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

## TL;DR

This study shows that strict monitoring and reversal of muscle relaxant effects can prevent post-surgery complications.

## Contribution

The study uses real-time data and a PK–PD model to simulate and prevent post-operative recurarization.

## Key findings

- Strict maintenance of TOFC at 1 and reversal with SGX prevented recurarization in all cases.
- Ce_Rb increased after reaching the lowest point but did not exceed recovery levels.
- Average time to reach TOFR ≥0.9 was 2.9 minutes with an average SGX dose of 2.2 mg/kg.

## Abstract

Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.