
微创应用肺表面活性物质治疗早产儿呼吸窘迫综合征失败的高危因素分析
刘慧强, 童笑梅, 韩彤妍, 张慧, 郭明, 张雪峰, 刘新建, 张翔, 张铭涛, 刘芳, 暴丽莎, 郑军, 田秀英, 高琦, 张婉娴, 段洋, 孙夫强, 郭玮, 李玲, 肖敏, 刘伟力, 姜瑞
中国当代儿科杂志 ›› 2020, Vol. 22 ›› Issue (3) : 231-237.
微创应用肺表面活性物质治疗早产儿呼吸窘迫综合征失败的高危因素分析
Risk factors for minimally invasive surfactant administration failure in preterm infants with respiratory distress syndrome
目的 探讨肺表面活性物质微创给药方式(MISA)治疗早产儿呼吸窘迫综合征(RDS)失败的高危因素及其对早产儿的影响。方法 回顾性分析2017年7月1日至2018年12月31日京津冀地区8家三级医院新生儿重症监护病房应用MISA给予牛肺表面活性物质(PS)治疗胎龄≤ 32周,且临床考虑为RDS早产儿(n=148)的基本信息、围产期情况、用药情况、合并症、临床转归等病例资料。根据MISA治疗是否失败(MISA失败定义为MISA后72 h内需要机械通气)分为MISA失败组(n=16)和MISA成功组(n=132)。应用logistic回归分析MISA失败的高危因素及其对早产儿的影响。结果 MISA失败率为10.8%(16/148)。logistic回归分析结果显示用药前RDS > Ⅱ级发生率高、用药前平均动脉压低、用药前脉压差大、首次给药剂量低、注药时间及总操作时间长是MISA失败的危险因素(分别OR=5.983、1.210、1.183、1.055、1.036、1.058,P < 0.05)。控制上述高危因素后行logistic回归分析结果显示MISA失败组BPD的发生率高(OR=8.537,P < 0.05)。结论 给药前RDS程度重、血压监测平均动脉压低、脉压差大是MISA失败的独立危险因素;首次PS给药剂量低、注药时间及总操作时间长可能增加MISA失败的风险;MISA失败可能导致早产儿BPD发生率增加。
Objective To identify risk factors for minimally invasive surfactant administration (MISA) failure in the treatment of preterm infants with respiratory distress syndrome (RDS) and the influence of MISA failure on neonatal outcome. Methods A retrospective analysis was performed for the clinical data of 148 preterm infants with a gestational age of ≤ 32 weeks and a clinical diagnosis of RDS, who were admitted to the neonatal intensive care unit of eight tertiary hospitals in Beijing, Tianjin and Hebei Province from July 1, 2017 to December 31, 2018 and were treated with MISA (bovine pulmonary surfactant, PS). According to whether MISA failure (defined as the need for mechanical ventilation within 72 hours after MISA) was observed, the infants were divided into two groups:MISA failure group (n=16) and MISA success (n=132). A logistic regression analysis was used to investigate the risk factors for MISA failure and its influence on neonatal outcome. Results The MISA failure rate was 10.8% (16/148). The logistic regression analysis showed that a high incidence rate of grade > II RDS before PS administration, low mean arterial pressure and high pulse pressure before administration, a low dose of initial PS administration, and long injection time and operation time were the risk factors for MISA failure (OR=5.983, 1.210, 1.183, 1.055, 1.036, and 1.058 respectively, P < 0.05). After the control for the above risk factors, the logistic regression analysis showed that the MISA failure group had a significantly higher incidence rate of bronchopulmonary dysplasia (BPD) (OR=8.537, P < 0.05). Conclusions A high grade of RDS, a low mean arterial pressure, and a high pulse pressure before administration are independent risk factors for MISA failure, and a low dose of initial PS administration, a long injection time, and a long operation time may increase the risk of MISA failure. MISA failure may increase the incidence rate of BPD in preterm infants.
新生儿呼吸窘迫综合征 / 微创给药 / 肺表面活性物质 / 早产儿
Neonatal respiratory distress syndrome / Minimally invasive surfactant administration / Pulmonary surfactant / Preterm infant
[1] Aguar M, Nuñez A, Cubells E, et al. Administration of surfactant using less invasive techniques as a part of a non-aggressive paradigm towards preterm infants[J]. Early Hum Dev, 2014, 90(Suppl 2):S57-S59.
[2] Sweet DG, Carnielli V, Greisen G, et al. European consensus guidelines on the management of respiratory distress syndrome-2016 update[J]. Neonatology, 2017, 111(2):107-125.
[3] 邵肖梅, 叶鸿瑁, 丘小汕. 实用新生儿学[M]. 第4版. 北京:人民卫生出版社, 2011:395-398, 534-535, 408-410, 706-715, 715-719, 401-405, 340-347, 887-892, 416-423.
[4] Sweet DG, Carnielli V, Greisen G, et al. European consensus guidelines on the management of respiratory distress syndrome-2019 update[J]. Neonatology, 2019, 115(4):432-450.
[5] Verder H, Agertoft L, Albertsen P, et al. Surfactant treatment of newborn infants with respiratory distress syndrome primarily treated with nasal continuous positive air pressure. A pilot study[J]. Ugeskr Laeger, 1992, 154(31):2136-2139.
[6] Kribs A, Pillekamp F, Hünseler C, et al. Early administration of surfactant in spontaneous breathing with nCPAP:feasibility and outcome in extremely premature infants (postmenstrual age ≤ 27 weeks)[J]. Paediatr Anaesth, 2007, 17(4):364-369.
[7] Dargaville PA, Aiyappan A, De Paoli AG, et al. Minimallyinvasive surfactant therapy in preterm infants on continuous positive airway pressure[J]. Arch Dis Child Fetal Neonatal Ed, 2013, 98(2):F122-F126.
[8] Göpel W, Kribs A, Ziegler A, et al. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV):an open-label, randomised, controlled trial[J]. Lancet, 2011, 378(9803):1627-1634.
[9] Isayama T, Iwami H, McDonald S, et al. Association of noninvasive ventilation strategies with mortality and bronchopulmonary dysplasia among preterm infants:a systematic review and meta-analysis[J]. JAMA, 2016, 316(6):611-624.
[10] Janssen LC, Van Der Spil J, van Kaam AH, et al. Minimally invasive surfactant therapy failure:risk factors and outcome[J]. Arch Dis Child Fetal Neonatal Ed, 2019, 104(6):F636-F642.
[11] 朱佳骏. LISA/MIST技术与早产儿呼吸系统疾病的预后[J]. 中国实用儿科杂志, 2018, 33(5):338-334.
[12] Clyman RI. The role of patent ductus arteriosus and its treatments in the development of bronchopulmonary dysplasia[J]. Semin Perinatol, 2013, 37(2):102-107.
[13] Aguar M, Cernada M, Brugada M, et al. Minimally invasive surfactant therapy with a gastric tube is as effective as the intubation, surfactant, and extubation technique in preterm babies[J]. Acta Paediatr, 2014, 103(6):e229-e233.
[14] De Luca D, Minucci A, Gentile L, et al. Surfactant inadvertent loss using feeding catheters or endotracheal tubes[J]. Am J Perinatol, 2014, 31(3):209-212.
[15] Niemarkt HJ, Kuypers E, Jellema R, et al. Effects of lessinvasive surfactant administration on oxygenation, pulmonary surfactant distribution, and lung compliance in spontaneously breathing preterm lambs[J]. Pediatr Res, 2014, 76(2):166-170.
[16] Rigo V, Debauche C, Maton P, et al. Rigid catheters reduced duration of less invasive surfactant therapy procedures in manikins[J]. Acta Paediatr, 2017, 106(7):1091-1096.
[17] Niemarkt HJ, Hütten MC, Kramer BW. Surfactant for respiratory distress syndrome:new ideas on a familiar drug with innovative applications[J]. Neonatology, 2017, 111(4):408-414.
[18] Cogo PE, Facco M, Simonato M, et al. Dosing of porcine surfactant:effect on kinetics and gas exchange in respiratory distress syndrome[J]. Pediatrics, 2009, 124(5):e950-e957.
[19] Manuck TA, Levy PT, Gyamfi-Bannerman C. Dosing of porcine surfactant:effect on kinetics and gas exchange in respiratory distress syndrome[J]. JAMA Pediatr, 2016, 170(5):e154577.
[20] 高永祥, 张晋昕. Logistic回归分析的样本量确定[J]. 循证医学, 2018, 18(2):122-124.
[21] Peduzzi P, Concato J, Kemper E, et al. A simulation study of the number of events per variable in logistic regression analysis[J]. J Clin Epidemiol, 1996, 49(12):1373-1379.