雾化肺表面活性物质联合无创辅助通气治疗新生儿呼吸窘迫综合征

doi:10.3969/j.issn.1000-8535.2022.02.001

摘要/Abstract

摘要： 目的为初步评估在无创辅助通气基础上进行雾化肺表面活性物质(AS)治疗呼吸窘迫综合征(RDS)早产儿的安全性及效果,开展了此项临床研究。方法 2019年7月—2020年6月,经监护人知情同意,符合入选标准的RDS早产儿,入院后在经鼻间歇正压通气(NIPPV)基础上,通过振动筛网雾化器系统给予100 mg/kg注射用牛肺表面活性剂,雾化完毕继续无创辅助通气。详细观察及记录患儿在雾化初期的生命体征及血气分析结果,记录在雾化治疗期间不良反应发生情况以及患儿病情转归情况。结果 20例患儿参与研究,1例出生后26天死亡,其余均存活出院。5例在AS治疗后3天内无创辅助通气失败。和雾化前比较,AS治疗后1小时患儿血气分析主要指标均改善,血氧饱和度上升,心率下降(P＜0.05),但血压及呼吸机参数无明显变化(P＞0.05)。在雾化过程中,所有患儿无明显不良反应发生。结论此项临床研究初步显示AS联合无创辅助通气治疗早产儿RDS是安全可行的,但尚需进一步临床研究评估其效果。

关键词: 肺表面活性物质, 雾化, 无创辅助通气, 新生儿呼吸窘迫综合征, 早产儿

Abstract: Objective To evaluate the safety and efficacy of non-invasive ventilation with aerosolized surfactant (AS) in the treatment of premature infants with respiratory distress syndrome (RDS). Methods From July 2019 to June 2020, in this unblinded Phase I study, the premature infants with RDS who met the criteria with the informed consent of their guardians were enrolled. They were treated with nasal intermittent positive pressure ventilation (NIPPV) and received one dose (100 mg/kg) of aerosolized surfactant by vibrating mesh system (Aeroneb Solo) after hospitalization. The vital signs, adverse reactions and blood gas during areosolizing were recorded and prognosis of them also recorded in detail. Results Twenty infants were enrolled, nineteen completed the study, one died in 26 days. Five infants still required endotracheal intubation and mechanical ventilation after AS treatment. One hour after AS treatment, infants' oxygen saturation and indicators of pulse oximetry improved (P＜0.05), and heart rate decreased (P＜0.05) , but blood pressure and parameters of ventilator had no change (P＞0.05). Infants all tolerated the aerosol treatment well. No other significant adverse events were identified. Conclusion We have demonstrated the feasibility and safety of AS treatment in preterm infants with RDS receiving non-invasive respiratory support. The treatment was well tolerated by infants and clinical caregivers , but still need further study.

Key words: surfactant, aerosol, non-invasive ventilation, respiratory distress syndrome, prematurity

刘颖, 段顺艳, 杜岚岚, 王柱, 陈佳, 高薇薇. 雾化肺表面活性物质联合无创辅助通气治疗新生儿呼吸窘迫综合征[J]. 广州医药, 2022, 53(2): 1-6.

LIU Ying, DUAN Shunyan, DU Lanlan, WANG Zhu, CHEN Jia, GAO Weiwei. Aerosolized surfactant with non-invasive ventilation in respiratory distress syndrome: Phase I study[J]. Guangzhou Medical Journal, 2022, 53(2): 1-6.

参考文献

[1] SWEET D G, 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.
[2] ENGLE W A. Surfactant-replacement therapy for respiratory distress in the preterm and term neonate[J]. Pediatrics, 2008, 121(2): 419-432.
[3] FINER N N, CARLO W A, WALSH M C, et al. Early CPAP versus surfactant in extremely preterm infants[J]. N Engl J Med, 2010, 362(21): 1970-1979.
[4] BERLINSKI A, WILLIS J R. Albuterol delivery by 4 different nebulizers placed in 4 different positions in a pediatric ventilator in vitro model[J]. Respir Care, 2012, 58(7): 1124-1133.
[5] DIJK P H, HEIKANYS A, BAMBANG OETOMO S. Surfactant nebulisation: lung function, surfactant distribution and pulmonary blood flow distribution in lung lavaged rabbits[J]. Intensive Care Med, 1997, 23(10): 1070-1076.
[6] SOOD B G, THOMAS R, DELANEY-BLACK V, et al. Aerosolized beractant in neonatal respiratory distress syndrome: a randomized fixed-dose parallel-arm phase Ⅱ trial[J]. Pulm Pharmacol Ther, 2021(66): 101986.
[7] CUMMINGS J J, GERDAY E, MINTON S, et al. Aerosolized calfactant for newborns with respiratory distress: a randomized trial[J]. Pediatrics,2020, 146(5): e20193967.
[8] 谭艳芳, 王柱, 高薇薇, 等. 经鼻间歇正压通气联合振动网格雾化肺表面活性物质治疗新生儿肺透明膜病1例[J]. 广东医学, 2019, 40(S1): 1-3.
[9] 邵肖梅, 叶鸿瑁, 丘小汕. 实用新生儿学[M]. 5版. 北京: 人民卫生出版社, 2019: 575-578.
[10] 中国医师协会新生儿科医师分会. 早产儿经鼻间歇正压通气临床应用指南(2019年版)[J].中华儿科杂志, 2019, 57(4): 248-251.
[11] BERGGREN E, LILJEDAHL M, WINBLADH B, et al. Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome[J]. Acta Paediatr, 2000, 89(4): 460-464.
[12] FINER N N, MERRITT A T, BERNSTEIN G, et al. An open label, pilot study of serosurf^® combined with nCPAP to prevent RDS in preterm neonates[J]. J Aerosol Med Pulm Drug Deliv, 2010, 23(5): 303-310.
[13] MINOCCHIERI S, BERRY C A, PILLOW J J, et al. Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomised controlled trial[J]. Arch Dis Child Fetal Neonatal Ed, 2019, 104(3): F313-F319.
[14] SOODA B G, CORTEZD J, KOLLIC M, et al. Aerosolized surfactant in neonatal respiratory distress syndrome: Phase I study[J]. Early Hum Dev, 2019(134): 19-25.
[15] DUBUS J C, VECELLIO L, de MONTE M, et al. Aerosol deposition in neonatal ventilation[J]. Pediatr Res, 2005, 58(1) :10-14.
[16] PILLOW J J, MINOCCHIERI S. Innovation in surfactant therapy II: surfactant administration by aerosolization[J]. Neonatology, 2012, 101(4): 337-344.
[17] JORCH G, HARTEL H, ROTH B, et al. Surfactant aerosol treatment of respiratory distress syndrome in spontaneously breathing premature infants[J]. Pediatr Pulmonol, 1997, 24(3): 222-224.
[18] ARROE M, PEDERSEN-BJERGAARD L, ALBERTSEN P, et al. Inhalation of aerosolized surfactant (Exosurf) to neonates treated with nasal continuous positive airway pressure[J]. Prenat Neonat Med, 1998(3): 346-352.
[19] BIANCO F, RICCI F, CATOZZI C, et al. From bench to bedside: in vitro and in vivo evaluation of a neonate-focused nebulized surfactant delivery strategy[J]. Respir Res, 2019, 20(1): 134.
[20] ARI A, HARWOOD R, LING H, et al. Comparisons of the RAM cannula with high flow nasal cannula (HFNC) on aerosol drug delivery in a simulated neonatal lung model[J]. Respir Care, 2012, 57 (10): 1704.