Optimization of thrombolytic dose for treatment of pulmonary emboli using endobronchial ultrasound-guided transbronchial needle injection

Abstract

Objective: Severe pulmonary embolism is often managed with thrombolysis. We sought to determine whether endobronchial ultrasound (EBUS)-guided transbronchial thrombolysis remained effective at lower alteplase doses, with the goal of minimizing potential bleeding risk.

Methods: Yorkshire pigs were anesthetized and ventilated. Preformed autologous blood clots were administered into bilateral pulmonary arteries via EBUS-guided transbronchial injection. After documenting baseline clot sizes, alteplase was injected into the clots using a 25-gauge transbronchial needle and clot dissolution was monitored over 30 minutes. The study was performed in 2 phases. First, alteplase doses of 5 and 12.5 mg were evaluated. These results informed dose selection for the second phase. Results were compared with 25-mg dose data using EBUS from a previous study.

Results: In the first phase, 3 clots were evaluated. Distilled water, 5 mg, and 12.5 mg alteplase were administered. The dissolved clot volume (Vdis) and percentage clot volume loss (Rdis) were -10.9, 111.6, and 160.3 mm³, and -1.6%, 11.0%, and 59.3%, respectively. In the second phase, alteplase doses of 5, 10, and 15 mg were evaluated in 12 clots across 6 pigs. The Vdis were 247.5 mm³ (Rdis, 20.1%), 910.8 mm³ (Rdis, 80.9%), and 798.3 mm³ (Rdis, 76.0%) for 5, 10, and 15 mg alteplase, respectively. Remakably reduced performance was observed with 5 mg alteplase versus 10 mg (Vdis: P < .001, Rdis: P < .001), and 15 mg (Vdis: P = .004; Rdis: P < .001). No complications were observed.

Conclusions: Alteplase doses ≥10 mg were optimal for EBUS-guided transbronchial thrombolysis. This technique might represent an effective alternative therapy for central pulmonary embolism.

Keywords: endobronchial ultrasound; preclinical animal model; pulmonary embolism; thrombolysis; transbronchial needle injection.