band entropies. A dataset of 16-channel EEG signals collected from CA patients undergoing hypothermia at Long Beach Memorial Medical Center was used to test the hypothesis. Following preprocessing of the signals and implementation of the wavelet transform, the wavelet sub-band entropies were calculated for different frequency bands and EEG channels. Then the values of wavelet sub-band entropies were compared among two groups of patients: survived vs. non-survived. Our results revealed that the brain high frequency oscillations (between 64100 Hz) captured from the inferior frontal lobes are significantly more complex in the CA patients who survived (p-value <; 0.02). Given that the non-invasive measurement of EEG is part of the standard clinical assessment for CA patients, the results of this study can enhance the management of the CA patients treated with hypothermia.

  4. Clinical outcomes using modest intravascular hypothermia after acute cervical spinal cord injury.

    PubMed

    Levi, Allan D; Casella, Gizelda; Green, Barth A; Dietrich, W Dalton; Vanni, Steven; Jagid, Jonathan; Wang, Michael Y

    2010-04-01

    Although a number of neuroprotective strategies have been tested after spinal cord injury (SCI), no treatments have been established as a standard of care. We report the clinical outcomes at 1-year median follow-up, using endovascular hypothermia after SCI and a detailed analysis of the complications. We performed a retrospective analysis of American Spinal Injury Association and International Medical Society of Paraplegia Impairment Scale (AIS) scores and complications in 14 patients with SCI presenting with a complete cervical SCI (AIS A). All patients were treated with 48 hours of modest (33 degrees C) intravascular hypothermia. The comparison group was composed of 14 age- and injury-matched subjects treated at the same institution. Six of the 14 cooled patients (42.8%) were incomplete at final follow-up (50.2 [9.7] weeks). Three patients improved to AIS B, 2 patients improved to AIS C, and 1 patient improved to AIS D. Complications were predominantly respiratory and infectious in nature. However, in the control group, a similar number of complications was observed. Adverse events such as coagulopathy, deep venous thrombosis, and pulmonary embolism were not seen in the patients undergoing hypothermia. This study is the first phase 1 clinical trial on the safety and outcome with the use of endovascular hypothermia in the treatment of acute cervical SCI. In this small cohort of patients with SCI, complication rates were similar to those of normothermic patients with an associated AIS A conversion rate of 42.8%.

  5. Hypothermia for neonatal hypoxic-ischemic encephalopathy: NICHD Neonatal Research Network contribution to the field.

    PubMed

    Shankaran, Seetha; Natarajan, Girija; Chalak, Lina; Pappas, Athina; McDonald, Scott A; Laptook, Abbot R

    2016-10-01

    In this article, we summarize the NICHD Neonatal Research Network (NRN) trial of whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy in relation to other randomized controlled trials (RCTs) of hypothermia neuroprotection. We describe the NRN secondary studies that have been published in the past 10 years evaluating clinical, genetic, biochemical, and imaging biomarkers of outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Extending the duration of hypothermia does not further improve white matter protection after ischemia in term-equivalent fetal sheep.

    PubMed

    Davidson, Joanne O; Yuill, Caroline A; Zhang, Frank G; Wassink, Guido; Bennet, Laura; Gunn, Alistair J

    2016-04-28

    A major challenge in modern neonatal care is to further improve outcomes after therapeutic hypothermia for hypoxic ischemic encephalopathy. In this study we tested whether extending the duration of cooling might reduce white matter damage. Term-equivalent fetal sheep (0.85 gestation) received either sham ischemia followed by normothermia (n = 8) or 30 minutes of bilateral carotid artery occlusion followed by three days of normothermia (n = 8), three days of hypothermia (n = 8) or five days of hypothermia (n = 8) started three hours after ischemia. Histology was assessed 7 days after ischemia. Ischemia was associated with loss of myelin basic protein (MBP) and Olig-2 positive oligodendrocytes and increased Iba-1-positive microglia compared to sham controls (p < 0.05). Three days and five days of hypothermia were associated with a similar, partial improvement in MBP and numbers of oligodendrocytes compared to ischemia-normothermia (p < 0.05). Both hypothermia groups had reduced microglial activation compared to ischemia-normothermia (p < 0.05). In the ischemia-five-day hypothermia group, but not ischemia-three-day, numbers of microglia remained higher than in sham controls (p < 0.05). In conclusion, delayed cerebral hypothermia partially protected white matter after global cerebral ischemia in fetal sheep. Extending cooling from 3 to 5 days did not further improve outcomes, and may be associated with greater numbers of residual microglia.

  7. BIOMARKERS S100B AND NSE PREDICT OUTCOME IN HYPOTHERMIA-TREATED ENCEPHALOPATHIC NEWBORNS

    PubMed Central

    Massaro, An N.; Chang, Taeun; Baumgart, Stephen; McCarter, Robert; Nelson, Karin B.; Glass, Penny

    2014-01-01

    Objective To evaluate if serum S100B protein and neuron specific enolase (NSE) measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy (NE). Design Prospective longitudinal cohort study Setting A level IV neonatal intensive care unit in a free-standing children’s hospital. Patients Term newborns with moderate to severe NE referred for therapeutic hypothermia during the study period. Interventions Serum NSE and S100B were measured at 0, 12, 24 and 72 hrs of hypothermia. Measurements and Main Reseults Of the 83 infants were enrolled, fifteen (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development (BSID-II) at 15 months of age. Outcomes were assessed in 49/68 (72%) survivors at a mean age of 15.2±2.7 months. Neurodevelopmental outcome was classified by BSID-II Mental (MDI) and Psychomotor (PDI) Developmental Index scores, reflecting cognitive and motor outcomes respectively. Four-level outcome classifications were defined a priori: normal= MDI/PDI within 1SD (>85), mild= MDI/PDI <1SD (70–85), moderate/severe= MDI/PDI <2SD (<70), or died. Elevated serum S100B and NSE levels measured during hypothermia were associated with increasing outcome severity after controlling for baseline and soceioeconomic characteristics in ordinal regression models. Adjusted odds ratios for cognitive outcome were: S100B 2.5 (95% CI 1.3–4.8) and NSE 2.1 (1.2–3.6); for motor outcome: S100B 2.6 (1.2–5.6) and NSE 2.1 (1.2–3.6). Conclusions Serum S100B and NSE levels in babies with NE are associated with neurodevelopmental outcome at 15 months. These putative biomarkers of brain injury may help direct care during therapeutic hypothermia. PMID:24777302

  8. Dipyrone metabolite 4-MAA induces hypothermia and inhibits PGE2-dependent and -independent fever while 4-AA only blocks PGE2-dependent fever

    PubMed Central

    Malvar, David do C; Aguiar, Fernando A; Vaz, Artur de L L; Assis, Débora C R; de Melo, Miriam C C; Jabor, Valquíria A P; Kalapothakis, Evanguedes; Ferreira, Sérgio H; Clososki, Giuliano C; de Souza, Glória E P

    2014-01-01

    BACKGROUND AND PURPOSE The antipyretic and hypothermic prodrug dipyrone prevents PGE2-dependent and -independent fever induced by LPS from Escherichia coli and Tityus serrulatus venom (Tsv) respectively. We aimed to identify the dipyrone metabolites responsible for the antipyretic and hypothermic effects. EXPERIMENTAL APPROACH Male Wistar rats were treated i.p. with indomethacin (2 mg·kg−1), dipyrone, 4-methylaminoantipyrine (4-MAA), 4-aminoantipyrine (4-AA) (60–360 mg·kg−1), 4-formylaminoantipyrine, 4-acethylaminoantipyrine (120–360 mg·kg−1) or vehicle 30 min before i.p. injection of LPS (50 μg·kg−1), Tsv (150 μg·kg−1) or saline. Rectal temperatures were measured by tele-thermometry and dipyrone metabolite concentrations determined in the plasma, CSF and hypothalamus by LC-MS/MS. PGE2 concentrations were determined in the CSF and hypothalamus by elisa. KEY RESULTS In contrast to LPS, Tsv-induced fever was not followed by increased PGE2 in the CSF or hypothalamus. The antipyretic time-course of 4-MAA and 4-AA on LPS-induced fever overlapped with the period of the highest concentrations of 4-MAA and 4-AA in the hypothalamus, CSF and plasma. These metabolites reduced LPS-induced fever and the PGE2 increase in the plasma, CSF and hypothalamus. Only 4-MAA inhibited Tsv-induced fever. The higher doses of dipyrone and 4-MAA also induced hypothermia. CONCLUSIONS AND IMPLICATIONS The presence of 4-MAA and 4-AA in the CSF and hypothalamus was associated with PGE2 synthesis inhibition and a decrease in LPS-induced fever. 4-MAA was also shown to be an antipyretic metabolite for PGE2-independent fever induced by Tsv suggesting that it is responsible for the additional antipyretic mechanism of dipyrone. Moreover, 4-MAA is the hypothermic metabolite of dipyrone. PMID:24712707

  9. Dipyrone metabolite 4-MAA induces hypothermia and inhibits PGE2 -dependent and -independent fever while 4-AA only blocks PGE2 -dependent fever.

    PubMed

    Malvar, David do C; Aguiar, Fernando A; Vaz, Artur de L L; Assis, Débora C R; de Melo, Miriam C C; Jabor, Valquíria A P; Kalapothakis, Evanguedes; Ferreira, Sérgio H; Clososki, Giuliano C; de Souza, Glória E P

    2014-08-01

    The antipyretic and hypothermic prodrug dipyrone prevents PGE2 -dependent and -independent fever induced by LPS from Escherichia coli and Tityus serrulatus venom (Tsv) respectively. We aimed to identify the dipyrone metabolites responsible for the antipyretic and hypothermic effects. Male Wistar rats were treated i.p. with indomethacin (2 mg·kg(-1) ), dipyrone, 4-methylaminoantipyrine (4-MAA), 4-aminoantipyrine (4-AA) (60-360 mg·kg(-1) ), 4-formylaminoantipyrine, 4-acethylaminoantipyrine (120-360 mg·kg(-1) ) or vehicle 30 min before i.p. injection of LPS (50 μg·kg(-1) ), Tsv (150 μg·kg(-1) ) or saline. Rectal temperatures were measured by tele-thermometry and dipyrone metabolite concentrations determined in the plasma, CSF and hypothalamus by LC-MS/MS. PGE2 concentrations were determined in the CSF and hypothalamus by elisa. In contrast to LPS, Tsv-induced fever was not followed by increased PGE2 in the CSF or hypothalamus. The antipyretic time-course of 4-MAA and 4-AA on LPS-induced fever overlapped with the period of the highest concentrations of 4-MAA and 4-AA in the hypothalamus, CSF and plasma. These metabolites reduced LPS-induced fever and the PGE2 increase in the plasma, CSF and hypothalamus. Only 4-MAA inhibited Tsv-induced fever. The higher doses of dipyrone and 4-MAA also induced hypothermia. The presence of 4-MAA and 4-AA in the CSF and hypothalamus was associated with PGE2 synthesis inhibition and a decrease in LPS-induced fever. 4-MAA was also shown to be an antipyretic metabolite for PGE2 -independent fever induced by Tsv suggesting that it is responsible for the additional antipyretic mechanism of dipyrone. Moreover, 4-MAA is the hypothermic metabolite of dipyrone. © 2014 The British Pharmacological Society.

  10. Prolonged therapeutic hypothermia does not adversely impact neuroplasticity after global ischemia in rats

    PubMed Central

    Silasi, Gergely; Klahr, Ana C; Hackett, Mark J; Auriat, Angela M; Nichol, Helen; Colbourne, Frederick

    2012-01-01

    Hypothermia improves clinical outcome after cardiac arrest in adults. Animal data show that a day or more of cooling optimally reduces edema and tissue injury after cerebral ischemia, especially after longer intervention delays. Lengthy treatments, however, may inhibit repair processes (e.g., synaptogenesis). Thus, we evaluated whether unilateral brain hypothermia (∼33°C) affects neuroplasticity in the rat 2-vessel occlusion model. In the first experiment, we cooled starting 1 hour after ischemia for 2, 4, or 7 days. Another group was cooled for 2 days starting 48 hours after ischemia. One group remained normothermic throughout. All hypothermia treatments started 1 hour after ischemia equally reduced hippocampal CA1 injury in the cooled hemisphere compared with the normothermic side and the normothermic group. Cooling only on days 3 and 4 was not beneficial. Importantly, no treatment influenced neurogenesis (Ki67/Doublecortin (DCX) staining), synapse formation (synaptophysin), or brain-derived neurotropic factor (BDNF) immunohistochemistry. A second experiment confirmed that BDNF levels (ELISA) were equivalent in normothermic and 7-day cooled rats. Last, we measured zinc (Zn), which is important in plasticity, with X-ray fluorescence imaging in normothermic and 7-day cooled rats. Hypothermia did not alter the postischemic distribution of Zn within the hippocampus. In summary, cooling significantly mitigates injury without compromising neuroplasticity. PMID:22434072

  11. Severe hypothermia in myxoedema coma: a rewarming by extracorporeal circulation.

    PubMed

    Kogan, Alexander; Kassif, Yigal; Shadel, Mordechay; Shwarz, Yaron; Lavee, Jacob; Or, Jacob; Raanani, Ehud

    2011-12-01

    Myxoedema coma is the most lethal manifestation of hypothyroidism. It represents a true medical emergency, especially in the case of cardiovascular instability. Extracorporeal circulation is usually used for rewarming and for providing cardiac support in patients with severe hypothermia and, in addition, cardiovascular instability. We report the case of an 84-year-old woman who presented to the ED with accidental hypothermia associated with myxoedema that was successfully managed by veno-arterial extracorporeal blood rewarming. This case suggests that veno-arterial extracorporeal rewarming appears to achieve a rapid and consistent rewarming rate and is less invasive and more readily available than cardiopulmonary bypass. © 2011 The Authors. EMA © 2011 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  12. 13C NMR metabolomic evaluation of immediate and delayed mild hypothermia in cerebrocortical slices after oxygen-glucose deprivation.

    PubMed

    Liu, Jia; Segal, Mark R; Kelly, Mark J S; Pelton, Jeffrey G; Kim, Myungwon; James, Thomas L; Litt, Lawrence

    2013-11-01

    Mild brain hypothermia (32°-34°C) after human neonatal asphyxia improves neurodevelopmental outcomes. Astrocytes but not neurons have pyruvate carboxylase and an acetate uptake transporter. C nuclear magnetic resonance spectroscopy of rodent brain extracts after administering [1-C]glucose and [1,2-C]acetate can distinguish metabolic differences between glia and neurons, and tricarboxylic acid cycle entry via pyruvate dehydrogenase and pyruvate carboxylase. Neonatal rat cerebrocortical slices receiving a C-acetate/glucose mixture underwent a 45-min asphyxia simulation via oxygen-glucose-deprivation followed by 6 h of recovery. Protocols in three groups of N=3 experiments were identical except for temperature management. The three temperature groups were: normothermia (37°C), hypothermia (32°C for 3.75 h beginning at oxygen--glucose deprivation start), and delayed hypothermia (32°C for 3.75 h, beginning 15 min after oxygen-glucose deprivation start). Multivariate analysis of nuclear magnetic resonance metabolite quantifications included principal component analyses and the L1-penalized regularized regression algorithm known as the least absolute shrinkage and selection operator. The most significant metabolite difference (P<0.0056) was [2-C]glutamine's higher final/control ratio for the hypothermia group (1.75±0.12) compared with ratios for the delayed (1.12±0.12) and normothermia group (0.94±0.06), implying a higher pyruvate carboxylase/pyruvate dehydrogenase ratio for glutamine formation. Least Absolute Shrinkage and Selection Operator found the most important metabolites associated with adenosine triphosphate preservation: [3,4-C]glutamate-produced via pyruvate dehydrogenase entry, [2-C]taurine-an important osmolyte and antioxidant, and phosphocreatine. Final principal component analyses scores plots suggested separate cluster formation for the hypothermia group, but with insufficient data for statistical significance. Starting mild hypothermia

  13. [Severe apparent life-threatening event during "skin-to-skin": treatment with hypothermia].

    PubMed

    Marin, N; Valverde, E; Cabañas, F

    2013-10-01

    'Skin-to-skin' in healthy newborn infants is currently routine practice in Spanish maternity wards. This practice has shown benefits in increasing the duration of breast-feeding and maternal bonding behaviour with no significant adverse events. Early sudden deaths and severe apparent life-threatening events (ALTE) during the first 24 hours of life are infrequent, but well recognised. Risk factors during 'skin to skin' have been established. These events can lead to high neonatal morbidity and mortality. Hypothermia is now the standard of care for moderate to severe hypoxic-ischaemic encephalopathy and has shown to reduce mortality and neurological morbidity in children with hypoxic-ischaemic brain injury. Although there are no clinical trials that evaluate hypothermia after a severe ALTE, neonates who suffer it should be considered for this treatment. We present a case of a healthy newborn who had an ALTE during skin-to-skin with his mother and was treated with hypothermia. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  14. Use of self-heating gel mattresses eliminates admission hypothermia in infants born below 28 weeks gestation.

    PubMed

    Ibrahim, C P Hafis; Yoxall, C W

    2010-07-01

    Hypothermia at birth is strongly associated with mortality and morbidity in pre-term infants. A local audit showed limited effectiveness of occlusive wrapping in preventing admission hypothermia in very pre-term infants. Self-heating acetate gel mattresses were introduced as a result to prevent hypothermia at birth in infants born at or below 28 weeks gestation. A retrospective audit was conducted to evaluate the effectiveness of self-heating acetate gel mattresses at resuscitation of infants born at or below 28 weeks to prevent hypothermia at birth. All infants born at or below 28 weeks gestation during 18 months before and 18 months after self-heating acetate gel mattresses were introduced during resuscitation were included. One hundred five babies were born when acetate gel mattresses were not used, and 124 were born during the period when they were. Four (3.3%) babies were hypothermic (temperature <36 degrees C) at admission when the mattresses were used compared to 21 (22.6%) babies who were hypothermic during the period it was not (p < 0.001). Hyperthermia (temperature >37 degrees C) rose from 30.1% prior to use of gel mattresses to 49.6% when they were used (p = 0.004). Self-heating acetate gel mattresses are highly effective in reducing admission hypothermia in infants born at or below 28 weeks gestation. The use of these mattresses is associated with a significant increase in hyperthermia.

  15. Impact of hypothermia on implementation of CPAP for neonatal respiratory distress syndrome in a low-resource setting.

    PubMed

    Carns, Jennifer; Kawaza, Kondwani; Quinn, M K; Miao, Yinsen; Guerra, Rudy; Molyneux, Elizabeth; Oden, Maria; Richards-Kortum, Rebecca

    2018-01-01

    Neonatal hypothermia is widely associated with increased risks of morbidity and mortality, but remains a pervasive global problem. No studies have examined the impact of hypothermia on outcomes for preterm infants treated with CPAP for respiratory distress syndrome (RDS). This retrospective analysis assessed the impact of hypothermia on outcomes of 65 neonates diagnosed with RDS and treated with either nasal oxygen (N = 17) or CPAP (N = 48) in a low-resource setting. A classification tree approach was used to develop a model predicting survival for subjects diagnosed with RDS. Survival to discharge was accurately predicted based on three variables: mean temperature, treatment modality, and mean respiratory rate. None of the 23 neonates with a mean temperature during treatment below 35.8°C survived to discharge, regardless of treatment modality. Among neonates with a mean temperature exceeding 35.8°C, the survival rate was 100% for the 31 neonates treated with CPAP and 36.4% for the 11 neonates treated with nasal oxygen (p<0.001). For neonates treated with CPAP, outcomes were poor if more than 50% of measured temperatures indicated hypothermia (5.6% survival). In contrast, all 30 neonates treated with CPAP and with more than 50% of temperature measurements above 35.8°C survived to discharge, regardless of initial temperature. The results of our study suggest that successful implementation of CPAP to treat RDS in low-resource settings will require aggressive action to prevent persistent hypothermia. However, our results show that even babies who are initially cold can do well on CPAP with proper management of hypothermia.

  16. Adenosine 5'-monophosphate-induced hypothermia inhibits the activation of ERK1/2, JNK, p38 and NF-κB in endotoxemic rats.

    PubMed

    Wang, Yunlong; Zhang, Aihua; Lu, Shulai; Pan, Xinting; Jia, Dongmei; Yu, Wenjuan; Jiang, Yanxia; Li, Xinde; Wang, Xuefeng; Zhang, Jidong; Hou, Lin; Sun, Yunbo

    2014-11-01

    Many studies have shown that LPS mainly activates four signal transduction pathways to induce inflammation, namely the p38, ERK1/2, JNK and IKK/NF-κB pathways. Studies have demonstrated that 5'-AMP-induced hypothermia (AIH) exhibits high anti-inflammatory capabilities. In this study, we explore that how AIH inhibits the inflammatory response. Wistar rats were divided into five groups: a control group, an LPS group, a 5'-AMP pre-treatment group, a 5'-AMP post-treatment group and a 5'-AMP group. For each group, plasma and lung were collected from the rats at 6h and 12h after LPS injection. ELISA assays were used to detect plasma levels of CD14, CRP and MCP-1. Inflammatory pathway activation and TLR4 expression were assayed separately by Western blot analysis and immunohistochemistry. Our results showed that rats treated with AIH either before or after an LPS-challenge had a significant decrease in plasma levels of CD14, CRP and TLR4 compared with rats that received LPS only. Western blot analysis showed that AIH inhibited the activation of extracellular signal-regulated kinases (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) and NF-κB in inflammatory rats. Our study concluded that AIH attenuated LPS-induced inflammation mainly by inhibiting activation on the ERK1/2, p38, JNK and NF-κB signaling pathways. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Effects of desmopressin on platelet function under conditions of hypothermia and acidosis: an in vitro study using multiple electrode aggregometry*.

    PubMed

    Hanke, A A; Dellweg, C; Kienbaum, P; Weber, C F; Görlinger, K; Rahe-Meyer, N

    2010-07-01

    Hypothermia and acidosis lead to an impairment of coagulation. It has been demonstrated that desmopressin improves platelet function under hypothermia. We tested platelet function ex vivo during hypothermia and acidosis. Blood samples were taken from 12 healthy subjects and assigned as follows: normal pH, pH 7.2, and pH 7.0, each with and without incubation with desmopressin. Platelet aggregation was assessed by multiple electrode aggregometry. Baseline was normal pH and 36 degrees C. The other samples were incubated for 30 min and measured at 32 degrees C. Acidosis significantly impaired aggregation. Desmopressin significantly increased aggregability during hypothermia and acidosis regardless of pH, but did not return it to normal values at low pH. During acidosis and hypothermia, acidosis should be corrected first; desmopressin can then be administered to improve platelet function as a bridge until normothermia can be achieved.

  18. Comparison of Electronic Learning Versus Lecture-based Learning in Improving Emergency Medicine Residents' Knowledge About Mild Induced Hypothermia After Cardiac Arrest.

    PubMed

    Soleimanpour, Maryam; Rahmani, Farzad; Naghizadeh Golzari, Mehrad; Ala, Alireza; Morteza Bagi, Hamid Reza; Mehdizadeh Esfanjani, Robab; Soleimanpour, Hassan

    2017-08-01

    The process of medical education depends on several issues such as training materials, students, professors, educational fields, and the applied technologies. The current study aimed at comparing the impacts of e-learning and lecture-based learning of mild induced hypothermia (MIH) after cardiac arrest on the increase of knowledge among emergency medicine residents. In a pre- and post-intervention study, MIH after cardiac arrest was taught to 44 emergency medicine residents. Residents were randomly divided into 2 groups. The first group included 21 participants (lecture-based learning) and the second had 23 participants (e-learning). A 19-item questionnaire with approved validity and reliability was employed as the pretest and posttest. Then, data were analyzed with SPSS software version 17.0. There was no statistically significant difference in terms of the learning method between the test scores of the 2 groups (P = 0.977). E-learning and lecture-based learning methods was effective in augmentation of residents of emergency medicine knowledge about MIH after cardiac arrest; nevertheless, there was no significant difference between these mentioned methods.

  19. Severe carbon monoxide poisoning complicated by hypothermia: a case report.

    PubMed

    Kamijo, Yoshito; Ide, Toshimitsu; Ide, Ayako; Soma, Kazui

    2011-03-01

    It is proposed that the significant elevation of interleukin-6 (>400 pg/mL) in cerebrospinal fluid during the early phase of carbon monoxide poisoning may be a predictive biomarker for the development of delayed encephalopathy. A 52-year-old man presented to the emergency department with severe carbon monoxide poisoning. On arrival, the patient was comatose with decorticate rigidity (Glasgow Coma Scale, E1V1M3). His core body temperature, measured in the urinary bladder, was 32.4°C. Laboratory blood analysis revealed elevated CO-Hb (36.0%) and metabolic acidosis with elevated lactate (pH 7.081; base excess [BE], -19.2 mmol/L; HCO3, -9.8 mmol/L; lactate, 168.8 mg/dL). After treatment with hyperbaric oxygen and several different rewarming techniques, he became alert and his core body temperature increased to normal. Interleukin-6 in cerebrospinal fluid at 5.5 hours after his last exposure to carbon monoxide was significantly elevated (752 pg/mL). However, he did not develop delayed encephalopathy. In this case, hypothermia in the range of therapeutic hypothermia (32°C to 34°C) may have suppressed formation of reactive oxygen species and subsequent lipid peroxydation, preventing the development of delayed encephalopathy. Therapeutic hypothermia initiated soon after the last exposure to carbon monoxide may be an effective prophylactic method for preventing the development of delayed encephalopathy.

  20. [Continual venous haemofiltration in severe hypothermia].

    PubMed

    Nielsen, Jane Stab; Gilsaa, Torben

    2010-02-22

    A seventy-year-old male was brought to the emergency department severely hypothermic with a core temperature of 27 degrees C. He had sustained circulation and was actively rewarmed for 6,5 hours using central veno-venous haemofiltration. The rewarming was uneventful and the patient was discharged without sequelae. This case is an example of efficient and fast rewarming of severe accidental hypothermia by use of CVVH - a method currently available at most intensive care units in Denmark.

  1. Differences in the profile of protection afforded by TRO40303 and mild hypothermia in models of cardiac ischemia/reperfusion injury.

    PubMed

    Hansson, Magnus J; Llwyd, Osian; Morin, Didier; de Paulis, Damien; Arnoux, Thomas; Gouarné, Caroline; Koul, Sasha; Engblom, Henrik; Bordet, Thierry; Tissier, Renaud; Arheden, Haakan; Erlinge, David; Halestrap, Andrew P; Berdeaux, Alain; Pruss, Rebecca M; Schaller, Sophie

    2015-08-05

    The mode of protection against cardiac reperfusion injury by mild hypothermia and TRO40303 was investigated in various experimental models and compared to MitoQ in vitro. In isolated cardiomyocytes subjected to hypoxia/reoxygenation, TRO40303, MitoQ and mild hypothermia delayed mPTP opening, inhibited generation of mitochondrial superoxide anions at reoxygenation and improved cell survival. Mild hypothermia, but not MitoQ and TRO40303, provided protection in a metabolic starvation model in H9c2 cells and preserved respiratory function in isolated rat heart mitochondria submitted to anoxia/reoxygenation. In the Langendorff-perfused rat heart, only mild hypothermia provided protection of hemodynamic function and reduced infarct size following ischemia/reperfusion. In biopsies from the left ventricle of pigs subjected to in vivo occlusion/reperfusion, TRO40303 specifically preserved respiratory functions in the peri-infarct zone whereas mild hypothermia preserved both the ischemic core area and the peri-infarct zones. Additionally in this pig model, only hypothermia reduced infarct size. We conclude that mild hypothermia provided protection in all models by reducing the detrimental effects of ischemia, and when initiated before occlusion, reduced subsequent reperfusion damage leading to a smaller infarct. By contrast, although TRO40303 provided similar protection to MitoQ in vitro and offered specific protection against some aspects of reperfusion injury in vivo, this was insufficient to reduce infarct size. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Kangaroo mother care for the prevention of neonatal hypothermia: a randomised controlled trial in term neonates.

    PubMed

    Ramani, Manimaran; Choe, Eunjoo A; Major, Meggin; Newton, Rebecca; Mwenechanya, Musaku; Travers, Colm P; Chomba, Elwyn; Ambalavanan, Namasivayam; Carlo, Waldemar A

    2018-05-01

    To test the hypothesis that kangaroo mother care (KMC) initiated either at birth or at 1 hour after birth reduces moderate or severe hypothermia in term neonates at (A) 1 hour after birth and (B) at discharge when compared with standard thermoregulation care. Term neonates born at a tertiary delivery centre in Zambia were randomised in two phases (phase 1: birth to 1 hour, phase 2: 1 hour to discharge) to either as much KMC as possible in combination with standard thermoregulation care (KMC group) or to standard thermoregulation care (control group). The primary outcomes were moderate or severe hypothermia (axillary temperature <36.0°C) at (A) 1 hour after birth and (B) at discharge. The proportion of neonates with moderate or severe hypothermia did not differ between the KMC and control groups at 1 hour after birth (25% vs 27%, relative risk (RR)=0.93, 95% CI 0.59 to 1.4, P=0.78) or at discharge (7% vs 2%, RR=2.8, 95% CI 0.6 to 13.9, P=0.16). Hypothermia was not found among the infants who had KMC for at least 9 hours or 80% of the hospital stay. KMC practised as much as possible in combination with standard thermoregulation care initiated either at birth or at 1 hour after birth did not reduce moderate or severe hypothermia in term infants compared with standard thermoregulation care. The current study also shows that duration of KMC either for at least 80% of the time or at least 9 hours during the day of birth was effective in preventing hypothermia in term infants. NCT02189759. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. The history of therapeutic hypothermia and its use in neurosurgery.

    PubMed

    Bohl, Michael A; Martirosyan, Nikolay L; Killeen, Zachary W; Belykh, Evgenii; Zabramski, Joseph M; Spetzler, Robert F; Preul, Mark C

    2018-05-25

    Despite an overwhelming history demonstrating the potential of hypothermia to rescue and preserve the brain and spinal cord after injury or disease, clinical trials from the last 50 years have failed to show a convincing benefit. This comprehensive review provides the historical context needed to consider the current status of clinical hypothermia research and a view toward the future direction for this field. For millennia, accounts of hypothermic patients surviving typically fatal circumstances have piqued the interest of physicians and prompted many of the early investigations into hypothermic physiology. In 1650, for example, a 22-year-old woman in Oxford suffered a 30-minute execution by hanging on a notably cold and wet day but was found breathing hours later when her casket was opened in a medical school dissection laboratory. News of her complete recovery inspired pioneers such as John Hunter to perform the first complete and methodical experiments on life in a hypothermic state. Hunter's work helped spark a scientific revolution in Europe that saw the overthrow of the centuries-old dogma that volitional movement was created by hydraulic nerves filling muscle bladders with cerebrospinal fluid and replaced this theory with animal electricity. Central to this paradigm shift was Giovanni Aldini, whose public attempts to reanimate the hypothermic bodies of executed criminals not only inspired tremendous scientific debate but also inspired a young Mary Shelley to write her novel Frankenstein. Dr. Temple Fay introduced hypothermia to modern medicine with his human trials on systemic and focal cooling. His work was derailed after Nazi physicians in Dachau used his results to justify their infamous experiments on prisoners of war. The latter half of the 20th century saw the introduction of hypothermic cerebrovascular arrest in neurosurgical operating rooms. The ebb and flow of neurosurgical interest in hypothermia that has since persisted reflect our continuing

  4. Superior cerebral protection with profound hypothermia during circulatory arrest.

    PubMed

    Gillinov, A M; Redmond, J M; Zehr, K J; Troncoso, J C; Arroyo, S; Lesser, R P; Lee, A W; Stuart, R S; Reitz, B A; Baumgartner, W A

    1993-06-01

    The optimal temperature for cerebral protection during hypothermic circulatory arrest is not known. This study was undertaken to test the hypothesis that deeper levels of cerebral hypothermia (< 10 degrees C) confer better protection against neurologic injury during prolonged hypothermic circulatory arrest ("colder is better"). Twelve male dogs (20 to 25 kg) were placed on closed-chest cardiopulmonary bypass via femoral artery and femoral/external jugular vein. Using surface and core cooling, tympanic membrane temperature was lowered to 18 degrees to 20 degrees C (deep hypothermia, n = 6) or 5 degrees to 7 degrees C (profound hypothermia, n = 6). After 2 hours of hypothermic circulatory arrest, animals were rewarmed to 35 degrees to 37 degrees C on cardiopulmonary bypass. All were mechanically ventilated and monitored in an intensive care unit setting for 20 hours. Neurologic assessment was performed every 12 hours using a species-specific behavior scale that yielded a neurodeficit score ranging from 0% to 100%, where 0 = normal and 100% = brain dead. After 72 hours, animals were sacrificed and examined histologically for neurologic injury. Histologic injury scores were assigned to each animal (range, 0 [normal] to 100 [severe injury]). At the end of the observation period, profoundly hypothermic animals had better neurologic function (neurodeficit score, 5.7% +/- 4.0%) compared with deeply hypothermic animals (neurodeficit score, 41% +/- 9.3%; p < 0.006). Every animal had histologic evidence of neurologic injury, but profoundly hypothermic animals had significantly less injury (histologic injury score, 19.2 +/- 1.2 versus 48.3 +/- 1.5; p < 0.0001).

  5. Management of hypothermia: impact of lecture-based interactive workshops on training of pediatric nurses.

    PubMed

    Altun, Insaf; Karakoç, Ali

    2012-05-01

    This study aimed to determine the efficacy of interactive workshop on the management of hypothermia and its impact on pediatric nurses' training. This is a pretest-to-posttest quasi-experimental descriptive study. Thirty pediatric nurses attended an interactive lecture-based interactive workshop on the management of hypothermia. Participants had to accept an invitation to the presentation before the training event. They completed the lecture, and a multiple-choice question test before and after the lecture was given. There was a significant improvement in mean test scores after the lecture when compared with those before the lecture (mean [SD], 15.5 [1.3] vs 5.0 [1.7], P < 0.001). The information gained in this study will be valuable as a baseline for further research and help guide improvements in the management of hypothermia with the ultimate goal of enhancing safe and quality patient care.

  6. Biothermal Model of Patient for Brain Hypothermia Treatment

    NASA Astrophysics Data System (ADS)

    Wakamatsu, Hidetoshi; Gaohua, Lu

    A biothermal model of patient is proposed and verified for the brain hypothermia treatment, since the conventionally applied biothermal models are inappropriate for their unprecedented application. The model is constructed on the basis of the clinical practice of the pertinent therapy and characterized by the mathematical relation with variable ambient temperatures, in consideration of the clinical treatments such as the vital cardiopulmonary regulation. It has geometrically clear representation of multi-segmental core-shell structure, database of physiological and physical parameters with a systemic state equation setting the initial temperature of each compartment. Its step response gives the time constant about 3 hours in agreement with clinical knowledge. As for the essential property of the model, the dynamic temperature of its face-core compartment is realized, which corresponds to the tympanic membrane temperature measured under the practical anesthesia. From the various simulations consistent with the phenomena of clinical practice, it is concluded that the proposed model is appropriate for the theoretical analysis and clinical application to the brain hypothermia treatment.

  7. Impact of hypothermia on implementation of CPAP for neonatal respiratory distress syndrome in a low-resource setting

    PubMed Central

    Kawaza, Kondwani; Quinn, MK; Miao, Yinsen; Guerra, Rudy; Molyneux, Elizabeth; Oden, Maria; Richards-Kortum, Rebecca

    2018-01-01

    Background Neonatal hypothermia is widely associated with increased risks of morbidity and mortality, but remains a pervasive global problem. No studies have examined the impact of hypothermia on outcomes for preterm infants treated with CPAP for respiratory distress syndrome (RDS). Methods This retrospective analysis assessed the impact of hypothermia on outcomes of 65 neonates diagnosed with RDS and treated with either nasal oxygen (N = 17) or CPAP (N = 48) in a low-resource setting. A classification tree approach was used to develop a model predicting survival for subjects diagnosed with RDS. Findings Survival to discharge was accurately predicted based on three variables: mean temperature, treatment modality, and mean respiratory rate. None of the 23 neonates with a mean temperature during treatment below 35.8°C survived to discharge, regardless of treatment modality. Among neonates with a mean temperature exceeding 35.8°C, the survival rate was 100% for the 31 neonates treated with CPAP and 36.4% for the 11 neonates treated with nasal oxygen (p<0.001). For neonates treated with CPAP, outcomes were poor if more than 50% of measured temperatures indicated hypothermia (5.6% survival). In contrast, all 30 neonates treated with CPAP and with more than 50% of temperature measurements above 35.8°C survived to discharge, regardless of initial temperature. Conclusion The results of our study suggest that successful implementation of CPAP to treat RDS in low-resource settings will require aggressive action to prevent persistent hypothermia. However, our results show that even babies who are initially cold can do well on CPAP with proper management of hypothermia. PMID:29543861

  8. White matter apoptosis is increased by delayed hypothermia and rewarming in a neonatal piglet model of hypoxic ischemic encephalopathy.

    PubMed

    Wang, B; Armstrong, J S; Reyes, M; Kulikowicz, E; Lee, J-H; Spicer, D; Bhalala, U; Yang, Z-J; Koehler, R C; Martin, L J; Lee, J K

    2016-03-01

    Therapeutic hypothermia is widely used to treat neonatal hypoxic ischemic (HI) brain injuries. However, potentially deleterious effects of delaying the induction of hypothermia and of rewarming on white matter injury remain unclear. We used a piglet model of HI to assess the effects of delayed hypothermia and rewarming on white matter apoptosis. Piglets underwent HI injury or sham surgery followed by normothermic or hypothermic recovery at 2h. Hypothermic groups were divided into those with no rewarming, slow rewarming at 0.5°C/h, or rapid rewarming at 4°C/h. Apoptotic cells in the subcortical white matter of the motor gyrus, corpus callosum, lateral olfactory tract, and internal capsule at 29h were identified morphologically and counted by hematoxylin & eosin staining. Cell death was verified by terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay. White matter neurons were also counted, and apoptotic cells were immunophenotyped with the oligodendrocyte marker 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase). Hypothermia, slow rewarming, and rapid rewarming increased apoptosis in the subcortical white matter relative to normothermia (p<0.05). The number of white matter neurons was not lower in groups with more apoptosis after hypothermia or rapid rewarming, indicating that the apoptosis occurred among glial cells. Hypothermic piglets had more apoptosis in the lateral olfactory tract than those that were rewarmed (p<0.05). The promotion of apoptosis by hypothermia and rewarming in these regions was independent of HI. In the corpus callosum, HI piglets had more apoptosis than shams after normothermia, slow rewarming, and rapid rewarming (p<0.05). Many apoptotic cells were myelinating oligodendrocytes identified by CNPase positivity. Our results indicate that delaying the induction of hypothermia and rewarming are associated with white matter apoptosis in a piglet model of HI; in some regions these temperature effects are

  9. Efficacy outcome selection in the therapeutic hypothermia after pediatric cardiac arrest trials.

    PubMed

    Holubkov, Richard; Clark, Amy E; Moler, Frank W; Slomine, Beth S; Christensen, James R; Silverstein, Faye S; Meert, Kathleen L; Pollack, Murray M; Dean, J Michael

    2015-01-01

    The Therapeutic Hypothermia After Pediatric Cardiac Arrest trials will determine whether therapeutic hypothermia improves survival with good neurobehavioral outcome, as assessed by the Vineland Adaptive Behavior Scales Second Edition, in children resuscitated after cardiac arrest in the in-hospital and out-of-hospital settings. We describe the innovative efficacy outcome selection process during Therapeutic Hypothermia After Pediatric Cardiac Arrest protocol development. Consensus assessment of potential outcomes and evaluation timepoints. None. We evaluated practical and technical advantages of several follow-up timepoints and continuous/categorical outcome variants. Simulations estimated power assuming varying hypothermia benefit on mortality and on neurobehavioral function among survivors. Twelve months after arrest was selected as the optimal assessment timepoint for pragmatic and clinical reasons. Change in Vineland Adaptive Behavior Scales Second Edition from prearrest level, measured as quasicontinuous with death and vegetative status being worst-possible levels, yielded optimal statistical power. However, clinicians preferred simpler multicategorical or binary outcomes because of easier interpretability and favored outcomes based solely on postarrest status because of concerns about accurate parental assessment of prearrest status and differing clinical impact of a given Vineland Adaptive Behavior Scales Second Edition change depending on prearrest status. Simulations found only modest power loss from categorizing or dichotomizing quasicontinuous outcomes because of high expected mortality. The primary outcome selected was survival with 12-month Vineland Adaptive Behavior Scales Second Edition no less than two SD below a reference population mean (70 points), necessarily evaluated only among children with prearrest Vineland Adaptive Behavior Scales Second Edition greater than or equal to 70. Two secondary efficacy outcomes, 12-month survival and

  10. The pathophysiological mechanisms of the onset of death through accidental hypothermia and the presentation of "The little match girl" case.

    PubMed

    Jeican, Ionuţ Isaia

    2014-01-01

    Hypothermia and death caused by hypothermia may be found in a number of fiction works, mainly in novels. In the well-known story "The Little Match Girl" by Hans Christian Andersen, one can notice that the descriptions of the phenomena occurring before the girl's death are in fact a literary presentation of the pathophysiological mechanisms of the onset of death through accidental hypothermia. This essay presents the medical aspects of the story written by Andersen.

  11. Human touch vs. axillary digital thermometry for detection of neonatal hypothermia at community level.

    PubMed

    Agarwal, Siddharth; Sethi, Vani; Pandey, Ravindra Mohan; Kondal, Dimple

    2008-06-01

    We examined the diagnostic accuracy of human touch (HT) method in assessing hypothermia against axillary digital thermometry (ADT) by a trained non-medical field investigator (who supervised activities of community health volunteers) in seven villages of Agra district, Uttar Pradesh, India. Body temperature of 148 newborns born between March and August 2005 was measured at four points in time for each enrolled newborn (within 48 h and on days 7, 30 and 60) by the field investigator under the axilla using a digital thermometer and by HT method using standard methodology. Total observations were 533. Hypothermia assessed by HT was in agreement with that assessed by ADT (<36.5 degrees C) in 498 observations. Hypothermia assessed by HT showed a high diagnostic accuracy when compared against ADT (kappa 0.65-0.81; sensitivity 74%; specificity 96.7%; positive predictive value 22; negative predictive value 0.26). HT is a simple, quick, inexpensive and programmatically important method. However, being a subjective assessment, its reliability depends on the investigator being adequately trained and competent in making consistently accurate assessments. There is also a need to assess whether with training and supervision even the less literate mothers, traditional birth attendants and community health volunteers can accurately assess mild and moderate hypothermia before promoting HT for early identification of neonatal risk in community-based programs.

  12. Field Management of Accidental Hypothermia during Diving

    DTIC Science & Technology

    1990-01-01

    diving operations. 4 3. Diving after tending for prolonged periods leading to hypothermia before diving. 4. Dry suit undergarments that are wet due to...dives, reducing insulation of the undergarment, and then remaining at rest for prolonged decompressiofi stops. 6. Inadequate thermal insulation: wet ...suit instead of dry suit, undergarment selection too thin, too compressible or of poor insulation when wet (63-64), inadequate thermal insulation of the

  13. Benefits of starting hypothermia treatment within 6 h vs. 6-12 h in newborns with moderate neonatal hypoxic-ischemic encephalopathy.

    PubMed

    Jia, Wen; Lei, Xiaoping; Dong, Wenbin; Li, Qingping

    2018-02-12

    It has been suggested that mild hypothermia treatment of hypoxia-ischemic encephalopathy (HIE) should start within 6 h after HIE, but many children are admitted to the hospital > 6 h, particularly in developing areas. We aimed to determine whether hypothermia treatment could remain effective within 12 h after birth. According to their admission, 152 newborns were enrolled in the < 6 h and 6-12 h after HIE groups. All newborns received conventional treatment combined with mild head hypothermia therapy, according to our routine clinical practice. Some newborns only received conventional treatment (lacking informed consent). All newborns received amplitude-integrated electroencephalography (aEEG) monitoring for 4 h and neuron-specific enolase (NSE) measurement before and after 3 days of therapy. Compared to the conventional treatment, hypothermia significantly improved the aEEG scores and NSE values in all newborns of the < 6-h group. In the 6-12-h group, the aEEG scores (F = 5.67, P < 0.05) and NSE values (F = 4.98, P < 0.05) were only improved in newborns with moderate HIE. Hypothermia treatment seems to have no effect in newborns with severe HIE after 6 h (P > 0.05). Hypothermia improved the rates of neonatal death and 18-month disability (all P < 0.01). In newborns with moderate HIE, starting hypothermia therapy < 6 h and 6-12 h after HIE showed curative effects. In those with severe HIE, only starting hypothermia therapy within 6 h showed curative effects.

  14. Spontaneous hypothermia ameliorated inflammation and neurologic deficit in rat cardiac arrest models following resuscitation

    PubMed Central

    Zhou, Minggen; Wang, Peng; Yang, Zhengfei; Wu, Haidong; Huang, Zitong

    2018-01-01

    Cardiac arrest (CA) is a leading cause of mortality worldwide. The majority of the associated mortalities are caused by post-CA syndrome, which includes symptoms, such as neurologic damage, myocardial dysfunction and systemic inflammation. Following CA, return of spontaneous circulation (ROSC) leads to a brain reperfusion injury, which subsequently causes adverse neurologic outcomes or mortality. Therefore, investigating the underlying mechanisms of ROSC-induced neurologic deficits and establishing potential treatments is critical to prevent and treat post-CA syndrome. In the current study, CA rat models were established by asphyxia. Following ROSC, the temperature was controlled to achieve hypothermia. The general neurologic status was assessed using the neurologic deficit scale. Changes in the concentrations of interleukin (IL)-18 and IL-1β were measured with ELISA and the dynamic change in NACHT, LRR and PYD domains-containing protein 3 inflammasome components was determined by western blot analysis and immunohistochemistry. Neuronal death and apoptosis were measured via TUNEL assays. In the CA rat models, increasing the duration of CA before cardiopulmonary resuscitation was found to aggravate the neural deficit and increase the incidence of inflammation. Following ROSC, the expression level of the inflammasome components was observed to increase in CA rat models, which was accompanied by increased secretion of IL-18 and IL-1β, indicating the promotion of inflammation. In addition, the study identified the beneficial role of spontaneous hypothermia in ameliorating the ROSC-induced inflammation and neurologic deficit in CA rat models, including the downregulation of inflammasome components and attenuating neuronal apoptosis. The present study contributes to the understanding of underlying mechanisms in CA-evoked inflammation and the subsequent neurologic damage following ROSC. A novel potential therapeutic strategy that may increase survival times and the

  15. The effect of ephedrine on intraoperative hypothermia

    PubMed Central

    Jo, Youn Yi; Kim, Ji Young; Kim, Joon-Sik; Kwon, Youngjun

    2011-01-01

    Background Prevention of intraoperative hypothermia has become a standard of operative care. Since ephedrine has a thermogenic effect and it is frequently used to treat hypotension during anesthesia, this study was designed to determine the effect of ephedrine on intraoperative hypothermia of patients who are undergoing spine surgery. Methods Twenty-four patients were randomly divided to receive an ephedrine (the ephedrine group, n = 12) or normal saline (the control group, n = 12) infusion for 2 h. The esophageal temperature (the core temperature), the index finger temperature (the peripheral temperature) and the hemodynamic variables such as the mean blood pressure and heart rate were measured every 15 minutes after the intubation. Results At the end of the study period, the esophageal temperature and hemodynamic variables were significantly decreased in the control group, whereas those in the ephedrine group were stably maintained. The index finger temperature was significantly lower in the ephedrine group compared to that in the control group, suggesting the prevention of core-to-peripheral redistribution of the heat as the cause of temperature maintenance. Conclusions An intraoperative infusion of ephedrine minimized the decrease of the core temperature and it stably maintained the hemodynamic variables during spine surgery with the patient under general anesthesia. PMID:21602974

  16. [Effects of craniocerebral hypothermia on the course of climacteric syndrome].

    PubMed

    Grishenko, V I; Sherbina, N A; Lipko, O P

    1992-01-01

    Craniocerebral hypothermia was used in the treatment of 43 women aged 48 to 55, suffering from the climacteric syndrome of varying severity. The treatment efficacy was confirmed by EEG data and changes in blood levels of ACTH, LH, prolactin, and hydrocortisone.

  17. Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

    PubMed

    Moler, Frank W; Silverstein, Faye S; Holubkov, Richard; Slomine, Beth S; Christensen, James R; Nadkarni, Vinay M; Meert, Kathleen L; Browning, Brittan; Pemberton, Victoria L; Page, Kent; Gildea, Marianne R; Scholefield, Barnaby R; Shankaran, Seetha; Hutchison, Jamie S; Berger, John T; Ofori-Amanfo, George; Newth, Christopher J L; Topjian, Alexis; Bennett, Kimberly S; Koch, Joshua D; Pham, Nga; Chanani, Nikhil K; Pineda, Jose A; Harrison, Rick; Dalton, Heidi J; Alten, Jeffrey; Schleien, Charles L; Goodman, Denise M; Zimmerman, Jerry J; Bhalala, Utpal S; Schwarz, Adam J; Porter, Melissa B; Shah, Samir; Fink, Ericka L; McQuillen, Patrick; Wu, Theodore; Skellett, Sophie; Thomas, Neal J; Nowak, Jeffrey E; Baines, Paul B; Pappachan, John; Mathur, Mudit; Lloyd, Eric; van der Jagt, Elise W; Dobyns, Emily L; Meyer, Michael T; Sanders, Ronald C; Clark, Amy E; Dean, J Michael

    2017-01-26

    Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse

  18. Incidence of Inadvertent Intraoperative Hypothermia and Its Risk Factors in Patients Undergoing General Anesthesia in Beijing: A Prospective Regional Survey

    PubMed Central

    Deng, Xiaoming; Fan, Ting; Fu, Runqiao; Geng, Wanming; Guo, Ruihong; He, Nong; Li, Chenghui; Li, Lei; Li, Min; Li, Tianzuo; Tian, Ming; Wang, Geng; Wang, Lei; Wang, Tianlong; Wu, Anshi; Wu, Di; Xue, Xiaodong; Xu, Mingjun; Yang, Xiaoming; Yang, Zhanmin; Yuan, Jianhu; Zhao, Qiuhua; Zhou, Guoqing; Zuo, Mingzhang; Pan, Shuang; Zhan, Lujing; Yao, Min; Huang, Yuguang

    2015-01-01

    Background/Objective Inadvertent intraoperative hypothermia (core temperature <360 C) is a recognized risk in surgery and has adverse consequences. However, no data about this complication in China are available. Our study aimed to determine the incidence of inadvertent intraoperative hypothermia and its associated risk factors in a sample of Chinese patients. Methods We conducted a regional cross-sectional survey in Beijing from August through December, 2013. Eight hundred thirty patients who underwent various operations under general anesthesia were randomly selected from 24 hospitals through a multistage probability sampling. Multivariate logistic regression analyses were applied to explore the risk factors of developing hypothermia. Results The overall incidence of intraoperative hypothermia was high, 39.9%. All patients were warmed passively with surgical sheets or cotton blankets, whereas only 10.7% of patients received active warming with space heaters or electric blankets. Pre-warmed intravenous fluid were administered to 16.9% of patients, and 34.6% of patients had irrigation of wounds with pre-warmed fluid. Active warming (OR = 0.46, 95% CI 0.26–0.81), overweight or obesity (OR = 0.39, 95% CI 0.28–0.56), high baseline core temperature before anesthesia (OR = 0.08, 95% CI 0.04–0.13), and high ambient temperature (OR = 0.89, 95% CI 0.79–0.98) were significant protective factors for hypothermia. In contrast, major-plus operations (OR = 2.00, 95% CI 1.32–3.04), duration of anesthesia (1–2 h) (OR = 3.23, 95% CI 2.19–4.78) and >2 h (OR = 3.44, 95% CI 1.90–6.22,), and intravenous un-warmed fluid (OR = 2.45, 95% CI 1.45–4.12) significantly increased the risk of hypothermia. Conclusions The incidence of inadvertent intraoperative hypothermia in Beijing is high, and the rate of active warming of patients during operation is low. Concern for the development of intraoperative hypothermia should be especially high in patients undergoing major

  19. Passive hypothermia (≥35 - <36°C) during transport of newborns with hypoxic-ischaemic encephalopathy.

    PubMed

    Sellam, Aurélie; Lode, Noëlla; Ayachi, Azzedine; Jourdain, Gilles; Dauger, Stéphane; Jones, Peter

    2017-01-01

    Hypothermia initiated in the first six hours of life in term infants with hypoxic ischemic encephalopathy reduces the risk of death and severe neurological sequelae. Our study's principal objective was to evaluate transport predictors potentially influencing arrival in NICU (Neonatal Intensive Care Unit) at a temperature ≥35-<36°C. A multi-centric, prospective cohort study was conducted during 18 months by the three Neonatal Transport Teams and 13 NICUs. Newborns were selected for inclusion according to biological and clinical criteria before transport using passive hypothermia using a target temperature of ≥35-<36°C. Data on 120 of 126 inclusions were available for analysis. Thirty-three percent of the children arrived in NICU with the target temperature of ≥35-<36°C. The mean temperature for the whole group of infants on arrival in NICU was 35.4°C (34.3-36.5). The median age of all infants on arrival in NICU was 3h03min [2h25min-3h56min]. Three infants arrived in NICU with a temperature of <33°C and eleven with a temperature ≥37°C. Adrenaline during resuscitation was associated with a lower mean temperature on arrival in NICU. Our strategy using ≥35-<36°C passive hypothermia combined with short transport times had little effect on temperature after the arrival of Neonatal Transport Team although did reduce numbers of infants arriving in NICU in deep hypothermia. For those infants where hypothermia was discontinued in NICU our strategy facilitated re-warming. Re-adjustment to a lower target temperature to ≥34.5-<35.5°C may reduce the proportion of infants with high/normothermic temperatures.

  20. Does Whole-Body Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy Affect Surfactant Disaturated-Phosphatidylcholine Kinetics?

    PubMed

    Nespeca, Matteo; Giorgetti, Chiara; Nobile, Stefano; Ferrini, Ilaria; Simonato, Manuela; Verlato, Giovanna; Cogo, Paola; Carnielli, Virgilio Paolo

    2016-01-01

    It is unknown whether Whole-Body Hypothermia (WBH) affects pulmonary function. In vitro studies, at relatively low temperatures, suggest that hypothermia may induce significant changes to the surfactant composition. The effect of WBH on surfactant kinetics in newborn infants is unknown. We studied in vivo kinetics of disaturated-phosphatidylcholine (DSPC) in asphyxiated newborns during WBH and in normothermic controls (NTC) with no or mild asphyxia. Both groups presented no clinically apparent lung disease. Twenty-seven term or near term newborns requiring mechanical ventilation were studied (GA 38.6±2.2 wks). Fifteen during WBH and twelve NTC. All infants received an intra-tracheal dose of 13C labelled DSPC and tracheal aspirate were performed. DSPC amount, DSPC half-life (HL) and pool size (PS) were calculated. DSPC amount in tracheal aspirates was 0.42 [0.22-0.54] and 0.36 [0.10-0.58] mg/ml in WBH and NTC respectively (p = 0.578). DSPC HL was 24.9 [15.7-52.5] and 25.3 [15.8-59.3] h (p = 0.733) and DSPC PS was 53.2 [29.4-91.6] and 40.2 [29.8-64.6] mg/kg (p = 0.598) in WBH and NTC respectively. WBH does not alter DSPC HL and PS in newborn infants with no clinical apparent lung disease.

  1. Hypothermia in a combined intoxication with doxepin and moclobemide in an adolescent.

    PubMed

    Armbrust, Sven; Nikischin, Werner; Rochholz, Gertrud; Franzelius, Cornelia; Bielstein, Andreas; Kramer, Hans-Heiner

    2010-02-25

    Intoxication with antidepressants, frequently encountered in pediatric emergency medicine, can often lead to life threatening situations. While hyperthermia, hypertonicity and rigidity are symptoms indicative of a serotonin syndrome triggered by an intoxication with serotonin reuptake inhibitors or monoamine oxidase inhibitors, cardiotoxicity, coma and ECG changes are typical of an intoxication with tricyclic antidepressants. Hypothermia (instead of the expected hyperthermia) is described for the first time as a persistent symptom during the course of a combined moclobemide-doxepin intoxication in an attempted suicide of a 16-year-old adolescent. The administration of serotonin reuptake inhibitors alone or in combination with other medication which increases the level of 5-hydroxytryptamine, i.e. serotonin, in the synaptic cleft mainly leads to hyperthermia. According to a recent study, however, the application of a selective 5-HT(1a) agonist to transgenic mice with a prominent overexpression of the 5-HT(1a) receptor lead to immobility and hypothermia. These findings might help to explain the hypothermia observed in the case of the intoxicated 16-year-old. Intoxication with antidepressants should not be excluded a priori in a hypothermic patient who displays other clinical signs of the said intoxication. 2009. Published by Elsevier Ireland Ltd.

  2. A tale of two climbers: hypothermia, death, and survival on Mount Everest.

    PubMed

    Moore, G W Kent; Semple, John L

    2012-03-01

    Hypothermia is an acknowledged risk for those who venture into high altitude regions. There is however little quantitative information on this risk that can be used to implement mitigation strategies. Here we provide an analysis of the meteorological and hypothermic risk parameters, wind chill temperature, and facial frostbite time, during the spring 2006 Mount Everest climbing season. This season was marked by two high profile events where a solo climber was forced to spend the night in highly exposed conditions near the summit. One climber survived, while the other did not. Although this retrospective examination of two individual cases has admittedly a small sample size, and there are other factors that undoubtedly contributed to the difference in outcomes, we show that wind chill temperature and facial frostbite time experienced by the two climbers were dramatically different. In particular, the climber who did not survive experienced conditions that were approximately one standard deviation more severe that usual for that time of the year; while the climber who survived experienced conditions that were approximately one standard deviation less severe then usual. This suggests that the environmental conditions associated with hypothermia played an important role in the outcomes. This report confirms the importance of providing quantitative guidance to climbers as the risk of hypothermia on high mountains.

  3. Quantitative measurement of cerebral blood flow during hypothermia with a time-resolved near-infrared technique

    NASA Astrophysics Data System (ADS)

    Fazel Bakhsheshi, Mohammad; Diop, Mamadou; St Lawrence, Keith; Lee, Ting-Yim

    2012-02-01

    Hypothermia, in which the brain is cooled to 32-33 °C, has been shown to be neuroprotective for brain injury caused by hypoxia-ischemia, head trauma, or neonatal asphyxia. Neuroprotective effect of Hypothermia is partly due to suppression of brain metabolism and cerebral blood flow (CBF). The ability to measure CBF at the bedside provides a means of detecting, and thereby preventing, secondary ischemia during neuro intensive care before brain injury occurs. The purpose of the present study is to investigate the ability of a time-resolved near-infrared (TR-NIR) bolus-tracking method using indocyanine green as an intravascular flow tracer to measure CBF during cooling in a newborn animal model. For validation, CBF was independently measured by computed tomography (CT) perfusion. The results show a good agreement between CBF obtained with the two methods (R2 ~ 0.84, Δ ~ 5.84 ml. min -1.100 g -1, 32-38.5 °C), demonstrating the ability of the TR-NIR technique to non-invasively measure absolute CBF in-vivo during dynamic hypothermia. The TR-NIR technique reveals that CBF decreases from 54.3 +/- 5.4 ml. min -1.100 g -1, at normothermia (Tbrain of 38.5 °C), to 33.8 +/- 0.9 ml. min -1.100 g -1 at Tbrain of 32 °C during the hypothermia treatment.

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

    PubMed

    Slack, Donald F; Corwin, Douglas S; Shah, Nirav G; Shanholtz, Carl B; Verceles, Avelino C; Netzer, Giora; Jones, Kevin M; Brown, Clayton H; Terrin, Michael L; Hasday, Jeffrey D

    2017-07-01

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

  5. The pathophysiological mechanisms of the onset of death through accidental hypothermia and the presentation of “The little match girl” case

    PubMed Central

    JEICAN, IONUŢ ISAIA

    2014-01-01

    Hypothermia and death caused by hypothermia may be found in a number of fiction works, mainly in novels. In the well-known story “The Little Match Girl” by Hans Christian Andersen, one can notice that the descriptions of the phenomena occurring before the girl’s death are in fact a literary presentation of the pathophysiological mechanisms of the onset of death through accidental hypothermia. This essay presents the medical aspects of the story written by Andersen. PMID:26527999

  6. A retrospective analysis on the relationship between intraoperative hypothermia and postoperative ileus after laparoscopic colorectal surgery.

    PubMed

    Choi, Ji-Won; Kim, Duk-Kyung; Kim, Jin-Kyoung; Lee, Eun-Jee; Kim, Jea-Youn

    2018-01-01

    Postoperative ileus (POI) is an important factor prolonging the length of hospital stay following colorectal surgery. We retrospectively explored whether there is a clinically relevant association between intraoperative hypothermia and POI in patients who underwent laparoscopic colorectal surgery for malignancy within the setting of an enhanced recovery after surgery (ERAS) program between April 2016 and January 2017 at our institution. In total, 637 patients were analyzed, of whom 122 (19.2%) developed clinically and radiologically diagnosed POI. Overall, 530 (83.2%) patients experienced intraoperative hypothermia. Although the mean lowest core temperature was lower in patients with POI than those without POI (35.3 ± 0.5°C vs. 35.5 ± 0.5°C, P = 0.004), the independence of intraoperative hypothermia was not confirmed based on multivariate logistic regression analysis. In addition to three variables (high age-adjusted Charlson comorbidity index score, long duration of surgery, high maximum pain score during the first 3 days postoperatively), cumulative dose of rescue opioids used during the first 3 days postoperatively was identified as an independent risk factor of POI (odds ratio = 1.027 for each 1-morphine equivalent [mg] increase, 95% confidence interval = 1.014-1.040, P <0.001). Patients with hypothermia showed significant delays in both progression to a soft diet and discharge from hospital. In conclusion, intraoperative hypothermia was not independently associated with POI within an ERAS pathway, in which items other than thermal measures might offset its negative impact on POI. However, as it was associated with delayed discharge from the hospital, intraoperative maintenance of normothermia is still needed.

  7. A retrospective analysis on the relationship between intraoperative hypothermia and postoperative ileus after laparoscopic colorectal surgery

    PubMed Central

    Kim, Jin-Kyoung; Lee, Eun-Jee; Kim, Jea-Youn

    2018-01-01

    Postoperative ileus (POI) is an important factor prolonging the length of hospital stay following colorectal surgery. We retrospectively explored whether there is a clinically relevant association between intraoperative hypothermia and POI in patients who underwent laparoscopic colorectal surgery for malignancy within the setting of an enhanced recovery after surgery (ERAS) program between April 2016 and January 2017 at our institution. In total, 637 patients were analyzed, of whom 122 (19.2%) developed clinically and radiologically diagnosed POI. Overall, 530 (83.2%) patients experienced intraoperative hypothermia. Although the mean lowest core temperature was lower in patients with POI than those without POI (35.3 ± 0.5°C vs. 35.5 ± 0.5°C, P = 0.004), the independence of intraoperative hypothermia was not confirmed based on multivariate logistic regression analysis. In addition to three variables (high age-adjusted Charlson comorbidity index score, long duration of surgery, high maximum pain score during the first 3 days postoperatively), cumulative dose of rescue opioids used during the first 3 days postoperatively was identified as an independent risk factor of POI (odds ratio = 1.027 for each 1-morphine equivalent [mg] increase, 95% confidence interval = 1.014–1.040, P <0.001). Patients with hypothermia showed significant delays in both progression to a soft diet and discharge from hospital. In conclusion, intraoperative hypothermia was not independently associated with POI within an ERAS pathway, in which items other than thermal measures might offset its negative impact on POI. However, as it was associated with delayed discharge from the hospital, intraoperative maintenance of normothermia is still needed. PMID:29309435

  8. Behavioral hypothermia of a domesticated lizard under treatment of the hypometabolic agent 3-iodothyronamine.

    PubMed

    Ha, Kyoungbong; Shin, Haksup; Ju, Hyunwoo; Chung, Chan-Moon; Choi, Inho

    2017-05-03

    Ectothermic animals rely on behavioral thermoregulation due to low capacity of heat production and storage. Previously, lizards were shown to achieve 'fever' during microbial infection by increasing their preferred body temperature (PBT) behaviorally, thereby attaining a relatively high survival rate. The purpose of this study was to investigate whether domesticated lizards pursued 'behavioral hypothermia' induced by a hypometabolic agent 3-iodothyronamine (T1AM). We found that treatment with 8.0 mg/kg T1AM caused a lizard species, the leopard gecko (Eublepharis macularius), to decrease its ventilation and oxygen consumption rates 0.64- and 0.76-fold, respectively, compared to those of the control (P<0.05). The lizards, habituated at an ambient temperature of 30 ± 0.5°C, also showed a significant decrease in the PBT range over a freely accessible thermal gradient between 5°C and 45°C. The upper limit of the PBT in the treated lizards lowered from 31.9°C to 30.6°C, and the lower limit from 29.5°C to 26.3°C (P<0.001). These findings demonstrate that the treated lizards pursued behavioral hypothermia in conjunction with hypoventilation and hypometabolism. Because prior studies reported a similar hypometabolic response in T1AM-injected laboratory mice, the domesticated lizards, as a part of the vertebrate phylogeny, may be a useful laboratory model for biological and pharmacological researches such as drug potency test.

  9. Comparison of two passive warming devices for prevention of perioperative hypothermia in dogs.

    PubMed

    Potter, J; Murrell, J; MacFarlane, P

    2015-09-01

    To compare effects of two passive warming methods combined with a resistive heating mat on perioperative hypothermia in dogs. Fifty-two dogs were enrolled and randomly allocated to receive a reflective blanket (Blizzard Blanket) or a fabric blanket (VetBed). In addition, in the operating room all dogs were placed onto a table with a resistive heating mat covered with a fabric blanket. Rectal temperature measurements were taken at defined points. Statistical analysis was performed comparing all Blizzard Blanket-treated to all VetBed-treated dogs, and VetBed versus Blizzard Blanket dogs within spay and castrate groups, spay versus castrate groups and within groups less than 10 kg or more than 10 kg bodyweight. Data from 39 dogs were used for analysis. All dogs showed a reduction in perioperative rectal temperature. There were no detected statistical differences between treatments or between the different groups. This study supports previous data on prevalence of hypothermia during surgery. The combination of active and passive warming methods used in this study prevented the development of severe hypothermia, but there were no differences between treatment groups. © 2015 British Small Animal Veterinary Association.

  10. Salvage techniques in traumatic cardiac arrest: thoracotomy, extracorporeal life support, and therapeutic hypothermia.

    PubMed

    Tisherman, Samuel A

    2013-12-01

    Survival from traumatic cardiac arrest is associated with a very high mortality despite aggressive resuscitation including an Emergency Department thoracotomy (EDT). Novel salvage techniques are needed to improve these outcomes. More aggressive out-of-hospital interventions, such as chest decompression or thoracotomy by emergency physicians or anesthesiologists, seem feasible and show some promise for improving outcomes. For trauma patients who suffer severe respiratory failure or refractory cardiac arrest, there seems to be an increasing role for the use of extracorporeal life support (ECLS), utilizing heparin-bonded systems to avoid systemic anticoagulation. The development of exposure hypothermia is associated with poor outcomes in trauma patients, but preclinical studies have consistently demonstrated that mild, therapeutic hypothermia (34 °C) improves survival from severe hemorrhagic shock. Sufficient data exist to justify a clinical trial. For patients who suffer a cardiac arrest refractory to EDT, induction of emergency preservation and resuscitation by rapid cooling to a tympanic membrane temperature of 10 °C may preserve vital organs long enough to allow surgical hemostasis, followed by resuscitation with cardiopulmonary bypass. Salvage techniques, such as earlier thoracotomy, ECLS, and hypothermia, may allow survival from otherwise lethal injuries.

  11. Protein ubiquitination in postsynaptic densities after hypoxia in rat neostriatum is blocked by hypothermia.

    PubMed

    Capani, Francisco; Saraceno, Gustavo Ezequiel; Botti, Valeria; Aon-Bertolino, Laura; de Oliveira, Diêgo Madureira; Barreto, George; Galeano, Pablo; Giraldez-Alvarez, Lisandro Diego; Coirini, Héctor

    2009-10-01

    Synaptic dysfunction has been associated with neuronal cell death following hypoxia. The lack of knowledge on the mechanisms underlying this dysfunction prompted us to investigate the morphological changes in the postsynaptic densities (PSDs) induced by hypoxia. The results presented here demonstrate that PSDs of the rat neostriatum are highly modified and ubiquitinated 6 months after induction of hypoxia in a model of perinatal asphyxia. Using both two dimensional (2D) and three dimensional (3D) electron microscopic analyses of synapses stained with ethanolic phosphotungstic acid (E-PTA), we observed an increment of PSD thickness dependent on the duration and severity of the hypoxic insult. The PSDs showed clear signs of damage and intense staining for ubiquitin. These morphological and molecular changes were effectively blocked by hypothermia treatment, one of the most effective strategies for hypoxia-induced brain injury available today. Our data suggest that synaptic dysfunction following hypoxia may be caused by long-term misfolding and aggregation of proteins in the PSD.

  12. Predict the neurological recovery under hypothermia after cardiac arrest using C0 complexity measure of EEG signals.

    PubMed

    Lu, Yueli; Jiang, Dineng; Jia, Xiaofeng; Qiu, Yihong; Zhu, Yisheng; Thakor, Nitish; Tong, Shanbao

    2008-01-01

    Clinical trials have proven the efficacy of therapeutic hypothermia in improving the functional outcome after cardiac arrest (CA) compared with the normothermic controls. Experimental researches also demonstrated quantitative electroencephalogram (qEEG) analysis was associated with the long-term outcome of the therapeutic hypothermia in brain injury. Nevertheless, qEEG has not been able to provide a prediction earlier than 6h after the return of spontaneous circulation (ROSC). In this study, we use C0 complexity to analyze the nonlinear characteristic of EEG, which could predict the neurological recovery under therapeutic hypothermia during the early phase after asphyxial cardiac arrest in rats. Twelve Wistar rats were randomly assigned to 9-min asphyxia injury under hypothermia (33 degrees C, n=6) or normothermia (37 degrees C, n=6). Significantly greater C0 complexity was found in hypothermic group than that in normothermic group as early as 4h after the ROSC (P0.05). C0 complexity at 4h correlated well with the 72h neurodeficit score (NDS) (Pearson's correlation = 0.882). The results showed that the C0 complexity could be an early predictor of the long-term neurological recovery from cardiac arrest.

  13. Therapeutic effect of hypothermia and dizocilpine maleate on traumatic brain injury in neonatal rats.

    PubMed

    Celik, Suat Erol; Oztürk, Hülya; Tolunay, Sahsine

    2006-09-01

    This study was undertaken to evaluate the therapeutic effect of hypothermia and dizocilpine maleate in traumatic brain injury (TBI) on newborn rats. After induction of TBI, physiologic and histopathological assessments were performed on both the control and therapeutic groups to evaluate the effects of both agents. Rats were assigned into four groups as follows: normothermic (n = 23), hypothermic (n = 18), normothermia plus dizocilpine maleate (n = 18) and hypothermia plus dizocilpine maleate (n = 18). All the rats were injured using a weight-drop head injury model, artificially ventilated with a 33% O(2) and 66% NO(2) mixture, and physiological parameters, intracranial pressure, and brain and rectal temperatures were recorded. Mortality, physiological, neurological parameters, and histopathological changes were assessed after 24 h. As a result, intracranial pressure, cerebral perfusion pressure, morbidity, weight loss, and microscopic changes were significantly worse in the normothermic group (p <0.05). There was no statistical difference between other groups (p > 0.05). Hypothermia and dizocilpine maleate displayed similar neuroprotective effects in TBI on newborn rats, but no additive effect was observed.

  14. Induction of therapeutic hypothermia by pharmacological modulation of temperature-sensitive TRP channels: theoretical framework and practical considerations.

    PubMed

    Feketa, Viktor V; Marrelli, Sean P

    2015-01-01

    Therapeutic hypothermia has emerged as a remarkably effective method of neuroprotection from ischemia and is being increasingly used in clinics. Accordingly, it is also a subject of considerable attention from a basic scientific research perspective. One of the fundamental problems, with which current studies are concerned, is the optimal method of inducing hypothermia. This review seeks to provide a broad theoretical framework for approaching this problem, and to discuss how a novel promising strategy of pharmacological modulation of the thermosensitive ion channels fits into this framework. Various physical, anatomical, physiological and molecular aspects of thermoregulation, which provide the foundation for this text, have been comprehensively reviewed and will not be discussed exhaustively here. Instead, the first part of the current review, which may be helpful for a broader readership outside of thermoregulation research, will build on this existing knowledge to outline possible opportunities and research directions aimed at controlling body temperature. The second part, aimed at a more specialist audience, will highlight the conceptual advantages and practical limitations of novel molecular agents targeting thermosensitive Transient Receptor Potential (TRP) channels in achieving this goal. Two particularly promising members of this channel family, namely TRP melastatin 8 (TRPM8) and TRP vanilloid 1 (TRPV1), will be discussed in greater detail.

  15. Feasibility of adjunct therapeutic hypothermia treatment for hyperammonemia and encephalopathy due to urea cycle disorders and organic acidemias.

    PubMed

    Lichter-Konecki, Uta; Nadkarni, Vinay; Moudgil, Asha; Cook, Noah; Poeschl, Johannes; Meyer, Michael T; Dimmock, David; Baumgart, Stephen

    2013-08-01

    Children with urea cycle disorders (UCDs) or organic acidemias (OAs) and acute hyperammonemia and encephalopathy are at great risk for neurological injury, developmental delay, intellectual disability, and death. Nutritional support, intravenous alternative pathway therapy, and dialysis are used to treat severe hyperammonemia associated with UCDs and nutritional support and dialysis are used to treat severe hyperammonemia in OAs. Brain protective treatment while therapy is initiated may improve neurological and cognitive function for the lifetime of the child. Animal experiments and small clinical trials in hepatic encephalopathy caused by acute liver failure suggest that therapeutic hypothermia provides neuroprotection in hyperammonemia associated encephalopathy. We report results of an ongoing pilot study that assesses if whole body cooling during rescue treatment of neonates with acute hyperammonemia and encephalopathy is feasible and can be conducted safely. Adjunct whole body therapeutic hypothermia was conducted in addition to standard treatment in acutely encephalopathic, hyperammonemic neonates with UCDs and OAs requiring dialysis. Therapeutic hypothermia was initiated using cooling blankets as preparations for dialysis were underway. Similar to standard therapeutic hypothermia treatment for neonatal hypoxic ischemic encephalopathy, patients were maintained at 33.5°C±1°C for 72h, they were then slowly rewarmed by 0.5°C every 3h over 18h. In addition data of age-matched historic controls were collected for comparison. Seven patients were cooled using the pilot study protocol and data of seven historic controls were reviewed. All seven patients survived the initial rescue and cooling treatment, 6 patients were discharged home 2-4weeks after hospitalization, five of them feeding orally. The main complication observed in a majority of patients was hypotension. Adjunct therapeutic hypothermia for neonates with UCDs and OAs receiving standard treatment was

  16. Preliminary feasibility study of a new method of hypothermia in an experimental canine model

    PubMed Central

    Sert, İbrahim Ünal; Akand, Murat; Kılıç, Özcan; Yavru, Nuri; Bulut, Ersan

    2017-01-01

    Objective To build up a new microcontroller thermoelectric system to achieve renal hypothermia. Material and methods Renal hypothermia system was tested under in vivo conditions in the kidneys of ten Mongrel dogs. Ambient temperature was evaluated using two different microcontrollers. In order to ensure hypothermia in the renal parenchyma, selection can be made among 4 modules and sensors which detect the temperature of the area. The temperature range of the system was adjusted between −50°C and +50°C. Results When single and double poles of the kidney were cooled, initial mean intraperitoneal temperature values were found 37.7°C for rectum and 36.5°C for renal cortex and medulla. After the temperature of the cooling module was set to 12°C, the module was placed on the poles of the kidney. After fifteen minutes, temperature was 15.4°C in the lower pole of the kidney, 28.1°C in the cortex of the other side and 29.2°C in the intramedullary region. The temperature was found to be 15°C in the vicinity and 26.1°C in the cortex across the module. After the system was stabilized, a very slight change was observed in the temperature. Conclusion Hypothermia system developed ensured desired cooling of the targeted part of the kidney; however, it did not cause a change in the temperature of other parts of the kidney or general body temperature. Thus, it was possible to create a long-term study area for renal parenchymal surgery. PMID:28861307

  17. Preliminary feasibility study of a new method of hypothermia in an experimental canine model.

    PubMed

    Sert, İbrahim Ünal; Akand, Murat; Kılıç, Özcan; Yavru, Nuri; Bulut, Ersan

    2017-09-01

    To build up a new microcontroller thermoelectric system to achieve renal hypothermia. Renal hypothermia system was tested under in vivo conditions in the kidneys of ten Mongrel dogs. Ambient temperature was evaluated using two different microcontrollers. In order to ensure hypothermia in the renal parenchyma, selection can be made among 4 modules and sensors which detect the temperature of the area. The temperature range of the system was adjusted between -50°C and +50°C. When single and double poles of the kidney were cooled, initial mean intraperitoneal temperature values were found 37.7°C for rectum and 36.5°C for renal cortex and medulla. After the temperature of the cooling module was set to 12°C, the module was placed on the poles of the kidney. After fifteen minutes, temperature was 15.4°C in the lower pole of the kidney, 28.1°C in the cortex of the other side and 29.2°C in the intramedullary region. The temperature was found to be 15°C in the vicinity and 26.1°C in the cortex across the module. After the system was stabilized, a very slight change was observed in the temperature. Hypothermia system developed ensured desired cooling of the targeted part of the kidney; however, it did not cause a change in the temperature of other parts of the kidney or general body temperature. Thus, it was possible to create a long-term study area for renal parenchymal surgery.

  18. Regulation of body temperature and nociception induced by non-noxious stress in rat.

    PubMed

    Vidal, C; Suaudeau, C; Jacob, J

    1984-04-09

    The effects of 3 different non-noxious stressors on body temperature (Tb) were investigated in the rat: (1) loose restraint in cylinders, (2) removal of the rats from cylinders, exposure to a novel environment and replacement in cylinders, a stressor called here 'novelty', and (3) gentle holding of the rats by the nape of the neck. Loose restraint and 'novelty' produced hyperthermia. On the contrary, holding induced hypothermia. Hypophysectomy (HX) reduced basal Tb, abolished restraint hyperthermia and reduced both 'novelty' hyperthermia and holding hypothermia. Dexamethasone ( DEXA ) had no effect upon either restraint or novelty hyperthermia but reduced the hypothermia. Naloxone (Nx) produced a slight fall in basal Tb accounting for its reduction of restraint and 'novelty' hyperthermias ; it did not affect holding hypothermia. The inhibitory effects of HX suggest a participation of the pituitary in the hyperthermias ; the neurointermediate lobe would be involved as the hyperthermias were not affected by DEXA , which is known to block the stress-induced release of pituitary secretions from the anterior lobe but not from the neurointermediate lobe. In contrast, substances from the anterior lobe might participate in hypothermia due to holding since it is reduced by HX and DEXA . As to the effects of Nx, endogenous opioids would not be significantly involved in the thermic effects of the stressors used in this study; they might play, if any, only a minor role in the regulation of basal Tb. These results are compared with those previously obtained on nociception using the same non-noxious stressors. It emerges that, depending on the stressor, different types of association between thermoregulation and nociception may occur, i.e. hyperthermia with analgesia, hyperthermia with hyperalgesia and hypothermia with hyperalgesia.

  19. Hypothermia in a Rural Setting: An Emergency Medicine Simulation Scenario

    PubMed Central

    Jong, Robert; Heroux, Aron; Dubrowski, Adam

    2017-01-01

    Patients presenting with hypothermia in a rural emergency department can be quite challenging to manage without significant mortality and morbidity. Standard medical school curricula do not fully prepare trainees for the unique aspects of practice in northern rural and remote communities. Training opportunities on site may provide a solution to this lack of experience. However, these communities often have limited simulation-based resources and expertise for conducting and developing simulation scenarios. In this technical report, we outline a hypothermia simulation that utilizes only basic resources and is, thus, practical for rural and remote facilities. The aim of this report is to better equip trainees, clinicians, and emergency department staff who may encounter such a scenario in their practice. While the simulation is specifically designed for medical students, resident doctors, and emergency department staff, it could also be applicable in other low-resource settings, such as military bases, search and rescue stations, and arctic travel and tourism infirmaries. PMID:29511605

  20. Acoustothermometric study of the human hand under hyperthrmia and hypothermia

    NASA Astrophysics Data System (ADS)

    Anosov, A. A.; Belyaev, R. V.; Vilkov, V. A.; Dvornikova, M. V.; Dvornikova, V. V.; Kazanskii, A. S.; Kuryatnikova, N. A.; Mansfel'd, A. D.

    2013-01-01

    The results of an acoustothermometric study of the human hand under local hyperthermia and hypothermia are presented. Individuals under testing plunged their hands in hot or cold water for several minutes. Thermal acoustic radiation was detected by two sensors placed near the palm and near the backside of the tested hand. The internal temperature profiles of the hand were reconstructed. The indirect estimate of the reconstruction error was 0.6°C, which is acceptable for medical applications. Hyperthermia was achieved by placing the hand in water with a maximal temperature of 44°C for 2 min. In this case, the internal temperature was 35.4 ± 0.6°C. Hypothermia was achieved by placing the hand in water with a temperature of 17.8°C for 15 min. In this case, the internal temperature decreased from 26 to 24°C. The use of a four-sensor planar receiving array allowed dynamic mapping of the acoustic brightness temperature of the hand.

  1. Characterization of Death in Neonatal Encephalopathy in the Hypothermia Era.

    PubMed

    Lemmon, Monica E; Boss, Renee D; Bonifacio, Sonia L; Foster-Barber, Audrey; Barkovich, A James; Glass, Hannah C

    2017-03-01

    This study aimed to characterize the circumstances of death in encephalopathic neonates treated with therapeutic hypothermia. Patients who died after or during treatment with therapeutic hypothermia between 2007-2014 were identified. Patient circumstance of death was characterized using an established paradigm. Thirty-one of 229 patients died (14%) at a median of 3 days of life. Most who died were severely encephalopathic on examination (90%) and had severely abnormal electroencephalographic (EEG) findings (87%). All those who had magnetic resonance images (n = 13) had evidence of moderate-severe brain injury; 6 had near-total brain injury. Cooling was discontinued prematurely in 61% of patients. Most patients (90%) were physiologically stable at the time of death; 81% died following elective extubation for quality of life considerations. Three patients (10%) died following withholding or removal of artificial hydration and nutrition. Characterization of death in additional cohorts is needed to identify differences in decision making practices over time and between centers.

  2. Neostriatal cytoskeleton changes following perinatal asphyxia: effect of hypothermia treatment.

    PubMed

    Cebral, Elisa; Capani, Francisco; Selvín-Testa, Asia; Funes, Manuel Rey; Coirini, Héctor; Loidl, C Fabián

    2006-06-01

    Long-term changes of different types of neurofilaments (NF) and glial fibrillar acid protein (GFAP) were studied in neostriatal rat subjected to perinatal asphyxia (PA) under normothermic and hypothermic (15 degrees C) conditions, using immunohistochemistry for light and electron microscopy. Neostriatal neurons of 6-month-old rats that were subjected to 19 and 20 min of PA, showed an increase of NF 200 kDa immunostaining mainly in the axon fascicles in comparison with the control and hypothermia groups. In contrast, no alterations were seen with NF68 and NF160 neurofilament antibodies. Furthermore, the same PA groups showed astroglial cells with enhanced GFAP immunoreactivity, evidencing a typical astroglial reaction with a clear hypertrophy of these cells. A quantitative image analysis confirmed these observations. Hypothermic treated animals did show neither astroglial nor neuronal cytoskeletal changes in comparison to the control group. These findings showed that PA produces chronic cytoskeletal alterations in the neostriatum cells that can be prevented by hypothermia.

  3. Phenobarbital and temperature profile during hypothermia for hypoxic-ischemic encephalopathy

    PubMed Central

    Sant’Anna, Guilherme; Laptook, Abbot R.; Shankaran, Seetha; Bara, Rebecca; McDonald, Scott A.; Higgins, Rosemary D.; Tyson, Jon E.; Ehrenkranz, Richard A.; Das, Abhik; Goldberg, Ronald N.; Walsh, Michele C.

    2012-01-01

    Data from the whole body hypothermia trial was analyzed to examine the effects of phenobarbital administration prior to cooling (+PB) on the esophageal temperature (Te) profile, during the induction phase of hypothermia. A total of 98 infants were analyzed. At enrollment, +PB infants had a higher rate of severe HIE and clinical seizures and lower Te and cord pH than infants that have not received PB (−PB). There was a significant effect of PB itself and an interaction between PB and time in the Te profile. Mean Te in the +PB group was lower than in the −PB group and the differences decreased over time. In +PB infants the time to surpass target Te of 33.5°C and to reach the minimum Te during overshoot were shorter. In conclusion, the administration of PB prior to cooling was associated with changes that may reflect a reduced thermogenic response associated with barbiturates. PMID:21960671

  4. Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI)

    PubMed Central

    2012-01-01

    Background Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2–3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment. Methods/Design Term newborns (gestational age ≥ 36 weeks and birth weight ≥ 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial

  5. Effects of anesthetic induction with a benzodiazepine plus ketamine hydrochloride or propofol on hypothermia in dogs undergoing ovariohysterectomy.

    PubMed

    Bornkamp, Jennifer L; Robertson, Sheilah; Isaza, Natalie M; Harrison, Kelly; DiGangi, Brian A; Pablo, Luisito

    2016-04-01

    To assess the effect of anesthetic induction with a benzodiazepine plus ketamine or propofol on hypothermia in dogs undergoing ovariohysterectomy without heat support. 23 adult sexually intact female dogs undergoing ovariohysterectomy. Baseline rectal temperature, heart rate, and respiratory rate were recorded prior to premedication with buprenorphine (0.02 mg/kg, IM) and acepromazine (0.05 mg/kg, IM). Anesthesia was induced with midazolam or diazepam (0.25 mg/kg, IV) plus ketamine (5 mg/kg, IV; n = 11) or propofol (4 mg/kg, IV; 12) and maintained with isoflurane in oxygen. Rectal temperature was measured at hospital intake, prior to premedication, immediately after anesthetic induction, and every 5 minutes after anesthetic induction. Esophageal temperature was measured every 5 minutes during anesthesia, beginning 30 minutes after anesthetic induction. After anesthesia, dogs were covered with a warm-air blanket and rectal temperature was measured every 10 minutes until normothermia (37°C) was achieved. Dogs in both treatment groups had lower rectal temperatures within 5 minutes after anesthetic induction and throughout anesthesia. Compared with dogs that received a benzodiazepine plus ketamine, dogs that received a benzodiazepine plus propofol had significantly lower rectal temperatures and the interval from discontinuation of anesthesia to achievement of normothermia was significantly longer. Dogs in which anesthesia was induced with a benzodiazepine plus propofol or ketamine became hypothermic; the extent of hypothermia was more profound for the propofol combination. Dogs should be provided with adequate heat support after induction of anesthesia, particularly when a propofol-benzodiazepine combination is administered.

  6. Hypothermia is associated with increased mortality in patients undergoing repair of ruptured abdominal aortic aneurysm.

    PubMed

    Quiroga, Elina; Tran, Nam T; Hatsukami, Thomas; Starnes, Benjamin W

    2010-06-01

    To evaluate the impact of hypothermia on mortality in patients presenting with ruptured abdominal aortic aneurysms (rAAA). Between July 2007 and September 2009, 73 patients with ruptured AAAs presented to our Emergency Department (ED). Thirteen patients did not receive surgical treatment; of the 60 patients (46 men; mean age 76 years, range 63-90) who did, 35 had endovascular aneurysm repair (EVAR) and 25 open repair. Body temperatures, which were recorded upon arrival to the ED and operating room, during the procedure, and just prior to leaving the operating room, were analyzed for any association with mortality or hypotension. The primary outcome measure was the 30-day mortality rate. Six (17%) patients in the EVAR group and 10 (40%) patients in the open group died during the 30-day period. Temperature upon arrival to OR, lowest temperature recorded during the procedure, and temperature at the end of the procedure were higher among survivors (p<0.005), independent of the repair technique implemented. Patients in the EVAR group left the OR with a mean temperature of 35.5 degrees C versus 35.0 degrees C for patients in the open group (p = 0.12). Hypothermia is associated with increased mortality after repair of rAAA. Efforts to correct hypothermia are more frequently successful in patients undergoing EVAR. Increased communication with anesthesia providers, as well as aggressive measures to correct hypothermia, including active intravascular rewarming methods, should be considered to improve mortality in this gravely ill patient population.

  7. Effect of 7-nitroindazole on body temperature and methamphetamine-induced dopamine toxicity.

    PubMed

    Callahan, B T; Ricaurte, G A

    1998-08-24

    The present study was undertaken to examine the role of temperature on the ability of 7-nitroindazole (7-NI) to prevent methamphetamine-induced dopamine (DA) neurotoxicity. Male Swiss-Webster mice received methamphetamine alone or in combination with 7-NI at either room temperature (20+/-1 degrees C) or at 28+/-1 degrees C. At 20+/-1 degrees C, 7-NI produced hypothermic effects and afforded total protection against methamphetamine-induced DA depletions in the striatum. At 28+/-1 degrees C, 7-NI produced minimal effects on body temperature and failed to prevent methamphetamine-induced DA reductions. These findings indicate that the neuroprotection afforded by 7-NI is likely related to its ability to produce hypothermia because agents that produce hypothermia and/or prevent hyperthermia are known to attenuate methamphetamine-induced neurotoxicity.

  8. Olanzapine causes hypothermia, inactivity, a deranged feeding pattern and weight gain in female Wistar rats.

    PubMed

    Evers, S S; Calcagnoli, F; van Dijk, G; Scheurink, A J W

    2010-11-01

    Olanzapine is an a-typical antipsychotic drug antagonizing predominantly 5-HT and dopamine, but also histamine, muscarin, and α-adrenergic receptors. In humans, Olanzapine induces weight gain and increases the risk of type 2 diabetes. The underlying mechanisms of Olanzapine-induced weight gain are unclear. To study this we administered Olanzapine (5mg/kg) in female Wistar rats on a medium fat diet for 14 days via a permanent gastric catheter twice a day, just prior to the onset and at the middle of dark phase. Food and water intake, locomotor activity and body temperature were measured. Olanzapine acutely induced hypothermia, markedly decreased locomotor activity and increased body weight during 14 days of treatment. Olanzapine treatment did not result in an alteration of 24h food intake, but diurnal patterns of feeding behavior and body temperature were dramatically changed. We conclude that in female Wistar rats Olanzapine has an acute hypothermic effect, that the effect of Olanzapine on feeding behavior is secondary to the effect on activity, and that Olanzapine-induced weight gain is primarily the result of reduction in locomotor activity. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. Molecular pathology of pulmonary surfactants and cytokines in drowning compared with other asphyxiation and fatal hypothermia.

    PubMed

    Miyazato, Takako; Ishikawa, Takaki; Michiue, Tomomi; Maeda, Hitoshi

    2012-07-01

    Drowning involves complex fatal factors, including asphyxiation and electrolyte/osmotic disturbances, as well as hypothermia in cold water. The present study investigated the molecular pathology of pulmonary injury due to drowning, using lung specimens from forensic autopsy cases of drowning (n = 21), acute mechanical asphyxia due to neck compression and smothering (n = 24), and hypothermia (cold exposure, n = 11), as well as those of injury (n = 23), intoxication (n = 13), fire fatality (n = 18), and acute cardiac death (n = 9) for comparison. TaqMan real-time reverse transcription polymerase chain reaction was used to quantify messenger RNA (mRNA) expressions of pulmonary surfactant-associated proteins A and D (SP-A and SP-D), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10. SP-A and SP-D mRNA levels were lower for drowning, mechanical asphyxiation, fire fatality, and acute cardiac deaths than for hypothermia and injury. TNF-α, IL-1β, and IL-10 mRNA levels were higher for drowning or for drowning and injury than for other groups; there was no significant difference between fire fatality, involving airway injury due to inhalation of hot/irritant gases, and other control groups. These observations suggest characteristic molecular biological patterns of pulmonary injury involving suppression of pulmonary surfactants and activation of early-phase mediators of inflammation in drowning, with high mRNA expression levels of pulmonary surfactants in fatal hypothermia; however, there was no significant difference among these markers in immunohistochemical detection, except for SP-A. These mRNA expressions can be used as markers of pulmonary injury to assist in investigations of the pathophysiology of drowning and fatal hypothermia in combination with other biochemical and biological markers.

  10. Pressure Infusion Cuff and Blood Warmer during Massive Transfusion: An Experimental Study About Hemolysis and Hypothermia.

    PubMed

    Poder, Thomas G; Pruneau, Denise; Dorval, Josée; Thibault, Louis; Fisette, Jean-François; Bédard, Suzanne K; Jacques, Annie; Beauregard, Patrice

    2016-01-01

    Blood warmers were developed to reduce the risk of hypothermia associated with the infusion of cold blood products. During massive transfusion, these devices are used with compression sleeve, which induce a major stress to red blood cells. In this setting, the combination of blood warmer and compression sleeve could generate hemolysis and harm the patient. We conducted this study to compare the impact of different pressure rates on the hemolysis of packed red blood cells and on the outlet temperature when a blood warmer set at 41.5°C is used. Pressure rates tested were 150 and 300 mmHg. Ten packed red blood cells units were provided by Héma-Québec and each unit was sequentially tested. We found no increase in hemolysis either at 150 or 300 mmHg. By cons, we found that the blood warmer was not effective at warming the red blood cells at the specified temperature. At 150 mmHg, the outlet temperature reached 37.1°C and at 300 mmHg, the temperature was 33.7°C. To use a blood warmer set at 41.5°C in conjunction with a compression sleeve at 150 or 300 mmHg does not generate hemolysis. At 300 mmHg a blood warmer set at 41.5°C does not totally avoid a risk of hypothermia.

  11. Effectiveness of heat moisture exchangers (hmes) in preventing perioperative hypothermia among adult patients undergoing abdominal surgery under general endotracheal anaesthesia.

    PubMed

    Anaegbu, Nc; Olatosi, Oj; Tobi, Ku

    2013-01-01

    Heat Moisture Exchangers (HMEs) conserve heat and moisture during expiration and make this available to inspired gases during subsequent inspiration. We sought to evaluate the effectiveness of HMEs in the prevention of perioperative hypothermia in patients scheduled for abdominal surgery under general anaesthesia relaxant technique with endotrachael intubation (GART.) Lagos University Teaching Hospital, in Modular theatre, Anaesthesia unit. The study was a randomized, controlled, longitudinal, interventional study Methods: 100 ASA I, II and III patients aged 18 to 65 years scheduled for abdominal surgery under GART were randomly assigned to 2 groups, groups H and C. Group H had HMEs, while group C served as controls. Core temperature measured using tympanic probe was every 10 minutes till end of anaesthesia Data from total 99 patients, 49 in group H and 50 in group C were eventually analysed. Although patients in both groups developed hypothermia in the course of anaesthesia, core temperature was significantly lower p< 0.05 after one hour in the control group than the intervention group. The use of HMEs during general anaesthesia with endotrachael intubation did not prevent hypothermia but resulted in higher core temperature and should be part of a multimodal approach in the prevention of perioperative hypothermia. Heat Moisture Exchangers, General endotracheal anaesthesia, Hypothermia, abdominal surgery.

  12. Biomarkers S100B and neuron-specific enolase predict outcome in hypothermia-treated encephalopathic newborns*.

    PubMed

    Massaro, An N; Chang, Taeun; Baumgart, Stephen; McCarter, Robert; Nelson, Karin B; Glass, Penny

    2014-09-01

    To evaluate if serum S100B protein and neuron-specific enolase measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy. Prospective longitudinal cohort study. A level IV neonatal ICU in a freestanding children's hospital. Term newborns with moderate to severe neonatal encephalopathy referred for therapeutic hypothermia during the study period. Serum neuron-specific enolase and S100B were measured at 0, 12, 24, and 72 hours of hypothermia. Of the 83 infants enrolled, 15 (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development-II at 15 months. Outcomes were assessed in 49 of 68 survivors (72%) at a mean age of 15.2 ± 2.7 months. Neurodevelopmental outcome was classified by Bayley Scales of Infant Development-II Mental Developmental Index and Psychomotor Developmental Index scores, reflecting cognitive and motor outcomes, respectively. Four-level outcome classifications were defined a priori: normal = Mental Developmental Index/Psychomotor Developmental Index within 1 SD (> 85), mild = Mental Developmental Index/Psychomotor Developmental Index less than 1 SD (70-85), moderate/severe = Mental Developmental Index/Psychomotor Developmental Index less than 2 SD (< 70), or died. Elevated serum S100B and neuron-specific enolase levels measured during hypothermia were associated with increasing outcome severity after controlling for baseline and socioeconomic characteristics in ordinal regression models. Adjusted odds ratios for cognitive outcome were 2.5 (95% CI, 1.3-4.8) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase, and for motor outcome, 2.6 (95% CI, 1.2-5.6) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase. Serum S100B and neuron-specific enolase levels in babies with neonatal encephalopathy are associated with neurodevelopmental outcome at 15 months. These putative biomarkers of brain injury may help direct

  13. Effects of the HEET garment in the prevention of hypothermia in a porcine model.

    PubMed

    Johnson, Don; Gegel, Brian; Burgert, James; Duncklee, Geoffrey W; Robison, Ricci R; Lewis, Eric J; Crum, Paul M; Kuhns, William; Moore, Daniel; O'Brien, Scott; Elliott, Joel; Washington, Jason; Boyle, John; Seigler, Dale

    2010-11-01

    Hypothermia is a common battlefield trauma occurrence. This study compared the effectiveness of the hypothermia, environmental, exposure, and trauma (HEET) garment (Trident Industries, Beaufort, SC) with and without thermal inserts with a control group of two wool blankets in the prevention of hypothermia in a treated hypovolemic porcine model. Five female swine (Sus scrofa-Yorkshire cross) were assigned to each of three groups: HEET with thermal inserts (n=5); HEET without thermal inserts (n=5); or control (n=5). After the animals were anesthetized and stabilized for 30 min, the swine were hemorrhaged to a mean arterial pressure (MAP) of 30 mm Hg, simulating a battlefield injury. Hetastarch 6% (500 mL) was rapidly administered, simulating initial field resuscitation. One hour later, the animals' shed blood was reinfused, simulating transfusion at a field medical facility. The investigators moved the animal into a cooler set at 10°C ± 0.5°C. A pulmonary artery catheter was used to monitor core body temperature over a 6-h period. A repeated measures ANOVA and Tukey's post hoc test were used to analyze the data. There was a significant difference between the groups. At the end of 6h, the mean core temperature for the HEET with inserts group was 32.69°C ± 1.5; the HEET without inserts, 31.02°C ± 1.8; and control, 34.78°C ± 1.2 (P<0.05). While all groups became hypothermic, the wool blanket group was most effective in maintaining body temperature closer to normothermia. The HEET garments with and without heaters are ineffective in preventing hypothermia. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Interventions to prevent hypothermia at birth in preterm and/or low birthweight infants.

    PubMed

    McCall, Emma M; Alderdice, Fiona; Halliday, Henry L; Jenkins, John G; Vohra, Sunita

    2010-03-17

    Keeping vulnerable preterm infants warm is problematic even when recommended routine thermal care guidelines are followed in the delivery suite. To assess efficacy and safety of interventions designed for prevention of hypothermia in preterm and/or low birthweight infants applied within 10 minutes after birth in the delivery suite compared with routine thermal care. We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG). The review was updated in October 2009. Trials using randomised or quasi-randomised allocations to test a specific intervention designed to prevent hypothermia, (apart from 'routine' thermal care) applied within 10 minutes after birth in the delivery suite to infants of < 37 weeks' gestational age or birthweight hypothermia when compared to conventional incubator care for infants (1 study, n = 31; RR 0.09; 95% CI 0.01, 0.64). The transwarmer mattress reduced the incidence of hypothermia on admission to NICU in VLBW infants (1

  15. [Morphological characteristic of Langerhans cells from the human epidermis in case of general hypothermia].

    PubMed

    Stefanenko, E V; Miadelets, O D; Kukhnovets, O A; Miadelets, V O

    2009-01-01

    The objective of this work was to study morphological changes in the Langerhans cells of epidermis and epithelium of hair follicles from subjects who died as a result of general hypothermia. A total of 105 cadaveric skin samples from subjects of either gender aged from 19 to 83 years were available for analysis. Postmortem examination 1-2 days after death was performed at the Department of Forensic Medical Examination for the Vitebsk region. Skin samples were frozen in liquid nitrogen and studied as cryostat sections. Langerhans cells were detected using the ATPase assay as described by Wachstein and Meisel and modified by Robins and Brendon. The Langerhans cells of subjects who died from general hypothermia were shown to undergo marked morphological changes. Moreover, their number significantly decreased as a result of disintegration and transformation into fine-grain material. Surviving cells lost many of their outgrowths and exhibited enhanced ATPase activity in pericarion. The Langerhans cells from dorsal and ventral skin as well as from interfollicular epidermis and the outer sheath of hair follicles underwent virtually identical changes. A unique morphological feature of the skin in those who died from general hypothermia was formation of intraepidermal, subepidermal, and dermal blisters.

  16. Hypothermia inhibits translocation of CaM kinase II and PKC-alpha, beta, gamma isoforms and fodrin proteolysis in rat brain synaptosome during ischemia-reperfusion.

    PubMed

    Harada, Kazuki; Maekawa, Tsuyoshi; Tsuruta, Ryosuke; Kaneko, Tadashi; Sadamitsu, Daikai; Yamashima, Tetsumori; Yoshida Ki, Ken-ichi

    2002-03-01

    To clarify the involvement of intracellular signaling pathway and calpain in the brain injury and its protection by mild hypothermia, immunoblotting analyses were performed in the rat brain after global forebrain ischemia and reperfusion. After 30 min of ischemia followed by 60 min of reperfusion, Ca2+/calmodulin-dependent kinase II (CaM kinase II) and protein kinase C (PKC)-alpha, beta, gamma isoforms translocated to the synaptosomal fraction, while mild hypothermia (32 degrees C) inhibited the translocation. The hypothermia also inhibited fodrin proteolysis caused by ischemia-reperfusion, indicating the inhibition of calpain. These effects of hypothermia may explain the mechanism of the protection against brain ischemia-reperfusion injury through modulating synaptosomal function.

  17. Implementation of therapeutic hypothermia guidelines for post-cardiac arrest syndrome at a glacial pace: seeking guidance from the knowledge translation literature.

    PubMed

    Brooks, Steven C; Morrison, Laurie J

    2008-06-01

    The 2005 International Liaison Committee on Resuscitation (ILCOR) Consensus on Science and Treatment Recommendations document represents the most extensive and rigorous systematic review of the resuscitation literature to date and included evidence-based recommendations for post-resuscitation care. A new recommendation for the induction of mild therapeutic hypothermia for comatose cardiac arrest survivors was included in this document. Accordingly, constituent national member associations of ILCOR, including the American Heart Association, incorporated the recommendation for therapeutic hypothermia into their respective guidelines. Despite these endorsements there is a concern that therapeutic hypothermia is not being used in practice. Data from a number of surveys in Europe and the United States suggest that rates of use among physicians may be as low as 30-40%. Despite the cost and effort associated with the production of these guidelines and the potential impact on patient care, current efforts in implementing the guideline have not achieved widespread success. This commentary explores the issue of underutilization of the American Heart Association guidelines for therapeutic hypothermia and looks to the knowledge translation literature to inform a new approach to implementation. We will review the underlying phenomenon of research implementation into practice, specific barriers to guideline implementation and interventions that may improve therapeutic hypothermia uptake.

  18. Retrospective study of the prevalence of postanaesthetic hypothermia in dogs.

    PubMed

    Redondo, J I; Suesta, P; Serra, I; Soler, C; Soler, G; Gil, L; Gómez-Villamandos, R J

    2012-10-13

    The anaesthetic records of 1525 dogs were examined to determine the prevalence of postanaesthetic hypothermia, its clinical predictors and consequences. Temperature was recorded throughout the anaesthesia. At the end of the procedure, details coded in were: hyperthermia (>39.50°C), normothermia (38.50°C-39.50°C), slight (38.49°C-36.50°C), moderate (36.49°C-34.00°C) and severe hypothermia (<34.00°C). Statistical analysis consisted of multiple regression to identify the factors that are associated with the temperature at the end of the procedure. Before premedication, the temperature was 38.7 ± 0.6°C (mean ± sd). At 60, 120 and 180 minutes from induction, the temperature was 36.7 ± 1.3°C, 36.1 ± 1.4°C and 35.8 ± 1.5°C, respectively. The prevalence of hypothermia was: slight, 51.5 per cent (95 per cent CI 49.0 to 54.0 per cent); moderate, 29.3 per cent (27.1-31.7 per cent) and severe: 2.8% (2.0-3.7%). The variables that associated with a decrease in the temperature recorded at the end of the anaesthesia were: duration of the preanesthetic time, duration of the anaesthesia, physical condition (ASA III and ASA IV dogs showed lower temperatures than ASA I dogs), the reason for anaesthesia (anaesthesia for diagnostic procedures or thoracic surgery reduce the temperature when compared with minor procedures), and the recumbency during the procedure (sternal and dorsal recumbencies showed lower temperatures than lateral recumbency). The temperature before premedication and the body surface (BS) were associated with a higher temperature at the end of the anaesthesia, and would be considered as protective factors.

  19. [Cardiac arrest due to accidental hypothermia and prolonged cardiopulmonary resuscitation].

    PubMed

    Kot, P; Botella, J

    2010-11-01

    In cardiac arrest produced by accidental hypothermia, cardiopulmonary resuscitation must be prolonged until normal body temperature is achieved. There are different rewarming methods. In theory, the more invasive ones are elective in patients with cardiac arrest because of their higher rewarming speed. However, it has not been proven that these methods are better than the non-invasive ones. We present a case report of a patient with cardiac arrest due to accidental hypothermia who was treated without interruption for three hours with heart massage. This is the longest successful cardiopulmonary resuscitation known up-to-date in Spain. In order to rewarm the body, a combination of non-invasive methods was used: active external rewarming with convective warm air, gastric and bladder lavage with warm saline solution and intravenous warm saline infusion. This case shows that it is possible to treat hypothermic cardiac arrest successfully through these rewarming methods, which are both easy to apply and feasible in any hospital. Copyright © 2009 Elsevier España, S.L. y SEMICYUC. All rights reserved.

  20. The impact of mild induced hypothermia on the rate of transfusion and the mortality in severely injured patients: a retrospective multi-centre study.

    PubMed

    Jensen, Kai Oliver; Held, Leonhard; Kraus, Andrea; Hildebrand, Frank; Mommsen, Philipp; Mica, Ladislav; Wanner, Guido A; Steiger, Peter; Moos, Rudolf M; Simmen, Hans-Peter; Sprengel, Kai

    2016-10-06

    Although under discussion, induced hypothermia (IH) is an established therapy for patients with cardiac arrest or traumatic brain injuries. The influences on coagulopathy and bleeding tendency in severely injured patients (SIP) with concomitant traumatic brain injury are most widely unclear. Therefore, the aim of this study was to quantify the effect of mild IH in SIP with concomitant severe traumatic brain injuries on transfusion rate and mortality. In this retrospective multi-centre study, SIP from three European level-1 trauma centres with an ISS ≥16 between 2009 and 2011 were included. At hospital A, patients qualified for IH with age ≤70 years and a severe head injury with an abbreviated injury scale (AIS Head ) of ≥3. IH was defined as target core body temperature of 35 °C. Hypothermic patients were matched with two patients, one from hospital B and one from hospital C using age and AIS Head . The effect of IH on the transfusion rate, complications and mortality was quantified with 95 % confidence intervals (CI). Patients not treated with IH in hospital A and those from hospital B and C, who were not matched, were used to adjust the CI for the effect of inter-hospital therapy protocol differences. Mean age of patients in the IH-group (n = 43) was 35.7 years, mean ISS 30 points and sex distribution showed 83.7 % male. Mean age of matched patients in the normotherm-group (n = 86) was 36.7 years, mean ISS 33 points and there were 75.6 % males. For the hypothermic patients, we pointed out an estimate of mean difference for the number of transfused units of packed red blood cells as well as for mortality which does not indicate a decrease in the benefit gained by hypothermia. It is suggested that hypothermic patients tend to a higher rate of lung failure and thromboembolisms. Though tending to an increased rate of complications, there is no evidence for a difference in both; rate of transfusion and mortality in SIP. Mild IH as an option for

  1. Hypothermia and Fever after organophosphorus poisoning in humans--a prospective case series.

    PubMed

    Moffatt, Alison; Mohammed, Fahim; Eddleston, Michael; Azher, Shifa; Eyer, Peter; Buckley, Nick A

    2010-12-01

    There have been many animal studies on the effects of organophosphorus pesticide (OP) poisoning on thermoregulation with inconsistent results. There have been no prospective human studies. Our aim was to document the changes in body temperature with OP poisoning. A prospective study was conducted in a rural hospital in Polonnaruwa, Sri Lanka. We collected data on sequential patients with OP poisoning and analyzed 12 patients selected from 53 presentations who had overt signs and symptoms of OP poisoning and who had not received atropine prior to arrival. All patients subsequently received specific management with atropine and/or pralidoxime and general supportive care. Tympanic temperature, ambient temperature, heart rate, and clinical examination and interventions were recorded prospectively throughout their hospitalization. Initial hypothermia as low as 32°C was observed in untreated patients. Tympanic temperature increased over time from an early hypothermia (<35°C in 6/12 patients) to later fever (7/12 patients >38°C at some later point). While some of the late high temperatures occurred in the setting of marked tachycardia, it was also apparent that in some cases fever was not accompanied by tachycardia, making excessive atropine or severe infection an unlikely explanation for all the fevers. In humans, OP poisoning causes an initial hypothermia, and this is followed by a period of normal to high body temperature. Atropine and respiratory complications may contribute to fever but do not account for all cases.

  2. Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials.

    PubMed

    Moler, Frank W; Silverstein, Faye S; Meert, Kathleen L; Clark, Amy E; Holubkov, Richard; Browning, Brittan; Slomine, Beth S; Christensen, James R; Dean, J Michael

    2013-09-01

    To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Multicenter randomized controlled trials. Pediatric intensive care and cardiac ICUs in the United States and Canada. Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent. Therapeutic hypothermia or therapeutic normothermia. From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015. Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials.

  3. Medical instrument based on a heat pipe for local cavity hypothermia

    NASA Astrophysics Data System (ADS)

    Vasil'Ev, L. L.; Zhuraviyov, A. S.; Molodkin, F. F.; Khrolenok, V. V.; Zhdanov, V. L.; Vasil'Ev, V. L.; Adamov, S. I.; Tyurin, A. A.

    1996-05-01

    The design and results of tests of an instrument based on a heat pipe for local cavity hypothermia are presented. The instrument is a part of a device for noninvasive nonmedical treatment of inflammatory diseases of the organs of the small pelvis, pathologies of alimentary canal, etc.

  4. Therapeutic Hypothermia Following Traumatic Spinal Injury: Morphological and Functional Correlates.

    DTIC Science & Technology

    1999-01-01

    oxide synthase inhibitor ( agmatine ) following traumatic spinal cord injury. The major findings of these studies have shown that significant...Similarly, significant differences were observed following systemic administration of agmatine for 14 days post-injury. Unfortunately, no synergistic or...additive effects were achieved when agmatine and hypothermia were combined. Overall, the results support the original hypothesis of this proposal that

  5. Preventing chemotherapy-induced alopecia.

    PubMed

    Smith, F P; McCabe, M S

    1983-07-01

    Chemotherapy-induced alopecia is now potentially preventable. Although scalp tourniquets and hypothermia are neither universally applicable nor always successful, they represent simple and relatively inexpensive methods for reducing hair loss. When successful, these techniques help maintain the patient's self-image and thereby diminish the devastating psychologic effects that accompany a diagnosis of cancer.

  6. Thrombelastography is Better Than PT, aPTT, and Activated Clotting Time in Detecting Clinically Relevant Clotting Abnormalities After Hypothermia, Hemorrhagic Shock and Resuscitation in Pigs

    DTIC Science & Technology

    2008-09-01

    hypothermia group using a cold blanket with 4°C circulating water. In the combined group, hemorrhagic shock and LR re- suscitation were induced the same... circulation and a decrease in platelet counts. Fibrinogen levels, in con- trast, were not changed significantly from baseline by hypo- thermia in this...et al. Effect of skin temperature on platelet function in patients undergoing extracorporeal bypass. J Thorac Cardiovasc Surg. 1992;104:108–116. The

  7. Hypothermia Severely Effects Performance of Nitinol-Based Endovascular Grafts In Vitro

    PubMed Central

    Robich, Michael P.; Hagberg, Robert; Schermerhorn, Marc L.; Pomposelli, Frank B.; Nilson, Michael C.; Gendron, Michelle L.; Sellke, Frank W.; Rodriguez, Roberto

    2012-01-01

    Background Nitinol is an alloy that serves as the base for numerous medical devices, including the GORE TAG Thoracic Endoprosthesis (W.L. Gore & Associates, Flagstaff, AZ) thoracic aortic graft device. Given the increasing use of therapeutic hypothermia used during the placement these devices and in post– cardiac arrest situations, we sought to understand the impact of hypothermia on this device. Methods Five 34-mm TAG devices were deployed in a temperature-controlled chamber at 20°C, 25°C, 30°C, 35°, and 37°C (25 total devices). A halographic measurement device was used to measure radial expansive force and normalized to the force at 37°C. Three 34-mm TAG devices were similarly deployed in a temperature-controlled water bath at each of the above temperatures. A laser micrometer was utilized to measure deployed diameter. Results A statistically significant decrease in expansive force at 20°C, 25°C, and 30°C of 65%, 46%, and 6%, respectively, was noted. A statistically significant decrease in radial diameter at 20°C and 25°C of 17% and 11%, respectively, was noted. Although a 9% difference was noted at 30°C, it was not significant. Conclusions The nitinol-based TAG device shows marked decreases in radial expansive force and deployed diameter at temperatures at or below 30°C. Surgeons should be aware of the potential implications of placing nitinol-based endoprostheses in hypothermic conditions. In addition, all health care providers should be aware of the changes that occur in nitinol-based endoprostheses during therapeutic hypothermia. PMID:22385821

  8. Pressure Infusion Cuff and Blood Warmer during Massive Transfusion: An Experimental Study About Hemolysis and Hypothermia

    PubMed Central

    Pruneau, Denise; Dorval, Josée; Thibault, Louis; Fisette, Jean-François; Bédard, Suzanne K.; Jacques, Annie; Beauregard, Patrice

    2016-01-01

    Background Blood warmers were developed to reduce the risk of hypothermia associated with the infusion of cold blood products. During massive transfusion, these devices are used with compression sleeve, which induce a major stress to red blood cells. In this setting, the combination of blood warmer and compression sleeve could generate hemolysis and harm the patient. We conducted this study to compare the impact of different pressure rates on the hemolysis of packed red blood cells and on the outlet temperature when a blood warmer set at 41.5°C is used. Methods Pressure rates tested were 150 and 300 mmHg. Ten packed red blood cells units were provided by Héma-Québec and each unit was sequentially tested. Results We found no increase in hemolysis either at 150 or 300 mmHg. By cons, we found that the blood warmer was not effective at warming the red blood cells at the specified temperature. At 150 mmHg, the outlet temperature reached 37.1°C and at 300 mmHg, the temperature was 33.7°C. Conclusion To use a blood warmer set at 41.5°C in conjunction with a compression sleeve at 150 or 300 mmHg does not generate hemolysis. At 300 mmHg a blood warmer set at 41.5°C does not totally avoid a risk of hypothermia. PMID:27711116

  9. Hypothermia for Traumatic Brain Injury in Children-A Phase II Randomized Controlled Trial.

    PubMed

    Beca, John; McSharry, Brent; Erickson, Simon; Yung, Michael; Schibler, Andreas; Slater, Anthony; Wilkins, Barry; Singhal, Ash; Williams, Gary; Sherring, Claire; Butt, Warwick

    2015-07-01

    To perform a pilot study to assess the feasibility of performing a phase III trial of therapeutic hypothermia started early and continued for at least 72 hours in children with severe traumatic brain injury. Multicenter prospective randomized controlled phase II trial. All eight of the PICUs in Australia and New Zealand and one in Canada. Children 1-15 years old with severe traumatic brain injury and who could be randomized within 6 hours of injury. The control group had strict normothermia to a temperature of 36-37°C for 72 hours. The intervention group had therapeutic hypothermia to a temperature of 32-33°C for 72 hours followed by slow rewarming at a rate compatible with maintaining intracranial pressure and cerebral perfusion pressure. Of 764 children admitted to PICU with traumatic brain injury, 92 (12%) were eligible and 55 (7.2%) were recruited. There were five major protocol violations (9%): three related to recruitment and consent processes and two to incorrect temperature management. Rewarming took a median of 21.5 hours (16-35 hr) and was performed without compromise in the cerebral perfusion pressure. There was no increase in any complications, including infections, bleeding, and arrhythmias. There was no difference in outcomes 12 months after injury; in the therapeutic hypothermia group, four (17%) had a bad outcome (pediatric cerebral performance category, 4-6) and three (13%) died, whereas in the normothermia group, three (12%) had a bad outcome and one (4%) died. Early therapeutic hypothermia in children with severe traumatic brain injury does not improve outcome and should not be used outside a clinical trial. Recruitment rates were lower and outcomes were better than expected. Conventional randomized controlled trials in children with severe traumatic brain injury are unlikely to be feasible. A large international trials group and alternative approaches to trial design will be required to further inform practice.

  10. Biothermal Model of Patient and Automatic Control System of Brain Temperature for Brain Hypothermia Treatment

    NASA Astrophysics Data System (ADS)

    Wakamatsu, Hidetoshi; Gaohua, Lu

    Various surface-cooling apparatus such as the cooling cap, muffler and blankets have been commonly used for the cooling of the brain to provide hypothermic neuro-protection for patients of hypoxic-ischemic encephalopathy. The present paper is aimed at the brain temperature regulation from the viewpoint of automatic system control, in order to help clinicians decide an optimal temperature of the cooling fluid provided for these three types of apparatus. At first, a biothermal model characterized by dynamic ambient temperatures is constructed for adult patient, especially on account of the clinical practice of hypothermia and anesthesia in the brain hypothermia treatment. Secondly, the model is represented by the state equation as a lumped parameter linear dynamic system. The biothermal model is justified from their various responses corresponding to clinical phenomena and treatment. Finally, the optimal regulator is tentatively designed to give clinicians some suggestions on the optimal temperature regulation of the patient’s brain. It suggests the patient’s brain temperature could be optimally controlled to follow-up the temperature process prescribed by the clinicians. This study benefits us a great clinical possibility for the automatic hypothermia treatment.

  11. Efficacy of external warming in attenuation of hypothermia in surgical patients.

    PubMed

    Zeba, Snjezana; Surbatović, Maja; Marjanović, Milan; Jevdjić, Jasna; Hajduković, Zoran; Karkalić, Radovan; Jovanović, Dalibor; Radaković, Sonja

    2016-06-01

    Hypothermia in surgical patients can be the consequence of long duration of surgical intervention, general anaesthesia and low temperature in operating room. Postoperative hypothermia contributes to a number of postoperative complications such as arrhythmia, myocardial ischemia, hypertension, bleeding, wound infection, coagulopathy, and prolonged effect of muscle relaxants. External heating procedures are used to prevent this condition. The aim of this study was to evaluate the efficiency of external warming system in alleviation of cold stress and hypothermia in patients who underwent major surgical procedures. The study was conducted in the Military Medical Academy in Belgrade. A total of 30 patients of both genders underwent abdominal surgical procedures, randomly divided into two equal groups: the one was externally warmed using warm air mattress (W), while in the control group (C) surgical procedure was performed in regular conditions, without additional warming. Oesophageal temperature (Te) was used as indicator of changes in core temperature, during surgery and awakening postoperative period, and temperature of control sites on the right hand (Th) and the right foot (Tf) reflected the changes in skin temperatures during surgery. Te and skin temperatures were monitored during the intraoperative period, with continuous measurement of Te during the following 90 minutes of the postoperative period. Heart rates and blood pressures were monitored continuously during the intraoperative and awakening period. In the W group, the average Te, Tf and Th did not change significantly during the intraoperative as well as the postoperative period. In the controls, the average Te significantly decreased during the intraoperative period (from 35.61 ± 0.35 °C at 0 minute to 33.86 ± 0.51°C at 120th minute). Compared to the W group, Te in the C group was significantly lower in all the observed periods. Average values of Tf and Th significantly decreased in the C group (from

  12. An experimental study and finite element modeling of head and neck cooling for brain hypothermia.

    PubMed

    Li, Hui; Chen, Roland K; Tang, Yong; Meurer, William; Shih, Albert J

    2018-01-01

    Reducing brain temperature by head and neck cooling is likely to be the protective treatment for humans when subjects to sudden cardiac arrest. This study develops the experimental validation model and finite element modeling (FEM) to study the head and neck cooling separately, which can induce therapeutic hypothermia focused on the brain. Anatomically accurate geometries based on CT images of the skull and carotid artery are utilized to find the 3D geometry for FEM to analyze the temperature distributions and 3D-printing to build the physical model for experiment. The results show that FEM predicted and experimentally measured temperatures have good agreement, which can be used to predict the temporal and spatial temperature distributions of the tissue and blood during the head and neck cooling process. Effects of boundary condition, perfusion, blood flow rate, and size of cooling area are studied. For head cooling, the cooling penetration depth is greatly depending on the blood perfusion in the brain. In the normal blood flow condition, the neck internal carotid artery temperature is decreased only by about 0.13°C after 60min of hypothermia. In an ischemic (low blood flow rate) condition, such temperature can be decreased by about 1.0°C. In conclusion, decreasing the blood perfusion and metabolic reduction factor could be more beneficial to cool the core zone. The results also suggest that more SBC researches should be explored, such as the optimization of simulation and experimental models, and to perform the experiment on human subjects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Unilateral brain hypothermia as a method to examine efficacy and mechanisms of neuroprotection against global ischemia.

    PubMed

    Silasi, Gergely; Colbourne, Frederick

    2011-01-01

    Hypothermia, especially applied during ischemia, is the gold-standard neuroprotectant. When delayed, cooling must often be maintained for a day or more to achieve robust, permanent protection. Most animal and clinical studies use whole-body cooling-an arduous technique that can cause systemic complications. Brain-selective cooling may avoid such problems. Thus, in this rat study, we used a method that cools one hemisphere without affecting the contralateral side or the body. Localized brain hypothermia was achieved by flushing cold water through a metal tube attached to the rats' skull. First, in anesthetized rats we measured temperature in the cooled and contralateral hemisphere to demonstrate selective unilateral cooling. Subsequent telemetry recordings in awake rats confirmed that brain cooling did not cause systemic hypothermia during prolonged treatment. Additionally, we subjected rats to transient global ischemia and after recovering from anesthesia they remained at normothermia or had their right hemisphere cooled for 2 days (∼32°C-33°C). Hypothermia significantly lessened CA1 injury and microglia activation on the right side at 1 and 4 week survival times. Near-complete injury and a strong microglia response occurred in the left (normothermic) hippocampus as occurred in both hippocampi of the untreated group. Thus, this focal cooling method is suitable for evaluating the efficacy and mechanisms of hypothermic neuroprotection in global ischemia models. This method also has advantages over many current systemic cooling protocols in rodents, namely: (1) lower cost, (2) simplicity, (3) safety and suitability for long-term cooling, and (4) an internal control-the normothermic hemisphere.

  14. Rationale, Timeline, Study Design, and Protocol Overview of the Therapeutic Hypothermia After Pediatric Cardiac Arrest Trials

    PubMed Central

    Moler, Frank W.; Silverstein, Faye S.; Meert, Kathleen L.; Clark, Amy E.; Holubkov, Richard; Browning, Brittan; Slomine, Beth S.; Christensen, James R.; Dean, Michael

    2014-01-01

    Objective To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Design Multicenter randomized controlled trials. Setting Pediatric intensive care and cardiac ICUs in the United States and Canada. Patients Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent. Interventions Therapeutic hypothermia or therapeutic normothermia. Measurements and Main Results From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015. Conclusions Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials. PMID:23842585

  15. Thermal insulation for preventing inadvertent perioperative hypothermia.

    PubMed

    Alderson, Phil; Campbell, Gillian; Smith, Andrew F; Warttig, Sheryl; Nicholson, Amanda; Lewis, Sharon R

    2014-06-04

    Inadvertent perioperative hypothermia occurs because of interference with normal temperature regulation by anaesthetic drugs and exposure of skin for prolonged periods. A number of different interventions have been proposed to maintain body temperature by reducing heat loss. Thermal insulation, such as extra layers of insulating material or reflective blankets, should reduce heat loss through convection and radiation and potentially help avoid hypothermia. To assess the effects of pre- or intraoperative thermal insulation, or both, in preventing perioperative hypothermia and its complications during surgery in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 2), MEDLINE, OvidSP (1956 to 4 February 2014), EMBASE, OvidSP (1982 to 4 February 2014), ISI Web of Science (1950 to 4 February 2014), and CINAHL, EBSCOhost (1980 to 4 February 2014), and reference lists of articles. We also searched Current Controlled Trials and ClinicalTrials.gov. Randomized controlled trials of thermal insulation compared to standard care or other interventions aiming to maintain normothermia. Two authors extracted data and assessed risk of bias for each included study, with a third author checking details. We contacted some authors to ask for additional details. We only collected adverse events if reported in the trials. We included 22 trials, with 16 trials providing data for some analyses. The trials varied widely in the type of patients and operations, the timing and measurement of temperature, and particularly in the types of co-interventions used. The risk of bias was largely unclear, but with a high risk of performance bias in most studies and a low risk of attrition bias. The largest comparison of extra insulation versus standard care had five trials with 353 patients at the end of surgery and showed a weighted mean difference (WMD) of 0.12 ºC (95% CI -0.07 to 0.31; low quality evidence). Comparing extra insulation

  16. Heart rate monitored hypothermia and drowning in a 48-year-old man. survival without sequelae: a case report.

    PubMed

    Lund, Fredrik Koller; Torgersen, Johan G R; Flaatten, Hans Kristian

    2009-08-18

    Victims of severe hypothermia and cardiac arrest may appear dead. They are often unresponsive to on-scene resuscitation including defibrillation while profoundly hypothermic. Several cases of extreme hypothermia and prolonged cardiac arrest with good outcome have been published. We present a case of heart rate monitored (by pulse-watch) hypothermia, prolonged cardiac arrest and survival with complete recovery of neurological functions. On December 22nd 2007 a physically fit, ethnic Norwegian 48-year-old male kayaker set out to paddle alone around an island in a Norwegian fjord. 3 hours 24 min into his trip the kayak capsized in 3.5 degrees C seawater about 500m from the closest shore. The accident was not observed. He managed to call for help using his cellular phone. After a search and rescue operation he was found by our air ambulance helicopter floating, prone, head submerged, with cardiopulmonary arrest and profound hypothermia. He was wearing a personal heart rate monitor/pulse watch. Following extraction, he received cardiopulmonary resuscitation during transport by air ambulance helicopter to hospital. He was warmed on cardiopulmonary bypass from 20.6 degrees C core temperature and return of spontaneous circulation was achieved 3h 27 m after cardiac arrest occurred. After 21 days of intensive care he was discharged from hospital 32 days after his accident. Testing revealed normal cognitive functions one year after the incident. He has returned to his job as an engineer, and has also taken up kayaking again. We provide heart rate and time data leading up to his cardiac arrest. Hypothermia has well established neuro-protective effects in cardiac arrest, as our case also shows. Simple cardiopulmonary resuscitation without use of drugs or defibrillation, should be continued until the patients can be re-warmed, preferably using cardiopulmonary bypass. This approach can be highly effective even in seemingly lost cases.

  17. Automatic Incubator-type Temperature Control System for Brain Hypothermia Treatment

    NASA Astrophysics Data System (ADS)

    Gaohua, Lu; Wakamatsu, Hidetoshi

    An automatic air-cooling incubator is proposed to replace the manual water-cooling blanket to control the brain tissue temperature for brain hypothermia treatment. Its feasibility is theoretically discussed as follows: First, an adult patient with the cooling incubator is modeled as a linear dynamical patient-incubator biothermal system. The patient is represented by an 18-compartment structure and described by its state equations. The air-cooling incubator provides almost same cooling effect as the water-cooling blanket, if a light breeze of speed around 3 m/s is circulated in the incubator. Then, in order to control the brain temperature automatically, an adaptive-optimal control algorithm is adopted, while the patient-blanket therapeutic system is considered as a reference model. Finally, the brain temperature of the patient-incubator biothermal system is controlled to follow up the given reference temperature course, in which an adaptive algorithm is confirmed useful for unknown environmental change and/or metabolic rate change of the patient in the incubating system. Thus, the present work ensures the development of the automatic air-cooling incubator for a better temperature regulation of the brain hypothermia treatment in ICU.

  18. Effects of Sex and Mild Intrainsult Hypothermia on Neuropathology and Neural Reorganization following Neonatal Hypoxic Ischemic Brain Injury in Rats

    PubMed Central

    Smith, Amanda L.; Rosenkrantz, Ted S.; Fitch, R. Holly

    2016-01-01

    Hypoxia ischemia (HI) is a recognized risk factor among late-preterm infants, with HI events leading to varied neuropathology and cognitive/behavioral deficits. Studies suggest a sex difference in the incidence of HI and in the severity of subsequent behavioral deficits (with better outcomes in females). Mechanisms of a female advantage remain unknown but could involve sex-specific patterns of compensation to injury. Neuroprotective hypothermia is also used to ameliorate HI damage and attenuate behavioral deficits. Though currently prescribed only for HI in term infants, cooling has potential intrainsult applications to high-risk late-preterm infants as well. To address this important clinical issue, we conducted a study using male and female rats with a postnatal (P) day 7 HI injury induced under normothermic and hypothermic conditions. The current study reports patterns of neuropathology evident in postmortem tissue. Results showed a potent benefit of intrainsult hypothermia that was comparable for both sexes. Findings also show surprisingly different patterns of compensation in the contralateral hemisphere, with increases in hippocampal thickness in HI females contrasting reduced thickness in HI males. Findings provide a framework for future research to compare and contrast mechanisms of neuroprotection and postinjury plasticity in both sexes following a late-preterm HI insult. PMID:27042359

  19. Difficulties in funding of VA-ECMO therapy for patients with severe accidental hypothermia.

    PubMed

    Kosiński, Sylweriusz; Darocha, Tomasz; Jarosz, Anna; Czerw, Aleksandra; Podsiadło, Paweł; Sanak, Tomasz; Gałązkowski, Robert; Piątek, Jacek; Konstanty-Kalandyk, Janusz; Ziętkiewicz, Mirosław; Kusza, Krzysztof; Krzych, Łukasz J; Drwiła, Rafał

    2017-01-01

    Severe accidental hypothermia is defined as a core temperature below 28 Celsius degrees. Within the last years, the issue of accidental hypothermia and accompanying cardiac arrest has been broadly discussed and European Resuscitation Council (ERC) Guidelines underline the importance of Extracorporeal Rewarming (ECR) in treatment of severely hypothermic victims. The study aimed to evaluate the actual costs of ECR with VA-ECMO and of further management in the Intensive Care Unit of patients admitted to the Severe Accidental Hypothermia Centre in Cracow, Poland. We carried out the economic analysis of 31 hypothermic adults in stage III-IV (Swiss Staging) treated with VA ECMO. Twenty-nine individuals were further managed in the Intensive Care Unit. The actual treatment costs were evaluated based on current medication, equipment, and dressing pricing. The costs incurred by the John Paul II Hospital were then collated with the National Health Service (NHS) funding, assessed based on current financial contract. In most of the cases, the actual treatment cost was greater than the funding received by around 10000 PLN per patient. The positive financial balance was achieved in only 4 (14%) individuals; other 25 cases (86%) showed a financial loss. Performed analysis clearly shows that hospitals undertaking ECR may experience financial loss due to implementation of effective treatment recommended by international guidelines. Thanks to new NHS funding policy since January 2017 such loss can be avoided, what shall encourage hospitals to perform this expensive, yet effective method of treatment.

  20. [Hypothermia as the cause of death in forensic pathology: autopsy study].

    PubMed

    Nikolić, Slobodan; Zivković, Magdalena; Zivković, Vladimir; Juković, Fehim

    2010-01-01

    The body cooling process goes through few clinical phases. These are followed by some morphological thanatological changes such as frost erythema and Wischnewsky's spots, which are used in diagnosis of death due to hypothermia. In such cases there is no any specific autopsy finding. To establish the frequency of hypothermia as the cause of death for a ten-year-period, and to analyze the sample according to gender and age, risk factors and autopsy findings of subjects. A retrospective autopsy study was performed for a ten-year-period (total of 12,765 forensic autopsies). The relevant data were collected from autopsy records, police reports and heteroanamnestic interviews. The sample was analyzed according to gender, age, scene of death, blood alcohol concentration, risk factors, and autopsy findings of all observed subjects. The sample included 67 subjects, 42 males and 25 females (chi2 = 4.31; p < 0.05), of average age 63.9 +/- 14.7 years (min=27, max=92; med=65, mod=55). Nineteen of subjects were found at in-door places. In 13 subjects blood alcohol concentration ranged from 0.50 to 3.32 promille (average 1.81 +/- 0.93). The younger the observed subject was, the higher the blood alcohol concentration (p = -0.251; p = 0.04). One third of the observed subjects were chronic alcohol abusers. Thirteen persons had psychiatric diseases. In 43 observed subjects the concomitant appearance of frost erythema and Wischniewsky's spots were established (chi2 = 49.59; df = 3; p < 0.001). In the analyzed ten-year period hypothermia was not often the cause of death; it was disclosed only in 0.5% of the total number of the studied autopsies. The most of the deceased were older males with cardiovascular problems found in unprotected open-air places. The most frequent thanatological findings in the analyzed subjects were frost erythema and Wischnewsky's spots.

  1. Reducing hypothermia in preterm infants with polyethylene wrap.

    PubMed

    Rohana, Jaafar; Khairina, Wan; Boo, Nem Yun; Shareena, Ishak

    2011-08-01

    Occlusive plastic applied immediately after birth to reduce evaporative heat loss has been proven effective in preterm infants <28 weeks' gestation. However its effectiveness on preterm infants >28 weeks' gestation has not been shown. This study aimed to determine the effect of occlusive wrap at birth on the temperature at neonatal intensive care unit (NICU) admission among infants of greater than or equal to 24 weeks' and less than 34 weeks' gestation. Study infants were randomly assigned to "wrap" or "control" groups. Newborns in the wrap group were wrapped with polyethylene plastic sheets within the first min after birth. Infants randomized to the control group were dried immediately after birth with warmed towels under a warmer, according to the guidelines of Neonatal Resuscitation. Infants' axillary temperatures were measured on admission to the NICU, and after having been stabilized in incubators in the NICU. A total of 110 infants were recruited into the study. The mean admission temperature was significantly higher in the wrap group (35.8 vs 34.8°C, P < 0.01). Admission hypothermia (axillary temperature <36.5°C) was present in 38 (78%) and 58 (98%) infants in the wrap and control groups, respectively. Among infants of <28 weeks' gestation, the post-stabilization temperature was significantly higher in the wrap group. Wrapping premature infants with gestational age <34 weeks in polyethylene plastics immediately after birth is associated with lower incidence of hypothermia. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

  2. Pharmacokinetics and clinical efficacy of phenobarbital in asphyxiated newborns treated with hypothermia: a thermopharmacological approach.

    PubMed

    van den Broek, M P H; Groenendaal, F; Toet, M C; van Straaten, H L M; van Hasselt, J G C; Huitema, A D R; de Vries, L S; Egberts, A C G; Rademaker, C M A

    2012-10-01

    Therapeutic hypothermia can influence the pharmacokinetics and pharmacodynamics of drugs, the discipline which is called thermopharmacology. We studied the effect of therapeutic hypothermia on the pharmacokinetics of phenobarbital in asphyxiated neonates, and the clinical efficacy and the effect of phenobarbital on the continuous amplitude-integrated electroencephalography (aEEG) in a prospective study. Data were obtained from the prospective SHIVER study, performed in two of the ten Dutch level III neonatal intensive care units. Phenobarbital data were collected between 2008 and 2010. Newborns were eligible for inclusion if they had a gestational age of at least 36 weeks and presented with perinatal asphyxia and encephalopathy. According to protocol in both hospitals an intravenous (repeated) loading dose of phenobarbital 20 mg/kg divided in 1-2 doses was administered if seizures occurred or were suspected before or during the hypothermic phase. Phenobarbital plasma concentrations were measured in plasma using a fluorescence polarization immunoassay. aEEG was monitored continuously. A one-compartmental population pharmacokinetic/pharmacodynamic model was developed using a multi-level Markov transition model. No (clinically relevant) effect of moderate therapeutic hypothermia on phenobarbital pharmacokinetics could be identified. The observed responsiveness was 66%. While we still advise an initial loading dose of 20 mg/kg, clinicians should not be reluctant to administer an additional dose of 10-20 mg/kg. An additional dose should be given before switching to a second-line anticonvulsant drug. Based on our pharmacokinetic/pharmacodynamic model, administration of phenobarbital under hypothermia seems to reduce the transition rate from a continuous normal voltage (CNV) to discontinuous normal voltage aEEG background level in hypothermic asphyxiated newborns, which may be attributed to the additional neuroprotection of phenobarbital in infants with a CNV pattern.

  3. Hypothermia translocates nitric oxide synthase from cytosol to membrane in snail neurons.

    PubMed

    Rószer, Tamás; Kiss-Tóth, Eva; Rózsa, Dávid; Józsa, Tamás; Szentmiklósi, A József; Bánfalvi, Gáspár

    2010-11-01

    Neuronal nitric oxide (NO) levels are modulated through the control of catalytic activity of NO synthase (NOS). Although signals limiting excess NO synthesis are being extensively studied in the vertebrate nervous system, our knowledge is rather limited on the control of NOS in neurons of invertebrates. We have previously reported a transient inactivation of NOS in hibernating snails. In the present study, we aimed to understand the mechanism leading to blocked NO production during hypothermic periods of Helix pomatia. We have found that hypothermic challenge translocated NOS from the cytosol to the perinuclear endoplasmic reticulum, and that this cytosol to membrane trafficking was essential for inhibition of NO synthesis. Cold stress also downregulated NOS mRNA levels in snail neurons, although the amount of NOS protein remained unaffected in response to hypothermia. Our studies with cultured neurons and glia cells revealed that glia-neuron signaling may inhibit membrane binding and inactivation of NOS. We provide evidence that hypothermia keeps NO synthesis "hibernated" through subcellular redistribution of NOS.

  4. Hypothermia in VGKC antibody-associated limbic encephalitis.

    PubMed

    Jacob, S; Irani, S R; Rajabally, Y A; Grubneac, A; Walters, R J; Yazaki, M; Clover, L; Vincent, A

    2008-02-01

    Voltage-gated potassium channel antibody (VGKC-Ab)-associated limbic encephalitis (LE) is a recently described syndrome that broadens the spectrum of immunotherapy-responsive central nervous system disorders. Limbic encephalitis is typically characterised by a sub-acute onset of disorientation, amnesia and seizures, but the clinical spectrum is not yet fully defined and the syndrome could be under-diagnosed. We here describe the clinical profile of four patients with VGKC-Ab-associated LE who had intermittent, episodic hypothermia. One of the patients also described a prodrome of severe neuropathic pain preceding the development of limbic symptoms. Both of these novel symptoms responded well to immunosuppressive therapy, with concurrent amelioration of amnesia/seizures.

  5. Conversion of elderly to Alzheimer's dementia: role of confluence of hypothermia and senescent stigmata--the plausible pathway.

    PubMed

    Daulatzai, Mak Adam

    2010-01-01

    Aging is a consequence of progressive decline in special and somatosensory functions and specific brain stem nuclei. Many senescent stigmata, including hypoxia, hypoxemia, depressed cerebral blood flow and glucose metabolism, diseases of senescence, and their medications all enhance hypothermia as do alcohol, cold environment, and malnutrition. Hypothermia is a critical factor having deleterious impact on brain stem and neocortical functions. Additionally, anesthesia in elderly also promotes hypothermia; anesthetics not only cause consciousness (sensory and motor) changes, but memory impairment as well. Anesthesia inhibits cholinergic pathways, reticular and thalamocortical systems, cortico-cortical connectivity, and causes post-operative delirium and cognitive dysfunction. Increasing evidence indicates that anesthetic exposures may contribute to dementia onset and Alzheimer's disease (AD) in hypothermic elderly. Inhaled anesthetics potentiate caspases, BACE, tau hyperphosphorylation, and apoptosis. This paper addresses the important question: "Why do only some elderly fall victim to AD"? Based on information on the pathogenesis of early stages of cognitive dysfunction in elderly (i.e., due to senescent stigmata), and the effects of anesthesia superimposed, a detailed plausible neuropathological substrate (mechanism/pathway) is delineated here that reveals the possible cause(s) of AD. Basically, it encompasses several risk factors for cognitive dysfunction during senescence plus several hypothermia-enhancing routes; they all converge and tip the balance towards dementia onset. This knowledge of the confluence of heterogeneous risk factors in perpetuating dementia relentlessly is of importance in order to: (a) avoid their convergence; (b) take measures to stop/reverse cognitive dysfunction; and (c) to develop therapeutic strategies to enhance cognitive function and attenuate AD.

  6. Fulfilling caloric demands according to indirect calorimetry may be beneficial for post cardiac arrest patients under therapeutic hypothermia.

    PubMed

    Oshima, Taku; Furukawa, Yutaka; Kobayashi, Michihiko; Sato, Yumi; Nihei, Aya; Oda, Shigeto

    2015-03-01

    We sought to investigate the energy requirements for patients under therapeutic hypothermia, and the relationship of energy fulfillment to patient outcome. Adult patients admitted to our ICU after successful resuscitation from cardiac arrest for post resuscitation therapeutic hypothermia from April, 2012 to March, 2014 were enrolled. Body temperature was managed using the surface cooling device (Arctic Sun(®), IMI). Calorimeter module on the ventilator (Engström carestation(®), GE) was used for indirect calorimetry. Energy expenditure (EE) and respiratory quotient (RQ) were recorded continuously, as the average of the recent 2h. Measurements were started at the hypothermic phase and continued until the rewarming was completed. Cumulative energy deficit was calculated as the sum of difference between EE and daily energy provision for the 4 days during hypothermia therapy. Seven patients were eligible for analysis. Median EE for the hypothermic phase (day 1) was 1557.0kcald(-1). EE was elevated according with the rise in body temperature, reaching 2375kcald(-1) at normothermic phase. There was significant association between cumulative energy deficit and the length of ICU stay, among patients with good neurologic recovery (cerebral performance category (CPC): 1-3). The EE for patients under therapeutic hypothermia was higher than expected. Meeting the energy demand may improve patient outcome, as observed in the length of ICU stay for the present study. A larger, prospective study is awaited to validate the results of our study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. A Proposed Methodology to Control Body Temperature in Patients at Risk of Hypothermia by means of Active Rewarming Systems

    PubMed Central

    Costanzo, Silvia; Cusumano, Alessia; Giaconia, Carlo; Mazzacane, Sante

    2014-01-01

    Hypothermia is a common complication in patients undergoing surgery under general anesthesia. It has been noted that, during the first hour of surgery, the patient's internal temperature (T core) decreases by 0.5–1.5°C due to the vasodilatory effect of anesthetic gases, which affect the body's thermoregulatory system by inhibiting vasoconstriction. Thus a continuous check on patient temperature must be carried out. The currently most used methods to avoid hypothermia are based on passive systems (such as blankets reducing body heat loss) and on active ones (thermal blankets, electric or hot-water mattresses, forced hot air, warming lamps, etc.). Within a broader research upon the environmental conditions, pollution, heat stress, and hypothermia risk in operating theatres, the authors set up an experimental investigation by using a warming blanket chosen from several types on sale. Their aim was to identify times and ways the human body reacts to the heat flowing from the blanket and the blanket's effect on the average temperature T skin and, as a consequence, on T core temperature of the patient. The here proposed methodology could allow surgeons to fix in advance the thermal power to supply through a warming blanket for reaching, in a prescribed time, the desired body temperature starting from a given state of hypothermia. PMID:25485278

  8. [Pinealon and Cortexin influence on behavior and neurochemical processes in 18-month aged rats within hypoxia and hypothermia].

    PubMed

    Mendzheritsky, A M; Karantysh, G V; Ryzhak, G A; Prokofiev, V N

    The research of Cortexin and Pinealon within two models of stress, acute hypobaric hypoxia and mild hypothermia, within 18-month aged rats has been held. The peculiarities of peptide preparations' influence on behavior and neurochemical indeces have been identified. Cortexin shows a more pronounced effect on free radical processes and caspase 3 activity in brain than Pinealon. Both preparations forward an accumulation of adrenergic mediator within rats' brains in the model of acute hypobaric hypoxia, as well as serotonin within cerebrum cortex in the model of mild hypothermia, which may underlie their geroprotective effects.

  9. Secondary Increase of Lactate Levels in Asphyxiated Newborns during Hypothermia Treatment: Reflect of Suboptimal Hemodynamics (A Case Series and Review of the Literature)

    PubMed Central

    Al Balushi, Asim; Guilbault, Marie-Pier; Wintermark, Pia

    2015-01-01

    Objective To evaluate whether a secondary increase of serum lactate levels in asphyxiated newborns during hypothermia treatment may reflect suboptimal dynamics. Methods–Retrospective case series and review of the literature. We present the clinical course of four asphyxiated newborns treated with hypothermia who presented with hypotension requiring inotropic support, and who displayed a secondary increase of serum lactate levels during hypothermia treatment. Serial serum lactate levels are correlated with blood pressure and inotropic support within the first 96 hours of life. Results Lactate levels initially decreased in the four patients. However, each of them started to present lower blood pressure, and lactate levels started to increase again. Inotropic support was started to raise blood pressure. The introduction of an epinephrine drip consistently worsened the increase of lactate levels in these newborns, whereas dopamine and dobutamine enabled the clearance of lactate in addition to raising the blood pressure. Rewarming was associated with hemodynamics perturbations (a decrease of blood pressure and/or an increase of lactate levels) in the three newborns who survived. Conclusions Lactate levels during the first 4 days of life should be followed as a potential marker for suboptimal hemodynamic status in term asphyxiated newborns treated with hypothermia, for whom the maintenance of homeostasis during hypothermia treatment is of utmost importance to alleviate brain injury. PMID:26929870

  10. A Comparison of the Protection against Immersion Hypothermia Provided by Coast Guard Anti-Exposure Clothing in Calm Versus Rough Seas

    DTIC Science & Technology

    1985-06-01

    34 insulated garments excluded cold-water entry, tightness-of-fit was not an important factor in thermal performance. The "dry" garments in this study were...Supplemertary Notes I 16. Abstruct The puirpose of this study was to caopare the protection against immersion hypothermia provided by various types of Coat...survival tize pro ons fron calmr-veter studies . 17. Key Words 18. Distribution Statement Hypothermia Rough water Immersion Protective clothing Sea

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

    PubMed

    Zafren, Ken; Giesbrecht, Gordon G; Danzl, Daniel F; Brugger, Hermann; Sagalyn, Emily B; Walpoth, Beat; Weiss, Eric A; Auerbach, Paul S; McIntosh, Scott E; Némethy, Mária; McDevitt, Marion; Dow, Jennifer; Schoene, Robert B; Rodway, George W; Hackett, Peter H; Bennett, Brad L; Grissom, Colin K

    2014-12-01

    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. Copyright © 2014 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  12. Beta blocker infusion decreases the magnitude of core hypothermia after anesthesia induction.

    PubMed

    Inoue, S; Abe, R; Kawaguchi, M; Kobayashi, H; Furuya, H

    2010-12-01

    Beta-1-receptor blockade reduces heart rate, cardiac output, and arterial pressure while increasing peripheral vascular resistance. It is possible that beta blockers not only inhibit the core-to-peripheral re-distribution of body heat and cutaneous heat loss due to vasodilation after anesthesia induction but also reduce the convective transfer of heat from the core to peripheral tissues by decreasing cardiac output. The authors investigated whether the co-administration of esmolol or landiolol, ultra-short-acting beta blockers, attenuates the magnitude of initial re-distribution hypothermia after anesthesia induction and tracheal intubation. Immediately prior to the induction of anesthesia, patients were randomly assigned to receive 0.2 mg kg-1 of landiolol (landiolol group; N=30), 1 mg kg-1 of esmolol (esmolol group; N=30), or 0.1 mL kg-1 of saline (control group; N=30). Heart rate, blood pressure, cardiac output, and tympanic, forearm, and digit temperatures were recorded. Forearm minus fingertip skin-surface temperature gradients (temperature gradient) were calculated. Tympanic membrane temperatures 15 to 60 min after the induction of anesthesia were significantly higher in the esmolol group than in the control group although the temperature gradient was similar among the three groups. Both esmolol and landiolol inhibited the increase in HR and MAP after the induction of anesthesia and tracheal intubation. The cardiac index in the esmolol group was significantly lower than in the control group. The degree of hemodynamic attenuation after induction by esmolol was larger than that of landiolol. The co-administration of esmolol, but not landiolol, attenuated the magnitude of initial re-distribution hypothermia after anesthesia induction and tracheal intubation. Esmolol likely prevented initial hypothermia because it attenuated the convective transfer of heat from the core to peripheral tissues by decreasing cardiac output.

  13. Systemic hypothermia to prevent radiocontrast nephropathy (from the COOL-RCN Randomized Trial).

    PubMed

    Stone, Gregg W; Vora, Kishor; Schindler, John; Diaz, Claro; Mann, Tift; Dangas, George; Best, Patricia; Cutlip, Donald E

    2011-09-01

    Radiocontrast nephropathy (RCN) develops in a substantial proportion of patients with chronic kidney disease (CKD) after invasive cardiology procedures and is strongly associated with subsequent mortality and adverse outcomes. We sought to determine whether systemic hypothermia is effective in preventing RCN in patients with CKD. Patients at risk for RCN (baseline estimated creatinine clearance 20 to 50 ml/min) undergoing cardiac catheterization with iodinated contrast ≥50 ml were randomized 1:1 to hydration (control arm) versus hydration plus establishment of systemic hypothermia (33°C to 34°C) before first contrast injection and for 3 hours after the procedure. Serum creatinine levels at baseline, 24 hours, 48 hours, and 72 to 96 hours were measured at a central core laboratory. The primary efficacy end point was development of RCN, defined as an increase in serum creatinine by ≥25% from baseline. The primary safety end point was 30-day composite rate of adverse events consisting of death, myocardial infarction, dialysis, ventricular fibrillation, venous complication requiring surgery, major bleeding requiring transfusion ≥2 U, or rehospitalization. In total 128 evaluable patients (mean creatinine clearance 36.6 ml/min) were prospectively randomized at 25 medical centers. RCN developed in 18.6% of normothermic patients and in 22.4% of hypothermic patients (odds ratio 1.27, 95% confidence interval 0.53 to 3.00, p = 0.59). The primary 30-day safety end point occurred in 37.1% versus 37.9% of normothermic and hypothermic patients, respectively (odds ratio 0.97, 95% confidence interval 0.47 to 1.98, p = 0.93). In conclusion, in patients with CKD undergoing invasive cardiology procedures, systemic hypothermia is safe but is unlikely to prevent RCN. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. The Thompson Encephalopathy Score and Short-Term Outcomes in Asphyxiated Newborns Treated With Therapeutic Hypothermia.

    PubMed

    Thorsen, Patricia; Jansen-van der Weide, Martine C; Groenendaal, Floris; Onland, Wes; van Straaten, Henrika L M; Zonnenberg, Inge; Vermeulen, Jeroen R; Dijk, Peter H; Dudink, Jeroen; Rijken, Monique; van Heijst, Arno; Dijkman, Koen P; Cools, Filip; Zecic, Alexandra; van Kaam, Anton H; de Haan, Timo R

    2016-07-01

    The Thompson encephalopathy score is a clinical score to assess newborns suffering from perinatal asphyxia. Previous studies revealed a high sensitivity and specificity of the Thompson encephalopathy score for adverse outcomes (death or severe disability). Because the Thompson encephalopathy score was developed before the use of therapeutic hypothermia, its value was reassessed. The purpose of this study was to assess the association of the Thompson encephalopathy score with adverse short-term outcomes, defined as death before discharge, development of severe epilepsy, or the presence of multiple organ failure in asphyxiated newborns undergoing therapeutic hypothermia. The study period ranged from November 2010 to October 2014. A total of 12 tertiary neonatal intensive care units participated. Demographic and clinical data were collected from the "PharmaCool" multicenter study, an observational cohort study analyzing pharmacokinetics of medication during therapeutic hypothermia. With multiple logistic regression analyses the association of the Thompson encephalopathy scores with outcomes was studied. Data of 142 newborns were analyzed (male: 86; female: 56). Median Thompson score was 9 (interquartile range: 8 to 12). Median gestational age was 40 weeks (interquartile range 38 to 41), mean birth weight was 3362 grams (standard deviation: 605). All newborns manifested perinatal asphyxia and underwent therapeutic hypothermia. Death before discharge occurred in 23.9% and severe epilepsy in 21.1% of the cases. In total, 59.2% of the patients had multiple organ failure. The Thompson encephalopathy score was not associated with multiple organ failure, but a Thompson encephalopathy score ≥12 was associated with death before discharge (odds ratio: 3.9; confidence interval: 1.3 to 11.2) and with development of severe epilepsy (odds ratio: 8.4; confidence interval: 2.5 to 27.8). The Thompson encephalopathy score is a useful clinical tool, even in cooled asphyxiated

  15. Nurses' Attitudes toward Clinical Research: Experience of the Therapeutic Hypothermia after Pediatric Cardiac Arrest Trials

    PubMed Central

    Browning, Brittan; Page, Kent E.; Kuhn, Renee L.; DiLiberto, Mary Ann; Deschenes, Jendar; Taillie, Eileen; Tomanio, Elyse; Holubkov, Richard; Dean, J. Michael; Moler, Frank W.; Meert, Kathleen; Pemberton, Victoria L.

    2016-01-01

    Objectives To understand factors affecting nurses' attitudes towards the Therapeutic Hypothermia after Pediatric Cardiac Arrest (THAPCA) trials and association with approach/consent rates. Design, setting and participants Cross sectional survey of pediatric/cardiac intensive care nurses' perceptions of the trials, conducted at 16 of 38 self-selected study sites. Measurements The primary outcome was the proportion of nurses with positive perceptions, as defined by agree or strongly agree with the statement “I am happy to take care of a THAPCA patient”. Associations between perceptions and study approach/consent rates were also explored. Results Of 2241 nurses invited, 1387 (62%) completed the survey and 77% reported positive perceptions of the trials. Nurses, who felt positively about the scientific question, the study team, and training received, were more likely to have positive perceptions of the trials (p <0.001). Nurses who had previously cared for a research patient had significantly more positive perceptions of THAPCA compared with those who had not (79% vs. 54%, p<0.001). Of the 754 nurses who cared for a THAPCA patient, 82% had positive perceptions, despite 86% reporting it required more work. Sixty-nine percent believed that hypothermia reduces brain injury and mortality; sites had lower consent rates when their nurses believed that hypothermia was beneficial. Institution-specific approach rates were positively correlated with nurses' perceptions of institutional support for the trial (r=0.54, p=0.04), intensive care unit support (r=0.61, p=0.02), and the importance of conducting the trial in children (r=0.61, p=0.01). Conclusions The majority of nurses had positive perceptions of the THAPCA trials. Institutional, colleague and study team support and training were contributing factors. Despite increased work, nurses remained enthusiastic demonstrating that studies with intensive bedside nursing procedures are feasible. Institutions whose nurses

  16. Prediction of outcome in asphyxiated newborns treated with hypothermia: Is a MRI scoring system described before the cooling era still useful?

    PubMed

    Al Amrani, Fatema; Marcovitz, Jaclyn; Sanon, Priscille-Nice; Khairy, May; Saint-Martin, Christine; Shevell, Michael; Wintermark, Pia

    2018-05-01

    To determine whether an MRI scoring system, which was validated in the pre-cooling era, can still predict the neurodevelopmental outcome of asphyxiated newborns treated with hypothermia at 2 years of age. We conducted a retrospective cohort study of asphyxiated newborns treated with hypothermia. An MRI scoring system, which was validated in the pre-cooling era, was used to grade the severity of brain injury on the neonatal brain MRI. Their neurodevelopment was assessed around 2 years of age; adverse outcome included cerebral palsy, global developmental delay, and/or epilepsy. One hundred and sixty-nine newborns were included. Among the 131 newborns who survived and had a brain MRI during the neonatal period, 92% were evaluated around 2 years of age or later. Of these newborns, 37% displayed brain injury, and 23% developed an adverse outcome. Asphyxiated newborns treated with hypothermia who had an adverse outcome had a significantly higher MRI score (p <0.001) compared to those without an adverse outcome. An MRI scoring system that was validated before the cooling era is still able to reliably differentiate which of the asphyxiated newborns treated with hypothermia were more prone to develop an adverse outcome around 2 years of age. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  17. Too cold may not be so cool: spontaneous hypothermia as a marker of poor outcome after cardiac arrest.

    PubMed

    Wörner, Jakobea; Oddo, Mauro

    2010-01-01

    In a recent issue of Critical Care, den Hartog and colleagues show an association between spontaneous hypothermia, defined by an admission body temperature < 35°C, and poor outcome in patients with coma after cardiac arrest (CA) treated with therapeutic hypothermia (TH). Given that TH alters neurological prognostication, studies aiming to identify early markers of injury severity and outcome are welcome, since they may contribute overall to optimize the management of comatose CA patients. This study provides an important message to clinicians involved in post-resuscitation care and raises important questions that need to be taken into account in future studies.

  18. Model-based investigation of intracellular processes determining antibody Fc-glycosylation under mild hypothermia.

    PubMed

    Sou, Si Nga; Jedrzejewski, Philip M; Lee, Ken; Sellick, Christopher; Polizzi, Karen M; Kontoravdi, Cleo

    2017-07-01

    Despite the positive effects of mild hypothermic conditions on monoclonal antibody (mAb) productivity (q mAb ) during mammalian cell culture, the impact of reduced culture temperature on mAb Fc-glycosylation and the mechanism behind changes in the glycan composition are not fully established. The lack of knowledge about the regulation of dynamic intracellular processes under mild hypothermia restricts bioprocess optimization. To address this issue, a mathematical model that quantitatively describes Chinese hamster ovary (CHO) cell behavior and metabolism, mAb synthesis and mAb N-linked glycosylation profile before and after the induction of mild hypothermia is constructed. Results from this study show that the model is capable of representing experimental results well in all of the aspects mentioned above, including the N-linked glycosylation profile of mAb produced under mild hypothermia. Most importantly, comparison between model simulation results for different culture temperatures suggests the reduced rates of nucleotide sugar donor production and galactosyltransferase (GalT) expression to be critical contributing factors that determine the variation in Fc-glycan profiles between physiological and mild hypothermic conditions in stable CHO transfectants. This is then confirmed using experimental measurements of GalT expression levels, thereby closing the loop between the experimental and the computational system. The identification of bottlenecks within CHO cell metabolism under mild hypothermic conditions will aid bioprocess optimization, for example, by tailoring feeding strategies to improve NSD production, or manipulating the expression of specific glycosyltransferases through cell line engineering. Biotechnol. Bioeng. 2017;114: 1570-1582. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals Inc. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals Inc.

  19. Apoplastic sugars and cell-wall invertase are involved in formation of the tolerance of cold-resistant potato plants to hypothermia.

    PubMed

    Deryabin, A N; Burakhanova, E A; Trunova, T I

    2015-01-01

    We studied the involvement of apoplastic sugars (glucose, fructose, and sucrose) and the cell-wall invertase (CWI) in the formation of the tolerance of cold-resistant potato plants (Solanum tuberosum L., cv Désirée) to hypothermia. The activity of CW1 and the content in the cell and the apoplast substrate (sucrose) and the reaction products of this enzyme (glucose and fructose) have a significant influence on the formation of the tolerance of cold-resistant potato plants to hypothermia.

  20. Interventions to prevent hypothermia at birth in preterm and/or low birthweight infants.

    PubMed

    McCall, E M; Alderdice, F A; Halliday, H L; Jenkins, J G; Vohra, S

    2008-01-23

    Hypothermia incurred during routine postnatal resuscitation is a world-wide issue (across all climates), associated with morbidity and mortality. Keeping vulnerable preterm infants warm is problematic even when recommended routine thermal care guidelines are followed in the delivery suite. To assess efficacy and safety of interventions designed for prevention of hypothermia in preterm and/or low birthweight infants applied within ten minutes after birth in the delivery suite compared with routine thermal care. The standard search strategy of The Cochrane Collaboration was followed. Electronic databases were searched: MEDLINE (1966 to July Week 4 2007 ), CINAHL (1982 to July Week 4 2007), EMBASE (1974 to 01/08/2007), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), Database of Abstracts of Reviews of Effects (DARE 1994 to July 2007), conference/symposia proceedings using ZETOC (1993 to 17/08/2007), ISI proceedings (1990 to 17/08/2007) and OCLC WorldCat (July 2007). Identified articles were cross-referenced. No language restrictions were imposed. All trials using randomised or quasi-randomised allocations to test a specific intervention designed to prevent hypothermia, (apart from 'routine' thermal care) applied within 10 minutes after birth in the delivery suite to infants of < 37 weeks' gestational age or birthweight

  1. Interventions to prevent hypothermia at birth in preterm and/or low birthweight babies.

    PubMed

    McCall, E M; Alderdice, F A; Halliday, H L; Jenkins, J G; Vohra, S

    2005-01-25

    Hypothermia incurred during routine postnatal resuscitation is a world-wide issue (across all climates), with associated morbidity and mortality. Keeping vulnerable preterm infants warm is problematic even when recommended routine thermal care guidelines are followed in the delivery suite. To assess efficacy and safety of interventions, designed for prevention of hypothermia in preterm and/or low birthweight infants, applied within 10 minutes after birth in the delivery suite compared with routine thermal care. The standard search strategy of The Cochrane Collaboration was followed. Electronic databases were searched: MEDLINE (1966 to May Week 4 2004 ), CINAHL (1982 to May Week 4 2004), EMBASE (1974 to 09/07/04), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), Database of Abstracts of Reviews of Effects (DARE 1994 to July 2004), conference/symposia proceedings using ZETOC (1993 to July 2004), ISI proceedings (1990 to 09/07/2004) and OCLC WorldCat (July 2004). Identified articles were cross-referenced. No language restrictions were imposed. All trials using randomised or quasi-randomised allocations to test a specific intervention designed to prevent hypothermia, (apart from 'routine' thermal care) applied within 10 minutes after birth in the delivery suite to infants of < 37 weeks' gestational age or birthweight

  2. Radioprotection in depressed metabolic states: The physiology of helium-cold hypothermia

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.

    1973-01-01

    The use of hypothermia as a means of radiation protection was studied on a variety of mammals exposed to 80% helium-20% oxygen atmospheres at low ambient temperatures. Results show that the LD for normothermic animals significantly increased compared with hypothermic animals; similar results were obtained for hibernating mammalians. Pre-exposure of animals to cold temperatures increased their ability to withstand radiation levels close to LD sub 50.

  3. Bumetanide augments the neuroprotective efficacy of phenobarbital plus hypothermia in a neonatal hypoxia-ischemia model

    PubMed Central

    Liu, YiQing; Shangguan, Yu; Barks, John D.E.; Silverstein, Faye S.

    2014-01-01

    The NaKCl cotransporter NKCC1 facilitates intraneuronal chloride accumulation in the developing brain. Bumetanide, a clinically available diuretic, inhibits this chloride transporter, and augments the antiepileptic effects of phenobarbital in neonatal rodents. In a neonatal cerebral hypoxia-ischemia (HI) model, elicited by right carotid ligation, followed by 90 min 8% O2 exposure in 7-day-old(P7) rats, phenobarbital(PB) increases the neuroprotective efficacy of hypothermia. We evaluated whether bumetanide influenced the neuroprotective efficacy of combination treatment with PB and hypothermia(HT). P7 rats underwent HI lesioning; 15 min later, all received PB (30 mg/kg). 10 min later, half received bumetanide (10 mg/kg, PB-HT+BUM) and half received saline (PB-HT+SAL). One hour after HI, all were cooled (30°C, 3h). Contralateral forepaw sensorimotor function and brain damage were evaluated 1 to 4 weeks later. Forepaw functional measures were close to normal in the PB-HT+BUM group, while deficits persisted in PB-HT+SAL controls; there were corresponding reductions in right cerebral hemisphere damage (at P35, % damage: PB-HT+BUM, 21±16 versus 38±20 in controls). These results provide evidence that NKCC1 inhibition amplifies phenobarbital bioactivity in the immature brain, and suggest that co-administration of phenobarbital and bumetanide may represent a clinically feasible therapy to augment the neuroprotective efficacy of therapeutic hypothermia in asphyxiated neonates. PMID:22398701

  4. A recommended early goal-directed management guideline for the prevention of hypothermia-related transfusion, morbidity, and mortality in severely injured trauma patients.

    PubMed

    Perlman, Ryan; Callum, Jeannie; Laflamme, Claude; Tien, Homer; Nascimento, Barto; Beckett, Andrew; Alam, Asim

    2016-04-20

    Hypothermia is present in up to two-thirds of patients with severe injury, although it is often disregarded during the initial resuscitation. Studies have revealed that hypothermia is associated with mortality in a large percentage of trauma cases when the patient's temperature is below 32 °C. Risk factors include the severity of injury, wet clothing, low transport unit temperature, use of anesthesia, and prolonged surgery. Fortunately, associated coagulation disorders have been shown to completely resolve with aggressive warming. Selected passive and active warming techniques can be applied in damage control resuscitation. While treatment guidelines exist for acidosis and bleeding, there is no evidence-based approach to managing hypothermia in trauma patients. We synthesized a goal-directed algorithm for warming the severely injured patient that can be directly incorporated into current Advanced Trauma Life Support guidelines. This involves the early use of warming blankets and removal of wet clothing in the prehospital phase followed by aggressive rewarming on arrival at the hospital if the patient's injuries require damage control therapy. Future research in hypothermia management should concentrate on applying this treatment algorithm and should evaluate its influence on patient outcomes. This treatment strategy may help to reduce blood loss and improve morbidity and mortality in this population of patients.

  5. 1H-MRSI pattern perturbation in a mouse glioma: the effects of acute hyperglycemia and moderate hypothermia.

    PubMed

    Simões, R V; Delgado-Goñi, T; Lope-Piedrafita, S; Arús, C

    2010-01-01

    MR spectroscopic Imaging (MRSI), with PRESS localization, is used here to monitor the effects of acute hyperglycemia in the spectral pattern of 11 mice bearing GL261 gliomas at normothermia (36.5-37.5 degrees C) and at hypothermia (28.5-29.5 degrees C). These in vivo studies were complemented by ex vivo high resolution magic angle spinning (HR-MAS) analysis of GL261 tumor samples from 6 animals sacrificed by focused microwave irradiation, and blood glucose measurements in 12 control mice. Apparent glucose levels, monitored by in vivo MRSI in brain tumors during acute hyperglycemia, rose to an average of 1.6-fold during hypothermia (p < 0.05), while no significant changes were detected at normothermia, or in control experiments performed at euglycemia, or in normal/peritumoral brain regions. Ex vivo analysis of glioma-bearing mouse brains at hypothermia revealed higher glucose increases in distinct regions during the acute hyperglycemic challenge (up to 6.6-fold at the tumor center), in agreement with maximal in vivo blood glucose changes (5-fold). Phantom studies on taurine plus glucose containing solutions explained the differences between in vivo and ex vivo measurements. Our results also indicate brain tumor heterogeneity in the four animal tumors investigated in response to a defined metabolic challenge.

  6. Prevention of hypothermia by infusion of warm fluid during abdominal surgery.

    PubMed

    Xu, Hong-xia; You, Zhi-Jian; Zhang, Hong; Li, Zhiqing

    2010-12-01

    Perioperative hypothermia can lead to a number of complications for patients after surgery. The aim of this pilot study was to evaluate the efficacy of warm fluids in maintaining normal core temperature during the intraoperative period. We studied 30 American Society of Anesthesiologists (ASA) physical status I or II adult patients who required general anesthesia for abdominal surgery. In the control group (n = 15), fluids were infused at room temperature; in the test group (n = 15), fluids were infused at 37° C. In the control group, core temperature decreased to 35.5 ± 0.3° C during the first 3 hours, and then stabilized at the end of anesthesia. In the test group, core temperature decreased during the first 60 minutes, but increased to 36.9 ± 0.3° C at the end of anesthesia. In the control group, eight patients shivered at grade ≥2. In the test group, none of the patients reached grade ≥2 (P < .01). Infusion of warm fluid is effective in keeping patients nearly normothermic and preventing postanesthetic shivering. It may provide an easy and effective method for prevention of perioperative hypothermia. Copyright © 2010 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

  7. Patient Outcomes After Palliative Care Consultation Among Patients Undergoing Therapeutic Hypothermia.

    PubMed

    Pinto, Priya; Brown, Tartania; Khilkin, Michael; Chuang, Elizabeth

    2018-04-01

    To compare the clinical outcomes of patients who did and did not receive palliative care consultation among those who experienced out-of-hospital cardiac arrest and underwent therapeutic hypothermia. We identified patients at a single academic medical center who had undergone therapeutic hypothermia after out-of-hospital cardiac arrest between 2009 and 2013. We performed a retrospective chart review for demographic data, hospital and critical care length of stay, and clinical outcomes of care. We reviewed the charts of 62 patients, of which 35 (56%) received a palliative care consultation and 27 (44%) did not. Palliative care consultation occurred an average of 8.3 days after admission. Patients receiving palliative care consultation were more likely to have a do-not-resuscitate (DNR) order placed (odds ratio: 2.3, P < .001). The mean length of stay in the hospital was similar for patients seen by palliative care or not (16.7 vs 17.1 days, P = .90). Intensive care length of stay was also similar (11.3 vs 12.6 days, P = .55). Palliative care consultation was underutilized and utilized late in this cohort. Palliative consultation was associated with DNR orders but did not affect measures of utilization such as hospital and intensive care length of stay.

  8. Bolus oral or continuous intestinal amino acids reduce hypothermia during anesthesia in rats.

    PubMed

    Imoto, Akinobu; Yokoyama, Takeshi; Suwa, Kunio; Yamasaki, Fumiyasu; Yatabe, Tomoaki; Yokoyama, Reiko; Yamashita, Koichi; Selldén, Eva

    2010-01-01

    We hypothesized that, with oral or intestinal administration of amino acids (AA), we may reduce hypothermia during general anesthesia as effectively as with intravenous AA. We, therefore, examined the effect of bolus oral and continuous intestinal AA in preventing hypothermia in rats. Male Wistar rats were anesthetized with sevoflurane for induction and with propofol for maintenance. In the first experiment, 30 min before anesthesia, rats received one bolus 42 mL/kg of AA solution (100 g/L) or saline orally. Then for the next 3 h during anesthesia, they received 14 mL/kg/h of AA and/or saline intravenously. They were in 4 groups: I-A/A, both AA; I-A/S, oral AA and intravenous saline; I-S/A, oral saline and intravenous AA; I-S/S, both saline. In the second experiment, rats received 14 mL/kg/h duodenal AA and/or saline for 2 h. They were in 3 groups: II-A/S, duodenal AA and intravenous saline; II-S/A, duodenal saline and intravenous AA; II-S/S, both saline. Core body temperature was measured rectally. After the second experiment, serum electrolytes were examined. In both experiments, rectal temperature decreased in all groups during anesthesia. However, the decrease in rectal temperature was significantly less in groups receiving AA than in groups receiving only saline. In the second experiment, although there was no significant difference in the decrease in body temperature between II-A/S and II-S/A, Na(+) concentration was significantly lower in II-S/A. In conclusion, AA, administered orally or intestinally, tended to keep the body temperature stable during anesthesia without disturbing electrolyte balance. These results suggest that oral or enteral AA may be useful for prevention of hypothermia in patients.

  9. Plastic bags for prevention of hypothermia in preterm and low birth weight infants.

    PubMed

    Leadford, Alicia E; Warren, Jamie B; Manasyan, Albert; Chomba, Elwyn; Salas, Ariel A; Schelonka, Robert; Carlo, Waldemar A

    2013-07-01

    Hypothermia contributes to neonatal mortality and morbidity, especially in preterm and low birth weight infants in developing countries. Plastic bags covering the trunk and extremities of very low birth weight infants reduces hypothermia. This technique has not been studied in larger infants or in many resource-limited settings. The objective was to determine if placing preterm and low birth weight infants inside a plastic bag at birth maintains normothermia. Infants at 26 to 36 weeks' gestational age and/or with a birth weight of 1000 to 2500 g born at the University Teaching Hospital in Lusaka, Zambia, were randomized by using a 1:1 allocation and parallel design to standard thermoregulation (blanket or radiant warmer) care or to standard thermoregulation care plus placement inside a plastic bag at birth. The primary outcome measure was axillary temperature in the World Health Organization-defined normal range (36.5-37.5°C) at 1 hour after birth. A total of 104 infants were randomized. At 1 hour after birth, infants randomized to plastic bag (n = 49) were more likely to have a temperature in the normal range as compared with infants in the standard thermoregulation care group (n = 55; 59.2% vs 32.7%; relative risk 1.81; 95% confidence interval 1.16-2.81; P = .007). The temperature at 1 hour after birth in the infants randomized to plastic bag was 36.5 ± 0.5°C compared with 36.1 ± 0.6°C in standard care infants (P < .001). Hyperthermia (>38.0°C) did not occur in any infant. Placement of preterm/low birth weight infants inside a plastic bag at birth compared with standard thermoregulation care reduced hypothermia without resulting in hyperthermia, and is a low-cost, low-technology tool for resource-limited settings.

  10. Plastic Bags for Prevention of Hypothermia in Preterm and Low Birth Weight Infants

    PubMed Central

    Leadford, Alicia E.; Warren, Jamie B.; Manasyan, Albert; Chomba, Elwyn; Salas, Ariel A.; Schelonka, Robert

    2013-01-01

    BACKGROUND AND OBJECTIVES: Hypothermia contributes to neonatal mortality and morbidity, especially in preterm and low birth weight infants in developing countries. Plastic bags covering the trunk and extremities of very low birth weight infants reduces hypothermia. This technique has not been studied in larger infants or in many resource-limited settings. The objective was to determine if placing preterm and low birth weight infants inside a plastic bag at birth maintains normothermia. METHODS: Infants at 26 to 36 weeks’ gestational age and/or with a birth weight of 1000 to 2500 g born at the University Teaching Hospital in Lusaka, Zambia, were randomized by using a 1:1 allocation and parallel design to standard thermoregulation (blanket or radiant warmer) care or to standard thermoregulation care plus placement inside a plastic bag at birth. The primary outcome measure was axillary temperature in the World Health Organization–defined normal range (36.5–37.5°C) at 1 hour after birth. RESULTS: A total of 104 infants were randomized. At 1 hour after birth, infants randomized to plastic bag (n = 49) were more likely to have a temperature in the normal range as compared with infants in the standard thermoregulation care group (n = 55; 59.2% vs 32.7%; relative risk 1.81; 95% confidence interval 1.16–2.81; P = .007). The temperature at 1 hour after birth in the infants randomized to plastic bag was 36.5 ± 0.5°C compared with 36.1 ± 0.6°C in standard care infants (P < .001). Hyperthermia (>38.0°C) did not occur in any infant. CONCLUSIONS: Placement of preterm/low birth weight infants inside a plastic bag at birth compared with standard thermoregulation care reduced hypothermia without resulting in hyperthermia, and is a low-cost, low-technology tool for resource-limited settings. PMID:23733796

  11. A Tourette-like syndrome following cardiopulmonary bypass and hypothermia: MRI volumetric measurements.

    PubMed

    Singer, H S; Dela Cruz, P S; Abrams, M T; Bean, S C; Reiss, A L

    1997-07-01

    We present the case of an adolescent boy who developed a variety of simple and complex motor and vocal tics (Tourette-like syndrome), along with inattentiveness and obsessive-compulsive behaviors after cardiac surgery with cardiopulmonary bypass and profound hypothermia. A single photon emission computed tomography study 2 months after surgery showed reduced uptake in the left hemisphere and 2 years later a perfusion defect in the basal ganglia. Serial magnetic resonance imaging (MRI) studies were normal. Volumetric MRI studies were obtained 4 years after surgery and compared with published values for normal individuals and children with Tourette syndrome (TS), including subsets matched for age, sex, and handedness. Measurement of basal ganglia structures showed a right-dominant asymmetry of the caudate and putamen, in part similar to findings previously reported in patients with TS. Other volumetric abnormalities included a > 2-SD reduction of cortical gray matter, a small decrease of total cerebral volume, and increase in cerebral white matter. Although a variety of neurological problems may occur after cardiopulmonary bypass, to our knowledge this case represents the first report of a chronic tic disorder following cardiac surgery with cardiopulmonary bypass and hypothermia.

  12. Angiogenesis Dysregulation in Term Asphyxiated Newborns Treated with Hypothermia

    PubMed Central

    Shaikh, Henna; Boudes, Elodie; Khoja, Zehra; Shevell, Michael; Wintermark, Pia

    2015-01-01

    Background Neonatal encephalopathy following birth asphyxia is a major predictor of long-term neurological impairment. Therapeutic hypothermia is currently the standard of care to prevent brain injury in asphyxiated newborns but is not protective in all cases. More robust and versatile treatment options are needed. Angiogenesis is a demonstrated therapeutic target in adult stroke. However, no systematic study examines the expression of angiogenesis-related markers following birth asphyxia in human newborns. Objective This study aimed to evaluate the expression of angiogenesis-related protein markers in asphyxiated newborns developing and not developing brain injury compared to healthy control newborns. Design/Methods Twelve asphyxiated newborns treated with hypothermia were prospectively enrolled; six developed eventual brain injury and six did not. Four healthy control newborns were also included. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study the plasma concentration of 49 angiogenesis-related proteins. Mean protein concentrations were compared between each group of newborns. Results Compared to healthy newborns, asphyxiated newborns not developing brain injury showed up-regulation of pro-angiogenic proteins, including fatty acid binding protein-4, glucose-6-phosphate isomerase, neuropilin-1, and receptor tyrosine-protein kinase erbB-3; this up-regulation was not evident in asphyxiated newborns eventually developing brain injury. Also, asphyxiated newborns developing brain injury showed a decreased expression of anti-angiogenic proteins, including insulin-growth factor binding proteins -1, -4, and -6, compared to healthy newborns. Conclusions These findings suggest that angiogenesis pathways are dysregulated following birth asphyxia and are putatively involved in brain injury pathology and recovery. PMID:25996847

  13. High-dose amrinone is required to accelerate rewarming from deliberate mild intraoperative hypothermia for neurosurgical procedures.

    PubMed

    Inoue, Satoki; Kawaguchi, Masahiko; Sakamoto, Takanori; Kitaguchi, Katsuyasu; Furuya, Hitoshi; Sakaki, Toshisuke

    2002-07-01

    Since the time available to provide the cooling and rewarming is limited during deliberate mild hypothermia, the technique to accelerate the cooling and rewarming rate of core temperature has been studied. Amrinone has been reported to accelerate the cooling rate but not the rewarming rate of core temperature during deliberate mild hypothermia. The failure of amrinone effect on the rewarming rate might be due to an insufficient dose of amrinone during hypothermic conditions. The authors therefore tested whether higher doses of amrinone can accelerate the rewarming rate of core temperature during deliberate mild hypothermia for neurosurgery. After institutional approval and informed consent, 30 patients were randomly assigned to one of three groups. Patients in the control group (n = 10) did not receive amrinone; patients in the AMR 15 group (n = 10) received 15 microg x kg(-1) x min(-1) amrinone with a 1.0-mg/kg loading dose of amrinone at the beginning of cooling; and patients in the ReAMR group (n = 10) received 5 microg x kg(-1) x min(-1) amrinone with 1.0-mg/kg loading and reloading doses of amrinone at the beginning of cooling and rewarming, respectively. Administration of amrinone was started just after the induction of cooling and continued until the end of anesthesia. Anesthesia was maintained with nitrous oxide in oxygen, propofol, and fentanyl. After induction of anesthesia, patients were cooled, and tympanic membrane temperature was maintained at 34.5 degrees C. After completion of the main surgical procedures, patients were actively rewarmed and extubated in the operating room. The cooling and rewarming rates of core temperature were both significantly faster in both amrinone groups than in the control group. During the cooling and rewarming periods, forearm minus fingertip temperature gradient was significantly smaller in both amrinone groups than in the control group. During the rewarming period, heart rate and mean arterial pressure in the AMR 15

  14. EEG Monitoring Technique Influences the Management of Hypoxic-Ischemic Seizures in Neonates Undergoing Therapeutic Hypothermia.

    PubMed

    Jan, Saber; Northington, Frances J; Parkinson, Charlamaine M; Stafstrom, Carl E

    2017-01-01

    Electroencephalogram (EEG) monitoring techniques for neonatal hypoxia-ischemia (HI) are evolving over time, and the specific type of EEG utilized could influence seizure diagnosis and management. We examined whether the type of EEG performed affected seizure treatment decisions (e.g., the choice and number of antiseizure drugs [ASDs]) in therapeutic hypothermia-treated neonates with HI from 2007 to 2015 in the Johns Hopkins Hospital Neonatal Intensive Care Unit. During this period, 3 different EEG monitoring protocols were utilized: Period 1 (2007-2009), single, brief conventional EEG (1 h duration) at a variable time during therapeutic hypothermia treatment, i.e., ordered when a seizure was suspected; Period 2 (2009-2013), single, brief conventional EEG followed by amplitude-integrated EEG for the duration of therapeutic hypothermia treatment and another brief conventional EEG after rewarming; and Period 3 (2014-2015), continuous video-EEG (cEEG) for the duration of therapeutic hypothermia treatment (72 h) plus for an additional 12 h during and after rewarming. One hundred and sixty-two newborns were included in this retrospective cohort study. As a function of the type and duration of EEG monitoring, we assessed the risk (likelihood) of receiving no ASD, at least 1 ASD, or ≥2 ASDs. We found that the risk of a neonate being prescribed an ASD was 46% less during Period 3 (cEEG) than during Period 1 (brief conventional EEG only) (95% CI 6-69%, p = 0.03). After adjusting for initial EEG and MRI results, compared with Period 1, there was a 38% lower risk of receiving an ASD during Period 2 (95% CI: 9-58%, p = 0.02) and a 67% lower risk during Period 3 (95% CI: 23-86%, p = 0.01). The risk ratio of receiving ≥2 ASDs was not significantly different across the 3 periods. In conclusion, in addition to the higher sensitivity and specificity of continuous video-EEG monitoring, fewer infants are prescribed an ASD when undergoing continuous forms of EEG monitoring (aEEG or

  15. Early Absent Pupillary Light Reflexes After Cardiac Arrest in Patients Treated with Therapeutic Hypothermia.

    PubMed

    Dhakal, Laxmi P; Sen, Ayan; Stanko, Carlene M; Rawal, Bhupendra; Heckman, Michael G; Hoyne, Jonathan B; Dimberg, Elliot L; Freeman, Michelle L; Ng, Lauren K; Rabinstein, Alejandro A; Freeman, William D

    2016-08-01

    Loss of pupillary light reactivity is one recognized indicator of poor prognosis after cardiopulmonary resuscitation (CPR). However, drug overdose, low cardiac output, and/or resuscitation drugs can lead to impaired pupillary light reflex. To investigate pupillary light reflex status before therapeutic hypothermia (TH) in relation to neurological outcome, we retrospectively reviewed the data of a prospectively implemented TH protocol in patients with cardiac arrest (CA) at Mayo Clinic in Jacksonville, Florida (January 2006-January 2012), and Mayo Clinic in Scottsdale, Arizona (August 2010-March 2014). During this period, all CA patients who underwent hypothermia were included. These patients were selected from an institutional database and hypothermia data set. The Cerebral Performance Category (CPC) at time of discharge was our primary outcome measure. A CPC of 1 to 2 was defined as good outcome and a CPC from 3 to 5 was defined as poor outcome. We identified 99 patients who had CA treated with TH. Twenty-nine patients (29%) had pupils that were nonreactive to light on admission examination before TH, eight of whom later had return of pupil reactivity by day 3. Two of these 29 patients (6.9%) had good outcome, compared to 24 of 70 patients (34.3%) with pupils that were reactive to light (p = 0.005). Both of these patients had CA after illicit drug overdose. Early nonreactive pupils occurred in almost a third of patients after CPR and before TH in our patient population. Recovery of pupillary light reactivity is possible, and in a small minority of those cases (particularly when CA is preceded by the use of illicit drugs), a good outcome can be achieved.

  16. A randomized controlled trial of the Arctic Sun Temperature Management System versus conventional methods for preventing hypothermia during off-pump cardiac surgery.

    PubMed

    Grocott, Hilary P; Mathew, Joseph P; Carver, Elizabeth H; Phillips-Bute, Barbara; Landolfo, Kevin P; Newman, Mark F

    2004-02-01

    In this trial we compared the hypothermia avoidance abilities of the Arctic Sun Temperature Management System (a servo-regulated system that circulates temperature-controlled water through unique energy transfer pads adherent to the patient's body) with conventional temperature control methods. Patients undergoing off-pump coronary artery bypass (OPCAB) surgery were randomized to either the Arctic Sun System alone (AS group) or conventional methods (control group; increased room temperature, heated IV fluids, convective forced air warming system) for the prevention of hypothermia (defined by a temperature <36 degrees C). The AS group had nasopharyngeal temperature servo-regulated to a target of 36.8 degrees C. Temperature was recorded throughout the operative period and comparisons were made between groups for both the time and area under the curve (AUC) for a temperature <36 degrees C (AUC<36 degrees C). Twenty-nine patients (AS group = 14, control group = 15) were studied. The AS group had significantly less hypothermia than the control group, both for duration of time <36 degrees C (2.5 [0-22] min, median [interquartile range] AS group versus 118 [49-192] min, control group; P = 0.0008) as well as for AUC<36 degrees C (0.3 [0-2.2] degrees C x min, AS group versus 17.1 [3.6-173.4] degrees C x min, control group; P = 0.002). The Arctic Sun Temperature Management System significantly reduced intraoperative hypothermia during OPCAB surgery. Importantly, this was achieved in the absence of any other temperature modulating techniques, including the use of IV fluid warming or increases in the ambient operating room temperature. The Arctic Sun Temperature Management System was more effective than conventional methods in preventing hypothermia during off-pump coronary artery bypass graft surgery.

  17. Very Mild Hypothermia (35°C) Postischemia Reduces Infarct Volume and Blood/Brain Barrier Breakdown Following tPA Treatment in the Mouse.

    PubMed

    Cechmanek, Brian K; Tuor, Ursula I; Rushforth, David; Barber, Philip A

    2015-12-01

    Reperfusion therapies for stroke diminish in effectiveness and safety as time to treatment increases. Hypothermia neuroprotection for stroke is established, but its clinical translation has been hampered by uncertainties regarding optimal temperature and complications associated with moderate hypothermia. Also, hypothermia targeting temperatures of 32-33°C is associated with clinical and logistical problems related to induction and adverse side effects. We hypothesized that ischemic damage and tPA-exacerbated blood/brain barrier (BBB) breakdown produced following 30 minutes of middle cerebral artery occlusion and either 1 hour of saline or tPA infusion would be reduced by treatment with very mild cooling of 1.5°C for 48 hours followed by 24 hours of gradual rewarming. Infarct volume was reduced by 29.6% (p<0.001) and 41.9% (p<0.001) in hypothermic-tPA (Hypo_tPA)-treated and hypothermic-saline (Hypo_Sal)-treated animals compared to normothermic-tPA (Norm_tPA) and saline (Norm_Sal)-treated animals, respectively. Hypothermia also reduced IgG extravasation in tPA-treated, but not saline-treated groups compared to their normothermic controls (p<0.001). The ipsilateral-contralateral changes in optical density for IgG extravasation were 18.4% greater in the Norm_tPA than Norm_Sal (p<0.001) group. The ipsilateral-contralateral changes in optical density for IgG extravasation were reduced by 17.8% (p<0.001) in the Hypo_tPA compared to Norm_tPA group. No significant mean difference in IgG extravasation was seen between Hypo_tPA and Hypo_Sal groups (p>0.05). Very modest hypothermia to reduce the BBB breakdown could improve the availability and safety of reperfusion treatments for stroke.

  18. The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study.

    PubMed

    Wisnowski, Jessica L; Wu, Tai-Wei; Reitman, Aaron J; McLean, Claire; Friedlich, Philippe; Vanderbilt, Douglas; Ho, Eugenia; Nelson, Marvin D; Panigrahy, Ashok; Blüml, Stefan

    2016-06-01

    Therapeutic hypothermia has emerged as the first empirically supported therapy for neuroprotection in neonates with hypoxic-ischemic encephalopathy (HIE). We used magnetic resonance spectroscopy ((1)H-MRS) to characterize the effects of hypothermia on energy metabolites, neurotransmitters, and antioxidants. Thirty-one neonates with HIE were studied during hypothermia and after rewarming. Metabolite concentrations (mmol/kg) were determined from the thalamus, basal ganglia, cortical grey matter, and cerebral white matter. In the thalamus, phosphocreatine concentrations were increased by 20% during hypothermia when compared to after rewarming (3.49 ± 0.88 vs. 2.90 ± 0.65, p < 0.001) while free creatine concentrations were reduced to a similar degree (3.00 ± 0.50 vs. 3.74 ± 0.85, p < 0.001). Glutamate (5.33 ± 0.82 vs. 6.32 ± 1.12, p < 0.001), aspartate (3.39 ± 0.66 vs. 3.87 ± 1.19, p < 0.05), and GABA (0.92 ± 0.36 vs. 1.19 ± 0.41, p < 0.05) were also reduced, while taurine (1.39 ± 0.52 vs. 0.79 ± 0.61, p < 0.001) and glutathione (2.23 ± 0.41 vs. 2.09 ± 0.33, p < 0.05) were increased. Similar patterns were observed in other brain regions. These findings support that hypothermia improves energy homeostasis by decreasing the availability of excitatory neurotransmitters, and thereby, cellular energy demand. © The Author(s) 2015.

  19. Reducing the risk of unplanned perioperative hypothermia.

    PubMed

    Lynch, Susan; Dixon, Jacqueline; Leary, Donna

    2010-11-01

    Maintaining normothermia is important for patient safety, positive surgical outcomes, and increased patient satisfaction. Causes of unplanned hypothermia in the OR include cold room temperatures, the effects of anesthesia, cold IV and irrigation fluids, skin and wound exposure, and patient risk factors. Nurses at Riddle Memorial Hospital in Media, Pennsylvania, performed a quality improvement project to evaluate the effectiveness of using warm blankets, warm irrigation fluids, or forced-air warming on perioperative patients to maintain their core temperature during the perioperative experience. Results of the project showed that 75% of patients who received forced-air warming perioperatively had temperatures that reached or were maintained at 36° C (96.8° F) or higher within 15 minutes after leaving the OR. Copyright © 2010 AORN, Inc. Published by Elsevier Inc. All rights reserved.

  20. Effects of hypothermia on S100B and glial fibrillary acidic protein in asphyxia rats after cardiopulmonary resuscitation.

    PubMed

    Liu, Sha; Zhang, Yibing; Zhao, Yong; Cui, Haifeng; Cao, Chunyu; Guo, Jianyou

    2015-01-01

    The aim of the study was to investigate the effects of hypothermia on S100B and glial fibrillary acidic protein (GFAP) in serum and hippocampus CA1 area in asphyxiated rats after cardiopulmonary resuscitation (CPR). A total of 100 SD rats were designated into four groups: group A, sham operation group; group B, rats received conventional resuscitation; group C, rats received conventional resuscitation and hypothermia at cardiac arrest; group D, rats received conventional resuscitation and hypothermia at 30 min after restoration of spontaneous circulation (ROSC). Rats were then killed by cardiac arrest at 2 and 4 h after ROSC; brain tissue was taken to observe dynamic changes of S100B and GFAP in serum and hippocampus CA1 area. Following ROSC, S100B levels increased from 2 to 4 h in group B, C, and D. In addition, S100B in serum and hippocampus CA1 area was all significantly increased at different time points compared with group A (P < 0.05). Following ROSC, serum S100B level at 2 h in group C was significantly decreased compared with group B, but the difference was not statistically significant (P > 0.05). Moreover, S100B in serum at 4 h after ROSC was significantly decreased (P < 0.05), S100B in cortex was significantly decreased (P < 0.05). The expression of GFAP was also examined. GFAP level in hippocampus CA1 area was significantly decreased in group B, C, and D at 4 h after ROSC compared with group A (P < 0.05). S100B and GFAP were expressed in rat serum and hippocampus CA2 area at early stage after ROSC, which can be used as sensitive markers for brain injury diagnosis and prognosis prediction. Hypothermia is also shown to reduce brain injury after CPR.

  1. The accuracy of PiCCO® in measuring cardiac output in patients under therapeutic hypothermia: Comparison with transthoracic echocardiography.

    PubMed

    Souto Moura, T; Aguiar Rosa, S; Germano, N; Cavaco, R; Sequeira, T; Alves, M; Papoila, A L; Bento, L

    2018-03-01

    Invasive cardiac monitoring using thermodilution methods such as PiCCO® is widely used in critically ill patients and provides a wide range of hemodynamic variables, including cardiac output (CO). However, in post-cardiac arrest patients subjected to therapeutic hypothermia, the low body temperature possibly could interfere with the technique. Transthoracic Doppler echocardiography (ECHO) has long proved its accuracy in estimating CO, and is not influenced by temperature changes. To assess the accuracy of PiCCO® in measuring CO in patients under therapeutic hypothermia, compared with ECHO. Thirty paired COECHO/COPiCCO measurements were analyzed in 15 patients subjected to hypothermia after cardiac arrest. Eighteen paired measurements were obtained at under 36°C and 12 at ≥36°C. A value of 0.5l/min was considered the maximum accepted difference between the COECHO and COPiCCO values. Under conditions of normothermia (≥36°C), the mean difference between COECHO and COPiCCO was 0.030 l/min, with limits of agreement (-0.22, 0.28) - all of the measurements differing by less than 0.5 l/min. In situations of hypothermia (<36°C), the mean difference in CO measurements was -0.426 l/min, with limits of agreement (-1.60, 0.75), and only 44% (8/18) of the paired measurements fell within the interval (-0.5, 0.5). The calculated temperature cut-off point maximizing specificity was 35.95°C: above this temperature, specificity was 100%, with a false-positive rate of 0%. The results clearly show clinically relevant discordance between COECHO and COPiCCO at temperatures of <36°C, demonstrating the inaccuracy of PiCCO® for cardiac output measurements in hypothermic patients. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  2. Motion sickness increases the risk of accidental hypothermia.

    PubMed

    Nobel, Gerard; Eiken, Ola; Tribukait, Arne; Kölegård, Roger; Mekjavic, Igor B

    2006-09-01

    Motion sickness (MS) has been found to increase body-core cooling during immersion in 28 degrees C water, an effect ascribed to attenuation of the cold-induced peripheral vasoconstriction (Mekjavic et al. in J Physiol 535(2):619-623, 2001). The present study tested the hypothesis that a more profound cold stimulus would override the MS effect on peripheral vasoconstriction and hence on the core cooling rate. Eleven healthy subjects underwent two separate head-out immersions in 15 degrees C water. In the control trial (CN), subjects were immersed after baseline measurements. In the MS-trial, subjects were rendered motion sick prior to immersion, by using a rotating chair in combination with a regimen of standardized head movements. During immersion in the MS-trial, subjects were exposed to an optokinetic stimulus (rotating drum). At 5-min intervals subjects rated their temperature perception, thermal comfort and MS discomfort. During immersion mean skin temperature, rectal temperature, the difference in temperature between the non-immersed right forearm and 3rd finger of the right hand (DeltaTff), oxygen uptake and heart rate were recorded. In the MS-trial, rectal temperature decreased substantially faster (33%, P < 0.01). Also, the DeltaTff response, an index of peripheral vasomotor tone, as well as the oxygen uptake, indicative of the shivering response, were significantly attenuated (P < 0.01 and P < 0.001, respectively) by MS. Thus, MS may predispose individuals to hypothermia by enhancing heat loss and attenuating heat production. This might have significant implications for survival in maritime accidents.

  3. Bradycardia during therapeutic hypothermia is associated with good neurologic outcome in comatose survivors of out-of-hospital cardiac arrest.

    PubMed

    Stær-Jensen, Henrik; Sunde, Kjetil; Olasveengen, Theresa M; Jacobsen, Dag; Drægni, Tomas; Nakstad, Espen Rostrup; Eritsland, Jan; Andersen, Geir Øystein

    2014-11-01

    Comatose patients resuscitated after out-of-hospital cardiac arrest receive therapeutic hypothermia. Bradycardia is frequent during therapeutic hypothermia, but its impact on outcome remains unclear. We explore a possible association between bradycardia during therapeutic hypothermia and neurologic outcome in comatose survivors of out-of-hospital cardiac arrest. Retrospective cohort study, from January 2009 to January 2011. University hospital medical and cardiac ICUs. One hundred eleven consecutive comatose out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. Patients treated with standardized treatment protocol after cardiac arrest. All out-of-hospital cardiac arrest patients' records were reviewed. Hemodynamic data were obtained every fourth hour during the first days. The patients were in temperature target range (32-34°C) 8 hours after out-of-hospital cardiac arrest and dichotomized into bradycardia and nonbradycardia groups depending on their actual heart rate less than or equal to 60 beats/min or more than 60 beats/min at that time. Primary endpoint was Cerebral Performance Category score at hospital discharge. More nonbradycardia group patients received epinephrine during resuscitation and epinephrine and norepinephrine in the early in-hospital period. They also had lower base excess at admission. Survival rate with favorable outcome was significantly higher in the bradycardia than the nonbradycardia group (60% vs 37%, respectively, p = 0.03). For further heart rate quantification, patients were divided into quartiles: less than or equal to 49 beats/min, 50-63 beats/min, 64-77 beats/min, and more than or equal to 78 beats/min, with respective proportions of patients with good outcome at discharge of 18 of 27 (67%), 14 of 25 (56%), 12 of 28 (43%), and 7 of 27 (26%) (p = 0.002). Patients in the lowest quartile had significantly better outcome than the higher groups (p = 0.027), whereas patients in the highest quartile had

  4. The Effects of Hypothermia on Fibrinogen Metabolism and Coagulation Function in Swine

    DTIC Science & Technology

    2007-01-01

    blanket with circulating water at 48C. Fibrinogen synthesis and breakdown were quantified using a 6-hour stable isotope infusion with subsequent gas...tion and sufficient fibrinogen in the circulation . The effects of hypothermia on the coagulation process have been estimated 0026-0495/$ – see front...and released to circulation in 1 hour. Fibrinogen breakdown rate is the total loss of fibrinogen (expressed as milligram per kilogram of body weight

  5. Nitric oxide in the nucleus raphe magnus modulates cutaneous blood flow in rats during hypothermia.

    PubMed

    Arami, Masoumeh Kourosh; Zade, Javad Mirnajafi; Komaki, Alireza; Amiri, Mahmood; Mehrpooya, Sara; Jahanshahi, Ali; Jamei, Behnam

    2015-10-01

    Nucleus Raphe Magnus (NRM) that is involved in the regulation of body temperature contains nitric oxide (NO) synthase. Considering the effect of NO on skin blood flow control, in this study, we assessed its thermoregulatory role within the raphe magnus. To this end, tail blood flow of male Wistar rats was measured by laser doppler following the induction of hypothermia. Intra-NRM injection of SNP (exogenous NO donor, 0.1- 0.2 μl, 0.2 nM) increased the blood flow. Similarly, unilateral microinjection of glutamate (0.1- 0.2 μl, 2.3 nM) into the nucleus increased the blood flow. This effect of L-glutamate was reduced by prior intra NRM administration of NO synthase inhibitor N(G)-methyl-L-arginine or N(G)-nitro-L-arginine methyl ester (L-NAME, 0.1 µl, 100 nM). It is concluded that NO modulates the thermoregulatory response of NRM to hypothermia and may interact with excitatory amino acids in central skin blood flow regulation.

  6. Revisited: A Systematic Review of Therapeutic Hypothermia for Adult Patients Following Traumatic Brain Injury.

    PubMed

    Watson, Hannah I; Shepherd, Andrew A; Rhodes, Jonathan K J; Andrews, Peter J D

    2018-06-01

    Therapeutic hypothermia has been of topical interest for many years and with the publication of two international, multicenter randomized controlled trials, the evidence base now needs updating. The aim of this systematic review of randomized controlled trials is to assess the efficacy of therapeutic hypothermia in adult traumatic brain injury focusing on mortality, poor outcomes, and new pneumonia. The following databases were searched from January 1, 2011, to January 26, 2018: Cochrane Central Register of Controlled Trial, MEDLINE, PubMed, and EMBASE. Only foreign articles published in the English language were included. Only articles that were randomized controlled trials investigating adult traumatic brain injury sustained following an acute, closed head injury were included. Two authors independently assessed at each stage. Quality was assessed using the Cochrane Collaboration's tool for assessing the risk of bias. All extracted data were combined using the Mantel-Haenszel estimator for pooled risk ratio with 95% CIs. p value of less than 0.05 was considered statistically significant. All statistical analyses were conducted using RevMan 5 (Cochrane Collaboration, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Twenty-two studies with 2,346 patients are included. Randomized controlled trials with a low risk of bias show significantly more mortality in the therapeutic hypothermia group (risk ratio, 1.37; 95% CI, 1.04-1.79; p = 0.02), whereas randomized controlled trials with a high risk of bias show the opposite with a higher mortality in the control group (risk ratio, 0.70; 95% CI, 0.60-0.82; p < 0.00001). Overall, this review is in-keeping with the conclusions published by the most recent randomized controlled trials. High-quality studies show no significant difference in mortality, poor outcomes, or new pneumonia. In addition, this review shows a place for fever control in the management of traumatic brain injury.

  7. An atypical case of successful resuscitation of an accidental profound hypothermia patient, occurring in a temperate climate.

    PubMed

    Coleman, E; Doddakula, K; Meeke, R; Marshall, C; Jahangir, S; Hinchion, J

    2010-03-01

    Cases of accidental profound hypothermia occur most frequently in cold, northern climates. We describe an atypical case, occurring in a temperate climate, where a hypothermic cardiac-arrested patient was successfully resuscitated using extracorporeal circulation (ECC).

  8. Use of hypothermia in the intensive care unit

    PubMed Central

    Corry, Jesse J

    2012-01-01

    Used for over 3600 years, hypothermia, or targeted temperature management (TTM), remains an ill defined medical therapy. Currently, the strongest evidence for TTM in adults are for out-of-hospital ventricular tachycardia/ventricular fibrillation cardiac arrest, intracerebral pressure control, and normothermia in the neurocritical care population. Even in these disease processes, a number of questions exist. Data on disease specific therapeutic markers, therapeutic depth and duration, and prognostication are limited. Despite ample experimental data, clinical evidence for stroke, refractory status epilepticus, hepatic encephalopathy, and intensive care unit is only at the safety and proof-of-concept stage. This review explores the deleterious nature of fever, the theoretical role of TTM in the critically ill, and summarizes the clinical evidence for TTM in adults. PMID:24701408

  9. Brugada sign in a patient with hyperkalemia due to rhabdomyolysis in hypothermia.

    PubMed

    Tomcsányi, Kristóf; Tomcsányi, János

    The Brugada sign may appear as an indication of severe hyperkalemia. This phenomena has recently been called as the "Brugada phenocopy". Hyperthermia and hypothermia may lead to rhabdomyolysis. Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle constituents into the circulation. We present a case where rhabdomyolysis-related delayed hyperkalemia showed Brugada sign on the ECG mimicking ventricular tachycardia. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Influence of continuous haemofiltration-related hypothermia on haemodynamic variables and gas exchange in septic patients.

    PubMed

    Matamis, D; Tsagourias, M; Koletsos, K; Riggos, D; Mavromatidis, K; Sombolos, K; Bursztein, S

    1994-07-01

    To investigate the influence of continuous haemofiltration (CHF) on haemodynamics, gas exchange and core temperature in critically ill septic patients with acute renal failure. In 20 patients (17 male, 3 female) ultrafiltration rate, core temperature, gas exchange and haemodynamic variables were measured at regular intervals during the first 48 h of haemofiltration. Baseline data were compared to those obtained 30 min after initiating CHF and also to those during hypothermia (if observed). Haemodynamic variables remained remarkably constant throughout the study period. In patients with a relatively low ultrafiltration rate (855 +/- 278 ml/h) temperature did not change, while in patients with a high ultrafiltration rate (1468 +/- 293 ml/h) core temperature significantly decreased from 37.6 +/- 0.9 degrees C to 34.8 +/- 0.8 degrees C (p < 0.001). There was a statistically significant correlation between temperature decrease and ultrafiltration rate (r = -0.68, Y = 1.8-0.003 X, p < 0.01). Hypothermic patients also showed a mean decrease in VO2 from 141 +/- 22 ml/min/m2 to 112 +/- 22 ml/min/m2 (p < 0.01) with a concomitant increase in PaO2 from 103 +/- 37 mmHg to 140 +/- 42 mmHg (p < 0.001) and in PvO2 from 35 +/- 4 mmHg to 41 +/- 5 mmHg (p < 0.001). 1) Continuous haemofiltration does not cause significant alternations in haemodynamic variables. 2) Hypothermia frequently occurs in patients undergoing continuous haemofiltration with high ultrafiltration rates. These hypothermic patients show a reduction in VO2 leading to an increase in PvO2 and PaO2. This mild hypothermia in these circumstances has no evident deleterious effects.

  11. Neuroprotective body hypothermia among newborns with hypoxic ischemic encephalopathy: three-year experience in a tertiary university hospital. A retrospective observational study.

    PubMed

    Magalhães, Mauricio; Rodrigues, Francisco Paulo Martins; Chopard, Maria Renata Tollio; Melo, Victoria Catarina de Albuquerque; Melhado, Amanda; Oliveira, Inez; Gallacci, Clery Bernardi; Pachi, Paulo Roberto; Lima Neto, Tabajara Barbosa

    2015-01-01

    Neonatal hypoxic-ischemic encephalopathy is associated with high morbidity and mortality. Studies have shown that therapeutic hypothermia decreases neurological sequelae and death. Our aim was therefore to report on a three-year experience of therapeutic hypothermia among asphyxiated newborns. Retrospective study, conducted in a university hospital. Thirty-five patients with perinatal asphyxia undergoing body cooling between May 2009 and November 2012 were evaluated. Thirty-nine infants fulfilled the hypothermia protocol criteria. Four newborns were removed from study due to refractory septic shock, non-maintenance of temperature and severe coagulopathy. The median Apgar scores at 1 and 5 minutes were 2 and 5. The main complication was infection, diagnosed in seven mothers (20%) and 14 newborns (40%). Convulsions occurred in 15 infants (43%). Thirty-one patients (88.6%) required mechanical ventilation and 14 of them (45%) were extubated within 24 hours. The duration of mechanical ventilation among the others was 7.7 days. The cooling protocol was started 1.8 hours after birth. All patients showed elevated levels of creatine phosphokinase, creatine phosphokinase- MB and lactate dehydrogenase. There was no severe arrhythmia; one newborn (2.9%) presented controlled coagulopathy. Four patients (11.4%) presented controlled hypotension. Twenty-nine patients (82.9%) underwent cerebral ultrasonography and 10 of them (34.5%) presented white matter hyper-echogenicity. Brain magnetic resonance imaging was performed on 33 infants (94.3%) and 11 of them (33.3%) presented hypoxic-ischemic changes. The hospital stay was 23 days. All newborns were discharged. Two patients (5.8%) needed gastrostomy. Hypothermia as therapy for asphyxiated newborns was shown to be safe.

  12. [Case report: severe hypothermia in a newborn infant - challenges in preclinical emergency medicine].

    PubMed

    Knacke, Peer G; Strauss, Jochen; Gräsner, Jan-Thorsten; Saur, Petra; Scholz, Jens

    2008-04-01

    On the basis of a case report the prehospital management of a newborn child with deep accidental hypothermia (22oC) is discussed. The child was found in a garbage can. The continuous resuscitation during the transport into the clinic is done in an incubator and the child survives without neurologic damages. The used measures of the resuscitation are discussed on the basis of the therapy.

  13. Hyperoxia is Associated with Increased Mortality in Patients Treated with Mild Therapeutic Hypothermia after Sudden Cardiac Arrest

    PubMed Central

    Janz, David R.; Hollenbeck, Ryan D.; Pollock, Jeremy S.; McPherson, John A.; Rice, Todd W.

    2012-01-01

    Objective To determine if higher levels of partial pressure of arterial oxygen are associated with in-hospital mortality and poor neurologic status at hospital discharge in patients treated with mild therapeutic hypothermia after sudden cardiac arrest. Design Retrospective analysis of a prospective cohort study Patients A total of 170 consecutive patients treated with therapeutic hypothermia in the cardiovascular care unit of an academic tertiary care hospital. Interventions None. Measurements and Main Results Of 170 patients, 77 (45.2%) survived to hospital discharge. Survivors had a significantly lower maximum partial pressure of arterial oxygen(198 mmHg, IQR 152.5–282) measured in the first 24 hours following cardiac arrest compared to nonsurvivors (254 mmHg, IQR 172–363, p = .022). A multivariable analysis including age, time to return of spontaneous circulation, the presence of shock, bystander CPR, and initial rhythm revealed that higher levels of the partial pressure of arterial oxygen were significantly associated with increased in-hospital mortality (odds ratio 1.439, 95% confidence interval 1.028–2.015, p = 0.034) and poor neurologic status at hospital discharge (odds ratio 1.485, 95% confidence interval 1.032–2.136, p = 0.033). Conclusions Higher levels of the maximum measured partial pressure of arterial oxygen are associated with increased in-hospital mortality and poor neurologic status on hospital discharge in patients treated with mild therapeutic hypothermia after sudden cardiac arrest. PMID:22971589

  14. HYPOTHERMIA AND HYPOMETABOLISM: SENSITIVE INDICES OF WHOLE-BODY TOXICITY FOLLOWING EXPOSURE TO METALLIC SALTS IN THE MOUSE

    EPA Science Inventory

    To investigate the practicality of hypothermia and hypometabolism as sensitive indices of toxicity in the mouse, oxygen consumption was monitored continuously and body temperature was measured at 30 min post-injection following the intraperitoneal administration of various metal ...

  15. The impact of hypothermia on emergence from isoflurane anesthesia in orexin neuron-ablated mice.

    PubMed

    Kuroki, Chiharu; Takahashi, Yoshiko; Ootsuka, Youichirou; Kanmura, Yuichi; Kuwaki, Tomoyuki

    2013-05-01

    Orexin neurons regulate the sleep/wake cycle and are proposed to influence general anesthesia. In animal experiments, orexin neurons have been shown to drive emergence from general anesthesia. In human studies, however, the role of orexin neurons remains controversial, owing at least, in part, to the fact that orexin neurons are multifunctional. Orexin neurons regulate not only the sleep/wake cycle, but also body temperature. We hypothesized that orexin neurons do not directly regulate emergence from anesthesia, but instead affect emergence indirectly through thermoregulation because anesthesia-induced hypothermia can greatly influence emergence time. To test our hypothesis, we used simultaneous measurement of body temperature and locomotor activity. We used male orexin neuron-ablated (ORX-AB) mice and their corresponding wild-type (WT) littermates to investigate the role of orexin neurons in emergence. Body temperature was recorded using an intraperitoneally implanted telemetric probe, and locomotor activity was measured using an infrared motion sensor. Induction of anesthesia and emergence from anesthesia were defined behaviorally as loss and return, respectively, of body movement. Mice received general anesthesia with 1.5% isoflurane in 100% oxygen for 30 minutes under 3 conditions. In the first experiment, the anesthesia chamber was warmed (32 °C), ensuring a constant body temperature of animals during anesthesia. In the second experiment, the anesthesia chamber was maintained at room temperature (25 °C), allowing body temperature to fluctuate. In the third experiment in WT mice, the anesthesia chamber was cooled (23 °C) so that their body temperature would decrease to the comparable value to that obtained in the ORX-AB mice during room temperature condition. In the warmed condition, there were no significant differences between the ORX-AB and control mice with respect to body temperature, locomotor activity, induction time, or emergence time. In the room

  16. Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy

    PubMed Central

    Laptook, Abbot R.; Shankaran, Seetha; Tyson, Jon E.; Munoz, Breda; Bell, Edward F.; Goldberg, Ronald N.; Parikh, Nehal A.; Ambalavanan, Namasivayam; Pedroza, Claudia; Pappas, Athina; Das, Abhik; Chaudhary, Aasma S.; Ehrenkranz, Richard A.; Hensman, Angelita M.; Van Meurs, Krisa P.; Chalak, Lina F.; Hamrick, Shannon E. G.; Sokol, Gregory M.; Walsh, Michele C.; Poindexter, Brenda B.; Faix, Roger G.; Watterberg, Kristi L.; Frantz, Ivan D.; Guillet, Ronnie; Devaskar, Uday; Truog, William E.; Chock, Valerie Y.; Wyckoff, Myra H.; McGowan, Elisabeth C.; Carlton, David P.; Harmon, Heidi M.; Brumbaugh, Jane E.; Cotten, C. Michael; Sánchez, Pablo J.; Hibbs, Anna Maria; Higgins, Rosemary D.

    2018-01-01

    IMPORTANCE Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks’ or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. OBJECTIVE To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks’ or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. INTERVENTIONS Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C–34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C–37.3°C). MAIN OUTCOMES AND MEASURES The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. RESULTS Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks’ gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, −1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or

  17. Insomnia Caused by Serotonin Depletion is Due to Hypothermia

    PubMed Central

    Murray, Nicholas M.; Buchanan, Gordon F.; Richerson, George B.

    2015-01-01

    Study Objective: Serotonin (5-hydroxytryptamine, 5-HT) neurons are now thought to promote wakefulness. Early experiments using the tryptophan hydroxylase inhibitor para-chlorophenylalanine (PCPA) had led to the opposite conclusion, that 5-HT causes sleep, but those studies were subsequently contradicted by electrophysiological and behavioral data. Here we tested the hypothesis that the difference in conclusions was due to failure of early PCPA experiments to control for the recently recognized role of 5-HT in thermoregulation. Design: Adult male C57BL/6N mice were treated with PCPA (800 mg/kg intraperitoneally for 5 d; n = 15) or saline (n = 15), and housed at 20°C (normal room temperature) or at 33°C (thermoneutral for mice) for 24 h. In a separate set of experiments, mice were exposed to 4°C for 4 h to characterize their ability to thermoregulate. Measurements and Results: PCPA treatment reduced brain 5-HT to less than 12% of that of controls. PCPA-treated mice housed at 20°C spent significantly more time awake than controls. However, core body temperature decreased from 36.5°C to 35.1°C. When housed at 33°C, body temperature remained normal, and total sleep duration, sleep architecture, and time in each vigilance state were the same as controls. When challenged with 4°C, PCPA-treated mice experienced a precipitous drop in body temperature, whereas control mice maintained a normal body temperature. Conclusions: These results indicate that early experiments using para-chlorophenylalanine that led to the conclusion that 5-hydroxytryptamine (5-HT) causes sleep were likely confounded by hypothermia. Temperature controls should be considered in experiments using 5-HT depletion. Citation: Murray NM, Buchanan GF, Richerson GB. Insomnia caused by serotonin depletion is due to hypothermia. SLEEP 2015;38(12):1985–1993. PMID:26194567

  18. The effects of the β1 antagonist, metoprolol, on methamphetamine-induced changes in core temperature in the rat.

    PubMed

    Harrell, Ricki; Speaker, H Anton; Mitchell, Scott L; Sabol, Karen E

    2015-11-16

    Methamphetamine (METH) results in hyperthermia or hypothermia depending on environmental conditions. Here we studied the role of the β1 adrenergic receptor in mediating METH's temperature effects. Core temperature measurements were made telemetrically over a 7.5h session, two days/week, in test chambers regulated at either 18°C, 24°C, or 30°C ambient temperature. Rats were treated with the β1 antagonist metoprolol (5.0, 10.0, and 15.0mg/kg) alone (Experiment 1), or in combination with 5.0mg/kg METH (Experiment 2). In experiment 3, we combined a lower dose range of metoprolol (0.75, 1.5, and 3.0mg/kg) with 5.0mg/kg METH at 18°C and 30°C. Confirming prior findings, METH alone resulted in hyperthermia in warm (30°) and hypothermia in cool environments (18°C). Metoprolol alone induced small but significant increases in core temperature. In combination, however, metoprolol reduced METH-induced changes in core temperature. Specifically, at 30°C, 3.0, 5.0, 10.0, and 15.0mg/kg metoprolol decreased METH-induced hyperthermia; at 18°C, all six doses of metoprolol enhanced METH-induced hypothermia. Our metoprolol findings suggest that one component of METH's temperature effects involves increasing core temperature at all ambient conditions via β1 receptors. Since β receptors are involved in brown adipose tissue (BAT)-mediated thermogenesis, skeletal muscle-mediated thermogenesis, heart rate, and the metabolism of glucose and lipids, we discuss each of these as possible mechanisms for metoprolol's effects on METH-induced changes in core temperature. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Sinus bradycardia during hypothermia in comatose survivors of out-of-hospital cardiac arrest - a new early marker of favorable outcome?

    PubMed

    Thomsen, Jakob Hartvig; Hassager, Christian; Bro-Jeppesen, John; Søholm, Helle; Nielsen, Niklas; Wanscher, Michael; Køber, Lars; Pehrson, Steen; Kjaergaard, Jesper

    2015-04-01

    Bradycardia is a common finding in patients undergoing therapeutic hypothermia (TH) following out-of-hospital cardiac arrest (OHCA), presumably as a normal physiological response to low body temperature. We hypothesized that a normal physiological response with sinus bradycardia (SB) indicates less neurological damage and therefore would be associated with lower mortality. We studied 234 consecutive comatose survivors of OHCA with presumed cardiac etiology and shockable primary rhythm, who underwent a full 24-h TH-protocol (33°C) at a tertiary heart center (years: 2004-2010). Primary endpoint was 180-day mortality; secondary endpoint was favorable neurological outcome (180-day cerebral performance category: 1-2). SB, defined as sinus rhythm <50 beats per minute during TH, was present in 115 (49%) patients. Baseline characteristics including sex, witnessed arrest, bystander cardiopulmonary resuscitation and time to return of spontaneous circulation were not different between SB- and no-SB patients. However, SB-patients were younger, 57±14 vs. 63±14 years, p<0.001 and less frequently had known heart failure (7% vs. 20%, p<0.01). Patients experiencing SB during the hypothermia phase of TH had a 17% 180-day mortality rate compared to 38% in no-SB patients (p<0.001), corresponding to a 180-day hazard ratio (HRadjusted=0.45 (0.23-0.88, p=0.02)) in the multivariable analysis. Similarly, SB during hypothermia was directly associated with lower odds of unfavorable neurological outcome (ORunadjusted=0.42 (0.23-0.75, p<0.01). Sinus bradycardia during therapeutic hypothermia is independently associated with a lower 180-day mortality rate and may thus be a novel, early marker of favorable outcome in comatose survivors of OHCA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Increased Brain Perfusion Persists over the First Month of Life in Term Asphyxiated Newborns Treated with Hypothermia: Does it Reflect Activated Angiogenesis?

    PubMed

    Shaikh, Henna; Lechpammer, Mirna; Jensen, Frances E; Warfield, Simon K; Hansen, Anne H; Kosaras, Bela; Shevell, Michael; Wintermark, Pia

    2015-06-01

    Many asphyxiated newborns still develop brain injury despite hypothermia therapy. The development of brain injury in these newborns has been related partly to brain perfusion abnormalities. The purposes of this study were to assess brain hyperperfusion over the first month of life in term asphyxiated newborns and to search for some histopathological clues indicating whether this hyperperfusion may be related to activated angiogenesis following asphyxia. In this prospective cohort study, regional cerebral blood flow was measured in term asphyxiated newborns treated with hypothermia around day 10 of life and around 1 month of life using magnetic resonance imaging (MRI) and arterial spin labeling. A total of 32 MRI scans were obtained from 24 term newborns. Asphyxiated newborns treated with hypothermia displayed an increased cerebral blood flow in the injured brain areas around day 10 of life and up to 1 month of life. In addition, we looked at the histopathological clues in a human asphyxiated newborn and in a rat model of neonatal encephalopathy. Vascular endothelial growth factor (VEGF) was expressed in the injured brain of an asphyxiated newborn treated with hypothermia in the first days of life and of rat pups 24-48 h after the hypoxic-ischemic event, and the endothelial cell count increased in the injured cortex of the pups 7 and 11 days after hypoxia-ischemia. Our data showed that the hyperperfusion measured by imaging persisted in the injured areas up to 1 month of life and that angiogenesis was activated in the injured brain of asphyxiated newborns.

  1. Investigation of oxyhemoglobin and carboxyhemoglobin ratios in right and left cardiac blood for diagnosis of fatal hypothermia and death by fire.

    PubMed

    Kanto-Nishimaki, Yuko; Saito, Haruka; Watanabe-Aoyagi, Miwako; Toda, Ritsuko; Iwadate, Kimiharu

    2014-11-01

    Few large-scale investigations have looked at the oxyhemoglobin ratio (%O2-Hb) or the carboxyhemoglobin ratio (%CO-Hb) in fatal hypothermia and death by fire as applicable to forensic medicine. We therefore retrospectively examined right and left cardiac blood samples for both %O2-Hb and %CO-Hb in 690 forensic autopsy cases. We therefore sought to establish reference values for the above forensic diagnoses, to compare %O2-Hb in fatal hypothermia with or without cardiopulmonary resuscitation (CPR), and to compare the relationship between %CO-Hb and smoking history. All %O2-Hb and %CO-Hb data were obtained during or immediately after autopsies using a portable CO-oximeter. Death by carbon monoxide (CO) intoxication and death by fire were excluded from the analysis involving smoking history. In fatal hypothermia, %O2-Hb in the left cardiac blood was significantly higher than that in the right cardiac blood, providing important evidence for fatal hypothermia. Furthermore, %O2-Hb in the left cardiac blood increases with CPR but that in the right cardiac blood increases in parallel. No correlation was observed between rectal temperature and %O2-Hb in the right and left cardiac blood, indicating that it is unlikely that postmortem cooling increases %O2-Hb in cardiac blood. %CO-Hb in smokers was significantly higher than that in non-smokers, although the number of cigarettes smoked did not appear to be significant. When assessing death by fire, we identified that %CO-Hb of >10% was a reliable marker of antemortem CO inhalation, regardless of smoking history. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Comparison of three different prehospital wrapping methods for preventing hypothermia - a crossover study in humans

    PubMed Central

    2011-01-01

    Background Accidental hypothermia increases mortality and morbidity in trauma patients. Various methods for insulating and wrapping hypothermic patients are used worldwide. The aim of this study was to compare the thermal insulating effects and comfort of bubble wrap, ambulance blankets / quilts, and Hibler's method, a low-cost method combining a plastic outer layer with an insulating layer. Methods Eight volunteers were dressed in moistened clothing, exposed to a cold and windy environment then wrapped using one of the three different insulation methods in random order on three different days. They were rested quietly on their back for 60 minutes in a cold climatic chamber. Skin temperature, rectal temperature, oxygen consumption were measured, and metabolic heat production was calculated. A questionnaire was used for a subjective evaluation of comfort, thermal sensation, and shivering. Results Skin temperature was significantly higher 15 minutes after wrapping using Hibler's method compared with wrapping with ambulance blankets / quilts or bubble wrap. There were no differences in core temperature between the three insulating methods. The subjects reported more shivering, they felt colder, were more uncomfortable, and had an increased heat production when using bubble wrap compared with the other two methods. Hibler's method was the volunteers preferred method for preventing hypothermia. Bubble wrap was the least effective insulating method, and seemed to require significantly higher heat production to compensate for increased heat loss. Conclusions This study demonstrated that a combination of vapour tight layer and an additional dry insulating layer (Hibler's method) is the most efficient wrapping method to prevent heat loss, as shown by increased skin temperatures, lower metabolic rate and better thermal comfort. This should then be the method of choice when wrapping a wet patient at risk of developing hypothermia in prehospital environments. PMID:21699720

  3. Methods for study of cardiovascular adaptation of small laboratory animals during exposure to altered gravity. [hypothermia for cardiovascular control and cancer therapy

    NASA Technical Reports Server (NTRS)

    Popovic, V.

    1973-01-01

    Several new techniques are reported for studying cardiovascular circulation in small laboratory animals kept in metabolic chambers. Chronical cannulation, miniaturized membrane type heart-lung machines, a prototype walking chamber, and a fluorocarbon immersion method to simulate weightlessness are outlined. Differential hypothermia work on rat cancers provides localized embedding of radionuclides and other chemotherapeutical agents in tumors and increases at the same time blood circulation through the warmed tumor as compared to the rest of the cold body. Some successful clinical applications of combined chemotherapy and differential hypothermia in skin cancer, mammary tumors, and brain gliomas are described.

  4. Warming of intravenous and irrigation fluids for preventing inadvertent perioperative hypothermia.

    PubMed

    Campbell, Gillian; Alderson, Phil; Smith, Andrew F; Warttig, Sheryl

    2015-04-13

    Inadvertent perioperative hypothermia (a drop in core temperature to below 36°C) occurs because of interference with normal temperature regulation by anaesthetic drugs, exposure of skin for prolonged periods and receipt of large volumes of intravenous and irrigation fluids. If the temperature of these fluids is below core body temperature, they can cause significant heat loss. Warming intravenous and irrigation fluids to core body temperature or above might prevent some of this heat loss and subsequent hypothermia. To estimate the effectiveness of preoperative or intraoperative warming, or both, of intravenous and irrigation fluids in preventing perioperative hypothermia and its complications during surgery in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 2), MEDLINE Ovid SP (1956 to 4 February 2014), EMBASE Ovid SP (1982 to 4 February 2014), the Institute for Scientific Information (ISI) Web of Science (1950 to 4 February 2014), Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCOhost (1980 to 4 February 2014) and reference lists of identified articles. We also searched the Current Controlled Trials website and ClinicalTrials.gov. We included randomized controlled trials or quasi-randomized controlled trials comparing fluid warming methods versus standard care or versus other warming methods used to maintain normothermia. Two review authors independently extracted data from eligible trials and settled disputes with a third review author. We contacted study authors to ask for additional details when needed. We collected data on adverse events only if they were reported in the trials. We included in this review 24 studies with a total of 1250 participants. The trials included various numbers and types of participants. Investigators used a range of methods to warm fluids to temperatures between 37°C and 41°C. We found that evidence was of moderate quality because descriptions of trial design were

  5. Relationships between cerebral autoregulation and markers of kidney and liver injury in neonatal encephalopathy and therapeutic hypothermia.

    PubMed

    Lee, J K; Perin, J; Parkinson, C; O'Connor, M; Gilmore, M M; Reyes, M; Armstrong, J; Jennings, J M; Northington, F J; Chavez-Valdez, R

    2017-08-01

    We studied whether cerebral blood pressure autoregulation and kidney and liver injuries are associated in neonatal encephalopathy (NE). We monitored autoregulation of 75 newborns who received hypothermia for NE in the neonatal intensive care unit to identify the mean arterial blood pressure with optimized autoregulation (MAP OPT ). Autoregulation parameters and creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed using adjusted regression models. Greater time with blood pressure within MAP OPT during hypothermia was associated with lower creatinine in girls. Blood pressure below MAP OPT related to higher ALT and AST during normothermia in all neonates and boys. The opposite occurred in rewarming when more time with blood pressure above MAP OPT related to higher AST. Blood pressures that optimize cerebral autoregulation may support the kidneys. Blood pressures below MAP OPT and liver injury during normothermia are associated. The relationship between MAP OPT and AST during rewarming requires further study.

  6. Biomarkers of Brain Injury in Neonatal Encephalopathy Treated with Hypothermia

    PubMed Central

    Massaro, An N.; Chang, Taeun; Kadom, Nadja; Tsuchida, Tammy; Scafidi, Joseph; Glass, Penny; McCarter, Robert; Baumgart, Stephen; Vezina, Gilbert; Nelson, Karin B.

    2012-01-01

    Objective To determine if early serum S100B and neuron-specific enolase (NSE) levels are associated with neuroradiographic and clinical evidence of brain injury in newborns with encephalopathy. Study design Patients who received therapeutic whole-body hypothermia were prospectively enrolled in this observational study. Serum specimens were collected at 0, 12, 24, and 72 hours of cooling. S100B and NSE levels were measured by enzyme linked immunosorbent assay. Magnetic resonance imaging was performed in surviving infants at 7–10 days of life. Standardized neurologic examination was performed by a child neurologist at 14 days of life. Multiple linear regression analyses were performed to evaluate the association between S100B and NSE levels and unfavorable outcome (death or severe magnetic resonance imaging injury/significant neurologic deficit). Cutoff values were determined by receiver operating curve analysis. Results Newborns with moderate to severe encephalopathy were enrolled (n = 75). Median pH at presentation was 6.9 (range, 6.5–7.35), and median Apgar scores of 1 at 1 minute, 3 at 5 minutes, and 5 at 10 minutes. NSE and S100B levels were higher in patients with unfavorable outcomes across all time points. These results remained statistically significant after controlling for covariables, including encephalopathy grade at presentation, Apgar score at 5 minutes of life, initial pH, and clinical seizures. Conclusion Elevated serum S100B and NSE levels measured during hypothermia were associated with neuroradiographic and clinical evidence of brain injury in encephalopathic newborns. These brain-specific proteins may be useful immediate biomarkers of cerebral injury severity. PMID:22494878

  7. Biomarkers of brain injury in neonatal encephalopathy treated with hypothermia.

    PubMed

    Massaro, An N; Chang, Taeun; Kadom, Nadja; Tsuchida, Tammy; Scafidi, Joseph; Glass, Penny; McCarter, Robert; Baumgart, Stephen; Vezina, Gilbert; Nelson, Karin B

    2012-09-01

    To determine if early serum S100B and neuron-specific enolase (NSE) levels are associated with neuroradiographic and clinical evidence of brain injury in newborns with encephalopathy. Patients who received therapeutic whole-body hypothermia were prospectively enrolled in this observational study. Serum specimens were collected at 0, 12, 24, and 72 hours of cooling. S100B and NSE levels were measured by enzyme linked immunosorbent assay. Magnetic resonance imaging was performed in surviving infants at 7-10 days of life. Standardized neurologic examination was performed by a child neurologist at 14 days of life. Multiple linear regression analyses were performed to evaluate the association between S100B and NSE levels and unfavorable outcome (death or severe magnetic resonance imaging injury/significant neurologic deficit). Cutoff values were determined by receiver operating curve analysis. Newborns with moderate to severe encephalopathy were enrolled (n = 75). Median pH at presentation was 6.9 (range, 6.5-7.35), and median Apgar scores of 1 at 1 minute, 3 at 5 minutes, and 5 at 10 minutes. NSE and S100B levels were higher in patients with unfavorable outcomes across all time points. These results remained statistically significant after controlling for covariables, including encephalopathy grade at presentation, Apgar score at 5 minutes of life, initial pH, and clinical seizures. Elevated serum S100B and NSE levels measured during hypothermia were associated with neuroradiographic and clinical evidence of brain injury in encephalopathic newborns. These brain-specific proteins may be useful immediate biomarkers of cerebral injury severity. Copyright © 2012 Mosby, Inc. All rights reserved.

  8. Temperature control can abolish anesthesia-induced tau hyperphosphorylation and partly reverse anesthesia-induced cognitive impairment in old mice.

    PubMed

    Xiao, Haibing; Run, Xiaoqin; Cao, Xu; Su, Ying; Sun, Zhou; Tian, Cheng; Sun, Shenggang; Liang, Zhihou

    2013-11-01

    Anesthesia is related to cognitive impairment and the risk for Alzheimer's disease. Hypothermia during anesthesia can lead to abnormal hyperphosphorylation of tau, which has been speculated to be involved in anesthesia-induced cognitive impairment. The aim of this study was to investigate whether maintenance of the tau phosphorylation level by body temperature control during anesthesia could reverse the cognitive dysfunction in C57BL/6 mice. Eighteen-month-old mice were repeatedly anesthetized during a 2-week period with or without maintenance of body temperature, control mice were treated with normal saline instead of anesthetics. Tau phosphorylation level in mice brain was detected on western blot, and cognitive performance was measured using the Morris water maze (MWM). After anesthesia-induced hypothermia in old mice, tau was hyperphosphorylated and the cognitive performance, measured on MWM, was impaired. When body temperature was controlled during anesthesia, however, the tau hyperphosphorylation was completely avoided, and there was partial recovery in cognitive impairment measured on the MWM. Hyperphosphorylation of tau in the brain after anesthesia is an important event, and it might be, although not solely, responsible for postoperative cognitive decline. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

  9. Regional traumatic limb hypothermia attenuates distant hepatic and renal injury following blast limb trauma in rats.

    PubMed

    Zhao, Hongzhi; Ning, Jiaolin; Duan, Jiaxiang; Gu, Jianteng; Yi, Bin; Lu, Kaizhi; Mo, Liwen; Lai, Xinan; Hennah, Lindsay; Ma, Daqing

    2014-09-01

    Blast limb injury was reported to result in distant organ injury including the lungs, which can be attenuated with transient regional hypothermia (RH) to the injured limb. We aimed to further study hepatic and renal injuries following blast limb trauma and also to evaluate the protective effects of regional traumatic limb hypothermia on such injuries in rats. Blast limb trauma (BLT) was created using chartaceous electricity detonators in anesthetized male Sprague-Dawley rats. The BLT rats were randomly allocated to undergo regional traumatic limb hypothermic treatment (RH) for 30 minutes, 60 minutes, or 6 hours immediately after the onset of blast or without RH (n = 8 per group). The severity of hepatic and renal injury was assessed through histologic examination and water content (wet/dry weight) in all animals 6 hours later. The level of plasma tumor necrosis factor α (TNF-α), interleukin 6, hydrogen sulfide (H2S), and myeloperoxidase (MPO) together with hepatic and renal MPO, malondialdehyde (MDA), superoxide dismutase, and total antioxidant capacity were measured 6 hours after the blast injury. Following BLT, hepatic injury was evidenced by histopathologic changes, increased water content, as well as plasma alanine aminotransferase and aspartate aminotransferase. Renal histopathologic but not functional changes were also found. RH treatment for all durations attenuated this distant renal injury, but only RH treatment for 60 minutes and 6 hours attenuated distant hepatic injury following BLT. RH treatment for all durations decreased plasma TNF-α and interleukin 6, reduced liver and kidney MPO activity and kidney MDA, and elevated superoxide dismutase and total antioxidant capacity in both liver and kidneys. RH treatment for 60 minutes is the most effective duration to reduce hepatic MPO activity, plasma TNF-α, and kidney MDA. This study indicates that BLT-induced distant renal and hepatic injury could be attenuated by RH treatment through reduction of

  10. Fluid extravasation during cardiopulmonary bypass in piglets--effects of hypothermia and different cooling protocols.

    PubMed

    Farstad, M; Heltne, J K; Rynning, S E; Lund, T; Mongstad, A; Eliassen, F; Husby, P

    2003-04-01

    Hypothermic cardiopulmonary bypass (CPB) is associated with capillary fluid leak and edema generation which may be secondary to hemodilution, inflammation and hypothermia. We evaluated how hypothermia and different cooling strategies influenced the fluid extravasation rate during CPB. Fourteen piglets were given 60 min normothermic CPB, followed by randomization to two groups: 1: rapid cooling (RC-group) ( approximately 15 min to 28 degrees C); 2: slow cooling (SC-group) ( approximately 60 min to 28 degrees C). Ringer's solution was used as CPB prime and for fluid supplementation. Fluid input/losses, plasma volume, colloid osmotic pressures (plasma, interstitial fluid), hematocrit, serum-proteins and total tissue water (TTW) were measured and fluid extravasation rates calculated. Start of normothermic CPB resulted in a 25% hemodilution. During the first 5-10 min the fluid level of the reservoir fell markedly due to an intravascular volume loss necessitating fluid supplementation. Thereafter a steady state was reached with a constant fluid need of 0.14 +/- 0.04 ml kg-1 min-1. After start of cooling the fluid needs increased in the following 30 min to 0.91 +/- 0.11 ml kg-1 min-1 in the RC group (P < 0.001) and 0.63 +/- 0.10 ml kg-1 min-1 in the SC-group (P < 0.001) with no statistical between-group differences. Fluid extravasation rates after start of hypothermic CPB increased from 0.20 +/- 0.08 ml kg-1 min-1 to 0.71 +/- 0.13 (P < 0.01) and 0.62 +/- 0.13 ml kg-1 min-1 (P < 0.05) in the RC- and SC-groups, respectively, without any changes in degree of hemodilution. TTW increased in most tissues, whereas the intravascular albumin and protein masses remained constant with no between group differences. Hypothermia increased fluid extravasation during CPB independent of cooling strategy. Intravascular albumin and protein masses remained constant. Since inflammatory fluid leakage usually results in protein rich exudates, our data with no net protein leakage may indicate

  11. Heated intravenous fluids alone fail to prevent hypothermia in cats under general anaesthesia.

    PubMed

    Jourdan, Geraldine; Didier, Caroline; Chotard, Erwan; Jacques, Sandra; Verwaerde, Patrick

    2017-12-01

    Objectives The objective was to evaluate the clinical efficiacy of a constant rate infusion of heated fluid as the sole means of preventing intraoperative hypothermia in cats. Methods This randomised, prospective, clinical study was conducted at a university teaching veterinary hospital. Female cats (American Society of Anesthesiologists [ASA] grade I) undergoing elective surgery by laparotomy under general anaesthesia (acepromazine 0.05 mg/kg SC; morphine 0.2 mg/kg IV; propofol IV titrated, isoflurane 2% in 100% oxygen) were randomised in two groups. Both groups were infused with fluid (NaCl 0.9%, 5 ml/kg/h) either at room temperature (control group) or prewarmed at 43°C (warmed group) using an Astoflo Plus eco (Stihler Electronic) fluid heating device. No other heating device was used. Temperature, heart rate, respiratory rate and SpO 2 were evaluated after induction (T0) and every 15 mins for 1 h (T15, T30, T45, T60). Mean arterial blood pressure was recorded every 30 mins (T0, T30 and T60). Results Thirty-four female cats (ASA grade I) were enrolled in the study. There was no difference in age, weight, propofol dose or room temperature (22.4 ± 1.1°C vs 22.0 ± 1.5°C; P = 0.363) between control and warmed groups, respectively. In both groups, oesophageal temperature significantly decreased during anaesthesia ( P <0.0001). The temperature decrease after 1 h was -3.6 ± 0.7°C in the warmed group and was not significantly different from the control group (-3.4 ± 0.7°C; P = 0.307). The slopes of the temperature decrease did not significantly differ between the two groups (-0.058 ± 0.013°C/min vs -0.060 ± 0.010°C/min for the control and warmed groups, respectively; P = 0.624). Conclusions and relevance This study provides clinical evidence that a constant rate infusion of heated fluid alone fails to prevent intraoperative hypothermia in cats. The low infusion rate (5 ml/kg/h) could partly explain the ineffectiveness of this active warming device in

  12. The effects of profound hypothermia on pancreas ischemic injury: a new experimental model.

    PubMed

    Rocha-Santos, Vinicius; Ferro, Oscar Cavalcante; Pantanali, Carlos Andrés; Seixas, Marcel Povlovistsch; Pecora, Rafael Antonio Arruda; Pinheiro, Rafael Soares; Claro, Laura Carolina López; Abdo, Emílio Elias; Chaib, Eleazar; D'Albuquerque, Luiz Augusto Carneiro

    2014-08-01

    Pancreatic ischemia-reperfusion (IR) has a key role in pancreas surgery and transplantation. Most experimental models evaluate the normothermic phase of the IR. We proposed a hypothermic model of pancreas IR to evaluate the benefic effects of the cold ischemic phase. We performed a reproducible model of hypothermic pancreatic IR. The ischemia was induced in the pancreatic tail portion (1-hour ischemia, 4-hour reperfusion) in 36 Wistar rats. They are divided in 3 groups as follows: group 1 (control), sham; group 2, normothermic IR; and group 3, hypothermic IR. In group 3, the temperature was maintained as close to 4.5°C. After reperfusion, serum amylase and lipase levels, inflammatory mediators (tumor necrosis factor α, interleukin 6), and pancreas histology were evaluated. In pancreatic IR groups, amylase, cytokines, and histological damage were significantly increased when compared with group 1. In the group 3, we observed a significant decrease in tumor necrosis factor α (P = 0.004) and interleukin 6 (P = 0.001) when compared with group 2. We did not observe significant difference in amylase (P = 0.867), lipase (P = 0.993), and histology (P = 0.201). In our experimental model, we reproduced the cold phase of pancreas IR, and the pancreas hypothermia reduced the inflammatory mediators after reperfusion.

  13. Case Report: A Case of Severe Cerebral Malaria Managed with Therapeutic Hypothermia and Other Modalities for Brain Edema.

    PubMed

    Gad, AbdAllah; Ali, Sajjad; Zahoor, Talal; Azarov, Nick

    2018-04-01

    Malarial infections are uncommon in the United States and almost all reported cases stem from recent travelers coming from endemic countries. Cerebral malaria (CM) is a severe form of the disease usually affecting children and individuals with limited immunity. Despite proper management, mortality from CM can reach up to 25%, especially when it is associated with brain edema. Inefficient management of the edema may result in brain herniation and death. Uniform guidelines for management of CM-associated brain edema are lacking. In this report, we present a case of CM with associated severe brain edema that was successfully managed using a unique combination of therapeutic hypothermia, hypertonic saline, mannitol, and hyperventilation along with the antimalarial drugs quinidine and doxycycline. Our use of hypothermia was based on its proven benefit for improving neurological outcomes in post-cardiac arrest patients and previous in vitro research, suggesting its potential inhibitory role on malaria growth.

  14. Factors influencing survival of mammalian cells exposed to hypothermia. VI. Effects of prehypothermic hypoxia followed by aerobic or hypoxic storage at various hypothermic temperatures.

    PubMed

    Kruuv, J; Lepock, J R

    1995-04-01

    The Arrhenius plot of inactivation (killing) rates of V-79 Chinese hamster cells exposed to hypothermia in air-equilibrated (aerobic) medium contains a break at about 8 degrees C, which corresponds to the minimum inactivation rate, implying that there are distinct hypothermic damage mechanisms above (range I, 8 to 25 degrees C) and below (range II, 0 to 8 degrees C) 8 degrees C. Prehypothermic hypoxia (PHH) for 75 min at room temperature sensitizes cells to subsequent aerobic hypothermia at both 5 and 10 degrees C (range II and I). However, PHH followed by severe hypoxia (0.03 microM oxygen in the medium) protected cells during 10 degrees C (range I) storage by increasing the shoulder, but not the slope, of the cell survival curve compared to the PHH plus 10 degrees C aerobic hypothermia case. On the other hand, PHH plus severe hypoxia during 5 degrees C storage (range II) protected cells by decreasing the slope, but not the shoulder, of the cell survival curve compared to the PHH plus 5 degrees C aerobic hypothermia case. Furthermore, PHH plus severe hypoxia during 5 degrees C storage was not significantly worse than aerobic storage without PHH at 5 degrees C. With or without severe hypoxia, 10 degrees C storage is preferable to 5 degrees C storage in this cell line. Extrapolated to organ storage, the results may imply that if warm ischemia (PHH) has occurred, subsequent hypoxic hypothermic perfusion storage may be preferable to aerobic hypothermic perfusion storage.

  15. Examining potential side effects of therapeutic hypothermia in experimental intracerebral hemorrhage.

    PubMed

    Wowk, Shannon; Fagan, Kelly J; Ma, Yonglie; Nichol, Helen; Colbourne, Frederick

    2017-08-01

    Studies treating intracerebral hemorrhage (ICH) with therapeutic hypothermia (TH) have shown inconsistent benefits. We hypothesized that TH's anti-inflammatory effects may be responsible as inflammatory cells are essential for removing degrading erythrocytes. Here, we subjected rats to a collagenase-induced striatal ICH followed by whole-body TH (∼33℃ for 11-72 h) or normothermia. We used X-ray fluorescence imaging to spatially quantify total and peri-hematoma iron three days post-injury. At three and seven days, we measured non-heme iron levels. Finally, hematoma volume was quantified on one, three, and seven days. In the injured hemisphere, total iron levels were elevated ( p < 0.001) with iron increasing in the peri-hematoma region ( p = 0.007). Non-heme iron increased from three to seven days (p < 0.001). TH had no effect on any measure of iron ( p ≥ 0.479). At one and three days, TH did not affect hematoma volume ( p ≥ 0.264); however, at seven days there was a four-fold increase in hematoma volume in 40% of treated animals ( p = 0.032). Thus, even when TH does not interfere with initial increases in total and non-heme iron or its containment, TH can cause re-bleeding post-treatment. This serious complication could partly account for the intermittent protection previously observed. This also raises serious concerns for clinical usage of TH for ICH.

  16. Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial.

    PubMed

    Laptook, Abbot R; Shankaran, Seetha; Tyson, Jon E; Munoz, Breda; Bell, Edward F; Goldberg, Ronald N; Parikh, Nehal A; Ambalavanan, Namasivayam; Pedroza, Claudia; Pappas, Athina; Das, Abhik; Chaudhary, Aasma S; Ehrenkranz, Richard A; Hensman, Angelita M; Van Meurs, Krisa P; Chalak, Lina F; Khan, Amir M; Hamrick, Shannon E G; Sokol, Gregory M; Walsh, Michele C; Poindexter, Brenda B; Faix, Roger G; Watterberg, Kristi L; Frantz, Ivan D; Guillet, Ronnie; Devaskar, Uday; Truog, William E; Chock, Valerie Y; Wyckoff, Myra H; McGowan, Elisabeth C; Carlton, David P; Harmon, Heidi M; Brumbaugh, Jane E; Cotten, C Michael; Sánchez, Pablo J; Hibbs, Anna Maria; Higgins, Rosemary D

    2017-10-24

    Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks' or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C). The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks' gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, -1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval

  17. Postnatal hypothermia and cold stress among newborn infants in Nepal monitored by continuous ambulatory recording.

    PubMed

    Ellis, M; Manandhar, N; Shakya, U; Manandhar, D S; Fawdry, A; Costello, A M

    1996-07-01

    To describe the pattern of hypothermia and cold stress after delivery among a normal neonatal population in Nepal; to provide practical advice for improving thermal care in a resource limited maternity hospital. The principal government funded maternity hospital in Kathmandu, Nepal, with an annual delivery rate of 15,000 (constituting 40% of all Kathmandu Valley deliveries), severe resource limitations (annual budget Pounds 250,000), and a cold winter climate provided the setting. Thirty five healthy term neonates not requiring special care were enrolled for study within 90 minutes of birth. Continuous ambulatory temperature monitoring, using microthermistor skin probes for forehead and axilla, a flexible rectal probe, and a black ball probe placed next to the infant for ambient temperature, was carried out. All probes were connected to a compact battery powered Squirrel Memory Logger, giving a temperature reading to 0.2 degree C at five minute intervals for 24 hours. Severity and duration of hypothermia, using cutoff values of core temperature less than 36 degrees C, 34 degrees C, and 32 degrees C; and cold stress, using cutoff values of skin-core (forehead-axilla) temperature difference greater than 3 degrees C and 4 degrees C were the main outcome measures. Twenty four hour mean ambient temperatures were generally lower than the WHO recommended level of 25 degrees C (median 22.3 degrees C, range 15.1-27.5 degrees C). Postnatal hypothermia was prolonged, with axillary core temperatures only reaching 36 degrees C after a mean of 6.4 hours (range 0-21.1; SD 4.6). There was persistent and increasing cold stress over the first 24 hours with the core-skin (axillary-forehead) temperature gap exceeding 3 degrees C for more than half of the first 24 hours. Continuous ambulatory recording identifies weak links in the "warm chain" for neonates. The severity and duration of thermal problems was greater than expected even in a hospital setting where some of the WHO

  18. Temporal and spatial dispersion of human body temperature during deep hypothermia.

    PubMed

    Opatz, O; Trippel, T; Lochner, A; Werner, A; Stahn, A; Steinach, M; Lenk, J; Kuppe, H; Gunga, H C

    2013-11-01

    Clinical temperature management remains challenging. Choosing the right sensor location to determine the core body temperature is a particular matter of academic and clinical debate. This study aimed to investigate the relationship of measured temperatures at different sites during surgery in deep hypothermic patients. In this prospective single-centre study, we studied 24 patients undergoing cardiothoracic surgery: 12 in normothermia, 3 in mild, and 9 in deep hypothermia. Temperature recordings of a non-invasive heat flux sensor at the forehead were compared with the arterial outlet temperature of a heart-lung machine, with the temperature on a conventional vesical bladder thermistor and, for patients undergoing deep hypothermia, with oesophageal temperature. Using a linear model for sensor comparison, the arterial outlet sensor showed a difference among the other sensor positions between -0.54 and -1.12°C. The 95% confidence interval ranged between 7.06 and 8.82°C for the upper limit and -8.14 and -10.62°C for the lower limit. Because of the hysteretic shape, the curves were divided into phases and fitted into a non-linear model according to time and placement of the sensors. During cooling and warming phases, a quadratic relationship could be observed among arterial, oesophageal, vesical, and cranial temperature recordings, with coefficients of determination ranging between 0.95 and 0.98 (standard errors of the estimate 0.69-1.12°C). We suggest that measured surrogate temperatures as indices of the cerebral temperature (e.g. vesical bladder temperature) should be interpreted with respect to the temporal and spatial dispersion during cooling and rewarming phases.

  19. Critical time window for intra-arrest cooling with cold saline flush in a dog model of cardiopulmonary resuscitation.

    PubMed

    Nozari, Ala; Safar, Peter; Stezoski, S William; Wu, Xianren; Kostelnik, Scott; Radovsky, Ann; Tisherman, Samuel; Kochanek, Patrick M

    2006-06-13

    Mild hypothermia improves outcome when induced after cardiac arrest in humans. Recent studies in both dogs and mice suggest that induction of mild hypothermia during cardiopulmonary resuscitation (CPR) greatly enhances its efficacy. In this study, we evaluate the time window for the beneficial effect of intra-arrest cooling in the setting of prolonged CPR in a clinically relevant large-animal model. Seventeen dogs had ventricular fibrillation cardiac arrest no flow of 3 minutes, followed by 7 minutes of CPR basic life support and 50 minutes of advanced life support. In the early hypothermia group (n=9), mild hypothermia (34 degrees C) was induced with an intravenous fluid bolus flush and venovenous blood shunt cooling after 10 minutes of ventricular fibrillation. In the delayed hypothermia group (n=8), hypothermia was induced at ventricular fibrillation 20 minutes. After 60 minutes of ventricular fibrillation, restoration of spontaneous circulation was achieved with cardiopulmonary bypass for 4 hours, and intensive care was given for 96 hours. In the early hypothermia group, 7 of 9 dogs survived to 96 hours, 5 with good neurological outcome. In contrast, 7 of 8 dogs in the delayed hypothermia group died within 37 hours with multiple organ failure (P=0.012). Early application of mild hypothermia with cold saline during prolonged CPR enables intact survival. Delay in the induction of mild hypothermia in this setting markedly reduces its efficacy. Our data suggest that if mild hypothermia is used during CPR, it should be applied as early as possible.

  20. Hemodynamics and vasopressor support in therapeutic hypothermia after cardiac arrest: prognostic implications.

    PubMed

    Bro-Jeppesen, John; Kjaergaard, Jesper; Søholm, Helle; Wanscher, Michael; Lippert, Freddy K; Møller, Jacob E; Køber, Lars; Hassager, Christian

    2014-05-01

    Inducing therapeutic hypothermia (TH) in Out-of-Hospital Cardiac Arrest (OHCA) can be challenging due to its impact on central hemodynamics and vasopressors are frequently used to maintain adequate organ perfusion. The aim of this study was to assess the association between level of vasopressor support and mortality. In a 6-year period, 310 comatose OHCA patients treated with TH were included. Temperature, hemodynamic parameters and level of vasopressors were registered from admission to 24h after rewarming. Level of vasopressor support was assessed by the cardiovascular sub-score of Sequential Organ Failure Assessment (SOFA). The population was stratified by use of dopamine as first line intervention (D-group) or use of dopamine+norepinephrine/epinephrine (DA-group). Primary endpoint was 30-day mortality and secondary endpoint was in-hospital cause of death. Patients in the DA-group carried a 49% all-cause 30-day mortality rate compared to 23% in the D-group, plog-rank<0.0001, corresponding to an adjusted hazard ratio (HR) of 2.0 (95% CI: 1.3-3.0), p=0.001). The DA-group had an increased 30-day mortality due to neurological injury (HR=1.7 (95% CI: 1.1-2.7), p=0.02). Cause of death was anoxic brain injury in 78%, cardiovascular failure in 18% and multi-organ failure in 4%. The hemodynamic changes of TH reversed at normothermia, although the requirement for vasopressor support (cardiovascular SOFA≥3) persisted in 80% of patients. In survivors after OHCA treated with TH the induced hemodynamic changes reversed after normothermia, while the need for vasopressor support persisted. Patients requiring addition of norepinephrine/epinephrine on top of dopamine had an increased 30-day all-cause mortality, as well as death from neurological injury. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. 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

    PubMed Central

    Shimansky, Yury P.; Oliveira, Daniela L.; Eales, Justin R.; Coimbra, Cândido C.

    2017-01-01

    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

  2. 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.

    PubMed

    Wanner, Samuel P; Almeida, M Camila; Shimansky, Yury P; Oliveira, Daniela L; Eales, Justin R; Coimbra, Cândido C; Romanovsky, Andrej A

    2017-07-19

    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

  3. Neither xenon nor fentanyl induces neuroapoptosis in the newborn pig brain.

    PubMed

    Sabir, Hemmen; Bishop, Sarah; Cohen, Nicki; Maes, Elke; Liu, Xun; Dingley, John; Thoresen, Marianne

    2013-08-01

    Some inhalation anesthetics increase apoptotic cell death in the developing brain. Xenon, an inhalation anesthetic, increases neuroprotection when combined with therapeutic hypothermia after hypoxic-ischemic brain injury in newborn animals. The authors, therefore, examined whether there was any neuroapoptotic effect of breathing 50% xenon with continuous fentanyl sedation for 24 h at normothermia or hypothermia on newborn pigs. Twenty-six healthy pigs (<24-h old) were randomized into four groups: (1) 24  h of 50% inhaled xenon with fentanyl at hypothermia (Trec = 33.5 °C), (2) 24 h of 50% inhaled xenon with fentanyl at normothermia (Trec = 38.5 °C), (3) 24 h of fentanyl at normothermia, or (4) nonventilated juvenile controls at normothermia. Five additional nonrandomized pigs inhaled 2% isoflurane at normothermia for 24 h to verify any proapoptotic effect of inhalation anesthetics in our model. Pathological cells were morphologically assessed in cortex, putamen, hippocampus, thalamus, and white matter. To quantify the findings, immunostained cells (caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphate nick-end labeling) were counted in the same brain regions. For groups (1) to (4), the total number of apoptotic cells was less than 5 per brain region, representing normal developmental neuroapoptosis. After immunostaining and cell counting, regression analysis showed that neither 50% xenon with fentanyl nor fentanyl alone increased neuroapoptosis. Isoflurane caused on average a 5- to 10-fold increase of immunostained cells. At normothermia or hypothermia, neither 24 h of inhaled 50% xenon with fentanyl sedation nor fentanyl alone induces neuroapoptosis in the neonatal pig brain. Breathing 2% isoflurane increases neuroapoptosis in neonatal pigs.

  4. Accidental hypothermia: rewarming treatments, complications and outcomes from one university medical centre.

    PubMed

    van der Ploeg, Gert-Jan; Goslings, J Carel; Walpoth, Beat H; Bierens, Joost J L M

    2010-11-01

    Accidental hypothermia (AH) is a complex and life threatening condition. Knowledge about epidemiology, rewarming treatments, complications and outcome is limited. This study was initiated to obtain data on causes, rewarming treatments and complications. A retrospective cohort study of all patients with a body temperature ≤ 35°C admitted to the Emergency Department (ED) of the VU university medical centre, Amsterdam, The Netherlands, between January 1, 2000 and August 31, 2008. A predefined set of epidemiological and clinical data was retrieved. Eighty-four patients were included (median age: 47 years). Categories of hypothermia included immersion (18), submersion (29) and exposure to cold (37); concomitant factors were intoxication (26), trauma (40) and homelessness (7). Temperature at admission in the ED was 31.6 ± 2.6°C (mean ± SD), lowest temperature 24.2°C. Fourteen different rewarming treatments were used resulting in a wide range of rewarming speeds. Seventy-nine complications occurred: pulmonary, renal and neurological complications in 20, 17 and 10 patients respectively. Seventeen patients had 2 or more late complications. Twenty-four patients (28.6%) died: 10 during rewarming and 14 after rewarming was completed. Prognosis was poor in older and colder patients and after indoor exposure and submersion. AH is a rare diagnosis in an inhomogeneous population, treated with a large variety of rewarming techniques. Most complications and death occurred late, after rewarming was completed. Because individual teams gain little clinical experiences, we suggest multiple centre data collection as a first step towards an evidence-based standard of care. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Resistive-heating or forced-air warming for the prevention of redistribution hypothermia.

    PubMed

    De Witte, Jan L; Demeyer, Caroline; Vandemaele, Els

    2010-03-01

    We evaluated the efficacy of resistive-heating or forced-air warming versus no prewarming, applied before induction of anesthesia for prevention of hypothermia. Twenty-seven patients scheduled for laparoscopic colorectal surgery were randomized into 1 of 3 groups: no prewarming; 30 minutes of prewarming with a carbon fiber total body cover at 42 degrees C; or 30 minutes of preoperative forced-air warming at 42 degrees C. The forced-air warming cover excluded the shoulders, ankles, and feet. The prewarming period was exactly 30 minutes. At the 31st minute, a total IV anesthesia technique was initiated, and all patients were actively warmed with a lithotomy blanket. Tympanic and distal esophageal temperatures were measured. Categorical data were analyzed using chi(2) test, and continuous data were analyzed with analysis of variance. P <0.05 was considered statistically significant. The mean esophageal temperatures differed significantly between the control and the carbon fiber group from 40 to 90 minutes of anesthesia. After 50 minutes of anesthesia, the mean esophageal temperatures in the control, carbon fiber, and forced-air groups were 35.9 degrees C +/- 0.3 degrees C, 36.5 degrees C +/- 0.4 degrees C, and 36.2 degrees C +/- 0.3 degrees C, respectively. No statistically significant difference was found between the forced-air and control groups. After 30 minutes of prewarming with resistive heating, patients had an esophageal temperature that was significantly higher than the control group. Prewarming should be considered part of the anesthetic management when patients are at risk for postoperative hypothermia.

  6. Hypoxia, an adjunct in helium-cold hypothermia - Sparing effect on hepatic and cardiac metabolites.

    NASA Technical Reports Server (NTRS)

    Anderson, G. L.; Resch, G. E.; Musacchia, X. J.

    1973-01-01

    Investigation of the effect of hypoxia on the depletion of metabolites that occurs in helium-aided induction of hypothermia. Hypoxic slowing of the heart of a hamster while exposed to cold helox is demonstrated. An attempt is made to evaluate the relative importance of cardiac slowing and limitation of thermogenesis in determining the effect of hypoxia. In explanation of the results presented, it is suggested that hypoxia limits the energy expenditure by the heart during induction.

  7. Rewarming affects EEG background in term newborns with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia.

    PubMed

    Birca, Ala; Lortie, Anne; Birca, Veronica; Decarie, Jean-Claude; Veilleux, Annie; Gallagher, Anne; Dehaes, Mathieu; Lodygensky, Gregory A; Carmant, Lionel

    2016-04-01

    To investigate how rewarming impacts the evolution of EEG background in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). We recruited a retrospective cohort of 15 consecutive newborns with moderate (9) and severe (6) HIE monitored with a continuous EEG during TH and at least 12h after its end. EEG background was analyzed using conventional visual and quantitative EEG analysis methods including EEG discontinuity, absolute and relative spectral magnitudes. One patient with seizures on rewarming was excluded from analyses. Visual and quantitative analyses demonstrated significant changes in EEG background from pre- to post-rewarming, characterized by an increased EEG discontinuity, more pronounced in newborns with severe compared to moderate HIE. Neonates with moderate HIE also had an increase in the relative magnitude of slower delta and a decrease in higher frequency theta and alpha waves with rewarming. Rewarming affects EEG background in HIE newborns undergoing TH, which may represent a transient adaptive response or reflect an evolving brain injury. EEG background impairment induced by rewarming may represent a biomarker of evolving encephalopathy in HIE newborns undergoing TH and underscores the importance of continuously monitoring the brain health in critically ill neonates. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  8. CHOLINESTERASE INHIBITION AND HYPOTHERMIA FOLLOWING EXPOSURE TO BINARY MIXTURES OF ANTICHOLINESTERASE AGENTS: LACK OF EVIDENCE FOR CAUSE-AND-EFFECT

    EPA Science Inventory

    Dose-additivity has been the default assumption in risk assessments of pesticides with a common mechanism of action but it has been suspected that there could be non-additive effects. Inhibition of plasma cholinesterase (ChE) activity and hypothermia were used as benchmarks of e...

  9. Effects of In Vitro Hemodilution, Hypothermia and rFVIIa Addition on Coagulation in Human Blood

    DTIC Science & Technology

    2012-03-30

    primary fluids used by many trauma units and the US Army for pre-hospital resuscitation [17]. HX, a hetastarch-based product in a balanced electro...and has been associated with dilution of coagulation factors and hypothermia. Recombinant activated Factor VII (rFVIIa) has been used, often as a...of rFVIIa results in an enhancement of thrombin generation on the platelet surface at the site of injury independent of the presence of Factor VIII

  10. Alteration in the level of endogenous hypothalamic prostaglandins induced by delta 9-tetrahydrocannabinol in the rat.

    PubMed Central

    Coupar, I. M.; Taylor, D. A.

    1982-01-01

    1 Whole brain and regional brain levels of prostaglandin E2 (PGE2)-like material have been determined following administration of delta 9-tetrahydrocannabinol (delta 9 -THC) in rats. 2 Intravenous administration of delta 9-THC 2 mg/kg, resulted in marked behavioural changes and hypothermia. The behavioural changes consisted mainly of catatonia (most apparent at 30 min after administration of delta 9-THC), followed by sedation (most evident at 60 min). Hypothermia was marked from 30 min after administration of delta 9-THC. 3 delta 9-THC did not after the whole brain levels of PGE2-like material 30, 60 or 120 min after administration. 4 delta 9-THC did not alter the levels of PGE2-like material in the medulla oblongata/pons, midbrain, cortex and cerebellum, 30 min after administration. However, there was a significant reduction of PGE2-like material in the hypothalamus, 30 min after delta 9-THC. 5 It is suggested that the delta 9-THC-induced decrease in hypothalamic PGE2-like material may contribute to the hypothermia observed following delta 9-THC administration. PMID:6282371

  11. Accuracy of the Defining Characteristics of the Nursing Diagnosis Hypothermia in Newborns.

    PubMed

    de Aquino, Wislla Ketlly Menezes; Lopes, Marcos Venícios de Oliveira; da Silva, Viviane Martins; Fróes, Nathaly Bianka Moraes; de Menezes, Angélica Paixão; Almeida, Aline de Aquino Peres; Sobreira, Bianca Alves

    2017-09-18

    To analyze the accuracy of the defining characteristics of hypothermia in newborns and to verify associations between defining characteristics and clinical variables. A cross-sectional accuracy study with statistical analysis. Slow capillary refill, decrease in ventilation, peripheral vasoconstriction, and insufficient weight gain were the defining characteristics with the highest specificity values, while slow gastric emptying, skin cool to touch, irritability, and bradycardia were the defining characteristics with the highest values for both sensitivity and specificity. Slow gastric emptying, skin cool to touch, irritability, and bradycardia are good clinical indicators to infer initial stages of hypothermia and to confirm its presence. Accuracy measures may contribute to the improvement of the diagnostic inferential process. Analisar acurácia das características definidoras de Hipotermia em recém-nascidos e identificar a associação delas com variáveis clínicas. MÉTODO: Estudo de acurácia transversal com análise estatística. Preenchimento capilar lento, diminuição da ventilação, vasoconstrição periférica e ganho de peso insuficiente apresentaram valores altos de especificidade enquanto esvaziamento gástrico lento, pele fria, irritabilidade e bradicardia apresentaram valores elevados de sensibilidade e especificidade. CONCLUSÃO: Esvaziamento gástrico lento, pele fria, irritabilidade e bradicardia são úteis para inferir estágios iniciais de hipotermia e para confirmação diagnóstica. IMPLICAÇÕES PARA PRÁTICA DE ENFERMAGEM: Medidas de acurácia podem contribuir para o processo de inferência do diagnóstico hipotermia. © 2017 NANDA International, Inc.

  12. Therapeutic whole-body hypothermia reduces mortality in severe traumatic brain injury if the cooling index is sufficiently high: meta-analyses of the effect of single cooling parameters and their integrated measure.

    PubMed

    Olah, Emoke; Poto, Laszlo; Hegyi, Peter; Szabo, Imre; Hartmann, Petra; Solymar, Margit; Petervari, Erika; Balasko, Marta; Habon, Tamas; Rumbus, Zoltan; Tenk, Judit; Rostas, Ildiko; Weinberg, Jordan; Romanovsky, Andrej A; Garami, Andras

    2018-04-21

    Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the mortality of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure inter-study homogeneity. We extracted data on TBI severity, body temperature, mortality, and cooling parameters; then we calculated the cooling index, an integrated measure of therapeutic hypothermia. Forest plot of all identified studies showed no difference in the outcome of TBI between cooled and not cooled patients, but inter-study heterogeneity was high. On the contrary, by meta-analysis of RCTs which were homogenous with regards to statistical, clinical designs and precisely reported the cooling protocol, we showed decreased odds ratio for mortality in therapeutic hypothermia compared to no cooling. As independent factors, milder and longer cooling, and rewarming at < 0.25°C/h were associated with better outcome. Therapeutic hypothermia was beneficial only if the cooling index (measure of combination of cooling parameters) was sufficiently high. We conclude that high methodological and statistical inter-study heterogeneity could underlie the contradictory results obtained in previous studies. By analyzing methodologically homogenous studies, we show that cooling improves the outcome of severe TBI and this beneficial effect depends on certain cooling parameters and on their integrated measure, the cooling index.

  13. Autonomic changes induced by provocative motion in rats bred for high (HAB) and low (LAB) anxiety-related behavior: Paradoxical responses in LAB animals.

    PubMed

    Carnevali, Luca; Andrews, Paul L; Neumann, Inga D; Nalivaiko, Eugene; Sgoifo, Andrea

    2016-12-01

    In humans, associations between anxiety and nausea (including motion-induced) are reported but the underlying mechanisms are not known. Hypothermia is proposed to be an index of nausea in rats. Utilising hypothermia and heart rate as outcome measures we investigated the response to provocative motion in rats selectively bred for high (HAB) and low (LAB) anxiety-related behaviors and in non-selected (NAB) rats to further elucidate the potential relationship between hypothermia and nausea-like state. Core temperature and electrocardiogram were monitored in each group (n=10 per group) using telemetry, with or without circular motion (40min; 0.75Hz) and vehicle or diazepam (2mg/kg, i.p.) pre-treatment. Heart rate and time- and frequency-domain parameters of heart rate variability were derived from the electrocardiogram. There was no baseline difference in core temperature between the three groups (mean 38.0±0.1°C), but HAB animals had a significantly lower resting heart rate (330±7bpm) compared to LAB (402±5bpm) and NAB (401±9bpm). Animals in all groups exhibited hypothermia during motion (HAB: 36.3±0.1°C; NAB: 36.4±0.1°C; LAB: 34.9±0.2°C) with the magnitude (area under the curve, AUC) of the response during 40-min motion being greater in LAB compared to NAB and HAB rats, and this was also the case for the motion-induced bradycardia. Diazepam had minimal effects on baseline temperature and heart rate in all groups, but significantly reduced the hypothermia response (AUC) to motion in all groups by ~30%. Breeding for extremes in anxiety-related behavior unexpectedly selects animals with low trait anxiety that have enhanced bradycardia and hypothermic responses to motion; consequently, this animal model appears to be not suitable for exploring relationships between anxiety and autonomic correlates of nausea. Thermal and cardiovascular responses to motion were little different between HAB and NAB rats indicating that either hypothermia is not an index of a

  14. Novel approach for independent control of brain hypothermia and systemic normothermia: cerebral selective deep hypothermia for refractory cardiac arrest.

    PubMed

    Wang, Chih-Hsien; Lin, Yu-Ting; Chou, Heng-Wen; Wang, Yi-Chih; Hwang, Joey-Jen; Gilbert, John R; Chen, Yih-Sharng

    2017-08-01

    A 38-year-old man was found unconscious, alone in the driver's seat of his car. The emergency medical team identified his condition as pulseless ventricular tachycardia. Defibrillation was attempted but failed. Extracorporeal membrane oxygenation (ECMO) was started in the emergency room 52 min after the estimated arrest following the extracorporeal cardiopulmonary resuscitation (ECPR) protocol in our center. The initial prognosis under the standard protocol was <25% chance of survival. A novel adjunctive to our ECPR protocol, cerebral selective deep (<30°C) hypothermia (CSDH), was applied. CSDH adds a second independent femoral access extracorporeal circuit, perfusing cold blood into the patient's common carotid artery. The ECMO and CSDH circuits demonstrated independent control of cerebral and core temperatures. Nasal temperature was lowered to below 30°C for 12 hours while core was maintained at normothermia. The patient was discharged without significant neurological deficit 32 days after the initial arrest. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Hepatic gene expression profiling of 5'-AMP-induced hypometabolism in mice.

    PubMed

    Zhao, Zhaoyang; Miki, Takao; Van Oort-Jansen, Anita; Matsumoto, Tomoko; Loose, David S; Lee, Cheng Chi

    2011-04-12

    There is currently much interest in clinical applications of therapeutic hypothermia. Hypothermia can be a consequence of hypometabolism. We have recently established a procedure for the induction of a reversible deep hypometabolic state in mice using 5'-adenosine monophosphate (5'-AMP) in conjunction with moderate ambient temperature. The current study aims at investigating the impact of this technology at the gene expression level in a major metabolic organ, the liver. Our findings reveal that expression levels of the majority of genes in liver are not significantly altered by deep hypometabolism. However, among those affected by hypometabolism, more genes are differentially upregulated than downregulated both in a deep hypometabolic state and in the early arousal state. These altered gene expression levels during 5'-AMP induced hypometabolism are largely restored to normal levels within 2 days of the treatment. Our data also suggest that temporal control of circadian genes is largely stalled during deep hypometabolism.

  16. Effects of adenosine monophosphate on induction of therapeutic hypothermia and neuronal damage after cardiopulmonary resuscitation in rats.

    PubMed

    Knapp, Jürgen; Schneider, Andreas; Nees, Corinna; Bruckner, Thomas; Böttiger, Bernd W; Popp, Erik

    2014-09-01

    Animal studies and pathophysiological considerations suggest that therapeutic hypothermia after cardiopulmonary resuscitation is the more effective the earlier it is induced. Therefore this study is sought to examine whether pharmacological facilitated hypothermia by administration of 5'-adenosine monophosphate (AMP) is neuroprotective in a rat model of cardiac arrest (CA) and resuscitation. Sixty-one rats were subjected to CA. After 6 min of ventricular fibrillation advanced cardiac life support was started. After successful return of spontaneous circulation (ROSC, n=40), animals were randomized either to placebo group (n=14) or AMP group (800 mg/kg body weight, n=14). Animals were kept at an ambient temperature of 18°C for 12 h after ROSC and core body temperature was measured using a telemetry temperature probe. Neuronal damage was analyzed by counting Nissl-positive (i.e. viable) neurons and TUNEL-positive (i.e. apoptotic) cells in coronal brain sections 7 days after ROSC. Functional status evaluated on days 1, 3 and 7 after ROSC by a tape removal test. Time until core body temperature dropped to <34.0°C was 31 min [28; 45] in AMP-treated animals and 125 min [90; 180] in the control group (p=0.003). Survival until 7 days after ROSC was comparable in both groups. Also number of Nissl-positive cells (AMP: 1 [1; 7] vs. placebo: 2 [1; 3] per 100 pixel; p=0.66) and TUNEL-positive cells (AMP: 56 [44; 72] vs. placebo: 53 [41; 67] per 100 pixel; p=0.70) did not differ. Neither did AMP affect functional neurological outcome up to 7 days after ROSC. Mean arterial pressure 20 min after ROSC was 49 [45; 55] mmHg in the AMP group in comparison to 91 [83; 95] mmHg in the control group (p<0.001). Although application of AMP reduced the time to reach a core body temperature of <34°C neither survival was improved nor neuronal damage attenuated. Reason for this is probably induction of marked hypotension as an adverse reaction to AMP treatment. Copyright © 2014 Elsevier

  17. Mild intraoperative hypothermia reduces free tissue transfer thrombosis.

    PubMed

    Liu, Yuen-Jong; Hirsch, Brandon P; Shah, Asad A; Reid, Marjorie A; Thomson, J Grant

    2011-02-01

    Patients undergoing free tissue transfer are particularly susceptible to hypothermia. The goal was to investigate the impact of intraoperative core body temperature on free flap thrombosis. Two hundred twelve cases of free flap reconstruction at Yale-New Haven Hospital between 1992 and 2008 were reviewed. Free flap thrombosis was defined by complete flap necrosis or direct visualization of arterial or venous thrombosis. Temperature measurements were calibrated to bladder temperatures as measured by Foley catheter sensor. Through logistic regression analysis, maximum and minimum intraoperative temperatures were determined to be statistically significant predictors of free flap thrombosis. The optimal temperature was calculated to be 36.2 °C, and maximum intraoperative temperatures between 36.0 °C and 36.4 °C showed lower thrombosis rates than super-warmed patients ( P < 0.03). Therefore, free flap patients should be mildly hypothermic at 36.0 °C to 36.4 °C, compared with normothermia at 37.5 °C, as measured in the bladder. A prospective randomized trial investigating thrombosis rates and intraoperative temperature should be undertaken. © Thieme Medical Publishers.

  18. Tau hyperphosphorylation in the brain of ob/ob mice is due to hypothermia: Importance of thermoregulation in linking diabetes and Alzheimer's disease.

    PubMed

    Gratuze, Maud; El Khoury, Noura B; Turgeon, Andréanne; Julien, Carl; Marcouiller, François; Morin, Françoise; Whittington, Robert A; Marette, André; Calon, Frédéric; Planel, Emmanuel

    2017-02-01

    Over the last few decades, there has been a significant increase in epidemiological studies suggesting that type 2 diabetes (T2DM) is linked to a higher risk of Alzheimer's disease (AD). However, how T2DM affects AD pathology, such as tau hyperphosphorylation, is not well understood. In this study, we investigated the impact of T2DM on tau phosphorylation in ob/ob mice, a spontaneous genetic model of T2DM. Tau phosphorylation at the AT8 epitope was slightly elevated in 4-week-old ob/ob mice while 26-week-old ob/ob mice exhibited tau hyperphosphorylation at multiple tau phospho-epitopes (Tau1, CP13, AT8, AT180, PHF1). We then examined the mechanism of tau hyperphosphorylation and demonstrated that it is mostly due to hypothermia, as ob/ob mice were hypothermic and normothermia restored tau phosphorylation to control levels. As caffeine has been shown to be beneficial for diabetes, obesity and tau phosphorylation, we, therefore, used it as therapeutic treatment. Unexpectedly, chronic caffeine intake exacerbated tau hyperphosphorylation by promoting deeper hypothermia. Our data indicate that tau hyperphosphorylation is predominately due to hypothermia consequent to impaired thermoregulation in ob/ob mice. This study establishes a novel link between diabetes and AD, and reinforces the importance of recording body temperature to better assess the relationship between diabetes and AD. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Fever control and application of hypothermia using intravenous cold saline

    PubMed Central

    Fink, Ericka L.; Kochanek, Patrick M.; Clark, Robert S. B.; Bell, Michael J.

    2013-01-01

    Objective To describe the use and feasibility of cold saline to decrease body temperature in pediatric neurocritical care. Design Retrospective chart review. Setting Pediatric tertiary care university hospital. Patients Children between 1 week and 17 yrs of age admitted to the pediatric intensive care unit with acute brain injury and having received intravenous cold saline between June-August 2009. Intervention(s) None. Measurements and Main Results Eighteen subjects accounted for 20 infusions with mean infusion volume 18 ± 10 cc/kg. Eight subjects had traumatic brain injury (TBI), 2 had intracranial hemorrhage, 6 had cardiac arrest, and one each had ischemic stroke and status epilepticus. The mean age was 9.5 ± 4.8 yrs. Temperature decreased from 38.7 ± 1.1°C to 37.7 ± 1.2°C and 37.0 ± 2.0 to 35.3 ± 1.6°C one h after infusion for fever (n=14, p<.05) or hypothermia (HT) induction (n=6, p=.05), respectively. Cold saline was not bolused, rather infused over 10–15 minutes. Mean arterial blood pressure and oxygenation parameters (PaO2/FiO2 ratio, mean airway pressure) were unchanged, but heart rate decreased in HT subjects (121 ± 4 vs. 109 ± 12; p<.05). Serum sodium concentration and International normalized ratio were significantly increased after cold saline infusion. There were no differences between pre- and post-infusion serum glucose and hematocrit, nor cerebral perfusion pressure or intracranial pressure in TBI patients. Conclusions Cold saline was an effective method of reducing temperature in children with acute brain injury. This approach can be considered to treat fever or to induce HT. Prospective study comparing safety and efficacy versus other cooling measures should be considered. PMID:21037507

  20. The Effect of Hypothermia on Prolonged Distal Aortic Balloon Occlusion in a Porcine Model (Sus scrofa) of Hemorrhage

    DTIC Science & Technology

    2017-06-12

    REBOA.Methods: 12 swine were anesthetized, instrumented, then underwent 15 blood volume hemorrhage. Animals were randomized to hypothermia or...normothermia followed by 4 hours of zone III REBOA, resuscitation with shed blood , and 3 hours of critical care. Physiologic parameters were continuously...significant differences between groups at baseline or after hemorrhage. No histologic differences were observed in hind limb skeletal muscle. Maximum