A Cohort Study of the Safety and Feasibility of Intraventricular Urokinase for Nonaneurysmal Spontaneous Intraventricular Hemorrhage

Abstract

Background and Purpose-Small case series have reported potential benefit from thrombolysis after spontaneous intraventricular hemorrhage (IVH). Our objective was to review our experience using intraventricular urokinase (UK) in treating selected patients with IVH. Methods-Using medical records, we identified all patients who received ventriculostomies for CT-confirmed nonaneurysmal nontraumatic spontaneous IVH from December 1992 through November 1996. We reviewed charts and CT images and examined the data for associations with specific outcomes. Results-We identified 40 patients, 18 treated with ventriculostomy alone and 22 receiving adjunctive intraventricular UK.The initial Glasgow Coma Scale (GCS) scores of the two groups were similar (Pϭ0.5). While there was a trend for patients with any intraparenchymal hemorrhage (IPH) to receive UK (Pϭ0.07), the mean size of IPH in those who received ventriculostomy alone was larger than in those who received adjunctive UK (Pϭ0.002). There was lower mortality in the group treated with UK (31.8 versus 66.7%; Pϭ0.03), but there was only a trend toward an increase in favorable outcome (22.2% versus 36.4%; Pϭ0.3). Overall, the most significant association with outcome was neurological condition at presentation (GCS Ͼ5 versus Յ5; Pϭ0.003). Receiving UK did not increase the occurrence of complications or hospital length of stay for survivors (Pϭ0.5). Conclusions-Intraventricular UK remains a safe and potentially beneficial intervention. While it appeared to lower mortality, a randomized, placebo-controlled trial is needed to explore whether the therapy can increase the incidence of favorable outcomes.

External ventricular drainage alone versus endoscopic surgery for severe intraventricular hemorrhage: a comparative retrospective analysis on outcome and shunt dependency

“…41,49 Hematoma and perihematoma regions after intracerebral hemorrhage are biochemically active environments known to undergo potent oxidizing reactions. 9,11 After ICH, amounts of unconjugated bilirubin in the hematoma can be substantial, as can levels of iron and hemoglobin. 11 Oxidation of unconjugated bilirubin to yield bioactive molecules, such as BOXes (bilirubin oxidation products), is an important discovery, expanding the role of bilirubin in pathological processes seen after ICH.…”

“…9,11 After ICH, amounts of unconjugated bilirubin in the hematoma can be substantial, as can levels of iron and hemoglobin. 11 Oxidation of unconjugated bilirubin to yield bioactive molecules, such as BOXes (bilirubin oxidation products), is an important discovery, expanding the role of bilirubin in pathological processes seen after ICH. Blood degradation products are responsible for oxidative stress in brain surrounding the hematoma, and the spreading through the CSF may be responsible for late damage to the ventricle-facing structures.…”

“…Thrombolytic therapy was found to result in significantly lower mortality (31.8% vs 66.7%; p = 0.03). Previous reports that have included a control group 11 or comparison group 39,43,48 in their analysis have similarly reported that treatment with intraventricular u-PA in patients with IVH reduces mortality by 30%-35%. What is not clear from the literature, however, is whether such treatment results in an improved neurological outcome of the survivors.…”

“…24 Blood may remain for weeks after hemorrhage; acute clots obstruct ventricular CSF pathways, and clot degradation products obstruct extraventricular CSF pathways. When present, blood degradation products continue to contribute to patients' poor clinical statuses 5,6,[9][10][11] and are responsible for chronic shunt-dependent hydrocephalus in more than 30% of them. [15][16][17]30 At present, reduction in the ventricular clot size seems to be the only method for reducing mortality rates after the ICH has stabilized.…”

“…Tush et al 48 have been the only authors to report complications encountered with intraventricular u-PA, including 1 case of rebleeding and 2 cases of ventriculitis (in a series of 5 patients). Coplin et al 11 conducted a retrospective cohort study in 1998, which included the largest number of patients thus far treated with intraventricular u-PA under a given protocol. Similar to other reports, the median time for clearance of blood from the third ventricle was 7.0 days and that from the lateral ventricles was 16.0 days.…”