The 90% minimum effective volume and concentration of lidocaine for ultrasound-guided stellate ganglion blocks in adults: a biased-coin design, up-and-down sequential allocation trial

Shujun Sun; Qinghua Yin; Jiwei Shen; Yang Lv; Long Li; Zhangyan Mao; Yun Lin; Xiangdong Chen; Dong Yang

doi:10.4097/kja.24607

Korean J Anesthesiol > Volume 78(5); 2025 > Article

Running title	The MEV90/MEC90 of lidocaine in SGBs
Authors Initials	S Sun, Q Yin, J Shen

Sun, Yin, Shen, Lv, Li, Mao, Lin, Chen, and Yang: The 90% minimum effective volume and concentration of lidocaine for ultrasound-guided stellate ganglion blocks in adults: a biased-coin design, up-and-down sequential allocation trial

Clinical Research Article

Korean Journal of Anesthesiology 2025;78(5):471-481.

Published online: July 1, 2025

DOI: https://doi.org/10.4097/kja.24607

The 90% minimum effective volume and concentration of lidocaine for ultrasound-guided stellate ganglion blocks in adults: a biased-coin design, up-and-down sequential allocation trial

Shujun Sun^1,^2,^3,^4,^*

, Qinghua Yin^1,^2,^3,^4,^*

, Jiwei Shen^1,^3,^4,^*

, Yang Lv^2,^3,⁴

, Long Li^2,^3,⁴

, Zhangyan Mao^1,^2,^3,⁴

, Yun Lin^1,^3,^4,^†

, Xiangdong Chen^1,^3,^4,^†

, Dong Yang^1,^2,^3,^4,^†

¹Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

²Department of Pain, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

³Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

⁴Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan, China

Corresponding author: Dong Yang, Ph.D.

Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China

Tel: +86-27-85351606

Fax: +86-27-85351660

Email: yangdong@hust.edu.cn

^*Shujun Sun, Qinghua Yin, and Jiwei Shen have contributed equally to this work as co-first authors.

^†Yun Lin, Xiangdong Chen, and Dong Yang are co-corresponding authors of this work.

Received August 27, 2024 Revised March 17, 2025 Accepted March 19, 2025

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

As ultrasound imaging technology matured, stellate ganglion blocks (SGBs) have become increasingly precise and safe, and their use in clinical practice has become widespread. However, the 90% minimum effective volume (MEV₉₀) and concentration (MEC₉₀) of lidocaine for ultrasound-guided SGB remain unclear. We aimed to determine the MEV₉₀ and MEC₉₀ of lidocaine used in ultrasound-guided SGBs.

Methods

Patients with indications for an SGB were recruited, without restrictions on sex or disease type. In this two-part study, we first determined the MEV₉₀, and then used these results to determine the MEC₉₀. The MEV₉₀ and MEC₉₀ of lidocaine for each subsequent patient were determined based on the previous patient’s response, using a biased-coin design, up-and-down sequential allocation trial. The lidocaine volume and concentration intervals were 0.2 ml and 0.1%, respectively.

Results

In total, 110 patients were enrolled (58 and 52 patients in the MEV₉₀ and MEC₉₀ studies, respectively). The MEV₉₀ for 1% lidocaine was found to be 3.83 ml (95% CI [3.19–3.91]) and the extrapolated MEV₉₉ was 3.97 ml (95% CI [3.95–5.29]). The MEC₉₀ for lidocaine (4.0 ml) was found to be 0.38% (95% CI [0.32–0.41]) and the extrapolated MEC99 was 0.47% (95% CI [0.46–2.55]). Four patients in this study developed hoarseness, but no serious adverse events occurred.

Conclusions

For ultrasound-guided SGB in adults, we have determined the MEV₉₀ of 1% lidocaine as 3.83 ml, and identified the MEC₉₀ of 4 ml of lidocaine as 0.38%.

Keywords: Anesthetics, local; Dose-response relationship, drug; Lidocaine; Nerve block; Stellate ganglion; Ultrasonography.

Introduction

The stellate ganglion is a part of the cervical sympathetic nervous system. It's formed by the merging of the inferior cervical ganglion and the T1 ganglion, and it sits between the C6 and C7 vertebrae. It contains sympathetic preganglionic fibers that innervate the head and neck, and sympathetic postganglionic fibers that innervate the upper limbs and heart [1,2].

Stellate ganglion blocks (SGBs) are widely used in clinical practice to treat a wide range of painful and non-painful conditions, such as pain in the head, face, ear, nose, throat, mouth, neck, shoulder, and upper limbs, as well as refractory angina pectoris, arrhythmia, and depression [3–6]. In the past, SGB was often performed by using the body surface positioning method. However, in recent years, as ultrasound imaging technology matured and ultrasound equipment gained popularity in the clinic, ultrasound-guided SGB has gradually become a viable alternative for physicians [7]. Ultrasound imaging technology allows precise visualization of the SGB: under ultrasound guidance, thereby largely improving the safety and effectiveness of the technique. With ultrasound, the puncture process can be observed in real time, adjacent vital organs and blood vessels can be avoided, and the diffusion of drugs can be monitored [8,9].

While the use of ultrasonography has helped clinicians to ensure the safety of nerve blocks, gaps remain regarding the optimal doses (volume and concentration) of local anesthetic to use in nerve blocks. Determining the lowest effective dose of a local anesthetic for ultrasound-guided SGB, i.e., the dose that could minimize the adverse effects caused by a local anesthetic overdose while ensuring a good blocking effect, forms the basis for the clinically rational use of this drug treatment. Nevertheless, the minimum effective volume and concentration of local anesthetic to use for ultrasound-guided SGB have not yet been reported.

The biased-coin design (BCD), up-and-down sequential allocation method (UDM) allows determination of the optimal drug dose by minimizing the number of trials required as well as the resource consumption, and is the preferred study-design method for higher-percentile dose-effect estimation [10,11]. Furthermore, lidocaine belongs to the amide class of local anesthetics. It has a rapid onset of action, wide dispersion, strong penetration, lacks a significant vasodilator effect, and causes almost no irritation to tissues, making it one of the most commonly used local anesthetics for SGBs [12]. In this study, we aimed to determine the 90% minimum effective volume (MEV₉₀) and concentration (MEC₉₀) of lidocaine for use in ultrasound-guided SGBs.

Materials and Methods

This study was approved by the Medical Ethics Committee of Union Hospital of Tongji Medical College, Huazhong University of Science and Technology (No. UHCT230596) and adhered to the tenets of the Helsinki Declaration 2013. Written informed consent was obtained from all participants. The trial was registered prior to patient enrollment at https://www.chictr.org.cn (ChiCTR2300078277) on December 4, 2023. Patients were enrolled from December 4, 2023, to April 16, 2024.

Study population

Patients who underwent ultrasound-guided SGBs at the Department of Pain in Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, due to head, face, or upper-limb pain, insomnia, or facial paralysis, who were aged 18–80 years, had an American Society of Anesthesiologists (ASA) class Ⅰ–Ⅲ, with a body mass index (BMI) of 18.0–27.9 kg/m², of either sex, were included. The exclusion criteria were as follows: allergy to local anesthetics; contraindications to nerve block (coagulation disorders, sepsis, tumor at the puncture site, infection, and other related diseases); neck deformity; neck trauma or surgery with obvious scars; mental disorders or diseases of the central nervous system, or inability to cooperate; serious cardiopulmonary and other major organ insufficiencies; and pregnancy or breastfeeding.

Ultrasound-guided SGB

After entering the treatment room, intravenous access was routinely established; oxygen was administered by nasal cannula at 2 L/min; and electrocardiography, and noninvasive blood pressure and peripheral oxygen saturation (SpO₂) monitoring were conducted. The ultrasound-guided SGB was administered by a pain physician familiar with ultrasound and nerve block operations (attending physicians with at least 3 years of work experience), and the operation process adhered strictly to the principles of asepsis. The patient was placed in the supine position with the head tilted slightly to the opposite side, with a thin pillow under the shoulder, and the head tilted slightly back to expose the neck fully.

A high-frequency linear array probe (Labat PG, Shenzhen Wisonic Medical Technology Co., Ltd.) was placed at approximately the level of the cricoid cartilage. This allowed localization of key anatomical landmarks for the SGB, including the common carotid artery, the internal jugular vein, the cervical transverse process and its protruding anterior and posterior nodules, as well as the long neck muscle covered by the prevertebral fascia that is located on the superficial surface of the transverse process. The ultrasound probe was then moved caudally until the anterior nodule of the C6 transverse process disappeared, the puncture path was not obstructed by bony structures, and no important neurovascular structures were present in the puncture path. After determining the skin-puncture point, applying local disinfection, and laying a sterile dressing, the operator proceeded with in-plane insertion of a 20-gauge short-beveled puncture needle. Under ultrasound guidance, the puncture needle was passed through the sternocleidomastoid muscle and the anterior scalene muscle, to the lower part of the common carotid artery, the surface of the longus colli, and the deep surface of the prevertebral fascia. The operator then injected lidocaine slowly after checking that no blood or gas was withdrawn [13,14]. After the drug injection was completed, the ultrasound probe was used in a sweeping motion to observe the diffusion of the drug, and to confirm that the drug had diffused between the longus colli and the prevertebral fascial space. The puncture needle was then removed, and the puncture point was sterilized and covered with aseptic dressing. The patient was returned to the ward if no obvious adverse reactions had occurred after 30 min of observation.

The MEV₉₀ of lidocaine for ultrasound-guided SGB

The expert consensus for SGB therapy in China (2022) recommends using a lidocaine concentration of 0.5%–1.0% for ultrasound-guided SGBs [13]. To ensure adequate blockage of the stellate ganglion and to avoid block failures caused by a low concentration, we chose to use 1% lidocaine in the study of the MEV₉₀. The present study used a BCD-UDM design in which the first patient was injected with 2 ml of 1% lidocaine, and the volume used for each subsequent patient depended on the block results of the previous patient, with an adjacent volume-step of 0.2 ml. If the block failed in the previous patient, the volume for the next patient was increased by 0.2 ml. However, if the block was successful, the volume received by the next patient was biased-coin randomized, with an 11% probability of a volume reduction by 0.2 ml and an 89% probability of the volume remaining unchanged. This part of the study was concluded once 45 successful block instances were achieved.

Sequential allocation in the BCD-UDM was performed using a computer-generated list of random numbers prepared in Excel (Microsoft Corp.) by a statistician. Investigator accessed the list and prepared the corresponding syringes for lidocaine in the drug-preparation room, and then transported the syringes to a treatment room. In this way, the patient, physician, and caregiver were blinded to the volume allocation.

The sign of a successful SGB was defined as the presence of Horner's syndrome on the blocked side, or a temperature increase of ≥ 1°C in the head, face, or upper limbs on the blocked side, as indicated by infrared thermography [15,16].

Finally, using R statistical software (https://www.r-project.org/), the MEV₉₀ and 99% minimum effective volume (MEV₉₉) of 1% lidocaine for ultrasound-guided SGBs were calculated by using centered isotonic regression. The 95% CI for the results was calculated using a bootstrap algorithm.

The MEC₉₀ of lidocaine for ultrasound-guided SGB

Based on the results obtained with 1% lidocaine SGBs in the first part of the study, we extrapolated the MEV₉₉ of lidocaine. This value was used to decide on the volume of lidocaine injected in the second part of the study. In the second part, we employed the same study design as described for the first part; thus, the concentration of lidocaine for the first patient was set to 0.2%. The concentration for each subsequent patient was adjusted based on the outcome of the block in the previous patient, with an adjacent concentration-step of 0.1%. If the block failed, the concentration for the next patient was increased by 0.1%. However, if the block succeeded, the concentration for the next patient was randomly selected using a biased coin, with an 11% probability of decreasing by 0.1% and an 89% probability of remaining unchanged. The study was terminated after 45 successful block instances had been achieved.

The same statistical method was used to calculate the MEC₉₀, 99% minimum effective concentration (MEC₉₉), and 95% CI of lidocaine for ultrasound-guided SGB.

The detailed flow of this study is depicted in Fig. 1.

Data collection and outcome assessment

General patient information, including age, sex, BMI, ASA class, and underlying diseases, were recorded. A separate investigator (a physician who did not perform the nerve block) recorded the occurrence of Horner's syndrome in patients within 10 min after SGB. Infrared thermography was used to capture the changes in skin temperature of the head, face, and upper limb on the blocked side before and 5 and 10 min after block administration, for comprehensive assessment of whether the SGB block was successful. The occurrence of adverse reactions, including hoarseness, dysphagia, upper-limb weakness on the block side, local hematoma, pneumothorax, and local anesthetic poisoning, after the block was recorded. The heart rate, SpO₂, and mean arterial pressure were recorded before and 10 min after block administration.

Statistical analysis

A two-stage BCD-UDM design was used in this study. Statistically, at least 45 patients with successful blockade were require to calculate the MEV₉₀ and MEC₉₀ by isotonic regression [17,18]. The 95% CI of the results was calculated by using a bootstrapping algorithm, with 2000 repeated samples. Graphing was performed using GraphPad Prism 8 (GraphPad, Inc.). We used the pooled-adjacent-violators algorithm (PAVA) for isotonic regression (package source: isotone_1.1-1.tar.gz; https://CRAN.R-project.org/package=isotone) to obtained the adjusted positive rate. The PAVA has three dose estimators, of which μ3 is the most accurate [18]. The dose estimator μ3 was defined as the interpolated dose with an estimated toxicity equal to exactly 0.9 [18]. Hence, in this study, μ3 represents the dose of the drug when the target effect (0.9) was achieved. We then performed point and interval estimations via centered isotonic regression (package source: cir_2.5.0.tar.gz; https://CRAN.R-project.org/package=cir) to derive MEV99 and MEC99 and their 95% CIs from the data. Statistical analyses were performed using R v.4.3.1 (R Foundation for Statistical Computing). Continuous variables are presented as mean ± standard deviation. Categorical variables are presented as numbers and percentages.

Results

Overall, 110 patients were included in this study; 58 participated in the first part of the study (minimum effective volume) and 52 participated in the second part of the study (minimum effective concentration). The BCD sequences for lidocaine volume and concentration are shown in Fig. 2.

Effective volume of lidocaine

In the study on the effective volume of lidocaine, the mean age of the 58 patients was 52.3 years, and 67.2% of this group were female. SGBs were successful in 45 of the patients and failed in 13 patients. No significant differences were found between the successful and failed SGB groups in terms of age, sex, BMI, or ASA class. The general information of this study group is shown in Table 1.

Effective concentration of lidocaine

In the second part of the study, investigating the effective concentration of lidocaine for SGB, the results of the volumetric study were used. Fifty-two patients were included in this part of the study; in 45 of these, the SGB was successful, while it failed in seven. The mean age of the group was 46.5 years, while 67.3% were female. The descriptive statistics of the group are presented in Table 2.

The MEV₉₀, MEV₉₉, MEC₉₀, and MEC₉₉ of lidocaine for ultrasound-guided SGBs

The MEV₉₀ of 1.0% lidocaine was 3.83 ml (95% CI [3.19–3.91]) and the MEC₉₀ of 4.0 ml lidocaine was 0.38% (95% CI [0.32–0.41]). We further extrapolated that the MEV₉₉ of 1.0% lidocaine is 3.97 ml (95% CI [3.95–5.29]) and that the MEC₉₉ of 4.0 ml lidocaine is 0.47% (95% CI [0.46–2.55]).

Overall incidence of side effects after ultrasound-guided SGBs

In the 1% lidocaine ultrasound-guided SGB MEV₉₀ study, 11 steps were used, including 2 ml, 2.2 ml, 2.4 ml, 2.6 ml, 2.8 ml, 3.0 ml, 3.2 ml, 3.4 ml, 3.6 ml, 3.8 ml, and 4.0 ml. The positive response rates for these different volumes were 0%, 0%, 0%, 0%, 0%, 0%, 66.7%, 70%, 88.9%, 87.5%, and 100%, respectively. Among the 58 patients included, four experienced hoarseness after blockage, but the symptoms disappeared within 1 h after block administration, and the volume of 1% lidocaine resulting in hoarseness in these individuals was 3.4 ml, 3.6 ml, 3.8 ml, and 4.0 ml, respectively. In the 4-ml lidocaine ultrasound-guided SGB MEC₉₀ study, four steps were used (0.2%, 0.3%, 0.4%, and 0.5%), with corresponding positive response rates of 0%, 61.5%, 96.6%, and 100%, respectively. No adverse events occurred in any of the patients enrolled in the concentration study.

Infrared Thermography Findings

Infrared thermography demonstrated progressive temperature increases on the blocked side in successful SGB cases, as shown in Fig. 3A. In the MEV₉₀ study (1% lidocaine volume), significant temperature elevations (P < 0.001) occurred at both 5 min and 10 min post-block across all measured sites (forehead, cheek, upper limb) among successful blocks (n = 45), with the cheek exhibiting the most pronounced change (∆T: +1.17℃ at 5 min, +1.41℃ at 10 min), as shown in Figs. 3B-D. Conversely, the failure group (n = 13) showed only marginal forehead warming at 10 min (∆T: +0.53℃, P = 0.019), which remained below the clinical success threshold (≥ 1℃). Baseline temperatures did not differ significantly between groups (P > 0.050). Similarly, in the MEC₉₀ study (4 ml lidocaine concentration), successful blocks (n = 45) displayed significant temperature elevations (P < 0.010) at both the 5 min and 10 min time points, as illustrated in Figs. 3E-G, most notably in the forehead (∆T: +1.05℃) and cheek (∆T: +1.33℃) at 10 min. The failure group (n = 7) exhibited no statistically significant changes (∆T < 0.5℃, P > 0.050) at any site or timepoint, with comparable baseline temperatures between groups (P > 0.050).

Discussion

SGBs are widely used in clinical practice and has therapeutic value in many diseases, such as postherpetic neuralgia, insomnia, tinnitus, and facial paralysis. However, the dose of local anesthetics currently used in ultrasound-guided SGBs in clinical practice remains empirical. In the present study, the MEV₉₀ and MEC₉₀ of the SGB were revealed using the BCD-UDM method. The results showed that the MEV₉₀ for 1% lidocaine in ultrasound-guided SGBs was 3.83 ml (95% CI [3.19–3.91]), while the MEC₉₀ for 4.0 ml of lidocaine was 0.38% (95% CI [0.32–0.41]); these can be used as reference values in clinical practice. Of the 110 patients included in the present study, the SGB failed in 20 overall. Fig. 2 shows that the dose of lidocaine used in almost all of the failed cases was less than the 90% of the minimum effective dose, which reflects the reliability and trustworthiness of our results.

An SGB involves the injection of local anesthetics into the tissues around the stellate ganglion and its vicinity, including the cervical sympathetic trunk, cervical sympathetic ganglion, preganglionic and postganglionic nerves, and their innervation areas [19]. Thus, an SGB disrupts signaling of the sympathetic nerves that innervate the head, face, neck, scapula, upper limbs, chest, and back. It modulates the tension of the sympathetic nervous system and ultimately regulates the body's autonomic nervous, circulatory, endocrine, and immune systems to maintain a dynamic equilibrium [1,2,13]. It can be used to treat a variety of chronic pain conditions and non-painful diseases. SGBs are currently widely used in clinical work, particularly since the maturation of ultrasound technology, which has significantly improved the accuracy and safety of SGBs, making its application more promising [13,19]. However, in our clinical practice, we found that the optimal volume and concentration of local anesthetics used for ultrasound-guided SGBs remain empirical, with no expert consensus or guidelines providing precise, evidence-based recommendations for these parameters. In practice, patients often experience side effects, such as recurrent laryngeal nerve block, causing hoarseness; diaphragmatic nerve block, which causes difficulty breathing, due to a high volume or concentration; or block failure, due to a low volume or concentration [20]. Based on these results, the present study sought to determine the MEV₉₀ and MEC₉₀ for ultrasound-guided SGBs and objectively assessed the effects of the SGB by combining it with the advanced technology of infrared thermography. Our results are expected to provide guidance for clinical practice.

In pharmacology, the smallest dose of a drug that can cause pharmacological effects is called the lowest effective dose (minimum effective volume or concentration). The experimental designs commonly used to determine this dose include the fixed-dose grouping method, the up-and-down sequential method (UDM), and the BCD-UDM, among which using the UDM for MEV₅₀ and MEC₅₀ is more classical and accepted by most statisticians [21,22]. However, for clinicians, higher-percentile data (e.g., MEV₉₀/MEC₉₀ and MEV₉₉/MEC₉₉) are more meaningful clinically. Studies have confirmed that the extrapolation of MEV₅₀/MEC₅₀, derived by UDM, to MEV₉₀/MEC₉₀ has a high degree of error and is of limited clinical value [23,24]. The BCD-UDM is a method for estimating the effect of an intervention by introducing a coin bias, which allows for the simple and rapid random intervention assignment. By using a cyclical process of gradual dose adjustment and observation of effects, the optimal drug dose can be determined while minimizing the number of trials and resource consumption. This approach is more suitable than the conventional UDM for estimating dose-response at higher or lower percentiles (e.g., MEV₉₀/MEC₉₀ or MEV₁₀/MEC₁₀) [10,21,23].

Although the BCD-UDM design can reduce the required sample size in drug studies, a minimum of 45 successful responses (a value greater than 40 and a multiple of 9) are necessary to estimate the 90% effective dose (ED₉₀) with sufficient precision [25,26]. To study the 95% effective dose (ED₉₅) and 99% effective dose (ED₉₉), the number of successful responses required would increase significantly to 95 and 495, respectively. Thus, increasing the response rate from 90% to 95% or 99% requires a substantial increase in sample size. In the typical S-shaped dose-response curve of a drug, the curve is flatter at the ends, while the steepest slope occurs at the ED₅₀ response. The ED₉₀ is usually near or at the plateau of the curve and is close to the ED₉₉. Therefore, focusing on determining the 90% minimum effective dose of lidocaine required for ultrasound-guided SGBs was deemed more practical, as this provides a balance between statistical robustness and practical feasibility.

Lidocaine is a commonly used amide-type, intermediate-acting local anesthetic, with the characteristics of having a rapid onset of action, strong penetration, and wide dispersion, without causing obvious vasodilatation. Lidocaine is widely used in surface, local infiltration, epidural, and peripheral nerve block anesthesia, and is also one of the most commonly used local anesthetics in SGBs [27,28]. Nevertheless, optimization of the dosage of local anesthetics for achieving a satisfactory blockade by using the smallest possible dose warrants in-depth discussion and research. Hence, our study explored the MEV₉₀/MEC₉₀ of lidocaine in ultrasound-guided SGBs by using a BCD-UDM design, with a view to guiding clinical practice.

Several previous studies have explored the optimal dose of local anesthetics for SGB; however, the vast majority were randomized controlled studies using fixed gradients. Lee et al. [29] explored the minimum volume of 0.5% mepivacaine required for ultrasound-guided SGBs by setting three volume-steps (2, 3, and 4 ml), and showed that the stellate ganglion could be successfully blocked by using 2 ml of this anesthetic. Jung et al. [30] explored ropivacaine dosage by setting four volume-steps (6, 4, 3, and 2 ml) and found that the optimal volume of 0.2% ropivacaine for ultrasound-guided SGBs was 4 ml. Yoo et al. [31] found that 4 ml of 1% lidocaine for ultrasound-guided SGBs had the same effect as 6 and 8 ml, although 8 ml was associated with a higher incidence of adverse effects; these results were similar to our findings.

On the other hand, few studies have investigated the concentration of local anesthetics used for SGB, Hardy [32] found that the minimum concentration of bupivacaine required for successful SGBs was 325–406 µmol/L, but bupivacaine solution containing 5 mmol/L potassium reduced the minimum concentration to 81–162 µmol/L. In our study, the MEV₉₉ (3.97 ml) was obtained by extrapolating the results of MEV₉₀. In order to ensure that any SGB block failure observed was due to a low concentration of local anesthetics rather than to insufficient volume, and given the precision of the volume of the syringes used in the clinic, we chose to use 4 ml to explore the minimum concentration of lidocaine required for ultrasound-guided SGB.

The appearance of Horner syndrome on the blocked side indicates successful SGB. This manifests as pupil narrowing, eyelid ptosis, sunken eyes, little or no sweating on the ipsilateral side, conjunctival congestion, facial flushing, nasal congestion, and elevated skin temperature [33]. Notably, patients consciously perceive warmth in the head, face, and upper limbs after successful administration of an SGB. Moreover, vasodilatation can result in a 1–3℃ increase in the skin temperature of the ipsilateral upper limb; this change in temperature can be detected by infrared thermography or skin temperature detectors [13,34,35]. Toshniwal et al. [36] demonstrated an increase in the ipsilateral limb temperature after an SGB. Stevens et al. [37] found that, in most patients, a 2℃ increase in skin temperature over the contralateral limb implied complete sympathetic blockade. Usually, an average increase of 1°C–2°C in the ipsilateral limb implies a successful SGB, and the degree of skin temperature increase correlates with the pain reduction in patients; nevertheless, some studies have shown no correlation between the skin temperature changes and long-term outcomes [38,39]. In the present study, we recorded the skin temperature changes before and after SGB administration by using infrared thermography. We found that the ipsilateral frontal, facial, and upper extremities showed different degrees of skin temperature elevation after the block, with changes in the facial area being the most significant (Fig. 3). However, notably, among the 90 patients with successful block, we observed that 10 cases (11.11%) showed only elevated skin temperature (≥ 1℃), without presenting Horner's syndrome, while 5 patients (5.55%) showed manifestations of Horner's syndrome on the side of the block, without significant elevation of skin temperature (< 1℃). In this study, four patients developed hoarseness after block administration, which disappeared after half an hour and was considered to be due to recurrent laryngeal nerve block. No serious adverse events, such as local anesthetic toxicity and vascular nerve injury, occurred.

Our study had some limitations. First, the MEV₉₀ and MEC₉₀ in this study were limited to lidocaine, and did not include other types of local anesthetics. Second, the patient's age and BMI may influence the spatial structure of neck tissues [40]. The subjects in our study were aged 18–80 years and had a BMI of 18.0–27.9 kg/m². Thus, the results of the study are not applicable to children or patients with obesity. Further subgroup analysis should be performed in future to explore dose differences among children, the youth, and older individuals. Third, although we measured the change in skin temperature on the side of the block by means of infrared thermography, we did not assess the relationship between the magnitude of the change in skin temperature after SGB administration and the prognosis. The purpose of our study was to determine the lowest effective dose of lidocaine for ultrasound-guided SGBs, and the underlying condition was not the same in all patients. In future, the effect of the degree of skin temperature elevation on prognosis under the same disease conditions will be a promising research focus. Finally, the primary observations in our study were changes related to Horner's syndrome and skin temperature by 10 min after SGB administration, and the time to resolution of Horner's syndrome was not tracked and recorded in detail. Therefore, our outcome metrics did not evaluate the effect of different volumes and concentrations of lidocaine used in the SGB on onset and maintenance time. Whether the initiation and maintenance time of the SGB and the severity of positive features affect its efficacy warrant further study. In addition, the morphology, innervation areas, and physiological roles of the stellate ganglion on both sides are not exactly the same; for example, the regulation of cardiac function by the bilateral stellate ganglia differ, and generally, a left SGB should be used for treating cardiac conditions. However, to date, no study has explored the dosage difference of drugs required for SGBs between the left and right sides. Thus, future studies should endeavor to refine the relevant details to ensure clinical treatment precision.

In conclusion, lidocaine can be safely used for ultrasound-guided SGB. For people aged 18–80 years with a BMI of 18.0–27.9 kg/m² who are undergoing ultrasound-guided SGB, the MEV₉₀ for 1% lidocaine is 3.83 ml (95% CI [3.19–3.91]), while the 4.0-ml lidocaine MEC₉₀ for this population is 0.38% (95% CI [0.32–0.41]).

Funding

This study was supported by the Fundamental Research Funds for the Central Universities (HUST: 2024JYCXJJ021), the 2023 Freedom Innovation Pre-research Fund (F016020042300116206), and the Hubei Provincial Natural Science Foundation (2023AFB761).

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author Contributions

Shujun Sun (Methodology; Writing – original draft)

Qinghua Yin (Data curation; Investigation)

Jiwei Shen (Writing – original draft; Writing – review & editing)

Yang Lv (Investigation; Methodology)

Long Li (Data curation; Investigation)

Zhangyan Mao (Methodology; Writing – original draft)

Yun Lin (Conceptualization; Funding acquisition; Validation)

Xiangdong Chen (Funding acquisition; Methodology)

Dong Yang (Funding acquisition)

Fig. 1.

Flowchart of the MEV₉₀ and MEC₉₀ studies of lidocaine for ultrasound-guided SGB. SGB: stellate ganglion block, BCD: biased-coin design, MEV₉₀: 90% minimum effective volume, MEC₉₀: 90% minimum effective concentration.

Fig. 2.

Responses of patients to ultrasound-guided SGB with different volumes and concentrations of lidocaine. (A) Lidocaine volume and (B) lidocaine concentration in each patient, with their response. Orange squares denote negative cases and blue circles denote positive cases. The horizontal line indicates the estimated value of MEV₉₀/MEC₉₀ and the error bars represent the 95% CIs. SGB: stellate ganglion block, MEV₉₀: 90% minimum effective volume, MEC₉₀: 90% minimum effective concentration.

Fig. 3.

Skin temperature changes after ultrasound-guided SGB administration. (A) Infrared thermography of patients at different time points after SGB administration; (B–D) MEV₉₀ study (1% lidocaine volume) showing temperature variation in the forehead (B), cheek (C), and upper limb (D); (E–G) MEC₉₀ study (4 mL lidocaine concentration) demonstrating temperature changes in the forehead (E), cheek (F), and upper limb (G). *P < 0.010. SGB: stellate ganglion block, MEV₉₀: 90% minimum effective volume, MEC₉₀: 90% minimum effective concentration.

Table 1.

Demographic Characteristics of the Patients Included in Determining the Effective Volume of Lidocaine

Variable	Total (n = 58)	Success (n = 45)	Failure (n = 13)
Age (yr)	52.3 ± 16.9	52.0 ± 15.5	53.5 ± 21.6
Sex (M/F)	19/39	15/30	4/9
BMI (kg/m²)	21.2 ± 2.6	21.3 ± 2.3	20.9 ± 3.6
ASA (І/Ⅱ/Ⅲ)
Ⅰ	16 (27.6)	11 (24.4)	5 (38.5)
Ⅱ	36 (62.1)	29 (64.4)	7 (53.8)
Ⅲ	6 (10.3)	5 (11.1)	1 (7.7)

Values are presented as mean ± SD, number or number (%). Comparisons of demographic characteristics between success and failure groups showed no statistically significant differences (P > 0.050 for all variables). BMI: body mass index, ASA: American Society of Anesthesiologists.

Table 2.

Demographic Characteristics of the Patients Included in Determining the Effective Concentration of Lidocaine

Variable	Total (n = 52)	Success (n = 45)	Failure (n = 7)
Age (yr)	46.5 ± 15.0	46.1 ± 14.6	48.9 ± 18.4
Sex (M/F)	17/35	13/32	4/3
BMI (kg/m²)	20.3 ± 2.7	20.2 ± 2.7	20.8 ± 3.3
ASA (І/Ⅱ/Ⅲ)
Ⅰ	23 (44.2)	20 (44.4)	3 (42.9)
Ⅱ	27 (51.9)	24 (53.3)	3 (42.9)
Ⅲ	2 (3.8)	1 (2.2)	1 (14.3)

References

1. Deng JJ, Zhang CL, Liu DW, Huang T, Xu J, Liu QY, et al. Treatment of stellate ganglion block in diseases: its role and application prospect. World J Clin Cases 2023; 11: 2160-7.

2. Lee YS, Wie C, Pew S, Kling JM. Stellate ganglion block as a treatment for vasomotor symptoms: clinical application. Cleve Clin J Med 2022; 89: 147-53.

3. Mori T, Terai T, Hatano M, Oda Y, Asada A, Moriwaki M. Stellate ganglion block improved loss of visual acuity caused by retrobulbar optic neuritis after herpes zoster. Anesth Analg 1997; 85: 870-1.

4. Salvaggio I, Adducci E, Dell'Aquila L, Rinaldi S, Marini M, Zappia L, et al. Facial pain: a possible therapy with stellate ganglion block. Pain Med 2008; 9: 958-62.

5. Feigin G, Velasco Figueroa S, Englesakis MF, D'Souza R, Hoydonckx Y, Bhatia A. Stellate ganglion block for non-pain indications: a scoping review. Pain Med 2023; 24: 775-81.

6. Kumar A, Sinha C, Kumar A, Sinha AK. Ultrasound-guided stellate ganglion block for resistant ventricular tachycardia. Saudi J Anaesth 2017; 11: 372-3.

7. Kim H, Song SO, Jung G. A lateral paracarotid approach for ultrasound-guided stellate ganglion block with a linear probe. J Anesth 2017; 31: 458-62.

8. Koscielniak-Nielsen ZJ. Ultrasound-guided peripheral nerve blocks: what are the benefits? Acta Anaesthesiol Scand 2008; 52: 727-37.

9. Pu S, Chen J, Gu X, Xu Y, Wu J, Lv Y, et al. Effects of ultrasound-guided stellate ganglion block on cervical vascular blood flow: study protocol for a randomized controlled trial. Trials 2018; 19: 426.

10. Zhou D, Yang XD, Wu HY, Xiong GL, Wang LK. Determination of the ED90 of dexmedetomidine infusion to prevent emergence agitation in children undergoing dental rehabilitation with sevoflurane anesthesia: a biased-coin up-and-down sequential allocation trial. Anesth Analg 2024; 139: 761-9.

11. Hemraj C, Kalaivani M, Binu H, Ramachandran R. Application of isotonic regression in estimating EDg and its 95% confidence interval by bootstrap method for a biased coin up-and-down sequential dose-finding design. Indian J Anaesth 2023; 67: 828-31.

12. Kuroda H, Katagiri N, Kagawa K, Imaizumi U, Ishikawa N, Shibukawa Y, et al. Comparison of lidocaine and mepivacaine for variation in regional tissue oxygenation in stellate ganglion block: a randomized, double-blind, crossover trial. Cureus 2023; 15: e47938.

13. Yan Min, Liu Xiaoli, Wang Lin, Tao Wei, Zhang Xianwei, Wang Suoliang, et al. Expert consensus for stellate ganglion block therapy in China (2022)]. Chin J Painol 2022; 18: 293-301.

14. Lao WL, Sang S, Huang LC, Yi SH, Guo MC, Dong HM, et al. Effect of ultrasound-guided stellate ganglion block on inflammatory cytokines and postoperative recovery after partial hepatectomy: a randomised clinical trial. BMC Anesthesiol 2024; 24: 7.

15. Rathmell JP. Atlas of Image-Guided Intervention in Regional Anesthesia and Pain Medicine. Philadelphia, Lippincott Williams & Wilkins. 2011, pp 1-224.

16. Viswanath O, Aner M. Dramatic extremity temperature increase and Horner's syndrome after stellate ganglion block. Postgrad Med J 2018; 94: 237.

17. Stylianou M, Flournoy N. Dose finding using the biased coin up-and-down design and isotonic regression. Biometrics 2002; 58: 171-7.

18. Stylianou M, Proschan M, Flournoy N. Estimating the probability of toxicity at the target dose following an up-and-down design. Stat Med 2003; 22: 535-43.

19. Kirkpatrick K, Khan MH, Deng Y, Shah KB. A review of stellate ganglion block as an adjunctive treatment modality. Cureus 2023; 15: e35174.

20. Tüz M, Erodlu F, Dodru H, Uygur K, Yavuz L. Transient locked-in syndrome resulting from stellate ganglion block in the treatment of patients with sudden hearing loss. Acta Anaesthesiol Scand 2003; 47: 485-7.

21. Görges M, Zhou G, Brant R, Ansermino JM. Sequential allocation trial design in anesthesia: an introduction to methods, modeling, and clinical applications. Paediatr Anaesth 2017; 27: 240-7.

22. Saranteas T, Finlayson RJ, Tran DQ. Dose-finding methodology for peripheral nerve blocks. Reg Anesth Pain Med 2014; 39: 550-5.

23. Pace NL, Stylianou MP. Advances in and limitations of up-and-down methodology: a précis of clinical use, study design, and dose estimation in anesthesia research. Anesthesiology 2007; 107: 144-52.

24. Fils JF, Kapessidou P, Van der Linden P, Guntz E. A Monte Carlo simulation study comparing the up and down, biased-coin up and down and continual reassessment methods used to estimate an effective dose (ED95 or ED90) in anaesthesiology research. BJA Open 2023; 8: 100225.

25. Durham SD, Flournoy N, Rosenberger WF. A random walk rule for phase I clinical trials. Biometrics 1997; 53: 745-60.

26. Tran DQ, Dugani S, Dyachenko A, Correa JA, Finlayson RJ. Minimum effective volume of lidocaine for ultrasound-guided infraclavicular block. Reg Anesth Pain Med 2011; 36: 190-4.

27. Dusi V, Angelini F, Baldi E, Toscano A, Gravinese C, Frea S, et al. Continuous stellate ganglion block for ventricular arrhythmias: case series, systematic review, and differences from thoracic epidural anaesthesia. Europace 2024; 26: euae074.

28. Wang X, Deng L, Wu Y, Wang L, Qiu Y, Hou H. The effect of perioperative intravenous lidocaine infusion on postoperative sleep of elderly patients with colorectal cancer: a randomized controlled study. J Anesth Transl Med 2024; 3: 117-22.

29. Lee MH, Kim KY, Song JH, Jung HJ, Lim HK, Lee DI, et al. Minimal volume of local anesthetic required for an ultrasound-guided SGB. Pain Med 2012; 13: 1381-8.

30. Jung G, Kim BS, Shin KB, Park KB, Kim SY, Song SO. The optimal volume of 0.2% ropivacaine required for an ultrasound-guided stellate ganglion block. Korean J Anesthesiol 2011; 60: 179-84.

31. Yoo Y, Lee CS, Kim YC, Moon JY, Finlayson RJ. A randomized comparison between 4, 6 and 8 mL of local anesthetic for ultrasound-guided stellate ganglion block. J Clin Med 2019; 8: 1314.

32. Hardy PA. Stellate ganglion block with bupivacaine. Minimum effective concentration of bupivacaine and the effect of added potassium. Anaesthesia 1989; 44: 398-9.

33. Khan Z, Bollu PC. Horner Syndrome. StatPearls [serial on the Internet]. 2023 April [2025 June 24]. Available from www.ncbi.nlm.nih.gov/books/NBK500000/

34. Datta R, Agrawal J, Sharma A, Rathore VS, Datta S. A study of the efficacy of stellate ganglion blocks in complex regional pain syndromes of the upper body. J Anaesthesiol Clin Pharmacol 2017; 33: 534-40.

35. van Eijs F, Geurts J, van Kleef M, Faber CG, Perez RS, Kessels AG, et al. Predictors of pain relieving response to sympathetic blockade in complex regional pain syndrome type 1. Anesthesiology 2012; 116: 113-21.

36. Toshniwal G, Sunder R, Thomas R, Dureja GP. Management of complex regional pain syndrome type I in upper extremity-evaluation of continuous stellate ganglion block and continuous infraclavicular brachial plexus block: a pilot study. Pain Med 2012; 13: 96-106.

37. Stevens RA, Stotz A, Kao TC, Powar M, Burgess S, Kleinman B. The relative increase in skin temperature after stellate ganglion block is predictive of a complete sympathectomy of the hand. Reg Anesth Pain Med 1998; 23: 266-70.

38. Hermanns H, Werdehausen R, Hollmann MW, Stevens MF. Assessment of skin temperature during regional anaesthesia-What the anaesthesiologist should know. Acta Anaesthesiol Scand 2018; 62: 1280-9.

39. Samen CD, Sutton OM, Rice AE, Zaidi MA, Siddarthan IJ, Crimmel SD, et al. Correlation between temperature rise after sympathetic block and pain relief in patients with complex regional pain syndrome. Pain Med 2022; 23: 1679-89.

40. Kocur P, Tomczak M, Wiernicka M, Goliwąs M, Lewandowski J, Łochyński D. Relationship between age, BMI, head posture and superficial neck muscle stiffness and elasticity in adult women. Sci Rep 2019; 9: 8515.