吸入一氧化氮治疗大鼠缺氧性肺动脉高压

目的　 观察吸入一氧化氮 (NO)对慢性和急性缺氧所致大鼠肺动脉高压的作用。 方法 　分别利用雄性Wistar大鼠 3 0只 ,制备慢性和急性缺氧肺动脉高压模型。实验中监测肺动脉压、血气、高铁血红蛋白含量 (Met % )等指标。 结果 　慢性缺氧大鼠吸入 2 0 ppm、40ppmNO ,肺动脉平均压 (MPAP)由治疗前 (2 5 2± 3 5 )mmHg降到 (2 2 4± 3 5 )mmHg及 (2 1 8± 3 3 )mmHg ,而对动物体循环血压无明显影响 ;急性缺氧大鼠吸入 2 0 ppm、40 ppmNO 1hMPAP分别由缺氧时 (2 2 8± 2 7)mmHg、(2 4± 2 8)mmHg下降到 (19 6± 4 7)mmHg和 (2 0 5± 4 1)mmHg。吸入NO 4h ,2 0ppm组Met %由 (0 40± 0 3 9) %升到 (0 95±0 75 ) % ,40 ppm组由 (0 3 9± 0 3 2 ) %升到 (1 2 6± 0 49) %。肺病理组织检查显示 :2 0 ppm、40 ppm组与对照组无显著差别。 结论 　吸入NO对慢性和急性缺氧肺动脉高压具有选择性扩张肺血管的作用 ,急性缺氧大鼠持续吸入NO 4h不会引起高铁血红蛋白血症 ,对肺组织结构无重要影响     

一氧化氮吸入治疗新生儿持续肺动脉高压

目的 探讨吸入一氧化氮治疗新生儿持续肺动脉高压(persistent pulmonary hypertension of newborn,PPHN)的疗效及安全性.方法 22例PPHN患儿在机械通气下,将NO气源加入呼吸机环路中,NO浓度从(15～20)×10-6开始,每4小时下降5×10-6,治疗前后动态观测患儿心率、血压、动脉血气、氧合指数变化及不良反应.结果 22例PPHN患儿吸入NO治疗48 h后肺部氧合得到改善.氧合指数由25.79±16.94降至4.97±3.74(P＜0.05);平均气道压由(13.43±1.51)cm H2O降至(9.71±1.25)cm H2O(P＜0.05);血气分析中氧分压由(50.86±21.06)mmHg上升至(128.29±41.94)mm Hg,差异有统计学意义(P＜0.05).20例患儿显效,2例患儿死亡.治疗过程中心率、血压无明显变化.结论 吸入一氧化氮对治疗由肺血管痉挛导致的PPHN是有效的,能改善氧合,对心血管无明显不良反应.     

一氧化氮吸入治疗新生儿持续肺动脉高压

新生儿持续肺动脉高压（persistent pulmonary hypertension of newborn，PPHN）治疗困难，病死率高。近年来由于机械通气技术的改进，尤其应用体外膜肺（extracorporeal membrance oxygenation，ECMO）治疗后。病死率有所下降，但EMCO设备昂贵，在新生儿应用技术要求复杂，普遍推广有困难。1992年起美国开始用一氧化氮（NO）吸入治疗PPHN，获得良好效果。我们对8例确诊为PPHN的患儿在机械通气同时应用NO吸入治疗。并动态监测相关指标变化，现报告如下。     

一氧化氮吸入治疗新生儿持续肺动脉高压

新生儿持续肺动脉高压 (ＰＰＨＮ)是新生儿时期严重的临床综合征 ,其特点是持续肺高压和右向左分流。引起持续性肺高压的主要因素是肺血管痉挛。常见病因有窒息、呼吸窘迫综合征、胎粪吸入和肺炎等。新生儿严重的低氧血症通常都与ＰＰＨＮ有关 ［１］。近年来国外应用一氧化氮 (ＮＯ)吸入治疗ＰＰＨＮ和严重低氧血症 ,取得良好效果。一、ＮＯ吸入降低肺动脉高压的机制ＮＯ是简单小分子物质 ,具有一额外电子 ,其化学性质活跃且不稳定 ,半衰期仅３秒～５秒。可溶于水和脂肪 ,能自由弥散于细胞周围。ＮＯ与Ｏ２ 反应产生的ＮＯ２ 和过氧亚硝酸…     

一氧化氮吸入治疗新生儿持续肺动脉高压

】　目的　探讨吸入一氧化氮（NO）对新生儿持续肺动脉高压（PPHN）的治疗效果。方法　对6例窒息后PPHN进行NO吸入治疗,入院后经呼吸机支持,应用NO前呼吸机吸入氧浓度平均为0.93±0.10,平均气道压力为(12.7±2.7)cmH     

一氧化氮治疗小儿急性呼吸衰竭和肺动脉高压

用我科自行研制的NO吸入装置对5例急性肺损伤伴呼吸衰竭(ALI ARF)和5例先天性心脏病伴肺动脉高压(CHD PH)患儿进行NO吸入治疗后,气体交换和血流动力学参数变化的观察,结果显示:ALI ARF组PaO_2/FiO_2上升48±17(54±15%)(T=4.52,P<0.01),氧合指数(OI)下降9±3(26±6%)(T=4.63,P<0.01),3例ARDS的 V_D/V_t下降5±1%(T=5.00,P<0.05);CHD PH组平均肺动脉压(mPAP)下降17±10%(T=5.345,P<0.01),肺血管阻力下降18±11%(T=5.432,P<0.01)。结论:NO吸入可改善ALI ARF患儿的动脉氧合,降低CHD PH患儿的肺动脉高压。     

吸入一氧化氮逆转幼猪急性缺氧性肺动脉高压

目的 观察吸入不同浓度一氧化氮（ＮＯ）是否可逆转幼猪急性缺氧性肺动脉高压。方法 选用１０头上海种白猪。利用低氧建立急性缺氧性肺动脉高压模型。吸入不同浓度ＮＯ（０,１０,２０,４０,８０,１２０ｐｐｍ）。在各时相分别进行血液动力学指标、二氧化氮和高铁血红蛋白浓度监测。结果 吸入不同浓度ＮＯ可明显降低肺动脉平均压（ＭＰＡＰ）、肺循环阻力指数（ＰＶＲＩ）、跨肺压（ＴＰＧ）、体肺动脉压之比（Ｐｐ／Ｐｓ）、     

吸入一氧化氮治疗新生儿持续性肺动脉高压研究进展

新生儿持续性肺动脉高压(persistent pulmonary hypertension of the newborn,PPHN)是胎儿从宫内生活过渡到宫外生活期间,肺动脉压力及肺血管阻力持续升高导致血液经过卵圆孔和(或)动脉导管的右向左分流,临床表现为严重紫绀、进行性低氧血症的严重新生儿疾病。最新研究报道PPHN发病率为2/1 000活产婴儿,病死率为11.6%[1]。临床研究[2]和Meta分析[3]证实吸入一氧化氮(inhaled     

雾化吸入一氧化氮供体治疗肺动脉高压研究进展

一氧化氮（NO）吸入作为一种选择性的肺血管扩张剂,临床上已应用于多种疾病的治疗,并取得了良好疗效,但由于NO吸入治疗需要气管插管和借助于呼吸机,操作相对复杂,价格昂贵,临床应用受到一定的限制;并且NO的半衰期很短,NO吸入突然中断会造成反跳性肺动脉高压。因此,寻找一种更为简单有效、价格低廉且作用时间相对长的肺动脉高压治疗方法具有临床实用价值。     

一氧化氮治疗新生儿持续肺动脉高压42例疗效观察

目的　探讨一氧化氮 (NO)吸入疗法治疗新生儿持续肺动脉高压 (PPHN)的疗效。方法　对 4 2例新生儿PPHN和呼吸衰竭患儿按解剖性血管梗阻和肺血管痉挛分为Ⅰ组和Ⅱ组 ,分别在呼吸机机械通气情况下 ,将NO气源加入呼吸机环路中 ,NO质量浓度从 2 0× 10 -6mg/L(2 0 ppm)开始 ,每经 15～ 30min无效者增加 (5～10 )× 10 -6mg/L(5～ 10 ppm) ,达到 4 0× 10 -6mg/L仍无效者停用。有效者经予吸入较高浓度NO 6h后 ,每 30min降低NO质量浓度 (5～ 10 )× 10 -6mg/L ,如患儿的PaO2 下降不超过 15 % ,可降至 6× 10 -6mg/L后维持 36～ 72h ,治疗时观察全身氧合情况的变化 ,监测心率、血压、吸入前后血高铁血红蛋白 (MHb)定量及凝血功能。结果　Ⅱ组 33例患儿中 2 7例 (81 82 % )治疗后氧合情况显著改善 ;Ⅰ组治疗后氧合情况无改善。两组心率、血压、凝血功能无明显改变 ,MHb定量的改变无临床意义。结论　低浓度短期NO吸入疗法治疗肺血管痉挛所致持续肺动脉高压有显著疗效 ,且未见明显副作用 ,但对解剖性血管梗阻所致持续肺动脉高压疗效欠佳。     

Low-dose inhaled nitric oxide for neonates with pulmonary hypertension

Objective : Inhaled nitric oxide (iNO) has been shown to cause selective pulmonary vasodilatation and improve ventilation-perfusion matching and may be an important therapeutic option for the treatment of persistent pulmonary hypertension of the newborn (PPHN). We report our experience on the use of iNO in neonates with severe PPHN.
Methodology : Inhaled NO was administered to 10 infants with PPHN and persistent hypoxaemia (meconium aspiration syndrome, n = 9; pneumonia, n = 1) after failure of conventional therapy to improve oxygenation. With the exception of one infant, iNO was commenced at 10 ppm.
Results : After 30 min exposure to iNO, the arterial oxygen tension (PaO₂) rose from a median of 49 mmHg (6.5 kPa) [range 12-82 mmHg (1.6-10.9 kPa)] to 75 mmHg (10 kPa) [range 17-450 mmHg (2.3-60 kPa)] ( P = 0.005), while the median oxygenation index fell (pre-iNO of 37 vs post-iNO 20) ( P = 0.005) and median systemic arterial pressure rose (pre-iNO 46.5 mmHg (6.2 kPa) [range 32-63 mmHg (4.3 to 8.4 kPa vs post-iNO 54.5 mmHg (7.3 kPa) [range 36-74 kPa]) P = 0.005). All infants subsequently continued to receive iNO with the duration of exposure to iNO ranging from 12 to 168 h (median duration 100 h). Three infants died despite showing an initial beneficial response to iNO. The mean duration of intubation for survivors was 11.9 ± 2.6 days. Methaemoglobinaemia and toxic levels of nitrogen dioxide were not seen during iNO administration. Of the seven survivors, 12 month follow up in two infants and 4 month follow up in four infants showed age-appropriate neurodevelopmental skills, with one infant having very mild hearing loss.
Conclusions : Inhaled NO reduces the oxygenation index by improving the PaO₂ and decreasing ventilation pressures, and appears to be clinically useful in severely hypoxaemic infants with PPHN refractory to conventional treatment.     

Contribution of pulmonary surfactant with inhaled nitric oxide for treatment of pulmonary hypertension

BACKGROUND: Combined therapy of inhaled nitric oxide (iNO) with pulmonary surfactant replacement was reported to improve oxygenation in patients or animal models of persistent pulmonary hypertension of the newborn with pulmonary surfactant deficiency lung. To evaluate the potential of iNO for the treatment of persistent pulmonary hypertension of the newborn, pulmonary arterial pressure (PAP) was measured during iNO before and after pulmonary surfactant replacement in an animal model of pulmonary hypertension with surfactant deficiency. METHODS: Seven newborn piglets were injected with L-nitro-arginine-methylester to produce an animal model of pulmonary hypertension. After PAP increased, iNO (30 p.p.m.) was introduced. Then iNO was stopped, and animals were subjected to lung lavage with saline. After recording the effect of iNO, all animals then received exogenous pulmonary surfactant installation. After surfactant treatment, iNO was again introduced. RESULTS: Pulmonary arterial pressure and systemic arterial pressure were increased significantly by >30% after infusion of L-nitro-arginine-methylester. During iNO only PAP was reduced significantly. Respiratory system compliance decreased significantly after lung lavage, and increased significantly after pulmonary surfactant replacement with concomitant increase of PaO2. In contrast, significant reduction of PAP with iNO before and after pulmonary surfactant replacement were also observed. The reduction ratios of PAP under each condition were 75.2 +/- 7.4%, 81.3 +/- 3.1%, and 79.1 +/- 5.3%, respectively (not significant among conditions). CONCLUSION: These results suggest that iNO is still a potent pulmonary arterial vasodilator even under pulmonary surfactant deficiency in an animal model of pulmonary hypertension.     

吸入一氧化氮治疗先天性心脏病术后肺动脉高压的疗效观察

目的 探讨吸入一氧化氮(NO)治疗先天性心脏病术后肺动脉高压患儿的疗效.方法 选择32例先天性心脏病术后传统治疗无效的、难治的、反应性肺动脉高压或肺动脉高压危象患儿,吸入NO(10～25)×10-6,定时记录各项血流动力学和呼吸功能指标,定期监测二氧化氮、高铁血红蛋白含量.结果 吸入NO后,平均肺动脉压(mPAP)从(38.0±3.2)mm Hg(1 mm Hg=0.133 kPa)降至(28.0±2.1)mm Hg,肺血管阻力从(62.2±6.7)kPa/(L·S)降至(49.9±5.6)kPa/(L·S),氧合指数从(67.0±30.1)mm Hg升至(92.6±25.0)mm Hg,动脉血氧饱和度从0.78±0.14升至0.84±0.09,差异均有非常显著性(P＜0.01).吸入NO期间,二氧化氮和高铁血红蛋白含量均在安全范围.结论 NO可以明显降低先天性心脏病术后肺动脉压力和肺血管阻力,是一种安全且理想的肺血管扩张剂.     

Dose response to inhaled nitric oxide in pediatric patients with pulmonary hypertension and acute respiratory distress syndrome

Objective: To determine the pulmonary vascular functional dose response to inhaled nitric oxide (NO) for infants and children with acute respiratory distress syndrome and pulmonary artery hypertension.Design: Prospective, clinical observational study.Setting: Thirteen-bed pediatric intensive care unit at a 168-bed children’s hospital.Patients: Infants and children requiring mechanical ventilation with an oxygenation index greater than 10.Methods: Children with severe acute respiratory distress syndrome received inhalation therapy with NO after conventional mechanical ventilation failed to result in improvement. Inhaled NO was sequentially titrated from 10 parts per million to 20, 40, 60, and 80 ppm at 10-minute intervals. A reduction of at least 30% in the pulmonary vascular resistance index (PVRI), or a reduction in mean pulmonary artery pressure of at least 10%, or an increase in the hypoxemia score of at least 20%, or a decrease in the oxygenation index of at least 20% from pretreatment values was considered a therapeutic response. After sequential titration, children who responded received continuous inhaled NO at the lowest dose associated with a therapeutic response.Results: Fourteen children received 15 trials with inhaled NO (median age, 63.4 months; range, 0.4 to 201 months). One patient’s condition deteriorated during the titration phase, unrelated to NO treatment, and the patient was withdrawn from the study protocol. The mean (±SD) pretreatment oxygenation index was 35 ± 15, which decreased to 32 ± 20 at 80 ppm of inhaled NO ( p = 0.01). Ten children had pulmonary artery catheter measurements. The PVRI decreased by 30% or greater in seven children (70%). One child had a minimal decrease in PVRI during the titration phase but demonstrated an increase of more than 30% after NO therapy was discontinued. Mean pretreatment PVRI (270 ± 105) decreased to 207 ± 92 dynes/sec per cubic centimeter per square meter at 80 ppm of inhaled NO ( p = 0.06). Pretreatment mean pulmonary artery pressure (31 ± 7) decreased to 28 ± 5 mm Hg at 80 ppm of inhaled NO ( p = 0.04). Six trials (43%) showed an increase of 20% or greater in their hypoxemia score. Maximum improvement in the hypoxemia score and reduction in OI, PVRI, and mean pulmonary artery pressure occurred at 20 to 40 ppm of NO. Ten trials led to continuous inhaled NO therapy ranging from 7 to 661.5 hours, with a median of 47 hours. Systemic hypotension was not observed in any patient, and the maximum methemoglobin level was 5%.Conclusion: Inhaled NO appears to be a safe, although variably effective, therapy for the treatment of infants and children with acute respiratory distress syndrome. The maximum dose response occurs between 20 and 40 ppm of inhaled NO. Systemic side effects did not occur in any child who received NO therapy. (J Pediatr 1997;131:63-9)     

Low dose inhaled nitric oxide causing selective pulmonary vasodilation in child with idiopathic pulmonary hypertension

Low dose (3 ppm) inhaled nitric oxide caused selective pulmonary vasodilation with improved systemic arterial pressure, cardiac index and arterial oxygenation in an infant with primary pulmonary hypertension. Methaemoglobin levels did not exceed 0.6 %, and nitrogen dioxide concentrations remained within 0.05 ppm.     

Weaning strategy with inhaled nitric oxide treatment in persistent pulmonary hypertension of the newborn

AIM—To determine if infants who had become dependent on inhaled nitric oxide treatment could be successfully weaned off it if FIO₂ was increased briefly during withdrawal.
METHODS—Sixteen infants admitted for conditions associated with increased pulmonary vascular resistance responded well to inhaled nitric oxide treatment with a significant increase in PaO₂ (maximum inhaled nitric oxide given 25 ppm). Weaning from inhaled nitric oxide in 5 ppm decrements was initiated once the FIO₂ requirement was less than 0.5. When patients were stable on 5 ppm of inhaled nitric oxide, the gas was then discontinued. If a patient showed inhaled nitric oxide dependence—that is, oxygen saturation fell by more than 10% or below 85%—inhaled nitric oxide was reinstated at 5 ppm and the patient allowed to stabilise for 30 minutes. At this time, FIO₂ was increased by 0.40 and weaning from inhaled nitric oxide was attempted again.
RESULTS—Nine infants were successfully weaned on the first attempt. The seven infants who failed the initial trial were all successfully weaned following the increase in FIO₂. After successful weaning, FIO₂ was returned to the pre-weaning level in mean 148(SD 51) minutes and inhaled nitric oxide was never reinstated.
CONCLUSION—Infants showing inhaled nitric oxide dependency can be successfully weaned by increasing FIO₂ transiently.

     

常频通气联合一氧化氮吸入治疗新生儿持续肺动脉高压

Objective To evaluate the effects of inhaled nitric oxide (iNO) therapy combined with conventional ventilation in the infants with persistent pulmonary hypertension of the newborn (PPHN).Methods NO inspiration was added for 22 infants with PPI-IN ventilated with FiO2≥0. 9,PIP≥30 cm H2O,PEEP≥3 cm H2O,RR≥50 bpm for 4～6 hours,with SpO2 still < 90% and PaO2 <55 mm Hg. The iNO concentration started at (10～20)×10-6 for 20 infants,and (20～40)×10-6 for 2 infants. The iNO would be stopped when the concentration reached 40×10 -6 without any sign of improvement. The SpO2 ,blood gas analyses,blood pressure, heart rate and NO: concentration were moraitored during therapy and the resulting data compared to readings before administration of int. Results Clinical situation were significantly improved in 20 (91%) of the infants with SpO2 gradually going up after 10 minutes of int. Before iNO,mean Fit2 was 0. 9±0. 1 ,SpO2 was(76. 3±13.3)% ,and Pat2 was (46. 4±10. 1 ) man Hg. From 1 to 6 hours after iNO,SpO2 increased to(95. 1±3.8)% ,Pat2 increased to(92. 8±24.7) mm Hg,FiO2 decreased to 0.6 s0. 1.The differences were significant (P < 0. 01 ). Eighteen of 22 (82%) infants surviving. Conclusion iNO is effective in alleviating PPHN in infants. There are no remarkable side effects. It is more beneficial to start the iNO concentration at (10～20)×10-6 while some infants may need NO concentration at up to (20～40)×10-6.