Best evidence in critical care medicine
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Thrombolysis is considered to be standard therapy for patients with pulmonary embolism presenting with shock, despite a paucity of large clinical trials. The benefit of thrombolysis in submassive pulmonary embolism (right ventricular dysfunction without shock) is debated.
Is anticoagulation plus thrombolytic therapy more effective than anticoagulation alone for submassive pulmonary embolism?
Prospective, randomized, double-blind, placebo-controlled trial in 49 German medical centres.
Two hundred fifty-six normotensive patients (48% male, mean age 62 yr) with proven acute pulmonary embolism and echocardiographic, electrocardiographic or pulmonary artery catheter evidence of right ventricular dysfunction were randomized within 96 hr of presentation. Baseline characteristics were similar save for an excess number of patients with the S1Q3 electrocardiographic pattern in the anticoagulation arm.
Patients received 5,000 U unfractionated heparin iv prior to diagnostic workup, followed by alteplase 10 mg iv bolus and 90 mg iv over two hours or matching placebo. Heparin was started in all patients at 1,000 U·hr−1, and titrated to activated partial prothrombin time of two to 2.5 times the upper limit of normal.
Combined in-hospital mortality or clinical deterioration requiring escalation of treatment (catecholamine infusion, secondary thrombolysis, endotracheal intubation, cardiopulmonary resuscitation, or embolectomy/thrombus fragmentation).
Thrombolysis reduced the primary endpoint by 13.7% (P= 0.006, number-needed-to-treat ~ 7), driven by reduction in the need for secondary thrombolysis. There was no mortality benefit (3.4% vs 2.2%, P = 0.71) or difference in complications and only one fatal bleeding episode (in the anticoagulation arm). Adequacy of anticoagulation was equivalent by 12 hr.
The addition of alteplase to heparin therapy for submassive pulmonary embolism does not reduce mortality, but does reduce the need for escalation of treatment due to clinical deterioration.
KeywordsPulmonary Embolism Ventricular Dysfunction Thrombolytic Therapy Alteplase Pulmonary Artery Catheter