Microbubble Mediated Thrombus Dissolution with Diagnostic Ultrasound for the Treatment of Chronic Venous Thrombi

BACKGROUND: Central 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 RESULTS: A 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 cm(2) respectively in Group A; compared to 0.24 and 0.21 cm(2) 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. CONCLUSIONS: Guided 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

Thrombotic obstruction of the central venous catheter in patients undergoing hematopoietic stem cell transplantation Obstrucción trombótica del catéter venoso central en pacientes sometidos al trasplante de células-tronco hematopoyéticas Obstrução trombótica do cateter venoso central em pacientes submetidos ao transplante de células-tronco hematopoéticas

This is an integrative literature review with the aim of summarizing the prevention measures and treatment of thrombotic obstruction of long-term semi-implanted central venous catheters, in patients undergoing hematopoietic stem cell transplantation. The sample consisted of seven studies, being two randomized controlled clinical trials, three cohort studies and two case series. Regarding the prevention measures, one single study demonstrated effectiveness, which was a cohort study on the oral use of warfarin. In relation to the treatment measures, three studies evidenced effectiveness, one highlighted the efficacy of streptokinase or urokinase, one demonstrated the benefit of using low-molecular-weight heparin and the other treated the obstruction with heparin or urokinase. Catheter patency research shows a restricted evolution that does not follow the evolution of transplantations, mainly regarding nursing care.<br>Se trata de una revisión integradora de la literatura con objeto de sintetizar las medidas de prevención y tratamiento de obstrucción trombótica del catéter venosos central de larga permanencia y semi-implantado, en pacientes sometidos al trasplante de células-tronco hematopoyéticas. La muestra abarcó a siete estudios: dos ensayos clínicos controlados aleatorizados, tres estudios de cohorte y dos series de casos. Respecto a las medidas de prevención, fue identificado un único estudio efectivo, uno cohorte sobre el uso de la warfarina oral. Sobre las medidas de tratamiento, tres estudios evidenciaron efectividad, uno apuntó la eficacia de la estreptoquinasa o uroquinasa, otro mostró beneficio del uso de heparina de bajo peso molecular y otro trató la obstrucción con heparina o uroquinasa. Se observa que la evolución de la investigación sobre la permeabilidad del catéter fue limitada, no acompañando la evolución del trasplante, principalmente respecto a los cuidados de enfermería.<br>Trata-se de revisão integrativa da literatura, cujo objetivo foi sintetizar as medidas de prevenção e tratamento da obstrução trombótica no cateter venoso central de longa permanência e semi-implantado, em pacientes submetidos ao transplante de células-tronco hematopoéticas. A amostra foi constituída por sete estudos, sendo dois ensaios clínicos controlados randomizados, três estudos de coorte e duas séries de casos. Quanto às medidas de prevenção, um único estudo que se mostrou efetivo abordando pesquisa de coorte sobre o uso da varfarina oral. Em relação às medidas de tratamento, três estudos evidenciaram efetividade: um apontou a eficácia da estreptoquinase ou uroquinase, outro estudo mostrou benefício no uso de heparina de baixo peso molecular e outro tratou a obstrução com heparina ou uroquinase. Nota-se que a evolução da pesquisa referente à perviedade do cateter foi restrita, não acompanhando a evolução do transplante, principalmente no que tange aos cuidados de enfermagem