The two solutions used most widely for sclerotherapy worldwide are polidocanol and sodium tetradecyl sulfate (STS), both of which are detergent-type agents that damage the inner lining of targeted blood vessels on contact. These are the only sclerosants licensed in most European countries, and they dominate clinical practice in North America and elsewhere as well. But the full list of solutions is longer than most patients realize, spanning detergents, concentrated salt solutions, and chemical irritants like glycerin, each suited to different vein sizes and clinical situations.
The Two Workhorse Detergents
Polidocanol and STS belong to the detergent (or surfactant) category of sclerosants. When injected into a vein, they strip away the lipid layer of the cells lining the vessel wall, triggering a cascade of damage that leads to cell death and eventual closure of the vein. Polidocanol works through concentration-dependent cell injury: at higher concentrations, it kills endothelial cells faster and more completely, while also activating calcium signaling and nitric oxide pathways inside those cells before they die.1PubMed Central. Polidocanol for Endovenous Microfoam Sclerosant Therapy STS operates through a similar membrane-disrupting mechanism.
European guidelines recognize both drugs as first-line agents for varicose veins and venous malformations.2PubMed. European guidelines for sclerotherapy in chronic venous disorders In head-to-head comparisons, however, polidocanol tends to come out ahead on patient satisfaction. In a double-blind trial comparing the two agents for spider veins and reticular veins, roughly 85 to 88 percent of patients treated with polidocanol were satisfied at 12 and 26 weeks, compared with about 63 to 64 percent for STS.3PubMed. Sclerotherapy of telangiectases and reticular veins: a double-blind, randomized, comparative clinical trial of polidocanol, sodium tetradecyl sulphate and isotonic saline (EASI study) Polidocanol is also generally considered to have a better safety profile, with fewer allergic reactions and less pain on injection.4PubMed. Polidocanol in Sclerotherapy for Lymphovenous Disorders: Mechanisms, Clinical Uses, and Future Prospects
That said, STS remains a mainstay for larger veins and for vascular malformations where a more aggressive sclerosing effect is wanted. One study treating venous malformations in the mouth and throat of children with STS reported an overall response rate of 83 percent, with a third achieving complete resolution.5PubMed. Sodium tetradecyl sulphate sclerotherapy for treating venous malformations of the oral and pharyngeal regions in children The choice between the two often comes down to vein size, clinical setting, and local licensing.
Osmotic and Chemical Irritant Solutions
Not every sclerosant is a detergent. A second broad category is hypertonic (concentrated salt or sugar) solutions, which work by pulling water out of the cells lining the vessel wall through osmotic stress. Hypertonic saline, typically at concentrations around 11.7 to 23.4 percent, is one of the oldest sclerosing agents still in clinical use. It is inexpensive, carries virtually no allergy risk since it is just salt water, and has a long track record. Its downsides include significant pain on injection and a tendency to cause skin damage if the solution leaks outside the vein. In animal models, hypertonic saline at 11.7 percent produced immediate endothelial damage and blood clotting within the vessel without causing skin necrosis even when extravasated, though it did not always produce enough deep damage to permanently close the vein.6PubMed. A comparison of sclerosing agents. Clinical and histologic effects of intravascular sodium morrhuate, ethanolamine oleate, hypertonic saline (11.7%), and sclerodex in the dorsal rabbit ear vein
Chromated glycerin sits in its own niche as a mild chemical irritant. It is particularly popular in parts of Europe and South America for treating the finest spider veins and telangiectasias. It works gently enough that the risk of hyperpigmentation and skin damage is low, but it is also known for being painful during injection.7PubMed. A double-blind, randomized study comparing pure chromated glycerin with chromated glycerin with 1% lidocaine and epinephrine for sclerotherapy of telangiectasias and reticular veins Some practitioners mix it with lidocaine to take the edge off. Because of its mild action, glycerin is rarely used on anything larger than very small cosmetic veins.
Other agents that appear in the literature include ethanolamine oleate, sodium morrhuate, and concentrated glucose solutions. Ethanolamine oleate is still used for esophageal varices in some countries. Sodium morrhuate, derived from cod liver oil, was once common but has largely fallen out of favor due to allergic reactions. Historically, the list of substances injected into varicose veins was startlingly broad: 5 percent phenol, iron perchloride, 20 percent sodium chloride, 60 percent glucose, iodine solutions, alcohol solutions, and chromic alum of glycerol were all tried, often with toxic consequences including severe infections, skin necrosis, and sepsis.8Phlebological Review. Sclerotherapy – from historical research to the modern and efficient method of phlebological treatment Modern practice has narrowed the field considerably.
Why Foam Changed Everything
The same detergent solutions take on different properties when mixed with a gas to create foam. Foam sclerotherapy uses the identical drug as liquid sclerotherapy, just delivered in a different physical form. The foam displaces blood from the vein rather than mixing with it, which means the active drug stays in contact with the vessel wall longer and at a higher effective concentration. This translates into substantially better results for larger veins. Reviews of clinical evidence consistently find that foam is far more effective than liquid for treating varicose veins, and ultrasound guidance allows the foam to be directed precisely into the target vessel.9PubMed. Foam and liquid sclerotherapy for varicose veins
The most common method for making foam at the point of care is the Tessari technique, which involves connecting two syringes with a three-way stopcock and rapidly pushing the liquid and gas back and forth to create a uniform foam. A typical preparation uses one part polidocanol liquid to four parts gas.10PubMed Central. Comparative analysis of endovenous laser ablation versus ultrasound‐guided foam sclerotherapy for the treatment of venous leg ulcers A commercially manufactured version, polidocanol endovenous microfoam, is also available and offers more consistent bubble size.
The choice of gas matters. Room air works, but physiological gas mixtures of carbon dioxide and oxygen appear to reduce side effects. In one trial, using a CO₂/O₂ mixture instead of room air cut the rate of skin staining from about 7 percent to 3 percent and improved vein closure rates from 86 to 91 percent.11European Journal of Vascular and Endovascular Surgery. Air versus Physiological Gas for Ultrasound Guided Foam Sclerotherapy Treatment of Varicose Veins Another study found that foam made with a 70 percent CO₂ and 30 percent O₂ blend resulted in significantly less chest tightness, coughing, and dizziness compared to air-based foam.12PubMed. Incidence of side effects using carbon dioxide-oxygen foam for chemical ablation of superficial veins of the lower extremity CO₂ is absorbed by the body much faster than nitrogen from room air, which is probably why it causes fewer systemic symptoms.
Matching the Solution to the Vein
No single concentration works for every situation. The fundamental principle is straightforward: the volume and concentration of the sclerosant should be matched to the size of the vessel being treated.13PubMed. Standard guidelines for care: Sclerotherapy in dermatology Using too high a concentration on tiny spider veins risks skin damage and hyperpigmentation; using too low a concentration on a large varicose vein means the treatment won’t work.
In practice, this means polidocanol concentrations typically range from 0.5 percent for small reticular veins up to 3 percent for larger truncal veins. One study treating venous leg ulcers used 2 to 3 percent polidocanol foam for the main trunk veins and dropped to 0.5 to 1 percent for the smaller side branches feeding the ulcer.10PubMed Central. Comparative analysis of endovenous laser ablation versus ultrasound‐guided foam sclerotherapy for the treatment of venous leg ulcers STS follows a similar gradient, with lower concentrations reserved for cosmetic spider veins and higher ones for larger feeder veins. For tiny telangiectasias, glycerin or very dilute polidocanol may be preferred precisely because they are less likely to cause the brown discoloration that stronger agents can leave behind.
Uses Beyond Leg Veins
Sclerotherapy solutions are not limited to varicose veins and spider veins in the legs. The same agents appear across a range of clinical problems.
Hemorrhoid treatment is one of the most common non-cosmetic applications. Injection sclerotherapy has become a popular office-based procedure for internal hemorrhoids, particularly for patients who are poor candidates for surgery.14PubMed Central. Sclerotherapy in Hemorrhoids Polidocanol has shown particularly good results here. In a randomized trial of 150 patients with bleeding internal hemorrhoids, about 95 percent of those receiving polidocanol were treated successfully after two sessions, needing fewer sessions and less total volume than patients treated with phenol in oil.15PubMed Central. Polidocanol versus phenol in oil injection sclerotherapy in treatment of internal hemorrhoids: A randomized controlled trial Polidocanol foam has even been used safely in patients taking blood thinners who presented with hemorrhoid bleeding, a group that often cannot undergo standard surgical options.16PubMed Central. Application of Polidocanol Foam Injection Sclerotherapy in Patients with Antithrombotic Therapy Combined with Mixed Hemorrhoid Bleeding
Vascular malformations represent another major indication. These are congenital tangles of abnormal blood vessels that can appear anywhere in the body and are notoriously difficult to treat. Polidocanol foam is commonly used for slow-flow venous malformations. Research has also explored combining bleomycin, an anti-cancer drug, with polidocanol foam, finding that the combination appears to be more effective than polidocanol foam alone while maintaining a similar safety profile.17Journal of Vascular Surgery: Venous and Lymphatic Disorders. Comparison of polidocanol foam versus bleomycin polidocanol foam for treatment of venous malformations Ethanol (pure alcohol) is another agent used for vascular malformations, particularly aggressive ones, though it carries a higher risk of complications than the detergent agents.
Complications That Vary by Agent
All sclerosants can cause side effects, but the type and frequency differ depending on which solution is used. Hyperpigmentation, a brownish discoloration along the treated vein, occurs in roughly 10 to 30 percent of patients regardless of agent. Telangiectatic matting, where new tiny vessels appear near the treatment site, happens in about 15 to 20 percent of cases. These are the most common cosmetic complications, and neither necessarily reflects a mistake by the practitioner.18PubMed. Cutaneous necrosis, telangiectatic matting, and hyperpigmentation following sclerotherapy. Etiology, prevention, and treatment
Hypertonic saline tends to sting or burn more than the detergent agents, and its pain profile is one reason it has been gradually displaced by polidocanol in many practices. Glycerin is also painful, though its mildness makes it less likely to cause tissue damage if it leaks into surrounding skin. Polidocanol, by contrast, was originally developed as a local anesthetic, so it often causes less injection pain than the other options.
Foam sclerotherapy, regardless of which drug is foamed, introduces a unique set of systemic concerns. A small number of patients experience visual disturbances resembling migraine aura after foam injections. Researchers have proposed two competing explanations: either micro-bubbles of gas cross from the venous system to the arterial side through a small heart defect called a patent foramen ovale, temporarily blocking tiny blood vessels in the brain or retina, or the sclerosant triggers the release of endothelin-1, a powerful blood-vessel-constricting substance, from the treated vein wall, which then causes vasospasm in the brain’s circulation.19PubMed Central. Migraine aura‐like episodes following sclerotherapy for varicose veins of the lower extremities—A systematic review20PubMed. High production of endothelin after foam sclerotherapy: a new pathogenetic hypothesis for neurological and visual disturbances after sclerotherapy These episodes are almost always transient and resolve within minutes to hours. The switch to CO₂/O₂ gas mixtures may reduce their frequency, and practitioners are advised to exercise particular caution in patients with known cardiac defects.21Journal of Vascular Surgery. Neurological complications of sclerotherapy for varicose veins
Who Should Not Receive These Solutions
The International Union of Phlebology’s 2023 consensus document lays out a clear set of absolute contraindications. Sclerotherapy should not be performed in anyone with a known allergy to the sclerosant being used, anyone with active deep vein thrombosis, anyone who has had a severe neurological or cardiac event after a previous sclerotherapy session, anyone with severe acute illness or infection, or anyone with critical limb ischemia where arterial blood supply is dangerously compromised.22PubMed. Sclerotherapy of lower limb veins: Indications, contraindications and treatment strategies to prevent complications – A consensus document of the International Union of Phlebology-2023
Relative contraindications, where the risks need to be weighed carefully against benefits, include pregnancy and breastfeeding, blood-clotting disorders that increase the chance of thrombosis, and conditions that raise the risk of neurological or cardiac side effects from the procedure. In these situations, treatment is not automatically ruled out, but the choice of agent, volume, and form (liquid versus foam) all become more consequential decisions.
How Foam Sclerotherapy Stacks Up Against Heat-Based Procedures
For patients with larger varicose veins, sclerotherapy is one option alongside endovenous laser ablation, radiofrequency ablation, and traditional surgical stripping. All of these approaches ultimately aim to close or remove the malfunctioning vein. The choice of solution matters here because foam sclerotherapy’s success rates, while good, run somewhat behind the heat-based methods for the biggest veins.
A trial comparing endovenous laser ablation, foam sclerotherapy, and conventional surgery found anatomic success rates of about 89 percent for both laser and surgery at one year, versus roughly 72 percent for foam sclerotherapy.23Journal of Vascular Surgery. Comparing endovenous laser ablation, foam sclerotherapy, and conventional surgery for great saphenous varicose veins At three years, the gap widened further: the foam group had a recanalization rate of about 26 percent, compared with 6 to 7 percent for laser and radiofrequency ablation.24Journal of Vascular Surgery: Venous and Lymphatic Disorders. Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy, and surgical stripping for great saphenous varicose veins with 3-year follow-up That said, quality-of-life scores improved equally across all treatment groups, and foam sclerotherapy has clear advantages in cost, convenience, and the absence of anesthesia requirements. It is also the only option that works well for tortuous or very small tributary veins that a laser catheter cannot navigate.
In practice, many patients end up receiving a combination: a heat-based procedure for the main trunk vein, followed by foam sclerotherapy of the remaining smaller branches. The flexibility of having multiple sclerosant concentrations and delivery forms means the solutions can be tailored to whichever vessels remain problematic after the primary treatment.
Experimental Agents and Combination Approaches
Researchers continue to look for improved sclerosant formulations. One recent line of investigation involves designing agents that combine two mechanisms of action in a single molecule. A study explored a compound that pairs a cationic surfactant, which disrupts cell membranes the way traditional detergents do, with a component that inhibits the plasmin system involved in clot breakdown.25Biochemical and Biophysical Research Communications. Study of vascular sclerosing agent based on the dual mechanism of vascular endothelial cell damage-plasmin system inhibition The idea is to damage the vein wall and simultaneously prevent the body from dissolving the resulting clot, potentially improving long-term closure rates.
Bleomycin-polidocanol foam, mentioned earlier for vascular malformations, represents another combination strategy already being tested in patients. Rather than reinventing the sclerosant molecule, this approach adds an anti-proliferative drug to the standard foam, aiming to prevent the abnormal vessels from regrowing after treatment.17Journal of Vascular Surgery: Venous and Lymphatic Disorders. Comparison of polidocanol foam versus bleomycin polidocanol foam for treatment of venous malformations These combination approaches reflect a broader trend: rather than searching for a single perfect sclerosant, the field is moving toward smarter delivery methods and cocktails tailored to the specific vascular problem being treated.