【摘要】：早產(chǎn)兒呼吸暫停(apnea of prematurity,AOP)是早產(chǎn)兒尤其是極低出生體重兒呼吸管理中較為常見的疾病[1],并且與早產(chǎn)兒出生體重和胎齡有著非常密切的關系,胎齡、體重越小,AOP發(fā)生的可能性越大,體重小于1000g的早產(chǎn)兒即超低出生體重兒呼吸暫停發(fā)生率高達80%左右[2]。胎齡在三十周至三十二周的早產(chǎn)兒呼吸暫停發(fā)生率為50%左右。呼吸暫停可引起心動過緩、低氧血癥,增加腦積水、腦室內(nèi)出血及神經(jīng)系統(tǒng)發(fā)育異常的風險[3],嚴重時可能出現(xiàn)死亡。目前國際上治療AOP的主要藥物是甲基黃嘌呤類藥物,枸櫞酸咖啡因和氨茶堿均屬于黃嘌呤類藥物。有研究表明枸櫞酸咖啡因可以減少低氧血癥時間及機械通氣時間、降低支氣管肺發(fā)育不良(Brochopulmonary dysplasia,BPD)的發(fā)生率。但目前對有呼吸暫停的患兒肺發(fā)育情況研究不多。早產(chǎn)兒肺功能檢測是判斷呼吸系統(tǒng)發(fā)育程度[4]、探究呼吸系統(tǒng)疾病及尋找其生長發(fā)育規(guī)律的十分重要方法[5]。在臨床上可以根據(jù)肺功能檢測結果判斷呼吸系統(tǒng)疾病的性質、嚴重程度及監(jiān)控疾病發(fā)展過程,也可以在治療的過程中評估治療效果、協(xié)助選擇呼吸機的參數(shù)、指導并判斷預后。常規(guī)的肺功能檢查通常要求受試者非常積極的配合,這大大的阻礙了常規(guī)肺功能檢測在兒童和新生兒中的應用。潮氣呼吸肺功能的檢測只是需要平靜呼吸,操作相對簡單,更加適合不能配合的患者,比如說新生兒及年齡小的兒童,所以在臨床上獲得了越來越多的重視和應用。本文通過枸櫞酸咖啡因對有AOP的極低出生體重兒治療后不同時期潮氣呼吸肺功能的分析及動態(tài)隨訪,以進一步探討枸櫞酸咖啡因對其肺部發(fā)育所造成的影響。目的通過對住院期間有AOP的極低出生體重兒進行潮氣呼吸肺功能檢測及重要肺功能參數(shù)的比較,以探討枸櫞酸咖啡因對極低出生體重兒肺功能的影響。方法1.研究對象分組本次試驗研究對象為在2015年12月至2016年12月期間在鄭州大學第三附屬醫(yī)院新生兒病房住院的120例有原發(fā)性呼吸暫停的極低出生體重兒(出生體重1000g~1499g),隨機根據(jù)數(shù)字法分為氨茶堿應用組(P1)和枸櫞酸咖啡因應用組(P2),每組各60例。排除標準:(1)圍生期有重度窒息史、神經(jīng)系統(tǒng)疾病或功能紊亂;(2)一級親屬中有哮喘史;(3)母親有吸煙史;(4)存在嚴重的呼吸窘迫綜合征等呼吸系統(tǒng)疾病;(5)顱內(nèi)出血;(6)敗血癥等感染性疾病;(7)消化系統(tǒng)疾病及電解質紊亂;(8)嚴重的先天性心臟疾病(9)遺傳代謝性疾病;(10)藥物應用療程不足者、評估之前死亡者、放棄治療者;(11)其他因素所引發(fā)的繼發(fā)性呼吸暫停[4]。2.方法本次試驗研究選用潮氣呼吸法,在患兒自然睡眠或藥物睡眠(藥物選用10%水合氯醛0.3~0.5m1/kg口服或灌腸)、平靜呼吸狀態(tài)下,將受試者口鼻用面罩扣緊,經(jīng)流速傳感器將流速信號積分成容量,測得值可經(jīng)電腦自動生成并做好記錄。測時前還需要常規(guī)記錄患兒的性別、胎齡,并測量患兒的身長和體質量,測定的主要參數(shù)有:潮氣量(Tidal volume,TV)、吸氣時間(Inspiratory time,TI)、呼氣時間(Expiratory time,TE)、呼吸頻率(Respiratory rate,RR)、達峰時間比(Ratio of TPEF and total tE,TPEF/TE)、達峰容積比(Ratio of VPEF and totalVE,VPEF/VE)。本試驗已經(jīng)獲得我院人體試驗委員會批準及患兒監(jiān)護人書面知情同意書。對研究對象進行第一次潮氣呼吸肺功能檢測在患兒停用枸櫞酸咖啡因或氨茶堿后(最遲不超過生后34周)進行;并對兩組患兒隨訪,分別在校正胎齡40周時和出生后3個月對兩組患兒進行潮氣呼吸肺功能的檢測,并采用統(tǒng)計學方法進行分析,研究枸櫞酸咖啡因對極低出生體重兒在不同時期潮氣呼吸肺功能的影響。結果1.兩組一般資料比較兩組極低出生體重兒胎齡、出生體重、5minApgar評分均無統(tǒng)計學差異(P0.05)。2.停藥后(最遲不超過生后34周)測定兩組潮氣呼吸肺功能主要參數(shù)的差異試驗組即咖啡因組潮氣量、達峰容積比、達峰時間比、25%潮氣量時呼氣流速均高于對照組即氨茶堿組,并且與氨茶堿組相比有統(tǒng)計學意義(p0.05),余各項潮氣呼吸肺功能指標無明顯統(tǒng)計學差異(p0.05)。3.極低出生體重兒在校正胎齡40周時兩組潮氣呼吸肺功能主要參數(shù)的差異在極低出生體重兒在校正胎齡40周時試驗組即咖啡因組潮氣量、達峰時間比及50%潮氣量時呼氣流速、25%潮氣量時呼氣流速均高于對照組即氨茶堿組,其差異有統(tǒng)計學意義(p0.05),余各項潮氣呼吸肺功能指標無明顯統(tǒng)計學差異(p0.05)。4.出生后3個月兩組肺功潮氣呼吸肺功能主要參數(shù)的差異極低出生體重兒出生后3個月時試驗組即咖啡因組潮氣量較對照組即氨茶堿組高,并且差異有統(tǒng)計學意義(p0.05);而達峰容積比、達峰時間比及75%潮氣量時呼氣流速、50%潮氣量時呼氣流速、25%潮氣量時呼氣流速與氨茶堿組相比無統(tǒng)計學意義(p0.05)。結論枸櫞酸咖啡因治療極低出生體重兒呼吸暫停近遠期潮氣呼吸肺功能均有明顯改善。
[Abstract]:Premature apnea of prematurity (AOP) is a common disease in respiratory management of premature infants, especially very low birth weight infants [1], and has a very close relationship with the birth weight and gestational age of premature infants. The smaller the gestational age and weight, the greater the possibility of AOP. Premature infants weighing less than 1000g are called very low birth weight infants. The incidence of apnea is as high as 80%[2]. The incidence of apnea is about 50% in preterm infants between 30 and 32 weeks of gestation. Apnea can cause bradycardia, hypoxemia, increase the risk of hydrocephalus, intraventricular hemorrhage and abnormal nervous system development [3], and may lead to death in severe cases. Caffeine citrate and aminophylline are xanthine drugs. Studies have shown that caffeine citrate can reduce the duration of hypoxemia and mechanical ventilation, and reduce the incidence of bronchopulmonary dysplasia (BPD). Premature infants'pulmonary function test is a very important method to judge the degree of respiratory system development, explore the respiratory system diseases and find out their growth and development rules [5].In clinic, according to the results of pulmonary function test, we can judge the nature of respiratory system diseases, severity and monitor the process of disease development, and can also be treated too. Routine pulmonary function tests usually require very active cooperation, which greatly hinders the application of routine pulmonary function tests in children and newborns. More and more attention has been paid to the use of caffeine citrate in the treatment of very low birth weight (VLBW) infants with AOP. In this paper, we analyzed the tidal respiratory and pulmonary function of infants with AOP at different stages after treatment and followed up dynamically. Objective To investigate the effects of caffeine citrate on pulmonary function in very low birth weight infants with AOP during hospitalization by tidal breathing pulmonary function test and comparison of important pulmonary function parameters. Methods 1. Subjects were divided into two groups: subjects from December 2015 to December 2015. 120 very low birth weight infants with primary apnea (birth weight 1000g ~ 1499g) hospitalized in the neonatal ward of the Third Affiliated Hospital of Zhengzhou University in December 2016 were randomly divided into aminophylline application group (P1) and caffeine citrate application group (P2), 60 in each group. Exclusive criteria: (1) severe asphyxia occurred during perinatal period. Nervous system disease or dysfunction; (2) First degree relatives have a history of asthma; (3) mothers have a history of smoking; (4) severe respiratory distress syndrome and other respiratory diseases; (5) intracranial hemorrhage; (6) septicemia and other infectious diseases; (7) digestive system disease and electrolyte disorders; (8) serious congenital heart disease; (9) genetic metabolic diseases; (10) Methods In this study, tidal breathing was used to treat the children with spontaneous sleep or drug sleep (10% chloral hydrate 0.3-0.5m1/kg orally or enema) and the subjects were given oral sedation breathing. The nasal mask is fastened tightly, and the flow signal is integrated into volume by flow sensor. The measured value can be automatically generated and recorded by computer. Expiratory time (TE), Respiratory rate (RR), Ratio of TPEF and total time (TPEF/TE), Ratio of VPEF and total volume (VPEF/VE). This experiment has been approved by the Human Trial Committee of our hospital and written informed consent of the patient's guardian. Pulmonary function test was performed after cessation of caffeine citrate or aminophylline (no later than 34 weeks after birth); and two groups of children were followed up, respectively at the adjusted gestational age of 40 weeks and 3 months after birth, tidal breathing pulmonary function of the two groups of children were tested, and statistical methods were used to analyze the effect of caffeine citrate on very low levels. Results 1. There was no significant difference in gestational age, birth weight and 5-minute Apgar score between the two groups (P 0.05). 2. After stopping medication (no later than 34 weeks after birth) to determine the main parameters of tidal breathing lung function between the two groups: caffeine group Tidal volume, peak volume ratio, peak time ratio, expiratory flow rate at 25% tidal volume were higher than those in the control group, that is, aminophylline group, and there was statistical significance compared with aminophylline group (p0.05). There was no significant difference in the remaining tidal respiratory lung function indicators between the two groups (p0.05). 3. The difference of main parameters was that the tidal volume, peak time ratio, expiratory velocity at 50% tidal volume, and expiratory velocity at 25% tidal volume of very low birth weight infants were higher than those of the control group (aminophylline group) at 40 weeks of corrected gestational age (p0.05). 3 months after birth, the main parameters of pulmonary function were different between the two groups. 3 months after birth, the tidal volume of caffeine group was higher than that of aminophylline group, and the difference was statistically significant (p0.05); and the peak volume ratio, peak time ratio and 75% tidal volume, expiratory velocity, 50% tidal volume Respiratory flow at expiratory volume and at 25% tidal volume were not significantly different from those in aminophylline group (p0.05). Conclusion Caffeine citrate can significantly improve the lung function in very low birth weight infants with apnea.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R722.6

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