Performance of endovenous foam sclerotherapy in the USA

Introduction

Despite the ready availability of endovenous foam sclerotherapy (EFS) for the treatment of venous disease, there are few US studies that document its widespread use or provide guidelines regarding methodology. ¹ Many observational studies performed worldwide report the relative efficacy and safety of the procedure, but a paucity of trials have been performed in the USA. A common perception is that foam sclerotherapy is used widely throughout the USA for the treatment of chronic venous diseases including varicose veins, congenital venous malformations and venous ulcers. However, no formal investigation has been performed to document its usage. Moreover, no standards of care or quality improvement guidelines exist for the safe and efficacious performance of EFS for treatment of patients suffering with chronic venous disease in the USA.

EFS for treatment of venous disorders has been described since the 1940s when it was noticed that injection of a ‘soapy froth obtained by shaking up 1 cm³ of ethanolamine in a 2 cm³ syringe’ was effective in displacing blood in the vein. ² In the 1950s, sclerotherapy injection techniques were refined further many years before the advent of ultrasound technology. Cabrera has been credited with the use of ultrasound-guided foam sclerotherapy after publishing his personal series of this technique in the mid-1990s. ³ Today, EFS is most commonly performed by combining a sclerosant agent, usually sodium tetradecyl sulphate or polidocanol, with air, carbon dioxide or a carbon dioxide/oxygen mix creating a foam using a double syringe system and injecting this foam into the affected vein. Numerous case series and randomized trials have documented the safety and efficacy of EFS in the treatment of venous disorders. Several countries and organizations including Germany and a European group of 29 experts have produced guidelines for performance of EFS. ^4,5 However, despite perceived use, no guidelines exist for practitioners in the USA.

In 2009, a multidisciplinary consensus panel of US experts was convened with three purposes: (1) to conduct a systematic review of the published literature with the goal of providing quality improvement guidelines regarding safety and efficacy for the performance of EFS where evidence exists; (2) to identify important areas of needed research where there is lack of evidence; and (3) to conduct a comprehensive questionnaire of those performing foam sclerotherapy in the USA to describe practice patterns, and identify areas of common usage and methodology. The panel consisted of seven representatives from the American College of Phlebology, the Society for Vascular Medicine, the Society for Interventional Radiology and the American Venous Forum as well as a biostatistician and epidemiologist. This publication reports the results of the comprehensive questionnaire performed at the annual meeting of the American College of Phlebology held in November 2009.

Methods

The comprehensive questionnaire (Appendix 1) was developed to target key areas in the performance of EFS for the treatment of venous disorders. These areas included demographic information, practice specialty and site, indications for sclerotherapy, type of sclerosant used, method of foam preparation, method of foam injection, postprocedural care and follow-up, and measurements of efficacy and patient safety. The questionnaire was initially developed by the principal investigator and reviewed by the biostatistician for accuracy and validity. It was then circulated to all members of the consensus panel for comment. Edits were completed in response to the feedback received. The questionnaire and study protocol were then submitted to the institutional review board of the University of Oklahoma Health Sciences Center for review and approval.

Participation was solicited from US attendees at the time of registration on site at the 2009 annual meeting of the American College of Phlebology and was voluntary and anonymous. Participants were asked to complete a five-page questionnaire consisting of 30 finite answer questions. Non-US residents were not asked to participate and the state of residency was collected to confirm eligibility.

Questionnaires were numbered so that duplicate survey distribution was avoided and the number returned could be accurately calculated. The questionnaires were collected on site and additionally by facsimile return for the two weeks following the meeting. The questionnaires were reviewed and the data for each respondent entered into a database. Initial results were reviewed by the principal investigator and biostatistician and then forwarded to members of the consensus panel for comment.

Statistical analysis

Descriptive statistics were used to summarize the distribution of questionnaire responses for each question. Percentage values were calculated among non-missing response values. A 95% confidence interval, based on a normal approximation to the binomial distribution, was estimated for the proportion of respondents who reported using foam sclerotherapy. Respondent characteristics were compared between groups defined by use of foam sclerotherapy using a chi-squared test or Fisher's exact test when at least 20% of expected cell counts were less than 5. Data were analysed using SAS (SAS System for Windows, ver. 9.1, SAS Institute Inc, Cary, NC, USA).

Results

Of 776 questionnaires distributed to US attendees at the annual meeting of the American College of Phlebology held in November 2009, 239 were returned for a response rate of 31%. Four questionnaires returned from non-US residents were deducted from the number distributed and the number returned.

Demographic information

The results are presented in a series of summary tables. Of the 239 respondents, 208 (87, 95% CI: 83–91%) reported using endovascular foam sclerotherapy for the treatment of venous disease. Foam sclerotherapy is used widely by providers in every geographic region of the USA (Table 1). The regional distribution of providers using EFS differed significantly from non-users with a higher percentage of users in the western USA and the south and a higher percentage of non-users in the northeast (P = 0.038). Among respondents, nearly 90% of EFS users were in private practice compared with non-users who were less likely to be in private practice (61%, P < 0.0001). EFS is used widely across medical specialties (Table 2). Most EFS users identified themselves as surgeons with internal medicine, family medicine and interventional radiology also heavily represented. Other specialties include emergency medicine, dermatology, cardiology, obstetrics and gynaecology, and radiology among others. For non-users of EFS (n = 31), the most frequently cited reasons for non-use included lack of experience (n = 14, 45%), uncertainty regarding safety (n = 11, 35%) or efficacy (n = 2, 6%), lack of need for EFS in their practice (n = 3, 10%) and concern about lack of Food and Drug Administration (FDA) approval (n = 5, 16%), where subjects could select multiple reasons. Among those using EFS (n = 208), roughly half had been performing the procedure for no more than five years (n = 113, 56%) but a majority performed more than 10 procedures per month (n = 131, 65%).

Indications for EFS

EFS is used for a wide variety of indications. Most used EFS for treatment of recurrent great saphenous, small saphenous or tributary varicosities (n = 163, 79%), but many reported use for initial treatment of varicose veins (n = 107, 52%), reticular veins (n = 156, 76%), venous malformations (n = 69, 34%), and venous ulcers (n = 125, 61%). Some also reported use of EFS for the treatment of perforator veins (n = 29, 14%) and, less commonly, spider veins (n = 7, 3%). Respondents to the questionnaire also indicated common contraindications for EFS including septal defect, patent foramen ovale or other cardiac malformation, and previous allergy or neurological adverse effects (Table 3). Nearly all respondents reported using EFS for treatment of venous disease in the legs (n = 202, 100% of those responding to the question). Less common anatomic sites included the feet (n = 77, 38%), hands (n = 46, 23%), face (n = 13, 6%), and pelvic and labial veins (n = 5, 2%).

Methods of performance

Methods of performance of EFS varied widely. A majority of respondents (55%) typically use sodium tetradecyl sulphate 0.1–3.0% as a single agent, compared with 16% who use polidocanol as a single agent and fewer using multiple agents (Table 4). It is important to note polidocanol was not available in the USA at the time of the survey. A majority prepare foam using 1–2 mL of sclerosant combined with room air in a ratio of 1:4 for foam preparation primarily by the Tessari method. The maximum total volume of foam per vein tends to be <5 mL with 5–10 mL used about a third of the time. The maximum total volume of foam used per session was usually no more than 10 mL with roughly a third of respondents using 11–20 mL per session. Few perform echocardiographic screening for detection of septal defects or patent foramen ovale prior to the procedure (Table 5). However, the majority use ultrasound guidance while injecting foam and immediately after the procedure to verify foam distribution. A minority elevate the limb prior to the procedure and approximately half elevate the limb following the procedure. Less than half ask the patient to pump their foot immediately after the procedure, but a majority asked patients to walk within 30 minutes after the procedure. Most providers apply compression stockings after the procedure (n = 180, 88%) with a minority applying compression wraps (all cotton elastic [ACE] wrap n = 27, 13%; short-stretch compression wrap n = 32, 16%), where respondents could select multiple types of garments. Very few apply no compression following the procedure (n = 7, 3%). There was wide variation in the duration of compression garment use with roughly half prescribing stockings for 3–7 days (n = 92, 45%) and 43% (n = 89) more than one week. A minority (n = 48, 23%) of respondents prescribed anticoagulation either before or after the procedure, and only for patients with a history of deep vein thrombosis (DVT).

Surveillance and follow-up

The time to first follow-up visit after the procedure also varied widely, with about one-third seeing patients within one week, another third by two weeks and a third within 4–6 weeks. A majority (72%) performed ultrasound at the first follow-up visit to check for sclerosis of the vein and two-thirds to evaluate for DVT. Less than 10% of respondents did not perform ultrasound surveillance for either purpose, when each is considered separately. Approximately half of the subjects responded that degree of anatomic closure was the most important measure of efficacy (n = 98, 48%) followed by relief of patient symptoms (n = 71, 35%).

Discussion

This questionnaire represents the largest survey of US practitioners to date regarding the performance of EFS. The questionnaire was administered to a wide variety of specialists who were encouraged to respond freely and anonymously, and was devoid of commercial bias. Based on the results of this questionnaire, several conclusions can be made. First and most importantly, EFS is performed by a wide variety of specialists in every region of the USA. Geographically, EFS was performed in all nine census regions. It is crucial to highlight this widespread use for patients with venous disorders who may have failed other therapies, or who may be ideal candidates for this procedure.

Second, roughly half of the responding practitioners have been performing EFS for no more than five years, consistent with the perception that EFS is a new and growing technology in the USA. With the recent US FDA approval of a second sclerosant, it is anticipated that use of EFS will increase since now two biologically approved sclerosants are available: sodium tetradecyl sulphate and polidocanol. Non-users of EFS most commonly indicated that they were uncertain of the efficacy or safety of EFS, and were less likely than users to be in private practice. It is clear that the relative risk profile and criteria for patient selection have not been well documented and further research is needed in this area.

Third, the most common indication for performance of EFS was sclerosis of recurrent truncal or tributary veins of the legs, with half also performing the procedure as primary treatment. Surprisingly, a majority also performed EFS for the treatment of venous ulcers. At this time, it is unclear which patients with venous ulcers may benefit most from invasive treatments and at what juncture EFS of, in particular, perforator veins, may be attempted. Similarly, while most responded that they did not routinely order preprocedural surveillance for septal defects or patent foramen ovale, there was no consensus on whether these abnormalities represented an absolute contraindication for EFS.

Fourth, the method of foam preparation, injection and immediate postprocedural care varied. Almost all used room air as their preferred gas admixture in combination with sodium tetradecyl sulphate as the sclerosant, with a minority currently using polidocanol. However, the volume of foam injected varied between <5 and 20 mL. There was little consensus on postprocedural manoeuvres such as leg elevation, or foot pumping. Most had compression wrapping or a stocking applied but the duration of use was variable. Further research is being performed in this area. Similarly, the time to first follow-up was variable ranging from 72 hours to 4–6 weeks with the degree of anatomic closure the primary measure of efficacy.

Limitations

While the results of this questionnaire represent the most comprehensive review of use of EFS in the USA performed to date, extrapolation of the findings may be limited. First, sample selection was limited to attendees at the American College of Phlebology meeting and may not reflect the practice of those who did not respond or attend the meeting. However, this annual meeting specifically targets physicians in the USA treating patients with venous disease with many disciplines represented, and there is no larger meeting with this specific purpose currently held in the USA. Second, the response rate was 31%. Although this is an acceptable response for any survey, less than 100% response may limit the generalizability of the conclusions. However, the questionnaire was performed anonymously encouraging participation and free expression of ideas. Third, this questionnaire does not provide guidelines for appropriate methodology for performance of EFS or address efficacy or safety concerns beyond perception. The questionnaire was intended to show common usage, and a separate systematic review and meta-analysis of all published literature is underway to address the questions of efficacy and safety.

The questionnaire has identified important areas of needed research. Many respondents were unclear regarding patient selection, the methodological performance of EFS, timing of surveillance and follow-up, and the overall safety and efficacy of the procedure.

Standard of care

Many practitioners question whether the performance of EFS for the treatment of venous disorders meets the standard of care. The most common legal definition of medical standard of care is how similarly qualified practitioners would have managed the patient's care under similar circumstances. ⁶ The standard of care reflects both the consensus of opinion of clinical judgement, and the science including the published peer-reviewed literature. It is the best combination of risk and benefit. ⁷ It is desirable that the standard of care has a national and clinical basis, rather than a local community or payer review basis. ⁸ While the results of this questionnaire do not definitively establish the performance of EFS as the standard of care, it is a first step in creating a national standard of care for performance of EFS intended to establish improved and more uniform guidelines for physician practice. Our multidisciplinary panel has been charged with creating such a standard.

The results of this questionnaire clearly establish that EFS is performed throughout the USA by a multitude of specialists for treatment of a wide variety of venous disorders. A second publication reporting the results of the rigorous scientific literature review evaluating the efficacy and safety of EFS will be critical in development of these quality improvement guidelines.

Conclusions

This questionnaire reporting the use of EFS for the treatment of venous disorders in the USA describes its widespread geographical use. There is variation among practitioners in the indications for use, pre- and postprocedural evaluation and procedure methodology. Documentation of relative efficacy and safety is important for those less familiar with the technique, and is the subject of a rigorous meta-analysis in progress. Future questionnaires should include a larger group of diverse participants and target specific methodologies and measures of efficacy and safety. The results of this questionnaire will be important in the development of national quality improvement guidelines for the performance of EFS.