Pharmacokinetics of sufentanil administered with 0.2% ropivacaine as a continuous epidural infusion for postoperative pain relief in infants.

Abstract

Our objective was to assess plasma sufentanil concentrations and postinfusion pharmacokinetics in infants receiving 0.2% ropivacaine with sufentanil as a continuous epidural infusion for postoperative pain relief. With consent of local ethics committee and informed parental consent, 20 infants 3-36months old (m.o.) (median 9.3m.o., 9.0 [3.5-15] kg, ASA PS I/II) were enrolled. Epidural catheter was placed under general anesthesia in L3-L4, L4-L5, or L2-L3 interspace and threaded not farther than 4cm into epidural space. After initial bolus of 0.2% ropivacaine, 0.5ml·kg(-1) and sufentanil 200ng·kg(-1) , continuous infusion of 0.2% ropivacaine, 0.3mg·kg(-1) ·h(-1) with sufentanil 112ng·kg(-1) ·h(-1) was started. For the postoperative period, sufentanil dose was reduced to 37ng·kg(-1) ·h(-1) . Blood samples were drawn at the end of surgery, 24h later, by the end of 2nd day of infusion and after 3, 6, and 18h from the end of infusion. Sufentanil was measured using liquid-liquid extraction (LLE) procedure and HPLC-MS/MS method with LOQ=5pg·ml(-1) . Elimination of sufentanil following epidural administration was very slow, with MRT=28.25 [18.36-44.75] h and t1/2 MRT =19.57 [12.72-31.01] h. In infants, during a long-term infusion of sufentanil with ropivacaine, the opioid concentration in plasma increases during the postoperative infusion itself, then increases even further after discontinuation of the infusion, in some cases reaching the values consistent with a potential risk of respiratory depression. Meticulous monitoring of the infants' vital signs is therefore mandatory not only during the infusion, but also for several hours after its discontinuation.