目的 评价不同剂量国产牛肺表面活性剂治疗呼吸窘迫综合征(respiratory distress syndrome,RDS)早产儿的疗效及安全性. 方法 研究对象为2015年4月1日至12月31日在河北省、山东省、天津市13家医院新生儿重症监护病房(neonatal intensive care unit,NICU)收治的RDS早产儿.采用前瞻性临床随机对照研究方法,将180例符合纳入标准的早产儿分为低剂量组(92例)和高剂量组(88例),首次给药剂量分别为70和140 mg/kg.收集患儿临床资料,比较2组早产儿治疗前后的相关指标,以及病死率和并发症的发生率.采用Student's t检验、Wilcoxon Mann-Whitney秩和检验、x2检验或Fisher's精确检验进行统计学分析. 结果 (1)2组早产儿的累计使用肺表面活性剂剂量比较,差异有统计学意义(P＜0.05),但用药前的氧合指数、血气分析参数等比较,差异均无统计学意义(P值均＞ 0.05).(2)与低剂量组相比,高剂量组在用药后6h动脉血氧分压[(65.3±24.5)与(82.7±36.7) mmHg (1 mmHg=0.133 kPa),t-2.913,P=0.005]及氧合指数(207.2±100.9与268.1±117.8,t=2.897,P=0.005)均较高,但需要插管机械通气时间较短[89 (109)与69 (95)h,Z=2.1 09,P=0.035],应用肺表面活性剂≥2次的比例较低[31.5％(29/92)与18.2％(16/88),x2=4.269,P=0.039],动脉导管未闭发生率较高[15.2％(14/92)与27.3％(24/88),x2=3.925,P=0.048].2组早产儿在无创辅助通气时间、住院天数、住院费用等差异均无统计学意义(P值均＞0.05).(3) 180例中,45例出院前死亡,总的病死率为25.0％(45/180);116例极低出生体重儿中,36例出院前死亡,病死率为31.0％ (36/116).45例死亡早产儿中,31例(68.9％)系放弃治疗后死亡.2组早产儿的病死率及支气管肺发育不良等主要并发症发生率差异均无统计学意义(P值均＞ 0.05). 结论 应用较大剂量珂立苏治疗RDS早产儿,可在短期较好地改善氧合,利于早期拔管,减少再次用药,但并未显著降低院内病死率及主要并发症的发生率.%Objective To evaluate the efficacy and safety of low and high doses of calf pulmonary surfactant (PS) for preterm infants with respiratory distress syndrome (RDS).Methods Subjects recruited in this study were preterm infants with RDS who were admitted to neonatal intensive care unit in 13 hospitals in Tianjin municipality,Hebei and Shandong provinces of China from April 1,2015 to December 31,2015.A prospective randomized controlled clinical trial was conducted on 180 premature infants who met the inclusion criteria.Those infants were randomly divided into two groups:low dosage group (70 mg/kg initially,n=92) and high dosage group (140 mg/kg initially,n=88).Several relevant parameters and primary outcomes including the in-hospital mortality and incidence of major complications were comparatively analyzed between the two groups.Student's t test,Mann-Whitney U test,Chi-square test or Fisher's exact test were used for statistical analysis.Results (1) There were no significant difference between the two groups in gestational age,birth weight,age at admission,male/female ratio,PaO2/FiO2 ratio and blood gas parameters at enrollment (all P＞0.05).But the cumulative dose of PS was higher in the high dosage group than that of the low dosage group.(2) Compared with the low dosage group,oxygenation status in the high dosage group was better at 6 h after PS treatment [PaO2:(65.3±24.5) vs (82.7±36.7) mmHg (1 mmHg=0.133 kPa),t=2.913,P=0.005;PaO2/FiO2:207.2±100.9 vs 268.1 ± 117.8,t=2.897,P=0.005].Moreover,fewer infants received more than two dose of PS [35.1％(29/92) vs 18.2％(16/88),x2=4.269,P=0.039] and shorter median invasive ventilation time [89 (109) vs 69 (95) h,Z=2.109,P=0.035] was needed in the high dosage group.However,incidence of systematic patent ductus arteriosus (PDA) was higher in the high dosage group than that of the low dosage group [27.3％ (24/88) vs 15.2％(14/92),x2=3.925,P=0.048].There were no significant difference between the two groups in the time of non-invasive respiratory support,length and cost of hospital stay (all P＞0.05).(3) The in-hospital mortality rates were about 25％ (45/180) in 180 cases and 31％ (36/116) in 116 cases of very low birth weight infants.Totally,45 preterm infants did not survive among which 31 (68.9％) because of discontinuation of treatment.No significant difference was found between the two groups in the mortality and incidence of major complications such as bronchopulmonary dysplasia,pneumorrhagia and severe intracranial hemorrhage (all P＞0.05).Conclusions A dose of 140 mg/kg calsurf given to preterm infants with RDS can assure better oxygenation index values within a short time,earlier extubation and fewer retreatments.However,there are no significant reduction in the in-hospital mortality and incidence of major complications.
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