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Chapter 18

Functional outcome of critical limb ischemiaGregory J. Landry, MD, Portland, Ore

Results of treatment for critical limb ischemia have traditionally focused on physician-oriented end points related to limbsalvage surgery. Although numerous studies have demonstrated excellent patency and limb salvage after surgicalrevascularization procedures, survival in this patient population is poor, comorbidities reducing quality of life arerampant, and recovery from limb salvage surgery can be prolonged and complicated despite success as defined bytraditional reporting methods. Patient-oriented outcome end points, such as health- related quality of life and functionalstatus, are essential in defining optimal treatment options for the population of patients with critical limb ischemia. Thisarea of research remains in its infancy, but will become increasingly important as the population of patients with criticallimb ischemia and treatment options for these patients continue to expand. The current status and future outlook offunctional and quality of life assessment of patients with critical limb ischemia is reviewed. ( J Vasc Surg 2007;45:141A-148A.)

It is increasingly recognized that traditional methods ofassessingoutcomes and quality of care in patients with criticallimb ischemia (CLI) do not fully address the broad range ofconcerns in these patients. The physician-oriented view ofsuccess has traditionally focused on graft patency, limb sal-vage, and survival.1It is a testimony to the skills of surgeonsinvolved in the treatment of patients with CLI that consis-tently excellent results have been reported for these variablesfor many years. Overall patency rates at 5 years of 60% to 80%for lower extremity arterial reconstructions, with limb salvagerates of 70% to 90%, have been consistently reported.2How-ever, the relatively poor 5-year survival of the patient group

with CLI, typically about 50%,3-8 underscores the fragilenature of this patient group, one typically associated withoverall poor health with multiple comorbidities.

The technical feasibility of limb salvage surgery is axi-omatic, and the endovascular revolution is rapidly expand-ing the repertoire of invasive therapy available to patientswith CLI. To add to this perfect storm, the general agingof the population, persistently high smoking rates (20.9%of the United States adult population in 1995),9and therapid increase of other cardiovascular risk factors, such asdiabetes, obesity, and renal failure, virtually assures a steadygrowth of the population at risk and seeking treatment forCLI. Overall quality of life is improving in elderly pa-

tients,10

but patients with peripheral arterial disease have asignificantly worse quality of life than their counterpartswithout peripheral arterial disease.

Although technical proficiency in performing invasive re-vascularization and in maintaining limb salvage can certainlybe attained, it is clearly recognized, at least anecdotally, thatlimb salvage surgery takes a significant toll on patients. Incontrast to the well-developed body of publications on surgi-caloutcomes, thecurrent statusof researchinpatient-orientedoutcomes remains in its infancy. This has been identified as acritical issue by the TransAtlantic Intersociety Consensus,an international consortium of physicians involved in themanagement of peripheral arterial disease, who stated

Currently there are no quality-of-life instruments that

have been standardized in a large population of patientsrequiring treatment for critical limb ischemia. . .. Im-

provement in functional status is often difficult to define in

patients with critical limb ischemiabecauseof the presenceof

numerous and often severe comorbid conditions. Simple

assessment of walking distance, though useful in some pa-

tients, does not apply to many. . . . Therefore, specific instru-

ments capable of detecting improvement in functional sta-

tus in this diverse patient population must be developed.11

This review will discuss the available body of literatureon patient-oriented outcomes research in the treatment ofpatients with CLI.

RETROSPECTIVE QUALITY-OF-LIFE STUDIES

In an attempt to evaluate outcomes of CLI from apatient-oriented point of view, a number of retrospectivestudies have been performed to assess patient functionoutside of the hospital setting. The retrospective nature ofthese studies inevitably limits their scope; in general, theoutcomes measured have included maintenance of ambu-latory and independent living status.

One of the earliest reports to evaluate patient-orientedfunctional outcomes was published by Abou-Zamzam etal12 from the Oregon Health & Sciences University. Pre-operative and postoperative living situation and ambulatorystatus were evaluated in 513 patients undergoing lower

From the Division of Vascular Surgery, Oregon Health & Science Univer-

sity.

Dr Landry is supported by NHLBI K23 HL80232-01.

Competition of interest: none.

Reprint requests: Gregory J. Landry, MD, Division of Vascular Surgery,

Oregon Health & Science University, 3181 SW Sam Jackson Park Rd,

Mail Code OP11, Portland, OR 97239-3098 (e-mail: landryg@

ohsu.edu).

0741-5214/$32.00

Copyright 2007 by The Society for Vascular Surgery.

doi:10.1016/j.jvs.2007.02.052

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extremity bypass from 1980 to 1995. Ambulatory andliving status before surgery for CLI and 6 months aftersurgery are summarized inTable I.At 6 months, 99% of

patients who were living independently preoperatively hadmaintained independent living status and 97% of patientswho were ambulatory preoperatively remained ambulatory.Conversely, very fewpeoplewhowere in a dependent livingsituation preoperatively went on to live independently at 6months (4%), and only 21% of patients who did not ambu-late independently preoperatively were independently am-bulatory at 6 months.

Multivariate analysis confirmed the importance of pre-operative living situation and ambulatory status in predict-ing outcome at 6 months (P .0001). Amputation (P.0001) and loss of primary patency (P.025) were pre-dictive of poor ambulatory status at 6 months. Other

reports also demonstrated that ambulatory and living statuswere maintained after surgical revascularization forCLI.13-15

Although 6-month functional outcome appeared fa-vorable, it was the impression of the investigators thatpatients undergoing surgery for CLI had a frequent, ongo-ingneed for care of their extremity, with prolonged periodsof wound healing and subsequent operations to maintaingraft patency. The authors defined an ideal outcome oflower extremity surgery for critical limb ischemia as a singleoperation with prompt wound healing, no perioperativecomplications, and no need for further lower extremityinterventions.

The records of 112 consecutive patients undergoingsurgery for critical limb ischemia followed up for 5 to 7years were reviewed for operative complications, graft pa-tency, limb salvage, survival, living and ambulatory status,time to achieve wound healing (both operative and isch-emic), need for repeat operations and recurrence of isch-emia.16Mean follow-up was 42 months. Ambulatory andliving status are presented inTable II.In contrast with theprior study in which patients were monitored for 6 months,with longer follow-up there is a greater decline in indepen-dent ambulation and living status. Healing of all wounds,both operative and ischemic, required a mean of 4.2months, and completed wound healing had not been

achieved in 25 patients (22%) at the time of the last fol-low-up or death.

Repeat operations to maintain graft patency, treatwound complications, or treat recurrent or contralateralischemia were required in 61 patients (54%, mean 1.6reoperations per patient). Major amputation of the indexor contralateral extremity was ultimately required in 26patients. Types of reoperative procedures are listed inTable III.

As assessed by the objective of the ideal outcome,optimal results of revascularization for CLI occurred infre-quently. Only 14% of patients had an uncomplicated oper-ation, relief of symptoms, complete wound healing, noneed for repeat operation, and maintenance of functionalstatus. For the 86% of patients who did not have an idealresult, wound care, repeat hospitalizations and repeat sur-gery, frequent clinic visits, and declining functional statusmeant that a major portion of their remaining life was spentwith ongoing treatment for CLI.

Methods used in the previous study were used toevaluate functional outcomes after lower extremity veingraft revisions vs primary operations.17This study was doneto question the hypothesis that lower extremity vein graftrevisions were well-tolerated procedures with minimalmorbidity. The results of 137 patients undergoing primarylower extremity bypasses were compared with their resultsafter revision. As expected, operative revisions were associ-ated with less morbidity than initial procedures; however,complication rates were still high with revisions, with anoverall complication rate 36% after the initial operation vs22% after revision (P .015). Return to normal preopera-tive ambulatory status at discharge occurred in 71% of

patients after primary operations vs 92%after revisions (P.001). Return to independent living status at the time ofdischarge was 66% after the primary operation and 80%after revision (P .01). At 6 months 90% of patients hadreturned to their preoperative living and ambulatory statusafter both initial operations and revisions.

Taylor et al18 retrospectively evaluated similar func-tional outcomes at 5 years in 1000 patients undergoingsurgical revascularization for CLI. Ambulatory and livingstatuswere evaluated in addition to the traditional outcomemeasures of graft patency, limb salvage, and survival. Notsurprisingly, 5-year overall graft patency (72.4%) and limbsalvage (72.1%) were excellent, with predictably lower

5-year survival (41.9%) in this patient group. Independentambulatory (70.6%) and living status (81.3%) was wellmaintained, with impaired ambulatory status at presenta-tion and dementia predictive of poor functional outcomes.Limb loss was also associated with poor functional out-comes. The anatomic location and type of reconstructiondid not predict functional outcomes, nor did other associ-ated comorbidities such as age, diabetes, history of coro-nary artery disease, or renal failure, among others.

Additional evidence in support of the inadequacy oftraditional reporting standards to fully address the impactof limb salvage surgery on patients overall health wereaddressed independently by the vascular surgery groups

Table I. Functional status of surviving patients beforesurgery and 6 months after surgical revascularization forcritical limb ischemia*

Before surgery 6 months after surgery, %

Living situation Independent Dependent

Independent 99 1.4Dependent 4 96

Ambulatory status Ambulatory Nonambulatory

Ambulatory 97 3Nonambulatory 21 79

*Adapted from Abou-Zamzam et al12with permission of the authors.

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from the University of Arizona,19 and the University ofColorado and Southern Illinois University.20In the formerstudy, 318 patients undergoing lower extremity revascular-ization, 72% of which were for CLI, were retrospectivelyanalyzed for need for hospital readmissions and repeatoperations and wound healing. In the CLI patient group,approximately 50% of patients required at least one reop-eration 3 months and at least one hospital readmission6 months. More than half of the patients required at least3 months for complete healing of surgical or ischemicwounds. Multivariate analysis revealed tissue loss, renalfailure, diabetes, and minority status as independent factorspredicting adverse outcomes.

In the latter study, 334 patients at the two institutionsundergoing revascularization for CLI were assessed forwound healing as well as ambulatory and living status.Complete wound healing was achieved in only 42% at 6months and 75% at 1 year. Independent ambulatory statusdecreased from 91% at baseline to 72% at 6 months, butindependent living status decreased from 96% to 91% dur-ing the same time period, implying that although livingstatus can be maintained, ambulatory status, perhaps a

better surrogate of overall health, is subjected to a greaterdegree of decline.

The above studies are important in terms of realigningtraditional methods of reporting outcomes in CLI. Asnoted, they are limited by their retrospective nature, andperhaps more important, by their relatively limited scope inassessing functional outcome. Few would argue against thenotion that independent ambulatory and living status aregood things; however, they do not really tell the wholestory. For instance:

Does the distance one can ambulate independentlyaffect quality of life?

Does someone who can walk independently automat-ically have a better quality of life than one who requiresassistance?

Can quality of life be achieved in an assisted livingenvironment, perhaps to an even better degree thansomeone living independently but without a devel-oped support structure?

Do other comorbidities affect function and quality of

life to an even greater degree than a patients vascularstatus?

These and other important questions have been ad-dressed in numerous recent studies using general anddisease-specific quality-of-life questionnaires.

QUALITY-OF-LIFE QUESTIONNAIRES INCRITICAL LIMB ISCHEMIA

Prospective data are conspicuously lacking in theassessment of outcomes of CLI. The prospective datathat are available are primarily studies involving patientquestionnaires. Patient assessment of quality of life is animportant element of functional outcome assessment

that has been inconsistently defined in patients undergo-ing interventions for CLI. General questionnaires thataddress components of overall well-being and diseasespecific questionnaires that focus on more directly rele-vant domains have been used to evaluate patients withperipheral arterial disease.

Of the generalized questionnaires, the Short Form 36(SF36) and Nottingham Health Profile (NHP) have beenmost widely used in patients with peripheral arterial diseaseand serve as an assessment of global health status. The SF36addresses eight health concepts: physical function, rolelimitation due to physical problems, bodily pain, generalhealth perception, social function, emotional well-being,

and role limitation due to emotional problems. The NHPcovers six types of experience that maybe affected by illness:pain, physical mobility, sleep, emotional reactions, energy,and social isolation.21

Generalized questionnaires are advantageous in assess-ing overall quality of life and are applicable across multipledisease states. The disadvantageof generic questionnaires isthat they are less able to detect small changes related totreatment of specific disease states.22Although there is noconsensus on which generic quality-of-life questionnaire ismost appropriate in patients with CLI, a recent study fromSweden found the NHP to be more responsive to change inpatients with CLI.23

Table II. Ambulatory and living status of 112 patients before and after limb salvage surgery*

StatusAt last follow-up

or death, %Pre-op, % Post-op, %

Living independently 88 (99/112) 66 (66/99) 73 (72/99)Ambulatory 92 (103/112) 84 (87/103) 70 (72/103)Living independently and ambulatory 86 (96/112) 56 (54/96) 68 (65/96)

*Adapted from Abou-Zamzam et al12with permission of authors.

Table III. Repeat operations in 61 patients undergoinglimb salvage surgery for critical limb ischemia*

Type of repeat operation Total number (%)

Wound dbridement 32 (18)Major amputation 26 (15)Minor amputation 26 (15)Skin graft 3 (2)New bypass graft construction 42 (24)

Bypass graft revision 32 (18)Inflow procedure 15 (9)

*Adapted from Nicoloff et al16with permission of authors.


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Disease-specific questionnaires are theoretically moreresponsive to subtle effects after treatment. The PeripheralArterial Disease-Walking Impairment Questionnaire, de-veloped by Regensteiner et al,24 is a disease-specific ques-tionnaire that has previously been validated in patients withintermittent claudication. A similar questionnaire for CLIhas not been developed. The Vascular Quality of Life

Questionnaire (VascuQol) was designed as a disease-specific questionnaire for patients with peripheral arterialdisease, and is generally felt to be more applicable topatients with CLI. Thequestionnaire contains 25 questionsin 5 domains (pain, symptoms, activities, social, and emo-tional), with each question graded on a 7-point scale rang-ing from 1 (worst) to 7 (best).25

A link between depressed mood and peripheral arterialdisease has been suggested. Cross-sectional studies using ashort form of the Geriatric Depression Scale26-28 haveconfirmed increased depression among elderly patientswith peripheral arterial disease compared with those with-out peripheral arterial disease. It is not known if depression

symptoms improve with lower extremity revascularization,and this is an important quality-of-life parameter that willneed to be addressed in future studies.

Unfortunately, to date there is no consensus on theideal questionnaire(s) to be used in evaluating patients withCLI. A number of smaller, single-institution studies haveused a variety of generic and disease-specific instruments toassess patients undergoing revascularization for CLI (TableIV).29-44The results of these studies are generally favor-able, with most showing improvements in at least some, ifnot all, quality-of-life domains. A variety of primarily ge-neric questionnaires were used in these studies, makingcomparisons between studies difficult.

The largest study performed to date that prospec-tively analyzed patient quality of life after surgical revas-cularization for CLI was the Edifoligide for the Preven-tion of Infrainguinal Vein Graft Failure (PREVENT III)trial, a prospective, randomized, double-blinded, multi-center phase III trial of a novel molecular therapy ofedifoligide (E2F decoy) for the prevention of vein graft

failure.45

Patients undergoing lower extremity revas-cularization for CLI were randomized to intraproce-dural treatment of autogenous vein grafts with the E2Fdecoy vs placebo. The primary study end point was graftfailure; however, a prospective quality-of-life analysisusing the VascuQol questionnaire was simultaneouslyperformed.46

The study result was negative with respect to theprimary end point, but significant improvements in qual-ity of life were identified in patients after surgical revas-cularization at 3 and 12 months compared with baseline.The overall VascuQol score increased from a mean of 2.8 1.1 at baseline to 4.7 1.4 and 5.1 1.4 at 3 and 12

months, respectively. Significant improvement was seenacross all domains. Factors associated with failure ofquality-of-life improvement included diabetes and agraft-related event.

The study did have significant flaws in data acquisitionwith respect to the quality-of-life data. Of the 1404 patientsenrolled in the study, questionnaires were completed by1296 (92%) at baseline, 862 (61%) at 3 months, and 732(52%) at 12 months. The reasons for incomplete data areunclear; however, a subsequent analysis showed that pa-tients not completing the quality-of-life assessment weremore likely to have had an adverse outcome. Therefore it ispossible, if not likely, that the inclusion of the nonre-

Table IV. Prospective health-related quality-of-life studies in patients undergoing surgical and catheter-based treatmentfor critical limb ischemia*

Surgical treatment n QOL instrument Follow-up Result

Duggan30(1994) 38 Other (Rand 36) 19 months No change (compared to amputation)

Gibbons31

(1995) 156 SF36 6 Improved (multiple domains)Johnson32(1995) 47 Multiple 6 Mixed (compared to amputation)Paaske33(1995) 153 Other (QOL score) Variable Improved (mobility, emotional)Albers34(1996) 38 Other (QL index) 12 Improved 6 months, no change 12 monthsJohnson35(1997) 150 Multiple 12 Improved (multiple domains)Chetter36(1998) 55 SF36 12 Improved (multiple domains)Tretinyak37(2001) 46 SF36 4.3 Improved (physical function)Klevsgard38(2001) 62 NHP 12 Improved (pain, sleep, mobility)Klevsgard39 (2002) 40 SF36/NHP 1 Improved (multiple domains)Kalbaugh40(2004) 105 SF36 6 Improved (multiple domains)Martemianov41(2004) 28 SF36 3 Improved (pain, physical function)Wann-Hansson42(2005) 62 NHP 12 Improved (pain, sleep)Bradbury43(2005) 195 EuroQol/SF36 12 Improved (multiple domains)Engelhardt44(2006) 86 SF36 6 Improved (all domains)

Percutaneous treatment n QOL instrument Follow-up Result

Kgler47(2005) 17 Other (PAOD 86) 1 week ImprovedBradbury43(2005) 216 EuroQol/SF36 12 Improved (multiple domains)Kalbaugh48(2006) 30 SF36 12 Improved (pain)

*Table format adapted from Nehler et al29with permission of authors.




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sponders would lessen, if not negate, the positive quality-of-life outcomes identified in this study.Onecanstill argue,however, that patients with good outcomes of lower ex-tremity revascularization for CLI will experience improve-ments in quality of life sustainable for up to a year afterrevascularization.

QUALITY OF LIFE AFTER PERCUTANEOUSINTERVENTIONS

The data on functional outcomes after surgery for CLIis scarce, but even less is known about functional outcomesafter percutaneous interventions for lower extremity isch-emia. This is clearly an area of importance owing to thegrowing number of percutaneous interventions being per-formedand the increasing number of percutaneous optionsavailable for use; for example, angioplasty with or withoutstenting, subintimal angioplasty, cryoplasty, and atherec-tomy, among others. Given the growing numbers of inter-ventions and the expense of percutaneous devices, carefully

documented outcomes will be critical to determine optimalpercutaneous therapy for appropriate patients.

Several small series have attempted to evaluate patientoutcomes after percutaneous interventions, although inmost series, most patients were treated for claudicationrather than CLI. Few series have specifically addressedoutcomes in patients with CLI (Table IV). Kgler et al47

evaluated 102 consecutive patients with symptomatic pe-ripheral arterial disease (83% with claudication, 17% CLI)one week after intervention by using a quality-of-life ques-tionnaire specifically designed for German-speaking coun-tries.47 Not surprisingly, patients with the most severeperipheral arterial disease exhibited the most severe quality-

of-life impairment before intervention; however, thesewere the same patients that exhibited the greatest improve-ment in quality of life measured 1 week after intervention.Age and comorbidities did not influence improvements inquality of life.

In contrast, Kalbaugh et al48 recently published a1-year prospective quality-of-life outcome study of patientsundergoing angioplasty for symptomatic peripheral arterialdisease (54 with claudication, 30 CLI). Health-relatedquality of life was assessed with the SF36 questionnaire.Although patients with claudication experienced improve-ment at 1 year in all domains, patients with CLI experi-enced improvement only in the pain domain.

The recently published Bypass vs Angioplasty in SevereIschaemia of the Leg(BASIL) trial evaluatedhealth-relatedquality of life using the EuroQol Groups EQ5D and SF36questionnaires.43In this multicenter United Kingdom trial,patientswith CLI were randomized toeithera surgery-first orangioplasty-first treatment regimen. In both treatmentarms, similarly improved health related quality of life wasrecorded at 3 months with sustained, although not contin-ually improved, quality of life reported thereafter. Withlonger follow-up, there was a trend toward improvedhealth-related quality of life in the surgery group comparedwith the angioplasty group, although no significant differ-ence was noted.

FUNCTIONAL MEASUREMENTS IN THEELDERLY

A weakness of health-related quality-of-life question-naire studies is that they rely on patient perceptions ratherthan objectively measuring performance. There has been

little research in lower extremity functional performance inthe vascular surgery literature, but the field of geriatrics hassupplied us with several validated methods of assessingfunction in thegeriatricpatient population. In this area, thework of McDermott and associates in the Walking and LegCirculation Study (WALCS) has been instrumental. In thislongitudinal cohort study,700 patients with and withoutperipheral arterial disease are being prospectively moni-tored to identify clinical characteristics associated withpoorer baseline functioning in peripheral arterial diseaseand subsequent functional decline. Subjects with lowerankle-brachial indices at baseline experienced impairedlower extremity functioning, increased disability, and re-

duced lower extremity strength compared with patientswith normal ankle-brachial indices.49-51Although not spe-cifically designed to evaluate patients with CLI, the post-procedural battery of functional evaluations have been usedextensively in studies of elderly patients with peripheralarterial disease to evaluate functional abilities.

Walking distance. Walking distance has traditionallybeen measured with treadmill testing. Both constant-load,in which patients walk at a constant speed and grade, andgraded treadmill walking, in which grade and velocity aregradually increased during the test, have been used, withgraded treadmill testing currently felt to be the preferredmethod.52Treadmill testing is well tolerated and reproduc-ible in patients with claudication, but it is less well suited topatients with CLI with limited functional reserve.

Six-minute walk test.A monitored 6-minute walkhas been shown to be a valid method of walking assessmentin elderly patients.53-55The test is performed in a 100-foot-long flathallway, where patients are instructed to walk backand forth as far as they can in 6 minutes. Trained personnelwalk directly behind the subjects and give standardizedinstructions of encouragement at set intervals. Becausesubjects are allowed to walk at their own pace and areallowed to rest in a chair if necessary, results of a 6-minutewalk are a more accurate reflection of walking abilities aswell as being less anxiety provoking, than treadmill walking.

Summary performance score. The summary perfor-

mance score, developed by Guralnik et al,56,57grades sub-jects abilities to perform multiple activities involving dif-ferent aspects of leg function:

Usualwalking speedisevaluatedwith a timed4-meter walk.

Balance is evaluated with the Tinetti Balance Evalua-tion, which assesses a patients ability to maintain avariety of standing positions. In the side-by-side stand,subjects are required to stand with both feet together.In the semi-tandem stand,one foot is placed in front ofand to the side of the other. In the tandem-stand, onefoot is placed in front of the other such that the heel ofone foot touches the toe of the other.




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Muscle power is tested by asking the subject to standandsit repetitively from a seatedposition with thearmsfolded across the chest. The time taken to perform thistask five times is recorded.

Each of these three tasks is graded on a 4-point scale.The

scores are based on published norms from the EstablishedPopulations for the Epidemiologic Study of the Elderly. Thetabulated score has been shown to correlate with the need fornursing home placement, morbidity, and mortality.56,57

Measured daily physical activity.The Caltrac verticalaccelerometer (Muscle Dynamics Fitness Network, Inc,Torrance, Calif) has been extensively evaluated and vali-dated as a measure of physical activity in the elderly patientpopulation.58-60 The device is worn like a beeper at thewaistline for a period of 7 days. Activity units are recordedin a digital display and are converted to caloric expenditure.The device gives an accurate measurement of patients levelof function in the community.61

Muscle strength. An additional validated method ofmeasuring lower extremity muscle strength in the elderly is amuscle function evaluation chair (Good Strength Chair, Me-titur, Jyvskyl, Finland). Participants are seated in the chairand areasked to sequentiallyflex andextendtheir hips, knees,or ankles against a paddedpost or strap. Theenergy transmit-ted by flexion and extension of the isolated muscle group isrecorded. Isometric muscle strengthis evaluated in thistest. Inthe elderly patient population, muscle strength measured bythe muscle function evaluation chair correlates closely withlower extremity function.51,60

To date, only one study has objectively evaluated theseindicators in a groupof patients undergoing revascularization

for CLI. Gardner et al,

62

in a recent small prospective series,examined 20 patients with limb-threatening ischemia preop-eratively and postoperatively with a 6-minute and 20-meterwalk, daily physical activity measured with an accelerometer,and questionnaires examining patient perceptions of changesin walking ability.62 Subjects were evaluated preoperativelyand with a single postoperative measurement at 3 to 4months. Of interest wasthat no objective improvements weremeasured in any of the functional measures tested; however,significant improvements were noted inpatient-perceivedlev-els of function. This was a small study with only a singlepostoperative point evaluated, so it is difficult to make gener-alizations to the overall population of patients undergoingrevascularization for CLI. Changes in functional status mayoccur for several months to years after intervention and areclearly multifactorial in nature.

NONOPERATIVE MANAGEMENT OFCRITICAL LIMB ISCHEMIA

CLI is universally accepted as an absolute indication forinvasive therapy. In selected cases, however, nonoperativetherapy may be appropriate therapyand even preferable.The rationale for pursuing nonoperative management isbased on studies showing that patients managed withoutsurgery do not inevitably progress to limb loss. This wasclearly shown in two large prospective, placebocontrolled

clinical trials of treatment with prostaglandins in patientswith limb threatening ischemia, in which approximately50% of patients with rest pain or ulcer improved onplacebo.63,64In situations in which patients refuse surgeryor are not surgical candidates (secondary to severe comor-bidities or lack of target vessels), small ulcers or rest painimprove on occasion without operative therapy. No cur-rently available pharmacologic therapy has been shown toaugment wound healing in this patient population.

Intermittent pneumatic compression therapy is anemerging form of nonoperative therapy for CLI. Intermit-tent pneumatic compression has been used widely as amethod of prophylaxis against deep venous thrombosis inhospitalized patients. Recent studies have also demon-strated a favorable effect of compression therapy on arterialhemodynamics. Transcutaneous oxygen pressures and ar-terialflow asmeasured by laser Doppler flux have bothbeendemonstrated to improve with compression therapy.65-68

The proposed mechanisms of increased arterial perfusion

include an increased arterial-venous pressure gradient due toaugmented venous emptying and increased nitric oxide andtissue factor pathway inhibitor due to increased blood shearrates from rapid cuff inflation and deflation. Increased shearforces inhibit platelet and macrophage deposition, with aresultant decrease in endothelial inflammation.

Patients with intermittent claudication treated withcompression therapy have had favorable results in increas-ing walking distance,69as well as significant improvementin health-related quality of life.70The maximal benefit ofcompression therapy was obtained with the use of thedevices 4 hours a day for 3 months. Benefits were main-tained for 1 year after treatment. Initial and absolute clau-

dication distances were improved 146% and 108%, respec-tively, with an improvement in resting ankle-brachial indexof 18%. Intermittent pneumatic compression has not beensystematically evaluated in patients with CLI.

AMPUTATION

The last several decades have been characterized by thedevelopment of innovative techniques to prevent limb loss inpatients with CLI. It is clear that one of the main goals oflower extremity revascularization is the preservation of limbsalvage and function. As has been pointed out, however,surgical treatment for limb salvage can lead to severe, long-term disability even if the limb is preserved. For some patients

with CLI, amputation is the optimal treatment. Recent stud-ies have demonstrated thatpatients undergoing amputations,although functionally impaired, can achieve a good quality oflife.71Although the goal of amputation is generally to reha-bilitate the patients to ambulate with a prosthesis, many am-putees never reach independent ambulatory status. Nehler etal72 demonstrated that at 1 year after amputation, 65% ofbelow knee amputees were ambulatory, with approximatelyhalf of these only ambulatory indoors. Only 29% of aboveknee amputeeswere ambulatory, with twothirdsof these onlyambulatory indoors. Thus, for patients to have any hope ofreturning to ambulatory status, preserving the knee joint iscritical. Of interest is that the same report demonstrated that




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loss of ambulatory status did not inevitably lead to loss ofindependence. Very few patients who were independent be-fore amputation required placement in a care facility afteramputation. For most patients, independent living with theuse of a wheelchair was possible.

Limb salvage will continue to be the overriding goal formost patients referred for vascular therapy, but a subset ofpatients with CLIareclearly better servedwith amputation.Unfortunately, it is not always clear ahead of time whichpatients will benefit from primary amputation vs attemptedlimb salvage with revascularization.

CONCLUSION

Outcomes research in CLI is entering a new phase wherepatient-oriented outcomes are replacing traditional surgeon-oriented or lesion-orientedoutcomes.A numberof question-naires and objective functional assessments are available, butthe optimal methodof assessing interventions for critical limb

ischemia is yet to be defined. This will become increasinglyimportant froma publichealthstandpointas thepopulationofpatients with critical limb ischemia and the number of treat-ment options for this disease continues to grow.

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Submitted Jan 19, 2007; accepted Feb 21, 2007.



20- progn. functional ischemie critica membru- 2007

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