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... tinged skin or pale skin Low body temperature (hypothermia) Passing out (unconsciousness) and can't be awakened ... level may drop low enough to cause seizures. Hypothermia. Your body temperature may drop so low that ...

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

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.

Biphasic Effect of Melanocortin Agonists on Metabolic Rate and Body Temperature

PubMed Central

Lute, Beth; Jou, William; Lateef, Dalya M.; Goldgof, Margalit; Xiao, Cuiying; Piñol, Ramón A.; Kravitz, Alexxai V.; Miller, Nicole R.; Huang, Yuning George; Girardet, Clemence; Butler, Andrew A.; Gavrilova, Oksana; Reitman, Marc L.

2014-01-01

Summary The melanocortin system regulates metabolic homeostasis and inflammation. Melanocortin agonists have contradictorily been reported to both increase and decrease metabolic rate and body temperature. We find two distinct physiologic responses occurring at similar doses. Intraperitoneal administration of the nonselective melanocortin agonist MTII causes a melanocortin-4 receptor (Mc4r) mediated hypermetabolism/hyperthermia. This is preceded by a profound, transient hypometabolism/hypothermia that is preserved in mice lacking any one of Mc1r, Mc3r, Mc4r, or Mc5r. Three other melanocortin agonists also caused hypothermia, which is actively achieved via seeking a cool environment, vasodilation, and inhibition of brown adipose tissue thermogenesis. These results suggest that the hypometabolic/hypothermic effect of MTII is not due to a failure of thermoregulation. The hypometabolism/hypothermia was prevented by dopamine antagonists and MTII selectively activated arcuate nucleus dopaminergic neurons; these neurons may contribute to the hypometabolism/hypothermia. We propose that the hypometabolism/hypothermia is a regulated response, potentially beneficial during extreme physiologic stress. PMID:24981835

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.

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

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

[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.

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 trauma. Therefore, induced hypothermia might represent a potential therapeutic strategy to avoid posttraumatic organ dysfunction.

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.

[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.

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.

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.

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.

[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.

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.

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.

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

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.

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

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.

Brain Resuscitation in the Drowning Victim

PubMed Central

Topjian, Alexis A.; Berg, Robert A.; Bierens, Joost J. L. M.; Branche, Christine M.; Clark, Robert S.; Friberg, Hans; Hoedemaekers, Cornelia W. E.; Holzer, Michael; Katz, Laurence M.; Knape, Johannes T. A.; Kochanek, Patrick M.; Nadkarni, Vinay; van der Hoeven, Johannes G.

2013-01-01

Drowning is a leading cause of accidental death. Survivors may sustain severe neurologic morbidity. There is negligible research specific to brain injury in drowning making current clinical management non-specific to this disorder. This review represents an evidence-based consensus effort to provide recommendations for management and investigation of the drowning victim. Epidemiology, brain-oriented prehospital and intensive care, therapeutic hypothermia, neuroimaging/monitoring, biomarkers, and neuroresuscitative pharmacology are addressed. When cardiac arrest is present, chest compressions with rescue breathing are recommended due to the asphyxial insult. In the comatose patient with restoration of spontaneous circulation, hypoxemia and hyperoxemia should be avoided, hyperthermia treated, and induced hypothermia (32–34 °C) considered. Arterial hypotension/hypertension should be recognized and treated. Prevent hypoglycemia and treat hyperglycemia. Treat clinical seizures and consider treating non-convulsive status epilepticus. Serial neurologic examinations should be provided. Brain imaging and serial biomarker measurement may aid prognostication. Continuous electroencephalography and N20 somatosensory evoked potential monitoring may be considered. Serial biomarker measurement (e.g., neuron specific enolase) may aid prognostication. There is insufficient evidence to recommend use of any specific brain-oriented neuroresuscitative pharmacologic therapy other than that required to restore and maintain normal physiology. Following initial stabilization, victims should be transferred to centers with expertise in age-specific post-resuscitation neurocritical care. Care should be documented, reviewed, and quality improvement assessment performed. Preclinical research should focus on models of asphyxial cardiac arrest. Clinical research should focus on improved cardiopulmonary resuscitation, re-oxygenation/reperfusion strategies, therapeutic hypothermia, neuroprotection, neurorehabilitation, and consideration of drowning in advances made in treatment of other central nervous system disorders. PMID:22956050

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.

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

Brain temperature: heat production, elimination and clinical relevance.

PubMed

Bertolizio, Gianluca; Mason, Linda; Bissonnette, Bruno

2011-04-01

Neurological insults are a leading cause of morbidity and mortality, both in adults and especially in children. Among possible therapeutic strategies to limit clinical cerebral damage and improve outcomes, hypothermia remains a promising and beneficial approach. However, its advantages are still debated after decades of use. Studies in adults have generated conflicting results, whereas in children recent data even suggest that hypothermia may be detrimental. Is it because brain temperature physiology is not well understood and/or not applied properly, that hypothermia fails to convince clinicians of its potential benefits? Or is it because hypothermia is not, as believed, the optimal strategy to improve outcome in patients affected with an acute neurological insult? This review article should help to explain the fundamental physiological principles of brain heat production, distribution and elimination under normal conditions and discuss why hypothermia cannot yet be recommended routinely in the management of children affected with various neurological insults. © 2011 Blackwell Publishing Ltd.

9 CFR 3.116 - Care in transit.

Code of Federal Regulations, 2010 CFR

2010-01-01

... such methods as intermittent spraying of water or application of a nontoxic emollient; (2) Assuring... related stress; and (5) Calming the marine mammals to avoid struggling, thrashing, and other unnecessary.../or warmed sufficiently to prevent overheating, hypothermia, or temperature related stress; and (2...

9 CFR 3.116 - Care in transit.

Code of Federal Regulations, 2011 CFR

2011-01-01

... such methods as intermittent spraying of water or application of a nontoxic emollient; (2) Assuring... related stress; and (5) Calming the marine mammals to avoid struggling, thrashing, and other unnecessary.../or warmed sufficiently to prevent overheating, hypothermia, or temperature related stress; and (2...

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.

Forced-Air Warmers and Surgical Site Infections in Patients Undergoing Knee or Hip Arthroplasty.

PubMed

Austin, Paul N

2017-01-01

The majority of the evidence indicates preventing inadvertent perioperative hypothermia reduces the incidence of many perioperative complications. Among the results of inadvertent perioperative hypothermia are increased bleeding, myocardial events, impaired wound healing, and diminished renal function. Most researchers agree there is an increased incidence of surgical site infections in patients who experience inadvertent perioperative hypothermia. Forced-air warming is effective in preventing inadvertent perioperative hypothermia. Paradoxically, forced-air warmers have been implicated in causing surgical site infections in patients undergoing total knee or hip arthroplasty. The results of investigations suggest these devices harbor pathogens and cause unwanted airflow disturbances. However, no significant increases in bacterial counts were found when forced-air warmers were used according to the manufacturer's directions. The results of one study suggested the incidence of surgical site infections in patients undergoing total joint arthroplasty was increased when using a forced-air warmer. However these researchers did not control for other factors affecting the incidence of surgical site infections in these patients. Current evidence does not support forced-air warmers causing surgical site infections in patients undergoing total knee or hip arthroplasty. Clinicians must use and maintain these devices as per the manufacturer's directions. They may consider using alternative warming methods. Well-conducted studies are needed to help determine the role of forced-air warmers in causing infections in these patients.

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.

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

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.

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.

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 relatively easy, addressing this widespread challenge might play a substantial role in reaching Millennium Development Goal 4, a reduction of child mortality. PMID:23369256

Anesthetic management of intestinal obstruction: A postgraduate educational review.

PubMed

Parthasarathy, S; Sripriya, R; Krishnaveni, N

2016-01-01

Intestinal obstruction is associated with significant morbidity and mortality. Scientific assessment of the cause, site of obstruction, appropriate correction of the fluid deficit and electrolyte imbalance with preoperative stabilization of blood gases is ideal as a preoperative workup. Placement of a preoperative epidural catheter especially in the thoracic interspace takes care of perioperative pain and stress reduction. Intraoperative management by controlled general anesthesia administering a relative high inspired fraction of oxygen with invasive monitoring in selected sick cases is mandatory. Preoperative monitoring and stabilizing raised intra-abdominal pressure reduces morbidity. Caution should be exercised during opening and closure of abdomen to avoid cardiorespiratory ill effects. There should be an emphasis on avoiding hypothermia. The use of nonsteroidal anti-inflammatory drugs may worsen sick, fragile patients. The use of sugammadex rather than neostigmine will obscure certain controversies in the healing of intestinal anastomotic site. Replacement of blood loss continued correction of fluids and electrolytes with possible postoperative mechanical ventilation in sick cases may improve outcomes in these patients.

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

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.

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...

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. By contrast, in SHR aortae, TRPV4 channels are opened, resulting in endothelial production of acetylcholine, which, in an autocrine manner, activates muscarinic receptors on neighboring cells to elicit endothelium-dependent relaxations in response to mild hypothermia. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

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 mortality in hypothermic patients is primarily caused by the injury severity and does not reflect an independent adverse effect of hypothermia. Furthermore, hypothermia was not shown to be an independent risk factor for posttraumatic complications. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

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

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.

[Mesenteric circulation evaluation during myocardial revascularization with different temperature modes of extracorporeal circulation].

PubMed

Iavorovskiĭ, A G; Novikova, O V; Aksel'rod, B A; Guleshov, V A; Amelina, M A; Bulganina, N A; Morozov, Iu A

2013-01-01

The Mesenteric blood circulation during myocardium revasculization was investigated 40 patients were divided in 2 groups: 1st group - normothermia CPB, 2nd group hypothermia CPB. It was found that reduced mesenteric perfusion occurred in both groups, but it was more pronounced in hypothermia CPB group and was caused by a significant deterioration of the microcirculation.

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.

Intravenous administration of levothyroxine for treatment of suspected myxedema coma complicated by severe hypothermia in a dog.

PubMed

Henik, R A; Dixon, R M

2000-03-01

A 7-year-old male English Coonhound with suspected myxedema coma complicated by severe hypothermia and metabolic abnormalities was treated with a combination of active external and core rewarming techniques, i.v. and oral administration of levothyroxine, supplemental oxygen, and administration of fluids (0.9% NaCl solution). Myxedema coma develops as a consequence of severe hypothyroidism and is characterized by a hypometabolic, stuporous state. Myxedema coma is associated with a high mortality rate, and most reported cases have involved Doberman Pinschers. Intravenous administration of levothyroxine can be used successfully in combination with oral administration to restore normal metabolic function and assist in warming and thermoregulation, although dosages should be conservative to avoid adverse cardiovascular effects.

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.

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.

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.

Severe bradycardia with a prominent J wave refractory to atropine: was it a cause or a result of a fall? A case report and a brief review on the treatment of hypothermia.

PubMed

Qadir, Rehana; Kanjwal, Khalil

2010-01-01

We report on an eighty five year old male who had presented with bradycardia and a prominent J wave on EKG. Initial attemps to treat bradycardia with atropine were unsuccessful and on further evaluation the patient was found to have hypothermia.

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.

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.

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

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.

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.

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 techniques are not used. It may be expected that personnel education and the development of management procedures will brighten the prognosis and increase the survival rate in accidental hypothermia.

Effects of sazetidine-A, a selective α4β2* nicotinic receptor desensitizing agent, on body temperature regulation in mice and rats

PubMed Central

Rezvani, Amir H.; Timofeeva, Olga; Sexton, Hannah G.; DeCuir, Damien; Xiao, Yingxian; Gordon, Christopher J.; Kellar, Kenneth J.; Levin, Edward D.

2014-01-01

Nicotine-induced hypothermia is well established, but the nicotinic receptor actions underlying this effect are not clear. Nicotine causes activation and desensitization at a variety of nicotinic receptor subtypes. Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a novel compound that potently and selectively desensitizes α4β2* nicotinic receptors. The main goal of this study was to investigate the effects of sazetidine-A, on core body temperature (Tc) in mice and rats. Sazetidine-A effects on Tc and the interactions of sazetidine-A with nicotine and selective nicotinic antagonists were investigated to determine the receptor actions underlying nicotine-induced hypothermia. Adult male mice were injected with different dose of nicotine (0.2, 0.4 and 0.8 mg/kg), sazetidine-A (0.3, 1, and 3 mg/kg), a mixture of nicotine (0.4 or 0.8 mg/kg) and sazetidine-A (0.3 or 0.6 mg/kg) or saline and Tc was monitored telemetrically. In another set of experiments, the interaction between sazetidine-A and dihydro-β-erythroidine (DHβE), an α4β2* nicotinic receptors antagonist, and methyllycaconitine (MLA), an α 7 antagonist, was investigated. Tc of mice was monitored following DHβE (1, 3 and 6 mg/kg), a combination of DHβE (3 mg/kg) and sazetidine-A (0.6 mg/kg), MLA (1.5, 3 or 6 mg/kg) or combination of MLA (6 mg/kg) and sazetidine (0.6 mg/kg) or saline. The acute effect of sazetidine-A (1, 3, and 6 mg/kg) on rats Tc was also studied. Acute sazetidine-A caused a pronounced and long-lasting hypothermia in mice; Tc decreased to about 28 °C at 100 min and recovered within 230 min. The hypothermic effect of sazetidine in rats was much less in magnitude (about 3°C) and shorter in duration compared with that in mice. Nicotine co-administration with low doses of sazetidine potentiated the magnitude and duration of hypothermia in mice. The α4β2* nicotinic receptors antagonist DHβE significantly prolonged sazetidine-A-induced hypothermia but did not increase its depth. The α7 antagonist MLA caused a modest degree of hypothermia with relatively short duration in mice. MLA failed to counteract the sazetidine-A-induced hypothermia. Overall, our results show that pharmacological modulation of α4β2* nicotinic receptors elicits changes in body temperature that may involve desensitization of these receptors. PMID:22387853

Permissive hypofiltration

PubMed Central

2012-01-01

Acute kidney injury (AKI) is a syndrome with a multitude of causes and is associated with high mortality and a permanent loss of renal function. Our current understanding of the most common causes of AKI is limited, and thus a silver bullet therapy remains elusive. A change in the approach to AKI that shifts away from the primary composite endpoint of death/dialysis, and instead focuses on improving survival and mitigating permanent renal damage, is likely to be more fruitful. We suggest that the current approach of augmenting renal function by increasing the renal blood flow or glomerular filtration rate during AKI may actually worsen outcomes. Analogous to the approach towards adult respiratory distress syndrome that limits ventilator-induced lung injury, we propose the concept of permissive hypofiltration. The primary goals of this approach are: resting the kidney by providing early renal replacement therapy, avoiding the potentially injurious adverse events that occur during AKI (for example, fluid overload, hypophosphatemia, hypothermia, and so forth), and initiating therapies focused on improving survival and mitigating permanent loss of kidney function. PMID:22839207

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.

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.

How I Cool Children in Neurocritical Care

PubMed Central

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

2010-01-01

Brain injury is the leading cause of death in our pediatric ICU 1. Clinical care for brain injury remains largely supportive. Therapeutic hypothermia has been shown to be effective in improving neurological outcome after adult ventricular-arrhythmia induced cardiac arrest and neonatal asphyxia, and is under investigation as a neuroprotectant after cardiac arrest and traumatic brain injury in children in our ICU and other centers. We routinely induce hypothermia in children comatose after cardiac arrest targeting 32–34°C using cooling blankets and intravenous iced saline as primary methods for induction, for 24–72 hours duration and vigilant re-warming. The objective of this article is to share our hypothermia protocol for cooling children with acute brain injury. PMID:20146026

Resuscitation and Transfusion Principles for Traumatic Hemorrhagic Shock

DTIC Science & Technology

2009-11-01

hyperfibrinolysis. We also describe the concept of damage control resuscitation (DCR), an early and aggressive prevention and treatment of hemorrhagic shock... prevention and treatment of acidosis, hypothermia, and hypocalcemia, avoidance of hemodilution, and hemostatic resuscitation with transfusion of red...are potentially preventable and 66–80% of these deaths occur from hemorrhage.3,4 Rural civilian data indicate that approximately 10% of traumatic

[Trauma-induced coagulopathy--mechanisms and state of the art treatment].

PubMed

Misgav, Mudi; Martinowitz, Uri

2011-02-01

Uncontrolled bleeding is a major cause for early death in both military and civilian trauma. The process of massive bleeding which begins as "surgical bleed" from injured vessels may rapidly evolve into a complex coagulopathy that can be detected early, sometimes within minutes of injury. The magnitude of coagulopathy is directly related to the severity of the injury and its presence is also an independent predictor of early mortality. Therefore, an early "hemostatic resuscitation" is now the "state of the art" in trauma management. Combined mechanisms contribute to the complex coagulopathy as described herein: excessive consumption of coagulation factors and platelets, dilutional coagulopathy due to administration of large volumes of fluids, especially high molecular solutions such as Hydroxyethyl starch (HES); the use of multiple red blood cells (RBC) transfusion without sufficient fresh frozen plasma (FFP) and platelets; acidosis that markedly attenuates thrombin generation and platelets function; hypothermia that slows down enzymatic reactions and platelets function and hyperfibrinolysis which accelerates the degradation of fibrin and might cause platelet dysfunction. An important breakthrough was the understanding that abnormal coagulation tests early in the process of trauma are not the consequences of disseminated intravascular coagulation (DIC). Supported by these new data, an aggressive approach to hemostatic resuscitation was developed which is based on the following principles: permissive hypotension to avoid "dilutional" coagulopathy, awareness of the prevention of hypothermia and acidosis and the use of hemostatic agents such as rFVIIa, fibrinogen concentrate and tranexamic acid early in the course of trauma. Importantly, the common practice of blood component therapy was revised and it is recommended that RBC, FFP and platelets will be transfused early and preferably in 1:1:1 ratio.

Heat defense control in an experimental heat disorder

NASA Astrophysics Data System (ADS)

Romanovsky, A. A.; Blatteis, C. M.

Both whole-body heat exposure and intraperitoneal heating (IPH) result in a body temperature (Tb) fall that occurs once heating is abated (''hyperthermia- induced hypothermia''). This phenomenon involves a decrease in the threshold Tb (Tb-thresh) for activation of metabolic heat production (cold defense). Whether the Tb-thresh for ear skin vasodilation (heat defense) also changes during hyperthermia-induced hypothermia remains unknown. In experiment 1, we applied IPH to guinea pigs by perfusing water through a preimplanted intraperitoneal thermode and delivered the total heat load of either approximately 1.5 kJ (''short'' IPH; perfusion duration: 14 min) or approximately 3.0 kJ (''long'' IPH; 40 min). Short IPH caused skin vasodilation and a 1.1°C rise in Tb; no hypothermia occurred when IPH ceased. Long IPH caused vasodilation and hyperthermia of a comparable magnitude (1.4°C) that were followed by a Tb fall to 1.9°C below the preheating value. In experiment 2, the Tb-thresh for skin vasodilation was measured twice: at the beginning of long IPH and at the nadir of the post-IPH hypothermia. The two Tb-thresh values were 39.0 (SEM 0.1)°C and 39.2 (SEM 0.2)°C respectively. In the controls, the Tb-thresh was measured at the beginning and after short IPH; both control values were 39.0 (SEM 0.2)°C. We conclude that the hyperthermia- induced hypothermia, although previously shown to be coupled with a decrease in the Tb-thresh for cold defense, occurs without any substantial change in the Tb-thresh for heat defense. We speculate that postheating thermoregulatory disorders are associated with threshold dissociation, thus representing the poikilothermic (wide dead-band) type of Tb control.

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.

Post-mortem CT: Hounsfield unit profiles obtained in the lungs with respect to the cause of death assessment.

PubMed

Schober, Daniel; Schwendener, Nicole; Zech, Wolf-Dieter; Jackowski, Christian

2017-01-01

Segmentation of the lungs using post-mortem computed tomography (PMCT) data was so far not feasible due to post-mortem changes such as internal livores. Recently, an Osirix plug-in has been developed allowing automatically segmenting lungs also in PMCT data. The aim of this study was to investigate if the Hounsfield unit (HU) profiles obtained in PMCT data of the segmented lung tissue present with specific behaviour in relation to the cause of death. In 105 PMCT data sets of forensic cases, the entire lung volumes were segmented using the Mia Lite plug-in on Osirix. HU profiles of the lungs were generated and correlated to cause of death groups as assessed after forensic autopsy (cardiac death, fatal haemorrhage, craniocerebral injury, intoxication, drowning, hypothermia, hanging and suffocation). Especially cardiac death cases, intoxication cases, fatal haemorrhage cases and hypothermia cases showed very specific HU profiles. In drowning, the profiles showed two different behaviours representing wet and dry drowning. HU profiles rather varied in craniocerebral injury cases, hanging cases as well as in suffocation cases. HU profiles of the lungs segmented from PMCT data may support the cause of death diagnosis as they represent specific morphological changes in the lungs such as oedema, congestion or blood loss. Especially in cardiac death, intoxication, fatal haemorrhage, hypothermia and drowning cases, HU profiles may be very supportive for the forensic pathologist.

Comparison of the WarmCloud and Bair Hugger Warming Devices for the Prevention of Intraoperative Hypothermia in Patients Undergoing Orthotopic Liver Transplantation: A Randomized Clinical Trial

PubMed Central

Pearce, Brett; Mattheyse, Linda; Ellard, Louise; Desmond, Fiona; Pillai, Param; Weinberg, Laurence

2018-01-01

Background The avoidance of hypothermia is vital during prolonged and open surgery to improve patient outcomes. Hypothermia is particularly common during orthotopic liver transplantation (OLT) and associated with undesirable physiological effects that can adversely impact on perioperative morbidity. The KanMed WarmCloud (Bromma, Sweden) is a revolutionary, closed-loop, warm-air heating mattress developed to maintain normothermia and prevent pressure sores during major surgery. The clinical effectiveness of the WarmCloud device during OLT is unknown. Therefore, we conducted a randomized controlled trial to determine whether the WarmCloud device reduces hypothermia and prevents pressure injuries compared with the Bair Hugger underbody warming device. Methods Patients were randomly allocated to receive either the WarmCloud or Bair Hugger warming device. Both groups also received other routine standardized multimodal thermoregulatory strategies. Temperatures were recorded by nasopharyngeal temperature probe at set time points during surgery. The primary endpoint was nasopharyngeal temperature recorded 5 minutes before reperfusion. Secondary endpoints included changes in temperature over the predefined intraoperative time points, number of patients whose nadir temperature was below 35.5°C and the development of pressure injuries during surgery. Results Twenty-six patients were recruited with 13 patients randomized to each group. One patient from the WarmCloud group was excluded because of a protocol violation. Baseline characteristics were similar. The mean (standard deviation) temperature before reperfusion was 36.0°C (0.7) in the WarmCloud group versus 36.3°C (0.6) in the Bairhugger group (P = 0.25). There were no statistical differences between the groups for any of the secondary endpoints. Conclusions When combined with standardized multimodal thermoregulatory strategies, the WarmCloud device does not reduce hypothermia compared with the Bair Hugger device in patients undergoing OLT. PMID:29707629

Breathing and temperature control disrupted by morphine and stabilized by clonidine in neonatal rats.

PubMed

Kesavan, Kalpashri; Ezell, Tarrah; Bierman, Alexis; Nunes, Ana Rita; Northington, Frances J; Tankersley, Clarke G; Gauda, Estelle B

2014-09-15

Sedative-analgesics are often given to newborn infants and are known to affect many components of the autonomic nervous system. While morphine is most frequently used, α-2 adrenergic receptor agonists are being increasingly used in this population. Alpha-2 adrenergic receptors agonists also have anti-shivering properties which may make it a desirable drug to give to infants undergoing therapeutic hypothermia. The aim of this study was to systematically compare two different classes of sedative-analgesics, morphine, a μ-opioid receptor agonist, and clonidine an α-2 adrenergic receptor agonist on breathing, metabolism and core body temperature (CBT) in neonatal rodents. Breathing parameters, oxygen consumption (VO2) and carbon dioxide production (VCO2), were measured prior to, 10 and 90 min after intraperitoneal (IP) administration of morphine (2, 10 or 20 mg/kg), clonidine (40, 200 or 400 μg/kg), or saline in Sprague-Dawley rat pups at postnatal day 7 (p7) while continuously monitoring CBT. Morphine reduced the respiratory rate, VO2 and VCO2 greater than clonidine at all dosages used (p<0.05, morphine vs. clonidine, for all metabolic and respiratory parameters). Furthermore, morphine induced prolonged respiratory pauses, which were not observed in animals treated with clonidine or saline. Morphine caused hypothermia which was dose dependent, while clonidine stabilized CBT in comparison to saline treated animals (p<0.0001). In the newborn rat, morphine causes profound respiratory depression and hypothermia while clonidine causes minimal respiratory depression and stabilizes CBT. All together, we suggest that clonidine promotes autonomic stability and may be a desirable agent to use in infants being treated with therapeutic hypothermia. Copyright © 2014 Elsevier B.V. All rights reserved.

BREATHING AND TEMPERATURE CONTROL DISRUPTED BY MORPHINE AND STABILIZED BY CLONIDINE IN NEONATAL RATS

PubMed Central

Kesavan, Kalpashri; Ezell, Tarrah; Bierman, Alexis; Nunes, Ana Rita; Northington, Frances J.; Tankersley, Clarke G.; Gauda, Estelle B.

2014-01-01

Background Sedative-analgesics are often given to newborn infants and are known to affect many components of the autonomic nervous system. While morphine is most frequently used, α-2 adrenergic receptor agonists are being increasingly used in this population. Alpha-2 adrenergic receptors agonists also have anti-shivering properties which may make it a desirable drug to give to infants undergoing therapeutic hypothermia. The aim of this study was to systematically compare two different classes of sedative-analgesics, morphine, a μ-opioid receptor agonist, and clonidine an α-2 adrenergic receptor agonist on breathing, metabolism and core body temperature (CBT) in neonatal rodents. Methods Breathing parameters, oxygen consumption (VO2) and carbon dioxide production (VCO2), were measured prior to, 10 and 90 minutes after intraperitoneal (IP) administration of morphine (2, 10 or 20mg/kg), clonidine (40, 200 or 400 μg/kg), or saline in Sprague-Dawley rat pups at postnatal day 7 (p7) while continuously monitoring CBT. Results Morphine reduced the respiratory rate, VO2 and VCO2 greater than clonidine at all dosages used (p<0.05, morphine vs. clonidine, for all metabolic and respiratory parameters). Furthermore, morphine induced prolonged respiratory pauses, which were not observed in animals treated with clonidine or saline. Morphine caused hypothermia which was dose dependent, while clonidine stabilized CBT in comparison to saline treated animals (p<0.0001). Conclusion In the newborn rat, morphine causes profound respiratory depression and hypothermia while clonidine causes minimal respiratory depression and stabilizes CBT. All together, we suggest that clonidine promotes autonomic stability and may be a desirable agent to use in infants being treated with therapeutic hypothermia. PMID:25008573

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 respiratory distress syndrome and the feasibility of studying acute respiratory distress syndrome patients receiving neuromuscular blockade.

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.

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.

A study on the mortality patterns of missing and deceased persons with dementia who died due to wandering.

PubMed

Kikuchi, Kazunori; Ijuin, Mutsuo; Awata, Shuichi; Suzuki, Takao

2016-01-01

To clarify the mortality patterns derived from differences in the causes of death and to subsequently promote search activity and prevent the death of missing persons. The Ministry of Health, Labour and Welfare (MHLW) performed a mail survey using a self-administered questionnaire. The families of all 388 deceased dementia patients from among all of the missing persons reports involving dementia patients that were submitted to the police in 2013, and the 10,322 missing persons with dementia (or suspected cases) were the subjects of this survey. The survey was conducted from January 5 to February 2 in 2015. We analyzed the data provided by the MHLW on 61 cases in which the cause of death was recorded; the factors that were related to the differences in the causes of death were examined using a chi-squared test (Fisher's direct method) and a residual analysis. Based on previous studies, we classified the causes of death into three categories: "drowning," "hypothermia," and "others (e.g., traumatic injury, disease progression)." When the cause of death was hypothermia, death often occurred between three to four days from the time that the deceased individual went missing. A significantly higher number of patients who died of other causes were found to have died on the day that they went missing. More than 40% of the drowning cases occurred on the day that the deceased individual went missing. We identified 3 patterns of mortality: (1) death on the day that the deceased individual went missing due to traumatic injury, disease progression, drowning, and other causes; (2) death due to hypothermia within a few days after the deceased individual went missing; and (3) patterns other than (1) and (2).

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 improving the long-term outcome for these infants. Future studies of therapeutic hypothermia should include the categories of newborns excluded from the published clinical trials, that is infants <36 weeks gestation, PNC or stroke, or admitted outside of the established 6-hour window, and with encephalopathy not imputable to HIE. New entry criteria will allow significant number of newborns to benefit from the treatment.

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 rights reserved.

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 functions and causes the release of AVP to induce hypothermia.

Hyperalgesia, low-anxiety, and impairment of avoidance learning in neonatal caffeine-treated rats.

PubMed

Pan, Hong-Zhen; Chen, Hwei-Hsien

2007-03-01

The nonselective adenosine receptor antagonist caffeine is used clinically to treat apnea in preterm infants. The brain developmental stage of preterm infants is usually at a period of rapid brain growth, referred as brain growth spurt, which occurs during early postnatal life in rats and is highly sensitive to central nervous system (CNS) acting drugs. The aim of this work was to study whether caffeine treatment during brain growth spurt produces long-term effects on the adenosine receptor-regulated behaviors including nociception, anxiety, learning, and memory. Neonatal male and female Sprague-Dawley rats were administered either deionized water or caffeine (15-20 mg kg(-1) day(-1)) through gavage (0.05 ml/10 g) over postnatal days (PN) 2-6. The hot-plate test, elevated plus-maze, dark-light transition test, and step-through inhibitory avoidance learning task were examined in juvenile rats. Furthermore, the responses to adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA)-induced hypothermia and A(2A) receptor agonist CGS21680-induced locomotor depression were also compared. Caffeine-treated rats showed hyperalgesia in hot-plate test, less anxiety than controls in the elevated plus-maze and dark-light transition, and impairment in step-through avoidance learning test. Moreover, the responses to CPA-induced hypothermia and CGS21680-induced locomotor depression were enhanced in caffeine-treated rats. These results indicate that caffeine exposure during brain growth spurt alters the adenosine receptor-regulated behaviors and the responsiveness to adenosine agonists, suggesting the risk of adenosine receptor-related behavioral dysfunction may exist in preterm newborns treated for apnea with caffeine.

Review and Outcome of Prolonged Cardiopulmonary Resuscitation

PubMed Central

Youness, Houssein; Al Halabi, Tarek; Hussein, Hussein; Awab, Ahmed; Jones, Kellie; Keddissi, Jean

2016-01-01

The maximal duration of cardiopulmonary resuscitation (CPR) is unknown. We report a case of prolonged CPR. We have then reviewed all published cases with CPR duration equal to or more than 20 minutes. The objective was to determine the survival rate, the neurological outcome, and the characteristics of the survivors. Measurements and Main Results. The CPR data for 82 patients was reviewed. The median duration of CPR was 75 minutes. Patients mean age was 43 ± 21 years with no significant comorbidities. The main causes of the cardiac arrests were myocardial infarction (29%), hypothermia (21%), and pulmonary emboli (12%). 74% of the arrests were witnessed, with a mean latency to CPR of 2 ± 6 minutes and good quality chest compression provided in 96% of the cases. Adjunct therapy included extracorporeal membrane oxygenation (18%), thrombolysis (15.8%), and rewarming for hypothermia (19.5%). 83% were alive at 1 year, with full neurological recovery reported in 63 patients. Conclusion. Patients undergoing prolonged CPR can survive with good outcome. Young age, myocardial infarction, and potentially reversible causes of cardiac arrest such as hypothermia and pulmonary emboli predict a favorable result, especially when the arrest is witnessed and followed by prompt and good resuscitative efforts. PMID:26885387

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.

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.

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

Brain Activation by H1 Antihistamines Challenges Conventional View of Their Mechanism of Action in Motion Sickness: A Behavioral, c-Fos and Physiological Study in Suncus murinus (House Musk Shrew)

PubMed Central

Tu, Longlong; Lu, Zengbing; Dieser, Karolina; Schmitt, Christina; Chan, Sze Wa; Ngan, Man P.; Andrews, Paul L. R.; Nalivaiko, Eugene; Rudd, John A.

2017-01-01

Motion sickness occurs under a variety of circumstances and is common in the general population. It is usually associated with changes in gastric motility, and hypothermia, which are argued to be surrogate markers for nausea; there are also reports that respiratory function is affected. As laboratory rodents are incapable of vomiting, Suncus murinus was used to model motion sickness and to investigate changes in gastric myoelectric activity (GMA) and temperature homeostasis using radiotelemetry, whilst also simultaneously investigating changes in respiratory function using whole body plethysmography. The anti-emetic potential of the highly selective histamine H1 receptor antagonists, mepyramine (brain penetrant), and cetirizine (non-brain penetrant), along with the muscarinic receptor antagonist, scopolamine, were investigated in the present study. On isolated ileal segments from Suncus murinus, both mepyramine and cetirizine non-competitively antagonized the contractile action of histamine with pKb values of 7.5 and 8.4, respectively; scopolamine competitively antagonized the contractile action of acetylcholine with pA2 of 9.5. In responding animals, motion (1 Hz, 4 cm horizontal displacement, 10 min) increased the percentage of the power of bradygastria, and decreased the percentage power of normogastria whilst also causing hypothermia. Animals also exhibited an increase in respiratory rate and a reduction in tidal volume. Mepyramine (50 mg/kg, i.p.) and scopolamine (10 mg/kg, i.p.), but not cetirizine (10 mg/kg, i.p.), significantly antagonized motion-induced emesis but did not reverse the motion-induced disruptions of GMA, or hypothermia, or effects on respiration. Burst analysis of plethysmographic-derived waveforms showed mepyramine also had increased the inter-retch+vomit frequency, and emetic episode duration. Immunohistochemistry demonstrated that motion alone did not induce c-fos expression in the brain. Paradoxically, mepyramine increased c-fos in brain areas regulating emesis control, and caused hypothermia; it also appeared to cause sedation and reduced the dominant frequency of slow waves. In conclusion, motion-induced emesis was associated with a disruption of GMA, respiration, and hypothermia. Mepyramine was a more efficacious anti-emetic than cetirizine, suggesting an important role of centrally-located H1 receptors. The ability of mepyramine to elevate c-fos provides a new perspective on how H1 receptors are involved in mechanisms of emesis control. PMID:28659825

Tips to Protect Workers in Cold Environments

MedlinePlus

A to Z Index | Newsroom | Contact Us | FAQs | ... may cause serious health problems such as trench foot, frostbite and hypothermia. In extreme cases, including cold water immersion, exposure can lead ...

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.

[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.

Parallel temperature dependence of contracture-associated enzyme release due to anoxia, 2,4-dinitrophenol (DNP), or caffeine and the calcium paradox.

PubMed Central

Ganote, C. E.; Sims, M. A.

1984-01-01

Hypothermia during calcium-free perfusion of hearts protects them from injury caused by subsequent calcium repletion at 37 C (calcium paradox). Injury to calcium-free hearts is also associated with contracture caused by anoxia, 2,4-dinitrophenol (DNP), or caffeine. This study was done for the purpose of determining whether hypothermia during calcium-free perfusions protects hearts from contracture-associated injury. Langendorff-perfused rat hearts were studied in four experimental groups: I) Anoxia: Thirty minutes of anoxic perfusion at 37 C was followed by thirty minutes of anoxic calcium-free perfusion at 37-18 C. II) Calcium paradox: Five minutes of calcium-free perfusion at 37-18 C was followed by calcium repletion at 37 C. III, IVa) Caffeine or DNP: Five minutes of calcium-free perfusion at 37-18 C was followed by addition of 10 mM caffeine or 1 mM DNP in calcium-free medium at 37 C or, IVb) 1 mM DNP in calcium-free medium at 22 C. Injury was assessed by measurement of serial releases of creatine kinase (CK) in effluents and by cellular morphology. The results show that progressive hypothermia to 22 C during calcium-free perfusion periods produced a progressive reduction of CK release and morphologic evidence of injury due to anoxia, caffeine, or DNP, which closely paralleled protection of hearts from the calcium paradox. Protection from injury in all experimental groups was associated with preservation of sarcolemmal membrane integrity and prevention of cell separations at intercalated disk junctions. It is proposed that weakening of intercalated disks occurs during calcium-free perfusions and may be a cause of mechanical fragility of the sarcolemma. Hypothermia may protect hearts from contracture-associated injury by preserving the integrity of intercalated disk junctions during periods of extracellular calcium depletion. Images Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:6742111

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's solution via micro-catheter is a safe and effective method for selective cerebral hypothermia. This cooling method could potentially be developed as a new treatment in acute ischemic stroke.

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 feasible and could be conducted safely in pediatric and neonatal intensive care units experienced in the application of therapeutic hypothermia in critically ill neonates. However, including adjunct therapeutic hypothermia in the already involved treatment regimen of critically ill patients with hyperammonemia and encephalopathy adds to the complexity of care and should not be done unless it is proven efficacious in a randomized clinical trial. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Animal welfare implications of neonatal mortality and morbidity in farm animals.

PubMed

Mellor, D J; Stafford, K J

2004-09-01

Much has been learnt during the last 50 years about the causes of neonatal mortality and morbidity and about practical means for minimising them in newborn lambs, kids, bovine calves, deer calves, foals and piglets. The major causes of problems in these newborns are outlined briefly and include hypothermia due to excessive heat loss or to hypoxia-induced, starvation-induced or other forms of inhibited heat production. They also include maternal undernutrition, mismothering, infection and injury. The published literature reveals that the scientific investigations which clarified these causes and led to practical means for minimising the problems, involved iterative successions of self-reinforcing laboratory and field or clinical investigations conducted over many years. These studies focused largely on solutions to the problems, not on the suffering that the newborn might experience, so that an analysis of the associated welfare insults had not apparently been conducted until now. The present assessment focuses on potentially noxious subjective experiences the newborn may have. The account of the causes of neonatal mortality and morbidity outlined early in this review indicates that the key subjective experiences which require analysis in animal welfare terms are breathlessness, hypothermia, hunger, sickness and pain. Reference to documented responses of farm animals and, where appropriate, to human experience, suggests that breathlessness and hypothermia usually represent less severe neonatal welfare insults than do hunger, sickness and pain. Major science-based improvements in the management of pregnancy and birth have markedly reduced the overall amount of welfare compromise experienced by newborn farm animals and further improvements may be expected as knowledge is refined and extended in the future.

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

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...

Intraosseous access in neonates and infants: risk of severe complications - a case report.

PubMed

Suominen, P K; Nurmi, E; Lauerma, K

2015-11-01

Gaining vascular access in a neonate during cardiopulmonary resuscitation is crucial and challenging. Intraosseous (IO) access can offer a fast and reliable method for achieving emergency access for fluids and drugs when venous access fails in a critically ill child. IO access can however result in rare, but serious adverse events including compartment syndrome and amputation. We describe a case resulting in leg amputation due to IO infusion in a neonate after resuscitation and therapeutic hypothermia. We compared 10 tibia X-rays in three age groups. The mean medullary diameter of the proximal tibia at the recommended site for IO access was 7 mm in neonate, 10 mm in 1- to 12-month-old infants, and 12 mm in 3- to 4-year-old children. This provides a narrow margin of safety for the correct positioning and the avoidance of dislodgement of the IO needle. The correct position of the IO needle should be confirmed by bone marrow aspiration and fluid bolus. Unnecessary touching of the IO needle after fixing it in place should be avoided by inserting a luer-lock catheter with a three-way stop-cock for IO drug and fluid administration. Regular observation of the circulation and possible swelling of the leg should be performed. The IO administration of inotropic infusions should also be avoided after the initial resuscitation phase. When treating with therapeutic hypothermia, it may be wise to remove the IO needle much earlier than the currently recommended 24 h because of the problems in peripheral circulation and its monitoring. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

[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.

Modification of core body temperature by amino acid administration.

PubMed

Yamaoka, Ippei

2008-01-01

The feeling of warmth after a meal is caused by the ingestion of nutrients and the sensation is known as nutrition-induced thermogenesis or specific dynamic action. Core body temperature (Tb) is constantly maintained within a narrow range, but thermoregulation can become impaired by the inhalation or intravenous administration of anesthetics that inhibit hypothalamic thermoregulation. Hypothermia during surgery is directly associated with postoperative complications. Devices are available to maintain heat during surgery and thus prevent hypothermia. On the other hand, intravenous amino acid (AA) administration can attenuate hypothermia during anaesthesia, prompting many clinical trials of AA mixtures to maintain Tb. However, although the thermal effect of AA during anaesthesia is obvious, the underlying mechanism of metabolic heat production and accumulation remains obscure. A nutritional physiological approach using a rat model will be introduced in this symposium. Data from our recent studies suggest that the administration of an AA mixture during anaesthesia stimulates muscle protein synthesis via insulin-mTOR-dependent activation of the translation initiation factors, 4E-BP 1 and S6K1, as a result of increased insulin concentrations. Thus, heat accumulation in the body is facilitated. Furthermore, the content of the AA mixture applied during anaesthesia alters the thermal effect and branched chain AAs are necessary, but not sufficient, for the prevention of hypothermia.

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

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.

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.

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.

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 is known concerning heat and cold mortality. A lack of health outcome or health information to develop website information/wind chill alerts was noted. Overall, it was determined that hypothermia is a good metric for assessing cold weather-related vulnerability and that implementing health outcome-based information will help limit the hazards associated with this public health problem.

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.

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.

Ca++ induced hypothermia in a hibernator /Citellus beechyi/

NASA Technical Reports Server (NTRS)

Hanegan, J. L.; Williams, B. A.

1975-01-01

Results of perfusion of excess Ca++ and Na+ into the hypothalamus of the hibernating ground squirrel Citellus beechyi are presented. The significant finding is that perfused excess Ca++ causes a reduction in core temperature when ambient temperature is low (12 C). Ca++ also causes a rise in rectal temperature at high ambient temperature (33 C). Thus hypothalamic Ca++ perfusion apparently causes a nonspecific depression of thermoregulatory control.

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

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 (p=0.04). Postarrival incremental change in troponin-T at 72 hours was significantly less in the Xenon+mild therapeutic hypothermia group (p=0.04). Xenon treatment in combination with hypothermia is feasible and has favorable cardiac features in survivors of out-of-hospital cardiac arrest.

[Analysis of accidental deaths in mountain tourism and sport according to statistics from the Republic of Kabardino-Balkariia].

PubMed

Mechukaev, A M; Mechukaev, A A

2006-01-01

Lethal cases in mountain tourism and sports in the Republic of Kabardino-Balkaria were studied for 1978-1995. A total of 152 accidental deaths were analysed. Most of the victims were males under 30 years of age. The greatest number of the accidents took place on Monday, in July and August. Many amateur visitors from abroad were among the victims. The main cause of death in the mountains of Kabardino-Balkaria for the 18 years studied was multitrauma of the body (69.7%). Hypothermia and obturation asphyxia with snow and compression asphyxia due to snowbreak account for 11.8 and 13.2% deaths, respectively; lightning killed 4%. Combination of high mountain hypoxia with exacerbated chronic somatic disease or hypothermia caused death in 1% victims. The authors propose how to improve forensic-medical expert examination of accidental death and safety in the mountains.

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)

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.

[Therapeutic hypothermia for severe traumatic brain injury].

PubMed

Bouzat, P; Francony, G; Oddo, M; Payen, J-F

2013-11-01

Therapeutic hypothermia (TH) is considered a standard of care in the post-resuscitation phase of cardiac arrest. In experimental models of traumatic brain injury (TBI), TH was found to have neuroprotective properties. However, TH failed to demonstrate beneficial effects on neurological outcome in patients with TBI. The absence of benefits of TH uniformly applied in TBI patients should not question the use of TH as a second-tier therapy to treat elevated intracranial pressure. The management of all the practical aspects of TH is a key factor to avoid side effects and to optimize the potential benefit of TH in the treatment of intracranial hypertension. Induction of TH can be achieved with external surface cooling or with intra-vascular devices. The therapeutic target should be set at a 35°C using brain temperature as reference, and should be maintained at least during 48 hours and ideally over the entire period of elevated intracranial pressure. The control of the rewarming phase is crucial to avoid temperature overshooting and should not exceed 1°C/day. Besides its use in the management of intracranial hypertension, therapeutic cooling is also essential to treat hyperthermia in brain-injured patients. In this review, we will discuss the benefit-risk balance and practical aspects of therapeutic temperature management in TBI patients. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

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.

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.

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.

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 cEEG) than those receiving conventional EEG. We recommend that use of continuous video-EEG be considered whenever possible, both to treat seizures more specifically and to avoid overtreatment. © 2017 S. Karger AG, Basel.

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.

Myxoedema coma: an almost forgotten, yet still existing cause of multiorgan failure

PubMed Central

Salomo, Louise Havkrog; Laursen, Adam Hoegsbro; Reiter, Nanna; Feldt-Rasmussen, Ulla

2014-01-01

A 48-year-old man was admitted to department of emergency medicine at a tertiary referral hospital due to dizziness and fatigue. Clinical features on admission were non-pitting oedema, dry skin, very sparse hair, a hoarse voice, hypothermia (rectal temperature 28.7°C), macroglossia, sinus bradycardia and slow cerebration. Blood tests revealed severe hypothyroidism. During admission, the patient developed respiratory failure, renal failure, bleeding symptoms and diffuse colitis. The patient was treated with hydrocortisone and levothyroxine and he survived miraculously. This case describes a patient with myxoedema coma with severe hypothermia and cardiac involvement with development of multiorgan dysfunction all linked to the severe depletion of triiodothyronine. PMID:24481020

Myxoedema coma: an almost forgotten, yet still existing cause of multiorgan failure.

PubMed

Salomo, Louise Havkrog; Laursen, Adam Hoegsbro; Reiter, Nanna; Feldt-Rasmussen, Ulla

2014-01-30

A 48-year-old man was admitted to department of emergency medicine at a tertiary referral hospital due to dizziness and fatigue. Clinical features on admission were non-pitting oedema, dry skin, very sparse hair, a hoarse voice, hypothermia (rectal temperature 28.7°C), macroglossia, sinus bradycardia and slow cerebration. Blood tests revealed severe hypothyroidism. During admission, the patient developed respiratory failure, renal failure, bleeding symptoms and diffuse colitis. The patient was treated with hydrocortisone and levothyroxine and he survived miraculously. This case describes a patient with myxoedema coma with severe hypothermia and cardiac involvement with development of multiorgan dysfunction all linked to the severe depletion of triiodothyronine.

Pharmacology of the hypothermic response to 5-HT1A receptor activation in humans.

PubMed

Lesch, K P; Poten, B; Söhnle, K; Schulte, H M

1990-01-01

The selective 5-HT1A receptor ligand ipsapirone (IPS) caused dose-related hypothermia in humans. The response was attenuated by the nonselective 5-HT1/2 receptor antagonist metergoline and was completely antagonized by the nonselective beta-adrenoceptor antagonist pindolol, which interacts stereoselectively with the 5-HT1A receptor. The selective beta 1-adrenergic antagonist betaxolol had no effect. The findings indicate that IPS-induced hypothermia specifically involves activation of (presynaptic) 5-HT1A receptors. Therefore, the hypothermic response to IPS may provide a convenient in vivo paradigma to assess the function of the presynaptic 5-HT receptor in affective disorders and its involvement in the effects of psychotropic drugs.

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.

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

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.

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.

Myxedema coma: A case report of pediatric emergency care.

PubMed

Zhu, Yueniu; Qiu, Wenjuan; Deng, Mengyan; Zhu, Xiaodong

2017-05-01

Myxedema coma (MC) is extremely rare but lethal in pediatric patients with hypothyroidism leading to altered mental status and hypothermia. But there is no clinical guideline for such cases. A 6-year-old Chinese girl presented with coma and hypothermia preceded by pneumonia. Her lab results were: free thyroxin (T4) 4.18 pmol/L and thyroid-stimulating hormone (TSH) > 150 μIU/mL with extremely elevated anti-thyroid peroxidase (TPO-Ab) and anti-thyroglobulin. Pneumonia, mild pleural, and pericardial effusion were seen on computed tomographic (CT) scan. MC, autoimmune hypothyroidism, pneumonia and sepsis were diagnosed. Gastric levothyroxine, intravenous dexamethasone and antibiotics were administered. Her consciousness was restored and temperature returned to normal 2 days after starting levothyroxine. She was discharged two weeks later. MC is rare but may be the initial presentation in pediatric patients with prolonged untreated hypothyroidism. Autoimmune thyroiditis could cause hypothyroidism in children. MC should be suspected in pediatric patients with altered mental status, hypothermia and cardiovascular instability. Treatment with 100 mg/m of gastric levothyroxine is an option for pediatric patients with MC.

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

Management of pyothorax.

PubMed

Holmberg, D L

1979-05-01

Pyothorax is a serious disease process which requires both medical and surgical intervention. Late recognition, management problems, and likely recurrence make successful treatment difficult and often frustrating. Aims of therapy should be to avoid undue stress to the patient, to relieve respiratory distress by thoracocentesis, to eliminate infectious agents with antimicrobials, to remove pleural exudate, and to provide supportive care. Close monitoring of the patient is necessary to prevent iatrogenic complications such as pneumothorax, hemothorax, hypothermia, or hypoproteinemia. Exploratory thoracotomy for removal of granulomatous material and fibroelastic pleural "peels" is occasionally necessary to resolve compressive cardiopulmonary lesions.

Management of Intracranial Hypertension

PubMed Central

Rangel-Castillo, Leonardo; Gopinath, Shankar; Robertson, Claudia S.

2008-01-01

Effective management of intracranial hypertension involves meticulous avoidance of factors that precipitate or aggravate increased intracranial pressure. When intracranial pressure becomes elevated, it is important to rule out new mass lesions that should be surgically evacuated. Medical management of increased intracranial pressure should include sedation, drainage of cerebrospinal fluid, and osmotherapy with either mannitol or hypertonic saline. For intracranial hypertension refractory to initial medical management, barbiturate coma, hypothermia, or decompressive craniectomy should be considered. Steroids are not indicated and may be harmful in the treatment of intracranial hypertension resulting from traumatic brain injury. PMID:18514825

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.

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.

Ondansetron and promethazine have differential effects on hypothermic responses to lithium chloride administration and to provocative motion in rats

PubMed Central

Guimaraes, Drielle D; Andrews, Paul L R; Rudd, John A; Braga, Valdir A; Nalivaiko, Eugene

2015-01-01

We recently reported that provocative motion (rotation in a home cage) causes hypothermic responses in rats, similar to the hypothermic responses associated with motion sickness in humans. Many stimuli inducing emesis in species with an emetic reflex also provoke hypothermia in the rat, therefore we hypothesized that a fall in body temperature may reflect a “nausea-like” state in these animals. As rats do not possess an emetic reflex, we employed a pharmacological approach to test this hypothesis. In humans, motion- and chemically-induced nausea have differential sensitivity to anti-emetics. We thus tested whether the hypothermia induced in rats by provocative motion (rotation at 0.7 Hz) and by the emetic LiCl (63 mg/kg i.p.) have a similar differential pharmacological sensitivity. Both provocations caused a comparable robust fall in core body temperature (−1.9 ± 0.3°C and −2.0 ± 0.2°C for chemical and motion provocations, respectively). LiCl−induced hypothermia was completely prevented by ondansetron (2mg/kg, i.p., a 5-HT3 receptor antagonist that reduces cancer chemotherapy-induced nausea and vomiting), but was insensitive to promethazine (10 mg/kg, i.p., a predominantly histamine-H1 and muscarinic receptor antagonist that is commonly used to treat motion sickness). Conversely, motion-induced hypothermia was unaffected by ondansetron but promethazine reduced the rate of temperature decline from 0.20 ± 0.02 to 0.11 ± 0.03°C/min (P < 0.05) with a trend to decrease the magnitude. We conclude that this differential pharmacological sensitivity of the hypothermic responses of vestibular vs. chemical etiology in rats mirrors the observations in other pre-clinical models and humans, and thus supports the idea that a “nausea-like” state in rodents is associated with disturbances in thermoregulation. PMID:27227074

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.

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.

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.

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 Pharmacologie et de Thérapeutique.

NCAM deficiency in the mouse forebrain impairs innate and learned avoidance behaviours.

PubMed

Brandewiede, J; Stork, O; Schachner, M

2014-06-01

The neural cell adhesion molecule (NCAM) has been implicated in the development and plasticity of neural circuits and the control of hippocampus- and amygdala-dependent learning and behaviour. Previous studies in constitutive NCAM null mutants identified emotional behaviour deficits related to disturbances of hippocampal and amygdala functions. Here, we studied these behaviours in mice conditionally deficient in NCAM in the postmigratory forebrain neurons. We report deficits in both innate and learned avoidance behaviours, as observed in elevated plus maze and passive avoidance tasks. In contrast, general locomotor activity, trait anxiety or neophobia were unaffected by the mutation. Altered avoidance behaviour of the conditional NCAM mutants was associated with a deficit in serotonergic signalling, as indicated by their reduced responsiveness to (±)-8-hydroxy-2-(dipropylamino)-tetralin-induced hypothermia. Another serotonin-dependent behaviour, namely intermale aggression that is massively increased in constitutively NCAM-deficient mice, was not affected in the forebrain-specific mutants. Our data suggest that genetically or environmentally induced changes of NCAM expression in the late postnatal and mature forebrain determine avoidance behaviour and serotonin (5-HT)1A receptor signalling. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

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.

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.

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.

The Information Age and Hot Air.

PubMed

Austin, Paul N

2015-08-01

Forced-air warmers have been used for over twenty years to help prevent and treat inadvertent perioperative hypothermia. One result of hypothermia can be an increased risk of surgical site infection. Paradoxically, the question has been raised about the role of forced-air warmers in causing surgical site infections. A manufacturer of a competing device has been sending information directly to clinicians with warnings about using forced-air warmers with patients undergoing total joint arthroplasty. Three reviews have been published and none of these condemned the use of forced-air warmers in the operating room including with patients undergoing total joint arthroplasty. Clinicians must continue to seek information about this problem from peer-reviewed journals and not rely on interpretation by others such as manufacturers.

Characterization of the hypothermic effect of the synthetic cannabinoid HU-210 in the rat. Relation to the adrenergic system and endogenous pyrogens.

PubMed

Ovadia, H; Wohlman, A; Mechoulam, R; Weidenfeld, J

1995-02-01

In the present study we have characterized the hypothermic effect of the psychoactive cannabinoid HU-210, by investigating its interaction with the endogenous pyrogens, IL-1 and PGE2. We also studied the involvement of the adrenergic system in mediation of this hypothermic effect. Injection of HU-210 directly into the preoptic area caused a dose dependent reduction of rectal temperature from 37 to 32.1 degrees C. Injection of the non-psychoactive analog, HU-211 which does not bind to brain cannabinoid receptor, did not affect body temperature. Injection of the adrenergic agonists, CGP-12177 and clonidine (beta, and alpha adrenergic agonists, respectively) abrogated the hypothermia induced by HU-210. Injection of the adrenergic antagonists, prazosin (alpha 1) and propranolol (beta) enhanced the hypothermic effect of HU-210. Intracerebral administration of IL-1 or PGE2 to rats pretreated with HU-210 caused a transient inhibition of the hypothermia. The ex vivo rate of basal or bacterial endotoxin-induced synthesis of PGE2 by different brain regions, including the preoptic area was not affected by HU-210 administration. These results suggest that the synthetic cannabinoid HU-210 acts in the preoptic area, probably via the brain cannabinoid receptor to induce hypothermia. The hypothermic effect can be antagonized by adrenergic agonists and enhanced by adrenergic antagonists. HU-210 does not interfere with the pyrogenic effect of IL-1 or PGE2.

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.

[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.

THE EFFECTS OF CHRONIC EXERCISE CONDITIONING ON THERMOREGULATORY RESPONSE TO CHLORPYRIFOS IN FEMALE RATS.

EPA Science Inventory

Chronic exercise conditioning has been shown to alter basal thermoregulatory processes (change in thermoregulatory set-point) as well as the response to infectious fever. Chlorpyrifos (CHP), an organophosphate pesticide, causes an acute period of hypothermia followed by a delaye...

[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.

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.

[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.

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

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 adults in the autonomic consequences of ethanol were dramatically influenced by whether animals were familiarized with the handling/injection process before testing. Under these circumstances, adolescents were less susceptible than adults to the impact of experimental perturbation on ethanol-induced hypothermia. These findings suggest that seemingly innocuous aspects of experimental design can influence conclusions reached on ontogenetic differences in sensitivity to ethanol, at least when indexed by ethanol-induced hypothermia. PMID:17374036

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 ethanol were dramatically influenced by whether animals were familiarized with the handling/injection process before testing. Under these circumstances, adolescents were less susceptible than adults to the impact of experimental perturbation on ethanol-induced hypothermia. These findings suggest that seemingly innocuous aspects of experimental design can influence conclusions reached on ontogenetic differences in sensitivity to ethanol, at least when indexed by ethanol-induced hypothermia.

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 controlling for confounders.

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 certainty. Instructing users to act when the device's transition colour appears could improve accuracy. If reliable, ThermoSpots may offer simple, acceptable and continuous temperature measurement for high-burden areas and reduce the workload of over-stretched staff.

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.

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.

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.

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

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. Therapeutic hypothermia can have a positive impact on patient outcome, but more research is required. © 2016 British Association of Critical Care Nurses.

A systematic review of randomised controlled trials of the effects of warmed irrigation fluid on core body temperature during endoscopic surgeries.

PubMed

Jin, Yinghui; Tian, Jinhui; Sun, Mei; Yang, Kehu

2011-02-01

The purpose of this systematic review was to establish whether warmed irrigation fluid temperature could decrease the drop of body temperature and incidence of shivering and hypothermia. Irrigation fluid, which is used in large quantities during endoscopic surgeries at room temperature, is considered to be associated with hypothermia and shivering. It remains controversial whether using warmed irrigation fluid to replace room-temperature irrigation fluid will decrease the drop of core body temperature and the occurrence of hypothermia. A comprehensive search (computerised database searches, footnote chasing, citation chasing) was undertaken to identify all the randomised controlled trials that explored temperature of irrigation fluid in endoscopic surgery. An approach involving meta-analysis was used. We searched PubMed, EMBASE, Cochrane Library, SCI, China academic journals full-text databases, Chinese Biomedical Literature Database, Chinese scientific journals databases and Chinese Medical Association Journals for trials that meet the inclusion criteria. Study quality was assessed using standards recommended by Cochrane Library Handbook 5.0.1. Disagreement was resolved by consensus. Thirteen randomised controlled trials including 686 patients were identified. The results showed that room-temperature irrigation fluid caused a greater drop of core body temperature in patients, compared to warmed irrigation fluid (p < 0.00001; I(2) = 85%). The occurrence of shivering [odds ratio (OR) 5.13, 95% CI: 2.95-10.19, p < 0.00001; I(2) = 0%] and hypothermia (OR 22.01, 95% CI: 2.03-197.08, p = 0.01; I(2) = 64%) in the groups having warmed irrigation fluid were lower than the group of studies having room-temperature fluid. In endoscopic surgeries, irrigation fluid is recommended to be warmed to decrease the drop of core body temperature and the risk of perioperative shivering and hypothermia. Warming irrigating fluid should be considered standard practice in all endoscopic surgeries. © 2011 Blackwell Publishing Ltd.

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 ...

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.

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

Have Fun in the Snow--But Be Careful!

ERIC Educational Resources Information Center

Sparano, Vin T.

1977-01-01

During the winter months especially, many people do not protect themselves against the cold weather. This article discusses the causes, symptoms, and first aid treatment of hypothermia and frostbite. Methods for rescuing someone who has fallen through the ice on a lake are also mentioned. (MA)

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.

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.

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

Opioid, cannabinoid, and transient receptor potential (TRP) systems: effects on body temperature

PubMed Central

Rawls, Scott M.; Benamar, Khalid

2014-01-01

Cannabinoid and opioid drugs produce marked changes in body temperature. Recent findings have extended our knowledge about the thermoregulatory effects of cannabinoids and opioids, particularly as related to delta opioid receptors, endogenous systems, and transient receptor potential (TRP) channels. Although delta opioid receptors were originally thought to play only a minor role in thermoregulation compared to mu and kappa opioid receptors, their activation has been shown to produce hypothermia in multiple species. Endogenous opioids and cannabinoids also regulate body temperature. Mu and kappa opioid receptors are thought to be in tonic balance, with mu and kappa receptor activation producing hyperthermia and hypothermia, respectively. Endocannabinoids participate in the febrile response, but more studies are needed to determine if a cannabinoid CB1 receptor tone exerts control over basal body temperature. A particularly intense research focus is TRP channels, where TRPV1 channel activation produces hypothermia whereas TRPA1 and TRPM8 channel activation causes hyperthermia. The marked hyperthermia produced by TRPV1 channel antagonists suggests these warm channels tonically control body temperature. A better understanding of the roles of cannabinoid, opioid, and TRP systems in thermoregulation may have broad clinical implications and provide insights into interactions among neurotransmitter systems involved in thermoregulation. PMID:21622235

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.

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

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.

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 risk [RR] 1·08, 95% CI 0·76–1·53; p=0·67). 12 patients in the hypothermia group died compared with eight in the normothermia group (RR 1·30, 95% CI 0·58–2·52; p=0·52). Interpretation This trial did not confirm the utility of hypothermia as a primary neuroprotective strategy in patients with severe traumatic brain injury. Funding National Institute of Neurological Disorders and Stroke. PMID:21169065

Diagnosis of myxedema coma complicated by renal failure: a case report.

PubMed

Takamura, Akiteru; Sangen, Ryusho; Furumura, Yoshiki; Usuda, Daisuke; Kasamaki, Yuji; Kanda, Tsugiyasu

2017-04-01

Myxedema coma, caused by severe lack of thyroid hormone, is characterized by deterioration of mental status, hypothermia, hypotension, hyponatremia, and hypoventilation. We describe an 84-year-old woman who presented with renal failure and new onset severe hypothyroidism leading to challenges in the recognition of myxedema coma.

The Use of Adenosine Agonists to Treat Nerve Agent-Induced Seizure and Neuropathology

DTIC Science & Technology

2016-09-01

Status epilepticus may be caused by loss of adenosine anticonvulsant mechanisms. Neuroscience. 58: 245-261. 37. Bueters, T. J., et al. 2002...Pharmacology. 113: 1386-1390. 57. Niquet, J., et al. 2015. Neuroprotective effects of deep hypothermia in refractory status epilepticus . Annals of

A Novel Swine Model for Evaluation of Potential Intravascular Hemostatic Agents

DTIC Science & Technology

2007-06-01

bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine. Shock 24:145–152. 2. Bellamy RF. 1984. The causes of death in...WZ, Pusateri AE, Uscilowicz JM, Delgado AV, Holcomb JB. 2005. Independent contributions of hypothermia and acidosis to coagulopathy in swine. J

[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 the observed group was 53.8%, and 24% in the control group (p < 0.01). In the observed group, the frequency of pH < 7.25 was 38.71%, and 14% in the control group (p < 0.05). The frequency of hyperbilirubinaemia was 38.71% in the observed group, and 16% in the control group (p < 0.01). The frequency of hypocalcaemia was 32.26% in the observed, and 12% in the control group (p < 0.01). Transitory hypothermia in the first ten hours of life represents a significant risk factor for deepening hypoglycaemia, asphyxia, hyperbilirubinaemia and hypocalcaemia in term newborns with IUGR.

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.

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.

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

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.

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

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.

Cerebral ischemia and neuroregeneration

PubMed Central

Lee, Reggie H. C.; Lee, Michelle H. H.; Wu, Celeste Y. C.; Couto e Silva, Alexandre; Possoit, Harlee E.; Hsieh, Tsung-Han; Minagar, Alireza; Lin, Hung Wen

2018-01-01

Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke (a form of cerebral ischemia)-related costs are expected to reach 240.67 billion dollars by 2030, options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics (i.e., tissue plasminogen activator) and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies against stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism(s) underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies (i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells) as it relates to cerebral ischemia. PMID:29623912

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 summary, addition of 2-IB during hypothermia is able to attenuate hypoxia-induced neuronal cell damage in vitro . Combination treatment of hypothermia with 2-IB could be a promising strategy to reduce hypoxia-induced neuronal cell damage and should be considered in further animal and clinical studies.

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 patients received prehospital cooling. Hypothermia on presentation to the ED was noted in 1.6% of all burn victims in this trauma registry. Hypothermia was more common in very large burns and was associated with high mortality. In this series, prehospital cooling did not appear to contribute to hypothermia.

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 in its SSEP latency, as compared with the control. In addition, 5- and 8-hour hypothermia rats' spinal cord showed higher percentage of parenchyma preservation. Early local moderate hypothermia can be induced for extended periods of time post SCI in the rodent model. Such intervention improves functional electrophysiological outcome and motor behavior recovery for a long time, lasting until 8 weeks. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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

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.

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

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.

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 standard care to reduce intracranial pressure did not result in outcomes better than those with standard care alone. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN34555414.).

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.

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.

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.

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.

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.

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.

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.

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.

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...

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

Drownproofing and the Water Safety Spectrum.

ERIC Educational Resources Information Center

Smith, David S.

1982-01-01

Drowning has three major causes: (1) inability to swim and/or lack of a personal flotation device; (2) hypothermia; and (3) abuse of alcohol or drugs. Defenses against drowning include: (1) proper use of personal flotation devices; (2) learning swimming and flotation techniques; (3) understanding reduction of heat loss in cold water; and (4)…

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.

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.

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.

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.

Effect of stimulus type and temperature on EEG reactivity in cardiac arrest.

PubMed

Fantaneanu, Tadeu A; Tolchin, Benjamin; Alvarez, Vincent; Friolet, Raymond; Avery, Kathleen; Scirica, Benjamin M; O'Brien, Molly; Henderson, Galen V; Lee, Jong Woo

2016-11-01

Electroencephalogram (EEG) background reactivity is a reliable outcome predictor in cardiac arrest patients post therapeutic hypothermia. However, there is no consensus on modality testing and prior studies reveal only fair to moderate agreement rates. The aim of this study was to explore different stimulus modalities and report interrater agreements. We studied a multicenter, prospectively collected cohort of cardiac arrest patients who underwent therapeutic hypothermia between September 2014 and December 2015. We identified patients with reactivity data and evaluated interrater agreements of different stimulus modalities tested in hypothermia and normothermia. Of the 60 patients studied, agreement rates were moderate to substantial during hypothermia and fair to moderate during normothermia. Bilateral nipple pressure is more sensitive (80%) when compared to other modalities in eliciting a reactive background in hypothermia. Auditory, nasal tickle, nailbed pressure and nipple pressure reactivity were associated with good outcomes in both hypothermia and normothermia. EEG reactivity varies depending on the stimulus testing modality as well as the temperature during which stimulation is performed, with nipple pressure emerging as the most sensitive during hypothermia for reactivity and outcome determination. This highlights the importance of multiple stimulus testing modalities in EEG reactivity determination to reduce false negatives and optimize prognostication. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Is moderate hypothermic circulatory arrest with selective antegrade cerebral perfusion superior to deep hypothermic circulatory arrest in elective aortic arch surgery?

PubMed

Poon, Shi Sum; Estrera, Anthony; Oo, Aung; Field, Mark

2016-09-01

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether moderate hypothermia circulatory arrest with selective antegrade cerebral perfusion (SACP) is more beneficial than deep hypothermic circulatory arrest in elective aortic arch surgery. Altogether, 1028 papers were found using the reported search, of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. There were four retrospective observational studies, one prospective randomized controlled trial and one meta-analysis study. There were no local or neuromuscular complications related to axillary arterial cannulation reported. In the elective setting, four studies showed that the in-hospital mortality for moderate hypothermia is consistently low, ranging from 1.0 to 4.3%. In a large series of hemiarch replacement comparing 682 cases of deep hypothermia with 94 cases of moderate hypothermia with SACP, 20 cases (2.8%) of permanent neurological deficit were reported, compared to 3 cases (3.2%) in moderate hypothermia. Three observational studies and a meta-analysis study did not identify an increased risk of postoperative renal failure and dialysis following either deep or moderate hypothermia although a higher incidence of stroke was reported in the meta-analysis study with deep hypothermia (12.7 vs 7.3%). Longer cardiopulmonary bypass time and circulatory arrest time were reported in four studies for deep hypothermia, suggesting an increased time required for systemic cooling and rewarming in that group. Overall, these findings suggested that in elective aortic arch surgery, moderate hypothermia with selective antegrade cerebral perfusion adapted to the duration of circulatory arrest can be performed safely with acceptable mortality and morbidity outcomes. The risk of spinal cord and visceral organ complications is low with the use of this cerebral adjunct. Current studies did not identify an advantage in terms of postoperative bleeding when compared with deep hypothermia. The moderate hypothermia strategy reduced operative time without increasing the mortality and morbidity of surgery. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

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 quality of life for patients suffering from post-CA syndrome is proposed in the present study. PMID:29207113

Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

PubMed Central

Hu, Heng; Doll, Danielle N.; Sun, Jiahong; Lewis, Sara E.; Wimsatt, Jeffrey H.; Kessler, Matthew J.; Simpkins, James W.; Ren, Xuefang

2016-01-01

Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for stroke severity in experimental stroke animal models and may have translational significance for clinical stroke patients - targeting endothelial mitochondria may be a clinically useful approach for stroke therapy. PMID:26816660

Usefulness of postmortem biochemistry in identification of ketosis: Diagnosis of ketoacidosis at the onset of autoimmune type 1 diabetes in an autopsy case with cold exposure and malnutrition.

PubMed

Tani, Naoto; Michiue, Tomomi; Chen, Jian-Hua; Oritani, Shigeki; Ishikawa, Takaki

2016-09-01

A severely malnourished, Japanese female in her twenties was found dead in her apartment. On autopsy, most of the findings from the internal examination were suggestive of hypothermia. Postmortem biochemistry, however, showed severely increased levels of glycated hemoglobin (HbA1c) and blood and urine glucose levels. Levels of acetone, 3-hydroxybutyric acid, and acetoacetate in various body fluids were also highly increased, indicating ketosis. The serum insulin and c-peptide levels were severely low, and subsequent testing was positive for anti-GAD antibodies. Immunohistochemical examination of the pancreatic islet cells revealed few insulin-positive cells but many glucagon-positive cells on staining. Furthermore, slight invasion of CD8-positive lymphocytes in the pancreatic islets of Langerhans was observed. Results of immunostaining of the pancreatic and bronchial epithelial tissues were partly positive for the Influenza A virus. We concluded that severe ketoacidosis associated with rapid-onset hyperglycemia due to autoimmune type 1 diabetes (AT1D) had occurred shortly before death. However, the ketosis was accompanied by hypothermia and malnutrition as well as diabetic ketoacidosis (DKA). Therefore, we retrospectively collected biochemical data on cases of hypothermia and malnutrition and compared them with the present case. Serum glucose, acetone, 3-hydroxybutyric acid, and acetoacetic acid can be used for screening and diagnosis to distinguish DKA from ketosis due to hypothermia and malnutrition. Therefore, in the present case, we diagnosed that the natural cause of death was due to AT1D. In conclusion, screening investigations for relevant biochemical markers can provide essential information for the diagnosis of metabolic disturbances, which fail to demonstrate characteristic autopsy findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Reduction in sympathetic nerve activity as a possible mechanism for the hypothermic effect of oseltamivir, an anti-influenza virus drug, in normal mice.

PubMed

Ono, Hideki; Iwajima, Yui; Nagano, Yuko; Chazono, Kaori; Maeda, Yasuhiro; Ohsawa, Masahiro; Yamamoto, Shohei

2013-07-01

Oseltamivir, an anti-influenza virus drug, has strong antipyretic effects in mice (Biological and Pharmaceutical Bulletin, 31, 2008, 638) and patients with influenza. In addition, hypothermia has been reported as an adverse event. The prodrug oseltamivir is converted to oseltamivir carboxylate (OC), an active metabolite of influenza virus neuraminidase. In this study, core body temperature was measured in mice, and oseltamivir and OC were administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p). Low i.c.v. doses of oseltamivir and OC dose-dependently produced hypothermia. Zanamivir (i.c.v.), another neuraminidase inhibitor, did not produce hypothermia. These results suggested that the hypothermic effects of oseltamivir (i.p. and i.c.v.) and OC (i.c.v.) are not due to neuraminidase inhibition. OC (i.p.) did not lower body temperature. Although mecamylamine (i.c.v.) blocked the hypothermic effect of nicotine-administered i.c.v., the hypothermic effects of oseltamivir and OC (i.c.v.) were not blocked by mecamylamine (i.c.v.). The effect of oseltamivir (i.p.) was markedly increased by s.c.-pre-administered mecamylamine and also hexamethonium, a peripherally acting ganglionic blocker, suggesting their potentiating interaction at peripheral sites. The hypothermic effect of nicotine (i.c.v.) was decreased by lower doses of oseltamivir (i.c.v.), suggesting the anti-nicotinic action of oseltamivir. These results suggest that oseltamivir (i.p.) causes hypothermia through depression of sympathetic temperature regulatory mechanisms via inhibition of nicotinic receptor function and through unknown central mechanisms. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

Heating Pad Performance and Efficacy of 2 Durations of Warming after Isoflurane Anesthesia of Sprague-Dawley Rats (Rattus norvegicus).

PubMed

Zhang, Emily Q; Knight, Cameron G; Pang, Daniel Sj

2017-11-01

Anesthetic agents depress thermoregulatory mechanisms, causing hypothermia within minutes of induction of general anesthesia. The consequences of hypothermia include delayed recovery and increased experimental variability. Even when normothermia is maintained during anesthesia, hypothermia may occur during recovery. The primary aim of this study was to identify an effective warming period for maintaining normothermia during recovery. Adult male (n = 8) and female (n = 9) Sprague-Dawley rats were randomized to 30 min (post30) or 60 min (post60) of warming after recovery from anesthesia. During a 40-min anesthetic period, normothermia (target, 37.5 ± 1.1 °C) was maintained by manual adjustment of an electric heating pad in response to measured rectal temperatures (corrected to estimate core body temperature). Warming was continued in a recovery cage according to treatment group. Rectal temperature was measured for a total of 120 min after anesthesia. Heating pad performance was assessed by measuring temperatures at various sites over its surface. One female rat in the post30 group was excluded from analysis. Normothermia was effectively maintained during and after anesthesia without significant differences between groups. In the post60 group, core temperature was slightly but significantly increased at 90 and 100 min compared with baseline. One rat in each treatment group became hyperthermic (>38.6 °C) during recovery. During recovery, the cage floor temperature required approximately 30 min to stabilize. The heating pad produced heat unevenly over its surface, and measured temperatures frequently exceeded the programmed temperature. Providing 30 min of warming immediately after anesthesia effectively prevented hypothermia in rats. Shorter warming periods may be useful when recovery cages are preheated.

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 apparent among larger babies. The need for year-round thermal care, early breastfeeding and maternal thermal care should be emphasized. Further work is needed to quantify the benefits of other simple neonatal thermal care practices.

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 H nuclear magnetic resonance metabolomics. MTHT can significantly reduce the mortality of severe TBI patients. Metabolomics research showed that this strategy could effectively improve brain metabolism, suggesting that reducing the metabolic rate to 50% to 60% should be set as the hypothermia therapy target. Therapeutic study, Level I.

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

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

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.

Inhaled Xenon Attenuates Myocardial Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The Xe-Hypotheca Trial.

PubMed

Arola, Olli; Saraste, Antti; Laitio, Ruut; Airaksinen, Juhani; Hynninen, Marja; Bäcklund, Minna; Ylikoski, Emmi; Wennervirta, Johanna; Pietilä, Mikko; Roine, Risto O; Harjola, Veli-Pekka; Niiranen, Jussi; Korpi, Kirsi; Varpula, Marjut; Scheinin, Harry; Maze, Mervyn; Vahlberg, Tero; Laitio, Timo

2017-11-28

The authors previously reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). A pre-defined secondary objective was to assess the effect of inhaled xenon on myocardial ischemic damage in the same study population. A total of 110 comatose patients who had experienced OHCA from a cardiac cause were randomized to receive either inhaled xenon (40% end-tidal concentration) combined with hypothermia (33°C) for 24 h (n = 55; xenon group) or hypothermia treatment alone (n = 55; control group). Troponin-T levels were measured at hospital admission, and at 24 h, 48 h, and 72 h post-cardiac arrest. All available cases were analyzed for troponin-T release. Troponin-T measurements were available from 54 xenon patients and 54 control patients. The baseline characteristics did not differ significantly between the groups. After adjustments for age, sex, study site, primary coronary percutaneous intervention (PCI), and norepinephrine dose, the mean ± SD post-arrival incremental change of the ln-transformed troponin-T at 72 h was 0.79 ± 1.54 in the xenon group and 1.56 ± 1.38 in the control group (adjusted mean difference -0.66; 95% confidence interval: -1.16 to -0.16; p = 0.01). The effect of xenon on the change in the troponin-T values did not differ in patients with or without PCI or in those with a diagnosis of ST-segment elevation myocardial infarction (group by PCI or ST-segment elevation myocardial infarction interaction effect; p = 0.86 and p = 0.71, respectively). Among comatose survivors of OHCA, in comparison with hypothermia alone, inhaled xenon combined with hypothermia suggested a less severe myocardial injury as demonstrated by the significantly reduced release of troponin-T. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

Endocrine regulation of carbohydrate metabolism in hypometabolic animals

NASA Technical Reports Server (NTRS)

Musacchia, X. J.

1988-01-01

Experimental hypothermia and natural hibernation are two forms of hypometabolism with recognized physiological changes, including depression of endocrine and metabolic functions. To better understand functional changes, helox (i.e., helium and oxygen (80:20) mixtures) and low ambient temperatures have been used to induce hypothermia in hamsters and rats. Both clinical and biological survival, i.e., survival without recovery and survival with recovery from hypothermia, respectively, are related to depth and length of hypothermia. In the rat, body temperatures of 15 degrees C for periods greater than 6-10 h greatly restrict biological survival. The role of glucocorticoids in enhancing thermogenic capacity of rats was assessed using triamcinolone [correction of triamcinalone] acetonide. In the hamster, treatment with cortisone acetate prolonged both clinical and biological survival. Hypothermic hamsters continue utilizing circulating glucose until they become hypoglycemic and die. Hypothermic rats do not utilize glucose and respond with a significant hypoinsulinema. The role of endocrines in the regulation of carbohydrate homeostasis and metabolism differs in hibernation and hypothermia. Glucocorticoids influence the hypothermic response in both species, specifically by prolonging induction of hypothermia in rats and by prolonging survival in hypothermic hamsters.

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.

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 simultaneously with oxygen-glucose deprivation, compared with delayed starting or no hypothermia, has higher pyruvate carboxylase throughput, suggesting that better glial integrity is one important neuroprotection mechanism of earlier hypothermia.

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 extended period of time after cooling. Pharmacokinetic interactions between hypothermia and medications should be considered when caring for children receiving this therapy. PMID:23896831

The expression of '150-kDa oxygen regulated protein (ORP-150)' in human brain and its relationship with duration time until death.

PubMed

Ikematsu, Kazuya; Tsuda, Ryouichi; Kondo, Toshikazu; Kondo, Hisayoshi; Ozawa, Kentaro; Ogawa, Satoshi; Nakasono, Ichiro

2004-04-01

The expression of oxygen regulated protein 150-kDa (ORP-150) was strongly induced in human brain under the hypoxic conditions. We examined the expression of ORP-150 in the brain samples, and discussed its significance in forensic practice. The cerebral cortexes of 31 cases (asphyxia: 9 cases, hypothermia: 4, exsanguinations: 5, CO intoxication (CO): 6, sudden cardiac death (SCD): 7) were used for this study. Each tissue section was incubated with anti-ORP-150 polyclonal antibody and the number of ORP-150 positive cells were counted. In the multiple linear regression method, the estimated regression coefficient of ORP-150 on age was significant (P=0.039) thus, we could find that the ORP-150 expression level depended on age. Using analysis of covariance, we compared the means of ORP-150, LSMEAN, which means hypothetic average value excluding influence of age, for each cause of death. The LSMEAN+/-SE was 84.74+/-9.03 in hypothermia, 57.52+/-6.34 in asphyxia, 46.68+/-6.70 in CO, 24.84+/-8.05 in exsanguinations, and 16.24+/-7.35 in SCD. As a result of the analysis, the LSMEAN of the ORP-150 expression level was related to the cause of death. There might be differences in the duration of brain ischemia before death. For example, SCD is presumed to be instant death, while brain ischemia continues for several minutes in asphyxia, CO and exsanguinations, and for several hours in hypothermia cases. Therefore, the immunohistochemical and morphometrical analysis of ORP-150 in the brain may be very useful to determine the duration of brain ischemia before death in forensic autopsy cases.

Humidification during laparoscopic surgery: overview of the clinical benefits of using humidified gas during laparoscopic surgery.

PubMed

Binda, Maria Mercedes

2015-11-01

The peritoneum is the serous membrane that covers the abdominal cavity and most of the intra-abdominal organs. It is a very delicate layer highly susceptible to damage and it is not designed to cope with variable conditions such as the dry and cold carbon dioxide (CO2) during laparoscopic surgery. The aim of this review was to evaluate the effects caused by insufflating dry and cold gas into the abdominal cavity after laparoscopic surgery. A literature search using the Pubmed was carried out. Articles identified focused on the key issues of laparoscopy, peritoneum, morphology, pneumoperitoneum, humidity, body temperature, pain, recovery time, post-operative adhesions and lens fogging. Insufflating dry and cold CO2 into the abdomen causes peritoneal damage, post-operative pain, hypothermia and post-operative adhesions. Using humidified and warm gas prevents pain after surgery. With regard to hypothermia due to desiccation, it can be fully prevented using humidified and warm gas. Results relating to the patient recovery are still controversial. The use of humidified and warm insufflation gas offers a significant clinical benefit to the patient, creating a more physiologic peritoneal environment and reducing the post-operative pain and hypothermia. In animal models, although humidified and warm gas reduces post-operative adhesions, humidified gas at 32 °C reduced them even more. It is clear that humidified gas should be used during laparoscopic surgery; however, a question remains unanswered: to achieve even greater clinical benefit to the patient, at what temperature should the humidified gas be when insufflated into the abdomen? More clinical trials should be performed to resolve this query.

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.

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.

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

[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.

[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.

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

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.

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

Perioperative thermal insulation.

PubMed

Bräuer, Anselm; Perl, Thorsten; English, Michael J M; Quintel, Michael

2007-01-01

Perioperative hypothermia remains a common problem during anesthesia and surgery. Unfortunately, the implementation of new minimally invasive surgical procedures has not lead to a reduction of this problem. Heat losses from the skin can be reduced by thermal insulation to avoid perioperative hypothermia. However, only a small amount of information is available regarding the physical properties of insulating materials used in the Operating Room (OR). Therefore, several materials using validated manikins were tested. Heat loss from the surface of the manikin can be described as:"Q = h . DeltaT . A" where Q = heat flux, h = heat exchange coefficient, DeltaT = temperature gradient between the environment and surface, and A = covered area. Heat flux per unit area and surface temperature were measured with calibrated heat flux transducers. Environmental temperature was measured using a thermoanemometer. The temperature gradient between the surface and environment (DeltaT) was varied and "h" was determined by linear regression analysis as the slope of "DeltaT" versus heat flux per unit area. The reciprocal of the heat exchange coefficient defines the insulation. The insulation values of the materials varied between 0.01 Clo (plastic bag) to 2.79 Clo (2 layers of a hospital duvet). Given the range of insulating materials available for outdoor activities, significant improvement in insulation of patients in the OR is both possible and desirable.

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.

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 neurotoxicity and, consequently, may play a unique role in opening up new therapeutic avenues for treating severe TBI and improving its devastating effects. Furthermore, greater understanding of the pathophysiology of TBI, new data from both basic and clinical research, the good clinical results obtained in randomized clinical trials in cardiac arrest and better and more reliable cooling methods have given hypothermia a second chance in treating TBI patients. A critical evaluation of hypothermia is therefore mandatory to elucidate the reasons for previous failures and to design further multicenter randomized clinical trials that would definitively confirm or refute the potential of this therapeutic modality in the management of severe traumatic brain injuries.

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.

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

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

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.

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.

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.

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.

[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.

History of accidental hypothermia☆

PubMed Central

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. PMID:21036455

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

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

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

A patient with Graves' disease who survived despite developing thyroid storm and lactic acidosis.

PubMed

Yoshino, Tetsuhiro; Kawano, Daisuke; Azuhata, Takeo; Kuwana, Tsukasa; Kogawa, Rikimaru; Sakurai, Atsushi; Tanjoh, Katsuhisa; Yanagawa, Tatsuo

2010-11-01

A 56-year-old woman with Graves' disease presented with the complaints of diarrhea and palpitations. Physical examination and laboratory data revealed hypothermia and signs of mild hyperthyroidism, heart failure, hepatic dysfunction with jaundice, hypoglycemia, and lactic acidosis. The patient was diagnosed as having developed the complication of thyroid storm in the absence of marked elevation of the thyroid hormone levels, because of the potential hepatic and cardiac dysfunctions caused by heavy alcohol drinking. A year later, after successful treatment, the patient remains well without any clinical evidence of heart failure or hepatic dysfunction. Thyroid storm associated with lactic acidosis and hypothermia is a serious condition and has rarely been reported. Prompt treatment is essential even if the serum thyroid hormone levels are not markedly elevated. We present a report about this patient, as her life could eventually be saved.

Maintaining Perioperative Normothermia: Sustaining an Evidence-Based Practice Improvement Project.

PubMed

Levin, Rona F; Wright, Fay; Pecoraro, Kathleen; Kopec, Wendy

2016-02-01

Unintentional perioperative hypothermia has been shown to cause serious patient complications and, thus, to increase health care costs. In 2009, an evidence-based practice improvement project produced a significant decrease in unintentional perioperative hypothermia in colorectal surgical patients through monitoring of OR ambient room temperature. Project leaders engaged all interdisciplinary stakeholders in the original project, which facilitated the sustainability of the intervention method. An important aspect of sustainability is ongoing monitoring and evaluation of a new intervention method. Therefore, continued evaluation of outcomes of the protocol developed in 2009 was scheduled at specific time points after the initial small test of change with colorectal patients. This article focuses on how attention to sustainability factors during implementation of an improvement project led to the sustainability of a protocol for monitoring OR ambient room temperature with all types of surgical patients five years after the initial project. Copyright © 2016 AORN, Inc. Published by Elsevier Inc. All rights reserved.

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

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

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.

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.

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.

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.

TRPA1 mediates the hypothermic action of acetaminophen

PubMed Central

Gentry, Clive; Andersson, David A.; Bevan, Stuart

2015-01-01

Acetaminophen (APAP) is an effective antipyretic and one of the most commonly used analgesic drugs. Unlike antipyretic non-steroidal anti-inflammatory drugs, APAP elicits hypothermia in addition to its antipyretic effect. Here we have examined the mechanisms responsible for the hypothermic activity of APAP. Subcutaneous, but not intrathecal, administration of APAP elicited a dose dependent decrease in body temperature in wildtype mice. Hypothermia was abolished in mice pre-treated with resiniferatoxin to destroy or defunctionalize peripheral TRPV1-expressing terminals, but resistant to inhibition of cyclo-oxygenases. The hypothermic activity was independent of TRPV1 since APAP evoked hypothermia was identical in wildtype and Trpv1−/− mice, and not reduced by administration of a maximally effective dose of a TRPV1 antagonist. In contrast, a TRPA1 antagonist inhibited APAP induced hypothermia and APAP was without effect on body temperature in Trpa1−/− mice. In a model of yeast induced pyrexia, administration of APAP evoked a marked hypothermia in wildtype and Trpv1−/− mice, but only restored normal body temperature in Trpa1−/− and Trpa1−/−/Trpv1−/− mice. We conclude that TRPA1 mediates APAP evoked hypothermia. PMID:26227887

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

Implementation of a multidisciplinary guideline improves preterm infant admission temperatures.

PubMed

Harer, M W; Vergales, B; Cady, T; Early, A; Chisholm, C; Swanson, J R

2017-11-01

Hypothermia is a common problem in preterm infants immediately following delivery.Local problem:The rate of admission hypothermia in our neonatal intensive care unit (NICU) was above the rate of comparable NICUs in the Vermont Oxford Network. To reduce the rate of preterm admission hypothermia, a quality improvement (QI) project was implemented, utilizing the plan-do-study-act (PDSA) methodology. A guideline for delivery room thermoregulation management in <35-week infants at the University of Virginia was created and put into practice by a multidisciplinary team. Clinical practice changes in the guideline included: increasing operating room temperatures, obtaining a 10-min axillary temperature, using an exothermic mattress for all infants <35 weeks, and using a polyethylene wrap for infants <32 weeks. The baseline rate of hypothermia (<36.5 °CC) was 63%. Three PDSA cycles data were completed on 168 consecutive preterm births. The post-implementation rate of hypothermia (<36.5 °C) was reduced to 30% (P<0.001). The incidence of moderate hypothermia (< 36 °C) was reduced from a baseline of 29% to a rate of 9% (P<0.001). Use of a multidisciplinary guideline to increase preterm NICU admission temperatures resulted in a decrease in hypothermic infants.

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.

Docosahexaenoic acid augments hypothermic neuroprotection in a neonatal rat asphyxia model.

PubMed

Berman, Deborah R; Mozurkewich, Ellen; Liu, Yiqing; Shangguan, Yu; Barks, John D; Silverstein, Faye S

2013-01-01

In neonatal rats, early post-hypoxia-ischemia (HI) administration of the omega-3 fatty acid docosahexaenoic acid (DHA) improves sensorimotor function, but does not attenuate brain damage. To determine if DHA administration in addition to hypothermia, now standard care for neonatal asphyxial brain injury, attenuates post-HI damage and sensorimotor deficits. Seven-day-old (P7) rats underwent right carotid ligation followed by 90 min of 8% O2 exposure. Fifteen minutes later, pups received injections of DHA 2.5 mg/kg (complexed to 25% albumin) or equal volumes of albumin. After a 1-hour recovery, pups were cooled (3 h, 30°C). Sensorimotor and pathology outcomes were initially evaluated on P14. In subsequent experiments, sensorimotor function was evaluated on P14, P21, and P28; histopathology was assessed on P28. At P14, left forepaw function scores (normal: 20/20) were near normal in DHA + hypothermia-treated animals (mean ± SD 19.7 ± 0.7 DHA + hypothermia vs. 12.7 ± 3.5 albumin + hypothermia, p < 0.0001) and brain damage was reduced (mean ± SD right hemisphere damage 38 ± 17% with DHA + hypothermia vs. 56 ± 15% with albumin + hypothermia, p = 0.003). Substantial improvements on three sensorimotor function measures and reduced brain damage were evident up to P28. Unlike post-HI treatment with DHA alone, treatment with DHA + hypothermia produced both sustained functional improvement and reduced brain damage after neonatal HI. Copyright © 2013 S. Karger AG, Basel.

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.

The Impact of Vasoactive Drugs on Oxygenation and Tissue Perfusion

DTIC Science & Technology

1992-01-01

blood. Diffusion defects are seen in patients with pulmonary fibrosis and adult respiratory distress syndrome among others (Von Rueden, 1989; Reischman...increased oxyhemoglobin affinity include alkalosis , hypocarbia, hypothermia, hypophosphatemia and decreased levels of 2,3 - DPG (Mims, 1989; Von Rueden...which cause degranulation of mast cells, basophils and neutrophils. Neutrophils are responsible for respiratory bursts. These bursts are actually

Use of Normothermic Default Humidifier Settings Causes Excessive Humidification of Respiratory Gases During Therapeutic Hypothermia.

PubMed

Tanaka, Shoichiro; Iwata, Sachiko; Kinoshita, Masahiro; Tsuda, Kennosuke; Sakai, Sayaka; Saikusa, Mamoru; Shindo, Ryota; Harada, Eimei; Okada, Junichiro; Hisano, Tadashi; Kanda, Hiroshi; Maeno, Yasuki; Araki, Yuko; Ushijima, Kazuo; Sakamoto, Teruo; Yamashita, Yushiro; Iwata, Osuke

2016-12-01

Adult patients frequently suffer from serious respiratory complications during therapeutic hypothermia. During therapeutic hypothermia, respiratory gases are humidified close to saturated vapor at 37°C (44 mg/L) despite that saturated vapor reduces considerably depending on temperature reduction. Condensation may cause serious adverse events, such as bronchial edema, mucosal dysfunction, and ventilator-associated pneumonia during cooling. To determine clinical variables associated with inadequate humidification of respiratory gases during cooling, humidity of inspiratory gases was measured in 42 cumulative newborn infants who underwent therapeutic hypothermia. Three humidifier settings of 37-default (chamber outlet, 37°C; distal circuit, 40°C), 33.5-theoretical (chamber outlet, 33.5°C; distal circuit, 36.5°C), and 33.5-adjusted (optimized setting to achieve 36.6 mg/L using feedback from a hygrometer) were tested to identify independent variables of excessively high humidity >40.7 mg/L and low humidity <32.9 mg/L. The mean (SD) humidity at the Y-piece was 39.2 (5.2), 33.3 (4.1), and 36.7 (1.2) mg/L for 37-default, 33.5-theoretical, and 33.5-adjusted, respectively. The incidence of excessive high humidity was 10.3% (37-default, 31.0%; 33.5-theoretical, 0.0%; 33.5-adjusted, 0.0%), which was positively associated with the use of a counter-flow humidifier (p < 0.001), 37-default (compared with 33.5-theoretical and 33.5-adjusted, both p < 0.001) and higher fraction of inspired oxygen (p = 0.003). The incidence of excessively low humidity was 17.5% (37-default, 7.1%; 33.5-theoretical, 45.2%; 33.5-adjusted, 0.0%), which was positively associated with the use of a pass-over humidifier and 33.5-theoretical (both p < 0.001). All patients who used a counter-flow humidifier achieved the target gas humidity at the Y-piece (36.6 ± 0.5 mg/L) required for 33.5-adjusted with 33.5-theoretical. During cooling, 37-default is associated with excessively high humidity, whereas 33.5-theoretical leads to excessively low humidity. Future studies are needed to assess whether a new regimen with optimized Y-piece temperature and humidity control reduces serious respiratory adverse events during cooling.

Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma (EPR-CAT)

DTIC Science & Technology

2014-12-01

SUBJECT TERMS Trauma, hemorrhagic shock, cardiac arrest, cardiopulmonary resuscitation, hypothermia 16. SECURITY CLASSIFICATION OF: 17...EPR) was developed to rapidly preserve the organism during ischemia, using hypothermia , drugs, and fluids, to “buy time” for transport and...resuscitative surgery. The purpose of this study is to test the feasibility of rapidly inducing profound hypothermia (< 10oC) with an aortic flush in trauma

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 independent of HI. Vulnerable cells include myelinating oligodendrocytes. This study identifies a deleterious effect of therapeutic hypothermia in the developing brain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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 operations, requiring long periods of anesthesia, and receiving un-warmed intravenous fluids. PMID:26360773

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.

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.

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.

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

Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma (EPR-CAT)

DTIC Science & Technology

2015-10-01

cardiac arrest, cardiopulmonary resuscitation, hypothermia 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a...the organism during ischemia, using hypothermia , drugs, and fluids, to “buy time” for transport and resuscitative surgery. The purpose of this study...is to test the feasibility of rapidly inducing profound hypothermia (< 10oC) with an aortic flush in trauma victims that have suffered CA and

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.

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.

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.

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

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.

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.

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.

Hibernation, sleep, and thermogulation

NASA Technical Reports Server (NTRS)

South, F. E.

1973-01-01

Nerve activity adaptation to hypothermia and the differences in CNS activity during hypothermia are studied on marmots. Thermoregulatory experiments on hibernating animals indicated a sympathetic response.

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 rights reserved.

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 that the quality of evidence is very low. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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 may contribute to alleviating chemotherapy dose limitation due to CIPN and increase the likelihood of success of chemotherapy.

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

Post-hypothermic cardiac left ventricular systolic dysfunction after rewarming in an intact pig model

PubMed Central

2010-01-01

Introduction We developed a minimally invasive, closed chest pig model with the main aim to describe hemodynamic function during surface cooling, steady state severe hypothermia (one hour at 25°C) and surface rewarming. Methods Twelve anesthetized juvenile pigs were acutely catheterized for measurement of left ventricular (LV) pressure-volume loops (conductance catheter), cardiac output (Swan-Ganz), and for vena cava inferior occlusion. Eight animals were surface cooled to 25°C, while four animals were kept as normothermic time-matched controls. Results During progressive cooling and steady state severe hypothermia (25°C) cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), maximal deceleration of pressure in the cardiac cycle (dP/dtmin), indexes of LV contractility (preload recruitable stroke work, PRSW, and maximal acceleration of pressure in the cardiac cycle, dP/dtmax) and LV end diastolic and systolic volumes (EDV and ESV) were significantly reduced. Systemic vascular resistance (SVR), isovolumetric relaxation time (Tau), and oxygen content in arterial and mixed venous blood increased significantly. LV end diastolic pressure (EDP) remained constant. After rewarming all the above mentioned hemodynamic variables that were depressed during 25°C remained reduced, except for CO that returned to pre-hypothermic values due to an increase in heart rate. Likewise, SVR and EDP were significantly reduced after rewarming, while Tau, EDV, ESV and blood oxygen content normalized. Serum levels of cardiac troponin T (TnT) and tumor necrosis factor-alpha (TNF-α) were significantly increased. Conclusions Progressive cooling to 25°C followed by rewarming resulted in a reduced systolic, but not diastolic left ventricular function. The post-hypothermic increase in heart rate and the reduced systemic vascular resistance are interpreted as adaptive measures by the organism to compensate for a hypothermia-induced mild left ventricular cardiac failure. A post-hypothermic increase in TnT indicates that hypothermia/rewarming may cause degradation of cardiac tissue. There were no signs of inadequate global oxygenation throughout the experiments. PMID:21092272

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 adjustment for age, presenting heart rhythm, APACHE II and SOFA scores (OR 3.8, CI 1.3 to 11.0). In this observational cohort study, spontaneous hypothermia on ICU admission was the strongest predictor of an unfavorable neurological outcome in patients resuscitated for primary cardiac arrest.

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.

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 interleukin-6 and interleukin-10 expression during induced hypothermia.

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

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 .).

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.

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.

Early Prognostication Markers in Cardiac Arrest Patients Treated with Hypothermia

PubMed Central

Karapetkova, Maria; Koenig, Matthew A.; Jia, Xiaofeng

2015-01-01

Background and purpose Established prognostication markers, such as clinical findings, electroencephalography (EEG), and biochemical markers, used by clinicians to predict neurologic outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain. Methods MEDLINE and EMBASE were searched for evidence on the current standards for neurologic outcome prediction for out-of-hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers, and multimodal approaches for prognostication were included and reviewed. Results While the prognostic accuracy of various tests has been questioned after TH, pupillary light reflexes and somatosensory evoked potentials (SSEP) are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 hours after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as MRI and CT, can identify functional and structural brain injury, but are not readily available at the patient’s bedside because of limited availability and high costs. Conclusions A multimodal algorithm composed of neurological examination, EEG-based quantitative testing, and SSEP, in conjunction with newer MRI sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed later than 72 hours after CA. PMID:26228521

Early prognostication markers in cardiac arrest patients treated with hypothermia.

PubMed

Karapetkova, M; Koenig, M A; Jia, X

2016-03-01

Established prognostication markers, such as clinical findings, electroencephalography (EEG) and biochemical markers, used by clinicians to predict neurological outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain. MEDLINE and Embase were searched for evidence on the current standards for neurological outcome prediction for out-of-hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers and multimodal approaches for prognostication are included and reviewed. Whilst the prognostic accuracy of various tests after TH has been questioned, pupillary light reflexes and somatosensory evoked potentials are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 h after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as magnetic resonance imaging and computed tomography, can identify functional and structural brain injury but are not readily available at the patient's bedside because of limited availability and high costs. A multimodal algorithm composed of neurological examination, EEG-based quantitative testing and somatosensory evoked potentials, in conjunction with newer magnetic resonance imaging sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed more than 72 h after CA. © 2015 EAN.

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.

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.

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

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.

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.

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.

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

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 ...

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 with forced air warming at the end of surgery gave a WMD of -0.67 ºC (95% CI -0.95 to -0.39; very low quality evidence) indicating a higher temperature with forced air warming. Major cardiovascular outcomes were not reported and so were not analysed. There were no clear effects on bleeding, shivering or length of stay in post-anaesthetic care for either comparison. No other adverse effects were reported. There is no clear benefit of extra thermal insulation compared with standard care. Forced air warming does seem to maintain core temperature better than extra thermal insulation, by between 0.5 ºC and 1 ºC, but the clinical importance of this difference is unclear.

Suspected paradoxical undressing in a homicide case.

PubMed

Kettner, Mattias; Schnabel, Axel; Ramsthaler, Frank

2012-12-01

Paradoxical undressing is a phenomenon associated with fatalities due to severe hypothermia, which is characterized by the act of active undressing, despite low ambient temperatures, as a consequence of peripheral vasodilation. A 51-year-old man was found lying naked and inanimate on a road. Articles of his clothing were scattered in surrounding bushes. A nearby handrail showed a partially washed away bloodstain pattern. A forensic autopsy was used to distinguish whether death was due to a hypothermic fatality or whether the deceased was a victim of an accident or homicide. Medicolegal autopsy revealed craniofacial dissociation with injuries to the thorax and extremities and established choking/asphyxia due to deep aspiration of blood in combination with external blood loss as the cause of death. In the absence of hypothermia-related signs and toxicological findings the case was considered to be a homicide. Police investigation led to the conviction of a man who confessed to having kicked and hit the victim and forced him to take off his clothes in a humiliation-related scenario.

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.

Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice.

PubMed

Gainetdinov, R R; Bohn, L M; Walker, J K; Laporte, S A; Macrae, A D; Caron, M G; Lefkowitz, R J; Premont, R T

1999-12-01

G protein-coupled receptor kinase 5 (GRK5) is a member of a family of enzymes that phosphorylate activated G protein-coupled receptors (GPCR). To address the physiological importance of GRK5-mediated regulation of GPCRs, mice bearing targeted deletion of the GRK5 gene (GRK5-KO) were generated. GRK5-KO mice exhibited mild spontaneous hypothermia as well as pronounced behavioral supersensitivity upon challenge with the nonselective muscarinic agonist oxotremorine. Classical cholinergic responses such as hypothermia, hypoactivity, tremor, and salivation were enhanced in GRK5-KO animals. The antinociceptive effect of oxotremorine was also potentiated and prolonged. Muscarinic receptors in brains from GRK5-KO mice resisted oxotremorine-induced desensitization, as assessed by oxotremorine-stimulated [5S]GTPgammaS binding. These data demonstrate that elimination of GRK5 results in cholinergic supersensitivity and impaired muscarinic receptor desensitization and suggest that a deficit of GPCR desensitization may be an underlying cause of behavioral supersensitivity.

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.

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.

Does wet hair in cold weather cause sinus headache and posterior eye pain? A possible mechanism through selective brain cooling system.

PubMed

Kaya, Abdullah; Calışkan, Halil

2012-12-01

As a general observation, wet hair in cold weather seems to be a predisposing factor for sinus headache and posterior eye pain. We offer a mechanism through selective brain cooling system for this observation. Selective brain cooling (SBC) is a mechanism to protect brain from hyperthermia. Components of SBC are head skin and upper respiratory tract (nose and paranasal sinuses). Cool venous blood from head skin and mucous membranes of nose and paranasal sinuses drains to intracranial dural sinuses and provide brain cooling. Brain will be cooled very much when head skin exposes to hypothermia such a condition like wet hair in cold weather. We suggest that, in order to reduce brain cooling activity, some alterations are being occurred within paranasal sinuses. For this purpose, sinus ostiums may close and mucus may accumulate to reduce air within sinuses. Also there may be some vasomotor changes to prevent heat loss. We hypothesize that this possible alterations may occur within paranasal sinuses as a control mechanism for brain temperature control during exposure of head skin to hypothermia. Paranasal sinuses may also cool brain directly by a very thin layer of bone separates the posterior ethmoid air sinus from the subarachnoid space and only thin plates of bone separate the sphenoidal sinuses from internal carotid artery and cavernous sinuses. Because of their critical role in the SBC, posterior ethmoid air sinus and sphenoidal sinuses may be affected from this alterations more than other paranasal sinuses. This situation may cause posterior eye pain. This mechanism can explain why a person who expose to hypothermia with wet hair or a person who don't use a beret or a hat during cold weather gets sinus headache and posterior eye pain. These symptoms could lead to an incorrect diagnosis of sinusitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

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 Health and the Eunice Kennedy Shriver NICHD Neonatal Research Network; ClinicalTrials.gov number, NCT00005772.).

Deep skin structural and microcirculation imaging with extended-focus OCT

NASA Astrophysics Data System (ADS)

Blatter, Cedric; Grajciar, Branislav; Huber, Robert; Leitgeb, Rainer A.

2012-02-01

We present an extended focus OCT system for dermatologic applications that maintains high lateral resolution over a large depth range by using Bessel beam illumination. More, Bessel beams exhibit a self-reconstruction property that is particularly useful to avoid shadowing from surface structures such as hairs. High lateral resolution and high-speed measurement, thanks to a rapidly tuning swept source, allows not only for imaging of small skin structures in depth but also for comprehensive visualization of the small capillary network within the human skin in-vivo. We use this information for studying temporal vaso-responses to hypothermia. In contrast to other perfusion imaging methods such as laser Doppler imaging (LDI), OCT gives specific access to vascular responses in different vascular beds in depth.

A primer on clothing systems for cold-weather field work

USGS Publications Warehouse

Denner, Jon

1990-01-01

Conducting field work in cold weather is a demanding task. The most important safety consideration for field personnel is to maintain normal body temperature and avoid hypothermia.The human body adjusts to cold temperatures through different physiological processes. Heat production is enhanced by increases in the rates of basal metabolism, specific dynamic action, and physical exercise, and heat loss is reduced by vasoconstriction.Physiological adaptations alone are inadequate to stop rapid heat loss in cold temperatures. Additional insulation in the form of cold-weather clothing is necessary to retain heat.The most practical method of dressing for winter conditions is the layering system. Wearing multiple thin layers allows one to fine tune the insulation needed for different temperatures and activity levels.

Towards evidence-based resuscitation of the newborn infant.

PubMed

Manley, Brett J; Owen, Louise S; Hooper, Stuart B; Jacobs, Susan E; Cheong, Jeanie L Y; Doyle, Lex W; Davis, Peter G

2017-04-22

Effective resuscitation of the newborn infant has the potential to save many lives around the world and reduce disabilities in children who survive peripartum asphyxia. In this Series paper, we highlight some of the important advances in the understanding of how best to resuscitate newborn infants, which includes monitoring techniques to guide resuscitative efforts, increasing awareness of the adverse effects of hyperoxia, delayed umbilical cord clamping, the avoidance of routine endotracheal intubation for extremely preterm infants, and therapeutic hypothermia for hypoxic-ischaemic encephalopathy. Despite the challenges of performing high-quality clinical research in the delivery room, researchers continue to refine and advance our knowledge of effective resuscitation of newborn infants through scientific experiments and clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Costs and cost-effectiveness of training traditional birth attendants to reduce neonatal mortality in the Lufwanyama Neonatal Survival study (LUNESP).

PubMed

Sabin, Lora L; Knapp, Anna B; MacLeod, William B; Phiri-Mazala, Grace; Kasimba, Joshua; Hamer, Davidson H; Gill, Christopher J

2012-01-01

The Lufwanyama Neonatal Survival Project ("LUNESP") was a cluster randomized, controlled trial that showed that training traditional birth attendants (TBAs) to perform interventions targeting birth asphyxia, hypothermia, and neonatal sepsis reduced all-cause neonatal mortality by 45%. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness, and factors that might improve cost-effectiveness. We calculated LUNESP's financial and economic costs and the economic cost of implementation for a forecasted ten-year program (2011-2020). In each case, we calculated the incremental cost per death avoided and disability-adjusted life years (DALYs) averted in real 2011 US dollars. The forecasted 10-year program analysis included a base case as well as 'conservative' and 'optimistic' scenarios. Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. The estimated financial and economic costs of LUNESP were $118,574 and $127,756, respectively, or $49,469 and $53,550 per year. Fixed costs accounted for nearly 90% of total costs. For the 10-year program, discounted total and annual program costs were $256,455 and $26,834 respectively; for the base case, optimistic, and conservative scenarios, the estimated cost per death avoided was $1,866, $591, and $3,024, and cost per DALY averted was $74, $24, and $120, respectively. Outcomes were robust to variations in local costs, but sensitive to variations in intervention effect size, number of births attended by TBAs, and the extent of foreign consultants' participation. Based on established guidelines, the strategy of using trained TBAs to reduce neonatal mortality was 'highly cost effective'. We strongly recommend consideration of this approach for other remote rural populations with limited access to health care.

Costs and Cost-Effectiveness of Training Traditional Birth Attendants to Reduce Neonatal Mortality in the Lufwanyama Neonatal Survival Study (LUNESP)

PubMed Central

Sabin, Lora L.; Knapp, Anna B.; MacLeod, William B.; Phiri-Mazala, Grace; Kasimba, Joshua; Hamer, Davidson H.; Gill, Christopher J.

2012-01-01

Background The Lufwanyama Neonatal Survival Project (“LUNESP”) was a cluster randomized, controlled trial that showed that training traditional birth attendants (TBAs) to perform interventions targeting birth asphyxia, hypothermia, and neonatal sepsis reduced all-cause neonatal mortality by 45%. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness, and factors that might improve cost-effectiveness. Methods and Findings We calculated LUNESP's financial and economic costs and the economic cost of implementation for a forecasted ten-year program (2011–2020). In each case, we calculated the incremental cost per death avoided and disability-adjusted life years (DALYs) averted in real 2011 US dollars. The forecasted 10-year program analysis included a base case as well as ‘conservative’ and ‘optimistic’ scenarios. Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. The estimated financial and economic costs of LUNESP were $118,574 and $127,756, respectively, or $49,469 and $53,550 per year. Fixed costs accounted for nearly 90% of total costs. For the 10-year program, discounted total and annual program costs were $256,455 and $26,834 respectively; for the base case, optimistic, and conservative scenarios, the estimated cost per death avoided was $1,866, $591, and $3,024, and cost per DALY averted was $74, $24, and $120, respectively. Outcomes were robust to variations in local costs, but sensitive to variations in intervention effect size, number of births attended by TBAs, and the extent of foreign consultants' participation. Conclusions Based on established guidelines, the strategy of using trained TBAs to reduce neonatal mortality was ‘highly cost effective’. We strongly recommend consideration of this approach for other remote rural populations with limited access to health care. PMID:22545117

National athletic trainers' association position statement: lightning safety for athletics and recreation.

PubMed

Walsh, K M; Bennett, B; Cooper, M A; Holle, R L; Kithil, R; López, R E

2000-10-01

To educate athletic trainers and others about the dangers of lightning, provide lightning-safety guidelines, define safe structures and locations, and advocate prehospital care for lightning-strike victims. Lightning may be the most frequently encountered severe-storm hazard endangering physically active people each year. Millions of lightning flashes strike the ground annually in the United States, causing nearly 100 deaths and 400 injuries. Three quarters of all lightning casualties occur between May and September, and nearly four fifths occur between 10:00 AM and 7:00 PM, which coincides with the hours for most athletic or recreational activities. Additionally, lightning casualties from sports and recreational activities have risen alarmingly in recent decades. The National Athletic Trainers' Association recommends a proactive approach to lightning safety, including the implementation of a lightning-safety policy that identifies safe locations for shelter from the lightning hazard. Further components of this policy are monitoring local weather forecasts, designating a weather watcher, and establishing a chain of command. Additionally, a flash-to-bang count of 30 seconds or more should be used as a minimal determinant of when to suspend activities. Waiting 30 minutes or longer after the last flash of lightning or sound of thunder is recommended before athletic or recreational activities are resumed. Lightning- safety strategies include avoiding shelter under trees, avoiding open fields and spaces, and suspending the use of land-line telephones during thunderstorms. Also outlined in this document are the prehospital care guidelines for triaging and treating lightning-strike victims. It is important to evaluate victims quickly for apnea, asystole, hypothermia, shock, fractures, and burns. Cardiopulmonary resuscitation is effective in resuscitating pulseless victims of lightning strike. Maintenance of cardiopulmonary resuscitation and first-aid certification should be required of all persons involved in sports and recreational activities.

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

Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. The CHILL-MI trial: a randomized controlled study of the use of central venous catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction.

PubMed

Erlinge, David; Götberg, Matthias; Lang, Irene; Holzer, Michael; Noc, Marko; Clemmensen, Peter; Jensen, Ulf; Metzler, Bernhard; James, Stefan; Bötker, Hans Erik; Omerovic, Elmir; Engblom, Henrik; Carlsson, Marcus; Arheden, Håkan; Ostlund, Ollie; Wallentin, Lars; Harnek, Jan; Olivecrona, Göran K

2014-05-13

The aim of this study was to confirm the cardioprotective effects of hypothermia using a combination of cold saline and endovascular cooling. Hypothermia has been reported to reduce infarct size (IS) in patients with ST-segment elevation myocardial infarctions. In a multicenter study, 120 patients with ST-segment elevation myocardial infarctions (<6 h) scheduled to undergo percutaneous coronary intervention were randomized to hypothermia induced by the rapid infusion of 600 to 2,000 ml cold saline and endovascular cooling or standard of care. Hypothermia was initiated before percutaneous coronary intervention and continued for 1 h after reperfusion. The primary end point was IS as a percent of myocardium at risk (MaR), assessed by cardiac magnetic resonance imaging at 4 ± 2 days. Mean times from symptom onset to randomization were 129 ± 56 min in patients receiving hypothermia and 132 ± 64 min in controls. Patients randomized to hypothermia achieved a core body temperature of 34.7°C before reperfusion, with a 9-min longer door-to-balloon time. Median IS/MaR was not significantly reduced (hypothermia: 40.5% [interquartile range: 29.3% to 57.8%; control: 46.6% [interquartile range: 37.8% to 63.4%]; relative reduction 13%; p = 0.15). The incidence of heart failure was lower with hypothermia at 45 ± 15 days (3% vs. 14%, p < 0.05), with no mortality. Exploratory analysis of early anterior infarctions (0 to 4 h) found a reduction in IS/MaR of 33% (p < 0.05) and an absolute reduction of IS/left ventricular volume of 6.2% (p = 0.15). Hypothermia induced by cold saline and endovascular cooling was feasible and safe, and it rapidly reduced core temperature with minor reperfusion delay. The primary end point of IS/MaR was not significantly reduced. Lower incidence of heart failure and a possible effect in patients with early anterior ST-segment elevation myocardial infarctions need confirmation. (Efficacy of Endovascular Catheter Cooling Combined With Cold Saline for the Treatment of Acute Myocardial Infarction [CHILL-MI]; NCT01379261). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

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.

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.

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.

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.

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 selection of a cool ambient temperature facilitates the reduction in Tc. The recovery of Tc during N(2)O administration (i.e., acute tolerance development) could have been facilitated by selection of ambient temperatures that were warmer than those chosen during control administrations, but interestingly, this did not occur. Copyright © 2011 Elsevier Inc. All rights reserved.

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 regulated hypothermia because the selection of a cool ambient temperature facilitates the reduction in Tc. The recovery of Tc during N2O administration (i.e., acute tolerance development) could have been facilitated by selection of ambient temperatures that were warmer than those chosen during control administrations, but interestingly, this did not occur. PMID:21184766

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 representation of cold-seeking behavior at the ventral border of the dorsomedial nucleus. We also built maps for cold-induced thermogenesis in unanesthetized rats and found the dorsal hypothalamic area to be its main representation site. Our work identifies the neural substrate of cold-seeking behavior in systemic inflammation and expands the functional topography of the DMH, a structure that modulates autonomic, endocrine, and behavioral responses and is a potential therapeutic target in anxiety and panic disorders. PMID:28630253

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 representation of cold-seeking behavior at the ventral border of the dorsomedial nucleus. We also built maps for cold-induced thermogenesis in unanesthetized rats and found the dorsal hypothalamic area to be its main representation site. Our work identifies the neural substrate of cold-seeking behavior in systemic inflammation and expands the functional topography of the DMH, a structure that modulates autonomic, endocrine, and behavioral responses and is a potential therapeutic target in anxiety and panic disorders. Copyright © 2017 Wanner et al.

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.

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.

Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study.

PubMed

Aly, H; Elmahdy, H; El-Dib, M; Rowisha, M; Awny, M; El-Gohary, T; Elbatch, M; Hamisa, M; El-Mashad, A-R

2015-03-01

Melatonin has been shown to be neuroprotective in animal models. The objective of this study is to examine the effect of melatonin on clinical, biochemical, neurophysiological and radiological outcomes of neonates with hypoxic-ischemic encephalopathy (HIE). We conducted a prospective trial on 45 newborns, 30 with HIE and 15 healthy controls. HIE infants were randomized into: hypothermia group (N=15; received 72-h whole-body cooling) and melatonin/hypothermia group (N=15; received hypothermia and five daily enteral doses of melatonin 10 mg kg(-1)). Serum melatonin, plasma superoxide dismutase (SOD) and serum nitric oxide (NO) were measured at enrollment for all infants (N=45) and at 5 days for the HIE groups (N=30). In addition to electroencephalography (EEG) at enrollment, all surviving HIE infants were studied with brain magnetic resonance imaging (MRI) and repeated EEG at 2 weeks of life. Neurologic evaluations and Denver Developmental Screening Test II were performed at 6 months. Compared with healthy neonates, the two HIE groups had increased melatonin, SOD and NO. At enrollment, the two HIE groups did not differ in clinical, laboratory or EEG findings. At 5 days, the melatonin/hypothermia group had greater increase in melatonin (P<0.001) and decline in NO (P<0.001), but less decline in SOD (P=0.004). The melatonin/hypothermia group had fewer seizures on follow-up EEG and less white matter abnormalities on MRI. At 6 months, the melatonin/hypothermia group had improved survival without neurological or developmental abnormalities (P<0.001). Early administration of melatonin to asphyxiated term neonates is feasible and may ameliorate brain injury.

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.

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.

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.

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...

Targeted Temperature Management After Pediatric Cardiac Arrest Due To Drowning: Outcomes and Complications.

PubMed

Moler, Frank W; Hutchison, Jamie S; Nadkarni, Vinay M; Silverstein, Faye S; Meert, Kathleen L; Holubkov, Richard; Page, Kent; Slomine, Beth S; Christensen, James R; Dean, J Michael

2016-08-01

To describe outcomes and complications in the drowning subgroup from the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital trial. Exploratory post hoc cohort analysis. Twenty-four PICUs. Pediatric drowning cases. Therapeutic hypothermia versus therapeutic normothermia. An exploratory study of pediatric drowning from the Therapeutic Hypothermia After Pediatric Cardiac Arrest Out-of-Hospital trial was conducted. Comatose patients aged more than 2 days and less than 18 years were randomized up to 6 hours following return-of-circulation to hypothermia (n = 46) or normothermia (n = 28). Outcomes assessed included 12-month survival with a Vineland Adaptive Behavior Scale score of greater than or equal to 70, 1-year survival rate, change in Vineland Adaptive Behavior Scale-II score from prearrest to 12 months, and select safety measures. Seventy-four drowning cases were randomized. In patients with prearrest Vineland Adaptive Behavior Scale-II greater than or equal to 70 (n = 65), there was no difference in 12-month survival with Vineland Adaptive Behavior Scale-II score of greater than or equal to 70 between hypothermia and normothermia groups (29% vs 17%; relative risk, 1.74; 95% CI, 0.61-4.95; p = 0.27). Among all evaluable patients (n = 68), the Vineland Adaptive Behavior Scale-II score change from baseline to 12 months did not differ (p = 0.46), and 1-year survival was similar (49% hypothermia vs 42%, normothermia; relative risk, 1.16; 95% CI, 0.68-1.99; p = 0.58). Hypothermia was associated with a higher prevalence of positive bacterial culture (any blood, urine, or respiratory sample; 67% vs 43%; p = 0.04); however, the rate per 100 days at risk did not differ (11.1 vs 8.4; p = 0.46). Cumulative incidence of blood product use, serious arrhythmias, and 28-day mortality were not different. Among patients with cardiopulmonary resuscitation durations more than 30 minutes or epinephrine doses greater than 4, none had favorable Pediatric Cerebral Performance Category outcomes (≤ 3). In comatose survivors of out-of-hospital pediatric cardiac arrest due to drowning, hypothermia did not result in a statistically significant benefit in survival with good functional outcome or mortality at 1 year, as compared with normothermia. High risk of culture-proven bacterial infection was observed in both groups.

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.

Therapeutic hypothermia in Italian Intensive Care Units after 2010 resuscitation guidelines: still a lot to do.

PubMed

Gasparetto, Nicola; Scarpa, Daniele; Rossi, Sandra; Persona, Paolo; Martano, Luigi; Bianchin, Andrea; Castioni, Carlo Alberto; Ori, Carlo; Iliceto, Sabino; Cacciavillani, Luisa

2014-03-01

Therapeutic hypothermia (TH) is one of three interventions that have demonstrated to improve patients' neurological outcome after cardiac arrest. The aim of this study was to investigate the effect of the 2010 resuscitation guidelines on TH implementation in various Italian Intensive Care Units (ICU). A structured questionnaire was submitted to Italian ICU. The questionnaire was addressed to determine the procedures of TH in each ICU or, on the contrary, the reason for not employing the therapy. We obtained complete information from 770 of 847 Italian ICU (91%). Out of 405 Units included in the analysis only 223 (55.1%) reported to use TH in comatose patients after return of spontaneous circulation. The trend of TH implementation shows a stable increase, particularly after 2006 but there is no evident acceleration after the strong indication of the 2010 guidelines. There was a rise of about 3.4 times in the number of Italian ICU using TH as compared to the 2007 survey (an increase of 68% per year). One hundred and eighty-two (44.9%) units did not use TH mainly because of lack of equipment, economic issues or the conviction of the difficulty of execution. TH is still under-used in Italy (55.1%) even though the therapy is strongly recommended in the 2010 guidelines. However, the increase in the adoption of hypothermia has been significant in the past 5 years (68%/years) and the awareness of the efficacy is almost consolidated among intensivists, being logistic problems the leading cause for non-adoption. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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.

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.

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.

Phenobarbital Augments Hypothermic Neuroprotection

PubMed Central

Barks, John D.; Liu, Yi-Qing; Shangguan, Yu; Silverstein, Faye S.

2010-01-01

Seizures are associated with adverse outcome in infants with hypoxic-ischemic encephalopathy. We hypothesized that early administration of the anticonvulsant phenobarbital after cerebral hypoxia-ischemia could enhance the neuroprotective efficacy of delayed-onset hypothermia. We tested this hypothesis in a neonatal rodent model. Seven-day-old rats (n=104) underwent right carotid ligation, followed by 90 min 8%O2 exposure; 15 min later, they received injections of phenobarbital (40 mg/kg) or saline. One or 3h later, all were treated with hypothermia (30°C, 3h). Function and neuropathology were evaluated after 7 days (“early outcomes”) or 1 month (“late outcomes”). Early outcome assessment demonstrated better sensorimotor performance and less cortical damage in phenobarbital-treated groups; there were no differences between groups in which the hypothermia delay was shortened from 3h to 1h. Late outcome assessment confirmed sustained benefits of phenobarbital+hypothermia treatment; sensorimotor performance was better (persistent attenuation of contralateral forepaw placing deficits and absence of contralateral forepaw neglect); neuropathology scores were lower (medians, phenobarbital 2, saline 8.5, p<0.05), and less ipsilateral cerebral hemisphere %Damage (mean±SD, 11±17 vs. 28±22, p<0.05). These results suggest that early post-hypoxia-ischemia administration of phenobarbital may augment the neuroprotective efficacy of therapeutic hypothermia. PMID:20098339

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.

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 hypothermic-inducing compounds that have a strong potential in the management of TBI. PMID:24731132

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...

[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.

Transient dysautonomia in an acute phase of encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Ichimiya, Yuko; Kaku, Noriyuki; Sakai, Yasunari; Yamashita, Fumiya; Matsuoka, Wakato; Muraoka, Mamoru; Akamine, Satoshi; Mizuguchi, Soichi; Torio, Michiko; Motomura, Yoshitomo; Hirata, Yuichiro; Ishizaki, Yoshito; Sanefuji, Masafumi; Torisu, Hiroyuki; Takada, Hidetoshi; Maehara, Yoshihiko; Ohga, Shouichi

2017-08-01

Paroxysmal sympathetic hyperactivity (PSH) is a dysautonomic condition that is associated with various types of acquired brain injuries. Traumatic brain lesions have been documented as the leading cause of PSH. However, detailed clinical features of pediatric PSH caused by intrinsic brain lesions remain to be elusive. We present a 3-year-old boy, who had been diagnosed as having cerebral palsy, developmental delay and epilepsy after perinatal hypoxia-induced brain injury. He developed status epilepticus with fever on the third day of respiratory infection. Whereas the seizure was terminated by systemic infusion of midazolam, consciousness remained disturbed for the next 48h. Serial magnetic resonance imaging studies revealed that acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) evolved on 3days after the seizure. Therapeutic hypothermia was immediately introduced, however, the brain lesion extended to the whole subcortical white matters on day 8. The intermittent bilateral dilation of pupils with increased blood pressure and tachycardia were observed until day 12. Real-time monitoring of electroencephalograms ruled out the recurrent attacks of seizures. The abnormal signs of autonomic nervous system gradually ceased and never relapsed after recovery from the hypothermia. PSH or a transient condition of dysautonomia may emerge and persist during the acute phase of AESD. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

The Frequency and Severity of Magnetic Resonance Imaging Abnormalities in Infants with Mild Neonatal Encephalopathy.

PubMed

Walsh, Brian H; Neil, Jeffrey; Morey, JoAnn; Yang, Edward; Silvera, Michelle V; Inder, Terrie E; Ortinau, Cynthia

2017-08-01

To assess and contrast the incidence and severity of abnormalities on cerebral magnetic resonance imaging (MRI) between infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia. This retrospective cohort studied infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia at a single tertiary neonatal intensive care unit between 2013 and 2015. Two neuroradiologists masked to the clinical condition evaluated brain MRIs for cerebral injury after therapeutic hypothermia using the Barkovich classification system. Additional abnormalities not included in this classification system were also noted. The rate, pattern, and severity of abnormalities/injury were compared across the grades of neonatal encephalopathy. Eighty-nine infants received therapeutic hypothermia and met study criteria, 48 with mild neonatal encephalopathy, 35 with moderate neonatal encephalopathy, and 6 with severe neonatal encephalopathy. Forty-eight infants (54%) had an abnormality on MRI. There was no difference in the rate of overall MRI abnormalities by grade of neonatal encephalopathy (mild neonatal encephalopathy 54%, moderate neonatal encephalopathy 54%, and severe neonatal encephalopathy 50%; P= .89). Basal ganglia/thalamic injury was more common in those with severe neonatal encephalopathy (mild neonatal encephalopathy 4%, moderate neonatal encephalopathy 9%, severe neonatal encephalopathy 34%; P = .03). In contrast, watershed injury did not differ between neonatal encephalopathy grades (mild neonatal encephalopathy 36%, moderate neonatal encephalopathy 32%, severe neonatal encephalopathy 50%; P = .3). Mild neonatal encephalopathy is commonly associated with MRI abnormalities after therapeutic hypothermia. The grade of neonatal encephalopathy during the first hours of life may not discriminate adequately between infants with and without cerebral injury noted on MRI after therapeutic hypothermia. Copyright © 2017 Elsevier Inc. All rights reserved.

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).

Status epilepticus caused by a myxoedema coma.

PubMed

Jansen, H J; Doebé, S R Oedit; Louwerse, E S; van der Linden, J C; Netten, P M

2006-06-01

The case of a 63-year-old woman who presented with status epilepticus, coma and hypoventilation is reported. A primary neurological cause was considered. Hypothermia led to further investigations and a diagnosis of severe hypothyroidism. The neurological complications of hyperthyriodism include alteration in mental status with slowness, decreased concentration and lethargy, headache, cranial nerve palsies, dysarthria, hoarseness, myopathy, neuropathy, reflex changes, ataxia, and psychotic episodes. Our patient suffered from a rare consequence of severe hypothyroidism presenting with status epilepticus and she died despite treatment. To our knowledge this is the second patient to be reported with myxoedema coma with this kind of presentation. Despite therapeutic options, there is a high mortality rate.

The effect of inhalant anesthetic and body temperature on peri-anesthetic serum concentrations of transdermally administered fentanyl in dogs.

PubMed

Pettifer, Glenn R; Hosgood, Giselle

2004-04-01

To determine whether moderate hypothermia during anesthesia significantly affects the serum concentration of transdermally delivered fentanyl and whether halothane or isoflurane affect these concentrations. Randomized cross-over experimental trial. Six mature, healthy Beagles (three males, three females) weighing 10.6 +/- 0.43 kg. A 50-microg hour(-1) fentanyl patch was applied 36 hours prior to anesthesia. Anesthesia was induced at time 0 (t = 0). Each dog received four treatments: isoflurane + normothermia (ISO-NORM), isoflurane + hypothermia (ISO-HYPO), halothane + normothermia (HAL-NORM), and halothane + hypothermia (HAL-HYPO). Dogs were intubated and maintained at 1.5 times MAC. Animals in the hypothermia treatments were cooled to 35 degrees C during anesthesia. Serum fentanyl analysis was performed at -36, -24, -12, 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 18, and 26 hours. Direct arterial blood pressures and arterial blood gases were monitored. The mean body temperatures (+/-SEM) during the anesthetic period for the four treatments were: ISO-NORM = 37.7 +/- 0.07 degrees C, ISO-HYPO = 35.8 +/- 0.1 degrees C, HAL-NORM = 37.7 +/- 0.06 degrees C, and HAL-HYPO = 35.8 +/- 0.13 degrees C. The mean (+/-SEM) serum fentanyl concentrations (SFC) for both hypothermia treatments were significantly lower than baseline concentrations at t = 1 hour and persisted for the duration of anesthesia for the ISO-HYPO treatment but only from t = 1 to 2 hours for the HAL-HYPO treatment. Serum fentanyl concentrations returned to baseline within one hour of the end of anesthesia, regardless of body temperature. There were no significant differences between treatments for systolic or diastolic blood pressure but mean blood pressures were higher during normothermia versus hypothermia during the last hour of anesthesia. Hypothermia during inhalation anesthesia produced a significant reduction in SFC using transdermal administration and was more protracted with isoflurane than halothane anesthesia. While significant reductions in SFC occurred, the SFC were still within the range believed to confer analgesia.

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 correct hypothermia-induced primary haemostasis impairment under the influence of aspirin during the perioperative period. ClinicalTrials.gov: NCT01382134.

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.

[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.

[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.

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.

Impact of Hypothermic Stress During Special Operations Training of Chilean Military Forces.

PubMed

Nieto Jimenez, Claudio; Cajigal Vargas, Jorge; Triantafilo Vladilo, Vjera Sofia; Naranjo Orellana, Jose

2018-02-07

The Chilean Army considers processes that can optimize physical capacities for responding to the impact of situations and given stressors. The study of the effect of hypothermia as a stressor agent (HSA) and its relationship with cardiovascular, hematological, anthropometric, endocrine, and immunological parameters has not been fully addressed experimentally in military populations. To identify the endocrine, hematological, cardiovascular, and immunological changes caused by HSA and to associate these variables with body composition and physical fitness in the military special operation courses of the Chilean Army. Forty-two male subjects were exposed to remain in cold water (10.6 °C) in the context of regular military operations training, the longest time of exposure was determined by individual volitional limits. The measurements were taken in pre-hypothermia conditions, then 2 d later under acute hypothermia condition, and finally during the course period of lesser physical and psychological stressors where the baseline measurements were taken. The statistical analysis consisted of testing normality of the distribution through the Shapiro-Wilk test, assessing the equality of variances through the Levene test, and variance analysis by applying the ANOVA test (analysis of variance). The Bonferroni test was used for multiple comparison correction and the Pearson test for correlations between two variables. The level of significance was of p < 0.05. The main finding of this study is that HSA has a significant impact at the cardiovascular level and produces an increment in the cell population of the immune and hematologic systems. Significant hormonal changes were observed: ACTH (r = 0.50, p < 0.002), cortisol (r = 0.32, p < 0.03), free testosterone (r = 0.13, p < 0.002), total testosterone r = 0.31, p < 0.002), and anthropometrics (r= -0.51, p < 0.05). However, there is no significant correlation between physical fitness and HAS. All subjects experienced hypothermia stress elicited by immersion in cold water. This was evidenced by the decrease in core temperature as well as cardiovascular, endocrine, anthropometric, and immunological changes. Individual differences exist between subjects and their resistance to hypothermia in cold water. These differences are not explained by the physical fitness profile but rather respond to a greater body adiposity index and minor changes in the adrenocorticotropic hormone and cortisol hormone. An acute hypothermia stress condition also affects the anabolic/catabolic environment. Finally, HSA produces an increase in the cell population of the immune system. The authors believe that this study allows to standardize HSA exposure times during regular military operations training by identifying the physiological impacts under this extreme environment. At present, the availability of intra-abdominal temperature measurement apparatus with capsule thermometers raises the interest of corroborating the findings of the current study through the use of such measuring devices. Likewise, an interesting line of research for the future would be to compare the HSA against a psychological evaluation with the purpose of identifying the stress management mechanisms among subjects of these characteristics and include heart rate variability measurements as an indicator of sympathetic stress. © Association of Military Surgeons of the United States 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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 ...

Prognostic EEG patterns in patients resuscitated from cardiac arrest with particular focus on Generalized Periodic Epileptiform Discharges (GPEDs).

PubMed

Milani, P; Malissin, I; Tran-Dinh, Y R; Deye, N; Baud, F; Lévy, B I; Kubis, N

2014-04-01

We assessed clinical and early electrophysiological characteristics, in particular Generalized Periodic Epileptiform Discharges (GPEDs) patterns, of consecutive patients during a 1-year period, hospitalized in the Intensive Care Unit (ICU) after resuscitation following cardiac arrest (CA). Consecutive patients resuscitated from cardiac arrest (CA) with first EEG recordings within 48hours were included. Clinical data were collected from hospital records, in particular therapeutic hypothermia. Electroencephalograms (EEGs) were re-analyzed retrospectively. Sixty-two patients were included. Forty-two patients (68%) were treated with therapeutic hypothermia according to international guidelines. Global mortality was 74% but not significantly different between patients who benefited from therapeutic hypothermia compared to those who did not. All the patients who did not have an initial background activity (36/62; 58%) died. By contrast, initial background activity was present in 26/62 (42%) and among these patients, 16/26 (61%) survived. Electroencephalography demonstrated GPEDs patterns in 5 patients, all treated by therapeutic hypothermia and antiepileptic drugs. One of these survived and showed persistent background activity with responsiveness to benzodiazepine intravenous injection. Patients presenting suppressed background activity, even when treated by hypothermia, have a high probability of poor outcome. Thorough analysis of EEG patterns might help to identify patients with a better chance of survival. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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.

Association between Urinary Lactate to Creatinine Ratio and Neurodevelopmental Outcome in Term Infants with Hypoxic-Ischemic Encephalopathy

PubMed Central

Oh, William; Perritt, Rebecca; Shankaran, Seetha; Merritts, Matthew; Donovan, Edward F.; Ehrenkranz, Richard A.; O’Shea, T. Michael; Tyson, Jon E.; Laptook, Abbot R.; Das, Abhik; Higgins, Rosemary D.

2010-01-01

Objective To assess the association between urinary lactate to creatinine ratio (ULCR) and neurodevelopmental outcome in term infants with hypoxic ischemic encephalopathy and examine the effect of hypothermia on the change in ULCR. Study design Spot urine samples were collected in 58 term infants (28 hypothermia, 30 control subjects) with hypoxic ischemic encephalopathy. Urinary lactate and creatinine were measured by using 1H nuclear magnetic resonance spectroscopy and expressed as ULCR. Survivors were examined at 18 months of age. Results The ULCR was significantly higher in infants who died or had moderate/severe neurodevelopmental disability. Logistic regression analysis controlling for hypothermia and severity of encephalopathy confirmed the association (adjusted odds ratio, 5.52; 95% CI, 1.36, 22.42; P < .02). Considerable overlap in ULCR was observed between infants with normal/mild disability and those who died or survived with moderate/severe disability. ULCR fell significantly between 6 and 24 hours and 48 and 72 hours of age for all infants. The magnitude of decline did not differ between hypothermia and control groups. Conclusions High ULCR is associated with death or moderate/severe neurodevelopmental disability. Significant overlap in values between the normal/mild and moderate/severe disability groups limits predictive value of this measure. Whole-body hypothermia did not affect the decline in ULCR. PMID:18534246

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.

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

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.

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.

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.

Bridging the Gap between In- and Out-of-Hospital Care: the Role and Limitations of Technology

DTIC Science & Technology

2015-07-13

11. Hypotensive resuscitation with Hextend 12. Oxygen use for TBI 13. More rapid and effective battlefield analgesia 14. Prevention of hypothermia ... hypothermia management kits 15. Battlefield use of antibiotics to reduce infections 16. Tactical scenario-based combat trauma training 17. Use of 1

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.

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…

Arctic Cold Weather Medicine and Accidental Hypothermia

DTIC Science & Technology

1990-03-01

due to the rotor wash or behind air craft with prop wash causing vary high wind chill factors freezing exposed skin in seconds. The windchill 0hart in...references 7-9. 3. Snow blindness The ultraviolet rays of the sun, even on a cloudy day, reflect off the snow and can burn the outer layer of the eye...the cornea. Symptoms may not appear for 2 to 12 hours after exposure. Common symptoms are a burning or gritty sensation, excessive tearing, and eye

Total intravenous anesthesia with propofol and remifentanil in a patient with MELAS syndrome -A case report-

PubMed Central

Park, Jin Suk; Kang, Hyun; Cha, Su Man; Park, Jung Won; Jung, Yong Hun; Woo, Young-Cheol

2010-01-01

A 23-year-old woman with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) underwent a laparoscopy-assisted appendectomy. MELAS syndrome is a multisystemic disease caused by mitochondrial dysfunction. General anesthesia has several potential hazards to patients with MELAS syndrome, such as malignant hyperthermia, hypothermia, and metabolic acidosis. In this case, anesthesia was performed with propofol, remifentanil TCI, and atracurium without any surgical or anesthetic complications. We discuss the anesthetic effects of MELAS syndrome. PMID:20508802

Total intravenous anesthesia with propofol and remifentanil in a patient with MELAS syndrome -A case report-.

PubMed

Park, Jin Suk; Baek, Chong Wha; Kang, Hyun; Cha, Su Man; Park, Jung Won; Jung, Yong Hun; Woo, Young-Cheol

2010-04-01

A 23-year-old woman with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) underwent a laparoscopy-assisted appendectomy. MELAS syndrome is a multisystemic disease caused by mitochondrial dysfunction. General anesthesia has several potential hazards to patients with MELAS syndrome, such as malignant hyperthermia, hypothermia, and metabolic acidosis. In this case, anesthesia was performed with propofol, remifentanil TCI, and atracurium without any surgical or anesthetic complications. We discuss the anesthetic effects of MELAS syndrome.

Brain microvascular function during cardiopulmonary bypass

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

Sorensen, H.R.; Husum, B.; Waaben, J.

1987-11-01

Emboli in the brain microvasculature may inhibit brain activity during cardiopulmonary bypass. Such hypothetical blockade, if confirmed, may be responsible for the reduction of cerebral metabolic rate for glucose observed in animals subjected to cardiopulmonary bypass. In previous studies of cerebral blood flow during bypass, brain microcirculation was not evaluated. In the present study in animals (pigs), reduction of the number of perfused capillaries was estimated by measurements of the capillary diffusion capacity for hydrophilic tracers of low permeability. Capillary diffusion capacity, cerebral blood flow, and cerebral metabolic rate for glucose were measured simultaneously by the integral method, different tracersmore » being used with different circulation times. In eight animals subjected to normothermic cardiopulmonary bypass, and seven subjected to hypothermic bypass, cerebral blood flow, cerebral metabolic rate for glucose, and capillary diffusion capacity decreased significantly: cerebral blood flow from 63 to 43 ml/100 gm/min in normothermia and to 34 ml/100 gm/min in hypothermia and cerebral metabolic rate for glucose from 43.0 to 23.0 mumol/100 gm/min in normothermia and to 14.1 mumol/100 gm/min in hypothermia. The capillary diffusion capacity declined markedly from 0.15 to 0.03 ml/100 gm/min in normothermia but only to 0.08 ml/100 gm/min in hypothermia. We conclude that the decrease of cerebral metabolic rate for glucose during normothermic cardiopulmonary bypass is caused by interruption of blood flow through a part of the capillary bed, possibly by microemboli, and that cerebral blood flow is an inadequate indicator of capillary blood flow. Further studies must clarify why normal microvascular function appears to be preserved during hypothermic cardiopulmonary bypass.« less

Dissociating anxiolytic and sedative effects of GABAAergic drugs using temperature and locomotor responses to acute stress

PubMed Central

Klanker, Marianne; Groenink, Lucianne; Korte, S. Mechiel; Cook, James M.; Van Linn, Michael L.; Hopkins, Seth C.; Olivier, Berend

2009-01-01

Rationale The stress-induced hyperthermia (SIH) model is an anxiety model that uses the transient rise in body temperature in response to acute stress. Benzodiazepines produce anxiolytic as well as sedative side effects through nonselective binding to GABAA receptor subunits. The GABAA receptor α1 subunit is associated with sedation, whereas the GABAA receptor α2 and α3 subunits are involved in anxiolytic effects. Objectives We therefore examined the effects of (non) subunit-selective GABAA receptor agonists on temperature and locomotor responses to novel cage stress. Results Using telemetric monitoring of temperature and locomotor activity, we found that nonsubunit-selective GABAA receptor agonist diazepam as well as the α3 subunit-selective receptor agonist TP003 dose-dependently attenuated SIH and locomotor responses. Administration of GABAA receptor α1-selective agonist zolpidem resulted in profound hypothermia and locomotor sedation. The GABAA receptor α1-selective antagonist βCCt antagonized the hypothermia, but did not reverse the SIH response attenuation caused by diazepam and zolpidem. These results suggest an important regulating role for the α1 subunit in thermoregulation and sedation. Ligands of extrasynaptic GABAA receptors such as alcohol and nonbenzodiazepine THIP attenuated the SIH response only at high doses. Conclusions The present study confirms a putative role for the GABAA receptor α1 subunit in hypothermia and sedation and supports a role for α2/3 subunit GABAA receptor agonists in anxiety processes. In conclusion, we show that home cage temperature and locomotor responses to novel home cage stress provide an excellent tool to assess both anxiolytic and sedative effects of various (subunit-selective) GABAAergic compounds. PMID:19169673

Therapeutic hypothermia for neonatal encephalopathy: JSPNM & MHLW Japan Working Group Practice Guidelines Consensus Statement from the Working Group on Therapeutic Hypothermia for Neonatal Encephalopathy, Ministry of Health, Labor and Welfare (MHLW), Japan, and Japan Society for Perinatal and Neonatal Medicine (JSPNM).

PubMed

Takenouchi, Toshiki; Iwata, Osuke; Nabetani, Makoto; Tamura, Masanori

2012-02-01

Neonatal encephalopathy (NE) secondary to intrapartum asphyxia remains a major cause of post-natal death and permanent neurological deficits worldwide. Supportive therapy has been the mainstay of the treatment until recent series of large clinical trials demonstrating benefit of therapeutic hypothermia (TH) in this high risk population. Now the International Liaison Committee on Resuscitation (ILCOR) recommends TH as a standard of care with the protocols used in the large clinical trials as tentative standard protocols. Our goal is to develop a nationwide consensus practice guideline not only consistent with the international standard protocols but also practical and compatible with the current medical system in Japan. In summary, TH should be offered to newborn infants born ≥36 weeks gestational age and birth weight ≥1800 g exhibiting clinical signs of moderate to severe NE as well as evidence of hypoxia-ischemia, i.e. 10 min Apgar score ≤5, a need for resuscitation at 10 min, blood pH<7.00, or base deficit ≥16 mmol/L. TH should be conducted in the NICUs capable of multidisciplinary care and under the standard protocols, i.e. utilization of cooling device, target (rectal or esophageal) temperatures at 33.5±0.5 and 34.5±0.5°C for whole body and selective head cooling respectively, duration of TH for 72 h, gradual rewarming not exceeding the rate of 0.5°C/h. Long term follow-up with multidisciplinary approach including standardized psychological assessment is warranted. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Magnesium Sulfate Only Slightly Reduces the Shivering Threshold in Humans

PubMed Central

Wadhwa, Anupama; Sengupta, Papiya; Durrani, Jaleel; Akça, Ozan; Lenhardt, Rainer; Sessler, Daniel I.

2005-01-01

Background: Hypothermia may be an effective treatment for stroke or acute myocardial infarction; however, it provokes vigorous shivering, which causes potentially dangerous hemodynamic responses and prevents further hypothermia. Magnesium is an attractive antishivering agent because it is used for treatment of postoperative shivering and provides protection against ischemic injury in animal models. We tested the hypothesis that magnesium reduces the threshold (triggering core temperature) and gain of shivering without substantial sedation or muscle weakness. Methods: We studied nine healthy male volunteers (18-40 yr) on two randomly assigned treatment days: 1) Control and 2) Magnesium (80 mg·kg-1 followed by infusion at 2 g·h-1). Lactated Ringer's solution (4°C) was infused via a central venous catheter over a period of approximately 2 hours to decrease tympanic membrane temperature ≈1.5°C·h-1. A significant and persistent increase in oxygen consumption identified the threshold. The gain of shivering was determined by the slope of oxygen consumption vs. core temperature regression. Sedation was evaluated using verbal rating score (VRS, 0-10) and bispectral index of the EEG (BIS). Peripheral muscle strength was evaluated using dynamometry and spirometry. Data were analyzed using repeated-measures ANOVA; P<0.05 was statistically significant. Results: Magnesium reduced the shivering threshold (36.3±0.4 [mean±SD] vs. 36.6±0.3°C, P=0.040). It did not affect the gain of shivering (Control: 437±289, Magnesium: 573±370 ml·min-1·°C-1, P=0.344). The magnesium bolus did not produce significant sedation or appreciably reduce muscle strength. Conclusions: Magnesium significantly reduced the shivering threshold; however, due to the modest absolute reduction, this finding is considered to be clinically unimportant for induction of therapeutic hypothermia. PMID:15749735

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.

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.

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…

Effects of the Sazetidine-a Family of Compounds on the Body Temperature in Wildtype, Nicotinic Receptor B2(-/-) and a7(-/-) Mice

EPA Science Inventory

Nicotine elicits hypothermic responses in rodents. This effect appears to be related to nicotinic receptor desensitization because sazetidine-A, an a4B2 nicotinic receptor desensitizing agent, produces marked hypothermia and potentiates nicotine-induced hypothermia in mice. To de...

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.

Supportive Cryotherapy: A Review from Head to Toe

PubMed Central

Kadakia, Kunal C.; Rozell, Shaina A.; Butala, Anish A.; Loprinzi, Charles L.

2013-01-01

Context Conventional chemotherapy leads to multiple adverse mucocutaneous complications including oral mucositis, alopecia, ocular toxicity, and onycholysis. Limited pharmacologic interventions are available for preventing these clinical problems. Objectives This study aimed to critically review the role of cryotherapy (regional hypothermia) for alleviating these adverse symptoms. Methods A narrative review was performed, with an emphasis on randomized controlled trials. A comprehensive search using PubMed, Ovid, Embase, and MEDLINE® was completed. References of all cited articles also were reviewed. Data from the review were comprised of articles published between 1970 to May 2013. Results Available evidence suggests that regional hypothermia decreases the burden of chemotherapy-related oral mucositis, alopecia, ocular toxicity, and onycholysis. The major limitations of studies include the absence of blinded control groups and variable clinical endpoints. Conclusion Regional hypothermia decreases the burden of these four chemotherapy-induced complications and is well tolerated. More research is needed to determine what subgroups of cancer patients are most likely to respond to different types of regional hypothermia, the ideal duration of cooling needed, and to further improve the ease of use of the cooling devices. PMID:24210702

The effect of coverings, including plastic bags and wraps, on mortality and morbidity in preterm and full-term neonates.

PubMed

Oatley, H K; Blencowe, H; Lawn, J E

2016-05-01

Neonatal hypothermia is an important risk factor for mortality and morbidity, and is common even in temperate climates. We conducted a systematic review to determine whether plastic coverings, used immediately following delivery, were effective in reducing the incidence of mortality, hypothermia and morbidity. A total of 26 studies (2271 preterm and 1003 term neonates) were included. Meta-analyses were conducted as appropriate. Plastic wraps were associated with a reduction in hypothermia in preterm (⩽29 weeks; risk ratio (RR)=0.57; 95% confidence interval (CI) 0.46 to 0.71) and term neonates (RR=0.76; 95% CI 0.60 to 0.96). No significant reduction in neonatal mortality or morbidity was found; however, the studies were underpowered for these outcomes. For neonates, especially preterm, plastic wraps combined with other environmental heat sources are effective in reducing hypothermia during stabilization and transfer within hospital. Further research is needed to quantify the effects on mortality or morbidity, and investigate the use of plastic coverings outside hospital settings or without additional heat sources.

[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.

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.

The effect of coverings, including plastic bags and wraps, on mortality and morbidity in preterm and full-term neonates

PubMed Central

Oatley, H K; Blencowe, H; Lawn, J E

2016-01-01

Neonatal hypothermia is an important risk factor for mortality and morbidity, and is common even in temperate climates. We conducted a systematic review to determine whether plastic coverings, used immediately following delivery, were effective in reducing the incidence of mortality, hypothermia and morbidity. A total of 26 studies (2271 preterm and 1003 term neonates) were included. Meta-analyses were conducted as appropriate. Plastic wraps were associated with a reduction in hypothermia in preterm (⩽29 weeks; risk ratio (RR)=0.57; 95% confidence interval (CI) 0.46 to 0.71) and term neonates (RR=0.76; 95% CI 0.60 to 0.96). No significant reduction in neonatal mortality or morbidity was found; however, the studies were underpowered for these outcomes. For neonates, especially preterm, plastic wraps combined with other environmental heat sources are effective in reducing hypothermia during stabilization and transfer within hospital. Further research is needed to quantify the effects on mortality or morbidity, and investigate the use of plastic coverings outside hospital settings or without additional heat sources. PMID:27109095

Hospital in the field: prehospital management of GHB intoxication by medical assistance teams.

PubMed

Dutch, Martin J; Austin, Kristy B

2012-10-01

Recreational use of gamma-hydroxybutyrate (GHB) is increasingly common at mass-gathering dance events in Australia. Overdose often occurs in clusters, and places a significant burden on the surrounding health care infrastructure. To describe the clinical presentation, required interventions and disposition of patrons with GHB intoxication at dance events, when managed by dedicated medical assistance teams. Retrospective analysis of all patrons attending St. John Ambulance medical assistance teams at dance events in the state of Victoria (Australia), from January 2010 through May 2011. Main outcome measures Clinical presentation, medical interventions and discharge destination. Sixty-one patients with GHB intoxication attended medical teams during the study period. The median age was 22 years, and 64% were male. Altered conscious state was present in 89% of attendances, and a GCS <9 in 44%. Hypotension, bradycardia and hypothermia were commonly encountered. Endotracheal intubation was required in three percent of patrons. Median length of stay onsite was 90 minutes. Ambulance transport to hospital was avoided in 65% of presentations. The deployment of medical teams at dance events and music festivals successfully managed the majority of GHB intoxications onsite and avoided acute care ambulance transfer and emergency department attendance.

Thermoregulatory disorders and illness related to heat and cold stress.

PubMed

Cheshire, William P

2016-04-01

Thermoregulation is a vital function of the autonomic nervous system in response to cold and heat stress. Thermoregulatory physiology sustains health by keeping body core temperature within a degree or two of 37°C, which enables normal cellular function. Heat production and dissipation are dependent on a coordinated set of autonomic responses. The clinical detection of thermoregulatory impairment provides important diagnostic and localizing information in the evaluation of disorders that impair thermoregulatory pathways, including autonomic neuropathies and ganglionopathies. Failure of neural thermoregulatory mechanisms or exposure to extreme or sustained temperatures that overwhelm the body's thermoregulatory capacity can also result in potentially life-threatening departures from normothermia. Hypothermia, defined as a core temperature of <35.0°C, may present with shivering, respiratory depression, cardiac dysrhythmias, impaired mental function, mydriasis, hypotension, and muscle dysfunction, which can progress to cardiac arrest or coma. Management includes warming measures, hydration, and cardiovascular support. Deaths from hypothermia are twice as frequent as deaths from hyperthermia. Hyperthermia, defined as a core temperature of >40.5°C, may present with sweating, flushing, tachycardia, fatigue, lightheadedness, headache, and paresthesia, progressing to weakness, muscle cramps, oliguria, nausea, agitation, hypotension, syncope, confusion, delirium, seizures, and coma. Mental status changes and core temperature distinguish potentially fatal heat stroke from heat exhaustion. Management requires the immediate reduction of core temperature. Ice water immersion has been shown to be superior to alternative cooling measures. Avoidance of thermal risk and early recognition of cold or heat stress are the cornerstones of preventive therapy. Copyright © 2016 The Author. Published by Elsevier B.V. All rights reserved.

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%.

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.

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.

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.

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.

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.

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.

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

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 care during therapeutic hypothermia.

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.

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 has been shown to play a role in the effectiveness of cocaine reward.

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 neurologic and neuroradiologic examinations. Visual function will be evaluated by means of behavioural standardized tests. Discussion This pilot study will explore the possible therapeutic role of topiramate in combination with moderate hypothermia. Any favourable results of this research might open new perspectives about the reduction of cerebral damage in asphyxiated newborns. Trial registration Current Controlled Trials ISRCTN62175998; ClinicalTrials.gov Identifier NCT01241019; EudraCT Number 2010-018627-25 PMID:22950861

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 Organization.

Early Detection of Hypothermic Neuroprotection Using T2-Weighted Magnetic Resonance Imaging in a Mouse Model of Hypoxic Ischemic Encephalopathy.

PubMed

Doman, Sydney E; Girish, Akanksha; Nemeth, Christina L; Drummond, Gabrielle T; Carr, Patrice; Garcia, Maxine S; Johnston, Michael V; Kannan, Sujatha; Fatemi, Ali; Zhang, Jiangyang; Wilson, Mary Ann

2018-01-01

Perinatal hypoxic-ischemic encephalopathy (HIE) can lead to neurodevelopmental disorders, including cerebral palsy. Standard care for neonatal HIE includes therapeutic hypothermia, which provides partial neuroprotection; magnetic resonance imaging (MRI) is often used to assess injury and predict outcome after HIE. Immature rodent models of HIE are used to evaluate mechanisms of injury and to examine the efficacy and mechanisms of neuroprotective interventions such as hypothermia. In this study, we first confirmed that, in the CD1 mouse model of perinatal HIE used for our research, MRI obtained 3 h after hypoxic ischemia (HI) could reliably assess initial brain injury and predict histopathological outcome. Mice were subjected to HI (unilateral carotid ligation followed by exposure to hypoxia) on postnatal day 7 and were imaged with T2-weighted MRI and diffusion-weighted MRI (DWI), 3 h after HI. Clearly defined regions of increased signal were comparable in T2 MRI and DWI, and we found a strong correlation between T2 MRI injury scores 3 h after HI and histopathological brain injury 7 days after HI, validating this method for evaluating initial injury in this model of HIE. The more efficient, higher resolution T2 MRI was used to score initial brain injury in subsequent studies. In mice treated with hypothermia, we found a significant reduction in T2 MRI injury scores 3 h after HI, compared to normothermic littermates. Early hypothermic neuroprotection was maintained 7 days after HI, in both T2 MRI injury scores and histopathology. In the normothermic group, T2 MRI injury scores 3 h after HI were comparable to those obtained 7 days after HI. However, in the hypothermic group, brain injury was significantly less 7 days after HI than at 3 h. Thus, early neuroprotective effects of hypothermia were enhanced by 7 days, which may reflect the additional 3 h of hypothermia after imaging or effects on later mechanisms of injury, such as delayed cell death and inflammation. Our results demonstrate that hypothermia has early neuroprotective effects in this model. These findings suggest that hypothermia has an impact on early mechanisms of excitotoxic injury and support initiation of hypothermic intervention as soon as possible after diagnosis of HIE.

Early Detection of Hypothermic Neuroprotection Using T2-Weighted Magnetic Resonance Imaging in a Mouse Model of Hypoxic Ischemic Encephalopathy

PubMed Central

Doman, Sydney E.; Girish, Akanksha; Nemeth, Christina L.; Drummond, Gabrielle T.; Carr, Patrice; Garcia, Maxine S.; Johnston, Michael V.; Kannan, Sujatha; Fatemi, Ali; Zhang, Jiangyang; Wilson, Mary Ann

2018-01-01

Perinatal hypoxic-ischemic encephalopathy (HIE) can lead to neurodevelopmental disorders, including cerebral palsy. Standard care for neonatal HIE includes therapeutic hypothermia, which provides partial neuroprotection; magnetic resonance imaging (MRI) is often used to assess injury and predict outcome after HIE. Immature rodent models of HIE are used to evaluate mechanisms of injury and to examine the efficacy and mechanisms of neuroprotective interventions such as hypothermia. In this study, we first confirmed that, in the CD1 mouse model of perinatal HIE used for our research, MRI obtained 3 h after hypoxic ischemia (HI) could reliably assess initial brain injury and predict histopathological outcome. Mice were subjected to HI (unilateral carotid ligation followed by exposure to hypoxia) on postnatal day 7 and were imaged with T2-weighted MRI and diffusion-weighted MRI (DWI), 3 h after HI. Clearly defined regions of increased signal were comparable in T2 MRI and DWI, and we found a strong correlation between T2 MRI injury scores 3 h after HI and histopathological brain injury 7 days after HI, validating this method for evaluating initial injury in this model of HIE. The more efficient, higher resolution T2 MRI was used to score initial brain injury in subsequent studies. In mice treated with hypothermia, we found a significant reduction in T2 MRI injury scores 3 h after HI, compared to normothermic littermates. Early hypothermic neuroprotection was maintained 7 days after HI, in both T2 MRI injury scores and histopathology. In the normothermic group, T2 MRI injury scores 3 h after HI were comparable to those obtained 7 days after HI. However, in the hypothermic group, brain injury was significantly less 7 days after HI than at 3 h. Thus, early neuroprotective effects of hypothermia were enhanced by 7 days, which may reflect the additional 3 h of hypothermia after imaging or effects on later mechanisms of injury, such as delayed cell death and inflammation. Our results demonstrate that hypothermia has early neuroprotective effects in this model. These findings suggest that hypothermia has an impact on early mechanisms of excitotoxic injury and support initiation of hypothermic intervention as soon as possible after diagnosis of HIE.

Insomnia Caused by Serotonin Depletion is Due to Hypothermia.

PubMed

Murray, Nicholas M; Buchanan, Gordon F; Richerson, George B

2015-12-01

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. 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. 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. 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. © 2015 Associated Professional Sleep Societies, LLC.

[Oxidative stress in perinatal asphyxia and hypoxic-ischaemic encephalopathy].

PubMed

Nuñez, Antonio; Benavente, Isabel; Blanco, Dorotea; Boix, Héctor; Cabañas, Fernando; Chaffanel, Mercedes; Fernández-Colomer, Belén; Fernández-Lorenzo, José Ramón; Loureiro, Begoña; Moral, María Teresa; Pavón, Antonio; Tofé, Inés; Valverde, Eva; Vento, Máximo

2018-04-01

Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

[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.

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.

The feasibility of using a portable xenon delivery device to permit earlier xenon ventilation with therapeutic cooling of neonates during ambulance retrieval.

PubMed

Dingley, John; Liu, Xun; Gill, Hannah; Smit, Elisa; Sabir, Hemmen; Tooley, James; Chakkarapani, Ela; Windsor, David; Thoresen, Marianne

2015-06-01

Therapeutic hypothermia is the standard of care after perinatal asphyxia. Preclinical studies show 50% xenon improves outcome, if started early. During a 32-patient study randomized between hypothermia only and hypothermia with xenon, 5 neonates were given xenon during retrieval using a closed-circuit incubator-mounted system. Without xenon availability during retrieval, 50% of eligible infants exceeded the 5-hour treatment window. With the transportable system, 100% were recruited. Xenon delivery lasted 55 to 120 minutes, using 174 mL/h (117.5-193.2) (median [interquartile range]), after circuit priming (1300 mL). Xenon delivery during ambulance retrieval was feasible, reduced starting delays, and used very little gas.

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.

Warmed, humidified CO2 insufflation benefits intraoperative core temperature during laparoscopic surgery: A meta‐analysis

PubMed Central

Dean, Meara; Ramsay, Robert; Heriot, Alexander; Mackay, John; Hiscock, Richard

2016-01-01

Abstract Background Intraoperative hypothermia is linked to postoperative adverse events. The use of warmed, humidified CO2 to establish pneumoperitoneum during laparoscopy has been associated with reduced incidence of intraoperative hypothermia. However, the small number and variable quality of published studies have caused uncertainty about the potential benefit of this therapy. This meta‐analysis was conducted to specifically evaluate the effects of warmed, humidified CO2 during laparoscopy. Methods An electronic database search identified randomized controlled trials performed on adults who underwent laparoscopic abdominal surgery under general anesthesia with either warmed, humidified CO2 or cold, dry CO2. The main outcome measure of interest was change in intraoperative core body temperature. Results The database search identified 320 studies as potentially relevant, and of these, 13 met the inclusion criteria and were included in the analysis. During laparoscopic surgery, use of warmed, humidified CO2 is associated with a significant increase in intraoperative core temperature (mean temperature change, 0.3°C), when compared with cold, dry CO2 insufflation. Conclusion Warmed, humidified CO2 insufflation during laparoscopic abdominal surgery has been demonstrated to improve intraoperative maintenance of normothermia when compared with cold, dry CO2. PMID:27976517

National Athletic Trainers' Association Position Statement: Lightning Safety for Athletics and Recreation

PubMed Central

Walsh, Katie M.; Bennett, Brian; Cooper, Mary Ann; Holle, Ronald L.; Kithil, Richard; López, Raul E.

2000-01-01

Objective: To educate athletic trainers and others about the dangers of lightning, provide lightning-safety guidelines, define safe structures and locations, and advocate prehospital care for lightning-strike victims. Background: Lightning may be the most frequently encountered severe-storm hazard endangering physically active people each year. Millions of lightning flashes strike the ground annually in the United States, causing nearly 100 deaths and 400 injuries. Three quarters of all lightning casualties occur between May and September, and nearly four fifths occur between 10:00 AM and 7:00 PM, which coincides with the hours for most athletic or recreational activities. Additionally, lightning casualties from sports and recreational activities have risen alarmingly in recent decades. Recommendations: The National Athletic Trainers' Association recommends a proactive approach to lightning safety, including the implementation of a lightning-safety policy that identifies safe locations for shelter from the lightning hazard. Further components of this policy are monitoring local weather forecasts, designating a weather watcher, and establishing a chain of command. Additionally, a flash-to-bang count of 30 seconds or more should be used as a minimal determinant of when to suspend activities. Waiting 30 minutes or longer after the last flash of lightning or sound of thunder is recommended before athletic or recreational activities are resumed. Lightning- safety strategies include avoiding shelter under trees, avoiding open fields and spaces, and suspending the use of land-line telephones during thunderstorms. Also outlined in this document are the prehospital care guidelines for triaging and treating lightning-strike victims. It is important to evaluate victims quickly for apnea, asystole, hypothermia, shock, fractures, and burns. Cardiopulmonary resuscitation is effective in resuscitating pulseless victims of lightning strike. Maintenance of cardiopulmonary resuscitation and first-aid certification should be required of all persons involved in sports and recreational activities. PMID:16558665

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.

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.

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.

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.

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.

Brain temperature profiles during epidural cooling with the ChillerPad in a monkey model of traumatic brain injury.

PubMed

King, Christopher; Robinson, Timothy; Dixon, C Edward; Rao, Gutti R; Larnard, Donald; Nemoto, C Edwin M

2010-10-01

Therapeutic hypothermia remains a promising treatment for patients with severe traumatic brain injury (TBI). Multiple animal studies have suggested that hypothermia is neuroprotective after TBI, but clinical trials have been inconclusive. Systemic hypothermia, the method used in almost all major clinical trials, is limited by the time to target temperature, the depth of hypothermia, and complications, problems that may be solved by selective brain cooling. We evaluated the effects on brain temperature of a cooling device called the ChillerPad,™ which is applied to the dura in a non-human primate TBI model using controlled cortical impact (CCI). The cortical surface was rapidly cooled to approximately 15°C and maintained at that level for 24 h, followed by rewarming over about 10 h. Brain temperatures fell to 34-35°C at a depth of 15 mm at the cortical gray/white matter interface, and to 28-32°C at 10 mm deep. Intracranial pressure was mildly elevated (8-12 mm Hg) after cooling and rewarming, likely due to TBI. Other physiological variables were unchanged. Cooling was rapidly diminished at points distant from the cooling pad. The ChillerPad may be useful for highly localized cooling of the brain in circumstances in which a craniotomy is clinically indicated. However, because of the delay required by the craniotomy, other methods that are more readily available for inducing hypothermia may be used as a bridge between the time of injury to placement of the ChillerPad.

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.

Role of α1-adrenoceptor subtypes in the effects of methylenedioxy methamphetamine (MDMA) on body temperature in the mouse

PubMed Central

Bexis, S; Docherty, J R

2007-01-01

Background and purpose: We have investigated the ability of α1-adrenoceptor antagonists to affect the hyperthermia produced by methylenedioxy methamphetamine (MDMA) in conscious mice. Experimental approach: Mice were implanted with temperature probes under ether anaesthesia and allowed 2 weeks recovery. MDMA (20 mg kg−1) was administered subcutaneously 30 min after vehicle or test antagonist or combination of antagonists and effects on body temperature monitored. Key results: Following vehicle, MDMA produced a hyperthermia, reaching a maximum increase of 1.8 °C at 140 min. Prazosin (0.1 mg kg−1) revealed an early significant hypothermia to MDMA of −1.94 °C. The α1A-adrenoceptor antagonist RS 100329 (0.1 mg kg−1), or the α1D-adrenoceptor antagonist BMY 7378 (0.5 mg kg−1) given alone, did not reveal a hypothermia to MDMA, but the combination of the two antagonists revealed a significant hypothermia to MDMA. The putative α1B-adrenoceptor anatagonist cyclazosin (1 mg kg−1) also revealed a significant hypothermia to MDMA, but actions of cyclazosin at the other α1-adrenoceptor subtypes cannot be excluded. Conclusions and implications: More than one subtype of α1-adrenoceptor is involved in a component of the hyperthermic response to MDMA in mouse, probably both α1A- and α1D-adrenoceptors, and removal of this α1-adrenoceptor-mediated component reveals an initial hypothermia. PMID:18037913

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.

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

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.

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

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.

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.

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.

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.

[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.

[Analysis of violent deaths of mountaineers and tourists at high altitudes].

PubMed

Pigolkin, Iu I; Mechukaev, A A; Mechukaev, A M

2012-01-01

The principal causes of violent death of mountaineers and tourists at high altitudes are described with special reference to the character of injuries to the skin, soft tissues, bones, and internal organs inflicted by mechanical impacts. The cases of violent death from other factors are described, such as general hypothermia, atmospheric electricity, compression and obturation asphyxia of mountaineers and tourists who died in the epicenter of an avalanche. The additional criteria for forensic medical diagnostics of violent death of montaineers and tourists at high altitudes are considered.

Cooling for newborns with hypoxic ischaemic encephalopathy.

PubMed

Jacobs, Susan E; Berg, Marie; Hunt, Rod; Tarnow-Mordi, William O; Inder, Terrie E; Davis, Peter G

2013-01-31

Newborn animal studies and pilot studies in humans suggest that mild hypothermia following peripartum hypoxia-ischaemia in newborn infants may reduce neurological sequelae without adverse effects. To determine the effect of therapeutic hypothermia in encephalopathic asphyxiated newborn infants on mortality, long-term neurodevelopmental disability and clinically important side effects. We used the standard search strategy of the Cochrane Neonatal Review Group as outlined in The Cochrane Library (Issue 2, 2007). Randomised controlled trials evaluating therapeutic hypothermia in term and late preterm newborns with hypoxic ischaemic encephalopathy were identified by searching the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2007, Issue 2), MEDLINE (1966 to June 2007), previous reviews including cross-references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching. We updated this search in May 2012. We included randomised controlled trials comparing the use of therapeutic hypothermia with standard care in encephalopathic term or late preterm infants with evidence of peripartum asphyxia and without recognisable major congenital anomalies. The primary outcome measure was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling and 'early' indicators of neurodevelopmental outcome. Four review authors independently selected, assessed the quality of and extracted data from the included studies. Study authors were contacted for further information. Meta-analyses were performed using risk ratios (RR) and risk differences (RD) for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals (CI). We included 11 randomised controlled trials in this updated review, comprising 1505 term and late preterm infants with moderate/severe encephalopathy and evidence of intrapartum asphyxia. Therapeutic hypothermia resulted in a statistically significant and clinically important reduction in the combined outcome of mortality or major neurodevelopmental disability to 18 months of age (typical RR 0.75 (95% CI 0.68 to 0.83); typical RD -0.15, 95% CI -0.20 to -0.10); number needed to treat for an additional beneficial outcome (NNTB) 7 (95% CI 5 to 10) (8 studies, 1344 infants). Cooling also resulted in statistically significant reductions in mortality (typical RR 0.75 (95% CI 0.64 to 0.88), typical RD -0.09 (95% CI -0.13 to -0.04); NNTB 11 (95% CI 8 to 25) (11 studies, 1468 infants) and in neurodevelopmental disability in survivors (typical RR 0.77 (95% CI 0.63 to 0.94), typical RD -0.13 (95% CI -0.19 to -0.07); NNTB 8 (95% CI 5 to 14) (8 studies, 917 infants). Some adverse effects of hypothermia included an increase sinus bradycardia and a significant increase in thrombocytopenia. There is evidence from the 11 randomised controlled trials included in this systematic review (N = 1505 infants) that therapeutic hypothermia is beneficial in term and late preterm newborns with hypoxic ischaemic encephalopathy. Cooling reduces mortality without increasing major disability in survivors. The benefits of cooling on survival and neurodevelopment outweigh the short-term adverse effects. Hypothermia should be instituted in term and late preterm infants with moderate-to-severe hypoxic ischaemic encephalopathy if identified before six hours of age. Further trials to determine the appropriate techniques of cooling, including refinement of patient selection, duration of cooling and method of providing therapeutic hypothermia, will refine our understanding of this intervention.

Heat stroke risk for open-water swimmers during long-distance events.

PubMed

Macaluso, Filippo; Barone, Rosario; Isaacs, Ashwin W; Farina, Felicia; Morici, Giuseppe; Di Felice, Valentina

2013-12-01

Open-water swimming is a rapidly growing sport discipline worldwide, and clinical problems associated with long-distance swimming are now better recognized and managed more effectively. The most prevalent medical risk associated with an open-water swimming event is hypothermia; therefore, the Federation Internationale De Natation (FINA) has instituted 2 rules to reduce this occurrence related to the minimum water temperature and the time taken to complete the race. Another medical risk that is relevant to open-water swimmers is heat stroke, a condition that can easily go unnoticed. The purpose of this review is to shed light on this physiological phenomenon by examining the physiological response of swimmers during long-distance events, to define a maximum water temperature limit for competitions. We conclude that competing in water temperatures exceeding 33°C should be avoided. Copyright © 2013 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

A focus on reward in anorexia nervosa through the lens of the activity-based anorexia rodent model.

PubMed

Foldi, C J; Milton, L K; Oldfield, B J

2017-10-01

Patients suffering anorexia nervosa (AN) become anhedonic, unable or unwilling to derive normal pleasures and tend to avoid rewarding outcomes, most profoundly in food intake. The activity-based anorexia model recapitulates many of the pathophysiological and behavioural hallmarks of the human condition, including a reduction in food intake, excessive exercise, dramatic weight loss, loss of reproductive cycles, hypothermia and anhedonia, and therefore it allows investigation into the underlying neurobiology of anorexia nervosa. The use of this model has directed attention to disruptions in central reward neurocircuitry, which may contribute to disease susceptibility. The purpose of this review is to demonstrate the utility of this unique model to provide insight into the mechanisms of reward relevant to feeding and weight loss, which may ultimately help to unravel the neurobiology of anorexia nervosa and, in a broader sense, the foundation of reward-based feeding. © 2017 British Society for Neuroendocrinology.

Changing pattern of drugs used for self-poisoning.

PubMed Central

Proudfoot, A T; Park, J

1978-01-01

In 1967-76 the annual number of admissions to a poisoning treatment centre rose from 964 to 2134. The proportion of admissions caused by taking barbiturate hypnotics and methaqualone fell considerably while that caused by taking benzodiazepines and tricyclic antidepressants increased. As a result the proportion of patients admitted unconscious fell from 23% to 15%. The declining contributions of barbiturates and methaqualone and increased importance of tricyclic antidepressants were significant in all grades of coma. The change in drugs taken, however, has not yet reduced the percentage of unconscious patients needing endotracheal intubation or assisted ventilation, and hypothermia remains as common. Only hypotension has become less frequent as antidepressants replace barbiturates as the main cause of drug-induced coma. The use of salicylates for self-poisoning is declining slowly, and paracetamol poisoning is now as common. PMID:620215

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

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

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 quasicontinuous Vineland Adaptive Behavior Scales Second Edition change from prearrest level, will be evaluated among all randomized children, including those with compromised function prearrest. Extensive discussion of optimal efficacy assessment timing, and of the advantages versus drawbacks of incorporating prearrest status and using quasicontinuous versus simpler outcomes, was highly beneficial to the final Therapeutic Hypothermia After Pediatric Cardiac Arrest design. A relatively simple, binary primary outcome evaluated at 12 months was selected, with two secondary outcomes that address the potential disadvantages of primary outcome.

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 will have broad implications by showing that a knowledge translation strategy shared across a collaborative network of hospitals can increase the number of patients that receive this lifesaving intervention in a timely manner. ClinicalTrials.gov Trial Identifier: NCT00683683.

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 rectal toxicity following a single large dose of radiation. Funding support provided by RSNA research seed grant.« less

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 the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

Artificial sweeteners and mixture of food additives cause to break oral tolerance and induce food allergy in murine oral tolerance model for food allergy.

PubMed

Yamashita, H; Matsuhara, H; Miotani, S; Sako, Y; Matsui, T; Tanaka, H; Inagaki, N

2017-09-01

Processed foods are part of daily life. Almost all processed foods contain food additives such as sweeteners, preservatives and colourants. From childhood, it is difficult to avoid consuming food additives. It is thought that oral tolerance for food antigens is acquired during early life. If tolerance fails, adverse immune responses to food proteins may occur. We hypothesized that food additives prevent acquisition of oral tolerance and aimed to verify the safety of food additives. We induced experimental oral tolerance in mice for ovalbumin (OVA), a food antigen, by previous oral treatment with OVA before sensitization with OVA injections. Food additives were administered at the induction of oral tolerance, and food allergy was induced by repeated administration of OVA. Symptoms of food allergy were defined as a change in body temperature and allergic diarrhoea. Saccharin sodium and a mixture of food additives inhibited acquisition of oral tolerance. Hypothermia and allergic diarrhoea with elevation of OVA-specific IgE were induced in the murine model of oral tolerance. Analyses of antigen-presenting cells in mesenteric lymph nodes showed that food additives affected their manner of migration. Additionally, food additives decreased the proportion of CD25 hi regulatory T cells among CD4 + T cells in the mesenteric lymph nodes. A large amount of food additives may prevent acquisition of oral tolerance. Intake of food additives in early life may increase the risk of food allergies. © 2017 John Wiley & Sons Ltd.

Clinical considerations in the use of forced-air warming blankets during orthognathic surgery to avoid postanesthetic shivering

PubMed Central

Park, Fiona Daye; Park, Sookyung; Chi, Seong-In; Kim, Hyun Jeong; Kim, Hye-Jung; Han, Jin-Hee; Han, Hee-Jeong; Lee, Eun-Hee

2015-01-01

Background During head and neck surgery including orthognathic surgery, mild intraoperative hypothermia occurs frequently. Hypothermia is associated with postanesthetic shivering, which may increase the risk of other postoperative complications. To improve intraoperative thermoregulation, devices such as forced-air warming blankets can be applied. This study aimed to evaluate the effect of supplemental forced-air warming blankets in preventing postanesthetic shivering. Methods This retrospective study included 113 patients who underwent orthognathic surgery between March and September 2015. According to the active warming method utilized during surgery, patients were divided into two groups: Group W (n = 55), circulating-water mattress; and Group F (n = 58), circulating-water mattress and forced-air warming blanket. Surgical notes and anesthesia and recovery room records were evaluated. Results Initial axillary temperatures did not significantly differ between groups (Group W = 35.9 ± 0.7℃, Group F = 35.8 ± 0.6℃). However, at the end of surgery, the temperatures in Group W were significantly lower than those in Group F (35.2 ± 0.5℃ and 36.2 ± 0.5℃, respectively, P = 0.04). The average body temperatures in Groups W and F were, respectively, 35.9 ± 0.5℃ and 36.2 ± 0.5℃ (P = 0.0001). In Group W, 24 patients (43.6%) experienced postanesthetic shivering, while in Group F, only 12 (20.7%) patients required treatment for postanesthetic shivering (P = 0.009, odds ratio = 0.333, 95% confidence interval: 0.147–0.772). Conclusions Additional use of forced-air warming blankets in orthognathic surgery was superior in maintaining normothermia and reduced the incidence of postanesthetic shivering. PMID:28879279

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.

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.

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.

Non-receptor tyrosine kinases ITK and BTK negatively regulate mast cell pro-inflammatory responses to lipopolysaccharide

PubMed Central

Huang, Weishan; Morales, J. Luis; Gozivoda, Victor P.; August, Avery

2015-01-01

Background Mast cells are indispensible for LPS-induced septic hypothermia, in which TNF-α plays an essential role to initiate septic responses. ITK and BTK regulate mast cell responses to allergen, but their roles in mast cell responses in LPS-induced sepsis are unclear. Objectives We sought to investigate the roles of ITK and BTK in mast cell responses during LPS-induced septic inflammation. Methods Mice (genetically modified or BMMC-reconstituted Sash) were given LPS to induce septic hypothermia, in the presence or absence of indicated inhibitors. Flow cytometry was used to determine LPS-induced cell influx and TNF-α production in peritoneal cells. Microarray was used for genome-wide gene expression analysis on BMMCs. Quantitative PCR and multiplex were used to determine transcribed and secreted pro-inflammatory cytokines. Microscopy and western blotting were used to determine activation of signal transduction pathways. Results The absence of ITK and BTK leads to exacerbation of LPS-induced septic hypothermia and neutrophil influx. Itk−/−Btk−/− mast cells exhibit hyperactive preformed and LPS-induced TNF-α production, and lead to more severe LPS-induced septic hypothermia when reconstituted into mast cell deficient Sash mice. LPS-induced NF-κB, Akt and p38 activation is enhanced in Itk−/−Btk−/− mast cells, and blockage of PI3K, Akt or p38 downstream MNK1 activation significantly suppresses TNF-α hyper-production and attenuates septic hypothermia. Conclusions ITK and BTK regulate thermal homeostasis during septic response through mast cell function in mice. They share regulatory function downstream of TLR4/LPS in mast cells, through regulating the activation of canonical NF-κB, PI3K/Akt and p38 signaling pathways. PMID:26581914

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.

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.

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.

Characterization of the hypothermic effects of imidazoline I2 receptor agonists in rats

PubMed Central

Thorn, David A; An, Xiao-Fei; Zhang, Yanan; Pigini, Maria; Li, Jun-Xu

2012-01-01

BACKGROUND AND PURPOSE Imidazoline I2 receptors have been implicated in several CNS disorders. Although several I2 receptor agonists have been described, no simple and sensitive in vivo bioassay is available for studying I2 receptor ligands. This study examined I2 receptor agonist-induced hypothermia as a functional in vivo assay of I2 receptor agonism. EXPERIMENTAL APPROACH Different groups of rats were used to examine the effects of I2 receptor agonists on the rectal temperature and locomotion. The pharmacological mechanisms were investigated by combining I2 receptor ligands and different antagonists. KEY RESULTS All the selective I2 receptor agonists examined (2-BFI, diphenyzoline, phenyzoline, CR4056, tracizoline, BU224 and S22687, 3.2–56 mg·kg–1, i.p.) dose-dependently and markedly decreased the rectal temperature (hypothermia) in rats, with varied duration of action. Pharmacological mechanism of the observed hypothermia was studied by combining the I2 receptor agonists (2-BFI, BU224, tracizoline and diphenyzoline) with imidazoline I2 receptor/ α2 adrenoceptor antagonist idazoxan, selective I1 receptor antagonist efaroxan, α2 adrenoceptor antagonist/5-HT1A receptor agonist yohimbine. Idazoxan but not yohimbine or efaroxan attenuated the hypothermic effects of 2-BFI, BU224, tracizoline and diphenyzoline, supporting the I2 receptor mechanism. In contrast, both idazoxan and yohimbine attenuated hypothermia induced by the α2 adrenoceptor agonist clonidine. Among all the I2 receptor agonists studied, only S22687 markedly increased the locomotor activity in rats. CONCLUSIONS AND IMPLICATIONS Imidazoline I2 receptor agonists can produce hypothermic effects, which are primarily mediated by I2 receptors. These data suggest that I2 receptor agonist-induced hypothermia is a simple and sensitive in vivo assay for studying I2 receptor ligands. PMID:22324428

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.

Hypothermic inhibition of apoptotic pathways for combined neurotoxicity of iron and ascorbic acid in differentiated PC12 cells: reduction of oxidative stress and maintenance of the glutathione redox state.

PubMed

Hasegawa, Masashi; Ogihara, Tohru; Tamai, Hiroshi; Hiroi, Mayo

2009-08-04

Recent clinical trials have demonstrated the efficacy and safety of therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy (HIE). We previously reported that the levels of non-protein-bound iron and ascorbic acid (AA) are increased in the CSF of infants with HIE. In this study, we investigated the effect of hypothermia on the combined cytotoxicity of Fe and AA for differentiated PC12 cells. The optimal settings for hypothermic treatment were a temperature of 30-32 degrees C, rescue time window of less than 6 h, and minimum duration of at least 24 h. Hypothermia effectively prevented the loss of the mitochondrial transmembrane potential from 6 h to 72 h (end of the study period) and attenuated the release of apoptotic proteins (cytochrome c and apoptosis-inducing factor) at 6 h of exposure to Fe-AA. Activation of caspase-3 was also delayed until 24 h. Akt was transiently activated, although no influence of temperature was observed. Elevation of oxidative stress markers, including ortho-, meta-, and di-tyrosine (markers of protein oxidation) and 4-hydroxynonenal (lipid peroxidation) was significantly attenuated when the temperature was reduced by 5 degrees C. The half-cell reduction potential (Ehc) of GSSG/2GSH redox couple ranged from -220 to -180 mV in unstressed differentiated PC12 cells, and apoptosis was triggered when Ehc exceeded -180 mV. Hypothermia prevented Ehc from rising above -180 mV within 24 h of exposure to Fe-AA. In conclusion, hypothermia prevented cell death due to Fe-AA toxicity by inhibiting apoptotic pathways through maintenance of a reduced cellular environment, as well as by alleviating oxidative stress.

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.