Intraventricular Fibrinolysis Does Not Increase Perihemorrhagic Edema After Intracerebral Hemorrhage

Abstract

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

Fibrinolysis for Intraventricular Hemorrhage

“…Of the remaining 31 articles, 9 were excluded for the following reasons: 3 studies were excluded because they had no control group [20][21][22] and 6 studies were excluded because there was insufficient information for analysis. [23][24][25][26][27][28] One study identified through the previous meta-analysis was unpublished data and excluded from our analysis. Two additional studies were incorporated from a search of the reference lists of inclusion articles, resulting in 24 studies eligible for analysis ( Figure 1).…”

Current management of spontaneous intracerebral haemorrhage

“…Intraventricular fibrinolysis with rtPA was an emerging therapy for clearing IVH as soon as possible. It was shown to clear IVH without increasing perihaemorrhagic oedema 40. Recently, a large, phase III, multicentre, randomised, placebo controlled clinical trial evaluating the use of intraventricular tPA administration in patients with IVH has completed enrolment.…”

Protease activated receptor 1 (PAR1) enhances Src-mediated tyrosine phosphorylation of NMDA receptor in intracerebral hemorrhage (ICH)

“…As a first identified receptor of thrombin, PAR1 is one of the most important PARs involved in neurotoxicity and neuronal apoptosis 31 32 . Studies showed that excess thrombin could induce neurotoxic effects and neuronal apoptosis via PAR1 activation 33 34 35 36 . Based on these lines of evidence, we speculated that thrombin directly activated PAR1 in the course of ICH, leading to the activation of a series of downstream signaling pathways that mediate ICH injuries.…”