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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain edema with intracranial hypertension is a major complication in patients with acute liver failure. Current therapies for this complication include a variety of pharmacologic and interventional measures, some of which are frequently associated with adverse effects or contraindications. Even though these measures usually allow the control of intracranial hypertension for a certain period of time, recurrence is common. New therapies are therefore needed. Increasing clinical and experimental evidence suggests that induction of mild hypothermia (32 degrees C-35 degrees C) may be a therapeutic alternative. Similar to traumatic brain injury or brain stroke, induction of mild hypothermia seems highly effective to reduce intracranial pressure in patients with acute liver failure. Several mechanisms by which mild hypothermia may prevent brain edema and intracranial hypertension in this condition have been disclosed and may include beneficial effects on ammonia metabolism, as well as on the disturbances of brain osmolarity, cerebrovascular hemodynamics, brain glucose metabolism, inflammation, and others. Improvement of systemic hemodynamics and amelioration of liver injury may be other benefits of the systemic induction of mild hypothermia, but the impact of potential adverse events, such as infection, should also be taken into account. At a time when mild hypothermia is increasingly used in several specialized centers, performance of a randomized controlled trial seems critical to confirm the benefits of mild hypothermia in acute liver failure and to provide adequate guidelines for its use.
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PMID:Mild hypothermia for acute liver failure: a review of mechanisms of action. 1575 51

Hypoxia-ischemia is a leading cause of morbidity and mortality in the perinatal period with an incidence of 1/4000 live births. Biochemical events such as energy failure, membrane depolarization, brain edema, an increase of neurotransmitter release and inhibition of uptake, an increase of intracellular Ca(2+), production of oxygen-free radicals, lipid peroxidation, and a decrease of blood flow are triggered by hypoxia-ischemia and may lead to brain dysfunction and neuronal death. These abnormalities can result in mental impairments, seizures, and permanent motor deficits, such as cerebral palsy. The physical and emotional strain that is placed on the children affected and their families is enormous. The care that these individuals need is not only confined to childhood, but rather extends throughout their entire life span, so it is very important to understand the pathophysiology that follows a hypoxic-ischemic insult. This review will highlight many of the mechanisms that lead to neuronal death and include the emerging area of white matter injury as well as the role of inflammation and will provide a summary of therapeutic strategies. Hypothermia and oxygen will also be discussed as treatments that currently lack a specific target in the hypoxic/ischemic cascade.
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PMID:Pathophysiology of an hypoxic-ischemic insult during the perinatal period. 1584 8

Brain edema leading to intracranial hypertension is a cause of death in acute liver failure (ALF). The pathogenesis of this unique complication has been investigated in man, in experimental models and in isolated cell systems. From this experience, an integrated view has emerged, pointing at several mechanisms that contribute to cerebral swelling; an osmotic derangement in astrocytes, changes in cellular metabolism as well as alterations of cerebral blood flow. The ability of mild hypothermia to counteract each of these changes in experimental systems has supported the organization of a clinical trial of mild cooling in this disease. Such an advance can be viewed as the clinical translation of 20 years of research in this area.
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PMID:The pathophysiology of brain edema in acute liver failure. 1596 Nov 87

Brain hypothermia treatment is used as a neuroprotectant to decompress the elevated intracranial pressure (ICP) in acute neuropatients. However, a quantitative relationship between decompression and brain hypothermia is still unclear, this makes medical treatment difficult and ineffective. The objective of this paper is to develop a general mathematical model integrating hemodynamics and biothermal dynamics to enable a quantitative prediction of transient responses of elevated ICP to ambient cooling temperature. The model consists of a lumped-parameter compartmental representation of the body, and is based on two mechanisms of temperature dependence encountered in hypothermia, i.e. the van't Hoff's effect of metabolism and the Arrhenius' effect of capillary filtration. Model parameters are taken from the literature. The model is verified by comparing the simulation results to population-averaged data and clinical evidence of brain hypothermia treatment. It is possible to assign special model inputs to mimic clinical maneuvers, and to adjust model parameters to simulate pathophysiological states of intracranial hypertension. Characteristics of elevated ICP are quantitatively estimated by using linear approximation of step response with respect to ambient cooling temperature. Gain of about 4.9 mmHg degrees C(-1), dead time of about 1.0 h and a time constant of about 9.8h are estimated for the hypothermic decompression. Based on the estimated characteristics, a feedback control of elevated ICP is introduced in a simulated intracranial hypertension of vasogenic brain edema. Simulation results suggest the possibility of an automatic control of the elevated ICP in brain hypothermia treatment.
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PMID:A mathematical model of intracranial pressure dynamics for brain hypothermia treatment. 1609 39

Encephalopathy, brain edema and intracranial hypertension are neurological complications responsible for substantial morbidity/mortality in patients with acute liver failure (ALF), where, aside from liver transplantation, there is currently a paucity of effective therapies. Mirroring its cerebro-protective effects in other clinical conditions, the induction of mild hypothermia may provide a potential therapeutic approach to the management of ALF. A solid mechanistic rationale for the use of mild hypothermia is provided by clinical and experimental studies showing its beneficial effects in relation to many of the key factors that determine the development of brain edema and intracranial hypertension in ALF, namely the delivery of ammonia to the brain, the disturbances of brain organic osmolytes and brain extracellular amino acids, cerebro-vascular haemodynamics, brain glucose metabolism, inflammation, subclinical seizure activity and alterations of gene expression. Initial uncontrolled clinical studies of mild hypothermia in patients with ALF suggest that it is an effective, feasible and safe approach. Randomized controlled clinical trials are now needed to adequately assess its efficacy, safety, clinical impact on global outcomes and to provide the guidelines for its use in ALF.
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PMID:Keeping cool in acute liver failure: rationale for the use of mild hypothermia. 1624 52

Molecular biological approaches continue to lead to the identification of alterations in expression of genes coding for key central nervous system proteins involved in water homeostasis, energy metabolism and neurotransmitter regulation in acute liver failure (ALF). However, studies aimed at elucidating the pathophysiological consequences of these changes in gene expression are impeded by the lack of a suitable mouse model of ALF. A previous report described hepatic pathology characteristic of ALF resulting from the administration of azoxymethane (AOM) in mice [Matkowskyj, K.A., Marrero, J.A., Carroll, R.E., Danilkovich, A.V., Green, R.M., Benya, R.V., 1999. Azoxymethane-induced fulminant hepatic failure in C57BL/6J mice: characterization of a new animal model. Am. J. Physiol. 277, G455-G462]. In a series of experiments to further assess this treatment as an effective model of ALF, the effects of administration of AOM to male C57BL mice on hepatic and cerebral function were studied. With maintenance of body temperature at 37 degrees C and control of hypoglycemia, mice developed signs of encephalopathy (decreased locomotor activity followed by loss of righting and corneal reflexes) within 16 h of AOM treatment. AOM-treated mice were hyperammonemic, developed spontaneous hypothermia and brain edema. Brain ammonia concentrations were increased to 0.98+/-0.12 mM at coma stages of encephalopathy. Brain amino acid profiles determined by HPLC were typical of ALF in other species including humans. Mild hypothermia (35 degrees C) led to significant attenuation of brain edema, ammonia, and amino acid changes. These findings demonstrate that AOM treatment affords a simple, reproducible mouse model of ALF which may be suitable for the study of the effects of gene manipulation on the cerebral complications of ALF.
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PMID:Neurobiological characterization of an azoxymethane mouse model of acute liver failure. 1656 65

Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multifactorial, combining a cytotoxic brain edema due to the astrocytic accumulation of glutamine, and an increase in cerebral blood volume and cerebral blood flow, in part due to inflammation, to glutamine and to toxic products of the diseased liver. Validated methods to control intracranial hypertension in fulminant hepatic failure patients mainly include mannitol, hypertonic saline, indomethacin, thiopental, and hyperventilation. However all these measures are often not sufficient in absence of liver transplantation, the only curative treatment of intracranial hypertension in fulminant hepatic failure to date. Induced moderate hypothermia seems very promising in this setting, but has to be validated by a controlled, randomized study. Artificial liver support systems have been under investigation for many decades. The bioartificial liver, based on both detoxification and swine liver cells, has shown some efficacy on reduction of intracranial pressure but did not show survival benefit in a controlled, randomized study. The Molecular Adsorbents Recirculating System has shown some efficacy in decreasing intracranial pressure in an animal model of liver failure, but has still to be evaluated in a phase III trial.
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PMID:Brain edema and intracranial hypertension in fulminant hepatic failure: pathophysiology and management. 1716 26

To clarify the role of brain temperature in permeability of the blood-brain barrier (BBB), rats were injected with methamphetamine (METH 9 mg/kg) at normal (23 degrees C) and warm (29 degrees C) environmental conditions and internal temperatures were monitored both centrally (nucleus accumbens, NAcc) and peripherally (skin and nonlocomotor muscle). Once NAcc temperatures peaked or reached 41.5 degrees C (a level suggesting possible lethality), animals were administered Evans blue dye (protein tracer that does not normally cross the BBB), rapidly anaesthetized, perfused and had their brains removed. All METH-treated animals showed brain and body hyperthermia associated with relative skin hypothermia, suggesting metabolic activation coupled with peripheral vasoconstriction. While METH-induced NAcc temperature elevation varied from 37.60 to 42.46 degrees C (or 1.2-5.1 degrees C above baseline), it was stronger at 29 degrees C (+4.13 degrees C) than 23 degrees C (+2.31 degrees C). Relative to control, METH-treated animals had significantly higher brain levels of water, Na(+), K(+) and Cl(-), suggesting brain edema, and intense immunostaining for albumin, indicating breakdown of the BBB. METH-treated animals also showed strong immunoreactivity for glial fibrillary acidic protein (GFAP), possibly suggesting acute abnormality or damage of astrocytes. METH-induced changes in brain water, albumin and GFAP correlated linearly with NAcc temperature (r = 0.93, 0.98 and 0.98, respectively), suggesting a key role of brain hyperthermia in BBB permeability, development of brain edema and subsequent functional and structural neural abnormalities. Therefore, along with a direct destructive action on neural cells and functions, brain hyperthermia, via breakdown of the BBB, may be crucial for both decompensation of brain functions and cell injury following acute METH intoxication, possibly contributing to neurodegeneration resulting from chronic drug use.
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PMID:Brain edema and breakdown of the blood-brain barrier during methamphetamine intoxication: critical role of brain hyperthermia. 1776 2

Life-threatening, space-occupying brain edema occurs in up to 10% of patients with supratentorial infarcts and is traditionally associated with a high mortality rate of up to 80%. Management of these patients is currently being changed to an earlier and more aggressive treatment regimen. Early surgical decompression has recently been proven effective to reduce mortality and increase the number of patients with a favorable outcome in randomized controlled trials and is now the "antiedema" therapy of first choice for patients with large middle cerebral artery infarction aged 60 years or younger. Several medical treatment strategies have been proposed to control brain edema and reduce intracranial pressure, including different osmotherapeutics, hyperventilation, tromethamine, hypothermia, and barbiturate coma. None of these treatments is supported by level 1 evidence of efficacy in clinical trials, and some of them may even be detrimental. Preliminary results on hypothermia for space-occupying hemispheric infarction are encouraging, but far from definitive.
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PMID:Antiedema therapy in ischemic stroke. 1790 84

The patient in this study was a 43-year-old woman who had become unconscious after contracting influenza virus type A infection. Brain CT showed severe brain swelling. Brain MRI also showed brain edema with no specific abnormality on T2-weighted images. We diagnosed her as having influenza type A virus-associated encephalopahty and treated her with Oseltamivir, methylprednisolone pulse therapy, and a high dose of intravenous immunoglobulins. In addition, we treated her with hypothermia and a high dose of intravenous ATIII because of the severe brain swelling and possibility of DIC. After the treatments, brain swelling had improved, and she regained consciousness without any sequelae. Adult influenza virus-associated encephalopathy is rare. We were able to successfully treat our patient with primary multidisciplinary treatments without causing sequelae.
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PMID:[Case of adult influenza type A virus-associated encephalopathy successfully treated with primary multidisciplinary treatments]. 1809 96


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