Current Options in the Diagnosis and Management of Acute Limb Ischemia

Karthikeshwar Kasirajan, MD, Kenneth Ouriel, MD

Disclosures

Prog Cardiovasc Nurs. 2002;17(1) 

In This Article

Management Options

In the 1960s and the 1970s, balloon catheter thrombectomy, first introduced by Fogarty et al.,[5] became the cornerstone of therapy. Interestingly, this marked the beginning of catheter-based endovascular therapeutic options that introduced the concept of remote, rather than direct, open surgical intervention for management of occlusive vascular disease.

While improvements in open surgical techniques have diminished the rate of limb loss associated with ALI, the mortality rate remains unacceptably high.[6] In fact, patient survival has not changed dramatically since the report of Blaisdell and colleagues[4] more than 20 years ago. The discordance of limb salvage and patient survival is explained by the specific factors controlling the two events. While mortality occurs as a result of concurrent medical comorbidities and the fragile baseline medical state of patients presenting with ALI, limb loss is related to an unsuccessful revascularization procedure. As such, the rate of amputation has diminished over the decades, presumably because of improvements in surgical technique.

Open surgical techniques for salvage of an ischemic limb include: 1) balloon catheter thrombectomy (Figure 1); 2) bypass procedures to direct blood flow beyond the occlusion (Figure 2); 3) endarterectomy with or without patch angioplasty (Figure 3); and 4) intraoperative isolated limb thrombolysis. Unfortunately, the ability to rapidly restore arterial flow to the extremity with an operative procedure represents a significant insult to medically compromised individuals -- one that all too frequently culminates in patient demise. A review of three large, recent clinical trials[7,8,9] on open surgical revascularization for treatment of ALI is given in Table 2 .

Balloon catheter used to withdrawn an acute thrombotic occlusion. Reprinted with the permission of The Cleveland Clinic Foundation.

Vein graft used to bypass the site of arterial occlusion. Reprinted with the permission of The Cleveland Clinic Foundation.

Direct surgical thrombectomy and closure of arteriotomy with patch angioplasty. Reprinted with the permission of The Cleveland Clinic Foundation.

The search for less invasive revascularization strategies has been ongoing, with the goal of lessening the morbidity of the procedures without compromising the quite satisfactory rate of limb salvage that has been achieved with contemporary surgical procedures. Pharmacologic thrombolysis and, more recently, percutaneous mechanical thrombectomy (PMT) hold potential in this regard. Both techniques can effect clearance of the occluding thrombus from a peripheral artery in a minimally invasive fashion, restoring blood flow to the extremity and allowing the identification of any underlying lesion that was responsible for the occlusive event. The unmasked culprit lesion can then be addressed in a directed manner with angioplasty, stenting, or a limited operative procedure performed electively in a well prepared patient.

The introduction of catheter-directed, locally-administered thrombolytic agents has challenged three decades of dominance of the Fogarty catheter thrombectomy. Thrombolytic agents are in widespread use for the dissolution of arterial and venous pathologic thrombi. Thrombolytic agents have been successfully employed to dissolve the occluding thrombus, reconstitute blood flow, and improve the status of the tissue bed supplied by the involved vascular segment. All thrombolytic agents in clinical use today are actually plasminogen activators. As such, they do not directly degrade fibrinogen. Rather, they are trypsin-like serine proteases that have high specific activity directed at the cleavage of a single peptide bond in the plasminogen zymogen, converting it to plasmin. Plasmin is the active molecule that cleaves fibrin polymer to cause the dissolution of thrombus. Peripheral thrombolytic therapy is administered through a catheter-directed approach to achieve regional thrombus dissolution with minimal systemic fibrinolysis. However, a moderate systemic proteolytic state often results from the use of thrombolytic agents, limiting their use to patients with no contraindications ( Table 3 ). The concurrent use of a therapeutic dose of heparin increases the risk of hemorrhagic complications. Nevertheless, fixed-dose heparin in the range of 500 U/hour or less is routinely used to prevent pericatheter thrombosis and may also increase the likelihood of successful thrombolysis.[10]

Since the removal of urokinase (Abbokinase, Abbott Labs, Abbott Park, IL) from the US market, either recombinant tissue plasminogen activator (rt-PA) (Alteplase, Genentech, South San Francisco, CA) or reteplase (Retevase, Centocor, Malvern, PA) is commonly used for thrombolytic procedures. The thrombolytic agent rt-PA (50 mg) is usually reconstituted in sterile water or saline immediately before use, to a concentration of 1 mg/mL. Dilution to 0.05 mg/mL will reduce drug activity to 25%, due to adherence to the plastic i.v. tubing and bag. Hence, dilution below 0.2 mg/mL is not recommended. When kept at room temperature, rt-PA should be used within 8 hours. It is incompatible with heparin (1 mg/mL and heparin 100 U/mL), and iodinated contrast agents reduce the fibrinolytic activity of rt-PA.

Reteplase has recently been used for peripheral thrombolysis. Reteplase can be diluted in sterile water to 0.04 U/mL and remains stable for 24 hours. No prospective dosage trials for this agent have been reported.

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