Disease-related response to inhaled nitric oxide in newborns with severe hypoxaemic respiratory failure

Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10–80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was significantly reduced in either preterm neonates (51 ± 21 vs 23 ± 17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45 ± 20 vs 20 ± 17, P < .0001), `idiopathic' PPHN (39 ± 14 vs 14 ± 9, P < .0001), and sepsis (55 ± 25 vs 26 ± 20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less significant and sustained (OI = 41 ± 16 vs 28 ± 18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI = 58 ± 25 vs 46 ± 32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age ≥34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants. Received: 24 April 1997 / Accepted in revised form 3 January 1998     

Variable oxygenation response to inhaled nitric oxide in severe persistent pulmonary hypertension of the newborn

The causes of variable responsiveness to inhaled nitric oxide (NO) in Persistent Pulmonary Hypertension of the Newborn (PPHN) are unknown. The changes in the severity of respiratory failure after the onset of inhaled NO (maximal dose 20ppm) were studied in 13 consecutive neonates with severe PPHN. Response was defined as a sustained decrease of alveolar-arterial oxygen gradient (AaD0₂) by > 20%, or a decrease in oxygenation index (OI) by > 40%. Six neonates had a rapid response within 30min, three had an intermediate response within 8h, and three had a delayed response within 12 h after the onset of NO. Three infants with birth asphyxia responded rapidly to inhaled NO. One infant with sepsis did not respond, and two with suspected sepsis had a delayed response. The infants with Meconium Aspiration Syndrome and idiopathic PPHN had a variable response time. Twelve neonates required 4 to 14 days of mechanical ventilation and survived. Infants with PPHN may benefit from a trial of inhaled NO therapy that exceeds 30min. The variability of the response time to inhaled NO is likely to be multifactorial and dependent on the disease process associated with PPHN.     

Successful reversal of persistent fetal circulation by inhaled nitric oxide in a newborn with overwhelming sepsis

The authors report a case of successful reversal of persistent fetal circulation (PFC) by inhaled nitric oxide (NO) therapy in a child with overwhelming sepsis. Criteria for extracorporeal membrane oxygenation (ECMO) were reached but due to an intracranial hemorrhage ECMO was contraindicated. Inhaled NO in combination with surfactant administration caused a dramatic reversal of the PFC. Inhaled NO therapy may be a useful and easily accessible measure for the treatment of PFC. It is more simple, and therefore may be more widely applicable, than ECMO.     

Inhaled nitric oxide therapy during the transport of neonates with persistent pulmonary hypertension or severe hypoxic respiratory failure

Our aim was to determine whether starting inhaled nitric oxide (iNO) on critically ill neonates with severe hypoxemic respiratory failure and/or persistent pulmonary hypertension (PPH), at a referring hospital at the start of transport, decreases the need for extracorporeal membrane oxygenation (ECMO), lessens the number of hospital days and improves survival in comparison with those patients who were started on iNO only at the receiving facility. The study was a retrospective review of 94 charts of neonates that had iNO initiated by the transport team at a referring hospital or only at the tertiary neonatal intensive care unit (NICU) of the receiving hospital. Data collected included demographics, mode of transport, total number of hospital days, days on inhaled nitric oxide and ECMO use. Of the 94 patients, 88 were included. Of these, 60 were started on iNO at the referring facility (Field-iNO) and 28 were started at the receiving NICU (CHLA-iNO). All patients survived transport to the receiving NICU. Death rates and ECMO use were similar in both groups. Overall, patients who died were younger and had lower birth weights and Apgar scores. For all surviving patients who did not require ECMO, the length of total hospital stay (median days 22 versus 38, P = 0.018), and the length of the hospital stay at the receiving hospital (median days 18 versus 29, P = 0.006), were significantly shorter for the Field-iNO patients than for the CHLA-iNO patients, respectively. Earlier initiation of iNO may decrease length of hospital stay in surviving neonates with PPH not requiring ECMO.     

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.

     

Changes in oxygenation and pulmonary haemodynamics in preterm infants treated with inhaled nitric oxide

AIM—To investigate changes in various cardiorespiratory variables with inhaled nitric oxide (NO), as part of a randomised controlled trial.METHODS—Infants were treated with inhaled NO for 72 hours. Changes in oxygenation were assessed using the oxygenation index (OI). Serial changes in pulmonary artery pressure (PAP) were assessed using the Doppler derived acceleration time to right ventricular ejection time ratio (AT:RVET). Doppler measurements of right ventricular output, pulmonary blood flow, and systolic PAP was performed in a subset of infants.RESULTS—Twenty infants received inhaled NO and 22 acted as controls. Infants were treated at a median dose of 5 (range 5 to 20) ppm. There was a fall in median OI by 17% in treated infants within 30 minutes of treatment. The fall in OI in treated infants was significantly different from the response in controls until 96 hours. Infants treated with inhaled NO showed a rapid response with a median rise in AT:RVET of 0.04 (range ?0.06 to 0.12) within 30 minutes. The change in AT:RVET was significantly different from controls until 4 hours. Median systolic PAP also fell in treated infants by 6.1 (range ?14.4 to ?4.4) mm Hg within 1 hour. Changes in OI were significantly associated with changes in PBF (r = 0.44), but not with changes in AT:RVET.CONCLUSION—Treatment with inhaled NO rapidly improves oxygenation and lowers PAP in preterm infants. However, these effects are transient and treatment does not influence long term outcome.     

Early functional echocardiogram and inhaled nitric oxide: usefulness in managing neonates born following extreme preterm premature rupture of membranes (PPROM)

Aim: Poor neonatal outcome of preterm premature rupture of membranes (PPROM) <24 weeks' gestational age (GA) is probably a result of abnormalities in both airway and vascular developments, ventilation perfusion mismatch, and possibly persistent pulmonary hypertension of the newborn (PPHN). Perinatal mortality of 50–90% has been reported in the past, with recent literature reporting significant improvement in neonatal survival. We report our 8‐year experience in this group of infants using early diagnostic functional echocardiography (fECHO), high‐frequency ventilation (HFV) and inhaled nitric oxide (iNO). Methods: The obstetric and neonatal databases were searched to identify babies with PPROM (<20 weeks' gestation) or rupture earlier than 25 weeks for more than 14 days. Results: Twenty‐six infants were identified, of whom 20 were admitted to the neonatal intensive care unit (NICU; mean GA 27.8 weeks, mean birth weight (BW) 1207 g). Early echocardiographic data were available in 12/15 infants requiring mechanical ventilation of whom 10 had evidence of PPHN. All infants who received iNO therapy survived to discharge and only two infants died. Survival to discharge was 69% for the whole cohort of infants and 90% for infants admitted to the NICU. In contrast, for the cohort from pre‐iNO and ‐HFV era, the overall survival to discharge was 62% and 66% for the infants admitted to the NICU. Conclusion: Premature infants with PPROM and presumed severe hypoxemic respiratory failure because of hypoplastic lungs often have significant PPHN and may show improvement in oxygenation after treatment with HFV and iNO. Early fECHO results in earlier identification and treatment of infants with PPHN in this high‐risk group.     

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.     

Contemporary neonatal outcome following rupture of membranes prior to 25 weeks with prolonged oligohydramnios

Background

Prolonged oligohydramnios following early preterm prelabour rupture of membranes (PPROM) is traditionally associated with high neonatal mortality and significant risk of pulmonary hypoplasia. However, recent evidence points to an apparent improvement in outcome.

Aims

To document current neonatal outcomes following rupture of membranes prior to 25 weeks with severe persistent oligohydramnios and a latency to delivery of at least 14 days.

Methods

A retrospective case note analysis over a 28-month period at Saint Luc University Hospital, Brussels.

Results

From 23 pregnancies that were complicated by PPROM prior to 25 weeks, 15 infants were born after 24 weeks with a latency of more than 14 days and persistent oligohydramnios. Nine infants (60%) had severe respiratory failure and clinical signs compatible with pulmonary hypoplasia. Seven of these infants (78%) responded to high frequency ventilation and inhaled nitric oxide therapy with good clinical outcome but two died from severe respiratory failure. Five infants showed no clinical signs of pulmonary hypoplasia and responded to conventional neonatal management. One of these infants died at 77 days of age of necrotising enterocolitis. One infant was not resuscitated and died within minutes of birth, following prior discussion with the perinatal team and the parents. Survivors in this high-risk group (73%) had low morbidity at the time of discharge.

Summary

The favourable neonatal survival and morbidity figures are in keeping with recent published evidence. This study confirms improved outcome even amongst the highest risk infants with documented persistent oligohydramnios.     

吸入低浓度一氧化氮对胎粪吸入综合征患儿机体抗氧化能力的影响

目的 探讨吸入低浓度一氧化氮(iNO)对胎粪吸入综合征(MAS)患儿机体氧化-抗氧化平衡的影响.方法 将我院新生儿科病房的55例MAS患儿随机分为机械通气+iNO组(A组,n=25)、机械通气组(B组,n=30),并选择我院同期的健康足月新生儿为对照组(C组,n=30).iNO前A、B组均接受气管插管、气管内吸痰、机械通气及静脉滴注抗生素等一般治疗.A组于入院后1～2 h给予iNO治疗,分别在0、24、72 h监测各组患儿静脉血血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、总抗氧化能力(T-AOC)水平.结果 三组患儿一般情况比较差异无显著性.随着NO吸入.A组SOD、T-AOC渐增高,MDA含量降低(P＜0.05).B组SOD在24 h降低,而在72 h呈增高改变,MDA含量变化与之相反,T-AOC呈渐增高改变(P＜0.05).A组机械通气时间及氧暴露时间分别为(77.38±13.97)h与(158.70±47.23)h,明显低于B组[(104.27±10.53)h与(202.15±61.92)h],差异有显著性(P＜0.05),但两组患儿病死率及气漏、肺出血、颅内出血(Ⅱ～Ⅳ级)的发生率差异无显著性(P＞0.05).结论 iNO可减少机械通气及氧暴露时间.MAS患儿体内存在不同程度的氧化-抗氧化失衡,iNO多显示抗氧化活性,有助于机体氧化-抗氧化平衡的调节,对机体具有保护性作用.     

钙敏感受体对持续性肺动脉高压新生小鼠内皮型一氧化氮合酶及一氧化氮的影响

目的 探讨钙敏感受体（CaSR）在持续性肺动脉高压（PPH）新生小鼠模型中对内皮型一氧化氮合酶（eNOS）表达及一氧化氮（NO）浓度的影响。方法 将80只新生C57BL/6小鼠随机分为对照组、PPH组、激动剂组和抑制剂组。对照组小鼠暴露于空气中,PPH组、激动剂组和抑制剂组小鼠暴露于12%的氧浓度中。激动剂组和抑制剂组分别腹腔注射CaSR激动剂（GdCl₃）16 mg/kg、CaSR抑制剂（NPS2390）1 mg/kg,PPH组和对照组以生理盐水替代,共14 d。采用苏木精-伊红染色检测各组小鼠肺泡和肺血管变化;采用Westernblot、qRT-PCR和免疫组化检测各组小鼠肺组织中eNOS蛋白、mRNA的表达;采用ELISA法分别检测肺组织匀浆中脑利钠肽（BNP）及NO的含量。结果 与对照组相比,PPH组和激动剂组肺泡平均内衬间隔、肺小动脉血管壁厚度、右心室与左心室壁厚度比（RV/LV）及BNP浓度均明显增大,径向肺泡计数明显减少（P < 0.05）;除RV/LV外,上述指标在抑制剂组均较PPH组和激动剂组有所改善（P < 0.05）。与对照组相比,eNOS蛋白、mRNA表达量及NO浓度在PPH组明显增高,在激动剂组中表达水平进一步增加,而在抑制剂组中表达减少（P < 0.05）。结论 CaSR可能通过影响eNOS的表达和NO浓度在新生小鼠PPH发病中发挥重要作用。     

Effects of cardiopulmonary bypass and inhaled nitric oxide on platelets in children with congenital heart defects

Nitric oxide (NO) reduces platelet aggregation in vitro. However, repeated measurements of platelet aggregation in infants and small children are impossible due to the large blood samples required. Instead, the expression of different platelet receptors mediating platelet adhesion (CD 36 and CD 42b), activation (CD 42b and CD 61) and aggregation (CD 41a) was measured repeatedly by flow cytometry. First, the expression of platelet receptors was quantified in platelet suspensions of 20 healthy volunteers after incubation with different concentrations of NO (0, 25, 100 and 640 ppm) and compared to changes in platelet aggregation and intrathrombocytic cGMP levels. It was then studied in 21 infants and children before, during and up to 3 days after cardiopulmonary bypass surgery. Seven of these patients required NO inhalation postoperatively. The in vitro experiments showed a reduced expression of the CD 41a, CD 42b and CD 61 receptors with increasing doses of NO, predominantly affecting the CD 41a receptor (−11% at 100 ppm and −20% at 640 ppm). This significant effect is in keeping with the observed NO-induced inhibition of platelet aggregation (−44% at 100 ppm) and the rise in platelet cGMP levels (+69% at 100 ppm). In patients without inhaled NO, the expression of CD 41a was slightly attenuated during cardiopulmonary bypass surgery (−15%) but increased significantly afterwards (2 h: +31%, 1st day: +129%, 2nd day: +120%, 3rd day: +111%). Comparable results were obtained regarding the other adhesion molecules CD 36, CD 42b and CD 61. In patients with inhaled NO the same pattern was observed and analysis of variance did not reveal any significant difference between both groups of patients. Conclusions NO (≥100 ppm) decreases the expression of different platelet adhesion molecules and platelet aggregation, presumably via an increase in intracellular cGMP. However, due to the low dose range used in the clinical setting (1–40 ppm) this is clinically not relevant. Immediately after cardiopulmonary bypass surgery the expression of these adhesion molecules is reduced, but recovers on the 1st postoperative day. Received: 20 February 1997 / Accepted: revised form: 2 September 1997     

高频振荡通气结合一氧化氮吸入治疗大鼠急性肺损伤的实验研究

目的　观察高频振荡通气 (HFO)联合一氧化氮 (NO)吸入疗法对急性肺损伤 (ALI)大鼠气体交换、血流动力学参数及血中高铁血红蛋白 (MetHb)含量的影响 ,并与常规机械通气 (CMV)、CMV +NO、HFO等通气方式作比较。同时观察此疗法是否可取得较为稳定的NO输送浓度。　方法选择健康雄性Wistar大鼠 32只 ,应用油酸制作ALI模型 ,稳定 30min后 ,随机分为四组 :CMV组、CMV+NO组、HFO组、HFO +NO组。所有大鼠在基础状态、治疗 0 5h、治疗 1h记录气体交换、血流动力学参数。每组各有 4只在NO吸入前后测量血中MetHb含量。实验中用化学发光法持续监测NO的输送浓度。结果　各组大鼠基础状态时各指标差异无显著性 (P >0 0 5 )。治疗 1h后 ,HFO +NO组氧分压 [(2 13± 7)mmHg]较CMV、CMV +NO、HFO组 [分别为 (10 8± 5 )mmHg、(140± 9)mmHg、(15 8± 8)mmHg]明显提高 ,分流比例 [(4 0 4± 0 15 ) %]明显降低 [(14 0 6± 0 5 9) %、(9 4 8± 0 35 ) %、(7 0 3±0 36 ) %](P均 <0 0 5 )。与各自对照组的平均肺动脉压 [(2 2 3± 2 8)mmHg、(2 2 4± 2 9)mmHg]相比 ,HFO +NO组 [(16 8± 2 9)mmHg]及CMV +NO组 [(16 9± 2 7)mmHg]均有明显降低 (P <0 0 5 ) ,但两组间的平均肺动脉压各时点差异无显著性 (P >0 0     

常频通气联合一氧化氮吸入治疗新生儿持续肺动脉高压

目的 探讨常频通气联合一氧化氮吸入(iNO)治疗新生儿持续肺动脉高压(PPHN)的疗效.方法 对22例确诊为PPHN且入院时采取常频通气疗效不满意的患儿给予iNO.NO初始吸入浓度上,20例为(10～20)×10-6,2例为(20～40)×10-6.当SpO2≥93%并已经稳定20min以上,开始下调呼吸机参数,并逐渐下调NO吸入浓度.当NO吸入浓度降至(5～10)×10-6时,再持续2～3h后,若PaO2>55mm Hg(1 mm Hg=0.133 kPa)、SpO2>93%时停止吸入.在NO吸入前和吸入后1～6 h分别进行血气分析,连续记录生命体征、SpO2和监测NO2值等.结果 20例在吸人NO后5～20 min左右SpO2逐渐升高,临床缺氧状态逐步改善.有效率达91%.吸入NO 1～6 h,SpO2、PaO2分别由吸入前的(76.3±13.3)%、(46.4±10.1)mm Hg升到(94.4±2.9)%和(92.8±24.7)mm Hg,FiO2由(0.9±0.1)降至(0.6±0.1),差异均有非常显著性(P<0.001).患儿生命体征平稳,未发现急性合并症.全组治愈18例,治愈率达82%,自动放弃4例.结论 iNO能有效地缓解PPHN患儿的乏氧状态.提高氧分压和治愈率.NO吸入不良反应小、易操作.iNO初始吸人浓度以(10～20)×10-6开始为宜,极个别病例可以(20～40)×10-6开始.     

Early risk factors for death in neonates with persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide北大核心CSCD

Objective To evaluate the early risk factors for death in neonates with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (iNO). Methods A retrospective analysis was performed on 105 infants with PPHN (gestational age ≥34 weeks and age <7 days on admission) who received iNO treatment in the Department of Neonatology, Children's Hospital of Nanjing Medical University, from July 2017 to March 2021. Related general information and clinical data were collected. According to the clinical outcome at discharge, the infants were divided into a survival group with 79 infants and a death group with 26 infants. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for death in infants with PPHN treated with iNO. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values of the factors in predicting the death risk. Results A total of 105 infants with PPHN treated with iNO were included, among whom 26 died (26/105, 24.8%). The multivariate Cox regression analysis showed that no early response to iNO (HR=8.500, 95%CI: 3.024-23.887, P<0.001), 1-minute Apgar score ≤3 points (HR=10.094, 95%CI: 2.577-39.534, P=0.001), a low value of minimum PaO2/FiO2 within 12 hours after admission (HR=0.067, 95%CI: 0.009-0.481, P=0.007), and a low value of minimum pH within 12 hours after admission (HR=0.049, 95%CI: 0.004-0.545, P=0.014) were independent risk factors for death. The ROC curve analysis showed that the lowest PaO2/FiO2 value within 12 hours after admission had an area under the ROC curve of 0.783 in predicting death risk, with a sensitivity of 84.6% and a specificity of 73.4% at the cut-off value of 50, and the lowest pH value within 12 hours after admission had an area under the ROC curve of 0.746, with a sensitivity of 76.9% and a specificity of 65.8% at the cut-off value of 7.2. Conclusions Infants with PPHN requiring iNO treatment tend to have a high mortality rate. No early response to iNO, 1-minute Apgar score ≤3 points, the lowest PaO2/FiO2 value <50 within 12 hours after admission, and the lowest pH value <7.2 within 12 hours after admission are the early risk factors for death in such infants. Monitoring and evaluation of the above indicators will help to identify high-risk infants in the early stage. © 2022 Xiangya Hospital of CSU. All rights reserved.     

Effect of inhaled nitric oxide on intrapulmonary right-to-left-shunting in two rabbit models of saline lavage induced surfactant deficiency and meconium instillation

Marked hypoxia secondary to intrapulmonary right-to-left shunting is a characteristic of respiratory failure in human neonates and can sometimes be complicated by additional extrapulmonary right-to-left shunting. To investigate the effect of inhaled nitric oxide (iNO) on intrapulmonary shunting, two typical pulmonary diseases of the newborn (respiratory distress syndrome and meconium aspiration) were reproduced in 32 mechanically ventilated rabbits weighing approximately 2 kg each. After tracheotomy, catheters were inserted into a jugular vein, a carotid artery and the right ventricle (to measure systolic right ventricular pressure [SRVP] and mixed venous oxygen content for calculation of shunt by Fick equation). Repeated airway lavages (LAV) with normal saline or repeated instillations of a suspension of human meconium (MEC) were continued until both the a/A-ratio was ≤0.14 and a peak inspiratory pressure ≥22 mbar was needed to keep the tidal volume constant at 10 ml/kg of body weight. Measurements of shunt, SRVP, systolic systemic pressure, physiological dead space, tidal volume and a ventilation index were performed before and after completion of lung damage and at 20 and 60 min after administering iNO at 80 ppm. Four groups of rabbits were studied (n = 8 in each group): LAV control and intervention, Mec control and intervention. 60 min after starting iNO, there was a decrease in shunt (LAV: 67.6% ± [SD] 11.3% vs 56.2 ± 16.4, P = 0.05; MEC: 52.6 ± 6.3 vs 44.3 ± 8.3, P < 0.05), in SRVP (LAV: 29.7 mmHg ± 10.1 mmHg vs 20.0 ± 8.2, P < 0.01; MEC: 25.1 ± 4.4 vs 22.3 ± 5.0, P = 0.46) and in dead space (% of tidal volume, LAV: 32.7% ± 10.5% vs 25.9 ± 10.1, P < 0.01; MEC: 26.1 ± 16.6 vs 18.9 ± 10.1, P = 0.05). These results demonstrate that iNO decreases intrapulmonary shunt (as well as SRVP and dead space). We suggest that iNO may be beneficial in human newborns with severe respiratory failure even if no extrapulmonary shunting via ductus or foramen ovale is apparent. Received: 18 March 1997 and revised form 6 September 1997 / Accepted: 7 September 1997     

哮喘患儿呼出气一氧化氮水平与肺功能相关性研究

目的 探讨处于稳定期哮喘患儿呼出气一氧化氮水平(FeNO)与肺功能中第一秒用力呼气容积(FEVl)的相关性.方法 选取2009年2月至2009年7月于中国医科大学附属盛京医院小儿哮喘门诊就诊的5～14岁的稳定期哮喘患儿53例,根据其是否应用吸入糖皮质激素规范化治疗分为激素治疗组和非激素治疗组,分别测定其FeNO水平和肺功能,分析FeNO水平和肺功能在两组患儿之间是否存在统计学差异,并比较两组患儿FeNO水平和肺功能指标是否存在相关性.结果 非激素治疗组患儿FeNO水平明显高于激素治疗组,且差异有显著性(P=0.005).激素治疗组患儿FEV1平均值为(95.152±8.993)%,非激素治疗组患儿FEVl平均值为(91.350±11.690)%,两组差异无显著性(P=0.932).非激素治疗组患儿FeNO水平与FEV1呈显著负相关性(r=-0.465,P=0.039).激素治疗组哮喘患儿FcNO水平与FEV1参数不相关(r=0.058,P=0.747).结论 处于稳定期的哮喘患儿,未应用吸入糖皮质激素规范化治疗时,其FeNO水平明显高于已用激素规范治疗患儿,测定FeNO水平可以作为一项很好的指标来评价哮喘患儿的气道炎症.     

Nitric oxide inhalation therapy in very low-birthweight infants with hypoplastic lung due to oligohydramnios

BACKGROUND: Although nitric oxide inhalation (iNO) therapy improves arterial oxygenation and reduces the rate of extracorporeal membrane oxygenation in term neonates, the efficacy of this therapy in premature infants is controversial. The objective of the present study was to determine whether iNO therapy improves the survival of very low-birthweight infants with pulmonary hypoplasia due to prolonged rupture of membrane. METHODS: A retrospective comparative study of very low-birthweight infants with pulmonary hypoplasia due to oligohydramnios who had or had not been treated with iNO therapy, was performed (iNO-treated group, eight infants; control group, 10 infants). A neonate was considered to have pulmonary hypoplasia due to oligohydramnios if the following conditions were satisfied: (i) artificial surfactant treatment did not improve the respiratory distress; (ii) prolonged rupture of membrane (PROM) continued for more than 5 days with oligohydramnios; and (iii) sufficient arterial oxygenation did not occur even after giving 100% oxygen, and more than 8 cm H(2)O of mean airway pressure was needed to maintain arterial oxygenation. RESULTS: Nitric oxide inhalation improved arterial oxygenation rapidly and consistently in all eight infants with pulmonary hypoplasia. All eight iNO-treated infants survived longer than 28 days, while five of the 10 control infants died within 24 h of birth (P < 0.05). Before starting iNO, seven of the eight treated infants had shown persistent pulmonary hypertension, which was confirmed by echocardiography. No iNO-treated infant had IVH greater than grade 1, while one control infant had grade 2 IVH. All six long-term survivors in the iNO-treated group are developing normally, while only two of the control infants are developing normally as of February 2002. CONCLUSIONS: The majority of the infants with pulmonary hypoplasia due to oligohydramnios had persistent pulmonary hypertension. iNO improved the arterial oxygenation and significantly improved the survival rate. A controlled study to determine whether iNO therapy improves the survival rate of preterm infants with pulmonary hypoplasia due to oligohydramnios is necessary.     

一氧化氮吸入对新生鼠高氧肺损伤时表面活性蛋白A和肺甘露糖结合力的影响

目的：通过观察吸入一氧化氮(iNO)对新生大鼠高氧肺损伤时表面活性蛋白A(SP-A)和肺组织甘露糖结合力(MBA)的影响,探讨iNO对高氧肺损伤保护作用的可能机制。方法：新生大鼠随机分为对照组(空气);高氧组(>95%O2,6d);NO组(空气+10ppmNO,24h);高氧+NO组(>95%O2,6d+10ppmNO,24h)。观察暴露后2d和6d肺组织病理变化,肺SP-AmRNA基因表达、蛋白含量和MBA的变化。结果：高氧组病理损伤明显,暴露后2d时SP-A的mRNA含量(0.81±0.04vs1.53±0.25)和蛋白表达(59.45±18.37vs89.77±16.41)比对照组减少,6d时分别比对照组增加(0.81±0.02vs0.63±0.03),(93.57±13.71vs47.73±21.69),(P<0.05)。高氧+NO组暴露后2d时病理损伤比高氧组明显减轻,SP-AmRNA(0.55±0.91)比对照组和高氧组降低,SP-A蛋白表达(55.12±17.53)比对照组降低(P<0.01);6d时SP-A蛋白表达(67.33±18.59)比高氧组降低(P<0.05)。甘露糖结合力在暴露后2d时NO组比对照组增加(0.821±0.133vs0.580±0.158)、高氧+NO组比高氧组增加(0.430±0.175vs0.738±0.141)(P<0.05)。结论：小剂量NO吸入可降低高氧肺组织SP-A蛋白表达的升高,增加肺组织的MBA,减轻肺组织的病理损伤。