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Thrombolysis in Arterial Bypass Grafts
Arterial bypass grafting is the mainstay of surgical management of peripheral vascular disease. Since its earliest description, there has been an evolution in materials for bypass grafting as well as surgical techniques, with a gradual improvement in results. Despite significant progress, however, graft occlusions continue to be a significant source of morbidity and limb loss in patients with peripheral vascular disease. The frequency of graft occlusions is dependent in large part on the nature of the bypass graft, its location, and the adequacy of both inflow and outflow to the bypassed segment. The possible etiologies of graft occlusions are multiple but may be stratified by the age of the graft.1'2 Acute occlusions in the immediate postoperative period (up to 30 days) are often due to technical problems with the graft or to errors of surgical judgment and often require immediate reoperation and correction of the underlying abnormality. Later occlusions, including those occurring from 1 month to 1 year after placement of the graft, may be due to myointimal hyperplastic lesions within the graft or at its anastomoses. Beyond 1 year, occlusions are most likely to result from progression of atherosclerotic disease. In the management of patients with peripheral bypass grafts, the adage, "An ounce of prevention is worth a pound of cure," should be considered seriously. Because of the relatively poor long-term prognosis for patients with occlusive peripheral disease and their significant coexistent morbidities, every precaution should be taken to identify those patients who are at risk of failure prior to occlusion of their grafts. This mandates careful clinical monitoring with noninvasive evaluation, including, when feasible, hemodynamic assessment and anatomic evaluation, the latter often readily accomplished by duplex imaging. Patency rates for grafts,
From the Department of Radiology, The Alexandria Hospital, Alexandria, Virginia. Reprint requests: Dr. Van Breda, Department of Radiology, The Alexandria Hospital, 4320 Seminary Road, Alexandria, VA 22304.
revised prior to occlusions, are significantly better than outcome by any modality after occlusion.1, 3-5 Patients with occlusions of arterial bypass grafts vary widely in their clinical presentation, often presenting with severe, limb-threatening ischemia, but may present with only exacerbation of symptoms and a return to their preoperative clinical status. Patients presenting with more severe and limb-threatening ischemia require urgent intervention. Standard surgical techniques include thrombectomy of the bypass graft, with intraoperative arteriography to ensure patency of the graft and to identify factors responsible for graft thrombosis.1,5 This approach, although often successful, may result in failure to achieve the desired clinical improvement with repeated graft failure necessitating repeated thrombectomy. Since results of thrombectomy alone are often unsatisfactory, more extensive surgical revision may be necessary. Alternatively, the entire graft may be replaced utilizing the autogenous vein, if available, or prosthetic materials, if not.6'7 With careful surgical technique, graft and limb salvage is often feasible but long-term patency rates after salvage of thrombosed grafts remain poor. The poor results of operative management have led to interest in thrombolysis as a means of improving outcome in this group of patients. Thrombolytic therapy has been available for over two decades for use in occluded native arteries and bypass grafts. Initial descriptions of thrombolytic technique featured high doses of thrombolytic agent given intravenously to produce a systemic effect. The utility of this approach was limited by a relatively low and unpredictable rate of success and a high rate of bleeding complications.8,10 Coinciding with the development of selective angiographic technique, local intra-arterial application of low doses of lytic agents was proposed to improve efficacy of lysis and reduce the rate of complications.11,12 Low-dose local thrombolysis has undergone considerable evolution since initially described by Dotter in 1972,13 but the major tenents remain unchanged. Angiographic technique is used to position a
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catheter at the site of occlusion, allowing direct deposition of lytic agent into the thrombosis and angiographic monitoring of treatment success. Local intra-arterial thrombolytic therapy has become the modality of choice for interventional treatment of occluded arterial segments in the peripheral vasculature, whereas systemic thrombolytic therapy remains the preferred technique for treatment of most coronary artery occlusions and of deep vein thrombosis. Pulmonary emboli may be treated by either systemic or local lytic therapy. The decision to use a local versus a systemic approach for thrombolysis is dependent on clinical and technical factors. For acute coronary occlusions, the short interval during which lysis is effective in preventing irreversible myocardial damage precludes time-consuming coronary catheterization necessary for local thrombolysis, and results of high-dose systemic lysis rival those obtainable with local infusions.14 The risks of this therapy are outweighed by the advantages of myocardial salvage. With peripheral arterial and graft occlusions, a much longer therapeutic window coupled with the poor results of systemic therapy necessitated use of intra-arterial local infusions. The rationale of graft thrombolysis derived from the limitations of surgical management of occluded grafts. Lysis may avoid the need for reoperation and its attendant morbidity and mortality of up to 5%; it may allow prospective evaluation of the etiology of graft occlusion and thereby a more focused and appropriate interventional or surgical repair, and, lastly, it has been hoped that lysis would prolong the patency of vein grafts, avoiding revision with less desirable prosthetic material.15 These expectations, initially optimistic, have not been uniformly fulfilled, nor has the technique met with universal acceptance. This review will, it is hoped, provide some perspective on the role of graft thrombolysis in the current management of patients with occluded peripheral bypass grafts.
TECHNIQUE OF GRAFT THROMBOLYSIS Patient Selection Selection of patients for treatment of occluded peripheral bypass grafts requires consideration of a number of factors. First and foremost is the clinical status of the patient at the time of occlusion. Although patients with graft occlusions may exhibit a range of symptoms, acute occlusions frequently present with a relatively severe degree of ischemia. Judgment of outcome of prolonged ischemia should include consideration of the potential duration of infusion necessary to result in complete lysis and symptomatic relief. Ideally, this
judgment is made by collaboration of the interventionalist and the vascular surgeon. Patients with advanced degrees of ischemia, that is, those with a cold mottled extremity or with significant neurologic dysfunction, should not undergo thrombolytic therapy unless all other approaches for more rapid restoration of perfusion are deemed not feasible due to the low yield of limb salvage in this setting and the potential for life-threatening reperfusion injury.16 In this situation, a simple thrombectomy or revision of graft may be indicated to restore perfusion in the most expeditious manner possible. Patients presenting with less severe ischemia may be considered candidates for graft thrombolysis dependent on the relative risks and benefits of thrombolysis in that individual. This should include consideration of the nature of the graft material, the possible risks of thrombolysis, the position of the graft, the surgical alternatives, and the ability of the patient to cooperate during a possibly lengthy thrombolytic infusion. Consideration of surgical alternatives mandates knowledge of the likelihood of successful outcome with other treatment modalities. Evaluation of the patient's prior clinical history, and angiographic evaluation may help predict likelihood of success of management alternatives. Those patients with extremely poor outflow at the time of initial graft placement are unlikely to benefit from either thrombolysis or simple thrombectomy without improving outflow, possibly by distal bypass grafting. Our enthusiasm for treating these patients is considerably lower than in those patients with previously good outflow. We are frequently requested to perform graft thrombolysis due to the poor predicted outcome of surgical therapy or the increased risk of surgical therapy in some patients. For example, patients with multiple prior surgical procedures represent a daunting technical undertaking for the vascular surgeon. Similarly, long-term effects of repeated thrombectomies of native vessels proximal and distal to grafts are becoming better known with possible worsening of long-term outcome due to the results of this repeated trauma. 17-19 Thrombolysis offers a potential for "chemical" rather than mechanical thrombectomy with potentially better long-term effects. In those patients who present with mild symptoms such as nondisabling claudication, the risks of any further intervention may outweigh the potential benefits and in these patients, no further therapy may be appropriate. Factors that must be included in considerations for possible thrombolytic therapy include the nature and age of the occluded graft. Porous synthetic grafts of woven and knitted Dacron and polytetrafluoroethylene are dependent on the formation of a pseudointima, comprised of fibrinogen and fibrin, as well as collagen and platelet membrane elements for both the integrity and patency of the graft.20 The fibrinous element in this pseudointima
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and in the perigraft space is subject to lysis by fibrinolytic agents. This may lead to significant hemorrhagic complications if thrombolytic therapy is pursued prior to maturation of the graft by perigraft fibrosis. Although angiographic evidence of contrast extravasation through graft interstices is reported even in relatively mature grafts, significant hemorrhagic complications are unlikely unless therapy is attempted in grafts less than 3 months old. 21,22 That is probably due to lack of complete maturation of the perigraft structures. We therefore do not recommend fibrinolytic therapy of porous grafts that have been in place for less than 3 months, and with caution in grafts of less than 6 months, especially in intra-abdominal or retroperitoneal grafts where significant bleeding may occur prior to clinical detection. In the infrainguinal position, the extremity may be more readily monitored if signs of bleeding occur, and therefore these represent a less severe contraindication. However, as just noted, graft occlusions that occur in a relatively recent postoperative period are often due to technical factors and require surgical revision as a primary method of treatment. Other contraindications to the use of local fibrinolytic therapy are relatively few. Although low-dose, local therapy has a lower likelihood of significant bleeding complications at distant sites, major intracranial abnormalities likely to cause bleeding preclude patients from lytic therapy. A systemic fibrinolytic effect may result in embolization of thrombotic material from a central site, such as cardiac mural thrombi, and these patients should be treated with care to avoid the likelihood of this complication.23 Patients with coagulopathies are at greater risk for complications. Patients are screened for both thrombotic and hemorrhagic coagulopathies prior to treatment.24
Technique All patients undergoing fibrinolytic therapy should have a complete diagnostic angiography prior to institution of therapy. This may be facilitated by review of preoperative and postoperative angiograms and the operative report of prior surgical procedures. Duplex ultrasonography is useful in evaluating adjacent arterial segments for patency and focal abnormalities requiring treatment, such as pseudoaneurysms or stenoses. Prelysis angiography requires evaluation of both the proximal and distal vascular beds, with special attention to the status of the distal runoff vessels. In patients with occluded aorto-bifemoral grafts, use of venous digital subtraction angiography can avoid the need for an arterial puncture prior to the onset of fibrinolytic therapy. Once the occlusion has been defined, the optimal approach for lysis is selected. Often a
9 second arterial puncture is necessary. Lytic treatment of occluded bypass grafts requires catheter tip placement in the occluded segment. Whenever feasible, the catheter is introduced antegrade to the occluded segment and from as close to an access site as possible.25-27 Efforts are made to avoid traversing long segments of diseased artery or positioning the catheter distal to an occluded segment to minimize the risk of developing new thrombus around the treatment catheter.28 Direct puncture of the graft for initiation of lysis may occasionally be necessary and may be a useful access. When puncture of a bypass graft is necessary to perform thrombolytic therapy, prophylactic antibiotic coverage may be considered during the infusion. There is no clear-cut evidence that this is beneficial, but it is used empirically due to the potentially devastating results of graft infection.
DRUG AND DOSAGE CONSIDERATIONS Streptokinase was the agent initially used for the treatment of peripheral vascular occlusions;13,29,30 urokinase is now the generally preferred drug due to greater efficacy of lysis and a lower incidence of bleeding complications.25,26,31-33 Recombinant tissue plasminogen activator (r-tPA) has also been used for both native and graft arterial occlusions but has not as yet achieved widespread use. Early clinical experience with this agent demonstrated successful fibrinolysis with shorter duration infusions than that required with streptokinase or urokinase.34-38 Concerns about potential bleeding complications, however, have led to eventual lowering of the recommended dose for peripheral intra-arterial thrombolysis and the subsequent lengthening of the time of infusion. The optimum dose rate of this agent remains to be defined.39-41 Other agents are being evaluated for potential usefulness in this application.42,43 The ideal thrombolytic agent remains elusive, however, with some drawbacks to each agent used.14 The most widely used agent in the United States is urokinase. A "low-dose" and "high-dose" technique have been described; both represent less than systemic dose rates, however. With low-dose urokinase treatment, 60,000 to 100,000 U/hr urokinase are given, with average duration of infusion approximately 18 hours.25,26,31 Highdose local urokinase infusion uses an initial higher dose rate of 4000 U/min for the initial 2 to 3 hours, or until antegrade flow is achieved. The dose rate is then decreased to 60,000 U/hr.26 An alternative to the infusion technique is a combined pharmacomechanical approach that is more widely employed in Europe. Initially described by Hess et al, 44 this utilizes relatively small doses of streptokinase or urokinase injected directly into the clot, followed after several minutes by vigorous aspira-
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tion of the thrombus. 44-47 Still others have described a combination of the pharmacomechanical approach followed by low-dose infusions in those patients in whom incomplete results are achieved with the bolus technique.48 One of the advantages of the pharmacomechanical approach is shorter durations of infusion, with an average time of approximately 3 hours. Further development of this approach includes the use of a pulsatile spray with forceful injections of thrombolytic agents throughout the length of the thrombus by a mechanical pump. 49-51 Lower total doses of the thrombolytic agent may be required for successful infusion with significant shortening of the duration of thrombolysis. Early clinical evaluations are ongoing at this time. When using the infusion technique, a bolus of fibrinolytic agent may be given at the onset of therapy by "lacing" the graft in an attempt to improve the speed of fibrinolysis.52 To the greatest degree possible, a guidewire is used to penetrate the entire length of the clot in the occluded segment. A bolus of agent (250,000 U urokinase) is then deposited through the length of the graft during slow withdrawal of the injectable guidewire or catheter. The long length of most graft occlusions is an excellent indication for use of a coaxial technique, which allows distribution of fibrinolytic agents from two separate sites.25 In general, a 5 F catheter is used for the proximal infusion site, through which an injectable catheter or guidewire (0.035 to 0.038 inch or 2 to 3 F) is positioned at approximately the midportion of the occluded segment or somewhat more distally. The total dose of fibrinolytic agent is then divided between these two sites. Once fibrinolytic therapy is instituted, close frequent observation of the infused extremity for signs of restoration of pulses or deterioration is necessary. We prefer monitoring patients in an interventional recovery area or an intensive care unit during this phase of the procedure. Repeat angiographic evaluation is performed periodically, usually within 4 to 6 hours after the onset of therapy and then at approximately 12-hour intervals thereafter or when there is clinical evidence of lysis. Deterioration of the patient's clinical status is not an indication for repeat angiography unless this does not resolve spontaneously in a relatively short period of time. Acute clinical deterioration, that is, sudden worsening of pain, increased pallor, or other signs of worsening ischemia, are generally due to distal embolization of partially lysed thrombotic materials. During initial experience with thrombolytic therapy, this generally prompted termination of fibrinolysis and urgent repeat angiographic evaluation. It is our experience that most episodes of distal embolization resolve spontaneously with continued fibrinolytic infusions; this may occasionally necessitate repositioning of the catheter to maintain
maximum contact between the infused agent and the embolic fragment. As necessary, catheters are advanced to maintain the catheter tip in the thrombus, taking care not to introduce contaminated segments of catheter into the graft. Systemic heparinization is recommended by many investigators for routine use during intra-arterial fibrinolysis. The rationale for systemic heparinization includes prevention of pericatheter thrombus formation, prevention of propagating thrombosis distal to an occlusion in an acutely occluded segment, and the possible potentiation of fibrinolytic activity with heparin. 26-28,53,54 In less severely ischemic limbs, low-dose regional heparinization (200 to 400 U/hr) is an alterative that accomplishes the same objectives with fewer risks.25 With severe ischemia, there is greater risk of propagating thrombus, and systemic heparinization should be used. Laboratory monitoring of patients undergoing thrombolysis is performed to detect the development of a significant systemic lytic effect, which is most simply performed by measurements of fibrinogen and thrombin times. 27,31,55 Infusion duration should be limited to 24 hours whenever possible. Only in cases in which there is virtually complete lysis and a short-term continuation of the infusion will result in a clinically beneficial result, should infusions continue beyond this. Longer infusions are only warranted in those patients for whom there is no alternative to limb loss, who have angiographic demonstration of ongoing lysis, and who are able to tolerate further therapy. The increased risk of complications and decreased likelihood of eventual success when longer infusions are used, as well as the discomfort for the patient, have led us to limit infusions to shorter durations if at all possible. Repeat angiographic assessment should be performed immediately at the completion of fibrinolytic infusion with attention directed toward identifying the etiology of the graft occlusion. If feasible, angioplasty of anastomic stenoses or inflow-outflow lesions should be performed immediately after lysis; if surgery is necessary, this should be performed promptly to avoid interval rethrombosis. Low-dose thrombolysis should not cause significant derangement in coagulation parameters or produce a hemorrhagic tendency, and delay to correct lysis-induced coagulopathy should not be necessary. It is important, however, to ensure that lysis is complete prior to instituting angioplasty or other percutaneous treatment. Significant residual thrombus may cause distal embolization during angioplasty. We prefer to obtain maximum benefit of lysis prior to angioplasty. Occasionally, it may be necessary to perform angioplasty in the presence of incomplete lysis to restore some antegrade flow; this should be followed by sufficient subsequent
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lysis to prevent rethrombosis. Occasionally, no abnormality will be identified to explain the graft thrombosis. This is most frequently seen in infrainguinal grafts, which may have become occluded due to transient hemodynamic factors, such as decrease in cardiac output and inadvertent compression of a portion of the graft. In these instances, careful consideration should be given to what possible steps may be taken to correct the predisposing factors of thrombosis; occasionally, we have instituted long-term anticoagulation in these patients to prevent repeat thromboses.
RESULTS Evaluation of results of thrombolytic therapy is hampered by wide variations in definition of success and means of reporting results. A number of studies include results in both native vessel and graft occlusions. Several studies have concentrated on results solely in grafts. Initial clinical success has ranged from 10 to 70%. In several reports, success included patients in whom clinical benefit was derived by minimizing the extent of subsequent surgical repair. 15,56-59 As with peripheral arterial occlusions, higher success rates were noted with urokinase than with streptokinase.33,57 Later reports emphasized results of the long-term follow-up of treated grafts. In virtually all reports there was a high rate of reocclusion, with 1-year patency reported from 10 to 37%. Overall limb salvage (with secondary patency), however, was higher in all series, ranging from 50 to 60%. 57-60 In a study by Belkin et al59, following results of successful thrombolysis of saphenous vein graft occlusions, overall 1 year patency was 37%, but with a 1 year limb salvage rate of 67%. They, as others, noted a fairly advanced degree of disease in the patient population, but concluded that routine use of thrombolytic therapy for salvage of occluded venous bypass grafts was not warranted and should be reserved for patients in whom an autogenous vein was not available for repeat bypass grafting. Another analysis of 53 patients undergoing thrombolysis with venous and prosthetic grafts by Durham et al, 60 noted a mean patency rate of 162 days. In comparing the results of surgical therapy, these authors believed that surgical reconstruction was preferred for suprainguinal grafts and for venous infrainguinal grafts; however, they believed that thrombolysis was comparable to surgery for below-knee femoralpopliteal bypass graft revision. In one study by Graor et al,61 retrospective comparative analysis of surgically treated grafts versus those lysed with rt-PA noted significantly better patency rates at 30 days with thrombolysis versus thrombectomy. Long-term patencies, however, were not evaluated nor was comparison made with other
11 surgical techniques, such as graft revision or repeat bypass. In each of these studies, note was made of the extensive nature of the disease present in the patient population, with therapy often undertaken for limb salvage. This is reflected in a high rate of amputation reported when thrombolysis fails.57 Mortality in these reports ranges from 0 to 3%; morbidity is difficult to assess due to differences in reporting standards. Significant complications were noted to occur in 20 to 50% of cases. To place these results in perspective, familiarity with results of surgical procedures in this patient population is necessary. Currently, long-term primary patency rates for infrainguinal and extra-anatomic prosthetic bypass grafts range from 15 to 65% at 5 years. 1 ' 4 ' 6,62 ' 63 Long-term patency rates with autogenous vein are significantly better, with 5 year patency rates of up to 80%. 63,64 Mortality of bypass grafting ranges from 1 to 5%. Detection of the failing bypass graft by careful noninvasive follow-up allows excellent results for secondary patencies after revision. Again, as with primary patency, secondary patency after revision for a failing graft is better with autogenous vein graft than prosthetic graft. Five-year secondary patency of 85% may be achieved after revision of a failing vein graft.1'64 Those patients with thrombosed bypass grafts represent the most problematic spectrum of this patient population. Graft salvage procedures, including thrombectomy and revision for prosthetic graft occlusions, yield a 52% 3-year patency for above-knee bypasses, with only 13% 3-year patency below-knee bypasses. Improvement in these poor secondary patency rates can be achieved by total revision of the bypass graft, yielding a 3-year patency of 48% in below-knee bypass grafts.6 Results are equally poor for salvage of occluded vein grafts by thrombectomy with patencies of 19 to 28% at 5 years.3 Mortality with repeat surgery ranges from 1 to 5%. Unclear at this time is the effect of cost considerations on eventual role of thrombolysis versus surgery. One report indicates a significantly higher effective cost per complete success of thrombolytic therapy when compared with surgery for treatment of arterial and graft occlusions.65 This again, however, is a retrospective evaluation without randomization. The cost of thrombolytic therapy can be considerable due to the high cost of thrombolytic agent ($1000 to 2000 per treatment with urokinase) plus the associated cost of intensive care unit monitoring. Retrospective review of 173 thrombolytic infusions at Alexandria Hospital included treatment of 38 occluded bypass grafts. Of these, 71% were clinically beneficial. Hospital costs for patients successfully treated with thrombolysis and angioplasty were significantly
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lower than for those patients who required subsequent surgical revision.33 8.
CONCLUSIONS It appears that the role of thrombolysis in the treatment of occluded bypass grafts remains limited. Thus far, patency is not improved with lysis when compared with surgical therapy, yet in some instances lysis may be of benefit. Prospective comparative evaluation with randomization to surgery or thrombolysis has not been performed, nor does this appear to be likely. How, then, is the clinician to determine the role of thrombolysis? It is our current feeling that the decision to treat occluded bypass grafts with thrombolysis must be individualized based on the careful evaluation of all factors at the time of patient presentation. If surgical revision can be performed easily, and in those patients in whom this is likely to result in reasonable success, such as suprainguinal grafts or patients with available autogenous vein and anatomy suitable for repeat bypass grafting, surgery is the preferred therapy. In other instances, particularly in those patients without sufficient autogenous vein for repeat bypass grafting, or with a history of repeated occlusions after thrombectomies, thrombolysis may play a role in prolonging patency of bypass grafts with rates of long-term success similar to surgical treatment. Clearly, the long-term outlook for these patients remains poor, but thrombolysis may provide limb salvage with reasonable risks.
9.
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29. Katzen BT, A van Breda: Low dose streptokinase in the treatment of arterial occlusions. AJR 136:1171-1178, 1981. 30. Becker GJ, FE Rabe, BD Richmond, RW Holden, HY Yune, RS Dilley, NU Bang, JL Glover, EC Klatte: Low dose fibrinolytic therapy. Radiology 148:663-670, 1983. 31. van Breda A, BT Katzen, AS Deutsch: Urokinase vs streptokinase in local thrombolysis. Radiology 165:109, 1987. 32. Belkin M, B Belkin, CA Bucknam, JJ Straub, R Lowe: Intraarterial fibrinolytic therapy. Arch Surg 121:769-773, 1986. 33. van Breda A, RA Graor, BT Katzen, B Risius: The relative cost effectiveness of urokinase and streptokinase in the treatment of peripheral vascular disease. J Vasc Intervent Radiol 1:1991. 34. Risius B, RA Graor, MA Grisinger, MG Zelch, FV Lucas, JR Young, EB Grossbard: Recombinant human tissue-type plasminogen activator for thrombolysis in peripheral arteries and bypass grafts. Radiology 160:183-188, 1986. 35. Risius B, RA Graor, MA Geisinger, MG Zelch, FV Lucas, JR Young: Thrombolytic therapy with recombinant human tissue-type plasminogen activator: A comparison of two doses. Radiology 164:465, 1987. 36. Krupski WC, RK Feldman, JH Rapp: Recombinant human tissuetype plasminogen activator is an effective agent for thrombolysis of peripheral arteries and bypass grafts: Preliminary report. J Vasc Surg 10:491-500, 1989. 37. Koppensteiner R, E Minar, R Ahmadi, M Jung, H Ehringer, B Risius: Low doses of recombinant human tissue-type plasminogen activator for local thrombolysis in peripheral arteries. Radiology 168:877, 1988. 38. Verstraete M, H Hess, F Mahler, A Mietaschk, FJ Roth, E Schneider, AL Baert, R Verhaeghe: Femoro-popliteal artery thrombolysis with intra-arterial infusion of recombinant tissue-type plasminogen activator—report of a pilot trial. Eur J Vasc Surg 2:155-159, 1988. 39. Berridge DC, RHS Gregson, BR Hopkinson, GS Makin: Intraarterial thrombolysis using recombinant tissue plasminogen activator (rt-PA): the optimal agent, at the optimal dose? Eur J Vasc Surg 3:327-332, 1989. 40. Meyerovitz MF, SZ Goldhaber, K Reagan, JF Polak, K Kandarpa, CJ Grassi, BC Donovan, MA Bettmann, DP Harrington: Recombinant tissue-type plasminogen activator versus urokinase in peripheral arterial and graft occlusions: A randomized trial. Radiology 175:75-78, 1990. 41. Gardiner GA, AK Rao: Thrombolysis for peripheral arterial occlusions. Radiology 175:34-36, 1990. 42. Pernes JM, JF Vitous, P Brenoit, A Raynaud, JL Parola, JP Roth, CY Angel, JN Fissinger, M Roncato, JC Gaux: Acute peripheral arterial and graft occlusion: Treatment with selective infusion of urokinase and lysyl plasminogen. Radiology 158:481-485, 1986. 43. Pilger E, J Lammer, H Bertuch, H Steiner: Intraarterial fibrinolysis: In vitro and prospective clinical evaluation of three thrombolytic agents. Radiology 161:597-599, 1986. 44. Hess H, H Ingrisch, KA Mietasch, H Rath: Local low dose thrombolytic therapy of peripheral arterial occlusions. N Engl J Med 307:1626-1630, 1982. 45. Hess H, A Mietaschk, R Bruckl: Peripheral arterial occlusions: A 6-year experience with local low dose thrombolytic therapy. Radiology 163:753, 1987. 46. Verhaeghe R, G Wilms, J Vermylen: Local low-dose thrombolysis in arterial disease of the limbs. Semin Thromb Hemost 13:206211, 1987. 47. Lammer J, E Pilger, K Neumayer, H Shreyer: Intraarterial fibrinolysis: Long-term results. Radiology 161:159-163, 1986.
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48. Do D, F Mahler, J Triller, B Nachbur: Combination of short and long-term catheter thrombolysis for peripheral arterial occlusion. Eur J Radiol 7:235-238, 1987. 49. Davis GB, CF Dowd, JJ Bookstein, TP Maroney, EV Lang, N Halasz: Thrombosed dialysis grafts: Efficacy of intrathrombic deposition of concentrated urokinase, clot maceration, and angioplasty. AJR 149:177-181, 1987. 50. Bookstein JJ, B Fellmeth, A Roberts, K Valji, G Davis, T Machado: Pulsed-spray pharmacomechanical thrombolysis: Preliminary clinical results. AJR 152:1097-1100, 1989. 51. Kandarpa K, PA Drinker, SJ Singer, D Caramore: Forceful pulsatile local infusion of enzyme accelerates thrombolysis: In vivo evaluation of a new delivery system. Radiology 168:739-744, 1988. 52. Sullivan KL, GA Gardiner, MJ Shapiro, J Bonn, DC Levin: Acceleration of thrombolysis with a high dose transthrombus bolus technique. Radiology 173:805-808, 1989. 53. Susawa T, Y Yui, R Hattori, Y Takatsu, N Yui, M Takahashi, T Aoyama, Y Murohara, M Shirotani, C Kawai: Enhancement of coronary thrombolysis with plasminogen proactivator by pretreatment with heparin. Jpn Circ J 52:72-78, 1988. 54. Fears R: Kinetic studies on the effect of heparin and fibrin on plasminogen activators. Biochem J 249:77-81, 1988. 55. Shafer KE, SA Santoro, BE Sobel, AS Jaffe: Monitoring activity of fibrinolytic agents: A therapeutic challenge. Am J Med 76:879886, 1984. 56. Hargrove WC, HD Berkowitz, DB Freiman, G McLean, EJ Ring, B Roberts: Recanalization of totally occluded femoropopliteal vein grafts with low-dose streptokinase infusion. Surgery 92:890-895, 1982. 57. Gardiner GA: Thrombolysis of occluded femoropopliteal grafts. AJR 147:621-626, 1986. 58. Perler BA, RI White, CB Ernst, GM Williams: Low-dose thrombolytic therapy for infrainguinal graft occlusions: An idea whose time has passed? J Vasc Surg 2:799-805, 1985. 59. Belkin M, MC Donaldson, AD Whittemore, JF Polak, CJ Grassi, DP Harrington, JA Mannick: Observations on the use of thrombolytic agents for thrombotic occlusion of infrainguinal vein grafts. J Vasc Surg 11:289-296, 1990. 60. Durham JD, SC Geller, WM Abbott, H Shapiro, AC Waltman, TG Walker, DC Brewster, CA Athanasoulis: Regional infusion of urokinase into occluded lower-extremity bypass grafts: Long-term clinical results. Radiology 172:83, 1989. 61. Graor RA, B Risius, JR Young, FV Lucas, EG Beven, NR Hertzer, LP Krajewski, PJ O'Hara, J Olin, WF Ruschhaupt: Thrombolysis of peripheral arterial bypass grafts: Surgical thrombectomy compared with thrombolysis. J Vasc Surg 7:347-355, 1988. 62. Kent KC, MC Donaldson, CE Attinger, NP Couch, JA Mannick, AD Whittemore: Femoropopliteal reconstruction for claudication. Arch Surg 123:1196-1198, 1988. 63. Taylor LM, JM Porter: Current status of the reversed saphenous vein graft. In: Bergar JJ, JST Yao (Eds): Arterial Surgery: New Diagnostic and Operative Techniques. Grune & Stratton, New York, 1988, pp 483-505. 64. Taylor LM, JM Edwards, ES Phinney, JM Porter: Reserved vein bypass to infrapopliteal arteries: Modern results are superior to or equivalent to in situ bypass for patency and for vein utilization. Ann Surg 205:90-97, 1987. 65. Dacey LJ, RW Dow, DB Walsh, RM Zwolak, JL Cronenwett: Cost-effectiveness of intra-arterial thrombolytic therapy. Arch Surg 123:1218-1223, 1988.
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THROMBOLYSIS IN ARTERIAL GRAFTS—VAN BREDA
Thrombolysis in Arterial Bypass Grafts
Arterial bypass grafting is the mainstay of surgical management of peripheral vascular disease. Since its earliest description, there has been an evolution in materials for bypass grafting as well as surgical techniques, with a gradual improvement in results. Despite significant progress, however, graft occlusions continue to be a significant source of morbidity and limb loss in patients with peripheral vascular disease. The frequency of graft occlusions is dependent in large part on the nature of the bypass graft, its location, and the adequacy of both inflow and outflow to the bypassed segment. The possible etiologies of graft occlusions are multiple but may be stratified by the age of the graft.1'2 Acute occlusions in the immediate postoperative period (up to 30 days) are often due to technical problems with the graft or to errors of surgical judgment and often require immediate reoperation and correction of the underlying abnormality. Later occlusions, including those occurring from 1 month to 1 year after placement of the graft, may be due to myointimal hyperplastic lesions within the graft or at its anastomoses. Beyond 1 year, occlusions are most likely to result from progression of atherosclerotic disease. In the management of patients with peripheral bypass grafts, the adage, "An ounce of prevention is worth a pound of cure," should be considered seriously. Because of the relatively poor long-term prognosis for patients with occlusive peripheral disease and their significant coexistent morbidities, every precaution should be taken to identify those patients who are at risk of failure prior to occlusion of their grafts. This mandates careful clinical monitoring with noninvasive evaluation, including, when feasible, hemodynamic assessment and anatomic evaluation, the latter often readily accomplished by duplex imaging. Patency rates for grafts,
From the Department of Radiology, The Alexandria Hospital, Alexandria, Virginia. Reprint requests: Dr. Van Breda, Department of Radiology, The Alexandria Hospital, 4320 Seminary Road, Alexandria, VA 22304.
revised prior to occlusions, are significantly better than outcome by any modality after occlusion.1, 3-5 Patients with occlusions of arterial bypass grafts vary widely in their clinical presentation, often presenting with severe, limb-threatening ischemia, but may present with only exacerbation of symptoms and a return to their preoperative clinical status. Patients presenting with more severe and limb-threatening ischemia require urgent intervention. Standard surgical techniques include thrombectomy of the bypass graft, with intraoperative arteriography to ensure patency of the graft and to identify factors responsible for graft thrombosis.1,5 This approach, although often successful, may result in failure to achieve the desired clinical improvement with repeated graft failure necessitating repeated thrombectomy. Since results of thrombectomy alone are often unsatisfactory, more extensive surgical revision may be necessary. Alternatively, the entire graft may be replaced utilizing the autogenous vein, if available, or prosthetic materials, if not.6'7 With careful surgical technique, graft and limb salvage is often feasible but long-term patency rates after salvage of thrombosed grafts remain poor. The poor results of operative management have led to interest in thrombolysis as a means of improving outcome in this group of patients. Thrombolytic therapy has been available for over two decades for use in occluded native arteries and bypass grafts. Initial descriptions of thrombolytic technique featured high doses of thrombolytic agent given intravenously to produce a systemic effect. The utility of this approach was limited by a relatively low and unpredictable rate of success and a high rate of bleeding complications.8,10 Coinciding with the development of selective angiographic technique, local intra-arterial application of low doses of lytic agents was proposed to improve efficacy of lysis and reduce the rate of complications.11,12 Low-dose local thrombolysis has undergone considerable evolution since initially described by Dotter in 1972,13 but the major tenents remain unchanged. Angiographic technique is used to position a
Copyright © 1991 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
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catheter at the site of occlusion, allowing direct deposition of lytic agent into the thrombosis and angiographic monitoring of treatment success. Local intra-arterial thrombolytic therapy has become the modality of choice for interventional treatment of occluded arterial segments in the peripheral vasculature, whereas systemic thrombolytic therapy remains the preferred technique for treatment of most coronary artery occlusions and of deep vein thrombosis. Pulmonary emboli may be treated by either systemic or local lytic therapy. The decision to use a local versus a systemic approach for thrombolysis is dependent on clinical and technical factors. For acute coronary occlusions, the short interval during which lysis is effective in preventing irreversible myocardial damage precludes time-consuming coronary catheterization necessary for local thrombolysis, and results of high-dose systemic lysis rival those obtainable with local infusions.14 The risks of this therapy are outweighed by the advantages of myocardial salvage. With peripheral arterial and graft occlusions, a much longer therapeutic window coupled with the poor results of systemic therapy necessitated use of intra-arterial local infusions. The rationale of graft thrombolysis derived from the limitations of surgical management of occluded grafts. Lysis may avoid the need for reoperation and its attendant morbidity and mortality of up to 5%; it may allow prospective evaluation of the etiology of graft occlusion and thereby a more focused and appropriate interventional or surgical repair, and, lastly, it has been hoped that lysis would prolong the patency of vein grafts, avoiding revision with less desirable prosthetic material.15 These expectations, initially optimistic, have not been uniformly fulfilled, nor has the technique met with universal acceptance. This review will, it is hoped, provide some perspective on the role of graft thrombolysis in the current management of patients with occluded peripheral bypass grafts.
TECHNIQUE OF GRAFT THROMBOLYSIS Patient Selection Selection of patients for treatment of occluded peripheral bypass grafts requires consideration of a number of factors. First and foremost is the clinical status of the patient at the time of occlusion. Although patients with graft occlusions may exhibit a range of symptoms, acute occlusions frequently present with a relatively severe degree of ischemia. Judgment of outcome of prolonged ischemia should include consideration of the potential duration of infusion necessary to result in complete lysis and symptomatic relief. Ideally, this
judgment is made by collaboration of the interventionalist and the vascular surgeon. Patients with advanced degrees of ischemia, that is, those with a cold mottled extremity or with significant neurologic dysfunction, should not undergo thrombolytic therapy unless all other approaches for more rapid restoration of perfusion are deemed not feasible due to the low yield of limb salvage in this setting and the potential for life-threatening reperfusion injury.16 In this situation, a simple thrombectomy or revision of graft may be indicated to restore perfusion in the most expeditious manner possible. Patients presenting with less severe ischemia may be considered candidates for graft thrombolysis dependent on the relative risks and benefits of thrombolysis in that individual. This should include consideration of the nature of the graft material, the possible risks of thrombolysis, the position of the graft, the surgical alternatives, and the ability of the patient to cooperate during a possibly lengthy thrombolytic infusion. Consideration of surgical alternatives mandates knowledge of the likelihood of successful outcome with other treatment modalities. Evaluation of the patient's prior clinical history, and angiographic evaluation may help predict likelihood of success of management alternatives. Those patients with extremely poor outflow at the time of initial graft placement are unlikely to benefit from either thrombolysis or simple thrombectomy without improving outflow, possibly by distal bypass grafting. Our enthusiasm for treating these patients is considerably lower than in those patients with previously good outflow. We are frequently requested to perform graft thrombolysis due to the poor predicted outcome of surgical therapy or the increased risk of surgical therapy in some patients. For example, patients with multiple prior surgical procedures represent a daunting technical undertaking for the vascular surgeon. Similarly, long-term effects of repeated thrombectomies of native vessels proximal and distal to grafts are becoming better known with possible worsening of long-term outcome due to the results of this repeated trauma. 17-19 Thrombolysis offers a potential for "chemical" rather than mechanical thrombectomy with potentially better long-term effects. In those patients who present with mild symptoms such as nondisabling claudication, the risks of any further intervention may outweigh the potential benefits and in these patients, no further therapy may be appropriate. Factors that must be included in considerations for possible thrombolytic therapy include the nature and age of the occluded graft. Porous synthetic grafts of woven and knitted Dacron and polytetrafluoroethylene are dependent on the formation of a pseudointima, comprised of fibrinogen and fibrin, as well as collagen and platelet membrane elements for both the integrity and patency of the graft.20 The fibrinous element in this pseudointima
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and in the perigraft space is subject to lysis by fibrinolytic agents. This may lead to significant hemorrhagic complications if thrombolytic therapy is pursued prior to maturation of the graft by perigraft fibrosis. Although angiographic evidence of contrast extravasation through graft interstices is reported even in relatively mature grafts, significant hemorrhagic complications are unlikely unless therapy is attempted in grafts less than 3 months old. 21,22 That is probably due to lack of complete maturation of the perigraft structures. We therefore do not recommend fibrinolytic therapy of porous grafts that have been in place for less than 3 months, and with caution in grafts of less than 6 months, especially in intra-abdominal or retroperitoneal grafts where significant bleeding may occur prior to clinical detection. In the infrainguinal position, the extremity may be more readily monitored if signs of bleeding occur, and therefore these represent a less severe contraindication. However, as just noted, graft occlusions that occur in a relatively recent postoperative period are often due to technical factors and require surgical revision as a primary method of treatment. Other contraindications to the use of local fibrinolytic therapy are relatively few. Although low-dose, local therapy has a lower likelihood of significant bleeding complications at distant sites, major intracranial abnormalities likely to cause bleeding preclude patients from lytic therapy. A systemic fibrinolytic effect may result in embolization of thrombotic material from a central site, such as cardiac mural thrombi, and these patients should be treated with care to avoid the likelihood of this complication.23 Patients with coagulopathies are at greater risk for complications. Patients are screened for both thrombotic and hemorrhagic coagulopathies prior to treatment.24
Technique All patients undergoing fibrinolytic therapy should have a complete diagnostic angiography prior to institution of therapy. This may be facilitated by review of preoperative and postoperative angiograms and the operative report of prior surgical procedures. Duplex ultrasonography is useful in evaluating adjacent arterial segments for patency and focal abnormalities requiring treatment, such as pseudoaneurysms or stenoses. Prelysis angiography requires evaluation of both the proximal and distal vascular beds, with special attention to the status of the distal runoff vessels. In patients with occluded aorto-bifemoral grafts, use of venous digital subtraction angiography can avoid the need for an arterial puncture prior to the onset of fibrinolytic therapy. Once the occlusion has been defined, the optimal approach for lysis is selected. Often a
9 second arterial puncture is necessary. Lytic treatment of occluded bypass grafts requires catheter tip placement in the occluded segment. Whenever feasible, the catheter is introduced antegrade to the occluded segment and from as close to an access site as possible.25-27 Efforts are made to avoid traversing long segments of diseased artery or positioning the catheter distal to an occluded segment to minimize the risk of developing new thrombus around the treatment catheter.28 Direct puncture of the graft for initiation of lysis may occasionally be necessary and may be a useful access. When puncture of a bypass graft is necessary to perform thrombolytic therapy, prophylactic antibiotic coverage may be considered during the infusion. There is no clear-cut evidence that this is beneficial, but it is used empirically due to the potentially devastating results of graft infection.
DRUG AND DOSAGE CONSIDERATIONS Streptokinase was the agent initially used for the treatment of peripheral vascular occlusions;13,29,30 urokinase is now the generally preferred drug due to greater efficacy of lysis and a lower incidence of bleeding complications.25,26,31-33 Recombinant tissue plasminogen activator (r-tPA) has also been used for both native and graft arterial occlusions but has not as yet achieved widespread use. Early clinical experience with this agent demonstrated successful fibrinolysis with shorter duration infusions than that required with streptokinase or urokinase.34-38 Concerns about potential bleeding complications, however, have led to eventual lowering of the recommended dose for peripheral intra-arterial thrombolysis and the subsequent lengthening of the time of infusion. The optimum dose rate of this agent remains to be defined.39-41 Other agents are being evaluated for potential usefulness in this application.42,43 The ideal thrombolytic agent remains elusive, however, with some drawbacks to each agent used.14 The most widely used agent in the United States is urokinase. A "low-dose" and "high-dose" technique have been described; both represent less than systemic dose rates, however. With low-dose urokinase treatment, 60,000 to 100,000 U/hr urokinase are given, with average duration of infusion approximately 18 hours.25,26,31 Highdose local urokinase infusion uses an initial higher dose rate of 4000 U/min for the initial 2 to 3 hours, or until antegrade flow is achieved. The dose rate is then decreased to 60,000 U/hr.26 An alternative to the infusion technique is a combined pharmacomechanical approach that is more widely employed in Europe. Initially described by Hess et al, 44 this utilizes relatively small doses of streptokinase or urokinase injected directly into the clot, followed after several minutes by vigorous aspira-
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tion of the thrombus. 44-47 Still others have described a combination of the pharmacomechanical approach followed by low-dose infusions in those patients in whom incomplete results are achieved with the bolus technique.48 One of the advantages of the pharmacomechanical approach is shorter durations of infusion, with an average time of approximately 3 hours. Further development of this approach includes the use of a pulsatile spray with forceful injections of thrombolytic agents throughout the length of the thrombus by a mechanical pump. 49-51 Lower total doses of the thrombolytic agent may be required for successful infusion with significant shortening of the duration of thrombolysis. Early clinical evaluations are ongoing at this time. When using the infusion technique, a bolus of fibrinolytic agent may be given at the onset of therapy by "lacing" the graft in an attempt to improve the speed of fibrinolysis.52 To the greatest degree possible, a guidewire is used to penetrate the entire length of the clot in the occluded segment. A bolus of agent (250,000 U urokinase) is then deposited through the length of the graft during slow withdrawal of the injectable guidewire or catheter. The long length of most graft occlusions is an excellent indication for use of a coaxial technique, which allows distribution of fibrinolytic agents from two separate sites.25 In general, a 5 F catheter is used for the proximal infusion site, through which an injectable catheter or guidewire (0.035 to 0.038 inch or 2 to 3 F) is positioned at approximately the midportion of the occluded segment or somewhat more distally. The total dose of fibrinolytic agent is then divided between these two sites. Once fibrinolytic therapy is instituted, close frequent observation of the infused extremity for signs of restoration of pulses or deterioration is necessary. We prefer monitoring patients in an interventional recovery area or an intensive care unit during this phase of the procedure. Repeat angiographic evaluation is performed periodically, usually within 4 to 6 hours after the onset of therapy and then at approximately 12-hour intervals thereafter or when there is clinical evidence of lysis. Deterioration of the patient's clinical status is not an indication for repeat angiography unless this does not resolve spontaneously in a relatively short period of time. Acute clinical deterioration, that is, sudden worsening of pain, increased pallor, or other signs of worsening ischemia, are generally due to distal embolization of partially lysed thrombotic materials. During initial experience with thrombolytic therapy, this generally prompted termination of fibrinolysis and urgent repeat angiographic evaluation. It is our experience that most episodes of distal embolization resolve spontaneously with continued fibrinolytic infusions; this may occasionally necessitate repositioning of the catheter to maintain
maximum contact between the infused agent and the embolic fragment. As necessary, catheters are advanced to maintain the catheter tip in the thrombus, taking care not to introduce contaminated segments of catheter into the graft. Systemic heparinization is recommended by many investigators for routine use during intra-arterial fibrinolysis. The rationale for systemic heparinization includes prevention of pericatheter thrombus formation, prevention of propagating thrombosis distal to an occlusion in an acutely occluded segment, and the possible potentiation of fibrinolytic activity with heparin. 26-28,53,54 In less severely ischemic limbs, low-dose regional heparinization (200 to 400 U/hr) is an alterative that accomplishes the same objectives with fewer risks.25 With severe ischemia, there is greater risk of propagating thrombus, and systemic heparinization should be used. Laboratory monitoring of patients undergoing thrombolysis is performed to detect the development of a significant systemic lytic effect, which is most simply performed by measurements of fibrinogen and thrombin times. 27,31,55 Infusion duration should be limited to 24 hours whenever possible. Only in cases in which there is virtually complete lysis and a short-term continuation of the infusion will result in a clinically beneficial result, should infusions continue beyond this. Longer infusions are only warranted in those patients for whom there is no alternative to limb loss, who have angiographic demonstration of ongoing lysis, and who are able to tolerate further therapy. The increased risk of complications and decreased likelihood of eventual success when longer infusions are used, as well as the discomfort for the patient, have led us to limit infusions to shorter durations if at all possible. Repeat angiographic assessment should be performed immediately at the completion of fibrinolytic infusion with attention directed toward identifying the etiology of the graft occlusion. If feasible, angioplasty of anastomic stenoses or inflow-outflow lesions should be performed immediately after lysis; if surgery is necessary, this should be performed promptly to avoid interval rethrombosis. Low-dose thrombolysis should not cause significant derangement in coagulation parameters or produce a hemorrhagic tendency, and delay to correct lysis-induced coagulopathy should not be necessary. It is important, however, to ensure that lysis is complete prior to instituting angioplasty or other percutaneous treatment. Significant residual thrombus may cause distal embolization during angioplasty. We prefer to obtain maximum benefit of lysis prior to angioplasty. Occasionally, it may be necessary to perform angioplasty in the presence of incomplete lysis to restore some antegrade flow; this should be followed by sufficient subsequent
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lysis to prevent rethrombosis. Occasionally, no abnormality will be identified to explain the graft thrombosis. This is most frequently seen in infrainguinal grafts, which may have become occluded due to transient hemodynamic factors, such as decrease in cardiac output and inadvertent compression of a portion of the graft. In these instances, careful consideration should be given to what possible steps may be taken to correct the predisposing factors of thrombosis; occasionally, we have instituted long-term anticoagulation in these patients to prevent repeat thromboses.
RESULTS Evaluation of results of thrombolytic therapy is hampered by wide variations in definition of success and means of reporting results. A number of studies include results in both native vessel and graft occlusions. Several studies have concentrated on results solely in grafts. Initial clinical success has ranged from 10 to 70%. In several reports, success included patients in whom clinical benefit was derived by minimizing the extent of subsequent surgical repair. 15,56-59 As with peripheral arterial occlusions, higher success rates were noted with urokinase than with streptokinase.33,57 Later reports emphasized results of the long-term follow-up of treated grafts. In virtually all reports there was a high rate of reocclusion, with 1-year patency reported from 10 to 37%. Overall limb salvage (with secondary patency), however, was higher in all series, ranging from 50 to 60%. 57-60 In a study by Belkin et al59, following results of successful thrombolysis of saphenous vein graft occlusions, overall 1 year patency was 37%, but with a 1 year limb salvage rate of 67%. They, as others, noted a fairly advanced degree of disease in the patient population, but concluded that routine use of thrombolytic therapy for salvage of occluded venous bypass grafts was not warranted and should be reserved for patients in whom an autogenous vein was not available for repeat bypass grafting. Another analysis of 53 patients undergoing thrombolysis with venous and prosthetic grafts by Durham et al, 60 noted a mean patency rate of 162 days. In comparing the results of surgical therapy, these authors believed that surgical reconstruction was preferred for suprainguinal grafts and for venous infrainguinal grafts; however, they believed that thrombolysis was comparable to surgery for below-knee femoralpopliteal bypass graft revision. In one study by Graor et al,61 retrospective comparative analysis of surgically treated grafts versus those lysed with rt-PA noted significantly better patency rates at 30 days with thrombolysis versus thrombectomy. Long-term patencies, however, were not evaluated nor was comparison made with other
11 surgical techniques, such as graft revision or repeat bypass. In each of these studies, note was made of the extensive nature of the disease present in the patient population, with therapy often undertaken for limb salvage. This is reflected in a high rate of amputation reported when thrombolysis fails.57 Mortality in these reports ranges from 0 to 3%; morbidity is difficult to assess due to differences in reporting standards. Significant complications were noted to occur in 20 to 50% of cases. To place these results in perspective, familiarity with results of surgical procedures in this patient population is necessary. Currently, long-term primary patency rates for infrainguinal and extra-anatomic prosthetic bypass grafts range from 15 to 65% at 5 years. 1 ' 4 ' 6,62 ' 63 Long-term patency rates with autogenous vein are significantly better, with 5 year patency rates of up to 80%. 63,64 Mortality of bypass grafting ranges from 1 to 5%. Detection of the failing bypass graft by careful noninvasive follow-up allows excellent results for secondary patencies after revision. Again, as with primary patency, secondary patency after revision for a failing graft is better with autogenous vein graft than prosthetic graft. Five-year secondary patency of 85% may be achieved after revision of a failing vein graft.1'64 Those patients with thrombosed bypass grafts represent the most problematic spectrum of this patient population. Graft salvage procedures, including thrombectomy and revision for prosthetic graft occlusions, yield a 52% 3-year patency for above-knee bypasses, with only 13% 3-year patency below-knee bypasses. Improvement in these poor secondary patency rates can be achieved by total revision of the bypass graft, yielding a 3-year patency of 48% in below-knee bypass grafts.6 Results are equally poor for salvage of occluded vein grafts by thrombectomy with patencies of 19 to 28% at 5 years.3 Mortality with repeat surgery ranges from 1 to 5%. Unclear at this time is the effect of cost considerations on eventual role of thrombolysis versus surgery. One report indicates a significantly higher effective cost per complete success of thrombolytic therapy when compared with surgery for treatment of arterial and graft occlusions.65 This again, however, is a retrospective evaluation without randomization. The cost of thrombolytic therapy can be considerable due to the high cost of thrombolytic agent ($1000 to 2000 per treatment with urokinase) plus the associated cost of intensive care unit monitoring. Retrospective review of 173 thrombolytic infusions at Alexandria Hospital included treatment of 38 occluded bypass grafts. Of these, 71% were clinically beneficial. Hospital costs for patients successfully treated with thrombolysis and angioplasty were significantly
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lower than for those patients who required subsequent surgical revision.33 8.
CONCLUSIONS It appears that the role of thrombolysis in the treatment of occluded bypass grafts remains limited. Thus far, patency is not improved with lysis when compared with surgical therapy, yet in some instances lysis may be of benefit. Prospective comparative evaluation with randomization to surgery or thrombolysis has not been performed, nor does this appear to be likely. How, then, is the clinician to determine the role of thrombolysis? It is our current feeling that the decision to treat occluded bypass grafts with thrombolysis must be individualized based on the careful evaluation of all factors at the time of patient presentation. If surgical revision can be performed easily, and in those patients in whom this is likely to result in reasonable success, such as suprainguinal grafts or patients with available autogenous vein and anatomy suitable for repeat bypass grafting, surgery is the preferred therapy. In other instances, particularly in those patients without sufficient autogenous vein for repeat bypass grafting, or with a history of repeated occlusions after thrombectomies, thrombolysis may play a role in prolonging patency of bypass grafts with rates of long-term success similar to surgical treatment. Clearly, the long-term outlook for these patients remains poor, but thrombolysis may provide limb salvage with reasonable risks.
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REFERENCES 21. 1. Whittemore AD, AW Clowes, N Couch, JA Mannick: Secondary femoropopliteal reconstruction. Ann Surg 193:35-42, 1981. 2. Szilayi DE, JP Elliott, RF Smith, JH Hagement, RK Sood: Second arterial repair: The management of late failures in reconstructive arterial surgery. Arch Surg 110:485-493, 1975. 3. Cohen JR, JA Mannick, NP Couch, AD Whittemore: Recognition and management of impending vein graft failure. Arch Surg 121:758-759, 1986. 4. Veith FJ, SK Gupta, E Ascer, S White-Floves, RH Samson, LA Scher, JB Towne, VM Bernlyard, P Bonier, WR Flinn: Six year prospective multicenter randomized comparison of autologous saphenous vein and expanded polytetrafluoroethylene grafts in infrainguinal arterial reconstructions. J Vasc Surg 3:104-114, 1986. 5. Veith FJ, RK Weiser, SK Gupta, E Ascer, LA Scher, RH Samson, SA White-Flores, S Sprayregen: Diagnosis and management of failing lower extremity arterial reconstructions. J Cardiovasc Surg 25:381-384, 1984. 6. Ascer E, P Ollier, SK Gupta, FJ Veith: Reoperation for polytetrafluoroethylene bypass failure: The importance of distal outflow site and operative technique in determining outcome. J Vasc Surg 5:298-310, 1987. 7. Veith FJ, SK Gupta, V Daly: Management of early and late
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THROMBOLYSIS IN ARTERIAL GRAFTS—VAN BREDA
