Phase I study of intraventricular recombinant tissue plasminogen activator for treatment of posthaemorrhagic hydrocephalus.
OBJECTIVE
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 posthaemorrhagic 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 micrograms/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.


CONCLUSIONS
Intraventricular 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.
Whitelaw
A
A
Department of Paediatrics, Aker Hospital, University of Oslo, Norway.
Saliba
E
E
Fellman
V
V
Mowinckel
M C
MC
Acolet
D
D
Marlow
N
N
D002543:Cerebral Hemorrhage / Q000134:cerebrospinal fluid / Q000188:drug therapy; D006207:Half-Life; D006801:Humans; D006849:Hydrocephalus / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D007276:Injections, Intraventricular; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000627:therapeutic use*
D011994:Recombinant Proteins; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator