Asian Cardiovasc Thorac Ann 2007;15:405-407
© 2007 Asia Publishing EXchange Ltd
Urokinase Thrombolysis in Acute-on-Chronic Vascular Occlusion of Lower Limb
Chandra P Shrivastava, MCh,
Sanjeev Devgarha, MCh
Department of Cardiothoracic and Vascular Surgery, SMS Medical College & Hospital, Jaipur, India
For reprint information contact: Chandra P Shrivastava, MCh, Tel: 91 141 256 0291 Ext. 475, Fax: 91 141 237 6329, Email: cps_sms{at}hotmail.com, H-16, Chitranjan Marg, C-Scheme, Jaipur-302001, Rajasthan, India.
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ABSTRACT
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Between January 2000 and June 2003, 70 patients (63 men and 7 women) with acute-on-chronic lower limb vascular occlusion underwent thrombolysis with 1 million units of urokinase. Forty-eight patients had unilateral and 22 had bilateral involvement; 9 had gangrenous changes. The mean age was 47 ± 9 years, 73% were smokers, and 13% had diabetes. The definition of a good response was either return of distal pulses or a warm limb and relief of pain at rest. Fifty-three (76%) patients (including 5 with gangrenous changes) had symptomatic improvement with thrombolysis (group 1), and 17 (24%) did not respond (group 2). All 70 patients (including 7 who later required amputation) underwent surgical intervention with a polytetrafluoroethylene interposition graft or arterioplasty. A good response to surgical treatment was found in significantly more patients (49/53, 92%) in group 1 compared to group 2 (7/17, 41%). Claudication distance after 6 months of follow-up improved in a significantly higher percentage of patients in group 1 (85%) than group 2 (38%). Preoperative thrombolysis improved the outcome and predicted the result of arterial surgery.
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INTRODUCTION
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Streptokinase and urokinase are commonly used thrombolytic agents for coronary disease. Thrombolytic drugs are superior to heparin in patients with recent deep vein thrombosis in the pelvis or lower limbs and is the front-line treatment for patients with massive pulmonary embolism and major hemodynamic disturbance.1 Comparison of thrombolytic therapy for acute, subacute, and chronic lower extremity arterial occlusion showed that thrombolysis was more effective for acute and subacute occlusions. Long-term follow-up demonstrated a higher failure rate with chronic rather than acute occlusions, probably due to poorer peripheral vascular run-off.2 Chronic arterial occlusion of the leg becomes more painful when an acute attack is superimposed. The vascular surgeon has not only to buy time for investigation and surgery but also to relieve the pain, salvage the muscles, and improve the results of surgery. This study was carried out to assess the effectiveness of urokinase in relieving symptoms and improving postoperative outcome.
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PATIENTS AND METHODS
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The study was carried out retrospectively in all patients who presented to our department with an acute attack of arterial occlusion superimposed on chronic arterial occlusion of a lower extremity, between January 2000 and June 2003. There were 70 patients known to have chronic arterial occlusive disease who presented with complaints of severe pain and numbness developing in the previous 48 hours. Of these 70 patients, 51 (73%) were smokers, 9 (13%) had diabetes, and 7 (10%) had hypertension. Nine patients had gangrenous changes in the foot or a nonhealing ulcer in the leg with gangrenous patches near the knee and toes. There were 63 men and 7 women, with a mean age of 47 ± 9 years (range, 38–56 years). Any absent femoral, popliteal, posterior tibial, and dorsalis pedis arterial pulsations were recorded. The patients were immediately given thrombolytic treatment (within 8 hours after admission). After cannulating a peripheral vein, urokinase (0.5 million units) was infused over 30 min, followed by 0.5 million units over 2–3 hours. Angiography was performed subsequently to decide on definitive treatment. The patients underwent surgery within 2 weeks of thrombolysis. Surgical intervention in the form of arterioplasty or a polytetrafluoroethylene (PTFE) interposition graft was performed, depending on the site and type of vascular occlusion. A PTFE patch was used for arterioplasty, and both tubular and bifurcated Y-shaped PTFE grafts were used for interposition. A bifurcated PTFE interposition graft was used in aortoiliac and bilateral iliac disease, a tubular PTFE graft and PTFE patch arterioplasty were used in unilateral iliac, femoral, and femoropopliteal blockages. Heparin was administered intraoperatively and for 3 days postoperatively. Oral antiplatelet drugs were prescribed as long-term therapy.
The results were analyzed using the chi-squared test.
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RESULTS
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Urokinase infusion led to symptomatic improvement in 53 patients (including 5/9 with gangrenous changes, group 1) and 17 showed no improvement (group 2). The findings are summarized in Table 1
. Angiography was carried out in all 70 patients, which revealed aortoiliac block in 19, bilateral iliac artery block in 3, unilateral iliac artery block in 21, femoral artery block in 16, and femoropopliteal block in 11. Above-knee interventions were performed in 59 patients (aortoiliac, iliac, and femoral), and 11 had below-knee surgery (femoropopliteal). A PTFE bifurcation graft was used in 22 cases (19 aortoiliac, and 3 bilateral iliac) and a PTFE tubular graft was used in 31 (17 iliac, 6 femoral, and 8 femoropopliteal). PTFE patch arterioplasty was undertaken in 17 patients (4 iliac, 10 femoral, and 3 femoropopliteal). Three of the 9 patients with gangrenous changes had an aortoiliac bifurcation graft, 4 had femoral arterioplasty. In group 1, 49 patients responded well to surgery, including 5 with gangrenous changes; only 7 patients in group 2 responded well to surgery (Table 1). Of the 9 patients who had gangrenous changes, 7 underwent below-knee amputation with good healing of the wound (Table 1).
Five patients died of acute renal failure in the postoperative period (Table 1
), including 2 in group 2 with gangrenous changes (aortoiliac bifurcation graft in 1, femoral arterioplasty in 1). There was no incidence of intracranial hemorrhage. Amputation was carried out 1–3 months after vascular surgery, depending on the appearance of a line of demarcation. None of the 7 patients who underwent amputation died or were lost to follow-up. There were 4 patients lost to follow-up (Table 1). Follow-up at 6 months revealed that claudication distance improved by more than 50% in 41 of 48 (85%) group 1 patients (excluding 5 who had amputations, 1 death, and 1 lost to follow-up) compared to 3/8 (38%) in group 2 (excluding 2 who had amputations and 3 lost to follow-up; p < 0.01).
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DISCUSSION
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Successful thrombolysis with urokinase or streptokinase has been documented in acute myocardial infarction, with relief of angina and salvage of myocardium, leading to improved long-term prognosis. In coronary artery disease, hypertriglyceridemia predisposes to thrombosis through an increase in plasminogen activator inhibitor concentration, whereas urokinase activates plasminogen through proteolysis.3 Using the same concept, thrombolysis was used to salvage the muscles of the limbs and improve long-term prognosis. Anaphylaxis is not uncommon with streptokinase, with a frequency of 1.7%–18%.4 Urokinase, although more expensive, was preferred over streptokinase to avoid an anaphylactic reaction. Moreover, urokinase infusion can be repeated if needed, unlike streptokinase.
Lower extremity ischemia, both acute and chronic, presents a risk to life and limb, with mortality rates of 3% to 37%, and amputation rates in the same range. Byrne and colleagues5 reported no mortality and only 3.5% of patients required amputation when urokinase thrombolysis was used as the initial therapy for acute and non-acute limb ischemia. In this study, 7 patients needed amputation after initial urokinase therapy followed by surgery, but all of them had gangrenous patches prior to admission. There was no mortality attributed to urokinase directly; all 5 deaths were due to acute renal failure after surgery. Thrombolysis as an initial therapy reduces the risk of surgery and improves limb salvage in patients with peripheral arterial disease; later, underlying lesions can be treated.6 While open surgical procedures remain the gold standard for treatment of peripheral occlusion, thrombolytic agents have been employed as an alternative in acute limb ischemia.7 Local lysis with or without percutaneous transluminal angioplasty is an effective alternative to vascular surgery for peripheral arterial occlusion when the limb is not immediately endangered.8 In this series, urokinase was used as initial thrombolysis for immediately endangered lower limbs due to superimposition of an acute attack on chronic occlusion. It gave good results, reflecting the importance of urokinase in salvaging the muscles of ischemic extremities.
Some vascular surgeons use urokinase for lower limb bypass graft occlusion. Patients with graft occlusion > 14 days have a significantly better outcome when treated surgically, with a new bypass being the best option. However, in patients with acute limb ischemia < 14 days, successful thrombolysis of occluded bypass grafts improved limb salvage and reduced the extent of the planned surgical procedure.9 None of the patients in this series had bypass graft occlusion. Catheter thrombus aspiration in combination with thrombolysis is also highly effective and has been recommended as first-line treatment for acute and subacute infrainguinal arterial occlusion.10 Thrombolysis with urokinase has simplified the treatment of native arterial occlusion, providing the sole therapy in some patients, or a valuable adjunct by facilitating angioplasty of arterial lesions and avoiding open surgery in others. Furthermore, correction of inflow lesions reduces the magnitude of subsequent bypass procedures to achieve limb salvage. Successful thrombolysis of native artery occlusion has provided durable arterial patency and limb salvage, particularly in patients with new-onset claudication.11 In this series, urokinase was not considered as sole therapy, even after symptomatic improvement, because we felt that the native artery lesions required definitive surgical management. Angioplasty was not performed in any of these patients. PTFE patches and grafts were used to bypass the lesions; saphenous vein was not considered for interposition, to avoid hampered venous return, limb edema, and delayed wound healing after surgery.
A comparative study of recombinant urokinase and vascular surgery showed that despite its association with more hemorrhagic complications, intraarterial infusion of urokinase reduced the rate of open surgical procedures, with no significantly increased risk of amputation or death.12 In this series, urokinase infusion was given after cannulating a peripheral vein, and there was no incidence of intracranial hemorrhage. Even in patients with gangrenous changes, the amputation rate was low, with good wound healing. Our 90% success rate after surgery in urokinase-treated patients signifies its importance in overcoming acute crises.
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REFERENCES
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ABSTRACT
INTRODUCTION
