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.

Keywords: aneurysmal subarachnoid hemorrhage; delayed ischemic neurological deficit; intracisternal fibrinolysis; intraventricular fibrinolysis; meta-analysis.

Figure 1

Flow diagram showing the selection of eligible studies.

Figure 2

Risk-of-bias assessment for randomized controlled trials. A plus sign (+) indicates a low risk of bias, a minus sign (–) indicates a high risk of bias, and a question mark (?) indicates an unclear risk of bias.

Figure 3

Meta-analysis of associations between intracisternal fibrinolysis and the risk of poor neurologic recovery (A) or the incidence of DIND (B) in patients with aSAH. aSAH, aneurysmal subarachnoid hemorrhage; CI, confidence interval; DIND, delayed ischemic neurologic deficit; M-H, Mantel-Haenszel method; RCTs, randomized controlled trials.

Figure 4

Meta-analysis of associations between intraventricular fibrinolysis and the risk of poor neurologic recovery (A) or the risk of DIND (B) in aSAH patients. aSAH, aneurysmal subarachnoid hemorrhage; CI, confidence interval; DIND, delayed ischemic neurologic deficit; M–H, Mantel–Haenszel method; RCTs, randomized controlled trials.

Figure 5

Meta-analysis of associations between intracisternal fibrinolysis and the risk of poor neurologic recovery (A) or the incidence of DIND (B) in patients with aSAH (stratified by types of thrombolytic agents). aSAH, aneurysmal subarachnoid hemorrhage; CI, confidence interval; M–H, Mantel–Haenszel method; UK, urokinase; tPA, tissue plasminogen activator.

Figure 6

Meta-analysis of associations between intracisternal fibrinolysis and the risk of chronic hydrocephalus (A) or the risk of hemorrhagic complications (B) in patients with aSAH. aSAH, aneurysmal subarachnoid hemorrhage; CI, confidence interval; M–H, Mantel–Haenszel method; RCTs, randomized controlled trials.

Figure 7

Meta-analysis of associations between intraventricular fibrinolysis and the risk of chronic hydrocephalus (A) or the risk of hemorrhagic complications (B) in patients with aSAH. aSAH, aneurysmal subarachnoid hemorrhage; CI, confidence interval; M–H, Mantel–Haenszel method; RCTs, randomized controlled trials.