title: Pharmacologic Management of Subarachnoid Hemorrhage.
abstract: Subarachnoid hemorrhage (SAH) remains a condition with suboptimal functional outcomes, especially in the young population. Pharmacotherapy has an accepted role in several aspects of the disease and an emerging role in several others. No preventive pharmacologic interventions for SAH currently exist. Antiplatelet medications as well as anticoagulation have been used to prevent thromboembolic events after endovascular coiling. However, the main focus of pharmacologic treatment of SAH is the prevention of delayed cerebral ischemia (DCI). Currently the only evidence-based medical intervention is nimodipine. Other calcium channel blockers have been evaluated without convincing efficacy. Anti-inflammatory drugs such as statins have demonstrated early potential; however, they failed to provide significant evidence for the use in preventing DCI. Similar findings have been reported for magnesium, which showed potential in experimental studies and a phase 2 trial. Clazosentane, a potent endothelin receptor antagonist, did not translate to improve functional outcomes. Various other neuroprotective agents have been used to prevent DCI; however, the results have been, at best inconclusive. The prevention of DCI and improvement in functional outcome remain the goals of pharmacotherapy after the culprit lesion has been treated in aneurysmal SAH. Therefore, further research to elucidate the exact mechanisms by which DCI is propagated is clearly needed. In this article, we review the current pharmacologic approaches that have been evaluated in SAH and highlight the areas in which further research is needed.
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Department of Neurosurgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA. Electronic address: ay276@cam.ac.uk.
authors.forename: Adam M H
authors.initials: AM
authors.lastname: Young
authors.affiliation: Department of Neurosurgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Surya K
authors.initials: SK
authors.lastname: Karri
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Adel
authors.initials: A
authors.lastname: Helmy
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Karol P
authors.initials: KP
authors.lastname: Budohoski
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ramez W
authors.initials: RW
authors.lastname: Kirollos
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Diederik O
authors.initials: DO
authors.lastname: Bulters
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kirkpatrick
authors.affiliation: Department of Neurosurgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Ogilvy
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Rikin A
authors.initials: RA
authors.lastname: Trivedi
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D017209:Apoptosis; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003907:Dexamethasone / Q000008:administration & dosage; D004146:Dioxanes / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects; D019317:Evidence-Based Medicine; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008278:Magnesium Sulfate / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009553:Nimodipine / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011281:Pregnatrienes / Q000008:administration & dosage; D011374:Progesterone / Q000008:administration & dosage / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000187:drug effects; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000305:Adrenal Cortex Hormones; D000925:Anticoagulants; D002121:Calcium Channel Blockers; D004146:Dioxanes; D004365:Drugs, Chinese Herbal; D004967:Estrogens; D016166:Free Radical Scavengers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D010975:Platelet Aggregation Inhibitors; D011281:Pregnatrienes; D011725:Pyridines; D011743:Pyrimidines; D044022:Receptor, Endothelin A; D013449:Sulfonamides; D013777:Tetrazoles; C061091:lithospermate B; C109641:clazosentan; D011374:Progesterone; D009553:Nimodipine; D008278:Magnesium Sulfate; D003907:Dexamethasone; C053355:tirilazad
keywords: Mortality; Outcome; Subarachnoid hemorrhage; Therapy