The pharmacokinetics of continuous epidural sufentanil and bupivacaine infusion after thoracotomy

In a double-blind, randomized study in patients undergoing thoracic surgery the plasma and cerebrospinal fluid (CSF) pharmacokinetics of epidural sufentanil were studied by using radioimmunoassay analysis. Sufentanil was given as an infusion (1 mu g/mL) at the lumbar (Ls; n = 11), or thoracic (Ts; n = 12) level, or epidural sufentanil combined with bupivacaine (1 mg/mL) at the thoracic level (Tsb; n = 14). Postoperatively, the infusion was adjusted to optimize analgesia. During the infusion, the sufentanil plasma concentrations were related to the rate of epidural infusion and unrelated both to the epidural infusion regimen and to the postoperative pain scores. The elimination half-life in plasma (mean +/- SEM) was 9.9 +/- 1.7 h (Ls), 8.6 +/- 0.7 h (Ts), and 11.7 +/- 2.2 h (Tsb). The distribution volume was 15.2 +/- 3.5 L/kg (Ls), 14.8 +/- 2.4 L/kg (Ts), and 12.9 +/- 1.2 L/kg (Tsb). Total sufentanil clearance was 17.8 +/- 1.4 and 16.9 +/- 2.0 mL . kg(-1). min(-1) (Ls), 22.9 +/- 3.5 and 20.0 +/- 2.6 mL . kg(-1). min(-1) (Ts), and 22.4 +/- 3.0 and 14.5 +/- 1.3 mL . kg(-1). min(-1) (Tsb). The terminal elimination half-life of sufentanil in CSF was 7.2 +/- 0.6 h. During steady state the CSF concentrations were not homogeneously distributed and they were higher than those in plasma. These pharmacokinetic findings support the concept that epidural sufentanil analgesia is optimal when administered segmentally and tailored to the surgical incision.