Inhalation therapy with nitric oxide in pulmonary hypertension: Comparison of preterm infants versus newborn infants

BACKGROUND: Inhaled nitric oxide (iNO) is used as a vasodilator in pulmonary hypertension (PH) of the newborn infant. PATIENTS AND METHODS: Retrospective analysis of patients, who were treated at our department with iNO in the period from 1994-2001. Response was defined as an increase of the paO (2)/FiO (2) Ratio > or = 20 % and/or a decrease of the oxygenation index (OI) >/= 20 % after 2 h (early response), and consecutively after 24 h (late response). The patients were divided into a) primary persistent pulmonary hypertension of the newbom (PPHN), or b) pulmonary hypertension secondary to meconium aspiration syndrome (MAS), sepsis or congenital diaphragmatic hernia (CDH). RESULTS: Between 1994 and 2001 we treated 47 patients with iNO at our neonatal intensive care unit. We included 16 (35 %) preterm infants (GA 34,5 [25 - 37] weeks, GG 2061 [680 - 3410] g) (Median/Range) and 31 (65 %) newbom (GA 40 [38 - 42] weeks, GG 3510 [2550 - 4560] g). 18 (38 %) patients suffered from primary PPHN, 29 (62 %) from secondary PPHN (14 MAS [30 %], 8 sepsis [17 %], 4 CDH [8 %]). 8 (50 %) preterm and 20 (64 %) term infants showed a positive iNO response after 2 h, again 8 (50 %) preterm and 20 (64%) term infants showed a positive iNO response after 24 h. There was neither a significant difference between term and preterm infants at 2 h, nor at 24 h. Between 2 h and 24 h 10 patients changed in their response to iNO. 5 (18 %) patients with early response showed a significant degradation after 24 h, whereas 5 (26 %) of the patients without early response showed a significant improvement of the oxygenation alter 24 h. Alltogether 13 (72 %) patients with PPHN, 8 (57 %) with MAS, 2 (50 %) with CDH, 4 (50 %) with sepsis showed a positive iNO response after 24 h. In regard to the oxygenation parameters at start of iNO-therapy, the patients with early response did not differ from the patient without response (median OI: 20,0 versus 21,8, median paO (2)/FiO (2) Ratio: 59,3 versus 55,0 mmHg at the start of the iNO therapy). CONCLUSION: In regard to iNO response, there was no significant difference between term and preterm infants. Due to the changing response, a positive iNO-response after 2 h had no predictive value for the further prognosis of the oxygenation situation under iNO therapy.     

Randomised trial of three doses of inhaled nitric oxide in acute respiratory distress syndrome.

BACKGROUND: Inhaled nitric oxide (iNO) is a potential therapeutic agent for the management of acute respiratory distress syndrome (ARDS). Concerns remain, however, regarding the potential toxicity from iNO and/or its oxidative derivatives and methaemoglobinaemia. AIMS: To determine the risk of toxicity from iNO, which includes worsening of lung injury, a prospective study evaluating the acute effects of three concentrations of iNO on gas exchange and haemodynamics in 12 children with ARDS was performed in a tertiary paediatric intensive care unit. INTERVENTION: iNO was administered for one hour at three concentrations (1, 10, and 20 parts per million (ppm)) in a random order of possible dosing schedules to avoid dose accumulation bias. Arterial blood gas, methaemoglobin concentrations, and haemodynamic parameters were obtained at baseline before commencement of iNO, at the end of each study hour, and after iNO was discontinued. Nitric oxide and nitrogen dioxide concentrations were continuously monitored during the study. RESULTS: iNO significantly improved the oxygenation ratio (Pao2/Fio2) from a mean (SEM) baseline of 11.9 (1.7) kPa to 20 (3.9) kPa, 24 (4.5) kPa, and 21.6 (3.9) kPa at 1, 10, and 20 ppm iNO, respectively. There was no significant difference in the improvement in oxygenation achieved between the three concentrations. Correspondingly, there was a significant improvement in oxygenation index (pre-iNO 28.3 (5) v post-iNO 18 (3) (1 ppm), 15 (3) (10 ppm), 16 (3) (20 ppm)). No toxicity from methaemoglobinaemia or nitrogen dioxide was seen during iNO administration. CONCLUSION: The results show that a low concentration of iNO (1 ppm) is as effective as higher concentrations (10 and 20 ppm) in improving oxygenation in children with ARDS and may be important in minimising toxicity during iNO use.     

Inhaled nitric oxide therapy in the near-term or term neonate with hypoxic respiratory failure

Inhaled nitric oxide (iNO) has altered the management strategy for treating near-term and term infants with hypoxic respiratory failure (HRF). There is a strong relationship between HRF and persistent pulmonary hypertension of the newborn (PPHN). PPHN is characterized by elevated pulmonary resistance, pulmonary vasoconstriction, and altered vascular reactivity. The resulting high pulmonary pressure may lead to HRF, which is defined as a relative deficiency of oxygen in arterial blood and insufficient minute ventilation. iNO improves oxygenation and decreases the need for extracorporeal membrane oxygenation. Although iNO therapy is effective, its efficacy can depend on the fine points of its use and on other care the infant is receiving. Even in NICUs that do not have iNO available, those who care for term infants with HRF must be familiar with its use and know when and how to transfer these infants and how to help families through this difficult period. Because iNO therapy will probably be used more frequently in nurseries over the next few years, more information on the safety and efficacy of its use in the broader neonatal population needs to be available.     

Plasma arginine levels and the response to inhaled nitric oxide in neonates

Inhaled nitric oxide (iNO) can be an effective vasodilator in pulmonary hypertension of the newborn (PHN). The aim of this study was to determine whether differences in arginine levels, from which endogenous NO is produced, explain the variability in response to NO and whether the arginine levels were lower in term and preterm infants with PHN than in infants without PHN (controls). We prospectively studied 30 infants (17 born preterm) with clinically diagnosed PHN and treated with iNO and 22 controls (14 born preterm). Three NO levels (10, 20, 40 ppm) were administered to the PHN infants to identify that associated with maximum oxygenation. Twenty-seven infants with PHN improved following iNO and had lower arginine levels than those infants who did not respond to iNO (p < 0. 05). No significant relationship, however, was noted between the arginine levels and either the magnitude of change in the oxygenation index in response to iNO or the NO level associated with maximum oxygenation. The median plasma arginine level prior to iNO of the PHN infants was 12.5 (range 2-53) mu mol/l, but not significantly lower than that of the controls (median 24, range 3-82 mu mol/l). We conclude that differences in plasma arginine levels are unlikely to explain the variation in response to iNO and that, although arginine levels tended to be lower in infants with PHN, this is not a consistent finding in either the term or preterm infants.     

A dose response study of inhaled nitric oxide in hypoxic respiratory failure in preterm infants

BACKGROUND: Inhaled nitric oxide (iNO) is used widely in newborn infants with hypoxic respiratory failure, despite the known and theoretical toxicity of iNO, and a relative lack of information about appropriate doses. AIM: To determine whether a dose-response relationship existed for iNO in preterm infants. DESIGN: A four-period, four-dose, cross-over design was used with iNO given for 15 min in a randomised sequence in concentrations of 5, 10, 20 and 40 parts per million (ppm), with a minimum 5 min wash-out period. Data on ventilatory, blood gas and other physiological measurements were recorded before and at the end of each period. The relationship of clinical response with iNO dose and period was analysed using multivariate regression. SUBJECTS: Infants with gestational age < 34 weeks and < 28 days postnatal age with hypoxic respiratory failure were recruited. OUTCOME MEASURE: A clinically significant dose-response was defined as a rise in the post-ductal arterial oxygen tension (PaO(2)) of at least 3 kPa. RESULTS: Thirteen infants were recruited. At trial entry, ten were < 3 days of age; 11 were being treated with high frequency oscillatory ventilation; median (inter-quartile range) gestational age 27 (25-29) weeks; birthweight 983 (765-1120) g; oxygenation index 27.1 (21.8-28.8). Six infants (46%) showed a clinically significant response. After adjusting for period and patient effect, no evidence for an overall dose effect was identified (likelihood ratio test, p=0.34). CONCLUSION: No evidence of a dose-response relationship with iNO was found in this study of very preterm infants with respiratory failure.     

Three-year follow up of term and near-term infants treated with inhaled nitric oxide

BACKGROUND: The present study describes the outcome at 3 years in term and near-term infants treated with inhaled nitric oxide (iNO) for persistent pulmonary hypertension of the newborn (PPHN). METHODS: The study population consisted of 18 infants delivered at 34 weeks by best obstetric estimate who were admitted to the neonatal intensive care units with a diagnosis of PPHN. RESULTS: Eighteen infants (mean gestational age 38.5 +/- 2.6 weeks, mean birthweight 3015 +/- 587 g) were treated with iNO. The mean oxygenation index before iNO was 27.2 +/- 15.2. Responses to iNO were classified into three groups: (i) early response in eight infants; (ii) late response in two; and (iii) poor response in eight infants. Three infants died within seven postnatal days. Fifteen surviving infants were followed up to 3 years. The mean developmental scale was 98.4 +/- 9.0. One infant was diagnosed with severe neurodevelopmental disability due to cerebral palsy. Another infant was diagnosed with mild neurodevelopmental disability because of a low developmental scale. No infant showed significant hearing loss. Five infants had reactive airway disease (RAD) at 18 months, these infants required a significantly longer duration of mechanical ventilation in their neonatal period than non-RAD infants (P = 0.02). The frequency of survival with normal neurodevelopmental outcome was significantly higher in the early response group than the late or poor response groups (P = 0.03). CONCLUSION: In iNO-treated PPHN, mortality and neurodevelopmental outcome were associated with response to iNO, and pulmonary outcome was associated with duration of mechanical ventilation.     

Use of inhaled nitric oxide in the new born period: results from the European inhaled nitric oxide registry

Aims: The aim of this study was to present data relating to the use of inhaled nitric oxide (iNO) in newborn infants included in the European Inhaled Nitric Oxide Registry. Methods: Demographic, clinical and therapeutic data from seven European centres are reported. Univariate analyses were performed to identify factors associated with acute response to iNO and survival without extra corporeal membrane oxygenation (ECMO). Results: A total of 112 newborn infants received iNO, with 40% being less than 34 weeks gestational age. The commonest indication for iNO was secondary pulmonary hypertension. Acute response to iNO was more common in infants with a higher oxygenation index (median OI 32.7 vs 22.6, p = 0.040), although acute response did not predict survival without ECMO. Infants who survived without ECMO had a lower OI prior to therapy (median OI 24 vs 43, p = 0.009), were commenced on a higher starting dose (median dose 20 ppm vs 10 ppm p = 0.013) and received a lower maintenance dose (median dose 10 vs 17 ppm, p = 0.027) than those who died or received ECMO. Conclusion: Collating and reporting data about iNO therapy in neonates across a number of European centres using a web‐based system is feasible. These data may be used to monitor the clinical use of iNO, identify adverse effects, generate research hypotheses and promote high standards in the clinical use of iNO.     

Nitric oxide in neonatal transposition of the great arteries

Three newborn infants with transposition of the great arteries (TGA) and intact ventricular septum (IVS) developed postnatal persistent pulmonary hypertension of the newborn (PPHN) and were successfully treated with inhaled nitric oxide (iNO). Intervention with balloon atrial septostomy (BAS) was performed in two of the infants before the iNO treatment, but they continued to be severely hypoxic with metabolic acidosis. However, the iNO immediately improved oxygenation and the clinical condition. The third neonate had a moderately large atrial communication and echocardiographic signs of PPHN. He received iNO before BAS with dramatic clinical improvement, which therefore postponed BAS.

Conclusion: Early diagnosis of PPHN and treatment with iNO may improve final outcome in neonates with TGA and IVS. In the presence of moderately large atrial communication and PPHN, treatment with iNO might be considered before BAS.     

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     

吸入一氧化氮治疗早产儿低氧性呼吸衰竭的应用

动物实验表明,吸入一氧化氮（inhaled NO,iNO）可减少早产动物肺部炎症发生率,提高表面活性物质功能,促进肺生长。自20世纪90年代初iNO首次被用于治疗持续性肺动脉高压以来,已逐渐在新生儿重症监护病房得到应用。虽然多项研究结果均证实iNO治疗早产儿低氧性呼吸衰竭（hypoxic respiratory failure,HRF）的有效性,但至今尚无确切证据表明对早产儿可常规使用iNO治疗。本文结合国内外近年文献,就目前iNO治疗早产儿的作用机制、治疗的临床方案、iNO的有效性及安全性做一综述,以期为临床提供参考。     

Inhaled nitric oxide improves oxygenation in very premature infants with low pulmonary blood flow

AIM: Inhaled nitric oxide (iNO) is used to reduce right-to-left extrapulmonary shunting by decreasing pulmonary vascular resistance in term or near-term infants. The objectives of this study were to determine, first, the pulmonary blood flow status of very preterm infants with hypoxaemic respiratory failure, then the response of oxygenation to iNO therapy according to pulmonary blood flow (PBF) and, finally, to verify the lack of adverse side effects of iNO on the ductus arteriosus. METHODS: Infants below 32 wk gestational age (GA) with hypoxic respiratory failure and aAO2 < 0.22 were randomized as the control or iNO group. PBF was evaluated by pulsed Doppler measurement of mean pulmonary blood flow velocity (MPBFV) in the left pulmonary artery. Low PBF (LPBF) was defined as MPBFV < 0.2 m/s. RESULTS: Seventy infants of 23 to 31 wk GA with hypoxic respiratory failure were randomized either to receive or not to receive 5 ppm iNO in addition to optimal care. Twenty-eight infants were diagnosed with LPBF (11/35 in iNO vs 17/35 in the control groups). Thirty minutes after receiving iNO the number of LPBF infants dropped to 8/35. In the iNO group, aAO2 increased significantly from 0.14 +/- 0.05 to 0.24 +/- 0.08 after iNO, but only in the LPBF infants (mean +/- SD; p = 0.027). CONCLUSION: In infants below 32 wk GA with hypoxic respiratory failure, Doppler echocardiographic assessment of LPBF seems to be able to determine which patients are likely to benefit from iNO therapy on systemic oxygenation.     

Chest radiograph abnormalities in very low birthweight survivors of chronic neonatal lung disease

Objective : To determine whether the neonatal chest radiograph (CXR) at 28 days in very low birthweight (VLBW) infants who develop chronic neonatal lung disease (CNLD) predicts oxygen therapy duration or CXR abnormalities in early childhood. Also, to assess the inter-observer reliability of the radiologists scoring the CXR.
Methodology : Clinically well survivors of CNLD ( n = 46) had neonatal CXR scored (mean age 28.5 days) and compared with current CXR (mean age 40 months). The CXR were scored independently and 'blindly' by two paediatric radiologists using a standardized scoring system (range 0-10).
Results : There was no correlation between neonatal CXR scores and current CXR scores for either radiologist. There was no association between CXR severity scores and duration of oxygen therapy for either neonatal or current CXR. Radiologist A scored the current CXR significantly more abnormal than radiologist B [medians (range): 3 (1-6) vs 1 (0-5), P <0.001] with reasonable correlation ( r = 0.593, P <0.005) but worse than chance agreement (kappa = - 0.034). The median scores for the neonatal CXR were similar [1.5 (0-8) vs 2 (0-8), P = 0.789] and again there was good correlation ( r = 0.760, P <0.0005) although poor individual agreement (kappa = 0.243) between radiologists.
Conclusions : Follow-up CXR abnormalities in VLBW infants with CNLD are usually minor and are not predictive of the duration of oxygen therapy that will be required nor of the CXR appearance in early childhood. Considerable inter-observer variation exists in the interpretation of the CXR in CNLD.     

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.     

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.     

Neonatal persistent pulmonary hypertension treated with milrinone: four case reports

Current standard therapy for persistent pulmonary hypertension of the newborn (PPHN) consists of optimal lung inflation, hemodynamic support and selective vasodilation with inhaled nitric oxide (iNO). However, not all infants will respond. Milrinone, a phosphodiesterase (PDE) III inhibitor, is routinely used in pediatric cardiac intensive care units to improve inotropy and reduce afterload. Although its use in post-operative cardiac failure has been proven in a randomized trial, it has not been reported to be beneficial in PPHN. We report four cases with severe PPHN treated with a combination of iNO and Milrinone. All four cases were unresponsive to therapy including iNO, with a mean oxygenation index (OI) of 40 (standard deviation (SD) 12)) before Milrinone. Substantial improvement in OI (mean of 28; SD 16) was followed by extubation and survival. However, of 4 patients, 2 developed serious intraventricular hemorrhages (IVHs), and 1 had a small IVH. To clarify the risk benefit ratio, of death versus survival with impairment, a randomized controlled trial is needed.     

Inhaled nitric oxide use in newborns

Inhaled nitric oxide (iNO) is a pulmonary vasodilator that plays a major role in regulating vascular muscle tone. It has emerged as a treatment for hypoxemic respiratory failure in newly born infants that is associated with persistent high pulmonary vascular pressure and resultant right-to-left shunting of blood (persistent pulmonary hypertension of the newborn). Current evidence shows that iNO improves oxygenation and decreases the combined outcome of death or need for extracorporeal membrane oxygenation in infants ≥35 weeks’ gestational age at birth. Its role in managing preterm infants <35 weeks’ gestational age is not yet established. iNO is safe when administered in tertiary care settings using strict protocols and monitoring. The recommended starting dose is 20 ppm with gradual reduction of the dose following improvement in oxygenation.     

Inhaled nitric oxide therapy in preterm infants

According to a number of recently published, randomized controlled trials, treatment of persistent pulmonary hypertension of the newborn (PPHN) by the use of inhaled nitric oxide (iNO) has emerged as an established procedure in neonatology. The situation in premature infants appears to be more complicated than in the term infant. Due to the fact that nitric oxide interferes with platelet aggregation, the risk of intraventricular hemorrhage or its aggravation during iNO therapy is being discussed in a controversial manner. Since most studies are aimed at endpoints like oxygenation parameters, the presently available studies report extremely variable incidences of intraventricular hemorrhages (IVH). Meanwhile two large studies could demonstrate that clinical application of iNO in preterm infants is not associated with an increased incidence of IVH. Further randomized controlled trials of iNO in preterm neonates are highly desirable in order to establish the future role of this therapy and its indications.     

Experience with mobile inhaled nitric oxide during transport of neonates and children with respiratory insufficiency to an extracorporeal membrane oxygenation center.

OBJECTIVE: To share our experience with the use of inhaled nitric oxide (iNO) during the transport of ventilated neonates and children to an extracorporeal membrane oxygenation (ECMO) center and to discuss the efficacy and safety of iNO use in this situation. DATA SOURCES: Case note review of 55 consecutive patients transported while receiving iNO to Glenfield Hospital, Leicester, UK, for consideration of ECMO. STUDY SELECTION: Retrospective case note review. DATA EXTRACTION: The clinical condition of each patient recorded at arrival of the transport team at the referring hospital, during transport, and at arrival at Glenfield Hospital. Preclinical and postclinical conditions were compared using the paired Student's t-test. DATA SYNTHESIS: Overall data showed a significant improvement in transcutaneous oximetry measurements (Spo(2): 84.8% preclinical, 90.6% postclinical; p = .006) and Pao(2) (59 torr [7.87 kPa] preclinical, 84 torr [11.23 kPa] postclinical; p = .001) during transport in our patient group. Based on limited safety data, no untoward events or toxic metabolites were observed with iNO therapy during transport. CONCLUSIONS: iNO does appear to improve oxygenation during transfer of patients for ECMO in our series. Based on limited safety data, iNO appears safe to use in transport.     

Response to pulmonary vasodilators in infants with congenital diaphragmatic hernia

Background

Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia, cardiac dysfunction and pulmonary hypertension. Inhaled nitric oxide (iNO) and milrinone are commonly used pulmonary vasodilators in CDH. We studied the hemodynamic effects of iNO and milrinone in infants with CDH.

Methods

A retrospective chart review was performed of all CDH infants admitted to two regional perinatal centers and infants classified into three groups: No-iNO group; iNO-responders and iNO-nonresponders. Oxygenation and hemodynamic effects of iNO and milrinone were assessed by blood gases and echocardiography.

Results

Fifty-four percent (39/72) of infants with CDH received iNO and 31% of these infants (12/39) had complete oxygenation response to iNO. Oxygenation response to iNO was not associated with a decrease in right ventricular pressures (RVP) or ECMO use. Four infants (33%) in the iNO-responder group and eight infants (30%) in the iNO-nonresponder group received milrinone. Milrinone lowered RVP and improved ejection fraction (EF). Response to iNO was associated with improved oxygenation to milrinone and increased survival following ECMO (67 vs. 20% among nonresponders).

Conclusions

Response to inhaled nitric oxide in combination with milrinone may be associated with improved oxygenation and better survival after ECMO in infants with CDH.

     

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.