Treatment of chronic lower extremity critical limb ischemia
- David G Neschis, MD
David G Neschis, MD
- Clinical Associate Professor of Surgery
- University of Maryland School of Medicine
- Michael A Golden, MD
Michael A Golden, MD
- Associate Professor of Surgery
- University of Pennsylvania
- Section Editors
- John F Eidt, MD
John F Eidt, MD
- Section Editor — Vascular Surgery
- Professor of Surgery
- University of South Carolina School of Medicine Greenville
- Joseph L Mills, Sr, MD
Joseph L Mills, Sr, MD
- Section Editor — Vascular Surgery
- Professor of Surgery
- University of Arizona Health Sciences Center
INTRODUCTION AND DEFINITIONS
Eight to ten million Americans suffer from arterial occlusive disease, with approximately 500 to 1,000 new cases of chronic limb ischemia per million per year . Patients with critical ischemia present with rest pain, which is pain across the base of the metatarsal heads at rest relieved by dependency, or with tissue loss, which can be ulceration, dry gangrene or wet gangrene, occurring in the lower extremities due to atherosclerotic occlusive disease of the iliac, femoral or popliteal arteries . Signs of critical limb ischemia on noninvasive testing include an ankle-brachial index less than 0.4, a flat waveform on pulse volume recording, and low or absent pedal flow on duplex ultrasonography .
The different therapies for critical limb ischemia will be reviewed here, according to the site of the vascular lesion and the specific clinical setting. The clinical manifestations and diagnosis of this disorder and acute limb ischemia are discussed separately. (See "Overview of acute arterial occlusion of the extremities (acute limb ischemia)".)
Limb-threatening ischemia occurs in 1 to 2 percent of patients with PAD who are 50 years of age or older . The natural history of critical limb ischemia usually involves inexorable progression to amputation unless there is an intervention that results in the improvement of arterial perfusion. This is in contrast to the often benign natural history of mild and moderate claudication. (See "Clinical features and diagnosis of lower extremity peripheral artery disease".)
The ACC/AHA practice guidelines suggested the following distribution of outcomes at one year in these patients [2,3]:
●Alive with two limbs – 50 percent
- Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg 2007; 45 Suppl S:S5.
- Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation 2006; 113:e463.
- Dormandy J, Heeck L, Vig S. The fate of patients with critical leg ischemia. Semin Vasc Surg 1999; 12:142.
- 2011 WRITING GROUP MEMBERS, 2005 WRITING COMMITTEE MEMBERS, ACCF/AHA TASK FORCE MEMBERS. 2011 ACCF/AHA Focused Update of the Guideline for the Management of patients with peripheral artery disease (Updating the 2005 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2011; 124:2020.
- Wolf GL, Wilson SE, Cross AP, et al. Surgery or balloon angioplasty for peripheral vascular disease: a randomized clinical trial. Principal investigators and their Associates of Veterans Administration Cooperative Study Number 199. J Vasc Interv Radiol 1993; 4:639.
- Adam DJ, Beard JD, Cleveland T, et al. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet 2005; 366:1925.
- Bradbury AW, Adam DJ, Bell J, et al. Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: An intention-to-treat analysis of amputation-free and overall survival in patients randomized to a bypass surgery-first or a balloon angioplasty-first revascularization strategy. J Vasc Surg 2010; 51:5S.
- Abbott, WM, Kwolek, CJ. Aortofemoral bypass for atherosclerotic aortoiliac occlusive disease. In: Current Therapy in Vascular Surgery, Ernst, CB, Stanley, JC (Eds), Mosby-Year Book, St. Louis 1995. p.355.
- Harris RA, Hardman DT, Fisher C, et al. Aortic reconstructive surgery for limb ischaemia: immediate and long-term follow-up to provide a standard for endovascular procedures. Cardiovasc Surg 1998; 6:256.
- Poulias GE, Doundoulakis N, Prombonas E, et al. Aorto-femoral bypass and determinants of early success and late favourable outcome. Experience with 1000 consecutive cases. J Cardiovasc Surg (Torino) 1992; 33:664.
- Valentine RJ, Clagett GP. Aortic graft infections: replacement with autogenous vein. Cardiovasc Surg 2001; 9:419.
- Mannick, JA, Whittemore, AD. Aortoiliac occlusive disease. In: Vascular Surgery: A Comprehensive Review, Moore, WS (Ed), WB Saunders, Philadelphia 1991. p.350.
- Pursell R, Sideso E, Magee TR, Galland RB. Critical appraisal of femorofemoral crossover grafts. Br J Surg 2005; 92:565.
- Ahn SS, Hiyama DT, Rudkin GH, et al. Laparoscopic aortobifemoral bypass. J Vasc Surg 1997; 26:128.
- Wain RA, Veith FJ, Marin ML, et al. Analysis of endovascular graft treatment for aortoiliac occlusive disease: what is its role based on midterm results? Ann Surg 1999; 230:145.
- Veith, FJ, Gupta, SK, Wengerter, KR, et al. Femoral-popliteal-tibial occlusive disease. In: Vascular Surgery: A Comprehensive Review, Moore, WS (Ed), WB Saunders, Philadelphia 1991. p.364.
- Suggested standards for reports dealing with lower extremity ischemia. Prepared by the Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery/North American Chapter, International Society for Cardiovascular Surgery. J Vasc Surg 1986; 4:80.
- Dalman, RL, Taylor, LM Jr. Infrainguinal revascularization procedures. In: Basic Data Underlying Clinical Decision Making in Vascular Surgery, Porter, JM, Taylor, LM, Jr (Eds), Quality Medical Publishing, St. Louis 1994. p.141.
- Veith FJ, Gupta SK, Ascer E, et al. Six-year prospective multicenter randomized comparison of autologous saphenous vein and expanded polytetrafluoroethylene grafts in infrainguinal arterial reconstructions. J Vasc Surg 1986; 3:104.
- Berlakovich GA, Herbst F, Mittlböck M, Kretschmer G. The choice of material for above-knee femoropopliteal bypass. A 20-year experience. Arch Surg 1994; 129:297.
- Wilson YG, Wyatt MG, Currie IC, et al. Preferential use of vein for above-knee femoropopliteal grafts. Eur J Vasc Endovasc Surg 1995; 10:220.
- Green RM, Abbott WM, Matsumoto T, et al. Prosthetic above-knee femoropopliteal bypass grafting: five-year results of a randomized trial. J Vasc Surg 2000; 31:417.
- Johnson WC, Lee KK. A comparative evaluation of polytetrafluoroethylene, umbilical vein, and saphenous vein bypass grafts for femoral-popliteal above-knee revascularization: a prospective randomized Department of Veterans Affairs cooperative study. J Vasc Surg 2000; 32:268.
- Quiñones-Baldrich WJ, Prego AA, Ucelay-Gomez R, et al. Long-term results of infrainguinal revascularization with polytetrafluoroethylene: a ten-year experience. J Vasc Surg 1992; 16:209.
- Fichelle JM, Marzelle J, Colacchio G, et al. Infrapopliteal polytetrafluoroethylene and composite bypass: factors influencing patency. Ann Vasc Surg 1995; 9:187.
- Raftery KB, Belkin M, Mackey WC, O'Donnell TF. Are peroneal artery bypass grafts hemodynamically inferior to other tibial artery bypass grafts? J Vasc Surg 1994; 19:964.
- Nadal LL, Cynamon J, Lipsitz EC, Bolia A. Subintimal angioplasty for chronic arterial occlusions. Tech Vasc Interv Radiol 2004; 7:16.
- London NJ, Srinivasan R, Naylor AR, et al. Subintimal angioplasty of femoropopliteal artery occlusions: the long-term results. Eur J Vasc Surg 1994; 8:148.
- Lipsitz EC, Ohki T, Veith FJ, et al. Does subintimal angioplasty have a role in the treatment of severe lower extremity ischemia? J Vasc Surg 2003; 37:386.
- Nehler MR, Moneta GL, Edwards JM, et al. Surgery for chronic lower extremity ischemia in patients eighty or more years of age: operative results and assessment of postoperative independence. J Vasc Surg 1993; 18:618.
- O'Brien TS, Lamont PM, Crow A, et al. Lower limb ischaemia in the octogenarian: is limb salvage surgery worthwhile? Ann R Coll Surg Engl 1993; 75:445.
- Hearn AT, Smith JM, Welling RE, et al. Analysis of autogenous vein femoral-infrapopliteal bypass for limb salvage in the elderly. Cardiovasc Surg 1996; 4:105.
- Whittemore AD, Donaldson MC, Mannick JA. Infrainguinal reconstruction for patients with chronic renal insufficiency. J Vasc Surg 1993; 17:32.
- Johnson BL, Glickman MH, Bandyk DF, Esses GE. Failure of foot salvage in patients with end-stage renal disease after surgical revascularization. J Vasc Surg 1995; 22:280.
- Chiriano J, Bianchi C, Teruya TH, et al. Management of lower extremity wounds in patients with peripheral arterial disease: a stratified conservative approach. Ann Vasc Surg 2010; 24:1110.
- Prostanoids for chronic critical leg ischemia. A randomized, controlled, open-label trial with prostaglandin E1. The ICAI Study Group. Ischemia Cronica degli Arti Inferiori. Ann Intern Med 1999; 130:412.
- Takeshita S, Zheng LP, Brogi E, et al. Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest 1994; 93:662.
- Isner JM, Pieczek A, Schainfeld R, et al. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb. Lancet 1996; 348:370.
- Baumgartner I, Pieczek A, Manor O, et al. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 1998; 97:1114.
- Rajagopalan S, Shah M, Luciano A, et al. Adenovirus-mediated gene transfer of VEGF(121) improves lower-extremity endothelial function and flow reserve. Circulation 2001; 104:753.
- Tateishi-Yuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360:427.
- Higashi Y, Kimura M, Hara K, et al. Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia. Circulation 2004; 109:1215.
- Murphy MP, Lawson JH, Rapp BM, et al. Autologous bone marrow mononuclear cell therapy is safe and promotes amputation-free survival in patients with critical limb ischemia. J Vasc Surg 2011; 53:1565.
- Franz RW, Shah KJ, Johnson JD, et al. Short- to mid-term results using autologous bone-marrow mononuclear cell implantation therapy as a limb salvage procedure in patients with severe peripheral arterial disease. Vasc Endovascular Surg 2011; 45:398.
- Huang P, Li S, Han M, et al. Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care 2005; 28:2155.
- Nikol S, Baumgartner I, Van Belle E, et al. Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia. Mol Ther 2008; 16:972.
- Belch J, Hiatt WR, Baumgartner I, et al. Effect of fibroblast growth factor NV1FGF on amputation and death: a randomised placebo-controlled trial of gene therapy in critical limb ischaemia. Lancet 2011; 377:1929.
- Horsch S, Claeys L. Epidural spinal cord stimulation in the treatment of severe peripheral arterial occlusive disease. Ann Vasc Surg 1994; 8:468.
- Mingoli A, Sciacca V, Tamorri M, et al. Clinical results of epidural spinal cord electrical stimulation in patients affected with limb-threatening chronic arterial obstructive disease. Angiology 1993; 44:21.
- Klomp HM, Spincemaille GH, Steyerberg EW, et al. Spinal-cord stimulation in critical limb ischaemia: a randomised trial. ESES Study Group. Lancet 1999; 353:1040.
- Humphries MD, Pevec WC, Laird JR, et al. Early duplex scanning after infrainguinal endovascular therapy. J Vasc Surg 2011; 53:353.
- Shames ML. Duplex surveillance of lower extremity endovascular interventions. Perspect Vasc Surg Endovasc Ther 2007; 19:370.
- Bandyk, DF. Surveillance of lower extremity bypass grafts. In: Current Therapy in Vascular Surgery, Ernst, CB, Stanley, JC (Eds), Mosby-Year Book, St. Louis 1995. p. 492.
- Lindblad B, Wakefield TW, Stanley TJ, et al. Pharmacological prophylaxis against postoperative graft occlusion after peripheral vascular surgery: a world-wide survey. Eur J Vasc Endovasc Surg 1995; 9:267.
- Devereaux PJ, Mrkobrada M, Sessler DI, et al. Aspirin in patients undergoing noncardiac surgery. N Engl J Med 2014; 370:1494.
- Dörffler-Melly J, Koopman MM, Adam DJ, et al. Antiplatelet agents for preventing thrombosis after peripheral arterial bypass surgery. Cochrane Database Syst Rev 2003; :CD000535.
- Collins TC, Souchek J, Beyth RJ. Benefits of antithrombotic therapy after infrainguinal bypass grafting: a meta-analysis. Am J Med 2004; 117:93.
- Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral Anticoagulants or Aspirin Study): a randomised trial. Lancet 2000; 355:346.
- Johnson WC, Williford WO, Department of Veterans Affairs Cooperative Study #362. Benefits, morbidity, and mortality associated with long-term administration of oral anticoagulant therapy to patients with peripheral arterial bypass procedures: a prospective randomized study. J Vasc Surg 2002; 35:413.
- Belch JJ, Dormandy J, CASPAR Writing Committee, et al. Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial. J Vasc Surg 2010; 52:825.
- Sobel M, Verhaeghe R, American College of Chest Physicians, American College of Chest Physicians. Antithrombotic therapy for peripheral artery occlusive disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:815S.
- Alonso-Coello P, Bellmunt S, McGorrian C, et al. Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e669S.
- INTRODUCTION AND DEFINITIONS
- GENERAL PRINCIPLES
- TASC classification
- Bypass surgery first versus angioplasty first
- Thrombolytic therapy
- SURGERY FOR INFLOW DISEASE
- General principles
- Aortofemoral bypass graft
- - In situ autogenous reconstruction
- Extra-anatomic reconstruction
- - Axillobifemoral bypass graft
- - Femorofemoral bypass
- - Axillopopliteal bypass
- Minimally invasive operative alternatives
- Endovascular grafts
- SURGERY FOR INFRAINGUINAL DISEASE
- General principles
- Femoropopliteal bypass
- Distal bypass
- PERCUTANEOUS INTERVENTION
- PRIMARY AMPUTATION
- SPECIFIC ISSUES
- Infrainguinal bypass in older adults
- Infrainguinal bypass in chronic kidney disease
- MEDICAL THERAPY
- Risk factor reduction
- Aggressive wound care
- Pharmacologic therapy
- - Prostaglandin E1
- - Stimulation of angiogenesis
- Spinal cord stimulation
- POSTOPERATIVE FOLLOW-UP
- Duplex ultrasound surveillance
- ANTITHROMBOTIC THERAPY
- SUMMARY AND RECOMMENDATIONS