Abstract

BackgroundCentral venous catheter (CVC) thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB) enhanced sonothrombolysis for aged CVC associated thrombi in vivo. Methods and ResultsA model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently applied for repeated, sonothrombolytic treatments in 9 pigs (total 24 treatments). Baseline intracardiac echocardiography (ICE, 10.5F, Siemens), fluoroscopy and saline flushing confirmed the absence of any pre-existing CVC thrombus. A thrombus was then allowed to form and age over 24 hours. The created thrombus was localized and measured by ICE, and transthoracic image guided high mechanical index (MI) two-dimensional US treatments (1.1–1.7 MI; iE33, Philips) applied intermittently whenever intravenously infused MBs (3% MRX-801; NuVox) were visualized near the thrombus (n = 10; Group A). Control pigs (n = 10; Group B) received US without MB. All treatments were randomized. Post-treatment thrombus area by ICE planimetry was compared with pre-treatment measurements. Thrombus area measurements before and after treatment were 0.22 and 0.10 cm2 respectively in Group A; compared to 0.24 and 0.21 cm2 in Group B (p = 0.0003). Effectiveness of longer duration US and MB thrombolytic treatments were studied (n = 4), which suggested that near complete thrombus dissolution is possible. No pulmonary emboli, alterations in oxygen saturation, or hemodynamics occurred with either treatment.ConclusionsGuided high MI diagnostic US+systemic MB facilitates reduction of aged CVC associated thrombi in vivo. MB enhanced sonothrombolytic therapy may be a non-invasive safe alternative to thrombolytic agents in treating thrombotic CVC occlusions.

Highlights

  • Image guided high mechanical index (MI) impulses from a diagnostic ultrasound (US) system during a systemic microbubble (MB) infusion have the potential to dissolve intravascular arterial thrombi without the need for fibrinolytic therapy [1]

  • Cavitation and resultant shear forces are proposed mechanisms for sonothrombolysis [2].The mechanical effect of cavitation leads to axial fluid acceleration, resulting in acoustic streaming and the creation of high-velocity flow gradients that penetrate and destabilize the structure of the thrombus

  • We recently demonstrated that guided high MI impulses from diagnostic US and MB were successful at dissolving aged venous thrombi within pediatric sized catheters in vitro, due to shearing and dissolution of micro fragments from the outer surface of the thrombus [5]

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Summary

Introduction

Image guided high mechanical index (MI) impulses from a diagnostic ultrasound (US) system during a systemic microbubble (MB) infusion have the potential to dissolve intravascular arterial thrombi without the need for fibrinolytic therapy [1]. We recently demonstrated that guided high MI impulses from diagnostic US and MB were successful at dissolving aged venous thrombi within pediatric sized catheters in vitro, due to shearing and dissolution of micro fragments from the outer surface of the thrombus [5]. This was the first demonstration of the effectiveness of this technique in older venous thrombi that typically form in chronic indwelling central venous catheters (CVC), or in deep venous thromboses. We sought to investigate the therapeutic efficacy of microbubble (MB) enhanced sonothrombolysis for aged CVC associated thrombi in vivo

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