美沙酮在青少年围手术期的药代动力学。
Perioperative pharmacokinetics of methadone in adolescents.
机构信息
Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri 63110, USA.
出版信息
Anesthesiology. 2011 Dec;115(6):1153-61. doi: 10.1097/ALN.0b013e318238fec5.
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.
背景
美沙酮常用于接受麻醉和疼痛治疗的成人。美沙酮在成人中的药代动力学特征良好，包括围手术期。美沙酮也用于儿童。然而，对于任何年龄的儿童，都没有关于美沙酮药代动力学的信息。本研究旨在确定接受手术的儿童静脉内美沙酮的药代动力学。还评估了围手术期阿片类药物的节省作用。
方法
符合条件的研究对象为 5-18 岁接受全身麻醉和手术的儿童，预计术后住院时间超过 3 天。每组 10 至 11 名患者，每组 3 组，每组 10 至 11 名患者，分别接受递增剂量的 0.1、0.2 和 0.3mg/kg（最高 20mg）的盐酸美沙酮。否则，不改变麻醉护理。在 4 天内采集静脉血，用于立体选择性测定美沙酮及其代谢物。每天早上进行疼痛评估。确定每天和总阿片类药物消耗量。在第二队列中确定围手术期阿片类药物消耗和疼痛，该队列与年龄、性别、种族、民族、手术程序和住院时间相匹配，但不接受美沙酮。
结果
最终的美沙酮研究队列为 31 名青少年（14±2 岁，范围 10-18），因脊柱侧凸诊断接受主要脊柱手术。美沙酮药代动力学在 0.1-0.3mg/kg 剂量范围内呈线性。处置具有立体选择性。美沙酮给药并未剂量依赖性地影响术后疼痛评分，也未剂量依赖性地减少脊柱融合患者的每日或总术后阿片类药物消耗。
结论
手术中青少年美沙酮对映体的处置与健康成年人相似。
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