Phase I study of intraventricular recombinant tissue plasminogen activator for treatment of posthaemorrhagic hydrocephalus

Abstract

Aim - Phase I study to evaluate intraventricular fibrinolytic treatment with recombinant tissue plasminogen activator (tPA) as a method of clearing blood from the cerebrospinal fluid, and thus preventing permanent hydrocephalus. Methods - Twenty two preterm infants, aged 7 to 26 days, with progressive post; haemorrhagic ventricular dilatation (ventricular width > 4 mm over 97th centile) received one to five intraventricular bolus injections of 1.0 mg or 0.5 mg tPA at intervals of one to seven days. Results - The mean cerebrospinal fluid concentration of tPA 24 hours after 1 mg was 1860 μg/ml. The half life of tPA in cerebrospinal fluid was about 24 hours. Twenty one (95%) infants survived, 12 (55%) without shunt surgery. One infant had secondary intraventricular haemorrhage. Conclusion T-traventricular tPA resulted in survival without a shunt for most-of the infants, but with some risk. Failure may have been due to plasminogen deficiency, an inhibitor, or late intervention.