Muscle mass correlates with rocuronium distribution volume and guides dose optimization in obese colorectal cancer patients

Abstract

BACKGROUND

Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic characteristics including abnormal drug distribution and clearance. Rocuronium exhibits markedly different distribution patterns in obese patients, with conventional weight correction methods inadequately addressing individual muscle mass variations that critically influence drug distribution.

AIM

To investigate the quantitative relationship between skeletal muscle index (SMI) and rocuronium distribution volume in obese colorectal cancer patients, establish a population pharmacokinetic model, and develop individualized dosing strategies based on muscle mass.

METHODS

A retrospective cohort study was conducted, including 100 obese patients (body mass index ≥ 30 kg/m²) who underwent elective radical colorectal cancer surgery at our hospital from June 2023 to January 2025. Skeletal muscle mass was measured using InBody260 body composition analyzer and SMI was calculated to assess muscle mass, with male SMI < 7.0 kg/m² and female SMI < 5.7 kg/m² as diagnostic criteria for sarcopenia. Plasma rocuronium concentrations were detected by liquid chromatography-tandem mass spectrometry/mass spectrometry, and nonlinear mixed-effect modeling was used to establish population pharmacokinetic modeling. Stepwise regression was used to screen covariates, and dosing regimens were optimized through Monte Carlo simulation. The primary endpoint was targeted plasma concentration achievement rate, and the secondary endpoint was postoperative residual muscle relaxation incidence.

RESULTS

Among 100 patients, 35 (35.0%) had sarcopenia and 65 (65.0%) did not. Patients in the sarcopenia group were older (64.1 ± 9.8 years vs 54.2 ± 10.9 years, P < 0.001) and had significantly lower SMI (6.2 ± 0.8 kg/m² vs 8.4 ± 1.2 kg/m², P < 0.001). SMI showed strong positive correlation with rocuronium steady-state distribution volume (r = 0.718, P < 0.001) and moderate negative correlation with clearance (r = -0.502, P < 0.001). A two-compartment population pharmacokinetic model was successfully established, with SMI being the most important covariate affecting central compartment distribution volume (△OFV = -41.2, P < 0.001). Model validation showed bootstrap successful convergence rate of 92.3%, and 92.1% of observed values fell within prediction intervals in predicted concentration versus predicted concentration. The SMI-based individualized dosing regimen improved target exposure achievement rate from 82.0% in traditional regimen to 93.5% (P = 0.009), and reduced postoperative residual muscle relaxation incidence from 13.0% to 3.5% (P = 0.018). The sarcopenia group showed the most significant improvement in achievement rate, from 71.4% to 93.8% (P = 0.017).

CONCLUSION

SMI shows strong correlation with rocuronium distribution volume in obese colorectal cancer patients and is a key factor affecting drug distribution. SMI-based individualized dosing strategies can significantly improve target exposure achievement rate and reduce postoperative residual muscle relaxation incidence, providing scientific evidence for precision anesthesia management in obese patients.

Keywords: Obesity; Rocuronium; Skeletal muscle index; Population pharmacokinetics; Individualized dosing; Colorectal cancer; Sarcopenia

Core Tip: This study established a population pharmacokinetic model of rocuronium in obese patients with colorectal cancer, incorporating skeletal muscle index to explore its effect on drug distribution volume. Using nonlinear mixed-effects modeling and Monte Carlo simulation, we developed an individualized dosing strategy based on muscle mass. The findings reveal that skeletal muscle index is a significant covariate influencing rocuronium pharmacokinetic, providing a scientific basis for optimizing anesthetic dosing in obese surgical patients and enhancing patient safety during colorectal cancer surgery.