title: Locally-administered intrathecal thrombolytics following aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.
abstract: BACKGROUND
  The volume and clearance rate of blood in the basal cisterns and ventricles are important predictors of complications following aneurysmal subarachnoid hemorrhage (SAH). Thus, there is a strong rationale for interventions aimed at accelerating the clearance of blood.
  
  
  METHODS
  We systematically searched MEDLINE, EMBASE, Cochrane databases, references of review articles and gray literature sources to identify randomized controlled trials (RCTs) assessing the efficacy of locally-administered, intrathecal thrombolytics in patients with SAH. Primary outcomes included the occurrence of poor neurologic recovery and delayed neurologic deficits (DNDs). Secondary outcomes included angiographic vasospasm, chronic hydrocephalus and treatment-related complications. Data were extracted and appraised independently and in duplicate, using standardized forms. Fixed or random effects models, as appropriate based on the degree of study heterogeneity were applied to calculate summary measures.
  
  
  RESULTS
  Five RCTs, enrolling 465 patients, met eligibility criteria. The methodology, results and risk of bias varied considerably across individual studies. Overall, use of intrathecal thrombolytics was associated with significant reductions in the development of poor outcomes (OR 0.52, 0.34-0.78, P < 0.01), DNDs (OR 0.54, 0.34-0.87, P = 0.01), angiographic vasospasm (OR 0.32, 0.15-0.70, P < 0.01) and chronic hydrocephalus (OR 0.33, 0.15-0.74, P < 0.01), without any increment in hemorrhagic or infectious complications. These findings were dampened by the exclusion of a study which concomitantly administered intrathecal vasodilators and thrombolytics.
  
  
  CONCLUSIONS
  Current data suggests that intrathecal thrombolytics improve outcomes following SAH. However, there are important limitations to existing RCTs, with considerable risk of bias. Further standardization of techniques and evaluation in larger, more rigorous RCTs is required.
authors.affiliation: Departments of Critical Care Medicine & Clinical Neurosciences, University of Calgary, Room EG23 J, Foothills Medical Center, 403 29th St NW, Calgary, AB T2N 2T9, Canada. Andreas.Kramer@AlbertaHealthServices.ca
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Kramer
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fletcher
mesh_terms: D001925:Brain Damage, Chronic / Q000401:mortality / Q000517:prevention & control; D002533:Cerebral Angiography; D002908:Chronic Disease; D003428:Cross Infection / Q000401:mortality / Q000517:prevention & control; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D017052:Hospital Mortality; D006801:Humans; D006849:Hydrocephalus / Q000401:mortality / Q000517:prevention & control; D007278:Injections, Spinal; D002532:Intracranial Aneurysm / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D016032:Randomized Controlled Trials as Topic; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000401:mortality / Q000517:prevention & control
chemical_list: D005343:Fibrinolytic Agents