The Influence of Dexmedetomidine Added to Ropivacaine on Its Pharmacokinetic and Pharmacodynamic Effects During...

While ropivacaine-dexmedetomidine coadministration is widely used in surgical anesthesia, its pharmacokinetic effects in lumbar plexus blocks (LPB) remain uncharacterized. We therefore conducted a prospective randomized trial to evaluate dexmedetomidine's modulation of ropivacaine's pharmacokinetics and pharmacodynamics during unilateral lower limb surgery. Additionally, this study seeks to establish a dosing regimen for ropivacaine in combination with dexmedetomidine for LPB.

Patients undergoing unilateral lower limb surgery were randomly allocated to 1 of 3 groups using a random-number table. The study included a control group receiving only ropivacaine, and 2 experimental groups receiving ropivacaine combined with either 0.25 or 0.5 µg·kg -1 of dexmedetomidine, all administered perineurally. Clinical efficacy data were gathered and analyzed using statistical software to assess the pharmacodynamics of the three treatment regimens. Furthermore, data from all patients were used to develop a population pharmacokinetics model for ropivacaine, and pharmacokinetic parameters were determined. Using Bayesian estimation, we simulated ropivacaine dosing across body weights of 56 to 76 kg to identify doses where plasma concentrations exceed the toxicity threshold (4.3 ± 0.6 µg·mL -1 , mean ± standard deviation).

A total of 46 patients were enrolled in the study. Ropivacaine pharmacokinetics were best described by a 2-compartment model, with body weight and dexmedetomidine coadministration as significant covariates. Simulations indicated that for LPB, the modeled toxic dose decreased from 4.9 to 3.0 mg·kg -1 (with 0.5 µg·kg -1 dexmedetomidine) and from 3.3 to 2.1 mg·kg -1 (without dexmedetomidine) as body weight increased from 56 to 76 kg. The inclusion of 0.5 µg·kg -1 dexmedetomidine significantly reduced the maximum concentration of ropivacaine (mean difference, 0.8 µg·mL -1 ; 95% confidence interval [CI], 0.5-1.2 µg·mL -1 ; P < .0001), increased the apparent volume of distribution (33.1 L; 95% CI, 13.4-52.8 L; P = .013), prolonged the time to maximum concentration (5 minutes; 95% CI, 1-9; P = .011), and reduced the onset time of sensory blockade (5 minutes; 95% CI, 2-6; P < .0001), while also extending the duration of sensory blockade (175 minutes; 95% CI, 55-294; P = .005). The addition of 0.25 µg·kg -1 dexmedetomidine to ropivacaine did not change outcomes compared to ropivacaine alone.

Our research demonstrated that dexmedetomidine significantly influences the pharmacokinetics and pharmacodynamics of ropivacaine in LPB. When combining dexmedetomidine 0.5 µg·kg -1 with ropivacaine for LPB in a 66 kg adult, the maximum ropivacaine dose should not exceed 3.7 mg·kg -1 .