Embolization Therapy: Principles and Clinical Applications, 1 Ed.

Sclerosing Agents

Jordan C. Tasse • Bulent Arslan • Ulku Cenk Turba

Sclerosing agents represent another category of liquid embolic agents. They act by damaging endothelial cells, leading to an inflammatory fibrosis and irreversible vascular thrombosis. The sclerosant effect typically depends on the strength of the particular agent being used and the amount of time that it is in contact with the endothelial lining of the vessel.

ABSOLUTE ALCOHOL (ETHANOL)

Alcohol is one of the most potent of the liquid embolic agents. It can be injected using a catheter-based intravascular approach or using a direct percutaneous approach. Absolute alcohol is an effective permanent embolization agent that has been used in various scenarios. Some of the applications of absolute alcohol include percutaneous tumor ablation/treatment, presurgical embolization of renal cell carcinoma, and treatment of vascular malformations. Direct alcohol injection has been used for treatment of small (<2 cm) hepatocellular carcinomas and for sclerotherapy of painful abdominal cysts and postsurgical seromas.

Alcohol acts by denaturing endothelial proteins, leading to activation of the coagulation cascade inducing subsequent thrombosis.1 Ethanol also induces vasospasm. Occlusion is typically seen within seconds after injection and progresses for several days. The effect depends on ethanol concentration, time of exposure, and injection rate; rapid injection rates produce more endothelial damage and parenchymal necrosis with less thrombosis, whereas slower injection rates produce more thrombosis but less endothelial damage and necrosis.2 The use of alcohol as an embolic agent is not without risk. The disadvantages of alcohol include the risk of damage to surrounding tissues including nerves, skin, and mucosa due to its penetrative properties. Patients may experience severe procedural pain. Monitoring for systemic toxicity is also crucial when the dose of alcohol is greater than 1 mL/kg or if the total volume exceeds 60 mL. The side effects may include central nervous system depression, hemolysis, and cardiac arrest.

Given these possible effects, it is important to minimize the incidence of nontarget embolization. The techniques used to reduce this risk include slow injection, use of balloon occlusion of the arterial inflow, or balloon occlusion of the draining vein.

ETHANOLAMINE OLEATE

Ethamolin (QOL Medical, LLC, Kirkland, Washington)

Ethanolamine oleate is a salt of a fatty acid with excellent thrombogenic properties. It is typically injected as a mixture consisting of 5% ethanolamine oleate and nonionic contrast material or iodized oil (5:1 ratio) for radiopacity. It combines its inherent thrombogenic properties with an inflammatory response to oleic acid that occurs in the vascular wall. When compared to ethanol, ethanolamine oleate has a less penetrating effect in comparison and is therefore considered safer to use in vascular structures with close proximity to nerves, skin, and mucosa.

Ethanolamine oleate has most commonly been used for sclerosis of gastroesophageal varices, venous malformations, and sclerotherapy of cyst, seromas, etc. Some risks associated with ethanolamine oleate include renal failure, pulmonary edema, and anaphylaxis. Although it is considered experimental, haptoglobin can be administered with ethanolamine oleate to bind free hemoglobin and albumin before injection to prevent hemolysis-induced renal insufficiency.3

SODIUM TETRADECYL SULFATE

Sotradecol (AngioDynamics, Queesnbury, New York), FibroVein (STD Pharmaceuticals Ltd., Hereford, United Kingdom), Trombovar (Aventis Pharma, Le Trait, France), Tromboject (Omega Laboratories Ltd., Montreal, Quebec, Canada)

Sodium tetradecyl sulfate (STS; Sotradecol) is a long-chain fatty acid salt with detergent properties. It is an effective sclerosing agent that acts by inducing endothelial damage and dissolution of the endothelial cell membrane, which causes cell overhydration. Sotradecol is U.S. Food and Drug Administration (FDA) approved for distribution in 1% and 3% concentrations. It is typically mixed with a water-soluble contrast agent to provide radiopacity. It can also be mixed with iodized poppy seed oil (i.e., Lipiodol) with air or carbon dioxide to create a foam.4 Foamed detergent sclerosants have been reported to be more potent than their liquid counterpart.5

Sotradecol has been in use for more than 50 years and can be injected via an intravascular route or a direct percutaneous approach. Typical uses include the direct injection of varicose veins (0.1% to 3% concentration), sclerosis of gonadal veins in the management of varicoceles and pelvic congestion syndrome (1% to 3% concentration), sclerotherapy of peripheral venous malformation (1% to 3% concentration), as well as balloon-occluded retrograde transvenous obliteration (BRTO) procedures for bleeding gastric varices treatment (Fig. 11.1).

POLIDOCANOL

Asclera (Merz Aesthetics, San Mateo, California), Aethoxysclerol (Kreussler Pharma, Wiesbaden, Germany)

Polidocanol is the most widely used venous sclerosant in Europe and was recently approved by the FDA for use in the United States. It consists of 95% hydroxypolyethoxydodecane, a cationic detergent with anesthetic properties. Similar to STS, its detergent action induces rapid overhydration of endothelial cells, leading to vascular injury. Polidocanol can be obtained in 1% and 3% concentrations, and its potency is approximately half of Sotradecol. Polidocanol has been used to treat lower extremity varicosities and venous malformations. Its anesthetic properties have been reported to significantly reduce procedure-related pain.6

The risks of polidocanol administration include anaphylaxis and cardiac depression. The cardiac effects are due to its anesthetic properties, which cause depression in the electrical excitability of and conduction rate through the heart and spontaneous pacemaker activity in the sinus node, resulting in sinus bradycardia and possible sinus arrest.7

Table 11.1 summarizes the aforementioned agents.

SODIUM MORRHUATE

Scleromate (Glenwood LLC, Englewood, New Jersey)

Sodium morrhuate is a sclerosing agent composed of a sodium salt of fatty acids in cod liver oil. The agent has been used in the treatment of varicose veins and venous malformations. It has been reported to be 1.5 to 4 times less effective than Sotradecol.8 Additionally, high rates of anaphylaxis and complications from extravasation, including pain and tissue necrosis, have limited its use.

ETHIBLOC

Ethibloc (Ethicon, Norderstedt, Germany)

Ethibloc consists of a solution of zein, sodium amidotrizoate, oleum papaveris, and propylene glycol. It has been used effectively for the treatment of venous, lymphatic, and arteriovenous malformations. It requires approximately 15 minutes to solidify into a viscous solution, allowing it to remain static within the target lesion to cause intravascular thrombosis, necrosis, and fibrosis.

OTHERS

In general, there are various sclerosing agents. In addition to the aforementioned agents, any agent that has detergent properties, hyperosmolar agents, chemical irritants, and even antibiotics (doxycycline, erythromycin, etc.) may be used as sclerosing agents. The impact of the treatment is generally determined by the tissue/endothelium contact time and strength of the sclerosing agent.

TIPS AND TRICKS

Tips

• Ethanol injection is painful and anesthesia assistance should be considered.

• Always use a microcatheter coaxial to the diagnostic catheter or a triaxial system with elongated sheath to provide optimal stability.

• Be careful during diagnostic angiography for an arteriovenous malformation to identify high-flow versus low-flow lesion for potential alcohol injection.

• Perform thorough diagnostic angiography during BRTO to identify any complex outflow and ensure that occlusion balloon is above all outflow veins to maximize treatment and prevent nontarget embolization.

Tricks

• Contrast injection is helpful to estimate volume of sclerosant necessary in BRTO procedures.

• Ethanol should be mixed with nonionic contrast in a 1:1 ratio to allow optimal visualization.

• For limb lesions, use a tourniquet to decrease venous outflow and systemic effects of sclerosants.

• For small lesions, use small 1.7-Fr to 2.1-Fr microcatheters.

• Use vascular plugs to complement sclerosant for gonadal vein embolization to decrease coil use and procedure time and to maximize embolization effect.

CONCLUSION

Sclerosing agents can be used as an embolic agent for several different indications. Given their liquid form and mechanism of action, the potential does exist for unintended distal embolization and tissue effects not seen with other agents. Therefore, care must be taken when using these agents.

REFERENCES

 1. Do YS, Yakes WF, Shin SW, et al. Ethanol embolization of arteriovenous malformations: interim results. Radiology. 2005;235(2):674–682.

 2. Ellman BA, Parkhill BJ, Marcus PB, et al. Renal ablation with absolute ethanol: mechanism of action. Invest Radiol. 1984;19(5):416–423.

 3. Kato GJ. Haptoglobin halts hemoglobin’s havoc. J Clin Invest. 2009;119(8):2140–2142. doi:10.1172/JCI40258.

 4. Sabri SS, Swee W, Turba UC, et al. Bleeding gastric varices obliteration with balloon-occluded retrograde transvenous obliteration using sodium tetradecyl sulfate foam. J Vasc Interv Radiol. 2011;22(3):309–316.

 5. Cabrera J, Cabrera J Jr, Garcia-Olmedo MA, et al. Treatment of venous malformations with sclerosant in microfoam form. Arch Dermatol. 2003;139(11):1409–1416.

 6. Mimura H, Kanazawa S, Yasui K, et al. Percutaneous sclerotherapy for venous malformations using polidocanol under fluoroscopy. Acta Med Okayama. 2003;57(5):227–234.

 7. Marrocco-Trischitta MM, Guerrini P, Abeni D, et al. Reversible cardiac arrest after polidocanol sclerotherapy of peripheral venous malformation. Dermatol Surg. 2002;28(2):153–155.

 8. Woods JE. Extended use of sodium tetradecyl sulfate in treatment of hemangiomas and other related conditions. Plast Reconstr Surg. 1987;79(4):542–549.