对乙酰氨基酚和布洛芬治疗不同胎龄阶段早产儿动脉导管未闭的对照研究

郭利敏; 马进; 陈名武

doi:10.16766/j.cnki.issn.1674-4152.001779

对乙酰氨基酚和布洛芬治疗不同胎龄阶段早产儿动脉导管未闭的对照研究

doi: 10.16766/j.cnki.issn.1674-4152.001779

1.
蚌埠医学院第三附属医院儿科，安徽宿州 234000
2.
中国科技大学附属第一医院儿科，安徽合肥 230000

基金项目:

安徽省自然科学基金 1608085MH196

详细信息

通讯作者:
马进, E-mail: majinlcyx@163.com

中图分类号: R722.6
计量
- 文章访问数: 119
- HTML全文浏览量: 75
- PDF下载量: 0
- 被引次数: 0
出版历程
- 收稿日期: 2020-05-15
- 网络出版日期: 2022-02-19

A comparative study of paracetamol and ibuprofen on patent ductus arteriosus in preterm infants at different stages of gestational age

1.
Department of Pediatrics, Third Affiliated Hospital of Bengbu Medical College, Suzhou, Anhui 234000, China

摘要

摘要: 目的观察口服对乙酰氨基酚与布洛芬治疗不同胎龄早产儿动脉导管未闭(patent ductus arteriosus，PDA)的疗效和安全性。方法选取2016年1月—2018年1月在蚌埠医学院第三附属医院新生儿科住院的胎龄＜37周，体重＜2 500 g，口服布洛芬的56例PDA早产儿为对照组，2018年1月—2020年1月在蚌埠医学院第三附属医院新生儿科住院的胎龄＜37周, 体重＜2 500 g，54例PDA早产儿为观察组，予口服对乙酰氨基酚。所有患儿根据胎龄再分为3组，28~30⁺⁶周组，31~33⁺⁶周组，34~36⁺⁶周组；观察比较2种药物的疗效和安全性及3组不同胎龄早产儿PDA的关闭率差异。结果对乙酰氨基酚组动脉导管关闭率(79.63%)和布洛芬组(78.57%)比较差异无统计学意义(P＞0.05)。28~30⁺⁶周组、31~33⁺⁶周组、34~36⁺⁶周组动脉导管关闭率分别为62.5%、84.2%、87.5%。对乙酰氨基酚组和布洛芬组之间上消化道出血、脑室内出血(intraventricular hemorrhage，IVH)、坏死性小肠结肠炎(necrotizing enterocolitis，NEC)、早产儿视网膜病(retinopathy of prematurity，ROP)、支气管肺发育不良(bronchopulmonary dysplasia，BPD)、尿量减少及高胆红素血症的发生率比较差异无统计学意义(均P＞0.05)。结论对乙酰氨基酚与布洛芬均可有效治疗PDA；2种药物的不良反应发生率无显著差异；胎龄不同的早产儿动脉导管关闭率不完全相等，胎龄最小组关闭率最低。
- 动脉导管未闭 /
- 对乙酰氨基酚 /
- 布洛芬 /
- 疗效 /
- 安全性 /
- 早产儿
Abstract: Objective To observe the efficacy and safety of paracetamol and ibuprofen in the treatment of patent ductus arteriosus (PDA) in preterm infants of different gestational ages. Methods Total 110 preterm infants with gestational age ≤37 weeks, birthweight ≤2 500 g confirmed PDA were enrolled, including group Ⅰ (ibuprofen group, from January 2016 to January 2018, a total of 56 preterm infants received oral ibuprofen) and group Ⅱ (paracetamol group, from January 2018 to January 2020, a total of 54 preterm infants received oral paracetamol). According to gestational age, all the infants were divided into three groups: 28-30⁺⁶ weeks group, 31-33⁺⁶ weeks group, 34-36⁺⁶ weeks group. The efficacy and safety of the two drugs and the difference of PDA closure rate among the three groups were observed and compared. Results There was no significant difference in PDA closure rate between group Ⅰ (78.57%) and Ⅱ (79.63%), P>0.05. The closure rate of PDA were 62.5%, 84.2% and 87.5%, respectively, in 28-30⁺⁶ weeks group, 31-33⁺⁶ weeks group and 34-36⁺⁶ weeks. In addition, oral paracetamol was as safe as oral ibuprofen in terms of gastrointestinal bleeding, retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, intraventricular hemorrhage, hyperbilirubinemia, uri nary output (all P>0.05). Conclusion The efficacy and safety of paracetamol and ibuprofen on PDA are similar. There was no significant difference in the incidence of adverse reactions between the two drugs. The closure rate of patent ductus arteriosus is not equal in different gestational age and is inversely proportional to gestational age.
- Patent ductus arteriosus /
- Paracetamol /
- Ibuprofen /
- Treatment effect /
- Safety /
- Preterm infant

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表 1 2组PDA早产儿一般资料比较

组别	例数	性别(例)		胎龄(x±s，周)	出生体重(x±s，g)
组别	例数	男	女	胎龄(x±s，周)	出生体重(x±s，g)
观察组	54	29	25	32.57±2.00	1 791.91±371.97
对照组	56	26	30	32.47±2.03	1 782.21±390.19
统计量		0.045^a		0.254^b	0.133^b
P值		0.832		0.800	0.894
注：^a为χ²值，^b为t值。

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表 2 不同治疗方法动脉导管未闭患儿不良反应发生率比较[例(%)]

组别	例数	上消化道出血	NEC	ROP	BPD	IVH	尿量减少	高胆红素血症
观察组	54	5(9.26)	3(5.56)	3(5.56)	2(3.70)	2(3.70)	13(24.07)	16(29.63)
对照组	56	3(5.36)	4(7.14)	2(3.57)	5(8.93)	1(1.79)	11(19.64)	13(23.21)
χ²值							0.316	0.583
P值		0.485^a	>0.999^a	0.676^a	0.438^a	0.615^a	0.574	0.445
注：^a为采用Fisher精确检验。

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参考文献(25)

[1]	MEZU-NDUBUISI O J, AGARWAL G, RAGHAVAN A, et al. Patent ductus arteriosus in premature neonates[J]. Drugs, 2012, 72(7): 907-916. doi: 10.2165/11632870-000000000-00000
[2]	STOLLER J Z, DEMAURO S B, DAGLE J M, et al. Current perspectives on pathobiology of the ductus arteriosus[J]. J Clin Exp Cardiolog, 2012, 8(1): S8-001. http://www.omicsonline.org/2155-9880/pdfdownload.php?download=2155-9880-S8-001.pdf
[3]	GENTILE R, STEVENSON G, DOOLEY T, et al. Pulsed doppler echocardiographic determination of time of ductal closure in normal newborn infants[J]. J Pediatr, 1981, 98(3): 443-448. doi: 10.1016/S0022-3476(81)80719-6
[4]	SEMBEROVA J, SIRC J, MILETIN J, et al. Spontaneous closure of patent ductus arteriosus in infants ≤1 500 g[J]. Pediatrics, 2017, 140(2): e20164258. doi: 10.1542/peds.2016-4258
[5]	BENITZ W E. Patent ductus arteriosus in preterm infants[J]. Pediatrics, 2016, 137(1): 1-6.
[6]	OLGUN H, CEVIZ N, KARTAL I, et al. Repeated courses of oral ibuprofen in premature infants with patent ductus arteriosus: efficacy and safety[J]. Pediatr Neonatol, 2017, 58(1): 29-35. doi: 10.1016/j.pedneo.2015.04.017
[7]	ONCEL M Y, ERDEVE O. Safety of therapeutics used in management of patent ductus arteriosus in preterm infants[J]. Curr Drug Saf, 2015, 10(2): 106-112. doi: 10.2174/1574886309999141030142847
[8]	HÄRKIN P, HÄRMÄ A, AIKIO O, et al. Paracetamol accelerates closure of the ductus arteriosus after premature birth: a randomized trial[J]. J Pediatr, 2016, 177: 72-77. doi: 10.1016/j.jpeds.2016.04.066
[9]	CUZZOLIN L, BARDANZELLU F, FANOS V. The dark side of ibuprofen in the treatment of patent ductus arteriosus: could paracetamol be the solution?[J]. Expert Opin Drug Metab Toxicol, 2018, 14(8): 855-868. doi: 10.1080/17425255.2018.1492550
[10]	HAMMERMAN C, BIN-NUN A, MARKOVITCH E, et al. Ductal closure with paracetamol: a surprising new approach to patent ductus arteriosus treatment[J]. Pediatrics, 2011, 128(6): e1618-e1621. doi: 10.1542/peds.2011-0359
[11]	ONCEL M Y, YURTTUTAN S, ERDEVE O, et al. Oral paracetamol versus oral ibuprofen in the management of patent ductus arteriosus in preterm infants: a randomized controlled trial[J]. J Pediatr, 2014, 164(3): 510-514. doi: 10.1016/j.jpeds.2013.11.008
[12]	AL-LAWAMA M, ALAMMORI I, ABDELGHANI T, et al. Oral paracetamol versus oral ibuprofen for treatment of patent ductus arteriosus[J]. J Int Med Res, 2018, 46(2): 811-818. doi: 10.1177/0300060517722698
[13]	BAGHERI M M, NIKNAFS P, SABSEVARI F, et al. Comparison of oral acetaminophen versus ibuprofen in premature infants with patent ductus arteriosus[J]. Iran J Pediatr, 2016, 26(4): e3975. http://www.onacademic.com/detail/journal_1000040554459710_77c9.html
[14]	HUANG X, WANG F, WANG K. Paracetamol versus ibuprofen for the treatment of patent ductus arteriosus in preterm neonates: a meta-analysis of randomized controlled trials[J]. J Matern Fetal Neonatal Med, 2018, 31(16): 2216-2222. doi: 10.1080/14767058.2017.1338263
[15]	OHLSSON A, SHAH P S. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants[J]. Cochrane Database Syst Rev, 2020, 1(1): CD010061. http://pdfs.semanticscholar.org/b214/b66f09949060fa95dca663f5566a8977c21e.pdf
[16]	王乐, 赵婷, 李明霞. 早产儿动脉导管未闭高危因素及并发症分析[J]. 中国新生儿科杂志, 2015, 30(4): 273-276. https://cdmd.cnki.com.cn/Article/CDMD-10760-1014431911.htm
[17]	高瑛, 孙岩, 王席娟, 等. 极低出生体质量儿动脉导管未闭及动脉导管再次开放的高危因素分析[J]. 新乡医学院学报, 2017, 34(7): 574-578. https://www.cnki.com.cn/Article/CJFDTOTAL-XXYX201707006.htm
[18]	陈超, 张兰, 李登峰, 等. 动脉导管内径对早产儿有血流动力学改变的动脉导管未闭并发症影响分析[J]. 中华全科医学, 2020, 18(2): 191-193, 223. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY202002008.htm
[19]	MADELENEAU D, AUBELLE M S, PIERRON C, et al. Efficacy of a first course of Ibuprofen for patent ductus arteriosus closure in extremely preterm newborns according to their gestational age-specific Z-score for birth weight[J]. PLoS One, 2015, 10(4): e0124804. doi: 10.1371/journal.pone.0124804
[20]	杨波, 陈洋, 高翔羽, 等. 影响早产儿症状性动脉导管未闭发生及药物干预效果的相关因素分析[J]. 中华心脏与心律电子杂志, 2015, 3(1): 28-34.
[21]	EL-MASHAD A E, EL-MAHDY H, EL AMROUSY D, et al. Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates[J]. Eur J Pediatr, 2017, 176(2): 233-240. doi: 10.1007/s00431-016-2830-7
[22]	OHLSSON A, WALIA R, SHAH S S. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants[J]. Cochrane Database Syst Rev, 2020, 2(2): CD003481. http://pdfs.semanticscholar.org/83e7/3f0de5007b2e946538a7d58f96116c554e9c.pdf
[23]	ONCEL M Y, ERAS Z, URAS N, et al. Neurodevelopmental outcomes of preterm infants treated with oral paracetamol versus ibuprofen for patent ductus arteriosus[J]. Am J Perinatol, 2017, 34(12): 1185-1189. doi: 10.1055/s-0037-1601564
[24]	EL-FARRASH R A, EL SHIMY M S, EL-SAKKA A S, et al. Efficacy and safety of oral paracetamol versus oral ibuprofen for closure of patent ductus arteriosus in preterm infants: a randomized controlled trial[J]. J Matern Fetal Neonatal Med, 2019, 32(21): 3647-3654. doi: 10.1080/14767058.2018.1470235
[25]	KARABULUT B, PAYTONCU S. Efficacy and safety of oral paracetamol vs. oral ibuprofen in the treatment of symptomatic patent ductus arteriosus in premature infants[J]. Paediatr Drugs, 2019, 21(2): 113-121. doi: 10.1007/s40272-019-00331-z