Neuraxial analgesia in neonates and infants: a review of clinical and preclinical strategies for the development of safety and efficacy data.
Neuraxial analgesia in neonates and infants: a review of clinical and preclinical strategies for the development of safety and efficacy data.
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DOI：
10.1213/ane.0b013e31826253f2
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发表时间：
2012-09
影响因子：
5.7
通讯作者：
Yaksh TL
中科院分区：
文献类型：
--
作者：
Walker SM;Yaksh TL
神经轴剂提供了强大的疼痛控制，有可能改善结果，是围手术期儿童护理的重要组成部分。阿片类药物或可乐定加入围手术期硬膜外输注可改善镇痛效果;可乐定、氯胺酮、新斯的明或曲马多加入单次注射局麻药尾部注射可显著延长镇痛时间;在一些中心，新生儿鞘内麻醉/镇痛正在增加。然而，如果没有与镇痛要求、副作用和随访相关的详细和敏感的数据，很难确定不同技术和药物的相对风险效益。总结了与新生儿和婴儿获益和并发症相关的当前数据，但当前轴突药物使用的变异性反映了相对缺乏高质量证据。最近关于全身麻醉剂对发育中大脑的不良影响的临床前报告增加了对轴索麻醉/镇痛的潜在益处的认识，以避免或减少全身麻醉剂的剂量要求。然而，发育中的脊髓也容易受到药物相关毒性的影响，尽管有成熟的临床前模型和标准来评估成年动物的脊髓毒性，但直到最近，在早期生命中还没有系统的评估。因此，本综述的后半部分介绍了评价不同脊髓镇痛药药效学反应的年龄依赖性变化的临床前数据，以及最近在特定发育模型中评价脊髓毒性的研究。最后，我们提倡使用具有最大安全范围的神经轴药物，并建议在采用新的镇痛药或制剂进入常规临床实践之前进行临床前评估的最低标准。
Neuraxial agents provide robust pain control, have the potential to improve outcomes, and are an important component of the perioperative care of children. Opioids or clonidine improve analgesia when added to perioperative epidural infusions; analgesia is significantly prolonged by addition of clonidine, ketamine, neostigmine or tramadol to single shot caudal injections of local anesthetic; and neonatal intrathecal anesthesia/analgesia is increasing in some centers. However, it is difficult to determine the relative risk-benefit of different techniques and drugs without detailed and sensitive data related to analgesia requirements, side-effects, and follow-up. Current data related to benefits and complications in neonates and infants are summarized, but variability in current neuraxial drug use reflects the relative lack of high quality evidence. Recent preclinical reports of adverse effects of general anesthetics on the developing brain have increased awareness of the potential benefit of neuraxial anesthesia/analgesia to avoid or reduce general anesthetic dose requirements. However, the developing spinal cord is also vulnerable to drug-related toxicity, and although there are well-established preclinical models and criteria for assessing spinal cord toxicity in adult animals, until recently there had been no systematic evaluation during early life. Therefore, the second half of this review presents preclinical data evaluating age-dependent changes in the pharmacodynamic response to different spinal analgesics, and recent studies evaluating spinal toxicity in specific developmental models. Finally, we advocate use of neuraxial agents with the widest demonstrable safety margin and suggest minimum standards for preclinical evaluation prior to adoption of new analgesics or preparations into routine clinical practice.