Levobupivacaine plasma concentrations following major liver resection

Levobupivacaine is metabolized hepatically. Whether postoperative epidural analgesia with levobupivacaine can lead to critical accumulation in patients undergoing major hepatic resection is unknown. Therefore, levobupivacaine concentrations were prospectively monitored in patients undergoing major liver resection and compared to patients undergoing rectal resection, who served as controls. Furthermore, we correlated levobupivacaine plasma concentrations with established liver function tests.

We analyzed plasma concentrations of levobupivacaine in 20 patients each scheduled for major liver or anterior rectal resection. All patients received general and epidural anesthesia (10 ml levobupivacaine 0.5% followed by 10 ml levobupivacaine 0.375% every 90 min) and postoperative continuous epidural analgesia (levobupivacaine 0.2%). Intraoperatively, and for 3 days postoperatively, levobupivacaine plasma concentrations were measured and correlated with bilirubin, fibrinogen, indocyanine green (ICG) clearance, and cholinesterase activity. Data (mean ± SD) were analyzed by two-way analysis of variance (ANOVA) with post hoc analysis or regression analysis (P < 0.05).

Intraoperatively and postoperatively, patients undergoing liver resection revealed significantly higher levobupivacaine concentrations (P= 0.0013 and P = 0.0016, respectively). Furthermore, significant differences were found for bilirubin (P = 0.0002), fibrinogen (P = 0.0002), and ICG (P < 0.0001). Highest levobupivacaine concentration correlated significantly with lowest ICG (P = 0.0004; R = 0.69), highest bilirubin (P = 0.0267; R = 0.49), lowest fibrinogen concentration (R = 0.32), but not with cholinesterase activity (R = 0.02).

Patients undergoing liver resection revealed significantly higher levobupivacaine concentrations compared to patients undergoing anterior rectal resection. However, although intraoperative levobupivacaine concentrations remained below 2.0 μg/ml, postoperative concentrations accumulated to a concentration above this threshold. This risk of levobupivacaine accumulation in patients with compromised liver function correlated best with ICG clearance.