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      Safety and Efficacy of Transcatheter Administration of Tissue Plasminogen Activating Factor as Adjuvant Therapy for Intraventricular Hemorrhage

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          Abstract

          Objective

          Stroke is the fifth leading cause of death in the United States and the leading cause of disability. Hemorrhagic stroke has higher risks of mortality and neurologic deficit. Higher still, acute intraventricular hemorrhage (IVH) has mortality between 50% and 80% while complicating subarachnoid hemorrhage in 15% of cases and intracerebral hemorrhage in 40% of cases. We sought to demonstrate that early adjuvant intraventricular recombinant tissue plasminogen activating factor (rt-PA) improved outcomes.

          Methods

          Retrospective chart review was performed on patients aged 18-95 years with external ventricular drain (EVD) and intraventricular rt-PA for clot evacuation in IVH between 2005 and 2015. In total, 22 patients met the inclusion criteria. Generalized linear modeling was performed with factorial analysis using the Glasgow Coma Score (GCS) on arrival, GCS at EVD placement, EVD day of onset of rt-PA administration, GCS at onset of rt-PA administration, total duration of EVD, necessity of ventriculoperitoneal (VP) shunt, occurrence of ventriculitis, day of ventriculitis, GCS after rt-PA, length of stay (LOS) in the intensive care unit (ICU), and hospital disposition.

          Results

          Presenting GCS affected LOS significantly. Ventriculitis only significantly affected ICU LOS. GCS after rt-PA only significantly affected discharge GCS. EVD day of rt-PA protocol commencement demonstrated significant effects on EVD duration and cerebrospinal fluid (CSF) diversion requirement. Age affected ICU and hospital LOS.

          Conclusion

          These findings argue for larger prospective trials of EVD day two rt-PA protocol inception in acute IVH. Reported ventriculitis rates with EVDs are 8.8%, while we demonstrated a rate of 18% without significant effects except in ICU LOS. Transcatheter intraventricular rt-PA is safe and effective as an adjuvant in acute spontaneous intraventricular hemorrhage with the greatest benefit of rt-PA protocol at EVD day two.

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          Most cited references27

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          Meningiomas: the role of preoperative angiography and embolization.

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            Intraventricular thrombolysis speeds blood clot resolution: results of a pilot, prospective, randomized, double-blind, controlled trial.

            Animal models and clinical studies suggest that intraventricular thrombolysis improves clot resolution and clinical outcomes among patients with intraventricular hemorrhage. However, this intervention may increase the rates of rebleeding and infection. To assess the safety and efficacy of intraventricular thrombolysis, we conducted a pilot, randomized, double-blind, controlled, multicenter study. Patients with intraventricular hemorrhage requiring ventriculostomy were randomized to receive intraventricular injections of normal saline solution or urokinase (25000 international units) at 12-hour intervals. Injections continued until ventricular drainage was discontinued according to prespecified clinical criteria. Head computed tomographic scans were obtained daily, for quantitative determinations of intraventricular hemorrhage volumes. The rate of clot resolution was estimated for each group. Twelve subjects were enrolled (urokinase, seven patients; placebo, five patients). Commercial withdrawal of urokinase precluded additional enrollment. The urokinase and placebo groups were similar with respect to age (49.6 versus 55.2 yr, P = 0.43) and presenting Glasgow Coma Scale scores (7.14 versus 8.00, P = 0.72). Randomization to the urokinase treatment arm (P = 0.02) and female sex (P = 0.008) favorably affected the clot resolution rate. The sex-adjusted clot half-life for the urokinase-treated group was reduced 44.6%, compared with the value for the placebo group (4.69 versus 8.48 d). Intraventricular thrombolysis with urokinase speeds the resolution of intraventricular blood clots, compared with treatment with ventricular drainage alone.
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              Intraventricular fibrinolysis versus external ventricular drainage alone in intraventricular hemorrhage: a meta-analysis.

              The purpose of this study was to analyze the effect of intraventricular fibrinolysis (IVF) compared with external ventricular drainage alone on mortality and functional outcome in the management of intraventricular hemorrhage secondary to spontaneous supratentorial intracerebral hemorrhage. The authors conducted a systematic review and performed a meta-analysis. They reviewed the PubMed, Cochrane Library, and Liliacs databases. In addition, they conducted a manual review of article bibliographies. Using a prespecified search strategy, 4 randomized and 8 observational studies were included in a meta-analysis. These studies involved a total of 316 patients with intraventricular hemorrhage at baseline, of whom 167 had IVF (52.8%). Pooled odds ratios of the impact of IVF on patient mortality, functional outcomes, and complications were calculated. The overall mortality risk decreased from 46.7% in the external ventricular drainage alone group to 22.7% in the external ventricular drainage+IVF group, corresponding to an overall pooled Peto OR of 0.32 (95% CI, 0.19 to 0.52). This result was highly significant with urokinase, not with recombinant tissue-type plasminogen activator. IVF was also associated with an increase in good functional outcome. There was no difference between the 2 groups in terms of shunt dependence and complications. The combination of IVF and external ventricular drainage in the management of severe intraventricular hemorrhage secondary to small intracerebral hemorrhage in young patients was associated with better survival and functional outcome results. Urokinase and recombinant tissue-type plasminogen activator could not have the same therapeutic effects. Well-designed randomized trials with special considerations to the fibrinolytic agents are needed.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                27 September 2019
                September 2019
                : 11
                : 9
                : e5785
                Affiliations
                [1 ] Neurosurgery, Riverside University Health System Medical Center, Moreno Valley, USA
                [2 ] Neurosurgery, Arrowhead Regional Medical Center, Colton, USA
                Author notes
                Article
                10.7759/cureus.5785
                6825502
                b534cb2d-e20c-4d47-8dcd-08f545004cd4
                Copyright © 2019, Krel et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 February 2019
                : 27 September 2019
                Categories
                Neurosurgery

                cerebrovascular accident,cerebral hemorrhage,intraventricular injections,tpa,intraventricular hemorrhage,intracranial hemorrhage

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