Intraoperative infusion of 0.6-0.9 μg · kg^-1 · min^-1 remifentanil induces acute tolerance in young children after laparoscopic ureteroneocystostomy

Background: Intraoperative infusion of opioids has been associated with increased postoperative pain and analgesic requirements, but the development of tolerance in young children is less clear. This prospective, randomized, double-blinded study was designed to test the hypothesis that the intraoperative administration of remifentanil results in postoperative opioid tolerance in a dose-related manner in young children. Methods: We enrolled 60 children (aged 1-5 yr) who were undergoing elective laparoscopic ureteroneocystostomy. Patients were randomized and received an intraoperative infusion of 0, 0.3, 0.6, or 0.9 μg·kg·min remifentanil. Postoperative pain was managed by a parent/nurse-controlled analgesia pump using fentanyl. The primary outcome included the total fentanyl consumptions at 24 and 48 h postsurgery. Secondary outcomes were the postoperative pain scores and adverse effects. Results: The children who received 0.6 and 0.9 μg·kg·min remifentanil required more postoperative fentanyl than the children who received saline or 0.3 μg·kg·min remifentanil (all P < 0.001) for 24 h after surgery. The children who received 0.3-0.9 μg·kg·min intraoperative remifentanil reported higher pain scores at 1 h after surgery than the children who received saline (P = 0.002, P = 0.023, and P = 0.006, respectively). No significant intergroup differences in recovery variables were observed, but vomiting was more frequent in the 0.9 μg·kg·min remifentanil group than in the other groups (P = 0.027). Conclusions: The intraoperative use of 0.3 μg·kg·min remifentanil for approximately 3 h (range: 140-265 min) did not induce acute tolerance, but the administration of 0.6 and 0.9 μg·kg·min remifentanil to young children resulted in acute tolerance for 24 h after surgery in an apparently dose-related manner.