Merritt T A, Hallman M, Berry C, Pohjavuori M, Edwards D K, Jaaskelainen J, Grafe M R, Vaucher Y, Wozniak P, Heldt G
Department of Pediatrics, University of California, San Diego.
J Pediatr. 1991 Apr;118(4 Pt 1):581-94. doi: 10.1016/s0022-3476(05)83387-6.
A randomized, placebo-controlled trial of human surfactant given intratracheally at birth (prophylactic) versus rescue administration after the onset of severe respiratory distress syndrome (RDS) was conducted among preterm infants born at 24 to 29 weeks of gestation. Singleton fetuses were randomly assigned to receive (1) placebo (air), (2) prophylactic surfactant treatment, or (3) rescue surfactant treatment; infants of multiple births received either (1) prophylactic or (2) rescue treatment. Of 282 potentially eligible fetuses, 246 infants received treatments at birth and 200 infants had RDS. Outcomes are presented both as an intention-to-treat analysis (including infants who met exclusion criteria at or after birth) and as a full treatment protocol analysis for those infants with RDS and likely to benefit from surfactant. Preterm infants (mean 1.0 kg birth weight, 27 to 28 weeks of gestational age) randomly assigned to receive prophylactic treatment received surfactant soon after birth; those assigned to receive rescue surfactant had instillation at a mean age of 220 minutes if the lecithin-sphingomyelin ratio was less than or equal to 2.0 and no phosphatidylglycerol was detected in either amniotic fluid or initial airway aspirate, oxygen requirements were a fraction of inspired oxygen of greater than 0.5, and mean airway pressure was greater than or equal to 7 cm H2O from 2 to 12 hours after birth. Up to four treatment doses (or air) were permitted within 48 hours; approximately 60% of surfactant-treated infants required two or more doses. Surfactant-treated infants had significantly less pulmonary interstitial emphysema than placebo-treated infants (p = 0.02), but there were no other significant differences in mortality rates or morbidity. Indexes of oxygenation and ventilation were improved in surfactant recipients during the first 24 hours. An intention-to-treat analysis found no significant differences between infants given placebo and surfactant-treated infants or between prophylactic- and rescue-treated infants; an improved total mortality rate (p = 0.002) was found among surfactant-treated infants in Helsinki but not in San Diego. Among infants with RDS, the total mortality rate was significantly improved (p = 0.004) with surfactant treatment but not the proportion alive and without bronchopulmonary dysplasia at 28 days (p = 0.052), or the proportion alive and without bronchopulmonary dysplasia at 38 weeks of postconceptional age (p = 0.18) to adjust for differences in prematurity. Deaths caused by RDS or bronchopulmonary dysplasia were significantly reduced among surfactant recipients (p = 0.0001). Neither among singletons nor among multiple-birth infants was there a selective advantage to prophylactic versus rescue treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
在妊娠24至29周出生的早产儿中，开展了一项随机、安慰剂对照试验，比较出生时经气管内给予人表面活性剂（预防性）与在严重呼吸窘迫综合征（RDS）发作后给予挽救性给药的效果。单胎胎儿被随机分配接受：（1）安慰剂（空气），（2）预防性表面活性剂治疗，或（3）挽救性表面活性剂治疗；多胎婴儿接受（1）预防性或（2）挽救性治疗。在282名可能符合条件的胎儿中，246名婴儿在出生时接受了治疗，200名婴儿患有RDS。结果以意向性分析（包括出生时或出生后符合排除标准的婴儿）以及对那些患有RDS且可能从表面活性剂中获益的婴儿进行的完整治疗方案分析呈现。随机分配接受预防性治疗的早产儿（平均出生体重1.0kg，胎龄27至28周）在出生后不久接受表面活性剂；那些被分配接受挽救性表面活性剂治疗的婴儿，如果卵磷脂 - 鞘磷脂比值小于或等于2.0，且在羊水或初始气道吸出物中未检测到磷脂酰甘油，出生后2至12小时内吸入氧分数大于0.5，平均气道压大于或等于7cm H₂O，则在平均220分钟龄时进行滴注。48小时内允许给予最多四剂治疗（或空气）；约60%接受表面活性剂治疗的婴儿需要两剂或更多剂。接受表面活性剂治疗的婴儿肺间质肺气肿明显少于接受安慰剂治疗的婴儿（p = 0.02），但在死亡率或发病率方面没有其他显著差异。在最初24小时内，接受表面活性剂治疗的婴儿的氧合和通气指标有所改善。意向性分析发现，给予安慰剂的婴儿与接受表面活性剂治疗的婴儿之间或预防性治疗与挽救性治疗的婴儿之间没有显著差异；在赫尔辛基，接受表面活性剂治疗的婴儿总死亡率有所改善（p = 0.002），但在圣地亚哥则没有。在患有RDS的婴儿中，表面活性剂治疗使总死亡率显著改善（p = 0.004），但在出生后28天存活且无支气管肺发育不良的比例（p = 0.052）或孕龄38周时存活且无支气管肺发育不良的比例（p = 0.18）方面没有改善，以调整早产差异。接受表面活性剂治疗的婴儿中，由RDS或支气管肺发育不良导致的死亡显著减少（p = 0.0001）。无论是单胎还是多胎婴儿，预防性治疗与挽救性治疗相比均无选择性优势。（摘要截短至400字）
