Pharmacokinetic–Pharmacodynamic Simulation of Muscle Relaxation Antagonistic Conditions for Post-Operative Recurarization Prevention

<b>Background/Objectives:</b> No study has simulated rocuronium (Rb) effect-site concentrations (Ce_Rb) using real-time data-such as Rb concentrations, train-of-four (TOF) count (TOFC), and TOF ratio (TOFR)-under mechanical Rb administration. Therefore, we aimed to investigate post-operative recurarization and changes in the Ce_Rb after sugammadex (SGX) administration under conditions where Rb dosing was strictly administered using an automated delivery system for total intravenous anesthesia. <b>Methods:</b> This non-interventional, retrospective, observational study included 74 patients from an existing clinical trial who met the study criteria. Rb was automatically administered during surgery to maintain a TOFC of 1. SGX (2 mg/kg) was manually administered post-surgery, and the time until the TOFR reached ≥0.9 (if the time exceeded 3 min, 0.5 mg/kg SGX was added every minute). The results were analyzed using a pharmacokinetic (PK)-pharmacodynamic (PD) simulation model of the Rb-SGX complex. <b>Results:</b> The average total dose of administered SGX was 2.2 ± 0.4 mg/kg (mean ± standard deviation). The time from SGX administration till the TOFR reached ≥0.9 was 2.9 ± 1.1 min. Furthermore, Ce_Rb at recovery (Ce_r) was 0.3 ± 0.2 μg/mL. Notably, no cases showed post-operative recurarization within 24 h of surgery. PK-PD model simulations revealed that Ce_Rb increased again after reaching the lowest Ce_Rb in 72 cases, although no increase was recorded beyond Ce_r, suggesting no numerical risk of recurarization. <b>Conclusions:</b> Our results show that if TOFC of 1 is strictly maintained intraoperatively and SGX is administered till the TOFR reaches ≥0.9, post-operative recurarization does not occur.

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Journal
Journal of Clinical Medicine
Published
2025-03-17
DOI
https://doi.org/10.3390/jcm14062043
Primary Topic
Anesthesia and Sedative Agents
Type
article
Field-Weighted Citation Impact
0.00

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article

Pharmacokinetic–Pharmacodynamic Simulation of Muscle Relaxation Antagonistic Conditions for Post-Operative Recurarization Prevention

Yuka Matsuki, Kenji Shigemi, Fumiyo Yasuma, Osamu Nagata
Journal of Clinical Medicine
Anesthesia and Sedative Agents
article

Pharmacokinetic–Pharmacodynamic Simulation of Muscle Relaxation Antagonistic Conditions for Post-Operative Recurarization Prevention

Yuka Matsuki, Kenji Shigemi, Fumiyo Yasuma, Osamu Nagata
article en

Abstract

<b>Background/Objectives:</b> No study has simulated rocuronium (Rb) effect-site concentrations (Ce_Rb) using real-time data-such as Rb concentrations, train-of-four (TOF) count (TOFC), and TOF ratio (TOFR)-under mechanical Rb administration. Therefore, we aimed to investigate post-operative recurarization and changes in the Ce_Rb after sugammadex (SGX) administration under conditions where Rb dosing was strictly administered using an automated delivery system for total intravenous anesthesia. <b>Methods:</b> This non-interventional, retrospective, observational study included 74 patients from an existing clinical trial who met the study criteria. Rb was automatically administered during surgery to maintain a TOFC of 1. SGX (2 mg/kg) was manually administered post-surgery, and the time until the TOFR reached ≥0.9 (if the time exceeded 3 min, 0.5 mg/kg SGX was added every minute). The results were analyzed using a pharmacokinetic (PK)-pharmacodynamic (PD) simulation model of the Rb-SGX complex. <b>Results:</b> The average total dose of administered SGX was 2.2 ± 0.4 mg/kg (mean ± standard deviation). The time from SGX administration till the TOFR reached ≥0.9 was 2.9 ± 1.1 min. Furthermore, Ce_Rb at recovery (Ce_r) was 0.3 ± 0.2 μg/mL. Notably, no cases showed post-operative recurarization within 24 h of surgery. PK-PD model simulations revealed that Ce_Rb increased again after reaching the lowest Ce_Rb in 72 cases, although no increase was recorded beyond Ce_r, suggesting no numerical risk of recurarization. <b>Conclusions:</b> Our results show that if TOFC of 1 is strictly maintained intraoperatively and SGX is administered till the TOFR reaches ≥0.9, post-operative recurarization does not occur.

Journal of Clinical MedicineVol. 14(6)
University of Fukui (JP), National Center for Global Health and Medicine (JP), Maizuru Municipal Hospital (JP)
Japan Agency for Medical Research and Development
Openalex Percentile: Top 90%
Anesthesia and Sedative Agents
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