Aspects on intra-arterial thrombolysis for lower limb ischemia

Sammanfattning: Background: Acute ischemia of the lower limb is a vascular emergency associated with amputation and death. Patients suffering from acute limb ischemia are usually elderly, and multiple comorbidities are often present. Intra-arterial thrombolysis is, perhaps, the most important minimal-invasive treatment option available today. Although uncontrolled hemorrhage is a dreaded complication, it is considered beneficial to many patients with lower limb ischemia – not at least fragile individuals in whom extensive invasive surgery is not an option. The thrombolytic procedure is mainly standardized with minor local differences. Conjunctive infusion of heparine, for example, is not standard procedure everywhere. Aims: To study clinical outcome in terms of amputation-free survival rate, and factors associated with short- (paper IV) and long-term (paper I, II) major amputation and/or mortality in patients undergoing intra-arterial thrombolysis with low-dose recombinant tissue plasminogen activator (rt-PA) for lower limb ischemia. We also intended to assess factors associated with hemorrhagic complications in these patients (paper III, IV). Methods: Retrospective reviews of all consecutive patients subjected to intra-arterial thrombolysis due to lower limb ischemia at the vascular centers in Malmö and Uppsala, Sweden, between 2001 and 2010 or 2012, respectively. Results: A total of 749 thrombolytic procedures were carried out in 644 patients. Paper II showed an increase in thrombolyses of occluded endoprosthesis, and decrease in thrombolyses of occluded bypasses between 2001 and 2010 (p=0.001). Technical success rate for thrombolysis of occluded endoprosthesis, bypasses and native artery occlusion was 91%, 89% and 73%, respectively. Amputation-free survival rate at 1 year was 73%. Independent factors associated with dismal amputation-free survival at long-term were foot ulcers (HR 3.4; 95% CI 1.3-2.6), motor deficit (HR 1.7; 95% CI 1.2-2.5), renal insufficiency (HR 1.7, 95% CI 1.2-2.7) and anemia (HR 1.6; 95% CI 1.2-2.2). Paper IV showed that popliteal arterial aneurysm (OR 3.3; 95% CI 1.5-7.0) and anemia (OR 2.1; 95% CI 1.3-3.4) were associated with dismal amputation-free survival at short term. Major hemorrhage ocurred in 104 procedures (13.9%); of which 43 (5.7%) were so severe that thrombolysis was discontinued in advance. Preoperative severe limb ischemia with motor deficit was the only independent risk factor for major bleeding (OR 3.0; 95% CI 1.8-5.0). Conjunctive heparin infusion was neither associated with increased risk of major bleeding, nor improved leg salvage or survival. Conclusions: Intra-arterial thrombolysis with low-dose rt-PA for lower limb ischemia is effective, with few major complications. Although the study may have limitations attributed to its retrospective design, we have found several independent risk factors associated with adverse outcome, which may be helpful in decision-making. Thrombolysis with or without simultaneous infusion of heparin can be recommended, but conjunctive heparin is more labor intensive and offers no advantages in key outcomes.