Kattwinkel J, Bloom B T, Delmore P, Glick C, Brown D, Lopez S, Willett L, Egan E A, Conaway M, Patrie J
University of Virginia, Charlottesville, Virginia, USA.
Pediatrics. 2000 Aug;106(2 Pt 1):282-8. doi: 10.1542/peds.106.2.282.
Surfactant therapy has become an effective standard therapy for infants with respiratory distress syndrome (RDS). The first dose may be given either as prophylaxis immediately after delivery, or as rescue after an infant has developed RDS. Second and subsequent doses are currently recommended by the manufacturers to be administered at minimal levels of respiratory support.
This study compared the relative efficacy of administering second and subsequent doses of Infasurf surfactant at a low threshold (FIO(2) >30%, still requiring endotracheal intubation) versus a high threshold (FIO(2) >40%, mean airway pressure >7 cm H(2)O) of respiratory support.
A total of 2484 neonates received a first dose of surfactant; 1267 reached conventional retreatment criteria and were randomized to be retreated according to low- or high-threshold criteria. They were then retreated at a minimum of 6-hour intervals each time they reached their assigned threshold until receiving a maximum of 4 total doses. Subjects were stratified by whether they received their first dose by prophylaxis or rescue and by whether their lung disease was considered complicated (evidence of perinatal compromise or sepsis) or uncomplicated.
Among the patients randomized, 33% of prophylaxis and 23% of rescue subjects met criteria for the complicated stratum. Although infants allocated to the high-threshold strategy were receiving slightly more oxygen at 72 hours, there was no difference in the number receiving mechanical ventilation at 72 hours or in the secondary respiratory outcomes (requirement for supplemental oxygen or mechanical ventilation at 28 days, supplemental oxygen at 36 weeks' postconceptional age, inspired oxygen concentration >60% at any time). However, there was a significantly higher mortality for infants with complicated RDS who had received retreatment according to the high-threshold strategy.
We conclude that equal efficacy can be realized by delaying surfactant retreatment of infants with uncomplicated RDS until they have reached a higher level of respiratory support than is the current standard. We speculate that this would result in a substantial cost-saving from less utilization of drug. Conversely, we believe that infants with complicated RDS should continue to be treated by the low-threshold retreatment strategy, which is currently recommended by the manufacturers of the commercially available surfactants.
表面活性剂疗法已成为治疗呼吸窘迫综合征（RDS）婴儿的一种有效标准疗法。首剂可在分娩后立即作为预防用药给予，或在婴儿发生RDS后作为抢救用药给予。目前，制造商建议在最低呼吸支持水平下给予第二剂及后续剂量。
本研究比较了在低阈值（FIO₂>30%，仍需气管插管）与高阈值（FIO₂>40%，平均气道压>7 cm H₂O）呼吸支持下给予第二剂及后续剂量的英孚素表面活性剂的相对疗效。
共有2484例新生儿接受了首剂表面活性剂；1267例达到传统再治疗标准，并根据低阈值或高阈值标准随机分组进行再治疗。然后，他们每次达到指定阈值时至少间隔6小时进行再治疗，直至总共最多接受4剂。根据是否通过预防或抢救接受首剂以及肺部疾病是否被认为复杂（围产期并发症或败血症的证据）对受试者进行分层。
在随机分组的患者中，33%的预防组和23%的抢救组符合复杂分层标准。尽管分配到高阈值策略的婴儿在72小时时接受的氧气略多，但在72小时时接受机械通气的人数或次要呼吸结局（28天时需要补充氧气或机械通气、孕龄36周时补充氧气、任何时候吸入氧浓度>60%）方面没有差异。然而，接受高阈值策略再治疗的复杂RDS婴儿的死亡率显著更高。
我们得出结论，对于无并发症的RDS婴儿，将表面活性剂再治疗推迟到他们达到比当前标准更高的呼吸支持水平，可以实现相同的疗效。我们推测，这将因减少药物使用而大幅节省成本。相反，我们认为，有并发症的RDS婴儿应继续采用目前市售表面活性剂制造商推荐的低阈值再治疗策略。
