切换至 "中华医学电子期刊资源库"
高级检索
中华妇幼临床医学杂志(电子版)

中华妇幼临床医学杂志(电子版) ›› 2019, Vol. 15 ›› Issue (06) : 695 -702. doi: 10.3877/cma.j.issn.1673-5250.2019.06.014

所属专题： 文献；

论著

枸橼酸咖啡因联合加温湿化高流量鼻导管通气预防呼吸窘迫综合征早产儿拔管失败的临床研究
金宝1, 高翔羽1,†(), 杨波1, 黄迪1, 任漪1   
  1. 1. 东南大学附属徐州医院新生儿科　221009
  • 收稿日期:2019-06-18 修回日期:2019-11-01 出版日期:2019-12-01
  • 通信作者: 高翔羽

Clinical research of caffeine citrate combined with heated humidified high-flow nasal cannula for prevention of extubation failure in premature infants with respiratory distress syndrome

Bao Jin1, Xiangyu Gao1,†(), Bo Yang1, Di Huang1, Yi Ren1   

  1. 1. Department of Neonatology, Affiliated Xuzhou Hospital of Southeast University, Xuzhou 221009, Jiangsu Province, China
  • Received:2019-06-18 Revised:2019-11-01 Published:2019-12-01
  • Corresponding author: Xiangyu Gao
  • About author:
    Corresponding author: Gao Xiangyu, Email:
  • Supported by:
    Maternal and Child Health Research Project of Jiangsu Province Health and Family Planning Commission(F201752); Key Research and Development Project of Xuzhou Science and Technology Bureau(Social Development KC18188)
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

金宝, 高翔羽, 杨波, 黄迪, 任漪. 枸橼酸咖啡因联合加温湿化高流量鼻导管通气预防呼吸窘迫综合征早产儿拔管失败的临床研究[J]. 中华妇幼临床医学杂志(电子版), 2019, 15(06): 695-702.

Bao Jin, Xiangyu Gao, Bo Yang, Di Huang, Yi Ren. Clinical research of caffeine citrate combined with heated humidified high-flow nasal cannula for prevention of extubation failure in premature infants with respiratory distress syndrome[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2019, 15(06): 695-702.

目的

探讨枸橼酸咖啡因联合加温湿化高流量鼻导管通气(HHHFNC)与经鼻持续气道正压通气(NCPAP)预防呼吸窘迫综合征(RDS)早产儿拔管失败的有效性及安全性。

方法

选择2017年9月至2019年2月，于东南大学附属徐州医院新生儿重症监护病房，接受气管插管、有创机械通气治疗后，准备拔除气管插管转为无创辅助通气治疗的72例胎龄为28～32周的RDS早产儿为研究对象。采用随机数字表法，将其分为联合治疗组(n＝37，采用拔除气管插管前24 h开始应用枸橼酸咖啡因联合拔除气管插管后HHHFNC方案预防拔管失败)及对照组(n＝35，拔除气管插管后单独采用NCPAP方案预防拔管失败)。采用成组t检验或χ2检验，对2组患儿一般临床资料、临床疗效、无创辅助通气相关并发症等，进行统计学比较。本研究经过东南大学附属徐州医院医学伦理委员会审核批准(审批文号：2017伦审第13号)，患儿监护人均签署临床研究知情同意书。

结果

① 2组RDS早产儿性别构成比、出生胎龄、孕次、出生体重，以及母亲胎膜早破发生率、剖宫产术分娩率、受孕方式构成比、产前24 h至7 d糖皮质激素使用率、妊娠期高血压疾病发生率，Ⅲ级RDS发生率、生后1 min及5 min Apgar评分、肺表面活性物质(PS)使用率及有创机械通气时间等一般临床资料比较，差异均无统计学意义(P>0.05)。②联合治疗组RDS早产儿拔管失败率、无创辅助通气时间、总用氧时间、住院时间、呼吸暂停次数分别为8.1%(3/37)，3.5 d(1.0～15.0 d)，11.0 d(4.0～28.0 d)，15.5 d(6.0～29.0 d)，11.0次(7.0～15.0次)，均显著低于、短于或少于对照组的20.0%(7/35)，6.5 d(2.5～18.0 d)，15.0 d(6.0～32.0 d)，22.0 d(7.0～36.0 d)，18.0次(8.0～25.0次)，2组比较，差异均有统计学意义(χ2＝4.712、P＝0.030，Z＝－2.030、P＝0.018，Z＝－2.129、P＝0.012，Z＝－2.889、P＝0.008，Z＝－2.105、P＝0.022)。联合治疗组早产儿达到足量经口喂养时间较对照组缩短，分别为10.0 d(6.0～20.0 d)和16.0 d(8.0～28.0 d)，并且差异亦有统计学意义(Z＝－2.857、P＝0.010)。③联合治疗组RDS早产儿无创辅助通气相关并发症鼻损伤、腹胀及头部塑形发生率分别为10.8%(4/37)、10.8%(4/37)及8.1%(3/37)，均分别显著低于对照组的22.9%(8/35)、28.6%(10/35)及31.4%(11/35)，并且差异均有统计学意义(χ2＝4.782、5.140、5.982，P＝0.028、0.021、0.012)。

结论

较单独应用NCPAP，采用枸橼酸咖啡因联合HHHFNC方案预防RDS早产儿拔管失败，可降低拔管失败率、鼻损伤及腹胀等并发症发生率，缩短无创辅助通气及用氧时间，安全、有效。

关键词: 呼吸窘迫综合征，新生儿, 枸橼酸咖啡因, 加温湿化高流量鼻导管通气, 连续气道正压通气, 肺表面活性剂, 婴儿，早产
Objective

To investigate the clinical efficacy and safety of caffeine citrate combined with heated humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (NCPAP) for prevention of extubation failure in premature infants with respiratory distress syndrome (RDS).

Methods

From September 2017 to February 2019, a total of 72 premature infants with RDS (28 weeks≤gestational age<32 weeks) who were prepared for noninvasive mechanical ventilation after a period of invasive mechanical ventilation with an endotracheal tube in neonatal intensive care unit of the Affiliated Xuzhou Hospital of Southeast University, were chosen as research subjects. They were randomly divided into two groups by random digits table method. In the combined treatment group (n=47), they were given caffeine citrate 24 h before extubation combined with HHHFNC after extubation for prevention of extubation failure; and in the control group (n=43), they were given NCPAP after extubation without caffeine citrate for prevention of extubation failure. The general clinical data, incidence of extubation failure, duration of noninvasive ventilation and total duration of oxygen inhaling, the days of achieving adequate oral feeding and related complications of noninvasive mechanical ventilation between two groups of premature infants were compared by independent-samples t test or chi-square test. The study was reviewed and approved by the Medical Ethics Committee of the Affiliated Xuzhou Hospital of Southeast University (Approval No. 2017-13), and clinical research informed consents were signed by the guardians of all premature infants.

Results

① There were no significant differences between two groups in general clinical data including gender composition ratio, gestational age, gravidity, birth weight, and the rate of premature rupture of membranes, cesarean section rate, composition ratio of conception, glucocorticoid application rate 24 h to 7 d before delivery, incidence rate of hypertensive disorders complicating pregnancy of mother, incidence of grade Ⅲ RDS, 1 min and 5 min Apgar scores of RDS premature infants after birth, usage rate of pulmonary surfactant (PS) and duration of invasive mechanical ventilation (P>0.05). ② The incidence of extubation failure, duration of noninvasive ventilation and total duration of oxygen inhaling, length of hospitalization, times of apnea in combined treatment group were 8.1% (3/37), 3.5 d (1.0-15.0 d), 11.0 d (4.0-28.0 d), 15.5 d (6.0-29.0 d) and 11.0 times (7.0-15.0 times), respectively, which were significant less or lower or shorter than those in control group 20% (7/35), 6.5 d (2.5-18.0 d), 15.0 d (6.0-32.0 d), 22.0 d (7.0-36.0 d) and 18.0 times (8.0-25.0 times), and all the differences were statistically significant(χ2=4.712, P=0.030; Z=-2.030, P=0.018; Z=-2.129, P=0.012; Z=-2.889, P=0.008; Z=-2.105, P=0.022). The time for children in the combination treatment group to achieve adequate oral feeding was shorter than that in control group which were 10.0 d (6.0-20.0 d) and 16.0 d (8.0-28.0 d), respectively, and the difference was statistically significant (Z=—2.857, P=0.010). ③The incidence rates of nasal injury, abdominal distention and head shaping in combined treatment group were 10.8% (4/37), 10.8% (4/37) and 8.1% (3/37), respectively, which were significant lower than those in control group, 22.9% (8/35), 28.6% (10/35) and 31.4% (11/35), and all the differences were statistically significant (χ2=4.782, 5.140, 5.982; P=0.028, 0.021, 0.012).

Conclusions

Compared with the application of NCPAP alone, caffeine citrate combined with HHHFNC for prevention of extubation failure in premature infants with RDS can reduce the incidence of extubation failure, nasal injury, and abdominal distension, and shorten the duration of noninvasive mechanical ventilation and oxygen inhaling. It′s a safe and effective respiratory support model for premature infants with RDS.

Key words: Respiratory distress syndrome, newborn, Caffeine citrate, Heated humidified high-flow nasal cannula, Continuous positive airway pressure, Pulmonary surfactants, Infant, premature
表1 2组呼吸窘迫综合征早产儿一般临床资料比较
组别 例数 性别[例数(%)] 出生胎龄(周，±s) 孕次[次，M(P25～P75)] 出生体重(g，±s) 胎膜早破[例数(%)] 剖宫产术分娩[例数(%)] 受孕方式[例数(%)]
男 女 自然受孕 辅助生殖
联合治疗组 37 22(59.4) 15(40.5) 30.3±2.1 1(1～2) 1 325±404 10(27.0) 30(81.1) 31(83.8) 6(16.2)
对照组 35 19(54.3) 16(45.7) 30.0±2.0 1(1～2) 1 312±398 10(28.6) 26(74.2) 27(77.1) 8(22.9)
检验值 ? χ2＝0.018 t＝0.887 Z＝－1.458 t＝2.402 χ2＝0.268 χ2＝0.225 χ2＝0.187
P值 ? 0.852 0.375 0.217 0.231 0.601 0.655 0.708
组别 例数 母亲产前24 h至7 d使用糖皮质激素[例数(%)] 母亲罹患妊娠期高血压疾病[例数(%)] Ⅲ级RDS[例数(%)] 生后1 min Apgar评分[分，M(P25～P75)] 生后5 min Apgar评分[分，M(P25～P75)] 使用PS[例数(%)] 有创机械通气时间(h，±s)
联合治疗组 37 15(40.5) 14(37.8) 8(21.6) 5(3～6) 7(6～9) 22(64.8) 72.5±12.5
对照组 35 13(37.1) 14(40.0) 7(20.0) 5(4～7) 7(5～9) 22(62.9) 75.5±14.5
检验值 ? χ2＝0.032 χ2＝0.088 χ2＝0.201 Z＝－1.250 Z＝－1.545 χ2＝0.242 t＝1.628
P值 ? 0.789 0.725 0.664 0.904 0.912 0.621 0.281
表2 2组呼吸窘迫综合征早产儿临床疗效比较
组别 例数 拔管失败[例数(%)] 无创辅助通气时间[d，M(P25～P75)] 总用氧时间[d，M(P25～P75)] 住院时间[d，M(P25～P75)] 呼吸暂停次数[次，M(P25～P75)] 达到足量经口喂养时间[d，M(P25～P75)]
联合治疗组 37 3(8.1) 3.5(1.0～15.0) 11.0(4.0～28.0) 15.5(6.0～29.0) 11.0(7.0～15.0) 10.0(6.0～20.0)
对照组 35 7(20.0) 6.5(2.5～18.0) 15.0(6.0～32.0) 22.0(7.0～36.0) 18.0(8.0～25.0) 16.0(8.0～28.0)
检验值 ? χ2＝4.712 a Z＝－2.030 Z＝－2.129 Z＝－2.889 Z＝－2.105 Z＝－2.857
P值 ? 0.030 0.018 0.012 0.008 0.022 0.010
表3 2组呼吸窘迫综合征早产儿无创辅助通气相关并发症比较[例数(%)]
组别 例数 BPD Ⅰ～Ⅱ期ROP PVH-IVH 鼻损伤 腹胀 头部塑形
联合治疗组 37 8(21.6) 10(27.0) 6(16.2) 4(10.8) 4(10.8) 3(8.1)
对照组 35 9(24.3) 11(31.4) 5(14.3) 8(22.9) 10(28.6) 11(31.4)
χ2值 ? 0.535 0.014 0.207 4.782 5.140 5.982
P值 ? 0.465 0.904 0.649 0.028 0.021 0.012
[1]
Sweet DG, Carnielli V, Greisen G, et al. European consensus guidelines on the management of respiratory distress syndrome-2016 update[J]. Neonatology: 2017, 111(2): 107-125.
[2]
王华，母得志. 新生儿呼吸窘迫综合征的通气策略[J/CD]. 中华妇幼临床医学杂志(电子版), 2017, 13(1): 10-13.
[3]
李文星，唐军，陈超，等. 预防早产儿拔管失败：加温湿化高流量鼻导管通气与经鼻持续气道正压通气效果比较的Meta分析[J/CD]. 中华妇幼临床医学杂志(电子版), 2019, 15(2): 171-179.
[4]
邵肖梅，叶鸿瑁，丘小汕. 实用新生儿学[M]. 4版. 北京：人民卫生出版社，2011: 395-398.
[5]
《中华儿科杂志》编辑委员会，中华医学会儿科学分会新生儿学组. 新生儿机械通气常规[J]. 中华儿科杂志，2015, 53(5): 327-330.
[6]
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.
[7]
Lista G, Castoldi F, Fontana P, et al. Nasal continuous positive airway pressure (CPAP) versus bi-level nasal CPAP in preterm babies with respiratory distress syndrome: a randomised control trial [J]. Arch Dis Child Fetal Neonatal Ed, 2010, 95(2): F85-F89.
[8]
Lodeserto FJ, Lettich TM, Rezaie SR. High-flow nasal cannula: mechanisms of action and adult and pediatric indications [J]. Cureus, 2018, 10(11): e3639.
[9]
Schmid F, Olbertz DM, Ballmann M. The use of high-flow nasal cannula (HFNC) as respiratory support in neonatal and pediatric intensive care units in Germany: a nationwide survey [J]. Respir Med, 2017, 131: 210-214.
[10]
Shetty S, Hickey A, Rafferty GF, et al. Work of breathing during CPAP and heated humidified high-flow nasal cannula[J]. Arch Dis Child Fetal Neonatal Ed, 2016, 101(5): F404-F407.
[11]
Garg BD, Bajaj N, Sharma D. To compare the efficacy of heated humidified high-flow nasal cannula and continuous positive airway pressure in post-extubation period in VLBW infants [J]. J Trop Pediatr, 2018, 64(4): 262-266.
[12]
Soonsawad S, Swatesutipun B, Limrungsikul A, et al. Heated humidified high-flow nasal cannula for prevention of extubation failure in preterm infants [J]. Indian J Pediatr, 2017, 84(4): 262-266.
[13]
Wilkinson D, Andersen C, O′Donnell CP, et al. High flow nasal cannula for respiratory support in preterm infants [J]. Cochrane Database Syst Rev, 2016, 2: CD006405.
[14]
Hermeto F, Martins BM, Ramos JR, et al. Incidence and main risk factors associated with extubation failure in newborns with birth weight < 1, 250 grams [J]. J Pediatr (Rio J), 2009, 85(5): 397-402.
[15]
Abu-Shaweesh JM, Martin RJ. Caffeine use in the neonatal intensive care unit [J]. Semin Fetal Neonatal Med, 2017, 22(5): 342-347.
[16]
Dekker J, Hooper SB, van Vonderen JJ, et al. Caffeine to improve breathing effort of preterm infants at birth: a randomized controlled trial [J]. Pediatr Res, 2017, 82(2): 290-296.
[17]
Henderson-Smart DJ, Davis PG. Prophylactic methylxanthines for endotracheal extubation in preterm infants [J]. Cochrane Database Syst Rev, 2010, 12: CD000139.
[18]
Davis PG, Schmidt B, Roberts RS, et al. Caffeine for apnea of prematurity trial benefits may vary in subgroups[J]. J Pediatr, 2010, 156(3): 382-387.
[19]
Fleeman N, Mahon J, Bates V, et al. The clinical effectiveness and cost-effectiveness of heated humidified high-flow nasal cannula compared with usual care for preterm infants: systematic review and economic evaluation[J]. Health Technol Assess, 2016, 20(30): 1-68.
[20]
Yoder BA, Stoddard RA, Li M, et al. Heated, humidified high-flow nasal cannula versus nasal CPAP for respiratory support in neonates [J]. Pediatrics, 2013, 131(5): e1482-e1490.
[21]
Lavizzari A, Veneroni C, Colnaghi M, et al. Respiratory mechanics during NCPAP and HHHFNC at equal distending pressures [J]. Arch Dis Child Fetal Neonatal Ed, 2014, 99(4): F315-F320.
[22]
Al-Alaiyan S, Dawoud M, Al-Hazzani F. Positive distending pressure produced by heated, humidified high flow nasal cannula as compared to nasal continuous positive airway pressure in premature infants [J]. J Neonatal Perinatal Med, 2014, 7(2): 119-124.
[23]
Collins CL, Holberton JR, Barfield C, et al. A randomized controlled trial to compare heated humidified high-flow nasal cannulae with nasal continuous positive airway pressure postextubation in premature infants [J]. J Pediatr, 2013, 162(5): 949-954.
[24]
刘翠青，夏耀方，江雨桐，等. 加温湿化高流量经鼻导管正压通气治疗新生儿呼吸窘迫综合征[J]. 中华围产医学杂志，2013, 16(4): 240-243.
[25]
Soonsawad S, Tongsawang N, Nuntnarumit P. Heated humidified high-flow nasal cannula for weaning from continuous positive airway pressure in preterm infants: a randomized controlled trial [J]. Neonatology, 2016, 110 (3): 204-209.
[26]
Lemyre B, Davis PG, De Paoli AG, et al. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation [J]. Cochrane Database Syst Rev, 2017, 2: CD003212.
[27]
Lemyre B, Davis PG, De Paoli AG, et al. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation [J]. Cochrane Database Syst Rev, 2014, 9: CD003212.
[28]
Armanian AM, Iranpour R, Parvaneh M, et al. Heated humidified high flow nasal cannula (HHHFNC) is not an effective method for initial treatment of respiratory distress syndrome (RDS) versus nasal intermittent mandatory ventilation (NIMV) and nasal continuous positive airway pressure (NCPAP) [J]. J Res Med Sci, 2019, 24: 73.
[29]
Kugelman A, Riskin A, Said W, et al. A randomized pilot study comparing heated humidified high-flow nasal cannulae with NIPPV for RDS [J]. Pediatr Pulmonol, 2015, 50(6): 576-583.
Roberts CT, Owen LS, Manley BJ, et al. Nasal high-flow therapy for primary respiratory support in preterm infants[J]. N Engl J Med, 2016, 375(12): 1142-1151.
[30]
Poets CF, Lorenz L. Prevention of bronchopulmonary dysplasia in extremely low gestational age neonates: current evidence [J]. Arch Dis Child Fetal Neonatal Ed, 2018, 103(3): F285-F291.
[31]
Pakvasa MA, Saroha V, Patel RM. Optimizing caffeine use and risk of bronchopulmonary dysplasia in preterm infants: a systematic review, Meta-analysis, and application of grading of recommendations assessment, development, and evaluation methodology [J]. Clin Perinatol, 2018, 45(2): 273-291.
[32]
耿晓萌，刘俊丽，李桂芳，等. 咖啡因在早产儿机械通气中效果的临床研究[J]. 中华新生儿科杂志，2017, 32(6): 443-447.
[1] 戴瑞芝, 霍美池, 李峥. 无创高频振荡通气对早产儿呼吸窘迫综合征的临床疗效[J]. 中华危重症医学杂志(电子版), 2022, 15(05): 372-378.
[2] 胡诤贇, 史建伟, 申建伟, 王冰, 蒋春苗, 刘冲. 基于机器学习鉴定早产儿支气管肺发育不良的关键基因[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 446-454.
[3] 李敏, 熊菲. 母乳成分及其影响因素的研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(03): 267-272.
[4] 周美岑, 王华, 母得志. 早产儿疫苗预防接种及时性[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(03): 261-266.
[5] 杨萍, 许世敏, 李亮亮, 尹向云, 锡洪敏, 马丽丽, 李向红. 早产儿支气管肺发育不良合并代谢性骨病的影响因素[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(02): 202-211.
[6] 苏永维, 陈果. 早产儿非心脏手术的麻醉管理[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(02): 139-144.
[7] 张霭润, 招嘉樑, 李管明, 李嘉鸿, 陈静蓉, 王兰, 庄思齐, 房晓祎. 早产儿RhE合并Rhc溶血病1例并文献复习[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(01): 93-99.
[8] 张璐, 杨惠娟, 刘凯波. 2015—2021年北京市辅助生殖技术助孕活产及高龄孕母占比与不良妊娠结局变化趋势[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(01): 46-53.
[9] 袁冰, 颜凯. 人羊膜上皮干细胞治疗早产儿支气管肺发育不良的研究现状[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(06): 640-644.
[10] 伏洪玲, 刘瀚旻. 支气管肺发育不良及肺动脉高压有关信号通路研究现状[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(05): 497-505.
[11] 张璐, 杨惠娟, 刘凯波. 影响双胎消失综合征存活儿围生期结局危险因素研究[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(04): 400-409.
[12] 李子贤, 李向红, 孙梦雅, 李亮亮, 尹向云, 锡洪敏, 杨萍, 马丽丽. 早产单绒毛膜双胎新生儿坏死性小肠结肠炎临床特点分析及相关文献复习[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(03): 343-349.
[13] 李磊, 白辉科, 许婉婷, 蒋依伶, 吴晨, 刘丽, 李德渊. 2种机械通气模式在极低出生体重早产儿呼吸窘迫综合征中的呼吸支持作用[J]. 中华妇幼临床医学杂志(电子版), 2022, 18(02): 198-204.
[14] 翟敬芳, 吴杰斌, 刘枭, 金宝, 王彦波, 陈洋, 王云, 周广玲, 周彬. 无创高频振荡通气在极低出生体重早产儿呼吸窘迫综合征初始呼吸支持治疗中的应用[J]. 中华妇幼临床医学杂志(电子版), 2021, 17(05): 598-605.
[15] 季菊花, 徐明, 洪菲, 宋磊. 枸橼酸咖啡因联合苯巴比妥对早产儿脑损伤患儿NF-κB、TLR2的影响[J]. 中华临床医师杂志(电子版), 2022, 16(02): 141-145.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号