不同剂量枸橼酸咖啡因在早产儿拔管前对呼吸力学的影响
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摘要
目的探讨不同剂量枸橼酸咖啡因在早产儿拔管前对呼吸力学的影响,从而寻找有助于拔管的最佳剂量。方法将收治的90例机械通气超过48小时且胎龄小于37周的早产儿按随机原则分为枸橼酸咖啡因大剂量组和小剂量组及对照组三组,每组各30例。在积极抗感染、稳定内环境、静脉营养支持及机械通气等基础上,有呼吸窘迫症状和体征的给予肺表面活性物质(pulmonary surfactant,PS)(固尔苏)替代治疗(治疗剂量200mg/kg气管内给药,必要时可重复给药),大剂量组在准备拔管前24小时或非计划拔管6小时内用枸橼酸咖啡因20mg/kg.d(10min)维持治疗至成功拔管,小持剂量组准备拔管前24小时或非计划拔管6小时内用枸橼酸咖啡因按5mg/kg.d(10min)维持治疗至成功拔管,对照组只给予常规治疗而不给予枸橼酸咖啡因及氨茶碱或其他甲基黄嘌呤药物。记录患儿用药前及拔管前呼吸机参数及使用枸橼酸咖啡因药物前2小时内及拔管后2小时各组的血气分析指标,检测用药治疗前、拔管前及拔管后2小时患者的呼吸力学变化并记录患儿拔管后的通气模式,统计患儿的成功拔管率及不良反应。结果大剂量组、小剂量组及对照组三组患儿的呼吸力学在拔管前改变为呼吸功(WOB)、气道阻力(Raw)、顺应性(cdyn)比较差异具有统计学意义(P<0.05);大剂量组与小剂量组、对照组的血气分析指标PaCO2及PaO2差异均有统计学意义(P<0.05);拔管成功的整体有效率,差异有统计学意义(P<0.05);不良反应三组无明显统计学差异(P>0.05)。结论大剂量枸橼酸咖啡因对早产儿拔管前呼吸力学的影响积极有效,有助于拔管且成功率明显高于小剂量组及对照组,且不会增加药物的不良反应,可在临床推广运用。
Objective To explore the effects of different doses of caffeine citrate on respiratory mechanics before extubation in preterm infants and to guide extubation.Methods 90 preterm infants with mechanical ventilation more than 48 hours and gestational age less than 37 weeks admitted to our hospital from July 2015 to July 2017 were randomized into caffeine high-dose caffeine group,low-dose group and the control group.Under the treatment of the active anti-infective,stable internal environment,intravenous nutrition support and mechanical ventilation,pulmonary surfactant(pulmonary surfactant,PS)replacement therapy(reactive dose 200mg/kg)with symptoms and signs of respiratory distress intratracheal administration,the high-dose group was treated with caffeine 20mg/kg.d(10min),until successfully extracted 24 hours before extubation or within 6hours of unplanned extubation.Tubes,small holding dose groups were treated with caffeine citrate at 5mg/kg.d(10min)until extubation within 24 hours before preparation for extubation or within 6hours of unplanned extubation.The control group received only routine treatment instead of routine treatment.The clinical data were used to record the ventilator parameters before and after extubation and the blood gas analysis indicators of the groups within 2hours before and after 2hours of extubation with citrate caffeine,and before,before and after extubation.The patient's respiratory mechanics changes were recorded 2hours after the procedure and the ventilatory pattern after extubation was recorded.The successful extubation rate and adverse reactions were recorded.Results After different doses of caffeine citrate were used,the respiratory mechanics of the high-dose,low-dose and control groups changed to WOB before extubation(801±87.6)VS(902±90.3).VS(1217±99.5)g·cm/(min·Kg),airway resistance(Raw)(62.38±17.27)VS(68.73±14.46)VS(72.49±13.84)cmH2O/(L·s)Compliance(Cdyn)(2.0±0.39)vs(1.58±0.30)VS(1.43±0.37)mL/cmH2 O,P<0.05.The blood gas analysis of each group during the first 2hours of acid caffeine and 2hours after extubation was compared.The results showed that the blood gas analysis parameters PaCO2 and PaO2were high in the high-dose group and the low-dose group and the control group(P<0.05.The overall effective rate of successful extubation of he high-dose group,the low-dose group and the control group were 86.7%,73.3%and 56.7%(P<0.05).Among the adverse reactions,there was no significant difference between the high-dose caffeine caffeine group and the low-dose group and the control group.Conclusion The high-dose group(20mg/kg.d)of caffeine citrate had a positive effect on the pre-extubation respiratory mechanics.It was helpful for extubation and the success rate was significantly higher than that of the low-dose group and the control group.There was no statistically significant difference between the two groups in adverse reactions,so it is worthy of promotion and application in clinical practice.
Objective To explore the effects of different doses of caffeine citrate on respiratory mechanics before extubation in preterm infants and to guide extubation.Methods 90 preterm infants with mechanical ventilation more than 48 hours and gestational age less than 37 weeks admitted to our hospital from July 2015 to July 2017 were randomized into caffeine high-dose caffeine group,low-dose group and the control group.Under the treatment of the active anti-infective,stable internal environment,intravenous nutrition support and mechanical ventilation,pulmonary surfactant(pulmonary surfactant,PS)replacement therapy(reactive dose 200mg/kg)with symptoms and signs of respiratory distress intratracheal administration,the high-dose group was treated with caffeine 20mg/kg.d(10min),until successfully extracted 24 hours before extubation or within 6hours of unplanned extubation.Tubes,small holding dose groups were treated with caffeine citrate at 5mg/kg.d(10min)until extubation within 24 hours before preparation for extubation or within 6hours of unplanned extubation.The control group received only routine treatment instead of routine treatment.The clinical data were used to record the ventilator parameters before and after extubation and the blood gas analysis indicators of the groups within 2hours before and after 2hours of extubation with citrate caffeine,and before,before and after extubation.The patient's respiratory mechanics changes were recorded 2hours after the procedure and the ventilatory pattern after extubation was recorded.The successful extubation rate and adverse reactions were recorded.Results After different doses of caffeine citrate were used,the respiratory mechanics of the high-dose,low-dose and control groups changed to WOB before extubation(801±87.6)VS(902±90.3).VS(1217±99.5)g·cm/(min·Kg),airway resistance(Raw)(62.38±17.27)VS(68.73±14.46)VS(72.49±13.84)cmH2O/(L·s)Compliance(Cdyn)(2.0±0.39)vs(1.58±0.30)VS(1.43±0.37)mL/cmH2 O,P<0.05.The blood gas analysis of each group during the first 2hours of acid caffeine and 2hours after extubation was compared.The results showed that the blood gas analysis parameters PaCO2 and PaO2were high in the high-dose group and the low-dose group and the control group(P<0.05.The overall effective rate of successful extubation of he high-dose group,the low-dose group and the control group were 86.7%,73.3%and 56.7%(P<0.05).Among the adverse reactions,there was no significant difference between the high-dose caffeine caffeine group and the low-dose group and the control group.Conclusion The high-dose group(20mg/kg.d)of caffeine citrate had a positive effect on the pre-extubation respiratory mechanics.It was helpful for extubation and the success rate was significantly higher than that of the low-dose group and the control group.There was no statistically significant difference between the two groups in adverse reactions,so it is worthy of promotion and application in clinical practice.
引文
[1]杨庆南,朱建幸.新生儿机械通气时撤机失败原因分析[J].临床儿科杂志,2007,25(3):190-192.
[2]柳国胜.新生儿呼吸暂停[J].中华实用儿科临床杂志,2007,22(2):89-92.
[3] Abushaweesh J M,Martin R J.Neonatal apnea:what's new?[J].Pediatric Pulmonology,2010,43(10):937-944.
[4] Poets C F,Roberts R S,Schmidt B,et al.Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants[J].Jama,2015,314(6):595-603.
[5] Parikka V,Beck J,Zhai Q,et al.The effect of caffeine citrate on neural breathing pattern in preterm infants[J].Early Human Development,2015,91(10):565-568.
[6] Vliegenthart R J,Ten Hove C H,Onland W,et al.Doxapram Treatment for Apnea of Prematurity:A Systematic Review.[J].Neonatology,2017,111(2):162-171.
[7] Schoen K,Yu T,Stockmann C,et al.Use of Methylxanthine Therapies for the Treatment and Prevention of Apnea of Prematurity[J].Pediatric Drugs,2014,16(2):169-177.
[8] Aranda J V,Beharry K,Valencia G B,et al.Caffeine impact on neonatal morbidities[J].The journal of maternal-fetal&neonatal medicine,2010,23Suppl 3(3):20.
[9] Picone S,Bedetta M,Paolillo P.Caffeine citrate:when and for how long.A literature review[J].J Matern Fetal Neonatal Med,2012,25(sup3):11-14.
[10] Shrestha B,Jawa G.Caffeine citrate-Is it a silver bullet in neonatology[J].Pediatrics&Neonatology,2017,58(5)1-7.
[11] Migdal M,Dreizzen E,Praud J P,et al.Compliance of the total respiratory system in healthy preterm and full-term newborns[J].Pediatric Pulmonology,1987,3(4):214-218.
[12] Marcus C L,Meltzer L J,Roberts R S,et al.Long-term effects of caffeine therapy for apnea of prematurity on sleep at school age[J].Am J Respir Crit Care Med,2014,190(7):791-799.
[13] Mohammed S,Nour I,Shabaan A E,et al.High versus lowdose caffeine for apnea of prematurity:a randomized controlled trial[J].European Journal of Pediatrics,2015,174(7):949-956.
[14]刘雅竹,陈亚丹,李婷婷,付秀娟.不同剂量枸橼酸咖啡因用于早产儿呼吸暂停的疗效和安全性系统评价[J/OL].中国医院药学杂志,2018(02):1-7.
[15] ClinicalTrials.gov.Caffeine to reduce mechanical ventilation in preterm infants.Identifier NCT01751724.Bethesda,MD:US National Institutes of Health.
[16] Mcpherson C,Neil J J,Tjoeng T H,et al.A pilot randomized trial of high-dose caffeine therapy in preterm infants[J].Pediatric Research,2015,78(2):198-204.
[17]邵肖梅,叶鸿瑁,丘小汕.实用新生儿学.第4版.北京:人民卫生出版社,2011.245-247.
[18]姜赤秋,高源,洪艳,等.早期新生儿呼吸困难196例临床分析[J].中国妇幼保健,2012,27(9):1334-1335.
[19] Vesoulis Z A,Mcpherson C,Neil J J,et al.Early High-Dose Caffeine Increases Seizure Burden in Extremely Preterm Neonates:A Preliminary Study[J].Journal of Caffeine Research,2016,6(3):101-107.
[20]吴立志,刘云,阚清,等.经皮氧分压及二氧化碳分压与动脉血气分析在氧疗新生儿中的一致性分析[C]//泛长三角围产医学学术年会暨浙江省围产医学学术年会,2015.
[21]任艳丽,杨长仪,陈涵强,等.经皮二氧化碳分压及氧分压监测在新生儿重症监护病房的应用价值探讨[J].中国新生儿科杂志,2015,30(2):98-103.
[22] Bernetbuettiker V,Ugarte M J,Frey B,et al.Evaluation of a new combined transcutaneous measurement of PCO2/pulse oximetry oxygen saturation ear sensor in newborn patients[J].Pediatrics,2005,
[23]王少华,杨军,李志勇,等.新生儿呼吸衰竭机械通气撤机时的肺力学研究[J].中华急诊医学杂志,2005,14(12):1031-1034.
[24]韦秋文,徐平.机械通气之新生儿呼吸力学指标动态监测的临床应用[J].广西医学,2005,27(11):1745-1747.
[25]邵肖梅,叶鸿瑁,丘小汕.实用新生儿学.第4版.北京:人民卫生出版社,2011.59-63.
[26] Koch G,Datta A N,Jost K,et al.Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in Preterm Neonates[J].Journal of Pediatrics,2017,191:50-56.
[27] Shivakumar M,Jayashree P,Najih M,et al.Comparative Efficacy and Safety of Caffeine and Aminophylline for Apnea of Prematurity in Preterm(≤34 weeks)Neonates:A Randomized Controlled Trial[J].Indian Pediatrics,2017,54(10):870-870.
[28] Borszewska-Kornacka M K,Ho,Ejowski R,Rutkowska M,et al.Shifting the boundaries for early caffeine initiation in neonatal practice:Results of a prospective,multicenter study on very preterm infants with respiratory distress syndrome[J].Plos One,2017,12(12):e0189152.
[29] Parikka V,Beck J,Zhai Q,et al.The effect of caffeine citrate on neural breathing pattern in preterm infants[J].Early Human Development,2015,91(10):565-568.
[30]刘洪杰,朱艳萍.枸橼酸咖啡因在新生儿期的临床应用进展[J].中国医药导报,2015,12(33):69-73.
[31] Henderson-Smart D J,Davis P G.Prophylactic methylxanthines for extubation in preterm infants[M]//The Cochrane Library.John Wiley&Sons,Ltd,2003:CD000139.
[32] Hwang J,Kim YS,Shin JH,et al.Hemodynamic Effects on Systemic Blood Flow and Ductal Shunting Flow after Loading Dose of Intravenous Caffeine in Preterm Infants according to the Patency of Ductus Arteriosus[J].Journal of Korean Medical Science,2018,33(4):25.
[33] Steer P,Flenady V,Shearman A,et al.High dose caffeine citrate for extubation of preterm infants:a randomised controlled trial[J].Archives of Disease in Childhood Fetal&Neonatal Edition,2004,89(6):499-503.
[34] Mohammed S,Nour I,Shabaan A E,et al.High versus lowdose caffeine for apnea of prematurity:a randomized controlled trial[J].European Journal of Pediatrics,2015,174(7):949-956.
[2]柳国胜.新生儿呼吸暂停[J].中华实用儿科临床杂志,2007,22(2):89-92.
[3] Abushaweesh J M,Martin R J.Neonatal apnea:what's new?[J].Pediatric Pulmonology,2010,43(10):937-944.
[4] Poets C F,Roberts R S,Schmidt B,et al.Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants[J].Jama,2015,314(6):595-603.
[5] Parikka V,Beck J,Zhai Q,et al.The effect of caffeine citrate on neural breathing pattern in preterm infants[J].Early Human Development,2015,91(10):565-568.
[6] Vliegenthart R J,Ten Hove C H,Onland W,et al.Doxapram Treatment for Apnea of Prematurity:A Systematic Review.[J].Neonatology,2017,111(2):162-171.
[7] Schoen K,Yu T,Stockmann C,et al.Use of Methylxanthine Therapies for the Treatment and Prevention of Apnea of Prematurity[J].Pediatric Drugs,2014,16(2):169-177.
[8] Aranda J V,Beharry K,Valencia G B,et al.Caffeine impact on neonatal morbidities[J].The journal of maternal-fetal&neonatal medicine,2010,23Suppl 3(3):20.
[9] Picone S,Bedetta M,Paolillo P.Caffeine citrate:when and for how long.A literature review[J].J Matern Fetal Neonatal Med,2012,25(sup3):11-14.
[10] Shrestha B,Jawa G.Caffeine citrate-Is it a silver bullet in neonatology[J].Pediatrics&Neonatology,2017,58(5)1-7.
[11] Migdal M,Dreizzen E,Praud J P,et al.Compliance of the total respiratory system in healthy preterm and full-term newborns[J].Pediatric Pulmonology,1987,3(4):214-218.
[12] Marcus C L,Meltzer L J,Roberts R S,et al.Long-term effects of caffeine therapy for apnea of prematurity on sleep at school age[J].Am J Respir Crit Care Med,2014,190(7):791-799.
[13] Mohammed S,Nour I,Shabaan A E,et al.High versus lowdose caffeine for apnea of prematurity:a randomized controlled trial[J].European Journal of Pediatrics,2015,174(7):949-956.
[14]刘雅竹,陈亚丹,李婷婷,付秀娟.不同剂量枸橼酸咖啡因用于早产儿呼吸暂停的疗效和安全性系统评价[J/OL].中国医院药学杂志,2018(02):1-7.
[15] ClinicalTrials.gov.Caffeine to reduce mechanical ventilation in preterm infants.Identifier NCT01751724.Bethesda,MD:US National Institutes of Health.
[16] Mcpherson C,Neil J J,Tjoeng T H,et al.A pilot randomized trial of high-dose caffeine therapy in preterm infants[J].Pediatric Research,2015,78(2):198-204.
[17]邵肖梅,叶鸿瑁,丘小汕.实用新生儿学.第4版.北京:人民卫生出版社,2011.245-247.
[18]姜赤秋,高源,洪艳,等.早期新生儿呼吸困难196例临床分析[J].中国妇幼保健,2012,27(9):1334-1335.
[19] Vesoulis Z A,Mcpherson C,Neil J J,et al.Early High-Dose Caffeine Increases Seizure Burden in Extremely Preterm Neonates:A Preliminary Study[J].Journal of Caffeine Research,2016,6(3):101-107.
[20]吴立志,刘云,阚清,等.经皮氧分压及二氧化碳分压与动脉血气分析在氧疗新生儿中的一致性分析[C]//泛长三角围产医学学术年会暨浙江省围产医学学术年会,2015.
[21]任艳丽,杨长仪,陈涵强,等.经皮二氧化碳分压及氧分压监测在新生儿重症监护病房的应用价值探讨[J].中国新生儿科杂志,2015,30(2):98-103.
[22] Bernetbuettiker V,Ugarte M J,Frey B,et al.Evaluation of a new combined transcutaneous measurement of PCO2/pulse oximetry oxygen saturation ear sensor in newborn patients[J].Pediatrics,2005,
[23]王少华,杨军,李志勇,等.新生儿呼吸衰竭机械通气撤机时的肺力学研究[J].中华急诊医学杂志,2005,14(12):1031-1034.
[24]韦秋文,徐平.机械通气之新生儿呼吸力学指标动态监测的临床应用[J].广西医学,2005,27(11):1745-1747.
[25]邵肖梅,叶鸿瑁,丘小汕.实用新生儿学.第4版.北京:人民卫生出版社,2011.59-63.
[26] Koch G,Datta A N,Jost K,et al.Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in Preterm Neonates[J].Journal of Pediatrics,2017,191:50-56.
[27] Shivakumar M,Jayashree P,Najih M,et al.Comparative Efficacy and Safety of Caffeine and Aminophylline for Apnea of Prematurity in Preterm(≤34 weeks)Neonates:A Randomized Controlled Trial[J].Indian Pediatrics,2017,54(10):870-870.
[28] Borszewska-Kornacka M K,Ho,Ejowski R,Rutkowska M,et al.Shifting the boundaries for early caffeine initiation in neonatal practice:Results of a prospective,multicenter study on very preterm infants with respiratory distress syndrome[J].Plos One,2017,12(12):e0189152.
[29] Parikka V,Beck J,Zhai Q,et al.The effect of caffeine citrate on neural breathing pattern in preterm infants[J].Early Human Development,2015,91(10):565-568.
[30]刘洪杰,朱艳萍.枸橼酸咖啡因在新生儿期的临床应用进展[J].中国医药导报,2015,12(33):69-73.
[31] Henderson-Smart D J,Davis P G.Prophylactic methylxanthines for extubation in preterm infants[M]//The Cochrane Library.John Wiley&Sons,Ltd,2003:CD000139.
[32] Hwang J,Kim YS,Shin JH,et al.Hemodynamic Effects on Systemic Blood Flow and Ductal Shunting Flow after Loading Dose of Intravenous Caffeine in Preterm Infants according to the Patency of Ductus Arteriosus[J].Journal of Korean Medical Science,2018,33(4):25.
[33] Steer P,Flenady V,Shearman A,et al.High dose caffeine citrate for extubation of preterm infants:a randomised controlled trial[J].Archives of Disease in Childhood Fetal&Neonatal Edition,2004,89(6):499-503.
[34] Mohammed S,Nour I,Shabaan A E,et al.High versus lowdose caffeine for apnea of prematurity:a randomized controlled trial[J].European Journal of Pediatrics,2015,174(7):949-956.