XVI. Venous leg ulcer forum
XVI. Venous leg ulcer forum
Venous leg ulcer treatment – do we really have consensus? Summary of the existing guidelines
Giovanni Mosti (Italy)
Giovanni Mosti started his talk by citing the Evidence-based clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum, an intersocietal document endorsed by the American College of Phlebology and the Union Internationale de Phlébologie. He illustrated all the steps related to the management of venous leg ulcers. Ulcer cleansing is mandatory at each dressing change with a neutral, nonirritating, nontoxic solution. The debridement is mandatory in the initial inflammatory or infected stage. Ulcer dressings may be helpful even though they have not been proven to increase the healing rate of small ulcers. Antiseptics and systemic antibiotics have to be used only in infected ulcers. The peri-wound area should be maintained clean and hydrated. Compression therapy exerting strong pressure is mandatory. Bones and tendon prominences have to be protected. Compression pressure should be reduced when an arterial involvement coexists and is recommended providing that ankle-brachial index is >0.5 and perfusion pressure is >60 mm Hg. In addition, many guidelines addressed the issue of surgery in this context, recommending venous ablation in conjunction with compression to increase the rate of ulcer healing (grade 1A/1B to 2C depending on the guidelines and on the procedure). Concerning the usefulness of venoactive drugs, Giovanni Mosti stated that there is no consensus and evidence that is more consistent is needed (level of evidence usually 2B or 2C; 1B for micronized purified flavonoid fraction in the American Venous Forum and the Latino-American guidelines). Likewise, skin grafting is not a primary procedure and there is not a consensus. According to his personal experience, he suggested performing skin grafting in refractory ulcers when other therapeutical procedures failed after 6 weeks.
Global management of the venous leg ulcer in the pre-EVRA era
Sarah Onida (UK)
Sarah Onida discussed the results of a survey aimed at determining the management of leg ulcers worldwide prior to the release of the early venous reflux ablation results. A 26-question format was circulated by various venous and vascular societies worldwide and approximately 15 000 vascular surgeons, phlebologists, and general surgeons were involved. Approximately 800 clinicians, mostly vascular surgeons from Europe and North America, responded to the survey. Among clinicians, 60% performed or arranged an ankle-brachial index on the first visit, 84% performed a venous duplex ultrasonography in patients presenting with a leg ulcer, 53% prescribed compression bandaging, and 35% prescribed compression stockings. Almost 80% of the clinicians were confident that treatment of superficial venous reflux benefits ulcer healing and recurrence. Regarding the timing of the intervention, only 60% believed that it should be done prior to ulcer healing. In answering the question “would you change your practice if early venous reflux ablation has positive/negative results?” great uncertainty and divergence in opinions were expressed. In summary, the survey showed a diversity of referral and treatment pathways internationally. Sarah Onida concluded emphasizing that there is a clear need to develop robust, clear pathways for patients with leg ulcerations, which can be informed by the early venous reflux ablation trial results.
No ulcer treatment without hemodynamic analysis!
Johann Chrisof Ragg (Germany)
According to the Society for Vascular Surgery/American Venous Forum guidelines, a venous ulcer is defined as an “open skin lesion of the leg or foot that occurs in an area affected by venous hypertension.” The elimination of reflux (by an endovenous approach or surgery) is clearly recommended by the guidelines. Therefore, the analysis of venous hemodynamics and vein morphology from heart to foot, the comprehension of the individual history of insufficiency and the determination of reflux considered relevant for the ulcer are crucial aspects in the management of these patients. Indeed, major causes of venous hypertension should be eliminated. Changes in the ulcer area should be checked every 2 to 3 months. If the results seem unsatisfactory, additional reflux elimination should be considered and all supportive modalities (activation, compression, etc) should be applied. Therefore, in the opinion of Johann C. Ragg, the majority of hemodynamic disorders (reflux, hypertension) is treatable successfully. An exact analysis of hemodynamics is crucial for an appropriate treatment strategy and for the improvement inflow. The nearer a venous target is located to an ulcer or to diseased skin, the clearer the decision for endovenous methods should be. Endovenous techniques, in particular those with no heat and no need for tumescence, should be preferred.
Which compression in venous leg ulcer patients? – practical advice
Giovanni Mosti (Italy)
The most effective compression modality for venous leg ulcer patients is also the most efficient in reducing venous hypertension. Therefore, inelastic compression (bandages, Adjustable Velcro® compression device (AVCD) exerting strong/very strong pressure and high-pressure peaks), counteracting ambulatory venous hypertension, is the most effective modality. Indeed, inelastic material, exerting higher working pressure and working peaks to close the vein, is significantly more effective in decreasing venous reflux, in increasing venous pumping function, and in reducing ambulatory venous hypertension when compared with elastic material. Inelastic bandages are very effective, despite significant pressure loss, but they need expert personnel to apply them. AVCD (CircAid) can be safely used in ulcer treatment. Compared with inelastic bandages, it seems to increase the healing rate and shorten the healing time, ensuring cost savings with negligible side effects. AVCD (CircAid) does not require expert personnel for its application. After a brief introduction, it may be self-applied and readjusted to maintain consistent hemodynamic effectiveness (maintenance of pressure range). Elastic kit exerting a pressure >40 mm Hg could be effective in small and recent-onset ulcers. Compression therapy can be useful even in mixed ulcers when properly applied using a reduced pressure (<40 mm Hg in patients with a perfusion pressure >60 mm Hg and protecting bone and tendon prominences). Indeed, in patients with arterial impairment, compression may increase the arterial inflow due to the reduction in the arterovenous pressure gradient, the myogenic relaxation of the arterial wall and the release of vasoactive substances.
Venous leg ulcer treatment – does pharmacotherapy matter?
Arkadiusz Jawień (Poland)
The 2019 evidence-based guidelines from the Society for Vascular Surgery/American Venous Forum suggest using pentoxifylline or micronized purified flavonoid fraction in combination with compression to accelerate healing of venous ulcers (grade 2B). There are few pharmacologic agents available for the treatment of C5-C6 disease, ie, for those with healed or active venous ulcers.
Pentoxifylline is available in the United States and it is an effective adjunct to compression bandages for treating venous ulcers in a Cochrane review of 12 randomized trials involving 864 participants. Pentoxifylline plus compression was more effective than placebo plus compression (risk ratio [RR], 1.56; 95% CI, 1.14-2.13) in terms of complete ulcer healing or a significant improvement. Pentoxifylline in the absence of compression appeared to be more effective than placebo or no treatment (RR, 2.25; 95% CI, 1.49- 3.39). In a randomized controlled trial with a 24-week follow-up with blinded allocation to pentoxifylline (1200 mg) or placebo, pentoxifylline increased the healing proportion compared with placebo to the same extent as shown in recent systematic reviews, although this finding was only statistically significant when a secondary adjusted analysis was conducted (RR for healing, 1.4; 95% CI, 1.0-2.0). Randomized trials have similarly shown micronized purified flavonoid fraction, which is not available in the United States, to increase the odds of ulcer healing by 32% in comparison with compression and local wound care alone.
A meta-analysis of 5 randomized prospective studies using MPFF at a dose of 500 mg as an adjunct to conventional treatment (723 patients with venous ulcers) showed that, at 6 months, the chance of ulcer healing was 32% better in patients treated with adjunctive MPFF at a dose of 500 mg than in those managed by conventional therapy alone (relative risk reduction [RRR], 32%; 95% CI, 3-70). This translates to a number needed to treat of 7.3 (95% CI, 4.6-17.1). This difference was present from month 2 (RRR, 44%; 95% CI, 7-94) and was associated with a shorter time to healing (16 weeks vs 21 weeks; P=0.0034). The benefit of MPFF at a dose of 500 mg was found in the subgroup of ulcers between 5 and 10 cm2 in area (RRR, 40%; 95% CI, 6-87), as well as in patients with ulcers of 6 to 12 months’ duration (RRR, 44%; 95% CI, 6-97).
The results of a meta-analysis of four studies involving 482 patients and testing the effect of oral sulodexide plus compression vs placebo or compression alone at 2 months showed that sulodexide may have beneficial effects in ulcer healing in addition to conventional therapy vs placebo (RR, 1.70; 95% CI, 1.33-2.17; absolute risk difference, 0.19; 95% CI, 0.11-0.27).
According to the clinical practice guidelines of the European Society of Vascular Surgery, sulodexide and micronized purified flavonoid fraction should be considered as an adjuvant to compression therapy in patients with venous ulcers (grade IIa; level of evidence A). The latest guidelines on the management of chronic venous disorders developed under the auspices of the European Venous Forum, the International Union of Angiology, the Cardiovascular Disease Educational and Research Trust (UK), and the Union Internationale de Phlébologie suggest pentoxifylline, micronized purified flavonoid fraction, and sulodexide as adjuvants for the healing of venous ulcers as medication with a high level of evidence (grade A). Therefore, the speaker concluded his talk stating that pharmacotherapy matters because it is able to accelerate the healing of venous ulcers. Until recently, there has been a substantial amount of scientific evidence for pharmacotherapy, but further studies are desirable.
EVRA trial – early invasive reflux ablation brings benefits to the VLU leg ulcer patients
Alun Davies (UK)
The early invasive reflux ablation (EVRA) study provides the first level of evidence for the benefit of early endovenous treatment of superficial venous reflux in venous leg ulcers. Prompt endovenous ablation (within 2 weeks of randomization), in conjunction with compression therapy, accelerated ulcer healing compared with deferred interventions (after ulcer healing or at 6 months). More patients had healed ulcers in the early intervention group, and patients experienced additional ulcer-free time over the 1-year follow-up. Furthermore, early intervention resulted in significant improvements in disease-specific and general health-related quality of life, as well as body pain. Results from EVRA also found that early intervention was highly likely to be cost-effective at UK decision making thresholds. EVRA provides evidence that early venous reflux ablation benefits leg ulcer patients in terms of ulcer healing and quality of life, and it is cost-effective. The challenge is to implement these results globally, as current pathways of care for patients with leg ulcers, in general, do not include a provision for early assessment and treatment. The current UK guidelines (CG 168) recommend that patients with a venous leg ulcer (defined as a break in the skin below the knee that does not heal within 2 weeks) are referred to a vascular specialist for assessment. However, uptake of the guidelines has been slow and there is limited awareness in the communities where the majority of patients are treated. Although there has been an increase in patients referred with leg ulceration since the release of the guidelines, many are not referred until after they have had an ulcer for many months. Leg ulcer evaluation and treatment pathways are poorly developed across much of the NHS and around the world. Urgent action is required to improve care pathways between primary and secondary care and to ensure patients with a venous leg ulcer receive early diagnosis, referral, and treatment.
The role of the reflux sourcing and ablation in the venous leg ulcer treatment
Alfred Obermayer (Austria)
Venous ulcers are mostly due to local venous hypertension that affects the microcirculation of the skin. Alfred Obermayer showed the main results of a study involving 169 patients with venous leg ulcers. Venous function was assessed with duplex ultrasound. Furthermore, a “sourcing” technique was performed with duplex ultrasound investigation of the ulcer bed and the venous system under manual compression and release of the ulcer. The principle of “sourcing” is to follow venous reflux from the ulcer area to its proximal origin. A total of 20% of patients with ulcers showed no clinically visible varicose veins (CEAP C2). Reflux in the small saphenous vein occurred in 11% of the medially located ulcers (crossover type) and 14% of patients presenting with lateral ulcers showed great saphenous vein incompetence (crossover type). Identifying the specific route responsible for venous reflux can be crucial for planning a rational treatment of venous reflux ulcers (Obermayer A, Garzon K. J Vasc Surg. 2010;52(5):1255-1261). Indeed, a crossover pattern may lead to inaccurate treatment and early recurrence. Finally, Obermayer highlighted that the technique of lateral fasciectomy sparing the superficial peroneal nerve with mesh graft coverage could be a good treatment of nonhealing lateral leg ulcers of various vascular origin affecting the fascia (Obermayer A et al. Eur J Vasc Endovasc Surg. 2016;52(2):225- 232.)
Aggressive local venous leg ulcer treatment – does it help?
Dominik Heim (Switzerland)
Venous ulcers are associated with impaired quality of life, reduced mobility, pain, stress, and loss of dignity. The Society for Vascular Surgery/American Venous Forum guidelines do not advice using split-thickness skin grafting for the primary therapy of venous leg ulcers. Local surgical techniques, including fasciectomy, Reverdin pinch grafting, or shaving, are generally indicated in cases of nonhealing ulcers after 3 months of conservative treatment by the German Guidelines of Phlebology. Although few studies assessing the outcomes and the recurrence of ulcers treated with these techniques have been conducted, Heim expressed his confidence in the usefulness of aggressive local surgery in healing recalcitrant ulcers.
Update of the negative wound pressure therapy for the venous leg ulcer
Maciej Zieliński (Poland)
Despite the fact that venous leg ulcers fulfill the criteria of complicated chronic wounds, the majority of international organizations of phlebologists do not recommend negative pressure wound therapy (NPWT) as standard therapy for leg ulcers resulting from venous insufficiency. Nevertheless, there are some reports in the literature reporting a positive impact of topical negative pressure use on the effectiveness of the venous leg ulcer closure, which were summarized in the recommendations issued by international expert panel on NPWT, stating that if compression therapy is not efficacious, NPWT should be used to prepare the wound for surgical closure or to progress to wound closure by secondary intention. Maciej Zieliński presented the status of the application of NPWT and its potential perspective for an efficacy improvement in the different aspects of local treatment of venous leg ulcers.
In the discussion, the influence of hypobaric therapy on wound bed preparation by means of conducting a cleansing mechanism should also be mentioned. The explanation can be found in the active drainage phenomenon that decreases bacterial load and thus helps fight local infection. On the other hand, subatmospheric suction has the potential to generate a proper fluid balance by effectively removing exudate from the venous ulcer and its close vicinity, which also positively affects inflammatory conditions of the surrounding tissue and the degree of edema. The unique structure of foam occlusive dressing facilitates a moist environment, simultaneously providing proper oxygen diffusion through the drape membrane. Additionally, there is strong evidence of a beneficial effect of NPWT on the proliferation phase of chronic wound healing. Hypobaric conditions create local hyperemia and thus improve microcirculation and stimulate neoangiogenesis. It also promotes acceleration of fibroblast mitosis, resulting in faster granulation tissue formation. Lastly, NPWT was proven to have a beneficial effect on skin grafting procedures in different wound types, including venous leg ulcers. Further studies intended to define the real value of NPWT in the treatment of venous leg ulcers have to be encouraged.
Combined and simultaneous reflux ablation and local surgical treatment – lessons learned
Alfred Obermayer (Austria)
Alfred Obermayer reported his experience in the surgical treatment of worst-case scenarios of recalcitrant chronic leg ulcers. In his center, patients presenting with leg swelling underwent “lenient active bed rest” in the hospital to reduce edema before surgery. They performed special exercises in bed at least three times daily to support venous backflow and to reduce leg edema. Many patients underwent ulcer surgery in combination with reflux surgery or thermal ablation in the same session. This “single-shot surgery” appeared a good standard for enabling and accelerating ulcer healing, although it has not been established internationally (Obermayer A et al. Eur J Vasc Endovasc Surg. 2016;52(2):225-232).
Venous leg ulcer treatment based on the chronic venous disease pathophysiology – lessons learned
Angelo Scuderi (Brazil)
The Emeritus President of the International Union of Phlebology stated that there are so many ways to treat ulcers that probably no option is good enough. In this regard, we have little scientific evidence, few valid randomized works, and only a group of Good Practice Guidelines, meaning that there is no consensus. He emphasized that venous ulcers or varicose ulcers are wounds following the physiological principles of healing. Therefore, in treating an ulcer, we should aim to obtain physiological rest, ensuring good circulation and venous return; chemical rest, treating the wounds gently without put anything inside them; and mechanical rest with compression therapy or resting in the Tremdelemburg position.
1 year outcomes of VenaSeal glue ablation in diabetics with venous leg ulcer
Sriram Narayanan (Singapore)
Sriram Narayanan presented the results of a study involving 36 diabetic patients with venous ulcers who were treated in his center using a standardized protocol adapted to diabetic patients. VenaSeal glue ablation of venous leg ulcers in diabetic patients seems safe as long as a strict infection control regime is followed. In most cases, it allows for ulcer management without the need for compression therapy. The incidence of phlebitislike abnormal reactions seems lower than in nondiabetic patients. After a 1-year follow-up, outcomes in diabetic patients were comparable with those obtained in nondiabetic patients or in patients treated with endovenous ablation with additional compression.
Topical sevoflurane as a new treatment modality for painful venous leg ulcers
Manuel Gerónimo-Pardo (Spain)
Sevoflurane was very effective in controlling rest pain in 134 patients, even when a neuropathic component was present. Pain reduction was rapid, intense, and long-lasting. Remarkably, sevoflurane was also effective at controlling pain that had been refractory to other conventional systemic analgesic treatments. Sevoflurane was slightly less effective at controlling pain during debridement. Nearly all treated ulcers showed a reduction in both size and depth, and even complete ulcer healing was achieved in some cases. Concerning safety, mild pruritus in the surrounding skin has been the most frequent adverse effect reported so far. Of interest, no patient has experienced any systemic adverse effect.
