Management of chronic venous disease of the lower limb

Leo K M Chiu 趙啟明, Maket W C Wong 王慧聰

HK Pract 2007;29:304-310

Summary

Pathophysiology and updated information for clinical care of patients with lower limb chronic venous disease were reviewed. It is incumbent upon the clinician to differentiate signs and symptoms referable to chronic venous disease from other lower limb disorders. The importance of duplex scan in the management of chronic venous disease was stressed. Mild disease is treated conservatively with postural advice, calf muscle exercise, compression stocking and phlebotropic drugs. In advanced disease open surgery, endovenous ablation and microfoam sclerotherapy are the options. However, prospective controlled study to compare different modalities of treatment is not yet available. Microfoam sclerotherapy holds great potential and is the least invasive but most versatile and economical technique. Even in the best hands, there remains a failure rate associated with various modalities of treatment. Establishing realistic expectations and documentation of the extent of disease before and after treatment are important aspects of patient care.

摘要

本文回顧下肢靜脈病的病理生理及現行治療方案。強調此病與其它下肢疾病的臨床症狀、體症的鑑別， 以及應用「超聲多普勒掃描」的重要性。輕症病例多採用保守療法，包括─避免久立，抬高患肢，多作小腿運動， 穿著壓力襪及口服藥物等。切開手術、靜脈腔內剝離術及泡沫硬化劑注射等則適用於嚴重病例。 目前以上療法尚未有前瞻性的臨床比較測試資料。作者認為泡沫硬化劑注射療法是創傷最少、應用面最廣，最經濟的方法， 具有顯著潛在優勢。即使是最好技術的醫生，運用各種治療方法時都有失敗的機會，所以對療效要有合理實際期望，治療前後對病情做詳細紀錄也極為重要。

Introduction

Vast changes have occurred in the treatment of venous disorders of the lower limb. This article aims to provide updated information for clinical care of patients with lower limb venous disease. The reported prevalence of venous disease varies greatly because of differences in the criteria of definition and the methods of evaluation. Varicose vein is a descriptive term for dilated, elongated tortuous superficial vein often involving the two saphenous systems. Together with dilated cutaneous vein and telangiectasia, varicose vein is the commonest sign of chronic venous disease. The term chronic venous insufficiency (CVI) is reserved for the presence of irreversible skin damage in the lower limb as a result of sustained venous hypertension. Skin damages include hyperpigmentation, lipodermatosclerosis, atrophic blanche, healed or active ulcer. Varicose vein is only one of the contributing factors for venous hypertension and if severe may cause skin changes of chronic venous insufficiency.

Pathophysiology of chronic venous disease

Cutaneous tissue is under constant stress of a summation of hydrostatic and hydrodynamic forces. The resultant ambulatory venous hypertension set off a cascade of pathological events and microcirculatory dysfunction that initiate skin changes. Hydrostatic force is due to the weight of the blood column from the right atrium transmitted through the anatomically valveless vena cava and iliac veins then further down the femoral vein and calf vein if the valves inside these deep veins are incompetent. The more common path for the transmission of hydrostatic pressure is through the incompetent sapheno-femoral junction or the sapheno-popliteal junction and the two saphenous systems if valves inside these superficial veins are incompetent. A burst of hydrodynamic pressure is generated by contraction of the calf muscles and is transmitted through failed valves in the perforating veins to the subcutaneous tissue.

By and large incompetence of the valves causing reflux account for 90% of the cases of venous hypertension; the remaining 10% is secondary to outflow obstruction. Increased intra-abdominal pressure in morbid obesity, deep vein thrombosis (DVT) or extrinsic compression of the veins, are usual causes of venous outflow obstruction. Reflux exists in isolation or in combination. Prevalence of reflux is estimated to be 90% in superficial veins, compared to 30% in deep vein and 20% in perforator vein. Isolated deep vein reflux is not common, accounting for less than 10% of patients with venous ulcers. Most limbs in less severe cases have reflux limited to the superficial system. Those with more advanced disease have a complex reflux pattern involving various combination of the superficial, deep or perforator vein.¹

In addition to reflux and outflow obstruction, failure of the calf muscles to propel blood back to the heart also contributes to venous hypertension. Proper function of the calf muscle pump depends on muscle contraction with functioning one-way valve inside the deep vein. Hence prolonged standing, ankylosis of the ankle joint, myopathy or incompetence of valves inside the deep veins are causes of venous pump failure leading to venous hypertension often found in debilitated patient.

Assessment of patient with chronic venous disease

Heaviness in the legs, distending pain, sensation of swelling, night cramp, tiredness, itching, hyperpigmentation and dermatitis around gaiter area are common manifestations of chronic venous disease. However, none is specific for chronic venous disease and is not pathognomonic. Further characterization of the symptoms helps to increase the diagnostic accuracy. Symptoms related to venous disease often occur after prolonged standing, at the end of the day. The symptoms abate in the morning, by supine position or with the legs elevated. Venous symptoms usually exacerbated by warmth and regress with cold temperature. Swelling and pain referable to joints, even in the presence of varicosities are degenerative joint disease until proven otherwise.

The distribution and severity of skin changes, the site of reflux, function of the calf muscle pump and the mobility of the ankle joint are evaluated. Ulceration is often the reason for referral. However, not all wounds around the medial malleolus are venous ulcers. Concomitant signs and symptoms of chronic venous disease are key supportive evidence of venous origin of the ulcer. Failure to epithelialise is the hallmark of chronic venous ulcer. As distinct from ischaemic ulcer there are signs of healing with the presence of granulating tissue and serous discharge. Pedal pulses including the dorsalis pedis and posterior tibial pulses are appraised to detect any ischaemic component of the ulceration and as a precaution against the use of compression therapy in limb with compromised perfusion.

Further investigation is necessary when symptoms and signs do not concur or invasive treatment is planned. Duplex ultrasound is most useful for the evaluation of venous obstruction and reflux. The entire venous system of the lower extremity should be evaluated, as associated reflux in the deep and perforator systems might adversely affect the results of intervention on the saphenous system. The presence of accessory saphenous vein, which is a common cause of recurrence, can be detected by duplex scan. Duplex scan is also invaluable in selecting modality of intervention and assessing recurrence.

Treatment of chronic venous disease

Many patients need to be reassured as there are widespread misconceptions that varicose vein is associated with DVT, heart disease and amputation.² The chance of any individual with varicose veins developing skin damage is uncertain and was estimated to be between 3% and 6%.^3,4 In the Basle study, the risk of developing ulcers during an 11 years follow-up period was 0.8% for those with mild varicosities but 20% for those with severe varicose veins.⁵

Conservative management

Elevation, calf exercise and compression

Venous congestion occurs when the feet are dependent and at rest for a prolonged period. Raising the legs above the level of the heart by 10 to 12 inches for 15-30 minutes reduces symptom and oedema. This may be impractical for most but the badly symptomatic patients will find this useful. Ankle flexion activates the calf muscle pump and expels blood from the leg veins. Wearing of high heels prevents calf muscle contraction and should be avoided. Patients with chronic venous disease are encouraged to flex the ankle 5-10 times every few minutes, and if feasible walk for 1-2 minutes every hour.

Compression reduces the diameter of the veins, thereby increases flow velocity and reduces reflux. It also reduces filtration of fluid out of the intravascular space. Compression alleviates symptoms and retards the progression of the disease. Compression generated by the elastic stocking is gradual to create a gradient with highest pressure at the ankle and progressively reduced up the groin. Poorly fitted stocking may be counter-productive and act like a tourniquet and impedes venous outflow. Thus it is important that limbs should be measured and fit according to charts provided by the manufacturer. Trendelenburg position through-out the night is helpful for patients with significant oedema. Once the size of the elevated limb is maximally reduced, it should be measured and fit for a compression stocking to be worn during the day. Calf height stocking is often worn, as this is where the calf muscle pump needs support and compliance of calf height stocking is much better. Graduated compression stockings are intended for ambulation. TED stockings (Thrombo-Embolic Deterrent) are not appropriate for venous disease but for bedridden patients to prevent DVT. In Hong Kong with the sultry summer, many patients find compression hosiery unacceptable, and it tends to be used only by those highly motivated. Patient with symptomatic improvement after compression therapy often benefits from intervention designed to correct venous hypertension. Short-term compression stocking may be used as a therapeutic trial on patient with equivocal symptoms. I often prescribe class 2 stocking which generates a pressure of 30-40 mmHg at the ankle for patients with symptomatic varicose vein, chronic venous insufficiency or for short-term use after procedures for varicose vein.

Phlebotropic agents

It is not easy to confirm whether symptoms are related to venous disease. Evaluation of the severity of symptoms and the benefit of phlebotropic drugs is even more difficult because many confounding factors exist. Studies have demonstrated the efficacy of phlebotropic drugs on oedema.^6,7 Phlebotropic drugs may also decrease symptoms such as heaviness of the legs, pain, sensation of swelling and night cramps. Phlebotropic drugs represent first-line treatment for mild disease where invasive therapy does not warrant. In more advanced disease stages with skin changes, phlebotropic drugs have not been demonstrated to be beneficial.

Invasive procedures to ameliorate venous hypertension

Operations for varicose vein are one of the most commonly undertaken procedures. A wide range of symptoms is associated with varicose vein, but may not be directly attributable to the varicose vein.⁸ The extent of the visible veins is also not correlated with the severity of symptom experienced.⁹ Furthermore, after treatment of the primary site of reflux some patients develop insufficiency in other veins. Consequently, procedures for varicose vein are source of dissatisfaction and often reason for litigation. It is important to keep in mind that superficial venous disease is a chronic and progressive disorder that multiple sessions of treatment may be necessary to control the problem.

Identification of the site of valvular incompetence to abolish reflux is a prerequisite for all modalities of treatment. Removal or obliteration of the refluxing superficial system, disconnection of the incompetent perforator vein from the superficial system, valvuloplasty of the deep vein, and transposition of competent valve if valves inside the deep system are destroyed are procedures tailored to eliminate the transmission of abnormally high venous pressure.

Procedures to eliminate the proximal great saphenous vein

As 80% of reflux stem from incompetence of the saphenous system, various methods are developed to eliminate the saphenous system: remove by stripping, fibrotic obliteration by injection of foam sclerosant, ablating the vein wall using thermal energy delivered by radiofrequency probe or laser fiber. In our unit, various modalities of treatment for all but the very extensive bilateral diseases are performed under local anaesthesia. Many patients are discharged in full ambulation within hours after the procedure.

Foam sclerotherapy

The goal of sclerotherapy, is to occlude abnormal veins that carry retrograde flow without damaging the connected normal vessels that carry antegrade flow, and of most significance, the deep vein. Adjacent soft tissue injury and skin necrosis should also be avoided.

Tensio-active sclerosant such as sodium tetradecyl sulphate or polidocanol causes cell death by a mechanism known as "Protein theft denaturation". These detergent molecules dissolve away protein from the cell membrane and cause delayed death of the endothelial cell with exposure of the subendothelial layers. Compression dressing is then applied to appose the vein wall and encourage obliteration by inflammation with subsequent fibrosis. Multiple sessions are often necessary for complete obliteration. Contraindications to foam sclerotherapy are known allergy to sclerosant, thrombophilia and patent foramen ovale. Microfoam sclerotherapy should also be avoided in pregnancy, non-ambulatory status and concomitant lower limb ischaemia.

Liquid sclerosant is diluted as it diffuses from the site of injection and the sclerosing effect decreases as distance from site of injection increases. To overcome this problem, the sclerosant is applied in the form of microfoam which is prepared by mixing tensio-active sclerosant vigorously with air. Microfoam displaces intravenous blood and prevents progressive dilution. Moreover, as foam is mostly air it causes negligible damage if it is extravasated. Sclerosant in the state of microfoam has an enhanced sclerosing effect with a decreased side effect.

Access is gained by duplex guided percutaneous puncture. Catheter directed microfoam sclerotherapy allows foamed sclerosant to reach a long distance along the saphenous vein and the associated branches through a single puncture. Microfoam can also reach site that is inaccessible to surgical intervention. This includes the small interconnecting collaterals that often remain open after surgical closure of the perforator vein.

The reported primary venous occlusion rates after foam sclerotherapy is about 80%. The results approach to 95% after 3 sessions in cases of initial failure.¹⁰ The 5-years mid-term effectiveness reported by Cabrera was 86% after 2 injections.¹¹ Furthermore, treating recurrence by repeated microfoam injection is as simple and is at least as effective as primary injection. Major complications of microfoam sclerotherapy are allergic reaction, skin necroses and DVT. Fortunately, common complications such as thrombophlebitis and hyperpigmentation are predominantly minor and resolve spontaneously. Limiting the maximum volume of microfoam injection to less than 15ml helps to minimize the potential complication of micro-air embolism. Side effects including dry cough, transient ischaemic attacks and scotomas are rarely reported. Our experience with sodium tetradecyl sulphate microfoam sclerotherapy is also affirmative. The satisfactory outcomes achieved along with the low complication rate observed have verified that microfoam sclerotherapy is feasible. Common complication we encountered is trapped thrombus in large varices that required needle evacuation and caused local pain and cutaneous staining. Abrasion due to traction injury caused by the compression dressing is another adverse event.

Microfoam sclerotherapy holds great potential. Equipment used is basic, minimal local anaesthesia is required and the procedure can be office-based. It is the most versatile method and can be used to treat nearly all varicose vein, including truncal,¹² tributaries or perforator incompetence.¹³ Compared with other endovenous procedures, microfoam can flow along the vein and hence tortuosity is not a limiting factor. Outpatient foam sclerotherapy is likely to prevail as it is minimally invasive and can be repeated whenever necessary. Controlled trials on a standardised microfoam sclerotherapy are now required to confirm that microfoam is the preferred treatment. It is very likely that it may replace some of the currently used procedure.

Open surgery

Open surgery involves division of all the tributaries and transection of the junction between the superficial and deep venous system using a 3cm groin crease incision just medial to the femoral pulse. These together with retrograde perforate invaginate stripping of the saphenous trunk to just below the level of the knee through a 3mm stab wound disconnect the saphenous vein from the superficial tributaries and perforator veins.^14,15 Previously the procedures were performed under general or regional anaesthesia. We started to use tumescent anaesthesia in old and feeble patients with chronic venous ulcer. Subsequently tumescent anaesthesia was extended to young and low risk patients and conferred high patient satisfaction. Apart from avoiding unnecessary general or regional anaesthesia, tumescent anaesthesia also serves to exsanguinate the saphenous trunk thus decreases bleeding and subsequent haematoma formation. Patients can be discharged from hospital immediately after the procedure. At present we prefer to perform the procedure under tumescent anaesthesia.

The recurrence rate following saphenofemoral disconnection and saphenous vein stripping was reported to be between 20% and 28% at five years.^16,17 Saphenofemoral disconnection without stripping cannot control reflux and is ineffective in reducing the hydrostatic forces along the saphenous vein distal to the ligation.¹⁸ In comparison, saphenofemoral disconnection alone has a five-year recurrence rate that is about double that of disconnection and stripping.^16,19 Randomised trials showed that routine stripping of incompetent great saphenous vein to just below knee level improved results and reduced the rate of re-operation.^18,20,21 Significantly more patients in the attempted but incompletely stripped group underwent surgery for recurrent disease.²² Accessory saphenous vein existed in about 8% of patient and should also be stripped to prevent recurrence.²³ The overall rate of minor complications including wound haematoma, cellulitis and minor neurological symptoms was about 17%, whereas major complications such as femoral vein or arterial injuries occurred in 0.0017% to 0.3% of patients.²⁴ The reported prevalence of symptoms related to saphenous nerve injury after stripping to knee level was about 7%.^25,26 The risk of clinically diagnosed DVT after varicose vein surgery was estimated to be between 0.15% and 0.5%.^27-29

Endovenous procedures

Groin dissection to ligate the junction may be the cause of neovascularisation and subsequent recurrence.^30,31 The proximal saphenous trunk can be destroyed and the junction occluded without groin dissection by endovenous procedures. The short- and medium-term results of endovenous radiofrequency ablation (RFA) and endovenous laser therapy (EVLT) are excellent with an occlusion rate for RFA of almost 90% after 5 years and about 95% for EVLT after 2 years. Both procedures are performed using local anaesthetic. Access is by percutaneous puncture under ultrasound guidance. Using the Seldenger technique, an introducer sheath is advanced into the vein. The RFA probe or Laser fibre is inserted through the sheath to just distal to the sapheno-femoral junction. A large volume of dilute anaesthetic solutions is injected into the peri-venous space. Apart from providing a large anaesthetized area, the surrounding cuff of fluid also serve as a protective barrier to prevent heat damage of non-target tissues, including skin, nerves, arteries or the deep veins. Laser or radiofrequency energy is then delivered and the probe withdrawn gradually causing wall destruction on the way out. Following endovenous ablation, compression stocking is applied and the patient is immediately ambulatory.

Endovenous Radiofrequency Ablation (RFA)

The initial occlusion rate after RFA is nearly 100%. Multicentre prospective registry of 1222 limbs after RFA had a 5-year occlusion rate of 87.2%, and a 5-year absence of reflux rate of 83.8%. Symptomatic improvement was seen in 85-94% of limbs with anatomical success. Complications of RFA included focal paresthesia of 2% at 4 years. DVT and skin burn were uncommon.³² We have no experience with RFA but the following conditions are often considered as unsuitable for RFA. Patients with pacemaker insertion or tortuous vein that prevents advancement of the catheter. The need for direct contact of the prongs with the vein wall limits the treatable size of vein to 12mm.

RFA compared with open surgery

A small prospective randomised trial comparing 45 limbs after RFA with 40 limbs after ligation and stripping provided evidence that the 2-year results of RFA were at least equal to those after high ligation and stripping.³³ However, outcome of longer duration is not available and the size of the study precludes generalization of its finding.

Endovenous laser therapy

Prospective controlled study on endovenous laser therapy (EVLT) is not yet available. Although effectiveness of a new intervention cannot be properly assessed without comparative study, feasibility and safety can be gauged by follow-up data on prospective case series. Notwithstanding that most published series were of short-term results, only a few studies had more than 1 year of follow-up. Occlusion of the saphenous vein was achieved in 88 to 100% of the limbs in the published series.^34-36 However, with longer follow-up recanalisation and recurrence of reflux may occur. The experiences of the largest single centre of 1000 EVLT with 460 limbs followed up for more than 2 years had 99% (457/460) of treated veins remaining occluded.³⁷ Pain, ecchymosis, induration and phlebitis were common self-limiting adverse events associated with EVLT. Deep vein thrombosis was documented in only one patient. Our initial experience on 10 cases of EVLT was very encouraging with 100% of initial success. One patient had extension of thrombus to just proximal to the saphenofemoral junction with no further extension into the deep vein. Bruises, thrombophlebitis, slight tenderness and tightness along the treated vein lasting 3 days to 2 weeks were often encountered. There has been no major complication, skin burn nor paresthesia. Although follow-up period is still short, optimism for these procedures is rising. Patient acceptance is overwhelmingly better than with stripping.

EVLT compared with RFA

It remains uncertain which of the endovenous therapies is the best, as there are few reports comparing these treatments and none are randomised and prospective. The disadvantage of RFA is the slow pull-back rate. While bruising and moderate postoperative pain are more frequent after EVLT, nerve injury is more frequent after RFA. Severe complications are rare with both methods. Deep venous thrombosis seems to be more frequent after RFA than after EVLT. In most of the reported cases DVT occurred as propagation of the thrombus from the saphenous vein into the femoral vein. Most of these cases resolved after anticoagulation treatment.

Branch varicosity

Although branch varicosity may become less obvious after the main trunk is eliminated, it is often the main concern of the patient and is preferably removed.

Microphlebectomy

This is using phlebectomy hook to fish out and avulse varicose branches through multiple 2mm stab wounds.

Transilluminate powered phlebectomy (TriVex)

The TriVex vein resector consists of a rotating inner cannula encased in a stationary outer sheath with a small window at the tip. Vein is suctioned into the cannula through the window and subsequently morcellated then aspirated through the cannula. While this may reduce operation time and the number of incisions for large area of varicosity, the cosmetic results and the risk of nerve injury may not be on par with microphlebectomy.

Foam sclerotherapy

The least invasive alternative is microfoam injection to induce fibrotic obliteration of the branch varicosity.

Conclusion

Incompetent valve, outflow obstruction, and calf muscle pump failure are the causes of chronic venous disease. Balancing the extent and results of various invasive interventions of the deep venous system, conservative management is the present mode of management for deep vein problem. In treating reflux of the saphenous system, ligation of the junction and stripping of the saphenous trunk is still the "gold standard". In view of the high long- term recurrence rate, open surgery may only be the old standard that other new endovenous ablation techniques have to compare with and improve on. Initially treated with skepticism, optimism for endovenous ablation therapy is rising. Although patient acceptance of endovenous procedures is overwhelming, surgeons should resist the temptation to change their practice before long-term results from large prospective randomised comparative studies are available to help to select and tailor treatment to individual needs of the patient.

Open surgery or endovenous ablation are effective but are only partial treatments. Calf varicosities have to be treated separately with hook phlebectomy or sclerotherapy. Foam sclerotherapy is the least invasive but most versatile and economical technique to obliterate the saphenous trunk, perforating vein and branch varicosities.

Even in the best hands, there remains a failure rate associated with various modalities of treatment. Unrealistic expectations are often the cause of dissatisfaction and may even be the catalyst in this fertile field for litigation. Documentation of the extent of disease with pre-treatment photographs is helpful reminder to the physician and patient about progress.

Key messages

1. Varicose vein is only one of the contributing factors for venous hypertension and if severe may cause the skin changes of chronic venous insufficiency.
2. Venous reflux accounts for 90% of the cases of venous hypertension. It exists in isolated state or combined state involving the deep, superficial and perforator system. The remaining 10% is secondary to outflow obstruction.
3. Mild disease is treated conservatively with postural advice, calf muscle exercise, compression stocking and phlebotropic drugs.
4. In advanced disease open surgery, endovenous ablation and microfoam sclerotherapy are the options. However, calf varicosities have to be treated separately.
5. Establishing realistic expectations and documentation of the extent of disease are helpful reminders to the physician and patient about progress.