Cooling for Acute Ischemic Brain Damage (COOL AID)

Georgia, Michael A. De; Krieger, Derk; Aböu-Chebl, Alex; Devlin, Thomas; Jauß, M.; Davis, Stephen; Koroshetz, Walter J.; Rordorf, Guy; Warach, Steve

doi:10.1212/01.wnl.0000129840.66938.75

Cited by 354 publications

(247 citation statements)

References 16 publications

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“…In one study, 17 awake patients with acute stroke were cooled within 12 h (mean, 3.25 h) to 35.5°C with a forced-air surface-cooling blanket; meperidine was used to control shivering (Kammersgaard et al, 2000). In a second feasibility trial (Cooling for Acute Ischemic Brain Damage -COOL AID), 40 ischemic stroke patients were randomized within 12 hours of symptom onset to hypothermia of 33°C for 24 h via an endovascular cooling device; the procedure was generally well-tolerated (De Georgia et al, 2004). A third group used an endovascular cooling device in the inferior vena cava, plus a combination of buspirone, meperidine and cutaneous warming with a heating blanket to suppress shivering (Guluma et al, 2006).…”

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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“…Several small studies on antipyretic medication in febrile patients after stroke, most frequently using acetaminophen in various combinations, were either not at all or only moderately effective in lowering fever, and could not demonstrate valid effects on clinical outcome [30][31][32]. Invasive catheter-based heat exchange systems influence body temperature more effectively but may not be suitable for the general stroke unit setting, owing to technical and staff requirements, possible complications, and the substantial costs of this invasive technique requiring insertion of a large catheter into the femoral artery and propagation of the heat exchange device into the inferior vena [33][34][35][36][37]. Given the prognostic significance of fever and the limitations of its current symptomatic treatment options, it appears reasonable to ascertain and treat the causes of fever, and, if possible, to prevent its occurrence altogether.…”

Section: Rationale Behind Prophylactic Antibiotic Therapy In Strokementioning

confidence: 99%

Prophylactic Antibiotic Therapy for Preventing Poststroke Infection

Schwarz

2016

Neurotherapeutics

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Infections, in particular pneumonia, are common complications in patients with acute stroke and are associated with a less favorable neurologic and functional outcome. Patients with severe stroke and dysphagia are at highest risk of infection. Experimental and clinical data suggest stroke-induced immunodeficiency as a major factor contributing to the high incidence of infection after stroke. Preclinical studies support the potential benefit of preventive antibiotic therapy in acute stroke for lowering the incidence of infection and improving clinical outcome. Several smaller clinical trials on preventive antibiotic therapy in patients with stroke conducted during the last 10 years yielded inconclusive results. Recently, 2 large, open-label, controlled trials failed to demonstrate an improved clinical outcome after preventive antibiotic therapy in patients with acute stroke treated in specialized stroke units. In the BPreventive Antibiotics in Stroke Study^, antibiotic therapy lowered the rate of infection but did not influence outcome. In the STROKE-INF study, performed in patients with dysphagia after stroke, antibiotic therapy did not lower the incidence of pneumonia and had no prognostic significance. At present, preventive antibiotic therapy cannot be recommended as a therapeutic option for acute stroke.

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“…Several small human trials have investigated the safety and feasibility of TH after thrombolysis after ischemic stroke, given safety concerns of increased coagulopathy in TH [118][119][120][121][122]. Currently, a larger randomized, multicenter phase 2/3 trial is being conducted to further evaluate safety and efficacy of TH in ischemic stroke (Clinicaltrials.gov.…”

Section: Ischemic Strokementioning

confidence: 99%

Therapeutic Hypothermia for Acute Neurological Injuries

2012

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Therapeutic hypothermia (TH) is the intentional reduction of core body temperature to 32°C to 35°C, and is increasingly applied by intensivists for a variety of acute neurological injuries to achieve neuroprotection and reduction of elevated intracranial pressure. TH improves outcomes in comatose patients after a cardiac arrest with a shockable rhythm, but other off-label applications exist and are likely to increase in the future. This comprehensive review summarizes the physiology and cellular mechanism of action of TH, as well as different means of TH induction and maintenance with potential side effects. Indications of TH are critically reviewed by disease entity, as reported in the most recent literature, and evidence-based recommendations are provided.

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Cooling for Acute Ischemic Brain Damage (COOL AID)

Abstract: Induced moderate hypothermia is feasible using an endovascular cooling device in most patients with acute ischemic stroke. Further studies are needed to determine if hypothermia improves outcome.

Cited by 354 publications

References 16 publications

Neuroprotection for ischemic stroke: Past, present and future

Neuroprotection for ischemic stroke: Past, present and future

Prophylactic Antibiotic Therapy for Preventing Poststroke Infection

Therapeutic Hypothermia for Acute Neurological Injuries

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