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

Table 1 Comparison of baseline characteristics of study subjects

Characteristics	Total (n = 100)	Sarcopenia group (n = 35)	Non-sarcopenia group (n = 65)	Test statistic	P value
Age (years)	57.8 ± 11.2	64.1 ± 9.8	54.2 ± 10.9	t = 4.389	< 0.001
Sex, n (%)				χ2 = 8.142	0.004
Male	62 (62.0)	16 (45.7)	46 (70.8)
Female	38 (38.0)	19 (54.3)	19 (29.2)
Height (cm)	167.2 ± 8.7	165.4 ± 9.1	168.3 ± 8.4	t = -1.587	0.116
Weight-related indicators
TBW (kg)	88.4 ± 14.8	85.8 ± 13.2	89.8 ± 15.6	t = -1.254	0.213
BMI (kg/m²)	33.9 ± 4.0	34.8 ± 4.3	33.4 ± 3.8	t = 1.658	0.101
IBW (kg)	61.5 ± 8.2	59.8 ± 8.6	62.5 ± 7.9	t = -1.538	0.127
LBW (kg)	58.6 ± 9.1	54.2 ± 8.3	61.1 ± 8.9	t = -3.741	< 0.001
ABW (kg)	72.3 ± 9.8	71.2 ± 9.4	72.9 ± 10.0	t = -0.814	0.418
Muscle mass indicators
SMM (kg)	25.8 ± 6.4	18.2 ± 3.8	29.6 ± 5.2	t = -12.426	< 0.001
SMI (kg/m2)	7.2 ± 1.6	6.2 ± 0.8	8.4 ± 1.2	t = -10.874	< 0.001
Body fat percentage (%)	38.4 ± 6.8	42.6 ± 7.2	36.1 ± 5.9	t = 4.521	< 0.001
Laboratory indicators
Serum albumin (g/L)	37.4 ± 4.2	34.6 ± 3.7	39.1 ± 3.9	t = -5.642	< 0.001
Serum creatinine (μmol/L)	77.8 ± 18.2	79.4 ± 19.1	76.9 ± 17.8	t = 0.648	0.519
Total bilirubin (μmol/L)	15.6 ± 6.0	16.8 ± 6.4	15.0 ± 5.7	t = 1.426	0.157
Anesthesia-related indicators
ASA classification, n (%)				Z = -2.8471	0.004
Class I	18 (18.0)	3 (8.6)	15 (23.1)
Class II	68 (68.0)	22 (62.9)	46 (70.8)
Class III	14 (14.0)	10 (28.6)	4 (6.2)
Surgical time (h)	3.7 ± 1.1	4.1 ± 1.3	3.5 ± 1.0	t = 2.584	0.011
Intraoperative blood loss (mL)	182.6 ± 76.4	195.8 ± 81.2	175.2 ± 73.6	t = 1.268	0.208

¹Kruskal-Wallis rank sum test used.

TBW: Total body weight; BMI: Body mass index; IBW: Ideal body weight; LBW: Lean body weight; ABW: Adjusted body weight; SMM: Skeletal muscle mass; SMI: Skeletal muscle index; ASA: American Society of Anesthesiologists.

Table 2 Skeletal muscle index distribution and sarcopenia prevalence by gender

Gender	n	SMI (kg/m2)	Sarcopenia, n (%)	Diagnostic cutoff (kg/m2)	Test statistic	P value
Male	62	7.8 ± 1.4 (5.2-10.6)	16 (25.8)	< 7.0	χ2 = 12.847	< 0.001
Female	38	6.2 ± 1.2 (4.1-8.9)	19 (50.0)	< 5.7
Total	100	7.2 ± 1.6 (4.1-10.6)	35 (35.0)	-	t = 5.8461	< 0.0011

¹t-test result for SMI comparison between males and females.

SMI: Skeletal muscle index.

Table 3 Rocuronium non-compartmental model pharmacokinetic parameters

Parameter	Total (n = 100)	Sarcopenia group (n = 35)	Non-sarcopenia group (n = 65)	t-test	P value
Cmax (ng/mL)	3198.4 ± 642.7	3542.8 ± 718.2	2986.3 ± 551.4	4.126	< 0.001
Tmax (min)	4.9 ± 1.1	4.7 ± 1.0	5.0 ± 1.2	-1.243	0.217
AUC0-∞ (ng·h/mL)	4674.2 ± 1394.8	3986.4 ± 1186.3	5089.7 ± 1412.6	-3.847	< 0.001
t1/2 (h)	1.38 ± 0.36	1.24 ± 0.29	1.46 ± 0.38	-2.986	0.004
MRT (h)	1.84 ± 0.48	1.68 ± 0.42	1.93 ± 0.51	-2.417	0.018
Clearance (corrected by different weights)
CL/TBW (mL/min/kg)	3.92 ± 1.08	4.48 ± 1.21	3.61 ± 0.94	3.842	< 0.001
CL/ABW (mL/min/kg)	4.86 ± 1.34	5.41 ± 1.46	4.56 ± 1.25	2.892	0.005
CL/IBW (mL/min/kg)	5.71 ± 1.52	6.28 ± 1.68	5.42 ± 1.42	2.641	0.010
CL/SMM (mL/min/kg)	11.84 ± 3.26	14.68 ± 3.84	10.34 ± 2.48	6.124	< 0.001
Steady-state distribution volume (corrected by different weights)
Vss/TBW (L/kg)	0.372 ± 0.092	0.326 ± 0.078	0.398 ± 0.094	-3.842	< 0.001
Vss/ABW (L/kg)	0.488 ± 0.126	0.434 ± 0.108	0.518 ± 0.132	-3.164	0.002
Vss/IBW (L/kg)	0.542 ± 0.141	0.482 ± 0.118	0.576 ± 0.146	-3.267	0.002
Vss/SMM (L/kg)	1.184 ± 0.325	1.086 ± 0.286	1.234 ± 0.342	-2.184	0.032

Cmax: Maximum concentration; Tmax: Time to maximum concentration; AUC_0-∞: Area under the curve from zero to infinity; t₁/₂: Half-life; MRT: Mean residence time; CL: Clearance; TBW: Total body weight; ABW: Adjusted body weight; IBW: Ideal Body weight; SMM: Skeletal muscle mass; Vss: Volume of distribution at steady state.

Table 4 Correlation analysis between skeletal muscle index and rocuronium pharmacokinetic parameters

Pharmacokinetic parameter	Correlation coefficient (r)	95%CI	P value	Corrected P value
Cmax	-0.398	-0.551 to -0.223	< 0.001	< 0.005
AUC0-∞	0.412	0.236-0.568	< 0.001	< 0.005
t1/2	0.368	0.189-0.528	< 0.001	< 0.005
MRT	0.384	0.207-0.542	< 0.001	< 0.005
CL/TBW	-0.486	-0.623 to -0.326	< 0.001	< 0.005
CL/SMM	-0.502	-0.636 to -0.344	< 0.001	< 0.005
Vss/TBW	0.645	0.515-0.748	< 0.001	< 0.005
Vss/IBW	0.692	0.576-0.782	< 0.001	< 0.005
Vss/SMM	0.718	0.609-0.804	< 0.001	< 0.005
Vss/ABW	0.704	0.592-0.791	< 0.001	< 0.005

SMI: Skeletal muscle index; CI: Confidence interval; Cmax: Maximum concentration; AUC_0-∞: Area under the curve from zero to infinity; t₁/₂: Half-life; MRT: Mean residence time; CL: Clearance; TBW: Total body weight; SMM: Skeletal muscle mass; Vss: Volume of distribution at steady state; IBW: Ideal body weight; ABW: Adjusted body weight.

Table 5 Multiple linear regression analysis of skeletal muscle index and volume of distribution at steady state/skeletal muscle mass

Variable	β	Standardized β	t value	P value	95%CI
SMI (kg/m2)	0.142	0.612	7.486	< 0.001	0.104 to 0.180
Gender (Male = 1)	0.068	0.168	2.384	0.019	0.012 to 0.124
Serum albumin (g/L)	0.018	0.196	2.791	0.006	0.006 to 0.030
Body fat percentage (%)	-0.012	-0.174	-2.456	0.016	-0.021 to -0.003

Model statistics: Adjusted R² = 0.598, F = 37.84, P < 0.001. SMI: Skeletal muscle index; CI: Confidence interval.

Table 6 Structural model comparison

Model	Number of parameters	OFV	AIC	BIC	△OFV	P value	Parameter estimation stability
One-compartment	6	2847.3	2859.3	2877.8	-	-	Good
Two-compartment	8	2764.8	2780.8	2805.6	-82.5	< 0.001	Good
Three-compartment	10	2761.2	2781.2	2812.4	-3.6	0.165	Poor (RSE > 30%)

OFV: Objective function value; AIC: Akaike information criterion; BIC: Bayesian information criterion; RSE: Relative standard error.

Table 7 Covariate effects on pharmacokinetic parameters

Parameter	Covariate	△OFV	P value	Inclusion order	Impact
V1	SMI	-41.2	< 0.001	1	18% increase in V1 per 1 kg/m2 increase in SMI
V1	Gender	-12.4	< 0.001	2	24% increase in V1 for males vs females
CL	SMM	-38.6	< 0.001	3	52% increase in CL per 5 kg increase in SMM
CL	Serum albumin	-15.8	< 0.001	4	35% increase in CL per 10 g/L increase in albumin
V2	SMI	-28.3	< 0.001	5	22% increase in V2 per 1 kg/m2 increase in SMI

V1: Central volume of distribution; V2: Peripheral volume of distribution; SMI: Skeletal muscle index; CL: Clearance; SMM: Skeletal muscle mass; OFV: Objective Function value.

Table 8 Comparison of target exposure achievement rates between different dosing regimens

Patient population	Traditional regimen achievement rate (%)	Optimized regimen achievement rate (%)	χ2	P value	Drug dosage change (%)
Sarcopenia group	71.4	93.8	5.682	0.017	+14.2
Non-sarcopenia group	87.7	93.2	1.124	0.289	-6.8
Overall	82.0	93.5	6.824	0.009	+2.4

Table 9 Skeletal muscle index-based individualized rocuronium dosing regimen

Patient category	Induction dose	Maintenance dose	Dosing interval (min)	Expected achievement rate (%)	Recommended monitoring frequency	Accumulation risk assessment
Sarcopenia	0.52 mg/kg SMM	0.22 mg/kg SMM	50-65	93.8	Every 30 min	Low risk
Non-sarcopenia	0.64 mg/kg SMM	0.16 mg/kg SMM	45-60	93.2	Every 45 min	Low risk

SMM: Skeletal muscle mass.

Table 10 Train-of-Four monitoring and neuromuscular blockade effect evaluation

Indicator	Sarcopenia group (n = 35)	Non-sarcopenia group (n = 65)	t-test	P value
Time to TOF count = 0 for intubation (min)	2.3 ± 0.4	3.0 ± 0.6	-6.284	< 0.001
First supplemental dose time (min)	42.8 ± 10.2	58.4 ± 12.8	-6.124	< 0.001
TOF ratio recovery to 0.7 time (min)	55.2 ± 11.8	75.6 ± 16.2	-6.486	< 0.001
TOF ratio recovery to 0.9 time (min)	65.8 ± 13.6	89.2 ± 18.8	-6.824	< 0.001
Intubation condition score (excellent rate %)	100	100	-	-

TOF: Train-of-Four.