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Kim and Nam: Response to "Comment on Effects of remimazolam versus dexmedetomidine on recovery after transcatheter aortic valve replacement under monitored anesthesia care: a propensity score-matched, non-inferiority study"
Response to "Comment on Effects of remimazolam versus dexmedetomidine on recovery after transcatheter aortic valve replacement under monitored anesthesia care: a propensity score-matched, non-inferiority study"
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Ji-Hyeon Kim
, Jae-Sik Nam
- Received October 21, 2024 Accepted October 27, 2024
Dear Editor,
We appreciate the opportunity to respond to these comments by Wu et al. [1] on our study regarding the use of remimazolam versus dexmedetomidine during transcatheter aortic valve replacement (TAVR) procedures [2]. The letter’s comment raises several important points that will allow for a deeper understanding of our findings.
Agitation is indeed a significant concern during TAVR procedures, primarily resulting from pain or inadequate sedation. At our institution, lidocaine infiltration is administered prior to femoral cannulation for pain management. Whenever pain is determined to be the primary cause of agitation, additional local infiltration and an increased dosage of remifentanil may be recommended. However, given the analgesic properties of dexmedetomidine, the lower remifentanil usage in the remimazolam group may not be attributable to pain.
Dexmedetomidine is suitable for maintaining light sedation and can be adjusted for deeper sedation. However, patient responses to dexmedetomidine can vary significantly [3]. Although achieving the desired level of sedation using standard dosages may be difficult, administering higher dosages to achieve adequate sedation introduces risks, such as bradycardia. Therefore, increased remifentanil dosages and/or additional sedatives such as midazolam or propofol are the preferred options. In a study by Kitaura et al. [4], 20 mg propofol was routinely administered to the dexmedetomidine group. In our opinion, this approach may be a preemptive measure to prevent inadequate sedation when using dexmedetomidine.
In contrast, for our study, remimazolam consistently provided adequate procedural sedation without the need for rescue sedation. At a maintenance dose of 1 mg/kg/h in initial cases, we were able to perform the procedure using only local infiltration and no remifentanil. However, due to delayed awakening at this dose, we decreased the maintenance dose and routinely administered flumazenil after the procedure. Furthermore, as remimazolam and remifentanil have a synergistic effect [5], a minimal dose of remifentanil is recommended to optimize the analgesic and sedative effects.
In our institution, we use bispectral index (BIS) monitoring for TAVR procedures. However, the BIS was developed primarily for propofol or inhaled agents [6]. Additionally, with remimazolam, the correlation between BIS values and clinical depth assessments such as the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) is weak [7]. We used the BIS as a supplementary tool to titrate sedatives. Clinical assessment is the most critical consideration for dose adjustment.
The increased procedure time in the remimazolam group was not due to the sedative used, but rather to a change in the intervention team. Our institution periodically hosts visiting scholars who learn about cardiac interventions, including TAVR procedures. These scholars actively participate in the TAVR procedures and often play a significant role. A significant personnel change occurred in September 2021, coinciding with the pivotal period of our study. Until this change was made, an experienced visiting scholar was involved with the dexmedetomidine group to ensure high procedural competence. In September 2021, immediately after switching to remimazolam, a new visiting scholar started his program. The training and adaptation of the new scholar required additional time, which extended the duration of the procedures in the remimazolam group.
Finally, our study protocol did not include a cost analysis. In general, the cost of remimazolam for TAVR procedures, including flumazenil, is 24,425 KRW ($19 USD), while the cost of dexmedetomidine varies from 10,300 KRW ($8 USD) to 35,700 KRW ($28 USD), depending on the brand. Although remimazolam appears to be more expensive than generic dexmedetomidine, the price difference is not significant. Furthermore, the higher cost may not have a significant impact on the overall cost-effectiveness of remimazolam in clinical settings given the reduced need for vasopressors and temporary pacemakers.
We hope that this response clarifies the aspects highlighted in the letter and will allow for integrating our findings more confidently into clinical practice.
- References
- 1. Wu JH, Hee HZ, Lu CW. Comment on “Effects of remimazolam versus dexmedetomidine on recovery after transcatheter aortic valve replacement under monitored anesthesia care: a propensity score-matched, non-inferiority study”. Korean J Anesthesiol 2025; 78: 86-7.
[Article] [PubMed]2. Kim JH, Nam JS, Seo WW, Joung KW, Chin JH, Kim WJ, et al. Effects of remimazolam versus dexmedetomidine on recovery after transcatheter aortic valve replacement under monitored anesthesia care: a propensity score-matched, non-inferiority study. Korean J Anesthesiol 2024; 77: 537-45.
[Article] [PubMed] [PMC]3. Holliday SF, Kane-Gill SL, Empey PE, Buckley MS, Smithburger PL. Interpatient variability in dexmedetomidine response: a survey of the literature. ScientificWorldJournal 2014; 2014: 805013.
[Article] [PubMed] [PMC]4. Kitaura A, Tsukimoto S, Sakamoto H, Hamasaki S, Nakao S, Nakajima Y. A retrospective comparative study of anesthesia with remimazolam and remifentanil versus dexmedetomidine and remifentanil for transcatheter aortic valve replacement. Sci Rep 2023; 13: 17074.
[Article] [PubMed] [PMC]5. Kim SH, Fechner J. Remimazolam - current knowledge on a new intravenous benzodiazepine anesthetic agent. Korean J Anesthesiol 2022; 75: 307-15.
[Article] [PubMed] [PMC]