Effect of epinephrine on epidural, intrathecal, and plasma pharmacokinetics of ropivacaine and bupivacaine in sheep

Local vasoconstriction induced by epinephrine added to epidural local anaesthetics has been shown to improve their quality and duration of action in several clinical reports. There are several assumptions on the mechanisms. This study was designed to evaluate the influence of epinephrine on transmeningeal uptake of epidurally administered ropivacaine and bupivacaine by measuring local anaesthetic concentrations in the epidural and intrathecal spaces and in plasma. Ropivacaine (50 mg) and bupivacaine (30 mg) were administered epidurally in sheep with and without epinephrine (75 µg). A microdialysis technique was used to simultaneously measure epidural and intrathecal drug concentrations. Resulting dialysate and plasma concentrations were used to calculate pharmacokinetic parameters for ropivacaine and bupivacaine. Co-administration of epinephrine decreased epidural clearance for ropivacaine [0.6 (sd 0.1) vs 0.4 (0.1) ml min−1] but not significantly for bupivacaine [1.2 (0.4) vs 0.8 (0.3) ml min−1]. The resultant increase in epidural area under the concentration–time curves (31% for ropivacaine and 52% for bupivacaine) was also observed in the intrathecal space (21% increase for ropivacaine and 37% for bupivacaine). There was no significant influence of epinephrine on ropivacaine plasma pharmacokinetics. Plasma Cmax for bupivacaine was decreased. These results show that epinephrine decreases the clearance and distribution processes involved in epidural disposition of ropivacaine and bupivacaine, leading to an increased uptake into the intrathecal space with an apparent more pronounced effect for bupivacaine.