Objective: To evaluate intraventricular fibrinolytic treatment with recombinant tissue plasminogen activator (tPA) as a method of clearing blood from the CSF and thus preventing permanent hydrocephalus.

Methods: 22 preterm infants aged 7 to 26 days with progressive posthemorrhagic ventricular dilatation (ventricular width >4 mm over 90th centile) received between 1 and 5 intraventricular bolus injections of 1.0 mg or 0. 5 mg tPA at intervals of 1- 7 days. Pharmacokinetics of tPA in CSF were studied using an ELISA technique.

Results: Mean CSF concentration of tPA 24 hours after 1 mg was 1860 μg/ml. The half life of tPA in CSF was approximately 24 hours. 21(95%) infants survived, 12 without shunt surgery (55%). The proportion avoiding shunt surgery or death was significantly better than historical controls with identical inclusion criteria (29%). One infant had secondary intraventricular hemorrhage which was easily managed. No infant had systemic bleeding but two infants had laboratory evidence of a systemic fibrinolytic effect.

Conclusion: Intraventricular tPA therapy resulted in survival without a shunt for a majority of infants. Treatment failure is common and may be due to lack of plasminogen in the CSF, poor penetration of tPA into the thrombi, the presence of an inhibitor of fibrinolysis or treatment starting too late to prevent arachnoiditis.