The two solutions most widely used for sclerotherapy today are polidocanol and sodium tetradecyl sulfate, both classified as detergent sclerosants. These agents work by disrupting the inner lining of a targeted blood vessel, causing it to collapse, scar shut, and eventually be reabsorbed by the body. But the full picture of sclerotherapy solutions is broader than those two workhorses, encompassing hypertonic agents, chemical irritants, and even repurposed cancer drugs depending on what is being treated and where in the body the procedure takes place.
The Two Dominant Detergent Sclerosants
Polidocanol (often sold under the brand name Aethoxysklerol) and sodium tetradecyl sulfate (commonly known as Sotradecol) account for the vast majority of sclerotherapy procedures worldwide. Both are surfactants, meaning their molecular structure has one end that attracts water and another that repels it. That dual nature is what makes them effective: when injected into a vein, they insert themselves into the fatty membranes of the cells lining the vessel wall, tearing those membranes apart in a process called lysis. The result is damage to the endothelium, which triggers clotting, inflammation, and eventually fibrosis that seals the vein permanently.1PubMed. Interaction of detergent sclerosants with cell membranes
The amount of destruction depends on the concentration injected. At lower concentrations, these surfactants alter the membrane without fully destroying it; at higher concentrations, they dissolve it entirely. This is why practitioners adjust concentrations based on the size of the vessel being treated. Tiny spider veins on the surface of the skin might need only a dilute solution, while a large, incompetent saphenous vein requires a stronger one. Polidocanol concentrations typically range from about 0.5% for small cosmetic veins up to 3% for larger trunks. Sodium tetradecyl sulfate follows a similar sliding scale.
One practical difference between the two is that polidocanol has local anesthetic properties, so injections tend to hurt less. A randomized trial comparing them in leg varicosities found that patients treated with sodium tetradecyl sulfate reported more pain and higher rates of hyperpigmentation at one month than those treated with polidocanol, though both agents achieved vein closure.2International Surgery Journal. A study to compare outcomes of Sodium tetra-decyl sulphate and Polidocanol in the treatment of varicosities due to incompetent tributaries of superficial vein of leg: a randomized controlled trial Neither agent is categorically superior for every patient, but the milder side-effect profile has made polidocanol the more popular choice in many clinics.
Hypertonic and Other Less Common Agents
Before detergent sclerosants became the standard, hypertonic solutions were the go-to option. Hypertonic saline, usually at concentrations around 23.4%, damages endothelial cells by osmotic shock: the extreme salt concentration pulls water out of the cells, causing them to shrink and die. Hypertonic glucose works on the same principle. These agents are still used, especially for very small spider veins, and they have the advantage of leaving no allergenic residue because the body already contains saline and glucose. The downside is that injections can sting sharply, and extravasation (leakage outside the vein) tends to cause more tissue damage than with detergent agents.3PubMed Central. Pharmacology of sclerotherapy
Ethanolamine oleate sits somewhere between categories. It is both a surfactant and a fatty acid salt, and it has been widely used for treating bleeding esophageal varices endoscopically. Sodium morrhuate, derived from cod liver oil, is another older agent still encountered in some settings; after injection, it triggers thrombus formation and a strong inflammatory reaction in surrounding tissue.4Asian Journal of Oral and Maxillofacial Surgery. Histological Investigation of Veins and Venous Malformations after Injection of Sclerosing Agents Chromated glycerin (Scleremo) is sometimes used in Europe for tiny superficial veins because it produces minimal hyperpigmentation, though it is weak and impractical for larger vessels. Pure ethanol is reserved for specific interventional radiology applications, particularly vascular malformations, because it is extremely potent and carries a higher risk of tissue destruction if it reaches unintended areas.
Foam Versus Liquid
One of the most important advances in sclerotherapy over the past two decades has been the ability to turn liquid sclerosant into foam. The concept is simple: you mix the liquid solution with a gas to create microfoam, which has several advantages over straight liquid. Foam displaces blood inside the vein rather than mixing with it, so the sclerosant stays in undiluted contact with the vessel wall for longer. It is also visible on ultrasound, which makes it easier for the practitioner to see exactly where the agent is traveling. And because foam occupies more volume than the same amount of liquid, you can treat a longer segment of vein with a smaller dose of the active drug.
The most widely used technique for making foam is the Tessari method, which involves connecting two syringes through a three-way stopcock and pushing liquid sclerosant back and forth with a gas to create a uniform microfoam. The liquid-to-gas ratio is typically around 1:4 or 1:5, meaning you use four or five parts gas for every one part liquid. Foam sclerotherapy with polidocanol at 2% concentration has shown solid results for treating incompetent great saphenous veins; one study reported full occlusion in about 73% of cases at 12 months, with another 21% showing partial improvement.5PubMed Central. Ultrasound-guided foam sclerotherapy of great saphenous vein with 2% polidocanol – one-year follow-up results A separate series using refined technique parameters reported saphenous vein occlusion in about 92% of cases after five years of follow-up.6PubMed. Results of Ultrasound-Guided Foam Sclerotherapy of the Great Saphenous Vein With New Parameters of the Technique
Why the Gas in the Foam Matters
Early foam sclerotherapy used room air to create the bubbles, and it worked well enough, but air is roughly 78% nitrogen, a gas the body absorbs slowly. Carbon dioxide and oxygen, by contrast, dissolve rapidly into blood. Switching to physiological gases turned out to make a meaningful difference in side effects. A study comparing carbon dioxide foam with air-based foam found that overall side effects dropped from 39% of patients to 11% when COâ‚‚ replaced air. Chest tightness, dry cough, and dizziness all fell significantly.7PubMed. Comparisons of side effects using air and carbon dioxide foam for endovenous chemical ablation
Follow-up work tested a carbon dioxide-oxygen blend, which eliminated chest tightness and dry cough entirely and reduced dizziness further compared with both air and pure COâ‚‚ foam.8PubMed. Incidence of side effects using carbon dioxide-oxygen foam for chemical ablation of superficial veins of the lower extremity Visual disturbance, a symptom that worries patients and practitioners alike, occurred in about 2% of cases with the COâ‚‚-oxygen mix. The likely reason for these improvements is straightforward: physiological gases are reabsorbed from the bloodstream within seconds, so any bubbles that escape the target vein are cleared quickly rather than lingering and potentially causing transient ischemia in small vessels.
What Actually Happens Inside the Vein
For a long time, the textbook explanation was that sclerosants damage only the endothelium, the single-cell-thick inner lining of the vein, and the resulting clot and scarring do the rest. More recent immunohistochemical work has revised that picture. Detergent sclerosants like sodium tetradecyl sulfate induce apoptosis (programmed cell death) not just in the endothelium but throughout the full thickness of the vein wall, including the muscular media layer. The pattern of inflammatory and apoptotic markers matches the distribution of cell death in the media, suggesting that sclerotherapy works by triggering an inflammatory and apoptotic cascade across the entire wall rather than simply stripping the inner lining.9PubMed. Media Damage Following Detergent Sclerotherapy Appears to be Secondary to the Induction of Inflammation and Apoptosis
This matters practically because it helps explain why sclerotherapy can produce lasting closure even in veins where a superficial thrombus alone might have recanalized over time. The deeper wall damage leads to genuine fibrosis rather than just a temporary clot. It also explains why higher concentrations carry a higher risk of collateral damage to surrounding tissue: the inflammatory reaction does not stop neatly at the vein’s outer boundary.
Factors That Influence How the Solution Behaves
The same sclerosant at the same concentration can behave differently depending on how it is prepared and delivered. Research into the interaction between detergent sclerosants and cell membranes has shown that the effectiveness of these agents is influenced by their ionic charge, molecular structure, pH, and the diluent used to mix them. For instance, diluting with saline rather than sterile water changes the ionic environment and can alter the way the surfactant molecules organize at the membrane surface.1PubMed. Interaction of detergent sclerosants with cell membranes
For polidocanol specifically, pharmacokinetic studies have tracked where the drug goes after injection. Roughly 75% of the dose is excreted through urine within the first 24 hours, with small additional amounts leaving via feces and exhaled air. After six days, about 89% of the total dose has been cleared. The drug is broken down by splitting its ether bond and oxidizing its carbon chain, producing small polyethylene glycol-like fragments, carbon dioxide, and water.10PubMed Central. Polidocanol for Endovenous Microfoam Sclerosant Therapy This relatively rapid metabolism is one reason polidocanol has an attractive safety profile compared with older agents that linger longer in the body.
Ultrasound-Guided Delivery
The combination of foam sclerosant and real-time ultrasound guidance has transformed what sclerotherapy can treat. For larger veins like the great saphenous vein, the practitioner positions the needle or catheter under ultrasound, injects the foam, and watches it fill the vein on screen. Foam is echogenic, meaning it shows up brightly on ultrasound, allowing precise monitoring of how far the agent has traveled. In practice, about 4 milliliters of foam treats roughly 10 to 15 centimeters of a saphenous trunk with an average diameter of 8 millimeters or less, and fresh foam is injected at intervals along the vein to cover its full length.11Journal of Vascular Surgery: Venous and Lymphatic Disorders. Ultrasound-guided foam sclerotherapy of the saphenous trunks is associated with a low 5-year recurrence rate and improved quality of life in patients with chronic venous disease
Without ultrasound, liquid sclerotherapy for spider veins and small reticular veins is done by direct visualization: you can see the surface veins, inject them, and watch them blanch. That approach does not work for deeper, larger veins that are invisible through the skin. Ultrasound guidance made foam sclerotherapy a viable alternative to surgical stripping and thermal ablation procedures for saphenous incompetence, at lower cost and without the need for general anesthesia.
Side Effects and Complications
Most side effects of sclerotherapy are cosmetic annoyances rather than serious complications. Hyperpigmentation, a brownish discoloration along the treated vein, occurs in roughly 10 to 30% of patients. It results from hemosiderin (iron pigment from degraded red blood cells) depositing in the skin. The good news is that it resolves on its own in the vast majority of cases: about 70% clear by six months, and 99% within a year.12PubMed. Cutaneous necrosis, telangiectatic matting, and hyperpigmentation following sclerotherapy. Etiology, prevention, and treatment
Telangiectatic matting, the appearance of new tiny red vessels near a treatment site, happens in about 15 to 20% of patients. It can be frustrating because you came in to get rid of visible veins and new ones appeared, but it too is usually temporary, resolving within 3 to 12 months. Cutaneous necrosis (skin death) at the injection site is rarer and can occur with any sclerosant, even when technique is flawless, if a small amount reaches the surrounding tissue or an arteriole feeding the skin.12PubMed. Cutaneous necrosis, telangiectatic matting, and hyperpigmentation following sclerotherapy. Etiology, prevention, and treatment
Neurological events are uncommon but get the most attention. Across a large dataset of over 10,000 sclerotherapy sessions, neurological complications including transient ischemic attacks, visual disturbances, speech disturbances, and migraine occurred in under 1% of cases. Among patients who experienced more serious events like transient ischemic attack or stroke, many were found to have a patent foramen ovale, a small hole between the heart’s upper chambers that allows bubbles or clotted material to bypass the lungs and reach the brain.13PubMed Central. Neurological complications of sclerotherapy for varicose veins This is one reason some practitioners ask about a history of migraine with aura before performing foam sclerotherapy, since migraine with aura is associated with a higher prevalence of patent foramen ovale.
The Role of Compression After Treatment
Wearing compression stockings after sclerotherapy is standard advice, and there is evidence that it genuinely improves outcomes. A randomized trial found that wearing stockings after sclerotherapy of small surface veins significantly increased vessel disappearance rates and reduced the formation of micro-thrombi compared with no compression.14PubMed. Compression after sclerotherapy for telangiectasias and reticular leg veins: a randomized controlled study A systematic review confirmed these findings and added that for larger veins treated with foam, higher-pressure stockings (around 35 mmHg) improved post-treatment symptoms more than lower-pressure ones (around 23 mmHg).15PubMed. Postsclerotherapy compression: A systematic review
The duration of compression varies by practitioner and by the size of the veins treated. For spider veins, a few days to a week is common. For saphenous trunks, two to three weeks is more typical. A trial comparing 23 mmHg stockings with 35 mmHg stockings after foam sclerotherapy and phlebectomy found that most symptoms, especially pain and heaviness, were milder in the higher-pressure group at three days, seven days, and 40 days post-procedure.16PubMed. Compression with 23 mmHg or 35 mmHg stockings after saphenous catheter foam sclerotherapy and phlebectomy of varicose veins The underlying idea is that compression keeps the walls of the treated vein pressed together, preventing blood from refilling it and giving the inflammatory fibrosis process a head start.
Sclerotherapy Beyond Varicose Veins
Although varicose veins and spider veins are the most common reason for sclerotherapy, the same principle of chemically destroying a vessel or cyst lining applies in other medical contexts. Endoscopic sclerotherapy for bleeding esophageal varices uses polidocanol, butyl-cyanoacrylate, or sodium tetradecyl sulfate injected directly into engorged veins in the esophagus that rupture in patients with liver cirrhosis.17PubMed Central. Endoscopic sclerotherapy for hemostasis of acute esophageal variceal bleeding Lauromacrogol (another name for polidocanol) has also been used in colonoscopic sclerotherapy for bleeding internal hemorrhoids, with one series reporting effective treatment in about 95% of patients at three months.18Gastroenterology & Hepatology: Open Access. Successful colonoscopic sclerotherapy for bleeding internal hemorrhoids with Lauromacrogol
Congenital lymphatic and vascular malformations represent a different application entirely. These are structural anomalies present from birth, often in the head and neck, that can be disfiguring and difficult to remove surgically. Bleomycin, an antineoplastic drug originally developed for cancer treatment, has been repurposed as a sclerosant for these lesions. Injected directly into the malformation, bleomycin causes local inflammation and fibrosis that shrinks the lesion. In a series of children with congenital lymphatic and vascular malformations in the head and neck, more than half of those treated with intralesional bleomycin saw swelling reduced by 50% or more, with some achieving complete resolution.19PubMed. Bleomycin sclerotherapy in congenital lymphatic and vascular malformations of head and neck Case reports have documented successful bleomycin sclerotherapy even after multiple failed surgical attempts, sometimes avoiding further risk of nerve damage from repeated operations.20PubMed Central. Bleomycin sclerotherapy for lymphatic malformation after unsuccessful surgical excision
How Practitioners Choose a Solution
The choice of sclerosant is not one-size-fits-all, and it depends on a combination of the vessel size, the clinical context, local regulatory approval, and practitioner preference. For small cosmetic veins on the legs, many clinicians favor polidocanol at low concentration because of its built-in anesthetic effect and comparatively gentle side-effect profile. For medium-sized tributary veins, either polidocanol or sodium tetradecyl sulfate in liquid or foam form is standard. For larger truncal veins like the great saphenous vein, foam polidocanol at higher concentrations under ultrasound guidance has become a first-line option in many countries, sometimes competing with thermal ablation techniques like laser or radiofrequency.
Hypertonic saline tends to be preferred by practitioners who want to avoid any risk of allergic reaction, since the body cannot be allergic to salt water. However, it stings more, and extravasation with hypertonic saline is more likely to cause ulceration than extravasation with polidocanol. In the gastrointestinal space, polidocanol and ethanolamine oleate dominate for endoscopic injection of varices and hemorrhoids. For vascular malformations, the choice broadens to include ethanol and bleomycin, agents that would be too destructive or toxic for routine varicose vein work but are appropriate when dealing with abnormal, often deep-seated vascular structures.
Regulatory availability varies by country, which also shapes what practitioners use. Polidocanol is approved for sclerotherapy in much of Europe, Australia, and the United States (where the FDA-approved proprietary microfoam formulation Varithena is available). Sodium tetradecyl sulfate has been available in the U.S. for decades. In some regions, practitioners still compound their own foam from liquid sclerosant using the Tessari technique, while others rely on commercially manufactured proprietary foams that offer more standardized bubble size and gas composition.