Foamed Sclerosant Ablation of Saphenous Veins and Varices

Foamed sclerosant ablation is a safe and effective treatment for saphenous veins and superficial varicosities. Thermal ablation currently competes successfully with foam for treatment of saphenous veins in the United States, and ambulatory phlebectomy competes with foam for treatment of tributary veins and localized varicosities, especially when these are large.

Sclerotherapy is the chemical ablation of abnormal veins. The modern goal of therapy is irreversible fibrotic occlusion, followed by reabsorption of the target vessel. Absence of endothelium and subendothelial edema are seen within 2 minutes of foam injection. At 15 minutes, necrosis of the vein wall into the tunica media is seen.[1]

Sclerotherapy is an old technique that was revolutionized by technologic advances.[2, 3] Foaming detergent sclerosants offered increased potency and could be visualized by means of ultrasonography (US). US guidance allowed better anatomic visualization, greater hemodynamic understanding, more precise foam targeting and delivery, and monitoring for unwanted foam passage into deep veins.[4, 5] With these advances, sclerotherapy became a competitive treatment for any type or size of vein.

Sclerotherapy’s development has been limited somewhat by the wide range of techniques available. This practice variation has yielded varying results and has made generalizing about the procedure more difficult. The differences between techniques have now begun to be tested, however, and the resulting knowledge has improved overall results. Two European Consensus Meetings on Foam Sclerotherapy[6] determined consensus opinions on the basis of the views of a panel of experienced sclerotherapy experts. European guidelines for foam sclerotherapy in chronic venous disorders were published in 2014.[7]

Foam can be used to treat almost any abnormal vein. It is most effective for veins less than 6-7 mm in diameter but can be effective for veins of almost any diameter if excellent technique is employed.[8] Sclerotherapy produces minimal procedural and postprocedural pain. It is easier to perform than most alternative strategies. Even with improved recent techniques, however, the need to repeat treatment is significant.

Currently, in the United States, endovenous thermal ablation and surgical ligation and stripping are performed more often than sclerotherapy for saphenous veins.[9, 10]  Foam sclerosants have been combined with endovenous laser ablation (EVLA).[11]

Ambulatory phlebectomy is an alternative for tributary veins or localized varicosities, especially at larger vein diameters.

Surface laser therapy can be used for telangiectasias and reticular veins, but liquid sclerotherapy is considered first-line therapy for these veins on the lower extremity.

Relative contraindications for foam sclerotherapy include the following:

• Acute thrombosis
• High risk for deep venous thrombosis (DVT), as in patients with a history of multiple DVT episodes
• Allergy to sclerosants
• History of multiple drug allergies
• Inability to ambulate
• Inability to tolerate compression, as in patients with peripheral arterial disease (PAD)

Anatomy

Grossly, the venous system is composed of venules and small and great veins, which serve to return blood from tissues to the heart. The systemic venous system brings deoxygenated blood from tissues and organs back to the right atrium of the heart, whereas the pulmonary venous system brings oxygenated blood from the pulmonary circulation back to the left atrium of the heart.

The systemic venous channels are further classified as superficial veins, deep veins, or venous sinuses. The superficial, or cutaneous, veins reside just beneath the surface of the skin. They channel blood from cutaneous tissues to deep veins via perforations in the deep fascia. Most of the deep veins share routes with the arteries, and many are enclosed in the same sheaths. Venous sinuses are present only within the skull.

For more information about the relevant anatomy, see Venous Drainage Anatomy.

Procedural planning

Evaluation of the location and severity of venous disease should be carried out, and alternative diagnoses should be considered.

In patients with evidence of chronic venous disease (eg, varicose veins, telangiectasias, extremity pain or swelling worsened by standing and improved by elevation, or skin changes around the ankle area), a careful history and physical examination are necessary. Duplex US should be performed to permit assessment of the venous anatomy and hemodynamics. Superficial, perforator, and deep venous systems are examined for obstruction or reflux. Venous reflux is retrograde blood flow of over 0.5 seconds in the saphenous system.

The symptoms of chronic venous disease all have a large differential diagnosis. Because varicose veins (see the image below) produce symptoms ranging from none to severe, alternative explanations for patient symptoms should be entertained. Three related venous diseases that result in patient presentation with symptomatic varicose veins are iliac vein obstruction, pelvic congestion syndrome (PCS), and vascular malformation.

Iliac vein obstruction

Iliac vein obstruction can be caused by thrombosis or by anatomic compression of the iliac vein (usually by the iliac artery). The diagnosis is generally missed on standard lower-extremity duplex US. It should be considered in patients who have symptoms and signs that are out of proportion to the reflux seen. Patients with a history of thrombosis or duplex signs indicative of prior thrombosis are also to be at higher risk. Exercise claudication (pain with exercise) is a more specific but less sensitive symptom.

Intravascular US, magnetic resonance venography (MRV), computed tomographic venography (CTV), and standard venography are all used for diagnosis, depending on the practitioner's preference. Stent placement is often effective in relieving patient symptoms.

Pelvic congestion syndrome

Some extremity varices originate in the pelvis. PCS can produce varices at the vulva, the proximal medial thigh, the buttocks, and the perianal area. The source is typically in the ovarian or internal iliac vein systems. The pathophysiology is analogous to that of male varicocele. Pelvic pain that is worse with standing or after intercourse suggests PCS. Patients may have a history of vulvar varicosities during an earlier pregnancy. They may also have urinary frequency or irritable bowel syndrome.

US, standard venography, MRV, and CTV are all used for diagnosis, depending on practitioner preference. Typical treatment is ablation with coils with or without sclerotherapy.

Vascular malformation

Patients with evidence of a vascular malformation, such as lesions manifesting early (often at birth or puberty) or abnormal anatomy or blood flow on US, should undergo further testing, usually with magnetic resonance angiography (MRA), to determine whether the abnormality is a high-flow malformation or a low-flow malformation.[12]

Such malformations should be treated by a team comprising multiple disciplines, often including phlebology, vascular surgery, plastic surgery, dermatology, and orthopedic surgery. Low-flow venous malformations can often be treated successfully with foam sclerotherapy by practitioners experienced in handling these abnormalities.[13]

Complication prevention

Compression after foam injection improves the efficacy of the procedure and reduces the risk of DVT and superficial phlebitis. Some research suggests that there is a benefit to continuing postsclerotherapy compression for as long as 6 weeks, but these data must be balanced against the likelihood that many patients will be reluctant to comply with physician instructions for long-term compression.

The authors typically use a 20-30 mm Hg compression hose that covers the area treated (either knee high or thigh high) day and night for 2 weeks. Large varicosities are initially (ie, for the first 48 hours) compressed with a localized compression dressing of cotton gauze and self-adherent elastic wrap in the hope of reducing the risk of trapped blood.

In a randomized, controlled trial, polidocanol microfoam to be proved noninferior to nonspecific surgical therapy for treatment of saphenous vein reflux.[14]

In a meta-analysis, US-determined pooled saphenous ablation rates at 3 years were 77% for foam, 78% for stripping, 84% for radiofrequency ablation (RFA), and 94% for laser ablation.[15]

In one study, sclerofoam injection improved ulcer healing rates in patients with severe chronic venous insufficiency.[16]

Thermal ablation (ie, laser ablation or RFA) is currently recommended over foamed sclerosant ablation for saphenous veins.[17, 18, 19]

Neto et al evaluated the impact of US-guided great saphenous vein (GSV) foam sclerotherapy on quality of life and photoplethysmography findings for 29 legs in patients with chronic venous insufficiency who were followed for 1 year.[20]  They noted statistically significant improvements in quality-of-life and symptom scores and in venous filling time as measured by photoplethysmography, along with a reduction in GSV diameter, at 45, 180, and 360 days after treatment. Patient satisfaction levels were high.

In a randomized controlled trial (RCT) that included 50 patients with varicose veins, edema, and GSV incompetence (diameter 6-10 mm), Dos Santos et al evaluated the efficacy of catheter-directed foam sclerotherapy with tumescence of the GSV (group B) against that of US-guided foam sclerotherapy (group A).[21]  At 28 days, the full success rate for the treated GSV was 36% in group A and 80% in group B; 14 patients in group A and 3 in group B required retreatment sessions. At 6 and 12 months, success rates did not differ significantly. Complication rates were similar in the two groups. Quality of life improved in both.

In systematic review and network meta-analysis (51 articles; 36 RCTs; 7576 limbs) aimed at determining the most effective intervention for treating saphenous vein insufficiency, Gasior et al compared foam sclerotherapy, RFA, EVLA, mechanochemical ablation (MOCA), cyanoacrylate glue (CAE) closure, and high ligation and stripping (HLS).[22]  Although all of the interventions yielded improvements in the Venous Clinical Severity Score (VCSS), foam sclerotherapy was associated with the highest risk of recurrence. 

For the purposes of patient satisfaction, it is good practice to manage patient expectations and inform patients that any specific vein injected may later require retreatment.

Patient-centered information is available from the American College of Phlebology and the American Venous Forum.

Abnormal veins are usually treated in a specific order: superficial veins first, perforator veins next, and deep veins last. Superficial vein therapies have good efficacy and minimal side effects. When symptomatic reflux is present, the superficial veins are usually treated in the following order: saphenous veins, tributary veins, and localized veins.

Perforator vein treatments are technically efficacious but are of uncertain benefit to the patient in many cases. Deep vein treatments carry a higher risk, have more variable success rates, and are usually performed only in patients with particularly severe symptoms and only at specialized centers.

Duplex ultrasonography (US) should be used in the treatment of saphenous veins, perforator veins, veins near deep-superficial junctions, long veins, or large-diameter veins. If there is any doubt, this imaging modality is not discouraged during any use of foam. Wire-guided catheter access is generally used for saphenous veins and other longer veins.

Materials required for foam sclerotherapy include the following:

• Two 5-mL syringes
• Liquid sclerosant
• Three-way stopcock valve
• Butterfly needle, 27 gauge
• Isopropanol wipes
• 4 × 4 gauze pads
• Tape
• Compression stocking

Both sodium tetradecyl sulfate (STS) and polidocanol are approved by the US Food and Drug Administration (FDA) for use as a liquid sclerosant. In general, STS is twice as potent as polidocanol at the same concentration; thus, a physician could achieve similar effects with STS 0.5% and polidocanol 1.0%. By using varying concentrations and different foaming techniques, foam can be used to treat almost any type of vein.

STS and polidocanol at a concentration of 1% or higher are often used for saphenous veins. Local varicosities are usually treated with STS 0.25-1.0% or polidocanol 0.5-1.0%, depending on vessel diameter and treatment response. Some evidence, however, indicates that higher sclerosant concentrations may not always be more effective than lower concentrations, as had been previously assumed.[23]

No anesthesia is usually required for foamed sclerosant ablation. Patient positioning is important. The reverse Trendelenburg position facilitates venous access by increasing vein diameter.

In patients whose veins collapse with extremity elevation, veins can be accessed in a dependent position via a 27-gauge butterfly needle with normal saline, with the butterfly then taped in place. Subsequent extremity elevation decreases vein diameter, making foam administration more effective and less risky. Tumescent anesthesia can potentially be used to decrease vein diameter. Elevating the treated extremity 45º also theoretically limits the passage of bubbles into the systemic circulation.

In well-selected patients, current venous treatment techniques improve quality of life by decreasing pain and swelling and reducing ulcer recurrence risk; however, they are not curative. After successful treatment, patients can be followed annually, or more frequently if the condition recurs.

The Tessari method is the one most often used to foam detergent sclerosants.[24] A syringe of liquid sclerosant is connected to a syringe of air by a three-way stopcock valve. The stopcock valve is turned 30-45º from its flat position to make the foamed bubbles as small as possible while still allowing the two syringes to mix. The syringes are mixed vigorously back and forth at least 20 times.

The ratio of gas volume to liquid sclerosant volume is a significant variable. Dry foams (eg, 6 mL gas to 1 mL liquid) increase blood displacement distance and can decrease bubble size in comparison with wet foams (eg, 3 mL gas to 1 mL liquid). A 4:1 gas-to-liquid ratio is the consensus recommendation. The size of the sclerofoam bubbles and their stability (ie, how long they remain small) may be key variables in decreasing systemic symptoms.

With the above technique (ie, 4:1 gas-to-liquid ratio), the foam should be used within 60-90 seconds. Other techniques that are believed to reduce bubble size, enhance bubble stability, or both include using a mixture of carbon dioxide and oxygen (instead of the primarily nitrogen-oxygen mixture characteristic of air), using low-silicone-content syringes, using larger-bore needles, and using bubble-size filters.[25]

A 27-gauge butterfly needle can be used with a syringe for treatment of localized varicosities. The appearance of blood in the butterfly tubing indicates successful cannulation. The sclerosant is then injected into the target vein, and the vessel blanches, indicating the replacement of blood with sclerosant. The injection is halted immediately when the target vein is filled, with injection volume per site usually less than 0.5 mL. The injection is halted if any bleb appears. Magnification is useful in treating smaller varicosities. Keeping the needle flat to the skin surface and aiming very superficially also helps.

For larger veins or veins near deep junctions, ultrasonographic (US) guidance is commonly used to guide needle and catheter placement into the target vein and to monitor for foam migration into deep veins. In general, the catheter should be placed more than 10 cm from any major deep-superficial junctions (eg, the saphenofemoral junction).

After US-guided venous access, the patient can be placed in the Trendelenburg position. The sclerofoam is mixed, then injected into the target vein under US guidance; it will be easily visible on US as hyperdense bubbles displacing hypodense blood. To prevent foam passage into the deep system, foam placement should be stopped well short of (ie, at least 5 cm from) any deep saphenous junctions. The current consensus recommendation is to limit the total volume of foam injected to 2-4 mL per site and 10 mL per session.

In a randomized controlled trial assessing endovenous laser ablation (EVLA) combined with either direct-puncture US-guided foam sclerotherapy (UGFS) or transluminal (ie, through the access sheath) foam sclerotherapy (TLFS) in chronic venous disease patients with GSV reflux, Watanabe et al found that TLFS plus EVLA, as compared with UGFS plus EVLA, was safe and feasible, improved the 1-year venous clinical severity score (VCSS), and reduced the need for additional second-stage interventions.[26]

After sclerofoam injection, the extremity is kept with elevated for another 5-10 minutes to allow the foam to liquefy as much as possible, to dilute the sclerosant, and to prevent early proximal foam movement. If no symptoms develop, compression may then be applied, and the patient may be allowed to walk.

Clinical practice guidelines published in 2019 by the American Venous Forum, the Society for Vascular Surgery, the American College of Phlebology, the Society for Vascular Medicine, and the International Union of Phlebology suggested that compression therapy be initiated immediately after treatment of superficial veins with sclerotherapy in order to improve outcomes.[27]  With respect to the duration of such therapy, in the absence of convincing evidence, the guidelines recommended that it be determined on the basis of best clinical judgment.

Thrombotic complications include deep venous thrombosis (DVT) and superficial thrombophlebitis. The risk of DVT is low, well under 1% for most veins,[28] but may be higher in large-diameter veins. One study showed an increased risk of DVT in veins greater than 5 mm diameter and for total sclerofoam volumes over 10 mL.[29] Postsclerotherapy US is usually unnecessary except in the case of a higher-risk patient (eg, a less mobile person) or a higher-risk vein (eg, a larger vein or one near a major junction).

Treatment of DVT includes anticoagulation, close US surveillance (eg, repeat US every 2-3 days) for clot improvement and resolution, and compression stockings. Superficial thrombophlebitis can usually be treated with microphlebectomy or compression.

Superficial phlebitis at the site of foam injection is also called trapped blood or intravascular hematoma. It presents as a hard, tender vein in a recently treated area. It should be drained at around 2-3 weeks with a large-caliber (18-gauge) needle and pressure to reduce pain and lower the risk of hyperpigmentation.

Hyperpigmentation occurs in about 20% of sessions. It is a brown discoloration that occurs at injected sites as a consequence of hemosiderin deposition. Most hyperpigmentation resolves spontaneously within 1 year. For patients whose hyperpigmentation does not resolve within a year, surface laser or intense pulsed-light therapy may be considered. Topical bleaching agents are sometimes used as well.

Matting is the development of tiny red vessels around the site of an injected vein. It is probably a neovascularization phenomenon. Matting occurs in around 15-20% of sessions and usually resolves within 1 year. Sclerotherapy or surface laser can be considered for persistent matting.

On rare occasions, systemic symptoms occur after foam sclerotherapy. Visual disturbances similar to a migraine aura and migraine headaches are sometimes noted. Chest tightness and dry cough have been described. Foam therapy has been associated with very rare episodes of cerebrovascular accident (CVA) and transient ischemic attack (TIA). These systemic symptoms may be caused by gas emboli, which have been seen on transthoracic echocardiography (TTE) and transcranial Doppler US after foam injection.[30]

If, as is believed to be the case, some of these symptoms (especially CVA and TIA) are caused by gas-bubble occlusion of small arterioles, injecting smaller bubbles and using carbon dioxide (which diffuses more rapidly than nitrogen) may reduce the risk.

Other technique modifications that have been suggested for reducing risk include limiting the total foam volume to under 10 mL, elevating the extremity around 45º, keeping the patient immobile for 5-10 minutes after injection to allow the foam to turn into liquid, and occluding the saphenofemoral junction with direct pressure. The sclerosant itself has probably been "scrubbed off" and replaced with serum by the time it reaches a distant systemic target.[31]

Allergic reactions and anaphylaxis are rare complications with current sclerosants. Treatment of these complications depends on their severity but may include oxygen, intravenous fluids, epinephrine, antihistamines, and corticosteroids.

Arterial or arteriolar occlusion is a very rare complication that results in tissue necrosis. US needle guidance for veins not visible on the skin surface should prevent this complication. High-risk areas include the groin, the popliteal fossa, and the ankle. Skin necrosis can result from extravasation of sclerosant at higher concentrations, causing direct injury or inadvertent injection into skin arterioles. Routine wound care produces acceptable results.

Abnormal veins may recur either at injected sites or at new sites.[32] No currently available treatments cure chronic venous disease. Recurrence rates can be reduced by employing excellent technique.