Current Management of Delayed Cerebral Ischemia: Update from Results of Recent Clinical Trials
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REVIEW ARTICLE
Current Management of Delayed Cerebral Ischemia: Update from Results of Recent Clinical Trials Shakira Brathwaite & R. Loch Macdonald
Received: 10 September 2013 / Revised: 23 November 2013 / Accepted: 29 November 2013 # Springer Science+Business Media New York 2013
Abstract Subarachnoid hemorrhage (SAH) accounts for 5– 7 % of all strokes worldwide and is associated with high mortality and morbidity. Even after surgical intervention, approximately 30 % of patients develop long-term cognitive and neurological deficits that significantly affect their capacity to return to work or daily life unassisted. Much of this stems from a secondary ischemic phenomenon referred to as delayed cerebral ischemia (DCI). While DCI has been historically attributed to the narrowing of the large basal cerebral arteries, it is now recognized that numerous pathways contribute to its pathogenesis, including microcirculatory dysfunction, microthrombosis, cortical spreading depression, and early brain injury. This paper seeks to summarize some of the key pathophysiological events that are associated with poor Review Criteria The term “subarachnoid hemorrhage” was used to search Clinicaltrials.gov for ongoing randomized controlled trials, as well as those that had been completed within the last 5 years. All included trials were phase 2 and beyond, with a focus on preventive and therapeutic applications. Additionally, PubMed was searched for articles published after 1 January 2009, including electronic early release publications. The search term utilized was as follows: (delayed cerebral ischemia or delayed ischemic neurological deficits) and subarachnoid hemorrhage. The abstracts of the papers obtained were reviewed, and full articles were acquired when content was considered appropriate for inclusion. S. Brathwaite : R. L. Macdonald (*) Division of Neurosurgery, Department of Surgery, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8 e-mail: [email protected] S. Brathwaite : R. L. Macdonald Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8 S. Brathwaite : R. L. Macdonald Department of Surgery, University of Toronto, Toronto, Ontario, Canada
outcome after SAH, provide a general overview of current methods of treating SAH patients, and review the results of recent clinical trials directed at improving outcome after SAH. The scientific basis of these studies will be discussed, in addition to the available results and recommendations for effective patient management. Therapeutic methods under current clinical investigation will also be addressed. In particular, the mechanisms by which they are expected to elicit improved outcome will be investigated, as well as the specific study designs and anticipated time lines for completion. Keywords Subarachnoid hemorrhage . Delayed cerebral ischemia . Cerebral vasospasm . Nimodipine . Clazosentan . Magnesi
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