Exacerbation of Perihematomal Edema and Sterile Meningitis With Intraventricular Administration of Tissue Plasminogen Activator in Patients With Intracerebral Hemorrhage

Ducruet, Andrew F; Hickman, Zachary L.; Zacharia, Brad E.; Grobelny, Bartosz T.; Narula, Reshma; Guo, Kuang Hua; Claassen, Jan; Lee, Ki-Won; Badjatia, Neeraj; Mayer, Stephan A.; Connolly, E. Sander

doi:10.1227/01.neu.0000360374.59435.60

Cited by 42 publications

(31 citation statements)

References 31 publications

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“…When comparing those results with the present study, several important differences should be considered. First, the mean ICH volume in the treatment and control group of Ducruet et al 14 was larger compared with our cohort. Moreover, there was an imbalance in the ICH size between the 2 groups, although the difference was not significant.…”

Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 96%

“…6,22 Furthermore, Ducruet et al 14 also reported increased occurrence of aseptic meningitis in rtPA-treated patients. 14 In our study, only the occurrence of ventriculitis without any further differentiation was recorded, and no significant difference was found between patients treated with IVF and controls. In light of the relatively scarce experimental and clinical data, at this time, it still remains unclear whether mechanisms of rtPA-mediated neuronal damage, as described in ischemic injury, 22 play an important role in the setting of ICH with ventricular involvement.…”

Section: Discussionmentioning

confidence: 96%

“…17,21 Second, PHE is difficult to delineate and to assess on CT imaging. Ducruet et al 14 used the investigator-based ABC/2 method to determine ICH and PHE volumes on CT, which may have caused higher inaccuracy compared with the semiautomatic volumetric algorithm used in the present study. This algorithm has been developed within a prospective study and validated against PHE volume assessed on MRI.…”

Section: Discussionmentioning

confidence: 99%

“…Our finding is in contrast to the results of a previously published smaller study. 14 Ducruet et al 14 compared the evolution of PHE between 13 patients treated with intraventricular rtPA and 17 controls. The authors described significantly higher rPHE in patients treated with IVF.…”

Section: Discussionmentioning

confidence: 99%

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Intraventricular Fibrinolysis Does Not Increase Perihemorrhagic Edema After Intracerebral Hemorrhage

Volbers

Wagner

Willfarth

et al. 2013

Stroke

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PHE may play a role as a source of additional mass effect, especially in large ICH, and thereby lead to neurological Background and Purpose-Additional intraventricular hemorrhage leads to higher mortality and worse functional outcome after intracerebral hemorrhage (ICH). Intraventricular fibrinolysis (IVF) with recombinant tissue plasminogen activator (rtPA) is an emerging treatment strategy for such patients. However, experimental studies suggest that rtPA may exert proedematous effects and lead to increased perihemorrhagic edema (PHE) after ICH. We aimed to compare the course of PHE after ICH between patients who received IVF with rtPA and controls matched for ICH volume. Methods-Patients were identified retrospectively from our institutional ICH database. Sixty-four patients with ICH and intraventricular hemorrhage who were treated with IVF were compared with 64 controls, who did not receive IVF, matched for ICH volume. The course of PHE was assessed on computed tomography scans (day 1, days 2 and 3, days 4-6, 7-9, and 10-12) using a threshold-based semiautomatic volumetric algorithm. Relative PHE was calculated as a ratio of PHE volume and initial ICH volume. Results-The matching algorithm resulted in similar mean ICH volumes in both groups (20.01±17.5 mL, IVF vs 20.08±17.1 mL, control). Intraventricular hemorrhage volume was larger in the IVF group (26.8±19.2 mL vs 9.2±13.4 mL). The mean total rtPA dose used for IVF was 8±6 mg. PHE increased over time in both groups until day 12. At all investigated time points, there was no significant difference in relative PHE between the IVF group and controls (F=0.39; P=0.844). Conclusions-IVF

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Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Intraventricular Fibrinolysis Does Not Increase Perihemorrhagic Edema After Intracerebral Hemorrhage

Volbers

Wagner

Willfarth

et al. 2013

Stroke

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No exacerbation of perihematomal edema with intraclot urokinase in patients with spontaneous intracerebral hemorrhage

Lian

et al. 2014

Acta Neurochir

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Management of non-traumatic intraventricular hemorrhage

2012

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Intraventricular hemorrhage (IVH) is defined as the eruption of blood in the cerebral ventricular system and is mostly secondary to spontaneous intracerebral hemorrhage and aneurysmal and arteriovenous malformation rupture. IVH is a proven risk factor of increased mortality and poor functional outcome. Its seriousness is correlated not only with the amount of blood but also with the involvement of the third and fourth ventricles. There are four mechanisms that explain the pathophysiology of this event: acute obstructive hydrocephalus, the mass effect exerted by the blood clot, the toxicity of blood-breaking products on the adjacent brain parenchyma, and, lastly, the development of a chronic hydrocephalus. It is thus obvious that the clearance of blood from the ventricles should be a therapeutic goal. In cases of acute hydrocephalus, external ventricular drainage is a mandatory step, but proven often insufficient. The concomitant use of intraventricular fibrinolytics such as recombinant tissue plasminogen activator or urokinase seems to be beneficial at least in the context of spontaneous intracerebral hemorrhage, in which their use is now accepted but not yet validated by a randomized trial. Given the potential neurotoxicity of these agents, further research is needed in order to identify the best treatment for intraventricular fibrinolysis (IVF). The endoscopic retrieval of intraventricular blood was also described recently and seems to be as efficient as IVF, but its use is limited to specialized centers. IVH represents a therapeutic challenge for neurosurgeons, neurologists, and intensivists. Thus, a better understanding of this dramatic event will help in better tailoring the treatment strategies.

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Exacerbation of Perihematomal Edema and Sterile Meningitis With Intraventricular Administration of Tissue Plasminogen Activator in Patients With Intracerebral Hemorrhage

Abstract: Although IT-tPA hastens the resolution of IVH, it may worsen perihematomal edema formation. Larger prospective studies are required to confirm these findings and to determine whether outcome is adversely affected by IT-tPA administration.

Cited by 42 publications

References 31 publications

Intraventricular Fibrinolysis Does Not Increase Perihemorrhagic Edema After Intracerebral Hemorrhage

Intraventricular Fibrinolysis Does Not Increase Perihemorrhagic Edema After Intracerebral Hemorrhage

No exacerbation of perihematomal edema with intraclot urokinase in patients with spontaneous intracerebral hemorrhage

Management of non-traumatic intraventricular hemorrhage

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