Brett J. Manley

High-Flow Nasal Cannulae in Very Preterm Infants after Extubation

BACKGROUND The use of high-flow nasal cannulae is an increasingly popular alternative to nasal continuous positive airway pressure (CPAP) for noninvasive respiratory support of very preterm infants (gestational age, <32 weeks) after extubation. However, data on the efficacy or safety of such cannulae in this population are lacking. METHODS In this multicenter, randomized, noninferiority trial, we assigned 303 very preterm infants to receive treatment with either high-flow nasal cannulae (5 to 6 liters per minute) or nasal CPAP (7 cm of water) after extubation. The primary outcome was treatment failure within 7 days. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the margin of noninferiority was 20 percentage points. Infants in whom treatment with high-flow nasal cannulae failed could be treated with nasal CPAP; infants in whom nasal CPAP failed were reintubated. RESULTS The use of high-flow nasal cannulae was noninferior to the use of nasal CPAP, with treatment failure occurring in 52 of 152 infants (34.2%) in the nasal-cannulae group and in 39 of 151 infants (25.8%) in the CPAP group (risk difference, 8.4 percentage points; 95% confidence interval, -1.9 to 18.7). Almost half the infants in whom treatment with high-flow nasal cannulae failed were successfully treated with CPAP without reintubation. The incidence of nasal trauma was significantly lower in the nasal-cannulae group than in the CPAP group (P=0.01), but there were no significant differences in rates of serious adverse events or other complications. CONCLUSIONS Although the result for the primary outcome was close to the margin of noninferiority, the efficacy of high-flow nasal cannulae was similar to that of CPAP as respiratory support for very preterm infants after extubation. (Funded by the National Health and Medical Research Council; Australian New Zealand Clinical Trials Network number, ACTRN12610000166077.).

High-Flow Nasal Cannulae for Respiratory Support of Preterm Infants: A Review of the Evidence

Background: High-flow nasal cannulae (HFNC) are gaining in popularity as a form of non-invasive respiratory support for preterm infants in neonatal intensive care units around the world. They are proposed as an alternative to nasal continuous positive airway pressure (NCPAP) in a variety of clinical situations, including post-extubation support, primary therapy from birth and ‘weaning’ from NCPAP. Objectives: To present and discuss the available evidence for the use of HFNC in the preterm population. Methods: An internet-based literature search for relevant, original research articles (both randomised studies and not) on the use of HFNC in preterm infants was undertaken. Results: A total of 19 studies were included in the review. Distending pressure generated by HFNC in preterm infants increases with increasing flow rate and decreasing infant size and varies according to the amount of leak around the prongs. HFNC may be as effective as NCPAP at improving respiratory parameters such as tidal volume and work of breathing in preterm infants, but probably only at flow rates >2 litres/min. The efficacy and safety of HFNC in preterm infants remain to be determined. Conclusions: There is growing evidence of the feasibility of HFNC as an alternative to other forms of non-invasive ventilation in preterm infants. However, there remains uncertainty about the efficacy and safety of HFNC in this population. Until the results of larger randomised trials are known, widespread use of HFNC to treat preterm infants cannot be recommended.

High-flow nasal cannulae and nasal continuous positive airway pressure use in non-tertiary special care nurseries in Australia and New Zealand

Aim:  Non‐tertiary centres (NTCs) in Australia and New Zealand are increasingly providing non‐invasive respiratory support, including high‐flow nasal cannulae (HFNC) and nasal continuous positive airway pressure (nCPAP), to newborn infants. We aimed to determine the proportion of NTCs in these countries treating newborn infants with HFNC and nCPAP, and how these therapies are used.

Nasal high-flow therapy for primary respiratory support in preterm infants

BACKGROUND Treatment with nasal high-flow therapy has efficacy similar to that of nasal continuous positive airway pressure (CPAP) when used as postextubation support in neonates. The efficacy of high-flow therapy as the primary means of respiratory support for preterm infants with respiratory distress has not been proved. METHODS In this international, multicenter, randomized, noninferiority trial, we assigned 564 preterm infants (gestational age, ≥28 weeks 0 days) with early respiratory distress who had not received surfactant replacement to treatment with either nasal high-flow therapy or nasal CPAP. The primary outcome was treatment failure within 72 hours after randomization. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the chosen margin of noninferiority was 10 percentage points. Infants in whom high-flow therapy failed could receive rescue CPAP; infants in whom CPAP failed were intubated and mechanically ventilated. RESULTS Trial recruitment stopped early at the recommendation of the independent data and safety monitoring committee because of a significant difference in the primary outcome between treatment groups. Treatment failure occurred in 71 of 278 infants (25.5%) in the high-flow group and in 38 of 286 infants (13.3%) in the CPAP group (risk difference, 12.3 percentage points; 95% confidence interval [CI], 5.8 to 18.7; P<0.001). The rate of intubation within 72 hours did not differ significantly between the high-flow and CPAP groups (15.5% and 11.5%, respectively; risk difference, 3.9 percentage points; 95% CI, -1.7 to 9.6; P=0.17), nor did the rate of adverse events. CONCLUSIONS When used as primary support for preterm infants with respiratory distress, high-flow therapy resulted in a significantly higher rate of treatment failure than did CPAP. (Funded by the National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12613000303741 .).

Nursing perceptions of high‐flow nasal cannulae treatment for very preterm infants

This study aims to assess nursing perceptions of high‐flow nasal cannulae (HFNC) in comparison with nasal continuous positive airway pressure (NCPAP) as post‐extubation respiratory support for very preterm infants.

Towards evidence-based resuscitation of the newborn infant

Effective resuscitation of the newborn infant has the potential to save many lives around the world and reduce disabilities in children who survive peripartum asphyxia. In this Series paper, we highlight some of the important advances in the understanding of how best to resuscitate newborn infants, which includes monitoring techniques to guide resuscitative efforts, increasing awareness of the adverse effects of hyperoxia, delayed umbilical cord clamping, the avoidance of routine endotracheal intubation for extremely preterm infants, and therapeutic hypothermia for hypoxic-ischaemic encephalopathy. Despite the challenges of performing high-quality clinical research in the delivery room, researchers continue to refine and advance our knowledge of effective resuscitation of newborn infants through scientific experiments and clinical trials.

The evolution of modern respiratory care for preterm infants

Preterm birth rates are rising, and many preterm infants have breathing difficulty after birth. Treatments for infants with prolonged breathing difficulty include oxygen therapy, exogenous surfactant, various modes of respiratory support, and postnatal corticosteroids. In this Series paper, we review the history of neonatal respiratory care and its effect on long-term outcomes, and we outline the future direction of the research field. The delivery and monitoring of oxygen therapy remains controversial, despite being in use for more than 50 years. Exogenous surfactant replacement has been used for 25 years and has dramatically reduced mortality and morbidity, but more research on when and how it is administered is needed. Methods and techniques of neonatal respiratory support are evolving. Clinicians are moving away from routine intubation and ventilation, and new modes of non-invasive support are being investigated. Postnatal corticosteroids have a limited role in infants with evolving bronchopulmonary dysplasia, but more research is needed to identify the best timing, type, dose, and method of administration. Despite advances in neonatal care in the past 50 years, bronchopulmonary dysplasia, with all its adverse short-term and long-term consequences, is still a serious problem in neonatal care. The challenge remains to support breathing in preterm infants, with special attention to risk factors in the subpopulation of infants that are at highest risk of bronchopulmonary dysplasia, without damaging their lungs or adversely affecting their long-term health.

A multicentre, randomised controlled, non-inferiority trial, comparing high flow therapy with nasal continuous positive airway pressure as primary support for preterm infants with respiratory distress (the HIPSTER trial): study protocol

Introduction High flow (HF) therapy is an increasingly popular mode of non-invasive respiratory support for preterm infants. While there is now evidence to support the use of HF to reduce extubation failure, there have been no appropriately designed and powered studies to assess the use of HF as primary respiratory support soon after birth. Our hypothesis is that HF is non-inferior to the standard treatment—nasal continuous positive airway pressure (NCPAP)— as primary respiratory support for preterm infants. Methods and analysis The HIPSTER trial is an unblinded, international, multicentre, randomised, non-inferiority trial. Eligible infants are preterm infants of 28–36+6 weeks’ gestational age (GA) who require primary non-invasive respiratory support for respiratory distress in the first 24 h of life. Infants are randomised to treatment with either HF or NCPAP. The primary outcome is treatment failure within 72 h after randomisation, as determined by objective oxygenation, blood gas, and apnoea criteria, or the need for urgent intubation and mechanical ventilation. Secondary outcomes include the incidence of intubation, pneumothorax, bronchopulmonary dysplasia, nasal trauma, costs associated with hospital care and parental stress. With a specified non-inferiority margin of 10%, using a two-sided 95% CI and 90% power, the study requires 375 infants per group (total 750 infants). Ethics and dissemination Ethical approval has been granted by the relevant human research ethics committees at The Royal Womens Hospital (13/12), The Royal Childrens Hospital (33144A), The Mercy Hospital for Women (R13/34), and the South-Eastern Norway Regional Health Authority (2013/1657). The trial is currently recruiting at 9 centres in Australia and Norway. The trial results will be published in peer-reviewed international journals, and presented at national and international conferences. Trial registration number Australian New Zealand Clinical Trials Registry ID: ACTRN12613000303741.

The effects of non-invasive respiratory support on oropharyngeal temperature and humidity: a neonatal manikin study

Objective Heating and humidification of inspired gases is routine during neonatal non-invasive respiratory support. However, little is known about the temperature and humidity delivered to the upper airway. The International Standards Organization (ISO) specifies that for all patients with an artificial airway humidifiers should deliver ≥33 g/m3 absolute humidity (AH). We assessed the oropharyngeal temperature and humidity during different non-invasive support modes in a neonatal manikin study. Methods Six different modes of non-invasive respiratory support were applied at clinically relevant settings to a neonatal manikin, placed in a warmed and humidified neonatal incubator. Oropharyngeal temperature and relative humidity (RH) were assessed using a thermohygrometer. AH was subsequently calculated. Results Measured temperature and RH varied between devices. Bubble and ventilator continuous positive airway pressure (CPAP) produced temperatures >34°C and AH >38 g/m3. Variable flow CPAP resulted in lower levels of AH than bubble or ventilator CPAP, and AH decreased with higher gas flow. High-flow (HF) therapy delivered by Optiflow Junior produced higher AH with higher gas flow, whereas with Vapotherm HF the converse was true. Conclusions Different non-invasive devices deliver inspiratory gases of variable temperature and humidity. Most AH levels were above the ISO recommendation; however, with some HF and variable flow CPAP devices at higher gas flow this was not achieved. Clinicians should be aware of differences in the efficacy of heating and humidification when choosing modes of non-invasive respiratory support.

Interventions to improve rates of successful extubation in preterm infants a systematic review and meta-analysis

Importance Clinicians aim to extubate preterm infants as early as possible, to minimize the risks of mechanical ventilation. Extubation is often unsuccessful owing to lung disease or inadequate respiratory drive. Objective To conduct a systematic review and meta-analysis of interventions to improve rates of successful extubation in preterm infants. Data Sources Searches were undertaken in PubMed and The Cochrane Library. Study Selection The review was conducted using the methods of the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were included if they were randomized clinical trials published in English, enrolled intubated preterm infants (born <37 weeks’ gestation), and reported 1 or both of the primary outcomes. Data Extraction and Synthesis One thousand three hundred seventy-nine titles were screened independently by 2 investigators to assess need for full-text review. Disagreements were resolved via consensus of all authors. Where no Cochrane Review existed for an intervention, or not all identified studies were included, a new pooled analysis was performed. Main Outcomes and Measures Primary outcomes were treatment failure or reintubation within 7 days of extubation. Results Fifty studies were eligible for inclusion. Continuous positive airway pressure reduced extubation failure in comparison with head-box oxygen (risk ratio [RR], 0.59; 95% CI, 0.48-0.72; number needed to treat [NNT], 6; 95% CI, 3-9). Nasal intermittent positive pressure ventilation was superior to continuous positive airway pressure in preventing extubation failure (RR, 0.70; 95% CI, 0.60-0.81; NNT, 8; 95% CI, 5-13). High-flow nasal cannula therapy and continuous positive airway pressure had similar efficacy (RR, 1.11; 95% CI, 0.84-1.47). Methylxanthines reduced extubation failure (RR, 0.48; 95% CI, 0.32-0.71; NNT, 4; 95% CI, 2-7) compared with placebo or no treatment. Corticosteroids (RR, 0.18; 95% CI, 0.04-0.97; NNT, 12; 95% CI, 6-100) and chest physiotherapy (RR, 0.32; 95% CI, 0.13-0.82; NNT, 15; 95% CI, 7-50) both reduced extubation failure rates but were associated with significant adverse effects. Doxapram did not aid successful extubation (RR, 0.80; 95% CI, 0.22-2.97). Conclusions and Relevance Preterm infants should be extubated to noninvasive respiratory support. Caffeine should be used routinely, while corticosteroids should be used judiciously, weighing up the competing risks of bronchopulmonary dysplasia and neurodevelopmental harm.