In recent years, the incidence of thyroid-related diseases requiring surgical treatment has been gradually increasing (1). The operation space for thyroid and parathyroid surgery is small, and the anatomical protection of the recurrent laryngeal nerve (RLN) and parathyroid requires meticulous operation. The Da Vinci robotic surgical system has become an ideal auxiliary device for such surgeries due to its flexible operation and minimal damage (2, 3). Intraoperative neuromonitoring (IONM) can help reduce the incidence of RLN injury (4, 5). Neuromuscular blockers can provide good tracheal intubation conditions, improve surgical conditions, reduce surgical difficulty, and reduce iatrogenic injuries (6, 7).

However, studies have found that neuromuscular blockers can significantly affect IONM (8, 9). Currently, rocuronium is the most widely used neuromuscular blocker, and the recommended dose is based on open thyroid surgery (9–11). A lower dose of rocuronium (0.3 mg/kg, equivalent to 1 ED95) may be considered during anesthesia induction to accommodate intraoperative neuromonitoring (IONM) requirements. However, it’s important to acknowledge that this lower dosage not only has the potential to worsen intubation conditions but also carries the risk of increased patient movements, not only during tracheal intubation (11) but also throughout the first part of the intraoperative period. Inadequate neuromuscular blockade can result in intraoperative movement (12). In addition, during the robotic surgery process, patients need to be absolutely still because coughing or body movement can cause potential tissue damage and force the surgery to be terminated (13). At the same time, the time from the start of anesthesia to RLN monitoring in robotic surgery is significantly longer than that in open surgery (14). Therefore, based on these theoretical foundations, increasing the dose of neuromuscular blockers for robotic thyroid surgery within a certain range will not have a significant impact on IONM.

There are no reports on the optimal dose of rocuronium required for Da Vinci robotic thyroid surgery. Therefore, we designed a prospective randomized controlled trial to investigate the effect of different doses of rocuronium on RLN monitoring during Da Vinci robotic thyroid surgery. This study aims to determine the optimal dose of rocuronium to meet the needs of anesthesia and surgery.

This study included a total of 189 patients who underwent elective thyroidectomy for papillary thyroid carcinoma. Patients were randomly assigned to three different doses of rocuronium test groups: ROC1 group (0.3mg/kg, n=63), ROC2 group (0.6mg/kg, n=63), and ROC3 group (0.9mg/kg, n=63). The flow chart is shown in Figure 1 . There was no statistically significant difference in baseline characteristics such as age, weight, and height among the three groups of patients ( Table 1 ). All patients underwent IONM evaluation, obtained complete IONM signal data successfully, and underwent relevant analysis.

There is no significant difference in IONM evoked potential among the three patient groups, but there is a significant difference at each time point. The IONM evoked potential is not the same at different time points, and the rate of change at different times in different groups is not the same. The pairwise comparison shows that the relationship between different times is R120>R110>R100>R90>R1 ( Table 2 ; Figure 2 ).

In summary, there is no statistically significant difference in VHI-30 scores among the three patient groups. However, there is a statistically significant difference in VHI-30 scores at each time point, and there is no interaction between group and time. This means that the VHI-30 scores are the same at different time points and that the rate of change at different times in different groups is also the same. By comparing pairs, it can be seen that the relationship between different times is postoperative day 1 > postoperative day 10 > postoperative 2 months, and there is no statistically significant difference among the groups ( Table 3 ).

The statistical analysis revealed significant differences in SBP, DBP, and HR among the three groups at different time points. SBP exhibited a cross-effect between group and time, whereas DBP and HR had consistent rates of change at different time points. There was no significant difference in Ta, Tb, Tc, and Td time points between groups (all p>0.05) (For specific data, please refer to the supplementary materials). The results of Cooper scores and intraoperative body movements of the three groups of patients showed that all patients had successful tracheal intubation once. Compared with the ROC1 group, the intubation conditions of the ROC2 group and ROC3 group were better, and the difference was statistically significant (both p<0.001). Compared with the ROC1 group, the number of patients with intraoperative body movements in the ROC2 group and ROC3 group was less (both p<0.001), and there was no statistically significant difference between the ROC2 group and ROC3 group (p=0.285) ( Table 4 ).

With the advancement of diagnostic techniques for thyroid malignancies (20, 21), there is a rising trend in the number of patients requiring thyroid surgery. IONM technology has been widely utilized in thyroid surgery to real-time monitor the function of the recurrent laryngeal nerve. IONM technology has gained widespread use in thyroid surgery, enabling real-time monitoring of the recurrent laryngeal nerve’s function. For optimal protection of the RLN during thyroid surgery, IONM is strongly recommended (22). Therefore, it is crucial to examine the influence of muscle relaxant dosage on IONM. The muscle relaxation state must align with surgical requirements, minimize IONM impact, and avoid disrupting the surgical procedure. However, existing guidelines and studies lack information on the appropriate muscle relaxant dose for IONM in robotic thyroid surgery. Notably, the duration from anesthesia to IONM is longer in robotic procedures compared to open surgery (14), and laryngeal muscles tend to recover earliest from neuromuscular blockade (23), Moreover, in regular patients, neuromuscular blockers’ effect on IONM remains acceptable when the TOF count is ≥2 (24), Thus, in light of these factors, we initiated an RCT trial to explore the impact of varying rocuronium doses on IONM during robotic thyroid surgery. To our knowledge, this is the first RCT study to investigate the effect of different doses of rocuronium on IONM during robotic thyroid surgery.

Rocuronium, a commonly used neuromuscular blocker in clinical practice, is known for its rapid onset and moderate duration of action (25). The precise timing and quality of the IONM signal are of paramount importance when employing neuromuscular blockers in IONM. In our study, the average time from anesthesia induction to the first IONM signal in the three groups was recorded as 71.9 minutes, 70.9 minutes, and 71.6 minutes, respectively. Most patients experience a clinical duration of fewer than 60 minutes with a 0.9mg/kg dose of rocuronium (26). Overall, no statistically significant difference in the primary outcome measure, IONM peak value, was observed among the three groups. However, when compared to the 0.3mg/kg group, both group 0.6 and 0.9mg/kg groups demonstrated improved tracheal intubation conditions (p<0.001) and a lower incidence of intraoperative body movement (p<0.001). Intraoperative body movement, particularly involving the laryngeal muscles, can interfere with the accuracy of IONM monitoring and impact the surgeon’s interpretation of IONM signals (15). Our findings suggest that utilizing 0.6mg/kg and 0.9mg/kg mg/kg rocuronium during the anesthesia induction phase can yield stable IONM signals, improve tracheal intubation conditions, and reduce the occurrence of intraoperative body movement.

The VHI scores of the three groups of patients showed a downward trend over time, similar to that of Bea et al. (27). Given the similarities in surgical methods among all patients and the intact intraoperative IONM signals, it’s worth noting that the Cooper scores for all three patient groups were predominantly rated as “good” or higher. This might contribute to the absence of a significant difference in VHI scores among the groups. These findings are consistent with the results reported by Lee et al., reinforcing the notion that surgical method homogeneity and IONM signal integrity can influence VHI score parity (28).

At the T3 time point, we found that the hemodynamic changes in the ROC1 group were greater than those in the other two groups, but the difference was not statistically significant, which is consistent with the results of previous studies (29, 30). In the ROC1 group, the number of patients with intraoperative body movement increased significantly. Although the surgery was successfully performed after additional sedatives were added, one patient in the ROC1 group had a situation where the surgical instrument could not be inserted due to muscle tension. The ideal muscle relaxation for robotic thyroid surgery should meet the requirements of surgical operation, avoid affecting the operation, and not interfere with IONM. Studies have shown that appropriate neuromuscular blockade can provide appropriate neurophysiological monitoring conditions and improve the safety of anesthesia and surgery (24, 31). This indicates that our experiment has clinical significance. Overall, our study shows that a single dose of 0.6 and 0.9mg/kg rocuronium during anesthesia induction can provide stable IONM signals, reduce patient body movement, and have good tracheal intubation conditions. It is a more ideal dose in Da Vinci robotic thyroid surgery. However, it should be noted that the limitations of this study are that the sample size is relatively small and all patients are undergoing Da Vinci robot BABA approach thyroidectomy, and the results may be affected by specific surgical team experience and surgical methods. Despite the standardized anesthesia management, there was no recording and analysis of TOF and BIS values. Therefore, it is not possible to exclude the presence of significant unexamined confounding factors concerning patient movements in the three groups. Additionally, the routine use of video laryngoscopy for intubation could have influenced the results of this study, making intubation easier even at lower rocuronium dosages compared to direct laryngoscopy. At the same time, this study only compared the signals of recurrent laryngeal nerve, not V1, V2, R1, and R2 signals, which are different from the clinical practice specification, and the results obtained cannot be directly extended to the clinic. Additionally, most of the patients in this study are healthy young patients, and special populations (children, elderly) may have different research results due to differences in neuromuscular blocker metabolism. Therefore, caution is needed when applying the results of this study. In the future, more clinical trials and studies on the application of different doses of rocuronium in Da Vinci robotic thyroid surgery anesthesia in various approaches and special populations are still necessary to further ensure the safety and success rate of more patients.

For patients undergoing Da Vinci robot thyroidectomy, a single dose of rocuronium at 0.6 and 0.9mg/kg during anesthesia induction can provide stable IONM evoked potential. Additionally, compared to 0.3 mg/kg, it can offer better tracheal intubation conditions and lower incidence of body movements during surgery. It is worth noting that the use of higher doses of rocuronium should be adjusted based on the duration of IONM and local practices.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving humans were approved by the Ethics Committee of Fujian Medical University Affiliated Union Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Authors statement JL: Conceptualization, Data Acquisition, Writing – original draft, Writing – review & editing. JS: Conceptualization, Methodology, Software, Visualization hang: Data Curation, Investigation QH: Supervision. LZ: Conceptualization, Methodology, Supervision, Visualization, Writing – original draft, Writing – review & editing. All authors contributed to the article and approved the submitted version.