A Comparison of Differences Between the Systemic Pharmacokinetics of Levobupivacaine and Ropivacaine During Continuous Epidural Infusion: A Prospective, Randomized, Multicenter, Double-Blind Controlled Trial.

Epidural infusion of levobupivacaine and ropivacaine provides adequate postoperative pain management, minimizing the side effects related to IV opioids and improving patient outcome.1–5 Systemic toxicity of local anesthetics can lead to a progressive range of neurologic and cardiac complications, resulting in disability or death.6 The reported “toxic” plasma concentrations of levobupivacaine (1.74–2.7 μg/mL)7,8 and ropivacaine (1.24–6.0 μg/mL)9–21 only have been inferred from anecdotal data. Animal models of local anesthetic toxicity suggest that the systemic toxicity of levobupivacaine is midway between that of bupivacaine and ropivacaine.22 Clinical data in humans have suggested that ropivacaine 0.2% produces the same clinical effects as levobupivacaine 0.125%.23,24 The drug safety profile of different drugs can be judged by the evaluation of side effects under controlled concentrations. The differences in systemic absorption and disposition during epidural infusion between levobupivacaine and ropivacaine, however, have not yet been fully elucidated, even though these factors could be important in optimizing their clinical effectiveness, reducing the risk of systemic toxicity,25 and estimating the therapeutic index for these drugs. Because they have different pharmacokinetic properties, our aim was to compare the possible difference in the pharmacokinetic variability of the 2 drugs in a homogeneous population undergoing continuous epidural infusion. Because these 2 drugs have a different lipophilicity, several confounding factors may affect their pharmacokinetics during epidural infusion (i.e., patient age, the distribution of the epidural fat, and the type of surgery). This study attempts to study the “in vivo” effect of these factors on the pharmacokinetic of levobupivacaine and ropivacaine. This double-blind, multicenter, randomized, controlled trial study was designed to compare the pharmacokinetics of continuous thoracic epidural infusion of levobupivacaine 0.125% or ropivacaine 0.2% for postoperative pain management in adult patients who have undergone major abdominal, urological, or gynecologic surgery. This analysis allows us to assess the equivalence in systemic exposure and interindividual variability between levobupivacaine and ropivacaine, to verify the predictability of the concentration of these 2 drugs during continuous thoracic epidural infusion, and to investigate any difference in their pharmacokinetic variability in a homogeneous population who had undergone continuous epidural infusion.