Catheter-directed thrombolysis for acute limb ischemia

Abstract

Acute limb ischemia occurs due to a sudden decrease in blood flow to the limb, usually caused by a thrombus or embolus, resulting not only in a potential threat to the viability of the limb, but also a high risk of death. Endovascular techniques have become the preferred treatment over the last three decades, in particular catheter-directed thrombolysis. The benefits of catheter-directed thrombolysis compared with surgery are gentler and more complete clot removal, which allows the preservation of endothelium, its less invasiveness, and the possibility to visualize and, if necessary, to treat an underlying atherosclerotic lesion or anastomotic stenosis by endovascular means. The main limitation of this treatment is the occurrence of hemorrhagic complications. In a large cohort study in this thesis, the long-term outcomes of catheter-directed thrombolysis for acute occlusions of lower limb native arteries and prosthetic bypass grafts are compared. Despite initial promising results, long-term follow-up of catheter-directed thrombolysis for acute lower limb occlusions showed a poor amputation-free survival. No significant differences in amputation-free survival between native arteries and prosthetic bypass grafts were found. Multivariate analysis did show that age >65 years and cerebrovascular disease were significant negative predictors for amputation-free survival. Although catheter-directed thrombolysis has established its role in the treatment of acute lower limb ischemia, primary surgical intervention is still the most common treatment in acute upper limb ischemia. In a prospective study we show that catheter-directed thrombolysis is effective in over 60% of patients as first-line treatment of extensive acute upper limb ischemia and can prevent surgical intervention in these patients. Since the introduction of catheter-directed thrombolysis, there has been a vast development of new thrombolysis catheters and different infusion techniques. Simultaneous delivery of ultrasound (US) and thrombolytic agents, is a relatively new concept in the treatment of acute limb ischemia. Low-intensity US is used to augment enzymatic fibrinolysis by breaking linkage of fibrin strands. In a review of 340 patients treated with catheter-directed US-accelerated thrombolysis for various thromboembolic indications, we show that complete or partial lysis was achieved in almost 90% of patients. The overall (hemorrhagic) complication rates were low. In preparation of a randomized controlled clinical, we describe a feasibility study on the use of US-accelerated thrombolysis in arterial thromboembolic occlusions of the lower limbs. This study showed that US-accelerated thrombolysis is feasible and safe in the treatment of acute lower limb ischemia. Finally, we describe the results of the randomized controlled DUET trial, comparing standard catheter-directed thrombolysis with US-accelerated thrombolysis for thromboembolic infrainguinal disease. Thrombolysis time was significantly reduced with 12 hours in the US-accelerated thrombolysis group (n=28) as compared to the standard thrombolysis group (n=32) and subsequently significantly fewer units of urokinase were required in the US-accelerated thrombolysis group. Technical success rate and 30-day patency rate did not significantly differ between the groups. However there was a trend of higher complication rates in the US-accelerated thrombolysis group.