A. KURSAT BOZKURT, MDA. KURSAT BOZKURT, MD

University of Istanbul University of Istanbul Cerrahpasa Medical FacultyCerrahpasa Medical Faculty

20112011

SCLEROTHERAPY

Treatment of CEAP 1Treatment of CEAP 1

Guidelines for liquid or foamGuidelines for liquid or foam(Modified from: Handbook of venous disorders, Guidelines of the (Modified from: Handbook of venous disorders, Guidelines of the

American Venous Forum, 2009)American Venous Forum, 2009)

Vein sizeVein size Sodium Sodium TetradecylsulfateTetradecylsulfate

PolidocanolPolidocanol

TelangiectasiasTelangiectasias 0.124-0.25%0.124-0.25% 0.5%0.5%

1-3 mm1-3 mm 0.5-0.75%0.5-0.75% 0.75-1%0.75-1%

3-6 mm3-6 mm 1-3%1-3% 2-3%2-3%

>6 mm>6 mm FoamFoam FoamFoam

Sapheno-femoral Sapheno-femoral and sapheno-and sapheno-popliteal ins.popliteal ins.

FoamFoam FoamFoam

Treatment of ≥ CEAP 2Treatment of ≥ CEAP 2

≥ ≥ CEAP 2CEAP 2 OptionsOptions!!

SurgerySurgery

Interventional TechniquesInterventional Techniques• LaserLaser• RadiofrequencyRadiofrequency• Foam Foam SclerotherapySclerotherapy

Questions regarding Questions regarding Laser and Laser and RFRF!!

• CostsCosts (=surgery, > foam) (=surgery, > foam)• Long term dataLong term data

SafetySafety ComplicationsComplications

The aim of this presentation is toThe aim of this presentation is toreview the current data regarding review the current data regarding foam sclerotherapy for the treatment foam sclerotherapy for the treatment of superficial venous insufffiency of superficial venous insufffiency

In 1995, Antonio Luis Cabrera In 1995, Antonio Luis Cabrera reintroduced foam created using reintroduced foam created using carbon dioxide mixed with carbon dioxide mixed with polidocanolpolidocanol

Questions!Questions!1. Indications1. Indications2. Why foam instead of l2. Why foam instead of liquidiquid??3. Which sclerosant agent?3. Which sclerosant agent?4. How to make foam4. How to make foam

Concentration of agentConcentration of agent

5. How to administer (catheter directed ?)5. How to administer (catheter directed ?)6. Results6. Results7. Complications7. Complications

IndicationsIndications

Treating saphenous veins primarilyTreating saphenous veins primarily Incompetent tributariesIncompetent tributaries As complementing procedure to As complementing procedure to

endovenous laser, RF or surgeryendovenous laser, RF or surgery Postsurgical recurrencePostsurgical recurrence Venous malformationsVenous malformations Venous aneurysmsVenous aneurysms Saphenous and nonsaphenous perforating Saphenous and nonsaphenous perforating

veinsveins

Why foam?Why foam?

Liquid Sclerosants!Liquid Sclerosants!

May damage endothelium to cause May damage endothelium to cause fibrosisfibrosisBut: But:

Mixing with blood dilutes sclerosantMixing with blood dilutes sclerosant Causes sclero-thrombusCauses sclero-thrombus Leaves living adventia and mediaLeaves living adventia and media High recanalisation ratesHigh recanalisation rates

Foam!Foam!

Displaces bloodDisplaces blood Better endothelial Better endothelial

contactcontact Less sclero-thrombusLess sclero-thrombus CheaperCheaper Easy to follow Easy to follow

with Duplexwith Duplex

Foam SclerotherapyFoam Sclerotherapy

Ouvry P, Allaert FA, Desnos P, Hamel-Desnos C. Efficacy of polidocanol foam versus Ouvry P, Allaert FA, Desnos P, Hamel-Desnos C. Efficacy of polidocanol foam versus liquid in sclerotherapy of the great saphenous vein: a multicentre randomised controlled liquid in sclerotherapy of the great saphenous vein: a multicentre randomised controlled

trial with a 2-year follow-up. trial with a 2-year follow-up. Eur J Vasc Endovasc SurgEur J Vasc Endovasc Surg 2008; 2008;3636:366–70 :366–70

The relative efficacy of foam and liquid The relative efficacy of foam and liquid sclerotherapy has been investigatedsclerotherapy has been investigated

Either 2–2.5 mL of 3% POL liquid or foam Either 2–2.5 mL of 3% POL liquid or foam into the GSV under ultrasound guidanceinto the GSV under ultrasound guidance

On only one occasion.On only one occasion.

Successful obliteration•35% of liquid-treated patients and 85% of foam-treated patients after 3 weeks

•53% of foam-treated and 12% of liquid-treated patients after 2 years

SclerosantsSclerosants

PolidocanolPolidocanol Sodium tetradecyl sulphateSodium tetradecyl sulphate Sodium salicylateSodium salicylate Chromated glycerineChromated glycerine Hypertonic glucoseHypertonic glucose

Are there any difference?Are there any difference? Goldman MP. Treatment of varicose and telangiectatic leg veins: Goldman MP. Treatment of varicose and telangiectatic leg veins:

double-blind prospective comparative trial between aethoxyskerol and double-blind prospective comparative trial between aethoxyskerol and sotradecol Dermatol Surg. 2002 ;28(1):52-5sotradecol Dermatol Surg. 2002 ;28(1):52-5

129 patients were treated with either 129 patients were treated with either polidocanol or sodium tetradecyl sulfate polidocanol or sodium tetradecyl sulfate

All patients had an average of 70% All patients had an average of 70% improvement and were 70-72% satisfied improvement and were 70-72% satisfied in all vein categories treated with either in all vein categories treated with either solution solution

There was no significant difference in There was no significant difference in adverse effects between each group adverse effects between each group except for a decrease in ulcerations and except for a decrease in ulcerations and swelling in the polidocanol group swelling in the polidocanol group

Polidocanol might be better!Polidocanol might be better!(Mechanism of action of sclerotherapy, In: Goldman MP, Bergan JJ, (Mechanism of action of sclerotherapy, In: Goldman MP, Bergan JJ, Guex JJ. Sclerotherapy, 2007)Guex JJ. Sclerotherapy, 2007)

Less painLess pain Less cutaneous ulceration (<1% Less cutaneous ulceration (<1%

solution)solution) Allergic reactions Allergic reactions →→ rarerare Less pigmentationLess pigmentation

How to make foam?How to make foam?

Variety of Techniques to make foamVariety of Techniques to make foam– – Tessari, Monfreaux, machines Tessari, Monfreaux, machines

etcetc Variety of Concentrations (0.5% - Variety of Concentrations (0.5% -

3%)3%) Variety of GassesVariety of Gasses

– – Air, Oxygen / Carbon Dioxide Air, Oxygen / Carbon Dioxide mixesmixes

A 5 A 5 µµm intravenous filter can be m intravenous filter can be inserted between the syringes inserted between the syringes (Improves the quality of the foam!)(Improves the quality of the foam!)

One part of sclerosant to four parts of One part of sclerosant to four parts of gas seams idealgas seams ideal

The sclerosant may be sodium The sclerosant may be sodium tetradecyl sulphate 1–3% or tetradecyl sulphate 1–3% or polidocanol 0.5–3%.polidocanol 0.5–3%.

The mixture is oscillated vigorously The mixture is oscillated vigorously between the two syringes about 20 between the two syringes about 20 times times

Hamel-Desnos C, Ouvry P, Benigni JP, Hamel-Desnos C, Ouvry P, Benigni JP, et alet al. Comparison of 1% and 3% polidocanol foam . Comparison of 1% and 3% polidocanol foam in ultrasound guided sclerotherapy of the great saphenous vein: a randomised, double-in ultrasound guided sclerotherapy of the great saphenous vein: a randomised, double-

blind trial with 2 year-follow-up. ‘The 3/1 Study’. blind trial with 2 year-follow-up. ‘The 3/1 Study’. Eur J Vasc Endovasc SurgEur J Vasc Endovasc Surg 2007; 2007;3434:723–:723–9 9

Assessing the relative efficacy of 1% and Assessing the relative efficacy of 1% and 3% sclerosant foam3% sclerosant foam

Either 1% or 3% polidocanol foam, in a Either 1% or 3% polidocanol foam, in a single sessionsingle session

An average of 4.5 mL of foam An average of 4.5 mL of foam Immediate occlusion rates were 96% (3% Immediate occlusion rates were 96% (3%

foam) and 86% (1%) foamfoam) and 86% (1%) foam After two years saphenous occlusion was After two years saphenous occlusion was

seen in 69% and 68%seen in 69% and 68%

(In this study a rather small volume of foam was used (In this study a rather small volume of foam was used compared with the maximum of 10 mL recommended dose) compared with the maximum of 10 mL recommended dose)

The optimum ratio of gas to liquid is The optimum ratio of gas to liquid is 4:1, although a range of ratios is 4:1, although a range of ratios is reported in published work. reported in published work.

There is a wide variation in the There is a wide variation in the volume, but <10 ml seems safe and volume, but <10 ml seems safe and effective enaugheffective enaugh

How to administerHow to administer

Both saphenous trunks and major Both saphenous trunks and major tributaries may be treated through tributaries may be treated through an intravenous cannula or Butterfly an intravenous cannula or Butterfly needle needle (Foam and liquid sclerotherapy for varicose veins, P (Foam and liquid sclerotherapy for varicose veins, P Coleridge Smith, Phlebology. 2009;24 Suppl 1:62-72Coleridge Smith, Phlebology. 2009;24 Suppl 1:62-72

Catheter directed sclerotherapy Catheter directed sclerotherapy ((Catheter-Catheter-directed sclerotherapy, K Parsi directed sclerotherapy, K Parsi Phlebology 2009;24:98-107) Phlebology 2009;24:98-107)

Tumescent ELLE Tumescent ELLE (from Parsi et al)(from Parsi et al)

Access can be gained at the level of the knee to treat the proximal great saphenous vein or at medial ankle to treat the full length of the vein

Catheter is advanced to approximately 5 cm from the SFJ

Tumescent anaesthesia compresses the vein and achieves an ‘empty vein

Foam is injected as the catheter withdrawn

PainlessPainless Requires no power source and the cost of Requires no power source and the cost of

consumables lower than laser or consumables lower than laser or radiofrequency radiofrequency

Tumescent ensures minimal vessel Tumescent ensures minimal vessel diameter diameter → → especially useful for very large especially useful for very large veins veins

Progressive withdrawal of the catheter Progressive withdrawal of the catheter while injecting the sclerosant while injecting the sclerosant →→ good good distribution of foam along the length of the distribution of foam along the length of the target vessel. target vessel.

Parsi 2009Parsi 2009

Based on the current level of Based on the current level of evidence, no firm conclusion evidence, no firm conclusion regarding the efficacy of CDS regarding the efficacy of CDS techniques can be drawn in techniques can be drawn in comparison with EVLA or RFAcomparison with EVLA or RFA

Primary success rate is probably Primary success rate is probably higher than the standard UGShigher than the standard UGS

(No controlled trial!)(No controlled trial!)

Perforating vein treatmentPerforating vein treatment

The importance of compressionThe importance of compression

ResultsResults No good data!!No good data!!

Prospective, randomized Prospective, randomized controlled trials controlled trials comparing all comparing all endovascular modalities endovascular modalities (EVLA versus RFA (EVLA versus RFA versus foam) with versus foam) with traditional stripping are traditional stripping are necessarynecessary

Coleridge Smith P. Chronic venous disease treated by Coleridge Smith P. Chronic venous disease treated by ultrasound guided foam sclerotherapy. ultrasound guided foam sclerotherapy. Eur J Vasc Eur J Vasc

Endovasc SurgEndovasc Surg 2006; 2006;3232:577–83 :577–83

457 legs457 legs Follow-up: 6Follow-up: 6–46 –46 ((average 11average 11) )

monthsmonths DuDuplex examinationplex examination: O: Occlusion had cclusion had

been obtained in 322 of 364 been obtained in 322 of 364 GSV GSV (88%). SSV occlusion was present (88%). SSV occlusion was present in 118 of 143 (83%). in 118 of 143 (83%).

Mid Term Results of Ultrasound Guided Foam Sclerotherapy for Mid Term Results of Ultrasound Guided Foam Sclerotherapy for Complicated and Uncomplicated Varicose Veins. Complicated and Uncomplicated Varicose Veins. J.L. O'Hare et al, Eur J Vasc Endovasc Surg. 2008;36(1):109-13 . J.L. O'Hare et al, Eur J Vasc Endovasc Surg. 2008;36(1):109-13 .

Occlusion rates six months after foam sclerotherapy related to target vein

GSV SSV AASV Other Total

Occluded 48 (72%) 1 (20%) 12 (100%) 7 (88%) 68 (74%)

Partially occluded 7 (10%) 2 (40%) 0 (0%) 0 (0%) 9 (10%)

Patent 12 (18%) 2 (40%) 0 (0%) 1 (12%) 15 (16%)

Total 67 5 12 8 92

GSV great saphenous vein; SSV small saphenous vein, AASV anterior accessory saphenous

vein.

91% of the patients had single treatment session!

P Chapman-Smith and A Browne. Prospective five-year study of P Chapman-Smith and A Browne. Prospective five-year study of ultrasound-guided foam sclerotherapy in the treatment of great ultrasound-guided foam sclerotherapy in the treatment of great

saphenous vein reflux. saphenous vein reflux. Phlebology 2009;24:183-188Phlebology 2009;24:183-188

Number of treatments Average % Repeat UGFS N

Year 1 1–9 2.53 0 203

Year 2 1–7 2.0 16.5 188

Year 3 1–6 2.04 8.2 121

Year 4 1–6 2.43 6.7 75

Year 5 1–2 1.5 8.8 34

Rates of recurrence

Year 1 n = 167 (%)

Year 2 n = 108 (%)

Year 3 n = 72 (%)

Year 4 n = 32 (%)

Year 5 n = 23 (%)

Clinical recurrence

No venous symptoms

84 89 76 88 74

Minimal venous symptoms

16 11 18 12 22

Significant venous symptoms

0 0 6 0 4

Ultrasound recurrence

Venous closure 60 56 51 56 35

Any US recurrences

29 28 25 31 30

New varicose veins 4 8 8 0 17

Combined new/recurrent

7 7 15 13 17

Status of the saphenofemoral junction (SFJ) (n = 175)

Year 1 n = 120 (%)

Year 2 n = 78 (%)

Year 3 n = 55 (%)

Year 4 n = 28 (%)

Year 5 n = 18 (%)

SFJ closed 26 29 25 36 28

SFJ open and competent

33 34 35 21 28

SFJ open and incompetent

41 37 40 43 44

% efficacy 59 63 60 57 56

Comments of the authorsComments of the authors

All patients reported excellent resolution of All patients reported excellent resolution of venous symptoms after five years, despite venous symptoms after five years, despite demonstrable ultrasound recurrence. demonstrable ultrasound recurrence.

Further UGFS treatment maintained Further UGFS treatment maintained control of this recurrent diseasecontrol of this recurrent disease

Neovascularization characteristically seen Neovascularization characteristically seen after flush saphenous ligation is not seen after flush saphenous ligation is not seen after UGFS. after UGFS.

A statistically significant reduction in the A statistically significant reduction in the diameter of the GSV was demonstrated in diameter of the GSV was demonstrated in all cases of GSV reflux, sustained over the all cases of GSV reflux, sustained over the five-year period. five-year period.

The recent metaanalysis!The recent metaanalysis! van den Bos R, Arends L, Kockaert M, et al. Endovenous van den Bos R, Arends L, Kockaert M, et al. Endovenous

therapies of lower extremity varicosities are at least as therapies of lower extremity varicosities are at least as effective as surgical stripping or foam sclerotherapy: Meta-effective as surgical stripping or foam sclerotherapy: Meta-analysis and meta-regression of case series and analysis and meta-regression of case series and randomised clinical trials. J Vasc Surg 2009;49:230–239 randomised clinical trials. J Vasc Surg 2009;49:230–239

64 studies64 studies USG examinationUSG examination 12320 limbs12320 limbs Follow-up: 32monthsFollow-up: 32months

92,9

95,4

80,475,7

82,1

73,5

88,8

79,9

0

10

20

30

40

50

60

70

80

90

100

Laser Surg Foam RFA

3month

5year

ComplicationsComplications

Forlee reported a stroke patient Forlee reported a stroke patient following foam treatment that following foam treatment that highlights the potential hazard of highlights the potential hazard of injecting foam into varicose veinsinjecting foam into varicose veins

Such events are rare considering Such events are rare considering millions of patients who have been millions of patients who have been treated worldwide treated worldwide

Microembolism during Foam Sclerotherapy of Varicose Microembolism during Foam Sclerotherapy of Varicose Veins. Ceulen et al. NEJM, 358:1525-1526, 2008Veins. Ceulen et al. NEJM, 358:1525-1526, 2008

Transient scotoma and migraine attact in 2 Transient scotoma and migraine attact in 2 patients following foampatients following foam

Echocardiography detected a patent Echocardiography detected a patent foramen ovale in each foramen ovale in each

They monitored by echocardiography the They monitored by echocardiography the foam distribution during foam sclerotherapy foam distribution during foam sclerotherapy in 33 consecutive patientsin 33 consecutive patients

A single injection of 5 ml of 1% polidocanol A single injection of 5 ml of 1% polidocanol foam (air-to-liquid ratio, 4:1). foam (air-to-liquid ratio, 4:1).

In five patients, microembolism was also In five patients, microembolism was also detectable in the left atrium and ventricle detectable in the left atrium and ventricle

PFO and right-to-left shunt in 5 patientsPFO and right-to-left shunt in 5 patients

http://content.nejm.org/content/vol358/issue14/images/large/25f1.jpeg

Prevalence of PFO: 26% in the Prevalence of PFO: 26% in the general population.general population.

Serious neurologic symptoms Serious neurologic symptoms (scotomas, migraine, and stroke) (scotomas, migraine, and stroke) after foam sclerotherapy may occur after foam sclerotherapy may occur in 1-2% of patients in 1-2% of patients

Caution when foam sclerotherapy is Caution when foam sclerotherapy is performed in patients with a known performed in patients with a known patent foramen ovale!patent foramen ovale!

Routine echocardiography before Routine echocardiography before foam? foam?

Other complicationsOther complications

Respiratory problemsRespiratory problems Venous thromboembolismVenous thromboembolism Superficial thrombophlebitis (1-33%)Superficial thrombophlebitis (1-33%)

• Beyond the region treatedBeyond the region treated• Significantly worse inflammatonSignificantly worse inflammaton

Tissue necrosisTissue necrosis HematomasHematomas

Safety improvement techniquesSafety improvement techniques

Indwelling catheters (balloon Indwelling catheters (balloon tipped?)tipped?)

Volume reductionVolume reduction Non-air based foam Non-air based foam (70% CO(70% CO22/30%O/30%O22

would produce 7-40 times less adverse effects)would produce 7-40 times less adverse effects)

Pre-injection leg elevationPre-injection leg elevation Post-injection leg elevationPost-injection leg elevation

Personel viewPersonel view

LSV + SSV + PerforatorsLSV + SSV + PerforatorsCatheter thermoablation replaced Catheter thermoablation replaced open surgeryopen surgeryPersonel experience > 750 Personel experience > 750

patients! patients! Foam is a good option Foam is a good option →→ needs to needs to

prove safety and >5 years efficacy prove safety and >5 years efficacy for routine usagefor routine usage

Neurogical complications?Neurogical complications?

Importance of guidelinesImportance of guidelines

Guidelines for Radiofrequency (4.9.0)Guidelines for Radiofrequency (4.9.0)(Robert F. Merchant, Robert L. Kistner. In: Handbook of venous disorders, Guidelines of (Robert F. Merchant, Robert L. Kistner. In: Handbook of venous disorders, Guidelines of

the American Venous Forum, 2009)the American Venous Forum, 2009)

Grade of Grade of recommendation recommendation (1, we (1, we recommend; 2, we recommend; 2, we suggestsuggest

Grade of evidence Grade of evidence (A, high quality; (A, high quality; B,moderate B,moderate quality; C, low or quality; C, low or very low quality very low quality

Radiofrequency ablation of Radiofrequency ablation of the great saphenous vein is the great saphenous vein is safe and effective and we safe and effective and we recommend it for treatment recommend it for treatment for saphenous incompetencefor saphenous incompetence

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Clinical outcome after RF Clinical outcome after RF ablation of the saphenous ablation of the saphenous vein up to 5 years is vein up to 5 years is comparable to traditional comparable to traditional stripping and ligationstripping and ligation

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Guidelines for Endovenous Laser (4.10.0) Guidelines for Endovenous Laser (4.10.0) (Nick Morrison. In: Handbook of venous disorders, Guidelines of the American Venous (Nick Morrison. In: Handbook of venous disorders, Guidelines of the American Venous

Forum, 2009)Forum, 2009)

Grade of Grade of recommendation recommendation (1, we (1, we recommend; 2, we recommend; 2, we suggestsuggest

Grade of evidence Grade of evidence (A, high quality; (A, high quality; B,moderate B,moderate quality; C, low or quality; C, low or very low quality very low quality

Endovenous laser therapy of Endovenous laser therapy of the great saphenous vein is the great saphenous vein is safe and effective and we safe and effective and we recommend it for treatment recommend it for treatment for saphenous incompetencefor saphenous incompetence

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Clinical outcome after Clinical outcome after endovenous laser therapy 3 endovenous laser therapy 3 years is comparable to years is comparable to traditional stripping + traditional stripping + ligation and we recommend ligation and we recommend it for treatment of the it for treatment of the incompetent GSVincompetent GSV

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Guidelines for foam sclerotherapy (4.6.0)Guidelines for foam sclerotherapy (4.6.0)(Joshua I. Greenberg, Niren Angle, John Bergan. In: Handbook of venous disorders, (Joshua I. Greenberg, Niren Angle, John Bergan. In: Handbook of venous disorders,

Guidelines of the American Venous Forum, 2009)Guidelines of the American Venous Forum, 2009)

Grade of Grade of recommendation recommendation (1, we (1, we recommend; 2, we recommend; 2, we suggestsuggest

Grade of evidence Grade of evidence (A, high quality; (A, high quality; B,moderate B,moderate quality; C, low or quality; C, low or very low quality very low quality

We suggest the use of foam We suggest the use of foam sclerosant for the treatment sclerosant for the treatment of symptomatic reflux of the of symptomatic reflux of the GSV, C2-C6 varicose veins, GSV, C2-C6 varicose veins, and requrrent varicose veinsand requrrent varicose veins

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We suggest the use of foam We suggest the use of foam sclerotherapy to treat sclerotherapy to treat saphenous vein, tributary saphenous vein, tributary varicose vein, and perforator varicose vein, and perforator vein incompetence in vein incompetence in patients with venous ulcers, patients with venous ulcers, lipodermatosclerosis, and lipodermatosclerosis, and venous malformations when venous malformations when compared with conservative compared with conservative therapytherapy

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