Critical Limb Ischemia and Limb Salvage(Exerpted from Wound Care Practice, Best Publishing, Ed. Sheffield, Smith, and Fife)
Fernando Boccalandro MD – Richard W. Smalling, MD, PhD
From the Division of Cardiology -The University of Texas Houston Medical School at Houston
of Critical Limb Ischemia & Limb Salvage:
Peripheral vascular disease of the lower extremities comprise a clinical spectrum that goes from asymptomatic patients, to patients with chronic critical limb ischemia (CLI) that might result in amputation and limb loss. Critical limb ischemia is a persistent and relentless problem that severely impairs the patient functional status and quality of life, and is associated with an increased cardiovascular mortality and morbidity. It can present acutely (i.e. distal embolization, external compression, acute thrombosis, etc.) or, in the majority of cases, as chronic CLI which will be the main focus of this chapter.
Authors have proposed different definitions for chronic CLI taking into account a variety of hemodynamic measurements in combination with clinical findings, since the diagnosis based on the usual clinical manifestations of CLI (i.e. chronic non-healing wounds, resting pain, or gangrene) could also be caused by other non-vascular diseases. A practical and simple definition is the one proposed by the European Working Group on CLI. This group defined CLI as the presence of ischemic rest pain requiring analgesia for more than two weeks, or ulceration, or gangrene of the lower extremity with an ankle systolic blood pressure ≤ 50 mmHg and/or toe systolic pressure ≤ 30 mmHg.
Limb salvage can be defined as any revascularization procedure, surgical or percutaneous aimed at improving the blood flow in the ischemic limb with the purpose of preventing limb loss, and ideally achieving wound healing and resolution of chronic ischemic pain or gangrene.
Of Critical Limb Ischemia
Chronic CLI in the vast majority of cases are related to advanced atherosclerotic disease. Other diseases have to be kept in mind by the clinician, specially in young patients, those with ulcers in atypical locations, or those with few or no risk factors for CLI (Table 1). Chronic CLI secondary to atherosclerosis develops when arterial stenosis reaches a critical point in which the blood flow supplied to the distal extremity is insufficient to provide the basal tissue oxygen demand. This occurs despite two compensatory mechanisms: post-stenotic arteriolar vasodilatation and development of collateral circulation. When the basal tissue oxygen demand cannot be met by the peripheral vascular system, ischemic injury occurs in the tissues with the lowest blood supply and necrosis results leading to tissue destruction, the appearance of ulceration, gangrene, and rest-pain. Besides the tissue necrosis secondary to the poor oxygen demand/supply relationship seen in these patients, they are also threatened by severe microvascular dysfunction secondary to a local and systemic inflammatory response and a thrombotic milieu that worsens their poor capillary blood flow. Also reported in this group of patients are: impaired vasomotor response, vasospasm, increased platelet aggregation, impaired fibrinolysis, abnormal healing, micro-thrombus formation, increased leukocyte activation and adhesion, increased capillary permeability with interstitial edema, local activation of the immune system with increased levels of C-reactive protein and other systemic inflammatory mediators. These seem to be accentuated in diabetics, which present with a combination of macro and micro angiopathy due to accelerated atherosclerosis, increased blood viscosity, thrombosis and an enhanced inflammatory response, which leads to a more distal and diffuse disease that might significantly limit the possibility of an effective revascularization. The presence of neuropathy in this later group also plays an important role in the pathogenesis of CLI. Neuropathy increases the risk of severe toe and foot lesions due to the absence of pain during and after trauma and the lack of early recognition of wounds that require prompt attention. It also might alter the mechanics of normal gait, worsening the perfusion on certain points of repeated pressure on the foot and toes, and predisposing some of these areas for wound formation. The lack of blood flow predisposes the ischemic tissues in diabetics to have extensive wounds with poor healing potential even after minor trauma. Diabetes mellitus predisposes the formation of early wet gangrene with polymicrobial infections that are difficult to treat due to the limited blood supply, predisposing them to the formation of deep wound infections and osteomyelitis.
Of Critical Limb Ischemia
The first assessment in patients with suspected CLI should always be to look for the presence of signs of acute limb ischemia that will require immediate attention and emergent revascularization. They can be remembered by the rule of the 5-“P’s”: Absence of Pulse, presence of resting Pain, Pallor, Paresthesia and Paralysis.
Chronic CLI is present usually in patients with previous history of intermittent claudication, smokers, diabetics, history of cerebrovascular or coronary artery disease, who now present with one or all the four hallmarks of CLI: resting pain, non healing ulcers, dry gangrene, and absence of palpable pulses.
Resting Pain: Patients
with CLI usually describe their pain as a throbbing pain, dull ache,
or numbness that classically worsens when the patient
elevates the leg, and in the evenings or nights. It is relieved by
lowering the leg to a dependent position and, interestingly, in contrast
with intermittent claudication, the resting pain of CLI can actually
improve slightly with deambulation due to mild improvement in the arteriolar
flow caused by the effects of gravity.
For Patients With Suspected CLI
Transcutaneous Oxymetry: Tanscutaneous oxymetry measures the transcutaneous oxygen pressure at the skin surface produced by heat induced hyperemia. Different than the previous tests that give hemodynamic or anatomic information, transcutaneous oxymetry serves as a practical functional test that evaluates the oxygen delivery to the ischemic tissues. It is used not only to evaluate the need for revascularization in patients with CLI (transcutaneous oxymetry < 40 mmHg), but also predicts outcome of patients requiring amputation, survival of skin grafts, prognosis of wound healing with hyperbaric therapy and effective percutaneous or surgical revascularization.
Laser Doppler perfusion studies: As transcutaneous oxygen measurements, the use of laser Doppler perfusion with blood flow images are being used to assess tissue perfusion in compromised limbs. Its clinical use is currently limited, but has a good potential in the future for patients with CLI to determine need for revascularization, healing potential, amputation level determination, and revascularization success after percutaneous interventions.
Conventional angiography: Although it represents an invasive test, conventional contrast angiography with digital substraction is the “gold standard” for patients with CLI (Figure 4). It allows a detailed evaluation of all the different parts of the vascular tree and importantly of the distal circulation and plantar archs. It can be performed from the retrograde approach using a femoral access or antegrade through the common femoral artery or the brachial/transradial approach.
The use of digital substraction angiography that can eliminate the superimposing shadows of the underlying tissues, has enhanced the resolution of conventional angiography using modern digital technology. Emphasis must always be placed in having an adequate visualization of the distal run-offs and plantar circulation, which becomes critical in patient with CLI in which revascularization is considered. New digital angiographic systems with modern technology have improved its performance and now provide better resolution with less radiation, a better three-dimensional evaluation of the vasculature and new features that help in diagnostic and percutaneous interventions with less contrast use and radiation exposure (i.e. rotational angiography with or with out rapid computer three dimensional reconstructions, landmarking, view-trace and fluoro-trace modes, etc.).
Which diagnostic method to use? Clearly the most important is to gather a complete history and detailed physical examination with an ankle systolic blood pressure or ABI to confirm the diagnosis of CLI. Once the diagnosis of CLI is made, further tests depend largely on the experience of the center where the patient is evaluated and the clinical presentation. When resting pain or gangrene is present, a functional test is not needed and the patient should be evaluated with an MRA (or duplex ultrasound in centers with expertise in this technique) to assess the anatomic localization of the stenosis, the severity of the vascular compromise and the feasibility of revascularization. Based on this initial evaluation, a revascularization strategy is made using the preferred approach (surgical vs percutaneous) according to the patients individual situation to achieve the best short and long term results. If surgery or amputation is contemplated, MRA in experienced centers might suffice as the sole diagnostic tests. However, the information provided by the MRA is not definitive, a conventional contrast angiography with digital substraction will be needed to define the patient’s vasculature and establish the best surgical technique.
For wound healing purposes, the best approach is to start with a functional test to assess the possibility of wound healing (transcutaneous oxymetry or laser Doppler perfusion) or a simple toe systolic blood pressure. If these tests show a reasonable prognosis for wound healing, a trial of intensive wound care and medical therapy should be attempted first. If this fails to achieve wound healing, or if patients have limiting intermittent claudication, or if the functional tests are suggestive of a poor healing potential; a MRA or duplex ultrasound is recommended to establish the best method of revascularization (percutaneous versus surgical revascularization). This is followed by conventional angiography if the percutaneous approach is used or if the non-invasive evaluation is inconclusive or insufficient to get the needed information before surgical revascularization.
The primary care physician should identify the signs and symptoms of CLI as soon as they are present, and should refer the patient as early as possible to the wound care specialist or to the vascular specialist for further assessment and aggressive treatment. The wound care specialist plays a pivotal role in the care of this patient, not only in the wound care management before and after revascularization, but also assessing the potential for wound healing and making the decision with the vascular specialists on the best timing for revascularization. All the team involved in patient care should focus in improving the patient modifiable risk factors and optimize the patient medical therapy to attempt to arrest disease progression without forgetting the high incidence of concomitant heart and cerebrovascular diseases seen in this group of patients. The vascular specialist (interventional cardiologist/radiologist or vascular surgeon) must make the best decision regarding the preferred revascularization approach based upon the disease segment to treat, the inflow and outflow in the affected limb and the underlying operative risk to the patient. Three forms of revascularization therapy are available for patients for limb salvage: surgical revascularization, endovascular therapy and thrombolysis.
The type of graft in CLI is also an important consideration, prosthetic grafts are successfully used for aorto iliac disease with patency at 5-years close to 90%. However, the use of venous grafts have significantly improved patency rate compared with prosthetic grafts when anastomosed at the knee level (68% versus 38% at 5 yr.) or below (50% versus 12% at 5 yr); and therefore should be the preferred conduit for these anatomic sites.
One of the most important aspects of graft patency depends on the distal run-off. Patients with severe distal disease, poor pedal arches, and slow or poor distal run-offs have a very low patency rate. Thus, it is generally recommended to have at least two vessel runoffs before surgical revascularization is considered. Besides the quality of the runoffs and the severity of the vascular disease, graft failure is not uncommon in patients undergoing limb salvage due to spontaneous thrombus formation, disease progression and graft or anastomotic neointimal hyperplasia. To limit disease progression, an aggressive medical therapy should be instituted to try to the control risk factors and improve lipids, glucose, smoking and blood pressure control. The use of pharmacologic therapy to prevent graft failure remains uncertain, except for the use of antiplatelet agents that are recommended (i.e. aspirin and clopidrogel) and, in some cases, of prosthetic grafts going to the femoropopliteal or below. The use of coumadin is also advocated.
Although advances have been made in innovative technologies with emphasis in lesion modification, atheroablation and other ingenious approaches, the mainstay of endovascular therapy still is balloon dilatation and stenting (Figure 4).
Outcomes of endovascular therapy as in surgical revascularization are dependent on the distal run-off. mproved outcomes are also seen in the iliac vessels as compared with femoro-popliteal or distal disease revascularization procedures. Higher success rates are seen in patients with focal and short stenosis, with mild diffuse distal disease, in non-diabetics, in patients with reconstituted pedal arches after the procedure, and in non smokers.
The 5-year patency rates for aortoiliac disease have been reported close to 85% with stent implantation and for femoropopliteal disease, between 38 to 70% in combined series of balloon angioplasty with and with-out stenting. Although the immediate angiographic and clinical success are usually good, the long-term patency of these procedures are jeopardized by restenosis, especially at the femoropopliteal level and below the knee, requiring in many cases a repeat revascularization procedure to reestablish and maintain vessel patency.
For infrapopliteal disease, the use of angioplasty with coronary techniques have demonstrated generally a poor durability, but nevertheless its recognized role in limb salvage is now accepted (up to 80% of limb salvage was produced by Bakal et al. in carefully selected patients), preventing limb amputation and improving wound healing even in patients that are not candidates for surgical revascularization.
There have been no randomized studies comparing the current endovascular therapies with surgical revascularization for CLI, but data from different comparative studies and from series of patients suggest that they might have a similar outcome regarding limb salvage. However, the patients undergoing endovascular therapy might require repeat revascularization procedures due to the presence of restenosis to maintain patency, with the advantage of avoiding an initial surgical procedure. In patients undergoing endovascular therapy for CLI, it is also very important to aggressively modify their risk factors and maintain an adequate antiplatelet regimen with aspirin and most likely also combined with clopidrogel for long term.
With the current techniques must patients with CLI can benefit from revascularization. Initially, the percutaneous approach is preferred by many centers in order to avoid a surgical procedure in a group of patients that are at high operative risk. However, the best treatment to achieve the highest rates of limb salvage and long-lasting revascularization can not be generalized; and in the best interest of the patient, needs to be individualized based on their underlying risk factors, comorbidities, severity of peripheral vascular disease and particular anatomy.
Options for Limb Salvage
With this endovascular armamentarium, also novel pharmacologial approaches are being studied to try to improve the restenosis rates (i.e: iloprost and prostaglandin derivates, cilostazol, low molecular weight heparins and direct thrombin inhibitors, etc) and improved vascular growth and collateral vessels formation (gene therapy and vascular growth factors). Also newer graft materials are being tested and some novel techniques in which gene delivery is combined with new prosthetic graft materials are being developed to prevent graft thrombosis and to improve graft patency.
|Protocol For Limb Salvage
As a guide for the clinician, we provide this simple algorithm to help in the management of patients with CLI:
|Table 1: Differential diagnosis for chronic critical limb
Patent foramen ovale.
Left ventricular thrombus.
Antithrombin III deficiency
Protein C and S deficiency
Brown recluse spider.
Radiculopathies and spinal stenosis.
Giant cell arteridities
|Figure 1||Figure 4A|
|Figure 2||Figure 4B|
(a) Digital substraction angiography of the right leg of the patient in Figure 3 showing a stump in the take off of the superficial femoral artery.
(b) Regular angiography in the same patient following a percutaneous retrograde superficial femoral artery reconstruction using the popliteal approach. Note the nitinol stents placed in the superficial femoral artery with its reconstituted runoff and the differences in the quality between digital substracted and regular angiography.
|1.||Second European Consensus Document on chronic critical leg ischemia. Eur.J Vasc.Surg 1992; 6 Suppl A: 1-32.|
|2.||Criqui MH. Langer RD. Fronek A. Feigelson HS. Klauber MR. McCann TJ. Browner D. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl.J Med 1992; 326: 381-386.|
|3.||Forrest KY. Becker DJ. Kuller LH. Wolfson SK. Orchard TJ. Are predictors of coronary heart disease and lower-extremity arterial disease in type 1 diabetes the same? A prospective study. Atherosclerosis 2000; 148: 159-169.|
|4.||Anvar MD. Khiabani HZ. Kroese AJ. Stranden E. Alterations in capillary permeability in the lower limb of patients with chronic critical limb ischaemia and oedema. Vasa 2000; 29: 106-111.|
|5.||Bowers BL. Valentine RJ. Myers SI. Chervu A. Clagett GP. The natural history of patients with claudication with toe pressures of 40 mm Hg or less. J Vasc.Surg 1993; 18: 506-511.|
|6.||Orchard TJ. Strandness DE, Jr. Assessment of peripheral vascular disease in diabetes. Report and recommendations of an International Workshop sponsored by the American Heart Association and the American Diabetes Association 18-20 September 1992, New Orleans, Louisiana. J Am Podiatr.Med Assoc. 1993; 83: 685-695.|
|7.||Varty K. Nydahl S. Butterworth P. Errington M. Bolia A. Bell PR. Changes in the management of critical limb ischaemia. Br.J Surg 1996; 83: 953-956.|
|8.||Weitz JI. Byrne J. Clagett GP. Farkouh ME. Porter JM. Sackett DL. Strandness DE, Jr. Taylor LM. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation 1996; 94: 3026-3049.|
|9.||Maser RE. Wolfson SK, Jr.. Ellis D. Stein EA. Drash AL. Becker DJ. Dorman JS. Orchard TJ. Cardiovascular disease and arterial calcification in insulin-dependent diabetes mellitus: interrelations and risk factor profiles. Epidemiology of Diabetes Complications Study-V. Arterioscler.Thromb. 1991; 11: 958-965.|
|10.||Palumbo PJ. O'Fallon WM. Osmundson PJ. Zimmerman BR. Langworthy AL. Kazmier FJ. Progression of peripheral occlusive arterial disease in diabetes mellitus. What factors are predictive? Arch Intern Med 1991; 151: 717-721.|
|11.||McGee SR. Boyko EJ. Physical examination and chronic lower-extremity ischemia: a critical review. Arch Intern Med 1998; 158: 1357-1364.|
|12.||Jaff MR. Dorros G. The vascular laboratory: a critical component required for successful management of peripheral arterial occlusive disease. J Endovasc.Surg 1998; 5: 146-158.|
|13.||Owen RS. Baum RA. Carpenter JP. Holland GA. Cope C. Symptomatic peripheral vascular disease: selection of imaging parameters and clinical evaluation with MR angiography. Radiology 1993; 187: 627-635.|
|14.||Whelan JF. Barry MH. Moir JD. Color flow Doppler ultrasonography: comparison with peripheral arteriography for the investigation of peripheral vascular disease. J Clin Ultrasound 1992; 20: 369-374.|
|15.||Babb JD. Collins TJ. Cowley MJ. Dorros G. Freedman RJ, Jr.. Galichia J. Iannone IA. Kern MJ. Tommaso CL. Ramee SR. Rosenfield K. Roubin GS. Weintraub RA. White RA. White CJ. Revised guidelines for the performance of peripheral vascular intervention. Catheter.Cardiovasc.Interv. 1999; 46: 21-23.|
|16.||Norgren L. Pharmacotherapy for critical limb ischaemia. Diabetes Metab Res Rev 2000; 16 Suppl 1: S37-S41.|
|17.||Gottrup F. Holstein P. Jorgensen B. Lohmann M. Karlsmar T. A new concept of a multidisciplinary wound healing center and a national expert function of wound healing. Arch Surg 2001; 136: 765-772.|
|18.||de Vries SO. Visser K. de Vries JA. Wong JB. Donaldson MC. Hunink MG. Intermittent claudication: cost-effectiveness of revascularization versus exercise therapy. Radiology 2002; 222: 25-36.|
|19.||Dorros G. Jaff M. Mathiak L. He T. Multicenter Palmaz stent renal artery stenosis revascularization registry report: four-year follow-up of 1,058 successful patients. Catheter.Cardiovasc.Interv. 2002; 55: 182-188.|
|20.||Wholey MH. Maynar MA. Wholey MH. Pulido-Duque JM. Reyes R. Jarmolowski CR. Castaneda WR. Comparison of thrombolytic therapy of lower-extremity acute, subacute, and chronic arterial occlusions. Cathet.Cardiovasc.Diagn. 1998; 44: 159-169.|
|21.||Dorros G. Jaff MR. Murphy KJ. Mathiak L. The acute outcome of tibioperoneal vessel angioplasty in 417 cases with claudication and critical limb ischemia. Cathet.Cardiovasc.Diagn. 1998; 45: 251-256.|
|22.||Gray BH. Sullivan TM. Childs MB. Young JR. Olin JW. High incidence of restenosis/reocclusion of stents in the percutaneous treatment of long-segment superficial femoral artery disease after suboptimal angioplasty. J Vasc.Surg 1997; 25: 74-83.|
|23.||Bakal CW. Cynamon J. Sprayregen S. Infrapopliteal percutaneous transluminal angioplasty: what we know. Radiology 1996; 200: 36-43.|
|24.||Isner JM. Rosenfield K. Redefining the treatment of peripheral artery disease. Role of percutaneous revascularization. Circulation 1993; 88: 1534-1557.|
|25.||Weaver FA. Comerota AJ. Youngblood M. Froehlich J. Hosking JD. Papanicolaou G. Surgical revascularization versus thrombolysis for nonembolic lower extremity native artery occlusions: results of a prospective randomized trial. The STILE Investigators. Surgery versus Thrombolysis for Ischemia of the Lower Extremity. J Vasc.Surg PG. 1996.|
|26.||Ouriel K. Veith FJ. Sasahara AA. A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. Thrombolysis or Peripheral Arterial Surgery (TOPAS) Investigators. N Engl.J Med 1998; 338: 1105-1111.|
|27.||Carpenter JP. Golden MA. Barker CF. Holland GA. Baum RA. The fate of bypass grafts to angiographically occult runoff vessels detected by magnetic resonance angiography. J Vasc.Surg 1996; 23: 483-489.|
|28.||Ameli FM. Byrne P. Provan JL. Selection of amputation level and prediction of healing using transcutaneous tissue oxygen tension (PtcO2). J Cardiovasc.Surg 1989; 30: 220-224.|
|29.||Kram HB. Appel PL. Shoemaker WC. Prediction of below-knee amputation wound healing using noninvasive laser Doppler velocimetry. Am J Surg 1989; 158: 29-31.|
|30.||Isner JM. Walsh K. Symes J. Pieczek A. Takeshita S. Lowry J. Rosenfield K. Weir L. Brogi E. Jurayj D. Arterial gene transfer for therapeutic angiogenesis in patients with peripheral artery disease. Hum.Gene Ther 1996; 7: 959-988.|
|Top of Page|
The Memorial Hermann Center for Wound Healing
Houston, TX 77030-1501
Telephone: 713-704-5900 | Fax: 713-704-5793 | Emergency Telephone: 713-704-4268