Assessment of effectiveness and safety of thrombolytic therapy to pulmonary emboli by endobronchial ultrasound-guided transbronchial needle injection

Abstract

Objective: Endobronchial ultrasound-guided transbronchial needle injection (EBUS-TBNI) may effectively treat acute pulmonary embolisms (PEs). Here, we assessed the effectiveness of clot dissolution and safety of tissue plasminogen activator (t-PA) injection using EBUS-TBNI in a 1-week survival study of a porcine PE model.

Methods: Six pigs with bilateral PEs were used: 3 for t-PA injection using EBUS-TBNI (TBNI group) and 3 for systemic administration of t-PA (systemic group). Once bilateral PEs were created, each 25 mg of t-PA injection using EBUS-TBNI for bilateral PEs (a total of 50 mg t-PA) and 100 mg of t-PA systemic administration was performed on day 1. Hemodynamic parameters, blood tests, and contrast-enhanced computed tomography scans were carried out at several time points. On day 7, pigs were humanely killed to evaluate the residual clot volume in the pulmonary arteries.

Results: The average of percent change of residual clot volumes was significantly lower in the TBNI group than in the systemic group (%: systemic group 36.6 ± 22.6 vs TBNI group 9.6 ± 6.1, P < .01) on day 3. Considering the elapsed time, the average decrease of clot volume per hour at pre-t-PA to post t-PA was significantly greater in the TBNI group than in the systemic group (mm³/hour: systemic 68.1 ± 68.1 vs TBNI 256.8 ± 148.1, P < .05). No hemorrhage was observed intracranially, intrathoracically, or intraperitoneally on any contrast-enhanced computed tomography images.

Conclusions: This study revealed that t-PA injection using EBUS-TBNI is an effective and safe way to dissolve clots.

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

Graphical abstract

Injection of t-PA using endobronchial ultrasound–guided transbronchial needle injection.

Figure 1

This illustration shows the procedures on day 1. The green frame shows the collection time points for the hemodynamic parameter, the blood test, the CT scans, and the EBUS images. The red frame shows the time points for clot injection or t-PA administration. Note that the systemic group hemodynamic parameters were collected 30 minutes and 2 hours after t-PA administration. The other data: the blood tests, the EBUS images, and the CT scans were collected 2 hours' post-t-PA administration. Systemic group: t-PA systemic administration; TBNI group: t-PA injection using EBUS-TBNI. CT, Computed tomography; EBUS, endobronchial ultrasound; EBUS-TBNA, endobronchial ultrasound-guided transbronchial needle aspiration; t-PA, tissue plasminogen activator; EBUS-TBNI, endobronchial ultrasound-guided transbronchial needle injection; PE, pulmonary embolisms.

Figure 2

The changes in each hemodynamic parameter at each time point in the systemic group and TBNI group. The average changes of (A) systolic BP, (B) diastolic BP, (C) HR, (D) SpO₂, and (E) EtCO₂ were shown at each time point for each group. BP, Blood pressure; t-PA, tissue plasminogen activator; TBNI, transbronchial needle injection; HR, heart rate; SpO₂, oxygen saturation; EtCO₂, end-tidal carbon dioxide.

Figure 3

The changes in pulmonary artery pressure (PAP), d-dimer, and fibrinogen at each time point in the systemic group and TBNI group. The average changes of (A) systolic PAP, (B) diastolic PAP, (C) d-dimers, and (D) fibrinogen are shown at each time point for each group. t-PA, Tissue plasminogen activator; TBNI, transbronchial needle injection.

Figure 4

The changes in each blood test at each time point in the systemic group and TBNI group. The average changes of (A) pH, (B) HCO₃, (C) pO₂, (D) pCO₂, (E) PT, and (F) PTT were shown at each time point for each group. t-PA, Tissue plasminogen activator; HCO₃, bicarbonate; TBNI, transbronchial needle injection; po₂, oxygen tension; pco₂, carbon dioxide tension; PT, prothrombin time; PTT, partial thromboplastin time.

Figure 5

Analysis of the residual clot volumes. A, The comparison of the residual clot volumes between the systemic group and TBNI group at pre-t-PA and on day 3. B, The percentage change of clot volumes on day 3 compared with pre-t-PA. C, Amount of clot volume decrease per an hour from pre-t-PA to post-t-PA and from post-t-PA to day 3. ∗P < .05; ∗∗P < .01. The lower and upper borders of the box represent the lower and upper quartiles. The middle horizontal line represents the median. The lower and upper whiskers represent the minimum and maximum values of nonoutliers. Each value is plotted in the same color. t-PA, Tissue plasminogen activator; TBNI, transbronchial needle injection.

Figure 6

Summary of this study on the safety and effectiveness of endobronchial ultrasound–guided transbronchial needle injection (EBUS-TBNI) in a porcine survival model. A pig model of pulmonary embolism (PE) was created by injecting clots into the pulmonary artery of healthy pigs under EBUS guidance. One group received 100 mg of t-PA systemic administration to treat PE (systemic group); the other group received each 25 mg of t-PA injection into bilateral PEs using EBUS-TBNI (total of 50 mg t-PA). Hemodynamic parameters, blood tests, and CT scans were collected to evaluate the clot dissolving. In TBNI group, the speed of dissolving clot was significantly greater than in the systemic group. There were no complications in both groups. Twenty-five milligrams of t-PA injection using EBUS-TBNI can be a safe and effective procedure to treat acute massive PE. The promising efficacy data suggest a potential role for clinical practice. t-PA, Tissue plasminogen activator; CT, computed tomography.

Figure E1

The changes in systolic PAP and diastolic PAP in the systemic group and TBNI group. The average changes of (A) systolic PAP in the systemic group, (B) systolic PAP in TBNI group, (C) diastolic PAP in the systemic group, and (D) diastolic PAP in TBNI group. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. PAP, Pulmonary artery pressure; t-PA, tissue plasminogen activator; TBNI, transbronchial needle injection.

Figure E2

The comparison of the residual clot volumes between the systemic group and TBNI group on day 7. TBNI, Transbronchial needle injection; ns, not significant.