Intra-arrest systemic thrombolytic therapy during cardiopulmonary resuscitation: a systematic review and meta-analysis of randomized controlled trials

Systemic thrombolysis has been proposed as a routine treatment for cardiac arrest, given potential benefits in treating fibrin formation and/or in treating the etiology of the cardiac arrest (e.g. ST-elevation myocardial infarction and pulmonary embolism [PE]). This systematic review and meta-analysis aimed to evaluate the effect of intra-arrest thrombolysis on survival and neurological outcomes in patients with cardiac arrest. We searched MEDLINE, EMBASE, CENTRAL, and the Web of Science from inception until September 30, 2025 for randomized controlled trials evaluating systemic thrombolytic therapy versus standard care during cardiopulmonary resuscitation (CPR). The primary outcome was survival to hospital discharge, and the secondary outcomes were favourable neurological outcome at hospital discharge, return of spontaneous circulation (ROSC), and survival to hospital admission. We performed meta-analyses using a random-effects model. We evaluated bleeding complications and examined Utstein-based subgroups. We evaluated risk of bias using the Cochrane Risk of Bias 2 tool and evidence certainty using GRADE. We included three RCTs, which enrolled a total of 1,318 participants. Thrombolysis did not improve survival (RR 0.86; 95%CI 0.65–1.14) or favourable neurological outcome (RR 0.99; 95%CI 0.69–1.40) at hospital discharge. No benefit was observed for ROSC or survival to admission. Thrombolysis increased the risk of any intracranial hemorrhage (RR 6.96, 95%CI 1.59–30.47). Among cases with bystander CPR, thrombolysis led to decreased survival; other subgroup analyses were neutral. Available evidence demonstrates that routine intra-arrest thrombolysis in unselected patients does not improve hospital-discharge survival, however does increase bleeding risk.