Reduction In Bronchopulmonary Dysplasia Research Articles

664 - A data driven quality improvement initiative to reduce bronchopulmonary dysplasia in a level 3 NICU

664 - A data driven quality improvement initiative to reduce bronchopulmonary dysplasia in a level 3 NICU

Late (≥ 7 days) inhaled corticosteroids to reduce bronchopulmonary dysplasia in preterm infants.

Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks' postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation may be an effective and safe alternative. To assess the benefits and harms of inhaled corticosteroids versus placebo, initiated between seven days of postnatal life and 36 weeks' postmenstrual age, to preterm infants at risk of developing bronchopulmonary dysplasia. We searched CENTRAL, MEDLINE, Embase, CINAHL, and three trials registries to August 2022. We searched conference proceedings and the reference lists of retrieved articles for additional studies. We included randomised controlled trials (RCTs) comparing inhaled corticosteroids to placebo, started between seven days' postnatal age (PNA) and 36 weeks' PMA, in infants at risk of BPD. We excluded trials investigating systemic corticosteroids versus inhaled corticosteroids. We collected data on participant characteristics, trial methodology, and inhalation regimens. The primary outcomes were mortality, BPD, or both at 36 weeks' PMA. Secondary outcomes included short-term respiratory outcomes (mortality or BPD at 28 days' PNA, failure to extubate, total days of mechanical ventilation and oxygen use, and need for systemic corticosteroids) and adverse effects. We contacted the trial authors to verify the validity of extracted data and to request missing data. We analysed all data using Review Manager 5. Where possible, we reported the results of meta-analyses using risk ratios (RRs) and risk differences (RDs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, along with their 95% confidence intervals (CIs). We analysed ventilated and non-ventilated participants separately. We used the GRADE approach to assess the certainty of the evidence. We included seven trials involving 218 preterm infants in this review. We identified no new eligible studies in this update. The evidence is very uncertain regarding whether inhaled corticosteroids affects the combined outcome of mortality or BPD at 36 weeks' PMA (RR 1.10, 95% CI 0.74 to 1.63; RD 0.07, 95% CI -0.21 to 0.34; 1 study, 30 infants; very low-certainty) or its separate components: mortality (RR 3.00, 95% CI 0.35 to 25.78; RD 0.07, 95% CI -0.08 to 0.21; 3 studies, 61 infants; very low-certainty) and BPD (RR 1.00, 95% CI 0.59 to 1.70; RD 0.00, 95% CI -0.31 to 0.31; 1 study, 30 infants; very low-certainty) at 36 weeks' PMA. Inhaled corticosteroids may reduce the need for systemic corticosteroids, but the evidence is very uncertain (RR 0.51, 95% CI 0.26 to 1.00; RD -0.22, 95% CI -0.42 to -0.02; number needed to treat for an additional beneficial outcome 5, 95% CI 2 to 115; 4 studies, 74 infants; very low-certainty). There was a paucity of data on short-term and long-term adverse effects. Despite a low risk of bias in the individual studies, we considered the certainty of the evidence for all comparisons discussed above to be very low, because the studies had few participants, there was substantial clinical heterogeneity between studies, and only three studies reported the primary outcome of this review. Based on the available evidence, we do not know if inhaled corticosteroids initiated from seven days of life in preterm infants at risk of developing BPD reduces mortality or BPD at 36 weeks' PMA. There is a need for larger randomised placebo-controlled trials to establish the benefits and harms of inhaled corticosteroids.

Continuing interventions in a quality improvement bundle to reduce bronchopulmonary dysplasia.

Continuing interventions in a quality improvement bundle to reduce bronchopulmonary dysplasia.

Soluble Klotho, a biomarker and therapeutic strategy to reduce bronchopulmonary dysplasia and pulmonary hypertension in preterm infants

Preterm infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH) have accelerated lung aging and poor long-term outcomes. Klotho is an antiaging protein that modulates oxidative stress, angiogenesis and fibrosis. Here we test the hypothesis that decreased cord Klotho levels in preterm infants predict increased BPD–PH risk and early Klotho supplementation prevents BPD-like phenotype and PH in rodents exposed to neonatal hyperoxia. In experiment 1, Klotho levels were measured in cord blood of preterm infants who were enrolled in a longitudinal cohort study. In experiment 2, using an experimental BPD–PH model, rat pups exposed to room air or hyperoxia (85% O2) were randomly assigned to receive every other day injections of recombinant Klotho or placebo. The effect of Klotho on lung structure, PH and cardiac function was assessed. As compared to controls, preterm infants with BPD or BPD–PH had decreased cord Klotho levels. Early Klotho supplementation in neonatal hyperoxia-exposed rodents preserved lung alveolar and vascular structure, attenuated PH, reduced pulmonary vascular remodeling and improved cardiac function. Together, these findings have important implications as they suggest that perinatal Klotho deficiency contributes to BPD–PH risk and strategies that preserve Klotho levels, may improve long-term cardiopulmonary outcomes in preterm infants.

A multidisciplinary quality improvement effort to reduce bronchopulmonary dysplasia incidence.

BackgroundBronchopulmonary Dysplasia (BPD) is the most common prematurity complication. Although several practices have been proposed for BPD prevention, none of these in isolation prevent BPD.MethodsOur initiative focused on two key drivers: oxygen management and noninvasive ventilation strategies. We created best practice guidelines and followed outcome measures using Shewhart control charts.ResultsPDSAs of protocols preceded a large-scale rollout of a “0.21 by 28” campaign in 2014 leading to a special cause reduction in the “any BPD” rate, and a decrease in severe BPD (from 57 to 29%). At the end of 2017, we reinvigorated the project, which led to dramatic decreases in the “any BPD” rate to 41% and the “severe BPD” rate to 21%.ConclusionsA multidisciplinary QI initiative focused on process improvement geared towards the pathophysiological contributors of BPD has successfully reduced the rate of BPD in an all referral level IV NICU.

New Developments in Respiratory Support for Preterm Infants.

The evolution of neonatal respiratory support has been one of the cornerstones for the advancements in neonatal-perinatal medicine, allowing survival of infants previously considered not viable. There is an increasing focus on developing strategies which are not only lifesaving but also minimize lung and other organ systems injury, thereby reducing long-term morbidities. Respiratory support immediately after birth is an area that had lagged behind in terms of evidence base and technological advancements until recently. Some of these advancements include use of a respiratory function monitors for measuring flow and tidal volume, new evidence for oxygen supplementation and monitoring, and the efforts to formulate an ideal strategy for establishing functional residual capacity after birth. Increasing evidence for the benefits of avoiding invasive ventilation on reduction of bronchopulmonary dysplasia has resulted in efforts to further reduce the need for endotracheal intubation by applying newer strategies such as less invasive surfactant instillation, noninvasive high-frequency oscillatory ventilation, or use of high flow nasal cannula oxygen. For infants requiring mechanical ventilation, newer strategies such as volume targeted ventilation or neurally adjusted ventilation are being evaluated to reduce ventilator induced lung injury. Despite these advances, there are significant challenges, including lack of conclusive evidence base for many of currently used respiratory strategies, no reduction in the incidence of bronchopulmonary dysplasia in the last decade, and difficulties in defining outcome measures that better reflect long-term respiratory health.

High-versus low-dose caffeine in preterm infants: a systematic review and meta-analysis.

Though caffeine is a consolidated treatment in preterm infants, the efficacy and safety of a higher dose have not been systematically appraised. A systematic review was conducted to compare high (loading dose >20mg/kg and maintenance >10mg/kg/day) versus low dose of caffeine. MEDLINE, EMBASE, Central and conference proceedings for randomised controlled trials (RCTs) and quasi-RCTs were searched. Two authors independently screened the records, extracted the data and assessed the risk of bias. As only six RCTs enrolling a total of 816 preterm infants were included, the required information size was not reached. The loading and maintenance doses varied between 20 and 80mg/kg/day and 3 and 20mg/kg/day, respectively. The use of high dose had no impact on mortality (RR: 0.85; 95% CI: 0.53-1.38; RCTs = 4). However, it resulted in fewer cases of extubation failure, apnoeas and bronchopulmonary dysplasia (RR: 0.76; 95% CI: 0.60-0.96; studies = 4) and shorter duration of mechanical ventilation. The quality of the evidence was low due to imprecision of the estimates. Due to imprecision, it is not possible to determine whether high-dose caffeine is more effective and safe than a low dose. High dose might improve short-term respiratory function and reduce bronchopulmonary dysplasia.

Late (≥ 7 days) inhalation corticosteroids to reduce bronchopulmonary dysplasia in preterm infants.

Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative. To determine if administration of inhalation corticosteroids after the first week of life until 36 weeks PMA to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 4), MEDLINE via PubMed (1966 to 19 May 2017), Embase (1980 to 19 May 2017), and CINAHL (1982 to 19 May 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We included randomised controlled trials comparing inhalation corticosteroids, started ≥ 7 days postnatal age (PNA) but before 36 weeks PMA, to placebo in ventilated and non-ventilated infants at risk of BPD. We excluded trials investigating systemic corticosteroids versus inhalation corticosteroids. We collected data on participant characteristics, trial methodology, and inhalation regimens. The primary outcome was death or BPD at 36 weeks PMA. Secondary outcomes were the combined outcome death or BPD at 28 days PNA, the seperate outcomes of death and BPD at both 28 days PNA, and at 36 weeks PMA, and short-term respiratory outcomes, such as failure to extubate; total days of mechanical ventilation and oxygen use; and the need for systemic corticosteroids. We contacted the original trialists to verify the validity of extracted data and to provide missing data. We analysed all data using Review Manager 5. When possible, we performed meta-analysis using typical risk ratio (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes along with their 95% confidence intervals (CI). We analysed ventilated and non-ventilated participants separately.We used the GRADE approach to assess the quality of the evidence. We included eight trials randomising 232 preterm infants in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. The meta-analyses of the studies showed a reduced risk in favor of inhalation steroids regarding failure to extubate at seven days (typical RR (TRR) 0.80, 95% CI 0.66 to 0.98; 5 studies, 79 infants) and at the latest reported time point after treatment onset (TRR 0.60, 95% CI 0.45 to 0.80; 6 studies, 90 infants). However, both analyses showed increased statistical heterogeneity (I2 statistic 73% and 86%, respectively). Furthermore, inhalation steroids did not impact total duration of mechanical ventilation or oxygen dependency. There was a trend toward a reduction in the use of systemic corticosteroids in infants receiving inhalation corticosteroids (TRR 0.51, 95% CI 0.26 to 1.00; 4 studies, 74 infants; very low-quality evidence). There was a paucity of data on short- and long-term adverse effects. Our results should be interpreted with caution because the total number of randomised participants is relatively small, and most trials differed considerably in participant characteristics, inhalation therapy, and outcome definitions. Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.

Postnatal dexamethasone, respiratory and neurodevelopmental outcomes at two years in babies born extremely preterm.

ImportancePostnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes.ObjectiveOur aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors.Materials and methodsThe study included 412 infants born at 23–28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken.ResultsAfter adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26).ConclusionsPostnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities.

Patent Ductus Arteriosus and Short- and Long-Term Respiratory Outcomes.

The patency of the ductus arteriosus is very common in extremely premature infants. The increased pulmonary blood flow that results from left-to-right ductal shunting can produce an acute deterioration in lung function and some data suggest that it may increase the risk of chronic lung damage. However, there is no clear evidence that prophylactic or early closure of the patent ductus arteriosus (PDA) results in a clear reduction in bronchopulmonary dysplasia. For this reason, and because of the side effects of the available therapies to close the ductus, there is a wide variation in the approach to the PDA in this population and most clinicians will intervene to close the ductus only in cases of significant shunt with hemodynamic decompensation.

Prophylactic nasal continuous positive airway pressure for preventing morbidity and mortality in very preterm infants.

Cohort studies have suggested that nasal continuous positive airways pressure (CPAP) starting in the immediate postnatal period before the onset of respiratory disease (prophylactic CPAP) may be beneficial in reducing the need for intubation and intermittent positive pressure ventilation (IPPV) and in preventing bronchopulmonary dysplasia (BPD) in preterm or low birth weight infants. To determine if prophylactic nasal CPAP started soon after birth regardless of respiratory status in the very preterm or very low birth weight infant reduces the use of IPPV and the incidence of bronchopulmonary dysplasia (BPD) without adverse effects. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE via PubMed (1966 to 31 January 2016), EMBASE (1980 to 31 January 2016), and CINAHL (1982 to 31 January 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. All trials using random or quasi-random patient allocation of very preterm infants (under 32 weeks' gestation) or less than 1500 grams at birth were eligible. We included trials if they compared prophylactic nasal CPAP started soon after birth regardless of the respiratory status of the infant with 'standard' methods of treatment such as IPPV, oxygen therapy or supportive treatment. We excluded studies where prophylactic CPAP was compared with CPAP along with other interventions. We used the standard methods of Cochrane and its Neonatal Review Group, including independent study selection, assessment of trial quality and extraction of data by two authors. Data were analysed using risk ratio (RR) and the meta-analysis was performed using a fixed-effect model. Seven trials recruiting 3123 babies were included in the meta-analysis. Four trials recruiting 765 babies compared CPAP with supportive care and three trials (2364 infants) compared CPAP with mechanical ventilation. Apart from a lack of blinding of the intervention all studies were of low risk of bias.In the comparison of CPAP with supportive care there was a reduction in failed treatment (typical risk ratio (RR) 0.66, 95% confidence interval (CI) 0.45 to 0.98; typical risk difference (RD) -0.16, 95% CI -0.34 to 0.02; 4 studies, 765 infants, very low quality evidence). There was no reduction in bronchopulmonary dysplasia (BPD) or mortality.In trials comparing CPAP with assisted ventilation with or without surfactant, CPAP resulted in a small but clinically significant reduction in the incidence of BPD at 36 weeks, (typical RR 0.89, 95% CI 0.79 to 0.99; typical RD -0.04, 95% CI -0.08 to 0.00; 3 studies, 772 infants, moderate-quality evidence); and death or BPD (typical RR 0.89, 95% CI 0.81 to 0.97; typical RD -0.05, 95% CI -0.09 to 0.01; 3 studies, 1042 infants, moderate-quality evidence). There was also a clinically important reduction in the need for mechanical ventilation (typical RR 0.50, 95% CI 0.42 to 0.59; typical RD -0.49, 95% CI -0.59 to -0.39; 2 studies, 760 infants, moderate-quality evidence); and the use of surfactant in the CPAP group (typical RR 0.54, 95% CI 0.40 to 0.73; typical RD -0.41, 95% CI -0.54 to -0.28; 3 studies, 1744 infants, moderate-quality evidence). There is insufficient evidence to evaluate prophylactic CPAP compared to oxygen therapy and other supportive care. However when compared to mechanical ventilation prophylactic nasal CPAP in very preterm infants reduces the need for mechanical ventilation and surfactant and also reduces the incidence of BPD and death or BPD.

Oxygen Saturation Targets for Extremely Preterm Infants after the NeOProM Trials

Five randomized controlled trials comparing lower (85-89%) versus higher (91-95%) pulse oximeter saturation (SpO₂) targets for extremely preterm infants have now been reported from the United States of America, Canada, the United Kingdom, Australia and New Zealand. These trials included more than 4,800 infants, and they provide robust evidence to permit comparison of these target ranges and consider the next steps for clinicians and researchers. The lower SpO₂ range was associated with a significant increase in the risk of death. There was no significant difference between the two target ranges in the rate of disability at 18-24 months, including blindness. A significant difference between groups in the risk of the composite primary outcome of death or disability in favour of the higher SpO₂ range was mainly attributable to the difference between groups in the risk of death. The lower target range did not reduce bronchopulmonary dysplasia or severe visual impairment, but it did increase the risk of necrotizing enterocolitis requiring surgery or causing death. The trials provide no reason to prefer SpO₂ targets below 90% and indicate the importance of more trials to see if a further survival advantage can be identified. The safety of targets above 95% has not been evaluated. The five trials were designed to be similar to facilitate an individual patient data meta-analysis, and this Neonatal Oxygen Prospective Meta-Analysis (NeOProM) may provide further insights.

The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants < 29 weeks’ gestation

BackgroundBronchopulmonary dysplasia (BPD) is a major cause of mortality and long-term respiratory and neurological morbidity in very preterm infants. While survival rates of very preterm infants have increased over the past two decades there has been no decrease in the rate of BPD in surviving infants. Evidence from animal and human studies has suggested potential benefits of docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, in the prevention of chronic lung disease. This randomised controlled trial aims to determine the effectiveness of supplementary DHA in reducing the rate of BPD in infants less than 29 weeks’ gestation.Methods/designThis is a multicentre, parallel group, randomised, blinded and controlled trial. Infants born less than 29 weeks’ gestation, within 3 days of first enteral feed and with parent informed consent are eligible to participate. Infants will be randomised to receive an enteral emulsion containing DHA or a control emulsion without DHA. The DHA emulsion will provide 60 mg/kg/day of DHA. The study emulsions will continue to 36 weeks’ postmenstrual age (PMA). The primary outcome is BPD as assessed by the requirement for supplemental oxygen and/or assisted ventilation at 36 weeks’ PMA. Secondary outcomes include the composite of death or BPD; duration of respiratory support and hospitalisation, major neonatal morbidities. The target sample size is 1244 infants (622 per group), which will provide 90 % power to detect a clinically meaningful absolute reduction of 10 % in the incidence of BPD between the DHA and control emulsion (two tailed α =0.05).DiscussionDHA supplementation has the potential to reduce respiratory morbidity in very preterm infants. This multicentre trial will provide evidence on whether an enteral DHA supplement reduces BPD in very preterm infants.Trial registrationAustralia and New Zealand Clinical Trial Registry: ACTRN12612000503820. Registered 09 May 2012.

Late Surfactant Administration in Very Preterm Neonates With Prolonged Respiratory Distress and Pulmonary Outcome at 1 Year of Age: A Randomized Clinical Trial.

Although immature neonate survival has improved, there is an increased risk of developing bronchopulmonary dysplasia, leading to significant respiratory morbidity. Measures to reduce bronchopulmonary dysplasia are not always effective or have important adverse effects. To evaluate the effect of late surfactant administration in infants with prolonged respiratory distress on ventilation duration, respiratory outcome at 36 weeks' postmenstrual age, and at 1 year postnatal age. Double-blind randomized clinical trial at 13 level III French perinatal centers. Participants included 118 neonates at less than 33 weeks' gestation who still required mechanical ventilation on day 14 (SD, 2) with fraction of inspired oxygen of more than 0.30. All survivors were eligible for follow-up. We performed an intent-to-treat analysis. Infants received 200 mg/kg of poractant alfa (surfactant) or air after randomization. At 1 year, after parents' interview, infants underwent physical examination by pediatricians not aware of the randomization. The duration of ventilation was the primary outcome. The combined outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age and respiratory morbidity at 1 year of age were the main secondary outcome measures. Of the 118 infants who participated in the study, 65 (55%) were male. Fraction of inspired oxygen requirements dropped after surfactant, but not air, for up to 24 hours after instillation (0.36 [0.11] vs 0.43 [0.18]; P < .005). Severe bronchopulmonary dysplasia/death rates at 36 weeks' postmenstrual age were similar (27.1% vs 35.6%; P = .32). Less surfactant-treated infants needed rehospitalization for respiratory problems after discharge (28.3% vs 51.1%; P = .03); 39.5% vs 50% needed respiratory physical therapy (P = .35). No difference was observed for weight (7.8 [1.2] kg vs 7.6 [1.1] kg), height (69 [5] cm vs 69 [3] cm), and head circumference (44.4 [1.7] cm vs 44.2 [1.7] cm) measured at follow-up, nor for neurodevelopment outcome. Late surfactant administration did not alter the early course of bronchopulmonary dysplasia. However, surfactant-treated infants had reduced respiratory morbidity prior to 1 year of age. clinicaltrials.gov Identifier: NCT01039285.

Evaluation of a practice guideline for the management of respiratory distress syndrome in preterm infants: A quality improvement initiative

The use of mechanical ventilation to treat respiratory distress syndrome in preterm infants has been associated with the development of bronchopulmonary dysplasia. As part of a quality improvement initiative to reduce the incidence of bronchopulmonary dysplasia in preterm infants, a new practice guideline for the management of respiratory distress syndrome was developed and adopted into practice in a neonatal intensive care unit in February 2012. To evaluate the effects of implementing the new guideline in regard to the use of mechanical ventilation and surfactant, and the incidence of bronchopulmonary dypslasia. An historical cohort of very preterm infants (gestational age 26(0) to 32(6) weeks) born one year before guideline implementation was compared with a similar cohort of infants born one year following guideline implementation. Data were collected retrospectively from the local neonatal intensive care unit database. A total of 272 preterm infants were included in the study: 129 in the preguideline cohort and 143 in the postguideline cohort. Following the implementation of the guideline, the proportion of infants treated with ongoing mechanical ventilation was reduced from 49% to 26% (P<0.001) and there was a trend toward a reduction in bronchopulmonary dysplasia (27% versus 18%; P=0.07). There was no difference in the proportion of infants treated with surfactant (54% versus 50%). The implementation of the practice guideline helped to minimize the use of ongoing mechanical ventilation in preterm infants.

Respiratory support in preterm infants with respiratory distress syndrome

Neonatal respiratory distress syndrome (RDS) is most common in premature infants, the smaller the gestational age, the higher the incidence. Continuous positive airway pressure (CPAP) started in the delivery room has been shown in multicentre randomized controlled trials to reduce the need for mechanical ventilation (MV) and surfactant. The European Consensus Guidelines on the Management of Neonatal Respiratory Distress Syndrome in Preterm Infants–2013 Update recommended that CPAP should be started from birth in all babies at risk of RDS and a starting pressure of at least 6 cmH2O (1 cmH2O=0.098 kPa) should be applied. CPAP with early rescue surfactant should be considered the optimal management for babies with RDS. Using CPAP immediately after birth with subsequent selective surfactant administration may be considered as an alternative to routine intubation with prophylactic or early surfactant administration in preterm infants. If endotracheal intubation is needed, early administration of surfactant is preferable. Nasal intermittent positive pressure ventilation may reduce the risk of extubation failure in babies failing on CPAP. Several strategies have been employed specifically to improve the success of noninvasive ventilation and shorten the duration of MV. Caffeine should be used to facilitate weaning from MV and to reduce bronchopulmonary dysplasia. A short tapering course of low- or very low-dose dexamethasone should be considered to facilitate extubation in babies who remain on MV after 1~2 weeks. Very early steroid treatment and treatment with high doses cannot be recommended. Key words: Neonatal respiratory distress syndrome; Continuous positive airway pressure; Premature infant

Effects of caffeine on renal and pulmonary function in preterm newborn lambs

Caffeine administration is associated with a reduction in bronchopulmonary dysplasia, assisted ventilation, patent ductus arteriosus (DA) and cerebral palsy in preterm infants, but the mechanisms are unknown. Our aim was to determine the effects of acute caffeine administration on renal and pulmonary function in preterm lambs. Lambs were delivered by caesarean section at ~126 days of gestation and ventilated with a tidal volume of 5 ml/kg, 60 breaths/min and 5 cmH(2)O positive end-expiratory pressure. After 30 minutes, lambs received 40 mg/kg caffeine i.v (n=7) or saline (controls; n=6) over 30 minutes and were ventilated for 2 hours. Arterial caffeine concentrations reached 35.9 ± 7.8 mg/l. Urine output was significantly higher after caffeine treatment than in controls (5.86 ± 1.95 vs 0.76 ± 0.94 ml/kg, area under curve p=0.041). Mean heart rate was significantly higher after caffeine treatment than in controls (211 ± 8 vs 169 ± 15 beats per minute, p<0.05) and remained higher for the experimental period. Caffeine did not affect pulmonary artery or DA blood flows or other renal, respiratory or cardiovascular parameters examined. Neonatal caffeine administration increased heart rate and urine output but had little effect on pulmonary function in ventilated preterm lambs.

Recommendations for neonatal surfactant therapy – addendum

Francais en page 139 How should surfactant be used in preterm infants initially managed with nasal continuous positive airway pressure (CPAP)? Many centres providing neonatal intensive care have increased their use of CPAP as a first-line method of respiratory support for preterm infants. This practice shift started after several descriptive, as well as before/after cohort studies, suggested that avoiding intubation and mechanical ventilation may help to reduce bronchopulmonary dysplasia (BPD) (1,2). There has been concern, however, that adopting this practice might deprive some infants of the proven benefits of expeditiously administered exogenous surfactant, especially those born at the youngest gestational ages who have traditionally been provided with prophylactic treatment. Recent randomized trials comparing elective intubation and prophylactic surfactant to initial management with nasal CPAP and selective surfactant therapy, suggest that the latter approach is safe and reduces the number of infants intubated and given surfactant (3–7). In the largest of these studies, even the infants at highest risk for respiratory distress syndrome (RDS) and its associated complications (ie, those born at 24 to 25 weeks’ gestational age), appeared to fare as well, if not better, when initially managed with nasal CPAP (4). These studies suggest that application of nasal CPAP shortly after birth to very preterm infants is an acceptable alternative strategy to elective intubation and prophylactic surfactant treatment. However, the criteria for surfactant treatment of infants initially supported with nasal CPAP have been inconsistent. A short period of observation on CPAP is necessary to enable clinicians to identify infants with surfactant sufficiency or mild RDS, who may be effectively managed without endotracheal intubation and surfactant treatment. Yet, a delay in treating a newborn with significant surfactant deficiency could result in a suboptimal response and/or an increased risk of complications. Criteria for selective treatment of infants initially managed with CPAP are needed. Verder et al (8), who were early advocates of the INSURE (INtubate, SURfactant, Extubate) approach for infants with RDS, found that preterm infants with RDS initially managed with nasal CPAP had better outcomes when treated with surfactant when reaching a fraction of inspired oxygen (FiO2) of approximately 0.37 to 0.55 versus 0.57 to 0.77. A systematic review examining timing of surfactant administration to preterm infants with RDS initially managed with CPAP also found that earlier treatment was more effective (9). From this review, when a low treatment threshold (FiO2 ≤0.45) for intubation and surfactant administration in the early treatment group was used, protection from air leak and BPD was enhanced. Examining several recent, large randomized trials yields additional useful information that can be used to guide practice (3–7). The two studies that did not allow treatment with surfactant of infants initially managed with nasal CPAP, until the requirement for supplemental oxygen exceeded an FiO2 of 0.60, showed increased rates of pneumothorax compared with the group intubated and given surfactant shortly after birth (3,7). The studies in which selective treatment was provided at lower supplemental oxygen thresholds saw no increase in air leak (4–6). These observations are consistent with a previous systematic review that found that babies with or at high risk for RDS had better outcomes if surfactant was given earlier rather than later in the clinical course (10). However, the prophylactic administration of surfactant with rapid extubation to nasal CPAP for infants at risk of RDS does not appear to convey an additional advantage compared with selective treatment after a short period of nasal CPAP, as long as the threshold for treatment is not too high (5,6).

Multiple Utilization of Surfactant in Neonatology

Surfactant replacement therapy for the treatment of respiratory distress syndrome (RDS) and other respiratory diseases in newborns has become one of the most active research areas in neonatology. This research has resulted in improved survival for preterm babies since becoming a routine treatment in the 1990s. The main characteristics of pulmonary surfactant, including its composition, pool, metabolism, inactivation and immediate effects after administration, are well-established. However, some doubts still remain about the use of exogenous surfactants and must be addressed. The new generation of synthetic surfactants has raised questions regarding the choice of surfactant type, the ideal timing for treatment (prophylactic vs early rescue strategy), the adequate dose and number of doses, new administration routes and the effects of the association between the use of antenatal steroids and the surfactant replacement therapy. There is also controversy surrounding the choice between early surfactant administration and the use of a nasal CPAP as an initial strategy to treat RDS and to reduce bronchopulmonary dysplasia (BPD). This article reviews basic and clinical aspects of surfactant replacement therapy for RDS and other respiratory diseases in newborns. Keywords: Surfactant, respiratory distress syndrome, antenatal steroids, mechanical ventilation, newborn, respiratory insufficiency, bronchopulmonary dysplasia, Alveolar edema, atelectasis/hyperdistention, alveolar expansion

Shielding Parenteral Nutrition From Light: Does the Available Evidence Support a Randomized, Controlled Trial?

Exposure of total parenteral nutrition to ambient light induces the generation of peroxides, creating oxidant stress, which potentially compounds complications of prematurity. Photograph protection of total parenteral nutrition reduces the peroxide load and has been shown to be associated with nutritional and biochemical benefits in animals and humans. It is unclear whether this reduction in peroxides from total parenteral nutrition leads to a reduction in the complications of prematurity, such as bronchopulmonary dysplasia. Our hypothesis was that shielding total parenteral nutrition from ambient light is linked to clinical benefits. The purpose of this work was to determine whether photograph protection of total parenteral nutrition (light protected), as compared with no photoprotection (light exposed), reduces the occurrence of bronchopulmonary dysplasia or death in preterm infants. The Canadian Neonatal Network provided data for infants born in 2006 at <28 weeks' gestation admitted to level 3 NICUs in Canada. A retrospective analysis was performed comparing bronchopulmonary dysplasia and death in infants who received light-exposed or light-protected parenteral nutrition. Data were analyzed by using logistic regression models. RESULTS. Thirteen NICUs offered partial light-protected (total parenteral nutrition bag only, intravenous tubing exposed) and 13 offered light-exposed parenteral nutrition; not a single NICU offered complete light-protected parenteral nutrition (total parenteral nutrition bag plus intravenous tubing). The incidence of bronchopulmonary dysplasia or death was 66% with light-protected (n = 428) vs 59% with light-exposed (n = 438) parenteral nutrition. Partial photograph protection of total parenteral nutrition was not associated with a reduction in bronchopulmonary dysplasia or death as compared with no photograph protection; this relationship is confounded by covariates with strong associations with bronchopulmonary dysplasia. Partial photograph protection of total parenteral nutrition solutions confers no clinical benefit, while consuming valuable resources. A randomized, controlled trial is justified to determine whether there is a true "cause-and-effect" relationship between complete photoprotection of total parenteral nutrition and bronchopulmonary dysplasia or death.