Abstract
This guideline was drafted on behalf of 23 European Phlebological Societies during a Guideline Conference on 7th--10th May 2012 in Mainz. 1 The conference was organized by the German Society of Phlebology.
These guidelines review the present state of knowledge as reflected in published medical literature.
The recommendations of this guideline are graded according to the American College of Chest Physicians Task Force recommendations on Grading Strength of Recommendations and Quality of Evidence in Clinical Guidelines.
Complications and risks
If performed properly, sclerotherapy is an efficient treatment method with a low incidence of complications.2,3,4
Recommendation 3
Adverse events after sclerotherapy modified and updated from.
Anaphylaxis
Anaphylactic shock as well as inadvertent intra-arterial injection is extremely rare complications constituting an emergency situation.
Recommendation 4
If anaphylaxis is suspected we recommend stopping the injection immediately and to follow with standard emergency procedures including the administration of epinephrin when appropriate. (GRADE 1A).
Large tissue necrosis
Extensive necroses may occur after inadvertent intra-arterial injection. The risk of intra-arterial injection can be minimised by ultrasound guidance with adequate imaging and identification of arteries in close proximity to target veins. If severe pain occurs during injection, the injection should be stopped immediately. If intra-arterial injection is suspected, local catheter-directed anticoagulation and thrombolysis should be performed if possible. This may be completed by systemic anticoagulation. Early administration of systemic steroids may help to reduce inflammation. 7
Recommendation 5
To prevent inadvertent paravenous or intraarterial injection we recommend using ultrasound guidance for both foam and liquid sclerotherapy when the target vein is not visible or palpable (GRADE 1C)
Recommendation 6
We recommend local catheter-directed anticoagulation and thrombolysis if applicable possibly followed by systemic anticoagulation if intra-arterial injection is suspected. Early administration of systemic steroids may help to reduce inflammation. (GRADE 1C).
Skin necrosis and embolia cutis medicamentosa
Skin necroses have been described after paravenous injection of sclerosants in higher concentrations and rarely after properly performed intravascular injection with sclerosants in low concentrations. It has been shown that subcutaneous paravenous injection of liquid or foamed polidocanol was not responsible for skin necrosis after reticular veins or telangiectasias. In the latter case, a mechanism involving passage of the sclerosant into the arterial circulation via arteriovenous anastomoses or veno-arterial reflex-vasospasm has been suggested. In individual cases, this has been described as embolia cutis medicamentosa or Nicolau phenomenon.
Recommendation 7
To reduce the risk of skin necrosis we recommend to avoid high volume injections. The sclerosant should be injected with minimal pressure. (GRADE 1C).
Visual disturbances, headache and migraine
Transient migraine-like symptoms may be observed after any kind of sclerotherapy. They occur more common after foam sclerotherapy than after liquid sclerotherapy.5,6 It has been suggested that a right-to-left shunt (e.g. PFO), which is present in approximately 30% of the general population, might be a factor, allowing foam bubbles to pass into the arterial circulation.9,10
Visual disturbances occurring after sclerotherapy may correspond to migraine with aura and not to transient ischemic cerebro-vascular events. 11
Visual disturbances can be associated with paraesthesia and dysphasic speech disturbance depending on the extension of the cortical spreading depression which is the pathological correlate of migraine with aura. There is no clear evidence of a relationship between bubbles and visual or neurological disturbances. Recent evidence has shown release of endothelin 1 from the vessel injected with liquid or foamed sclerosants.11,12 Up to now, no abnormality has been observed at ophthalmic examination and no durable visual trouble has been reported.
Multiple injections with small single doses may possibly reduce the passage of the sclerosant into the deep veins.
Stroke and TIA
In early-onset neurological disturbances, also reported as “stroke” in published literature no intra-cerebral clots have been found. This entity seems not to correspond to thromboembolic pathology.6,7,8,9,13,14 In such cases air bubbles in brain arteries have been reported.8,9
Among strokes reported after sclerotherapy, we must distinguish strokes related to paradoxical clot venous embolism usually with a delayed onset of symptoms, which have also been reported following various methods of treatment of varicose veins, and strokes related to paradoxical air embolism with an early onset, which is a specific complication of foam sclerotherapy.9,13,14
It is essential to notice that all patients with stroke after sclerotherapy related to paradoxical air embolism with an early onset have had a complete or near complete recovery. No stroke with significant after effects has been reported in these cases to date. 13
Isolated cases of confirmed stroke or TIA with delayed onset have been described both after liquid and foam sclerotherapy representing paradoxical thromboembolism.
Recommendation 8
For patients who have experienced neurological symptoms including migraine after previous sclerotherapy sessions we recommend:
The patient should remain lying down for a longer period of time (GRADE 2C) Avoid injection of large volumes of foam or perform liquid sclerotherapy (GRADE 2C) The patient should avoid performing a Valsalva manoeuvre in the early period after the injection (GRADE 2C) Decide on a case-by-case basis (perform a benefit-risk assessment based on the particular indication) (GRADE 2C)
Deep venous thrombosis (DVT) and pulmonary embolism (PE)
In table 1, distal DVT is listed as “severe complication” even though it may individually correspond to “benign complications” (e.g. asymptomatic calf vein DVT). Few published data are available to assess the actual frequency of DVT occurring after liquid sclerotherapy. Most of the studies reporting the outcome in patients treated with liquid sclerotherapy are old and no duplex ultrasound assessment was carried out. Symptomatic and asymptomatic DVTs are not often clearly distinguished in studies, while the clinical consequences are probably different.
Severe thromboembolic events (proximal DVT, pulmonary embolism) occur very rarely after sclerotherapy. The overall frequency of thromboembolic events is <1%; in the meta-analysis of Jia 15 the frequency of DVT was 0.6%. Most of the DVTs are distal. Most of the cases detected by duplex ultrasound imaging during routine follow-up are asymptomatic.2,5,6,16 The use of larger volumes of sclerosant, particularly in the form of foam, increases the risk of a thrombosis. 17 The same applies to patients with a previous history of thromboembolism or thrombophilia. In such patients with these risk factors the benefit-risk-ratio must be well established and additional prophylactic measures should be taken.17,18 Other risk factors, such as overweight or lack of mobility, have to be considered.
Recommendation 9
In patients with a high risk of thromboembolism such as those with a history of spontaneous DVT or known severe thrombophilia we recommend:
Use of pharmacological thromboprophylaxis in line with current guidelines/recommendations (GRADE 1C) Implement physical prophylaxis (compression, movement) (GRADE 1C) Avoid the injection of large volumes of foam (GRADE 1C) Decide on a case-by-case basis (perform a benefit-risk assessment based on the particular indication) (GRADE 1C)
Superficial venous thrombosis
In literature frequencies between 0% and 45.8% with a mean value of 4.7% are reported;5,7,15 however, the definition of phlebitis after sclerotherapy in the literature is controversial. An inflammatory reaction in the injected part of the vein should not be interpreted as phlebitis, whereas superficial vein thrombosis in a non-injected vein would fulfil this definition. Superficial vein thrombosis after sclerotherapy occurs, but the real frequency is unknown.
Motor nerve injury
The incidence of nerve injury after sclerotherapy is very rare and lower than after other treatment methods for varicose veins.
Residual pigmentation
Skin pigmentation has been reported with frequencies ranging from 0.3% to 30% in the short term. In general, this phenomenon resolves slowly in weeks or months. The incidence of pigmentation is likely to be higher after foam sclerotherapy. Intravascular clots should be removed by needle aspiration or stab incision and coagulum expression to reduce the incidence of pigmentation. In addition, post-sclerotherapy UV exposition should be avoided for the first two weeks after sclerotherapy.
Recommendation 10
To reduce the risk of pigmentation we recommend the removal of superficial clots. (GRADE 1C)
Matting
Matting, new occurrence of fine telangiectasias in the area of a sclerosed vein, is an unpredictable individual reaction of the patient and can also occur after surgical or thermal ablation of a varicose vein. Inadequate or no treatment of the underlying reflux is the cause in many cases of matting. High initial concentrations or large volumes of sclerosant can also result in inflammation or excessive vein obstruction with subsequent angiogenesis. Treatment of matting should concentrate on the underlying reflux and residual patent veins using low concentrations of sclerosant or phlebectomy.
Others
Other general or local transient reactions after sclerotherapy include feeling of tightness in the chest, vaso-vagal reactions, nausea, metallic taste, intravascular coagula, haematomas, ecchymoses at the injection site, pain at the injection site, local swelling, indurations, wheals, blisters and erythema. Additionally, complications may arise due to the compression bandage, such as blister formation (e.g. blisters in the area of an adhesive plaster).
Recommendation 11
To improve general safety of foam sclerotherapy we recommend:
Injecting a highly viscous foam into varicose veins (C2) (Level 1C) Avoiding patient or leg movement for a few minutes after injection, avoiding an Valsalva manoeuvre by the patient (Level 1C)
The type of gas (air or physiological gas) used to prepare foam is a controversial topic. If high volumes of foam are injected, the use of low-nitrogen-sclerosing foam seems to reduce early-onset reversible side effects. Recently no benefits on neurological disturbances in patients treated with CO2-O2-based foam compared to air-based foam in low volumes have been demonstrated.
Contraindications
Recommendation 2
We recommend to consider the following absolute and relative contraindications (GRADE 1C)
Absolute contraindications17,19,20
○ Known allergy to the sclerosant ○ Acute deep vein thrombosis (DVT) and/or pulmonary embolism ○ Local infection in the area of sclerotherapy or severe generalised infection ○ Long-lasting immobility and confinement to bed ○ Known symptomatic right-to-left shunt (e.g. symptomatic patent foramen ovale)
For foam sclerotherapy in addition:
Relative contraindications (individual benefit-risk-assessment mandatory):19,20
○ Pregnancy ○ Breast feeding (interrupt breast feeding for 2–3 days) ○ Severe peripheral arterial occlusive disease ○ Poor general health ○ Strong predisposition to allergies ○ High thromboembolic risk (e.g. history of thromboembolic events, known severe thrombophilia, hypercoagulable state, active cancer) ○ Acute superficial venous thrombosis ○ Neurological disturbances, including migraine, following previous foam sclerotherapy
For foam sclerotherapy in addition:
Anticoagulation treatment per se is not a contraindication to sclerotherapy.
Patient informed consent
Recommendation 12
Before sclerotherapy, we recommend to inform the patients about:
Alternative treatment methods with their pros and cons (GRADE 1B) Details of the sclerotherapy procedure and the post-treatment management (GRADE 1B) Serious risks (GRADE 1B) Frequently occurring adverse events (GRADE 1B) With regard to the sclerotherapy treatment outcome to be expected, patients should be informed (GRADE 1B)
about the success rate and rate of recurrence to be expected that short- and mid-term follow-up may be required that further sclerotherapy may be necessary in some cases, especially in the treatment of large varicose veins that foam sclerotherapy is more effective than liquid sclerotherapy(GRADE 1A) and that ultrasound guidance may help prevent intra-arterial injection, but that certain adverse reactions may be more frequent (see section Complications and risks). Where applicable, the patient should be informed about the off label-use of medicinal products and foaming of the sclerosing agent (GRADE 1B)