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, doubleblinded 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 −1 ·min −1 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 −1 ·min −1 remifentanil required more postoperative fentanyl than the children who received saline or 0.3 µg·kg −1 ·min −1 remifentanil (all P < 0.001) for 24 h after surgery. The children who received 0.3-0.9 µg·kg −1 ·min −1 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−1 remifentanil to young children resulted in acute tolerance for 24 h after surgery in an apparently dose-related manner.T he unique pharmacodynamic and pharmacokinetic characteristics of remifentanil have increased its dominant intraoperative role in children.1,2 The context-sensitive halftime of remifentanil renders the offset for effect dose-independent, thus allowing prolonged infusion of large doses with little risk for delayed awakening or respiratory depression after surgery. 3,4 Similar to other potent opioids, however, intraoperative remifentanil may induce hyperalgesia and tolerance, manifesting as increased postoperative pain and analgesic requirements. [5][6][7] Opioid-induced hyperalgesia is a paradoxical pain sensitization of the nervous system whereby a patient receiving an opioid for the treatment of pain might actually have an increase in pain perception to noxious stimuli. 8 Tolerance is a pharmacologic concept defined as a progressive decrease in response to a drug and which can be overcome by increasing the dose of the drug. Although the difference between hyperalgesia and tolerance is difficult to tease out, opioid-induced hyperalgesia and tolerance may complicate the perioperative course of a patient who receives intraoperative opioid.In young children, however, only a few studies have investigated the development of tolerance after the intraoperative infusion of remifentanil, and the results were anecdotal and Intraoperative Infusion of 0.6-0.9 µg · kg