CHAPTER 9

CFIRONIC VENOUS INSUFFICIENCY WITFIULCERAfION: Review of the Literature andTleatment Recommendations

Gage M. Caudell, DPMMolly S Judge, DPMAdam, M. Buclny, DPMSubail B. Masadeb, DPMBonmie Lin, DPM

INTRODUCTION

An estimate d 25o/o of the United States population haschronic venous insr-rfficiency (CVI).' Of equal impor-tance is the fact that this involves a much youngerpopulation than do other more commonly describeddisease processes such as afierial occlusive diseaseand simple varicose veins, which receive much moreattention in the medical communiry. C\{, whensevere, frequentiy results in ulceration that can leadto significant morbidity. Left untreated, patients pre-dictably experience leg pain, edema, dermopathy,and ultimately r-rlceration. Venous ulcerations have a

prevalence between 7-50/o in westernized nations.l Itis important Lo realize that CM with ulceration isvastly different than straight forward varicose veinsand as such the prevalence of C\/I is repofieddistinctly in the medical literature. Cornpressiontherapy is the gold standard for treating thiscondition, and over time a variety of methods haveproven effective for reducing edema and resolvlngsuperficial ulcerations. When ulceration is present,adjunctive therapies such as loca1 wound care,topical wound healing agents, chemical debridement,and surgical debridement each have shown variousdegrees of efficacy. The goal of this article is toprovide clinicians with the background to diagnoseC\/1 and to select the most appropriate therapy.

GROSS ANATOMY

The anatomy of the venous circr-rlation within thelower extremity is complex in its arrangement ofvessels and one-way valves influencing venousblood flow. This arrangement is not unlike thechambers of the heart where there is a combination

of muscular pump action and passive flow thatmaintains optimal circulation within the system. Thevenous systems flow from the very distal lowerextremity into a proximal conduit within theabdominal caviry. More specifically, there are 2

systems of venous structures that return deoxlr-genated blood to the heafi, a deep and a superficialsystem. The cleep venous system consists ofnumerous calf veins that return oxygen depletedblood to the popliteal vein via the anterior andposterior tibial veins. The popliteal vein advancesblood to the femoral vein and then on to the iliacvein where blood is siphoned into the inferior venzr

cava (IVC). The inferior vena cava is the primaryconduit that transports deoxrygenated blood from theabdomen through the diaphragm and into the rightatrium of the heart. This deep venous system is

considered a high pressure system given themuscular pumping action of the calf muscle.

The superficial venous system, a low pressuresystem, begins anterior to the medial malleolousand is composed of the longest vein in the body;the great saphenous vein. A continuation of themedial marginal vein, the great (1ong) saphenousvein will join the femoral vein at a natural defectin the inguinal fascia; the foramen ovale. Inapproximately 700/ct of cases a duplication of thegreat saphenous vein can be seen between theknee and the foramen ovale, using dupleximaging.'z Throughout its superficial course, thegreat saphenous vein is associated with numerouscutaneous nelves; specifically the medial femoralcutaneous nefl/e in the thigh, the infra patellarnen/e branches about the knee and the saphenousnerve along the medial 1eg.3 One ftrfiher anatomicfact about the great saphenous vein is that it has

54 CHAPTER 9

only 10-20 valves throughout its entire length, themajority of which lie in the leg.a The short or lessersaphenous vein runs lateral to the Achilles tendon.In two-thirds of cases it extends toward the midlinewhere it penetrates the deep fascia between theheads of the gastrocnemius muscle within thepopliteal fossa and empties into the popliteal veinabove the knee. In one-third of cases the lessersaphenous vein may join the greater saphenor:svein in the upper thigh region.5

The deep system is separated from the super-ficial system by muscular fascia where perforatingveins provide communication between the two.These perforating (communicating) veins areequipped with one-way valves that preserue theproximal transport of venous blood toward theheart. There arc 3 medial perforating veins, withthe most abundant supply of these perforatorslocated behind the medial malleolous lying overthe posterior tibial vein; the lower perforating vein.The middle-perforating vein rests 7-10 cm proximalto the ankle and lies posterior to the tibia. Thesuperior perforating vein is located within theproximal one-third of the calf and rests posterior tothe tibia (Figure 1). The location of the perforatingveins is important to understand as this systemof veins is the source of dysfunction in a majorityof cases.

FUNCTIONAL ANATOMY

The cardiac system with its afierial and venouscomponents is a natural paralle1 to the venolissystem as it also consists of a muscular pump and a

passive venous return system. The venous system isbroadly composed of a high pressllre, deep systemand a low pressure, superficial system. Theperforating veins allow communication between the2 systems as they assist in propagation ofdeoxygenated blood toward the heart. Contractionof the calf muscle increases pressure in the deepsystem driving blood proximally while the one wayvalves of the perforators, like the cuspid valves inthe heafi, prevent the retrograde flow of fluid intothe low pressure (superficial) system. Relaxation ofthe calf muscle allows blood to be aspirated fromthe superficial system into the deep system viathe open valves of the perforating veins. If theperforating valves are weakened or are insufficientto prevent the retrograde flow of blood duringsystole, as the calf muscle pumps, this high pressure

Figure 1. Illustration de monstrating the anatomy of the greatsaphenous vein (Illustration adopted from Gra1,'s Anatomy 37thEclition: Angiology: Veins of tl're lower limb, edited by Peter L.

Williams, Longman Group tJK Limitecl 1989. FYI Pg.812).

pushes blood back into the superficial systemcausing a dilation of venous structures and laterresults in the stagnation of flow. It is this venollsdilation and stagnation of flow that creates varicosities,which result rn localized tissue hypoxia, dermopathy,and the development of ulcerations. Of clinicalimportance, the cutaneous nelves associated withthe great saphenous vein can become irritated as aconsequence of local tissue hypoxia and toxiciry dueto chronic venous insufficiency prompting commonclinical complaints such as aching and dull pain ofthe thigh and calf.

PATHOGENESIS

The cause of CVI and ulceration involves damageto the blood vessels leading to focal ischemia,inflammation, and vascular infiltration. Currentlythere are 2 popular theories as to why this occurs.The Fibrin Cuff theory suggests that there is anincrease in macromolecule leakage through thevessels secondary to an increased venous pressure.This blockade of macromolecules subsequentlycreates a barrier to diffusion of oxygen andnutrients.6'An alternate hypothesis for thedevelopment of CVI with ulceration is the VhiteCell Trapping Theory. This theory postulates thatleukocyes become entrapped in the capillaries andsubsequently are activated by venous hypertension

CHAPTER 9 55

callsing tissue destruction.'8 The degree ofdestruction is typically associated w-ith the severiryof the venous insufficiency. Regardless of thetheory, the r-rnderlying theme in C\/1 w-ith ulcerationis increased venous hypefiension in the presenceof incompetent superficial or deep system valr.esresr:lting in a leakage of macromolecules, activationof inflammatory mecliators, entrapment of growthfactors, the development of local ischemia andfinally ulceration.

DIAGNOSIS

Although loner e(remity ulcerations can be causedby pressure, peripheral arterial disease, and variousdermatological disorders, C\lI is a distinct entitv thathas a signature ciinical presentation. The symptomsof C.W w-ith or withor-rt ulceration may include butare not limited to pain, chronic muscle fatigue of the

Figure 2. Clinical appearance of patientand tl-rickcning of the skin (cobblestone

q,ith C\,'I \.ith licllenificationskin).

thigh and or calf, and musclrlar spasms in theposterior lnLrscle EJroups of the thigh and leg as n ellas the intrinsic muscles of the arch. The outwardsigns of C\/I u,ill vary with the severity of thecondition and inclucle: lower extremity edema,scaling and cobblestoninll of the skin, hyperpigmen-tation (e.g., hemosiderin deposits), vzrricosities, ancllipodermatosclerosis (Figures 2-4).' Patients mayrelate a history of previous deep vein thrombosis.Ulceration on or near the medial malleolous is a

common clinical finding associated with end stageincompetence of the great saphenous vein (Figure

5). Signature characteristics of venoLls ulcers includesuperficial dermal defects with irregular, flat, orslightly steep borders abotit a granular base."'Signature characteristics of venous ulcers includesuperficial dermal defects with irregr-r1ar, flat, orslightly steep borders about a granular base, anddrainage."r The steep border of these wounds is due

Figure I. Clinicel appealancc of patient $'ith previous sllrgery of thear-rk1e rvith resultant painfnl r':rricosities and hyperpigtrentation (hemo-sidcrin deposits).

Figure 5. Clinical appearance of C\rI witl'r full thickness ulceration atthc medial ankle, TI're patient presentcd u,ith l-rypopigmcntationaround u,ounc1, irregular borcler', and fibrotic base. The wound u,astreated \\''ith iociosoilr ancl llnna's boot.

Figure.i. Clinical appcarance ofancl engorgement of the n'rediai

multiple sma1l r'aricositics of the footnlarginal Jnrl ijrr':rl rspl's1og5 1qir1.

,:.r;:;;*;|i,il.i.

56 CHAPTER 9

to chronic edema as it causes lichenification ofthe skin giving the affected area a cobblestoneappearance. These ulcers are not painful as opposedto their afiertaT counter pafis. Alterial ulcers can beexquisitely sensitive and ischemic ulcers oftenrequire pain management in addition to local woundcare. In C\/I thigh or calf pain is not due to thecondition of the wound but rather is the resr-rlt ofyenous hypertension and its ill effect on localstftictures such as muscles and neryes.

\7hen C\/I is in question it is recommended thatthe patient undergoes duplex ultrasonographyto identfi the location and extent of valr,.urlar

insufficiency.lll2 It is impotant when ordering thistest that you indicate that you want to evaluate forvenous reflux. -W4ren the test is ordered specifyingevaluation for venous reflux, both the superficial anddeep venous system are examined.e''' -When thereis a question as to the natLrre of the vasculardysfunction other non-invasive testing is completedincluding pulse volume recordings (P\,aR), anklebrachial indexes (ABI), digital photo plethesmogra-phy (PPG) and transcutaneolrs oxygen pressure(TCPO2) measurements, and laser Doppler skinperfusion pressure.

An ABI of <0.8 is suggestive of severe afiertalinsufficienry and requires immediate vascular consul-tation. Compression therapy is contraindicated in theface of significant arterial dysfunction and properrevascularization takes precedence in this event.'3'a

MALIGNANCY

Any long standing venolls ulceration that has notshown signs of improvement durinp; 3 months of1ocal wound care should be suspect for malignancyand a biopsy is in order.15 Even though rare, bothbasal cell and squamous cell carcinoma canmanifest in these wounds. Squamous cell carcinoma,which has the higher incidence in venousulcerations, can be aggressive leading to metastasisand eventual death.e

TREATMENT

Compression TherapyEdema therapy is the mainstay in addressing CVI.There are numerous options when selecting a

modality to provide compression therapy.Although many are effective in reducing edema,multilayer dressings have shown demonstrable

superiority over single layer dressings.For years Unna's boot dressing was the treat-

ment of choice, but over the past 10 years the useof multilayer compression dressings have taken theforefiont in CVI therapy. Unna's boot dressing doesnot provide compression but rather removesedema by taking advantage of the action of the calfmuscle pump against a restrictive layer of fibrousmaterial.e Therefore in patients who are inactive ornonambulatory, an Unna's boot dressing is noteffective edema therapy.? The optimal amount ofcompression needed in treating CVI is 25 to 40 mmHg and such devices can be obtained over-the-counter.e

Multilayer compression bandages such as

Profore (Smith & Nephew, Largo, FL), Setopress(Seton Healthcare Group, UK), and Dynaflex(|ohnson & Johnson, Piscataway, NJ) have beenshown to decrease lower extremity edema andheip to resolve venoLls ulcerations in less time as

compared with compression stockings, single layerdressings, or therapy without compression devices.These bandages typically consist of an absorbentlayer next to the skin and 7 or 2 elastic layers withan additional self-adherent compressive shell(Figure 6). Another device that has proven efficacy

Figure 6. The Profore (Smith & Nepheu.) multilayer clressrng is a

commonly usecl con'rpression device. The clevice consist of A) a non-adherent 1ayer, placed over the wound. Next B) an absorbcnt Jayer isapplied to help in drying the nound(s). Compression is initiated. firstwith an C) absorbent compression iayer, :rnd then D) an elasticcompression layer, applied using a figure 8 technique. Last a E) finalself adhelent shell is appliecl to maintain the internal layers and to acldaclditional compression.

CHAPTER 9 57

Figure 7. Clinicei appearance of J-layerJones compression dressing.

is the three-layerJones compression bandage. Eachlayer consists of 2 rolls of Specialist cast padding(fohnson & Johnson, Raynham, MA) and a 6-inchace wrap. Alder et al determined that this devicecan provide a total compression of 27 mm Hg(Figures 7, B).'.

The Cochrane Group completed e meta-analysis of the literature consisting of 22 trialscomparing the effects of different compressiontherapy. They concluded that compression therapyincreased ulcer healing rates when compared withno compression. High compression multilayereddressings were also found to be more effective thanIow compression single-layer dressings for healingC\/I ulcerations.'8

Local TherapyTopical dressings can assist in decreasing bacterialcoLrntl debride fibrotic tissue, promote a moistenvironment, and facilitate healing. Silvadene (King

Pharmaceuticals, Bristol, TN), Iodosorb (Healthpoint,

Fofi Vorth, TX), and Accuzyme (Healthpoint, Fofih\fofth, TX) are just a few therapies on the market thatcan assist in the treatment of venous ulcers, but thereis little data to show if used alone they speed

healing. Most researchers agree these 1ocal dressings

should be used only as an acljunct to compressiontherapy and not as a solo form of ulcer care.e

There are some common local wound care

strategies that are suggested and are practical for usein the clinic or home settings. If these regimens are

simple to perform and arc inexpensive, patient com-pliance may be enhanced and clinical cure is muchmore likely to result. Local wound care should bemodified based Lrpon the ciinical appearance of the wound. Should the wound appear moistwith a beefii red granulation tissue then simple wetto dry dressings using 0.9% NaCl will be satisfactory.This type of wound bleeds well with debridement

Figure 8A. Cl:inrcal appearance of before ancl (8B)

after utilization of lones compression dressing.

Figure 813.

given the neovascuiarity of the granulation tissue

and so does not require any special topical agents toachieve wound healing. These dressing are typicallychanged 2-3 times per day for best results. If the care

plan does not include aggressive edema control, a

weeping dermatitis often develops and mandates

the use of a drying agent such as 0,50/o sodiumhypochlorite (Dakins solution). Caution is necessary

when using this agent as concentrations higher thanO.5o/o may inhibit angiogenesis, impair woundhealing and may result in irritation or even burninjury to the skin. This agent will bleach hair and

clothing so care should be taken to apply directly tothe affected area only. If an ulcer appearc to be

colonized by pseudomonas, a 3% Boric acid solution

58 CHAPTER 9

should be used in lieu of normal saline to eliminatethe gram negative rods and provide a healthierwound bed for granulation tissue in-growth. In theevent that fibrinous tissue in-growth is evident, analternate strategy is required as a simple wet to drydressing will not halt this adverse progression. \[henthis yellow, fibrous tissue is present in the base of a

venous ulcer benzoyl peroxide under occlusion willprove sufficient to eradicate fibrinous ingrowths andallows perpetuation of healthy p;ranulation tissue.This dressing should be prepared by applying apiece of gaLtze measuring the same size as thecenter of the ulcer. A few drops of 700/o benzoylperoxide are applied to the gauze and is covered bya piece of plastic wrap (Saran or other cling wrap).\(rith the benefit of this occlusive covering thebenzoyl peroxide is protected from evaporation andabsorption into the dressing. This occlusiontechnique drives the agent deep into the affectedtissue and provides a full potency agent to breakdown the fibrous tissue. The frequency of thesedressing changes are no diflerent than lbr other wetto dry dressings and changing qSh is suggested.

'When the quality of the skin has suffered from chronicedema, thickened verrucial or cobblestone appear-ance can be reversed with the benefit of potentemollient agents such as 720h ammonium lactate.Shor-rld a frank dermatitis develop in association withchronic venous stasis topical hydrocortisone cream,/ointment should be used and is commonly appliecl2-4 times per day for best results. It cannot be overstated that compression therapy is an integralcomponent of any wound care plan and the patientmust understand that compression devices are a lifelong therapy for chronic venous insufficiency.

Systemic TherapyThree pharmacologic agents in various trials haveshown effectiveness in resolving wouncls associatedwith C\|I, especially when used concuffently withcompression therapy. Aspirin 300 mg was shown tobe effective in ulcer healing in a double-b1indrandomized clinical trial involving 20 patients.le Thenumber of ulcers healed at 4 months with thebenefit of compression and ASA was higher thancompression and placebo. The authors concludedthat aspirin should be used as an adjunct intreatment. The authors could not determine theexact mechanism of how aspirin assist in healingC\rI ulcerations.'e This study was limited by a smallstudy group and results were based on a specific

size of the wound and not complete resolution.Horse chestnut seed extract (HCE) in several

placebo-controlled trials has shown improvementin C\/I as compared with placebo. HCE stimulatesthe release of PGF2-alpha (F series prostaglandin),which incluces venoconstriction and reduces the illeffects of venous congestion. This resuits in adecreased venous permeability and reduces theextravasation of 1ow molecular proteins, water, andelectrolytes. In one study, 50 mg of escin (theactive form of HCE) twice daily was equivalent tocompression stockings.']o

Pentoxifylline has been shown to be effectivein ulcer healing when combined with compressiontherapy. Pentoxifylline increases eq,throc),te (RBC)flexibility and has an inhibitory effect on RBCadhesion that may reduce the release of proteolyticenzymes that damage tissue as stated in the whitecell theory.'r Jull et al in 2002 published a review ofall randomized controlled trials using pentoxifyllinefor venous ulcers. Pentoxifylline was shown toprovide added benefit when used in conjunctionwith compression therapy and may possibly beefficacious as monotherapy." One str-rdy suggestedhigh close pentoxifylline (2,400mg daily) was betterat increasing healing time as compared to low dose(1,200rng daily) therapy." The most commonside-effect reported in both studies was gastroin-testinal disturbance and this was no different thanwith placebo.

Surgical TreatmentSurgical treatment is most often unnecessary in thetreatment ol venous ulcers. If significant fibrous non-viable tissue is present, aggressive debridement isrequired. If the ulcer is too sensitive for in officedebridement and autolyic agents have provenunsuccessful (or are not tolerated by the patient),surgical debridement may be indicated. Traditionalsurgical debridement utilizing dermal curettes can besuccessful, hou''ever new technologies and advancesin wound debridement have been developed. Onesuch device is the VersaJet Hydrosurgery system(Smith & Nephew, Largo FL), w-hich allows preciseremoval of fibrotic tissue and debris. Al1 non-viabletissue should be removed until a granular bleedingbed is present.

Plastic surgery consisting of autologous skingraft has been studied in the treatment of non-healing venoLls ulcers. Twelve-month healing rateshave been repofied as high as 74o/o and recurrence

CHAPTER 9 59

rates between 2B-950/o." Kjaer et a1 reported a 1-yearhealing rate of 53% with meshed split-thickness skingraft. More importantly, they showed that Diabetesmellitr-rs, initial ulcer size, minor local venoussl'rrgery, compression noncompliance, and insuffi-ciency in the popliteal vein was associated withincrease healing time, non-healing, and recurrence."

Bioengineered grafts have also been indicatedin the treatment of venous ulcers. Apligraf(Organogenesis, Canton, MA), Integra (IntegraLifesciences, Plainsboro, NJ), and GammaGraft(Promethean Health Sciences, Pittsburgh, PA) havebeen approved by the FDA for use in venousulcers. Falanga et al, in a controlled clinical trial,str-rdied patients with venous ulcers who receivedcompression or compression plus the bilayeredskin equivalent. A greater percentage of patientshealed with the skin equivalent and the time tohealing was 3-times faster.2r Among venous ulcerpatients, those with refractory wounds of greaterthan one year, the skin equivaient, r-rsed withcompression dressings, was 2 times more effectiveat complete closure when compared to compres-sion therapy alone.'n

The Cochrane Group examined all randomizedcontrolled trials of skin grafts in the treatment ofvenous leg r-rlcers in the literature and concludedthat bilayer artificial skin (e.g., Apligraf) when usedin conjunction with compression bandaging,increases the chance of healing a venous ulcer as

compared with compression and a simple dressing.They underlined the need for fuflher research toassess the effectiveness of other forms of skin grafts,

including autografts and al1ografts."

LONG-TERM TREATMENT

Once healing has been achieved, long-term use ofcompression stockings is necessary to preventrecurrence. It has been reported that 78-100% ofpatients who do not wear compression stockingswill have recuffence of C\1 ulcerations. It is

impofiant to educate patients on the importance ofthese devices and that they constitute long termtreatment not iust temporary care.'u The ThromboEmbolic Device (TED), commonly used in hospitals,only exert 8 to 10 mm Hg of pressure at the ankleand may be beneficial in the prevention of deepvenous thrombosis, but are not effective in chronicvenolrs insr-rfficiency. It is recommend that 25-40 mmHg of pressure is needed for CVI prevention.e In

more severe cases custom made compression hosemay be required and are considerably moreexpensive. Vhile it is unfoftunate, custom fit devicesare often cost prohibitive and this has a negativeimpact on patient compliance.

CONCLUSION

Chronic venous insufficiency with ulceration is

associated with increased morbidity and has a

negative impact on the quality of life. Treatmentbegins with the proper diagnosis and this is best

achievecl in addition to ru1ing out other culprits ofulceration such as ischemia. Understanding themechanics of chronic venous insufficiency andidentifiring the location and extent of valvularinsufficiency is paramount to successfill managementof this disorder. Successftil treatment consists ofpatient education, 1ocal wound care and compres-sion therapy. Mr-rltilayer compression dressings have

been shown to decrease edema and improveshealing time. Systemic therapy consisting of aspirin,

horse chestnut seed extract, ancl pentoxifylline has

shown some success in wound healing but moreresearch is needed. Educating patients about chronicvenous stasis, its potential complications and theneed for long term treatment are necessary toprevent recurrence.

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