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Adjunctive techniques in percutaneous mechanical thrombectomy
Adjunctive Techniques in Percutaneous Mechanical Thrombectomy Marc Kalinowski, MD and Hans-Joachim Wagner, MD, PhD
Percutaneous mechanical thrombectomy is an established method in interventional radiology and refers to the removal of acute embolic or thrombotic occlusive material in arteries, veins, or vascular grafts using percutaneous transluminal methods. However, initial complete removal of occlusive material can be achieved only in a minority of patients. The amount of removed material varies with the age and composition of the occlusive material. To achieve sufficient revascularization, adjunctive use of a variety of percutaneous endovascular recanalization techniques is necessitated. Additional treatment with local intraarterial fibrinolysis, balloon angioplasty, stent implantation, endoluminal atherectomy, and other measures results in primary technical success rates of 70% to 100% for revascularization of acutely occluded vessels. The above-mentioned different techniques should not be viewed as competitive treatment modalities, rather a synergistic approach should be offered. The aim of this report is to review different adjunctive techniques in percutaneous mechanical thrombectomy with emphasis on techniques, mechanisms of action, experimental and clinical results, potential complications, and their potential role in view of clinical pathways to treat acute limb ischemia. © 2003 Elsevier Inc. All rights reserved.
ercutaneous mechanical thrombectomy (PMT) is an established method in interventional radiology and refers to the removal of acute embolic or thrombotic occlusive material in arteries, veins or vascular grafts using percutaneous transluminal methods. Percutaneous thrombectomy techniques have evolved and offer alternative treatment options to conventional open surgical approaches, thereby reducing perioperative risk. As has been reported in previous chapters, the various techniques can be roughly divided into two main methods: percutaneous aspiration thrombectomy (PAT) in which thrombus is aspirated by wide-bore catheters and mechanical thrombectomy (MT) techniques including maceration, fragmentation and removal of thrombus.1 Many institutions use percutaneous mechanical thrombectomy as a primary measure to clear the occluded vessel from the entire thrombus/embolus. However, complete removal of the obstructive material can be achieved in only 19% to 49%.2-4 The amount of removed material varies with the age and composition of the occlusive material. To achieve sufficient revascularization, adjunctive use of a variety of percutaneous
P
From the Department of Diagnostic Radiology, University Hospital, Philipps University, Marburg, Germany. Address reprint requests to Hans-Joachim Wagner, MD, PhD, Department of Diagnostic Radiology, University Hospital, Philipps University, Baldingerstrasse, 35033 Marburg, Germany. © 2003 Elsevier Inc. All rights reserved. 1089-2516/03/0601-0003$30.00/0 doi:10.1053/tvir.2003.36437
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endovascular recanalization techniques is necessitated. Additional treatment with local intra-arterial fibrinolysis, balloon angioplasty, stent implantation, endoluminal atherectomy, and other endovascular measures results in primary technical success rates of 70% to 100% for revascularization of acutely occluded vessels.2-6 The different techniques should not be viewed as competitive treatment modalities; rather a synergistic approach should be offered (Fig 1). The aim of this report is to review different adjunctive techniques in percutaneous mechanical thrombectomy with emphasis on techniques, mechanisms of action, experimental and clinical results, potential complications, and their potential role in view of clinical pathways to treat acute limb ischemia (Fig 1). An overview of different adjunctive endovascular techniques is shown in Table 1.
Percutaneous Aspiration Thromboembolectomy (PAT) The idea of removing embolic material by percutaneous transluminal aspiration was first described in 1969 by Greenfield and coworkers.7 The application of this technique to iatrogenic arterial emboli was mentioned by Buxton and Mueller in 1974.8 This technique was later resumed by Snidermann and coworkers in 1984,9 who removed postangioplasty emboli successfully in 5 of 6 patients. Starck and coworkers were the first to apply the novel method to acute thrombotic occlusions of native lower limb arteries and infrainguinal bypass grafts.10 The efficacy of this simple and readily available technique has since then been well validated.4,5 The main indication for PAT are acute arterial and graft occlusions below the inguinal ligament. It can also be used to treat acute occlusions in iliac arteries and suprainguinal grafts. However, total clearance of thrombotic material from these areas is seldom achieved because of the larger caliber of these vessels with regard to the size of the catheters, which are limited to 8 to 9F. There is also a higher risk of dislodging thrombus into infrainguinal regions. PAT can be used successfully for treatment of occluded hemodialysis grafts and fistulas.11 Rare indications are removal of clot from renal, mesenteric, aortic, and pulmonary arteries.12,13 The equipment required for this technique is relatively simple and consists of a thin walled catheter, a vascular sheath with a removable hemostatic valve and a 50-mL syringe with a luer lock connector. The hemostatic valve is necessary to prevent retention of aspirated thrombus material within the sheath on removal from the vessel. In case of native vessel or graft occlusion, the catheter is advanced under fluoroscopic guidance through the sheath over a guide wire into the proximal part of the occlusion. The guide wire is removed and, under continuous suction, the catheter is moved slowly back. Taking care to
Techniques in Vascular and Interventional Radiology, Vol 6, No 1 (March), 2003: pp 6-13
Fig 1. Algorithm for treatment of acute limb ischemia with percutaneous mechanical thrombectomy and adjunctive endovascular techniques.
maintain suction to avoid dislodgement of the captured thrombus, the catheter is withdrawn. The contents within the syringe are expelled into a basin draped with gauze to separate the aspirated material from the blood. The procedure can be repeated several times as required. In clinical practice, catheters used for PAT are 4 to 8F according to the treated vessel size, with smaller catheters (4 to 5F) to be used in the infrapopliteal region. A long sheath allows aspiration of thrombi or emboli in cross-over procedures or in distant vasculature without the risk of thrombus propagation into nonaffected vascular territories (eg, aspiration of thromboembolic material from carotid arteries). Percutaneous aspiration thromboembolectomy is often effective alone in clearing embolic occlusions as well as short thrombotic occlusions or small amounts of thrombus. Although it is possible to clear longer thrombotic occlusions, wall-adherent or partially organized thrombus material requires adjunctive procedures. In the literature, success rates of
TABLE 1. Overview of Different Adjunctive Endovascular Techniques Percutaneous aspiration thrombectomy or suction thrombectomy Pharmacologic thrombolysis Ultrasound thrombolysis Atherectomy Manual catheter fragmentation Balloon angioplasty Stent implantation
ADJUNCTIVE TECHNIQUES IN PMT
PAT alone for acute occlusions ranged between 3% to 89% depending on the nature of the arterial occlusion. Adjunctive procedures such as angioplasty, thrombolysis, atherectomy, stent implantation resulted in primary technical success rates of 84% to 93%.4,5,13 For the treatment of acute infrainguinal embolic arterial occlusions, limb salvage rates of treated extremities are about 88% and thus comparable to surgical embolectomy.4,5,14,15 Serious complications for PAT are uncommon.13 Embolic or thrombotic material may embolize more distally during the attempted aspiration procedure, although it is usually possible to also remove this by further distal aspiration. Arterial wall dissection may occur because of blind catheter passages through the occluded vessel or in tortuous vessels. If PAT is used as a primary treatment and it is not completely successful, residual thrombus is usually treated by additional thrombolysis. In this situation the risk of hemorrhage around the puncture site may be increased if large access sheath is in use. Finally, it is possible to remove rather large volumes of blood during PAT, if the technique is not used appropriately. If successive passes only yield full 50 mL syringes of blood containing only small amounts of thrombotic material, PAT should be discontinued because it is likely that further catheter passages will not produce further improvements. Thirty-day mortality rates of PAT are 1% to 4% compared with 7% to 25% for surgical embolectomy.4,5,10,13-15 PAT is one of the most often used adjunctive techniques in percutaneous mechanical thrombectomy (Fig 1). It is especially
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helpful in removing wall-adherent material or older, partially organized thrombi/emboli, which are resistive to PMT (Fig 2).
Atherectomy Various atheroablative devices have been designed in recent years for mechanical maceration.16 These devices can be divided in two major classes: (1) with concomitant suction, eg, transluminal extraction catheter (TEC), Trac Wright catheter (Kensey catheter) or (2) without concomitant suction, eg, Simpson atherectomy catheter, percutaneous rotational thrombectomy catheter (Rotablator), Redha-Cut atherectomy catheter. However, clinical application of these modalities in thrombosed native arteries and hemodialysis fistulas has been restricted to small patient populations and feasibility studies.17-21 All of the currently available atherectomy catheters should not be used as a first choice device in acute or subacute vascular occlusions. But, in certain clinical situations such as large flowlimiting intimal flaps, wall-adherent thrombus resistive to percutaneous thrombectomy devices, organized old emboli not capable of percutaneous thrombectomy, or high-grade atherosclerotic eccentric obstructions not amenable for balloon angioplasty, adjunctive use of these devices in percutaneous mechanical thrombectomy procedures can be beneficial. We describe in detail three of these devices recently in use.
Simpson Atherectomy Catheter This device is widely used as a directional extirpative atherectomy device containing a distal cutting chamber housing a cup-shade blade and a side window in the cutting chamber. The device is available in 6 to 11 F in a fixed wire form or a wireguided form and requires a single use electric drive unit. Although mostly used as an atherectomy device in atherosclerotic peripheral obstructive disease, the Simpson catheter has proven effective in removing thrombus and may provide an alternative tool in refractory wall adherent and organized thrombus after standard percutaneous mechanical thrombectomy procedures.17,18
Transluminal Extraction Catheter (TEC) Initially developed as an atherectomy device, the TEC showed proven efficacy in thrombectomy.19 The device available in 5 to 14F consists of a rotating torque tube with two cutting blades mounted on its tip. By slowly advancing the TEC through the lesion, occlusive material, which can be either atheromatous or thromboembolic, is continuously cut off and aspirated into a vacuum bottle.19,20
Redha-Cut Atherectomy Catheter This device is a percutaneous nondirectional pull back atherectomy system. The cutting head consists of 6 or 8 specially shaped blades that can be opened and closed like an umbrella. By retracting the catheter with open blades back through stenosis or occlusion and subsequent closing of the device, occluding material is cut and retained by the catheter.21
Pharmacologic Thrombolysis Regional infusion of fibrinolytic drugs has been reported the first time over 20 years ago from Charles Dotter and cowork-
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ers.22 Since then, thrombolytic therapy has become an integral part of the management of patients with acute peripheral vascular occlusive disease in native arteries and bypass grafts, hemodialysis fistulas and veins. Thrombolysis can restore arterial flow by dissolving an occluding thrombus and can be followed by endovascular or open surgical procedures to correct any lesions unmasked by thrombolysis. However, thrombolysis is not a treatment of isolation and may be used in adjunct with mechanical methods of thrombectomy and percutaneous aspiration to aid in the rapid restoration of blood flow, thereby minimizing lysis time and dose of lytic agents to reduce systemic adverse events of the fibrinolytic substances. In peripheral vasculature, catheter based thrombolysis should be performed exclusively. The main delivery methods are divided into low dose and high dose fibrinolytic techniques. Some of the high dose techniques use forced periodical infusion (pulse spray technique) as opposed to continuous endhole infusion or intrathrombus bolusing.23-27 The primary indication for intra-arterial thrombolysis is an acute (duration ⬍14 days) arterial occlusion causing limb ischemia as a result of native artery occlusion, secondary to atherosclerotic disease or an embolus, acute graft occlusion or acute thrombosis at the site of endovascular procedures. Contraindications to this treatment are based on its most significant potential complication, systemic bleeding. Further, it has to be taken into account that thrombolysis may be time-consuming and the ischemic limb must be able to withstand the period of ischemia until blood flow is restored. Therefore, thrombolysis is contraindicated as initial procedure in the presence of paresthesia and paralysis of the affected limb or when a proximal embolus is suspected with an acutely ischemic limb, in which case immediate open surgical embolectomy is required.28 There are a number of agents which have been in clinical use for years (Table 2), eg, streptokinase (SK), urokinase (UK), and recombinant tissue plasminogen activator (rt-PA). Urokinase became used increasingly when studies showed it to be at least as effective as streptokinase without the antigenic complications of streptokinase.29 Recombinant tissue plasminogen activator seems to produce a more rapid lysis than streptokinase, resulting in superior limb salvage rates.24,30 Hemorrhagic events have also been reported to be less prevalant with UK and rt-PA than with SK.24,30 The STILE (Surgery versus Thrombolysis for Ischemia of the Lower Extremity) trial31 and an European multicenter prospective randomized trial30 showed that the efficacy for UK and rt-PA were equivalent. However, because of concerns regarding the manufacturing process of UK and the possible contamination of the drug with latent viruses the Food and Drug Administration (FDA) suspended sales and distribution of UK in the United States in 1999. Newer recombinant fibrinolytic drugs such as reteplase, saruplase, lanoteplase, and tenecteplase have been developed in recent years. They all show greater fibrin specificity in vitro and promising early clinical results, but are still under investigation and not all are commercially available at the time of writing. Because of several prospective randomized clinical trials (STILE, TOPAS [Thrombolysis or Peripheral Arterial Surgery]) there is good evidence that a major reduction in the magnitude of subsequent surgery for acute leg ischemia may be expected with a policy of initial thrombolysis in acute lower limb ischemia. Moreover, amputation free survival might be improved.31-33 KALINOWSKI AND WAGNER
Fig 2. Adjunctive use of percutaneous aspiration thromboembolectomy (PAT) after unsuccessful hydrodynamic PMT. A 79-year-old-female patient with embolic occlusion of the popliteal artery and trifurcation of tibial arteries. Angiogram before (A), after first pass (B) and final result after hydrodynamic thrombectomy with residual wall-attached embolic material (C). Result after first pass (D) and final result (E) after adjunctive percutaneous aspiration thrombectomy (PAT). Additionally removed emboli by PAT (F).
ADJUNCTIVE TECHNIQUES IN PMT
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TABLE 2. Thrombolytic Agents for Peripheral Vascular Occlusive Disease Tissue Cultured Agents Streptokinase (SK) Urokinase (UK) Anistreplase (APSAC) Recombinant Produced Agents Recombinant t-PA (rt-PA), Alteplase Recombinant wild type t-PA (r-PA), Reteplase Recombinant urokinase Pro-Urokinase (Pro-UK), Saruplase Recombinat Staphylokinase Lanoteplase TNK-t-PA
Summarizing a single uniform protocol for fibrinolysis from the numerous clinical studies is not possible because of the wide variability in treatment regimens. Therefore, an international group produced a consensus document in 1998 to establish uniform standards for thrombolytic therapy.34 Nevertheless, there is no generally accepted dosing regimen (high-dose versus low-dose), preferable injection method (continuous infusion versus pulsed spray) or consensus regarding the use of concomitant anticoagulation. Beside urokinase and streptokinase, rt-PA is one of the most often used thrombolytic agents. Rt-PA thrombolysis can be accomplished with a wide range of dosing regimens, weightbased (0.02 to 0.5 mg/kg/h) and nonweight-based (0.25 to 10 mg/h). Consensus in the field is that rt-PA infusion doses of 0.5 to 1 mg/h or 0.025 mg/kg/h are appropriate. Higher doses do not improve efficacy and are associated with a higher rate of bleeding complications. There is also general consensus that heparin should be administered sparingly. Full anticoagulation (ie, prolongation of PTT more than 2⫻ of the normal value) should be avoided during rt-PA infusion. Different recommended dosing regimens (UK high dose; UK low dose; rt-PA) are listed in Table 3. Recently, a combined therapeutic approach of local thrombolysis with glycoprotein IIb/IIIa platelet receptor antagonists (abciximab, tirofiban) and direct thrombin inhibitors (eptifibatide) have been proposed. Results of a prospective evaluation of reteplase and abciximab in peripheral arterial thrombolysis in acute and chronic arterial thrombosis suggest shorter thrombolysis times with reduced doses of reteplase when compared with studies using reteplase alone and with no increase in bleeding complications.35 First results of randomized trials using abciximab and urokinase showed similar results.36 How-
ever, these new strategies will need further assessment to evaluate whether these regimens are superior and whether they alter the current application of thrombolysis in the peripheral vasculature. One of the major advantages of intra-arterial thrombolysis is its inferior vessel wall alteration compared with surgical or endovascular techniques. Therefore, thrombolysis is a complementary measure to surgery and endovascular recanalization and can be used as initial treatment modality in acute thromboembolic vascular occlusions to remove the vast majority of occlusive material. Alternatively, it can be used as an adjunctive technique after initial mechanical thrombectomy, if there is residual thromboembolic material to clear the vessel completely. Most of the published trials on percutaneous mechanical thrombectomy have used local thrombolysis in the vast majority of cases. Mainly, fibrinolysis was used to clear the vasculature from residual wall-adherent thromboembolic material.
Ultrasound Thrombolysis Ultrasound thrombolysis can be achieved indirectly via transmitted longitudinal vibrations of a metallic probe coupled to a high-frequency, high-power ultrasound generator. Theoretically, with use of high-energy ultrasound selective disruption of the occlusive material can be induced without damaging the surrounding arterial wall. This selectivity is based on the differences in elasticity between thromboembolic material and the different layers of the vessel wall. Thus, ultrasound angioplasty has been used to disrupt arterial thrombus in vitro and has been also successfully applied in patients with coronary and peripheral arterial disease.37-40 The clinically used devices generate excessive thermal energy, requiring a pulse mode operation and continuous cooling to avoid device failure and vessel damage. Additionally, the need for energy transmission via a rigid coupling probe make these systems rigid and inflexible. Ultrasound fragmentation leads to the possibility of distal embolization. However, angiographically detected emboli were not described in the literature until to date. There is only little information about clinical indications and the future role of these devices in the management of acute ischemia is uncertain. Siegel and coworkers have shown in 50 lesions that ultrasound angioplasty reduces arterial stenosis and can be useful for recanalization of fibrous, calcific and thrombotic arterial occlusions.41 Further studies are mandatory to determine baseline characteristics such as
TABLE 3. Recommended Dosing Regimen Dosing
Anticoagulation
Maximum Dose
Comments
Rt-PA (SCVIR [23])
0.025 mg/kg/hr or 0.5-1 mg/hr
50 mg
Repeated angio 4-8 hr
Urokinase (TOPAS [32,33]) high dose
4,000 U/min for 4 hours followed by 2,000 U/min up to 48 hours 100,000 U/hr for 4-6 hours followed by 50,000 U/hr
IV bolus (2,500 U) heparin followed by IV infusion of 500 U/h heparin Thromboplastin time 1.5-2 times of control value IV infusion of heparin Thromboplastin time 1.5-2 times of control value IV bolus (5,000 U) heparin followed by IA infusion of heparin (1/2 catheter; 1/2 sheath) Thromboplastin time 1.5-2 times of control value
Urokinase (Marburg) low dose
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6,720,000 U 1,500,000 U
Repeated angio 4-8 hr
KALINOWSKI AND WAGNER
treatment times, length and types of occlusive material and coagulation parameters because rather large amounts of destroyed occlusive material are produced and released into the circulation. Recently, miniaturized catheter tip mounted ultrasound probes have been manufactured allowing the delivery of low energy ultrasound directly to the proximity of the thrombus, which can significantly potentiate the speed and efficacy of pharmacologic thrombolysis. This effect is thought to be largely mediated by acoustic cavitation in a liquid medium, a nonthermal process consisting of the formation and implosion of microscopic gas bubbles. Localized high-speed fluid currents are generated adjacent to the transducer resulting in increased admixture and penetration of the agent into the thrombus. Ultrasound enhanced thrombolysis also can be accelerated by the addition of echo-contrast material. Transcutaneously applied ultrasound energy has also been shown to augment thrombolysis in vivo.42-44 Currently there are no reports available on the combination of ultrasound and PMT for the treatment of acute vascular occlusions.
Manual Catheter Fragmentation and Other Techniques of Thrombus Management These techniques aim in the partial removal of thrombus with embolectomy, fragmentation, maceration or aspiration. Most of the currently described and used techniques do not totally eliminate the treated clots, but rather break down the thrombus into smaller fragments, which migrate peripherally. The technique of manual catheter fragmentation is mainly used in the pulmonary artery circulation, opening up the main pulmonary artery from large occlusive clots and thereby improving perfusion. Fragmentation of the clots exposes fresh surfaces for endogenous fibrinolytic agents and infused thrombolytic drugs to further break down the emboli. In addition, the clots gain more intimate contact with increased concentration of thrombolytics a result of increased blood flow.12 In theory, this method could be even used in the periperal vasculature, but the risk of distal emboli resulting in “trash foot” or “blue toe” syndromes seems disproportionately high. Rotating aspiration thromboembolectomy (RAT) represents another adjunctive fragmentation method. First developed in 1988, RAT is based on fragmentation and detachment of occlusive material from the wall with subsequent removal via PAT. For RAT two devices have been developed. First, a spiral can be used through a regular aspiration catheter. The manually rotating spiral allows a mechanically accelerated thrombolysis because of extensive mixture of concomitantly infused thrombolytics with the occlusive material. Simultaneously, occlusive material is fragmented into smaller particles amenable to subsequent aspiration using the PAT technique. Second, a basket can be used through the aspiration catheters, which allows detachment of wall-adherent material. Firm, organized thrombi or emboli can be captured with the device and retracted through the aspiration catheter (Fig 3). Stark and coworkers showed a primary clinical success rate of 90% for the RAT technique in patients with long thrombotic or embolic occlusions in which conventional PMT techniques had previously failed.45 Finally, the endovascular technique of “distal thrombus or embolus deposition” represents another, but rather seldomly ADJUNCTIVE TECHNIQUES IN PMT
used alternative in thrombus/embolus management. The technique relates to the fact that occlusive material that cannot be aspirated or fragmented is pushed forward into a nonrelevant collateral (eg, side branch of a crural artery) or distal artery. However, none of these described methods has gained major impact on daily clinical practice, but evidence suggests that embolus fragmentation can produce rapid improvement of clinical status especially in pulmonary arteries. Moreover, the equipment for mechanical fragmentation is inexpensive and available in every interventional department. In certain difficult clinical situations, its additional use may be extremely beneficial and the key to technical success.
Ballon Angioplasty and Stent Implantation In case of acute thrombotic occlusions of native vessels, atherosclerotic plaques are the underlying substrate in nearly all cases. Additionally, embolic occlusions can hit atherosclerotic diseased arteries, especially in increasingly older patient populations. Therefore, ballon angioplasty has to be performed after the intial revascularization procedure using PMT in nearly all cases. PTA should be performed only after percutaneous thrombectomy has been completed because of a high incidence of distal embolization of thromboembolic material initiated by the angioplasty maneuver, especially if residual thromboembolic material has been left. Stent implantation into acute thromboembolic occlusions following percutaneous mechanical thrombectomy is likewise possible. The idea of this technique is to compress thrombus by the stent and to fix it to the vessel wall, thereby preventing thrombus dislodgement. The technique also allows to treat residual thrombi or emboli, not capable of further percutaneous mechanical thrombectomy. However, to date there is only a single report about this procedure for treatment of venous thrombosis available.46
Discussion Acute critical limb ischemia because of occlusions of native arteries or bypass grafts is a rationale for rapid revascularization. Catheter-directed pharmacologic thrombolytic therapy and percutaneous thrombectomy procedures can be used as the initial revascularization procedure solely as well as a combined procedure for treatment of thromboembolic disease. Local intra-arterial thrombolysis represents one of the standard treatment modalities in acute thromboembolic occlusions. However, drawbacks of thrombolysis are prolonged procedure times, high costs for patient monitoring and an increased morbidity caused by hemorrhagic complications, rethrombosis, and distal embolization.24,27,28 Additionally, success rates are variable, depending on the amount, composition, chronicity, and location of thrombotic material. Surgical thrombectomy using the Fogarty catheter as another standard modality is an operative procedure, requires general anesthesia in most cases, has a significant morbidity and mortality rate and is usually performed without fluoroscopic guidance. This yields often in incomplete results, does not provide diagnostic information nor does it address underlying vascular disease.14,15 Percutaneous mechanical thrombectomy as alternative initial therapeutic approach for immediate reperfusion in case of acute occlusions has become an established method in interventional radiology and could overcome the shortcomings of
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Fig 3. Adjunctive use of rotating aspiration thrombectomy after incomplete PMT. Antegrade angiogram revealing a thrombotic occlusion of the superficial femoral artery (SFA) (A). Following PMT residual wall-adherent thrombotic material is visualized (B,C). With use of a manually rotated basket through an aspiration catheter (D) the wall-adherent thrombus could be detached and aspirated (E). Final angiogram revealing complete thrombus removal and minimal wall irregularity at the former thrombus site (ruptured atherosclerotic plaque) (F).
available modalities mentioned above. All of the various devices used for PMT are effective in removing fresh, nonorganized thrombus. Nevertheless, on the basis of current evidence, complete success using thrombectomy devices alone can be expected in a small portion of patients only, whereas the majority requires some form of adjunctive therapy to improve the outcome of revascularization. Nontechnical failures in PMT are caused in most cases by the presence of thrombectomy-refractory thrombotic material (chronic, organized, wall-adherent) or an underlying vascular process such as atherosclerosis, restenosis, recoil, or dissection. Therefore, devices designed for atherectomy as well as percutaneous aspiration thrombectomy are well suited for clearing residual or embolized organized thrombus. Moreover, stent placement in acute thromboembolic occlusions could be performed, especially when other treatment modalities have failed.
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However, it has to be realized that surgical reconstruction will be required and is appropriate in most cases of persistent occlusion after unsuccessful PMT and adjunctive endoluminal techniques because of severe underlying disease unsuitable for percutaneous management.
References 1. Sharafuddin MJA, Hicks ME: Current status of percutaneous mechanical thrombectomy. Part II. Devices and Mechanisms of action. J Vasc Interv Radiol 9:15-31, 1998 2. Vorwerk D, Schu¨ rmann K, Mu¨ ller-Leise K, et al: Hydrodynamic thrombectomy of hemodialysis fistulas: First clinical results. J Vasc Interv Radiol 5:813-821, 1994 3. Rillinger N, Go¨ rich J, Scharrer-Palmer R, et al: Short-term results with use of Amplatz thrombectomy device in the treatment of acute lower limb occlusions. J Vasc Interv Radiol 8:343-348, 1997 KALINOWSKI AND WAGNER
4. Wagner HJ, Starck EE: Acute embolic occlusions of the infrainguinal arteries: Percutaneous aspiration embolectomy in 102 patients. Radiology 182:403-407, 1992 5. Wagner HJ, Starck EE, Reuter P: Long-term results of percutaneous aspiration embolectomy. Cardiovasc Interv Radiol 17:241-246, 1994 6. Wagner HJ, Mu¨ ller-Hu¨ lsbeck S, Pitton MB, et al: Rapid thrombectomy with a hydrodynamic catheter: Results from a prospective multicenter trial. Radiology 205:675-681, 1997 7. Greenfield LJ, Kimmell GO, McCurdy WCD: Transvenous removal of pulmonary emboli by vacuum cup catheter technique. J Surg Res 9:347-352, 1969 8. Buxton DR Jr., Mueller CF: Removal of iatrogenic clot by transcatheter embolectomy. Radiology 111:39-41, 1974 9. Snidermann KW, Bodner L, Saddekni S, et al: Percutaneous embolectomy by transcatheter aspiration. Work in Progress. Radiology 150:357-361, 1984 10. Starck EE, McDermott JC, Crummy AB, et al: Percutaneous aspiration thrombembolectomy. Radiology 156:61-66, 1985 11. Turmel-Rodrigues L, Raynaud A, Louail B, et al: Manual catheterdirected aspiration techniques for declotting native fistulas for hemodialysis. J Vasc Interv Radiol 12:1365-1371, 2001 12. Lang EV, Barnhart BH, Walton DL, et al: Percutaneous pulmonary thrombectomy. J Vasc Interv Radiol 8:427-432, 1997 13. Starck EE, Wagner HJ: Percutaneous aspiration thromboembolectomy, in Castaneda-Zuniga WR, Tadavarthy SM (eds): Interventional Radiology (ed 2). Baltimore, MD, Williams & Wilkins, 1992, pp 652659 14. Abbot WM, Malony RD, McCabe CC, et al: Arterial embolism: A 44 year experience. Am J Surg 143:460-464, 1982 15. Dregelid EB, Stangeland LB, Eide GE, et al: Patient survival and limb prognosis after arterial embolectomy. Eur J Vasc Surg 1:263-271, 1987 16. Ahn S: Current status of atherectomy for peripheral arterial occlusive disease. World J Surg 20:635-642, 1996 17. Kim D, Gianturco LE, Porter DA: Peripheral directional atherectomy: 4-year experience. Radiology 183:773, 1992 18. Simpson JB, Selmon MR, Robertson GC, et al: Transluminal atherectomy for occlusive peripheral disease. Am J Cardiol 61:96-101, 1988 19. Matsumoto AH, Sarosi MG, Selby JB, et al: Thromboembolectomy with the transluminal extraction catheter (TEC) as adjunct to thrombolysis. J Vasc Interv Radiol 3:491-495, 1992 20. Wholey MH, Jarmolowski CR: New reperfusion devices: The Kensey catheter, the arthrolytic reperfusion wire, and the transluminal extraction catheter. Radiology 172:947-952, 1989 21. Do DD, Triller J, Baumgartner II, et al: A new approach to plaque removal: The Redha-cut device. J Invasive Cardiol 10:578-582, 1998 22. Dotter CT, Ro¨ sch J, Seaman AJ: Selective clot lysis with low dose streptokinase. Radiology 111:31-37, 1974 23. Valjii K: Evolving strategies for thrombolytic therapy of peripheral vascular occlusions. J Vasc Interv Radiol 11:411-420, 2000 24. McNamara TO, Fischer JR: Thrombolysis of peripheral arterial and graft occlusions: Improved results using high dose urokinase. AJR 144:769-775, 1985 25. Hess H, Ingrisch H, Mietaschk A, et al: Local low-dose thrombolytic therapy of peripheral arterial occlusions. N Engl J Med 307:16271630, 1982 26. Kandarpa K, Drinker PA, Singer SJ, et al: Forceful pulsatile local infusion of enzyme accelerates thrombolysis: In vivo evaluation of a new delivery system. Radiology 168:739-744, 1988
ADJUNCTIVE TECHNIQUES IN PMT
27. Sullivan KL, Gardiner GA, Shapiro MJ, et al: Acceleration of thrombolysis with a high dose transthrombus bolus technique. Radiology 173:805-808, 1989. 28. Palfreyman SJ, Booth A, Michaels JA: A systematic review of intraarterial thrombolysis therapy for lower limb ischemia. Eur J Vasc Endovasc Surg 19:143-157, 2000 29. Van Breda A, Katzen BT, Scales FE: Streptokinase vs. Urokinase in local thrombolytic therapy. Radiology 165:109-111, 1987 30. Mahler F, Schneider E, Hess H: Recombinant tissue plasminogen activator versus urokinase for local thrombolysis of femoro-popliteal artery occlusions: A prospective randomized multicenter trial. J Endovasc Ther 8:638-847, 2001 31. STILE Investigators: Results of a prospective randomized trial evaluating surgery versus thrombolysis for ischemia of the lower extremity: STILE trial. Ann Surg 220:251-268, 1994 32. Ouriel K, Veith FJ, Sashara AA: Thrombolysis or peripheral arterial surgery (TOPAS): Phase I results. J Vasc Surg 19:1021-1030, 1996 33. Ouriel K, Veith FJ, Sashara AA for the TOPAS investigators: A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. N Engl J Med 338:1105-1111, 1998 34. Working Party on Thrombolysis in the Management of Limb Ischemia: Thrombolysis in the management of lower limb peripheral arterial occlusion—a consensus document. Am J Cardiol 81:207218,1998 35. Drescher P, Crain MR, Rilling WS: Initial experience with the combination of reteplase and abiciximab for thrombolytic therapy in peripheral arterial occlusive disease: A pilot study. J Vasc Interv Radiol 13:37-43, 2002 36. Duda SH, Tepe G, Luz O, et al: Peripheral artery occlusion: Treatment with abciximab plus urokinase versus with urokinase alone—a randomized pilot trial (the PROMPT study). Radiology 221:689-696, 2001 37. Luo H, Nishioka T, Fishbein ME, et al: Transcutaneous ultrasound augments lysis of arterial thrombi in vivo. Circulation 94:775-778, 1996 38. Rosenschein U, Rozenszajn LA, Kraus L, et al: Ultrasonic angioplasty in totally occluded peripheral arteries. Initial, clinical, histological, and angiographic results. Circulation 83:1976-1986, 1991 39. Demer LL, Ariani M, Siegel RJ: High intensity ultrasound increases distensibility of calcified atherosclerotic arteries. J Am Coll Cardiol 18:1259-1262, 1991 40. Brosh D, Bartorelli AL, Cribier AT, et al: Percutaneous transluminal therapeutic ultrasound for high-risk thrombus containing lesions in native coronary arteries. Catheter Cardiovasc Interv 55:43-49, 2002 41. Siegel RJ, Don Michael TA, Fishbein MC, et al: In vivo ultrasound arterial recanalization of atherosclerotic total occlusions. J Am Coll Cardiol 15:345-351, 1990 42. Sehgal CM, Leveen RF, Shlansky-Goldberg RD: Ultrasound-assisted thrombolysis. Invest Radiol 28:939-943, 1993 43. Shlansky-Goldberg RD, Cines DB, Sehgal CM: Catheter-delivered ultrasound potentiates in vitro thrombolysis. J Vasc Interv Radiol 7:313-320, 1996 44. Tachibana K: Enhancement of fibrinolysis with ultrasound energy. J Vasc Interv Radiol 3:299-303, 1992 45. Starck EE, Wagner HJ: Rotating aspiration thromboembolectomy. Dtsch Med Wschr 116:1-6, 1991 [Article in German] 46. Vorwerk D, Guenther RW, Schurmann K: Stent placement on fresh venous thrombosis. Cardiovasc Interv Radiol 20:359-363, 1997
13
Percutaneous mechanical thrombectomy is an established method in interventional radiology and refers to the removal of acute embolic or thrombotic occlusive material in arteries, veins, or vascular grafts using percutaneous transluminal methods. However, initial complete removal of occlusive material can be achieved only in a minority of patients. The amount of removed material varies with the age and composition of the occlusive material. To achieve sufficient revascularization, adjunctive use of a variety of percutaneous endovascular recanalization techniques is necessitated. Additional treatment with local intraarterial fibrinolysis, balloon angioplasty, stent implantation, endoluminal atherectomy, and other measures results in primary technical success rates of 70% to 100% for revascularization of acutely occluded vessels. The above-mentioned different techniques should not be viewed as competitive treatment modalities, rather a synergistic approach should be offered. The aim of this report is to review different adjunctive techniques in percutaneous mechanical thrombectomy with emphasis on techniques, mechanisms of action, experimental and clinical results, potential complications, and their potential role in view of clinical pathways to treat acute limb ischemia. © 2003 Elsevier Inc. All rights reserved.
ercutaneous mechanical thrombectomy (PMT) is an established method in interventional radiology and refers to the removal of acute embolic or thrombotic occlusive material in arteries, veins or vascular grafts using percutaneous transluminal methods. Percutaneous thrombectomy techniques have evolved and offer alternative treatment options to conventional open surgical approaches, thereby reducing perioperative risk. As has been reported in previous chapters, the various techniques can be roughly divided into two main methods: percutaneous aspiration thrombectomy (PAT) in which thrombus is aspirated by wide-bore catheters and mechanical thrombectomy (MT) techniques including maceration, fragmentation and removal of thrombus.1 Many institutions use percutaneous mechanical thrombectomy as a primary measure to clear the occluded vessel from the entire thrombus/embolus. However, complete removal of the obstructive material can be achieved in only 19% to 49%.2-4 The amount of removed material varies with the age and composition of the occlusive material. To achieve sufficient revascularization, adjunctive use of a variety of percutaneous
P
From the Department of Diagnostic Radiology, University Hospital, Philipps University, Marburg, Germany. Address reprint requests to Hans-Joachim Wagner, MD, PhD, Department of Diagnostic Radiology, University Hospital, Philipps University, Baldingerstrasse, 35033 Marburg, Germany. © 2003 Elsevier Inc. All rights reserved. 1089-2516/03/0601-0003$30.00/0 doi:10.1053/tvir.2003.36437
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endovascular recanalization techniques is necessitated. Additional treatment with local intra-arterial fibrinolysis, balloon angioplasty, stent implantation, endoluminal atherectomy, and other endovascular measures results in primary technical success rates of 70% to 100% for revascularization of acutely occluded vessels.2-6 The different techniques should not be viewed as competitive treatment modalities; rather a synergistic approach should be offered (Fig 1). The aim of this report is to review different adjunctive techniques in percutaneous mechanical thrombectomy with emphasis on techniques, mechanisms of action, experimental and clinical results, potential complications, and their potential role in view of clinical pathways to treat acute limb ischemia (Fig 1). An overview of different adjunctive endovascular techniques is shown in Table 1.
Percutaneous Aspiration Thromboembolectomy (PAT) The idea of removing embolic material by percutaneous transluminal aspiration was first described in 1969 by Greenfield and coworkers.7 The application of this technique to iatrogenic arterial emboli was mentioned by Buxton and Mueller in 1974.8 This technique was later resumed by Snidermann and coworkers in 1984,9 who removed postangioplasty emboli successfully in 5 of 6 patients. Starck and coworkers were the first to apply the novel method to acute thrombotic occlusions of native lower limb arteries and infrainguinal bypass grafts.10 The efficacy of this simple and readily available technique has since then been well validated.4,5 The main indication for PAT are acute arterial and graft occlusions below the inguinal ligament. It can also be used to treat acute occlusions in iliac arteries and suprainguinal grafts. However, total clearance of thrombotic material from these areas is seldom achieved because of the larger caliber of these vessels with regard to the size of the catheters, which are limited to 8 to 9F. There is also a higher risk of dislodging thrombus into infrainguinal regions. PAT can be used successfully for treatment of occluded hemodialysis grafts and fistulas.11 Rare indications are removal of clot from renal, mesenteric, aortic, and pulmonary arteries.12,13 The equipment required for this technique is relatively simple and consists of a thin walled catheter, a vascular sheath with a removable hemostatic valve and a 50-mL syringe with a luer lock connector. The hemostatic valve is necessary to prevent retention of aspirated thrombus material within the sheath on removal from the vessel. In case of native vessel or graft occlusion, the catheter is advanced under fluoroscopic guidance through the sheath over a guide wire into the proximal part of the occlusion. The guide wire is removed and, under continuous suction, the catheter is moved slowly back. Taking care to
Techniques in Vascular and Interventional Radiology, Vol 6, No 1 (March), 2003: pp 6-13
Fig 1. Algorithm for treatment of acute limb ischemia with percutaneous mechanical thrombectomy and adjunctive endovascular techniques.
maintain suction to avoid dislodgement of the captured thrombus, the catheter is withdrawn. The contents within the syringe are expelled into a basin draped with gauze to separate the aspirated material from the blood. The procedure can be repeated several times as required. In clinical practice, catheters used for PAT are 4 to 8F according to the treated vessel size, with smaller catheters (4 to 5F) to be used in the infrapopliteal region. A long sheath allows aspiration of thrombi or emboli in cross-over procedures or in distant vasculature without the risk of thrombus propagation into nonaffected vascular territories (eg, aspiration of thromboembolic material from carotid arteries). Percutaneous aspiration thromboembolectomy is often effective alone in clearing embolic occlusions as well as short thrombotic occlusions or small amounts of thrombus. Although it is possible to clear longer thrombotic occlusions, wall-adherent or partially organized thrombus material requires adjunctive procedures. In the literature, success rates of
TABLE 1. Overview of Different Adjunctive Endovascular Techniques Percutaneous aspiration thrombectomy or suction thrombectomy Pharmacologic thrombolysis Ultrasound thrombolysis Atherectomy Manual catheter fragmentation Balloon angioplasty Stent implantation
ADJUNCTIVE TECHNIQUES IN PMT
PAT alone for acute occlusions ranged between 3% to 89% depending on the nature of the arterial occlusion. Adjunctive procedures such as angioplasty, thrombolysis, atherectomy, stent implantation resulted in primary technical success rates of 84% to 93%.4,5,13 For the treatment of acute infrainguinal embolic arterial occlusions, limb salvage rates of treated extremities are about 88% and thus comparable to surgical embolectomy.4,5,14,15 Serious complications for PAT are uncommon.13 Embolic or thrombotic material may embolize more distally during the attempted aspiration procedure, although it is usually possible to also remove this by further distal aspiration. Arterial wall dissection may occur because of blind catheter passages through the occluded vessel or in tortuous vessels. If PAT is used as a primary treatment and it is not completely successful, residual thrombus is usually treated by additional thrombolysis. In this situation the risk of hemorrhage around the puncture site may be increased if large access sheath is in use. Finally, it is possible to remove rather large volumes of blood during PAT, if the technique is not used appropriately. If successive passes only yield full 50 mL syringes of blood containing only small amounts of thrombotic material, PAT should be discontinued because it is likely that further catheter passages will not produce further improvements. Thirty-day mortality rates of PAT are 1% to 4% compared with 7% to 25% for surgical embolectomy.4,5,10,13-15 PAT is one of the most often used adjunctive techniques in percutaneous mechanical thrombectomy (Fig 1). It is especially
7
helpful in removing wall-adherent material or older, partially organized thrombi/emboli, which are resistive to PMT (Fig 2).
Atherectomy Various atheroablative devices have been designed in recent years for mechanical maceration.16 These devices can be divided in two major classes: (1) with concomitant suction, eg, transluminal extraction catheter (TEC), Trac Wright catheter (Kensey catheter) or (2) without concomitant suction, eg, Simpson atherectomy catheter, percutaneous rotational thrombectomy catheter (Rotablator), Redha-Cut atherectomy catheter. However, clinical application of these modalities in thrombosed native arteries and hemodialysis fistulas has been restricted to small patient populations and feasibility studies.17-21 All of the currently available atherectomy catheters should not be used as a first choice device in acute or subacute vascular occlusions. But, in certain clinical situations such as large flowlimiting intimal flaps, wall-adherent thrombus resistive to percutaneous thrombectomy devices, organized old emboli not capable of percutaneous thrombectomy, or high-grade atherosclerotic eccentric obstructions not amenable for balloon angioplasty, adjunctive use of these devices in percutaneous mechanical thrombectomy procedures can be beneficial. We describe in detail three of these devices recently in use.
Simpson Atherectomy Catheter This device is widely used as a directional extirpative atherectomy device containing a distal cutting chamber housing a cup-shade blade and a side window in the cutting chamber. The device is available in 6 to 11 F in a fixed wire form or a wireguided form and requires a single use electric drive unit. Although mostly used as an atherectomy device in atherosclerotic peripheral obstructive disease, the Simpson catheter has proven effective in removing thrombus and may provide an alternative tool in refractory wall adherent and organized thrombus after standard percutaneous mechanical thrombectomy procedures.17,18
Transluminal Extraction Catheter (TEC) Initially developed as an atherectomy device, the TEC showed proven efficacy in thrombectomy.19 The device available in 5 to 14F consists of a rotating torque tube with two cutting blades mounted on its tip. By slowly advancing the TEC through the lesion, occlusive material, which can be either atheromatous or thromboembolic, is continuously cut off and aspirated into a vacuum bottle.19,20
Redha-Cut Atherectomy Catheter This device is a percutaneous nondirectional pull back atherectomy system. The cutting head consists of 6 or 8 specially shaped blades that can be opened and closed like an umbrella. By retracting the catheter with open blades back through stenosis or occlusion and subsequent closing of the device, occluding material is cut and retained by the catheter.21
Pharmacologic Thrombolysis Regional infusion of fibrinolytic drugs has been reported the first time over 20 years ago from Charles Dotter and cowork-
8
ers.22 Since then, thrombolytic therapy has become an integral part of the management of patients with acute peripheral vascular occlusive disease in native arteries and bypass grafts, hemodialysis fistulas and veins. Thrombolysis can restore arterial flow by dissolving an occluding thrombus and can be followed by endovascular or open surgical procedures to correct any lesions unmasked by thrombolysis. However, thrombolysis is not a treatment of isolation and may be used in adjunct with mechanical methods of thrombectomy and percutaneous aspiration to aid in the rapid restoration of blood flow, thereby minimizing lysis time and dose of lytic agents to reduce systemic adverse events of the fibrinolytic substances. In peripheral vasculature, catheter based thrombolysis should be performed exclusively. The main delivery methods are divided into low dose and high dose fibrinolytic techniques. Some of the high dose techniques use forced periodical infusion (pulse spray technique) as opposed to continuous endhole infusion or intrathrombus bolusing.23-27 The primary indication for intra-arterial thrombolysis is an acute (duration ⬍14 days) arterial occlusion causing limb ischemia as a result of native artery occlusion, secondary to atherosclerotic disease or an embolus, acute graft occlusion or acute thrombosis at the site of endovascular procedures. Contraindications to this treatment are based on its most significant potential complication, systemic bleeding. Further, it has to be taken into account that thrombolysis may be time-consuming and the ischemic limb must be able to withstand the period of ischemia until blood flow is restored. Therefore, thrombolysis is contraindicated as initial procedure in the presence of paresthesia and paralysis of the affected limb or when a proximal embolus is suspected with an acutely ischemic limb, in which case immediate open surgical embolectomy is required.28 There are a number of agents which have been in clinical use for years (Table 2), eg, streptokinase (SK), urokinase (UK), and recombinant tissue plasminogen activator (rt-PA). Urokinase became used increasingly when studies showed it to be at least as effective as streptokinase without the antigenic complications of streptokinase.29 Recombinant tissue plasminogen activator seems to produce a more rapid lysis than streptokinase, resulting in superior limb salvage rates.24,30 Hemorrhagic events have also been reported to be less prevalant with UK and rt-PA than with SK.24,30 The STILE (Surgery versus Thrombolysis for Ischemia of the Lower Extremity) trial31 and an European multicenter prospective randomized trial30 showed that the efficacy for UK and rt-PA were equivalent. However, because of concerns regarding the manufacturing process of UK and the possible contamination of the drug with latent viruses the Food and Drug Administration (FDA) suspended sales and distribution of UK in the United States in 1999. Newer recombinant fibrinolytic drugs such as reteplase, saruplase, lanoteplase, and tenecteplase have been developed in recent years. They all show greater fibrin specificity in vitro and promising early clinical results, but are still under investigation and not all are commercially available at the time of writing. Because of several prospective randomized clinical trials (STILE, TOPAS [Thrombolysis or Peripheral Arterial Surgery]) there is good evidence that a major reduction in the magnitude of subsequent surgery for acute leg ischemia may be expected with a policy of initial thrombolysis in acute lower limb ischemia. Moreover, amputation free survival might be improved.31-33 KALINOWSKI AND WAGNER
Fig 2. Adjunctive use of percutaneous aspiration thromboembolectomy (PAT) after unsuccessful hydrodynamic PMT. A 79-year-old-female patient with embolic occlusion of the popliteal artery and trifurcation of tibial arteries. Angiogram before (A), after first pass (B) and final result after hydrodynamic thrombectomy with residual wall-attached embolic material (C). Result after first pass (D) and final result (E) after adjunctive percutaneous aspiration thrombectomy (PAT). Additionally removed emboli by PAT (F).
ADJUNCTIVE TECHNIQUES IN PMT
9
TABLE 2. Thrombolytic Agents for Peripheral Vascular Occlusive Disease Tissue Cultured Agents Streptokinase (SK) Urokinase (UK) Anistreplase (APSAC) Recombinant Produced Agents Recombinant t-PA (rt-PA), Alteplase Recombinant wild type t-PA (r-PA), Reteplase Recombinant urokinase Pro-Urokinase (Pro-UK), Saruplase Recombinat Staphylokinase Lanoteplase TNK-t-PA
Summarizing a single uniform protocol for fibrinolysis from the numerous clinical studies is not possible because of the wide variability in treatment regimens. Therefore, an international group produced a consensus document in 1998 to establish uniform standards for thrombolytic therapy.34 Nevertheless, there is no generally accepted dosing regimen (high-dose versus low-dose), preferable injection method (continuous infusion versus pulsed spray) or consensus regarding the use of concomitant anticoagulation. Beside urokinase and streptokinase, rt-PA is one of the most often used thrombolytic agents. Rt-PA thrombolysis can be accomplished with a wide range of dosing regimens, weightbased (0.02 to 0.5 mg/kg/h) and nonweight-based (0.25 to 10 mg/h). Consensus in the field is that rt-PA infusion doses of 0.5 to 1 mg/h or 0.025 mg/kg/h are appropriate. Higher doses do not improve efficacy and are associated with a higher rate of bleeding complications. There is also general consensus that heparin should be administered sparingly. Full anticoagulation (ie, prolongation of PTT more than 2⫻ of the normal value) should be avoided during rt-PA infusion. Different recommended dosing regimens (UK high dose; UK low dose; rt-PA) are listed in Table 3. Recently, a combined therapeutic approach of local thrombolysis with glycoprotein IIb/IIIa platelet receptor antagonists (abciximab, tirofiban) and direct thrombin inhibitors (eptifibatide) have been proposed. Results of a prospective evaluation of reteplase and abciximab in peripheral arterial thrombolysis in acute and chronic arterial thrombosis suggest shorter thrombolysis times with reduced doses of reteplase when compared with studies using reteplase alone and with no increase in bleeding complications.35 First results of randomized trials using abciximab and urokinase showed similar results.36 How-
ever, these new strategies will need further assessment to evaluate whether these regimens are superior and whether they alter the current application of thrombolysis in the peripheral vasculature. One of the major advantages of intra-arterial thrombolysis is its inferior vessel wall alteration compared with surgical or endovascular techniques. Therefore, thrombolysis is a complementary measure to surgery and endovascular recanalization and can be used as initial treatment modality in acute thromboembolic vascular occlusions to remove the vast majority of occlusive material. Alternatively, it can be used as an adjunctive technique after initial mechanical thrombectomy, if there is residual thromboembolic material to clear the vessel completely. Most of the published trials on percutaneous mechanical thrombectomy have used local thrombolysis in the vast majority of cases. Mainly, fibrinolysis was used to clear the vasculature from residual wall-adherent thromboembolic material.
Ultrasound Thrombolysis Ultrasound thrombolysis can be achieved indirectly via transmitted longitudinal vibrations of a metallic probe coupled to a high-frequency, high-power ultrasound generator. Theoretically, with use of high-energy ultrasound selective disruption of the occlusive material can be induced without damaging the surrounding arterial wall. This selectivity is based on the differences in elasticity between thromboembolic material and the different layers of the vessel wall. Thus, ultrasound angioplasty has been used to disrupt arterial thrombus in vitro and has been also successfully applied in patients with coronary and peripheral arterial disease.37-40 The clinically used devices generate excessive thermal energy, requiring a pulse mode operation and continuous cooling to avoid device failure and vessel damage. Additionally, the need for energy transmission via a rigid coupling probe make these systems rigid and inflexible. Ultrasound fragmentation leads to the possibility of distal embolization. However, angiographically detected emboli were not described in the literature until to date. There is only little information about clinical indications and the future role of these devices in the management of acute ischemia is uncertain. Siegel and coworkers have shown in 50 lesions that ultrasound angioplasty reduces arterial stenosis and can be useful for recanalization of fibrous, calcific and thrombotic arterial occlusions.41 Further studies are mandatory to determine baseline characteristics such as
TABLE 3. Recommended Dosing Regimen Dosing
Anticoagulation
Maximum Dose
Comments
Rt-PA (SCVIR [23])
0.025 mg/kg/hr or 0.5-1 mg/hr
50 mg
Repeated angio 4-8 hr
Urokinase (TOPAS [32,33]) high dose
4,000 U/min for 4 hours followed by 2,000 U/min up to 48 hours 100,000 U/hr for 4-6 hours followed by 50,000 U/hr
IV bolus (2,500 U) heparin followed by IV infusion of 500 U/h heparin Thromboplastin time 1.5-2 times of control value IV infusion of heparin Thromboplastin time 1.5-2 times of control value IV bolus (5,000 U) heparin followed by IA infusion of heparin (1/2 catheter; 1/2 sheath) Thromboplastin time 1.5-2 times of control value
Urokinase (Marburg) low dose
10
6,720,000 U 1,500,000 U
Repeated angio 4-8 hr
KALINOWSKI AND WAGNER
treatment times, length and types of occlusive material and coagulation parameters because rather large amounts of destroyed occlusive material are produced and released into the circulation. Recently, miniaturized catheter tip mounted ultrasound probes have been manufactured allowing the delivery of low energy ultrasound directly to the proximity of the thrombus, which can significantly potentiate the speed and efficacy of pharmacologic thrombolysis. This effect is thought to be largely mediated by acoustic cavitation in a liquid medium, a nonthermal process consisting of the formation and implosion of microscopic gas bubbles. Localized high-speed fluid currents are generated adjacent to the transducer resulting in increased admixture and penetration of the agent into the thrombus. Ultrasound enhanced thrombolysis also can be accelerated by the addition of echo-contrast material. Transcutaneously applied ultrasound energy has also been shown to augment thrombolysis in vivo.42-44 Currently there are no reports available on the combination of ultrasound and PMT for the treatment of acute vascular occlusions.
Manual Catheter Fragmentation and Other Techniques of Thrombus Management These techniques aim in the partial removal of thrombus with embolectomy, fragmentation, maceration or aspiration. Most of the currently described and used techniques do not totally eliminate the treated clots, but rather break down the thrombus into smaller fragments, which migrate peripherally. The technique of manual catheter fragmentation is mainly used in the pulmonary artery circulation, opening up the main pulmonary artery from large occlusive clots and thereby improving perfusion. Fragmentation of the clots exposes fresh surfaces for endogenous fibrinolytic agents and infused thrombolytic drugs to further break down the emboli. In addition, the clots gain more intimate contact with increased concentration of thrombolytics a result of increased blood flow.12 In theory, this method could be even used in the periperal vasculature, but the risk of distal emboli resulting in “trash foot” or “blue toe” syndromes seems disproportionately high. Rotating aspiration thromboembolectomy (RAT) represents another adjunctive fragmentation method. First developed in 1988, RAT is based on fragmentation and detachment of occlusive material from the wall with subsequent removal via PAT. For RAT two devices have been developed. First, a spiral can be used through a regular aspiration catheter. The manually rotating spiral allows a mechanically accelerated thrombolysis because of extensive mixture of concomitantly infused thrombolytics with the occlusive material. Simultaneously, occlusive material is fragmented into smaller particles amenable to subsequent aspiration using the PAT technique. Second, a basket can be used through the aspiration catheters, which allows detachment of wall-adherent material. Firm, organized thrombi or emboli can be captured with the device and retracted through the aspiration catheter (Fig 3). Stark and coworkers showed a primary clinical success rate of 90% for the RAT technique in patients with long thrombotic or embolic occlusions in which conventional PMT techniques had previously failed.45 Finally, the endovascular technique of “distal thrombus or embolus deposition” represents another, but rather seldomly ADJUNCTIVE TECHNIQUES IN PMT
used alternative in thrombus/embolus management. The technique relates to the fact that occlusive material that cannot be aspirated or fragmented is pushed forward into a nonrelevant collateral (eg, side branch of a crural artery) or distal artery. However, none of these described methods has gained major impact on daily clinical practice, but evidence suggests that embolus fragmentation can produce rapid improvement of clinical status especially in pulmonary arteries. Moreover, the equipment for mechanical fragmentation is inexpensive and available in every interventional department. In certain difficult clinical situations, its additional use may be extremely beneficial and the key to technical success.
Ballon Angioplasty and Stent Implantation In case of acute thrombotic occlusions of native vessels, atherosclerotic plaques are the underlying substrate in nearly all cases. Additionally, embolic occlusions can hit atherosclerotic diseased arteries, especially in increasingly older patient populations. Therefore, ballon angioplasty has to be performed after the intial revascularization procedure using PMT in nearly all cases. PTA should be performed only after percutaneous thrombectomy has been completed because of a high incidence of distal embolization of thromboembolic material initiated by the angioplasty maneuver, especially if residual thromboembolic material has been left. Stent implantation into acute thromboembolic occlusions following percutaneous mechanical thrombectomy is likewise possible. The idea of this technique is to compress thrombus by the stent and to fix it to the vessel wall, thereby preventing thrombus dislodgement. The technique also allows to treat residual thrombi or emboli, not capable of further percutaneous mechanical thrombectomy. However, to date there is only a single report about this procedure for treatment of venous thrombosis available.46
Discussion Acute critical limb ischemia because of occlusions of native arteries or bypass grafts is a rationale for rapid revascularization. Catheter-directed pharmacologic thrombolytic therapy and percutaneous thrombectomy procedures can be used as the initial revascularization procedure solely as well as a combined procedure for treatment of thromboembolic disease. Local intra-arterial thrombolysis represents one of the standard treatment modalities in acute thromboembolic occlusions. However, drawbacks of thrombolysis are prolonged procedure times, high costs for patient monitoring and an increased morbidity caused by hemorrhagic complications, rethrombosis, and distal embolization.24,27,28 Additionally, success rates are variable, depending on the amount, composition, chronicity, and location of thrombotic material. Surgical thrombectomy using the Fogarty catheter as another standard modality is an operative procedure, requires general anesthesia in most cases, has a significant morbidity and mortality rate and is usually performed without fluoroscopic guidance. This yields often in incomplete results, does not provide diagnostic information nor does it address underlying vascular disease.14,15 Percutaneous mechanical thrombectomy as alternative initial therapeutic approach for immediate reperfusion in case of acute occlusions has become an established method in interventional radiology and could overcome the shortcomings of
11
Fig 3. Adjunctive use of rotating aspiration thrombectomy after incomplete PMT. Antegrade angiogram revealing a thrombotic occlusion of the superficial femoral artery (SFA) (A). Following PMT residual wall-adherent thrombotic material is visualized (B,C). With use of a manually rotated basket through an aspiration catheter (D) the wall-adherent thrombus could be detached and aspirated (E). Final angiogram revealing complete thrombus removal and minimal wall irregularity at the former thrombus site (ruptured atherosclerotic plaque) (F).
available modalities mentioned above. All of the various devices used for PMT are effective in removing fresh, nonorganized thrombus. Nevertheless, on the basis of current evidence, complete success using thrombectomy devices alone can be expected in a small portion of patients only, whereas the majority requires some form of adjunctive therapy to improve the outcome of revascularization. Nontechnical failures in PMT are caused in most cases by the presence of thrombectomy-refractory thrombotic material (chronic, organized, wall-adherent) or an underlying vascular process such as atherosclerosis, restenosis, recoil, or dissection. Therefore, devices designed for atherectomy as well as percutaneous aspiration thrombectomy are well suited for clearing residual or embolized organized thrombus. Moreover, stent placement in acute thromboembolic occlusions could be performed, especially when other treatment modalities have failed.
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However, it has to be realized that surgical reconstruction will be required and is appropriate in most cases of persistent occlusion after unsuccessful PMT and adjunctive endoluminal techniques because of severe underlying disease unsuitable for percutaneous management.
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