肺泡表面活性物质对新生儿急性呼吸窘迫综合征氧合功能的影响

目的探讨早期应用肺泡表面活性物质（PS）对新生儿急性呼吸窘迫综合征（ARDS）氧合功能的影响。方法回顾性分析ARDS新生儿的临床资料,并按照是否使用PS分为治疗组及对照组,治疗组经气管插管注入PS 70~100 mg/kg,其余治疗两组相同。结果共入组64例ARDS新生儿,18例为治疗组,46例对照组。治疗组新生儿在治疗后6、12、24、48 h的PaO2/FiO2、呼吸机有效指数均高于对照组,而氧合指数、呼吸指数均低于对照组,差异有统计学意义（P均<0.05）;治疗组机械通气时间、用氧时间均较对照组缩短,差异有统计学意义(P均<0.05)。结论早期应用PS治疗新生儿ARDS可改善肺顺应性及氧合功能,缩短机械通气及氧疗时间,有利于改善预后。     

肺表面活性物质治疗新生儿急性呼吸窘迫综合征的疗效

目的 观察肺表面活性物质(PS)治疗急性呼吸窘迫综合征(ARDS)新生儿的疗效.方法 将66例ARDS新生儿随机分为对照组和观察组.对照组予机械通气和常规治疗;观察组在此基础上,应用PS制剂猪肺磷脂注射液1剂.观察二组肺氧合功能改变.对二组患儿住院天数、机械通气天数、用氧天数和呼吸机参数[包括吸气峰压(PIP)、呼气末正压(PEEP)、平均呼吸道压(MAP)和吸入氧体积分数(FiO2)]进行比较.结果 观察组经PS治疗后,Pa(O2)和动脉血氧分压/肺泡氧分雎比值[a/A p(O2)]较对照组明显增高,而氧合指数(OI)较对照组明显降低,差异均有统计学意义(Pa<0.05).观察组呼吸机参数PIP、MAP和FiO2均明显低于对照组,二组比较具有显著件差异(Pa<0.005);观察组PEEP与对照组比较,差异无显著性意义(P>0.05).观察组用氧天数、机械通气天数和住院天数均明显短于对照组,二组比较具有显著性差异(Pa<0.05).结论 PS替代治疗能明显改善ARDS新生儿的氧合功能,降低呼吸机参数,缩短用氧时间、机械通气时间和住院天数,减少并发症的发生.     

继发性肺表面活性物质异常

肺表面活性物质(PS)由肺泡Ⅱ型上皮细胞合成、分泌。PS异常可分为原发性(指肺Ⅱ型细胞未成熟,PS 合成减少,如HMD)和继发性(指其它多种因素致PS 异常)。本文就儿科领域继发性PS 异常,如呼吸衰竭、ARDS、肺炎、窒息、氧中毒、SIDS、肺水肿和肺纤维化等疾病时的PS 异常作一介绍,并提出应用外源性PS 作为治疗措施之一是可能的     

儿童急性肺损伤和呼吸窘迫综合征的非机械通气治疗

急性肺损伤(acute lung injury,ALI)/急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是各种原因导致肺毛细血管内皮细胞和肺泡上皮细胞损伤造成弥漫性肺间质及肺泡水肿导致的急性低氧性呼吸功能不全或呼吸衰竭.儿童ALI/ARDS的发生率为2.2～6/10万[1],在PICU住院患儿中ARDS的发生率为8.5～16/1000[2].国内有报道ARDS的住院病死率为44.8％[3].合适的呼吸末正压与合适的小潮气量通气治疗是目前公认的可以降低病死率的治疗方法.近年来,国内儿科及重症医学工作者通过全国儿科脓毒症的调查和2009至2010年甲型H1N1流感救治工作的开展,强化了对ALVARDS诊断和治疗的认识.除机械通气外,其他救治措施中依然有很多问题没有解决,现就ALVARDS非机械通气治疗热点问题进行讨论.     

肺表面活性物质治疗胎粪吸入综合征的研究进展

胎粪吸入综合征(MAS)是导致足月儿和过期产儿呼吸衰竭的重要原因,但至今仍无特效治疗手段.肺泡腔内肺表面活性物质(PS)活性的抑制是该病病理生理中的一个重要因素.使用气管内滴入PS治疗或用稀释PS通过支气管肺泡灌洗均能有效改善MAS患儿的肺氧合功能,并缩短病程.目前PS治疗MAS的最佳给药方式、给药时间和给药剂量是国内外研究的焦点.     

儿童肿瘤化疗后粒细胞减少期并发ARDS肺泡巨噬细胞活性检测

目的 研究儿童肿瘤化疗后粒细胞减少期并发感染后出现ARDS,肺泡巨噬细胞(AM)HLA-DR的表达情况.方法 收集13例儿童肿瘤化疗后并发ARDS患者,其中5例为粒细胞减少期,予粒细胞集落刺激因子治疗.所有患儿行纤维支气管镜检查,收集支气管肺泡灌洗液(BALF)进行细胞计数、分类,流式细胞仪检测AM HLA-DR表达率.结果 粒细胞减少组ARDS患儿肺泡细胞总数、AM绝对值和AM百分比分别为(62.6±9.6)/μl、(40.8±4.3)/μl和65.9%±9.0%,粒细胞正常组ARDS患儿分别为(124.0±6.7)/μl、(67.6±10.7)/μl和54.6%±8.7%,两组差异均有显著性(P＜0.05).粒细胞减少组BALF中AM HLA-DR表达率较粒细胞正常组明显下降(35.3%±5.8%vs62.2%±5.8%),差异有非常显著性(P＜0.01).结论 粒细胞减少的ARDS患儿呈"肺泡细胞减少症"状态,AM呈失活状态.     

早产儿肺透明膜病诊治进展

早产儿肺透明膜病(HMD)是由于肺表面活性物质(pulmonary surfactant,PS)不足导致弥漫性肺泡不张、水肿及细胞损伤,由于血浆蛋白漏至肺泡腔更抑制了PS的功能导致肺萎陷,气体交换面积不足出现呼吸困难症状并表现为进行性加剧,近年来对HMD处理的进展方面包括产前对HMD高危儿诊断试验、预防性治疗(包括激素及PS)、围生期处理,尤其呼吸支持的进展及PS的替代性治疗等。     

儿童急性呼吸窘迫综合征21例临床分析

目的分析不同病因所致儿童急性呼吸窘迫综合征(ARDS)的临床特点与治疗方法。方法对厦门大学附属第一医院儿科重症监护室2010年1月至2012年6月收治的21例ARDS患儿临床资料进行总结,并作回顾性分析。结果 21例中男13例,女8例。发病平均年龄1.5岁。病因包括重症肺炎12例(57%),严重脓毒症4例,吸入性肺炎4例,肺含铁血黄素沉着症1例。痊愈13例(65%)、死亡8例,其中4例吸入性肺炎所致ARDS经多次支气管肺泡灌洗、呼吸机支持等治疗,全部治愈;1例肺含铁血黄素沉着症痊愈;重症肺炎痊愈6例。4例患儿给予了血液净化(CBP)治疗,2例脓毒症患儿好转,另2例重症肺炎患儿病情无改善。8例死亡患儿最后均并发多脏器功能不全(MODS)。结论不同病因所致ARDS治疗的侧重点不同,吸入性肺炎者应尽早行支气管肺泡灌洗,重症肺炎予针对性抗感染,脓毒症者应尽早行血液净化治疗。早期诊断、合理治疗是降低病死率的关键。     

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目的探讨新生儿常见肺部疾病支气管肺泡灌洗液肺表面活性蛋白A(BALSPA)水平及其与临床的关系。方法收集2000年1月至2003年2月在广州市儿童医院新生儿重症监护室住院的需行机械通气治疗的新生儿重症肺炎、胎粪吸入综合征(MAS)、急性呼吸窘迫综合征(ARDS)以及新生儿呼吸窘迫综合征(RDS)患儿共57例。测定其BALSPA水平,监测血气、PaO2/FiO2水平。结果重症肺炎组与MAS组患儿BALSPA水平无明显差异,但MAS组患儿PaO2、PaCO2及PaO2/FiO2水平较重症肺炎组明显降低(P值<0.01,<0.05,<0.05);ARDS及RDS组患儿BALSPA水平均较上述两组低(P值均<0.001),而RDS组患儿BALSPA水平较ARDS组低(P<0.001),但ARDS组患儿PaO2水平较RDS组患儿低(P<0.05)。PS治疗组患儿的病死率较非PS治疗组明显降低(P=0.049),其PaO2/FiO2与BALSPA水平密切相关(r=0.741,P=0.000)。结论与重症肺炎患儿比较胎粪吸入综合征患儿BALSPA水平无明显降低;ARDS及RDS患儿BALSPA水平明显降低;BALSPA水平能反映新生儿肺损伤的严重程度,对于新生儿肺部疾病预后的判断有一定意义。     

肺表面活性物质联合布地奈德对急性呼吸窘迫综合征极低出生体质量儿肺功能的影响

目的 探讨肺表面活性物质(PS)联合布地奈德对急性呼吸窘迫综合征(ARDS)极低出生体质量儿肺功能的影响,并评价联合用药的治疗效果.方法 2010年8月-2011年3月南京市妇幼保健院收治的胎龄<34周、出生体质量<1 500 g、出生4 h内发生ARDS的早产儿30例,随机分为PS组和PS+布地奈德组.PS+布地奈德组(男9例,女6例)使用PS和布地奈德混合剂(每70 mg PS中加入0.25 mg布地奈德),剂量:PS 70 mg·kg-1,布地奈德0.25 mg·kg-1.PS组(男8例,女7例)单使用PS,70 mg·kg-1,出生30～60 min内由气管内滴入.监测2组患儿血气及肺功能.结果 PS+布地奈德组患儿动脉血气pH值第2、5、6天明显高于PS组(Pa<0.05),二氧化碳分压[pa(CO2)]第3、4、6天明显降低(Pa<0.05),氧合指数(OI)第3、4、6天明显升高(Pa<0.05);肺功能监测2组胸肺总顺应性(Crs)升高、呼吸道阻力(Raw)下降、潮气量(TV)增加,第5、6天与PS组比较有显著差异(Pa<0.05).结论 使用PS联合布地奈德对ARDS极低出生体质量儿能较快改善肺功能,尽早撤离呼吸机,减少肺损伤,减少早产儿支气管肺发育不良的发生.     

Experimental models of acute respiratory distress syndrome: clinical relevance and response to surfactant therapy

Surfactant therapy for acute respiratory distress syndrome (ARDS) has shown encouraging results in animal studies, but not always in clinical trials. Efficacy of this therapy may be limited to ARDS caused by indirect injury, but mistiming of its application in clinical trials may be responsible for the discouraging results. In addition, the therapy may not last long enough to be effective. In rats with acidified milk aspiration, the effects of aerosolized surfactant therapy followed by inhalation of aerosolized dextran (molecular weight, 40,000) last significantly longer than those of aerosolized surfactant therapy alone. This mode of surfactant therapy could lead to better results since it can be started and repeated at any time.     

Surfactant for pediatric acute lung injury

This article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is placed on reviewing clinical studies of surfactant therapy in pediatric and adult patients who have ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS.     

肺泡表面活性物质对新生儿急性肺损伤氧合功能的影响

目的 研究肺泡表面活性物质（pulmonary surfactant,PS）对新生儿急性肺损伤、急性呼吸窘迫综合征氧合功能的影响.方法 纳入符合急性肺损伤、急性呼吸窘迫综合征诊断标准的新生儿98例,分为PS治疗组30例及常规治疗组68例,PS治疗组经气管插管注入PS 70 ～ 100 mg/kg,其余治疗同常规治疗组.结果 两组新生儿的性别、胎龄、出生体重、肺损伤程度差异无统计学意义;PS治疗组在急性肺损伤、急性呼吸窘迫综合征治疗后6h、12h、24 h、48 h的PaO3/FiO2、呼吸机有效指数均高于常规治疗组,而氧合指数、呼吸指数均低于常规治疗组,差异有统计学意义（P＜0.05）;PS治疗组在急性肺损伤、急性呼吸窘迫综合征治疗后机械通气时间[（66±13）h、（82 ±26）h]和用氧时间[（86±13）h、（103±25）h）]均较常规治疗组[（80 ±18）h、（101 ±36）h和（104±16）h、（125 ±29） h]缩短,差异有统计学意义（P＜0.05）.结论 应用PS治疗新生儿急性肺损伤、急性呼吸窘迫综合征可改善肺顺应性及氧合功能,缩短机械通气及氧疗时间,有利于改善预后.     

Ventilation in special situations. Mechanical ventilation in acute respiratory distress syndrome/acute pulmonary lesion

Acute respiratory distress syndrome (ARDS), which was first described by Ashbaugh in 1967, consists of acute hypoxemic respiratory failure (PaO2/FiO2< or =200) associated with bilateral infiltrates on the chest radiograph caused by noncardiac diffuse pulmonary edema. Although ARDS is of multiple etiology, pulmonary or extrapulmonary injury can produce systemic inflammatory response that perpetuates lung disturbances once the initial cause has been eliminated. Most patients with ARDS require mechanical ventilation. Currently, the old standard is conventional ventilation optimized to protect against ventilator-associated lung injury. Other mechanical ventilation strategies such as high-frequency oscillatory ventilation, which is also based on alveolar recruitment and adequate lung volume, can be useful alternatives. In this review, the level of evidence for other therapies, such as prone positioning, nitric oxide and prostacyclin inhalation, exogenous surfactant, and extracorporeal vital support techniques are also analyzed.     

Treatment of acute (Adult) respiratory distress syndrome. The holy grail of surfactant therapy

The treatment of neonatal respiratory distress syndrome with surfactant represents a successful culmination of decades of basic and clinical research. In many babies, respiratory distress syndrome is a relatively pure expression of surfactant deficiency. Acute respiratory distress syndrome (ARDS) is a more common disease that is most frequently seen in adults, but the processes are common to lung injuries in newborns and children as well. While some impairment of production and secretion of surfactant constituents may be present in ARDS, surfactant inactivation is probably a more important factor in this disease. Until recently, surfactants available for human use have been easily susceptible to inactivation and this may explain why they have been less successful for treatment of ARDS than for neonatal respiratory distress syndrome. This review outlines recent information on surfactant inactivation and describes initiatives that may result in 'inactivation-proof' surfactants that may be of increased benefit in ARDS.     

Experiences with surfactant therapy of adult respiratory distress syndrome]

We report on 2 patients with ARDS, who underwent a therapy with surfactant. In both cases the underlying reason for the lung disease probably was a viral pneumonia. In both patients the gas exchange improved after tracheal instillation of surfactant. This improvement however was much less than we know it from therapy of the respiratory distress syndrome of the premature babies. Reasons for these differences in response to surfactant are discussed.     

Approaches in the management of acute respiratory failure in children

PURPOSE OF REVIEW: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are conditions that are associated with significant morbidity and mortality in children. There have been no advances in preventing ARDS, but this review highlights strategies directed at minimizing ventilator-induced lung injury and other new adjunctive therapies in the care of these patients. RECENT FINDINGS: High-frequency oscillatory ventilation, airway pressure release ventilation, and partial liquid ventilation are potential protective ventilatory modes for children with ALI or ARDS. Recruitment maneuvers, prone positioning, and kinetic therapy are all reported to improve oxygenation by opening the lung while positive end-expiratory pressure maintains functional residual capacity. Inhaled nitric oxide and surfactant are used to reduce inspired oxygen concentration and facilitate gas exchange, but their efficacy in ARDS continues to be investigated. Also, early investigations suggest that a specialized enteral formula can be a useful adjunctive therapy by reducing lung inflammation and improving oxygenation. When mechanical ventilation and adjunctive therapies fail, extracorporeal life support continues to be used as a rescue therapy. SUMMARY: It is likely that a combination of these therapies will maximize treatment and clinical outcomes in the future, but the only way that will be proven is through large controlled clinical trials in pediatric patients.     

儿童急性呼吸窘迫综合征的治疗进展

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that lacks definitive treatment. The cornerstone of management is sound intensive care treatment and early anticipatory ventilation support. A mechanical ventilation strategy aiming at optimal alveolar recruitment, judicious use of positive end-respiratory pressure (PEEP) and low tidal volumes (VT) remains the mainstay for managing this lung disease. Several treatments have been proposed in rescue settings, but confirmation is needed from large controlled clinical trials before they be recommended for routine care. Non-invasive ventilation (NIV) is suggested with a cautious approach and a strict selection of candidates for treatment. Mild and moderate cases can be efficiently treated by NIV, but this is contra-indicated with severe ARDS. The extra-corporeal carbon dioxide removal (ECCO₂R), used as an integrated tool with conventional ventilation, is playing a new role in adjusting respiratory acidosis and CO₂. The proposed benefits of ECCO₂R over extra-corporeal membrane oxygenation (ECMO) consist in a reduction of artificial surface contact, avoidance of pump-related side effects and technical complications, as well as lower costs. The advantages and disadvantages of inhaled nitric oxide (iNO) are better recognized today and iNO is not recommended for ARDS and acute lung injury (ALI) in children and adults because iNO results in a transient improvement in oxygenation but does not reduce mortality, and may be harmful. Several trials have found no clinical benefit from various surfactant supplementation methods in adult patients with ARDS. However, studies which are still controversial have shown that surfactant supplementation can improve oxygenation and decrease mortality in pediatric and adolescent patients in specific conditions and, when applied in different modes and doses, also in neonatal respiratory distress syndrome (RDS) of preemies. Management of ARDS remains supportive, aimed at improving gas exchange and preventing complications. Progress in the treatment of ARDS must be addressed toward the new paradigm of the disease pathobiology to be applied to the disease definition and to predict the treatment outcome, also with the perspective to develop predictive and personalized medicine that highlights new and challenging opportunities in terms of benefit for patient''s safety and doctor''s responsibility, with further medico-legal implication.     

表面活性蛋白C基因突变与儿童间质性肺疾病

表面活性蛋白 C 是唯一在肺泡Ⅱ型上皮细胞中表达的肺表面活性蛋白,其基因突变与儿童间质性肺疾病关系密切。该综述探讨表面活性蛋白 C 基因突变相关儿童间质性肺疾病的发病机制、诊断以及治疗的进展。     

Use of natural surfactant in an infant with aspiration syndrome

The remarkable effectiveness of surfactant in neonatology suggested its use also in adults as well as in children on the basis of the pulmonary pathophysiology. We describe a case of an 18 month-old child affected by acute respiratory distress syndrome (ARDS) due to asphyxy by gastric juice inhalation, successfully treated with porcine surfactant (Curosurf) associated with ventilatory therapy.