Nasal High-Flow Therapy for Newborn Infants in Special Care Nurseries.

BACKGROUND: Nasal high-flow therapy is an alternative to nasal continuous positive airway pressure (CPAP) as a means of respiratory support for newborn infants. The efficacy of high-flow therapy in nontertiary special care nurseries is unknown. METHODS: We performed a multicenter, randomized, noninferiority trial involving newborn infants (<24 hours of age; gestational age, ≥31 weeks) in special care nurseries in Australia. Newborn infants with respiratory distress and a birth weight of at least 1200 g were assigned to treatment with either high-flow therapy or CPAP. The primary outcome was treatment failure within 72 hours after randomization. Infants in whom high-flow therapy failed could receive CPAP. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome, with a noninferiority margin of 10 percentage points. RESULTS: A total of 754 infants (mean gestational age, 36.9 weeks, and mean birth weight, 2909 g) were included in the primary intention-to-treat analysis. Treatment failure occurred in 78 of 381 infants (20.5%) in the high-flow group and in 38 of 373 infants (10.2%) in the CPAP group (risk difference, 10.3 percentage points; 95% confidence interval [CI], 5.2 to 15.4). In a secondary per-protocol analysis, treatment failure occurred in 49 of 339 infants (14.5%) in the high-flow group and in 27 of 338 infants (8.0%) in the CPAP group (risk difference, 6.5 percentage points; 95% CI, 1.7 to 11.2). The incidences of mechanical ventilation, transfer to a tertiary neonatal intensive care unit, and adverse events did not differ significantly between the groups. CONCLUSIONS: Nasal high-flow therapy was not shown to be noninferior to CPAP and resulted in a significantly higher incidence of treatment failure than CPAP when used in nontertiary special care nurseries as early respiratory support for newborn infants with respiratory distress. (Funded by the Australian National Health and Medical Research Council and Monash University; HUNTER Australian and New Zealand Clinical Trials Registry number, ACTRN12614001203640.).

Predicting Nasal High-Flow Treatment Success in Newborn Infants with Respiratory Distress Cared for in Nontertiary Hospitals.

OBJECTIVE: To evaluate demographic and clinical variables as predictors of nasal high-flow treatment success in newborn infants with respiratory distress cared for in Australian nontertiary special care nurseries. STUDY DESIGN: A secondary analysis of the HUNTER trial, a multicenter, randomized controlled trial evaluating nasal high-flow as primary respiratory support for newborn infants with respiratory distress who were born ≥31 weeks of gestation and with birth weight ≥1200 g, and cared for in Australian nontertiary special care nurseries. Treatment success within 72 hours after randomization to nasal high-flow was determined using objective criteria. Univariable screening and multivariable analysis was used to determine predictors of nasal high-flow treatment success. RESULTS: Infants (n = 363) randomized to nasal high-flow in HUNTER were included in the analysis; the mean gestational age was 36.9 ± 2.7 weeks and birth weight 2928 ± 782 g. Of these infants, 290 (80%) experienced nasal high-flow treatment success. On multivariable analysis, nasal high-flow treatment success was predicted by higher gestational age and lower fraction of inspired oxygen immediately before randomization, but not strongly. The final model was found to have an area under the curve of 0.65, which after adjustment for optimism was found to be 0.63 (95% CI, 0.57-0.70). CONCLUSIONS: Gestational age and supplemental oxygen requirement may be used to guide decisions regarding the most appropriate initial respiratory support for newborn infants in nontertiary special care nurseries. Further prospective research is required to better identify which infants are most likely to be successfully treated with nasal high-flow. TRIAL REGISTRATION: ACTRN12614001203640.

Trends in the use of non-invasive respiratory support for term infants in tertiary neonatal units in Australia and New Zealand.

OBJECTIVE: To determine whether the use of non-invasive respiratory support, such as continuous positive airway pressure and nasal high flow, to treat term infants in Australian and New Zealand tertiary neonatal intensive care units (NICUs) has changed over time, and if so, whether there are parallel changes in short-term respiratory morbidities. DESIGN: Retrospective database review of patient-level data from the Australian and New Zealand Neonatal Network (ANZNN) from 2010 to 2018. Denominator data on the number of term inborn livebirths in each facility was only available as annual totals. PATIENTS AND SETTING: Term, inborn infants cared for in NICUs within the ANZNN. MAIN OUTCOME MEASURES: The primary outcome was the annual change in hospital-specific rates of non-invasive respiratory support per 1000 inborn livebirths, expressed as a percentage change. Secondary outcomes were the change in rates of mechanical ventilation, pneumothorax requiring drainage, exogenous surfactant treatment and death before hospital discharge. RESULTS: A total of 14 656 term infants from 21 NICUs were included from 2010 to 2018, of whom 12 719 received non-invasive respiratory support. Non-invasive respiratory support use increased on average by 8.7% per year (95% CI: 7.9% to 9.4% per year); the number of term infants receiving non-invasive respiratory support almost doubled from 980 in 2010 (10.8/1000 livebirths) to 1913 in 2018 (20.8/1000). There was no change over time in rate of mechanical ventilation or death. The rate of pneumothorax requiring drainage increased over time, as did surfactant treatment. CONCLUSIONS: Non-invasive respiratory support use to treat term infants cared for in NICUs within the ANZNN is increasing over time. Clinicians should be diligent in selecting infants most likely to benefit from treatment with non-invasive respiratory support in this relatively low-risk population of term newborn infants. Analysis of patient-level data by individual NICUs is recommended to control for potential confounding due to changes in population over time.

Cost-Effectiveness of Nasal High Flow Versus CPAP for Newborn Infants in Special-Care Nurseries.

BACKGROUND: Treating respiratory distress in newborns is expensive. We compared the cost-effectiveness of 2 common noninvasive therapies, nasal continuous positive airway pressure (CPAP) and nasal high-flow (nHF), for newborn infants cared for in nontertiary special care nurseries. METHODS: The economic evaluation was planned alongside a randomized control trial conducted in 9 Australian special care nurseries. Costs were considered from a hospital perspective until infants were 12 months of age. A total of 754 infants with respiratory distress, born ≥31 weeks' gestation and with birth weight ≥1200 g, <24 hours old, requiring noninvasive respiratory support and/or supplemental oxygen for >1 hour were recruited during 2015-2017. Inpatient costing records were obtained for 753 infants, of whom 676 were included in the per-protocol analysis. Two scenarios were considered: (1) CPAP versus nHF, with infants in the nHF group having "rescue" CPAP backup available (trial scenario); and (2) CPAP versus nHF, as sole primary support (hypothetical scenario). Effectiveness outcomes were rate of endotracheal intubation and transfer to a tertiary-level NICU. RESULTS: As sole primary support, CPAP is more effective and on average cheaper, and thus is superior. However, nHF with back-up CPAP produced equivalent cost and effectiveness results, and there is no reason to make a decision between the 2 treatments on the basis of the cost or effectiveness outcomes. CONCLUSIONS: Nontertiary special care nurseries choosing to use only 1 of the modes should choose CPAP. In units with both modes available, using nHF as first-line therapy may be acceptable if there is back-up CPAP.

A multicentre, randomised controlled, non-inferiority trial, comparing nasal high flow with nasal continuous positive airway pressure as primary support for newborn infants with early respiratory distress born in Australian non-tertiary special care nurseries (the HUNTER trial): study protocol.

INTRODUCTION: Nasal high-flow (nHF) therapy is a popular mode of respiratory support for newborn infants. Evidence for nHF use is predominantly from neonatal intensive care units (NICUs). There are no randomised trials of nHF use in non-tertiary special care nurseries (SCNs). We hypothesise that nHF is non-inferior to nasal continuous positive airway pressure (CPAP) as primary support for newborn infants with respiratory distress, in the population cared for in non-tertiary SCNs. METHODS AND ANALYSIS: The HUNTER trial is an unblinded Australian multicentre, randomised, non-inferiority trial. Infants are eligible if born at a gestational age ≥31 weeks with birth weight ≥1200 g and admitted to a participating non-tertiary SCN, are <24 hours old at randomisation and require non-invasive respiratory support or supplemental oxygen for >1 hour. Infants are randomised to treatment with either nHF or CPAP. The primary outcome is treatment failure within 72 hours of randomisation, as determined by objective oxygenation, apnoea or blood gas criteria or by a clinical decision that urgent intubation and mechanical ventilation, or transfer to a tertiary NICU, is required. Secondary outcomes include incidence of pneumothorax requiring drainage, duration of respiratory support, supplemental oxygen and hospitalisation, costs associated with hospital care, cost-effectiveness, parental stress and satisfaction and nursing workload. ETHICS AND DISSEMINATION: Multisite ethical approval for the study has been granted by The Royal Children's Hospital, Melbourne, Australia (Trial Reference No. 34222), and by each participating site. The trial is currently recruiting in eight centres in Victoria and New South Wales, Australia, with one previous site no longer recruiting. The trial results will be published in a peer-reviewed journal and will be presented at national and international conferences. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12614001203640; pre-results.

Continuous positive airway pressure therapy for infants with respiratory distress in non tertiary care centers: a randomized, controlled trial.

OBJECTIVE: Our objective was to determine whether continuous positive airway pressure therapy would safely reduce the need for up-transfer of infants with respiratory distress from nontertiary centers. METHODS: We randomly assigned 300 infants at >30 weeks of gestation with respiratory distress to receive either Hudson prong bubble continuous positive airway pressure therapy or headbox oxygen treatment (standard care). The primary end point was "up-transfer or treatment failure." Secondary end points included death, length of nursery stay, time receiving oxygen therapy, cost of care, and other measures of morbidity. RESULTS: Of 151 infants who received continuous positive airway pressure therapy, 35 either were up-transferred or experienced treatment failure, as did 60 of the 149 infants given headbox oxygen treatment. There was no difference in the length of stay or the duration of oxygen treatment. For every 6 infants treated with continuous positive airway pressure therapy, there was an estimated cost saving of $10,000. Pneumothorax was identified for 14 infants in the continuous positive airway pressure group and 5 in the headbox group. There was no difference in any other measure of morbidity or death. CONCLUSIONS: Hudson prong bubble continuous positive airway pressure therapy reduces the need for up-transfer of infants with respiratory distress in nontertiary centers. There is a clinically relevant but not statistically significant increase in the risk of pneumothorax. There are significant benefits associated with continuous positive airway pressure use in larger nontertiary centers.

CPAP use in babies with respiratory distress in Australian special care nurseries.

AIM: This study sought to identify the number of special care nurseries (SCNs) already using CPAP in 2004, and the number considering its use in the following 2 years, and to describe the characteristics of those hospitals. METHODS: All Australian hospitals with >200 registered deliveries in the year 2002, a SCN and at least one paediatrician were eligible (n = 157). Separate questionnaires were sent to the nurse unit manager (NUM) and the paediatrician responsible for the SCN in late 2004. RESULTS: Of 157 eligible SCNs, 143 (91%) responded. CPAP was being used in 24/143 (17%). Of those nurseries not already using CPAP a further 45/119 (38%) were considering doing so in 2005/2006. State/Territory, greater availability of junior medical staff, use of a helicopter/airplane for transferring infants to tertiary centres and number of paediatricians were significantly associated with use of CPAP (all P < 0.05). Consideration of use was significantly associated with greater availability of junior medical staff, larger numbers of births and time to nearest (tertiary) centre (all P < 0.05). CONCLUSION: There is a strong predisposition for the use of CPAP in SCNs despite the lack of evidence for its benefits or risks there. Studies are urgently required on the clinical benefits and risks of CPAP in a non-tertiary centre before the widespread introduction of CPAP takes place.

Practice variation in initial management and transfer thresholds for infants with respiratory distress in Australian hospitals. Who should write the guidelines?

AIM: In Australian hospitals: (i) to identify current practices in the initial oxygen management of infants with respiratory distress; (ii) to identify factors important in deciding to transfer an infant; and (iii) to identify thresholds for transfer. METHODS: All Australian hospitals with: >200 registered deliveries, a special care unit (SCU) or neonatal intensive care unit (NICU), and at least one paediatrician were surveyed in 2004 (n=176). The questionnaire sought information on the initial oxygen management and factors important in deciding to transfer. Three scenarios were also used to identify thresholds for pH, carbon dioxide and oxygen levels at which transfer should occur. Responses from SCU were compared with those from NICU. RESULTS: 15/19 (79%) NICUs and 118/157 (75%) SCUs responded. Initial oxygen management varies widely among SCUs and NICUs. NICUs set significantly lower saturation (SaO(2)) targets in two of the three scenarios. NICUs are statistically significantly more likely to regard 'Medical Staff Experience' and 'Time to Nearest NICU' as important compared with SCUs (P<0.05). NICUs would 'Probably' and 'Definitely Transfer' infants at significantly lower oxygen levels in all three cases (P<0.05). SCUs are significantly less likely to transfer babies with pH of <7.25 compared with NICUs. There was no difference between the centres for CO(2) level. CONCLUSION: The wide variation that exists between nurseries in the initial management of infants with respiratory distress and in the thresholds for transfer strongly suggests the need for the development of practice guidelines.