Tissue plasminogen activator for the treatment of intraventricular hematoma: The dose–effect relationship

Wang, Yeou-Chih; Lin, Chi-Wen; Shen, Chiung‐Chyi; Lai, Shu-Chen; Kuo, Jon‐Son

doi:10.1016/s0022-510x(02)00243-5

Cited by 52 publications

(31 citation statements)

References 26 publications

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“…5 This aspect has not been sufficiently studied in the clinical setting. Another important issue is the concern of an increased risk of bleeding complications with higher IVF dosage, as recently reported from the dose-finding part of the CLEAR-IVH trial.…”

Section: Discussionmentioning

confidence: 99%

Dose Effect of Intraventricular Fibrinolysis in Ventricular Hemorrhage

Staykov

Wagner²,

Volbers³

et al. 2011

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Background and Purpose-The aim of the current study was to investigate the dose-dependent efficacy of intraventricular fibrinolysis (IVF) in patients with severe intraventricular hemorrhage (IVH). Methods-Patients with intracerebral hemorrhage, severe IVH, and obstructive hydrocephalus with the need for external ventricular drainage were treated with IVF through external ventricular drainage. The time course of IVH resolution and the safety profile were compared between patients treated with high-dose IVF (4 mg alteplase every 12 hours, maximum 20 mg; nϭ32) and low-dose IVF (1 mg alteplase every 8 hours, maximum 12 mg; nϭ22). CT scans on Days 1 to 4, 7Ϯ1 and 10Ϯ1 after admission, were analyzed volumetrically. Outcome was assessed after 3 months. Results-The overall effect of IVF dosage was not significantly different between the 2 groups (Fϭ1.3, Pϭ0.25). The course of IVH volume in the third and fourth ventricles was similar with high-and low-dose IVF. High-dose IVF resulted in lower total IVH volumes on Days 7 (4.4Ϯ4.2 mL versus 8.8Ϯ8.1 mL; Pϭ0.01) and 10 (1.4Ϯ2.8 mL versus 4.9Ϯ65.8 mL; Pϭ0.005). Total clot half-life was 78Ϯ43 hours in the low-dose and 56Ϯ25 hours in the high-dose group (Pϭ0.02). One asymptomatic ventricular bleeding, 2 cases of ventriculitis, and 1 death due to pulmonary embolism occurred in the high-dose group. There was no difference in outcome at 3 months. Conclusions-Low-dose IVF (3 mg alteplase/day) has a similar effect on IVH clearance from the third and fourth ventricles and a similar safety profile when compared with high-dose IVF (8 mg alteplase/day).

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Section: Discussionmentioning

confidence: 99%

Dose Effect of Intraventricular Fibrinolysis in Ventricular Hemorrhage

Staykov

Wagner²,

Volbers³

et al. 2011

Stroke

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“…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.…”

Section: Discussionmentioning

confidence: 98%

“…4 Apart from this injury mechanism, ventricular blood has been shown to exert a mass effect and reduce cerebral blood flow in the periventricular brain tissue in animal models of IVH. 5,6 Especially the so-caused damage of brain stem structures may explain the prognostic significance of third and fourth ventricle blood volume, demonstrated in clinical studies. 7,8 Finally, blood and its breakdown products cause inflammation of the ependymal layer and the subependymal brain tissue, 5,6,9 and also inflammation and fibrosis of the arachnoid mater, thereby leading to a delayed communicating hydrocephalus.…”

mentioning

confidence: 99%

“…5,6 Especially the so-caused damage of brain stem structures may explain the prognostic significance of third and fourth ventricle blood volume, demonstrated in clinical studies. 7,8 Finally, blood and its breakdown products cause inflammation of the ependymal layer and the subependymal brain tissue, 5,6,9 and also inflammation and fibrosis of the arachnoid mater, thereby leading to a delayed communicating hydrocephalus. 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.…”

mentioning

confidence: 99%

“…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. 6 Moreover, a recent small retrospective clinical study has indicated that there may be an increase in perihemorrhagic edema (PHE) in ICH patients treated with intraventricular rtPA.…”

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confidence: 99%

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Intraventricular Fibrinolysis Does Not Increase Perihemorrhagic Edema After Intracerebral Hemorrhage

Volbers

Wagner

Willfarth

et al. 2013

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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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