Inhaled nitric oxide and extracorporeal membrane oxygenation in persistent pulmonary hypertension of the newborn

Persistent pulmonary hypertension of the newborn (PPHN) may occasionally require an invasive treatment with extracorporeal membrane oxygenation (ECMO). Inhaled nitric oxide (NO) has recently been introduced as a selective pulmonary vasodilator for treatment of PPHN. We describe a case of PPHN in which neither inhaled NO nor ECMO was effective in reversing pulmonary hypertension. The clinical course of the patient suggested a potential role of NO inhalation in predicting the outcome of ECMO treatment for PPHN.     

����Ĥ�����ϼ�����������Σ��֢�����е�Ӧ��

??Extracorporeal membrane oxygenation??ECMO?? is a kind of extra life support technique that can support cardiac and pulmonary function of critical neonates for a relatively long time. The principle and application of ECMO in foreign medical institutes and domestic medical institutes were summarized in order to improve the clinical application of ECMO in critically ill newborns to further improve the rescue success rate and reduce the neonatal mortality.     

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.     

体外膜肺氧合在儿科心肺功能衰竭救治中的临床应用

目的探讨体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)技术在儿科心肺功能衰竭救治中的应用。方法回顾性分析2012年6月至2014年10月接受ECMO支持的心肺功能衰竭重症患儿的临床资料。结果共24例心肺功能衰竭患儿接受ECMO支持,男18例,女6例;年龄1 d~7岁;体质量3~20 kg;共有15例成功脱离ECMO,总撤概率62.5%;存活10例(42.7%),死亡14例,其中9例因无法撤离ECMO死亡,3例撤离ECMO后死于并发症,2例撤离ECMO家属放弃治疗死亡;11例(45.8%)患儿在ECMO支持期间出现并发症。结论对于难治性呼吸循环衰竭重症患儿ECMO技术可以提供有效的心肺支持。     

静脉-静脉体外膜肺氧合在儿科急性呼吸衰竭的应用

静脉-静脉体外膜肺氧合技术近年来在新生儿和儿童急性呼吸衰竭治疗中应用日益增多,静脉-静脉体外膜肺氧合可暂时替代肺大部分或部分功能,减轻肺负荷,使其在病变可逆前提下,获得功能改善和病理修复的时间.大量证据表明,急性严重呼吸衰竭采用静脉-静脉体外膜肺氧合支持效果良好.

Abstract：

Veno-venous extracorporeal membrane oxygenation (V-V ECMO) provides support for the neonate,infants and children with acute severe reversible respiratory failure by substituting for the most or part of the lung function and providing enough time for disease resolution.Mounting evidence shows V-V ECMO is effective therapy for acute severe respiratory failure.     

体外膜肺氧合技术在新生儿呼吸衰竭中的应用

体外膜肺氧合（extracorporeal membran eoxygenation,ECMO）技术是一种能在较长时间内对心肺功能进行支持的体外生命支持技术。随着一氧化氮吸入、肺表面活性物质及高频通气等治疗手段的出现,需要ECMO支持的呼吸衰竭新生儿越来越少。但临床上仍有部分难治性呼吸衰竭新生儿对以上治疗无效或反应不良,仍需要ECMO支持。本文对国外ECMO技术在新生儿呼吸衰竭的应用情况进行介绍,并与国内的情况进行对比分析,希望有助于下一步我国新生儿ECMO技术的开展。     

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     

Survival in children on extracorporeal membrane oxygenation at the time of lung transplantation

Limited data exist on ECMO at the time of LTx in children. The UNOS database was queried from 2000 to 2013 for pediatric lung transplant recipients (<18 yr) to assess post‐transplant survival of patients on ECMO at the time of LTx. Of 587 pediatric recipients with 17 on ECMO, 585 were used for univariate and Kaplan–Meier function analysis, 535 for multivariate Cox models, and 24 for propensity score matching. Univariate Cox (HR = 1.777; 95% CI: 0.658, 4.803; p = 0.257) and Kaplan–Meier function (log‐rank test: chi‐square (df = 1): 1.32, p = 0.250) analyses did not identify a survival difference between ECMO and non‐ECMO, while multivariate Cox models (HR = 1.821; 95% CI: 0.654, 5.065; p = 0.251) did not demonstrate an increased risk for death. Propensity score matching analysis (HR = 1.500; 95% CI: 0.251, 8.977; p = 0.657) also failed to demonstrate a significantly increased hazard ratio. Using a contemporary cohort of pediatric lung transplant recipients, the use of ECMO at the time of lung transplantation did not negatively impact survival.     

High frequency oscillatory ventilation and extracorporeal membrane oxygenation in severe persistent pulmonary hypertension of the newborn

We report on 50 term and near-term neonates (birth weight > 1800 g, gestational age > 33 weeks) with severe persistent pulmonary hypertension of the newborn (PPHN), referred to us from January 1987 to July 1991 after failure of maximum conventional treatment. All infants had paO₂<45 mm Hg when ventilated with peak inspiratory pressure >38 cm H₂O and FiO₂=1.0, hence meeting entry criteria for extracorporeal membrane oxygenation (ECMO). High frequency oscillatory ventilation (HFOV) was tried in all patients. If sufficient oxygenation could not be achieved (paO₂<40 mm Hg for at least 2 h), ECMO therapy was begun, which was the case in 25 children. Neonates responding to HFOV (n=25) were of a slightly younger gestational age (37.0 weeks vs 38.8 weeks,P<0.05), had higher Apgar scores and were less hypoxaemic before HFOV (paO₂ 36.6 mm Hg vs 28.8 mm Hg,P<0.01); during HFOV there was a significant rise in paO₂ (> 150 mm Hg;P<0.001) and a fall in pCO₂ to 21.6 mm Hg (P<0.001). Due to air leaks, which was the main complication of HFOV (52%), ECMO therapy had to be begun in two additional infants after an initial positive effect. HFOV tended to be successful in cases of primary PPHN, meconium aspiration and sepsis, but not in infants with lung hypoplasia as a result of diaphragmatic hernia or other reasons. Success or failure of HFOV could not be reliably predicted by any parameter. Mean duration of HFOV was 37.8 h vs 84.9 h of ECMO. PPHN could be overcome in 88% of the HFOV-treated and in 76% of the ECMO-treated infants; overall survival rate was 74% (predicted probability of survival using maximum conventional treatment <10%). There were no significant differences between HFOV/ECMO groups with regard to duration of ventilation following HFOV/ECMO, total time in hospital, rate of bronchopulmonary dysplasia and neurological complications (intracranial haemorrhage, brain infarction). Among the survivors, the rate of mentally handicapped children was equal in both groups (overall 18.9%). Our analysis shows that about 50% of neonates with PPHN who fail to respond to conventional ventilatory support and maximum treatment can be treated successfully with HFOV, thus avoiding ECMO. By applying both forms of therapy, the survival rate of infants with severe PPHN can be increased from an estimated rate of <10% up to 80%.     

Outcome in neonates with congenital heart disease referred for respiratory extracorporeal membrane oxygenation

AIM: To evaluate the proportion of neonates referred for extracorporeal membrane oxygenation (ECMO) support in the modern era of advanced conventional treatments for respiratory failure who actually had congenital heart disease (CHD), and to assess the impact of this diagnostic route on patient condition and outcome. METHODS: A retrospective case-note review of neonatal ECMO and cardiac admissions to a single, tertiary ECMO and cardiac intensive care unit (ICU) between March 1999 and February 2002. RESULTS: 287 symptomatic neonates presented to the ICU with previously undiagnosed cardiac or respiratory disease. Eighty-two with presumed respiratory failure were referred for ECMO, and 205 with suspected CHD were referred for cardiac evaluation. Eight (10%) ECMO referrals, all with presumed persistent pulmonary hypertension of the newborn (PPHN), were found to have CHD (transposition: 3; total anomalous pulmonary venous connection: 3; left heart obstructive lesions: 2). Mortality in this group was 50%, compared with 11% for correctly identified CHD patients (odds ratio 8.2, 95% CI 1.92, 35.4, p<0.01). For all neonates with CHD, the risk of death was increased by the presence of cardiovascular collapse and end-organ dysfunction at presentation to the ICU (p<0.01 for both). CONCLUSION: Neonates with CHD may present as severe "PPHN" via the ECMO service. Poor outcome in these patients relates to the high incidence of cardiovascular collapse and end-organ dysfunction. Early echocardiography is recommended for neonates with presumed PPHN. Neonatal ECMO support should be based in centres with cardiac surgical services.     

体外膜肺氧合在中国儿童重症医学领域的开展现状

体外膜肺氧合技术是一种能够在较长时间内进行心肺支持的体外生命支持技术。该文分别对国内外体外膜肺氧合技术在临床应用情况进行介绍,并对制约体外膜肺氧合技术在国内儿童重症医学领域开展的因素进行分析。希望中国儿科体外膜肺氧合技术加快开展,促进儿童重症医学技术体系的建设和完善。     

Dexamethasone therapy in neonates treated with extracorporeal membrane oxygenation

OBJECTIVE: To test the hypothesis that infants who received dexamethasone would have a shorter length of time on extracorporeal membrane oxygenation (ECMO).Study design Infants placed on ECMO for respiratory failure were randomly assigned to receive either dexamethasone for 3 days or placebo. Chest radiographs were scored through the use of a validated standard scoring system to assess lung injury. RESULTS: Thirty infants received dexamethasone and 29 received placebo. The median (25th%, 75th%) duration of time on ECMO was 143.5 (100, 313) hours in the dexamethasone group and 160 (111, 303) hours in the placebo group (not significant). Survival was 80% in the dexamethasone group and 83% in the placebo group. Radiographic lung injury scores (mean+/-SEM) were significantly improved in the dexamethasone group (10.5+/-0.6) versus placebo (12.3+/-0.5) on day 3 of ECMO (P=.013). Hypertension developed in 27 of the 30 infants receiving dexamethasone and 13 of the 29 infants in the placebo group during ECMO (P<.01). CONCLUSIONS: Dexamethasone given during the first 3 days of ECMO results in significant improvement in lung injury scores by day 3 of ECMO but does not significantly decrease the duration of ECMO or improve survival. The preponderance of evidence would not support the use of dexamethasone in this setting.     

Inhaled nitric oxide in neonates and children with pulmonary hypertension

Fourteen critically ill neonatal and paediatric intensive care patients with various primary diagnoses and signs of associated pulmonary hypertension received inhaled nitric oxide (NO), 20–80 ppm, after failure of conventional therapy to improve oxygenation. NO administration was found to be associated with a significant improvement in postductal arterial oxygen tension (pre-NO: 3.75 (SD 1.39) kPa; post-NO: 6.05 (SD 1.70) kPa; p = 0.004). In 10 patients, NO was found to increase arterial oxygen tension with more than 1 kPa. In 2 of these patients, ECMO treatment could be avoided due to the pronounced improvement in gas exchange seen after the initiation of NO administration. The remaining 4 patients failed to respond to NO administration. One patient developed methaemoglobinaemia (13.9%) which required treatment with methylthionine. Since we were unable to produce any beneficial effect of NO in the late phase of the pulmonary disease process, we believe that, in order to be successful, inhaled NO should be instituted when conventional treatment has failed and the administration of an iv vasodilator is usually considered.     

ECMO患者心肌顿抑的诊治

体外膜肺氧合(extracorporeal membrane oxygenation,ECMO)是一种心肺支持技术,以血泵产生负压,从静脉引血,血液经膜式氧合器氧合后,重新灌入体内,用于较长时间的持续心肺替代支持,临床上主要用于呼吸功能衰竭和(或)心脏功能衰竭经传统治疗无效的患者.近些年,国内ECMO技术在临床应用逐渐增多,而有效防治ECMO并发症是决定该技术是否成功的重要因素.本文主要针对ECMO运转中的心肌顿抑的诊治进行讨论.     

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.