Prachi Mehndiratta, MD

Khan NR, Tsivgoulis G, Lee SL, Jones GM, Green CS, Katsanos AH, et al. Fibrinolysis for Intraventricular Hemorrhage: An Updated Meta-Analysis and Systematic Review of the Literature. Stroke. 2014

Intraventricular hemorrhage (IVH) results when parenchymal blood dissects or breaks the lining of the fluid filled cavities within the brain. IVH is associated with Intracerebral hemorrhage (ICH) in about 40% of cases and results in a varying but high mortality rate of 40-80%. When present, it requires placement of external ventricular drains to avoid complications such as hydrocephalus. The placement of such a drain for prolonged periods of time carries its own risks of infections such as ventricultis. Recently several studies such as the CLEAR IVH trial have been randomizing patients to receive intraventricular tissue plasminogen activator to decrease clot burden. The authors of this Meta analyses describe the pooled results of studies till date that have explored the use of intraventricular fibrinolysis (IVF).  

A total of 24 retrospective cohort, prospective cohort and randomized controlled studies that met the inclusion criteria of patients’ age >18years, non-traumatic IVH treated with IVF and provided control data were studied. Total sample size, number of patients in each arm, dosage and method of fibrinolysis, IVF complications and outcomes were carefully evaluated. The primary outcome was all cause mortality until one year after treatment whereas secondary outcome was defined as a good functional outcome (modified Rankin score 0-3), as well as lower rates of rehemorrhage, ventriculitis and shunt placement.

The pooled results were starkly in favor of IVF. There was a significantly decreased likelihood of mortality (RR= 0.55, 95%CI: 0.42-0.71; p<0.00001) with IVF and significantly increased likelihood of good functional outcome in the pooled analyses ((RR: 1.66, 95%CI: 1.27-2.19; p=0.0003). These results were primarily driven by the prospective and retrospective studies and only a trend towards significance was noted amongst randomized trials. There was no increase in the rates of ventriculitis, rehemorrhage or shunt requirement associated with IVF use.

These are promising results but should be understood with caution. The decreased relative risk for mortality and increased relative rate of good outcome were not observed in randomized studies. Additionally this Meta analyses represented a widely heterogeneous population with studies utilizing different fibrinolytics in varied doses. A well conducted randomized controlled trial would certainly provide some answers. Let us hope that our doubts about IVF are soon CLEARed.