Safety and efficacy of limited-dose tissue plasminogen activator in acute vascular occlusion.

OBJECTIVE: The purposes of this study were to evaluate the safety and efficacy of limited-dose tissue plasminogen activator (t-PA) in patients with acute vascular occlusion and to compare these results with those obtained in equivalent patients receiving urokinase. METHODS: We compared the results of 60 patients receiving catheter-directed urokinase from November 1997 to November 1998 (240,000 units/h x 4 h, 120,000 units/h thereafter for a maximum of 48 h) with those of 45 patients receiving catheter-directed t-PA from November 1998 to August 2000 (2 mg/h, total dose < or =100 mg) for acute arterial occlusion (AAO) and acute venous occlusion (AVO). Interventional approaches such as cross-catheter and coaxial techniques were used to reduce the dose of lytic agent needed to achieve pre-lysis-treatment goals (eg, complete lysis of all thrombus/unmasking graft stenosis or establishing outflow target). Statistical analysis was performed using Student t test and Fisher exact test. RESULTS: The urokinase and t-PA groups were comparable with regard to age, comorbidities (coronary artery disease, hypertension, diabetes, renal insufficiency, smoking), duration of ischemic or occlusive symptoms, location of occlusive process, pretreatment with warfarin, and thrombotic versus embolic and native versus graft occlusion in patients with AAO. In patients with AAO and in those with AVO, t-PA was equivalent to or better than urokinase with regard to percent of clot lysis, incidence of major bleeding complications, limb salvage, and mortality. Achievement of pretreatment goals (arterial patients only) was 50% for urokinase patients and 76% for t-PA patients (P =.02). Analysis of success in individual pretreatment-goal achievement showed urokinase and t-PA to be equivalent in unmasking stenoses (85% and 84%, respectively; P = NS), whereas t-PA was superior to urokinase in the more critical task of establishing run-off (39% versus 81% for urokinase and t-PA, respectively; P =.001). Additional interventions, either endovascular or surgical, were required in 60% and 51% (P = NS) of patients receiving urokinase and t-PA, respectively, for AAO, and in 54% and 62% (P = NS) of patients receiving urokinase and t-PA, respectively, for AVO. CONCLUSIONS: Limited-dose t-PA is a safe and effective therapy for AAO and AVO when administered by experienced teams using innovative but well-established interventional techniques.

Alcohol withdrawal after open aortic surgery.

This study was designed to test the hypothesis that unexpected alcohol withdrawal-like syndrome (AWLS) is more common following aortic, but not other, vascular or nonvascular procedures. All patients undergoing open aortic surgery at our institution in 1997 who survived at least 48 hr were identified, as were those undergoing carotid endarterectomy, infrainguinal bypass, and total colectomy. AWLS was defined as prolonged confusion or agitation and response to conventional treatment for withdrawal, providing that all other sources had been ruled out or a significant history was present. Our results show that, for unknown reasons, AWLS is more common after aortic surgery than after other vascular and high-stress, nonaortic intraabdominal procedures at our institution, and is associated with increased length of stay and morbidity. Because prophylaxis may improve outcome, better efforts to identify patients at risk are required.

Reperfusion and compartment syndromes: strategies for prevention and treatment.

Reperfusion syndrome refers to the damage done by restoration of blood flow to ischemic tissues and is distinct from the original ischemic insult itself, whereas compartment syndrome refers to the damage resulting from increased pressure within an enclosed fascial compartment that occurs after blood flow has been restored. Despite extensive experimental work directed toward the treatment of established reperfusion injury and prevention of compartment syndrome, clinical outcome over the past decade has not appreciably changed. Although the systemic insult, thought to be an inevitable result of reperfusion injury, may be less injurious than "conventional wisdom" would suggest, no better strategy for treating compartment syndrome other than early recognition and decompression has yet been developed.

Reduction in wound morbidity rates following endoscopic saphenous vein harvest.

To determine whether less-invasive saphenous vein harvest reduces morbidity in patients undergoing infrainguinal bypass, we retrospectively compared 61 patients undergoing endoscopic harvest (ENDO) with 49 patients undergoing conventional harvest (OPEN) over the past 13 months. Patients were classified as potential short-stay if adjunctive suprainguinal inflow procedures or foot amputations were not required and the patient was ambulatory prior to elective operation. Mean endoscopic harvest time was 50+/-18 (range 25-90) min, and no more than three 5-cm incisions were required in 87% of cases. Szilagyi class II or III wound complications occurred after 1 of the 61 (2%) ENDO procedures and 7 of the 49 (14%) OPEN (p < 0.01), and any complication occurred in 13 (21%) vs. 25 (51%) of ENDO and OPEN procedures, respectively (p < 0.002). Mean postoperative length of stay was significantly shorter in the 24 short-stay ENDO (4.0+/-2.4 days) vs. 25 short-stay OPEN (6.0+/-3.2 days) patients (p < 0.02). Thirty-day patency rates between the two groups were not different. Endoscopic saphenous vein harvest is associated with a reduced incidence of serious wound complications and, in selected patients, shortened postoperative hospital stay.

Combined free tissue transfer and infrainguinal bypass graft: an alternative to major amputation in selected patients.

OBJECTIVES: The purpose of this study was to document outcome and adverse prognostic factors in patients requiring combined free tissue transfer and distal bypass grafting for otherwise nonreconstructible infrainguinal arterial occlusive disease and advanced tissue necrosis. METHODS: Between July 1990 and November 1999, 65 patients, all of whom would have required at least below-knee amputation, underwent free tissue transfer in conjunction with infrainguinal bypass grafting at the University of Rochester. Preoperative variables were assessed for their influence on outcome with chi(2) and outcome with life-table analysis with Cox proportionate hazard testing. RESULTS: Free tissue transfer was performed synchronously with arterial reconstruction with autologous vein in 49 patients and after a previous functioning venous bypass graft in 16 patients. The 30-day mortality rate was 5%, and major complications occurred in another 16% of patients. Flap location, weight-bearing status, preexisting osteomyelitis, and the timing of bypass grafting relative to flap construction had no effect on outcome. All five free flap failures occurred within the first 30 days. All other flaps subsequently survived, even in seven patients whose bypass grafts thrombosed. Five-year limb salvage and patient survival rates were 57% and 60%, respectively, and 65% of patients regained meaningful ambulation. The combination of diabetes and dialysis-dependent renal failure was the strongest predictor of overall limb loss (P <.005; relative risk = 4.0), and diabetes alone was the strongest predictor of death (P <.02; relative risk = 5.2). CONCLUSION: Free tissue transfer combined with infrainguinal bypass grafting in selected patients is safe and effective. The combination of diabetes and chronic renal insufficiency, particularly the need for dialysis, is a powerful predictor of failure and should be considered a strong contraindication for this procedure.

Irradiation for intimal hyperplasia: implications for peripheral arterial bypass.

Irradiation has been shown to inhibit postangioplasty intimal hyperplasia ("restenosis") in unbranched tubes. It seems likely that irradiation will similarly be able to inhibit intimal hyperplasia after a surgical anastomosis at a biochemical and cellular level, but whether it will produce a clinically relevant or even clinically detectable difference is unproved. One possibility is that no clinical effect may occur; the search for a "cure" for intimal hyperplasia has been long and, as yet, unsuccessful. On the other hand, if a strong effect without insurmountable logistical problems could be produced, one major cause of bypass graft failure would be preventable. Not only would the incidence of late graft occlusion, need for reoperation, and limb loss be reduced, but, if patency of prosthetics could be sufficiently improved, the initial operation could be made much easier, faster, and perhaps safer.

Photoplethysmography and calf muscle pump function after subfascial endoscopic perforator ligation.

OBJECTIVE: Subfascial endoscopic perforator surgery (SEPS) results in acceptable healing and recurrence rates. The role of hemodynamic venous testing in this situation, however, is poorly understood and inconsistently used. Our ongoing experience was reviewed to explore how SEPS affects the photoplethysmographic assessment of the leg. METHODS: Preoperative and postoperative venous refill times (VRTs) were measured with photoplethysmography in 30 limbs in 28 patients who underwent SEPS and superficial ablation, when indicated, with complete clearing of the anterolateral surface of the tibia, thus opening the deep posterior compartment from mid calf to close to the malleolus. Postoperative healing and duplex scanning were used to assess clinical and anatomic success, respectively. The VRTs were classified as "interpretable" if the leg emptied or "uninterpretable" if the calf could not empty. The "interpretable" study results were further classified as "normal" if the refill took 20 seconds or more or "abnormal" if less. RESULTS: Before the patients underwent SEPS, six study results (20%) showed inability of the calf to empty and thus were judged uninterpretable. After the patients underwent SEPS, 12 study results (40%) were uninterpretable (NS; P =.09 with the chi(2) test). Of the 24 preoperative interpretable study results, two (8%) were normal, and of the 18 postoperative interpretable study results, seven (39%) were normal (P <.03). With the consideration of only interpretable study results, the mean VRT increased slightly from 12.0 +/- 5.1 seconds (mean +/- standard deviation) to 14.3 +/- 8.1 seconds (NS). Seventeen of 19 ulcers (89%) had healed at a mean follow-up period of 8.6 +/- 4.8 months. CONCLUSION: Although VRT is unpredictably affected by SEPS, the most consistent finding is the inability of the calf to empty, which invalidates the remainder of the test. In addition, most ulcers heal, even with uninterpretable or abnormal postoperative VRTs. This suggests that photoplethysmography is a poor method of assessment of venous reflux after SEPS.

Thrombolytic therapy for arterial thrombosis.

The major development in the field of intra-arterial thrombolytic therapy over the past year was the publication of the phase II results of the Thrombolysis or Peripheral Arterial Surgery study, which compared the safety and efficacy of catheter-directed thrombolysis and surgery as the initial treatment of acute arterial occlusion. The results are consistent with those of the prior two studies, showing little or no difference between surgery and thrombolysis in the most important endpoints of survival and amputation rate. Patients receiving thrombolysis needed fewer interventions, but this benefit was balanced by increased bleeding complications. Additional studies have, therefore, been aimed at identifying subsets of patients with acute arterial occlusion who are most likely to benefit from thrombolysis. These studies have refined the selection criteria for use of thrombolytic therapy over the past year. In addition, studies have been published evaluating new drug doses and regimens aimed at broadening the scope of thrombolytic therapy in patients with acute arterial occlusion.

Intracerebral hemorrhage after carotid endarterectomy: incidence, contribution to neurologic morbidity, and predictive factors.

PURPOSE: With a diminishing rate of cardiac and neurologic events after carotid endarterectomy, intracerebral hemorrhage is gaining increasing importance as a cause of perioperative morbidity and mortality. To date, information has been largely anecdotal, and there has been no comparison with a control group of patients. METHODS: The records of all patients experiencing symptomatic intracerebral hemorrhage after carotid endarterectomy were reviewed and compared with data from 50 randomly selected patients who did not experience intracranial bleeding. Univariate analyses were performed, using the Fisher exact test for dichotomous data and the Student t test for continuous data. RESULTS: During a 6-year period, symptomatic intracranial hemorrhage developed in 11 (0.75%) of 1471 patients undergoing carotid endarterectomy, accounting for 35% of the 31 total perioperative neurologic events. Hemorrhage occurred a median of 3 days postoperatively (range, 0 to 18 days). Signs and symptoms included hypertension in all 11 patients, headache in 7 conscious patients (64%), and bradycardia in 6 patients (55%). Massive hemorrhage with herniation and death occurred in 4 patients (36%). Moderate hemorrhage developed in 5 patients (45%); 3 of these patients had partial recovery, and 2 had complete recovery. Petechial hemorrhage occurred in the remaining 2 patients (18%), 1 with partial and 1 with complete recovery. In comparison with the control group, there were no differences in respect to sex, indication for operation, smoking or diabetic history, and antiplatelet therapy or perioperative heparin management. Patients with intracranial hemorrhage were, however, younger, more frequently hypertensive, had a higher degree of ipsilateral and contralateral carotid stenosis, and had a higher rate of contralateral carotid occlusion. CONCLUSION: Intracranial hemorrhage occurs with notable frequency after carotid endarterectomy and accounts for a significant proportion of neurologic morbidity and mortality. Younger patients, hypertensive patients, and patients with severe cerebrovascular occlusive disease appear to be at greatest risk for the complication.

Clinical review: irradiation for lower extremity arterial occlusive disease.

Lower extremity atherosclerosis, a disease of aging, is both widespread and increasing in prevalence-it is estimated that almost 100,000 patients per year in the United States require operative bypass for lower extremity ischemia. It is an axiom of vascular surgery that essentially every bypass graft will eventually fail. Many if not most such failures are due to the process of intimal hyperplasia at one or both anastomoses. The search for a "cure" for intimal hyperplasia has been long, but thus far unrewarding. Recent advances in therapeutic irradiation, however, offer a potential solution to this problem. This review is designed to acquaint the radiation oncologist with the basic concepts behind lower extremity atherosclerosis and its treatment, and to introduce briefly the special problems inherent in considering irradiation of an end-to-side anastomosis.

A model for merging vascular surgery and interventional radiology: clinical and economical implications.

BACKGROUND: The traditional separation of vascular surgery and interventional radiology into distinct units is associated with inefficiencies in patient care, practice management, and training. Traditional departmental politics, discrepant clinical backgrounds and philosophies, fear of decreasing remuneration, and basic differences in education, training, and practice have all rendered mergers difficult. METHODS: We have implemented a model that incorporates all the clinical, fiscal, and educational activities of the 2 former entities into a single unit. A 5-physician vascular surgery group, its noninvasive laboratory, and a 3-physician interventional radiology group were unified. The revenue was deposited into a single account from which all the expenses were paid. The net income of the joint unit was apportioned on a predetermined pro rata basis, with scaled percentages for each practitioner. In an effort to separate clinical decision making from economic pressures, the individual physician remuneration was not on the basis of productivity. Clinical volume, gross revenue, and remuneration were compared with the 12-month period that immediately preceded the merger and contrasted to the previous 3-year historical trend (HT). RESULTS: The number of vascular surgical procedures fell after the merger (-9.3%; HT, +4.7%). By contrast, the number of interventional radiology procedures rose (+56.1%; HT, +15.2%), as did the number of noninvasive testing (+9.2%; HT, +3.5%). In concordance with the number of procedures, the gross revenue of vascular surgery fell (-23.7%; HT, +1.1%) and that of interventional radiology rose (+53.5%; HT, +46.0%). The increased efficiencies allowed the total expenses of the 2 units to fall (-13.2%; HT, +7. 5%), and, despite the reduced revenue, the vascular surgeon remuneration was preserved (+0.7%; HT, -3.9%) and the radiology remuneration rose (+22.3%; HT, +8.3%). The merger allowed the vascular surgery fellows to actively participate in 26 interventional cases per month and the interventional radiology fellows to actively participate in 8 open surgical cases per month. CONCLUSION: The merger of vascular surgery and interventional radiology resulted in a decrease in the surgical procedures and revenue, with a corresponding increase in the interventional radiology procedures and revenue. Despite these effects, the physician remuneration increased as a result of the improved efficiencies in practice management and the reduction in expenses. The merger of the 2 units excludes the economic pressures from clinical decision making and appears to be warranted on the basis of the fiscal and educational benefits that are achieved.

Fetal internal iliac artery: case report and embryologic review.

A 25-year-old woman with anomalous circulation to the right leg was seen with a symptomatic aneurysm of the abnormal vessel. The artery, which did share some features of the classic persistent sciatic artery, also had important differences that were not previously described in the literature. The patient manifested several associated vascular and nonvascular congenital anomalies. She underwent resection of the aneurysm and primary operative repair of the artery without difficulty. An embryologic interpretation is offered, and the clinical implications and management strategy are discussed.

A condemnation of subcutaneous fasciotomy.

Controversy exists regarding the indications and methods for lower-extremity fasciotomy. Two recent cases at our institution in which recurrent, acute limb-threatening ischemia occurred despite adequate fascial division have convinced us that in certain situations subcutaneous fasciotomy is clearly inadequate. In both patients, both of whom were young, intact healthy skin between the lower extent of the incision and the malleolus acted as a tourniquet, causing recurrent compartment syndrome as reperfusion edema occurred after initial repair. We believe that therapeutic fasciotomy in young patients with relatively noncompliant skin should include division of skin from the knee to the ankle on at least one side to prevent a tourniquet effect by intact skin at the ankle.

Value of preoperative EEG for carotid endarterectomy.

PURPOSE: This study was designed to determine whether the preoperative, baseline electroencephalogram (EEG) can be used for intraoperative decision making during carotid endarterectomy, and to identify circumstances where the EEG can be eliminated. METHODS: The charts of all patients undergoing carotid endartectomy at the authors' institution from June 1991 to May 1995 were reviewed to identify those patients that had adequate pre- and intraoperative EEG monitoring. EEGs during 331 carotid endartectomies in 303 patients were coded without knowledge of outcome; primary and secondary endpoints were EEG changes with clamping and clinical outcome, respectively. RESULTS: The incidence of mortality and major neurological morbidity was 1.8%. Baseline-EEGs were abnormal in 105 patients (32%). Whereas baseline-EEG changes were highly predictive of EEG changes after anesthetic induction (P < .0001), they were not predictive of EEG changes with clamping or of clinical outcome. Prior stroke (CVA) predicted abnormal baseline-EEGs (P < .0001) and abnormal post-anesthetic EEGs (P < .0001) but did not predict changes with clamping or perioperative CVA. EEG changes with clamping occurred during 18% of operations; such changes were predicted only by contralateral occlusion (P < .0016) and EEG changes during a prior contralateral carotid endartectomy (P < .0001). The only variable that predicted an adverse neurological outcome was the presence of contralateral occlusion, which increased the likelihood of a perioperative neurological event seven-fold (P = .0038). Clinical outcomes in the 57 of 105 patients with abnormal baseline-EEGs and the 49 of 83 with prior CVA who were shunted were not different from those who were not. CONCLUSIONS: baseline-EEG is not of value for the prediction of adverse events during carotid endartectomy and can be eliminated. Because contralateral occlusion is highly predictive of changes with clamping, and patients undergoing a second carotid endartectomy will usually manifest EEG changes identical to those at the first, operative EEG monitoring can also be eliminated from both these circumstances. Finally, prior stroke does not lead to a higher incidence of clamp-induced EEG changes, and thus is not an indication for shunting in and of itself.

Ruptured popliteal artery aneurysm.

Popliteal artery aneurysms rarely rupture. We treated a 91-year-old man who presented with a deep venous thrombosis and anemia; rupture of a popliteal artery aneurysm was suspected only after compartment syndrome isolated to the thigh developed as the result of bleeding. Although fasciotomy was required on the basis of the clinical examination alone, the cause of the problem, operative strategy, and definitive treatment (i.e., resection and bypass) were clarified by the preoperative computed tomography scan. Ruptured popliteal aneurysm can manifest as a massively swollen leg with anemia and should be suspected if no other cause is evident.

Comparison of streptokinase, urokinase, and recombinant tissue plasminogen activator in an in vitro model of venous thrombolysis.

PURPOSE: Presumed differences in the thrombolytic activity and fibrinolytic specificity of the three commonly used thrombolytic agents, streptokinase, urokinase, and recombinant tissue plasminogen activator (rt-PA), are based on clinical study results, where variability renders meaningful comparisons difficult. An in vitro model of catheter-directed venous thrombolysis was used to compare the three agents. METHODS: Retracted iodine 125-radiolabeled clots that simulate those observed in the venous system were infused with thrombolytic agents at doses analogous to those used clinically. Perfusion with heparinized, whole human blood was undertaken for 60 minutes, measuring the efficacy of thrombolysis through serial quantification of radio tracer released into the circuit. Fibrinolytic specificity was determined by following decrements in perfusate fibrinogen concentration. RESULTS: Streptokinase was the agent associated with the slowest rate of clot lysis (p = 0.01 vs urokinase and rt-PA). Urokinase was associated with an intermediate rate of lysis but appeared to be the agent with the greatest degree of fibrinolytic specificity (p = 0.02 vs streptokinase, p = 0.05 vs rt-PA). Although rt-PA was associated with improved efficacy early in the perfusions, the differences between rt-PA and urokinase dissipated after 30 minutes. CONCLUSIONS: These laboratory observations suggest that urokinase may be the most appropriate agent for catheter-directed venous thrombolysis, offering an advantageous compromise between fibrinolytic specificity and thrombolytic speed.

Differential mechanisms of failure of autogenous and non-autogenous bypass conduits: an assessment following successful graft thrombolysis.

The advent of graft thrombolysis has provided an objective means for evaluating the etiology of graft occlusion. Over a 10-year period, intra-arterial urokinase (102 cases) or streptokinase (seven cases) was used in 109 infrainguinal conduits (30 autogenous and 79 non-autogenous) that failed 30 days or more after implantation. Thrombolysis was not achieved in 19 additional graft occlusions; these cases were excluded from study because of an inability to define the mechanism of failure. Non-invasive laboratory data were available within 6 months of graft occlusion in 82 (75%) of the cases, with Doppler segmental studies in 80 cases (73%) and duplex ultrasonography studies in 39 cases (36%). Pre-failure non-invasive laboratory abnormalities were detected more frequently in autogenous grafts (21 of 24 patients, 88%), while non-autogenous grafts usually occluded without prior hemodynamic change (11 of 58 patients had abnormalities, 19%) (P < 0.001). Thrombolysis uncovered anatomic defects responsible for thrombosis in 27 (90%) of 30 autogenous grafts compared with only 32 (41%) of non-autogenous conduits (P < 0.001). The most common lesions underlying autogenous graft failure comprised stenoses within the body of the graft (11 cases, 37%), while the most common lesions in failed non-autogenous grafts appeared to be stenoses at an anastomosis (21 cases, 27%). Thus, the mechanisms underlying the late failure of autogenous and non-autogenous grafts differ markedly; autogenous grafts most commonly fail as a result of the gradual development of lesions intrinsic to the graft, while non-autogenous grafts fail precipitously, presumably as a result of some non-anatomic mechanism.

Operative management of coexistent aortic disease and horseshoe kidney.

The presence of horseshoe kidney in conjunction with abdominal aortic disease significantly increases the technical difficulty of aortic reconstruction. Preservation of the renal blood supply and collecting system during the surgical procedure is the goal of operative management. The pertinent issues that remain unresolved include the need for specific preoperative studies, the optimal operative approach and the safety of isthmus division. From 1979 to 1994 eight patients with horseshoe kidney underwent operative intervention for aortic disease. Five men and three women who had a mean age of 66 years underwent seven reconstructions for aneurysmal disease and one for aortoiliac occlusive disease. All operations were elective and the transperitoneal approach was used in all cases. In the patients with aneurysmal disease the mean maximal aortic diameter was 7.3 cm. The mean preoperative serum creatinine value was 1.1 mg/dl. Preoperative identification of horseshoe kidney was accomplished in all seven patients with aneurysmal disease but not in the patient with occlusive disease. The anomaly was correctly identified by CT scan in seven of seven (100%) patients, arteriography in two of eight (25%) patients, ultrasonography in two of seven (29%) patients, and renal scan in one patient. In the three patients who underwent intravenous pyelography (IVP) the caliceal system was demonstrated to be completely separate from the isthmus. Renal artery anomalies were present in six (75%) patients; in three (50%) these anomalies could be not visualized on the preoperative arteriogram. Renal revascularization was accomplished by a variety of techniques, including reimplantation of multiple (one patient) and single (four patients) renal arteries and branch grafting to an individual renal artery (one patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute peripheral arterial occlusion: predictors of success in catheter-directed thrombolytic therapy.

PURPOSE: To determine predictors of clot dissolution in patients undergoing catheter-directed urokinase thrombolysis for peripheral arterial occlusion (PAO). MATERIALS AND METHODS: The study included 103 patients with limb-threatening symptoms of embolism lasting 14 days or less and resulting from embolism (n = 20) or thrombosis (n = 83). Successful lysis was defined as restitution of antegrade flow with less than 20% diameter reduction by residual thrombus. Stepwise logistic regression was used to analyze the data. RESULTS: Relevant clinical variables were diabetic status (odds ratio, 0.75; P = .04 for diabetic patients), conduit type (1.25; P = .04 for native artery and 1.51; P = .02 for prosthetic graft), and number of arterial segments involved (1.60; P = .02 for one level and 1.42; P = .03 for two levels). Important procedural variables included intrathrombus positioning of catheter ports (odds ratio, 7.40; P = .001) and guide wire passage through the occlusion (3.10; P = .003). Absolute thrombus volume was nonpredictive but correlated with reperfusion time (P = .02) and infusion time (P = .01). CONCLUSION: Predictive parameters may help in the selection of candidates with PAO for thrombolytic therapy.

A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia.

PURPOSE: Despite the widespread use of intraarterial thrombolytic therapy for peripheral arterial occlusive disease, a randomized study comparing its efficacy with that of operative intervention has never been performed. This study evaluates the potential of intraarterial urokinase infusion to provide clinical benefits in patients with acute peripheral arterial occlusion. METHODS: Patients with limb-threatening ischemia of less than 7 days' duration were randomly assigned to intraarterial catheter-directed urokinase therapy or operative intervention. Anatomic lesions unmasked by thrombolysis were treated with balloon dilation or operation. The primary end points of the study were limb salvage and survival. RESULTS: A total of 57 patients were randomized to the thrombolytic therapy group, and 57 patients were randomized to the operative therapy group. Thrombolytic therapy resulted in dissolution of the occluding thrombus in 40 (70%) patients. Although the cumulative limb salvage rate was similar in the two treatment groups (82% at 12 months), the cumulative survival rate was significantly improved in patients randomized to the thrombolysis group (84% vs 58% at 12 months, p = 0.01). The mortality differences seemed to be primarily attributable to an increased frequency of in-hospital cardiopulmonary complications in the operative treatment group (49% vs 16%, p = 0.001). The benefits of thrombolysis were achieved without significant differences in the duration of hospitalization (median 11 days) and with only modest increases in hospital cost in the thrombolytic treatment arm (median $15,672 vs $12,253, p = 0.02). CONCLUSIONS: Intraarterial thrombolytic therapy was associated with a reduction in the incidence of in-hospital cardiopulmonary complications and a corresponding increase in patient survival rates. These benefits were achieved without an appreciable increase in the duration of hospitalization and with only modest increases in hospital cost, suggesting that thrombolytic therapy may offer a safe and effective alternative to operation in the initial treatment of patients diagnosed with acute limb-threatening peripheral arterial occlusion.