Background and Objectives Although intravenous lipid emulsion has been proved a powerful antidote for local anesthetic toxicity, there are few pharmacokinetic data on using lipid infusion as a pretreatment for other clinical applications. We assessed the influence of lipid pretreatment on the pharmacodynamics and pharmacokinetics of levobupivacaine.
Methods Altogether, 12 patients undergoing below-knee surgery for a fracture were randomly assigned to 2 groups (6 patients per group): pretreatment with 1.5 mL/kg lipid infusion (lipid group) or saline infusion (control subjects) followed by complete femoral and sciatic nerve block with 0.375% levobupivacaine (2.5 mg/kg). Total and free (non–protein bound) plasma levobupivacaine concentrations and triglycerides in the lipid group were determined.
Results Results were given as means ± SD. Total and free maximum plasma levobupivacaine concentrations were lower in the lipid group than in control subjects (865 ± 98 vs 1145 ± 177 μg/L and 56.8 ± 7.5 vs 78.2 ± 13.7 μg/L, respectively; P < 0.01). Apparent volume of distribution and clearance were higher in the lipid group than in control subjects (211 ± 35 vs 170 ± 21 L and 35.1 ± 8.0 vs 25.8 ± 2.6 L/h, respectively; P < 0.05). Triglyceride level was significantly higher at the end of lipid infusion than baseline values (7.59 ± 1.32 vs 1.34 ± 0.39 mmol/L; P < 0.01).
Conclusions Lipid pretreatment increased the apparent volume of distribution and clearance and decreased the maximum total and free levobupivacaine concentrations, thus offering a reasonable explanation for the effects of lipids on local anesthesia–related toxicity in humans. Rapid lipid infusion induced hypertriglyceridemia without other apparent risks in this study.
Clinical Trial Registration This study was registered at the Chinese Clinical Trial Registry, identifier ChiCTR-TRC-14005203.
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This study was supported by the Fujian Provincial Health Department, Fujian, China.
Y.C. helped design the study and collect and analyze data and wrote the manuscript. J.Z. conceived and designed the research and performed the nerve block. Z. Chen conducted the blood samples for detecting levobupivacaine concentration. Q.W. helped analyze the data. B.L. reviewed the original study data and data analysis. R.L. observed the durations of femoral and sciatic nerve sensory block. X.X. approved the final manuscript. Z. Cao helped conceive and design this research. L.Y. author helped conceive and design this research. Y.C., J.Z., Z. Chen, Q.W., B.L., Z. Cao, and L.Y. attested to the integrity of the original data and the analysis reported in this article.
The authors declare no conflict of interest.