Induced Hypothermia for Acute Stroke

Hemmen, Thomas; Lyden, Patrick D.

doi:10.1161/01.str.0000247920.15708.fa

Cited by 101 publications

(61 citation statements)

References 76 publications

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“…Therapeutic hypothermia-Moderate therapeutic hypothermia represents one of the most solidly evidence-based neuroprotective strategies currently available (Hemmen et al, 2007). A large corpus of experimental studies over the past 20 years has provided incontrovertible evidence that moderate hypothermia is capable of conferring high-grade neuroprotection in focal and global cerebral ischemia by impeding a host of deleterious metabolic and biochemical injury-mechanisms, with a therapeutic window appropriate for clinical application in ischemic stroke (Ginsberg et Group, 2002).…”

Section: Part Ii: Neuroprotection --Moving From the Present Into The mentioning

confidence: 99%

Neuroprotection for ischemic stroke: Past, present and future

2008

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Neuroprotection for ischemic stroke refers to strategies, applied singly or in combination, that antagonize the injurious biochemical and molecular events that eventuate in irreversible ischemic injury. There has been a recent explosion of interest in this field, with over 1000 experimental papers and over 400 clinical articles appearing within the past 6 years. These studies, in turn, are the outgrowth of three decades of investigative work to define the multiple mechanisms and mediators of ischemic brain injury, which constitute potential targets of neuroprotection. Rigorously conducted experimental studies in animal models of brain ischemia provide incontrovertible proof-of-principle that high-grade protection of the ischemic brain is an achievable goal. Nonetheless, many agents have been brought to clinical trial without a sufficiently compelling evidence-based pre-clinical foundation. At this writing, around 160 clinical trials of neuroprotection for ischemic stroke have been initiated. Of the approximately 120 completed trials, two-thirds were smaller early-phase safetyfeasibility studies. The remaining one-third were typically larger (>200 subjects) phase II or III trials, but, disappointingly, only fewer than one-half of these administered neuroprotective therapy within the 4-6 hour therapeutic window within which efficacious neuroprotection is considered to be achievable. This fact alone helps to account for the abundance of "failed" trials.This review presents a close survey of the most extensively evaluated neuroprotective agents and classes and considers both the strengths and weakness of the pre-clinical evidence as well as the results and shortcomings of the clinical trials themselves. Among the agent-classes considered are calcium channel blockers; glutamate antagonists; GABA agonists; antioxidants/radical scavengers; phospholipid precursor; nitric oxide signal-transduction down-regulator; leukocyte inhibitors; hemodilution; and a miscellany of other agents. Among promising ongoing efforts, therapeutic hypothermia, high-dose human albumin therapy, and hyperacute magnesium therapy are considered in detail. The potential of combination therapies is highlighted. Issues of clinical-trial funding, the need for improved translational strategies and clinical-trial design, and "thinking outside the box" are emphasized. Part I: Neuroprotection -from Past to the PresentNeuroprotection for ischemic brain injury has emerged only recently as a topic of serious biomedical inquiry. A MEDLINE survey (PubMed, 2007) reveals virtually no publications on this topic until the early 1990's but a remarkable surge in publications over the past 10 years Correspondence and reprint requests to:

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Section: Part Ii: Neuroprotection --Moving From the Present Into The mentioning

confidence: 99%

Neuroprotection for ischemic stroke: Past, present and future

2008

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“…At the clinical level, however, the role of therapeutic hypothermia in the treatment of stroke remains unclear, due to certain problems in translating preclinical data to the clinical arena. 3,5,10,14) For instance, it is difficult to prevent shivering and other discomforts experienced because most stroke patients are awake and not endotracheally intubated. Hypothermia is most effective in preclinical models of transient ischemia.…”

Section: Discussionmentioning

confidence: 99%

Acute Cerebral Ischemia After Intracranial Bleeding in Unilateral Moyamoya Disease

Shibamoto¹,

Aoyama²,

Taki³

et al. 2012

Neurol. Med. Chir.(Tokyo)

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A 31-year-old male presenting with intracranial hemorrhage manifesting as deep coma and anisocoria underwent immediate emergency surgery. Three-dimensional computed tomography (CT) angiography revealed stenosis of the right middle cerebral artery (MCA) and perfusion CT immediately after the surgery suggested severe hypoperfusion in the right MCA territory. Postoperative angiography demonstrated right unilateral moyamoya disease. We predicted that brain edema and intracranial pressure (ICP) elevation occurring after the hemorrhage might result in cerebral infarction. Hyperosmotic drugs were contraindicated by dehydration. Therefore, therapeutic hypothermia was induced that controlled the ICP. We considered that the increased ICP, dehydration, vasospasm, and shrinkage of the ruptured vessel comprised the pathogenesis of acute cerebral ischemia after intracranial bleeding. Cerebral hemodynamics should be evaluated during the acute phase of cerebral hemorrhage to prevent subsequent cerebral infarction.

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“…However, many serine proteases are affected by temperature, and the activity of tPA may be reduced in hypothermia. [54] In vitro analysis shows that cooling to 30°C to 33°C decreases tPA activity by 2% to 4%. [55] Moreover, it has been reported that the response to tPA may be related to body temperature at stroke presentation.…”

Section: Hypothermia and Thrombolysismentioning

confidence: 99%

“…[47] In the ICTuS-L trial, the rate of ICH was similar among patients who received tPA with hypothermia and those treated with tPA alone. [51] Hypothermia has also been studied with other neuroprotective agents in the treatment of acute ischemic stroke. Twenty patients with acute ischemic stroke were treated with caffeinol (caffeine 8-9 mg/kg + ethanol 0.4 g/kg intravenously x 2 hours, started by 4 hours after symptom onset) and hypothermia (started by 5 hours and continued for 24 hours (33-35º C), followed by 12 hours of rewarming).…”

Section: Human Studies Of Hypothermia In Ischemic Strokementioning

confidence: 99%