肺表面活性物质治疗新生儿胎粪吸入综合征的临床研究

目的探讨肺表面活性物质（ＰＳ）治疗新生儿胎粪吸入综合征（ＭＡＳ）的有效性及临床价值。方法采用气管内滴入ＰＳ治疗８例ＭＡＳ患儿，其中６例接受ＰＳ２剂，２例接受ＰＳ３剂。结果给予首剂ＰＳ后１０分钟患儿青紫迅速消失，皮肤转红润，经皮测定血氧饱和度（ＴｃＳａＯ２）升高。３０分钟后患儿低氧血症迅速改善，动脉血氧分压、动脉血氧分压与吸入氧浓度比值、动脉肺泡血氧分压比值、呼吸机有效指数较治疗前显著增高，分别由原来的５２８±０９８ｋＰａ、８６６±３５２ｋＰａ、０１２±００６ｋＰａ及０１４±００６ｍｌ·ｋＰａ－１·ｋｇ－１增加到８９１±１４３ｋＰａ、１６８１±４１８ｋＰａ、０２１±００５ｋＰａ及０２６±００７ｍｌ·ｋＰａ－１·ｋｇ－１；而吸入氧浓度及平均气道压逐渐降低，由原来的０６８±０１９ｋＰａ及２２０±０４２ｋＰａ降低到０５３±００８ｋＰａ及１９３±０４８ｋＰａ。重复应用ＰＳ后亦有相似效果。结论ＰＳ能有效地改善ＭＡＳ患儿肺顺应性及氧合功能。重复应用ＰＳ可巩固和加强疗效。     

肺表面活性剂治疗新生儿呼吸衰竭的疗效分析

为评价肺表面活性剂（ＰＳ）治疗ＲＤＳ和重症肺炎的疗效，本文对１２例接受ＰＳ治疗的新生儿ＲＤＳ和重症肺炎病例进行分析。结果显示：治疗组患儿在病程不同时期的ａ／ＡＰＯ２均明显高于对照组（Ｐ均＜０．０５），肺部并发症的发生率低于对照组，机械通气时间、需氧时间及住院时间均明显短于对照组（Ｐ均＜０．０５）。治疗组患儿的存活率为７５％，对照组为３７％，两组比较，差异显著（Ｐ＜０．０５）。提示：ＰＳ治疗能有效地改善新生儿ＲＤＳ和肺炎患儿的肺氧合功能，减少肺部并发症的发生，缩短病程     

超未成熟儿肺透明膜病的肺表面活性物质替代治疗

本文应用气管内滴注ＰＳ对９例合并ＨＭＤ的ＥＩＩ进行治疗。治疗后，患儿紫绀迅速消失，皮肤转红润，经皮测血氧饱和度明显增高。血氧分压、血氧分压与吸入氧浓度比值及动脉与肺泡氧分压比值较用药前显著升高，差异存在显著性意义。Ｘ线片可见肺充气逐渐好转，肺透亮度增加。提示ＰＳ能够明显缓解临床症状，改善肺氧合功能。对ＥＩＩ的ＨＭＤ应早期、足量，反复用药，并加强用药后的呼吸管理，以减少并发症发生。     

一氧化氮对缺氧和急性肺损伤犬的血液动力学与气体交换的影响

应用化学发光法监测氮氧化物浓度，观察１０只缺氧和急性肺损伤犬在吸入不同浓度一氧化氮（ＮＯ）时血液动力学和气体交换功能的变化。结果显示，５～５０ＰＰＭＮＯ均可降低缺氧犬肺动脉压２５％±３％（Ｐ＜０．０１），降低肺血管阻力３７％±５％（Ｐ＜０．０１），并使急性肺损伤犬的动脉血氧分压／吸入氧浓度（ＰａＯ＿２／ＦｉＯ＿２）比值上升３３．４±２．３（Ｐ＜０．０５），肺内动静脉分流量与总血流量（Ｑ＿ｓ／Ｑ＿Ｔ）比值下降５％±２％（Ｐ＜０．０５）。提示，低浓度ＮＯ（５～２０ＰＰＭ）即可有效降低缺氧性和急性肺损伤犬肺动脉高压并改善其动脉氧合功能。     

重症新生儿呼吸窘迫综合征患儿吸入一氧化氮后肺血流与氧合动态变化

为探讨吸入一氧化氮（ＮＯ）对早产儿呼吸窘迫综合征（ＲＤＳ）的疗效，对１０例ＲＤＳ患儿进行了吸入ＮＯ治疗，浓度以２０ｐｐｍ开始，４小时后降为６ｐｐｍ，持续至２４小时。同时在吸入前、吸入后３０分钟及吸入后１２～１６小时动态观察平均肺动脉血流速度及体循环氧合变化。结果：吸入ＮＯ后有８例患儿血氧饱和度迅速上升；吸入３０分钟后平均肺动脉血流速度显著增加（Ｐ＜０．０５），氧合指数显著改善（Ｐ＜０．０５）；以６ｐｐｍ浓度维持至２４小时，氧合指数持续改善，肺动脉血流继续增加。提示：吸入ＮＯ能显著降低重症ＲＤＳ患儿的肺血管阻力，改善氧合；采用无创伤性方法测定平均肺动脉血流速度对选择吸入ＮＯ适应证、评价疗效有较大的价值     

高频振荡通气治疗重症新生儿肺疾病(附7例报告)

报道７例患重症肺疾病新生儿,平均出生体重１１７２±８２８ｇ,孕周３１±４．２周,表现为肺动态顺应性差（０．０２±０．０１２ｍｌ、ｋｐａ~（－１）．ｋｇ~（－１））,虽用高氧（０．８８±０．１３）,高平均气道压（１．１４±０．１３ｋｐａ）机械通气治疗仍不能维持正常血气或出现严重肺间质气肿,经改用高频振荡、高肺容量策略通气后、氧合在４小时内均改善、高碳酸血症在１２小时内得以纠正。７例中６例撤离成功,共存活４例,１例并发Ⅰ～Ⅲ度室管膜下－脑室内出血。表明新生儿重症肺疾病,经传统机械通气（ＣＭＶ）治疗失败时,改用高频振荡通气可改善气体交换,提示高频振荡通气可作为一种抢救重症新生儿呼吸衰竭新的有效手段。     

重症新生儿呼吸窘迫综合征患儿吸入一氧化氮后肺血流与氧合动…

为探讨吸入一氧化氮（ＮＯ）对早产儿呼吸窘迫综合征（ＲＤＳ）的疗效，对１０例ＲＳＤ患儿进行了吸入ＮＯ治疗，浓度以２０ｐｐｍ开始，４小时后降为６ｐｐｍ，持续至２４小时。同时在吸入前、吸入后３０分钟及吸入后１２￣１６小时动态观察平均肺动脉血流速度及体循环氧合变化。结果：吸入ＮＯ后有８例患儿血氧饱和度迅速上升；吸入３０分钟后平均肺动脉血流速度显著增加（Ｐ〈０．０５），氧合指数显著改善（Ｐ〈０．０５）；以６     

一氧化氮吸入治疗小儿急性呼吸衰竭

为观察一氧化氮（ＮＯ）治疗小儿急性呼吸衰竭的疗效，应用我院自行研制的ＮＯ吸入装置，对１５例急性呼吸窘迫综合征（ＡＲＤＳ）和急性呼吸衰竭（简称急性呼衰）患儿进行ＮＯ吸入治疗。结果：７例有效，ＮＯ吸入前后比较氧分压与吸入氧浓度比值上升４．１±２．３ｋＰａ（３０．５±１７ｍｍＨｇ，１ｋＰａ＝７．５ｍｍＨｇ）（ｔ＝４．５２，Ｐ＜０．０５），氧合指数降低９±３（ｔ＝４．６３，Ｐ＜０．０５）。对２例肺动脉导管压力监测显示，肺动脉压和肺血管阻力明显下降，体动脉压和心率无显著性变化。结论：ＮＯ吸入疗法对部分急性呼衰患儿有效，宜在急性低氧性呼衰、心功能未受严重损害时应用。     

肺表面活性物质治疗新生儿RDS呼吸衰竭的疗效

用肺表面活性物质（ＰＳ）抢救１５例新生儿呼吸窘迫综合征（ＮＲＤＳ）时的呼吸衰竭，ＰＳ首次剂量２００ｍｇ／ｋｇ．重复剂量１００ｍｇ／ｋｇ，用１～３次，经气管插管注入肺内，给ＰＳ后５～１５分钟ＰａＯ２和ＰａＯ２／ＦｉＯ２显著上升，随后ＦｉＯ２和平均气道压（ＭＡＰ）下调，５．５±０．８小时胸片即见改善，４０．２±１６．５小时胸片恢复，治疗组病死率比对照组低。结果表明ＰＳ对抢救ＮＲＤＳ呼吸衰竭有明显疗效。     

一氧化氮合酶mRNA在缺氧性肺动脉高压大鼠肺动脉的表达

目的探讨一氧化氮体系在缺氧性肺动脉高压形成机制中的作用。方法采用地高辛精标记的一氧化氮合酶（ＮＯＳ）ｃＲＮＡ探针对缺氧组大鼠（６只）及对照组大鼠（７只）进行原位杂交。结果缺氧２周后的大鼠肺动脉收缩压（３．８±０．７ｋＰａ）（２８±５ｍｍＨｇ，１ｋＰａ＝７．５ｍｍＨｇ）、肺动脉平均压（２．８±０．６ｋＰａ）及肺动脉舒张压（１．４±０．４ｋＰａ）与对照组（２．９±０．５ｋＰａ，１．９±０．５ｋＰａ及０．９±０．５ｋＰａ）相比均显著升高。缺氧组大鼠肺动脉内皮细胞中ＮＯＳｍＲＮＡ表达信号为弱阳性（３只）及阴性（３只），平滑肌细胞中表达信号均为阴性；对照组大鼠肺动脉内皮细胞中ＮＯＳｍＲＮＡ表达信号为阳性（７只），平滑肌细胞中表达信号均为阴性。ＮＯＳｍＲＮＡ的表达强度与大鼠肺动脉收缩压、肺动脉平均压及肺动脉舒张压分别呈负相关（ｒｓ＝－０．６７３、－０．５９６及－０．６２１，Ｐ均＜０．０５）。结论缺氧时肺动脉内皮细胞ＮＯＳｍＲＮＡ表达的改变可能参与慢性缺氧性肺动脉高压的形成。     

Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome

Thirty-four spontaneously breathing newborns with respiratory distress syndrome (RDS) requiring nasal continuous positive airway pressure (CPAP) and an arterial-to-alveolar oxygen tension ratio (a/A PO₂) of 0.15-0.22 were randomized to treatment with nebulized surfactant (Curosurf^®) or to serve as controls. All children were first supported by nasal CPAP according to normal clinical routines. Surfactant was administered using a modified Aiolos^® nebulizer, and a total of 480 mg was aerosolized in each case. The control group received no nebulized material, but had the same CPAP support. Acid-base status and a/A PO₂ were determined at regular intervals before, during and after surfactant administration. Both groups included in the study were similar with regard to gestational age, birthweight, steroids given before birth, sex and Apgar scores as well as a/A PO₂ when entering the study. There were no significant differences between the groups in a/A PO₂ 1-12 h after randomization, number of infants needing mechanical ventilation, time on ventilator or CPAP. Two children in the treated group developed bronchopulmonary dysplasia. No side effects of the surfactant therapy were noted. No beneficial effects of aerosolized surfactant were demonstrated in our trial, contrary to data from animal experiments. This finding probably reflects differences in administration techniques. Our findings do not justify large clinical trials with the same protocol. Further work is needed to optimize delivery of aerosolized surfactant to the neonatal lung in clinical practice.     

重症肺炎新生儿酸碱平衡紊乱分析

目的分析重症肺炎新生儿氧疗前后的酸碱平衡紊乱情况。方法分别在氧疗前和氧疗后12h抽取重症肺炎患儿静脉血行血清电解质检测,动脉血行血气分析,比较重症肺炎患儿氧疗前后其变化,并与对照组比较氧疗前酸碱平衡紊乱情况。结果重症肺炎治疗前45例均出现酸碱平衡紊乱,且以剩余碱（AG）增高的代谢性酸中毒并呼吸性酸中毒为主,明显高于对照组（t=1.27P〈0.05）。重症肺炎患儿氧疗后酸中毒例数较氧疗前明显减少（t=3.28P〈0.01）。结论新生儿重症肺炎致酸碱平衡紊乱以AG增高的酸中毒为主,不宜盲目补碱。     

Disturbed surface properties in preterm infants with pneumonia

Congenital pneumonia in preterm infants is often associated with respiratory insufficiency requiring mechanical ventilation. This study was performed to show whether pneumonia in these infants is associated with an inhibition or deficiency of surfactant. The ratio of lecithin and sphingomyelin (L/S ratio) and minimal surface tension were determined in pharyngeal aspirates from 90 term born infants (healthy) and in tracheal aspirates from preterm infants with wet lung (n = 13), congenital pneumonia (n = 21) and respiratory distress syndrome (RDS) (n = 90). The L/S ratio was lower (p < 0.0001) in the RDS group (8.6) when compared with healthy (48.6), wet lung (42.9) and pneumonia (28.9). Surface tension was higher (p < 0.001) in RDS (37 mN/m) and pneumonia (33.7) when compared with healthy (22.9) or wet lung (21.2). For infants with RDS, L/S ratio <16.5 detects surfactant deficiency with 96% specificity and 70% sensitivity, surface tension >29 mN/m represents surfactant inhibition (specificity 97%, sensitivity 92%). Using these cut-off values in infants with pneumonia, 81% had a sufficient amount of surfactant but only 21% of infants with pneumonia had appropriate surface tension. Our study shows that lung effluent of respiratory insufficient infants with pneumonia, who need mechanical ventilation, has disturbed surface properties despite a sufficient amount of surfactant. In these infants, surfactant substitution could be beneficial.     

肺表面活性物质治疗新生儿重症胎粪吸入综合征的疗效评价

目的评价外源性肺表面活性物质(PS)治疗重症胎粪吸入综合征(MAS)的疗效。方法将43例重症MAS病例随机分成两组,20例作治疗组,在上呼吸机及常规治疗同时应用PS治疗;23例患儿作对照组,予呼吸机及常规治疗,观察监测两组患儿的肺氧合功能、病程及预后。结果治疗后的不同时期,治疗组患儿的氧合指数低于对照组,差异有显著性(P<0.05);动脉/肺泡氧分压比值(a/APO2)高于对照组,差异有显著性(P<0.05);治疗组机械通气时间、用氧时间和住院时间均显著少于对照组(P<0.05)。结论PS治疗能有效地改善MAS患儿的肺氧合功能,可缩短应用机械通气及用氧的时间及病程。     

Response to bovine surfactant (surfactant TA) in two different HMD models (lambs and baboons)

The responses of Surfactant TA instillation in two groups of premature lambs (Group I, 124.8±1.1 days and Group II, 132.2±1.2 days, mean±SD) and one group of premature baboons (140±1.6 days) were compared to study the effectiveness of the same surfactant in different animal models. The treatment group received Surfactant TA 100 mg/kg surfactant lipid at 1 to 2 h of age. Control lambs and baboons did not receive surfactant. Sequential measurements of arterial blood gas tension, acid base status, mean airway pressure (MAP) and oxygen requirement (FiO₂) were carried out for 8h after surfactant instillation. The results show that the Group I surfactant-treated lambs improved significantly following instillation. The a/APO₂ improved from 0.08±0.02 before treatment to 0.31±0.12, and the MAP decreased from 15.8±0.9 cm H₂O to 13.3±1.3 cm H₂O 2.5 h after treatment. At 5.5 h after treatment, the lambs given surfactant deteriorated. Group II treated lambs showed sustained improvement throughout the study period, and improvement in the treated group was not significantly different from Group II control lambs. The surfactant-treated baboons, however showed sustained and significant improvement in a/APO₂ from the time of instillation to the end of the study. These data suggest that the differences in response to the same surfactant therapy between the lamb and baboon models were due to related differences in species, lung maturation, and the differences in response to surfactant, i.e., alveolar leak of protein.Abbreviations MAP mean air way pressure - FiO₂ oxygen requirement - PEEP positive end-expiratory pressore - ANOVA analysis of variance - a/APO₂ arterial/alveolar oxygen tension ratio - P-V pressure volume     

Randomized European multicenter trial of surfactant replacement therapy for severe neonatal respiratory distress syndrome: single versus multiple doses of Curosurf.

There is now convincing evidence that the severity of neonatal respiratory distress syndrome can be reduced by surfactant replacement therapy; however, the optimal therapeutic regimen has not been defined. This randomized European multicenter trial was designed to determine whether the beneficial effects of a single large dose of Curosurf (200 mg/kg) in babies with severe respiratory distress syndrome (arterial to alveolar oxygen tension ratio approximately 0.10) could be enhanced by using multiple doses of surfactant. Preterm neonates (birth weight 700 to 2000 g) with severe respiratory distress syndrome requiring artificial ventilation with fraction of inspired oxygen greater than or equal to 0.6 were randomized into two groups at an age of 2 to 15 hours. Both groups received the usual dose of Curosurf (200 mg/kg) immediately after randomization. In neonates randomized to receive multiple-dose treatment, two additional doses of Curosurf (100 mg/kg each) were instilled into the airways (12 and 24 hours after the initial dose) provided that the patients still needed artificial ventilation with fraction of inspired oxygen greater than 0.21. In both groups (single dose: n = 176, multiple doses: n = 167) there was a rapid improvement in oxygenation as reflected by a threefold increase in arterial to alveolar oxygen tension ratio within 5 minutes after surfactant instillation (P less than .001), and peak inspiratory pressure and mean airway pressure could be reduced significantly during the first 6 hours after surfactant treatment. In addition, ventilatory requirement (peak inspiratory pressure, ventilatory efficiency index) was reduced in the multiple-dose group 2 to 4 days after randomization (P less than .05 to .01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nitric oxide treatment and acute pulmonary inflammatory response in very premature infants with intractable respiratory failure shortly after birth

Aim: Premature infants with respiratory failure and early-onset pneumonia have low inducible nitric oxide synthase (NOS2) and no evidence of nitric oxide (NO) toxicity. However, inhalation of NO may not be indicated in sepsis because excessive NO generation has been reported. This prospective study was designed to test the hypothesis that inhaled NO is effective in a select group of small premature infants and that the responsiveness to NO is associated with low NOS2 enzyme. Methods: 246 very low birthweight infants (birthweight 31500 g, VLBW) were screened for severe, intractable respiratory failure (oxygenation index 340, arterial-alveolar ratio for oxygen tension 30.10) that does not respond to two doses of surfactant within 5 h from birth. Infants with severe cardiac failure or a bleeding disorder were excluded. Five of the nine eligible cases received inhaled NO. They all had prolonged rupture of foetal membranes, early-onset pneumonia and persistent pulmonary hypertension. Results: All five responded strikingly, survived and appeared normal in follow-up. Airway specimens during the first day of life revealed very low NOS2, interleukin-13 and surfactant protein A, compared with VLBW infants who had no acute infection despite histological chorioamnionitis. In early-onset pneumonia, NOS2 and other inflammatory mediators increased first during the recovery 1-2 d after birth. Conclusion: VLBW infants with progressive respiratory failure and infection at birth have deficient pulmonary NOS2 and cytokine response. After surfactant therapy, these infants responded strikingly to inhaled NO. An acute pulmonary inflammatory response may contribute to respiratory adaptation in early-onset pneumonia.     

Phospholipase A2 is present in meconium and inhibits the activity of pulmonary surfactant: an in vitro study

Atelectasis, a major contributor to pulmonary dysfunction in meconium aspiration syndrome (MAS), is produced by bronchiolar obstruction and surfactant inactivation. It has been shown that substances in meconium, e.g. fatty acids, inhibit surfactant activity. However, the role of the enzyme phospholipase A2 (PLA2), which hydrolyses surfactant in adult respiratory distress syndrome (ARDS), has not yet been studied. Our objective was to investigate whether PLA2 is present in meconium and inhibits pulmonary surfactant activity in vitro. Therefore, the presence of PLA2 activity in meconium, collected from 10 newborns, was measured by the formation of lysophosphatidylcholine after incubation of meconium with radioactively labelled dipalmitoylphosphatidylcholine. Meconium was fractionated by Sephadex G-100 column chromatography and the fractions were assayed for PLA2 activity. Also, their effect on the surface tension of surfactant (Curosurf) was measured using a pulsating bubble surfactometer (PBS). PLA2 activity was present in all meconium samples. Addition of meconium to surfactant significantly increased surface tension (mean +/- SD: 1.7 +/- 1.6 mN/m to 24.3 +/- 6.7 mN/m, p = 0.0001) and only the addition of the PLA2 containing fraction from meconium to surfactant also significantly increased surface tension (mean 1.7 +/- 1.6 mN/m to 19.0 +/- 3.58 mN/m, p < 0.0001). Conclusion: PLA2 is present in meconium and inhibits the activity of pulmonary surfactant in vitro. Therefore, PLA2 in meconium may contribute to surfactant inactivation and alveolar atelectasis in MAS.     

肺表面活性物质治疗肺透明膜病Ⅱ级的疗效评价

目的 探讨肺表面活性物质(PS)在治疗新生儿肺透明膜病(HMD)Ⅱ级的疗效。方法 对60例经X线胸片检查为HMDⅡ级的患儿。30例6小时内应用肺表面活性物质;30例无应用肺表面活性物质,通过用药后20小时(或约生后24小时)X线胸片的诊断与上呼吸机时间、并发症的比较分析,评价肺表面活性物质治疗肺透明膜病的疗效。结果 两组病例在生后24小时的X线胸片,平均上呼吸机时间,住院天数、死亡率,有显著性差异,P<0.05。并发症方面,肺炎发生率显著性差异,P<0.05。结论 PS在治疗HMD中可以明显改善肺透明膜病的转归,减少并发症,降低死亡率。     

Lung volume and pulmonary blood flow measurements following exogenous surfactant

Lung function in eight infants with clinical and radiological features of surfactant defiency treated with exogenous porcine surfactant was studied before and at 15 min, 2h and 6h after the intratracheal administration of porcine surfactant. We measured alveolar-arterial oxygen tension difference, dynamic lung compliance, lung volume and effective pulmonary blood flow in all infants. The alveolar-arterial oxygen tension difference fell from a mean (SD) 43.3 (14.5) kPa before treatment to 8.8 (8.8) kPa at 1 h and 12.2 (6.8) kPa 6h after treatment (P<0.001). There was no change in mean (SD) dynamic compliance (0.39 [0.10] ml/cmH₂O/kg pre dose; 0.36 [0.13] ml/cmH₂O/kg 6h post treatment). Accessible functional residual capacity and effective pulmonary blood flow were measured using an adaptation of the argon/freon rebreathing method and showed an increase in mean (SD) functional residual capacity from 7.5 (1.4) ml/kg predose to 10.8 (3.3) ml/kg within 15 min of treatment, 11.4 (3.4) ml/kg 2h later and 12.7 (3.1) ml/kg 6h after treatment (P=0.009). Mean (SD) effective pulmonary blood flow values did not differ significantly, changing from 78.2 (20.9) ml/kg per min predose to 88.7 (24.1) ml/kg per min 15 min post dose, 87.6 (21.7) ml/kg per min 2h post dose and 90.0 (22.7) ml/kg per min 6h post dose (P=0.711).Conclusion The improvement in oxygenation after surfactant treatment is associated with an increase in lung volume but is not related to an improvement in dynamic lung compliance or effective pulmonary blood flow. The change in lung volume is detectable within 15 min of administration of the surfactant.