Purpose
Nasal continuous positive airway pressure (nCPAP) is currently the gold standard for respiratory support for moderate to severe acute viral bronchiolitis (AVB). Although oxygen delivery via ...high flow nasal cannula (HFNC) is increasingly used, evidence of its efficacy and safety is lacking in infants.
Methods
A randomized controlled trial was performed in five pediatric intensive care units (PICUs) to compare 7 cmH
2
O nCPAP with 2 L/kg/min oxygen therapy administered with HFNC in infants up to 6 months old with moderate to severe AVB. The primary endpoint was the percentage of failure within 24 h of randomization using prespecified criteria. To satisfy noninferiority, the failure rate of HFNC had to lie within 15% of the failure rate of nCPAP. Secondary outcomes included success rate after crossover, intubation rate, length of stay, and serious adverse events.
Results
From November 2014 to March 2015, 142 infants were included and equally distributed into groups. The risk difference of −19% (95% CI −35 to −3%) did not allow the conclusion of HFNC noninferiority (
p
= 0.707). Superiority analysis suggested a relative risk of success 1.63 (95% CI 1.02–2.63) higher with nCPAP. The success rate with the alternative respiratory support, intubation rate, durations of noninvasive and invasive ventilation, skin lesions, and length of PICU stay were comparable between groups. No patient had air leak syndrome or died.
Conclusion
In young infants with moderate to severe AVB, initial management with HFNC did not have a failure rate similar to that of nCPAP. This clinical trial was recorded in the National Library of Medicine registry (NCT 02457013).
Background We report the occurrence of a severe pulmonary hypertension (PH) in a neonate affected by a left congenital diaphragmatic hernia (CDH). PH in this patient was associated with an abnormal ...origin of the right pulmonary artery from the right brachiocephalic artery. This malformation, sometimes named hemitruncus arteriosus, has to the best of our knowledge never been reported in association with a CDH. Case presentation A male newborn was hospitalized from birth in the neonatal intensive care unit after prenatal diagnosis of a left CDH. Ultrasound examination at 34 weeks of gestational age evaluated the observed-to-expected lung-to-head ratio at 49%. Birth occurred at 38.sup.+ 5 weeks of gestational age. Soon after admission, severe hypoxemia, i.e., preductal pulse oximetry oxygen saturation (SpO.sub.2) < 80%, prompted therapeutic escalation including the use of high frequency oscillatory ventilation with fraction of inspired oxygen (FiO.sub.2) 100% and inhaled nitric oxide (iNO). Echocardiography assessment revealed signs of severe PH and normal right ventricle function. Despite administration of epoprostenolol, milrinone, norepinephrine, and fluid loadings with albumin and 0.9% saline, hypoxemia remained severe, preductal SpO.sub.2 inconsistently greater than or equal to 80-85% and post ductal SpO.sub.2 lower on average by 15 points. This clinical status remained unchanged during the first 7 days of life. The infant's clinical instability was incompatible with surgical intervention, while chest X-ray showed a relatively preserved lung volume, especially on the right side. This prompted an additional echocardiography, aimed at searching an explanation of this unusual evolution and found an abnormal origin of the right pulmonary artery, which was confirmed on computed tomography angiography subsequently. A change in the medical strategy was decided, with the suspension of pulmonary vasodilator treatments, the administration of diuretics, and the decrease in norepinephrine dose to decrease the systemic-to-pulmonary shunt. Progressive improvement in the infant respiratory and hemodynamic status enabled to perform CDH surgical repair 2 weeks after birth. Conclusions This case recalls the interest of systematic analysis of all potential causes of PH in a neonate with CDH, a condition frequently associated with various congenital malformations. Keywords: Congenital diaphragmatic hernia, Congenital heart disease, Pulmonary hypertension, Poiseuille's law, Pediatrics
Objective To determine whether extrauterine growth is associated with neurologic outcomes and if this association varies by prenatal growth profile. Study design For 1493 preterms from the EPIPAGE ...(Étude Épidémiologique sur les Petits Âges Gestationnels Epidemiological Study on Small Gestational Ages) cohort, appropriate for gestational-age (AGA) was defined by birth weight >−2 SD and small for gestational-age (SGA) by birth weight ≤−2 SD. Extra-uterine growth was defined by weight gain or loss between birth and 6 months by z-score change. Growth following–the-curve (FTC) was defined as weight change −1 to +1 SD, catch-down-growth (CD) as weight loss ≥1 SD, and catch-up-growth (CU) as weight gain ≥1 SD. At 5 years, a complete medical examination (n = 1305) and cognitive evaluation with the Kauffman Assessment Battery for Children (n = 1130) were performed. Behavioral difficulties at 5 years and school performance at 8 years were assessed (n = 1095). Results Overall, 42.5% of preterms were AGA-FTC, 20.2% AGA-CD, 17.1% AGA-CU, 5.6% SGA-FTC, and 14.5% SGA-CU. Outcomes did not differ between CU and FTC preterm AGA infants. Risk of cerebral palsy was greater for AGA-CD compared with AGA-FTC (aOR 2.26 95% CI 1.37-3.72). As compared with children with SGA-CU, SGA-FTC children showed no significant increased risk of cognitive deficiency (aOR 1.410.94-2.12) or school difficulties (aOR 1.60 0.84-3.03). Compared with AGA-FTC, SGA showed increased risk of cognitive deficiency (SGA-FTC aOR 2.19 1.25-3.84) and inattention-hyperactivity (SGA-CU aOR 1.65 1.05-2.60). Conclusion Deficient postnatal growth was associated with poor neurologic outcome for AGA and SGA preterm infants. CU growth does not add additional benefits. Regardless of type of postnatal growth, SGA infants showed behavioral problems and cognitive deficiency.
IMPORTANCE: There is currently no consensus for the screening and treatment of patent ductus arteriosus (PDA) in extremely preterm infants. Less pharmacological closure and more supportive management ...have been observed without evidence to support these changes. OBJECTIVE: To evaluate the association between early screening echocardiography for PDA and in-hospital mortality. DESIGN, SETTING, AND PARTICIPANTS: Comparison of screened and not screened preterm infants enrolled in the EPIPAGE 2 national prospective population-based cohort study that included all preterm infants born at less than 29 weeks of gestation and hospitalized in 68 neonatal intensive care units in France from April through December 2011. Two main analyses were performed to adjust for potential selection bias, one using propensity score matching and one using neonatal unit preference for early screening echocardiography as an instrumental variable. EXPOSURES: Early screening echocardiography before day 3 of life. MAIN OUTCOMES AND MEASURES: The primary outcome was death between day 3 and discharge. The secondary outcomes were major neonatal morbidities (pulmonary hemorrhage, severe bronchopulmonary dysplasia, severe cerebral lesions, and necrotizing enterocolitis). RESULTS: Among the 1513 preterm infants with data available to determine exposure, 847 were screened for PDA and 666 were not; 605 infants from each group could be paired. Exposed infants were treated for PDA more frequently during their hospitalization than nonexposed infants (55.1% vs 43.1%; odds ratio OR, 1.62 95% CI, 1.31 to 2.00; absolute risk reduction ARR in events per 100 infants, −12.0 95% CI, −17.3 to −6.7). Exposed infants had a lower hospital death rate (14.2% vs 18.5% ; OR, 0.73 95% CI, 0.54 to 0.98; ARR, 4.3 95% CI, 0.3 to 8.3) and a lower rate of pulmonary hemorrhage (5.6% vs 8.9%; OR, 0.60 95% CI, 0.38 to 0.95; ARR, 3.3 95% CI, 0.4 to 6.3). No differences in rates of necrotizing enterocolitis, severe bronchopulmonary dysplasia, or severe cerebral lesions were observed. In the overall cohort, instrumental variable analysis yielded an adjusted OR for in-hospital mortality of 0.62 95% CI, 0.37 to 1.04. CONCLUSIONS AND RELEVANCE: In this national population-based cohort of extremely preterm infants, screening echocardiography before day 3 of life was associated with lower in-hospital mortality and likelihood of pulmonary hemorrhage but not with differences in necrotizing enterocolitis, severe bronchopulmonary dysplasia, or severe cerebral lesions. However, results of the instrumental variable analysis leave some ambiguity in the interpretation, and longer-term evaluation is needed to provide clarity.
Less invasive surfactant administration (LISA) has become increasingly popular in neonatal intensive care units (NICUs), but there are currently no guidelines for the premedication prior to this ...procedure. The aim of this observational study was to compare the efficacy and tolerance of intravenous administrations of ketamine and propofol before LISA in neonates born before 30 weeks of gestational age (GA). The primary outcome was requirement of intubation within 2 h of the procedure. One hundred and fourteen infants, with respective GA and birthweight of 27.6 (26.4, 28.7) weeks and 940 (805, 1140) g, were prospectively included from January 2016 to December 2019. Drug doses were 1 (0.5, 1) mg/kg for ketamine and 1 (1, 1.9) mg/kg for propofol, providing comparable comfort during LISA (
p
= 0.61). Rates of intubation within 2 h were 5/52 after ketamine, and 5/62 after propofol aOR 0.54 (0.11–2.68). No difference was observed for rates of intubation at 24 h and 72 h following LISA, mortality, or severe morbidity.
Conclusion
: Pending results from prospective trials, these findings suggest that ketamine or propofol can be used for premedication before LISA, as they show comparable efficacy and tolerance.
Trial registration
: This study was recorded on the National Library of Medicine registry (https://
clinicaltrials.gov
/ Identifier: NCT03705468).
What is Known?
• Less invasive surfactant administration (LISA) is increasingly used in spontaneously breathing premature infants supported with continuous positive airway pressure, but few data are available to guide adequate premedication for this procedure.
What is New?
• This observational study of 114 neonates, all less than 30-week gestational age and requiring surfactant without endotracheal tube in the delivery room, suggested that ketamine or propofol can be used for premedication before LISA with comparable efficacy and tolerance.
Background
Bronchiolitis is the leading cause of hospitalisation among infants in high‐income countries. Acute viral bronchiolitis is associated with airway obstruction and turbulent gas flow. ...Heliox, a mixture of oxygen and the inert gas helium, may improve gas flow through high‐resistance airways and decrease the work of breathing. In this review, we selected trials that objectively assessed the effect of the addition of heliox to standard medical care for acute bronchiolitis.
Objectives
To assess heliox inhalation therapy in addition to standard medical care for acute bronchiolitis in infants with respiratory distress, as measured by clinical endpoints (in particular the rate of endotracheal intubation, the rate of emergency department discharge, the length of treatment for respiratory distress) and pulmonary function testing (mainly clinical respiratory scores).
Search methods
We searched CENTRAL (2015, Issue 2), MEDLINE (1966 to March week 3, 2015), EMBASE (1974 to March 2015), LILACS (1982 to March 2015) and the National Institutes of Health (NIH) website (May 2009).
Selection criteria
Randomised controlled trials (RCTs) and quasi‐RCTs of heliox in infants with acute bronchiolitis.
Data collection and analysis
Two review authors independently extracted data and assessed trial quality.
Main results
We included seven trials involving 447 infants younger than two years with respiratory distress secondary to viral bronchiolitis. All children were recruited from a paediatric intensive care unit (PICU; 378 infants), except in one trial (emergency department; 69 infants). All children were younger than two (under nine months in two trials and under three months in one trial). Positive tests for respiratory syncytial virus (RSV) were required for inclusion in five trials. The two other trials were carried out in the bronchiolitis seasons. Seven different protocols were used for inhalation therapy with heliox.
When heliox was used in the PICU, we observed no significant reduction in the rate of intubation: risk ratio (RR) 2.73 (95% confidence interval (CI) 0.96 to 7.75, four trials, 408 infants, low quality evidence). When heliox inhalation was used in the emergency department, we observed no increase in the rate of discharge: RR 0.51 (95% CI 0.17 to 1.55, one trial, 69 infants, moderate quality evidence).
There was no decrease in the length of treatment for respiratory distress: mean difference (MD) ‐0.19 days (95% CI ‐0.56 to 0.19, two trials, 320 infants, moderate quality evidence). However, in the subgroup of infants who were started on nasal continuous positive airway pressure (nCPAP) right from the start, because of severe respiratory distress, heliox therapy reduced the length of treatment: MD ‐0.76 days (95% CI ‐1.45 to ‐0.08, one trial, 21 infants, low quality evidence). No adverse events related to heliox inhalation were reported.
We found that infants treated with heliox inhalation had a significantly lower mean clinical respiratory score in the first hour after starting treatment when compared to those treated with air or oxygen inhalation: MD ‐1.04 (95% CI ‐1.60 to ‐0.48, four trials, 138 infants, moderate quality evidence). This outcome had statistical heterogeneity, which remained even after removing the study using a standard high‐concentration reservoir mask. Several factors may explain this heterogeneity, including first the limited number of patients in each trial, and the wide differences in the baseline severity of disease between studies, with the modified Wood Clinical Asthma Score (m‐WCAS) in infants treated with heliox ranging from less than two to more than seven.
Authors' conclusions
Current evidence suggests that the addition of heliox therapy may significantly reduce a clinical score evaluating respiratory distress in the first hour after starting treatment in infants with acute RSV bronchiolitis. We noticed this beneficial effect regardless of which heliox inhalation protocol was used. Nevertheless, there was no reduction in the rate of intubation, in the rate of emergency department discharge, or in the length of treatment for respiratory distress. Heliox could reduce the length of treatment in infants requiring CPAP for severe respiratory distress. Further studies with homogeneous logistics in their heliox application are needed. Inclusion criteria must include a clinical severity score that reflects severe respiratory distress to avoid inclusion of children with mild bronchiolitis who may not benefit from heliox inhalation. Such studies would provide the necessary information as to the appropriate place for heliox in the therapeutic schedule for severe bronchiolitis.
To determine whether neonatal infections are associated with a higher risk of adverse neurodevelopment at 5 years of age in a population-based cohort of very preterm children.
We included all live ...births between 22 and 32 weeks of gestation, from 9 regions in France, in 1997 (EPIPAGE study). Of the 2665 live births, 2277 were eligible for a follow-up evaluation at 5 years of age: 1769 had a medical examination and 1495 underwent cognitive assessment. Cerebral palsy and cognitive impairment were studied as a function of early-onset sepsis (EOS) and late-onset sepsis (LOS), after adjustment for potential confounding factors, in multivariate logistic regression models.
A total of 139 (5%) of the 2665 live births included in the study presented with EOS alone (without associated LOS), 752 (28%) had LOS alone (without associated EOS), and 64 (2%) displayed both EOS and LOS. At 5 years of age, the frequency of cerebral palsy was 9% (157 of 1769) and that of cognitive impairment was 12% (177 of 1495). The frequency of cerebral palsy was higher in infants with isolated EOS (odds ratio OR: 1.70 95% confidence interval (CI): 0.84-3.45) or isolated LOS (OR: 1.71 95% CI: 1.14-2.56) than in uninfected infants, and this risk was even higher in cases of combined EOS and LOS (OR: 2.33 95% CI: 1.02-5.33). There was no association between neonatal infection and cognitive impairment.
Neonatal infections in these very preterm infants were associated with a higher risk of cerebral palsy at the age of 5 years, particularly in infants presenting with both EOS and LOS.
An increased risk for bronchopulmonary dysplasia (BPD) exists when moderate-to-large patent ductus arteriosus shunts (hsPDA) persist beyond 14 days.
To examine the interaction between prolonged ...exposures to tracheal ventilation (≥10 days) and hsPDA on the incidence of BPD in infants <28 weeks gestation.
Predefined definitions of prolonged ventilation (≥10 days), hsPDA (≥14 days), and BPD (room air challenge test at 36 weeks) were used to analyze deidentified data from the multicenter TRIOCAPI RCT in a secondary analysis of the trial.
Among 307 infants who survived >14 days, 41 died before 36 weeks. Among survivors, 93/266 had BPD. The association between BPD and hsPDA depended on the length of intubation. In multivariable analyses, prolonged hsPDA shunts were associated with increased BPD (odds ratio (OR) (95% confidence interval (CI)) = 3.00 (1.58-5.71)) when infants required intubation for ≥10 days. In contrast, there was no significant association between hsPDA exposure and BPD when infants were intubated <10 days (OR (95% CI) = 1.49 (0.98-2.26)). A similar relationship between prolonged hsPDA and length of intubation was found for BPD/death (n = 307): infants intubated ≥10 days: OR (95% CI) = 2.41 (1.47-3.95)); infants intubated <10 days: OR (95% CI) = 1.37 (0.86-2.19)).
Moderate-to-large PDAs were associated with increased risks of BPD and BPD/death-but only when infants required intubation ≥10 days.
Infants with a moderate-to-large hsPDA that persist beyond 14 days are only at risk for developing BPD if they also receive prolonged tracheal ventilation for ≥10 days. Infants who receive less ventilatory support (intubation for <10 days) have the same incidence of BPD whether the ductus closes shortly after birth or whether it persists as a moderate-to-large shunt for several weeks. Early PDA closure may be unnecessary in infants who require short durations of intubation since the PDA does not seem to alter the incidence of BPD in infants who require intubation for <10 days.
High-flow nasal cannula (HFNC) is a relatively new device for respiratory support. In pediatrics, HFNC use continues to increase as the system is easily set up and is well tolerated by patients. The ...use of nasal cannula adapted to the infant’s nares size to deliver heated and humidified gas at high flow rates has been associated with improvements in washout of nasopharyngeal dead space, lung mucociliary clearance, and oxygen delivery compared with other oxygen delivery systems. HFNC may also create positive pharyngeal pressure to reduce the work of breathing, which positions the device midway between classical oxygen delivery systems, like the high-concentration face mask and continuous positive airway pressure (CPAP) generators. Currently, most of the studies in the pediatric literature suggest the benefits of HFNC therapy only for moderately severe acute viral bronchiolitis. But, the experience with this device in neonatology and adult intensive care may broaden the pediatric indications to include weaning from invasive ventilation and acute asthma. As for any form of respiratory support, HFNC initiation in patients requires close monitoring, whether it be for pre- or inter-hospital transport or in the emergency department or the pediatric intensive care unit.
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