From the Department of Anesthesiology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri (M.C.M., L.J., A.S., E.D.K.) the Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina (E.D.K.).
Anesthesiology. 2019 Jun;130(6):936-945. doi: 10.1097/ALN.0000000000002664.
Opioids are a mainstay of perioperative analgesia. Opioid use in children with obstructive sleep apnea is challenging because of assumptions for increased opioid sensitivity and assumed risk for opioid-induced respiratory depression compared to children without obstructive sleep apnea. These assumptions have not been rigorously tested. This investigation tested the hypothesis that children with obstructive sleep apnea have an increased pharmacodynamic sensitivity to the miotic and respiratory depressant effects of the prototypic μ-opioid agonist remifentanil.
Children (8 to 14 yr) with or without obstructive sleep apnea were administered a 15-min, fixed-rate remifentanil infusion (0.05, 0.1, or 0.15 μg · kg · min). Each dose group had five patients with and five without obstructive sleep apnea. Plasma remifentanil concentrations were measured by tandem liquid chromatography mass spectrometry. Remifentanil effects were measured via miosis, respiratory rate, and end-expired carbon dioxide. Remifentanil pharmacodynamics (miosis vs. plasma concentration) were compared in children with or without obstructive sleep apnea.
Remifentanil administration resulted in miosis in both non-obstructive sleep apnea and obstructive sleep apnea patients. No differences in the relationship between remifentanil concentration and miosis were seen between the two groups at any of the doses administered. The administered dose of remifentanil did not affect respiratory rate or end-expired carbon dioxide in either group.
No differences in the remifentanil concentration-miosis relation were seen in children with or without obstructive sleep apnea. The dose and duration of remifentanil administered did not alter ventilatory parameters in either group.
阿片类药物是围手术期镇痛的主要药物。由于与无阻塞性睡眠呼吸暂停的儿童相比，人们认为阻塞性睡眠呼吸暂停儿童的阿片类药物敏感性增加，并且存在阿片类药物引起呼吸抑制的风险，因此儿童使用阿片类药物具有挑战性。这些假设尚未经过严格测试。本研究检验了这样一个假设，即阻塞性睡眠呼吸暂停的儿童对典型 μ-阿片类激动剂瑞芬太尼的缩瞳和呼吸抑制作用具有更高的药效敏感性。
患有或不患有阻塞性睡眠呼吸暂停的儿童（8 至 14 岁）给予 15 分钟的固定速率瑞芬太尼输注（0.05、0.1 或 0.15μg·kg·min）。每个剂量组有五名患有阻塞性睡眠呼吸暂停的儿童和五名没有阻塞性睡眠呼吸暂停的儿童。通过串联液质联用测定瑞芬太尼的血浆浓度。通过瞳孔缩小、呼吸频率和呼气末二氧化碳来测量瑞芬太尼的作用。比较了患有或不患有阻塞性睡眠呼吸暂停的儿童的瑞芬太尼药效学（瞳孔缩小与血浆浓度的关系）。
瑞芬太尼给药导致非阻塞性睡眠呼吸暂停和阻塞性睡眠呼吸暂停患者的瞳孔缩小。在给予的任何剂量下，两组之间都没有看到瑞芬太尼浓度与瞳孔缩小之间的关系存在差异。两组给予的瑞芬太尼剂量均不影响呼吸频率或呼气末二氧化碳。
在患有或不患有阻塞性睡眠呼吸暂停的儿童中，瑞芬太尼浓度与瞳孔缩小之间的关系没有差异。给予的瑞芬太尼剂量和持续时间在两组中均未改变通气参数。
