Median Effective Dose of Rocuronium for the Prevention of Succinylcholine-induced Fasciculation：An Age-Stratified Study

Median Effective Dose of Rocuronium for the Prevention of Succinylcholine-induced Fasciculation：An Age-Stratified Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Median Effective Dose of Rocuronium for the Prevention of Succinylcholine-induced Fasciculation：An Age-Stratified Study Shunping Tian, Chao Chen, Shuping Wang, Shantian Feng, Meng Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6998202/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Dec, 2025 Read the published version in BMC Anesthesiology → Version 1 posted 11 You are reading this latest preprint version Abstract Background Succinylcholine, a commonly used depolarizing neuromuscular blocking relaxant, may produce fasciculation and postoperative myalgia as adverse effects. Although rocuronium pretreatment may attenuate this adverse effect, the median effective dose (ED50) remains undetermined, as does the influence of age on it. This study was carried out to determine the ED50 of prophylactic intravenous rocuronium in preventing succinylcholine-induced fasciculation and to explore the effect of age on the ED50. Methods Seventy-two adult patients undergoing elective general anesthesia were stratified according to age: Group R1 (18-44 years), Group R2 (45-59 years), and Group R3 (60-80 years). The initial dose of prophylactic rocuronium was set at 0.04 mg/kg. Midazolam 0.05 mg/kg, sufentanil 0.4 μg/kg, propofol 1.5-2.5 mg/kg, and succinylcholine 2 mg/kg were then sequentially administered 1.5 min later, then fasciculation was assessed. The rocuronium doses were adjusted according to the assessment of fasciculation using Dixon sequential method, with a ratio of 1.1 between adjacent doses. The occurrence and grades of fasciculation, adverse reactions of rocuronium, and endotracheal intubating condition were recorded. The ED50 and 95% confidence interval (CI) of rocuronium were calculated. Results The ED50 and 95% CI of prophylactic rocuronium for the prevention of succinylcholine-induced fasciculation were 0.027 μg/kg (95%CI: 0.026-0.028 μg/kg), 0.026 μg/kg (95%CI: 0.024-0.02 μg/kg), and 0.026 μg/kg (95%CI: 0.025-0.027 μg/kg) in Group R1, Group R2, and Group R3, respectively. No significant differences exist in the ED 50 (95% CI) among the three groups ( P > 0.05). Only one patient experienced temporary diplopia in Group R2. No significant differences were found in fasciculation grades or endotracheal intubation conditions among the groups. Conclusion Prophylactic intravenous rocuronium can prevent succinylcholine-induced fasciculation, while its ED50 is independent of age. Clinical trial registration The study was registered at ClinicalTrials.gov (Registration number: NCT05909696) on June 10, 2023. URL: https://clinicaltrials.gov/. Median effective dose Rocuronium Succinylcholine Fasciculation Age Prevention Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Succinylcholine is a depolarizing muscle relaxant with the advantages of rapid-onset, short duration of action, and perfect muscle relaxation[ 1 ]. It is one of the muscle relaxant choices for patients requiring general anesthesia for rapid sequential induction of intubation with a wide range of clinical applications. However, it’s injection often produces involuntary fasciculation with the incidence up to 95%, which may lead to postoperative myalgia, hemodynamic instability, body movement during induction, and increase in intraocular pressure, gastric pressure, and intracranial pressure[ 2 , 3 ]. Reducing the occurrence of fasciculation during induction of general anesthesia has gained attention from anesthesiologists[ 4 – 6 ]. Low-dose rocuronium pretreatment has been reported to reduce the occurrence of fasciculation[ 7 – 9 ], while its dosage was usually empirically applied. Furthermore, there have been no studies on the age-related dose of rocuronium to inhibit succinylcholine-induced fasciculation, neither the median effective dose (ED 50 ) has been determined. This study was carried out to explore the ED 50 of rocuronium for inhibiting succinylcholine-induced fasciculation and to investigate the influence of age on ED 50 of rocuronium in preventing succinylcholine-induced fasciculation. Methods This study has been approved by the Ethics Committee of the Affiliated Hospital of Yangzhou University, Yangzhou, China (2023-YKL07-013) and registered on ClinicalTrials.gov (NCT05909696). The study was conducted in accordance with the Declaration of Helsinki and the principles of the International Conference on Harmonization Good Clinical Practice Guideline. All patients have signed written informed consent before the implementation of the study. Patients scheduled for elective tracheal intubation under general anesthesia, aged 18–80 years, body mass index (BMI) 18.5–28 kg/m 2 , and American Society of Anesthesiologists (ASA) grade I or II, were included from July 2023 to October 2023 in the Affiliated Hospital of Yangzhou University. Exclusion criteria were: possible airway difficulties, allergies or contraindications to rocuronium and succinylcholine, cardiac insufficiency, hepatic or renal dysfunction, neuromuscular disease, surgery lasting more than 2 hours, taking any known drug that has interaction with neuromuscular blockers. According to the age classification by the World Health Organization in 2012, patients were divided into three groups: Group R1 (18–44 years old), Group R2 (45–59 years old), and Group R3 (60–80 years old). No premedication was used in all patients. Upon entering the operating room, non-invasive blood pressure (NIBP), heart rate (HR), electrocardiogram (ECG), and pulse oxygen saturation (S P O 2 ) were monitored. The pressure cuff was routinely banded on the arm that was without venous canulation. A 20-G intravenous catheter was placed in the cephalic vein of the wrist, with compound sodium chloride solution administered at a rate of 8–10 mL/kg/min. The vertical distance from the infusion bottle to the intravenous catheter for all cases in this study was 80 cm, as was set in our previous studies focused on ED50 exploration[ 10 ]. All the patients were unknown of the applied medication. The induction process of general anesthesia was carried out by three anesthesiologists using Dixon sequential method[ 11 ], the whole process of which is shown in Fig. 1 . The first anesthesiologist prepared and injected rocuronium for pretreatment. The initial dose of rocuronium (EA2167, Zhejiang Xian Ju Pharmaceutical Co, China) for each group was set at 0.04 mg/kg, which was stored at 2–8 ℃. It was drawn up with a 1-mL syringe and diluted with normal saline to 5 mL in a 5-mL syringe before use. The pretreated rocuronium was injected slowly with the injection time of 5 sec. The timing at intravenous administration of the pretreated rocuronium was considered as 0 min time point, with oxygen administered concomitantly via a mask by the second anesthesiologist who was unaware of the rocuronium dosage. At 1 min time point, the patient was inquired also by the second anesthesiologist about any adverse reactions of rocuronium including injection pain, diplopia, heavy eyelids, dizziness, dysarthria, swallowing, and breathing difficulties. Then, standardized general anesthesia induction was performed by the third anesthesiologist who was unaware of the rocuronium dosage. Midazolam 0.05 mg/kg, sufentanil 0.4 µg/kg, propofol 1.5–2.5 mg/kg, and succinylcholine 2 mg/kg were sequentially administered at 1.5 min time point. After succinylcholine administration, the third anesthesiologist assessed and reported whether there was fasciculation in the eyelids, neck, and other areas. The second anesthesiologist performed tracheal intubation at 2 min time point, and assessed the intubation condition. General anesthesia maintenance was then implemented. Muscle fasciculation severity was assessed using a four-point scale[ 6 ] with 4 levels: 0, no fasciculation; 1, mild fasciculation, slight tremor in the eyes, face, neck, or fingers, without limb movement; 2, moderate fasciculation, occurring in more than 2 muscle groups or involving body or limb movement; 3, severe fasciculation, intense, sustained, widespread fasciculation, may require restraint. Tracheal intubation conditions were assessed and graded to 4 levels[ 12 ]: 1, excellent (good jaw relaxation, vocal cords open and immobile, with no response to intubation); 2, good (good jaw relaxation, vocal cords open and immobile, but minimal response to intubation; 3, poor (moderate jaw relaxation, moving vocal cord, intubation accompanied by coughing and/or bucking); 4, inadequate ( intubation impossible due to poor jaw relaxation or closed vocal cords). Ephedrine, phenylephrine, or atropine were used intraoperatively, if necessary, according to changes in vital signs. If mean arterial pressure (MAP) was decreased by more than 20% from the baseline, ephedrine or phenylephrine was administered intravenously. If HR decreased to less than 50 beats/min or the decrease was more than 20% of the base value, atropine was administered intravenously. Demographic data, including age, gender, weight, height, and ASA classification, hemodynamics, and the use of vasoactive medications during general anesthesia induction were recorded. The occurrence of adverse effects of rocuronium, including injection pain, diplopia, heavy eyelids, dizziness, dysarthria, swallowing, and breathing difficulties, were also recorded. According to the assessment of succinylcholine-induced fasciculation by the third anesthesiologist, the first anesthesiologist adjusted the dose of the pretreated rocuronium. If the patient did not experience fasciculation (grade 0, negative reaction), the dose of pretreated rocuronium for the next patient was reduced until fasciculation occurred. If the patient experienced fasciculation (grade 1, 2 or 3, positive reaction), the dose of rocuronium for the next patient was increased until fasciculation disappeared. The ratio of the adjacent doses of rocuronium was 1.1. All pre-treatment drugs and syringe colors were identical. In each group, the first patient who showed positive reaction was included as the second case, with the previous one included as the first case. When 7 alternating positive and negative reactions occurred in all the 3 groups, the trial was considered to be terminated. This study did not set up a control group and aimed to explore the ED50 of rocuronium for inhibiting succinylcholine-induced fasciculation. Based on the sample size termination criteria associated with the sequential allocation method, previous literature and initial experimental studies suggest that involving 20 to 40 patients can provide stable estimates for the ED50 parameters[ 13 ]. SPSS (version 25.0, SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Continuous data with a normal distribution were expressed as mean ± standard deviation and were analyzed using analysis of variance. Categorical data were analyzed using chi-square test. P < 0.05 was considered a statistically significant difference. The numbers of effective and ineffective cases for each rocuronium dose on prevention of succinylcholine-induced fasciculation in each group were recorded. The logarithm and the total number of cases for each rocuronium dose were calculated in each group. Meanwhile, the effective rate of succinylcholine-induced fasciculation prevention and the differences between the logarithms of two adjacent rocuronium doses were calculated. The Dixon–Massey formula[ 10 ] was used to calculate ED50 and 95% confidence interval (CI) of rocuronium for the prevention of succinylcholine-induced fasciculation as follows: ED 50 logarithm (lgED 50 )= \(\:\frac{\sum\:(n\text{l}\text{g}\text{X}）}{\sum\:n}\) Standard error of lgED 50 (S lgED50 ) = d \(\:\sqrt{\frac{p(1-p)}{n-1}}\) 95% CI of lgED 50 =(lgED 50 – 1.96S lgED50 , lgED 50 + 1.96S lgED50 ) In the above formulas, n is the total number of cases per rocuronium dose, lgx is the rocuronium dose-specific logarithm, d is the difference between the logarithms of two adjacent doses, and p is the effective rate of fasciculation prevention. The antilogs of the logarithms were ED50 and the corresponding 95% CI. Results A total of 72 patients completed the trial, with 21 in Group R1, 28 in Group R2, and 23 in Group R3, respectively. Table 2 shows patients characteristics. Demographic data were similar except age and ASA classification among the three groups ( P < 0.05). All patients had stable hemodynamics during the induction of general anesthesia and no vasopressor drugs were used. Table 1 Demographics of the three groups Group R1 R2 R3 P a P b P c Man/Female 10/11 12/16 12/11 0.740 0.507 0.763 Age (years) 31.6±7.8 53.3±4.4 67.9±4.0 <0.001 <0.001 <0.001 Height (cm) Weight (kg) BMI (kg/m 2 ) 166.7±8.0 68.6±13.8 24.5±4.0 165.6±6.5 65.0±10.1 23.5±2.4 163.9±6.5 63.8±10.3 23.7±3.5 0.600 0.276 0.298 0.379 0.713 0.837 0.188 0.168 0.421 ASA (I/II) 17/4 15/13 4/19 0.046 <0.001 <0.001 Data are presented as the mean ± standard deviation (SD) or number. BMI: body mass index; ASA: American Society of Anesthesiologists P a : Compared between Group R1 and Group R2; P b : Compared between Group R2 and Group R3; P c : Compared between Group R3 and Group R1. The ED 50 (95% CI) of pretreated rocuronium for preventing succinylcholine-induced fasciculation was 0.027 μg/kg (95% CI: 0.026-0.028 μg/kg), 0.026 μg/kg (95% CI: 0.024-0.029 μg/kg), and 0.026 μg/kg (95% CI: 0.025-0.027 μg/kg) in Group R1, Group R2, and Group R3, respectively. There were no significant differences in the ED 50 (95% CI) among the three groups ( P > 0.05). In Group R1, rocuronium pretreatment prevented succinylcholine-induced fasciculation effectively in 13 cases and ineffectively in 8 cases. In Group R2, pretreatment was effective in 17 cases and ineffective in 11 cases. In Group R3, pretreatment prevented fasciculation effectively in 15 cases and ineffectively in 8 cases (Table 2). There were no significant differences among the three groups ( P > 0.05). Table 2 The occurrence of fasciculation in each group Group Degree of fasciculation [n (%)] 0 1 2 3 R1 13 (61.9) 7 (33.3) 1 (4.8) 0 (0) R2 17 (60.7) 8 (28.6) 3 (10.7) 0 (0) R3 15 (65.2) 7(30.4) 1 (4.4) 0 (0) The sequential diagrams of pretreated rocuronium in preventing succinylcholine-induced fasciculation in each group are shown in Figs 2-4. Table 3 presented the assessment of intubation conditions for each group. The endotracheal intubating condition was not influenced by the pretreated rocuronium. No significant differences in endotracheal intubating conditions were found among the three groups ( P > 0.05). Table 3 Endotracheal intubating conditions in each group Grade Group R1 Group R2 Group R3 1 (excellent) 20 (95.2) 25 (89.2) 19 (82.6) 2 (good) 1 (4.8) 2 (7.1) 2 (8.6) 3 (poor) 0 (0) 1 (3.5) 2 (8.6) 4 (inadequate) 0 (0) 0 (0) 0 (0) There was one case of transient diplopia in Group R2. No complications occurred in the other groups. Discussion Pretreatment with rocuronium effectively inhibited succinylcholine-induced fasciculation. The ED50 (95% CI) in Group R1, Group R2, and Group R3 were 0.027 µg/kg (95% CI: 0.026–0.028 µg/kg), 0.026 µg/kg (95% CI: 0.024–0.029 µg/kg), and 0.026 µg/kg (95% CI: 0.025–0.027 µg/kg), respectively. Rocuronium pretreatment in preventing succinylcholine-induced fasciculation was age-independent. Succinylcholine's rapid onset of action can shorten intubation time, rapidly control the airway, and reduce the risk of regurgitation and aspiration[ 14 ]. However, its use can cause fasciculation. The fasciculation induced by succinylcholine is brief, involuntary skeletal muscle contractions of muscle fibers within seconds of administration, starting with contractions of the eyelid muscles, rapidly spreading to the face and neck, and eventually to the trunk. The occurrence of fasciculation could increase the risk of increased intra-gastric pressure, intraocular pressure, and intracranial pressure[ 15 ]. Succinylcholine acts on the nicotinic acetylcholine receptors at the motor nerve terminals, causing repetitive depolarization and reverse discharge, leading to uncoordinated muscle contractions[ 16 ], which may be the primary mechanism of fasciculation. Previous studies have explored various measures to reduce the occurrence of fasciculation[ 17 , 18 ], among which pretreatment with small doses of non-depolarizing neuromuscular blocking agents is one of the most effective strategies[ 19 ]. Low dose of non-depolarizing neuromuscular blocking agents binding to the prejunctional nicotinic receptor sites may block the binding sites of succinylcholine to prevent fasciculation. The efficacy of the pretreatment depends on the choice of non-depolarizing agents, the time interval between the pretreatment and succinylcholine, and their affinity for synaptic receptors[ 20 ]. Rocuronium is a non-depolarizing neuromuscular blocking agent used for inhibiting succinylcholine induced fasciculation. Senapati et al.[ 8 ] found that rocuronium 0.06 mg/kg was more effective than vecuronium 0.01 mg/kg in reducing the incidence and severity of succinylcholine-induced fasciculation, with good intubating condition. Compared to cisatracurium, rocuronium also demonstrated a significant advantage in inhibiting succinylcholine-induced fasciculation [ 21 , 22 ]. Based on a meta-analysis of randomized trials, Schreiber et al.[ 18 ] identified rocuronium as the main drug for preventing succinylcholine-induced fasciculation and muscle pain. However, the doses of rocuronium in previous studies were usually used empirically. Pretreatment with non-depolarizing neuromuscular blocking agents may carry dose-dependent risks, including difficulty in opening eyes, diplopia, speech difficulties, and even swallowing and breathing difficulties[ 18 , 23 ]. It is important to explore the ED50 of rocuronium in preventing succinylcholine-induced fasciculation. Although a higher pre-administered dose of rocuronium is more effective in reducing fasciculation, increasing the dose might significantly increase the risk of adverse reactions of the muscle relaxant. Furthermore, it can also affect the onset time of succinylcholine, thereby delaying the optimal intubation timing[ 9 ]. Currently, there has been a profound discussion on the optimal dose of rocuronium for preventing succinylcholine-induced fasciculation. Naoko Fukano et al.[ 11 ] compared pre-treatment doses of rocuronium 0.03 mg/kg and 0.06 mg/kg, with the latter resulting in TOF of 72% and 68% at 2 min and 3 min, respectively. Since awake patients with a TOF ratio below 90% may experience significant difficulty in swallowing due to a marked decrease in esophageal sphincter muscle tension[ 24 ], lower TOF levels could lead to unpleasant experiences and even respiratory difficulties. Literature has confirmed that rocuronium 0.04 mg/kg was a safe and effective dose[ 7 ], which was the initial dose explored for the ED50 in the current study. Regarding the time interval, for cisatracurium, the optimal pretreatment interval was recommended to be 3 min[ 25 ], while this long interval may lead to unpleasant experiences such as ptosis in awake patients. Consistent with previous study[ 26 ], we set rocuronium pretreatment as 1.5 min before succinylcholine injection for the relatively fast onset of action of rocuronium. However, there are also studies indicating that giving rocuronium bromide 1 min or 5 min before succinylcholine does not lead to significant biochemical changes in muscle tremor induction[ 27 ]. Previous studies have shown that racial and body mass index differences can affect the optimal dosing of pre-treated rocuronium. Asians are more sensitive to the blockade effect of rocuronium compared to Europeans[ 28 ]. In adult female patients with a BMI in the range of 15–30 kg/m 2 , the duration of action of rocuronium increases with BMI when the drug is administered on the basis of mg per actual kg body weight[ 29 ]. Age has been shown in the literature to be an influential factor in the blocking effect of non-depolarizing muscarinic agents[ 30 ]. However, there have been no literature indicating the influence of age on the effects of pre-treated rocuronium in preventing succinylcholine-induced fasciculation, which is the strength of this study. We found that pre-administration of intravenous rocuronium to prevent succinylcholine-induced fasciculation is age-independent. Pretreatment with nondepolarizing muscle relaxants might discount the intubating condition after succinylcholine. However, we found that the sub-paralyzing dosages of rocuronium in this study did not influence the endotracheal intubating condition, nor there were significant differences in endotracheal intubating conditions among all the groups. In the current study, a 1.1 ratio was set between the adjacent doses of rocuronium using the Dixon sequential method, as were utilized successfully in our previous studies[ 10 ]. Limitation still exists in this study. Only one case of transient diplopia occurred in Group R2, with no adverse reactions observed in the other groups in this trial. To avoid the adverse effects of rocuronium pretreatment to the maximum extent, further researches are needed to clarify the optimal administration interval between rocuronium pretreatment and succinylcholine injection. Second, to avoid causing pain and unpleasant experience to patients during induction of general anesthesia, we did not monitor the train-of-four stimulation. However, we monitored the vital signs including hemodynamics and respiratory parameters to ensure patients’ safety. Conclusion Prophylactic intravenous rocuronium can prevent succinylcholine-induced fasciculation, and its ED50 (95% CI) is independent of age, with 0.027 µg/kg (95%CI: 0.026–0.028 µg/kg), 0.026 µg/kg (95%CI: 0.024 − 0.02 µg/kg), and 0.026 µg/kg (95%CI: 0.025 − 0.02 µg/kg) in patients of 18–44 years, 45–59 years, and 60–80 years old, respectively. Abbreviations ED 50 : Median effective dose BMI: Body mass index ASA: American Society of Anesthesiologists HR: Heart rate MAP: Mean Arterial Pressure CI: Confidence interval Declarations Ethics approval and consent to participate This study has been approved by the Ethics Committee of the Affiliated Hospital of Yangzhou University, Yangzhou, China (2023-YKL07-013) and registered on ClinicalTrials.gov (NCT05909696). All patients have signed written informed consent before the implementation of the study. Consent for publication Not applicable. Competing interests The authors declare that there is no conflict of interest. Funding This work was supported by the Social Development General Project of Jiangsu Provincial Science and Technology Plan (BE2023749); and General Project of Jiangsu Province Traditional Chinese Medicine Technology Development (MS2022151). Author Contribution Shunping Tian, Chao Chen, Shuping Wang and Zhuan Zhang contributed to the study conception and design. Material preparation, data collection, and interpretation were performed by Shunping Tian, Chao Chen, Shuping Wang, Shantian Feng, Meng Wang, Xuhong Liu, and Tianxiu Bao. Furthermore, Shunping Tian, Chao Chen and Zhuan Zhang were in charge of statistical analysis. All authors read and approved the final version of the submitted manuscript. Acknowledgement The authors thank the surgeons and nurses in the operating room of the Affiliated Hospital of Yangzhou University for their cooperation. Data Availability The data associated with this paper are not publicly available but may be obtained from the corresponding author upon reasonable request. References Tran DT, Newton EK, Mount VA, Lee JS, Wells GA, Perry JJ: Rocuronium versus succinylcholine for rapid sequence induction intubation . Cochrane Database Syst Rev 2015, 2015 (10):Cd002788. Vélez PA, Lara-Erazo V, Caballero-Lozada AF, Botero A, Lozada G, Velásquez AF, Villegas LM, Zorrilla-Vaca A: Preoperative pregabalin prevents succinylcholine-induced fasciculation and myalgia: A meta-analysis of randomized trials . Rev Esp Anestesiol Reanim (Engl Ed) 2023. Huang L, Sang CN, Desai MS: A Chronology for the Identification and Disclosure of Adverse Effects of Succinylcholine . J Anesth Hist 2019, 5 (3):65-84. Bayable SD, Ayenew NT, Misganaw A, Fetene MB, Amberbir WD: The Effects of Prophylactic Intravenous Lignocaine vs Vecuronium on Succinylcholine-Induced Fasciculation and Postoperative Myalgia in Patients Undergoing Elective Surgery at Debre Markos Comprehensive Specialized Hospital, Ethiopia, 2022: Prospective Cohort Study . Int J Gen Med 2023, 16 :2663-2670. Shabanian G, Shabanian M, Shabanian A, Heidari-Soureshjani S: Comparison of atracurium and methocarbamol for preventing succinylcholine-induced muscle fasciculation: A randomized controlled trial . J Adv Pharm Technol Res 2017, 8 (2):59-62. Ahsan B, Rahimi E, Moradi A, Rashadmanesh N: The effects of magnesium sulphate on succinylcholine-induced fasciculation during induction of general anaesthesia . J Pak Med Assoc 2014, 64 (10):1151-1153. Fukano N, Suzuki T, Ishikawa K, Mizutani H, Saeki S, Ogawa S: A randomized trial to identify optimal precurarizing dose of rocuronium to avoid precurarization-induced neuromuscular block . J Anesth 2011, 25 (2):200-204. Senapati LK, Battini KP, Padhi PP, Samanta P: Effect of Non-depolarizing Muscle Relaxants Rocuronium Versus Vecuronium in the Assessment of Post-Succinylcholine Complications in Surgeries Under General Anesthesia: A Randomized Double-Blind Study at a Tertiary Care Hospital . Cureus 2021, 13 (11):e19793. Kim KN, Kim KS, Choi HI, Jeong JS, Lee HJ: Optimal precurarizing dose of rocuronium to decrease fasciculation and myalgia following succinylcholine administration . Korean J Anesthesiol 2014, 66 (6):451-456. Yan S, Wu H, Yu Y, Li N, Yu L, Wang Y, Li H, Zhang D, Zhang Z: Median Effective Dose of Remifentanil for the Prevention of Pain Caused by the Injection of Rocuronium: An Age-Stratified Study . Pain Ther 2023, 12 (3):683-694. Stocks GM, Hallworth SP, Fernando R, England AJ, Columb MO, Lyons G: Minimum local analgesic dose of intrathecal bupivacaine in labor and the effect of intrathecal fentanyl . Anesthesiology 2001, 94 (4):593-598; discussion 595A. Harvey SC, Roland P, Bailey MK, Tomlin MK, Williams A: A randomized, double-blind comparison of rocuronium, d-tubocurarine, and "mini-dose" succinylcholine for preventing succinylcholine-induced muscle fasciculations . Anesth Analg 1998, 87 (3):719-722. Cao X, Gui Q, Wei Y, Lan L, Xiao H, Wen S, Li X: The 50% effective dose of hydromorphone and morphine for epidural analgesia in the hemorrhoidectomy: a double-blind, sequential dose-finding study . BMC Anesthesiol 2024, 24 (1):41. Ramsey JT, Pache KM, Sayre MR, Maynard C, Johnson NJ, Counts CR: Comparison of Intubating Conditions with Succinylcholine Versus Rocuronium in the Prehospital Setting . Prehosp Emerg Care 2023:1-8. Zhang Z, Zhang DS, Sui W, Liu XH, Zhang L, Sun JH: Effects of pretreatment with different doses of cisatracurium on succinylcholine-induced fasciculations . Int J Clin Pharmacol Ther 2016, 54 (6):426-432. Wong SF, Chung F: Succinylcholine-associated postoperative myalgia . Anaesthesia 2000, 55 (2):144-152. Morris J, Cook TM: Rapid sequence induction: a national survey of practice . Anaesthesia 2001, 56 (11):1090-1097. Schreiber JU, Lysakowski C, Fuchs-Buder T, Tramèr MR: Prevention of succinylcholine-induced fasciculation and myalgia: a meta-analysis of randomized trials . Anesthesiology 2005, 103 (4):877-884. Fatemeh H, Mojgan R: Comparison of atracurium and "mini-dose" succinylcholine for preventing succinylcholine-induced muscle fasciculations: a randomized, double-blind, placebo-controlled study . Acta Anaesthesiol Taiwan 2010, 48 (1):28-32. Martyn JA, Fagerlund MJ, Eriksson LI: Basic principles of neuromuscular transmission . Anaesthesia 2009, 64 Suppl 1 :1-9. Joshi GP, Hailey A, Cross S, Thompson-Bell G, Whitten CC: Effects of pretreatment with cisatracurium, rocuronium, and d-tubocurarine on succinylcholine-induced fasciculations and myalgia: a comparison with placebo . J Clin Anesth 1999, 11 (8):641-645. True CA, Carter PJ: A comparison of tubocurarine, rocuronium, and cisatracurium in the prevention and reduction of succinylcholine-induced muscle fasciculations . Aana j 2003, 71 (1):23-28. Mencke T, Schreiber JU, Becker C, Bolte M, Fuchs-Buder T: Pretreatment before succinylcholine for outpatient anesthesia? Anesth Analg 2002, 94 (3):573-576; table of contents. Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI: The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium . Anesthesiology 2000, 92 (4):977-984. Pandey CK, Tripathi M, Joshi G, Karna ST, Singh N, Singh PK: Prophylactic use of gabapentin for prevention of succinylcholine-induced fasciculation and myalgia: a randomized, double-blinded, placebo-controlled study . J Postgrad Med 2012, 58 (1):19-22. Hernández-Palazón J, Noguera-Velasco J, Falcón-Araña LF, Doménech-Asensi P, Burguillos-López S, Nuño de la Rosa-Carrillo V: [Precurarization with rocuronium prevents fasciculations and biochemical changes after succinylcholine administration] . Rev Esp Anestesiol Reanim 2004, 51 (4):184-189. Farhat K, Pasha AK, Jaffery N: Biochemical changes following succinylcholine administration after pretreatment with rocuronium at different intervals . J Pak Med Assoc 2014, 64 (2):146-150. Gin T, Chan MT, Chan KL, Yuen PM: Prolonged neuromuscular block after rocuronium in postpartum patients . Anesth Analg 2002, 94 (3):686-689; table of contents. Fujimoto M, Tanahira C, Nishi M, Yamamoto T: In non-obese patients, duration of action of rocuronium is directly correlated with body mass index . Can J Anaesth 2013, 60 (6):552-556. Vested M, Kristensen CM, Pape P, Vang M, Hartoft M, Hjelmdal C, Rasmussen LS: Comparison of onset time, duration of action, and intubating conditions after cisatracurium 0.15 mg/kg in young and elderly patients . BMC Anesthesiol 2022, 22 (1):339. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 10 Dec, 2025 Read the published version in BMC Anesthesiology → Version 1 posted Editorial decision: Revision requested 29 Sep, 2025 Reviews received at journal 25 Sep, 2025 Reviewers agreed at journal 15 Sep, 2025 Reviews received at journal 22 Aug, 2025 Reviewers agreed at journal 08 Aug, 2025 Reviewers agreed at journal 06 Aug, 2025 Reviewers invited by journal 03 Aug, 2025 Editor invited by journal 08 Jul, 2025 Editor assigned by journal 07 Jul, 2025 Submission checks completed at journal 07 Jul, 2025 First submitted to journal 28 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6998202","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":495670815,"identity":"c8087f8f-e711-478c-a17d-300e8dd25c3d","order_by":0,"name":"Shunping Tian","email":"","orcid":"","institution":"the Affiliated Hospital of Yangzhou University","correspondingAuthor":false,"prefix":"","firstName":"Shunping","middleName":"","lastName":"Tian","suffix":""},{"id":495670817,"identity":"edbb215f-fae6-4922-8b21-7a8268253135","order_by":1,"name":"Chao Chen","email":"","orcid":"","institution":"Gaoyou People's Hospital, The Third Clinical Medical College of Yangzhou University","correspondingAuthor":false,"prefix":"","firstName":"Chao","middleName":"","lastName":"Chen","suffix":""},{"id":495670818,"identity":"4d8e9b14-9af0-4878-b003-d71d2f9cf6bb","order_by":2,"name":"Shuping Wang","email":"","orcid":"","institution":"Yancheng Maternal and Child Health Care Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shuping","middleName":"","lastName":"Wang","suffix":""},{"id":495670819,"identity":"2b36e477-3c72-469c-8083-a4892c9b3ac0","order_by":3,"name":"Shantian Feng","email":"","orcid":"","institution":"the Affiliated Hospital of Yangzhou University","correspondingAuthor":false,"prefix":"","firstName":"Shantian","middleName":"","lastName":"Feng","suffix":""},{"id":495670820,"identity":"1d7d73bb-3883-4f14-b6c4-cd1cdf7211cd","order_by":4,"name":"Meng Wang","email":"","orcid":"","institution":"the Affiliated Hospital of Yangzhou University","correspondingAuthor":false,"prefix":"","firstName":"Meng","middleName":"","lastName":"Wang","suffix":""},{"id":495670821,"identity":"f6f7c5d7-ff37-485b-8794-2c549b8964f8","order_by":5,"name":"Xuhong Liu","email":"","orcid":"","institution":"the Affiliated Hospital of Yangzhou University","correspondingAuthor":false,"prefix":"","firstName":"Xuhong","middleName":"","lastName":"Liu","suffix":""},{"id":495670823,"identity":"e032493f-b320-488f-924a-50295642f34d","order_by":6,"name":"Tianxiu Bao","email":"","orcid":"","institution":"the Affiliated Hospital of Yangzhou University","correspondingAuthor":false,"prefix":"","firstName":"Tianxiu","middleName":"","lastName":"Bao","suffix":""},{"id":495670825,"identity":"3449fc45-af99-45af-8912-b668cacb4aca","order_by":7,"name":"Zhuan Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYDACCTB5AML5YGBjR5oWxhkFacmkaWHm+XCIsYGQDvnZzc8efvlzJ7F/dvPj1zYGB5gZ2A8f3YBPC+OcY+bGMjzPEmfcOWZmnWNwh4+BJy3tBj4tzBIJZtISEocTG27ksBnnGDxjZpDgMcOrhU0i/Zu0hMHhxPkgLRYGhxkbCGnhkcgxk/yQcDhxw40c5scMxGiRkMgpk2Y4cNh44400M8Yeg7RkNkJ+kZ+Rvk3yx5/DsvNuJD/+8OOPjR0/++FjeLWAADMPzF9gkpByEGD8AdX6gRjVo2AUjIJRMPIAADheTcZ/zpKqAAAAAElFTkSuQmCC","orcid":"","institution":"the Affiliated Hospital of Yangzhou University","correspondingAuthor":true,"prefix":"","firstName":"Zhuan","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-06-28 13:53:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6998202/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6998202/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12871-025-03546-5","type":"published","date":"2025-12-10T15:58:28+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88490657,"identity":"4d96fc35-edbf-4443-90f3-0e2e2ec33880","added_by":"auto","created_at":"2025-08-07 04:14:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":340062,"visible":true,"origin":"","legend":"\u003cp\u003eStudy protocol\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6998202/v1/2a2fb56daefac033c75c8a9d.png"},{"id":88489411,"identity":"154f1f90-3101-4509-bcef-a99de2770685","added_by":"auto","created_at":"2025-08-07 04:06:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":45153,"visible":true,"origin":"","legend":"\u003cp\u003eSequential diagram of pretreated rocuronium in preventing succinylcholine-induced fasciculation in Group R1\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6998202/v1/4ce6ea783140405df8c3a176.png"},{"id":88489412,"identity":"5dc65cc8-78e5-4f3b-8834-b1f06e6fdeff","added_by":"auto","created_at":"2025-08-07 04:06:24","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":66016,"visible":true,"origin":"","legend":"\u003cp\u003eSequential diagram of pretreated rocuronium in preventing succinylcholine-induced fasciculation in Group R2\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6998202/v1/65dc4d9a960d926b64239cc1.png"},{"id":88489413,"identity":"44a50779-699d-41e2-a219-f309aef96f65","added_by":"auto","created_at":"2025-08-07 04:06:24","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":48846,"visible":true,"origin":"","legend":"\u003cp\u003eSequential diagram of pretreated rocuronium in preventing succinylcholine-induced fasciculation in Group R3.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6998202/v1/c4700958dc22f1ac811317a6.png"},{"id":98243903,"identity":"33bd477f-828b-4bfe-a866-b65018bb2e73","added_by":"auto","created_at":"2025-12-15 16:11:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2576868,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6998202/v1/0452a05b-2968-4ccd-b533-d09fbe6d111f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Median Effective Dose of Rocuronium for the Prevention of Succinylcholine-induced Fasciculation：An Age-Stratified Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSuccinylcholine is a depolarizing muscle relaxant with the advantages of rapid-onset, short duration of action, and perfect muscle relaxation[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It is one of the muscle relaxant choices for patients requiring general anesthesia for rapid sequential induction of intubation with a wide range of clinical applications. However, it’s injection often produces involuntary fasciculation with the incidence up to 95%, which may lead to postoperative myalgia, hemodynamic instability, body movement during induction, and increase in intraocular pressure, gastric pressure, and intracranial pressure[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eReducing the occurrence of fasciculation during induction of general anesthesia has gained attention from anesthesiologists[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e–\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Low-dose rocuronium pretreatment has been reported to reduce the occurrence of fasciculation[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e–\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], while its dosage was usually empirically applied. Furthermore, there have been no studies on the age-related dose of rocuronium to inhibit succinylcholine-induced fasciculation, neither the median effective dose (ED\u003csub\u003e50\u003c/sub\u003e) has been determined.\u003c/p\u003e\u003cp\u003eThis study was carried out to explore the ED\u003csub\u003e50\u003c/sub\u003e of rocuronium for inhibiting succinylcholine-induced fasciculation and to investigate the influence of age on ED\u003csub\u003e50\u003c/sub\u003e of rocuronium in preventing succinylcholine-induced fasciculation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This study has been approved by the Ethics Committee of the Affiliated Hospital of Yangzhou University, Yangzhou, China (2023-YKL07-013) and registered on ClinicalTrials.gov (NCT05909696). The study was conducted in accordance with the Declaration of Helsinki and the principles of the International Conference on Harmonization Good Clinical Practice Guideline. All patients have signed written informed consent before the implementation of the study.\u003c/p\u003e\u003cp\u003ePatients scheduled for elective tracheal intubation under general anesthesia, aged 18–80 years, body mass index (BMI) 18.5–28 kg/m\u003csup\u003e2\u003c/sup\u003e, and American Society of Anesthesiologists (ASA) grade I or II, were included from July 2023 to October 2023 in the Affiliated Hospital of Yangzhou University. Exclusion criteria were: possible airway difficulties, allergies or contraindications to rocuronium and succinylcholine, cardiac insufficiency, hepatic or renal dysfunction, neuromuscular disease, surgery lasting more than 2 hours, taking any known drug that has interaction with neuromuscular blockers.\u003c/p\u003e\u003cp\u003eAccording to the age classification by the World Health Organization in 2012, patients were divided into three groups: Group R1 (18–44 years old), Group R2 (45–59 years old), and Group R3 (60–80 years old).\u003c/p\u003e\u003cp\u003eNo premedication was used in all patients. Upon entering the operating room, non-invasive blood pressure (NIBP), heart rate (HR), electrocardiogram (ECG), and pulse oxygen saturation (S\u003csub\u003eP\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e) were monitored. The pressure cuff was routinely banded on the arm that was without venous canulation. A 20-G intravenous catheter was placed in the cephalic vein of the wrist, with compound sodium chloride solution administered at a rate of 8–10 mL/kg/min. The vertical distance from the infusion bottle to the intravenous catheter for all cases in this study was 80 cm, as was set in our previous studies focused on ED50 exploration[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. All the patients were unknown of the applied medication.\u003c/p\u003e\u003cp\u003eThe induction process of general anesthesia was carried out by three anesthesiologists using Dixon sequential method[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], the whole process of which is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The first anesthesiologist prepared and injected rocuronium for pretreatment. The initial dose of rocuronium (EA2167, Zhejiang Xian Ju Pharmaceutical Co, China) for each group was set at 0.04 mg/kg, which was stored at 2–8 ℃. It was drawn up with a 1-mL syringe and diluted with normal saline to 5 mL in a 5-mL syringe before use. The pretreated rocuronium was injected slowly with the injection time of 5 sec. The timing at intravenous administration of the pretreated rocuronium was considered as 0 min time point, with oxygen administered concomitantly via a mask by the second anesthesiologist who was unaware of the rocuronium dosage. At 1 min time point, the patient was inquired also by the second anesthesiologist about any adverse reactions of rocuronium including injection pain, diplopia, heavy eyelids, dizziness, dysarthria, swallowing, and breathing difficulties. Then, standardized general anesthesia induction was performed by the third anesthesiologist who was unaware of the rocuronium dosage. Midazolam 0.05 mg/kg, sufentanil 0.4 µg/kg, propofol 1.5–2.5 mg/kg, and succinylcholine 2 mg/kg were sequentially administered at 1.5 min time point. After succinylcholine administration, the third anesthesiologist assessed and reported whether there was fasciculation in the eyelids, neck, and other areas. The second anesthesiologist performed tracheal intubation at 2 min time point, and assessed the intubation condition. General anesthesia maintenance was then implemented.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eMuscle fasciculation severity was assessed using a four-point scale[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] with 4 levels: 0, no fasciculation; 1, mild fasciculation, slight tremor in the eyes, face, neck, or fingers, without limb movement; 2, moderate fasciculation, occurring in more than 2 muscle groups or involving body or limb movement; 3, severe fasciculation, intense, sustained, widespread fasciculation, may require restraint. Tracheal intubation conditions were assessed and graded to 4 levels[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]: 1, excellent (good jaw relaxation, vocal cords open and immobile, with no response to intubation); 2, good (good jaw relaxation, vocal cords open and immobile, but minimal response to intubation; 3, poor (moderate jaw relaxation, moving vocal cord, intubation accompanied by coughing and/or bucking); 4, inadequate ( intubation impossible due to poor jaw relaxation or closed vocal cords).\u003c/p\u003e\u003cp\u003eEphedrine, phenylephrine, or atropine were used intraoperatively, if necessary, according to changes in vital signs. If mean arterial pressure (MAP) was decreased by more than 20% from the baseline, ephedrine or phenylephrine was administered intravenously. If HR decreased to less than 50 beats/min or the decrease was more than 20% of the base value, atropine was administered intravenously.\u003c/p\u003e\u003cp\u003eDemographic data, including age, gender, weight, height, and ASA classification, hemodynamics, and the use of vasoactive medications during general anesthesia induction were recorded. The occurrence of adverse effects of rocuronium, including injection pain, diplopia, heavy eyelids, dizziness, dysarthria, swallowing, and breathing difficulties, were also recorded.\u003c/p\u003e\u003cp\u003eAccording to the assessment of succinylcholine-induced fasciculation by the third anesthesiologist, the first anesthesiologist adjusted the dose of the pretreated rocuronium. If the patient did not experience fasciculation (grade 0, negative reaction), the dose of pretreated rocuronium for the next patient was reduced until fasciculation occurred. If the patient experienced fasciculation (grade 1, 2 or 3, positive reaction), the dose of rocuronium for the next patient was increased until fasciculation disappeared. The ratio of the adjacent doses of rocuronium was 1.1. All pre-treatment drugs and syringe colors were identical. In each group, the first patient who showed positive reaction was included as the second case, with the previous one included as the first case. When 7 alternating positive and negative reactions occurred in all the 3 groups, the trial was considered to be terminated. This study did not set up a control group and aimed to explore the ED50 of rocuronium for inhibiting succinylcholine-induced fasciculation.\u003c/p\u003e\u003cp\u003eBased on the sample size termination criteria associated with the sequential allocation method, previous literature and initial experimental studies suggest that involving 20 to 40 patients can provide stable estimates for the ED50 parameters[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. SPSS (version 25.0, SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Continuous data with a normal distribution were expressed as mean ± standard deviation and were analyzed using analysis of variance. Categorical data were analyzed using chi-square test. \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 was considered a statistically significant difference.\u003c/p\u003e\u003cp\u003eThe numbers of effective and ineffective cases for each rocuronium dose on prevention of succinylcholine-induced fasciculation in each group were recorded. The logarithm and the total number of cases for each rocuronium dose were calculated in each group. Meanwhile, the effective rate of succinylcholine-induced fasciculation prevention and the differences between the logarithms of two adjacent rocuronium doses were calculated. The Dixon–Massey formula[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] was used to calculate ED50 and 95% confidence interval (CI) of rocuronium for the prevention of succinylcholine-induced fasciculation as follows:\u003c/p\u003e\u003cp\u003eED\u003csub\u003e50\u003c/sub\u003e logarithm (lgED\u003csub\u003e50\u003c/sub\u003e )= \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\frac{\\sum\\:(n\\text{l}\\text{g}\\text{X}）}{\\sum\\:n}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003cp\u003eStandard error of lgED\u003csub\u003e50\u003c/sub\u003e (S\u003csub\u003elgED50\u003c/sub\u003e) = \u003cem\u003ed\u003c/em\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sqrt{\\frac{p(1-p)}{n-1}}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003cp\u003e95% CI of lgED\u003csub\u003e50\u003c/sub\u003e=(lgED\u003csub\u003e50\u003c/sub\u003e – 1.96S\u003csub\u003elgED50\u003c/sub\u003e, lgED\u003csub\u003e50\u003c/sub\u003e + 1.96S\u003csub\u003elgED50\u003c/sub\u003e)\u003c/p\u003e\u003cp\u003eIn the above formulas, \u003cem\u003en\u003c/em\u003e is the total number of cases per rocuronium dose, lgx is the rocuronium dose-specific logarithm, \u003cem\u003ed\u003c/em\u003e is the difference between the logarithms of two adjacent doses, and \u003cem\u003ep\u003c/em\u003e is the effective rate of fasciculation prevention. The antilogs of the logarithms were ED50 and the corresponding 95% CI.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 72 patients completed the trial, with 21 in Group R1, 28 in Group R2, and 23 in Group R3, respectively. Table 2 shows patients characteristics. Demographic data were similar except age and ASA classification among the three groups (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.05).\u0026nbsp;All patients had stable hemodynamics during the induction of general anesthesia and no vasopressor drugs were used.\u003c/p\u003e\n\u003cp\u003eTable 1 Demographics of the three groups\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003eR1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003eR2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003eR3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csub\u003eb\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csub\u003ec\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003eMan/Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e10/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e12/16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e12/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.507\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.763\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e31.6\u0026plusmn;7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e53.3\u0026plusmn;4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e67.9\u0026plusmn;4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003eHeight (cm)\u003c/p\u003e\n \u003cp\u003eWeight (kg)\u003c/p\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e166.7\u0026plusmn;8.0\u003c/p\u003e\n \u003cp\u003e68.6\u0026plusmn;13.8\u003c/p\u003e\n \u003cp\u003e24.5\u0026plusmn;4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e165.6\u0026plusmn;6.5\u003c/p\u003e\n \u003cp\u003e65.0\u0026plusmn;10.1\u003c/p\u003e\n \u003cp\u003e23.5\u0026plusmn;2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e163.9\u0026plusmn;6.5\u003c/p\u003e\n \u003cp\u003e63.8\u0026plusmn;10.3\u003c/p\u003e\n \u003cp\u003e23.7\u0026plusmn;3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.600\u003c/p\u003e\n \u003cp\u003e0.276\u003c/p\u003e\n \u003cp\u003e0.298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.379\u003c/p\u003e\n \u003cp\u003e0.713\u003c/p\u003e\n \u003cp\u003e0.837\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.188\u003c/p\u003e\n \u003cp\u003e0.168\u003c/p\u003e\n \u003cp\u003e0.421\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003eASA (I/II)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e17/4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e15/13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e4/19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.046\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eData are presented as the mean \u0026plusmn; standard deviation (SD)\u0026nbsp;or number.\u003c/p\u003e\n\u003cp\u003eBMI: body mass index; ASA: American Society of Anesthesiologists\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csub\u003ea\u003c/sub\u003e: Compared between Group R1 and Group R2; \u003cem\u003eP\u003c/em\u003e\u003csub\u003eb\u003c/sub\u003e: Compared between Group R2 and Group R3; \u003cem\u003eP\u003c/em\u003e\u003csub\u003ec\u003c/sub\u003e: Compared between Group R3 and Group R1.\u003c/p\u003e\n\u003cp\u003eThe ED\u003csub\u003e50\u003c/sub\u003e (95% CI) of pretreated rocuronium for preventing succinylcholine-induced fasciculation was 0.027 \u0026mu;g/kg (95% CI: 0.026-0.028 \u0026mu;g/kg), 0.026 \u0026mu;g/kg (95% CI: 0.024-0.029 \u0026mu;g/kg), and 0.026 \u0026mu;g/kg (95% CI: 0.025-0.027 \u0026mu;g/kg) in Group R1, Group R2, and Group R3, respectively. There were no significant differences in the ED\u003csub\u003e50\u003c/sub\u003e (95% CI) among the three groups (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn Group R1, rocuronium pretreatment prevented succinylcholine-induced fasciculation effectively in 13 cases and ineffectively in 8 cases. In Group R2, pretreatment was effective in 17 cases and ineffective in 11 cases. In Group R3, pretreatment prevented fasciculation effectively in 15 cases and ineffectively in 8 cases (Table 2). There were no significant differences among the three groups (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 The occurrence of fasciculation in each group\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"551\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 478px;\"\u003e\n \u003cp\u003eDegree of\u0026nbsp;fasciculation [n (%)]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eR1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e13 (61.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e7 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eR2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e17 (60.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e8 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e3 (10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 73px;\"\u003e\n \u003cp\u003eR3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e15 (65.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e7(30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe sequential diagrams of pretreated rocuronium in preventing succinylcholine-induced fasciculation in each group are shown in Figs 2-4.\u003c/p\u003e\n\u003cp\u003eTable 3 presented the assessment of intubation conditions for each group. The endotracheal intubating condition was not influenced by the pretreated rocuronium. No significant differences in endotracheal intubating conditions were found among the three groups (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003eTable 3 Endotracheal intubating conditions in each group\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eGroup R1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eGroup R2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eGroup R3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e1 (excellent)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e20 (95.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e25 (89.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e19 (82.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e2 (good)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e1 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e2 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e2 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e3 (poor)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e1 (3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e2 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e4 (inadequate)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThere was one case of transient diplopia in Group R2. No complications occurred in the other groups.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePretreatment with rocuronium effectively inhibited succinylcholine-induced fasciculation. The ED50 (95% CI) in Group R1, Group R2, and Group R3 were 0.027 \u0026micro;g/kg (95% CI: 0.026\u0026ndash;0.028 \u0026micro;g/kg), 0.026 \u0026micro;g/kg (95% CI: 0.024\u0026ndash;0.029 \u0026micro;g/kg), and 0.026 \u0026micro;g/kg (95% CI: 0.025\u0026ndash;0.027 \u0026micro;g/kg), respectively. Rocuronium pretreatment in preventing succinylcholine-induced fasciculation was age-independent.\u003c/p\u003e\u003cp\u003eSuccinylcholine's rapid onset of action can shorten intubation time, rapidly control the airway, and reduce the risk of regurgitation and aspiration[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, its use can cause fasciculation. The fasciculation induced by succinylcholine is brief, involuntary skeletal muscle contractions of muscle fibers within seconds of administration, starting with contractions of the eyelid muscles, rapidly spreading to the face and neck, and eventually to the trunk. The occurrence of fasciculation could increase the risk of increased intra-gastric pressure, intraocular pressure, and intracranial pressure[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSuccinylcholine acts on the nicotinic acetylcholine receptors at the motor nerve terminals, causing repetitive depolarization and reverse discharge, leading to uncoordinated muscle contractions[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], which may be the primary mechanism of fasciculation. Previous studies have explored various measures to reduce the occurrence of fasciculation[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], among which pretreatment with small doses of non-depolarizing neuromuscular blocking agents is one of the most effective strategies[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Low dose of non-depolarizing neuromuscular blocking agents binding to the prejunctional nicotinic receptor sites may block the binding sites of succinylcholine to prevent fasciculation. The efficacy of the pretreatment depends on the choice of non-depolarizing agents, the time interval between the pretreatment and succinylcholine, and their affinity for synaptic receptors[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Rocuronium is a non-depolarizing neuromuscular blocking agent used for inhibiting succinylcholine induced fasciculation. Senapati et al.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] found that rocuronium 0.06 mg/kg was more effective than vecuronium 0.01 mg/kg in reducing the incidence and severity of succinylcholine-induced fasciculation, with good intubating condition. Compared to cisatracurium, rocuronium also demonstrated a significant advantage in inhibiting succinylcholine-induced fasciculation [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Based on a meta-analysis of randomized trials, Schreiber et al.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] identified rocuronium as the main drug for preventing succinylcholine-induced fasciculation and muscle pain.\u003c/p\u003e\u003cp\u003eHowever, the doses of rocuronium in previous studies were usually used empirically. Pretreatment with non-depolarizing neuromuscular blocking agents may carry dose-dependent risks, including difficulty in opening eyes, diplopia, speech difficulties, and even swallowing and breathing difficulties[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. It is important to explore the ED50 of rocuronium in preventing succinylcholine-induced fasciculation. Although a higher pre-administered dose of rocuronium is more effective in reducing fasciculation, increasing the dose might significantly increase the risk of adverse reactions of the muscle relaxant. Furthermore, it can also affect the onset time of succinylcholine, thereby delaying the optimal intubation timing[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Currently, there has been a profound discussion on the optimal dose of rocuronium for preventing succinylcholine-induced fasciculation. Naoko Fukano et al.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] compared pre-treatment doses of rocuronium 0.03 mg/kg and 0.06 mg/kg, with the latter resulting in TOF of 72% and 68% at 2 min and 3 min, respectively. Since awake patients with a TOF ratio below 90% may experience significant difficulty in swallowing due to a marked decrease in esophageal sphincter muscle tension[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], lower TOF levels could lead to unpleasant experiences and even respiratory difficulties. Literature has confirmed that rocuronium 0.04 mg/kg was a safe and effective dose[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], which was the initial dose explored for the ED50 in the current study.\u003c/p\u003e\u003cp\u003eRegarding the time interval, for cisatracurium, the optimal pretreatment interval was recommended to be 3 min[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], while this long interval may lead to unpleasant experiences such as ptosis in awake patients. Consistent with previous study[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], we set rocuronium pretreatment as 1.5 min before succinylcholine injection for the relatively fast onset of action of rocuronium. However, there are also studies indicating that giving rocuronium bromide 1 min or 5 min before succinylcholine does not lead to significant biochemical changes in muscle tremor induction[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePrevious studies have shown that racial and body mass index differences can affect the optimal dosing of pre-treated rocuronium. Asians are more sensitive to the blockade effect of rocuronium compared to Europeans[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In adult female patients with a BMI in the range of 15\u0026ndash;30 kg/m\u003csup\u003e2\u003c/sup\u003e, the duration of action of rocuronium increases with BMI when the drug is administered on the basis of mg per actual kg body weight[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Age has been shown in the literature to be an influential factor in the blocking effect of non-depolarizing muscarinic agents[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. However, there have been no literature indicating the influence of age on the effects of pre-treated rocuronium in preventing succinylcholine-induced fasciculation, which is the strength of this study. We found that pre-administration of intravenous rocuronium to prevent succinylcholine-induced fasciculation is age-independent. Pretreatment with nondepolarizing muscle relaxants might discount the intubating condition after succinylcholine. However, we found that the sub-paralyzing dosages of rocuronium in this study did not influence the endotracheal intubating condition, nor there were significant differences in endotracheal intubating conditions among all the groups. In the current study, a 1.1 ratio was set between the adjacent doses of rocuronium using the Dixon sequential method, as were utilized successfully in our previous studies[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eLimitation still exists in this study. Only one case of transient diplopia occurred in Group R2, with no adverse reactions observed in the other groups in this trial. To avoid the adverse effects of rocuronium pretreatment to the maximum extent, further researches are needed to clarify the optimal administration interval between rocuronium pretreatment and succinylcholine injection. Second, to avoid causing pain and unpleasant experience to patients during induction of general anesthesia, we did not monitor the train-of-four stimulation. However, we monitored the vital signs including hemodynamics and respiratory parameters to ensure patients\u0026rsquo; safety.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eProphylactic intravenous rocuronium can prevent succinylcholine-induced fasciculation, and its ED50 (95% CI) is independent of age, with 0.027 \u0026micro;g/kg (95%CI: 0.026\u0026ndash;0.028 \u0026micro;g/kg), 0.026 \u0026micro;g/kg (95%CI: 0.024\u0026thinsp;\u0026minus;\u0026thinsp;0.02 \u0026micro;g/kg), and 0.026 \u0026micro;g/kg (95%CI: 0.025\u0026thinsp;\u0026minus;\u0026thinsp;0.02 \u0026micro;g/kg) in patients of 18\u0026ndash;44 years, 45\u0026ndash;59 years, and 60\u0026ndash;80 years old, respectively.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eED\u003csub\u003e50\u003c/sub\u003e: Median effective dose\u003c/p\u003e\n\u003cp\u003eBMI: Body mass index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eASA: American Society of Anesthesiologists\u003c/p\u003e\n\u003cp\u003eHR: Heart rate \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMAP: Mean Arterial Pressure\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCI: Confidence interval\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThis study has been approved by the Ethics Committee of the Affiliated Hospital of Yangzhou University, Yangzhou, China (2023-YKL07-013) and registered on ClinicalTrials.gov (NCT05909696). All patients have signed written informed consent before the implementation of the study.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis work was supported by the Social Development General Project of Jiangsu Provincial Science and Technology Plan (BE2023749); and General Project of Jiangsu Province Traditional Chinese Medicine Technology Development (MS2022151).\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eShunping Tian, Chao Chen, Shuping Wang and Zhuan Zhang contributed to the study conception and design. Material preparation, data collection, and interpretation were performed by Shunping Tian, Chao Chen, Shuping Wang, Shantian Feng, Meng Wang, Xuhong Liu, and Tianxiu Bao. Furthermore, Shunping Tian, Chao Chen and Zhuan Zhang were in charge of statistical analysis. All authors read and approved the final version of the submitted manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThe authors thank the surgeons and nurses in the operating room of the Affiliated Hospital of Yangzhou University for their cooperation.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe data associated with this paper are not publicly available but may be obtained from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTran DT, Newton EK, Mount VA, Lee JS, Wells GA, Perry JJ: \u003cstrong\u003eRocuronium versus succinylcholine for rapid sequence induction intubation\u003c/strong\u003e. \u003cem\u003eCochrane Database Syst Rev \u003c/em\u003e2015, \u003cstrong\u003e2015\u003c/strong\u003e(10):Cd002788.\u003c/li\u003e\n\u003cli\u003eV\u0026eacute;lez PA, Lara-Erazo V, Caballero-Lozada AF, Botero A, Lozada G, Vel\u0026aacute;squez AF, Villegas LM, Zorrilla-Vaca A: \u003cstrong\u003ePreoperative pregabalin prevents succinylcholine-induced fasciculation and myalgia: A meta-analysis of randomized trials\u003c/strong\u003e. \u003cem\u003eRev Esp Anestesiol Reanim (Engl Ed) \u003c/em\u003e2023.\u003c/li\u003e\n\u003cli\u003eHuang L, Sang CN, Desai MS: \u003cstrong\u003eA Chronology for the Identification and Disclosure of Adverse Effects of Succinylcholine\u003c/strong\u003e. \u003cem\u003eJ Anesth Hist \u003c/em\u003e2019, \u003cstrong\u003e5\u003c/strong\u003e(3):65-84.\u003c/li\u003e\n\u003cli\u003eBayable SD, Ayenew NT, Misganaw A, Fetene MB, Amberbir WD: \u003cstrong\u003eThe Effects of Prophylactic Intravenous Lignocaine vs Vecuronium on Succinylcholine-Induced Fasciculation and Postoperative Myalgia in Patients Undergoing Elective Surgery at Debre Markos Comprehensive Specialized Hospital, Ethiopia, 2022: Prospective Cohort Study\u003c/strong\u003e. \u003cem\u003eInt J Gen Med \u003c/em\u003e2023, \u003cstrong\u003e16\u003c/strong\u003e:2663-2670.\u003c/li\u003e\n\u003cli\u003eShabanian G, Shabanian M, Shabanian A, Heidari-Soureshjani S: \u003cstrong\u003eComparison of atracurium and methocarbamol for preventing succinylcholine-induced muscle fasciculation: A randomized controlled trial\u003c/strong\u003e. \u003cem\u003eJ Adv Pharm Technol Res \u003c/em\u003e2017, \u003cstrong\u003e8\u003c/strong\u003e(2):59-62.\u003c/li\u003e\n\u003cli\u003eAhsan B, Rahimi E, Moradi A, Rashadmanesh N: \u003cstrong\u003eThe effects of magnesium sulphate on succinylcholine-induced fasciculation during induction of general anaesthesia\u003c/strong\u003e. \u003cem\u003eJ Pak Med Assoc \u003c/em\u003e2014, \u003cstrong\u003e64\u003c/strong\u003e(10):1151-1153.\u003c/li\u003e\n\u003cli\u003eFukano N, Suzuki T, Ishikawa K, Mizutani H, Saeki S, Ogawa S: \u003cstrong\u003eA randomized trial to identify optimal precurarizing dose of rocuronium to avoid precurarization-induced neuromuscular block\u003c/strong\u003e. \u003cem\u003eJ Anesth \u003c/em\u003e2011, \u003cstrong\u003e25\u003c/strong\u003e(2):200-204.\u003c/li\u003e\n\u003cli\u003eSenapati LK, Battini KP, Padhi PP, Samanta P: \u003cstrong\u003eEffect of Non-depolarizing Muscle Relaxants Rocuronium Versus Vecuronium in the Assessment of Post-Succinylcholine Complications in Surgeries Under General Anesthesia: A Randomized Double-Blind Study at a Tertiary Care Hospital\u003c/strong\u003e. \u003cem\u003eCureus \u003c/em\u003e2021, \u003cstrong\u003e13\u003c/strong\u003e(11):e19793.\u003c/li\u003e\n\u003cli\u003eKim KN, Kim KS, Choi HI, Jeong JS, Lee HJ: \u003cstrong\u003eOptimal precurarizing dose of rocuronium to decrease fasciculation and myalgia following succinylcholine administration\u003c/strong\u003e. \u003cem\u003eKorean J Anesthesiol \u003c/em\u003e2014, \u003cstrong\u003e66\u003c/strong\u003e(6):451-456.\u003c/li\u003e\n\u003cli\u003eYan S, Wu H, Yu Y, Li N, Yu L, Wang Y, Li H, Zhang D, Zhang Z: \u003cstrong\u003eMedian Effective Dose of Remifentanil for the Prevention of Pain Caused by the Injection of Rocuronium: An Age-Stratified Study\u003c/strong\u003e. \u003cem\u003ePain Ther \u003c/em\u003e2023, \u003cstrong\u003e12\u003c/strong\u003e(3):683-694.\u003c/li\u003e\n\u003cli\u003eStocks GM, Hallworth SP, Fernando R, England AJ, Columb MO, Lyons G: \u003cstrong\u003eMinimum local analgesic dose of intrathecal bupivacaine in labor and the effect of intrathecal fentanyl\u003c/strong\u003e. \u003cem\u003eAnesthesiology \u003c/em\u003e2001, \u003cstrong\u003e94\u003c/strong\u003e(4):593-598; discussion 595A.\u003c/li\u003e\n\u003cli\u003eHarvey SC, Roland P, Bailey MK, Tomlin MK, Williams A: \u003cstrong\u003eA randomized, double-blind comparison of rocuronium, d-tubocurarine, and \u0026quot;mini-dose\u0026quot; succinylcholine for preventing succinylcholine-induced muscle fasciculations\u003c/strong\u003e. \u003cem\u003eAnesth Analg \u003c/em\u003e1998, \u003cstrong\u003e87\u003c/strong\u003e(3):719-722.\u003c/li\u003e\n\u003cli\u003eCao X, Gui Q, Wei Y, Lan L, Xiao H, Wen S, Li X: \u003cstrong\u003eThe 50% effective dose of hydromorphone and morphine for epidural analgesia in the hemorrhoidectomy: a double-blind, sequential dose-finding study\u003c/strong\u003e. \u003cem\u003eBMC Anesthesiol \u003c/em\u003e2024, \u003cstrong\u003e24\u003c/strong\u003e(1):41.\u003c/li\u003e\n\u003cli\u003eRamsey JT, Pache KM, Sayre MR, Maynard C, Johnson NJ, Counts CR: \u003cstrong\u003eComparison of Intubating Conditions with Succinylcholine Versus Rocuronium in the Prehospital Setting\u003c/strong\u003e. \u003cem\u003ePrehosp Emerg Care \u003c/em\u003e2023:1-8.\u003c/li\u003e\n\u003cli\u003eZhang Z, Zhang DS, Sui W, Liu XH, Zhang L, Sun JH: \u003cstrong\u003eEffects of pretreatment with different doses of cisatracurium on succinylcholine-induced fasciculations\u003c/strong\u003e. \u003cem\u003eInt J Clin Pharmacol Ther \u003c/em\u003e2016, \u003cstrong\u003e54\u003c/strong\u003e(6):426-432.\u003c/li\u003e\n\u003cli\u003eWong SF, Chung F: \u003cstrong\u003eSuccinylcholine-associated postoperative myalgia\u003c/strong\u003e. \u003cem\u003eAnaesthesia \u003c/em\u003e2000, \u003cstrong\u003e55\u003c/strong\u003e(2):144-152.\u003c/li\u003e\n\u003cli\u003eMorris J, Cook TM: \u003cstrong\u003eRapid sequence induction: a national survey of practice\u003c/strong\u003e. \u003cem\u003eAnaesthesia \u003c/em\u003e2001, \u003cstrong\u003e56\u003c/strong\u003e(11):1090-1097.\u003c/li\u003e\n\u003cli\u003eSchreiber JU, Lysakowski C, Fuchs-Buder T, Tram\u0026egrave;r MR: \u003cstrong\u003ePrevention of succinylcholine-induced fasciculation and myalgia: a meta-analysis of randomized trials\u003c/strong\u003e. \u003cem\u003eAnesthesiology \u003c/em\u003e2005, \u003cstrong\u003e103\u003c/strong\u003e(4):877-884.\u003c/li\u003e\n\u003cli\u003eFatemeh H, Mojgan R: \u003cstrong\u003eComparison of atracurium and \u0026quot;mini-dose\u0026quot; succinylcholine for preventing succinylcholine-induced muscle fasciculations: a randomized, double-blind, placebo-controlled study\u003c/strong\u003e. \u003cem\u003eActa Anaesthesiol Taiwan \u003c/em\u003e2010, \u003cstrong\u003e48\u003c/strong\u003e(1):28-32.\u003c/li\u003e\n\u003cli\u003eMartyn JA, Fagerlund MJ, Eriksson LI: \u003cstrong\u003eBasic principles of neuromuscular transmission\u003c/strong\u003e. \u003cem\u003eAnaesthesia \u003c/em\u003e2009, \u003cstrong\u003e64 Suppl 1\u003c/strong\u003e:1-9.\u003c/li\u003e\n\u003cli\u003eJoshi GP, Hailey A, Cross S, Thompson-Bell G, Whitten CC: \u003cstrong\u003eEffects of pretreatment with cisatracurium, rocuronium, and d-tubocurarine on succinylcholine-induced fasciculations and myalgia: a comparison with placebo\u003c/strong\u003e. \u003cem\u003eJ Clin Anesth \u003c/em\u003e1999, \u003cstrong\u003e11\u003c/strong\u003e(8):641-645.\u003c/li\u003e\n\u003cli\u003eTrue CA, Carter PJ: \u003cstrong\u003eA comparison of tubocurarine, rocuronium, and cisatracurium in the prevention and reduction of succinylcholine-induced muscle fasciculations\u003c/strong\u003e. \u003cem\u003eAana j \u003c/em\u003e2003, \u003cstrong\u003e71\u003c/strong\u003e(1):23-28.\u003c/li\u003e\n\u003cli\u003eMencke T, Schreiber JU, Becker C, Bolte M, Fuchs-Buder T: \u003cstrong\u003ePretreatment before succinylcholine for outpatient anesthesia?\u003c/strong\u003e \u003cem\u003eAnesth Analg \u003c/em\u003e2002, \u003cstrong\u003e94\u003c/strong\u003e(3):573-576; table of contents.\u003c/li\u003e\n\u003cli\u003eSundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI: \u003cstrong\u003eThe incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium\u003c/strong\u003e. \u003cem\u003eAnesthesiology \u003c/em\u003e2000, \u003cstrong\u003e92\u003c/strong\u003e(4):977-984.\u003c/li\u003e\n\u003cli\u003ePandey CK, Tripathi M, Joshi G, Karna ST, Singh N, Singh PK: \u003cstrong\u003eProphylactic use of gabapentin for prevention of succinylcholine-induced fasciculation and myalgia: a randomized, double-blinded, placebo-controlled study\u003c/strong\u003e. \u003cem\u003eJ Postgrad Med \u003c/em\u003e2012, \u003cstrong\u003e58\u003c/strong\u003e(1):19-22.\u003c/li\u003e\n\u003cli\u003eHern\u0026aacute;ndez-Palaz\u0026oacute;n J, Noguera-Velasco J, Falc\u0026oacute;n-Ara\u0026ntilde;a LF, Dom\u0026eacute;nech-Asensi P, Burguillos-L\u0026oacute;pez S, Nu\u0026ntilde;o de la Rosa-Carrillo V: \u003cstrong\u003e[Precurarization with rocuronium prevents fasciculations and biochemical changes after succinylcholine administration]\u003c/strong\u003e. \u003cem\u003eRev Esp Anestesiol Reanim \u003c/em\u003e2004, \u003cstrong\u003e51\u003c/strong\u003e(4):184-189.\u003c/li\u003e\n\u003cli\u003eFarhat K, Pasha AK, Jaffery N: \u003cstrong\u003eBiochemical changes following succinylcholine administration after pretreatment with rocuronium at different intervals\u003c/strong\u003e. \u003cem\u003eJ Pak Med Assoc \u003c/em\u003e2014, \u003cstrong\u003e64\u003c/strong\u003e(2):146-150.\u003c/li\u003e\n\u003cli\u003eGin T, Chan MT, Chan KL, Yuen PM: \u003cstrong\u003eProlonged neuromuscular block after rocuronium in postpartum patients\u003c/strong\u003e. \u003cem\u003eAnesth Analg \u003c/em\u003e2002, \u003cstrong\u003e94\u003c/strong\u003e(3):686-689; table of contents.\u003c/li\u003e\n\u003cli\u003eFujimoto M, Tanahira C, Nishi M, Yamamoto T: \u003cstrong\u003eIn non-obese patients, duration of action of rocuronium is directly correlated with body mass index\u003c/strong\u003e. \u003cem\u003eCan J Anaesth \u003c/em\u003e2013, \u003cstrong\u003e60\u003c/strong\u003e(6):552-556.\u003c/li\u003e\n\u003cli\u003eVested M, Kristensen CM, Pape P, Vang M, Hartoft M, Hjelmdal C, Rasmussen LS: \u003cstrong\u003eComparison of onset time, duration of action, and intubating conditions after cisatracurium 0.15\u0026thinsp;mg/kg in young and elderly patients\u003c/strong\u003e. \u003cem\u003eBMC Anesthesiol \u003c/em\u003e2022, \u003cstrong\u003e22\u003c/strong\u003e(1):339.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Median effective dose, Rocuronium, Succinylcholine, Fasciculation, Age, Prevention ","lastPublishedDoi":"10.21203/rs.3.rs-6998202/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6998202/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eSuccinylcholine, a commonly used depolarizing neuromuscular blocking relaxant, may produce fasciculation and postoperative myalgia as adverse effects. Although rocuronium pretreatment may attenuate this adverse effect, the median effective dose (ED50) remains undetermined, as does the influence of age on it. This study was carried out to determine the ED50 of prophylactic intravenous rocuronium in preventing succinylcholine-induced fasciculation and to explore the effect of age on the ED50.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eSeventy-two adult patients undergoing elective general anesthesia were stratified according to age: Group R1 (18-44 years), Group R2 (45-59 years), and Group R3 (60-80 years). The initial dose of prophylactic rocuronium was set at 0.04 mg/kg. Midazolam 0.05 mg/kg, sufentanil 0.4 μg/kg, propofol 1.5-2.5 mg/kg, and succinylcholine 2 mg/kg were then sequentially administered 1.5 min later, then fasciculation was assessed. The rocuronium doses were adjusted according to the assessment of fasciculation using Dixon sequential method, with a ratio of 1.1 between adjacent doses. The occurrence and grades of fasciculation, adverse reactions of rocuronium, and endotracheal intubating condition were recorded. The ED50 and 95% confidence interval (CI) of rocuronium were calculated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e The ED50 and 95% CI of prophylactic rocuronium for the prevention of succinylcholine-induced fasciculation were 0.027 μg/kg (95%CI: 0.026-0.028 μg/kg), 0.026 μg/kg (95%CI: 0.024-0.02 μg/kg), and 0.026 μg/kg (95%CI: 0.025-0.027 μg/kg) in Group R1, Group R2, and Group R3, respectively. No significant differences exist in the ED\u003csub\u003e50\u003c/sub\u003e (95% CI) among the three groups (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05). Only one patient experienced temporary diplopia in Group R2. No significant differences were found in fasciculation grades or endotracheal intubation conditions among the groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion \u003c/strong\u003eProphylactic intravenous rocuronium can prevent succinylcholine-induced fasciculation, while its ED50 is independent of age.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial registration\u003c/strong\u003e The study was registered at ClinicalTrials.gov (Registration number: NCT05909696) on June 10, 2023. 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