ELSEVIE ARTICLE IN PRESS
The Stability of Physician-Compounded Foam is Influenced by the Angle of Connector
Xuanxuan Shi,1,2 Yiran Liu,3 Dongjian Li,4 Medina Tursun,4 Sajjad Azmoun,4 and Shaohua Liu,2 Jinan, Shandong, China
Xuanxuan Shi and Yiran Liu contributed equally to this work.
1Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
2Department of Oral and Maxillofacial Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
3Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
4Department of Plastic and Burn Surgery, Qilu Hostiptal of Shandong University, Jinan, Shandong, China.
Correspondence to: Shaohua Liu, Department of Oral and Maxillofacial Surgery, Qilu Hospital of Shandong University, No.107, Wenhua Xi Road, Jinan, Shandong 250012, China; E-mail: lshabccba@126.com Ann Vasc Surg 2023; ·: 1–6
https://doi.org/10.1016/j.avsg.2023.08.011
2023 Published by Elsevier Inc.
Manuscript received: July 18, 2023; manuscript accepted: August 4, 2023; published online:···
Background: Foam sclerotherapy is an effective treatment for varicose veins and venous malformations, with its efficacy influenced by foam stability. The methods for preparing physiciancompounded foam (PCF) are the double syringe system (DSS) and Tessari method. Few studies have been performed to compare the PCF stability produced by the 2 methods and their mechanisms. We aim to compare the stability of PCF produced by 2 two methods in the same connector and explore the reasons for the difference.
Methods: Foam was generated by the 2 methods under different circumstances. In the Tessari method, 2 syringes were connected at right angles (90°) by a 3-way tap. In the DSS method, 2 syringes were connected by the same 3-way tap in a straight line (180°). The stability and uniformity of foam produced by the 2 methods were compared using foam half-time and optical microscopy, respectively. Assuming that the difference in foam stability between the 2 methods was related to the angles of a connector, we compared the foam stability when 2 syringes were connected with a plastic connector bent to different angles.
Results: The DSS method could produce more uniform foam with longer foam half-time than the Tessari method, which was related to the angle of the connector.
Conclusions: The stability of PCF is influenced by the angle of the connector.
INTRODUCTION
Foam sclerotherapy is an effective and commonly used treatment for varicose veins and venous malformations.1,2 Foam stability is a characteristic of sclerosant foam that determines its sclerosing power.3The foam stability has been reported to be influenced by various factors such as different gases,4 liquid-to-air ratio,5 type of sclerosant and its concentration,4,6 temperature7 and syringes,8 among which the preparation method is an important factor affecting the sclerosant foam stability.9
The most commonly used techniques by clinicians to prepare physician-compounded foam (PCF) at present are the double syringe system (DSS) and the Tessari method.10 The quality of thefoam made by the 2 methods, respectively, is subject to different opinions, but most studies have concluded that the DSS method was able to producemore stable foam than the Tessari method.11 - 15 However, the comparison of the 2 methods in the relevant studies was made under different connectors, especially since it is not known whether the pore sizes of the connection channels were the same, so the qualities of the foam prepared by the 2 methods were not comparable. At the same time, few studies have been performed on the reasons for the quality difference in PCF.
Therefore, we aimed to compare the stability of PCF produced by the 2 methods in the same connector and explore the reasons for the difference.
MATERIALS AND METHODS
The materials included disposable 5-ml and 10-ml syringes (WEGO, Weihai City, China), medical 3- way tap (WEGO), disposable plastic connecting tube (Sujia, Jiaxing City, China), medical polidocanol 1% (POL) injection (Shanxi-Tianyu, Xian City, China), double-distilled water, and POL powder (Sigma-Aldrich (Shanghai) Trading Co., Ltd., Shanghai City, China).
The Tessari and DSS methods were used to generate the sclerosant foam. In both techniques, the sclerosant foam was formed by moving the plungers of both syringes back and forth 20 times while mixing the POL solution with air at room temperature. In the Tessari method, 2 syringes were connected using a medical 3-way tap (Fig. 1A), and the long axes of the 2 syringes were at right angles (90°). In the DSS method used in this study (Fig. 1B), the straight connector was replaced by a 3-way tap, with the 2 syringes in a straight line (180°). The syringe on 1 side was closely connected with the 3-way tap through a disposable plastic connecting tube, which only served to fix the syringe and the 3-way tap.
Fig. 1. The Tessari method (A) and the DSS method (B). In the DSS method in this study, 2 syringes were tightly connected with a 3-way tap, and the disposable plastic tube only served to connect 1 side of the syringe with the 3-way tap.
In the experiment, 3 groups were first designed to compare the stability of the foam produced by the 2 foam preparation methods. In group 1, it was prepared in syringes of different volumes: 2 ml of 1% POL solution and room air in a 1:4 liquid-to-air ratio in 5 ml + 10 ml or 10 ml + 10 ml syringes to produce foam; in group 2, different concentrations of POL were used: 2 ml of 0.5%, 1%, and 3% POL solution and room air in a 1:4 liquid-to-air ratio in 2 10 ml syringes to produce foam. Where 0.5% POL solution was prepared by 1% POL solution diluted with double-distilled water and 3% POL solution was prepared by POL powder with double-distilled water; in group 3, different liquid-to-air ratios were used: 2 ml of 1% POL solution and room air in a 1:3 or 1:4 liquid-to-air ratio in 2 10 ml syringes to produce foam. After that, the uniformity of foam prepared by the DSS method and the Tessari method in 2 10 ml syringes with 2 ml of 1% POL solution and air at 1:4 was compared.
We assumed that the difference in PCF between the DSS and Tessari methods was related to the angle of the 2 syringes by the connector when the foam was prepared. Therefore, the stability of the foam was compared when the 2 syringes were connected by the same disposable plastic connection tube and the tube was bent to 90 (A), 135° (B), and 180° (C) (Fig. 2).
Fig. 2. Two syringes connected by the same connector at different angles. The 2 syringes were connected through a plastic connection tube, and the tube was bent at 90° (A), 135° (B), and 180° (C) during foam preparation.
The foam half-time (FHT) is the time recorded from the end of foam manufacture until half of the liquid volume of the sclerosant was reduced, and it was used to assess the stability of the foam. The sclerosant foam was made by the same operator, and each set was repeated 10 times.
The glass plate method was used to compare the size and distribution of the bubbles produced bythe 2 methods.16 To quantify the characteristics ofthe foam produced by both methods, the prepared foam samples were immediately placed on a single-layer slide, and then the size of the bubbles within the foam and the uniformity of the foam were observed and photographed with an optical microscope (Lecia, DIM4000 B). The foam observed in the photographs was recorded using Nano Measurer 1.2 software (Department of Chemistry, Fudan University, China).
Statistical Analyses
Statistical analyses were performed using Prism software (GraphPad Software Inc., USA). Comparisons between the foam stability produced by the 3 different connector angles were performed using 1-way ANOVA.
RESULTS
We first compared the stability of foam prepared by the Tessari and DSS methods under different conditions. Table I showed the FHT values measured using both the Tessari and DSS methods for the same concentration and liquid-to-air ratio with different volumes of syringes. The FHT represents the stability of the foam, and the longer the FHT, the better the stability of the foam. As expected, different syringes affected the FHT of the foam at different volumes.17 Under the same conditions, the DSS method produced longer FHT with better stability of the foam than that of the Tessari method, and the difference was assessed to be statistically significant (P < 0.001).
Table II showed the FHT values measured using the Tessari method and the DSS method for the same volume of syringes and liquid-to-air ratio, with different concentrations of POL solution. As studied in previous articles, the higher the POL solution concentration, the more stable the resulting foam and the longer the FHT.18 At the same concentration, the DSS method produced longer FHT in foam than the Tessari method, and the difference was assessed to be statistically significant (P < 0.001).
Table III showed the FHT values measured using the Tessari method and the DSS method for the same volume of syringes and the same concentration of POL solution with different liquid-to-air ratios. As mentioned in previous articles, a 1:3 liquid-to-air ratio produced longer FHT than a 1:4 liquid-to-air ratio.5 The DSS method produced longer FHT and more stable foam than the Tessari method for the same liquid-to-air ratio, and the differences were assessed to be statistically significant (P < 0.001).
The bubble size and uniformity of the foam produced by the 2 methods were also classified. Compared with the Tessari method, the DSS method was able to produce bubbles with slightly narrower distribution and bubble distribution concentrated in smaller size bubbles (Fig. 3). The size distribution range of foam bubbles for DSS was 7.72e407.59 mm, with an average size of 77.71 mm; the size distribution range of foam bubbles for Tessari was 7.87e501.87 mm, with an average size of 98.92 mm. The narrower size distribution in DSS foam led to the conclusion that it might be more consistent and stable compared to Tessari foam.
Fig. 3. Foam surface profiles and particle size distribution of bubbles for the DSS method and the Tessari method. (Aea) The DSS method. (Beb) The Tessari method.
In conclusion, the comprehensive performance of the foam prepared by the DSS method is better than that of the Tessari method. We assumed that the better stability of the foam produced by the DSS method over the Tessari method was related to the connection angles of the 2 syringes between the 2 methods. Therefore, we designed 2 syringes connected with disposable plastic connecting tube that bent at different angles when preparing the foam. We compared the FHT of foam when the plastic connecting tube was bent at 90°, 135°, and 180° (Table IV). When the angle was 90°, the FHT was the shortest; when the angle was 180°, the FHT was the longest; when the angle was 135°, the FHT was in the middle, and the differences were assessed to be statistically significant (90° vs. 135°, P < 0.001; 90° vs. 180°, P < 0.001; 135° vs. 180°, P < 0.001). Therefore, the difference in foam stability between the 2 methods was related to the connection angle of the 2 syringes.
DISCUSSION
Foam stability is a characteristic of sclerosant foam that determines its sclerosing ability.3 It is reported that a wide bubble size distribution promotes foam coarsening and degradation,14 and a narrow bubble size distribution reduces neurological complications due to gas embolism after treatment.19 The ideal foam should have a longer FHT, smaller and more uniform bubbles, and a narrower bubble size distribution.
Currently, the main manual methods of PCF production commonly used in clinical practice are the DSS and the Tessari method.10 In the Tessari method, the 2 syringes are connected by a 3-way tap at right angles, while in the DSS method they are connected by a straight connector in a line.20 The reported straight connectors in the DSS method were varied. The connector used by Hamel-Desnos was a 2-way connector.21 Jaggi Rao used stainless steel 2-way, different brands of 2-way, and different brands of 3-way in comparing the effect of different connector silicone content on foam stability in the DSS method.22 Peterson used the B. Braun Adapter W/W connector in the preparation of the foam by the DSS method.4 Carugo,12,14,23 Bottaro,13 and Meghdadi15 used the Combidyn adapter to connect 2 syringes in their studies. Both the Tessari method and the DSS methods can be considered to be derived from the “Owen technique".20 Shirazi referred to these 2 methods collectively as the DSS method and considered both methods to belong to the same foam preparation technique.11 Most of the studies, however, suggested that the 2 foam preparation techniques belonged to different methods.12-15 In these studies, 2 syringes were connected in the DSS method using 1 Combidyn
adapter and in the Tessari method using a 3-way tap. However, it is not clear whether the pore sizes of the connector channels used in the 2 methods are the same, making the 2 methods not comparable.
in this study, the same 3-way tap was adapted to compare the 2 preparation methods. However, 1 side of the medical 3-way tap commonly used in clinical practice cannot be directly connected to the syringe, so in this study, we used a disposable plastic connecting tube to fix the 3-way tap and the syringe. The plastic tube involved in the experiment served to tightly connect the 3-way tap to the syringe. This design made the comparison of the 2 methods reliable. In this study, we found that the comprehensive foam (smaller, more uniformly distributed bubbles, and longer FHT) produced by the DSS method was better than the foam produced by the Tessari method in the same connector.
We assumed that the foam difference between the DSS method and the Tessari method under the same conditions was related to the angles at which the 2 syringes were connected by the connector. Therefore, in this study, 2 syringes were connected by a plastic connecting tube, and the tube was bent at different angles to prepare foam. The foam stability was worse when the 2 syringes were connected at 90° than at 180°. This may be related to the fact that when the foam was moving in the 2 syringes, changing direction would reduce the speed of the foam’s movement, thus reducing the foam’s stability. It can explain the better stability of foam prepared by the DSS method, where 2 syringes are connected in a straight line, compared to the Tessari method, where 2 syringes are connected at 90°. Therefore, the stability of the PCF prepared by the 2 methods was affected by the angle of the connector.
CONCLUSION
To sum up, compared with the Tessari method, the DSS method was able to produce more stable and uniform PCF, which was related to the angle of the connector.
This work was supported by Development Funding for Novel Clinical Technology, Qilu Hospital of Shandong University (2019-17).
