Intraventricular thrombolysis speeds blood clot resolution: results of a pilot, prospective, randomized, double-blind, controlled trial.
OBJECTIVE
Animal models and clinical studies suggest that intraventricular thrombolysis improves clot resolution and clinical outcomes among patients with intraventricular hemorrhage. However, this intervention may increase the rates of rebleeding and infection. To assess the safety and efficacy of intraventricular thrombolysis, we conducted a pilot, randomized, double-blind, controlled, multicenter study.


METHODS
Patients with intraventricular hemorrhage requiring ventriculostomy were randomized to receive intraventricular injections of normal saline solution or urokinase (25000 international units) at 12-hour intervals. Injections continued until ventricular drainage was discontinued according to prespecified clinical criteria. Head computed tomographic scans were obtained daily, for quantitative determinations of intraventricular hemorrhage volumes. The rate of clot resolution was estimated for each group.


RESULTS
Twelve subjects were enrolled (urokinase, seven patients; placebo, five patients). Commercial withdrawal of urokinase precluded additional enrollment. The urokinase and placebo groups were similar with respect to age (49.6 versus 55.2 yr, P = 0.43) and presenting Glasgow Coma Scale scores (7.14 versus 8.00, P = 0.72). Randomization to the urokinase treatment arm (P = 0.02) and female sex (P = 0.008) favorably affected the clot resolution rate. The sex-adjusted clot half-life for the urokinase-treated group was reduced 44.6%, compared with the value for the placebo group (4.69 versus 8.48 d).


CONCLUSIONS
Intraventricular thrombolysis with urokinase speeds the resolution of intraventricular blood clots, compared with treatment with ventricular drainage alone.
Naff
Neal J
NJ
Department of Neurosurgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. nnaff@hotmail.com
Hanley
Daniel F
DF
Keyl
Penelope M
PM
Tuhrim
Stanley
S
Kraut
Michael
M
Bederson
Joshua
J
Bullock
Ross
R
Mayer
Stephan A
SA
Schmutzhard
Eric
E
D000328:Adult; D000368:Aged; D001810:Blood Volume / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002552:Cerebral Ventricles; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007276:Injections, Intraventricular; D020766:Intracranial Embolism / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D015912:Thrombolytic Therapy / Q000379:methods*; D014057:Tomography, X-Ray Computed; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D014696:Ventriculostomy
D014568:Urokinase-Type Plasminogen Activator