Intraventricular urokinase for the treatment of intraventricular hemorrhage

Introduction: Currently, there are no FDA approved drug treatments for intraventricular hemorrhage (IVH). Urokinase, a catalyst for the conversion of plasminogen to plasmin, may be effective in the lysis of intraventricular clots in patients with IVH. This retrospective study describes the use of intraventricular urokinase in patients with IVH and compares their outcomes to those who did not receive urokinase. Methods: A retrospective chart review was conducted on patients diagnosed with IVH within the past 3 years. Five patients received urokinase via a ventricular catheter for the treatment of IVH during this period of time. The doses ranged from 5000 to 10000 units intraventricularly once or twice daily for 2-10 days. Data from the urokinase treated patients were compared to data from a control group of four patients that were diagnosed with IVH and did not receive intraventricular urokinase. Results: The demographic data were similar in both the treatment and control groups, with the exception of admission Glasgow Coma Scale (GCS) scores. The treatment group had a mean GCS score of 8 (range 3-14) versus 12 (range 3-15) in the control group. The mean percent change in GCS score was 71% (range -21 to 233%) in the treatment group, with a larger value indicating improved neurological status. The mean percent change in GCS scores in the control group was -11% (range -80 to 36%). The mean percent decrease in ventricular clot volume was 50% versus 60% in the treatment and control group, respectively. The Glasgow Outcome Scale scores for the control group were better than the treatment group in patients that survived. A VP shunt was required in one patient in the control group. Two patients treated with urokinase developed CSF infections, while no CSF infections developed in the control group. One patient died from a second cerebral hemorrhage in the urokinase group. In the control group, one had no neurological improvement and life support withdrawn while another died of multi-organ system failure. Conclusion: Treatment with intraventricular urokinase showed a trend toward improved acute neurological recovery, worse long term neurological outcomes in survivors, decreased shunt requirements, and an increase in CSF infections in patients diagnosed with IVH. This pilot study is limited by a small sample size. Prospective, randomized, controlled trials in larger patient populations should be conducted to determine the benefits and risks of urokinase for the treatment of IVH.