【摘要】：研究背景新生兒胎糞吸入綜合征(meconium aspiration syndrome,MAS)是因胎糞吸入呼吸道所致機(jī)械阻塞和化學(xué)炎癥引起的一系列反應(yīng),是產(chǎn)前或產(chǎn)時(shí)最常見(jiàn)的吸入性肺炎�；純旱闹饕R床表現(xiàn)為呼吸窘迫,病情嚴(yán)重者還可能因?yàn)楹粑ソ咧苯铀劳鯷1]。現(xiàn)今社會(huì),隨著二胎政策的全面開(kāi)放,人口主體逐漸傾向于低齡,新生兒漸成為中國(guó)人口的重要部分,如何提高這一群體的存活率和生存質(zhì)量,就顯得尤為重要。胎糞吸入綜合征的發(fā)生與家庭社會(huì)/經(jīng)濟(jì)地位、醫(yī)療資源情況以及孕婦初次妊娠年齡等因素有關(guān)。關(guān)于新生兒胎糞吸入綜合征的發(fā)病機(jī)制,顧名思義,其具體的機(jī)制與胎糞的排出、吸入過(guò)程有關(guān),因胎糞的形成和排出與胎齡的增長(zhǎng)有一定相關(guān)性,故MAS多見(jiàn)于足月兒,但引起宮內(nèi)胎糞排出的機(jī)制仍未十分清楚。一般情況下,即使羊水被胎糞污染,若未合并明顯的呼吸窘迫,正常的宮內(nèi)呼吸不會(huì)引起胎糞吸入,或者僅限于吸入上氣道或主氣管,但若胎兒在明顯的宮內(nèi)窘迫情況下,可使胎糞進(jìn)入小氣道或肺泡,生后呼吸開(kāi)始后可使胎糞進(jìn)入遠(yuǎn)端氣道,由此可見(jiàn),胎糞吸入綜合征與胎兒宮內(nèi)窘迫亦有一定程度的相關(guān)性。近年來(lái),有越來(lái)越多的學(xué)者研究關(guān)于PS的給藥方式、藥品選擇等方面,根據(jù)實(shí)際條件有選擇性的應(yīng)用氣管鏡灌洗,或者與鹽酸氨溴索灌洗相對(duì)比,評(píng)估PS氣管內(nèi)灌洗的必要性和有效性,以及對(duì)預(yù)后的影響。既往研究證實(shí),肺泡表面活性物質(zhì)(PS)失活在MAS發(fā)病機(jī)制過(guò)程中發(fā)揮重要作用。國(guó)內(nèi)外多中心隨機(jī)對(duì)照研究證實(shí),肺泡表面活性物質(zhì)氣管內(nèi)給藥可有效改善MAS患兒氧合及通氣功能[2-3],減少并發(fā)癥(PPHN、ARDS、肺氣漏、感染性肺炎,呼吸機(jī)相關(guān)肺炎等)發(fā)生率,降低死亡率。自從1978年纖維支氣管鏡首次應(yīng)用于兒科臨床以來(lái),纖支鏡在兒科呼吸道疾病的診斷和治療的作用受到廣泛認(rèn)同。近年來(lái)由于其大小和結(jié)構(gòu)的不斷改進(jìn),臨床纖支鏡醫(yī)師診治水平不斷提高,纖支鏡對(duì)于各種胎齡、體重的新生兒呼吸道疾病的診療起著非常重要的作用[4]。在我國(guó),由于國(guó)情問(wèn)題,醫(yī)療條件的限制,行纖支鏡檢查費(fèi)用較昂貴,纖支鏡目前尚未能廣泛應(yīng)用于兒科臨床。新生兒作為一個(gè)特殊的患者群體,需要更為專業(yè)、更為精細(xì)和高端的診療,希望本次研究能對(duì)新生兒胎糞吸入綜合征的臨床診療有一定的指導(dǎo)作用。目的本試驗(yàn)旨在探討早期行纖維支氣管鏡肺泡灌洗治療新生兒胎糞吸入綜合征(MAS)的療效及預(yù)后,并將稀釋PS灌洗組、NS灌洗組與未灌洗組互相對(duì)比,了解治療效果、并發(fā)癥及預(yù)后有無(wú)差異,進(jìn)一步研究胎糞吸入對(duì)新生兒肺部損傷的發(fā)病機(jī)制,為新生兒胎糞吸入的治療提供及時(shí)有效且可改善預(yù)后的治療新手段,有較好的臨床指導(dǎo)意義。方法本研究選取了2014年6月-2016年6月入住我院新生兒重癥監(jiān)護(hù)病房(nicu)確診為mas的足月患兒共48例,通過(guò)納入標(biāo)準(zhǔn)和排除標(biāo)準(zhǔn)共收集研究期間符合條件的患兒36例,剔除6例記錄信息不完整和中途放棄治療出院的患兒,最終30例患兒完成本研究,采取隨機(jī)抽簽法分為稀釋ps灌洗組,ns灌洗組,對(duì)照組,每組10例。本研究家屬均需簽署知情同意書(shū)。(1)稀釋ps灌洗組:在生后12小時(shí)內(nèi)予稀釋后的肺表面活性物質(zhì)(3~5ml/kg.次)行纖維支氣管鏡肺泡灌洗治療,灌洗后4h氣管內(nèi)滴入ps100mg/kg,然后給予呼吸支持;(2)生理鹽水(ns)灌洗組:在生后12小時(shí)內(nèi)行生理鹽水(3~5ml/kg)纖維支氣管鏡肺泡灌洗治療,灌洗后4h氣管內(nèi)滴入ps100mg/kg,后給予呼吸支持;(3)對(duì)照組:給予常規(guī)呼吸道清理及對(duì)癥支持治療,氣管插管后給予滴入肺泡表面活性物質(zhì)100mg/kg,后給予相應(yīng)的呼吸支持治療。治療過(guò)程中,根據(jù)患兒的病情考慮是否需行機(jī)械輔助通氣,必要時(shí)可反復(fù)給予ps,行一般治療中的所有常規(guī)監(jiān)測(cè)。ps氣管內(nèi)給藥后4~6小時(shí)內(nèi)不予氣管內(nèi)吸引。觀察指標(biāo):比較三組患兒治療前和治療后2,4,8,12,24,48,72h患兒經(jīng)皮血?dú)�、氧合指�?shù)(oi)、p/f值、機(jī)械通氣時(shí)間、肺部超聲表現(xiàn)、住院時(shí)間、并發(fā)癥(pphn、ards、肺氣漏、感染性肺炎,呼吸機(jī)相關(guān)肺炎等)發(fā)生率、治愈率、死亡率。呼吸支持和氧療方式[5]:三組患兒呼吸機(jī)支持和撤除呼吸機(jī)指征相同;有創(chuàng)通氣上機(jī)指征:(1)pao260mmhg而fio260%;(2)血?dú)夥治?ph7.2,pco260mmhg,be-8mmol/l。拔管指征:(1)自主呼吸可,能耐受氣道吸引時(shí)的屏氣和咳嗽反射24h以上;(2)血?dú)夥治?ph7.25,pco260mmhg,be-8mmol/l;(3)pip≤10~15cmh2o,呼氣末正壓(peep)4cmh2o,頻率≤10次/分,持續(xù)24~48h;(4)平均氣道壓8cmh2o,呼吸頻率30次/分,吸入氧濃度(fio2)40%,spo20.93,維持24小時(shí)以上。無(wú)創(chuàng)通氣指征(nippv)指征:(1)fio240%不能維持pao260mmhg;(2)血?dú)夥治?pco260mmhg;(3)拔管后再次出現(xiàn)明顯三凹征或(和)呼吸窘迫者。撤除nippv指征:(1)呼氣末正壓(peep)4cmh2o持續(xù)24~48h;(2)fio230%,呼吸頻率60次/分,spo2在0.91~0.95維持24h以上;(3)無(wú)呼吸暫停、心動(dòng)過(guò)緩,無(wú)sao2降低、呼吸做功不增加;(4)患兒可耐受護(hù)理時(shí)暫時(shí)脫離nippv。同時(shí)符合以上條件,且血?dú)夥治鲞_(dá)到如下要求:ph7.25,pco260mmhg,be-8mmol/l。撤除nippv后的患兒均給予高流量鼻導(dǎo)管給氧直至停氧。需反復(fù)給予肺泡表面活性物質(zhì)指征:(1)oi(氧合指數(shù))值無(wú)改善或200;(2)fio250%;(3)呼吸機(jī)主要參數(shù)pip和peep下調(diào)困難[6];(4)合并ards患兒;(5)合并pphn患兒。數(shù)據(jù)分析:采用spss19.0統(tǒng)計(jì)軟件進(jìn)行數(shù)據(jù)處理。計(jì)量數(shù)據(jù)以x—±s表示,兩組間均數(shù)的比較采用t檢驗(yàn),同組治療前后比較采用配對(duì)t檢驗(yàn);等級(jí)資料比較采用秩和檢驗(yàn);計(jì)數(shù)資料比較采用X2檢驗(yàn),以P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果最終30例本院MAS患兒納入本研究,每組10例。各組患兒性別、胎齡、入院時(shí)年齡、出生體重、Apgar評(píng)分差異均無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)。各組患兒在治療前、治療后2、4、8、12、24、48、72h氧合指數(shù)(OI)和P/F比較:PS組與NS組在灌洗后4-12小時(shí)期間OI和P/F的比較差異有統(tǒng)計(jì)學(xué)意義(p0.05),12-72小時(shí)期間OI和P/F比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。PS灌洗組和NS灌洗組在各觀察時(shí)段的OI和P/F與對(duì)照組差異均有顯著意義(p0.05)。各組呼吸支持和PS使用情況比較:PS灌洗組和NS灌洗組與對(duì)照組比較,拔管時(shí)間、使用NIPPV時(shí)間,高流量給氧的時(shí)間縮短,需要高頻支持的比率減少,差異均有統(tǒng)計(jì)學(xué)意義(p0.05)。PS灌洗組和NS灌洗組的PS使用總量和次數(shù)較對(duì)照組減少,差異有統(tǒng)計(jì)學(xué)意義(p0.05)。PS灌洗組和NS灌洗組對(duì)比,以上觀察指標(biāo)差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05)。各組并發(fā)癥情況比較:PS灌洗組和NS灌洗組與對(duì)照組比較,肺氣漏,感染性肺炎,VAP,合并PPHN,ARDS比率減少,差異均有統(tǒng)計(jì)學(xué)意義(p0.05)。PS灌洗組和NS灌洗組與對(duì)照組的死亡和放棄的比率比較明顯減少,差異有統(tǒng)計(jì)學(xué)意義(p0.05)。PS灌洗組和NS灌洗組對(duì)比,以上觀察指標(biāo)差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05)。結(jié)論早期行纖維支氣管鏡肺泡灌洗的療效明顯優(yōu)于未灌洗組;早期予稀釋PS灌洗與NS灌洗的療效無(wú)顯著差異;氣管內(nèi)滴入PS治療MAS的療效肯定�？偠灾�,早期予纖維支氣管鏡肺泡灌洗治療新生兒MAS可明顯改善患兒氧合和通氣功能,促進(jìn)病情恢復(fù),減少并發(fā)癥發(fā)生率,降低死亡率。本研究還存在樣本小,研究時(shí)間跨度短,暫無(wú)院外隨訪結(jié)局,機(jī)械輔助通氣未能統(tǒng)一設(shè)計(jì)等一些不足,因此需進(jìn)一步改進(jìn)和完善。
[Abstract]:BACKGROUND Meconium aspiration syndrome (MAS) is a series of reactions caused by mechanical obstruction and chemical inflammation of respiratory tract caused by meconium aspiration. It is the most common inhalation pneumonia in prenatal or intrapartum. The main clinical manifestation of MAS is respiratory distress, and the severe cases may also be due to respiratory failure directly. Death [1]. Nowadays, with the full-scale opening-up of the second-child policy, the main body of the population tends to be younger, and the newborn has gradually become an important part of the Chinese population. How to improve the survival rate and quality of life of this group is particularly important. As for the pathogenesis of meconium aspiration syndrome, the specific mechanism is related to the excretion and inhalation of meconium. Because the formation and excretion of meconium are related to the growth of gestational age, MAS is more common in full-term infants, but the mechanism of intrauterine meconium excretion is still unclear. Usually, even if amniotic fluid is contaminated by meconium, if there is no obvious respiratory distress, normal intrauterine respiration will not cause meconium inhalation, or only inhalation of the upper airway or the main trachea, but if the fetus is in obvious intrauterine distress, meconium can enter the small airway or alveoli, after the beginning of postnatal breathing, meconium can enter the distal end. In recent years, more and more scholars have studied the administration of PS, drug selection and other aspects. According to the actual conditions, selective application of bronchoscopic lavage, or compared with ambroxol hydrochloride lavage, to evaluate the endotracheal lavage of PS. Previous studies have confirmed that inactivation of alveolar surfactant (PS) plays an important role in the pathogenesis of MAS. Multicenter randomized controlled studies have confirmed that intratracheal administration of pulmonary surfactant can effectively improve oxygenation and ventilation function in children with MAS and reduce complications (P Since fiberoptic bronchoscopy was first used in pediatric clinic in 1978, its role in diagnosis and treatment of respiratory diseases in pediatrics has been widely recognized. In recent years, clinical fiberoptic bronchoscopy has been widely accepted because of its continuous improvement in size and structure. Fiberoptic bronchoscopy plays a very important role in the diagnosis and treatment of respiratory diseases in newborns of various gestational ages and weights [4].In China, due to the national conditions and the limitations of medical conditions, bronchoscopy is more expensive, bronchoscopy has not yet been widely used in pediatric clinics. We hope that this study can provide some guidance for the clinical diagnosis and treatment of meconium aspiration syndrome. Objective To investigate the effect and prognosis of early bronchoalveolar lavage with fiberoptic bronchoscopy in the treatment of meconium aspiration syndrome (MAS), and dilute PS irrigation. In the wash group, NS lavage group and non-lavage group, the therapeutic effect, complications and prognosis were compared, and the pathogenesis of lung injury in neonates by meconium inhalation was further studied, which provided a timely and effective treatment for the treatment of meconium inhalation in neonates and improved the prognosis. A total of 48 full-term neonates admitted to the neonatal intensive care unit (nicu) of our hospital from June 2014 to June 2016 were selected. 36 eligible neonates were collected by inclusion criteria and exclusion criteria. Six patients with incomplete records and discharged from hospital were excluded. Finally, 30 patients completed the study. The family members of this study were required to sign informed consent. (1) Diluted PS lavage group: the diluted pulmonary surfactant (3-5ml/kg. times) was given bronchoalveolar lavage by fiberoptic bronchoscopy within 12 hours after birth, and then the diluted pulmonary surfactant (3-5ml/kg. times) was given intratracheal instillation of 100 mg/kg of PS 4 hours after lavage. Respiratory support; (2) Normal saline (ns) lavage group: 12 hours after birth, normal saline (3-5ml/kg) bronchoscopic alveolar lavage treatment, 4 hours after lavage intratracheal instillation of ps100mg/kg, after giving respiratory support; (3) Control group: given routine respiratory tract cleaning and symptomatic support treatment, tracheal intubation was given to drip into the alveolar surfactant 100 In the course of treatment, mechanical ventilation was considered according to the patient's condition. If necessary, PS was given repeatedly, and all routine monitoring during general treatment was performed. No endotracheal aspiration was given within 4 to 6 hours after intratracheal administration of PS. 24,48,72 hours of children with percutaneous blood gas, oxygenation index (oi), P / F value, mechanical ventilation time, pulmonary ultrasound performance, length of stay, complications (pphn, ards, pneumonia, infectious pneumonia, ventilator-associated pneumonia, etc.) incidence, cure rate, mortality. Indications of ventilator: (1) Pao 260 mmHg and FIO 260%; (2) blood gas analysis: ph7.2, PCO 260 mmhg, be-8 mmol / L. (2) extubation indications: (1) spontaneous breath, can toleratbreathholding and cough reflex more than 24 hours; (2) blood gas analysis: ph7.25, pco260 mmhg, be-8 mmol / l; (3) PIP < 10-15 cm h2o, positive end expirexpiratory pressure (peep) 4cm h2, frequency < 24-10-10-15 cmh2fraction, frequency < 24-24-24-10-4, persistenfrequency < 24-10-10-10-10-10 cmh2 fraction, frequency < 24-4, frequency In the meantime, it is necessary to study the relationship between the two. 8 hours; (4) mean airway pressure 8 cm h2o, respiratory rate 30 times / min, inhaled oxygen concentration (fio2) 40%, spo20.93, maintained for more than 24 hours. Ep) 4 cmH2O lasted 24-48 hours; (2) FIO 230%, respiratory rate 60 times / min, SpO 2 maintained 24 hours above 0.91-0.95; (3) no apnea, bradycardia, no SaO 2 decreased, respiratory work did not increase; (4) children can tolerate nursing temporarily out of nippv. At the same time meet the above conditions, and blood gas analysis to meet the following requirements: ph7.25, pco260 mmhg, be-8 mmol / L. All the patients were given high-flow nasal catheter oxygen until oxygen was stopped. Repeated indications of pulmonary surfactant should be given: (1) oi (oxygenation index) value did not improve or 200; (2) FIO 250%; (3) the main parameters of ventilator PIP and peep were difficult to downregulate; (4) children with ards; (5) children with pphn. Data analysis: SPSS 19.0 statistical software was used for data analysis. The statistical data were expressed as x-+ s. The mean of the two groups was compared by t-test, and the matched t-test was used before and after treatment in the same group. Rank sum test was used to compare the grade data. The statistical difference was statistically significant between the two groups by X2 test and P 0.05 test. There were no significant differences in gestational age, age at admission, birth weight, Apgar score (P 0.05). Before treatment, 2,4,8,12,24,48,72 hours after treatment, the oxygenation index (OI) and P/F were compared between PS group and NS group. There were significant differences in OI and P/F between PS group and NS group at 4-12 hours after lavage (P 0.05), but no significant differences in OI and P/F between 12-72 hours after lavage. Respiratory support and PS usage were compared between the PS lavage group and NS lavage group. The extubation time, NIPPV usage time, high flow oxygen supply time and the ratio of high frequency support were shortened compared with the control group. PS lavage group and NS lavage group compared with the control group, the total amount and frequency of PS use, the difference was statistically significant (p0.05). PS lavage group and NS lavage group, the above observation indicators were not statistically significant (p0.05). Comparisons of complications in each group: PS lavage group and NS lavage group compared with the control group, lung qi. The mortality and abandonment rates of PS lavage group and NS lavage group were significantly lower than those of the control group (p0.05). Compared with PS lavage group and NS lavage group, there was no significant difference in the above indexes (p0.05). Fiberoptic bronchoscopic alveolar lavage is superior to non-lavage group, diluted PS lavage and NS lavage have no significant difference in curative effect, tracheal instillation of PS in the treatment of MAS is effective. There are still some shortcomings in this study, such as small sample size, short study time span, temporary no outcomes of outpatient follow-up, mechanical ventilation can not be unified design, and so on.
【學(xué)位授予單位】：長(zhǎng)江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R722.1

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