Jacqz-Aigrain E, Burtin P
Unité de Pharmacologie Clinique, Hôpital Robert Debré, Paris, France.
Clin Pharmacokinet. 1996 Dec;31(6):423-43. doi: 10.2165/00003088-199631060-00003.
Sedation is currently administered to neonates experiencing pain and stress during intensive care for medical diseases, as well as postoperatively. Drugs commonly used for sedation in neonates include benzodiazepines (midazolam and lorazepam), chloral hydrate and opioids (fentanyl and morphine). Sedation protocols and dosage schedules are, in most cases, adapted from those which have been developed in children and even adults. The effectiveness and safety of the sedative agents remain underevaluated, however, due to the difficulties of quantifying pain and stress in neonates, and because of the limited use of validated scoring methods by practitioners. Among the benzodiazepines, midazolam is probably the drug of choice for continuous sedation. However, its elimination is delayed in the neonatal period and hypotension may occur when given as a bolus injection or when taken with opioids. Lorazepam requires further evaluation to exclude severe neurotoxicity. Chloral hydrate is administered orally, but because of its delayed elimination and risk of accumulation, a single administration for short term sedation is recommended. Among opioids, fentanyl (which was initially administered for postoperative analgesia) is now prescribed for sedation during mechanical ventilation. Tolerance and dependence may develop rapidly, limiting its usefulness for prolonged sedation. Although extensively studied in neonates, the efficacy and safety of morphine are not clearly determined, because of the limited number of patients included in individual studies. In addition, important interindividual differences in metabolism render dosage recommendations difficult. Alfentanil and sufentanil need further investigations to define their pharmacokinetic-pharmacodynamic properties in neonates. Although the choice of drug is important, the way the drug is used and monitored is equally important. All the drugs used for the sedation of neonates have large inter- and intraindividual differences in disposition, justifying specific pharmacological knowledge and individual dosage adjustments based on clinical evaluation of the patient and the monitoring of drug concentrations.
目前，在对患有内科疾病的新生儿进行重症监护期间以及术后，会对经历疼痛和应激的新生儿实施镇静。新生儿常用的镇静药物包括苯二氮䓬类药物（咪达唑仑和劳拉西泮）、水合氯醛和阿片类药物（芬太尼和吗啡）。在大多数情况下，镇静方案和剂量表是根据儿童甚至成人制定的方案改编而来的。然而，由于难以量化新生儿的疼痛和应激，且从业者对经过验证的评分方法使用有限，镇静剂的有效性和安全性仍未得到充分评估。在苯二氮䓬类药物中，咪达唑仑可能是持续镇静的首选药物。然而，其在新生儿期的消除延迟，静脉推注或与阿片类药物合用时可能会发生低血压。劳拉西泮需要进一步评估以排除严重神经毒性。水合氯醛通过口服给药，但由于其消除延迟和蓄积风险，建议单次给药用于短期镇静。在阿片类药物中，芬太尼（最初用于术后镇痛）现在被用于机械通气期间的镇静。耐受性和依赖性可能迅速发展，限制了其在长时间镇静中的应用。尽管在新生儿中进行了广泛研究，但由于个体研究纳入的患者数量有限，吗啡的疗效和安全性尚未明确确定。此外代谢方面的个体差异很大，使得剂量推荐变得困难。阿芬太尼和舒芬太尼需要进一步研究以确定它们在新生儿中的药代动力学 - 药效学特性。尽管药物的选择很重要，但药物的使用和监测方式同样重要。所有用于新生儿镇静的药物在处置方面存在较大的个体间和个体内差异，这就需要基于对患者的临床评估和药物浓度监测的特定药理学知识和个体化剂量调整。
