Finer Neil N
University of California, San Diego, USA.
Paediatr Respir Rev. 2004;5 Suppl A:S289-97. doi: 10.1016/s1526-0542(04)90053-x.
Surfactant has led to a significant reduction in neonatal mortality for premature infants with lung immaturity and respiratory distress. However, surfactant therapy has been shown to be effective in the treatment of a number of other neonatal respiratory disorders and the evidence for surfactant use in such circumstances is presented. Meconium aspiration is characterised by severe atelectasis, the influx of neutrophils, edema, and hyaline membranes, with decreased levels of SP-A and SP-B and the large aggregate fraction of lung surfactant, and altered surfactant surface morphology. Meconium contains cholesterol, free fatty acids and bilirubin all of which can interfere with surfactant function in a dose-dependent fashion. Providing larger amounts of surfactant can overcome some of this inhibition. Animal models of meconium aspiration treated with surfactant have improved histology, lung mechanics and gas exchange. Studies in human infants with meconium aspiration have found elevated concentrations of total protein, albumin, and membrane-derived phospholipid in lung lavage fluid, and haemorrhagic pulmonary edema. Clinical studies in such neonates have reported improved gas exchange and clinical outcomes following surfactant treatment. More recently surfactant lavage has been shown to be a potentially efficacious therapy for such infants. The inflammatory exudate containing plasma proteins and cytokines which accompanies neonatal pneumonia may inactivate surfactant. Surfactant treatment given to animals following the tracheal instillation of group B Streptococcal resulted in significantly less bacterial growth and improved lung function. Small clinical experiences have demonstrated the benefit of surfactant to infants with pneumonia/sepsis. Pulmonary haemorrhage, which some consider a complication of surfactant therapy, has also been effectively managed using surfactant instillation. The hemoglobin and red blood cell lipids may act to inhibit natural surfactant and treatment with surfactant has been shown to improve outcome for infants with pulmonary haemorrhage. Animal models of congenital diaphragmatic hernia (CDH) have hypoplastic lungs with evidence of decreased lamellar bodies in their type II pneumocytes and resultant surfactant deficiency, and respond to surfactant replacement with improved gas exchange and lung mechanics. The lungs of human infants with CDH contain less phospholipids and phosphatidylcholine per milligram of DNA than control infants. Case reports have reported a benefit of surfactant for infants with CDH. In the near-term infants with severe respiratory distress, surfactant is one of the therapies along with inhaled nitric oxide and high frequency ventilations, that have resulted in improved outcomes. Surfactant treatment may be of significant benefit in newborn infants with respiratory compromise secondary to a number of insults, and further prospective evidence of its efficacy in such disorders is needed.
表面活性剂已使肺不成熟和呼吸窘迫的早产儿的新生儿死亡率显著降低。然而，表面活性剂疗法已被证明对治疗许多其他新生儿呼吸系统疾病有效，并在此介绍了在这种情况下使用表面活性剂的证据。胎粪吸入的特征是严重肺不张、中性粒细胞流入、水肿和透明膜，伴有表面活性蛋白-A（SP-A）和表面活性蛋白-B（SP-B）水平降低以及肺表面活性剂的大聚集体部分，并且表面活性剂表面形态改变。胎粪含有胆固醇、游离脂肪酸和胆红素，所有这些都能以剂量依赖的方式干扰表面活性剂的功能。提供大量表面活性剂可以克服部分这种抑制作用。用表面活性剂治疗的胎粪吸入动物模型的组织学、肺力学和气体交换得到改善。对患有胎粪吸入的人类婴儿的研究发现，肺灌洗液中总蛋白、白蛋白和膜衍生磷脂的浓度升高，以及出血性肺水肿。对此类新生儿的临床研究报告了表面活性剂治疗后气体交换和临床结局得到改善。最近，表面活性剂灌洗已被证明对此类婴儿是一种潜在有效的治疗方法。伴随新生儿肺炎的含有血浆蛋白和细胞因子的炎性渗出物可能会使表面活性剂失活。在气管内注入B族链球菌后给动物进行表面活性剂治疗，可使细菌生长显著减少并改善肺功能。小型临床经验已证明表面活性剂对患有肺炎/败血症的婴儿有益。一些人认为是表面活性剂治疗并发症的肺出血，使用表面活性剂滴注也得到了有效处理。血红蛋白和红细胞脂质可能会抑制天然表面活性剂，并且已证明用表面活性剂治疗可改善患有肺出血婴儿的结局。先天性膈疝（CDH）动物模型的肺发育不全，其II型肺细胞中板层小体减少，导致表面活性剂缺乏，并且对表面活性剂替代治疗有反应，气体交换和肺力学得到改善。患有CDH的人类婴儿的肺每毫克DNA所含的磷脂和磷脂酰胆碱比对照婴儿少。病例报告已报道表面活性剂对患有CDH的婴儿有益。在患有严重呼吸窘迫的近期婴儿中，表面活性剂是与吸入一氧化氮和高频通气一起的治疗方法之一，这些治疗已使结局得到改善。表面活性剂治疗可能对因多种损伤继发呼吸功能不全的新生儿有显著益处，并且需要进一步的前瞻性证据证明其在此类疾病中的疗效。
