Vein adhesives: The history of cyanoacrylate adhesives from their discovery to VenaSeal®

In addition, current studies, success rates, costs and the use at VenaZiel® – a vein center in Berlin – are presented. The information is aimed at both interested laypersons and medical professionals and provides a comprehensive overview of the history and current status of vein taping.

Discovery of cyanoacrylate and first medical applications

The success story of vein glue began with the discovery of the underlying substance: cyanoacrylate. This fast-curing adhesive – known as “superglue” – was first discovered during the Second World War by the American chemist Dr. Harry Coover at Eastman Kodak.

Its high adhesive strength was initially perceived as disruptive, but its enormous potential was soon recognized. As early as 1958, Eastman Kodak launched the first cyanoacrylate adhesive on the market, Eastman 910.

In the years that followed, it became apparent that cyanoacrylates could be useful not only in everyday life but also in medicine.

In 1964, the Eastman company submitted an application to the US Food and Drug Administration (FDA) for approval of cyanoacrylate adhesives for use on human tissue and for wound care.

The reason for the medical interest was the unique polymerization reaction of this adhesive: on contact with small amounts of water (as present in tissue or blood), cyanoacrylate hardens within seconds and firmly bonds the surfaces together.

This rapid bonding and the resulting tight sealing of a wound opened up a wide range of applications – from treating accident injuries to supporting surgical procedures.

Due to its ability to stop bleeding almost instantly, cyanoacrylate became a potentially important tool for surgeons in experiments that could save lives in an emergency.

First uses in war: The “superglue” was used in a military context even before it was officially approved for civilian use.

In the Vietnam War, from the mid-1960s, field doctors used spray bottles containing cyanoacrylate adhesive to quickly stop life-threatening bleeding in wounded soldiers.

The low-viscosity adhesive spray was sprayed directly onto gunshot or splinter wounds, quickly forming a polymer film that temporarily stopped the bleeding.

According to reports, many lives were saved in this way, as the wounded gained enough time to reach a military hospital. However, this purpose was initially limited to the military.

The early use of cyanoacrylate adhesives was not approved for the civilian population because the early adhesive formulations could cause skin irritation and other side effects.

The FDA was reluctant to approve a tissue adhesive that releases potentially toxic degradation products (e.g. formaldehyde) and generates heat during curing – both characteristics of the first generation of instant adhesives.

Breakthrough in 1998 with improved wound adhesive: It took until 1998 for a cyanoacrylate adhesive specially developed for medical purposes to receive FDA approval.

This was 2-octyl cyanoacrylate, a modified adhesive that is significantly more tissue-compatible than the original form. Under the trade name Dermabond, this octyl adhesive was used from 1998 as a skin adhesive to close surgical cuts or lacerations in accidents – as a kind of “liquid plaster” or spray bandage for civilian use.

The octyl cyanoacrylate hardens somewhat more slowly and generates less heat, which significantly reduced skin irritation. This breakthrough made a military-inspired wound adhesive available to the general public for the first time. It could replace sutures in many cases and enabled faster healing without the need for needles.

Widespread use in surgery: Parallel to the development of skin adhesives, cyanoacrylates found more and more applications in medicine over the following decades.

As early as the 1970s, surgeons and radiologists used variants such as N-butyl-2-cyanoacrylate (e.g. histoacryl) as a tissue adhesive, for example to close small blood vessels in neurosurgery or in interventional radiology (embolization of aneurysms and haemorrhages).

Certain cyanoacrylate adhesives have been approved for internal use in some countries since the 1960s. Almost all surgical disciplines experimented with these adhesives: from dermatology to ophthalmology and vascular surgery to oral surgery.

In many cases, the adhesives proved to be safe, effective and non-toxic alternatives or supplements to traditional suturing and stapling techniques. It was always important to improve tissue compatibility and minimize undesirable reactions through chemical modifications.

From wound adhesive to vein adhesive: development of varicose vein treatment

While cyanoacrylates were initially mainly used to close wounds, the idea of using the adhesive specifically to treat varicose veins (varicosis) matured in the 2000s.

Varicose veins are traditionally treated either surgically (by “stripping” the vein) or using endovenous procedures such as laser or radio wave ablation.

However, all of these methods have potential disadvantages – from post-operative pain and nerve damage caused by heat to longer recovery times with compression stockings.

An adhesive procedure, on the other hand, promised a gentle, non-thermal and non-tumescent approach without major trauma.

Research began around 2000: The development of a vein adhesive actually began around 2003, initiated by a small medical technology company (later called Sapheon).

Initially, laboratory and animal tests were carried out. One important study was the pig model experiment in 2011, in which it was shown that injecting a cyanoacrylate adhesive into a vein leads to reliable closure without causing dangerous complications. Building on these results, the company ventured into clinical application.

First clinical application: In 2011, the first people in Europe were successfully treated with vein glue. The innovative system – then still known as the “Sapheon Closure System” – received CE approval in Europe in the fall of 2011 .

In Germany, a few innovative vein centers started using the method in 2012; one of the first documented cases was in Berlin on August 1, 2012. Internationally, the first study on humans was published in 2013, in which 38 patients were treated using cyanoacrylate glue on the insufficient saphenous vein.

This pioneering work – led by J. Almeida and T. Proebstle – showed promising results in terms of the safety and effectiveness of the bonding technique.

From the Sapheon system to VenaSeal®: The positive study results quickly led to the technology being taken over by a large medical technology group. In 2014, Sapheon was acquired by Medtronic and the system was renamed VenaSeal® Closure System. Since then, the vein adhesive has been marketed worldwide under the brand name VenaSeal® and continuously developed further.

International approval followed quickly: in Canada, approval was granted in 2014, and in February 2015, the FDA in the USA also granted approval for VenaSeal® . This meant that the vein adhesive was also established in North America just a few years after its European premiere.

How does vein sealing work: But how exactly does this method work? VenaSeal® is a special medical N-butyl-2-cyanoacrylate adhesive. This is inserted into the diseased vein during a minimally invasive endovenous procedure.

Using a thin catheter, the doctor applies tiny amounts (~0.1 ml each) of the liquid adhesive to the inner wall of the vein at intervals of approx. 3 cm. The catheter is gradually withdrawn under ultrasound guidance while the adhesive is released at the defined points. The cyanoacrylate adhesive polymerizes within seconds, bonds the vein walls and thus permanently seals the vessel.

Important: Usually only a local anesthetic is required at the puncture site – a general anesthetic or tumescent local anesthetic along the entire vein is not necessary. The entire procedure is performed on an outpatient basis and usually takes less than 30 minutes per vein.

Fig.: Ultrasound-guided treatment of varicose veins. The VenaSeal® method uses a thin catheter to precisely insert the cyanoacrylate adhesive into the vein while the doctor monitors the placement using ultrasound.

After bonding, the polymerized adhesive initially remains in the vein as a kind of implant, similar to an inserted stent or a vascular clip.

The body reacts to this with a mild inflammatory reaction: the vein becomes obliterated and is gradually transformed into connective tissue (endothelialized and fibrosed).

In the long term, the cyanoacrylate is very slowly biodegraded by the body or converted into an inert, non-irritant form.

Studies indicate that no active adhesive is detectable in the vein after around 12-24 months – at this point the formerly insufficient vein is completely scarred and closed.

VenaSeal® – the modern vein adhesive at a glance

With VenaSeal®, cyanoacrylate adhesive has established itself as the third major endovenous therapy alongside laser and radiofrequency. The system combines several advantages that make it attractive for patients:

• High tissue compatibility: The acrylate adhesive used is non-toxic, non-carcinogenic and does not cause allergic reactions .
  Many patients are concerned about whether an “adhesive in the bloodstream” could be dangerous – but the composition has been optimized to be biocompatible and sterile.
  Interestingly, cyanoacrylate even has a bactericidal effect, i.e. it kills bacteria and thus reduces the risk of infection in the treated segment.
• Outpatient, painless procedure: The treatment only requires a small needle puncture for the catheter.
  Afterwards, the patient hardly feels anything – local anesthesia is usually only used at the puncture site, the rest of the vein is treated without anesthesia, as there is no heat or mechanical tearing (as with stripping).
  According to patient reports, the procedure is virtually painless; many are surprised at how quick and uncomplicated the procedure is.
• No scars, no downtime: Since neither incisions nor stitches are necessary, no scars remain. Plasters or support stockings are often not necessary.
  Most patients can return to their normal activities immediately after the treatment – a big difference compared to traditional surgery, which often involves several weeks of rest. The usual wearing of compression stockings for weeks is also generally not necessary with vein glue.
• No thermal risks: In contrast to laser or radio wave therapy, there is no risk of burns or nerve damage as no heat is applied .
  This is a considerable advantage, especially for veins near cutaneous nerves (e.g. on the lower legs).
• High success rates: We will go into this in more detail in the next section – but first things first: the closure rates of the treated veins are comparable to the best alternative methods, in some cases even higher, and this over a period of years.

VenaSeal® application system consisting of adhesive ampoule and dosing gun with disposable catheter. This system is used to inject a specially formulated cyanoacrylate into the vein, where it hardens in seconds and seals the vein.

In addition to VenaSeal® from Medtronic, other vein adhesive systems have also been developed in recent years. For example, there is VariClose® (Turkey) or VenaBlock®, which are also based on N-butyl cyanoacrylate. These systems work according to a similar principle, but are less widespread.

VenaSeal® continues to be regarded as the market leader and is the best-studied adhesive system – which means a degree of certainty for doctors and patients thanks to extensive data.

Effectiveness and study situation

Since the introduction of vein taping over a decade ago, numerous studies have been carried out to test the safety and effectiveness of this method.

The results are consistently very positive:

• High initial closure rates: The first clinical studies have already shown that the adhesive closes the veins extremely reliably.
  One of the largest randomized studies, the VeClose study, compared VenaSeal® with conventional radiofrequency ablation. After 12 months, over 95% of the saphenous veins treated with adhesive were successfully closed.
  VenaSeal® was therefore just as effective as the comparative method, but with less postoperative pain and faster patient recovery. Other studies also found initial occlusion rates of 98-100 % after a few months in some cases.
• Long-term successes: It is particularly important that the closure lasts in the long term. Data is now available from five-year observations.
  The VeClose study mentioned above, for example, still reports closure rates of around 91% after 5 years – an excellent value which shows that the method has a lasting effect.
  European registry studies and practical experience confirm this order of magnitude. A German multicenter study found similarly high persistence rates and very few recurrences after several years.
  In a large Berlin practice, more than 2,900 veins were glued over a period of 100 months with a sustained success rate of over 95%. The long-term data thus confirms that vein glue is not a short-lived fashion, but a sustainable treatment option.
• Patient satisfaction and symptom relief: The clinical results relate not only to the ultrasound image, but also to the patient’s symptoms.
  In studies, most patients report a significant improvement in symptoms after the procedure. The feeling of heaviness, pain and swelling in the legs decrease rapidly, often within a few days of treatment.
  As there are no large wounds, patients find the healing process very uncomplicated. Many are also cosmetically satisfied, as the treated varicose veins disappear without leaving any scars.
• Side effects and risks: No medical procedure is completely without risk, but the profile of vein glue is favorable. The most common adverse reaction is a mild local inflammatory reaction (a type of superficial phlebitis), which may be characterized by redness, mild pain or itching along the treated vein.
  This irritation is estimated to occur in 10-20% of patients, but is temporary and usually subsides within two weeks.
  It is assumed that this is a contact reaction of the immune system to the adhesive, which, however, remains limited.
  Cooling compresses and, if necessary, a short course of anti-inflammatory medication (e.g. ibuprofen) can provide relief. Severe allergic reactions to cyanoacrylate are extremely rare; only isolated cases have been documented worldwide (e.g. urticaria or a so-called foreign body granuloma) in which surgical removal of the glued vein was necessary.
  Deep vein thrombosis (displacement of the adhesive into the deep vein system with thrombus formation) has been observed in rare cases, but significantly less than 1% of treatments – and mostly when the correct technique was not observed.
  Overall, experts rate the method as safe. The official guidelines of several countries have now also included cyanoacrylate bonding as a recognized therapy.

In summary, it can be said that vein glue is in no way inferior to traditional methods and even offers clear advantages in some aspects.

Thanks to the large number of studies and publications, even more skeptical specialists feel increasingly convinced, so that the vein glue has taken a firm place in the treatment spectrum.

Costs of the VenaSeal treatment

An important practical aspect for patients is the cost of vein glue treatment. As this is a comparatively new procedure, there are differences depending on the country and health insurance:

• Cost framework: In Germany, the cost of a VenaSeal® treatment of a truncal vein typically ranges between €2,000 and €3,500 per leg, depending on the clinic, complexity and any additional services.
  This sum includes the manufacturer’s disposable kit (adhesive and catheter) as well as medical services and aftercare. Compared to conventional varicose vein stripping (which is performed in the operating theater), the material costs are higher, which makes the method more expensive.
• Reimbursement by health insurance companies: Statutory health insurance companies in Germany currently only cover the costs of vein glue in exceptional cases .
  As VenaSeal® is still considered a “new technology” and is not included in the standard benefits catalog, SHI patients often have to pay for it themselves.
  A few health insurance companies have covered the costs in pilot projects or in cases of medical necessity (e.g. if other procedures cannot be used) – it is worth asking your health insurance company about this on an individual basis .
  Private health insurance companies tend to be more open-minded and reimburse the treatment in most cases, especially if the phlebologist confirms a medical indication.
• Financing options: To lower the financial hurdle, some vein centers offer installment payments or financing solutions.
  The VenaZiel® Berlin vein center, for example, allows patients to pay in instalments so that they can spread the cost of treatment over several months. It is advisable to ask about such options at the consultation appointment.
  Ultimately, the decision for the optimal treatment method should not be made solely for cost reasons – especially as untreated varicose veins can also cause long-term follow-up costs (e.g. due to complications).

Conclusion: From war medicine to the modern vein clinic

The development of vein glue is an impressive example of how an accidental chemical discovery could become a life-saving innovation in medicine.

The cyanoacrylate adhesive has come a long way from improvised use in the Vietnam War to high-tech treatment in today’s clinics.

Today, both patients and specialists benefit equally: The former receive a gentle, quick solution for their vein problems, and the latter have one more effective tool in their treatment toolbox.

At VenaZiel®, a vein center in Berlin (and Frankfurt am Main), vein glue is used routinely if the diagnosis allows it.

The specialists there have both traditional phlebology and all modern procedures in their repertoire – including VenaSeal®, laser and radio wave. Detailed consultations are held to decide which method is best for each patient.

VenaSeal® is often the ideal therapy, especially for those who are afraid of surgery or need a short downtime.

Experience in recent years has shown that patients treated with vein glue can often go about their daily lives the very next day without any pain.

It will be interesting to see what further developments will be made in the field of endovenous adhesive technologies in the future.

For example, research is currently being carried out into whether the adhesive technique can also be used for smaller side branches, recurrent varicose veins or even other vascular diseases. The results so far are optimistic.

One thing is clear: cyanoacrylate adhesives have revolutionized phlebology – what once began on battlefields now enables pain-free legs without surgery. Patients should not be afraid to find out more about vein adhesives and ask about VenaSeal® when talking to a phlebologist.

Thanks to dedicated research and courageous doctors, we now have another excellent treatment option that is helping many people to have lighter legs and a better quality of life.