Neurocritical Care

, Volume 18, Issue 3, pp 354–361 | Cite as

No Exacerbation of Perihematomal Edema with Intraventricular Tissue Plasminogen Activator in Patients with Spontaneous Intraventricular Hemorrhage

  • Wendy Ziai
  • Tom Moullaali
  • Saman Nekoovaght-Tak
  • Natalie Ullman
  • Jay S. Brooks
  • Timothy C. Morgan
  • Daniel F. Hanley



In severe spontaneous intraventricular hemorrhage (IVH), intraventricular (IVR) administration of tissue plasminogen activator (rtPA) clears blood from the ventricles more rapidly than with external ventricular drainage (EVD) alone. However, experimental studies suggest tPA may be neurotoxic in compromised brain tissue and may exacerbate perihematomal edema.


We used computerized volumetrics to assess change in intracerebral hemorrhage (ICH), IVH, ventricular, and perihematomal edema (PHE) volumes at 2–4 (T1) and 5–9 (T2) days following diagnostic CT scans (T0) of 24 patients (12 tPA-treated; 12 controls) with IVH requiring EVD. Controls from a hospital registry were matched by IVH and ICH volume to tPA-treated patients who came from a multicenter trial involving 52 patients with IVH.


There were no significant differences between matched pairs in admission ICH and IVH volumes. IVR tPA resulted in more rapid clearance of IVH as determined by T2–T0 decrease in median IVH volume (tPA: −18.7 cc, iqr 14.9; control:−6.9 cc, iqr 6.4; P = 0.002). Median ratios of PHE to ICH volume were not significantly different in control versus tPA-treated patients at T1 and T2 [control:tPA = 0.55:0.56 (T1); P = 0.84 and 0.81:0.71 (T2); P = 1.00]. Total ventricular volume was significantly larger in the control group at T2 (mean: 57.57 ± 10.32 vs. tPA: 24.80 ± 2.67 cc; P = 0.01). Bacterial ventriculitis was more frequent in the control group (5 vs. 1 episodes; P = 0.06) as was shunt dependence (4 vs. 0 cases; P = 0.03).


For case matched large IVH with small ICH volume, IVR tPA enhances lysis of intraventricular blood clots and has no significant impact on PHE.


Intracerebral hemorrhage Intraventricular fibrinolysis Intraventricular hemorrhage Perihemorrhagic edema Recombinant tissue-type plasminogen activator Computed tomography 



The CLEAR B study was funded by the Food and Drug Administration, Division of Orphan Products, and National Institutes of Health ( Identifier: NCT00650858). DFH is funded by CLEAR III 5U01-NS062851-03, and MISITE II 5R01-NS046309-07.

Conflict of interest



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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Wendy Ziai
    • 1
  • Tom Moullaali
    • 2
  • Saman Nekoovaght-Tak
    • 2
  • Natalie Ullman
    • 2
  • Jay S. Brooks
    • 2
  • Timothy C. Morgan
    • 2
  • Daniel F. Hanley
    • 2
  1. 1.Division of Neurosciences Critical Care, Departments of Neurology, Anesthesia and Critical Care MedicineThe Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Division of Brain Injury Outcomes, Department of NeurologyThe Johns Hopkins University School of MedicineBaltimoreUSA

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