Bruns Luke A, Canter Charles E
Department of Pediatrics, Division of Pediatric Cardiology, Children's Heart Center of St Louis, St John's Mercy Medical Center, St Louis, MO, USA.
Paediatr Drugs. 2002;4(12):771-8. doi: 10.2165/00128072-200204120-00001.
In multiple clinical trials, beta-blockers have been shown to significantly improve morbidity and mortality in adults with chronic congestive heart failure, but there is little reported experience with their use in children. Heart failure involves activation of the adrenergic nervous system and other neurohumoral systems in order to maintain cardiovascular homeostasis. These compensatory mechanisms have been shown to cause myocardial damage with chronic activation, which has been hypothesized to be a major contributing factor to the clinical deterioration of adults with heart failure. Studies have demonstrated inhibition of this neurohumoral response and concomitant clinical benefits with beta-blockers. Consequently, beta-blockers have evolved to become an important part of comprehensive medical therapy for congestive heart failure in adults. Pediatric heart failure represents an entirely different spectrum of disease, caused more commonly by congenital heart disease than cardiomyopathy. Surgical palliation and correction are important components of pediatric heart failure therapy, and residual, postsurgical cardiac lesions can lead to chronic heart failure. Although neurohumoral activation in children is similar to that in adults with heart failure, there are important differences from adults in physiology and developmental changes that are especially observed in infants. Current published clinical experience with beta-blocker use in children with heart failure is limited to case series with relatively small numbers of patients. Nevertheless, these series show consistent symptomatic improvement, and improvement in ventricular systolic function in patients with cardiomyopathies and congenital heart disease, similar to findings in adults. Adverse effects were common and many patients in these studies had adverse outcomes (death and/or need for transplantation). One study has noted differences in pharmacokinetics in children compared with adults. However, a multicenter, randomized controlled trial to evaluate carvedilol in pediatric heart failure from systolic ventricular dysfunction is currently ongoing and should help to clarify the efficacy and tolerability of carvedilol in children.
在多项临床试验中，β受体阻滞剂已被证明能显著改善成人慢性充血性心力衰竭患者的发病率和死亡率，但关于其在儿童中的应用报道较少。心力衰竭涉及肾上腺素能神经系统和其他神经体液系统的激活，以维持心血管稳态。这些代偿机制已被证明会因长期激活而导致心肌损伤，据推测这是成人心力衰竭临床病情恶化的一个主要因素。研究表明，β受体阻滞剂可抑制这种神经体液反应并带来相应的临床益处。因此，β受体阻滞剂已逐渐成为成人充血性心力衰竭综合药物治疗的重要组成部分。小儿心力衰竭代表了一种完全不同的疾病谱，其更常见的病因是先天性心脏病而非心肌病。手术姑息治疗和矫正术是小儿心力衰竭治疗的重要组成部分，术后残留的心脏病变可导致慢性心力衰竭。尽管儿童的神经体液激活与成人心力衰竭患者相似，但在生理和发育变化方面与成人存在重要差异，这在婴儿中尤为明显。目前已发表的关于β受体阻滞剂用于儿童心力衰竭的临床经验仅限于患者数量相对较少的病例系列。然而，这些系列研究显示症状持续改善，心肌病和先天性心脏病患者的心室收缩功能也有所改善，这与成人的研究结果相似。不良反应很常见，这些研究中的许多患者出现了不良结局（死亡和/或需要移植）。一项研究指出儿童与成人在药代动力学方面存在差异。然而，一项评估卡维地洛治疗小儿收缩性心室功能障碍所致心力衰竭的多中心随机对照试验目前正在进行，该试验应有助于明确卡维地洛在儿童中的疗效和耐受性。
