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.

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.

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.

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.

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.

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.

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.

An Investigation on the Influence of Hyaluronic Acid on Polidocanol Foam Stability.

BACKGROUND: Foam sclerotherapy is an effective treatment strategy for varicose veins and venous malformations. Foam stability varies according to foam composition, volume, and injection technique. OBJECTIVE: To evaluate the stability of polidocanol (POL) foam with the addition of hyaluronic acid (HA). MATERIALS AND METHODS: Group A: 2 mL of 1% POL + 0 mL of 1% HA + 8 mL of air; Group B: 2 mL of 1% POL + 0.05 mL of 1% HA + 8 mL of air; Group C: 2 mL of 1% POL + 0.1 mL of 1% HA + 8 mL of air. Tessari's method was used for foam generation. The half-life, or the time for a volume of foam to be reduced to half of its original volume, was used to evaluate foam stability. Five recordings were made for each group. RESULTS: The half-life was 142.8 (±4.32) seconds for 1% POL without the addition of HA, 310.6 (±7.53) seconds with the addition of 0.05 mL of 1% HA, and 390.4 (±13.06) seconds with the addition of 0.1 mL of 1% HA. CONCLUSION: The stability of POL foam was highly increased by the addition of small amounts of HA.

Glue, steam and Clarivein--Best practice techniques and evidence.

In July 2013, the National Institute of Health and Clinical Excellence (NICE) recommended "endothermal" ablation (meaning endovenous thermal ablation) is the first line treatment for truncal venous reflux in varicose veins. The initial endovenous thermoablation devices were radiofrequency ablation and endovenous laser ablation. More recently, Glue (cyanoacrylate), endovenous steam and Clarivein (mechanochemical ablation or MOCA) have entered the market as new endovenous techniques for the treatment of varicose veins. Glue and Clarivein do not require tumescent anaesthesia and do not use heat and therefore termed non-tumescent non-thermal (NTNT). Steam both requires tumescence and is also a thermal technique (TT). This article reviews the current position of these 3 new technologies in the treatment of varicose veins.

A new method for using radiopaque sclerosing foam to treat venous malformations.

BACKGROUND: Sclerosing foam is recommended to treat venous malformations (VMs). However, determining the precise dosage for satisfactory efficacy and few side effects are still challenging. OBJECTIVE: To develop a new method of preparing sclerosing foam by adding contrast agent to treat patients with VMs visibly and precisely under radiologic guidance. MATERIALS AND METHODS: Sclerosant (polidocanol) and contrast agent (iopromide) were mixed to prepare a new sclerosing foam according to Tessari method, and different ratios of the 2 materials were used to study the stability (half-life) of the produced foams. X-ray absorption of the radiopaque foams was observed during patient treatment with digital subtraction angiography (DSA). RESULTS: The foams generated with the new method demonstrated a high x-ray absorption under DSA. The foam half-life among groups varied. The ratio of iopromide/polidocanol at 1:2 had a significantly longer half-life than the 1:1 or polidocanol-only group. The 1:2 group had a relative high x-ray absorption and was radiopaque to allow visualization of the sclerosing foam and lesion with DSA. CONCLUSION: Mixing contrast agent with sclerosant to prepare radiopaque foams is a new method for treating complex VMs with DSA, and a ratio of 1:2 is recommend for polidocanol and iopromide.

An analysis of 72% chromated glycerin used for sclerotherapy: sterility, potency, and cost after extended shelf life.

BACKGROUND: Sclerotherapy is the treatment of reticular veins and telangiectasias of the lower extremities. Sclerosants destroy endothelial tissue and expose subendothelial collagen fibers, which lead to subsequent fibrosis of vessels, thus preventing recanalization. There are several available sclerosants including sodium tetradecyl sulfate (STS), polidocanol (POL), and chromated glycerin (CG) with varying efficacy, potency, side effect profile, and cost. OBJECTIVE: To identify the possible bacterial contamination and potency of CG beyond the current recommended shelf life of 3 months and to prove if CG is as cost effective as other available sclerosants. METHODS: Samples of 72% CG underwent bacterial endotoxin, sterility, and potency analysis at Days 0, 24, and 183. In addition, cost comparison was performed with other commercially available sclerosants including STS and POL. RESULTS: No samples of CG showed any bacterial contamination. All aliquots of glycerin remained sterile at Day 14. Potency at Day 24 was 99.2%, which was the same at Day 183. Cost comparison with other sclerosants revealed that CG is lower cost per milliliter than STS and POL. CONCLUSION: Seventy-two percent CG has no contamination and maintains its reported potency up to 6 months while comparable with the cost of other commercially available sclerosants.

Fluoroscopy-guided endovenous sclerotherapy using a microcatheter prior to endovenous laser ablation: comparison between liquid and foam sclerotherapy for varicose tributaries.

OBJECTIVE: To compare the efficacy and adverse effects of endovenous foam sclerotherapy (EFS) and liquid sclerotherapy (ELS) using a microcatheter for the treatment of varicose tributaries. MATERIALS AND METHODS: From December 2007 to January 2009, patients with venous reflux in the saphenous vein were enrolled. The foam or liquid sclerosant was injected through a microcatheter just before endovenous laser ablation (EVLA). Patients were evaluated for the technical success, clinical success, and procedure-related complications during the procedure and follow-up visits. RESULTS: A total of 94 limbs were included: 48 limbs (great saphenous vein [GSV], 35; small saphenous vein [SSV], 13) were managed using EFS and EVLA (foam group; FG), and 46 limbs (GSV, 37; SSV, 9) were treated by ELS and EVLA (liquid group; LG). Varicose tributaries demonstrated complete sclerosis in 92.7% with FG and in 71.8% with LG (p = 0.014). Bruising (78.7% in FG vs. 73.2% in LG, p > 0.05), pain or tenderness (75.6% in FG vs. 51.2% in LG, p = 0.0237) were noted. Hyperpigmentation (51.2% in FG vs. 46.2% in LG, p > 0.05) was found. CONCLUSION: Endovenous foam sclerotherapy using a microcatheter is more effective than ELS for eliminating remnant varicose tributaries prior to EVLA. However, EFS is more commonly associated with local complications such as pain or tenderness than ELS. Furthermore, both techniques seem to prolong the duration of hyperpigmentation along with higher costs.

Sclerosant foam structure and stability is strongly influenced by liquid air fraction.

OBJECTIVES: To determine the effects of sclerosant foam preparation and composition on foam structure, the time course of liquid drainage, and foam coarsening. METHODS: Sodium tetradecyl sulphate (STS) and polidocanol (POL) foams were investigated in a range of concentrations (0.5-3%) and liquid-plus-air fractions (LAF; 1 + 2 to 1 + 8). Foam was injected into a vein simulation model (polyvinyl chloride tubing, inner diameter 3 mm, constant pressure 5-7 mmHg) filled with saline or blood. Liquid drainage, bubble count, and diameter were measured and documented by serial photography. RESULTS: Liquid drainage was faster in the vertical position than the horizontal one. In all variations, very small bubbles (diameter <30 µm) were generated initially that coarsened to form micro-foams (<250 µm). By 3 minutes mini-foams (>250 µm) and by 7.5 minutes macro-foams (>500 µm) were formed. Following injection, the upper regions of foam coarsened faster as liquid drained to the bottom of the vessel. Wet preparations produced significantly smaller bubbles. Low concentration POL foam produced significantly higher bubble counts and coarsened slower than STS. CONCLUSIONS: Foam structure is strongly influenced by the LAF. Despite the initial formation of micro-bubbles in the syringe, mini- and macro-bubbles are formed in target vessels with time post-injection.

Foam sclerosants are more stable at lower temperatures.

OBJECTIVES: Sclerosant foams are aqueous and break down under the influence of gravity, pressure, and temperature. The aim of this study was to investigate the effects of temperature on foam stability. METHODS: Sodium tetradecyl sulphate (STS) and polidocanol (POL) liquid and foam (1 + 4, liquid-plus-air fraction) were investigated in a range of concentrations (0.5%, 1.5%, 3.0%) and temperatures. Surface tension was measured by the Du Nuoy ring method. Liquid drainage from foam was measured and documented by serial photography. Both pre- and post-cooling variations were investigated. RESULTS: Surface tension decreased at higher temperatures. Surface tension of POL was higher than STS at concentrations tested. POL foam half-time increased significantly at higher concentrations while the half-time of STS foam was not affected by concentration. Heating the sclerosant foam above the ambient temperature reduced its half-time while cooling below the ambient temperature prolonged the half-time. Both pre- and post-cooling of the foams resulted in significant prolongation of half-times when compared to no cooling. Maximum stability of the two sclerosant foams tested was achieved at 10 °C. CONCLUSIONS: Foam sclerosants are more stable at cooler temperatures.