Bhatia J
Section of Neonatology, Medical College of Georgia, Augusta 30912, USA.
Clin Pediatr (Phila). 2000 Jun;39(6):327-36. doi: 10.1177/000992280003900602.
Apnea of prematurity (AOP) is a common problem that affects premature infants and, to a lesser degree, term infants. Apnea of prematurity appears to be due to immaturity of the infant's neurologic and respiratory systems. Apnea of prematurity is a diagnosis of exclusion that can be made only when other possible infectious, cardiologic, physiologic, and metabolic causes of apnea have been ruled out. The fundamental principles for managing apnea of prematurity include monitoring the infant closely while instituting supportive care measures such as tactile stimulation, continuous positive airway pressure, or mechanical ventilation. When necessary, pharmacologic therapy may be used to stimulate breathing. The first-line agents of choice for the management of AOP are the methylxanthines. And, for second-line therapy, a switch to a different class of agent, such as the respiratory stimulant doxapram, is an option. Of the methylxanthines, theophylline is the most extensively used. However, a review of the literature suggests that caffeine citrate may be the agent of choice for AOP. Comparative clinical studies have demonstrated that caffeine is at least as effective as theophylline, has a longer half-life, is associated with fewer adverse events, and, in addition, has a greater ease of administration. Caffeine stimulates the respiratory and central nervous systems more effectively and penetrates into the cerebrospinal fluid more readily than theophylline. In addition, because of stable plasma levels, caffeine has a wide therapeutic margin and few side effects. In contrast, theophylline plasma levels may fluctuate widely, which necessitates frequent monitoring and has a higher incidence of adverse events than caffeine. Before the FDA approval of caffeine citrate (Cafcit) for administration either intravenously and/or orally, caffeine preparations were "homemade." A few studies suggest that use of pharmacotherapy to treat AOP is not generally associated with long-term sequelae, although more data are needed before this can be definitively concluded.
早产儿呼吸暂停（AOP）是一个常见问题，影响早产儿，在较小程度上也影响足月儿。早产儿呼吸暂停似乎是由于婴儿神经和呼吸系统不成熟所致。早产儿呼吸暂停是一种排除性诊断，只有在排除了其他可能导致呼吸暂停的感染、心脏、生理和代谢原因后才能做出。管理早产儿呼吸暂停的基本原则包括在采取触觉刺激、持续气道正压通气或机械通气等支持性护理措施的同时密切监测婴儿。必要时，可使用药物治疗来刺激呼吸。治疗AOP的一线首选药物是甲基黄嘌呤。对于二线治疗，可以选择改用另一类药物，如呼吸兴奋剂多沙普仑。在甲基黄嘌呤类药物中，茶碱使用最为广泛。然而，文献综述表明，枸橼酸咖啡因可能是治疗AOP的首选药物。比较临床研究表明，咖啡因至少与茶碱一样有效，半衰期更长，不良事件更少，而且给药更方便。咖啡因比茶碱更有效地刺激呼吸和中枢神经系统，更容易渗透到脑脊液中。此外，由于血浆水平稳定，咖啡因具有较宽的治疗窗且副作用较少。相比之下，茶碱的血浆水平可能波动很大，这需要频繁监测，且不良事件发生率高于咖啡因。在FDA批准枸橼酸咖啡因（Cafcit）静脉和/或口服给药之前，咖啡因制剂都是“自制的”。一些研究表明，使用药物治疗AOP一般与长期后遗症无关，不过在得出明确结论之前还需要更多数据。
