肺出血后表面活性物质补充对胎龄<34周早产儿临床预后的改善效用

doi:10.12372/jcp.2025.25e0126

摘要/Abstract

摘要：

目的外源性肺表面活性物质（PS）给药是否可以延长早产儿肺出血后的存活时间，目前尚缺乏足够的证据。本研究旨在评估肺出血后给予表面活性物质对早产儿生存预后的影响。方法研究对象为2017年1月1日至2022年12月31日期间入院的胎龄（GA）<34周早产儿，住院期间罹患有肺出血。肺出血发生后经父母同意将于出血稳定期后额外给予患儿一剂PS治疗，给药时间为肺出血发生后2~4小时。因此，根据医院信息系统的记录，参与者回顾性地被分为肺出血后PS给药组（n=16）和肺出血后非PS给药组（n=40）。结果肺出血后PS给药组新生儿动脉血气数值更佳。此外，PS给药组咖啡因持续用药时间和有创通气持续时间更长（P<0.05）。组间比较显示肺出血后应用PS可以降低72小时及168小时内的短期全因死亡率（P<0.05），但对于702小时内及完整住院期间的全因死亡率，两组比较无显著差异。考虑生存时间应用生存曲线Log-rank检验显示肺出血后应用PS可以降低72小时内、168小时内和完整住院期间内的死亡风险（P<0.05），但对702小时内的死亡风险除外。而Breslow检验则显示肺出血后应用PS可以显著延长肺出血后72小时至出院的生存时间（P<0.05）。结论 GA<34周早产儿肺出血后给予PS可能具有潜在的获益，但是尚需要进一步临床研究以探索该治疗方式是否能够改善此类患儿的远期结局。

关键词: 肺出血, 预后, 死亡率, 肺表面活性物质, 机械通气

Abstract:

Objective Whether exogenous pulmonary surfactant (PS) administration could prolong the survival time of preterm infants after pulmonary hemorrhage is currently a lack of sufficient evidence. This study was conducted to evaluate the effect of surfactant administration after pulmonary hemorrhage on the survival prognosis of preterm infants. Methods The study participants were preterm babies, gestational age (GA) <34 weeks, with pulmonary hemorrhage admitted from January 1, 2017 to December 31, 2022. After pulmonary hemorrhage, infants would be given an additional dose of PS if the parents agreed. The timing of administration is usually 2-4 hours after the pulmonary hemorrhage stabilizes. Accordingly, the participants were retrospectively divided into the PS administration group after pulmonary hemorrhage (n=16) and the non-PS administration group after pulmonary hemorrhage (n=40) according to the records from hospital information system. Results It was found that the blood gas was better after PS administration. Moreover, the survival time, duration of caffeine administration, and duration of invasive ventilation were significantly longer in the PS administration group (P<0.05). The intergroup comparison showed that the application of PS after pulmonary hemorrhage could reduce the short-term all-cause mortality within 72 hours and 168 hours (P<0.05), but for the all-cause mortality within 702 hours and during the complete hospitalization period, there was no significant difference between the two groups. The Log-rank test of the survival curve showed that the application of PS after pulmonary hemorrhage could reduce the risk of death within 72 hours, within 168 hours, and during the full hospitalization period (P<0.05), except for the risk of death within 702 hours. The Breslow test showed that the application of PS after pulmonary hemorrhage could significantly prolong the survival time from 72 hours after pulmonary hemorrhage to discharge (P<0.05). Conclusion Administering PS to preterm infants with gestational age <34 weeks after pulmonary hemorrhage may have potential benefits, further clinical studies are needed to explore whether this treatment can improve the long-term outcomes.

Key words: pulmonary hemorrhage, prognosis, mortality, pulmonary surfactant, mechanical ventilation

中图分类号:

刘云, 潘晶晶, 沈金鑫, 邹芸苏, 程锐, 封云, 杨洋. 肺出血后表面活性物质补充对胎龄<34周早产儿临床预后的改善效用[J]. 临床儿科杂志, 2025, 43(9): 652-660.

LIU Yun, PAN Jingjing, SHEN Jinxin, ZOU Yunsu, CHENG Rui, FENG Yun, YANG Yang. Therapeutic efficacy of surfactant supplementation after pulmonary hemorrhage in improving clinical outcomes of preterm infants with gestational age <34 weeks[J]. Journal of Clinical Pediatrics, 2025, 43(9): 652-660.

图/表 6

图1

表1

表2

肺出血后给予PS和未给予PS两组的主要诊断、治疗、呼吸机参数和实验室检查的比较"

因素	PS应用组(n=16)	PS未应用组(n=40)	统计量	P
主要诊断
Ⅲ-Ⅳ级RDS[n(%)]	8(50.00)	28(70.00)	χ²=1.99	0.158
药物及手术治疗PDA[n(%)]	9(56.25)	26(65.00)	χ²=0.37	0.541
早发型败血症[n(%)]	3(18.75)	5(12.50)	χ²=0.03	0.856
呼吸系统主要治疗
肺出血前给予PS[n(%)]	14(87.50)	37(92.50)	-	0.617^1）
肺出血前给予2剂及以上PS[n(%)]	3(18.75)	12(30.00)	χ²=0.28	0.600
咖啡因用药时长[M(P₂₅~P₇₅)]/d	27.50(10.50~44.50)	5.50(2.00~38.50)	Z=2.02	0.044
肺出血后高频通气[n(%)]	7(43.75)	16(40.00)	χ²=0.07	0.797
有创通气时长[M(P₂₅~P₇₅)]/d	174.00(75.50~497.25)	88.00(39.75~255.75)	Z=2.10	0.036
无创通气时长[M(P₂₅~P₇₅)]/d	109.00(0.00~261.50)	0.00(0.00~322.00)	Z=0.90	0.371
有创通气次数(≥2次)[n(%)]	5(31.25)	13(32.50)	χ²=0.01	0.928
NO吸入[n(%)]	2(12.50)	6(15.00)	χ²=0.00	1.000
机械通气
肺出血前FiO₂[M(P₂₅~P₇₅)]/%	30.00(30.00~40.00)	30.00(27.50~40.00)	Z=0.65	0.519
肺出血后FiO₂[M(P₂₅~P₇₅)]/%	90.00(46.25~100.00)	100.00(55.00~100.00)	Z=0.84	0.403
血气分析[M(P₂₅~P₇₅)]
肺出血1小时内pH值	7.06(6.87~7.13)	7.02(6.85~7.15)	Z=0.13	0.900
肺出血1小时内BE/mmol·L^-1	-12.95(-17.98~-11.50)	-12.75(-18.18~-8.83)	Z=0.63	0.527
肺出血1小时内PaCO₂/mmHg	58.50(47.00~81.80)	70.00(53.40~82.80)	Z=0.59	0.559
肺出血1小时内PaO₂/mmHg	41.00(30.00~76.00)	51.00(27.00~86.25)	Z=0.41	0.684
肺出血6小时后pH值	7.23(7.13~7.35)	7.13(7.00~7.27)	Z=2.04	0.041
肺出血6小时后BE/mmol·L^-1	-4.45(-10.30~-1.58)	-10.10(-11.93~-6.48)	Z=2.11	0.035
肺出血6小时后PaCO₂/mmHg	53.40(37.00~60.10)	61.65(51.45~81.43)	Z=2.15	0.031
肺出血6小时后PaO₂/mmHg	74.00(45.00~95.00)	45.00(35.25~72.50)	Z=2.08	0.038
肺出血24小时后pH值	7.31(7.24~7.42)	7.21(7.12~7.34)	Z=2.19	0.028
肺出血24小时后BE/mmol·L^-1	-3.40(-5.70~-2.00)	-6.40(-8.88~-1.48)	Z=0.98	0.329
肺出血24小时后PaCO₂/mmHg	45.30(31.90~57.40)	58.30(43.05~62.13)	Z=1.93	0.054
肺出血24小时后PaO₂/mmHg	85.00(73.00~95.00)	60.00(50.00~79.50)	Z=2.42	0.016
凝血功能[M(P₂₅~P₇₅)]
肺出血后血小板×10⁹·L^-1	115.50(80.75~155.25)	135.00(63.50~181.75)	Z=0.62	0.537
肺出血后PT/s	17.80(15.70~22.20)	20.65(18.15~25.18)	Z=1.58	0.114
肺出血后APTT/s	90.20(57.60~125.10)	68.20(59.85~99.30)	Z=0.31	0.760
肺出血后TT/s	21.80(18.25~25.65)	22.20(18.53~25.60)	Z=0.02	0.988
肺出血后INR	1.59(1.41~1.99)	1.84(1.61~2.27)	Z=1.52	0.128

表2

表3

表4

图2

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因素	PS应用组（n=16）	PS未应用组（n=40）	统计量	P
母亲数据[n(%)]
足疗程产前激素	8(50.00)	10(25.00)	χ²=3.28	0.070
羊水污染	0(0.00)	2(5.00)	-	1.000^1）
剖宫产	10(62.50)	19(47.50)	χ²=1.03	0.310
母亲糖尿病^2）	4(25.00)	9(22.50)	χ²=0.00	1.000
母亲高血压^3）	2(12.50)	11(27.50)	χ²=0.72	0.395
胎膜早破>18小时	3(18.75)	11(27.50)	χ²=0.12	0.733
新生儿数据
生后6小时内气管插管[n(%)]	13(81.25)	37(92.50)	-	0.338^1）
1分钟Apgar [M（P₂₅~P₇₅）]	8.00(6.00~8.00)	7.00(5.00~8.00)	Z=0.81	0.417
5分钟Apgar [M（P₂₅~P₇₅）]	8.00(7.00~9.00)	8.00(8.00~9.00)	Z=0.38	0.706
出生体重（ x±s)/g	1 176.25±224.85	1 049.25±239.89	t=1.82	0.074
男性[n(%)]	10(62.50)	24(60.00)	χ²=0.03	0.863
胎龄( x±s)/周	28.92±2.01	28.05±1.59	t=1.72	0.092
小于胎龄儿[n(%)]	1(6.25)	4(10.00)	-	1.000^1）
出生时体温( x±s)/℃	35.81±0.63	35.58±0.80	t=0.99	0.328
血气分析[M（P₂₅~P₇₅）]
出生时pH值	7.23(7.14~7.38)	7.29(7.23~7.35)	Z=0.56	0.577
出生时BE值/mmol·L^-1	-5.90(-10.25~-2.50)	-6.00(-8.80~-3.80)	Z=0.31	0.754
出生时PaCO₂/mmHg	46.90(38.95~70.10)	45.10(33.90~57.45)	Z=0.80	0.422
出生时PaO₂/mmHg	94.00(50.75~101.25)	78.00(55.25~100.25)	Z=0.52	0.605
肺出血发生日龄[M（P₂₅~P₇₅）]/d	2.50(2.00~6.75)	3.00(2.00~6.00)	Z=0.60	0.547

因素	PS应用组(n=16)	PS未应用组(n=40)	统计量	P
BPD[n(%)]	7(43.75)	12(30.00)	χ²=0.96	0.326
中-重度BPD[n(%)]	2(12.50)	4(10.00)	-	1.000^1）
气胸[n(%)]	1(6.25)	2(5.00)	-	1.000^1）
NEC(≥Ⅱ期)[n(%)]	1(6.25)	7(17.50)	χ²=0.44	0.507
ROP[n(%)]	3(18.75)	4(10.00)	χ²=0.20	0.655
IVH(≥Ⅲ级)[n(%)]	5(31.25)	11(27.50)	χ²=0.00	1.000
住院时长[M(P₂₅~P₇₅)]/d	39.50(6.75~59.25)	4.50(2.00~54.50)	Z=1.87	0.061

因素	PS应用组	PS未应用组	统计量	P	把握度
院内死亡[n(%)]	7(43.75)	27(67.50)	χ²=2.70	0.100	0.377
肺出血后72小时内全因死亡[n(%)]	3(18.75)	22(55.00)	χ²=6.08	0.014	0.692
肺出血后168小时内全因死亡[n(%)]	5(31.25)	25(62.50)	χ²=4.49	0.034	0.563
肺出血后702小时内全因死亡[n(%)]	7(43.75)	25(62.50)	χ²=1.64	0.200	0.249
肺出血后生存时间[M(P₂₅~P₇₅)]/h	888.50(108.50~1389.50)	34.00(6.00~1191.00)	Z=2.42	0.015	0.999