title: Intraventricular tissue plasminogen activator in subarachnoid hemorrhage patients: a prospective, randomized, placebo-controlled pilot trial.
abstract: BACKGROUND
  The quantity of subarachnoid (SAH) and intraventricular hemorrhage (IVH) occurring in the setting of a ruptured cerebral aneurysm is strongly associated with subsequent complications and poor outcomes.
  
  
  METHODS
  We randomly allocated aneurysmal SAH patients with a modified Fisher score of 4, who had been treated with endovascular coil embolization and ventricular drainage, to receive either 2 mg intraventricular tissue plasminogen activator (TPA) every 12 h (maximum 10 mg) or placebo. Computed tomography scans were performed 12, 48, and 72 h after administration. Primary outcomes included feasibility (enrollment and consent rates), safety (assessed by prospectively screening for complications), and rate of intracranial blood clearance (measured using sequential IVH, modified Graeb, and SAH sum scores). Secondary outcomes included angiographic vasospasm, delayed cerebral ischemia, need for ventriculoperitoneal shunting, and 6-month neurological outcomes.
  
  
  RESULTS
  Seventy-seven patients were screened, 17 were eligible, and 12 were randomized. The consent rate was 87 %. There were no cases of new intracranial hemorrhage complicating use of TPA. Models fit using generalized estimating equations demonstrated more rapid reduction in IVH volume (p = 0.009), modified Graeb score (p < 0.001), and SAH sum score (p < 0.001) among patients treated with TPA. SAH clearance at 48 h was enhanced by earlier drug administration (p = 0.02). There were no differences in secondary outcomes.
  
  
  CONCLUSIONS
  Intraventricular TPA accelerates clearance of SAH and IVH, especially when administered early. A larger-scale clinical trial of intraventricular TPA is feasible, will need to be conducted at multiple centers, and is required to determine whether this practice reduces complications and improves outcomes.
authors.affiliation: Department of Critical Care Medicine, Foothills Medical Center, University of Calgary , McCaig Tower, 3134 Hospital Drive N.W., Calgary, AB, T2N 2T9, Canada, Andreas.Kramer@AlbertaHealthServices.ca.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Kramer
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Roberts
authors.forename: Jessalyn
authors.initials: J
authors.lastname: Holodinsky
authors.forename: Stephanie
authors.initials: S
authors.lastname: Todd
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hill
authors.forename: David A
authors.initials: DA
authors.lastname: Zygun
authors.forename: Peter
authors.initials: P
authors.lastname: Faris
authors.forename: John H
authors.initials: JH
authors.lastname: Wong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010919:Placebos; D011446:Prospective Studies; D011859:Radiography; D013345:Subarachnoid Hemorrhage / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010919:Placebos; D010959:Tissue Plasminogen Activator