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The History of Sclerosing Foams

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<strong>The</strong> <strong>History</strong> <strong>of</strong> <strong>Sclerosing</strong> <strong>Foams</strong><br />

JAN-CHRISTOPH G. R. WOLLMANN, MD<br />

Bad Kreuznach, Germany<br />

BACKGROUND. <strong>The</strong> use <strong>of</strong> foamed sclerosants in phlebology is<br />

undergoing a renaissance. <strong>The</strong> use <strong>of</strong> foam sclerotherapy was<br />

relaunched only a few years ago. Despite this, the early<br />

developments, pioneer findings, and improvements, especially<br />

in foaming techniques, are not widely recognized.<br />

OBJECTIVE. <strong>The</strong> objective <strong>of</strong> this study was to give an overview<br />

from the very beginnings <strong>of</strong> foam sclerotherapy until the most<br />

recent and progressive techniques, as described by Tessari or the<br />

double syringe system technique.<br />

RESULTS. <strong>The</strong> publications found after a thorough research for<br />

literature about foam sclerotherapy allow us to examine what<br />

has been invented between Orbach’s work in 1944 and now<br />

RESEARCH AND TRAVEL EXPENSES WERE PROVIDED BY KREUSSLER.<br />

THE USE <strong>of</strong> foamed sclerosants in phlebology is not<br />

new. Nevertheless, the worldwide use <strong>of</strong> this treatment<br />

was ‘‘relaunched’’ only a few years ago. <strong>The</strong> major<br />

national and international journals reflected the<br />

interest for this treatment option and for sclerotherapy<br />

in general, indicated by the increasing numbers <strong>of</strong><br />

lectures or publications on this subject. <strong>The</strong>y usually<br />

start with a reference to the ‘‘basic invention’’: the<br />

work <strong>of</strong> Egmont James Orbach in 1944. 1 Another<br />

frequently cited publication is the one by Juan Cabrera<br />

Garrido, who presented the results <strong>of</strong> his development<br />

in Spain in 1995. 2 A thorough research on literature<br />

about foam sclerotherapy revealed a series <strong>of</strong> highly<br />

interesting articles. <strong>The</strong>y allow us to look at what has<br />

been invented between 1944 and 1995, and—surprisingly—even<br />

before 1944. Basically, the literature<br />

shows that remarkable work was carried out in the<br />

field <strong>of</strong> noncommercial foam sclerotherapy and that<br />

sclerosing foams have been used by numerous doctors<br />

continuously for the past six decades, especially for the<br />

treatment <strong>of</strong> varicose veins <strong>of</strong> the lower limbs.<br />

Results<br />

A time table gives an overview <strong>of</strong> the major achievements<br />

and developments <strong>of</strong> sclerotherapy with foam<br />

(Figure 1). <strong>The</strong> following is a presentation <strong>of</strong> the<br />

Address correspondence and reprint requests to: Jan-Christoph G. R.<br />

Wollmann, MD, Rheinstrasse 29, D-55543 Bad Kreuznach, Germany,<br />

or e-mail: jan-christoph.wollmann@kreussler.de.<br />

r 2004 by the American Society for Dermatologic Surgery, Inc. Published by Blackwell Publishing, Inc.<br />

ISSN: 1076-0512/04/$15.00/0 Dermatol Surg 2004;30:694–703<br />

and—surprisingly—even before 1944. <strong>The</strong> contributions <strong>of</strong><br />

greatly reputed and also <strong>of</strong> unknown colleagues, such as Orbach,<br />

Sigg, Mayer, or Flückiger, are presented, giving a historical<br />

overview from the very beginnings <strong>of</strong> foam sclerotherapy until<br />

the most recent techniques. Basically, the literature shows that<br />

remarkable work was carried out in the field <strong>of</strong> noncommercial<br />

foam sclerotherapy and that sclerosing foams have been used by<br />

numerous doctors continuously for the past six decades,<br />

especially for the treatment <strong>of</strong> varicose veins <strong>of</strong> the lower limbs.<br />

CONCLUSION. <strong>The</strong> use <strong>of</strong> foamed sclerosing agents in therapy <strong>of</strong><br />

large or small varicose veins is not new. It started as early as<br />

1939 and has continuously been improved in the past decades.<br />

individual authors and an attempt to show their<br />

respective contributions.<br />

1939—Stuard McAusland: 3 First Use <strong>of</strong> Froth in<br />

Telangiectasia with Shaking-the-Vial Technique<br />

<strong>The</strong> literature database search did not reveal any<br />

earlier publication than the one <strong>of</strong> McAusland. He<br />

proposed the use <strong>of</strong> a ‘‘froth’’ in telangiectasia. <strong>The</strong><br />

foam he prepared was obtained by simply shaking the<br />

rubber-capped bottle that was filled with sodium<br />

morrhuate, and then the froth was aspirated into a<br />

syringe. He treated spider veins or telangiectasia,<br />

where he noticed that the ‘‘veins suddenly got pink,<br />

sometimes retracted and almost disappeared at once.’’<br />

This probably means (stronger) inflammatory reaction,<br />

vasospasm, and fast efficacy <strong>of</strong> the froth in<br />

telangiectasia.<br />

1944—Egmont James Orbach: 1 Air-Block Technique<br />

and Displacement <strong>of</strong> Blood<br />

Although frequently cited, Orbach’s 1944 publication<br />

does not deal with foam at all. Instead, he used two<br />

‘‘conventional liquid’’ techniques for his patients:<br />

smaller veins were punctured and treated while the<br />

patient was standing (‘‘full-vein technique’’); in contrast,<br />

he used the ‘‘empty-vein technique,’’ in which<br />

large-diameter varicose vein segments were first isolated<br />

between two tourniquets. <strong>The</strong>n, after venipuncture,<br />

the leg was elevated 451 to 901. By releasing the


Dermatol Surg 30:5:May 2004 WOLLMANN: THE HISTORY OF SCLEROSING FOAMS 695<br />

Figure 1. Overview about the contributions to foam sclerotherapy.<br />

proximal tourniquet, blood could flow into the central<br />

or more proximal direction, while the distal tourniquet<br />

reduced or eliminated the supply <strong>of</strong> new blood from<br />

distally. This technique caused less dilution <strong>of</strong> the<br />

liquid sclerosing agent.<br />

Nevertheless, he sometimes noticed therapeutic<br />

failures, so he had the ‘‘famous idea’’: to intensify the<br />

contact between the sclerosant and the endothelium,<br />

the diameter <strong>of</strong> the vein should not only be reduced as<br />

far as possible prior to injection, but the vein should be<br />

rather free from any blood. <strong>The</strong>refore, he injected a<br />

small amount <strong>of</strong> air into the venous segment to be<br />

treated to completely displace the remaining blood (see<br />

Figure 2).<br />

Experimentally, he had shown that 1 cm 2 <strong>of</strong> air<br />

injected into a 6-mm infusion tube pending vertically<br />

and filled with water did not separate into several<br />

ascending bubbles but remained in the area <strong>of</strong><br />

injection as one large bubble, if the injection was not<br />

given too slowly. He then injected a colored solution<br />

into this air bubble, which, over a period <strong>of</strong> 3 to 5 s,<br />

did not get mixed with water but remained undiluted<br />

in the ‘‘air pocket.’’<br />

Clinically, he used the ‘‘air-block technique’’ only<br />

for smaller and medium-sized varicose veins; He<br />

recommended the conventional technique, without<br />

air injection, for larger veins. Unfortunately, Orbach’s<br />

article does not reveal the reasons for this recommendation.<br />

It remains unclear why the method that he<br />

considered to be more effective should not be suited<br />

for large varicose veins which usually were more<br />

difficult to treat. In 1970, Stemmer 4 et al. showed in an<br />

experiment that the air-block technique was only<br />

reliable with vessel diameters <strong>of</strong> up to 4 mm and was<br />

never successful with diameters <strong>of</strong> more than 8 mm.<br />

Sclerosis was rather impeded with such diameters: <strong>The</strong><br />

air bubble floating on the blood column protected the<br />

vessel from contact with the sclerosant at the upper<br />

Figure 2. <strong>The</strong> air-block technique: a small amount <strong>of</strong> air was injected<br />

before (top) the injection <strong>of</strong> sclerosant (bottom) to avoid dilution <strong>of</strong> the<br />

liquid.<br />

Figure 3. <strong>The</strong> air-block technique in large vessels: A floating air<br />

bubble (top) was able to prevent contact between the endothelium on<br />

the upper vessel wall and the sclerosant.<br />

circumference (see Figure 3), thus being effective only<br />

partially. <strong>The</strong> original air-block technique is basically<br />

no longer used today, but its development to a ‘‘foam<br />

block’’ (air block with large-bubbled foams) is still<br />

used today by some phlebologists under various names<br />

for smaller vessels. Small advantages in efficacy<br />

(increase by 20%) are believed to be outweighed by<br />

the disadvantages (plus 100% side effects). 5 <strong>The</strong><br />

maximum amount <strong>of</strong> air injected was 3 mL, a limit<br />

that became an orientation for most physicians using<br />

the air-block technique.<br />

1944—Robert Rowden Foote: 6 Foam in Feeder<br />

Veins with Shaking-the-Syringe Technique<br />

In the same year as Orbach’s publication, a book by<br />

Robert Rowden Foote was published in London. In<br />

addition to an overview <strong>of</strong> his ‘‘empty-vein technique,’’<br />

he wrote about the treatment <strong>of</strong> spider veins: ‘‘<strong>The</strong><br />

feeder vein should be dealt with first, whenever<br />

possible. <strong>The</strong> best injection fluid is the soapy froth<br />

obtained by shaking up 1 cc <strong>of</strong> ethamoline (ethanolamine<br />

oleate) in a 2-cc syringe. [It should be<br />

mentioned that the ratio <strong>of</strong> 1 plus 1 is, strictly<br />

speaking, not foam but an air/liquid dispersion.<br />

Usually a mixture is defined as foam if the gas portion<br />

is higher than 0.52. 7 A characteristic order <strong>of</strong><br />

magnitude <strong>of</strong> gas/fluid systems is the gas proportion<br />

j. Depending on the gas proportion, distinction is<br />

made between gas dispersion, spherical foam (wet<br />

foam), and polyhedral foam (dry foam). In gas<br />

dispersions, there are individual air bubbles in liquid;<br />

the gas proportion j is less than 0.52. In the spherical<br />

foam, the number <strong>of</strong> individual bubbles is higher—<br />

there is still a rather high amount <strong>of</strong> liquid; the gas


696 WOLLMANN: THE HISTORY OF SCLEROSING FOAMS Dermatol Surg 30:5:May 2004<br />

proportion is 0.524j40.74. In the polyhedral foam,<br />

in contrast, the amount <strong>of</strong> liquid between the bubbles<br />

is so small that the individual bubbles get closer and<br />

closer to each other, thus forming polyhedrons. <strong>The</strong><br />

gas proportion j is greater than 0.74. In a foaming<br />

fluid (e.g., beer), all types generally occur, the<br />

polyhedral foam being above the spherical foam and<br />

the gas dispersion and liquid below.] Once the needle<br />

is in the vein, the bubbles can be made to course along<br />

the minute veins and can be followed visually in their<br />

transit.’’ Nowadays, ethanolamine oleate is no longer<br />

available in most countries. <strong>The</strong> ‘‘agitation technique’’<br />

was refined in the following years and is no longer in<br />

use. <strong>The</strong> air:sclerosant ratio <strong>of</strong> 1 plus 1 described by<br />

Foote suggests that the dispersion was very fluid so<br />

that it could not be used for displacing the blood in<br />

larger diameter veins.<br />

1949—Karl Sigg: 8 Foam-Block Technique and<br />

Viscosity <strong>of</strong> Foam<br />

In 1949, Karl Sigg picked up the air-block technique<br />

described 5 years before: Also for other varices than<br />

spider veins, i.e., larger veins, he used the new<br />

technique and reported more than 4000 treatments<br />

performed ‘‘without problems.’’ Sigg describes the<br />

rationale for the use <strong>of</strong> the air-block technique in a<br />

similar manner as Orbach and Foote: ‘‘<strong>The</strong> purpose is<br />

to prevent the dilution <strong>of</strong> the solutions for injection in<br />

the vein by the blood and to ensure that the sclerosant<br />

gets in contact with the intima <strong>of</strong> the vein in a rather<br />

concentrated formy. Even with this small-scale use,<br />

the air bubble chased the blood before the injection<br />

fluid arrived and thus cleared the way for a closer<br />

contact <strong>of</strong> the sclerosant with the venous intima.’’<br />

Later, Sigg combined Orbach’s air-block technique<br />

and Foote’s foam application and thus introduced a<br />

new aspect into the therapeutic options known to that<br />

date: ‘‘Orbach’s method becomes even more beneficial<br />

if foam is injected instead <strong>of</strong> airy. This foam is less<br />

rapidly washed away in the varicose vein than it<br />

happens with the pure injection <strong>of</strong> air.’’ Thus Sigg<br />

introduced for the first time the idea (even if not<br />

pronounced) <strong>of</strong> increased viscosity <strong>of</strong> foam. With the<br />

use <strong>of</strong> foam, he improved the air-block technique<br />

(introducing a foam block), but without omitting the<br />

fluid sclerosant (see Figure 4). Sigg described his own<br />

procedure for the manufacture <strong>of</strong> foam; the glass<br />

syringe filled with fluid sclerosant was held with the<br />

opening pointing downward. Approximately 1 mL <strong>of</strong><br />

air was aspirated through it, pearls developed in the<br />

solution, and thus more or less large bubbles were<br />

generated in the syringe.<br />

Figure 4. <strong>The</strong> foam-block technique: First, foam was injected to<br />

maintain the displacing effect <strong>of</strong> the air block for a longer time (top),<br />

and then normal liquid sclerosant was injected (bottom).<br />

1950—Egmont James Orbach: 9,10 Vasospasm<br />

after Foam Sclerotherapy<br />

A later publication by Orbach reveals the first attempt<br />

to compare the efficacy <strong>of</strong> foam (administered as air<br />

block and foam) with the efficacy <strong>of</strong> fluid sclerosants.<br />

<strong>The</strong> end point was the length <strong>of</strong> the sclerothrombus<br />

generated by the injection <strong>of</strong> the respective substance.<br />

<strong>The</strong> efficacy <strong>of</strong> the foam generated by agitation <strong>of</strong> the<br />

syringe or drug vial was increased approximately 3.5to<br />

4-fold compared with the same amount <strong>of</strong> ‘‘conventional’’<br />

fluid. <strong>The</strong> observation <strong>of</strong> a ‘‘marked<br />

vasospasm’’ after injection <strong>of</strong> foam is nowadays<br />

considered to be an important immediate end point<br />

for the assessment <strong>of</strong> the efficacy <strong>of</strong> modern sclerotherapy.<br />

11–13 This (reversible) vasospasm, which is<br />

<strong>of</strong>ten clearly detectable in duplex-guided sclerotherapy,<br />

can be considered to be a sign <strong>of</strong> initial vascular<br />

damage after sclerotherapy. After administration <strong>of</strong> a<br />

viscous foam, vasospasm is more common and more<br />

pronounced than after sclerotherapy with conventional<br />

fluid. 42 An important factor in this respect is<br />

that a given volume <strong>of</strong> a blood-displacing foam can<br />

spread over a much longer venous segment after a<br />

vasospasm occurs and can even act at a certain<br />

distance from the site <strong>of</strong> administration. (For example,<br />

1 mL <strong>of</strong> a viscous foam completely fills a vein <strong>of</strong> 8 mm<br />

in diameter over a length <strong>of</strong> approximately 20 mm. A<br />

reduction <strong>of</strong> the vessel diameter owing to spasm to<br />

2 mm distributes the same foam volume to a length <strong>of</strong><br />

almost 32 cm. In vivo, a spasm <strong>of</strong> a mean length <strong>of</strong><br />

28 cm could be provoked with vessels <strong>of</strong> 4 to 8 mm in<br />

diameter and a foam application <strong>of</strong> 2 to 2.5 mL <strong>of</strong><br />

double-syringe-system foam.) As long as vasospasm<br />

exists, venipuncture at the same site is aggravated. <strong>The</strong><br />

use <strong>of</strong> small venous cannulae or catheters may help<br />

dealing with this.<br />

Because foams in current use are very different from<br />

those used by Orbach, it is impossible to draw<br />

conclusions about the general efficacy <strong>of</strong> foam from<br />

this experiment. Nevertheless, according to all findings<br />

and based on theoretical considerations, the efficacy <strong>of</strong><br />

foam is always higher than that <strong>of</strong> the same amount<br />

and concentration <strong>of</strong> fluid. <strong>The</strong> level <strong>of</strong> increased<br />

efficacy cannot be predicted in the individual case<br />

without sufficient standardization. <strong>The</strong> increased


Dermatol Surg 30:5:May 2004 WOLLMANN: THE HISTORY OF SCLEROSING FOAMS 697<br />

strength <strong>of</strong> foams needs to be respected if thinking<br />

about sclerosing smaller vessels with foam.<br />

1953—Arve Ree: 14 First Use <strong>of</strong> ‘‘Pure Foam’’<br />

<strong>The</strong> Norwegian doctor Ree introduced a new era in<br />

1953: He was the first to inject ‘‘pure’’ foam, not in<br />

addition to air and common fluid sclerosant but<br />

instead <strong>of</strong> the sclerosant and, in particular, without<br />

the previous injection <strong>of</strong> air. With his technique<br />

(agitation <strong>of</strong> a detergent solution in the vial and<br />

subsequent aspiration <strong>of</strong> the bubbles into the syringe)<br />

he first treated a series <strong>of</strong> 50 patients very successfully.<br />

He injected 2 to 7 mL <strong>of</strong> foam, depending on the vessel<br />

diameter, corresponding to an amount <strong>of</strong> air <strong>of</strong> up to<br />

6.6 mL. <strong>The</strong> bubble sizes seem to have been in the<br />

millimeter range with that technique. Owing to the<br />

higher kinetic energy (agitation <strong>of</strong> a vial and subsequent<br />

passage through a bottleneck with turbulent<br />

flow), it may be considered that a foam with smaller<br />

bubbles than with the previous techniques could be<br />

generated.<br />

1956—Peter Flückiger: 15 Retrograde Injection,<br />

Aspiration Technique, and Leg Elevation<br />

Flückiger recommended the technique known as<br />

‘‘retrograde sclerotherapy,’’ a technique characterized<br />

by leg elevation and sclerosant injection into saphenous<br />

veins from a proximal injection site in the distal<br />

direction. Thus, the sclerosant could reach all insufficient<br />

collaterals and the saphenous vein by one<br />

injection. He obtained better results by using sclerosing<br />

foam than with fluid sclerosants: ‘‘Basically, the<br />

procedure consists in injecting y Varsyl foam (ethanolamine<br />

oleate) into an appropriate vein. Due to the<br />

buoyancy, the foam has only a low tendency to move<br />

in central direction with the blood flowy. After<br />

removal <strong>of</strong> the needle, the location <strong>of</strong> the ‘‘foam seal’’<br />

can be determined by palpationy. <strong>The</strong> foam usually<br />

spreads in the surrounding <strong>of</strong> the injection site in distal<br />

and proximal direction. After injection, the intravascular<br />

foam depot y is displaced by manual massage<br />

against the periphery.’’ Flückiger additionally mentioned<br />

major aspects <strong>of</strong> modern foam sclerotherapy in<br />

his publication: He saw that the foam he used<br />

remained in the region <strong>of</strong> the injection site as a<br />

‘‘depot,’’ noticed that it was able to displace the blood<br />

in the proximal direction and was not washed away<br />

from the blood, and noticed that the foam could be<br />

directed to other regions by manual manipulation.<br />

Moreover, he postulated and discussed further treatment-relevant<br />

foam properties for the first time:<br />

Increased efficacy by increase <strong>of</strong> the effective surface<br />

<strong>of</strong> foam compared to fluid sclerosants;<br />

A stronger sclerosing effect with smaller amounts <strong>of</strong><br />

sclerosants;<br />

Postulation <strong>of</strong> a minimized bubble size; and<br />

Postulation <strong>of</strong> homogeneity <strong>of</strong> foam.<br />

It is obvious that a given amount <strong>of</strong> sclerosant in the<br />

form <strong>of</strong> foam has a much larger surface than it has in<br />

an unchanged, fluid state: the smaller the bubbles <strong>of</strong><br />

the foam are, the greater the surface. Since damage to<br />

the intima y is based on the contact <strong>of</strong> the intima<br />

with the sclerosant, the use <strong>of</strong> foam allows an<br />

extended sclerosation with a small amount <strong>of</strong> sclerosant.<br />

<strong>The</strong> preparation <strong>of</strong> a homogenous, fine-bubbled<br />

foam is an important condition for the success <strong>of</strong> the<br />

procedure.<br />

(<strong>The</strong> homogeneity <strong>of</strong> foam, i.e., a foam whose<br />

bubbles are as homogenous as possible, is an<br />

important prerequisite for its flow behavior (viscosity)<br />

and its stability. Ideally, a foam has only bubbles <strong>of</strong> the<br />

same diameter, which is, in reality, barely or never<br />

feasible. Foam is subjected to aging, which involves<br />

mainly two aspects: In contrast, the fluid that is<br />

between the gas bubbles in a young foam drains owing<br />

to the force <strong>of</strong> gravity, so that the upper bubbles slowly<br />

break down because <strong>of</strong> the ‘‘fluid deficiency.’’ In<br />

contrast, bubbles disappear because a gas diffusion<br />

takes place between the foam bubbles. <strong>The</strong> internal gas<br />

pressure is higher in small bubbles owing to the higher<br />

surface tension, so that gas moves from those bubbles<br />

into larger bubbles. Smaller bubbles <strong>of</strong> a foam get even<br />

smaller and large ones even larger—until they break<br />

down. In a homogenous foam, all bubbles would have<br />

the same inner gas pressure. A gas diffusion from one<br />

bubble to the adjacent bubble would not take place<br />

and the foam would remain stable until just the drain<br />

process would contribute to aging.)<br />

Flückiger considered the various known foam<br />

manufacturing procedures, and suggested his own<br />

new technique: ‘‘In order to obtain a homogenous finebubbled<br />

foam, the procedure consisting in the agitation<br />

<strong>of</strong> a syringe filled with air and sclerosant<br />

[Orbach’s technique 1950] is completely inappropriate.<br />

<strong>The</strong> drawing <strong>of</strong> air through a sclerosant in the<br />

syringe [Sigg’s technique 1949] does not yield a small<br />

fine-bubbled foam either. Moreover, none <strong>of</strong> these<br />

methods is able to convert the entire amount <strong>of</strong><br />

sclerosant into foam. <strong>The</strong>re is always a certain amount<br />

<strong>of</strong> remaining fluid, which cannot be used for retrograde<br />

sclerotherapy with the elevated leg. A perfect,<br />

fine-bubbled foam is obtained by the simultaneous<br />

aspiration <strong>of</strong> sclerosant y and air through a thin<br />

injection needley. <strong>The</strong> thin injection needle (the<br />

narrower the lumen, the finer the foam) y is


698 WOLLMANN: THE HISTORY OF SCLEROSING FOAMS Dermatol Surg 30:5:May 2004<br />

Figure 5. <strong>The</strong> aspiration technique: <strong>The</strong> tip <strong>of</strong> the needle was placed<br />

at the liquid–air interface, thus allowing coaspiration <strong>of</strong> air and<br />

sclerosant that would generate foam in one run.<br />

introduced into the ampoule in such a way that<br />

approximately two thirds <strong>of</strong> the opening <strong>of</strong> the bevel<br />

are imbibed in the fluid (see Figure 5). When drawing<br />

back the plunger, the syringe fills with Varsyl foam<br />

under a sizzling noise, the foam remaining stable for<br />

several minutes.’’<br />

1957: Heinz Mayer and Hans Brücke: 16 First<br />

Micr<strong>of</strong>oam Device (Double-Piston Syringe)<br />

A milestone regarding the improvement and standardization<br />

<strong>of</strong> sclerosing foam was the publication by two<br />

surgeons Mayer and Brücke: they described the first<br />

device that had been developed specifically for the<br />

preparation <strong>of</strong> viscous sclerosing foams, a syringe with<br />

a double plunger (see Figure 6). (A double-plunger<br />

syringe following the principle <strong>of</strong> Mayer-Brücke was<br />

‘‘reinvented’’ several times in the following decades. A<br />

very homogenous, extremely fine microbubble foam<br />

can be produced using a simple reproduction <strong>of</strong> that<br />

syringe—unfortunately, the original is no longer<br />

available. More than 40 years ago, Mayer and Brücke<br />

worked with foams that are now suggested to be<br />

classified as ‘‘micr<strong>of</strong>oam.’’ 17 )<br />

‘‘Before the main plunger, there is a second, thin<br />

plunger with numerous holes, whose piston leads to a<br />

central bore <strong>of</strong> the main plunger and protrudes it.<br />

When the main plunger is fixed, the plunger provided<br />

with holes can rapidly be moved forward and backward<br />

and the Phlebocid (ethanolamin oleate) can be<br />

mixed with the air contained in the syringe. A finebubbled,<br />

viscous foam developsy. We have tested<br />

Figure 6. <strong>The</strong> Mayer-Brücke device: <strong>The</strong> inner plunger with numerous<br />

tiny holes can rapidly be moved forward and backward to mix<br />

sclerosant and air contained in the syringe. <strong>The</strong> outer plunger was used<br />

for injection <strong>of</strong> the viscous and fine-bubbled foam.<br />

most sclerosants <strong>of</strong> similar composition and selected<br />

Phlebocid, which provides the stiffest foam upon<br />

agitation with a homogenous distribution <strong>of</strong> air<br />

bubblesy. We consider the greatest advantage <strong>of</strong> the<br />

use <strong>of</strong> foam y to be the homogenous distribution <strong>of</strong><br />

the sclerosanty.’’ Clinically, they stated after administration<br />

<strong>of</strong> foam: ‘‘<strong>The</strong> fibrous tissue <strong>of</strong> the venous<br />

lumen is so complete that in general, recanalizationydoes<br />

not occur. We never observed recurrent<br />

varicose veins after using Phlebocid foam. We never<br />

observed complications after foam filling such as air<br />

embolisms or skin necroses.’’<br />

1962—Peter Flückiger: 18 Turbulent Flow<br />

In 1962, Flückiger described another technique for the<br />

preparation <strong>of</strong> foam: pumping <strong>of</strong> air and sclerosant<br />

forward and backward between a drug vial and the<br />

attached syringe. Later, this technique was modernized<br />

and improved by Alessandro Frullini 19,20 by adding an<br />

adapter between the syringe and the bottle seal.<br />

Furthermore, Flückiger changed some points since<br />

his first publication in 1956: he maintained leg<br />

elevation not only during sclerotherapy but also for<br />

some minutes thereafter, to allow the foam to degrade.<br />

He warned therapists to be cautious while ‘‘stroking’’<br />

the foam seal in a peripheral direction to prevent any<br />

unintended movement <strong>of</strong> foam into the deep venous<br />

system. Today, it is recommended that you wait some<br />

minutes after foam sclerotherapy <strong>of</strong> large veins before<br />

applying compression. 42<br />

1963—Peter Lunkenheimer: 21 First Use <strong>of</strong><br />

Polidocanol Foam<br />

Even before polidocanol received its first marketing<br />

authorization, a German physician had the chance to<br />

use the novel sclerosing solution for research purposes<br />

for the first time. Kreussler’s archives revealed a letter<br />

from that phlebologist, which contains a written ‘‘case<br />

report’’ about the first patient treatment: ‘‘<strong>The</strong> first<br />

patient was treated with 2 mL Aethoxysklerol s<br />

foamy.’’


Dermatol Surg 30:5:May 2004 WOLLMANN: THE HISTORY OF SCLEROSING FOAMS 699<br />

1969—Walter Gillesberger: 22 Low-Pressure<br />

Technique<br />

Gillesberger’s technique was based on the generation<br />

<strong>of</strong> a negative pressure in a (glass) syringe, so that air<br />

could enter through the capillary gap between the<br />

syringe piston and the plunger and thus generate<br />

bubbles (see Figure 7). Gillesberger’s syringe was not<br />

closed hermetically like the Monfreux syringe tip later<br />

on, but the negative pressure was strong enough to<br />

create a foam and was not compensated by the inflow<br />

<strong>of</strong> the sclerosant from the vial. <strong>The</strong> technique by<br />

Gillesberger or its refinement by Monfreux, who<br />

generated foam with an ‘‘absolute’’ negative pressure,<br />

is very simple. What is problematic is that there is no<br />

standardized ratio between air and sclerosant. <strong>The</strong>refore,<br />

the foams produced in that manner are different,<br />

depending on the syringe type, needle, generated<br />

suction, and the resulting gas content; they may be<br />

more fluid one time and more viscous another time.<br />

This leads to different behavior in the vessel (degree<br />

and duration <strong>of</strong> the displacement <strong>of</strong> blood) and thus<br />

probably to an unpredictable efficacy in vivo. (<strong>The</strong><br />

ability <strong>of</strong> foam to displace blood depends on its quality<br />

or characteristics: foams obtained with low sclerosant<br />

concentrations, with small amounts <strong>of</strong> air, and/or with<br />

rather large bubbles have a more or less fluid behavior;<br />

i.e., they are more easily washed away by liquids<br />

(blood) and have no or just a small and short-term<br />

displacing effect. Viscous foams (higher concentration,<br />

higher gas content, and small bubbles), in contrast,<br />

basically have a displacing effect in larger vessels. 41 If<br />

sclerosing foam is to be used for small diameter veins,<br />

precaution is recommended owing to the enhancement<br />

<strong>of</strong> the efficacy. A viscous foam would probably have<br />

too a strong effect in small veins; moreover, the foam<br />

breaks down as a result <strong>of</strong> the passage through the<br />

required fine needles. 42<br />

Figure 7. <strong>The</strong> low-pressure technique: Pulling down the piston<br />

allowed air to enter the syringe through the tiny gap between the<br />

syringe piston and the plunger.<br />

1984—Gerald Hauer: 23 Twin-Syringe Technique<br />

Hauer patented a twin-syringe set for foam preparation:<br />

Two parallel syringes, one filled with air, the<br />

other one filled with sclerosing solution, are simultaneously<br />

emptied into a ‘‘mixing chamber’’ by pressure,<br />

which leads to the formation <strong>of</strong> bubbles. <strong>The</strong> ratio <strong>of</strong> 1<br />

plus 1 (sclerosing agent and air) suggests a dispersion<br />

that should have the effect <strong>of</strong> a foam block.<br />

1986—Michael Grigg: 24 Double Syringes and<br />

Connecting Tubes<br />

In 1986, Grigg demonstrated a new foam production<br />

procedure: the principle was the generation <strong>of</strong> a<br />

turbulent flow between two syringes, connected via a<br />

plastic infusion tube, so that fluid and air could be<br />

pumped forward and backward. Belcaro later improved<br />

this technique by the addition <strong>of</strong> a further<br />

strongly foaming detergent solution in small amounts<br />

(0.1–0.2 mL). (‘‘Improved’’ in this context means<br />

prolongation <strong>of</strong> half-life. Owing to the commonly<br />

relevant amount <strong>of</strong> silicone in disposables (syringes<br />

and infusion tubes, etc.), the half-life <strong>of</strong> the foam was<br />

evidently limited because silicone, which destroys the<br />

surfactant arrangement <strong>of</strong> the foam lamellae, is a very<br />

strong foam breaker. <strong>The</strong>refore, anything that contributes<br />

to the maintenance <strong>of</strong> foam bubbles supports<br />

the foam stability: this is, in addition to an increase <strong>of</strong><br />

the surfactant concentration, in particular the minimization<br />

<strong>of</strong> the amount <strong>of</strong> silicone.) According to him,<br />

the foam half-life was approximately 4 min. This socalled<br />

‘‘Irvine technique’’ (named after the laboratory<br />

in which the technique was demonstrated) can be<br />

considered to be a precursor <strong>of</strong> Tessari’s technique and<br />

the double-syringe system (DSS). Belcaro and coworkers<br />

24 first performed investigations on the safety <strong>of</strong><br />

the foam generated according to that technique: 5 to<br />

10 mL <strong>of</strong> the foam produced with that technique did<br />

not cause any change <strong>of</strong> the pulmonary ventilation<br />

scintigraphy or perfusion scintigraphy in 12 patients.<br />

1995—Juan Cabrera Garrido: 2 Rotating Brush<br />

Technique<br />

In 1995, Cabrera Garrido published data from the<br />

clinical use <strong>of</strong> ‘‘micr<strong>of</strong>oam.’’ He had treated venous<br />

malformations and saphenous veins including collaterals<br />

with high volumes <strong>of</strong> foam. His objective was to<br />

fill the complete venous lumen by injecting high doses<br />

<strong>of</strong> foam at one time. A new aspect <strong>of</strong> the production<br />

was the use <strong>of</strong> a high-speed rotating brush (a modified<br />

dental bur), so that foam was agitated—like cream<br />

with a food mixer—and the facultative addition <strong>of</strong><br />

CO2 as a carrier gas. In experiments, CO2—if


700 WOLLMANN: THE HISTORY OF SCLEROSING FOAMS Dermatol Surg 30:5:May 2004<br />

Figure 8. Foam prepared with 3% polidocanol solution according to<br />

the double-syringe system (DSS). Sterile air or CO2 was used as gas.<br />

<strong>The</strong> degradation <strong>of</strong> foam is faster if CO2 is used instead <strong>of</strong> air and even<br />

more pronounced if the ratio is changed from 1:5 to 1:10.<br />

employed as the only gas—led to foams with quickly<br />

degrading bubbles (see Figure 8). Regarding the highdose<br />

treatment, more recent publications by Cabrera<br />

Garridos mentioned that the foam could flow from the<br />

greater saphenous vein into the deep venous system via<br />

the saphen<strong>of</strong>emoral junction or other connections,<br />

where it may provoke thromboses. 25 <strong>The</strong> number <strong>of</strong><br />

deep venous thromboses in a first study on this foam<br />

(6% thromboses when administering 20 mL <strong>of</strong><br />

Varisolve foam and more) 26 does not lend support to<br />

the high-dose foam therapy and requires special safety<br />

measures.<br />

1997—Alain Monfreux: 27 Low-Pressure<br />

Technique and ‘‘Méthode MUS’’<br />

Monfreux’s technique, published in 1997 under the<br />

name <strong>of</strong> ‘‘Méthode MUS,’’ was picked up primarily by<br />

French phlebologists. <strong>The</strong> principle was based on<br />

Gillesberger’s technique: generation <strong>of</strong> a negative<br />

pressure in the glass syringe filled with sclerosing<br />

solution, thus inlet <strong>of</strong> air through the fine gap between<br />

syringe barrel and plunger with corresponding pearling<br />

<strong>of</strong> the solution and transformation into a foam.<br />

Unlike Gillesberger, Monfreux generated an ‘‘absolute’’<br />

negative pressure by placing a cap on the syringe.<br />

Although all concentrations <strong>of</strong> sclerosants can be used<br />

with this method, the efficacy cannot be predicted in<br />

each individual case: a defined ratio <strong>of</strong> gas and<br />

sclerosant or a defined bubble size cannot be determined,<br />

because many variables (e.g., the width <strong>of</strong> the<br />

capillary gap between the syringe barrel and plunger,<br />

force, and duration <strong>of</strong> traction at the plunger and thus<br />

the order <strong>of</strong> magnitude <strong>of</strong> the effective shearing force<br />

which is responsible for the pearling <strong>of</strong> the solution)<br />

depend on the brand and on the user.<br />

1998—Symon Sadoun/Jean-Patric Benigni: 5,28<br />

Advanced Low-Pressure Technique<br />

Both authors improved Monfreux’s technique by<br />

making it usable for plastic syringes: <strong>The</strong> principle—<br />

generation <strong>of</strong> a negative pressure in a syringe closed by<br />

a Luer stopper—remained similar: pulling down the<br />

piston to generate subatmospheric pressure was<br />

followed by quickly releasing the piston several times.<br />

As with Monfreux and his predecessors, a defined<br />

gas:sclerosant ratio could not be stated.<br />

1998—Miguel Santos Gaston: 29 Advanced<br />

Low-Pressure Technique<br />

Gaston basically adopted the Monfreux technique, but<br />

added some more steps to the preparation procedure:<br />

once the foam was prepared according to Monfreux,<br />

he emptied the foam into a glass container and then<br />

aspirated the foam again. This was repeated several<br />

times, making—on the one hand—the foam more fine,<br />

but—on the other hand—more dry.<br />

1999—Javier Garcia Mingo: 30,31 High-Pressure<br />

Technique and ‘‘Foam Medical System’’<br />

Mingo was the first to describe a sterilizable, reusable<br />

device for the preparation <strong>of</strong> foam, which generates<br />

foam by the introduction <strong>of</strong> various gases from a<br />

pressure-gas cylinder and subsequent passage <strong>of</strong> the<br />

mixture through a fine nozzle, the ‘‘foam medical<br />

system.’’ <strong>The</strong> handling and cleaning <strong>of</strong> the device,<br />

which appears a little complicated, has prevented its<br />

wide use so far, although Mingo’s clinical results are<br />

considered very promising.<br />

2000—Lorenzo Tessari: 32,33 Double Syringes,<br />

Three-Way Tap, and the ‘‘Tourbillon Technique’’<br />

Tessari’s Tourbillon technique is at present, together<br />

with the similar DSS technique, the most commonly<br />

used technique. It corresponds basically to Irvine’s<br />

technique 24 but has clear advantages over the latter.<br />

Tessari uses two syringes as well (various sizes being<br />

described), but Tessari’s technique does not require<br />

‘‘foaming aids’’: <strong>The</strong> two syringes are connected by a<br />

three-way stopcock, and the sclerosing solution and air<br />

are drawn back and forth by pump movements. Owing<br />

to the absence <strong>of</strong> a connecting tube, a lot <strong>of</strong> disturbing<br />

silicone is no longer present. A more detailed<br />

description <strong>of</strong> the pumping procedure (at least 10<br />

times) to improve the standardization <strong>of</strong> the foam was<br />

given in 2001. 34<br />

<strong>The</strong> three-way stopcock has an additional ‘‘technical<br />

finesse’’: it is possible to vary the size <strong>of</strong> the passage


Dermatol Surg 30:5:May 2004 WOLLMANN: THE HISTORY OF SCLEROSING FOAMS 701<br />

by turning the cock—a narrow passage generates high<br />

turbulences and generates smaller blubbles than a wide<br />

passage. This procedures uses 2 to 2.5 mL <strong>of</strong> air and<br />

0.5 mL <strong>of</strong> sclerosing solution (all concentrations,<br />

mainly 1 and 3% for large and very large vessels).<br />

Irrespective <strong>of</strong> the concentration, the gas proportion j<br />

is approximately 0.7 to 0.83; the gas bubbles are very<br />

fine, and the half-life depends on the concentration and<br />

on the syringe. <strong>The</strong> foam prepared according to the<br />

Tessari method has successfully been tested in clinical<br />

trials. 35,36<br />

2000—Alessandro Frullini: 17–19 Advanced<br />

Turbulent Flow<br />

In 2000, Frullini improved the technique developed by<br />

Flückinger in 1962 and made it usable for disposable<br />

syringes by adding an adapter 18 and in 2001 by<br />

optionally using sterile air. 17,19<br />

2001—Gilles Gachet: 37 Aspiration Technique<br />

<strong>The</strong> aspiration technique published by Gachet in 2001<br />

is, regarding foam preparation, very similar with the<br />

description <strong>of</strong> Flückiger’s method from 1956.<br />

2001—Double-Syringe System (DSS), 11,12,38–40<br />

Two-Way Connector, and Pressure<br />

When searching for a suitable technique for the<br />

preparation <strong>of</strong> foam, it was noticed that the methods<br />

available to date all had at least one disadvantage that<br />

aggravated experiments with sclerosing foam or even<br />

made it impossible from the scientific point <strong>of</strong> view:<br />

the foams were not reproducible, because important<br />

foam characteristics (e.g., the gas proportion, the<br />

sclerosant concentration, the bubble size, or others)<br />

were stated incompletely or not at all, because the<br />

required materials were not described in detail, or<br />

because the very preparation was not defined clearly.<br />

<strong>The</strong> foams prepared for laboratory experiments and<br />

preclinical experiments all had a different consistence<br />

and an inhomogeneous flow behavior, if minor<br />

changes were made. Various types, manufacturers,<br />

and sizes <strong>of</strong> syringes; changes to the needle diameters<br />

and lengths; different temperatures during preparation;<br />

and other factors led to completely diverging<br />

results. <strong>The</strong>refore, a preparation variant was searched<br />

for that was simple, fast, sterile and especially<br />

reproducible. In a laboratory experimental series, the<br />

various variables that may affect the stability <strong>of</strong> the<br />

foam were changed systematically and the best<br />

possible combination <strong>of</strong> syringe type, gas:fluid ratio,<br />

sclerosant concentration, and manufacturing instructions<br />

was looked for.<br />

<strong>The</strong> most stable and fine-bubbled foam was obtained<br />

according to the following instructions: the required<br />

materials were a 10-mL Omnifix syringe, a 10-mL<br />

Inject syringe (each with a Luer-Lock connection), one<br />

Combidyn adapter (to connect the syringes), and a 0.2mm<br />

filter (for sterilization <strong>of</strong> air) (see Figure 9).<br />

Exactly 8 mL air is drawn into the Inject syringe via<br />

the sterile filter; afterwards, after removal <strong>of</strong> the filter,<br />

exactly one ampoule (2 mL) <strong>of</strong> polidocanol 3%<br />

(Aethoxysklerol). <strong>The</strong> two syringes are connected to<br />

the adapter. First some pumping movements (5 )are<br />

performed against resistance (by thumb pressure onto<br />

the other syringe piston) until the two components are<br />

well mixed. Afterward, the foam is pumped again<br />

quickly forth and back seven times between the two<br />

syringes without resistance like in the Tessari technique,<br />

until a homogenous foam has formed (see Figure 10).<br />

<strong>The</strong> double-syringe-system foam has a fixed sclerosant:air<br />

ratio <strong>of</strong> 1:5 ( 5 1 plus 4), a half-life <strong>of</strong><br />

approximately 150 s, with an initial mean bubble size<br />

<strong>of</strong> 70 mm. Divergent syringes, concentrations, scler-<br />

Figure 9. Components used in the double-syringe technique.<br />

Figure 10. Double-syringe-system (DSS) foam.


702 WOLLMANN: THE HISTORY OF SCLEROSING FOAMS Dermatol Surg 30:5:May 2004<br />

osant:air ratios, or pump procedures make the foam<br />

less stable and less viscous.<br />

<strong>The</strong> first prospective, randomized multicenter study<br />

compared foam sclerotherapy with double-syringe<br />

system with conventional fluid sclerotherapy in 88<br />

patients with greater saphenous vein insufficiency. A<br />

single injection (the protocol did not include further<br />

injections) <strong>of</strong> 2 to 2.5 mL <strong>of</strong> double-syringe-system<br />

foam or 3% liquid polidocanol showed a 2-year<br />

occlusion rate <strong>of</strong> 84% in the foam group versus 40%<br />

in the fluid group. Vasospasm was clearly more<br />

frequent and more pronounced in the group treated<br />

with foam (mean length 28 cm) than in the control<br />

group, the rate <strong>of</strong> side effects being identical. 11,12<br />

Conclusion and Discussion<br />

<strong>The</strong> use <strong>of</strong> foamed sclerosing agents in therapy <strong>of</strong> large<br />

or small varicose veins is not new. It started as early as<br />

1939. <strong>The</strong> publications about foam sclerotherapy<br />

found and presented in this text allow us to look at<br />

what has been invented between the very beginnings<br />

and now. <strong>The</strong> contributions <strong>of</strong> widely known and also<br />

<strong>of</strong> less known colleagues show that remarkable work<br />

was performed in the field <strong>of</strong> noncommercial foam<br />

sclerotherapy continuously for the past six decades,<br />

especially for the treatment <strong>of</strong> varicose veins <strong>of</strong> the<br />

lower limbs. But they also show that there sometimes<br />

is a lack <strong>of</strong> accuracy in describing the particular foams<br />

used, which does not make it easy to reproduce the<br />

individual reported results and/or findings. <strong>The</strong> suggestion<br />

therefore is to describe any foam used in<br />

nonclinical or clinical trials according to the ‘‘definition<br />

<strong>of</strong> sclerosing foams’’: <strong>Sclerosing</strong> foam is characterized<br />

by (at least) the following variables: type and<br />

concentration <strong>of</strong> the tensioactive sclerosing agent, type<br />

<strong>of</strong> gas, ratio <strong>of</strong> liquid to gas, the method <strong>of</strong><br />

preparation, the time between processing and use,<br />

and bubble sizes. This could really help to make<br />

sclerosing foams, and clinical results, comparable.<br />

References<br />

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[updated 2004 Feb 3]. Available from: http://www.cavezzi.it/.


Dermatol Surg 30:5:May 2004 WOLLMANN: THE HISTORY OF SCLEROSING FOAMS 703<br />

32. Tessari L. Extemporary sclerosing foam according to personal<br />

method: experimental clinical data and catheter usage. Int Angiol<br />

Suppl 2001;1:54.<br />

33. Tessari L. Nouvelle technique d’obtention de la scléro-mousse.<br />

Phlébologie 2000;53:129.<br />

34. Tessari L, Cavezzi A, Frullini A. Preliminary experience with a new<br />

sclerosing foam in the treatment <strong>of</strong> varicose veins. Dermatol Surg<br />

2001;27:58–60.<br />

35. Cavezzi A, Frullini A, Ricci S, Tessari L. Treatment <strong>of</strong> varicose<br />

veins by foam sclerotherapy: two clinical series. Phlebology 2002;<br />

17:13–8.<br />

36. Frullini A, Cavezzi A. Echosclérose par mousse de tétradécyl-sulfate<br />

de sodium et de polidocanol: deux années d’expérience. Phlébologie<br />

2000;53:431–5.<br />

37. Gachet G. Une nouvelle méthode simple et économique pour<br />

confectionner de la mousse pour sclérose échoguidée. Phlébologie<br />

2001;54:63–5.<br />

Commentary<br />

Many authors have claimed to have developed a technique for<br />

foaming detergent solutions to increase the efficacy <strong>of</strong><br />

sclerotherapy treatment <strong>of</strong> varicose veins. In this article, Dr.<br />

Wollmann has researched the literature to provide us with an<br />

accurate history <strong>of</strong> this therapeutic advance. As with ambulatory<br />

phlebectomy and many other surgical techniques, foaming<br />

sclerosing solutions is not new. This technique was first<br />

described in 1939 and has been reported using many different<br />

methods over the past six decades. Present ‘‘advances’’ in<br />

38. Ouvry P, Barrellier MT, Escalard JM, et al. Sclerotherapy <strong>of</strong> the<br />

long saphenous vein with foam <strong>of</strong> Lauromacrogol: a prospective<br />

duplex controlled randomized study protocol and first result. Int<br />

Angiol 2001;20(Suppl 1):343.<br />

39. Wollmann JC. Schaum zwischen Vergangenheit und Zukunft.<br />

Vasomed 2002;16:34–5.<br />

40. Hamel-Desnos C, Desnos P, Ouvry P, et al. Nouveautés thérapeutiques<br />

dans la prise en charge de la maladie variqueuse: échosclérothérapie<br />

et mousse. Phlébologie 2003;56:41–8.<br />

41. Wollmann JC. An Experimental Model to Pinpoint Properties and<br />

Behavior <strong>of</strong> <strong>Sclerosing</strong> <strong>Foams</strong>. 17th Annual Congress <strong>of</strong> the<br />

American College <strong>of</strong> Phlebology; 2003 Aug 27–31; San Diego,<br />

CA. Oakland, CA: ACP, 2003.<br />

42. Breu FX, Guggenbichler S. European Consensus Meeting on Foam<br />

Sclerotherapy April 4–6, 2003, Tegernsee, Gemany. Dermatol Surg<br />

2004;30:709–717.<br />

sclerotherapy technique represent minor modifications <strong>of</strong><br />

previously reported techniques and should not be named after<br />

their recent revivalists. One wonders whether a language barrier<br />

prevents a wider appreciation <strong>of</strong> the past achievements <strong>of</strong><br />

medicine. Perhaps a universal language <strong>of</strong> medical and scientific<br />

reports will better help to disseminate information. Certainly, in<br />

this, the ‘‘information–computer age’’ it is possible.<br />

MITCHEL GOLDMAN, MD<br />

La Jolla, California

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