Intrathecal Fibrinolysis for Aneurysmal Subarachnoid Hemorrhage: Evidence From Randomized Controlled Trials and Cohort Studies

Abstract

Background: The role of intrathecal fibrinolysis for the treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH) has been widely investigated; however, the results have been contradictory. In our study, we conducted a meta-analysis to evaluate the safety and efficacy of intrathecal (intracisternal or intraventricular) fibrinolysis for aSAH. Methods: PubMed, Web of Science, Embase, Medline, and the Cochrane library databases were searched up to February 1, 2019. The outcomes analyzed were neurologic recovery, delayed ischemic neurologic deficit (DIND), mortality, and the incidence of chronic hydrocephalus and hemorrhage. Results: A total of 21 studies comprising 1,373 patients were analyzed, including nine randomized controlled trials (RCTs) and 12 non-RCTs. The results showed that intracisternal fibrinolysis significantly decreased poor neurologic outcomes (RR = 0.62, 95% CI = 0.50–0.76, P < 0.001) and reduced the incidence of DIND (RR = 0.52, 95% CI = 0.41–0.65, P <0.001), chronic hydrocephalus (RR = 0.59, 95% CI = 0.42–0.82, P = 0.002) and mortality (RR = 0.58, 95% CI = 0.37, 0.93, P = 0.02). There was no significant difference in the occurrence of hemorrhage. Moreover, the results of the Egger test and Begg's funnel plot showed no evidence of publication bias. Conclusions: Current evidence suggests that intracisternal fibrinolysis has beneficial effects on the clinical outcomes of patients with aSAH. However, further well-designed randomized trials are needed to confirm the efficacy and safety of intracisternal fibrinolysis for the treatment of aSAH.

The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage

“…It has been shown that lumbar drainage after radiological permeation of the ventricular system (especially the third and fourth ventricles) is associated with a decrease in shunt dependency, and this promising strategy is now the subject of a randomized trial [ 111 , 114 ]. It has also been shown that intracisternal fibrinolysis reduces the incidence of hematoma in the basal cisterns at 48 h following aSAH, with significant, accompanying reductions in the proportions of patients with poor neurological outcomes and those who are shunt-dependent [ 115 ].…”

“…Tandem fenestration of the lamina terminalis and membrane of Liliequist has been shown to decrease shunt dependency following surgical clipping or bypass following aSAH (17.9% vs. 3.2%) [ 11 ]. In addition, intracisternal fibrinolysis has been shown to decrease shunt dependency and improve functional outcomes following aSAH [ 115 ]. Once again, as these techniques are usually not quantified in studies, further analysis and study may be necessary to verify the therapeutic effects.…”

Neurovascular Units and Neural-Glia Networks in Intracerebral Hemorrhage: from Mechanisms to Translation

“…First, the principal subjects of brain injury released from hematomas after ICH are hemoglobin and iron. Iron or hemoglobin overload can induce free radical generation (i.e., reactive oxygen species [ROS] and reactive nitrogen species [RNS]) and lipid peroxidation, leading to oxidative stress and brain damage [107][108][109]. Accumulation of these free radicals damages neurons, endothelial cells, pericytes, and astrocytes and also induces the activation of microglia, which are the primary components of the NVU.…”

Therapie der intrazerebralen und subarachnoidalen Blutung

“…7 % der SAB-Patienten) [49]. In einer Metaanalyse wurden günstige Effekte einer intrathekalen Fibrinolyse mittels intracisternaler Applikation hinsichtlich DCI (Risk-Ratio, RR 0,52), chronischem Hydrozephalus (RR 0,59), Mortalität (RR 0,58) und funktionellem Outcome (RR 0,62) berichtet [50]. Für die intraventrikuläre Fibrinolyse konnten ähnliche Ef-Dieses Dokument wurde zum persönlichen Gebrauch heruntergeladen.…”

“…fekte aufgrund der heterogenen Datenlage nicht festgestellt werden [50,51]. Vermutlich wird der Stellenwert der IVF erst durch die laufende FIVHeMA-Studie geklärt, die 440 SAB-Patienten mit EVD randomisieren will (clinical-trials.gov: NCT03187405) [52].…”