Predictors of successful neonatal intubation in inexperienced operators: a secondary, non-randomised analysis of the SHINE trial.

OBJECTIVE: Neonatal endotracheal intubation is a lifesaving but technically difficult procedure, particularly for inexperienced operators. This secondary analysis in a subgroup of inexperienced operators of the Stabilization with nasal High flow during Intubation of NEonates randomised trial aimed to identify the factors associated with successful intubation on the first attempt without physiological stability of the infant. METHODS: In this secondary analysis, demographic factors were compared between infants intubated by inexperienced operators and those intubated by experienced operators. Following this, for inexperienced operators only, predictors of successful intubation without physiological instability were analysed. RESULTS: A total of 251 intubations in 202 infants were included in the primary intention-to-treat analysis of the main trial. Inexperienced operators were more likely to perform intubations in larger and more mature infants in the neonatal intensive care unit where premedications were used. When intubations were performed by inexperienced operators, the use of nasal high flow therapy (nHF) and a higher starting fraction of inspired oxygen were associated with a higher rate of safe, successful intubation on the first attempt. There was a weaker association between premedication use and first attempt success. CONCLUSIONS: In inexperienced operators, this secondary, non-randomised analysis suggests that the use of nHF and premedications, and matching the operator to the infant and setting, may be important to optimise neonatal intubation success. TRIAL REGISTRATION NUMBER: ACTRN12618001498280.

Comparison of the Pharmacokinetic Profiles of Trientine Tetrahydrochloride and Trientine Dihydrochloride in Healthy Subjects.

BACKGROUND AND OBJECTIVE: Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism. Chelation of excessive copper is recommended but data on the pharmacokinetics of trientine are limited. The aim of this study was to compare the pharmacokinetics of a new trientine tetrahydrochloride formulation (TETA 4HCl) with those of an established trientine dihydrochloride (TETA 2HCl) salt. METHODS: A randomised single-centre crossover study to evaluate the pharmacokinetics, safety and tolerability of two different oral formulations of trientine (TETA 4HCl tablets vs TETA 2HCl capsules) in 23 healthy adult subjects receiving a single dose equivalent to 600 mg of trientine base was performed. RESULTS: Following oral administration, the median time to reach maximum plasma concentration (Tmax) was 2.00 h (TETA 4HCl) and 3.00 h (TETA 2HCl). The rate (maximum plasma concentration [Cmax]) and extent (area under the plasma concentration-time curve from time zero to infinity [AUC0-∞]) of absorption of the active moiety, trientine, were greater (by approximately 68% and 56%, respectively) for TETA 4HCl than for the TETA 2HCl formulation. The two formulations presented a similar terminal elimination rate (λz) and a similar terminal half-life (t½) for trientine. Differences between TETA 4HCl and TETA 2HCl in the levels of the two main mono- and diacetylated metabolites were less than seen for trientine. For both tested formulations, healthy male volunteers demonstrated higher trientine plasma levels but lower mono- and diacetylated metabolite levels compared with females, with no sex differences in terminal half-life (t½) observed. Single oral doses of both formulations were safe and well tolerated. CONCLUSIONS: Compared with an identical dose of a TETA 2HCl formulation, the TETA 4HCl formulation provided more rapid absorption of trientine and greater systemic exposure in healthy subjects. Clinical Trials Number EudraCT # 2015-002199-25.

Documentation during neonatal resuscitation: a systematic review.

OBJECTIVE: Accurate documentation in healthcare is necessary for ethical, legal, research and quality improvement purposes. In this review, we aimed to evaluate the accuracy of methods of documentation of delivery room resuscitations. METHODS: A systematic literature search in MEDLINE was conducted to identify original studies that reported the quality of documentation records during newborn resuscitation in the delivery room. Data extracted from the studies included population characteristics, methodology, documentation protocols, use of gold standard and main results (initial assessment of heart rate and peripheral oxygen saturation, respiratory support and supplementary oxygen). RESULTS: In total, 197 records were screened after initial database search, of which seven studies met the inclusion criteria and were finally included in this review. Four studies were chart reviews and three studies compared conventional documentation methods with video recording. Only one study tested an intervention to improve documentation. Documentation was often inaccurate and important resuscitation events and interventions were poorly recorded. Lack of uniformity among studies preclude pooled analysis, but it seems that complex or advanced procedures were more accurately reported than basic interventions. CONCLUSIONS: There is little literature regarding accuracy of documentation during neonatal resuscitation, but current quality of documentation seems to be unsatisfactory. There is a need for consensus guidelines and innovative solutions in newborn resuscitation documentation.

A multicentre, randomised trial of stabilisation with nasal high flow during neonatal endotracheal intubation (the SHINE trial): a study protocol.

INTRODUCTION: Neonatal endotracheal intubation is an essential but potentially destabilising procedure. With an increased focus on avoiding mechanical ventilation, particularly in preterm infants, there are fewer opportunities for clinicians to gain proficiency in this important emergency skill. Rates of successful intubation at the first attempt are relatively low, and adverse event rates are high, when compared with intubations in paediatric and adult populations. Interventions to improve operator success and patient stability during neonatal endotracheal intubations are needed. Using nasal high flow therapy extends the safe apnoea time of adults undergoing upper airway surgery and during endotracheal intubation. This technique is untested in neonates. METHODS AND ANALYSIS: The Stabilisation with nasal High flow during Intubation of NEonates (SHINE) trial is a multicentre, randomised controlled trial comparing the use of nasal high flow during neonatal intubation with standard care (no nasal high flow). Intubations are randomised individually, and stratified by site, use of premedications, and postmenstrual age (<28 weeks' gestation; ≥28 weeks' gestation). The primary outcome is the incidence of successful intubation on the first attempt without physiological instability of the infant. Physiological instability is defined as an absolute decrease in peripheral oxygen saturation >20% from preintubation baseline and/or bradycardia (<100 beats per minute). ETHICS AND DISSEMINATION: The SHINE trial received ethical approval from the Human Research Ethics Committees of The Royal Women's Hospital, Melbourne, Australia and Monash Health, Melbourne, Australia. The trial is currently recruiting in these two sites. The findings of this study will be disseminated via peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ACTRN12618001498280.

The OPTIMIST-A trial: evaluation of minimally-invasive surfactant therapy in preterm infants 25-28 weeks gestation.

BACKGROUND: It is now recognized that preterm infants ≤28 weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure. However, this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency, with the result that intubation and delayed surfactant therapy are then required. Infants following this path are known to have a higher risk of adverse outcomes, including death, bronchopulmonary dysplasia and other morbidities. In an effort to circumvent this problem, techniques of minimally-invasive surfactant therapy have been developed, in which exogenous surfactant is administered to a spontaneously breathing infant who can then remain on continuous positive airway pressure. A method of surfactant delivery using a semi-rigid surfactant instillation catheter briefly passed into the trachea (the "Hobart method") has been shown to be feasible and potentially effective, and now requires evaluation in a randomised controlled trial. METHODS/DESIGN: This is a multicentre, randomised, masked, controlled trial in preterm infants 25-28 weeks gestation. Infants are eligible if managed on continuous positive airway pressure without prior intubation, and requiring FiO2 ≥ 0.30 at an age ≤6 hours. Randomisation will be to receive exogenous surfactant (200 mg/kg poractant alfa) via the Hobart method, or sham treatment. Infants in both groups will thereafter remain on continuous positive airway pressure unless intubation criteria are reached (FiO2 ≥ 0.45, unremitting apnoea or persistent acidosis). Primary outcome is the composite of death or physiological bronchopulmonary dysplasia, with secondary outcomes including incidence of death; major neonatal morbidities; durations of all modes of respiratory support and hospitalisation; safety of the Hobart method; and outcome at 2 years. A total of 606 infants will be enrolled. The trial will be conducted in >30 centres worldwide, and is expected to be completed by end-2017. DISCUSSION: Minimally-invasive surfactant therapy has the potential to ease the burden of respiratory morbidity in preterm infants. The trial will provide definitive evidence on the effectiveness of this approach in the care of preterm infants born at 25-28 weeks gestation. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry: ACTRN12611000916943; ClinicalTrials.gov: NCT02140580.

How long should infants at risk of drug withdrawal be monitored after birth?

AIM: Neonatal abstinence syndrome (NAS) is an increasingly common disorder diagnosed in infants exposed to various drugs, causing immense financial and social burden. Recommendations from various bodies are for babies to be monitored for 4 to 7 days following birth so that prompt treatment can commence should symptoms develop. We aimed to determine the best post-natal observation period in babies at risk of NAS. METHODS: A retrospective review was undertaken of infants ≥35 weeks' gestation who received treatment for NAS in the period 2001-2010. During this time, the standard post-natal observation period was a minimum of 7 days. Data including drug exposure, day of admission and day of treatment were collected. RESULTS: Two hundred and ten babies were included. Drug exposure was predominantly to opiates (99%); however, most infants (58%) were exposed to additional substances (benzodiazepines, cannabis or amphetamines). Ninety-five per cent of infants were admitted by day 5 of life. Of the babies treated by day 7, 98.5% had been admitted to the nursery by day 5. Infants with polydrug exposure were admitted significantly earlier; however, time to treatment was not significantly different to those exposed to opiate replacement therapy alone. CONCLUSIONS: In our hospital, babies treated for NAS often required admission before day 5. This has implications for hospital resource allocation, suggesting that routine post-natal observation for NAS could be shortened to 5 days. Further research is needed to help identify neonates who require more careful post-natal observation.

Respiratory function monitor guidance of mask ventilation in the delivery room: a feasibility study.

OBJECTIVE: To investigate whether using a respiratory function monitor (RFM) during mask resuscitation of preterm infants reduces face mask leak and improves tidal volume (V(T)). STUDY DESIGN: Infants receiving mask resuscitation were randomized to have the display of an RFM (airway pressure, flow, and V(T) waves) either visible or masked. RESULT: Twenty-six infants had the RFM visible, and 23 had the RFM masked. The median mask leak was 37% (IQR, 21%-54%) in the visible RFM group and 54% (IQR, 37%-82%) in the masked RFM group (P = .01). Mask repositioning was done in 19 infants (73%) of the visible group and in 6 infants (26%) of the masked group (P = .001). The median expired V(T) was similar in the 2 groups. Oxygen was provided to 61% of the visible RFM group and 87% of the RFM masked group (P = .044). Continuous positive airway pressure use was greater in the visible RFM group (73% vs 43%; P = .035). Intubation in the delivery room was done in 21% of the visible group and in 57% of the masked group (P = .035). CONCLUSION: Using an RFM was associated with significantly less mask leak, more mask adjustments, and a lower rate of excessive V(T).