Abstract
Objective
To investigate the effect of agitation on foam temperature.
Methods
Sodium tetradecyl sulphate and polidocanol were used. Prior to foam generation, the sclerosant and all constituent equipment were cooled to 4–25℃ and compared with cooling the sclerosant only. Foam was generated using a modified Tessari method. During foam agitation, the temperature change was measured using a thermocouple for 120 s.
Results
Pre-cooling all the constituent equipment resulted in a cooler foam in comparison with only cooling the sclerosant. A starting temperature of 4℃ produced average foam temperatures of 12.5 and 13.2℃ for sodium tetradecyl sulphate and polidocanol, respectively. It was also found that only cooling the liquid sclerosant provided minimal cooling to the final foam temperature, with the temperature 20 and 20.5℃ for sodium tetradecyl sulphate and polidocanol, respectively.
Conclusion
The foam generation process has a noticeable impact on final foam temperature and needs to be taken into consideration when creating foam.
Introduction
Sodium tetradecyl sulphate (STS) and polidocanol (POL) are detergent sclerosants used in the treatment of vascular malformations and varicose veins. These agents are typically administered as a foam to minimise dilution and deactivation by plasma proteins and circulating blood cells. This foam is generated by the agitation of liquid sclerosant with a gas, most commonly room air. Most methods of foam generation rely upon two syringes combined with a three-way tap to allow for this agitation.
We have previously demonstrated that the addition of heat adversely affects the stability of sclerosant foams, whereas the cooling of sclerosant foams prolongs foam stability. 1 Other studies confirmed that foam at 3℃ was more stable than that at normal room ambient temperature. 2
As the process of foam generation requires mechanical agitation, a greater understanding of how this process affects temperature is necessary. This study aimed to quantify the temperature changes resulting from the mechanical agitation.
Methods
Materials
STS 3.0% (FIBRO-VEIN, Australasian Medical and Scientific, NSW, Australia); POL 3.0% (Aethoxysklerol, Chemische Fabrik Kreussler, Wiesbaden, Germany); sodium chloride 0.9% w/v (normal saline (NS), Baxter Healthcare, NSW, Australia); 1 mL luer-lock syringe (Becton Dickson (BD), NJ, USA); 3 mL luer-slip syringe (Terumo, NJ, USA); three-way stopcock (BD); 5 micron Sterifix filter (B-Braun, Melsungen, Germany); 8-channel Thermocouple Input Module – USB-4718 (Advantech, Taipei, Taiwan).
Sclerosant preparation
STS 3% and POL 3% (w/v) were diluted with sodium chloride 0.9% (w/v) to create solutions of 0.5% and 1.5% concentrations.
Sclerosant and constituent cooling
The experiments compared the effect of cooling only the sclerosant liquid with the effect of cooling the sclerosant along with all the apparatus used in foam generation. A water bath was used for the cooling process for a minimum of 10 min before testing at starting temperatures of 4, 10, 15, 20 or 25℃. The temperature of the water bath was monitored using a thermocouple. The apparatus constituents used in foam generation were: 1 mL syringe containing 0.3 mL sclerosant, 3 mL syringe containing 1.2 mL room air, three-way stopcock with attached thermocouple and two filter hubs (Figure 1).
Experimental setup for foam temperature measurement. (a) A thermocouple wire was inserted into a vacant port in a three-way stopcock to record temperatures within the foam apparatus. (b) Close up of thermocouple sitting inside three-way tap.
Foam generation
Foam was generated in open air at room temperature using a modified Tessari method. 3 This involved attaching a 1 mL syringe of sclerosant, and a 3 mL syringe of air to a three-way stopcock. Two five-micron filter hubs were used, one between each syringe and the three-way tap. A Liquid to Air Fraction (LAF) of 1 + 4 was used.1,3,4
Starting from the air syringe, the air and sclerosant was steadily pumped to and fro for 20 passages. A stopwatch was used to time a passing rate of two pumps per second – this resulted to a total of 10 s worth of passages.
Temperature measurements
A thermocouple was used to measure temperature by lodging it between the vacant port of the three-way stopcock used for foam generation (Figure 1). A thermocouple is a junction between two different metals that produces a voltage related to a temperature difference. The thermocouples were linked up to a data logger. The data logger was connected to a laptop and a calibration curve was used to convert the voltage into temperature readings. Prior to testing, the thermocouples were electronically calibrated and compared with ethanol and digital thermometers to ensure consistency.
After sclerosant cooling was completed, the equipment was assembled then foam was generated. The temperature was logged for all aspects of this process. On completion of the 20 passes, the setup was left to sit at room temperature. The graphs in the results section below show temperature change as measured from the foam generation step to a total of 120 s afterwards.
Statistical analysis
Each temperature and concentration combination was repeated at least 3 times, and the results are expressed as the mean ± the standard error of the mean (SEM). The p-values were based on a paired t-test and two tails with significance set at p < 0.05. The categories involved are: *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001.
Results
The effect of cooling the foam apparatus
When only the liquid sclerosant received cooling treatment, it can be seen that there is only a small effect on final temperature of foam in comparison to when all foam generation constituents received cooling treatment. In both STS and POL, using a setup that had been left at ambient temperature was only able to generate a final foam temperature of 20.0 and 20.5℃, respectively. In contrast, the final temperature was 12.5 and 13.2℃ (respectively for STS and POL) when all the constituents received the cooling treatment as can be seen in Figure 2. For both pre-cooling and no cooling, POL foam had a greater deviation from the starting temperature.
The effect of pre-cooling the foam apparatus. The effect of pre-cooling of all components (foam apparatus, gas and sclerosant liquid) was compared with pre-cooling the sclerosant liquid only for both (a) STS and (b) POL. The inferred liquid temperatures are shown as dashed lines. Our results show that pre-cooling the sclerosant liquid only is not as effective as the process of foam generation will increase the foam temperature up to the room temperature. By contrast, pre-cooling the entire assembly will only increase the foam temperature marginally and remains low. The shaded area corresponds to the foam generation period (10 s). Results are the mean ± SEM (n = 4).
The effect of starting temperature on foam final temperature
For both STS and POL, when foams and the foaming apparatus were pre-cooled at either 4, 10, 15, 20 or 25℃, the characteristic temperature plots demonstrated two phases of temperature change (Figure 3). For the period of agitation (i.e. the first 10 s), the rate of temperature change was higher than the remainder of the 2 min. This was more obvious for POL than for STS. This increase in temperature in the first 10 s is due to the conversion of mechanical energy in the agitation process to the internal energy of the sclerosant leading to a temperature increase, whereas subsequently, the temperature change in the next 110 s is due to the convective heat transfer between the syringes and the ambient air.
The effect of starting temperature on foam final temperatures. Foams were generated using either (a) STS or (b) POL for 10 s (shaded region) using sclerosants and apparatuses precooled at either 4, 10, 15, 20 or 25℃, with the mean foam temperatures measured using a thermocouple (n = 4). Our results show that pre-cooling is useful in maintaining the foam temperature at a lower figure over the next few minutes required for foam injection. Furthermore, we are showing that pre-cooled foams are best injected immediately after foam generation. Error bars represent the SEM.
The change in temperature over the 2-min period is shown in Figure 4. The ambient air temperature of the room was measured at 22.6℃. Foams at starting temperatures lower than ambient air had a positive temperature change, whereas foam at higher temperatures had a negative temperature change. Foams at the lowest temperatures also showed the largest temperature changes during the foam generation process.
The relationship between starting foam temperature and foam temperature changes. The difference between starting and final foam temperatures for both STS (red) and POL (blue) were calculated and are shown with respect to the ambient air temperature (22.6℃). The results show that the lower the starting foam temperature, the larger the kinetic change in temperature gain. Results are the mean ± SEM (n = 4).
The effect of sclerosant concentration on final foam temperatures
For both STS and POL, there were no significant differences between the various concentrations tested (Figure 5).
The effect of sclerosant concentration and final foam temperatures. Final foam temperatures were measured 120 s following foam generation for different concentrations (0.5, 1.5 and 3%) for (a) STS and (b) POL.
Discussion
Previous studies have demonstrated that foams cooled below ambient temperature increases half time and that the introduction of heat decreases foam half times.1,5 The current study examined the effects of the foam generation process on the foam temperature, and whether cooling the liquid sclerosant and the foam apparatus would affect the final foam temperature. We found that the precooling of both the sclerosant and the foam apparatus to a temperature of 4℃ was required to maintain foam at temperatures of approximately 10℃ after foam generation.
Foams generated at temperatures below room temperature displayed different changes in temperature, the magnitude of which was determined by the difference with the room air temperature. For foams generated at room temperature, there was little change in temperature. This result is consistent with another study, which looked at varying number of passages at room temperature and found no significant differences in foam half time. 6
The effect of temperature on foam is seen to have two major clinical implications – the microstructure of the foam itself and the stability of the foam. Literature shows that lowering temperature increases the time taken for half of the foam to coalesce into liquid, inferring that foam is more stable at lower temperatures. 1 By showing the magnitude of temperature change from foam generation, we can deduce a temperature effect on foam stability.
As expected, there was a larger rate of temperature change during periods of foam agitation. These experiments demonstrated that mechanical foam generation impacted the rate of temperature change of foam, and that cooling of all constituents as opposed to cooling only the liquid sclerosant, was required to result in a cooled foam.
There was also little effect of sclerosant type or concentration on the final foam temperatures. For ionic surfactants such as STS, the repulsive force of the head counterbalances any stabilising effect from increasing concentration. 7 This is consistent with studies showing little difference between concentrations in STS. 8
In a clinical setting, the rate of temperature change is important as it subsequently affects stability of the foam itself. This study adds an understanding of what temperature changes occur when sclerosant foam is prepared using common foam generation techniques.
There are several limitations in this study. A pumping pace of two passages per second was chosen as the speed of foam generation for this study. In practice, each surgeon has their own preferred passing rates, and passing rates are likely to be variable even within the same procedure. Future research could look into the impact of various pumping speeds, and changing the total number of passes at different temperatures.
It should also be noted that in these experiments, we used 1 and 3 mL syringes connected to two filters by a three way tap to generate foams. Other practitioners use other combinations for generating foams, such as 3 and 5 mL syringes. These and other combinations were not investigated in this study and the results may vary should these combinations be used. In addition, we only investigated the effect using room air; however, a number of practitioners now used alternative gases such as carbon dioxide alone or with oxygen and it is not known what the effect of these gases would be on foam temperature.
Whether or not foam temperature is important in vivo is also an area which has not been investigated. It is quite possible that the higher temperature of blood will cancel out the effect of cooled foam, and is an area for further research. In future experiments, the microstructure of the foam may be analysed to determine the impact of structure on stability. This will allow a more thorough optimisation of parameters to create the desired foam characteristics.
In conclusion, this study has demonstrated that mechanical agitation has a noticeable effect on foam temperature, wherein a larger temperature change occurred the further the apparatus was cooled beyond ambient temperature. Generating a desired cooled foam was only possible when all constituent equipment received precooling, as opposed to cooling only the liquid sclerosant.
Authors' contributions
The study was conceived and designed by all authors. LT, KW and BF performed the experiments and data were analysed by LT, KW, BF and DC. LT, KW and DC wrote the manuscript. All authors read and performed revisions of the manuscript.
Footnotes
Acknowledgements
The authors wish to express their gratitude to the Bioelectronics group (The University of Sydney) for their aid in troubleshooting equipment used in these experiments.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.