• C O Andrews and H H Engelhard.
• Department of Pharmacy Practice, College of Pharmacy, The University of Illinois at Chicago, 60612-7329, USA. coandrews1@juno.com
• Ann Pharmacother. 2001 Nov 1; 35 (11): 1435-48.

ObjectiveTo review the literature concerning intraventricular administration of fibrinolytic agents to treat patients with intraventricular hemorrhage (IVH).Data SourcesAn extensive literature search (MEDLINE, EMBASE, Conference Proceedings) was conducted to identify articles in English published between 1966 and May 2000 pertaining to the pathophysiology of IVH and its treatment by intraventricular administration of recombinant tissue plasminogen activator (alteplase) or urokinase (u-PA). The bibliographies of selected identified articles were also screened for publications not found in the computerized search.Study SelectionAll pertinent publications were reviewed and considered. Those describing the intraventricular administration of fibrinolytic agents to patients with IVH were included.Data SynthesisIVH has a poor prognosis, partly due to the mass effect of blood clots on the ventricular walls. The cerebrospinal fluid has a limited fibrinolytic system. Therefore, clots may remain in the ventricles for months after a hemorrhage. The management of IVH is primarily directed at controlling intracranial pressure through an external ventricular drain, but this catheter often becomes occluded by coagulated blood. To overcome this problem, and to dissolve the residual blood clot, investigators have administered alteplase or u-PA directly into the ventricles of patients with IVH. Complications of this therapy include infection and possible rebleeding. Clinical studies of fibrinolytic therapy for IVH have found a 30-35% reduction in mortality with treatment, but to date, have not clearly documented improved neurologic outcome of the survivors.ConclusionsFibrinolytic therapy with alteplase or u-PA may be life-saving in severe cases of IVH. Yet many technical issues remain to be resolved, such as the optimal dose, frequency, method, timing, and duration of administration of the agent. Additional randomized, double-blind, placebo-controlled studies need to be performed so that the true value of this therapy can be assessed.

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