title: Effects of prostacyclin on cerebral blood flow and vasospasm after subarachnoid hemorrhage: randomized, pilot trial.
abstract: OBJECTIVE
  Delayed ischemic neurological deficits (DINDs) are a major contributing factor for poor outcome in patients with subarachnoid hemorrhage. In this trial, we investigated the therapeutic potential of prostacyclin, an endogen substance with known effect on vascular tone and blood flow regulation, on factors related to DIND.
  
  
  METHODS
  This trial is a single-center, randomized, blinded, clinical, pilot trial with 3 arms. Ninety patients were randomized to continuous infusion of prostacyclin 1 ng/kg per minute, prostacyclin 2 ng/kg per minute, or placebo. The intervention was initiated day 5 after subarachnoid hemorrhage and discontinued day 10. Primary outcome was the difference in change from baseline in global cerebral blood flow. Secondary outcome measures were occurrence of DIND, angiographic vasospasm, and clinical outcome at 3 months.
  
  
  RESULTS
  No statistically significant difference in change of global cerebral blood flow was found between the intervention groups. The observed incidence of DIND and angiographic vasospasm was markedly higher in the placebo group, although this difference was not statistically significant. No statistically significant differences in safety parameters or clinical outcome were found between the 3 groups.
  
  
  CONCLUSIONS
  Administration of prostacyclin to patients with subarachnoid hemorrhage may be safe and feasible. Global cerebral blood flow after subarachnoid hemorrhage is not markedly affected by administration of prostacyclin in the tested dose range. It may be possible that the observed reduction in the point estimates of DIND and vasospasm in the prostacyclin groups represents an effect of prostacyclin as this trial was not powered to investigate the effect of prostacyclin on these outcomes.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT01447095.
authors.affiliation: From the Department of Neurosurgery, The Neuroscience Centre (R.R., M.J., J.S.-R.), Copenhagen Trial Unit, Centre for Clinical Intervention Research (J.W.), Department of Radiology, The Diagnostic Centre (T.S.), and Department of Neuroanesthesia, The Neuroscience Centre (N.V.O.), Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; Department of Anesthesia and Intensive Care, Institution of Clinical Sciences, Lund University Hospital, Lund, Sweden (P.O.G.); and Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (N.V.O.). rune333@gmail.com.
authors.forename: Rune
authors.initials: R
authors.lastname: Rasmussen
authors.affiliation: From the Department of Neurosurgery, The Neuroscience Centre (R.R., M.J., J.S.-R.), Copenhagen Trial Unit, Centre for Clinical Intervention Research (J.W.), Department of Radiology, The Diagnostic Centre (T.S.), and Department of Neuroanesthesia, The Neuroscience Centre (N.V.O.), Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; Department of Anesthesia and Intensive Care, Institution of Clinical Sciences, Lund University Hospital, Lund, Sweden (P.O.G.); and Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (N.V.O.).
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.affiliation: From the Department of Neurosurgery, The Neuroscience Centre (R.R., M.J., J.S.-R.), Copenhagen Trial Unit, Centre for Clinical Intervention Research (J.W.), Department of Radiology, The Diagnostic Centre (T.S.), and Department of Neuroanesthesia, The Neuroscience Centre (N.V.O.), Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; Department of Anesthesia and Intensive Care, Institution of Clinical Sciences, Lund University Hospital, Lund, Sweden (P.O.G.); and Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (N.V.O.).
authors.forename: Trine
authors.initials: T
authors.lastname: Stavngaard
authors.affiliation: From the Department of Neurosurgery, The Neuroscience Centre (R.R., M.J., J.S.-R.), Copenhagen Trial Unit, Centre for Clinical Intervention Research (J.W.), Department of Radiology, The Diagnostic Centre (T.S.), and Department of Neuroanesthesia, The Neuroscience Centre (N.V.O.), Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; Department of Anesthesia and Intensive Care, Institution of Clinical Sciences, Lund University Hospital, Lund, Sweden (P.O.G.); and Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (N.V.O.).
authors.forename: Marianne
authors.initials: M
authors.lastname: Juhler
authors.affiliation: From the Department of Neurosurgery, The Neuroscience Centre (R.R., M.J., J.S.-R.), Copenhagen Trial Unit, Centre for Clinical Intervention Research (J.W.), Department of Radiology, The Diagnostic Centre (T.S.), and Department of Neuroanesthesia, The Neuroscience Centre (N.V.O.), Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; Department of Anesthesia and Intensive Care, Institution of Clinical Sciences, Lund University Hospital, Lund, Sweden (P.O.G.); and Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (N.V.O.).
authors.forename: Jane
authors.initials: J
authors.lastname: Skjøth-Rasmussen
authors.affiliation: From the Department of Neurosurgery, The Neuroscience Centre (R.R., M.J., J.S.-R.), Copenhagen Trial Unit, Centre for Clinical Intervention Research (J.W.), Department of Radiology, The Diagnostic Centre (T.S.), and Department of Neuroanesthesia, The Neuroscience Centre (N.V.O.), Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; Department of Anesthesia and Intensive Care, Institution of Clinical Sciences, Lund University Hospital, Lund, Sweden (P.O.G.); and Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (N.V.O.).
authors.forename: Per Olof
authors.initials: PO
authors.lastname: Grände
authors.affiliation: From the Department of Neurosurgery, The Neuroscience Centre (R.R., M.J., J.S.-R.), Copenhagen Trial Unit, Centre for Clinical Intervention Research (J.W.), Department of Radiology, The Diagnostic Centre (T.S.), and Department of Neuroanesthesia, The Neuroscience Centre (N.V.O.), Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; Department of Anesthesia and Intensive Care, Institution of Clinical Sciences, Lund University Hospital, Lund, Sweden (P.O.G.); and Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark (N.V.O.).
authors.forename: Niels Vidiendal
authors.initials: NV
authors.lastname: Olsen
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000517:prevention & control*; D002533:Cerebral Angiography; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D011464:Epoprostenol / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D055420:Perfusion Imaging; D010865:Pilot Projects; D013345:Subarachnoid Hemorrhage / Q000000981:diagnostic imaging / Q000188:drug therapy*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000000981:diagnostic imaging / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D011464:Epoprostenol
keywords: epoprostenol; subarachnoid hemorrhage; vasospasm, intracranial