Intraventricular Fibrinolysis for Intracerebral Hemorrhage with Severe Ventricular Involvement

Abstract

Intraventricular hemorrhage (IVH) has been associated with poor prognosis in patients with spontaneous intracerebral hemorrhage. Several factors contribute to the deleterious effects of IVH, including direct mass effects of the ventricular blood clot on ependymal and subependymal brain structures, mechanical and inflammatory impairment of the Pacchioni granulations by blood and its breakdown products, and disturbance of physiological cerebrospinal fluid (CSF) circulation. Acute obstructive hydrocephalus represents a major life-threatening complication of IVH and is usually treated with an external ventricular drainage (EVD). However, treatment with EVD alone is frequently not sufficiently effective due to obstruction of the catheter by blood. In the past two decades, intraventricular fibrinolysis (IVF) has been increasingly used for maintenance of EVD functionality and acceleration of ventricular clot resolution in such patients. Unfortunately, there is no prospective, randomized controlled trial addressing the effect of IVF on clinical outcome. The available data on IVF consist of small retrospective case series, case reports, and a few prospective case-control studies, which are the subject of the present review article. All these studies, when considered in their entirety, suggest that IVF has a positive impact on mortality and functional outcome, and could be considered as a treatment option for selected patients.

Early Quantification of Hematoma Hounsfield Units on Noncontrast CT in Acute Intraventricular Hemorrhage Predicts Ventricular Clearance after Intraventricular Thrombolysis

“…Several meta-analyses (on observational studies and small randomized trials) all suggested that intraventricular rtPA may be an effective strategy for reducing mortality and improving functional outcome, with the potential for decreasing permanent shunt rates without significant increase in complications. [19][20][21] Adverse events in this study were lower than the reported rates and support data showing that intraventricular fibrinolysis does not significantly increase the risk of rehemorrhage or infection. 21 The soonto-be-completed Phase III multinational, randomized controlled trial (Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage [CLEAR-III]) of 500 patients with primary or secondary spontaneous IVH randomized to intraventricular fibrinolysis with rtPA or placebo should provide the highest quality evidence on the benefits and complications of this treatment.…”

Intraventricular Fibrinolysis Does Not Increase Perihemorrhagic Edema After Intracerebral Hemorrhage

“…Moreover, IVF using rtPA has been mainly investigated and is currently being evaluated in smaller ICH (<30 mL in the ongoing multicenter phase III CLEAR-IVH trial). 11,12,19 Concerning secondary rebleeding, we could not find a significant difference between the IVF group and controls. Compared with the published results of the phases A and B of the CLEAR-IVH trial, 12 rebleeding was slightly less common in our study but comparable in the IVF group.…”

“…10 Considering those pathomechanisms, there seems to be a clear rationale for the fast removal of blood and blood breakdown products from the ventricular system. Intraventricular fibrinolysis (IVF), that is, the administration of fibrinolytic agents as recombinant tissue plasminogen activator (rtPA) into the ventricles, seems to be an emerging and promising treatment strategy, 11 which is currently being investigated in a large phase III multicenter trial (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage [CLEAR-III]). 12,13 In the context of IVF, rtPA toxicity has been a source of concern because animal studies have shown that rtPA may exert dose-dependent proedematous and neurotoxic effects.…”

Significance of Intraventricular Hemorrhage in Acute Intracerebral Hemorrhage

“…Although the literature is consistent for IVH being a predictor of poor outcome in ICH, [10][11][12][13][14][15] there is uncertainty on the strength and pattern of association. One study suggests a curvilinear relationship between IVH volume and 30-day mortality, with 10 to 15 mL of IVH proposed as an appropriate threshold for predicting poor outcome in patients with comatose state (Glasgow Coma Scale scores <8), 5 whereas another study indicates IVH volumes >20 mL as being relevant for survival.…”