title: Bleeding and infection with external ventricular drainage: a systematic review in comparison with adjudicated adverse events in the ongoing Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR-III IHV) trial.
abstract: BACKGROUND
  Retrospective series report varied rates of bleeding and infection with external ventricular drainage (EVD). There have been no prospective studies of these risks with systematic surveillance, threshold definitions, or independent adjudication.
  
  
  OBJECTIVE
  To analyze the rate of complications in the ongoing Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III) trial, providing a comparison with a systematic review of complications of EVD in the literature.
  
  
  METHODS
  Patients were prospectively enrolled in the CLEAR III trial after placement of an EVD for obstructive intraventricular hemorrhage and randomized to receive recombinant tissue-type plasminogen activator or placebo. We counted any detected new hemorrhage (catheter tract hemorrhage or any other distant hemorrhage) on computed tomography scan within 30 days from the randomization. Meta-analysis of published series of EVD placement was compiled with STATA software.
  
  
  RESULTS
  Growing or unstable hemorrhage was reported as a cause of exclusion from the trial in 74 of 5707 cases (1.3%) screened for CLEAR III. The first 250 patients enrolled have completed adjudication of adverse events. Forty-two subjects (16.8%) experienced ≥1 new bleeds or expansions, and 6 of 250 subjects (2.4%) suffered symptomatic hemorrhages. Eleven cases (4.4%) had culture-proven bacterial meningitis or ventriculitis.
  
  
  CONCLUSIONS
  Risks of bleeding and infection in the ongoing CLEAR III trial are comparable to those previously reported in EVD case series. In the present study, rates of new bleeds and bacterial meningitis/ventriculitis are very low despite multiple daily injections, blood in the ventricles, the use of thrombolysis in half the cases, and generalization to >60 trial sites.
authors: ‡Section of Neurosurgery and Neurovascular Surgery Program, Division of Biological Sciences and the Pritzker School of Medicine, University of Chicago, Chicago, Illinois; §Pritzker School of Medicine, University of Chicago, Chicago, Illinois; ¶Johns Hopkins Medicine, Baltimore, Maryland; ‖Boston Medical Center, Boston, Massachusetts; #Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; **University of Maryland, Baltimore, Maryland; ‡‡Thomas Jefferson University, Philadelphia, Pennsylvania; §§University of Alberta, Edmonton, Alberta, Canada; ¶¶Stanford University, Stanford, California.
authors: Mahua
authors: M
authors: Dey
authors: Agnieszka
authors: A
authors: Stadnik
authors: Fady
authors: F
authors: Riad
authors: Lingjiao
authors: L
authors: Zhang
authors: Nichol
authors: N
authors: McBee
authors: Carlos
authors: C
authors: Kase
authors: J Ricardo
authors: JR
authors: Carhuapoma
authors: Malathi
authors: M
authors: Ram
authors: Karen
authors: K
authors: Lane
authors: Noeleen
authors: N
authors: Ostapkovich
authors: Francois
authors: F
authors: Aldrich
authors: Charlene
authors: C
authors: Aldrich
authors: Jack
authors: J
authors: Jallo
authors: Ken
authors: K
authors: Butcher
authors: Ryan
authors: R
authors: Snider
authors: Daniel
authors: D
authors: Hanley
authors: Wendy
authors: W
authors: Ziai
authors: Issam A
authors: IA
authors: Awad
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D002543:Cerebral Hemorrhage / Q000601:surgery; D002552:Cerebral Ventricles / Q000601:surgery; D002557:Cerebrospinal Fluid Shunts / Q000009:adverse effects / Q000379:methods; D004322:Drainage / Q000009:adverse effects / Q000379:methods; D004660:Encephalitis / Q000453:epidemiology / Q000209:etiology; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects; D015912:Thrombolytic Therapy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
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