title: Delayed cerebral ischaemia prevention and treatment after aneurysmal subarachnoid haemorrhage: a systematic review.
abstract: : The leading cause of morbidity and mortality after surviving the rupture of an intracranial aneurysm is delayed cerebral ischaemia (DCI). We present an update of recent literature on the current status of prevention and treatment strategies for DCI after aneurysmal subarachnoid haemorrhage. A systematic literature search of three databases (PubMed, ISI Web of Science, and Embase) was performed. Human clinical trials assessing treatment strategies, published in the last 5 yr, were included based on full-text analysis. Study data were extracted using tables depicting study type, sample size, and outcome variables. We identified 49 studies meeting our inclusion criteria. Clazosentan, magnesium, and simvastatin have been tested in large high-quality trials but failed to show a beneficial effect. Cilostazol, eicosapentaenoic acid, erythropoietin, heparin, and methylprednisolone yield promising results in smaller, non-randomized or retrospective studies and warrant further investigation. Topical application of nicardipine via implants after clipping has been shown to reduce clinical and angiographic vasospasm. Methods to improve subarachnoid blood clearance have been established, but their effect on outcome remains unclear. Haemodynamic management of DCI is evolving towards euvolaemic hypertension. Endovascular rescue therapies, such as percutaneous transluminal balloon angioplasty and intra-arterial spasmolysis, are able to resolve angiographic vasospasm, but their effect on outcome needs to be proved. Many novel therapies for preventing and treating DCI after aneurysmal subarachnoid haemorrhage have been assessed, with variable results. Limitations of the study designs often preclude definite statements. Current evidence does not support prophylactic use of clazosentan, magnesium, or simvastatin. Many strategies remain to be tested in larger randomized controlled trials.
  
  
  
  This systematic review was registered in the international prospective register of systematic reviews.
  
  
  
  CRD42015019817.
authors.affiliation: Department of Neurosurgery Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Veldeman
authors.affiliation: Department of Neurosurgery.
authors.forename: A
authors.initials: A
authors.lastname: Höllig
authors.affiliation: Department of Neurosurgery.
authors.forename: H
authors.initials: H
authors.lastname: Clusmann
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Stevanovic
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Rossaint
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH Aachen, Aachen, Germany mcoburn@ukaachen.de.
authors.forename: M
authors.initials: M
authors.lastname: Coburn
mesh_terms: D017130:Angioplasty; D002545:Brain Ischemia / Q000150:complications / Q000517:prevention & control* / Q000628:therapy*; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000628:therapy*
chemical_list: D018696:Neuroprotective Agents
keywords: brain ischaemia; subarachnoid haemorrhage; vasospasm, intracranial