不同维持剂量枸橼酸咖啡因对辅助通气早产儿的疗效评估:一项初步多中心研究

杨洋, 卢刻羽, 程锐, 周勤, 方广东, 李洪, 邵婕, 王淮燕, 李征瀛, 刘松林, 李振光, 蔡金兰, 薛梅, 陈筱青, 潘兆军, 高艳, 黄莉, 李海英, 宋磊, 王三南, 舒桂华, 邬薇, 余孟珠, 许准, 李红新, 徐艳, 包志丹, 吴新萍, 叶莉, 董雪萍, 殷其改, 殷小平, 周金君

中国当代儿科杂志 ›› 2022, Vol. 24 ›› Issue (3) : 240-248.

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中国当代儿科杂志 ›› 2022, Vol. 24 ›› Issue (3) : 240-248. DOI: 10.7499/j.issn.1008-8830.2109144
论著·临床研究

不同维持剂量枸橼酸咖啡因对辅助通气早产儿的疗效评估:一项初步多中心研究

  • 杨洋1, 卢刻羽1, 程锐1, 周勤2, 方广东2, 李洪3, 邵婕4, 王淮燕5, 李征瀛6, 刘松林7, 李振光8, 蔡金兰9, 薛梅10, 陈筱青11, 潘兆军12, 高艳13, 黄莉14, 李海英15, 宋磊16, 王三南17, 舒桂华18, 邬薇19, 余孟珠20, 许准21, 李红新22, 徐艳23, 包志丹24, 吴新萍25, 叶莉26, 董雪萍27, 殷其改28, 殷小平29, 周金君30
作者信息 +

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study

  • YANG Yang, LU Ke-Yu, CHENG Rui, ZHOU Qin, FANG Guang-Dong, LI Hong, SHAO Jie, WANG Huai-Yan, LI Zheng-Ying, LIU Song-Lin, LI Zhen-Guang, CAI Jin-Lan, XUE Mei, CHEN Xiao-Qing, PAN Zhao-Jun, GAO Yan, HUANG Li, LI Hai-Ying, SONG Lei, WANG San-Nan, SHU Gui-Hua, WU Wei, YU Meng-Zhu, XU Zhun, LI Hong-Xin, XU Yan, BAO Zhi-Dan, WU Xin-Ping, YE Li, DONG Xue-Ping, YIN Qi-Gai, YIN Xiao-Ping, ZHOU Jin-Jun
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文章历史 +

摘要

目的 探讨需要辅助通气和枸橼酸咖啡因治疗的早产儿枸橼酸咖啡因的最佳维持剂量。 方法 回顾性收集2019年1月1日至2019年12月31日江苏省30家三级医院新生儿重症监护病房中需要辅助通气和枸橼酸咖啡因治疗的早产儿566例(胎龄≤34周)的临床资料。依据生后24 h内给予枸橼酸咖啡因负荷剂量20 mg/kg后接受高(每日10 mg/kg)或低(每日5 mg/kg)维持剂量治疗将早产儿分为高剂量组(n=405)和低剂量组(n=161)。对两组早产儿咖啡因应用期间有创/无创通气相关数据进行比较分析。 结果 与低剂量组比较,高剂量组早产儿辅助通气时对高浓度氧的需求明显降低(P<0.05),无创通气撤除后的吸氧总时间及住院期间总吸氧时间均显著缩短(P<0.01),再次无创通气的比例明显降低(P<0.01),肺表面活性物质及吸入性布地奈德的使用率均显著减少(P<0.05),呼吸暂停及BPD的发生率显著降低(P<0.01),但早产儿喂养不耐受的发生率明显上升(P=0.032)。两组在体重变化、早产儿视网膜病变发生率、脑室内出血发生率、坏死性小肠结肠炎发生率、病死率、咖啡因应用时间等方面比较差异无统计学意义(P>0.05)。 结论 初步多中心研究表明高维持剂量枸橼酸咖啡因(每日10 mg/kg)对治疗我国早产儿人群总体是有益的,并未增加常见不良反应的发生。而对于喂养不耐受的风险,还需要进一步的论证分析,以尽可能排除混杂因素的干扰。

Abstract

Objective To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. Methods A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. Results Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). Conclusions This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

关键词

咖啡因 / 维持剂量 / 呼吸 / 早产儿

Key words

Caffeine / Maintenance dose / Respiration / Preterm infant

引用本文

导出引用
杨洋, 卢刻羽, 程锐, 周勤, 方广东, 李洪, 邵婕, 王淮燕, 李征瀛, 刘松林, 李振光, 蔡金兰, 薛梅, 陈筱青, 潘兆军, 高艳, 黄莉, 李海英, 宋磊, 王三南, 舒桂华, 邬薇, 余孟珠, 许准, 李红新, 徐艳, 包志丹, 吴新萍, 叶莉, 董雪萍, 殷其改, 殷小平, 周金君. 不同维持剂量枸橼酸咖啡因对辅助通气早产儿的疗效评估:一项初步多中心研究[J]. 中国当代儿科杂志. 2022, 24(3): 240-248 https://doi.org/10.7499/j.issn.1008-8830.2109144
YANG Yang, LU Ke-Yu, CHENG Rui, ZHOU Qin, FANG Guang-Dong, LI Hong, SHAO Jie, WANG Huai-Yan, LI Zheng-Ying, LIU Song-Lin, LI Zhen-Guang, CAI Jin-Lan, XUE Mei, CHEN Xiao-Qing, PAN Zhao-Jun, GAO Yan, HUANG Li, LI Hai-Ying, SONG Lei, WANG San-Nan, SHU Gui-Hua, WU Wei, YU Meng-Zhu, XU Zhun, LI Hong-Xin, XU Yan, BAO Zhi-Dan, WU Xin-Ping, YE Li, DONG Xue-Ping, YIN Qi-Gai, YIN Xiao-Ping, ZHOU Jin-Jun. Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study[J]. Chinese Journal of Contemporary Pediatrics. 2022, 24(3): 240-248 https://doi.org/10.7499/j.issn.1008-8830.2109144

参考文献

1 Donda K, Vijayakanthi N, Dapaah-Siakwan F, et al. Trends in epidemiology and outcomes of respiratory distress syndrome in the United States[J]. Pediatr Pulmonol, 2019, 54(4): 405-414. PMID: 30663263. DOI: 10.1002/ppul.24241.
2 Fauroux B, Hasco?t JM, Jarreau PH, et al. Risk factors for bronchiolitis hospitalization in infants: a French nationwide retrospective cohort study over four consecutive seasons (2009-2013)[J]. PLoS One, 2020, 15(3): e0229766. PMID: 32142528. PMCID: PMC7059917. DOI: 10.1371/journal.pone.0229766.
3 Nies?uchowska-Hoxha A, Cnota W, Czuba B, et al. A retrospective study on the risk of respiratory distress syndrome in singleton pregnancies with preterm premature rupture of membranes between 24+0 and 36+6 weeks, using regression analysis for various factors[J]. Biomed Res Int, 2018, 2018: 7162478. PMID: 30402491. PMCID: PMC6193337. DOI: 10.1155/2018/7162478.
4 Wielenga JM, van den Hoogen A, van Zanten HA, et al. Protocolized versus non-protocolized weaning for reducing the duration of invasive mechanical ventilation in newborn infants[J]. Cochrane Database Syst Rev, 2016, 3: CD011106. PMID: 26998745. DOI: 10.1002/14651858.CD011106.pub2.
5 Steer P, Flenady V, Shearman A, et al. High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial[J]. Arch Dis Child Fetal Neonatal Ed, 2004, 89(6): F499-F503. PMID: 15499141. PMCID: PMC1721801. DOI: 10.1136/adc.2002.023432.
6 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. PMID: 14241. DOI: 10.1016/s0022-3476(77)80718-x.
7 Sanchez-Solis M, Garcia-Marcos PW, Agüera-Arenas J, et al. Impact of early caffeine therapy in preterm newborns on infant lung function[J]. Pediatr Pulmonol, 2020, 55(1): 102-107. PMID: 31587528. DOI: 10.1002/ppul.24540.
8 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. PMID: 30974433. PMCID: PMC6604659. DOI: 10.1159/000499361.
9 Kinsella JP, Greenough A, Abman SH. Bronchopulmonary dysplasia[J]. Lancet, 2006, 367(9520):1421-1431. PMID: 16650652. DOI: 10.1016/S0140-6736(06)68615-7.
10 Jobe AH, Bancalari E. Bronchopulmonary dysplasia[J]. Am J Respir Crit Care Med, 2001, 163(7):1723-1729. PMID: 11401896. DOI: 10.1164/ajrccm.163.7.2011060.
11 International Committee for the Classification of Retinopathy of Prematurity. The international classification of retinopathy of prematurity revisited[J]. Arch Ophthalmol, 2005, 123(7): 991-999. PMID: 16009843. DOI: 10.1001/archopht.123.7.991.
12 Papile LA, Burstein J, Burstein R, et al. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm[J]. J Pediatr, 1978, 92(4): 529-534. PMID: 305471. DOI: 10.1016/s0022-3476(78)80282-0.
13 Volpe JJ. Neurology of the newborn[M]. 5th ed. Philadelphia: Saunders/Elsevier, 2008: 541.
14 Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging[J]. Ann Surg, 1978, 187(1):1-7. PMID: 413500. PMCID: PMC1396409. DOI: 10.1097/00000658-197801000-00001.
15 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: 610-612.
16 Richardson DK, Corcoran JD, Escobar GJ, et al. SNAP-II and SNAPPE-II: simplified newborn illness severity and mortality risk scores[J]. J Pediatr, 2001, 138(1): 92-100. PMID: 11148519. DOI: 10.1067/mpd.2001.109608.
17 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: 167-177.
18 Grier DG, Halliday HL. Management of bronchopulmonary dysplasia in infants: guidelines for corticosteroid use[J]. Drugs, 2005, 65(1): 15-29. PMID: 15610049. DOI: 10.2165/00003495-200565010-00002.
19 Schmidt B, Roberts RS, Davis P, et al. Caffeine therapy for apnea of prematurity[J]. N Engl J Med, 2006, 354(20): 2112-2121. PMID: 16707748. DOI: 10.1056/NEJMoa054065.
20 Schmidt B, Anderson PJ, Doyle LW, et al. Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity[J]. JAMA, 2012, 307(3): 275-282. PMID: 22253394. DOI: 10.1001/jama.2011.2024.
21 Kalikkot Thekkeveedu R, Guaman MC, Shivanna B. Bronchopulmonary dysplasia: a review of pathogenesis and pathophysiology[J]. Respir Med, 2017, 132: 170-177. PMID: 29229093. PMCID: PMC5729938. DOI: 10.1016/j.rmed.2017.10.014.
22 He X, Qiu JC, Lu KY, et al. Therapy for apnoea of prematurity: a retrospective study on effects of standard dose and genetic variability on clinical response to caffeine citrate in Chinese preterm infants[J]. Adv Ther, 2021, 38(1):607-626. PMID: 33180318. DOI: 10.1007/s12325-020-01544-2.
23 Turmen T, Davis J, Aranda JV. Relationship of dose and plasma concentrations of caffeine and ventilation in neonatal apnea[J]. Semin Perinatol, 1981, 5(4): 326-331. PMID: 7302607.
24 Wan LJ, Huang L, Chen PY. Caffeine citrate maintenance doses effect on extubation and apnea postventilation in preterm infants[J]. Pediatr Pulmonol, 2020, 55(10): 2635-2640. PMID: 32639634. DOI: 10.1002/ppul.24948.
25 Kou C, Han D, Li ZN, et al. Influence of prevention of caffeine citrate on cytokine profile and bronchopulmonary dysplasia in preterm infants with apnea[J]. Minerva Pediatr, 2020, 72(2): 95-100. PMID: 30961342. DOI: 10.23736/S0026-4946.19.05428-8.
26 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. PMID: 25644724. DOI: 10.1007/s00431-015-2494-8.
27 Gray PH, Flenady VJ, Charles BG, et al. Caffeine citrate for very preterm infants: effects on development, temperament and behaviour[J]. J Paediatr Child Health, 2011, 47(4): 167-172. PMID: 21244548. DOI: 10.1111/j.1440-1754.2010.01943.x.
28 Chen J, Jin L, Chen X. Efficacy and safety of different maintenance doses of caffeine citrate for treatment of apnea in premature infants: a systematic review and meta-analysis[J]. Biomed Res Int, 2018, 2018: 9061234. PMID: 30671477. PMCID: PMC6323495. DOI: 10.1155/2018/9061234.
29 Dobson NR, Hunt CE. Caffeine: an evidence-based success story in VLBW pharmacotherapy[J]. Pediatr Res, 2018, 84(3): 333-340. PMID: 29983414. DOI: 10.1038/s41390-018-0089-6.
30 Mitchell L, MacFarlane PM. Mechanistic actions of oxygen and methylxanthines on respiratory neural control and for the treatment of neonatal apnea[J]. Respir Physiol Neurobiol, 2020, 273: 103318. PMID: 31626973. PMCID: PMC6986994. DOI: 10.1016/j.resp.2019.103318.
31 Kraaijenga JV, Hutten GJ, de Jongh FH, et al. The effect of caffeine on diaphragmatic activity and tidal volume in preterm infants[J]. J Pediatr, 2015, 167(1): 70-75. PMID: 25982138. DOI: 10.1016/j.jpeds.2015.04.040.
32 Doyle J, Davidson D, Katz S, et al. Apnea of prematurity and caffeine pharmacokinetics: potential impact on hospital discharge[J]. J Perinatol, 2016, 36(2): 141-144. PMID: 26562367. DOI: 10.1038/jp.2015.167.
33 Le Guennec JC, Billon B, Paré C. Maturational changes of caffeine concentrations and disposition in infancy during maintenance therapy for apnea of prematurity: influence of gestational age, hepatic disease, and breast-feeding[J]. Pediatrics, 1985, 76(5): 834-840. PMID: 4058995.
34 Vliegenthart R, Miedema M, Hutten GJ, et al. High versus standard dose caffeine for apnoea: a systematic review[J]. Arch Dis Child Fetal Neonatal Ed, 2018, 103(6):F523-F529. PMID: 29437799. DOI: 10.1136/archdischild-2017-313556.
35 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. PMID: 26791921. DOI: 10.3760/cma.j.issn.0578-1310.2016.01.008.
36 Cox C, Hashem NG, Tebbs J, et al. Evaluation of caffeine and the development of necrotizing enterocolitis[J]. J Neonatal Perinatal Med, 2015, 8(4): 339-347. PMID: 26757002. DOI: 10.3233/NPM-15814059.
37 Taha D, Kirkby S, Nawab U, et al. Early caffeine therapy for prevention of bronchopulmonary dysplasia in preterm infants[J]. J Matern Fetal Neonatal Med, 2014, 27(16): 1698-1702. PMID: 24479608. DOI: 10.3109/14767058.2014.885941.


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