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Neurocritical Care
Published in: Neurocritical Care 2/2014

01-10-2014 | Original Article

Intraventricular Tissue Plasminogen Activator in Subarachnoid Hemorrhage Patients: A Prospective, Randomized, Placebo-Controlled Pilot Trial

Authors: Andreas H. Kramer, Derek J. Roberts, Jessalyn Holodinsky, Stephanie Todd, Michael D. Hill, David A. Zygun, Peter Faris, John H. Wong

Published in: Neurocritical Care | Issue 2/2014

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Abstract

Background

The quantity of subarachnoid (SAH) and intraventricular hemorrhage (IVH) occurring in the setting of a ruptured cerebral aneurysm is strongly associated with subsequent complications and poor outcomes.

Methods

We randomly allocated aneurysmal SAH patients with a modified Fisher score of 4, who had been treated with endovascular coil embolization and ventricular drainage, to receive either 2 mg intraventricular tissue plasminogen activator (TPA) every 12 h (maximum 10 mg) or placebo. Computed tomography scans were performed 12, 48, and 72 h after administration. Primary outcomes included feasibility (enrollment and consent rates), safety (assessed by prospectively screening for complications), and rate of intracranial blood clearance (measured using sequential IVH, modified Graeb, and SAH sum scores). Secondary outcomes included angiographic vasospasm, delayed cerebral ischemia, need for ventriculoperitoneal shunting, and 6-month neurological outcomes.

Results

Seventy-seven patients were screened, 17 were eligible, and 12 were randomized. The consent rate was 87 %. There were no cases of new intracranial hemorrhage complicating use of TPA. Models fit using generalized estimating equations demonstrated more rapid reduction in IVH volume (p = 0.009), modified Graeb score (p < 0.001), and SAH sum score (p < 0.001) among patients treated with TPA. SAH clearance at 48 h was enhanced by earlier drug administration (p = 0.02). There were no differences in secondary outcomes.

Conclusions

Intraventricular TPA accelerates clearance of SAH and IVH, especially when administered early. A larger-scale clinical trial of intraventricular TPA is feasible, will need to be conducted at multiple centers, and is required to determine whether this practice reduces complications and improves outcomes.
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Metadata
Title
Intraventricular Tissue Plasminogen Activator in Subarachnoid Hemorrhage Patients: A Prospective, Randomized, Placebo-Controlled Pilot Trial
Authors
Andreas H. Kramer
Derek J. Roberts
Jessalyn Holodinsky
Stephanie Todd
Michael D. Hill
David A. Zygun
Peter Faris
John H. Wong
Publication date
01-10-2014
Publisher
Springer US
Published in
Neurocritical Care / Issue 2/2014
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-014-9965-z

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