Search

Tubeless upper airway surgery in children is a complex procedure in which surgeons and anaesthetists share the same operating field. These procedures are often interrupted for rescue oxygen therapy. The efficacy of nasal high-flow oxygen to decrease the frequency of rescue interruptions in children undergoing upper airway surgery is unknown. In this multicentre randomised trial conducted in five tertiary hospitals in Australia, children aged 0–16 years who required tubeless upper airway surgery were randomised (1:1) by a web-based randomisation tool to either nasal high-flow oxygen delivery or standard oxygen therapy (oxygen flows of up to 6 L/min). Randomisation was stratified by site and age (<1 year, 1–4 years, and 5–16 years). Subsequent tubeless upper airway surgery procedures in the same child could be included if there were more than 2 weeks between the procedures, and repeat surgical procedures meeting this condition were considered to be independent events. The oxygen therapy could not be masked, but the investigators remained blinded until outcome data were locked. The primary outcome was successful anaesthesia without interruption of the surgical procedure for rescue oxygenation. A rescue oxygenation event was defined as an interruption of the surgical procedure to deliver positive pressure ventilation using either bag mask technique, insertion of an endotracheal tube, or laryngeal mask to improve oxygenation. There were ten secondary outcomes, including the proportion of procedures with a hypoxaemic event (SpO 2 <90%). Analyses were done on an intention-to-treat (ITT) basis. Safety was assessed in all enrolled participants. This trial is registered in the Australian New Zealand Clinical Trials Registry, ACTRN12618000949280, and is completed. From Sept 4, 2018, to April 12, 2021, 581 procedures in 487 children were randomly assigned to high-flow oxygen (297 procedures) or standard care (284 procedures); after exclusions, 528 procedures (267 assigned to high-flow oxygen and 261 assigned to standard care) in 483 children (293 male and 190 female) were included in the ITT analysis. The primary outcome of successful anaesthesia without interruption for tubeless airway surgery was achieved in 236 (88%) of 267 procedures on high-flow oxygen and in 229 (88%) of 261 procedures on standard care (adjusted risk ratio [RR] 1·02, 95% CI 0·96–1·08, p=0·82). There were 51 (19%) procedures with a hypoxaemic event in the high-flow oxygen group and 57 (22%) in the standard care group (RR 0·86, 95% CI 0·58–1·24). Of the other prespecified secondary outcomes, none showed a significant difference between groups. Adverse events of epistaxis, laryngospasm, bronchospasm, hypoxaemia, bradycardia, cardiac arrest, hypotension, or death were similar in both study groups. Nasal high-flow oxygen during tubeless upper airway surgery did not reduce the proportion of interruptions of the procedures for rescue oxygenation compared with standard care. There were no differences in adverse events between the intervention groups. These results suggest that both approaches, nasal high-flow or standard oxygen, are suitable alternatives to maintain oxygenation in children undergoing upper airway surgery. Thrasher Research Fund, the Australian and New Zealand College of Anaesthetists, the Society for Paediatric Anaesthesia in New Zealand and Australia. [ABSTRACT FROM AUTHOR]

Despite SARS-CoV-2 vaccines eliciting systemic neutralising antibodies (nAbs), breakthrough infections still regularly occur. Infection helps to generate mucosal immunity, possibly reducing disease transmission. Monitoring mucosal nAbs is predominantly restricted to lab-based assays, which have limited application to the public. In this multi-site study, we used lateral-flow surrogate neutralisation tests to measure mucosal and systemic nAbs in vaccinated and breakthrough infected individuals in Australia and Singapore. Using three lateral flow assays to detect SARS-CoV-2 nAbs, we demonstrated that nasal mucosal nAbs were present in 71.4 (95% CI 56.3–82.9%) to 85.7% (95% CI 71.8–93.7%) of individuals with breakthrough infection (positivity rate was dependent upon the type of test), whereas only 20.7 (95% CI 17.1–49.4%) to 34.5% (95% CI 19.8–52.7%) of vaccinated individuals without breakthrough infection had detectible nasal mucosal nAbs. Of the individuals with breakthrough infection, collective mucosal anti-S antibody detection in confirmatory assays was 92.9% (95% CI 80.3–98.2%) of samples, while 72.4% (95% CI 54.1–85.5%) of the vaccinated individuals who had not experienced a breakthrough infection were positive to anti-S antibody. All breakthrough infected individuals produced systemic anti-N antibodies; however, these antibodies were not detected in the nasal cavity. Mucosal immunity is likely to play a role in limiting the transmission of SARS-CoV-2 and lateral flow neutralisation tests provide a rapid readout of mucosal nAbs at the point-of-care. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship of the implementation of a nurse‐led high‐flow nasal cannula oxygen protocol on the clinical outcomes of infants with bronchiolitis in a regional paediatric unit. Background: Bronchiolitis is a common lower respiratory illness and is the leading cause for hospitalisation of infants globally. Standard care involves the provision of supportive measures. Historically, supplemental oxygen was provided by low‐flow nasal cannula. High‐flow nasal cannula oxygen has been increasingly adopted despite limited evidence of its efficacy. Methods: This study employed non‐equivalent, post‐implementation only design to explore clinical outcomes of infants with bronchiolitis admitted for high‐flow nasal cannula oxygen therapy. The study compared infants in the 24 months before and after the initiation of a high‐flow nasal cannula protocol. The primary clinical outcome was length of stay, secondary outcomes included time on high flow, weaning time, escalation of care and time outside of physiological parameters. Implementation strategy evaluation was measured by compliance with applying the protocol, reported as episodes of variance, and duration of variance. The StaRI checklist was selected as the most appropriate reporting guideline. Results: A total of 80 patients were admitted with bronchiolitis and received high‐flow nasal cannula oxygen therapy during a 48‐month period; 37 patients were prior, and 43 after, the introduction of a nurse‐led high‐flow nasal cannula protocol. Length of stay was significantly reduced in the post‐implementation group compared to the historical control group (83.8 vs. 61.3 h). Time on high flow and weaning time was decreased in the post‐implementation group compared to the control group (33.5 vs. 26.7 h and 26 vs.12.25 h, respectively); however, these did not reach statistical significance. There was varied application of the HFNC protocol. Conclusions: The implementation of a nurse‐led high‐flow nasal cannula protocol was associated with a reduced length of stay. Relevance to Clinical Practice: This study demonstrated that infants with bronchiolitis that were treated with a nurse‐led high‐flow nasal cannula (HFNC) therapy protocol had positive effects on clinical outcomes including a shorter length of stay than compared with those with physician‐directed care in a regional paediatric unit. A weight‐based (2 L/kg) HFNC therapy was safely administered to infants with bronchiolitis in a regional hospital paediatric ward with no paediatric intensive care unit (PICU). [ABSTRACT FROM AUTHOR]

Key Points: Question: Does the early use of nasal high-flow oxygen therapy in children aged 1 to 4 years with acute hypoxemic respiratory failure reduce the length of hospital stay compared with standard oxygen therapy? Findings: In this randomized clinical trial that included 1567 children with acute hypoxemic respiratory failure, use of nasal high-flow oxygen therapy resulted in a median hospital stay of 1.77 days compared with 1.50 days in the standard oxygen therapy group, a difference that was statistically significant. Meaning: Early use of nasal high-flow oxygen therapy in children aged 1 to 4 years with acute hypoxemic respiratory failure did not reduce the length of hospital stay compared with standard oxygen therapy. Importance: Nasal high-flow oxygen therapy in infants with bronchiolitis and hypoxia has been shown to reduce the requirement to escalate care. The efficacy of high-flow oxygen therapy in children aged 1 to 4 years with acute hypoxemic respiratory failure without bronchiolitis is unknown. Objective: To determine the effect of early high-flow oxygen therapy vs standard oxygen therapy in children with acute hypoxemic respiratory failure. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted at 14 metropolitan and tertiary hospitals in Australia and New Zealand, including 1567 children aged 1 to 4 years (randomized between December 18, 2017, and March 18, 2020) requiring hospital admission for acute hypoxemic respiratory failure. The last participant follow-up was completed on March 22, 2020. Interventions: Enrolled children were randomly allocated 1:1 to high-flow oxygen therapy (n = 753) or standard oxygen therapy (n = 764). The type of oxygen therapy could not be masked, but the investigators remained blinded until the outcome data were locked. Main Outcomes and Measures: The primary outcome was length of hospital stay with the hypothesis that high-flow oxygen therapy reduces length of stay. There were 9 secondary outcomes, including length of oxygen therapy and admission to the intensive care unit. Children were analyzed according to their randomization group. Results: Of the 1567 children who were randomized, 1517 (97%) were included in the primary analysis (median age, 1.9 years [IQR, 1.4-3.0 years]; 732 [46.7%] were female) and all children completed the trial. The length of hospital stay was significantly longer in the high-flow oxygen group with a median of 1.77 days (IQR, 1.03-2.80 days) vs 1.50 days (IQR, 0.85-2.44 days) in the standard oxygen group (adjusted hazard ratio, 0.83 [95% CI, 0.75-0.92]; P <.001). Of the 9 prespecified secondary outcomes, 4 showed no significant difference. The median length of oxygen therapy was 1.07 days (IQR, 0.50-2.06 days) in the high-flow oxygen group vs 0.75 days (IQR, 0.35-1.61 days) in the standard oxygen therapy group (adjusted hazard ratio, 0.78 [95% CI, 0.70-0.86]). In the high-flow oxygen group, there were 94 admissions (12.5%) to the intensive care unit compared with 53 admissions (6.9%) in the standard oxygen group (adjusted odds ratio, 1.93 [95% CI, 1.35-2.75]). There was only 1 death and it occurred in the high-flow oxygen group. Conclusions and Relevance: Nasal high-flow oxygen used as the initial primary therapy in children aged 1 to 4 years with acute hypoxemic respiratory failure did not significantly reduce the length of hospital stay compared with standard oxygen therapy. Trial Registration: anzctr.org.au Identifier: ACTRN12618000210279 This randomized clinical trial compares the effect of early high-flow oxygen therapy vs standard oxygen therapy on length of hospital stay in children with acute hypoxemic respiratory failure. [ABSTRACT FROM AUTHOR]

Aim: To determine the prevalence of high flow nasal cannula (HFNC) therapy in infants presenting to hospital in Australia and New Zealand with bronchiolitis over four bronchiolitis seasons. Secondary aims were to determine temporal trends in HFNC use, and associations between HFNC, hospital length of stay (LOS) and intensive care unit (ICU) admission. Methods: A planned sub‐study of a multi‐centre international cluster randomised controlled trial investigating knowledge translation strategies for a bi‐national bronchiolitis guideline. Demographics, management and outcomes data were collected retrospectively for infants presenting with bronchiolitis to 26 hospitals between 1 May 2014 and 30 November 2017. Prevalence data are presented as absolute frequencies (95% confidence interval (CI)) with differences between groups for continuous and categorical variables analysed using linear and logistic regression, respectively. Results: 11 715 infants were included with 3392 (29.0%, 95% CI (28.1–29.8%)) receiving oxygen therapy; of whom 1817 (53.6%, 95% CI (51.9–55.3%)) received HFNC. Use of oxygen therapy did not change over the four bronchiolitis seasons (P = 0.12), while the proportion receiving HFNC increased (2014, 336/2587 (43.2%); 2017, 609/3720 (57.8%); P ≤ 0.001). Infants who received HFNC therapy were not substantially different to infants who received oxygen therapy without HFNC. HFNC use was associated with increases in both hospital LOS (P < 0.001) and ICU admissions (P < 0.001). Conclusion: Use of HFNC therapy for infants with bronchiolitis increased over 4 years. Of those who received oxygen therapy, the majority received HFNC therapy without improvement in hospital LOS or ICU admissions. Strategies to guide appropriate HFNC use in infants with bronchiolitis are required. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To measure the nasal gas flow in infants treated with bubble continuous positive airway pressure (CPAP) and compare it with commonly used flows during nasal high flow (nHF) treatment.Design: This is a prospective, single-centre study. Bubble CPAP pressure was measured at the nasal prongs. Set gas flow was reduced until bubbling in the water chamber just ceased. Set gas flow without bubbling then approximated flow entering the infant's nose ('delivered flow').Setting: Neonatal intensive care at The Royal Women's Hospital, Melbourne, Australia.Patients: Clinically stable preterm infants receiving bubble CPAP therapy.Main Outcome Measure: Delivered flow (L/min) when bubbling stopped at a range of clinically set CPAP pressures (cm H2O).Results: Forty-four infants were studied, with a mean (SD) gestational age at birth of 28.4 (2.2) weeks and birth weight of 1154 (419) g. At the time of the study, infants had a median (IQR) age of 4.5 (2-12) days and a mean (SD) weight of 1205 (407) g. Delivered flow ranged from 0.5 to 9.0 L/min, and increased with higher set CPAP pressures (median 3.5 L/min at CPAP 5 cm H2O vs 6.3 L/min at CPAP 8 cm H2O) and heavier weights (median 3.5 L/min in infants <1000 g vs 6.5 L/min for infants >1500 g).Conclusions: Nasal gas flows during bubble CPAP in preterm infants are similar to flows used during nHF and increase with higher set bubble CPAP pressures and in larger infants. Trial registration number ACTRN12619000197134. [ABSTRACT FROM AUTHOR]

Objectives: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection.Trial Design: ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management.Participants: Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently.Intervention and Comparator: Participants will be randomised 1:1:1:1 to: Group 1: standard of care; Group 2: lopinavir (400mg) / ritonavir (100mg) twice daily for 10 days in tablet form; Group 3: hydroxychloroquine (800mg) 4x200mg administered 12 hours apart on Day 1, followed by 400mg twice a day for 6 days; Group 4: lopinavir /ritonavir plus hydroxychloroquine.Main Outcomes: Proportion of participants alive and not having required intensive respiratory support (invasive or non-invasive ventilation) at 15 days after enrolment. A range of clinical and virological secondary outcomes will also be evaluated.Randomisation: The randomisation schedule will be generated by an independent statistician. Randomisation will be stratified by site and will be in permuted blocks of variable block size. The randomised sequence allocation will only be accessible to the data management group, and site investigators will have individual participant allocation provided through a web-based trial enrolment platform.Blinding (masking): This is an open-label study, with researchers assessing the laboratory outcomes blinded to treatment allocation. No unblinding procedures relating to potential adverse effects are therefore required.Numbers To Be Randomised (sample Size): We assumed that 5% of participants receiving standard of care would meet the primary outcome, aimed to evaluate whether interventions could lead to a relative risk of 0.5, assuming no interaction between intervention arms. This corresponds to a required sample size of 610 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 2440.Trial Status: ASCOT protocol version 3, May 5, 2020. Recruitment opened April 4, 2020 and is ongoing, with planned completion of enrolment July 31, 2021.Trial Registration: Australian New Zealand Clinical Trials Registry ( ACTRN12620000445976 ). Prospectively registered April 6, 2020.Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to determine if oxygen delivered through humidified high flow nasal cannulae (HHFNC) reduced the need for escalation in ventilation management and work of breathing in the ED patients presenting with acute undif-ferentiated shortness of breath compared with standard oxygen therapy. Methods: This was an unblinded randomised control trial conducted at two hospital EDs in Sydney, Australia. Eligible patients presenting with shortness of breath were randomised to HHFNC or standard oxygen therapy. Primary outcomes were the need to escalate ventilation therapy or a reduction in respiratory rate of 20 % or more within 2 h of commencement. Results: One hundred patients were enrolled in the trial. The intervention group receiving HHFNC was associated with a higher proportion of patients with a reduced respiratory rate at 2 h (66.7% vs 38.5%, P = 0.005) and a lower proportion of patients requiring escalation in ventilation therapy (4.2% vs 19%, P = 0.02) compared with standard oxygen therapy. Conclusions: The use of high flow nasal cannula oxygenation was associated with improved respiratory state in selected patients presenting to the ED with acute undifferentiated shortness of breath. [ABSTRACT FROM AUTHOR]