Propofol: a review of its role in pediatric anesthesia and sedation.
Propofol: a review of its role in pediatric anesthesia and sedation.
复制标题
丙泊酚：对其在小儿麻醉和镇静中的作用进行回顾。
DOI：
10.1007/s40263-015-0259-6
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发表时间：
2015-07
期刊：
影响因子：
6
通讯作者：
D'Mello A
中科院分区：
文献类型：
--
作者：
Chidambaran V;Costandi A;D'Mello A
异丙酚是一种静脉麻醉剂，常用于儿童麻醉诱导和维持、手术和重症监护镇静。对中枢神经系统的作用机制涉及各种神经递质受体的相互作用，特别是γ-氨基丁酸A受体。1989年，联邦药品管理局（FDA）批准在美国使用，但其用于3岁以下儿童的麻醉诱导仍然是标签外使用。尽管其广泛用于儿科麻醉，但关于其安全性和对特定儿童亚群的严重不良反应的文献相互矛盾。特别是因为儿童不是“小成年人”，在这篇综述中，我们强调丙泊酚药代动力学的成熟方面。尽管有大量的丙泊酚药代动力学-药效学研究以及使用异速生长缩放来消除由于尺寸和年龄引起的差异的能力，但是没有可用于在儿童中提供闭环全静脉麻醉的靶控输注泵的最佳模型。由于丙泊酚的商业制剂是一种营养丰富的乳剂，尽管FDA强制添加抗菌防腐剂，要求制造商指示在六小时后丢弃打开的小瓶，但细菌污染的风险仍然存在。虽然丙泊酚比吸入麻醉具有优势，如儿童术后恶心和苏醒期谵妄较少，但即使使用新制剂，注射疼痛仍然是一个问题。已知丙泊酚通过其在氧化磷酸化中作为解偶联剂的作用抑制线粒体功能。这对患有线粒体疾病的儿童和异丙酚相关输液综合征的发生有影响，这是异丙酚的一种罕见但严重危及生命的并发症。在本次审查时，没有直接证据表明丙泊酚对婴儿大脑的神经毒性;然而，目前对丙泊酚诱导发育中大脑神经细胞凋亡的担忧仍然存在，并继续成为研究的焦点。
Propofol is an intravenous agent used commonly for induction and maintenance of anesthesia, procedural and critical care sedation in children. The mechanisms of action on the central nervous system involve interactions at various neurotransmitter receptors, especially gamma-aminobutyric acid A receptor. Approved for use in the United States by the Federal Drugs and Administration (FDA) in 1989, its use for induction of anesthesia in children less than 3 years of age still remains off-label. Despite its wide use in pediatric anesthesia, there is conflicting literature about its safety and serious adverse effects in particular subsets of children. Particularly as children are not “little adults”, in this review, we emphasize the maturational aspects of propofol pharmacokinetics. Despite the myriad of propofol pharmacokinetic-pharmacodynamic studies and the ability to use allometrical scaling to smooth out differences due to size and age, there is no optimal model that can be used in target controlled infusion pumps for providing closed loop total intravenous anesthesia in children. As the commercial formulation of propofol is a nutrient-rich emulsion, the risk for bacterial contamination exist despite the FDA mandating addition of antimicrobial preservative, calling for manufacturers’ directions to discard open vials after six hours. While propofol has advantages over inhalation anesthesia like less postoperative nausea and emergence delirium in children, pain on injection remains a problem even with newer formulations. Propofol is known to depress mitochondrial function by its action as an uncoupling agent in oxidative phosphorylation. This has implications for children with mitochondrial diseases and the occurrence of propofol-related infusion syndrome, a rare but seriously life-threatening complication of propofol. At the time of this review, there is no direct evidence in humans for propofol induced neurotoxicity to the infant brain; however, current concerns of neuroapoptosis in developing brains induced by propofol persist and continue to be a focus of research.