The History of Sclerosing Foams

The first recorded use of a foam sclerosant for the treatment of telangiectatic veins was in 1939 by Stuard McAusland. McAusland’s technique consisted of shaking a rubber-capped bottle filled with sodium morrhuate, creating a froth. This froth was then transferred into a syringe and injected into the varicose veins. The treated areas were observed to immediately turn pink, sometimes retract, and instantly disappear [17]. The next recorded treatment was that of Egmont James Orbach in 1944. Orbach took a different approach that did not include the use of foam. Instead, he used two “conventional liquid” techniques, one known as the “full-vein technique” for smaller veins, where the veins were injected while the patient was standing, and the empty-vein technique for larger veins. This technique required the varicose vein segment to first be isolated with two tourniquets. Then, following venipuncture, the leg was raised approximately 45° to 90°. The release of the proximal tourniquet allowed the blood to flow centrally. The purpose of the distal tourniquet was to reduce or even stop the blood supply to the area being treated. This technique lessened the dilution of the sclerosing liquid agent. Through trial and error, Orbach later discovered that reducing the diameter of the vein and clearing it of blood before injecting the sclerosing agent increased the contact between the sclerosing agent and the endothelium. He then injected small amounts of air into the veins to rid them of any remaining blood. Orbach used this air-blocking technique only on small and medium-sized veins [17]. That same year, Robert Rowden Foote’s sclerotherapy technique was published in London discussing his rendition of the empty-vein technique. He injected the veins with a soapy froth produced by shaking up 1 cc of ethamoline (ethanolamine oleate) in a 2-cc syringe. Foote believed the “feeder” vein should be treated first. In order to be distinguished as a foam, the gas portion must be greater than 0.52, so Foote’s sclerosant was not considered a foam. This technique was geared toward the treatment of smaller and medium-sized veins. Foote’s 1+1 air:sclerosant ratio froth was more a liquid than foam and thus could not be used to displace blood in larger veins. Today, ethanolamine oleate is not manufactured in most countries; consequently, this technique is no longer practiced [17].

In 1949, Karl Sigg embraced an air-block technique similar to that created by Orbach five years earlier. However, Sigg’s technique was to be used on larger as well as smaller veins. Sigg later combined the air-block technique created by Orbach and the foam technique created by Foote, forming the foam-block technique. He found that the air-block technique was more effective if foam instead of air was injected into the veins because foam has a heightened viscosity and a slower passage rate through the veins than air. Sigg produced his foam by aspirating 1 ml of air into a glass syringe filled with liquid sclerosant with the opening pointed down, thus forming bubbles [17].

One year later, a study conducted by Orbach was published comparing the effectiveness of foam sclerosants with the effectiveness of liquid sclerosants. Orbach used the length of the sclerothrombus, resulting from the injection of a particular sclerosant, to determine the endpoint. He found that the effectiveness of a foam sclerosant formed by agitating the syringe or drug vial was increased 3.5- to 4-fold compared with that of a liquid sclerosant using the same amounts and concentrations of each. Orbach also found that vasospasm was more common and more visible after the use of foam sclerosants because foam can spread throughout venous segments farther than liquids can after vasospasm and are more potent. Orbach’s study proved that the foam sclerosants have a greater efficacy than liquid sclerosants [17].

Three years later, in 1953, Arve Ree introduced the new technique of injecting a “pure” foam sclerosant into the venous system to treat telangiectasias and varicose veins.He agitated a solution of detergent in a vial and aspirated the bubbles into the syringe. Ree’s technique consisted of injecting 2–7 ml of foam sclerosant, corresponding to an amount of air of up to 6.6 ml. The exact measurements varied depending of the diameter of the veins.Using this technique, Ree successfully treated a series of 50 patients [17].

In 1956, Peter Flückiger advocated the technique “retrograde sclerotherapy.”His technique consisted of elevating the leg followed by injection of the foam sclerosant into the saphenous vein proximal to distal so that the sclerosant could reach all insufficient collaterals as well as the saphenous vein via a single injection. Like Foote, Flückiger also used ethanolamine oleate. He found that foam sclerosants yielded much better results than liquid sclerosants. Flückiger was the first to postulate and discuss the relevant properties of foam. He postulated foam has increased efficacy due to its ability to travel through the venous system further than liquid sclerosants and still maintain its potency. As a result of this increased efficacy, a lesser amount of sclerosant is needed.He determined that the smaller the bubble size, the greater the surface area of sclerosant exposed to the endothelium. He also postulated that the homogeneity of the foam is a very important factor in treatment success. He created a homogenous, fine-bubbled foam by simultaneously aspirating sclerosant and air through a fine-bore needle by submerging only two thirds of the opening of the bevel of the needle into the liquid when aspirating [17].

The following year Heinz Mayer and Hans Brücke introduced their double-piston syringe, a device designed specifically for the production of sclerosing foam. The invention of the double-piston syringe is considered a milestone in the ever-changing foam preparation process [17].

In 1962, Flückiger proposed another technique for the preparation of sclerosing foam. This technique involved pumping air and sclerosant forward and backward between a drug vial and the affixed syringe, forming bubbles and foam. His technique was later amended by Alessandro Frullini who added an adapter, making it possible to use disposable syringes. Then in 2001,Frullini added the option of using sterile air to generate the sclerosant [17].

Flückiger later recommended that following injection of a venous segment, a few minutes should be allowed for the foam to degrade before applying compression to avoid propulsion of foam into the deep venous system; this is still recommended today [17].

In 1963, the first sclerotherapy treatment with Aethoxysklerol (polidocanol) was recorded. This treatment was performed by Peter Lunkenheimer, who used 2 ml of the solution, which was not a known sclerosant at the time [17].

In 1969, Walter Gillesberger introduced the “low-pressure technique” based on generation of a negative pressure in a glass syringe, allowing the air to enter through the space between the syringe piston and the plunger and thus forming bubbles. This technique was modified in 1997 by Alain Monfreux who proposed the idea of capping the glass syringe, yielding an “absolute” negative pressure. Then, in 1998, Symon Sadoun and Jean-Patric Benigni modified Monfreux’s technique by making it possible to use plastic syringes instead of glass. Also in 1998, Miguel Santos Gaston adopted and modified Monfreux’s technique. After preparing the foam according to Monfreux, Gaston emptied the foam into a glass container and aspirated the foam again.He repeated this several times, producing a finer and drier foam [17].

In 1984, Gerald Hauer introduced his foam preparation technique. He patented his twinsyringe technique, in which he used a twin-syringe set for preparation.The twin syringe consisted of two parallel syringes, one filled with air, and the other filled with sclerosant.Both syringes were simultaneously emptied into a “mixing chamber,” under pressure, thus forming a 1+1 ratio foam (sclerosant and air) [17].

Two years later, Michael Grigg introduced a new foam preparation technique (also referred to as the Irvine technique). His technique was based on the concept of creating a turbulent flow between two syringes connected by a plastic infusion tube. The liquid sclerosant and air were pumped back and forth, creating bubbles. The Irvine technique, named after the laboratory where it was developed, was later improved by G. Belcaro and coworkers who added small increments of a heavily foaming detergent to prolong the half-life of the foam. Grigg’s technique was a precursor to the Tessari technique and the double-syringe technique, a technical variation of the Tessari technique [17].

In 1995, Juan Cabrera Garrido used high volumes of foam to treat venous malformations and saphenous veins. However, he added a high-speed rotating brush (a modified dental burr) to agitate the foam, and CO₂ as a carrier gas. His objective was to completely fill the venous lumen. Later, however, he reported that the foam could travel from the greater saphenous vein into the deep venous system through the saphenofemoral junction or other connections, thus provoking thrombosis. This technique does require special safety precautions and is not recommended [17].

In 1999, Javier Garcia Mingo became the first to advocate the use of a device for preparing foam that could be sterilized and used again. This device involved mixing of various gases from a pressure-gas cylinder then passing the mixture through a fine nozzle. This technique is referred to as the “foam medical system.” Handling and cleaning the device is complicated and prevents wide usage [17].

In 2000, Lorenzo Tessari introduced the tourbillon technique, or Tessari technique that, along with the technically varied double-syringe system (DSS), is the most commonly used technique to date. Tessari prepared the foam sclerosant using two syringes conjoined by a three-way stopcock. By pumping the liquid sclerosant and air back and forth between the two syringes, bubbles are generated and transformed into foam. The three-way stopcock has an additional advantage of allowing regulation of turbulence, and therefore the size of the bubbles, by turning the stopcock. A narrow passage generates high turbulence and smaller bubbles. This procedure uses 2–2.5 ml of air and 0.5 ml of liquid sclerosant. The concentration of sclerosant varies depending on the diameter of the vessel; generally, 1% Aethoxysklerol for smaller and medium veins and 3% Aethoxysklerol for larger veins. The gas proportion is approximately 0.7–0.83, and the gas bubbles are very fine. The half-life varies with the concentration of the sclerosant and type of syringe (half-life decreases with the presence of silicone in the syringe).Because of the absence of the connecting tube used by Grigg (Irvine technique), much of the silicone is no longer present, resulting in a decrease in the destruction of the foam lamellae [17].

In 2001, Gilles Gachet introduced the “aspiration technique”; this technique was very similar to the 1956 foam preparation technique published by Flückiger [17].

Also in 2001, the DSS, a technical variation of the Tessari technique, was formulated by a group of doctors seeking a quick, sterile, reproducible technique for producing the most stable and fine-bubbled sclerosing foam. Their technique consisted of connecting a 10-ml Injekt syringe and a 10-ml Omnifix syringe (each with a Luer-Lock connection), with a Combidyn adapter (to connect the two syringes) and a 0.2-µm filter for sterilization of air. After aspirating exactly 8 ml of air into the Omnifix syringe via the sterile filter, the filter is removed. Then, 2 ml of polidocanol 3% is drawn into the same syringe. The two syringes are connected to the Combidyn adapter, and pumping movements are first performed against resistance (five times) by applying thumb pressure on the opposite syringe piston until the two components are well mixed. The foam is then rapidly pumped back and forth between the two syringes seven times without resistance (like the Tessari technique), forming a homogenous foam, with a fixed sclerosant:air ratio of 1 : 5 (= 1+4). The half-life of the foam is approximately 150 s,with an initial mean bubble size of 70 µm [17].Variations in foam stability can occur with divergent syringes, sclerosant concentrations, sclerosant:air ratios, or pumping procedures, making the foam less stable and less viscous.