Morris John L, Rosen David A, Rosen Kathleen R
Department of Anesthesia, West Virginia University, Morgantown, West Virginia, USA.
Paediatr Drugs. 2003;5(6):385-405. doi: 10.2165/00128072-200305060-00004.
The use of NSAIDs has become routine for adults and children in the management of pain. NSAIDs (other than aspirin [acetylsalicylic acid]) are also enjoying greater popularity as antipyretics since the recognition of Reye's syndrome's putative association with aspirin. In neonates, NSAIDs have been used for many years in an attempt to pharmacologically close the ductus arteriosus. This review examines the various NSAIDs and their potential and real applications in the neonatal population. For completeness, acetaminophen (paracetamol), which has weak NSAID activity and is a widely used analgesic and antipyretic in this patient group, was also included. The prostaglandin system is important for healthy development, and conversely there are unique risks posed by pharmacologic interference with this system in the neonatal period. The prostanoid system in neonates has the capacity to modulate nociception, but comes at the expense of interfering with nearly every organ system. Physiologic effects of inhibition of prostaglandin synthesis applicable to neonates include disruption of the sleep cycle, increased risk of pulmonary hypertension, alterations in cerebral blood flow, decreased renal function, disrupted thermoregulation, and alterations in hemostasis balance, among others. Prostaglandins are also important for the normal development of the central nervous, cardiovascular, and renal systems, and there is evidence that the proper genesis of these systems may be adversely effected by NSAID exposure in utero and in the neonatal period. Gastrointestinal adverse effects have provided the impetus for the development and marketing of selective cyclo-oxygenase type 2 (COX-2) inhibitors. These agents' reputation for safety in adults may not be applicable to neonates. COX-2 is involved in the development of several organ systems, and its inhibition may induce a prothrombotic state. The advent of parenteral formulations of cyclo-oxygenase inhibitors, including COX-2-selective agents, increases the therapeutic flexibility of NSAIDs. However, objective data on the safety of these agents have not kept pace with their clinical availability.
非甾体抗炎药（NSAIDs）在成人和儿童疼痛管理中已成为常规用药。自认识到瑞氏综合征与阿司匹林可能存在关联以来，非甾体抗炎药（阿司匹林[乙酰水杨酸]除外）作为退热药也越来越受欢迎。在新生儿中，非甾体抗炎药已使用多年，试图通过药物作用使动脉导管闭合。本综述探讨了各种非甾体抗炎药及其在新生儿群体中的潜在和实际应用。为全面起见，还纳入了对乙酰氨基酚（扑热息痛），它具有较弱的非甾体抗炎药活性，是该患者群体中广泛使用的镇痛药和解热药。前列腺素系统对健康发育很重要，相反，在新生儿期对该系统进行药物干预会带来独特风险。新生儿的前列腺素系统有调节痛觉的能力，但代价是几乎会干扰每个器官系统。抑制前列腺素合成对新生儿的生理影响包括睡眠周期紊乱、肺动脉高压风险增加、脑血流改变、肾功能下降、体温调节紊乱以及止血平衡改变等。前列腺素对中枢神经、心血管和肾脏系统的正常发育也很重要，有证据表明这些系统的正常发育可能会受到子宫内和新生儿期接触非甾体抗炎药的不利影响。胃肠道不良反应推动了选择性环氧化酶-2（COX-2）抑制剂的研发和上市。这些药物在成人中的安全声誉可能不适用于新生儿。COX-2参与多个器官系统的发育，其抑制可能会诱导血栓形成状态。包括COX-2选择性药物在内的环氧化酶抑制剂注射用制剂的出现，增加了非甾体抗炎药的治疗灵活性。然而，关于这些药物安全性的客观数据并未跟上其临床应用的步伐。
