Background: Massive pulmonary embolism  defined as sustained hypotension (SBP <90mmHg)  has a high mortality which is why early recognition and thrombolytic therapy is typically recommended (AHA Class IIA; ESC Class IB) [1]. However, full-dose thrombolytic therapy (Alteplase 100mg (IV) is  associated with an increase in bleeding [2]. Because the lungs receive 100% of cardiac output, it has been hypothesized that a lower dose of thrombolytic therapy may still be effective with a better safety profile [3][4]. REBEL Cast Ep123:  Reduced-Dose Systemic Peripheral Alteplase in Massive PE? Click here for Direct Download of the Podcast Paper: Aykan AC et al. Reduced-Dose Systemic Fibrinolysis in Massive Pulmonary Embolism: A Pilot Study. Clin Exp Emerg Med 2023. PMID: 37188358 Clinical Question: What is the efficacy and safety  of low-dose (25mg) prolonged administration (over 6hrs) of alteplase in patients with massive PE? What They Did: Single-center, pilot prospective observational cohort trial in Turkey Thrombolysis 25mg of alteplase without a bolus was administered over 6 hours by peripheral IV infusion If hemodynamic instability persisted despite first dose of thrombolysis, a second 6hr infusion of 25mg alteplase without bolus was administered (No patients in the study required this) Did not use concomitant heparin anticoagulation with thrombolysis Heparin was administered as a 70U/kg bolus followed by a 1000U/h infusion with a target activated PTT between 1.5 and 2.5x the control started immediately after infusion of thrombolysis completed Patients were all converted to warfarin for discharge TTE All patients underwent TTE before thrombolysis, within an hour after thrombolysis, before discharge (5 to 7d) and a month after thrombolysis PASP estimated from tricuspid valve regurgitant jet velocity Maximum dimension of RA/LA measured in 4-chamber view Diameter and collapsibilit