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Postoperative pain control is essential to optimizing patient outcomes, improving satisfaction, and allowing patients to resume their baseline functional activities. Methadone, a synthetic mu‐opioid agonist, has multiple pharmacologic properties that may be optimal for perioperative use. Compared to other opioids, methadone has a longer duration of action, rapid onset, extended dosing intervals, high oral bioavailability, low cost, lack of active metabolites, and action on multiple receptors. The current literature examining the use of methadone in the perioperative care of children and adolescents is limited and most often reported within the context of spine or cardiothoracic surgery. Overall, these studies support the hypothesis that perioperative methadone in pediatric patients may decrease postoperative pain, opioid consumption, length‐of‐stay, and the incidence of some opioid‐related side effects, like constipation and urinary retention. A variety of protocols for the perioperative use of methadone have been described, including a single intraoperative dose as well as multiple small doses within multimodal pain protocols. The superiority of these protocols has not been established. Like all opioids, methadone has a side effect profile which includes nausea, vomiting, reduced GI motility, sedation, and respiratory depression at high doses. There is also a concern that it can cause QTc prolongation in patients. The primary aim of this educational review is to examine the pharmacologic data, published perioperative protocols, dosing considerations, and risks and benefits associated with inclusion of methadone in analgesic regimens for surgical patients. A secondary aim is to introduce opportunities for research around the perioperative use of methadone in children and adolescents. Based on our review, we would prioritize establishing optimal procedure‐specific methadone protocols, determining generalizability for use in routine pediatric surgeries, and investigating methadone safety and efficacy prospectively as the primary opioid for pain management in the postanesthesia care unit or postsurgical floors. [ABSTRACT FROM AUTHOR]

Background: Hydromorphone is an opioid agonist used for pediatric analgesia. Due to lack of data, pediatric dosing (based on adult pharmacokinetic models) is not optimal. Aim: This study characterizes hydromorphone population pharmacokinetics in pediatric surgical patients. Methods: In this prospective observational study, 34 children (4‐18 years, bodyweight 23‐89.6 kg) received multiple intravenous hydromorphone boluses followed by postoperative hydromorphone patient‐controlled analgesia. Arterial blood samples were collected before and at 3, 10, 30, and 90 (and few samples at 1350) minutes after the first dose. Hydromorphone concentrations were measured by validated LC‐MS/MS assay. Nonlinear mixed‐effects modeling was used for pharmacokinetic model development. The final population pharmacokinetic model was evaluated by visual predictive check and bootstrap analysis. Monte Carlo simulations based on the final pharmacokinetic model determined optimal patient‐controlled analgesia parameters to achieve a target of 20 ng/mL (as the median effective analgesic concentration), using minimum effective analgesic concentration of 4 ng/mL as a proxy for patient‐controlled analgesia dose demand, and not exceeding the defined safe upper threshold of 40 ng/mL. Results: Hydromorphone pharmacokinetic profiles were adequately described by a two‐compartmental model with first‐order elimination. Bodyweight was found to be a significant covariate for hydromorphone clearance. Allometrically scaledpharmacokinetic parameter estimates (per 70 kg), systemic clearance (0.748 L/min), volume of distribution (33 L), peripheral clearance (1.57 L/min), and peripheral volume of distribution (146 L) were similar to reported adult parameter estimates. Sex, race, age, and type of surgery were not identified as significant covariates. To identify optimal patient‐controlled analgesia dosing parameters, we simulated several initial loading doses, demand doses, and lockout intervals. Our simulations support an initial patient‐controlled analgesia loading dose of 15 µg/kg followed by a demand dose of 6 µg/kg with lockout intervals of 20 minutes. Conclusions: After intravenous hydromorphone, plasma pharmacokinetic profiles in children undergoing different surgeries were well described by a two‐compartment population allometric pharmacokinetic model using bodyweight as the size descriptor. Model informed simulations identified patient‐controlled analgesia parameters to inform initial settings, with adjustments as needed based on observed individual effects. [ABSTRACT FROM AUTHOR]