探讨早期行纤维支气管镜肺泡灌洗治疗新生儿胎粪吸入综合征的机制及疗效

发布时间：2018-08-13 11:26

【摘要】：研究背景新生儿胎粪吸入综合征(meconium aspiration syndrome,MAS)是因胎粪吸入呼吸道所致机械阻塞和化学炎症引起的一系列反应,是产前或产时最常见的吸入性肺炎。患儿的主要临床表现为呼吸窘迫,病情严重者还可能因为呼吸衰竭直接死亡[1]。现今社会,随着二胎政策的全面开放,人口主体逐渐倾向于低龄,新生儿渐成为中国人口的重要部分,如何提高这一群体的存活率和生存质量,就显得尤为重要。胎粪吸入综合征的发生与家庭社会/经济地位、医疗资源情况以及孕妇初次妊娠年龄等因素有关。关于新生儿胎粪吸入综合征的发病机制,顾名思义,其具体的机制与胎粪的排出、吸入过程有关,因胎粪的形成和排出与胎龄的增长有一定相关性,故MAS多见于足月儿,但引起宫内胎粪排出的机制仍未十分清楚。一般情况下,即使羊水被胎粪污染,若未合并明显的呼吸窘迫,正常的宫内呼吸不会引起胎粪吸入,或者仅限于吸入上气道或主气管,但若胎儿在明显的宫内窘迫情况下,可使胎粪进入小气道或肺泡,生后呼吸开始后可使胎粪进入远端气道,由此可见,胎粪吸入综合征与胎儿宫内窘迫亦有一定程度的相关性。近年来,有越来越多的学者研究关于PS的给药方式、药品选择等方面,根据实际条件有选择性的应用气管镜灌洗,或者与盐酸氨溴索灌洗相对比,评估PS气管内灌洗的必要性和有效性,以及对预后的影响。既往研究证实,肺泡表面活性物质(PS)失活在MAS发病机制过程中发挥重要作用。国内外多中心随机对照研究证实,肺泡表面活性物质气管内给药可有效改善MAS患儿氧合及通气功能[2-3],减少并发症(PPHN、ARDS、肺气漏、感染性肺炎,呼吸机相关肺炎等)发生率,降低死亡率。自从1978年纤维支气管镜首次应用于儿科临床以来,纤支镜在儿科呼吸道疾病的诊断和治疗的作用受到广泛认同。近年来由于其大小和结构的不断改进,临床纤支镜医师诊治水平不断提高,纤支镜对于各种胎龄、体重的新生儿呼吸道疾病的诊疗起着非常重要的作用[4]。在我国,由于国情问题,医疗条件的限制,行纤支镜检查费用较昂贵,纤支镜目前尚未能广泛应用于儿科临床。新生儿作为一个特殊的患者群体,需要更为专业、更为精细和高端的诊疗,希望本次研究能对新生儿胎粪吸入综合征的临床诊疗有一定的指导作用。目的本试验旨在探讨早期行纤维支气管镜肺泡灌洗治疗新生儿胎粪吸入综合征(MAS)的疗效及预后,并将稀释PS灌洗组、NS灌洗组与未灌洗组互相对比,了解治疗效果、并发症及预后有无差异,进一步研究胎粪吸入对新生儿肺部损伤的发病机制,为新生儿胎粪吸入的治疗提供及时有效且可改善预后的治疗新手段,有较好的临床指导意义。方法本研究选取了2014年6月-2016年6月入住我院新生儿重症监护病房(nicu)确诊为mas的足月患儿共48例,通过纳入标准和排除标准共收集研究期间符合条件的患儿36例,剔除6例记录信息不完整和中途放弃治疗出院的患儿,最终30例患儿完成本研究,采取随机抽签法分为稀释ps灌洗组,ns灌洗组,对照组,每组10例。本研究家属均需签署知情同意书。(1)稀释ps灌洗组:在生后12小时内予稀释后的肺表面活性物质(3~5ml/kg.次)行纤维支气管镜肺泡灌洗治疗,灌洗后4h气管内滴入ps100mg/kg,然后给予呼吸支持;(2)生理盐水(ns)灌洗组:在生后12小时内行生理盐水(3~5ml/kg)纤维支气管镜肺泡灌洗治疗,灌洗后4h气管内滴入ps100mg/kg,后给予呼吸支持;(3)对照组:给予常规呼吸道清理及对症支持治疗,气管插管后给予滴入肺泡表面活性物质100mg/kg,后给予相应的呼吸支持治疗。治疗过程中,根据患儿的病情考虑是否需行机械辅助通气,必要时可反复给予ps,行一般治疗中的所有常规监测。ps气管内给药后4~6小时内不予气管内吸引。观察指标:比较三组患儿治疗前和治疗后2,4,8,12,24,48,72h患儿经皮血气、氧合指数(oi)、p/f值、机械通气时间、肺部超声表现、住院时间、并发症(pphn、ards、肺气漏、感染性肺炎,呼吸机相关肺炎等)发生率、治愈率、死亡率。呼吸支持和氧疗方式[5]:三组患儿呼吸机支持和撤除呼吸机指征相同;有创通气上机指征:(1)pao260mmhg而fio260%;(2)血气分析:ph7.2,pco260mmhg,be-8mmol/l。拔管指征:(1)自主呼吸可,能耐受气道吸引时的屏气和咳嗽反射24h以上;(2)血气分析:ph7.25,pco260mmhg,be-8mmol/l;(3)pip≤10~15cmh2o,呼气末正压(peep)4cmh2o,频率≤10次/分,持续24~48h;(4)平均气道压8cmh2o,呼吸频率30次/分,吸入氧浓度(fio2)40%,spo20.93,维持24小时以上。无创通气指征(nippv)指征:(1)fio240%不能维持pao260mmhg;(2)血气分析:pco260mmhg;(3)拔管后再次出现明显三凹征或(和)呼吸窘迫者。撤除nippv指征:(1)呼气末正压(peep)4cmh2o持续24~48h;(2)fio230%,呼吸频率60次/分,spo2在0.91~0.95维持24h以上;(3)无呼吸暂停、心动过缓,无sao2降低、呼吸做功不增加;(4)患儿可耐受护理时暂时脱离nippv。同时符合以上条件,且血气分析达到如下要求:ph7.25,pco260mmhg,be-8mmol/l。撤除nippv后的患儿均给予高流量鼻导管给氧直至停氧。需反复给予肺泡表面活性物质指征:(1)oi(氧合指数)值无改善或200;(2)fio250%;(3)呼吸机主要参数pip和peep下调困难[6];(4)合并ards患儿;(5)合并pphn患儿。数据分析:采用spss19.0统计软件进行数据处理。计量数据以x—±s表示,两组间均数的比较采用t检验,同组治疗前后比较采用配对t检验;等级资料比较采用秩和检验;计数资料比较采用X2检验,以P0.05为差异有统计学意义。结果最终30例本院MAS患儿纳入本研究,每组10例。各组患儿性别、胎龄、入院时年龄、出生体重、Apgar评分差异均无统计学差异(P0.05)。各组患儿在治疗前、治疗后2、4、8、12、24、48、72h氧合指数(OI)和P/F比较:PS组与NS组在灌洗后4-12小时期间OI和P/F的比较差异有统计学意义(p0.05),12-72小时期间OI和P/F比较差异无统计学意义(P0.05)。PS灌洗组和NS灌洗组在各观察时段的OI和P/F与对照组差异均有显著意义(p0.05)。各组呼吸支持和PS使用情况比较:PS灌洗组和NS灌洗组与对照组比较,拔管时间、使用NIPPV时间,高流量给氧的时间缩短,需要高频支持的比率减少,差异均有统计学意义(p0.05)。PS灌洗组和NS灌洗组的PS使用总量和次数较对照组减少,差异有统计学意义(p0.05)。PS灌洗组和NS灌洗组对比,以上观察指标差异无统计学意义(p0.05)。各组并发症情况比较:PS灌洗组和NS灌洗组与对照组比较,肺气漏,感染性肺炎,VAP,合并PPHN,ARDS比率减少,差异均有统计学意义(p0.05)。PS灌洗组和NS灌洗组与对照组的死亡和放弃的比率比较明显减少,差异有统计学意义(p0.05)。PS灌洗组和NS灌洗组对比,以上观察指标差异无统计学意义(p0.05)。结论早期行纤维支气管镜肺泡灌洗的疗效明显优于未灌洗组;早期予稀释PS灌洗与NS灌洗的疗效无显著差异;气管内滴入PS治疗MAS的疗效肯定。总而言之,早期予纤维支气管镜肺泡灌洗治疗新生儿MAS可明显改善患儿氧合和通气功能,促进病情恢复,减少并发症发生率,降低死亡率。本研究还存在样本小,研究时间跨度短,暂无院外随访结局,机械辅助通气未能统一设计等一些不足,因此需进一步改进和完善。
[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.
【学位授予单位】：长江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R722.1

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