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

• Published in: Pediatric anesthesia 2014-09, Vol.24 (9), p.962-967
• Main Authors: Woloszczuk-Gebicka, Bogumila, Grabowski, Tomasz, Borucka, Beata, Karas-Trzeciak, Magdalena
• Format: Article
• Language: English
• Subjects: Amides - therapeutic use; Analgesia, Epidural - methods; Analgesics, Opioid - blood; Analgesics, Opioid - pharmacokinetics; Analgesics, Opioid - therapeutic use; anesthesia; anesthetics; Anesthetics, Local - therapeutic use; Child, Preschool; Chromatography, High Pressure Liquid; Drug Combinations; epidural; Female; Follow-Up Studies; Humans; Infant; local; Male; Pain, Postoperative - drug therapy; pharmacokinetics; sufentanil; Sufentanil - blood; Sufentanil - pharmacokinetics; Sufentanil - therapeutic use; Tandem Mass Spectrometry
• ISSN: 1155-5645; 1460-9592
• DOI: 10.1111/pan.12440

Summary Background and objectives 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. Methods With consent of local ethics committee and informed parental consent, 20 infants 3–36 months old (m.o.) (median 9.3 m.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 4 cm into epidural space. After initial bolus of 0.2% ropivacaine, 0.5 ml·kg−1 and sufentanil 200 ng·kg−1, continuous infusion of 0.2% ropivacaine, 0.3 mg·kg−1·h−1 with sufentanil 112 ng·kg−1·h−1 was started. For the postoperative period, sufentanil dose was reduced to 37 ng·kg−1·h−1. Blood samples were drawn at the end of surgery, 24 h later, by the end of 2nd day of infusion and after 3, 6, and 18 h from the end of infusion. Sufentanil was measured using liquid–liquid extraction (LLE) procedure and HPLC‐MS/MS method with LOQ = 5 pg·ml−1. Results and conclusions 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.