Journal of neurotrauma
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Journal of neurotrauma · Mar 2009
ReviewCombination therapy with hypothermia for treatment of cerebral ischemia.
Mild hypothermia is an established neuroprotectant in the laboratory, showing remarkable and consistent effects across multiple laboratories and models of brain injury. At the clinical level, mild hypothermia has shown benefits in patients who have suffered cardiac arrest and in some pediatric populations suffering hypoxic brain insults. However, a review of the literature has demonstrated that in order to appreciate the maximum benefits of hypothermia, brain cooling needs to begin soon after the insult, maintained for relatively long period periods of time, and, in the case of ischemic stroke, should be applied in conjunction with the re-establishment of cerebral perfusion. ⋯ However, the effects of thrombolytics are also temperature dependent, and the risk of hemorrhage is significant. The experimental data nevertheless seem to favor a combinatorial approach. Thus, in order to apply hypothermia to a broader range of patients, combination strategies should be further investigated.
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Therapeutic moderate hypothermia has been advocated for use in traumatic brain injury, stroke, cardiac arrest-induced encephalopathy, neonatal hypoxic-ischemic encephalopathy, hepatic encephalopathy, and spinal cord injury, and as an adjunct to aneurysm surgery. In this review, we address the trials that have been performed for each of these indications, and review the strength of the evidence to support treatment with mild/moderate hypothermia. ⋯ For traumatic brain injury, a recent meta-analysis suggests that cooling may increase the likelihood of a good outcome, but does not change mortality rates. For many of the other indications, such as stroke and spinal cord injury, trials are ongoing, but the data are insufficient to recommend routine use of hypothermia at this time.
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Journal of neurotrauma · Mar 2009
ReviewPerioperative hypothermia: use and therapeutic implications.
Perioperative cerebral ischemic insults are common in some surgical procedures. The notion that induced hypothermia can be employed to improve outcome in surgical patients has persisted for six decades. Its principal application has been in the context of cardiothoracic and neurosurgery. ⋯ There is little doubt of the protective efficacy of deep hypothermia, but continued efforts to refine its application may serve to enhance its utility. Recent evidence that mild hypothermia is efficacious in out-of-hospital cardiac arrest has implications for patients incurring anoxic or global ischemic brain insults during anesthesia and surgery, or perioperatively. Advances in preclinical models of ischemic/anoxic injury and cardiopulmonary bypass that allow definition of optimal cooling strategies and study of cellular and subcellular events during perioperative ischemia can add to our understanding of mechanisms of hypothermia efficacy and provide a rationale basis for its implementation in humans.
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Induced hypothermia after ischemic stroke is a promising neuroprotective therapy and is the most potent in pre-clinical models. Technological limitations and homeostatic mechanisms that maintain core body temperature, however, have limited the clinical application of hypothermia. Advances in intravascular cooling and successful trials of hypothermia after global cerebral ischemia, such as in cardiac arrest and neonatal asphyxia, have renewed interest in hypothermia for stroke.
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Journal of neurotrauma · Mar 2009
ReviewProtection in animal models of brain and spinal cord injury with mild to moderate hypothermia.
For the past 20 years, various laboratories throughout the world have shown that mild to moderate levels of hypothermia lead to neuroprotection and improved functional outcome in various models of brain and spinal cord injury (SCI). Although the potential neuroprotective effects of profound hypothermia during and following central nervous system (CNS) injury have long been recognized, more recent studies have described clinically feasible strategies for protecting the brain and spinal cord using hypothermia following a variety of CNS insults. In some cases, only a one or two degree decrease in brain or core temperature can be effective in protecting the CNS from injury. ⋯ This paper reviews the experimental data obtained in animal models of brain and SCI demonstrating the benefits of mild to moderate hypothermia. These studies have provided critical data for the translation of this therapy to the clinical arena. The mechanisms underlying the beneficial effects of mild hypothermia are also summarized.