Exacerbation of perihematomal edema and sterile meningitis with intraventricular administration of tissue plasminogen activator in patients with intracerebral hemorrhage

Neurosurgery. 2010 Apr;66(4):648-55. doi: 10.1227/01.NEU.0000360374.59435.60.


Objective: Intraventricular hemorrhage (IVH) is associated with a poor outcome. External ventricular drainage together with clot lysis through intrathecal tissue plasminogen activator (IT-tPA) has been proposed as a promising therapy. However, recent experimental work has implicated tissue plasminogen activator (tPA) in the pathogenesis of cerebral edema.

Methods: We reviewed the records of all patients with IVH caused by primary supratentorial intracerebral hemorrhage who underwent external ventricular drainage without surgical evacuation between January 2001 and June 2008. Of these 30 patients, we identified 13 who received IT-tPA. The remaining 17 patients served as controls. Hemorrhage, edema volume, and IVH score were determined on admission and by follow-up computed tomographic scans for 96 hours after admission. Discharge outcome was evaluated using the modified Rankin Scale.

Results: There were no significant differences between the treatment and controls in terms of age, Glasgow Coma Scale score, Graeb and LeRoux IVH scores, or intracerebral hemorrhage volume on admission. IT-tPA resulted in more rapid clearance of IVH as determined by the 96-hour decrease in both the Graeb IVH score (tPA, 3.00 +/- .55; control, 1.00 +/- 0.57; P = .05) and the LeRoux IVH score (tPA, 6.2 +/- 0.80; control, 2.25 +/- 1.32; P = .05). Patients treated with IT-tPA demonstrated significantly larger peak ratios of edema to intracerebral hemorrhage volume (1.24 +/- 0.14 vs 0.70 +/- 0.08 in controls; P = .002). Additionally, increased rates of sterile meningitis (46% vs 12%; P = .049) and a trend toward shunt dependence (38% vs 6%; P = .06) were observed in the tPA cohort. Nevertheless, no significant differences in outcome at discharge or length of hospital stay were observed between cohorts.

Conclusion: Although IT-tPA hastens the resolution of IVH, it may worsen perihematomal edema formation. Larger prospective studies are required to confirm these findings and to determine whether outcome is adversely affected by IT-tPA administration.

MeSH terms

  • Brain Edema / etiology*
  • Cerebral Hemorrhage / drug therapy*
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Humans
  • Injections, Intraventricular / adverse effects*
  • Injections, Intraventricular / methods
  • Magnetic Resonance Imaging / methods
  • Male
  • Meningitis / etiology*
  • Middle Aged
  • Retrospective Studies
  • Time Factors
  • Tissue Plasminogen Activator / administration & dosage*
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome


  • Fibrinolytic Agents
  • Tissue Plasminogen Activator