Portex Unit: Pain Research, UCL Institute of Child Health and Great Ormond Street Hospital NHS Trust, London, UK.
Anesth Analg. 2012 Sep;115(3):638-62. doi: 10.1213/ANE.0b013e31826253f2. Epub 2012 Jul 13.
Neuraxial drugs provide robust pain control, have the potential to improve outcomes, and are an important component of the perioperative care of children. Opioids or clonidine improves analgesia when added to perioperative epidural infusions; analgesia is significantly prolonged by the 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, in the second half of this review, we present 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 drugs with the widest demonstrable safety margin and suggest minimum standards for preclinical evaluation before adoption of new analgesics or preparations into routine clinical practice.
椎管内药物可提供强效的疼痛控制，具有改善结局的潜力，是儿童围手术期治疗的重要组成部分。阿片类药物或可乐定与围手术期硬膜外输注联合使用可改善镇痛效果；在单次骶管注射局麻药时加入可乐定、氯胺酮、新斯的明或曲马多可显著延长镇痛时间；一些中心正在增加新生儿椎管内麻醉/镇痛。然而，如果没有与镇痛需求、副作用和随访相关的详细和敏感数据，就很难确定不同技术和药物的相对风险效益。总结了目前与新生儿和婴儿的益处和并发症相关的数据，但目前椎管内药物使用的变异性反映了高质量证据相对缺乏。最近关于全身麻醉对发育中大脑的不良影响的临床前报告增加了对避免或减少全身麻醉剂量需求的椎管内麻醉/镇痛的潜在益处的认识。然而，发育中的脊髓也容易受到与药物相关的毒性影响，尽管已经有成熟的临床前模型和评估成年动物脊髓毒性的标准，但直到最近，在生命早期还没有进行系统评估。因此，在本综述的后半部分，我们介绍了评估不同脊髓镇痛药的药效学反应与年龄相关的变化的临床前数据，以及最近评估特定发育模型中脊髓毒性的研究。最后，我们主张使用具有最广泛证明安全性的椎管内药物，并建议在将新的镇痛药或制剂常规临床应用之前，制定临床前评估的最低标准。
