Local Fibrinolytic Therapy for Intraventricular Hemorrhage: A Meta-Analysis of Randomized Controlled trials

The safety and efficacy of intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) are unclear. We aimed to determine these issues and to evaluate whether there are differences between recombinant tissue-plasminogen activator (rt-PA) and urokinase according to subgroup analyses.

A meta-analysis was undertaken of randomized controlled trials in patients with IVH that compared the administration of rt-PA or urokinase through extraventricular drainage (EVD) with normal saline through EVD or EVD placement alone.

Six randomized controlled trials involving 607 patients with IVH were included; 2 trials investigated urokinase and 4 rt-PA. IVF reduced death from any cause at the end of follow-up (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.47-0.83), which was driven mostly by rt-PA (RR 0.65, 95% CI 0.48-0.86). Urokinase did not reduce mortality (RR 0.30, 95% CI 0.06-1.53). However, rt-PA did not reduce the proportion of survivors with poor functional outcome (RR 1.36, 95% CI 1.04-1.77), or the composite endpoint of death and poor functional outcome (RR 0.96, 95% CI 0.83-1.11). IVF neither reduced the need for shunt placement (RR 1.06, 95% CI 0.75-1.49) nor increased ventriculitis (RR 0.57, 95% CI 0.35-0.93) and rebleeding (RR 1.65, 95% CI 0.79-3.45).

Although the use of IVF in patients with IVH appears generally safe, its benefit is limited to a reduction in mortality at the expense of an increased number of survivors with moderately-severe to severe disability. Subgroup analyses do not suggest an advantage of IVF with urokinase over rt-PA.