Bupivacaine serum concentrations during chronic intrathecal infusion for pain management: an observational...

Intrathecal analgesia is recommended for the management of refractory cancer pain. Bupivacaine is the most commonly used local anesthetic in combination intrathecal therapies and is often administered at high doses. However, data on its systemic toxicity in this context remain limited. While the pharmacokinetics of bupivacaine have been described in epidural and spinal anesthesia, those studies involved substantially lower doses and minimal systemic absorption. A maximum serum concentration of 2 µg/mL (2000 µg/L) is generally considered the upper safety limit to prevent systemic toxicity, yet systemic exposure during chronic intrathecal infusion via an intrathecal drug delivery system has not been well characterized.

This single-center retrospective study aimed to quantify serum bupivacaine concentrations during intrathecal infusion and evaluate factors associated with systemic absorption. Serial bupivacaine plasma concentrations were measured with an in-house analytical assay on blood samples collected before each pump refill.

Thirty-one patients were included, with a total of 162 blood samples analyzed. The mean daily intrathecal bupivacaine dose was 39.5 mg/day (SD 31.4 mg/day), resulting in a mean serum concentration of 167.7 µg/L (SD 266.2 µg/L). Serum bupivacaine levels were positively correlated with the daily dose and were also influenced by body mass index. After adjustment for daily dose, higher infusion flow rates remained independently associated with increased serum concentrations.

Chronic intrathecal infusion of bupivacaine for cancer pain management results in systemic exposure well below the established toxicity threshold.