Origin and Evolution of Sclerotherapy for Varicose Veins

Sclerotherapy is a simple and common method used to treat telangiectasia, reticular veins, and varicose veins, especially when no other option is available. It has become a part of primary and secondary treatments offered for varicose veins. It has several alternate uses in vascular surgery (malformations), as well as being commonly used in other disciplines such as dermatology due to its simplicity and efficacy. It has a quick learning curve, is easily practiced, and has thus undergone several historical modifications by several authors. There are two main events which led to the development of modern-day sclerotherapy. The first important aspect of the technique is gaining intravenous access. The invention required for this is a syringe, hence most progress in sclerotherapy came after and alongside designs and improvements made to syringes. The second problem encountered was a high rate of complication due to the nature of early sclerosants used and a poor understanding of their mechanisms of action in varicose veins. This paved the way for phlebologists experimenting with several different substances and describing safety techniques which eventually led to modern-day safe sclerotherapy. The first methods of intravenous access were rudimentary. Sir Christopher Wren and Robert Boyle in 1656 used a goose quill attached to an animal bladder as the first syringe.[1] This allowed them to perform the first intravenous access in a dog. The experiment consisted of using this device to inject wine and alcohol into the leg vein of a dog and success was noted when the dog was found to be drunk. The syringe used was primitive but served its purpose and was presented in the first meetings of the Royal Society of London.[2] This apparatus was modified and used by Johann Sigismund Elsholtz who administered the first injection of sclerotherapy in 1665. Elsholtz was a state physician to Frederick William of Brandenburg, the Duke of Prussia (Germany before the First World War), which gave him an opportunity to experiment and write extensively.[3] One of these experiments, documented in the “Clysmatica Nova” in 1665 in Berlin, describes the first use of sclerotherapy [Figure 1].[4] Elsholtz was a botanist and the sclerosant he used was a plant alkaloid which he injected into the leg vein of the duke’s bodyguard who had a venous ulcer. The puncture was carried out by open access to the vein with a lancet, along with proximal compression to enlarge the vein, making it easy to observe and cannulate.[4] The needle used was a hollowed out chicken bone fitted with a pigeon’s bladder as a syringe. Although the instrument used was archaic, this was the first successfully recorded attempt at sclerotherapy.[5] Elsholtz intention at the time was to find different uses of a clyster (enema syringe) and unintentionally used it in a patient with a venous ulcer to perform the first recorded sclerotherapy.[4] The outcome was never reported.Figure 1: Picture demonstrating the first application of sclerotherapy to the leg and arm veins by Sigismund Johann Elsholtz from “Clysmatica Nova,” 1665, Berlin[ 2 ]Daniel Zollikofer from Switzerland, in 1682, is said to have injected an acid into a vein, but no supporting evidence could be found in this regard.[6] Despite these first unintentional attempts, sclerotherapy only advanced further after the invention of the modern-day syringe and as understanding of the pathology behind varicose veins progressed. The understanding of how sclerotherapy as a treatment, works, was first provided by Joseph Hodgson (1815) in “A treatise on the diseases of arteries and veins.” He theorized that superficial venous thrombosis, observed clinically as thrombophlebitis in major saphenous veins, leads to varicose veins being treated.[5] This understanding led to treating varicose veins with sclerotherapy to occlude the vein as against earlier methods of decompressing the thrombosed superficial veins by bloodletting.[7] In 1835, Alexander Wood (Edinburgh) and Charles Gabriel Pravaz (Lyon) independently invented the modern-day syringe. They used different types of material to construct the syringe. Although Wood used his invention to inject morphine to treat neuralgia, Pravaz used the syringe to inject sclerosant (iron chloride) into first arteries and then veins in an attempt to occlude them to relieve symptoms.[8] This along with the understanding of thrombosis treating varicose veins led to widespread use of sclerotherapy, especially in Lyon and Paris. This new treatment had become widely popular in France, at the time. Petrequin, Soquet, Desgranges, Valette, Barrier, and Guillermand used different sclerosing agents (ferric chloride, iodine-tannin, and acetic acid) in attempts to occlude veins, one being reported to be better than the other.[6,9] These earlier sclerosants when injected into veins led to several adverse effects such as skin necrosis, abscess, septic embolus, ulceration, pulmonary embolism, and thrombophlebitis due to their irritant nature. The complications were so common and life threatening that patients were kept in hospital for 12 days post injection treatment[8] as opposed to ambulatory treatments carried out today. Due to the significant number of unethical complications, sclerotherapy was banned at the medical congress at Lyon in 1894.[5] Since the Congress, most of the early 1900s work was carried out to try and make sclerotherapy safe. This led to Tavel in 1904 advocating sclerotherapy with simultaneous ligation of the saphenous vein to prevent pulmonary embolism.[9] In 1921, Linser carried out ambulatory sclerotherapy with lesser quantities of sclerosant to avoid deep vein thrombosis.[10] Thornhill in 1929 first described the technique of emptying the vein before injecting the sclerosant.[11] McAusland in 1939 was the first to use foam in sclerotherapy.[12] McAusland produced the first foam by shaking sodium morrhuate (sclerosant) with air in a bottle with a rubber cap and injecting it. He used this method in 1000 patients to treat varicose veins which he subsequently published. The benefits of foam as compared to liquid agents were shown by Orbach and Petretti in 1950.[13] Since then, foams were found to be better sclerosing agents and gained favor among many. Sodium tetradecyl sulfate was introduced by Leopold Reiner in Germany in 1946.[6] Many of the older sclerosant agents such as quinine and mercuric chloride were initially used to treat other ailments and their use extrapolated to varicose veins when they were found to cause sclerosis in veins. Polidocanol was similar, initially used as a local anesthetic in 1936 and abandoned, but later in 1961, was shown by Hershel to sclerose veins and was re-introduced as a sclerosant in 2000.[14,15] There have been several methods of foaming sclerosants described since the “air block” technique was first described by Orbach in 1944. These methods have undergone more than 16 modifications over the past half century (1950–2000), to the present-day, simplified, most commonly used technique described by Lorenzo Tessari in 2000. Each subsequent technique has been an improvement over the former. Schadeck in 1984 first described ultrasound-guided foam sclerotherapy, improving the safety of the technique.[16] The latest introduction to sclerotherapy in attempts to standardize the quality of foam is microfoam, introduced by Cabrera et al. (Spain) in 1995 obtained by mixing sclerosant with an inert gas.[17] The 21st-century developments in foam sclerotherapy have been to find ways to standardize and improve the quality of foam used, to achieve better results. Sclerotherapy is a simple procedure and history teaches us the different trials and errors made in trying to perfect the technique. As vascular surgeons, knowing this evolution of sclerotherapy [Table 1] helps understand how sclerotherapy was made safe in treating patients with varicose veins. It has become a common nonthermal technique alongside thermal techniques to treat varicose veins.Table 1: Evolution of sclerotherapyFinancial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.