CHRONIC VENOUS INSUFFICIENCY

I. Physiology and pathophysiology

1. Superficial venules and veins collect blood from skin and SQ fat
2. Drain toward deep venous system (underneath fascia) by 3 routes:

1. Through long or short saphenous vv. (join the deep system at saphenofemoral & saphenopopliteal junctions)
2. Through perforating vv. originating from the long or short saphenous vv.
3. Directly into the deep venous system or bypassing the deep system entirely to enter the pelvis

3. Deep veins

1. Divided into intramuscular and intermuscular
2. Intermuscular vv. = post. tibial, anterior tibial, and peroneal; join to form the popliteal v. which enters thigh to become the superficial femoral v., then joined by deep femoral v. to form the common femoral v., which enters the pelvis to become the common iliac v., joining the contralateral common iliac to become the inferior vena cava.

4. Superficial, perforating, and deep vv. have valves (generally bicuspid) which direct flow toward central circulation
5. Blood is moved toward the heart by the pumping action of the leg mm. which expels blood from the deep system, drawing more blood from the superficial to the deep system
6. If valves of superficial, perforating, and/or deep vv. are incompetent, reguritation will occur during calf mm. relaxation, and superficial vv. and capillaries will be subjected to abnormally high venous pressure (normal superficial venous pressure is 20-30 torr; can increase to 60-90 torr in the presence of valvular incompetence or venous obstruction)
7. The capillary hypertension can be aggravated by loss of normal reflexive constriction of precapillary arterioles during standing which normall helps to protect the capillary bed from surges in hydrostatic pressure
8. Sustained capillary HTN leads to various changes

1. Probably most sig. is increase type IV collage in basement membrane of the endothelium and formation of a pericapillary "fibrin cuff" with increased capillary permeability to large molecules but also decreased cutaneous oxygenation
2. Alteration in lymphatic circulation with decreased lymphatic flow (unknown mechanism)

II. Clinical features-attributable to pathophysiologic mechanisms discussed above

1. Varicose veins

1. Visible engorgement of the cutaneous veins
2. Traditionally thought to cause many different symptoms; However, in a cross-sectional study of 1566 pts, only itching, heaviness, and aching were correlated with presence of varicosities of the saphenous vein and its branches (BMJ 318:353, 1999--JW)
3. Treatments include vein stripping (ligation of the incompetent large vein and miniphlebectomy of superficial veins) and endovascular laser or RF coagulation.

2. Dependent edema
3. Tropic changes of the skin

1. Changes in pigmentation: tan or reddish-brown skin discoloration, particularly at medial ankle
2. Dermatitis ("In more advanced cases the skin may have small erosions with weeping and excoriations due to scratching"-JGIM rvw.)
3. "Lipodermatosclerosis"

1. A fibrosing panniculitis of the leg; the skin is bound down to the subcutaneous tissues
2. A late change in CVI
3. Firm induration at the medial ankle, occasionally extending circumferentially up to the mid-leg (in which case the leg proximal to the constriction is usually quite edematous-"upside-down champagne bottle" shape")

4. "Atrophie blanche"

1. An accompaniment to lipodermatosclerosis
2. 2-5mm macules of depigmentation within areas of increased pigmentation
3. Represent avascular, fibrotic skin
4. Thought to predispose to ulcer formation

4. Ulceration

1. Tend to occur on the medial ankle, in areas of lipodermatosclerosis
2. May be single or multiple and tend to last for months to years
3. Typically tender, shallow, with irregular borders and a red base that may be exudative; Can spread to be circumferential
4. Slightly more common in women; much more common in older pts.
5. Unclear pathogenesis; may be related to "leukocyte trapping" in cutaneous microcirculation with subsequnt activation and release of cytotoxic substances
6. Most are heavily contaminated w/multiple species of bacteria (Staph, Strep, E. coli, Proteus, Pseudomonas, etc.) which don't clear w/use of topical or systemic abx

5. Chronic edema, trophic skin changes, and ulceration often seen after DVT ("postphlebitic syndrome") but contribution of past DVT to the pathophysiology of these complications of CVI is unclear; often will occur in pts w/no known h/o DVT
6. Other sx: heaviness and aching of the LE's

III. Diagnostic testing

1. Differential dx includes diabetic changes and, if ulcers are present (particularly on the foot rather than the ankle or leg), arterial disease; these can coexist with venous insufficiency

1. Absence of lipodermatosclerosis, at least on medial malleolus, or absence of edema, should call into question the attribution a cutaneous ulcer to CVI

2. Can screen for arterial disease with ankle-brachial inddices (> 0.9 is normal)
3. Duplex ultrasonography (combines B-mode imaging of deep & superficial vv. with directional pulsed Doppler assessment of blood flow)-method of choice as of 1997

1. Can detect venous obstruction as well as venous reflux due to valvular incompetence
2. 84% sensitive and 88% specific in dx of deep venous insufficiency as c/w direct venous pressure measurements

IV. Treatment

1. Treatment goals: reduce edema, eliminate lipodermatosclerosis, and allow ulcers to heal
2. Mechanical tx

1. Elevation of legs above heart x 30min 3-4x/d can reduce edema and improve cutaneous microcirculation
2. In more advanced disease, compression stockings are used

1. Mechanism of action is unclear: seem to result in diminished venous reflux and reduced venous pressures; may improve cutaneous microcirculation
2. Arterial insufficiency and uncompensated CHF are relative contraindications
3. Review of 24 randomized trials of Tx for venous leg ulcers showed that compression vs. noncompression dressing improves healing rates; multilayer high-compression bandages vs. inelastic compression resulted in better healing rates at 3mos (BMJ 315:576, 1997-JW)
4. Also shown to reduce incidence of recurrence after healing (AFP)
5. Should exert 20-30 torr of pressure at the ankle and less at the knee ("graded compression"; BMJ review says use 30-40 torr if ulcer is present)
6. Knee-high stockings are us. sufficient; thigh-highs may impede venous flow at popliteal space w/knee flexion and are to be avoided
7. Apply hose first thing in the morning when edema is minimal, after dressing ulcers; turn stocking inside-out to the heel and pull up onto leg; may go on better if a silky, light hose or talcum powder is used first; note that some pts will have difficulty pulling on their stockings; some come with zippered back or Velcro fasteners to make this easier.
8. Different types of compression systems
   1. High elastic compression--can be worn continuously up to 1 week; can be washed & reused
   2. Light compression--low pressures, single was reduces pressures obtained
   3. Light support--for holding dressings in place or as a layer within a multilayer bandage; 40-60^ of pressure lost in first 20min after application
   4. Multilayer high compression--e.g. 4 layer bandages; provides graded compression sustainable for a week
   5. Inelastic compression bandage
   6. Compression stockings--light, medium, or strong support--us not for tx of ulcers?

3. Other compression tx ("non-eleastic compression"), for use in severe edema due to CVI

1. 4-layer bandaging
2. Unna paste boot (rolled gauze impregnated w/various things including calamine, ZnO, glycerin, etc. etc., applied from matatarsals to just below the knww, then covered with 4" rolled gauze to absorb moisture, then Ace wrap; stiffens after drying)
3. "CircAid" nonelastic compression leggings-pliable, inelastic, adjustable compression bands that wrap around the leg and are held in place by Velcro fasteners

4. For pts with massive edema or obesity, may not be able to get stocking on; can use intermittent pneumatic compression pumps

1. Arterial insufficiency and uncompensated CHF are relative contraindications

5. Dressing of ulcers before applying compression

1. Variety of dressings are used; no data to indicate advantage of any particular one: dry of wet nonadherent dressings; DuoDerm (occlusive hydrocolloid dressing; can be changed by pt at home Q3-7d); zinc-paste-impregnated bandages (Unna boot; need to be applied by trained personnel 1-2x/wk)

3. Pharmacologic tx

1. Diuretics short-term for tx of severe edema
2. Pentoxifylline for venous leg ulcers
   1. 200 nondiabetic pts with venous leg ulcers > 1cm x > 2mos randomized to pentoxyfilline 400mg TID vs. placebo; at 6mos, pentoxifylline group nonsig. more likely to have ulcers healed (64% vs. 52%) (BMJ 319:875, 1999--JW/AFP)
   2. In a systematic review of 8 trials involving 547 pts comparing pentoxifylline vs. placebo or placebo + compression for venous leg ulcers, pentoxifylline was ass'd with significantly better rates of healing than placebo or placebo + compression (Lancet 359:1550, 2002--JW)
3. Topical and systemic antibiotics (including topical silver sulfadiazine) are probably of no benefit in tx of ulcers
4. Oral flavonoids--May increase healing when used in combination with compression treatments
5. Oral sulodexide--May increase healing when used in combination with compression treatments
6. Mesoglycan--May increase healing when used in combination with compression treatments
7. "Enzyme debriding agents" are touted as improving healing by removing fibrin and pus and "clearing the way" for epithelialization, but no good evidence of efficacy
8. Growth factors (granulocyte-macrophage colony stimulating factor, platelet-derived growth factor, epidermal growth factor, fibroblast growth factor, etc.) are the subjects of ongoing clinical trials as of 1999
9. Hyperbaric oxygen-no evidence for benefit in healing of venous ulcers
10. Topical antiseptics impair wound epithelialization and are probably more harmful than helpful
11. Other tx's evaluated, w/o clear benefit: anabolic steroids (stanazole), chest-horsenut seed extract (Lancet 347:292, 1996; cited in JGIM rvw.), and hydroxyethylrutosides

4. Cultured allogenic bilayer skin replacement
   1. Shown to improve healing in one RCT as of 2005 (AFP)
5. Surgical tx

1. Few controlled or randomized trials examining clinically significant endpoints as of 2004
2. "Limited role" for surgery (JGIM rvw.), e.g. ligating incompetent perforating vv. (can be done endoscopically per BMJ rvw., limiting complications of skin incisions)
3. BMJ rvw. emphasized that in a substantial # (15-20%) of cases of CVI due to valvular reflux, the reflux is limited to the superficial vv. and thus amenable to tx w/vein stripping
4. Skin grafting and biological skin substitutes (e.g. cultured "human skin equivalent") sometimes used for ulcers
5. 500 pts with open or recently-healed leg ulcerations from CVI randomzied to compression tx alone vs. compression + surgery.  Recurrence rate 1y after randomization or healing (whichever came last) was sig. lower in surgery group (12% vs. 28%); benefit was limited to subgroup of pts whose venous reflux was limited to superficial veins and/or segments of deep veins (as opposed to total deep vein reflux) ("ESCHAR" study; Lancet 363:1854, 2004--JW)

6. Electrical stimulation may aid healing of venous insufficiency-related skin ulcers
   1. 27 pts with LE ulcer(s) x > 3mos (from DM, arterial insufficiency, or venous insufficiency) randomized to high-voltage pulsed current therapy 3x/wk x 4wks vs. sham tx.  Over 4wks, sig. greater reductions in wound size seen in active tx group (44% vs. 16%) (Phys Ther. 2003;83:17-28)

(Sources: J. Gen. Int. Med. 12:374, 1997; BMJ 314:1019, 1997; see also Morison MJ. A colour guide to the nursing management of wounds. London: Wolfe, 1992.)