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.     

The safety and efficacy of nitric oxide therapy in premature infants

OBJECTIVES: To assess the safety-efficacy balance of low-dose inhaled nitric oxide (iNO) in hypoxemic premature infants because no sustained beneficial effect has been demonstrated clearly and there are concerns about side effects. STUDY DESIGN: Eight hundred and sixty infants <32 weeks were randomized at birth to receive 5 ppm iNO or placebo when they presented with hypoxemic respiratory failure (HRF) defined by a requirement for mechanical ventilation, fraction of inspired oxygen (FIO 2 ) >40%, and arterio-alveolar ratio in oxygen (aAO 2 ) <0.22. The primary end point was intact survival at 28 days of age. RESULTS: Sixty-one of 415 infants presented with HRF and were compared with 84 of 445 controls who presented with HRF. There was no difference in the primary end point (61.4% in infants [23% with HRF who were treated with iNO] vs 61.1% in controls [21.4% in controls with HRF]; P = .943). For the infants with HRF who were treated with iNO, there was no significant difference from controls for intraventricular hemorrhage (IVH) (6% vs 7%), necrotizing enterocolitis (8% vs 6 %), or patent ductus arteriosus (PDA) (34% vs 37%). Compared with nonhypoxemic infants, the risk of bronchopulmonary displasia (BPD) increased significantly in HRF controls (OR = 3.264 [CI 1.461-7.292]) but not in infants with HRF who were treated with iNO (OR = 1.626 [CI 0.633-4.178]). CONCLUSIONS: iNO appears to be safe in premature infants but did not lead to a significant improvement in intact survival on day 28.     

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.     

Effect of initial nitric oxide concentration on outcome in infants with persistent pulmonary hypertension of the newborn

A randomized nonblinded comparison of two treatment groups was performed to determine whether treatment of infants with persistent pulmonary hypertension of the newborn using a continuous 6-ppm dose of inhaled nitric oxide (iNO) changes the likelihood of death or utilization of extracorporeal membrane oxygenation (ECMO) when compared to infants treated with 20 ppm iNO for 4 h followed by 6 ppm. Twenty-nine infants with a gestational age >/=34 weeks and a diagnosis of persistent pulmonary hypertension of the newborn were enrolled during the 3- year study period. The relative risk (20/6 vs. 6 ppm) for treatment with ECMO was 3.11 (p = 0.02), for death it was 2.80 (p = 0.32), and for either death or ECMO it was 3.42 (p = 0. 006). There was no apparent advantage of treatment with a higher dosage of iNO at the initiation of therapy in the reduction of death or utilization of ECMO. These data suggest that a continuous lower dose of iNO results in a comparable improvement in oxygenation as a short exposure of higher dose iNO at the initiation of therapy.     

Safety and efficacy of inhaled nitric oxide treatment for premature infants with respiratory distress syndrome: follow-up evaluation at early school age

Aims: The aims of the study were to assess the long‐term safety and compare neurodevelopmental outcomes in school‐age children born prematurely who received inhaled nitric oxide or placebo during the first week of life in a randomized, double‐blinded study. Children treated with inhaled nitric oxide had previously been shown to have decreased intraventricular haemorrhage and periventricular leukomalacia as newborns and decreased cognitive impairment at 2 years (L.W. Doyle and P.J. Anderson. (2005) Arch Dis Child Fetal Neonatal Ed, 90, F484–F8). Methods: It is follow‐up study of medical outcomes, neurodevelopmental assessment and school readiness in 135 of 167 (81%) surviving premature infants seen at 5.7 ± 1.0 years. Results: Compared to placebo‐treated children (n = 65), iNO‐treated children (n = 70) demonstrated no difference in growth parameters, school readiness or need for subsequent hospitalization. However, iNO‐treated children were less likely to have multiple chronic morbidities or technology dependence (p = 0.05). They also had less functional disability (p = 0.05). Conclusion: These results demonstrate the long‐term safety of iNO in premature infants. Furthermore, iNO treatment may improve health status by decreasing the incidence of severe ongoing morbidities and technology dependence and may also decrease the incidence of educational and community functional disability of premature infants at early school age.     

Neonatal morbidity in singleton late preterm infants compared with full-term infants

Aim: The aim of this study was to test the hypothesis that singleton late preterm infants (34 0/7 to 36 6/7 weeks of gestation) compared with full‐term infants have a higher incidence of short‐term morbidity and stay longer in hospital. Methods: In this retrospective, multicentre study, electronic data of children born at five hospitals in Switzerland were recorded. Short‐term outcome of late preterm infants was compared with a control group of full‐term infants (39 0/7 to 40 6/7 weeks of gestation). Multiple gestations, pregnancies complicated by foetal malformations, maternal consumption of illicit drugs and infants with incomplete documentation were excluded. The results were corrected for gender imbalance. Results: Data from 530 late preterm and 1686 full‐term infants were analysed. Compared with full‐term infants, late preterm infants had a significant higher morbidity: respiratory distress (34.7% vs. 4.6%), hyperbilirubinaemia (47.7% vs. 3.4%), hypoglycaemia (14.3% vs. 0.6%), hypothermia (2.5% vs. 0.6%) and duration of hospitalization (mean, 9.9 days vs. 5.2 days). The risk to develop at least one complication was 7.6 (95% CI: 6.2–9.6) times higher among late preterm infants (70.8%) than among full‐term infants (9.3%). Conclusion: Singleton late preterm infants show considerably higher rate of medical complications and prolonged hospital stay compared with matched full‐term infants and therefore need more medical and financial resources.     

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.     

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.     

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     

Management of asymptomatic neonates with prolonged rupture of membranes

Guidelines for management of asymptomatic term and preterm neonates born to mothers with prolonged rupture of membranes (PROM) have not been clearly established. A survey was conducted to identify current management practice of neonatologists in midwestern states and to find if there is consensus among physicians with regard to management of PROM without choriomnionitis, with chorioamnionitis but without treatment prior to delivery, and with intrapartum maternal antibiotic therapy prior to delivery. One hundred thirty seven responses to the questionnaire were received. Management of asymptomatic at risk neonates varied in different clinical scenarios. Preterm neonates were screened (94% vs 82%, p < 0.001) and treated (64% vs 41%, p<0.001) more often than term babies. In the absence of maternal symptoms of chorioamnionitis, term neonates were usually observed or treated based on screening test results. With maternal symptoms, 94% of physicians ordered screening test. Prematurity and perceived severity of maternal illness significantly influenced the decision to treat routinely irrespective of screening test results. Physicians favour routine treatment of infants born to mothers who had received intrapartum antibiotic therapy; opinion was divided about management of term asymptomatic infant born to mothers with chorioamnionitis without intrapartum antibiotic therapy. Lumbar punctures were not routinely done for term or preterm neonates prior to antibiotic therapy. Further studies are needed to answer questions regarding the benefits and risks of routine therapy of high risk neonates vs routine clinical observation and selective therapy of only infants who develop symptoms.     

Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia - a double-blind, randomized, controlled trial

Aim: To compare the incidence of hyponatremia in full‐term neonates with severe hyperbilirubinemia, receiving intravenous fluid supplementation with 0.2% saline in 5% dextrose versus 0.9% saline in 5% dextrose, to prevent blood exchange transfusion (BET). Methods: In this double‐blind, randomized, controlled trial, full ‐ term newborns (≥37 weeks), appropriate for gestational age, with severe non‐haemolytic hyperbilirubinemia (serum bilirubin ≥ 20 mg/dL) were enrolled. Eligible neonates were randomized to receive either 0.2% saline in 5% dextrose (hypotonic fluid group) or 0.9% saline in 5% dextrose (isotonic fluid group) over 8 hrs, in addition to phototherapy. The primary outcome was proportion of neonates developing hyponatremia (serum Na < 135 mmol/L) after 8 h. Results: Forty‐two neonates were analysed in each group. Proportion of neonates developing hyponatremia after 8 h was higher in hypotonic fluid group as compared to isotonic fluid group (48.8% vs. 10.5%, p < 0.001). However, a larger proportion in isotonic fluid group developed hypernatremia (39.5% vs. 12.2%, p < 0.001). The rate of BET was similar in both groups. Conclusion: In full‐term neonates with severe hyperbilirubinemia, administration of hypotonic fluid to prevent BET was associated with a higher incidence of hyponatremia while isotonic fluid was associated with an increased incidence of hypernatremia.     

Recombinant human erythropoietin: analysis of a policy of treatment in an hospital based population of very-low-birthweight infants]

AIM OF THE STUDY: To evaluate a policy of treatment with human recombinant erythropoietin (rhEPO) and to describe factors related to red blood cell transfusions (RBCTs) in treated neonates. STUDY: Prospective, observative study. PATIENTS AND METHODS: One-hundred and sixty-five neonates with gestational age (GA) < 30 weeks and/or birthweight < 1000g admitted between may 1998 and october 1999. Ninety were excluded (congenital malformations n = 6, deaths n = 16, referral to a general hospital before discharge n = 67, ECMO n = 1). Data about the characteristics of the population, the severity of the neonatal period, hemoglobin at birth, blood loses, treatment with rhEPO, number of red blood cells transfusions (RBCTs) and donors were recorded in all infants. RESULTS: Thirty-eight in seventy-five (51%) neonates received 112 blood transfusions. Eighty-eight were prescribed after day 15. In most of the cases (n = 68), RBCTs were done according to the protocol. In 20 cases (23%) infants were transfused during a late-onset infection. No difference was observed between the non-transfused (group I) and the transfused neonates (group II) with regards to the drug administration: first dose on day 3 +/- 2, number of injections (17 +/- 4 vs 18 +/- 1, ns). The start of oral supplementation with iron was late (12j +/- 8 vs 19j +/- 10, ns). Infants in group II had a lower birthweight (850 +/- 240 vs 1050 +/- 160 g, p < 0,01) for a similar GA (28 +/- 1SA vs 28 +/- 2SA, ns) in association with an increased number of small for date babies (p = 0.03). Antenatal stero?ds administration (89 vs 74%, ns), administration of surfactant (59 vs 81%, ns) were similar in the two groups. The Clinical Risk Index for Babies was higher in group II: 5 +/- 3 vs 2 +/- 1 (p < 0,001) as was the duration of oxygen delivery (53 +/- 44 vs 14 +/- 20 days, p < 0,01) and postnatal administration of corticostero?ds ( 38% vs 3%, p < 0.01). CONCLUSION: The quality of iron administration, RBCTs and the limitation of donors could be improved in our population. Transfusions among neonates born before 30 weeks and/or with a birthweight of less than 1000 g and treated with rhEPO are associated with intrauterine malnutrition and a worse clinical condition on admission. Early identification of at risk neonates could improve prevention of RBCTs and the efficacy of rhEPO administration to preterm infants.     

Long term gastric pH monitoring for determining optimal dose of ranitidine for critically ill preterm and term neonates

AIM—To determine the optimal doses of ranitidine for both preterm and term infants.METHOD—The effect of ranitidine treatment was measured from the long term intraluminal gastric pH in 16 preterm (gestational age under 37 weeks) and term infants treated in neonatal intensive care. The infants received three different bolus doses of ranitidine: 0.5 mg, 1.0 mg, and 1.5 mg per kilogram of body weight to keep the intraluminal gastric pH above 4 on a 24 hour basis.RESULTS—Critically ill neonates, including very low birth weight infants, were capable of gastric acid formation, and ranitidine treatment increased the intraluminal gastric pH. The effect of a single dose lasted longer in preterm than in term infants. The time needed for reaching the maximum gastric pH was significantly longer in preterm than in term infants. The ranitidine given correlated with the duration of increased gastric pH in a dose dependent manner both in preterm and term infants.CONCLUSION—Preterm infants need significantly smaller doses of ranitidine than term neonates to keep their intraluminal gastric pH over 4. The required optimal dose of ranitidine for preterm infants is 0.5 mg/kg/body weight twice a day and that for term infants 1.5 mg/kg body weight three times a day.     

Neurodevelopmental outcome in high-risk preterm infants treated with inhaled nitric oxide

Inhaled nitric oxide (iNO) is used to treat preterm infants with hypoxaemic respiratory failure. In this study we describe the long-term survival and neurodevelopmental status of high-risk preterm infants enrolled into a randomized controlled trial of iNO therapy. Information regarding long-term outcome was available for all 25 children enrolled in the original trial who survived until discharge from hospital. Formal, blinded, developmental assessment and neurological examinations were performed in 21 out of 22 children still alive at 30 mo of age, corrected for prematurity. No significant differences were found in long-term mortality (12/20 vs 8/22, RR 1.65, 95% CI 0.87-3.3), neurodevelopmental delay (4/7 vs 9/14, RR 0.89, 95% CI 0.37-1.75), severe neurodisability (0/7 vs 5/14, p = 0.12) or cerebral palsy (0/7 vs 2/14, p = 0.53) between iNO-treated and control infants. CONCLUSION: In this study there was no evidence of a significant effect on either survival or long-term neurodevelopmental status in infants treated with iNO.     

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.     

Cardiopulmonary effects of nebulized sodium nitroprusside in term infants with hypoxic respiratory failure

OBJECTIVE: To study whether nebulized nitroprusside (neb-NP) improves oxygenation in term infants with hypoxic respiratory failure (HRF). STUDY DESIGN: We studied 22 newborn term infants (gestational age, 39.7+/-0.4 weeks [mean+/-SEM]; birth weight, 3.6+/-0.1 kg) with hypoxia (Pao2<100 mm Hg) during mechanical ventilation (Fio2=1.0). Sodium nitroprusside (5 mg followed by 25 mg) was nebulized into the inspiratory arm of the ventilator circuit. Vital signs and arterial blood gas values were recorded after 20 minutes at each dose and before and after initiation of inhaled nitric oxide (iNO). RESULTS: Pao2 increased significantly with 5 mg neb-NP (from 64.6+/-5.6 to 90.1+/-15.3 mm Hg, P=.04) and with 25 mg neb-NP (113.2+/-20.4 mm Hg, P=.009). Differences between mean Pao2 at 5 mg versus 25 mg neb-NP were also statistically significant (P=.03). When comparing the effect of neb-NP to iNO, the treatment-induced increases in Pao2 were similar (52.1+/-18.7 vs 62.2+/-18.2 mm Hg, respectively, P=not significant). CONCLUSIONS: Neb-NP causes a dose-dependent increase in oxygenation in term infants with HRF, similar in magnitude to iNO* Neb-NP may be beneficial in infants with HRF when iNO is not readily available.     

Bedeutung von inhalativem Stickstoffmonoxid (iNO) für die Behandlung der pulmonalen Hypertonie Neugeborener

Nearly 25 years ago it could be shown that nitric oxide is an important modulator of vascular tone. The inhalation of nitric oxide (NO) resulted in a reduction of pulmonary hypertension without affecting the systemic vascular resistance. Up to now, twelve prospective trials randomized about 1300 newborns in the therapy and control groups. It is demonstrated, that infants born at or near term (>34 weeks gestational age) with severe respiratory failure or persistent pulmonary hypertension could benefit from inhaled NO (iNO) by improved oxygenation. In addition the combined incidence of death and need of extracorporeal membrane oxygenation was decreased. However, mortality was not reduced in neonates treated with iNO when compared with controls. Up to date, iNO has not been shown to be a risk-factor for neurodevelopmental sequelae. The survival-rate of premature newborns with a gestational age of <34 weeks was not improved by iNO in three of controlled randomized trials. The rates of bronchopulmonary dysplasia or intraventricular hemorrhage was not affected by iNO. There were 205 premature infants in the therapy and control groups. Newborns at or near to term (>34 weeks) can be treated with iNO in defined cases of severe respiratory illness. In all other cases iNO is still a non-registered therapy which should be applicated in clinical trials or as rescue treatment for infants with severe pulmonary hypertension. The legal implications have to be strictly considered by the responsible physician.     

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.     

Treatment of severe meconium aspiration syndrome with porcine surfactant: a multicentre, randomized, controlled trial

Aim: A randomized, controlled clinical trial was performed in 19 Chinese neonatal intensive care units to evaluate the safety and efficacy of exogenous surfactant replacement therapy for severe meconium aspiration syndrome (MAS) in term and near‐term neonates. Methods: Sixty‐one term infants with severe MAS were randomly assigned to either a surfactant or a control group within 36 h after birth. The infants in the surfactant group (n=31) received an initial dose of porcine lung‐derived surfactant (Curosurf®) at 200 mg/kg, and repeated doses of 200, 100 and 100 mg/kg were given at 6–12 h intervals to a maximum of four doses if oxygenation index (OI) deteriorated by >2 from baseline. The primary outcomes were a reduction of OI to less than 10 and an increase of the pre‐treatment a/A PO₂ ratio of 100% over baseline 24 h after surfactant treatment. The secondary outcomes were duration of mechanical ventilation, incidence of complications and survival to discharge from hospital. Results: The general demographic characteristics of the study subjects were similar. There was a trend for surfactant‐treated infants to have an improvement in arterial oxygenation compared to the control group. In comparison with the control group at 24 h, the surfactant group had a lower mean OI (8.1 vs 10.9), more infants with a 100% increase of a/A PO₂ (83% vs 48%, p<0.01) over baseline, and a larger area under the curve for PaO₂/FiO₂ over baseline (3762±1877 vs 2715±1644 mmHg^.h, p<0.05). Repeated measures of these parameters were also in favour of the surfactant group during 24 h to 3 and 7 d compared to the baseline (p<0.05). No differences were found in mean duration of mechanical ventilation, incidence of major complications and number of survivors between the two groups. Conclusion: Surfactant replacement therapy improved oxygenation in the study subjects, suggesting that surfactant may have a role in the treatment of severe MAS in term and near‐term infants.     

Targeted oxygen therapy in special care nurseries: Is uniformity a good thing?

Aim: There is wide variation in the commencement of inspired oxygen (FiO2) and the oxygen saturation (SpO₂) targets set in special care nurseries (SCNs). Evidence supports minimising unnecessary oxygen exposure. Does the introduction of a protocol advocating the uniform approach of commencing FiO2 at 30% and targeting SpO2 of 94–96% for infants ≥33 weeks gestation with respiratory distress reduce oxygen exposure? Methods: A ‘Before After’ study was undertaken in three SCNs. Data were recorded for all infants admitted to the SCNs who required oxygen over a 3‐year period. Infants were analysed in gestational age groups: 33–36 weeks (late preterm) and +37 weeks (term/post‐term). Results: Of the 19 830 infants born, 868 (4%) were treated with oxygen. The introduction of an oxygen‐targeting protocol resulted in a statistically and clinically significant reduction in the proportion of infants who were treated with any oxygen for 1 h or more, 4 h or more and in the proportion who received >30% FiO2 for 1 h or more (all P≤ 0.01). This reduction was significant for infants of both gestational age groups. The median duration of oxygen for term/post‐term infants was reduced from 12 h pre‐protocol to 10 h post‐protocol (P= 0.01); however, no significant difference was found for the preterm group (reduced from 11 to 8 h, P= 0.07). Conclusion: Introduction of a uniform oxygen protocol in SCNs for infants ≥33 weeks gestation with respiratory distress reduces the number of infants receiving oxygen and, in term infants, the duration of oxygen exposure.