Servier – Phlebolymphology

X. Foam sclerotherapy: from the
consensus document to the clinical
practice

Foam sclerotherapy in C₁ treatment
Neil Khilnani (US)
Neil Khilnani compared liquid and foam sclerotherapy and mentioned that liquid is better for small veins (>4 mm) because it dilutes and reduces the surface area of wall contact, which further dilutes the drug. According to a systematic review of more than 500 patients, the prevalence of visual disturbances is 0.09% to 2%; nearly all cases are associated with foam sclerotherapy. The frequency of visual disturbances increases after 15 mL of foam. Using CO₂ improves the results of foam sclerotherapy, possibly due to the increased stability and half-life of the foam. According to the literature, there is no difference in patient satisfaction, the average amount of injections per one sclerotherapy session, or the number of sessions needed, but the amount of matting and deep vein thrombosis is higher with foam. The European guidelines for sclerotherapy, the American Society for Dermatologic Surgery consensus for sclerotherapy, and the European Society for Vascular Surgery practice guidelines recommend using liquid sclerotherapy as the method of choice for ablation of telangiectasis and reticular varicose veins (C₁, C_1A). All guidelines consider foam acceptable and recommend lowering the concentration of foam to avoid side effects.

How sclerotherapy can replace phlebectomy in primary therapeutic attempt or in the recurrent varicose vein treatment?
Claudine Hamel-Desnos (France)
The indications for phlebectomy and sclerotherapy are the same, ie, primary or recurrent nonsaphenous veins (tributaries, accessory saphenous veins, pudendal veins, and reticular veins). The most controversial items are tributaries after thermal ablation of the trunk and the anterior accessory saphenous vein. There are many questions about the management of tributaries after thermal ablation, ie, which technique (phlebectomies or sclerotherapy), what is the timing (concomitant or delayed), and, if concomitant treatment, should it be an exhaustive/extensive treatment of all tributaries or only treatment of the largest tributaries? No study can answer all of these questions. Sometimes the tributaries disappear or shrink spontaneously after trunk ablation occurs, but there is no difference in recurrences between concomitant and delayed treatment and there is an increased number of deep vein thromboses if concomitant phlebectomies are performed. For treating the tributaries, either sclerotherapy or phlebectomies can be performed without preference. Sclerotherapy is possible for large veins that remain dilated at the end of a thermal ablation. For the elderly, the “wait and see” option is preferable and there is a growing tendency to wait 3 to 6 months for most patients. According to the personal experience of Claudine Hamel-Desnos, after thermal ablation, no phlebectomies and very few or no sclerotherapy sessions have been performed.

Anterior accessory saphenous veins can be treated successfully with sclerotherapy, with a 25% recurrence rate after 1 year and 37.5% after 2 years (2.1% for phlebectomies). For the treatment of pudendal varices, reticular veins, recurrent varicose veins, etc in daily practice, sclerotherapy is more versatile, simpler, and faster than phlebectomies, and easily repeatable if needed. In France, according the French Health Authorities in 2016, 12 million patients were treated with sclerotherapy, a few patients were treated with phlebectomies, and 8 million were treated with thermal ablation, foam, or surgery. In addition, about 1.5 million sclerotherapy procedures and only 12 000 phlebectomy (including those performed concomitantly with thermal ablation) were performed in France in 2016. Sclerotherapy can replace phlebectomies in many cases easily, but phlebectomies can only replace sclerotherapy in a few situations.

Is atrophy blanche irreversible? Effect of foam sclerotherapy
Marianne de Maeseneer (Belgium)
Localized white atrophy, which consists of circular whitish and atrophic skin areas that are surrounded by dilated capillaries, and sometimes hyperpigmentation are the signs of severe chronic venous disease, not to be confused with healed ulcer scars. Scars from healed ulcers may also exhibit atrophic skin with pigment changes, but they are distinguishable by a history of ulceration and the appearance from white atrophy, and are excluded from this definition. At the very base of white atrophy, there are microthromboses of skin capillaries with the following development of micronecroses, microvascular ischemia of avascular skin areas, and white atrophy. In an experiment, the increase in the diffusion speed of Na-fluorescein from 39.2 seconds under normal conditions to 40 minutes in case of white atrophy was mentioned. The slow diffusion of the tracer into the avascular field explains that white atrophy is a predilection site for venous ulcer formation. In addition, in the center, tcPO₂ levels were decreased to up to 0 mm Hg in the full absence of capillaries, and, in the border zone, enlarged capillaries, reduced the capillary density and the mean tcPO₂ to 24 mm Hg (vs 56 mm Hg under normal conditions). Available information in the literature about whether white atrophy is irreversible is very limited. As an example, two clinical cases on the successful regression of white atrophy were presented where a combined method was used, ie, thermal ablation (radiofrequency ablation of the great saphenous vein) plus phlebectomies of calf varicosities and ultrasound-guided foam sclerotherapy of prominent veins at the medial malleolus. White atrophy may be reversible in certain cases after extensive correction of the underlying venous problem. Ultrasound-guided foam sclerotherapy around the area of white atrophy seems to be useful. Based on preliminary experience, the effect of treatment on white atrophy is clinically obvious at the 1-year follow-up.

Foam sclerotherapy – lessons from physics and chemistry
Johann Chrisof Ragg (Germany)
According to John J. Bergan, sclerotherapy with microfoam eliminates varicose veins in all patients, with no limitations in the size, localization, or morphology of the vessel treated by this method.” However, according to Johann C. Ragg, sometimes foam sclerotherapyis the most versatile modality, but it is also the most underestimated and the most difficult modality. Constant success is dependent on education, skills, and devices more than any other method. There is no perfect sclerosant, ie, one that is complication free and 100% effective. In order to improve the treatment results, the laws of physics and chemistry must be considered. When producing foam, it should be made with a silicone-free syringe to achieve good dispersion of foam and produce small bubbles (<100 μm) for the foam to be stable for more than 1 minute. To create stable foam, it is possible to use CO2, cold preparation, and high forces. It is important to remember that only 85% of foam is left after 1 minute and only 40% is left after 5 additional minutes. There are chemical differences between the mechanisms of the two main sclerosants: sodium tetradecyl sulfate and polidocanol. Sodium tetradecyl sulfate consists of smaller molecules with a lower molecular weight, it is anionic, denatures tertiary complexes of proteins, including clotting factors. Polidocanol is nonionic and it has no effect on protein structures. Sodium tetradecyl sulfate and polidocanol have different effects on lipid membranes, target cells, and circulating proteins. Sodium tetradecyl sulfate is more potent then polidocanol by an estimated factor of 1.5 to 3. All sclerosants are deactivated binding to blood cells and blood proteins. Minimization of the target vein diameter improves the treatment results, which depends on patient positioning, manual drainage, aspiration of blood, injection of small foam quantities to obtain a primary spasm, and perivenous injection of tumescence. Decreasing the vein diameter by 50% reduces the consumption of foam by 4 times. Using systems, such as Sclerosafe (foam injection and blood aspiration via different outlets at the same time), helps decrease the contact of the sclerosant. Foam deployment during catheter withdrawal is more precise than injection. Detergents (sodium tetradecyl sulfate, polidocanol) dominate the market of sclerosants due to their excellent benefit-risk ratio, particularly for foams, and they can be used for veins of any size. There are differences between sodium tetradecyl sulfate and polidocanol concerning molecular size, ionic status, and protein attack mode, but the clinical sequelae are not yet well understood. Failures and complications of sclerotherapy are lower due to chemistry, but no physical issues and unqualified use. The “empty vein technique” is mandatory for optimal results, and the best way to obtain an empty vein depends on the anatomic situation. While chemistry acts invisibly, all physical effects can be monitored by ultrasound. Ultrasound monitoring is the first step for quality improvements.

New European guidelines on sclerotherapy – what is new?
Eberhard Rabe (Germany)
Eberhard Rabe reported on the changes that are necessary in the European guidelines on sclerotherapy, which were originally formulated by the Guideline Conference in Mainz, Germany in 2012. The indications remain the same, but additional evidence should be added concerning long-term results, alternative methods in large-diameter veins, patient-reported outcomes, and necessary reinterventions. Regarding contraindications, severe neurological complications due to previous sclerotherapy should be of concern. There are emergency indications for sclerotherapy (eg, variceal bleeding), which may be indicated in immobile patients or patients with other contraindications. Regarding relative contraindications, there are some weak points, such as severe peripheral arterial occlusive disease, which must be defined, poor general health, strong predisposition to allergies, high thromboembolic risk, which needs better clarification and evidence. A chapter on risks should be added. Concerning severe complications, an update of the frequency from recent studies is needed as well as a discussion on the International Union of Phlebology consensus proposals. Concerning diagnosis, a new discussion on the role of continuous wave Doppler in C₁ veins should be held and eventually an initial duplex investigation should be mandatory. Regarding foam production, a clear statement is needed that “sterile” gas is not mandatory. A reevaluation of concentrations in C₁ varicose veins should be carried out (a lower concentration is possible). Concerning C₁ and C₂ sclerotherapy, a reevaluation of recommendation 2B is needed. Concerning saphenous veins, differences in studies with a shorter (1 to 3 years) and a longer follow-up (5 years) should be evaluated, as well as the high recanalization rate in large-diameter veins. Regarding recommendations, EVRA trial results on ablation of the great saphenous vein in patients with an ulcer in addition to recommendation 32 should be added. Eberhard Rabe recommended adding a chapter on mechanochemical ablation and a chapter on combined treatment of surgery, thermal or nonthermal ablation, and sclerotherapy.

Tips and tricks for maintaining and injecting foam – what we should know
Andrew Bradbury (UK)
Andrew Bradbury discussed the topic of making and maintaining foam and stressed that the Tessary technique probably remains the “industry standard” method of making foam around the world. The optimal ratio is probably 1:4. Only “fresh” foam must be used because foam is rapidly deactivated by blood and nonblood proteins. Small volumes should be injected slowly to maximize both the venous spasm and the foam-endothelial contact and to minimize the foam “fly by” and side effects. Monitoring is also important to know where the foam goes. Short-stretch cohesive bandages (concentric) over wool padding (eccentric) compression for 2 to 3 days is recommended. European grade 2 compression hosiery should be worn for 2 to 3 weeks. It is also recommended to consider aspiration at 7 to 10 days or on “patient demand.” Andrew Bradbury finished by discussing the fact that many patients will develop and seek treatment for further varicose veins, but this need not be viewed as a failure.

Foam sclerotherapy – the safety issue
Lorenzo Tessari (Italy)
Lorenzo Tessari reported on a scintigraphic study about foam and lungs published in 2007. The study results showed that, after a single injection of 5 mL of foam, a very small pulmonary area could become diseased by the sclerosant. However, if repeated injections are performed over years, the authors cannot exclude progressive pulmonary arterial hypertension through sclerosis of a significant area of capillaries. Then Lorenzo Tessari presented his own study that quantitatively and qualitatively assessed the arrival and persistence of the microbubbles within the heart in sclerotherapy, observing that the elevation and immobility of the limb reduced and slowed down the flow of the bubbles toward the right heart. Another new study investigated the possibility of recognizing a pulmonary injury after foam sclerotherapy. The conclusion from this trial was that the sclerosant did not damage the lung. In a laboratory analysis, Lorenzo Tessari investigated the timing and modality of the sclerosant binding to human proteins, concluding that the sclerosant binds to blood proteins in less than 8 seconds. The high production of endothelin 1, histamine, serotonin after foam sclerotherapy might be responsible for neurovascular, respiratory, and visual disturbances. Therefore, Lorenzo Tessari recommends elevating the limb elevation 20 to 30 cm, immobility for 10 to 15 minutes, and advises against performing the Valsalva maneuver.

Saphenous vein sclerotherapy – does tumescence and blood irrigation make the difference?
Attilio Cavezzi (Italy)
Attilio Cavezzi introduced his method of sclerotherapy using a long catheter with ultrasound-guided tumescence infiltration and saphenous irrigation. He explained that, from a biochemical point of view, the higher the vein diameter and blood flow, the higher the recanalization rate. He discussed the studies by Kurosh Parsis on liquid and foam sclerosants and blood from 2007 to date. In these investigations, albumin significantly inhibited liquid or foamed sclerosants, detergent sclerosants were deactivated and consumed by circulating blood cells, and finally, the chemical action of foam in the great saphenous vein was inversely proportional to the distance from the entrance point. The in vivo and in vitro results documented that sclerosant activation by blood occurs just after a few seconds. From a mechanical point of view, there are two main negative prognostic factors in sclerotherapy outcomes: vein size and inflow from tributaries, perforators, etc. Tumescence increases transmural pressure with a reduction in vein diameter and in the size of tributary/perforators orifices with decreasing of inflow. Clinical results showed lower blood amounts for a prolonged time, lower thrombus formation, and a higher fibrotic component in the sclerothrombus. As a result, a lower foam amount is needed. By using irrigation (saline solution flushing), saphenous blood, as well as blood from inflowing tributaries/perforators/junctions can be cleared from multiple catheter points. Additionally, the sclerosant dilution can be decreased and the time of sclerosant contact with the vein wall can be increased. Clinical data confirming the “empty vein technique” was then presented. Attilio Cavezzi concluded that ultrasound-guided perisaphenous tumescence infiltration is a safe and inexpensive procedure, which enhances foam sclerotherapy possibilities and allows larger diameters to be treated with good efficacy and safety as well.