肺表面活性物质联合布地奈德气管内给药对早产儿支气管肺发育不良的防治效果
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摘要
目的探讨肺表面活性物质(PS)联合布地奈德气管内给药对早产儿支气管肺发育不良(BPD)的防治效果。方法选取2014年8月至2016年12月首都医科大学附属北京妇产医院新生儿重症监护病房(NICU)收治的胎龄<32周、出生体质量≤1 500 g、出生后即转入NICU并诊断新生儿呼吸窘迫综合征的早产儿86例为研究对象。完全随机分为观察组(40例,PS 100 mg/kg联合布地奈德0.25 mg/kg气管内给药)和对照组(46例,单纯应用PS 100 mg/kg气管内给药)。监测2组患儿血气及炎症因子等指标变化,记录给药频次及呼吸机应用时间,以及纠正胎龄36周时用氧情况。结果观察组和对照组给药前血氧分压差异无统计学意义(P>0. 05),给药后24、48 h时观察组明显高于对照组[60(56,63) mmHg(1 mmHg=0. 133 kPa)比56(53,57) mmHg、60(57,63) mmHg比56 (54,58) mmHg](P <0. 01)。观察组给药前血二氧化碳分压明显低于对照组[58 (53,67) mmHg比66 (59,71) mmHg](P<0.01),给药后8 h起2组血二氧化碳分压均降低,给药后24、48 h时2组间差异无统计学意义[49(45,50)mmHg比50(46,51)mmHg、48(45,50)mmHg比48(46,50)mmHg](P>0.05)。观察组给药频次明显少于对照组,住院治疗期间呼吸机应用时间明显短于对照组[7.00(4.00,8. 00)h比8.00(6.75,10.00)h](P<0.01)。2组纠正胎龄36周时用氧情况差异无统计学意义(P>0.05)。观察组患儿出生后2周血清白细胞介素1、6、8水平明显低于对照组[37(25,59)μg/L比61(37,81)μg/L、37(28,57)μg/L比48(31,90)μg/L、37(28,51)μg/L比50(29,86)μg/L](P<0. 05)。结论 PS联合布地奈德气管内滴入治疗可以改善早产儿出生后氧合情况,减少给药次数,缩短呼吸机使用时间,抑制炎症因子水平的升高,从而达到防治BPD的效果。
Objective To explore the effect of intratracheal administration of pulmonary surfactant( PS)plus budesonide on bronchopulmonary dysplasia( BPD) in premature infants. Methods From August 2014 to December 2016, a total of 86 preterm infants with gestational age <32 weeks, birth weight≤ 1 500 g, diagnosed of neonatal respiratory distress syndrome and transferred into neonatal intensive care unit( NICU) after birth were enroll in Beijing Obstetrics and Gynecology Hospital, Capital Medical University. They were randomly assigned into PS plus budesonide group(n =40) and PS-alone group(n =46); PS(100 mg/kg) and budesonide(0.25 mg/kg)were administered through intratracheal tube and instillation. Blood gas and inflammatory indicators, drug administration frequency, mechanical ventilation time and oxygenation status at 36-week corrected fetal age were analyzed.Results There was no statistical difference of oxygen partial pressure between groups before treatment(P >0. 05);oxygen partial pressure at 24, 48 h after treatment in PS plus budesonide group was significantly higher than that in PS-alone group[60(56,63) mmHg vs 56(53,57) mmHg; 60(57,63) mmHg vs 56(54,58) mmHg](P < 0. 01).Before treatment, carbon dioxide partial pressure in PS plus budesonide group was significantly lower than that in PS-alone group[58(53,67)mmHg vs 66(59,71) mmHg]( P < 0. 01) and it gradually decreased at 8, 24, 48 h after treatment. At 24, 48 h after treatment, carbon dioxide partial pressure showed no significant difference between groups[49(45,50) mmHg vs 50(46,51) mmHg, 48(45,50) mmHg vs 48(46,50) mmHg](P > 0. 05).The frequency of drug administration and the time of ventilator application [ 7.00( 4.00, 8. 00) h vs8. 00(6. 75,10. 00) h] in PS plus budesonide group were significantly less/shorter than those in PS-alone group(P <0. 01). There was no significant difference of oxygenation status at 36-week corrected fetal age between groups(P >0. 05). At 2 weeks after birth, levels of serum interleukin-1,-6,-8 in PS plus budesonide group were significantly lower than those in PS-alone group [ 37( 25,59)μg/L vs 61(37,81) μg/L; 37(28,57) μg/L vs48(31,90) μg/L; 37(28,51) μg/L vs 50(29,86) μg/L](P <0. 05). Conclusion Intratracheal administration of PS combined with budesonide can improve the oxygenation status of preterm infants, reduce the frequency of administration, shorten the application time of ventilator and inhibit the increase of inflammatory proteins, which can prevent the occurrence of BPD.
Objective To explore the effect of intratracheal administration of pulmonary surfactant( PS)plus budesonide on bronchopulmonary dysplasia( BPD) in premature infants. Methods From August 2014 to December 2016, a total of 86 preterm infants with gestational age <32 weeks, birth weight≤ 1 500 g, diagnosed of neonatal respiratory distress syndrome and transferred into neonatal intensive care unit( NICU) after birth were enroll in Beijing Obstetrics and Gynecology Hospital, Capital Medical University. They were randomly assigned into PS plus budesonide group(n =40) and PS-alone group(n =46); PS(100 mg/kg) and budesonide(0.25 mg/kg)were administered through intratracheal tube and instillation. Blood gas and inflammatory indicators, drug administration frequency, mechanical ventilation time and oxygenation status at 36-week corrected fetal age were analyzed.Results There was no statistical difference of oxygen partial pressure between groups before treatment(P >0. 05);oxygen partial pressure at 24, 48 h after treatment in PS plus budesonide group was significantly higher than that in PS-alone group[60(56,63) mmHg vs 56(53,57) mmHg; 60(57,63) mmHg vs 56(54,58) mmHg](P < 0. 01).Before treatment, carbon dioxide partial pressure in PS plus budesonide group was significantly lower than that in PS-alone group[58(53,67)mmHg vs 66(59,71) mmHg]( P < 0. 01) and it gradually decreased at 8, 24, 48 h after treatment. At 24, 48 h after treatment, carbon dioxide partial pressure showed no significant difference between groups[49(45,50) mmHg vs 50(46,51) mmHg, 48(45,50) mmHg vs 48(46,50) mmHg](P > 0. 05).The frequency of drug administration and the time of ventilator application [ 7.00( 4.00, 8. 00) h vs8. 00(6. 75,10. 00) h] in PS plus budesonide group were significantly less/shorter than those in PS-alone group(P <0. 01). There was no significant difference of oxygenation status at 36-week corrected fetal age between groups(P >0. 05). At 2 weeks after birth, levels of serum interleukin-1,-6,-8 in PS plus budesonide group were significantly lower than those in PS-alone group [ 37( 25,59)μg/L vs 61(37,81) μg/L; 37(28,57) μg/L vs48(31,90) μg/L; 37(28,51) μg/L vs 50(29,86) μg/L](P <0. 05). Conclusion Intratracheal administration of PS combined with budesonide can improve the oxygenation status of preterm infants, reduce the frequency of administration, shorten the application time of ventilator and inhibit the increase of inflammatory proteins, which can prevent the occurrence of BPD.
引文
[1]黄上明,陈丽芝,肖万祥,等.早产儿支气管肺发育不良的早期诊断和治疗(附3例报告)[J].中国煤炭工业医学杂志,2013,16(11):1896-1898. DOI:10.11723/mtgyyx1007-9564201311062.Huang SM, Chen LZ, Xiao WX, et al. Early diagnosis and treatment of bronchopulmonary dysplasia in premature infants(report of 3 cases)[J]. Chinese Journal of Coal Industry Medicine, 2013, 16(11):1896-1898. DOI:10. 11723/mtgyyx1007-9564201311062.
[2]董建敏,安丽.PS对早产儿外周血T淋巴细胞和NK细胞的影响[J].中华全科医学,2013,11(2):177-178.Dong JM, An L. Explore the effect of exogenous surfactant therapy on levels of T lymphocytes and NK cells in peripheral blood[J].Chinese Journal of General Practice, 2013,11(2):177-178.
[3]孔祥永,杨常栓,吴江永,等.预防性应用肺表面活性物质对早产儿早期预后的影响[J].中国医刊,2016,51(8):72-76.DOI:10.3969/j. issn. 1673-7210.2011.10.025.Kong XY, Yang CS, Wu JY, et al. Prophylactic surfactant replacement on the outcomes of neonates less than 32 complete weeks[J]. Chinese Journal of Medicine,2016,51(8):72-76.DOI:10.3969/j. issn. 1673-7210.2011. 10.025.
[4] Yeh TF, Chen CM, Wu SH, et al. Intra-tracheal administration of budesonide/surfactant to prevent bronchopulmonary dysplasia[J].Am J Respir Crit Care Med, 2016,193(1):86-95. DOI:10.1164/rccm. 201505-08610C.
[5] Venkataraman R, Kamaluddeen M, Hasan SU, et al. Intratracheal Administration of Budesonide-Surfactant in Prevention of bronchopulmonary dysplasia in very low birth weight infants:a systematic review and meta-analysis[J]. Pediatr Pulmonol, 2017,52(7):968-975. DOI:10.1002/ppul.23680.
[6]施弦,郁峰.布地奈德联合孟鲁司特对支气管哮喘患儿炎性因子及免疫功能的影响[J].中国医药,2018,13(1):55-58. D01:10.3760/cma. j. issn. 1673-4777. 2018.01.015.Shi X,Yu F. Effect of budesonide combined with montelukast on inflammatory factors and immune function in children with bronchial asthma[J]. China Medicine, 2018,13(1):55-58. DOI:10.3760/cma.j.issn. 1673-4777.2018.01.015.
[7]诸福堂,吴瑞萍,胡亚美.实用儿科学[M].4版.北京:人民卫生出版社,1994:416.Zhu FT, Wu RP, Hu YM. Practical pediatrics[M]. 4th ed. Beijing:People's Medical Publishing House,1994:416.
[8] Northway WH Jr, Rosan RC, Poter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia[J]. N Engl J Med, 1967,276(7):357-368. DOI:10.1056/NEJM196702162760701.
[9]王颖.支气管肺发育不良(新生儿慢性肺疾病)的诊断与治疗[J].实用医学杂志,2005,21(17):1859-1860. DOI:10.3969/j. issn. 1006-5725.2005. 17.002.Wang Y. Diagnosis and treatment of bronchopulmonary dysplasia(neonatal chronic pulmonary disease)[J]. The Journal of Practical Medicine, 2005,21(17):1859-1860. DOI:10.3969/j.issn.1006-5725.2005.17.002.
[10]吕勤,蔡成.早产儿支气管肺发育不良的诊治现状[J].现代实用医学,2011,23(6):610-612,658.DOI:10.3969/j.issn.1671-0800.2011.06.004.Lyu Q, Cai C. Status of diagnosis and treatment of premature bronchopulmonary dysplasia[J]. Modem Practical Medicine,2011,23(6):610-612,658. DOI:10. 3969/j. issn. 1671-0800.2011.06.004.
[11]吕改玲,吕爱红.早期干预治疗新生儿呼吸窘迫综合征的疗效及护理[J].中国煤炭工业医学杂志,2012,15(11):1769-1770.Lyu GL, Lyu AH. Effect of early intervention on neonatal respiratory distress syndrome and nursing care[J]. Chinese Journal of Coal Industry Medicine, 2012,15(11):1769-1770.
[12] Choi CW, Kim BI, Kim HS, et al. Increase of interleukin-6 in tracheal aspirate at birth:a predictor of subsequent bronchopulmonary dysplasia in preterm infants[J].Acta Paediatr,2006,95(1):38-43. DOI:10.1080/08035250500404085.
[13] Halliday HL, Ehrenkranz RA, Doyle LW. Early(<8 days)postnatal corticosteroids for preventing chronic lung disease in preterm infants[J].Cochrane Database Syst Rev, 2010(1):CD001146. DOI:10.1002/14651858. CD001146. pub3.
[14] Committee on Fetus and Newborn. Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants[J]. Pediatrics,2002,109(2):330-338.
[15] Halliday HL. Guideline on neonatal steroids[J]. Prenat Neonat Med, 2001(6):371-373.
[16] Onland W, Offringa M, van Kaam A, et al. Late(≥7 days)inhalation corticosteroids to reduce bronchopulmonary dysplasia in preterm infants[J].Cochrane Database Syst Rev, 2012(4):CD002311.DOI:10.1002/14651858. CD002311. pub3.
[17] Yeh TF, Lin HC, Chang CH, et al. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants:a pilot study[J]. Pediatrics, 2008,121(5):e0310-1318. DOI:10.1542/peds.2007-1973.
[18] Huang LT, Yeh TF, Kuo YL, et al. Effect of surfactant and budesonide on the pulmonary distribution of fluorescent dye in mice[J].Pediatr Neonatol, 2015,56(1):19-24. DOI:10. 1016/j. pedneo.2014.04.009.
[2]董建敏,安丽.PS对早产儿外周血T淋巴细胞和NK细胞的影响[J].中华全科医学,2013,11(2):177-178.Dong JM, An L. Explore the effect of exogenous surfactant therapy on levels of T lymphocytes and NK cells in peripheral blood[J].Chinese Journal of General Practice, 2013,11(2):177-178.
[3]孔祥永,杨常栓,吴江永,等.预防性应用肺表面活性物质对早产儿早期预后的影响[J].中国医刊,2016,51(8):72-76.DOI:10.3969/j. issn. 1673-7210.2011.10.025.Kong XY, Yang CS, Wu JY, et al. Prophylactic surfactant replacement on the outcomes of neonates less than 32 complete weeks[J]. Chinese Journal of Medicine,2016,51(8):72-76.DOI:10.3969/j. issn. 1673-7210.2011. 10.025.
[4] Yeh TF, Chen CM, Wu SH, et al. Intra-tracheal administration of budesonide/surfactant to prevent bronchopulmonary dysplasia[J].Am J Respir Crit Care Med, 2016,193(1):86-95. DOI:10.1164/rccm. 201505-08610C.
[5] Venkataraman R, Kamaluddeen M, Hasan SU, et al. Intratracheal Administration of Budesonide-Surfactant in Prevention of bronchopulmonary dysplasia in very low birth weight infants:a systematic review and meta-analysis[J]. Pediatr Pulmonol, 2017,52(7):968-975. DOI:10.1002/ppul.23680.
[6]施弦,郁峰.布地奈德联合孟鲁司特对支气管哮喘患儿炎性因子及免疫功能的影响[J].中国医药,2018,13(1):55-58. D01:10.3760/cma. j. issn. 1673-4777. 2018.01.015.Shi X,Yu F. Effect of budesonide combined with montelukast on inflammatory factors and immune function in children with bronchial asthma[J]. China Medicine, 2018,13(1):55-58. DOI:10.3760/cma.j.issn. 1673-4777.2018.01.015.
[7]诸福堂,吴瑞萍,胡亚美.实用儿科学[M].4版.北京:人民卫生出版社,1994:416.Zhu FT, Wu RP, Hu YM. Practical pediatrics[M]. 4th ed. Beijing:People's Medical Publishing House,1994:416.
[8] Northway WH Jr, Rosan RC, Poter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia[J]. N Engl J Med, 1967,276(7):357-368. DOI:10.1056/NEJM196702162760701.
[9]王颖.支气管肺发育不良(新生儿慢性肺疾病)的诊断与治疗[J].实用医学杂志,2005,21(17):1859-1860. DOI:10.3969/j. issn. 1006-5725.2005. 17.002.Wang Y. Diagnosis and treatment of bronchopulmonary dysplasia(neonatal chronic pulmonary disease)[J]. The Journal of Practical Medicine, 2005,21(17):1859-1860. DOI:10.3969/j.issn.1006-5725.2005.17.002.
[10]吕勤,蔡成.早产儿支气管肺发育不良的诊治现状[J].现代实用医学,2011,23(6):610-612,658.DOI:10.3969/j.issn.1671-0800.2011.06.004.Lyu Q, Cai C. Status of diagnosis and treatment of premature bronchopulmonary dysplasia[J]. Modem Practical Medicine,2011,23(6):610-612,658. DOI:10. 3969/j. issn. 1671-0800.2011.06.004.
[11]吕改玲,吕爱红.早期干预治疗新生儿呼吸窘迫综合征的疗效及护理[J].中国煤炭工业医学杂志,2012,15(11):1769-1770.Lyu GL, Lyu AH. Effect of early intervention on neonatal respiratory distress syndrome and nursing care[J]. Chinese Journal of Coal Industry Medicine, 2012,15(11):1769-1770.
[12] Choi CW, Kim BI, Kim HS, et al. Increase of interleukin-6 in tracheal aspirate at birth:a predictor of subsequent bronchopulmonary dysplasia in preterm infants[J].Acta Paediatr,2006,95(1):38-43. DOI:10.1080/08035250500404085.
[13] Halliday HL, Ehrenkranz RA, Doyle LW. Early(<8 days)postnatal corticosteroids for preventing chronic lung disease in preterm infants[J].Cochrane Database Syst Rev, 2010(1):CD001146. DOI:10.1002/14651858. CD001146. pub3.
[14] Committee on Fetus and Newborn. Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants[J]. Pediatrics,2002,109(2):330-338.
[15] Halliday HL. Guideline on neonatal steroids[J]. Prenat Neonat Med, 2001(6):371-373.
[16] Onland W, Offringa M, van Kaam A, et al. Late(≥7 days)inhalation corticosteroids to reduce bronchopulmonary dysplasia in preterm infants[J].Cochrane Database Syst Rev, 2012(4):CD002311.DOI:10.1002/14651858. CD002311. pub3.
[17] Yeh TF, Lin HC, Chang CH, et al. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants:a pilot study[J]. Pediatrics, 2008,121(5):e0310-1318. DOI:10.1542/peds.2007-1973.
[18] Huang LT, Yeh TF, Kuo YL, et al. Effect of surfactant and budesonide on the pulmonary distribution of fluorescent dye in mice[J].Pediatr Neonatol, 2015,56(1):19-24. DOI:10. 1016/j. pedneo.2014.04.009.