The Effect of Pushing Rate on Foam Stability in the Tessari Method.

BACKGROUND: The Tessari method is commonly used in sclerotherapy for producing foam, involving 2 syringes pushed back and forth 20 times with the use of a 3-way connector. Many factors affect the foam stability which is crucial for clinical efficacy. OBJECTIVE: This study aimed to identify the optimal pushing rate which may impact the foam stability. MATERIALS AND METHODS: Polidocanol (POL) solution (1% and 3%) was used to make sclerosant foam via the Tessari method, with a total of 20 pushes performed at different time durations: 10, 15, 20, 25, 30, 35, and 40 seconds. The foam stability was recorded using foam half-life time (FHT), and the pushing pressure to the syringe was recorded using a self-made electric device. Both FHT and the pressure among different groups were compared respectively. RESULTS: The FHT was decreased as pushing duration exceeding 20 seconds in POL 1% and 15 seconds in POL 3%. Both the highest FHT and pressure point were located in the 10-second group. CONCLUSION: It is recommended to complete 20 back-and-forth passages within 10 seconds to create stable foam.

An Optical Method for Immediate Evaluation of Microfoam Stability in Foam Sclerotherapy.

OBJECTIVES: The objective of our study was to develop an optical method that instantly evaluates the stability of sclerosing foam, which would enable early predictions of the clinical performance of the foam and reduce the occurrence of clinical side effects. METHODS: Based on the principle of light scattering, we developed a method to optically test foam stability and verified it experimentally using sodium morrhuate (2 mL; 0.05 g/mL) and carbon dioxide. A self-made foam preparation instrument was used to achieve a preparation speed of 275 mm/s. The liquid-gas ratios were considered as 1:3, 1:4, and 1:5. Curves of illuminance with respect to the drainage rate and decay time were obtained. By fitting the curve, the relationship between foam half-life time (FHT) and foam decay was obtained. Thus, foam stability was evaluated using the initial illuminance value; the foam transfer time was approximately 3 s. RESULTS: The experimental FHT varies between 205 and 232 s. Illuminance is exponentially related to drainage rate and linearly related with time. FHT can be expressed by the initial illuminance and illuminance curve fitting coefficients. The half-life of the foam decreases as the initial illuminance value increases, for the same sclerosing drug. The suitability of foam stability is determined by the position of the initial value in the chart. CONCLUSION: Optical methods are feasible for evaluating foam stability over a short period of time. Clinically predicting the stability of freshly prepared foam can reduce number of incidences of further complications. This will promote the development of foam sclerotherapy and provide a basic understanding of the internal mechanical properties of foam.

A Modiied 3-Way Tap to Enhance the Stability and Uniformity of Sclerosant Foam.

BACKGROUND: The Tessari method, mixing air with the sclerosant through a 3-way tap and 2 syringes, is the most widely used method to prepare foam in foam sclerotherapy. Uniform foam with smaller bubbles has great clinical significance for venous insufficiency. We aim to modify the traditional 3-way tap to produce more uniform and stable foam with smaller bubbles. METHODS: The traditional 3-way tap was modified by inserting a porous film within its channel. EXPERIMENT DESIGN: the foam was prepared with 2 mL polidocanol plus 8 mL air plus 0.05 mL hyaluronic acid; group 1, foam prepared with 20 quick passes through a traditional 3-way tap; and groups 2-7, foam prepared using the modified 3-way tap, with 10, 12, 14, 16, 18, and 20 quick passes, respectively. The uniformity of the foam was observed under optical microscopy, and the size of bubbles quantified using the Nano measurement software. The stability of the foam was evaluated using the foam half-life time. RESULTS: The foam half-life times of groups 1-7 were 306.4, 257.4, 285.6, 304.4, 318.6, 330.2, 331.3 sec, respectively. The modified tap also produced a more uniform distribution of smaller bubbles (group 7) compared with traditional tap (group 1). CONCLUSIONS: Modified 3-way tap enhanced the stability of the sclerosant foam, with a more uniform distribution of smaller bubbles.

Comparison of the Safety and Efficacy of Foam Sclerotherapy With 1: 2 Polidocanol to Air Ratio Versus 1: 4 Ratio for the Treatment of Reticular Veins of the Lower Extremities.

BACKGROUND: Foam sclerotherapy is a common treatment of lower extremity reticular veins. The effect of different liquid-gas ratios on foam stability and efficacy has been controversial. OBJECTIVE: To evaluate the use of 2 different polidocanol (POL) to air ratios for the treatment of reticular veins of the lower extremities. METHODS AND MATERIALS: Patients with lower extremity reticular veins were randomized to foam sclerotherapy with POL mixed with 4 mL of room air for one lower extremity or 2 mL for the other lower extremity. All telangiectasias were treated with glycerin immediately after treatment of the reticular veins. Adverse events (AEs) and efficacy were evaluated by both subject and blinded investigator. RESULTS: Thirty subjects completed the study. No statistically significant difference was seen in AEs between the 2 different POL to air ratios by subject questionnaire and blinded investigator scores at all time points. Subjects and blinded investigator reported a mean improvement between 0% and 50% at Day 21 and 26% to 75% at Day 90, which was not significantly different between groups. CONCLUSION: Two different POL to air ratios, 1:2 versus 1:4, were similarly safe and efficacious for the treatment reticular veins of the lower extremities.

A Novel Compound Sclerosant: Polidocanol-Bleomycin Foam.

BACKGROUND: Foam sclerotherapy is an effective treatment strategy for venous malformations. Both polidocanol (POL) and bleomycin are effective sclerosants; however, no studies have reported POL-bleomycin foam. OBJECTIVE: To introduce a method for producing POL-bleomycin foam and evaluate the stability of POL-bleomycin foam with bleomycin concentrations. MATERIALS AND METHODS: Group A: 2 mL of 1% POL + 8 mL of air; Group B: 2 mL of 1% POL + 3 U bleomycin + 8 mL of air; Group C: 2 mL of 1% POL + 6 U bleomycin + 8 mL of air; Group D: 2 mL of 1% POL + 12 U bleomycin + 8 mL of air. Tessari method was used for foam generation. The foam half-life time (FHT) was used to evaluate foam stability. Five recordings were made for each group. RESULTS: The FHT was 148.6 ± 2.9 seconds in Group A, 148.8 ± 4.0 seconds in Group B, 148.4 ± 2.6 seconds in Group C, and 148.8 ± 1.6 seconds in Group D. The FHT in different groups showed no significant differences. CONCLUSION: The POL-bleomycin foam was prepared successfully and its FHT was as long as the POL foam.

Bleomycin Polidocanol Foam (BPF) Stability - In Vitro Evidence for the Effectiveness of a Novel Sclerosant for Venous Malformations.

OBJECTIVE: This study investigated the in vitro stability of a novel sclerosant, bleomycin polidocanol foam (BPF), for venous malformation (VM) sclerotherapy. METHODS: The study was designed with control groups treated with polidocanol (0.5%, 1%, and 3%) only. The experimental groups included 21 BPFs, which was made by dissolving bleomycin at seven different concentrations (0.1%-1.5%) in polidocanol (0.5%, 1%, and 3%). The Tessari method was used to prepare sclerosant foam with a liquid:gas ratio of 1:4 at room temperature in vitro. The foam stability was measured for each group. The decay process, one component of foam stability, was recorded with a camera. Foam decay process experiments were performed 10 times per group. The stability indices included drainage rate, drainage time, half life, and microscopic measurement of the foams (mean bubble diameter, minimum and maximum bubble diameters, wall thickness, and bubble diameter distribution). RESULTS: Compared with the control groups, the half lives of BPFs mainly increased significantly with the addition of bleomycin (p < .001). BPF with 3% polidocanol and 0.1% bleomycin recorded the highest half life (246 ± 1.6 sec), and this group also achieved the smallest bubble diameter and wall thickness (69.9 µm and 5.80 µm) among the experimental groups. For the same polidocanol concentration, the bubble diameter and wall thickness increased when bleomycin was added. CONCLUSION: Bleomycin concentrations account for different BPF stability. BPF stability mainly increased significantly with the addition of a small amount of bleomycin but this advantage was no longer apparent with increasing bleomycin dose.

Identifying the Most Stable State of a Foam Sclerosant for Foam Sclerotherapy.

BACKGROUND: Foam sclerotherapy is an effective treatment strategy for vascular malformations, and its sclerosing power depends on foam stability. Twenty quick passages have been widely used as an indicator of the most stable state of sclerosants, but the universality of their effectiveness has not been proven yet. OBJECTIVE: We aimed to identify simple and objective indicators of the most stable state of commonly used sclerosants and provide practitioners with suggestions to judge when foam producing is completed in sclerotherapy. MATERIALS AND METHODS: The universality of the effectiveness of 20 passages was tested by producing bleomycin foam with different passages. Further study was performed by testing modified bleomycin, polidocanol, and sodium tetradecylsulfate foam. RESULTS: The bleomycin foam became denser as passages were added, and the sound of each passage became almost silent after 40 passages. The almost silent sound can be an indicator of foam stability for most sclerosants. It has a different application range compared with 20 quick passages. CONCLUSION: We suggest that practitioners choose a different indicator depending on the foam used.

A Review of Sclerosing Foam Stability in the Treatment of Varicose Veins.

BACKGROUND: Varicose veins are common clinical entities. Foam sclerotherapy is a minimally invasive and simple procedure; however, the side effects, efficacy, and stability of sclerosing foam are not ideal. OBJECTIVE: To summarize the current studies on sclerosing foam stability and promote foam sclerotherapy development. MATERIALS AND METHODS: We reviewed the literature before June 2018 and included only representatives studies on sclerosing foam stability. We summarized the foam half-life time (FHT) of polidocanol (POL) under 17 preparation conditions and the FHT of sodium tetradecyl sulfate under 21 preparation conditions. The preparation conditions included various combinations of temperature, liquid-gas ratio, preparation method, etc. RESULTS: The FHT of POL varied between 40 and 4,000 seconds under different conditions. The FHT of sodium tetradecyl sulfate varied from 25.7 to 390 seconds. The higher the drug concentration, the lower the temperature required to increase foam stability. The addition of surfactant greatly increased foam stability. For different gas compositions, the FHT sequence was as follows: CO2 < CO2 + O2 < O2 < air. CONCLUSION: Foam stability can be improved by changing the preparation conditions; therefore, the role of surfactants and predictive methods for FHT are worth investigating further.

Effects of Hyaluronic Acid on Stability of Bleomycin Foam.

BACKGROUND: Bleomycin (BLM) foam sclerotherapy is effective in the treatment of venous malformations (VMs). Foam stability is influenced by factors such as sclerosant concentration, viscosity, and liquid-gas ratio. OBJECTIVE: To investigate whether hyaluronic acid (HA) could increase the stability of BLM foam and to evaluate the safety and efficacy of HA-BLM foam. MATERIALS AND METHODS: Experiment: BLM 6.0 IU + human serum albumin (HSA, 2, 1.95, 1.90, and 1.85 mL, respectively) + 1% HA (0, 0.05, 0.10, and 0.15 mL, respectively) + air 6 mL to create foam using the Tessari method. The foam half-life (FHL) was used to evaluate foam stability. Clinical study: Twenty-eight patients with head and neck VMs were enrolled between June 2018 and August 2019 treated by HA-BLM foam to evaluate the safety and efficacy. RESULTS: The FHL of the BLM foam was 8.46, 8.95, 10.45, and 14.51 minutes, respectively. All patients achieved significant efficacy, and no obvious side effects were observed. CONCLUSION: Addition of HA could improve the stability of BLM foam.

Improper Potency and Impurities in Compounded Polidocanol

Polidocanol is an FDA-approved sclerosant indicated for treating uncomplicated spider veins and reticular veins in the lower extremities. Despite restrictions against compounding drugs that are essentially copies of FDA-approved or commercially available products, polidocanol is also available from compounding pharmacies and outsourcing facilites. Compounded drug products are not FDA-approved and have not undergone premarket FDA review for safety, effectiveness, and quality. Seven samples of polidocanol were obtained from three compounding pharmacies and analyzed using high pressure liquid chromatography. None of the samples contained the labeled concentration of polidocanol and five contained excessive levels of impurities. Since the potency and purity of compounded polidocanol injection cannot be assured, physicians who use these products should consider FDA-approved products to ensure optimal safety and efficacy. J Drugs Dermatol. 2019;18(11):1124-1127.

Particle size, distribution, and behavior of talc preparations: within the United States and beyond.

PURPOSE OF REVIEW: Talc remains a common sclerosant utilized for pleurodesis. However, the use of talc has documented complications and debate has persisted regarding the safety of talc as well as the differences in talc preparations available throughout the world. We sought to describe an up-to-date review of talc preparations available and the impact these preparations may have on the safety profile of talc. RECENT FINDINGS: Within laboratory-based examinations, talc particle size available within the United States appears to be more consistent with prior reported 'safe' particle sizes. The presence of talc within protein-based solutions appears to modify the overall milieu of the solution and likely results in particle aggregation. SUMMARY: The use of talc remains well accepted for pleurodesis as evidenced by inclusion by multiple guidelines. The medical fields' current understanding of talc and its basic interactions within the pleural space remain limited. Multiple questions related to the pleural space and pleurodesis remain unanswered.

Effects of sulodexide on stability of sclerosing foams.

BACKGROUND AND OBJECTIVES: Foam sclerotherapy is a clinical procedure for the treatment of unhealthy veins. The aim of this study was to investigate the effect of sulodexide (SUL) on stability of foams prepared using polidocanol (POL) and sodium tetradecyl sulfate (STS) detergents, more specifically with 0.25% aethoxysclerol and 0.2% Fibro-Vein sclerosing solutions. METHODS: Foams were produced by the Tessari method using three different weight ratios of POL-SUL and STS-SUL (1:0, 1:1, and 1:3). RESULTS: The half-life of STS foams resulted as follows: 82 ± 1.6 s, 101.8 ± 2.6 s, and 109.7 ± 2.1 s for 1:0, 1:1, and 1:3 STS-SUL weight ratios, respectively. The same ratios were used for POL foams with the following results: 90.6 ± 3 s, 106.8 ± 2.6 s, and 107.6 ± 2.7 s for 1:0, 1:1, and 1:3 POL-SUL weight ratios, respectively. CONCLUSION: The addition of SUL in sclerosing solutions can prolong the half-life of foams, and it could be potentially used as a foam stabilizer.

A comparison of different surfactants on foam stability in foam sclerotherapy in vitro.

OBJECTIVE: This article compares the effect of different surfactants on foam stability and determines the foam decay relationship, so that the suitability of surfactants in a clinical setting can be evaluated. METHODS: Five different surfactants were used to prepare sclerosing foam at room temperature using a liquid:gas ratio of 1:4 in vitro. Foam decay experiments were performed for each sample using a laboratory-made foaming apparatus, and the process was recorded using a video camera. The stability indices used included the drainage time, drainage rate, half-life, foam half-life volume, surfactant stability index, and foaming index. RESULTS: The sodium morrhuate foam was relatively more stable than the polidocanol foam, but exhibited weak foaming. After the addition of the surfactants, the foam half-life was less than 300 seconds. The effect of the surfactants on the stability of the sodium morrhuate foam was more pronounced. The surfactant stability indices could be arranged as follows: poloxamer 188 > Tween 80 > macrogol 4000 > propanediol > lecithin. However, the differences in the foaming indices were small. CONCLUSIONS: Of the five surfactants tested, poloxamer 188 has best performance to enhance sclerosing foam stability. The addition of the surfactants improved the stability of the sclerosing foams. It was observed that the relationships between the foam half-life and the surfactant stability index and the surfactant concentration follow the power law.

Polydocanol foam stabilized by liposomes: Supramolecular nanoconstructs for sclerotherapy.

Vascular pathology of the lower limbs is a widespread disease affecting the quality of life for more than 30% of the adult world population. Polydocanol foam is presently the main therapeutic option for treating varicosities, inflammation, and chronic disease which affect the vascular endothelium and blood vessels. Unfortunately, the commercial product contains detergents and surfactants which can provoke several side effects and decrease the efficacy of therapy. In an attempt to overcome these drawbacks, polydocanol foam was mixed with different liposomes before use. The resulting mixture was stable and generated supramolecular nanoconstructs, which may prevent the interaction of the components of the commercial polydocanol foam with the vascular endothelium. This effect depends on the presence of liposomes, which can induce polydocanol foam to change its structure from micelles to complex nanostructures, thus improving its stability. In this attempt, the physicochemical features of the resulting nanoconstructs were tested through dynamic- and multiple light scattering analyses, rheological studies and gel permeation chromatography, while the stability was tested in biological fluids. Our preliminary results showed that the nanoconstructs have some potential as therapeutic agents in sclerotherapy.

Effect of Multiple Factors on Foam Stability in Foam Sclerotherapy.

Foam sclerotherapy is a widely used treatment for varicose veins. However, complications caused by poor foam stability still remain. Most studies ignore multiple influencing factors and only study a single factor. Furthermore, a stable foam preparation using different preparation conditions has not been developed. This study aimed to explore the changing laws of foam stability under multifactorial conditions, and to determine the influence of various factors and optimal preparation conditions on the half-life of foam. A two-level orthogonal test was conducted using four factors (syringe size, surfactant, preparation temperature, and pump speed). Classifications were established as follows: syringe sizes, 2.5 mL and 5 mL; surfactant concentrations, 6% and 0%; preparation temperatures, 20 °C and 10 °C; and pump speeds, 250 mm/s and 125 mm/s, respectively. Eight experimental group (EG) multi-factor combinations were tested. Half-life and drainage time were recorded for analysis. The initial drainage time was within 200 s, but the difference between the groups was also about 200 s. The drainage rate curves of all EGs gradually increased over time. Conversely, the foam half-life extended by about 10 times for the four factors. In addition, the analyses revealed that the order of influence was surfactant >temperature >pump speed >syringe size. The most stable foam preparation was determined. Syringe size, surfactant, temperature, and pump speed had markedly observable influences on foam half-life. A combination of multiple factors can be used to prepare a more stable foam in clinical scenarios and to suitably superimpose favorable conditions to avoid unfavorable conditions.

Effects of Different Mixing Agents on the Stability of Sodium Tetradecyl Sulfate (STS) Foam: An Experimental Study.

PURPOSE: To evaluate the effect of air, CO2 and contrast medium-air on the dwell time (DT) stability of sodium tetradecyl sulfate (STS) foam. MATERIALS AND METHODS: Three types of foam sclerosants (air-foam, CO2-foam, contrast-air-foam) were injected eight times into an inclined straight plastic tube (internal diameters 4 mm and 10 mm) filled with a blood substitute. Injections were captured by CCD camera, and images were transferred for digital analysis and calculation of DT. RESULTS: Contrast-air-foam and air-foam in a 4-mm tube showed 5.6-/3.3-fold greater DT compared to CO2-foam, respectively (P = 0.001). Contrast-air-foam in a 10-mm tube showed 2.1-fold greater DT compared to CO2-foam (P = 0.0167). CONCLUSION: A mixture of air and iodinated contrast improves the stability of STS foam compared to mixtures using only air or CO2. Further, animal and clinical studies are needed to validate this in vitro result.

Novel developments in foam sclerotherapy: Focus on Varithena® (polidocanol endovenous microfoam) in the management of varicose veins.

Scope Varithena® is a recently approved commercially available drug/delivery unit that produces foam using 1% polidocanol for the management of varicose veins. The purpose of this review is to examine the benefits of foam sclerotherapy, features of the ideal foam sclerosant and the strengths and limitations of Varithena® in the context of current foam sclerotherapy practices. Method Electronic databases including PubMed, Medline (Ovid) SP as well as trial registries and product information sheets were searched using the keywords, 'Varithena', 'Varisolve', 'polidocanol endovenous microfoam', 'polidocanol' and/or 'foam sclerotherapy/sclerosant'. Articles published prior to 20 September 2016 were identified. Results Foam sclerosants have effectively replaced liquid agents due to their physiochemical properties resulting in better clinical outcomes. Medical practitioners commonly prepare sclerosant foam at the bedside by agitating liquid sclerosant with a gas such as room air, using techniques as described by Tessari or the double syringe method. Such physician-compounded foams are highly operator dependent producing inconsistent foams of different gas/liquid compositions, bubble size, foam behaviour and varied safety profiles. Varithena® overcomes the variability and inconsistencies of physician-compounded foam. However, Varithena® has limited applications due to its fixed sclerosant type and concentration, cost and lack of worldwide availability. Clinical trials of Varithena® have demonstrated efficacy and safety outcomes equivalent or better than physician-compounded foam but only in comparison to placebo alone. Conclusion Varithena® is a promising step towards the creation of an ideal sclerosant foam. Further assessment in independent randomised controlled clinical trials is required to establish the advantages of Varithena® over and above the current best practice physician-compounded foam.

Studies on Foam Decay Trend and Influence of Temperature Jump on Foam Stability in Sclerotherapy.

OBJECTIVES: This study investigated the influence of temperature jump and liquid-gas ratio on foam stability to derive the foam-decay law. METHODS: The experimental group conditions were as follows: mutation temperatures (10°C, 16°C, 20°C, 23°C, 25°C, and 27°C to >37°C) and liquid-gas ratios (1:1, 1:2, 1:3, and 1:4). The control group conditions were as follows: temperatures (10°C, 16°C, 20°C, 23°C, 25°C and 27°C) and liquid-gas ratios (1:1, 1:2, 1:3, and 1:4). A homemade device manufactured using the Tessari DSS method was used to prepare the foam. The decay process was videotape recorded. In the drainage rate curve, the temperature rose, and the liquid-gas ratio varied from 1:1 to 1:4, causing faster decay. RESULTS: In the entire process, the foam volume decreased with increasing drainage rate. The relationships were almost linear. Comparison of the experimental and control groups shows that the temperature jump results in a drainage time range of 1 to 15 seconds. The half-life ranges from 10 to 30 seconds. The maximum rate is 18.85%. Changes in the preparation temperature yields a drainage time range of 3 to 30 seconds. The half-life varies from 20 to 60 seconds. CONCLUSION: Decreasing the temperature jump range and liquid-gas ratio gradually enhances the foam stability. The foam decay time and drainage rate exhibit an exponential function distribution.

Chitosan-doxycycline hydrogel: An MMP inhibitor/sclerosing embolizing agent as a new approach to endoleak prevention and treatment after endovascular aneurysm repair.

The success of endovascular repair of abdominal aortic aneurysms remains limited due to the development of endoleaks. Sac embolization has been proposed to manage endoleaks, but current embolizing materials are associated with frequent recurrence. An injectable agent that combines vascular occlusion and sclerosing properties has demonstrated promise for the treatment of endoleaks. Moreover, the inhibition of aneurysmal wall degradation via matrix metalloproteinases (MMPs) may further prevent aneurysm progression. Thus, an embolization agent that promotes occlusion, MMP inhibition and endothelial ablation was hypothesized to provide a multi-faceted approach for endoleak treatment. In this study, an injectable, occlusive chitosan (CH) hydrogel containing doxycycline (DOX)-a sclerosant and MMP inhibitor-was developed. Several CH-DOX hydrogel formulations were characterized for their mechanical and sclerosing properties, injectability, DOX release rate, and MMP inhibition. An optimized formulation was assessed for its short-term ability to occlude blood vessels in vivo. All formulations were injectable and gelled rapidly at body temperature. Only hydrogels prepared with 0.075M sodium bicarbonate and 0.08M phosphate buffer as the gelling agent presented sufficient mechanical properties to immediately impede physiological flow. DOX release from this gel was in a two-stage pattern: a burst release followed by a slow continuous release. Released DOX was bioactive and able to inhibit MMP-2 activity in human glioblastoma cells. Preliminary in vivo testing in pig renal arteries showed immediate and delayed embolization success of 96% and 86%, respectively. Altogether, CH-DOX hydrogels appear to be promising new multifunctional embolic agents for the treatment of endoleaks. STATEMENT OF SIGNIFICANCE: An injectable embolizing chitosan hydrogel releasing doxycycline (DOX) was developed as the first multi-faceted approach for the occlusion of blood vessels. It combines occlusive properties with DOX sclerosing and MMP inhibition properties, respectively known to prevent recanalization process and to counteract the underlying pathophysiology of vessel wall degradation and aneurysm progression. After drug release, the biocompatible scaffold can be invaded by cells and slowly degrade. Local DOX delivery requires lower drug amount and decreases risks of side effects compared to systemic administration. This new gel could be used for the prevention or treatment of endoleaks after endovascular aneurysm repair, but also for the embolization of other blood vessels such as venous or vascular malformations.

Size of Sclerosing Foams Prepared by Ultrasound, Mechanical Agitation, and the Handmade Tessari Method for Treatment of Varicose Veins.

OBJECTIVES: Sclerotherapy is a therapeutic method used in the treatment of varicose veins and works by occluding damaged blood vessels with a chemical solution. Foam sclerotherapy is an attractive treatment because the results are more effective than those obtained by using liquid sclerosants. However, serious neurologic complications, which are likely related to air embolism, have been reported after treatment with foams generated by the handmade method (Tessari technique) most often used clinically. We present an alternative ultrasonic technique for preparation of sclerosing foams to treat varicose veins. METHODS: Three methods of foam generation were compared: ultrasound, mechanical agitation, and Tessari techniques. RESULTS: Optical microscopic analyses showed that low-frequency ultrasound can generate foams with smaller bubble distributions compared to those produced by handmade and mechanical agitation methods: 98% of the bubble population was less than 55 ± 10 µm for sonicated foams (mean ± SD, 19 ± 1.8 µm; maximum bubble size, <138.3 ± 32.5 µm), 196.7 ± 38.2 µm for mechanically agitated foams (mean, 37.1 ± 10.6 µm; maximum bubble size, <350 ± 70.9 µm), and 211.7 ± 20.8 µm for handmade foams (mean, 30.8 ± 3.8 µm; maximum bubble size, <445 ± 32.8 µm). CONCLUSIONS: Low-frequency ultrasonic foam generation yields smaller bubbles and more uniform size distributions than other investigated methods. These properties may reduce serious adverse events reported for sclerotherapy of varicose veins, increasing the safety of foam treatment.