AbstractPurposeThis study compared the efficacy of heat insulation between 5% dextrose and 0.9% saline in radiofrequency ablation (RFA). Accordingly, temperature variations and maximum temperatures were assessed at identical distances and heat field distributions.
MethodsCubes of porcine liver tissue, measuring 10 mm across, were selected to precisely align the ablation boundary with the tissue boundary. An 18-gauge electrode with a 7-mm tip was inserted into each cube (10 per group) in a stainless-steel cup containing 40 mL of 5% dextrose or 0.9% saline. Fixed ablation was performed for 3 minutes using continuous mode at 30 W, simulating the typical thermal environment during thyroid RFA. Real-time temperature measurements were recorded by sensors positioned 0, 1, 3, and 5 mm from the cube’s edge. A comparative analysis was conducted to assess the maximum temperature, temperature variation, and duration of temperatures exceeding 42℃.
ResultsIn both groups, the temperature curve declined with increasing distance from the edge of the ablated tissue. However, 0.9% saline exhibited higher maximum temperatures at 1, 3, and 5 mm compared to 5% dextrose (1 mm: 44.55°C±5.25°C vs. 34.68°C±3.07°C; 3 mm: 39.64°C±2.53°C vs. 29.22°C±2.21°C; 5 mm: 38.86°C±2.14°C vs. 28.74°C±2.51°C; all P<0.001). Considering a nerve injury threshold of 42°C, the 0.9% saline also displayed a greater proportion of samples reaching this temperature and a longer duration of temperatures exceeding it (P<0.05).
IntroductionRadiofrequency ablation (RFA) has become increasingly popular for the treatment of both benign and malignant tumors in various organs [1-5]. This technology generates a localized alternating electric field in the tissue, causing ion agitation and friction; the resulting high local temperatures lead to irreversible cell damage, tumor apoptosis, and coagulation necrosis [2]. However, this procedure carries a risk of thermal injury to adjacent sensitive structures, including nerves, bile ducts, and the diaphragm, potentially leading to a variety of complications [6-8].
The hydrodissection technique, also termed artificial ascites, is widely used as a thermoprotective adjunct to minimize thermal injury in RFA of abdominal organs. This is achieved through the injection of fluids, such as 5% dextrose and 0.9% saline [9,10]. The liquid is administered between the target site and adjacent critical structures to create a physical and thermal barrier during thermal ablation procedures [9-11]. While the efficacy of this technique in reducing complications from thermal injury has been established in clinical settings, the best choice of fluid to provide heat insulation during thyroid ablation has yet to be conclusively determined.
Some research suggests that in 0.9% saline, the alternating electric field generated by RFA may induce ion agitation and produce frictional heat. This phenomenon could increase the temperature and diminish the solution’s capacity to insulate against heat during RFA of the thyroid and liver [10,12,13]. In contrast, 5% dextrose contains macromolecular substances that are unaffected by the electric field and exhibit negligible electrical conductivity. When made to surround the target organ, this solution may offer dual protection against both electrical and thermal damage [10,14]. Laeseke et al. [12] observed that instilling 5% dextrose into the peritoneal cavity before hepatic RFA reduced the risk and severity of injuries to the diaphragm and lungs compared to 0.9% saline in domestic pigs. However, several clinical studies have demonstrated the efficacy of 0.9% saline in providing adequate heat insulation during various procedures, including RFA of liver tumors [9,11] and thyroid nodules [15].
The discrepancies in these findings may stem from several factors. First, studies have varied in the power and energy levels applied with the ablation needles [1,3,14], as well as in the distances covered by the liquid within the thyroid [14,16] and liver [17,18]. Higher energy levels and shorter liquid distances are potentially associated with an increased risk of thermal injury. Second, the thermal sensitivity of the tissues under protection differs. In RFA of liver tumors, the muscle tissues of the diaphragm and gastrointestinal tract are the primary tissues to be safeguarded, with a denaturation temperature of approximately 50°C [2,13]. In contrast, in RFA of thyroid nodules, nerves represent the structures most vulnerable to heat injury and are extremely temperature-sensitive, with neuroendothelial edema and collagen deposition occurring at a threshold of 42°C [19-21]. Consequently, to draw a more scientifically valid comparison of the heat insulation efficacy between 0.9% saline and 5% dextrose, it is crucial to examine temperature variations and maximum temperatures under identical distances and heat field distributions. However, no analogous studies have yet been conducted.
In this study, the efficacy of heat insulation was assessed by comparing temperature variations and maximums reached when using 5% dextrose versus 0.9% saline. These comparisons were made under the predominant thermal conditions of the surroundings observed during RFA of the thyroid. The objective was to determine which agent offers superior heat insulation during thyroid RFA, based on scientifically sound evidence.
Materials and MethodsThe experimental design of this study was divided into two parts, as shown in Fig. 1.
Determination of the Size of Porcine Liver TissueTo simulate an extreme scenario in which a nodule is adjacent to a vital structure, the size of the porcine liver tissue used should correspond to the actual ablation zone. To replicate the complete ablation of a thyroid nodule during RFA, various sizes of porcine liver tissue were ablated using an 18-gauge RFA electrode with a 7-mm tip. These trials were performed at a power setting of 30 W in continuous mode, utilizing a fixed ablation technique for a duration of 3 minutes. The procedure was conducted in a stainless-steel cup filled with 40 mL of either 5% dextrose or 0.9% saline. Subsequently, the liver tissue was sectioned along the longitudinal axis of the ablation zone, where the electrode had been inserted during the RFA procedure. The dimensions of the ablation zones were then measured. A 10-mm cube was chosen for the subsequent step, as it demonstrated precise alignment between the ablation boundary and the tissue boundary.
Comparison of Heat Insulation Efficacy between 5% Dextrose and 0.9% SalineThe experiment involved two groups: one treated with 5% dextrose and the other with 0.9% saline. Each group contained 10 tissue samples. Porcine liver tissue was ablated using an 18-gauge RFA electrode with a 7-mm tip, operating at 30 W in continuous mode with a fixed ablation technique. Temperature variations were continuously recorded by four temperature sensors placed at distances of 0 mm, 1 mm, 3 mm, and 5 mm from the edge of the 10-mm porcine liver tissue. The measurement point at the top of the optical fiber was confirmed to align with the needle tip. During ablation, real-time temperature measurements were acquired with fluorescent optical fiber temperature sensors using specialized software (Indigo Precision, Suzhou, China). The maximum temperature, temperature variations, and duration for which temperatures exceeded 42°C were compared between the two groups. The proportion of temperatures exceeding 42°C was recorded across the 10 ablations conducted in each group. For every ablation, each measuring point was categorized based on whether the temperature exceeded 42°C, with an indicated score of 1 if yes and 0 if no.
Statistical AnalysisContinuous variables were described as mean±standard deviation. The two-independent-samples t-test or the Mann-Whitney U test was used to compare groups of continuous variables. Comparisons across multiple groups were performed using the F test, with a Bonferroni correction for multiple comparisons. P-values less than 0.05 were considered to indicate statistical significance. Statistical analysis was conducted using SPSS version 23.0 (IBM Corp., Armonk, NY, USA).
ResultsMaximum Temperature and the Ratio of Temperatures Exceeding 42°C in the Two GroupsThe maximum temperatures recorded at each site for the two groups are presented in Table 1.
In RFA, thermal injury to adjacent structures relates to both the maximum temperature reached and its duration. Thus, a comparative analysis was performed of the maximum temperatures recorded at each measurement point for the two groups. Based on the average maximum temperatures across the 10 samples in each group, the temperatures at 1 mm, 3 mm, and 5 mm from the edge of the porcine liver tissue were significantly lower in the 5% dextrose group than in the 0.9% saline group (1 mm: 34.68°C±3.07°C vs. 44.55°C±5.25°C, P<0.001; 3 mm: 29.22°C±2.21°C vs. 39.64°C±2.53°C, P<0.001; 5 mm: 28.74°C±2.51°C vs. 38.86°C±2.14°C, P<0.001).
Next, considering the temperature threshold of 42°C associated with nerve injury, the proportion of tissue samples reaching this threshold was analyzed. The maximum temperature exceeded 42°C at 0 mm in both groups and at 1 mm for 0.9% saline only. At 3 mm and 5 mm, the maximum temperatures were below 42°C for both groups. Furthermore, at 0 mm, the maximum value exceeded 42°C for all 10 samples in the 0.9% saline group and for eight samples in the 5% dextrose group. However, at greater distances, only the saline solution displayed maximum temperatures exceeding 42°C, occurring six times at 1 mm and once at 3 mm. Additionally, 0.9% saline was associated with a longer duration of temperatures exceeding 42°C compared to 5% dextrose (163.46±52.62 seconds vs. 59.87±53.24 seconds, P<0.001).
Finally, a comparative analysis examined the energy delivered to the samples in the two groups. The energy delivered for the 5% dextrose solution was significantly lower than that for the 0.9% saline solution at both 2 and 3 minutes (2 minutes: 0.37±0.31 kcal vs. 0.79±0.27 kcal, P<0.001; 3 minutes: 0.55±0.36 kcal vs. 1.21±0.30 kcal, P<0.001).
To ensure comparable energy delivery, the ablation time for the 5% dextrose group was extended to 4 minutes. Notably, the energy delivered to this group over 4 minutes was statistically comparable to the energy delivered to the 0.9% saline group over 2 minutes.
Average Temperature Variation Trend According to Temporal and Spatial Variations of the Two GroupsThe average temperature variations detected by the temperature sensor at distances of 0 mm, 1 mm, 3 mm, and 5 mm from the edge of the porcine liver tissue in 40 mL of 5% dextrose and 0.9% saline are presented in Fig. 2.
The average temperature variation of the ambient liquid showed a comparable pattern in the 5% dextrose and 0.9% saline groups. Initially, a decreasing trend was observed with increasing distances from the edge of the ablation tissue, peaking at 0 mm and then leveling off at 3 mm and 5 mm. However, the average temperatures in the 0.9% saline group were higher than those in the 5% dextrose group.
DiscussionThis study compared the temperature variations and maximum temperature differences in samples insulated with 0.9% saline and 5% dextrose under identical distances and heat field distributions. For both solutions, the temperature curves decreased as the distance from the edge of the ablated tissue increased. However, the 0.9% saline samples reached higher maximum temperatures than the 5% dextrose samples at 0, 1, 3, and 5 mm from the tissue edge. Considering a 42°C threshold for nerve injury, the proportion of samples reaching this critical temperature was also greater for 0.9% saline.
This study involved the use of an 18-gauge RFA electrode with a 7-mm tip. A fixed ablation technique was applied for 3 minutes in continuous mode at 30 W, reflecting the most common thermal environment of the surroundings during thyroid RFA [2,14,22-24]. The moving-shot technique has been recommended as the preferred clinical method for complete ablation in the RFA of benign thyroid nodules [10,14]. However, due to the limited size of the porcine liver tissue in this study, achieving precise control over the heat field distribution using the moving-shot technique would have been challenging and may have introduced uncontrollable variables, such as displacement of the liver tissue and temperature sensors. In contrast, fixed ablation enabled a controlled distribution of the heat field without movement of the needle tip or liver tissue, while maintaining a consistent distance between the temperature sensors and the tissue [23,24]. After preliminary testing, a cuboid tissue sample measuring 10 mm across was selected to simulate a scenario in which the heat field precisely coincided with the posterior medial thyroid capsule. At this location, the heat field closely borders the recurrent laryngeal nerve, representing a situation of high vulnerability that is commonly encountered in clinical practice. Furthermore, the use of fixed ablation technique with prolonged duration and higher ambient temperatures increases the risk to adjacent structures, thus requiring greater insulation efficacy [6,7]. In conclusion, the size of the porcine liver tissue was adjusted to match the boundaries of the heat field. The heat insulation efficacy of 0.9% saline and 5% dextrose on vital adjacent structures was then compared within the RFA heat field, with fixed ablation employed to control key parameters such as the field and the distance for temperature sensor variables.
For both 0.9% saline and 5% dextrose, the temperature curves decreased in conjunction with increasing distance from the edge of the ablated tissue. However, significant differences were observed between the temperature curves of the two groups. Specifically, the 0.9% saline group displayed higher maximum temperatures at the same distances (1, 3, and 5 mm), along with a greater proportion of samples reaching 42°C, compared to 5% dextrose. Notably, nerve injury may occur when the ambient temperature exceeds 42°C. Complications from nerve injuries, such as hoarseness, Horner syndrome, and brachial plexus injury, are well-documented and can necessitate prolonged recovery periods or extended hospital stays [6,7]. These findings suggest that 5% dextrose may offer greater insulation efficacy than 0.9% saline, thereby providing superior protection for thermally sensitive nerves during RFA of the thyroid.
The findings of this study align with an experimental investigation by Laeseke et al. [12], which demonstrated that the instillation of 5% dextrose into the peritoneal cavity during hepatic RFA reduces the risk and severity of diaphragm and lung injuries compared to 0.9% saline in domestic pigs. However, other clinical studies have indicated that artificial ascites established with either 0.9% saline or 5% dextrose can provide effective protection during RFA of hepatic carcinoma [17]. The discrepancies between these findings may stem from two factors. First, the gastrointestinal tract, gallbladder, and other liver-adjacent structures are less thermosensitive than the nerves. Second, the volume of artificial ascites injected during liver ablation was substantial, up to 1,000-2,000 mL [9,17], which increased the distance between the adjacent structures and the edge of the heat field. In such cases, 0.9% saline can also provide satisfactory heat insulation. This difference highlights the superior nerve protection achieved with the use of 5% dextrose as a hydrodissection fluid during RFA in anatomically confined areas such as the neck (for instance, the thyroid and lymph nodes).
This study had several limitations. First, it utilized porcine liver tissue for in vitro experiments, with the procedure reflecting the specific experimental setting and heat field conditions. However, this tissue differs in density, conductivity, and specific heat capacity relative to thyroid and kidney tissues. Second, due to the non-conductivity of 5% dextrose, the porcine liver tissue needed to maintain constant contact with the bottom of the stainless-steel cup during the ex vivo experiment. In contrast, the human body exhibits excellent electrical conductivity, and the electrical conductivity of hydrodissection fluid may exceed that observed in vitro, particularly with 5% dextrose. Nerve protection during RFA of benign thyroid nodules is a multifaceted process that involves hydrodissection, the maintenance of a precise distance between the nerve and the edge of the ablation zone, and considerations regarding ablation method, duration, and power settings. This study solely compared the heat insulation properties of 5% dextrose and 0.9% saline under identical conditions of distance, ablation method, time, and power. Although the findings are limited in scope, they still hold clinical significance.
At 1 to 5 mm, the heat insulation efficacy of 5% dextrose surpasses that of 0.9% saline when both are tested at the same distance and under thermal conditions of the surrounding structure typical for thyroid RFA.
NotesAuthor Contributions Conceptualization: Ma Y, Wang J, Wu T, Zheng B, Yin T, Lian Y, Ren J. Data acquisition: Ma Y, Wang J, Wu T, Zheng B, Yin T, Lian Y, Ren J. Data analysis or interpretation: Ma Y, Wang J, Wu T, Zheng B, Yin T, Lian Y, Ren J. Drafting of the manuscript: Ma Y, Wang J, Wu T, Zheng B, Yin T, Lian Y, Ren J. Critical revision of the manuscript: Ma Y, Wu T, Zheng B, Yin T, Ren J. Approval of the final version of the manuscript: all authors. AcknowledgementsThis work was supported by the National Natural Science Foundation of China under Grant No. 81971632; the 5010 Clinical Research Project of Sun Yat-sen University (Grant No. 2022010); and the fifth Five-Year Project of the Third Affiliated Hospital of Sun Yat-Sen University (Grant No. 2023WW102).
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