Interventional procedure consultation document

Ultrasound-guided foam sclerotherapy for varicose veins

Treating varicose veins with foam injections using ultrasound guidance

Small valves inside the veins help blood flow properly through them. Varicose veins develop when these valves weaken, allowing blood to collect in the veins. This enlarges them and causes the valves to weaken further. Varicose veins commonly occur in the legs and symptoms include heaviness, aching, throbbing, itching, cramps or tiredness in the legs. In severe cases, patients may have skin discolouration or inflammation, or skin ulcers. Foam sclerotherapy involves mixing a chemical with air or another gas to produce a foam, which is injected into the affected vein. This blocks the vein by causing inflammation and making it shrink. Sometimes patients may need more than 1 injection to block the vein.

The National Institute for Health and Clinical Excellence (NICE) is examining ultrasound-guided foam sclerotherapy for varicose veins and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. NICE’s Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about ultrasound-guided foam sclerotherapy for varicose veins.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

• comments on the provisional recommendations
• the identification of factual inaccuracies
• additional relevant evidence, with bibliographic references where possible.

Note that this document is not NICE’s formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that NICE will follow after the consultation period ends is as follows.

• The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
• The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.

For further details, see the Interventional Procedures Programme manual, which is available from the NICE website (www.nice.org.uk/ipprogrammemanual).

Through its guidance NICE is committed to promoting race and disability equality, equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our interventional procedures guidance. In particular, we aim to encourage people and organisations from groups who might not normally comment on our guidance to do so.

In order to help us promote equality through our guidance, we should be grateful if you would consider the following question:

Are there any issues that require special attention in light of NICE’s duties to have due regard to the need to eliminate unlawful discrimination and promote equality and foster good relations between people with a characteristic protected by the equalities legislation and others?

Please note that NICE reserves the right to summarise and edit comments received during consultations or not to publish them at all where in the reasonable opinion of NICE, the comments are voluminous, publication would be unlawful or publication would otherwise be inappropriate.

Closing date for comments: 20 November 2012

Target date for publication of guidance: February 2013

1   Provisional recommendations

1.1   Current evidence on the efficacy of ultrasound-guided foam sclerotherapy for varicose veins is adequate. The evidence on safety is adequate, and provided that patients are warned of the small but significant risks of foam embolisation (see section 1.2), this procedure may be used with normal arrangements for clinical governance, consent and audit.

1.2   During the consent process, clinicians should inform patients that there are reports of temporary chest tightness, dry cough, headaches and visual disturbance, and rare but significant complications including myocardial infarction, seizures, transient ischaemic attacks and stroke.

1.3   The procedure should only be undertaken using liquid sclerosants licensed for treating varicose veins. The practice of mixing liquid sclerosant with air or another gas to create a foam constitutes off-label use.

2   The procedure

2.1   Indications and current treatments

2.1.1   Varicose veins are enlarged tortuous veins with deficient valves. Venous insufficiency occurs when blood collects in them rather than being pumped back to the heart. Most people with varicose veins have no symptoms, but venous insufficiency may cause fatigue, heaviness, aching, throbbing, itching and cramps in the legs. Chronic venous insufficiency can lead to skin discolouration, inflammatory dermatitis and ulceration. Long saphenous vein insufficiency is the most common form of venous insufficiency in people presenting with symptoms.

2.1.2   In most people varicose veins do not cause serious health problems, and treatment is not usually needed on medical grounds. Conservative methods such as compression hosiery (support stockings or tights) may help people with symptomatic varicose veins. If symptoms are severe the main treatment options include surgery (usually stripping and ligation of the long and short saphenous veins, and phlebectomies), liquid sclerotherapy, endovenous laser treatment and radiofrequency ablation.

2.2   Outline of the procedure

2.2.1   The aim of ultrasound-guided foam sclerotherapy for varicose veins is to damage the endothelial surface of the vein causing scarring and preventing blood flow through the varicose veins. The perceived benefit of this procedure compared with liquid sclerotherapy is that foam has increased contact with the inside of the vein walls and remains in the vein for a longer period of time.

2.2.2   The procedure is carried out with local anaesthesia. Sclerosant foam is injected into the affected veins using ultrasound guidance. The foam causes an inflammatory reaction in the vein wall blocking the vein. Compression bandages are applied after the procedure and are typically worn for between a week and a month.

2.2.3   More than 1 vein may be treated during the same session. If any vein is incompletely treated, further injections may be given in the same or subsequent sessions. Various sclerosants and aeration methods may be used to produce the foam for this procedure.

Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview, available at www.nice.org.uk/guidance/IP/244/overview

2.3   Efficacy

2.3.1   A randomised controlled trial (RCT) of 73 patients (82 legs), in which foam sclerotherapy plus saphenofemoral ligation (n=39) was compared with standard surgery (n=43), reported above-the-knee vein obliteration in 58% (19/33) of legs in patients treated in the foam plus saphenofemoral ligation group and 54% (14/26) of legs in patients treated by standard surgery alone at 5-year follow-up (p=0.19). Below-the-knee vein obliteration was reported in 24% (8/33) of legs in patients treated by foam plus saphenofemoral ligation and 39% (10/26) of legs in patients treated by standard surgery alone at 5-year follow-up (p=0.34).

2.3.2    A meta-analysis of 2 RCTs (included in a systematic review) with 340 patients reported that foam sclerotherapy was not significantly more efficacious (n=174) than liquid (n=166) in occluding the vein (relative risk [RR] 1.5; 95% confidence interval [CI] 0.6 to 3.6, I²=95%, indicating significant heterogeneity), with follow-up ranging from 1 to 10 years.

2.3.3   In a case series of 146 patients (203 limbs), the clinical recurrence rate with significant venous symptoms (visible or palpable varices, aching, oedema or venous skin changes) was 4%, the clinical recurrence rate with minimal venous symptoms was 22%, and recurrence with no venous symptoms was 74% at 5-year follow-up.

2.3.4   In the RCT of 73 patients the median Venous Clinical Severity scores (graded from 0 [absent] to 3 [severe]; maximum score 30) decreased from 5 to 1 in patients treated by foam sclerotherapy plus saphenofemoral ligation and decreased from 5 to 3 in patients treated by surgery alone at 5-year follow-up (p=0.35 between groups; p values for change within groups not reported).

2.3.5   The RCT of 73 patients reported that the median Aberdeen Varicose Vein Questionnaire scores (range 0–100, with higher scores indicating more severe effects) decreased from 12 at baseline to 7 in patients treated by foam sclerotherapy plus saphenofemoral ligation, and from 16 at baseline to 6 in patients treated by surgery. The difference between the groups was statistically significant but not considered ‘clinically significant’ at 5-year follow-up (p=0.02).

2.3.6   The Specialist Advisers listed additional key efficacy outcomes as mobility and recurrence of leg ulceration.

2.4   Safety

2.4.1   Stroke was reported in a case report of 3 patients, all of whom were subsequently diagnosed with a patent foramen ovale. In 1 patient middle cerebral arterial air was detected immediately after being treated by foam sclerotherapy and ambulatory phlebectomy (treated with tissue plasminogen activator), and in the other 2 patients middle cerebral arterial ischaemic change was confirmed (1 day after the procedure in 1 patient and 2 days after the procedure in the other patient). All 3 patients recovered completely with no further neurological or thrombotic events reported at follow-up ranging from 3 months to 2 years. A transient ischaemic attack after injection was reported in 1 patient in a case series of 1025 patients. Complete clinical recovery occurred in 30 minutes.

2.4.2   Myocardial infarction was reported in 1 patient 30 minutes after injection (unpublished report included in the systematic review; no further details available).

2.4.3   A grand mal epileptic seizure was reported in 1 patient 40 minutes after injection (based on an unpublished report included in the systematic review; no further details available).

2.4.4   Foam embolisation was reported in 73% (60/82) of patients in a case series of 82 patients with right-to-left shunts. ‘Most’ emboli were detected within 15 minutes of the foam injection and no new neurological symptoms were detected at follow-up (assessed at 1, 7 and/or 28 days).

2.4.5   Transient visual disturbance was reported in 5 patients, during or shortly after, treatment in a case series of 977 patients treated by foam sclerotherapy.

2.4.6   Headache was reported in 3 patients immediately after the procedure in the case series of 977 patients (resolved in 24 hours after treatment by analgesia).

2.4.7   Pulmonary embolism was reported in 1 patient in the case series of 977 patients 5 weeks after treatment (treated by an anticoagulant).

2.4.8   Facial rash was reported in 1 patient in the case series of 977 patients. The rash appeared 24 hours after treatment and disappeared spontaneously.

2.4.9   Complications including coughing, chest tightness/heaviness, panic attack, malaise and vasovagal fainting occurred at a rate of 0–3% across the studies in the systematic review (follow-up ranged between 1 month and 5 years).

2.4.10   The Specialist Advisers listed an additional theoretical adverse event to be extravasation.

2.5   Other comments

2.5.1   The Committee noted that there was considerable variability in foam preparation and insufficient evidence to draw conclusions on the relative safety of different types and strengths of sclerosing agents, volumes of foam and foam-producing techniques.

3   Further information

3.1   This guidance is a review of ‘Ultrasound-guided foam sclerotherapy for varicose veins’. NICE interventional procedures guidance 314 (2009).

3.2   For related NICE guidance see www.nice.org.uk

Barrie White

Vice Chairman, Interventional Procedures Advisory Committee

October 2012