Perioperative Pharmacokinetics of Methadone in Adolescents
Perioperative Pharmacokinetics of Methadone in Adolescents
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DOI：
10.1097/aln.0b013e318238fec5
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发表时间：
2011-12-01
期刊：
影响因子：
8.8
通讯作者：
Kharasch, Evan D.
中科院分区：
文献类型：
--
作者：
Sharma, Anshuman;Tallchief, Danielle;Kharasch, Evan D.
背景：美沙酮经常用于接受麻醉和接受疼痛治疗的成年人。美沙酮在成人中的药代动力学已得到充分表征，包括围手术期。美沙酮也用于儿童。然而，没有任何年龄儿童中美沙酮药代动力学的信息。本研究的目的是确定接受手术的儿童静脉注射美沙酮的药代动力学。还评估了围手术期阿片类药物的节约效果。方法：符合条件的受试者是接受全身麻醉和手术的 5-18 岁儿童，预计术后住院时间超过 3 天。三组每组 10 至 11 名患者，麻醉诱导后分别接受静脉注射盐酸美沙酮，剂量递增，剂量组为 0.1、0.2 和 0.3 mg/kg（最高 20 mg）。麻醉护理没有其他改变。连续 4 天采集静脉血，用于立体选择性测定美沙酮和代谢物。每天早上进行疼痛评估。确定每日和总阿片类药物消耗量。在第二个队列中确定了围手术期阿片类药物的消耗量和疼痛情况，该队列与年龄、性别、种族、民族、手术程序和住院时间相匹配，但没有接受美沙酮治疗。 结果：最终的美沙酮研究队列是 31 名青少年（14 +/- 2 岁，范围 10-18），他们接受了脊柱侧凸的大型脊柱手术。美沙酮药代动力学在 0.1-0.3 mg/kg 剂量范围内呈线性。处置是立体选择性的。美沙酮给药不会剂量依赖性地影响术后疼痛评分，并且不会剂量依赖性地减少脊柱融合患者的每日或术后总阿片类药物消耗量。结论：接受手术的青少年中美沙酮对映体的分布与健康成人相似。
Background: Methadone is frequently administered to adults experiencing anesthesia and receiving pain treatment. Methadone pharmacokinetics in adults are well characterized, including the perioperative period. Methadone is also used in children. There is, however, no information on methadone pharmacokinetics in children of any age. The purpose of this investigation was to determine the pharmacokinetics of intravenous methadone in children undergoing surgery. Perioperative opioid-sparing effects were also assessed.Methods: Eligible subjects were children 5-18 yr undergoing general anesthesia and surgery, with an anticipated postoperative inpatient stay exceeding 3 days. Three groups of 10 to 11 patients each received intravenous methadone hydrochloride after anesthetic induction in ascending dose groups of 0.1, 0.2, and 0.3 mg/kg (up to 20 mg). Anesthetic care was not otherwise changed. Venous blood was obtained for 4 days, for stereoselective determination of methadone and metabolites. Pain assessments were made each morning. Daily and total opioid consumption was determined. Perioperative opioid consumption and pain was determined in a second cohort, which was matched to age, sex, race, ethnicity, surgical procedure, and length of stay, but not receiving methadone.Results: The final methadone study cohort was 31 adolescents (14 +/- 2 yr, range 10-18) undergoing major spine surgery for a diagnosis of scoliosis. Methadone pharmacokinetics were linear over the dose range 0.1-0.3 mg/kg. Disposition was stereoselective. Methadone administration did not dose-dependently affect postoperative pain scores, and did not dose-dependently decrease daily or total postoperative opioid consumption in spinal fusion patients.Conclusions: Methadone enantiomer disposition in adolescents undergoing surgery was similar to that in healthy adults.