不同剂量咖啡因防治早产儿呼吸暂停的Meta分析
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摘要
目的系统评价不同剂量咖啡因防治早产儿呼吸暂停(AOP)的疗效及安全性。方法计算机检索中国知网、万方、维普、中国生物医学、Pub Med、EMbase、Cochrane Library等数据库关于不同剂量的咖啡因治疗AOP的随机对照试验(RCTs),检索时限从建库至2018年5月31日,采用Rev Man 5. 3软件对纳入文献进行Meta分析。结果共纳入10篇RCTs,共904例患儿。Meta分析结果显示,与低剂量组相比,高剂量组可降低支气管肺发育不良(RR=0. 76,95%CI 0. 62～0. 95,P=0. 01)、拔管失败(RR=0. 53,95%CI 0. 41～0. 69,P <0. 000 01)的发生风险,但有增加心动过速(> 180次/min)(RR=2. 74,95%CI 1. 63～4. 60,P=0. 000 1)、喂养不耐受(RR=1. 32,95%CI1. 02～1. 70,P=0. 03)的风险。结论高剂量咖啡因防治AOP疗效显著,除心动过速(> 180次/min)及喂养不耐受,无其他不良反应,最佳剂量范围不能明确,需更多高质量的RCTs证实。
Objective To evaluate the efficacy and safety of different doses of caffeine in the treatment of apnea of prematurity( AOP). Methods CNKI,WAN FANG,WEI PU,CBM,Pub Med,EMbase,Cochrane Library were searched by computer for randomized controlled trials( RCTs) about different doses of caffeine in the treatment of AOP from the time of database establishment to May 31 st,2018,and the literatures that met the inclusion criteria were analyzed by Rev Man 5. 3.Results We included a total of 904 premature infants from 10 RCTs. The results of meta-analysis indicated that high dose caffeine could reduce the bronchial pulmonary dysplasia( RR = 0. 76,95% CI 0. 62-0. 95,P = 0. 01) and risk of extubation failure( RR = 0. 53,95% CI 0. 41-0. 69,P < 0. 000 01),but it might increase the risk of tachycardia( > 180 times/min)( RR = 2. 74,95% CI 1. 63-4. 60,P = 0. 000 1) and feed intolerance( RR = 1. 32,95% CI 1. 02-1. 70,P = 0. 03) compared with low doses caffeine. Conclusion High dose caffeine has significant efficacy in treating AOP,with no adverse reactions except tachycardia( > 180 times/min) and feed intolerance. The optimal range of caffeine dose in preventing AOP is indefinite,and more high-quality relevant RCTs are needed for confirmation.
Objective To evaluate the efficacy and safety of different doses of caffeine in the treatment of apnea of prematurity( AOP). Methods CNKI,WAN FANG,WEI PU,CBM,Pub Med,EMbase,Cochrane Library were searched by computer for randomized controlled trials( RCTs) about different doses of caffeine in the treatment of AOP from the time of database establishment to May 31 st,2018,and the literatures that met the inclusion criteria were analyzed by Rev Man 5. 3.Results We included a total of 904 premature infants from 10 RCTs. The results of meta-analysis indicated that high dose caffeine could reduce the bronchial pulmonary dysplasia( RR = 0. 76,95% CI 0. 62-0. 95,P = 0. 01) and risk of extubation failure( RR = 0. 53,95% CI 0. 41-0. 69,P < 0. 000 01),but it might increase the risk of tachycardia( > 180 times/min)( RR = 2. 74,95% CI 1. 63-4. 60,P = 0. 000 1) and feed intolerance( RR = 1. 32,95% CI 1. 02-1. 70,P = 0. 03) compared with low doses caffeine. Conclusion High dose caffeine has significant efficacy in treating AOP,with no adverse reactions except tachycardia( > 180 times/min) and feed intolerance. The optimal range of caffeine dose in preventing AOP is indefinite,and more high-quality relevant RCTs are needed for confirmation.
引文
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[2]许景林,王瑞泉,陈冬梅,等.枸橼酸咖啡因与氨茶碱治疗早产儿原发性呼吸暂停的比较[J].中国当代儿科杂志,2014,16(4):1129-1132.
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[6]Scanlon JE,Chin KC,Morgan ME,et al.Caffeine or theophylline for neonatal apnoea?[J].Arch Dis Child,1992,67(4):425-428.
[7]Steer PA,Flenady VJ,Shearman A,et al.Periextubation caffeine in preterm neonates:A randomized dose response trial[J].J Pediatr Child Health,2003,39(7):511-515.
[8]Gray PH,Flenady VJ,Charles BG,et al.Caffeine citrate for very preterm infants:Effects on development,temperament and behaviour[J].J Pediatr Child Health,2011,47(4):167-172.
[9]Mc Pherson C,Neil JJ,Tjoeng TH,et al.A pilot randomized trial of high-dose caffeine therapy in preterm infants[J].Pediatr Res,2015,78(2):198-204.
[10]Mohammed S,Nour I,Shabaan AE,et al.High versus low-dose caffeine for apnea of prematurity:A randomized controlled trial[J].Eur J Pediatr,2015,174(7):949-956.
[11]赵颖,田秀英,刘鸽.不同剂量咖啡因治疗早产儿原发性呼吸暂停临床效果评估[J].中华儿科杂志,2016,54(1):33-36.
[12]Chaudhari SK,陈厚炎,谭举方,等.不同剂量枸橼酸咖啡因和氨茶碱治疗早产儿呼吸暂停的研究[J].中国新生儿科杂志,2016,11(5):348-352.
[13]范莉莉,王婷,王佐.不同剂量咖啡因治疗早产儿原发性呼吸暂停的临床疗效研究[J].中国全科医学,2017,20(10):1204-1207.
[14]杨伊琳.不同维持量枸橼酸咖啡因治疗早产儿呼吸暂停的效果比较[J].广东医学,2017,38(s1):246-248.
[15]Julien CA,Joseph V,Bairam A.Caffeine reduces apnea frequency and enhances ventilatory long-term facilitation in rat pups raised in chronic intermittent hypoxia[J].Pediatr Res,2010,68(2):105-111.
[16]Nagatomo T,Jiménez J,Richter J,et al.Caffeine prevents hyperoxia-induced functional and structural lung damage in preterm rabbits[J].Neonatology,2016,109(4):274-281.
[17]Lane Andrew JP,Coombs RC,Evans DH,et al.Effect of caffeine on neonatal splanchnic blood flow[J].Arch Dis Child Fetal Neonatal Ed,1999,80(2):F128-129.
[18]Lundstrm KE,Larsen PB,Brendstrup L,et al.Cerebral blood flow and left ventricular output in spontaneously breathing,newborn preterm infants treated with caffeine or aminophylline[J].Acta Paediatr,1995,84(1):6-9.
[19]Hoecker C,Nelle M,Poeschl J,et al.Caffeine impairs cerebral and intestinal blood flow velocity in preterm infants[J].Pediatrics,2002,109(5):784-787.
[20]Vesoulis ZA,Mc Pherson C,Neil JJ,et al.Early high-dose caffeine increases seizure burden in extremely preterm neonates:A preliminary study[J].J Caffeine Res,2016,6(3):101-107.
[21]Back SA,Craig A,Luo NL,et al.Protective effects of caffeine on chronic hypoxia-induced perinatal white matter injury[J].Ann Neurol,2006,60(6):696-705.
[22]Ravichandran S,Chouthai NS,Patel B,et al.Higher daily doses of caffeine lowered the incidence of moderate to severe neurodevelopmental disabilities in very low birth weight infants[J].Acta Paediatr,2018,108(3):430-435.
[23]Firman B,Gray PH.High loading dose of caffeine citrate in preterm infants and the effects on cranial ultrasound findings and neurological outcomes[J].J Matern Fetal Neo M,2016,29(S1):64-65.
[24]Gray PH,Molnar A,Firman B.Early high-dose caffeine citrate:Neonatal and neurodevelopmental outcomes[J].Amer J Perinatol,2018,35(S 01):S1-26.
[25]Volpe JJ.Cerebellum of the premature infant:Rapidly developing,vulnerable,clinically important[J].J Child Neurol,2009,24(9):1085-1104.
[2]许景林,王瑞泉,陈冬梅,等.枸橼酸咖啡因与氨茶碱治疗早产儿原发性呼吸暂停的比较[J].中国当代儿科杂志,2014,16(4):1129-1132.
[3]Aranda JV,Gorman W,Bergsteinsson H,et al.Efficacy of caffeine in treatment of apnea in the low-birth-weight infant[J].J Pediatr,1977,90(3):467-472.
[4]罗德惠,万翔,刘际明,等.如何实现从样本量,中位数,极值或四分位数到均数与标准差的转换[J].中国循证医学杂志,2017,17(11):1350-1356.
[5]Romagnoli C,De Carolis MP,Muzii U,et al.Effectiveness and side effects of two different doses of caffeine in preventing apnea in premature infants[J].Ther Drug Monit,1992,14(1):14-19.
[6]Scanlon JE,Chin KC,Morgan ME,et al.Caffeine or theophylline for neonatal apnoea?[J].Arch Dis Child,1992,67(4):425-428.
[7]Steer PA,Flenady VJ,Shearman A,et al.Periextubation caffeine in preterm neonates:A randomized dose response trial[J].J Pediatr Child Health,2003,39(7):511-515.
[8]Gray PH,Flenady VJ,Charles BG,et al.Caffeine citrate for very preterm infants:Effects on development,temperament and behaviour[J].J Pediatr Child Health,2011,47(4):167-172.
[9]Mc Pherson C,Neil JJ,Tjoeng TH,et al.A pilot randomized trial of high-dose caffeine therapy in preterm infants[J].Pediatr Res,2015,78(2):198-204.
[10]Mohammed S,Nour I,Shabaan AE,et al.High versus low-dose caffeine for apnea of prematurity:A randomized controlled trial[J].Eur J Pediatr,2015,174(7):949-956.
[11]赵颖,田秀英,刘鸽.不同剂量咖啡因治疗早产儿原发性呼吸暂停临床效果评估[J].中华儿科杂志,2016,54(1):33-36.
[12]Chaudhari SK,陈厚炎,谭举方,等.不同剂量枸橼酸咖啡因和氨茶碱治疗早产儿呼吸暂停的研究[J].中国新生儿科杂志,2016,11(5):348-352.
[13]范莉莉,王婷,王佐.不同剂量咖啡因治疗早产儿原发性呼吸暂停的临床疗效研究[J].中国全科医学,2017,20(10):1204-1207.
[14]杨伊琳.不同维持量枸橼酸咖啡因治疗早产儿呼吸暂停的效果比较[J].广东医学,2017,38(s1):246-248.
[15]Julien CA,Joseph V,Bairam A.Caffeine reduces apnea frequency and enhances ventilatory long-term facilitation in rat pups raised in chronic intermittent hypoxia[J].Pediatr Res,2010,68(2):105-111.
[16]Nagatomo T,Jiménez J,Richter J,et al.Caffeine prevents hyperoxia-induced functional and structural lung damage in preterm rabbits[J].Neonatology,2016,109(4):274-281.
[17]Lane Andrew JP,Coombs RC,Evans DH,et al.Effect of caffeine on neonatal splanchnic blood flow[J].Arch Dis Child Fetal Neonatal Ed,1999,80(2):F128-129.
[18]Lundstrm KE,Larsen PB,Brendstrup L,et al.Cerebral blood flow and left ventricular output in spontaneously breathing,newborn preterm infants treated with caffeine or aminophylline[J].Acta Paediatr,1995,84(1):6-9.
[19]Hoecker C,Nelle M,Poeschl J,et al.Caffeine impairs cerebral and intestinal blood flow velocity in preterm infants[J].Pediatrics,2002,109(5):784-787.
[20]Vesoulis ZA,Mc Pherson C,Neil JJ,et al.Early high-dose caffeine increases seizure burden in extremely preterm neonates:A preliminary study[J].J Caffeine Res,2016,6(3):101-107.
[21]Back SA,Craig A,Luo NL,et al.Protective effects of caffeine on chronic hypoxia-induced perinatal white matter injury[J].Ann Neurol,2006,60(6):696-705.
[22]Ravichandran S,Chouthai NS,Patel B,et al.Higher daily doses of caffeine lowered the incidence of moderate to severe neurodevelopmental disabilities in very low birth weight infants[J].Acta Paediatr,2018,108(3):430-435.
[23]Firman B,Gray PH.High loading dose of caffeine citrate in preterm infants and the effects on cranial ultrasound findings and neurological outcomes[J].J Matern Fetal Neo M,2016,29(S1):64-65.
[24]Gray PH,Molnar A,Firman B.Early high-dose caffeine citrate:Neonatal and neurodevelopmental outcomes[J].Amer J Perinatol,2018,35(S 01):S1-26.
[25]Volpe JJ.Cerebellum of the premature infant:Rapidly developing,vulnerable,clinically important[J].J Child Neurol,2009,24(9):1085-1104.