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Background/objective Endotracheal suction is one of the most common and harmful procuedres performed on mechanically ventilated children. The aim of the study was to establish the feasibility of a randomised controlled trial (RCT) examining the effectiveness of normal saline instillation (NSI) and a positive end-expiratory pressure recruitment manoeuvre (RM) with endotracheal suction in the paediatric intensive care unit. Methods Pilot 2 × 2 factorial RCT. The study was conducted at a 36-bed tertiary paediatric intensive care unit in Australia. Fifty-eight children aged less than 16 years undergoing tracheal intubation and invasive mechanical ventilation. (i) NSI or no NSI and (ii) RM or no RM with endotracheal suction . The primary outcome was feasibility; secondary outcomes were ventilator-associated pneumonia (VAP), change in end-expiratory lung volume assessed by electrical impedance tomography, dynamic compliance, and oxygen saturation-to-fraction of inspired oxygen (SpO2/FiO2) ratio. Results/Findings Recruitment, retention, and missing data feasibility criteria were achieved. Eligibility and protocol adherence criteria were not achieved, with 818 patients eligible and 58 enrolled; cardiac surgery was the primary reason for exclusion. Approximately 30% of patients had at least one episode of nonadherence. Children who received NSI had a reduced incidence of VAP; however, this did not reach statistical significance (incidence rate ratio = 0.12, 95% confidence interval = 0.01–1.10; p = 0.06). NSI was associated with a significantly reduced SpO2/FiO2 ratio up to 10 min after suction. RMs were not associated with a reduced VAP incidence (incidence rate ratio = 0.31, 95% confidence interval = 0.05–1.88), but did significantly improve end-expiratory lung volume at 2 and 5 min after suction, dynamic compliance, and SpO2/FiO2 ratio. Conclusion RMs provided short-term improvements in end-expiratory lung volume and oxygenation. NSI with suction led to a reduced incidence of VAP; however, a definitive RCT is needed to test statistical differences. A RCT of study interventions is worthwhile and may be feasible with protocol modifications including the widening of participant eligibility.

BACKGROUND Extracorporeal membrane oxygenation (ECMO) provides support for the pulmonary or cardiovascular function of children in whom the predicted mortality risk remains very high. The inevitable host inflammatory response and activation of the coagulation cascade due to the extracorporeal circuit contribute to additional morbidity and mortality in these patients. Mixing nitric oxide (NO) into the sweep gas of ECMO circuits may reduce the inflammatory and coagulation cascade activation during ECMO support. OBJECTIVE The purpose of this study is to test the feasibility and safety of mixing NO into the sweep gas of ECMO systems and assess its effect on inflammation and coagulation system activation through a pilot randomized controlled trial. METHODS The Nitric Oxide on Extracorporeal Membrane Oxygenation in Neonates and Children (NECTAR) trial is an open-label, parallel-group, pilot randomized controlled trial to be conducted at a single center. Fifty patients who require ECMO support will be randomly assigned to receive either NO mixed into the sweep gas of the ECMO system at 20 ppm for the duration of ECMO or standard care (no NO) in a 1:1 ratio, with stratification by support type (veno-venous vs veno-arterial ECMO). RESULTS Outcome measures will focus on feasibility (recruitment rate and consent rate, and successful inflammatory marker measurements), the safety of the intervention (oxygenation and carbon dioxide control within defined parameters and methemoglobin levels), and proxy markers of efficacy (assessment of cytokines, chemokines, and coagulation factors to assess the impact of NO on host inflammation and coagulation cascade activation, clotting of ECMO components, including computer tomography scanning of oxygenators for clot assessments), bleeding complications, as well as total blood product use. Survival without ECMO and the length of stay in the pediatric intensive care unit (PICU) are clinically relevant efficacy outcomes. Long-term outcomes include neurodevelopmental assessments (Ages and Stages Questionnaire, Strength and Difficulties Questionnaire, and others) and quality of life (Pediatric Quality of Life Inventory and others) measured at 6 and 12 months post ECMO cannulation. Analyses will be conducted on an intention-to-treat basis. CONCLUSIONS The NECTAR study investigates the safety and feasibility of NO as a drug intervention during extracorporeal life support and explores its efficacy. The study will investigate whether morbidity and mortality in patients treated with ECMO can be improved with NO. The intervention targets adverse outcomes in patients who are supported by ECMO and who have high expected mortality and morbidity. The study will be one of the largest randomized controlled trials performed among pediatric patients supported by ECMO. CLINICALTRIAL Australian New Zealand Clinical Trials Registry ACTRN12619001518156; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376869 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/43760

The placement of an endotracheal tube for children with acute or critical illness is a low frequency and high-risk procedure, associated with high rates of first attempt failure and adverse events, including hypoxaemia. To reduce the frequency of these adverse events the provision of oxygen to the patient during the apnoeic phase of intubation has been proposed as a method to prolong the time available for the operator to insert the endotracheal tube, prior to the onset of hypoxaemia. However, there are limited data from randomised controlled trials to validate the efficacy of this technique in children. The technique known as Transnasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE) uses high oxygen flow rates (approximately 2L/kg/min) delivered through nasal cannulae during apnoea. It has been shown to at least double the amount of time available for safe intubation in healthy children undergoing elective surgery. The technique and its application in real time has not previously been studied in acutely ill or injured children presenting to the emergency department or admitted to an intensive care unit. The Kids THRIVE trial is a multicentre, international, randomised controlled trial (RCT) in children less than 16 years old undergoing emergent intubation in either the intensive care unit or emergency department of participating hospitals. Participants will be randomised to receive either the THRIVE intervention or standard care (no apnoeic oxygenation) during their intubation. The primary objective of the trial is to determine if the use of THRIVE reduces the frequency of oxygen desaturation and increases frequency of first attempt success without hypoxaemia in emergent intubation of children compared with standard practice. The secondary objectives of the study are to assess the impact of the use of THRIVE on the rate of adverse events, length of mechanical ventilation and length of stay in intensive care. In this paper we describe the detailed statistical analysis plan as an update the previously published protocol.

Background. Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available. Methods. This was a phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In part 1 patients (n=24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In part 2 patients (n=48) were randomized 2:1 to receive AK0529 at 0.5, 1 or 2 mg/kg bid or placebo for five days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, signs and symptoms were assessed daily during treatment. Results. No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurred in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 hours was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in RSV signs and symptom score from baseline to 96 hours was observed in the 2 mg/kg group, compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group. Conclusions. AK0529 was well tolerated in hospitalized RSV-infected infants. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and clinical signs and symptoms.

Background Intravenous fluid therapy represents the most common intervention critically ill patients are exposed to. Hyperchloremia and metabolic acidosis associated with 0.9% sodium chloride have been observed to lead to worse outcomes, including mortality. Balanced solutions, such as Plasma-Lyte 148 and Compound Sodium Lactate, represent potential alternatives but the evidence on optimal fluid choices in critically ill children remains scarce. This study aims to demonstrate whether balanced solutions, when used as intravenous fluid therapy, are able to reduce the incidence of a rise in serum chloride level compared to 0.9% sodium chloride in critically ill children. Methods This is a single-centre, open-label randomized controlled trial with parallel 1:1:1 assignment into three groups: 0.9% sodium chloride, Plasma-Lyte 148, and Compound Sodium Lactate solutions for intravenous fluid therapy. The intervention includes both maintenance and bolus fluid therapy. Children aged < 16 years admitted to intensive care and receiving intravenous fluid therapy during the first 4 h of admission are eligible. The primary outcome measure is a ≥ 5mmol/L increase in serum chloride level within 48 h post-randomization. The enrolment target is 480 patients. The main analyses will be intention-to-treat. Discussion This study tests three types of intravenous fluid therapy in order to compare the risk of hyperchloremia associated with normal saline versus balanced solutions. This pragmatic study is thereby assessing the most common intervention in paediatric critical care. This is a single-centre open-label study with no blinding at the level of delivery of the intervention. Certain paediatric intensive care unit (PICU) patient groups such as those admitted with a cardiac condition or following a traumatic brain injury are excluded from this study. Trial registration The study has received ethical approval (HREC/19/QCHQ/53177: 06/06/2019). It is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12619001244190) from 9th September 2019. Recruitment commenced on 12th November 2019. The primary results manuscript will be published in a peer-reviewed journal.

To evaluate in a pre-planned secondary analysis of our parent randomized controlled trial predictors of intensive care admission in infants with bronchiolitis and analyze if these predictors are equally robust for children receiving high-flow or standard-oxygen.A secondary analysis of a multi-center, randomized trial of infants aged12 months with bronchiolitis and an oxygen requirement was performed using admission and outcome data of all 1472 enrolled infants. The primary outcome was intensive care admission. The predictors evaluated were baseline characteristics including physiological data and medical history.Of the 1472 enrolled infants, 146 were admitted to intensive care. Multivariate predictors of intensive care admission were age (weeks) (odds ratio [OR]: 0.98 [95% confidence interval (CI) 0.96-0.99]), pre-enrolment heart rate160/min (OR: 1.80 [95% CI: 1.23-2.63]), pre-enrolment SpOAge2 months, pre-enrolment heart rate160/min, pre-enrolment SpO

OBJECTIVE: Intubation of children in the emergency setting is a high-risk, low incidence event. Standardisation of clinical practice has been hampered by a lack of high-quality evidence to support one technique over another. The aim of the present study is to determine clinician preference in intubation practice of children in EDs and ICUs in Australia and New Zealand to provide baseline information to allow future targeted research focused on improving the safety and efficacy of paediatric emergency airway management. METHODS: The present study was a voluntary questionnaire undertaken by medical staff at registrar level or above in EDs and ICUs associated with the Paediatric Research in Emergency Departments International Collaborative (PREDICT) and Australia and New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG) research networks. Respondents reported on their individual intubation practices, with a focus on pre-oxygenation and apnoeic oxygenation techniques, and the use of video laryngoscopy. RESULTS: A total of 502 clinicians were invited to complete the survey between May and October 2018 with 336 (66.9%) responded. There was marked variation in practice between ED clinicians and ICU clinicians in the techniques used for pre-oxygenation, the frequency of use of apnoeic oxygenation and the reported use of video laryngoscopy. CONCLUSIONS: Within Australia and New Zealand there is considerable variation in paediatric emergency airway clinical practice, in particular with respect to pre-oxygenation, apnoeic oxygenation and use of video laryngoscopy. Definitive clinical trials are required to best inform clinical practice in this area.

Objective The objective of this study was to determine the incidence of endotracheal tube (ETT) suction–related adverse events (AEs) and to examine associations between AEs and patient and suction characteristics. Secondary objectives were to describe ETT suction practices in an Australian paediatric intensive care unit (PICU). Methods A prospective, observational study was undertaken in a mixed cardiac and general PICU. Children were eligible for inclusion if they were intubated and mechanically ventilated. Data on patient and suction variables (indication for ETT suction, number of suction episodes per mechanical ventilation episode, indication for normal saline instillation [NSI] and NSI dose) including potential predictive variables (age, Paediatric Index of Mortality 3 [PIM3], NSI, positive end-expiratory pressure, and hyperoxygenation) were collected. The main outcome variable was a composite measure of any AE. Main results A total of 955 suction episodes were recorded in 100 children. AEs occurred in 211 (22%) ETT suctions. Suction-related AEs were not associated with age, diagnostic category, or index of mortality score. Desaturation was the most common AE (180 suctions; 19%), with 69% of desaturation events requiring clinician intervention. Univariate logistic regression showed the odds of desaturation decreased as the internal diameter of the ETT increased (odds ratio [OR]: 0.59; 95% confidence interval [CI]: 0.37–0.95; p = 0.028). Multivariable modelling revealed NSI was significantly associated with an increased risk of desaturation (adjusted OR [aOR]: 3.23; 95% CI: 1.99–5.40; p Conclusions ETT suction–related AEs are common and associated with NSI and the requirement for pre-suction increases in FiO2. Clinical trial data are needed to identify high-risk patient groups and to develop interventions which optimise practice and reduce the occurrence of ETT suction–related AEs.

Up to 37% of children admitted to the PICU develop acute kidney injury as defined by Kidney Disease: Improving Global Outcomes criteria. We describe the prevalence of acute kidney injury in a mixed pediatric intensive care cohort using this criteria. As tools to stratify patients at risk of acute kidney injury on PICU admission are lacking, we explored the variables at admission and day 1 that might predict the development of acute kidney injury. Single-center retrospective observational study. Thirty-six-bed surgical/medical tertiary PICU. Children from birth to less than or equal to 16 years old admitted between 2015 and 2018. None. Clinical data were extracted from the PICU clinical information system. Patients with baseline creatinine at admission greater than 20 micromol/L above the calculated normal creatinine level were classified as "high risk of acute kidney injury." Models were created to predict acute kidney injury at admission and on day 1. Out of the 7,505 children admitted during the study period, 738 patients (9.8%) were classified as high risk of acute kidney injury at admission and 690 (9.2%) developed acute kidney injury during PICU admission. Compared to Kidney Disease: Improving Global Outcomes criteria as the reference standard, high risk of acute kidney injury had a lower sensitivity and higher specificity compared with renal angina index greater than or equal to 8 on day 1. For the admission model, the adjusted odds ratio of developing acute kidney injury for high risk of acute kidney injury was 4.2 (95% CI, 3.3-5.2). The adjusted odds ratio in the noncardiac cohort for high risk of acute kidney injury was 7.3 (95% CI, 5.5-9.7). For the day 1 model, odds ratios for high risk of acute kidney injury and renal angina index greater than or equal to 8 were 3.3 (95% CI, 2.6-4.2) and 3.1 (95% CI, 2.4-3.8), respectively. The relationship between high risk of acute kidney injury and acute kidney injury needs further evaluation. High risk of acute kidney injury performed better in the noncardiac cohort.

OBJECTIVES: Antithrombin is a cofactor in the coagulation cascade with mild anticoagulant activity and facilitates the action of heparin as an anticoagulant. Antithrombin concentrate dosing guidelines vary but most commonly suggest that each unit of antithrombin concentrate per body weight increases the plasma antithrombin level by 1.5% to 2.2% (depending on manufacturer). We aimed to establish a dosing recommendation dependent on age and disease state. DESIGN: A retrospective analysis of all antithrombin concentrate doses over a period of 5 years. We calculated the increase any respective antithrombin concentrate dose achieved, indexed by body weight, and performed a multivariable analysis to establish independent factors associated with the effectiveness of antithrombin concentrate. SETTING: A PICU at a university-affiliated children's hospital. PATIENTS: One hundred fifty-five patients treated in a PICU.None. MEASUREMENTS AND MAIN RESULTS: The effect of 562 doses of antithrombin concentrate on plasma antithrombin levels administered to 155 patients, of which 414 (73.7%) antithrombin concentrate doses administered during extracorporeal life support treatment, were analyzed. For all patients, each unit of antithrombin concentrate/kg increased plasma antithrombin level by 0.86% (SD 0.47%). Plasma antithrombin level increase was influenced by body weight (increase of 0.76% [interquartile range, 0.6-0.92%] for patients 20 kg), disease state (liver failure having the poorest antithrombin increase) and whether patients were treated with extracorporeal circulatory support (less antithrombin increase on extracorporeal life support). Heparin dose at the time of administration did not influence with amount of change in antithrombin level. CONCLUSIONS: Current antithrombin concentrate dosing guidelines overestimate the effect on plasma antithrombin level in critically ill children. Current recommendations result in under-dosing of antithrombin concentrate administration. Age, disease state, and extracorporeal life support should be taken into consideration when administering antithrombin concentrate.

Objectives To determine current management of critically ill children and gather views regarding high flow nasal cannula therapy and to evaluate research priorities for a large prospective randomized controlled trial of noninvasive respiratory support in children. Design Multinational cross-sectional questionnaire survey conducted in 2018. Setting The sample included pediatric intensive care physicians in North and South America, Asia, Europe, and Australia/New Zealand. Measurement Questions consisted of: 1) characteristics of intensivists and hospital, 2) practice of high flow nasal cannula, 3) supportive treatment, and 4) research of high flow nasal cannula. Interventions None. Main results We collected data from 1,031 respondents; 919 (North America, 215; Australia/New Zealand, 34; Asia, 203; South America, 186; Europe, 281) were analyzed. Sixty-nine percent of the respondents used high flow nasal cannula in non-PICU settings in their institutions. For a case of bronchiolitis/pneumonia infant, 2 L/kg/min of initial flow rate was the most commonly used. For a scenario of pneumonia with 30 kg weight, more than 60% of the respondents initiated flow based on patient body weight; while, 18% applied a fixed flow rate. Noninvasive ventilation was considered as a next step in more than 85% of respondents when the patient is failing with high flow nasal cannula. Significant practice variations were observed in clinical practice markers used, flow weaning strategy, and supportive practices. Views comparing high flow nasal cannula to continuous positive airway pressure also noticeably varied across the respondents. Conclusions Significant practice variations including views of high flow nasal cannula compared to continuous positive airway pressure was found among pediatric intensive care physicians. To expedite establishment and standardization of high flow nasal cannula practice, research aimed at understanding the heterogeneity found in this study should be undertaken.

ImportanceNasal 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.ObjectiveTo determine the effect of early high-flow oxygen therapy vs standard oxygen therapy in children with acute hypoxemic respiratory failure.Design, Setting, and ParticipantsA 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.InterventionsEnrolled 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 MeasuresThe 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.ResultsOf 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 Conclusions and RelevanceNasal 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 Registrationanzctr.org.au Identifier: ACTRN12618000210279

Bronchiolitis is a common viral disease that significantly affects infants less than 12 months of age. The purpose of this review is to present a review of the current knowledge of the uses of respiratory support in the management of infants with bronchiolitis presenting to hospital. We electronically searched MEDLINE, Cochrane, CINAHL and EMBASE (inception to 25th March 2018), to manually search for clinical trials that address the management strategies for respiratory support of infants with bronchiolitis. We identified 120 papers who met the inclusion criteria, of which 33 papers were relevant for this review with only nine randomized controlled trials. This review demonstrated that non-invasive respiratory support reduced the need for escalation of therapy, particularly the proportion of intubations required for infants with bronchiolitis. Additionally, clear economic benefits have been demonstrated when non-invasive ventilation has been used. The potential early use of non-invasive respiratory supports such as nasal high flow therapy and non-invasive ventilation may have an impact on health care costs and reduction in ICU admissions and intubation rates. High-grade evidence demonstrates safety and quality of high flow therapy in general ward settings.

Continuous capnography has been recognised as an essential monitoring device in all anaesthetised patients, despite which airway device is in use, regardless of their location, as a measure to improve patient safety . Capnography is the non-invasive measurement of a sample of the exhaled carbon dioxide (CO ) which has multiple clinical uses including as a method to confirm placement of a tracheal tube and/or to assess ventilation, perfusion and metabolism. Notably, capnography is used during routine paediatric anaesthesia to assess ventilation and as a surrogate measure for arterial carbon dioxide pressure (PaCO ). The inaccuracies associated with these surrogate measures need to be considered to inform improved ventilation management of infants and children. This review highlights some major principles to understand the CO elimination, the physiology of paediatric capnography, the clinical application and the limitations of capnography during anaesthesia for neonates, infants and small children.

The last two decades have seen the emergence of systems capable of delivering heated, humidified high-flow air and oxygen via nasal cannula to neonatal, paediatric and adult patients requiring respiratory support in emergency, critical care and general ward areas. These delivery systems (high-flow nasal cannula—HFNC) are regarded as an alternative to traditional oxygen delivery systems such as face masks and low-flow nasal cannula, and, increasingly, as a possible alternative to more invasive forms of oxygenation and ventilation such as non-invasive ventilation (NIV) and invasive mechanical ventilation. The HFNC delivery system consists of a gas blender and flow meter; an active humidifier; a heated inspiratory circuit; and the nasal cannula interface. HFNC provides a constant flow of humidified gas that can more accurately match the inspiratory flow of an acutely unwell patient whilst providing continuous positive airway pressure. Oxygen therapy is generally added into the flow and can be titrated to the patients’ oxygen requirements. Technical aspects of this therapy and considerations for its usage are outlined in this chapter. Further research is required to establish optimal HFNC commencement time frames and flow rates, in addition to early predictors of non-response to therapy so that appropriate treatment escalation is instituted.

IntroductionApproximately 20%–40% of comatose children with risk factors in intensive care have electrographic-only seizures; these go unrecognised due to the absence of continuous electroencephalography (EEG) monitoring (cEEG). Utility of cEEG with high-quality assessment is currently limited due to high-resource requirements. New software analysis tools are available to facilitate bedside cEEG assessment using quantitative EEG (QEEG) trends. The primary aim of this study is to describe accuracy of interpretation of QEEG trends by paediatric intensive care unit (PICU) nurses compared with cEEG assessment by neurologist (standard clinical care) in children at risk of seizures and status epilepticus utilising diagnostic test statistics. The secondary aims are to determine time to seizure detection for QEEG users compared with standard clinical care and describe impact of confounders on accuracy of seizure detection.Methods and analysisThis will be a single-centre, prospective observational cohort study evaluating a paediatric QEEG programme utilising the full 19 electrode set. The setting will be a 36-bed quaternary PICU with medical, cardiac and general surgical cases. cEEG studies in PICU patients identified as ‘at risk of seizures’ will be analysed. Trained bedside clinical nurses will interpret the QEEG. Seizure events will be marked as seizures if >3 QEEG criteria occur. Post-hoc dedicated neurologists, who remain blinded to the QEEG analysis, will interpret the cEEG. Determination of standard test characteristics will assess the primary hypothesis. To calculate 95% (CIs) around the sensitivity and specificity estimates with a CI width of 10%, the sample size needed for sensitivity is 80 patients assuming each EEG will have approximately 9 to 18 1-hour epochs.Ethics and disseminationThe study has received approval by the Children’s Health Queensland Human Research Ethics Committee (HREC/19/QCHQ/58145). Results will be made available to the funders, critical care survivors and their caregivers, the relevant societies, and other researchers.Trial registration numberAustralian New Zealand Clinical Trials Registry (ANZCTR) 12621001471875.

Acute kidney injury (AKI) is a major cause of morbidity and mortality in critically ill children. The aim of this paper was to describe the prevalence and course of AKI in critically ill children and to compare different AKI classification criteria.We conducted a retrospective observational study in our multi-disciplinary Pediatric Intensive Care Unit (ICU) from January 2015 to December 2018. All patients from birth to 16 years of age who were admitted to the pediatric ICU were included. The Kidney Disease Improving Global Outcomes (KDIGO) definition was considered as the reference standard. We compared the incidence data assessed by KDIGO, pediatric risk, injury, failure, loss of kidney function and end- stage renal disease (pRIFLE) and pediatric reference change value optimised for AKI (pROCK).Out of 7505 patients, 9.2% developed AKI by KDIGO criteria. The majority (59.8%) presented with stage 1 AKI. Recovery from AKI was observed in 70.4% of patients within 7 days from diagnosis. Both pRIFLE and pROCK were less sensitive compared to KDIGO criteria for the classification of AKI. Patients who met all three-KDIGO, pRIFLE and pROCK criteria had a high mortality rate (35.0%).Close to one in ten patients admitted to the pediatric ICU met AKI criteria according to KDIGO. In about 30% of patients, AKI persisted beyond 7 days. Follow-up of patients with persistent kidney function reduction at hospital discharge is needed to reveal the long-term morbidity due to AKI in the pediatric ICU.

BackgroundBronchiolitis is the most common reason for hospital admission in infants. High-flow oxygen therapy has emerged as a new treatment; however, the cost-effectiveness of using it as first-line therapy is unknown.ObjectiveTo compare the cost of providing high-flow therapy as a first-line therapy compared with rescue therapy after failure of standard oxygen in the management of bronchiolitis.MethodsA within-trial economic evaluation from the health service perspective using data from a multicentre randomised controlled trial for hypoxic infants (≤12 months) admitted to hospital with bronchiolitis in Australia and New Zealand. Intervention costs, length of hospital and intensive care stay and associated costs were compared for infants who received first-line treatment with high-flow therapy (early high-flow, n=739) or for infants who received standard oxygen and optional rescue high-flow (rescue high-flow, n=733). Costs were applied using Australian costing sources and are reported in 2016–2017 AU$.ResultsThe incremental cost to avoid one treatment failure was AU$1778 (95% credible interval (CrI) 207 to 7096). Mean cost of bronchiolitis treatment including intervention costs and costs associated with length of stay was AU$420 (95% CrI −176 to 1002) higher per infant in the early high-flow group compared with the rescue high-flow group. There was an 8% (95% CrI 7.5 to 8.6) likelihood of the early high-flow oxygen therapy being cost saving.ConclusionsThe use of high-flow oxygen as initial therapy for respiratory failure in infants with bronchiolitis is unlikely to be cost saving to the health system, compared with standard oxygen therapy with rescue high-flow.

AIMS: High-flow is increasingly used in children with acute hypoxaemic respiratory failure (AHRF), despite limited evidence. The primary feasibility endpoint for this pilot-study was the proportion of treatment failure, secondary outcomes being intensive care unit (ICU) admissions and proportion of patients requiring escalation of care. We measured duration of hospital stay, duration of oxygen therapy and rates of ICU admission. METHODS: An open-labelled randomised controlled trial feasibility design was used in two tertiary children's hospitals in the emergency department and general wards. Children aged 0-16 years with AHRF were randomised (1:1) to either high-flow or standard-oxygen. Children on standard-oxygen received rescue high-flow in general wards if failure criteria were met. RESULTS: Of 563 randomised, 283 received high-flow and 280 standard-oxygen with no adverse events. The proportion of children who failed treatment and receiving escalation of care was 11.7% (32/283 children) on high-flow and 18.1% (50/280 infants) on standard-oxygen (odds ratio 0.68, 95% confidence interval 0.38-1.00). In children with obstructive airway disease, 9.7% on high-flow and 17.4% on standard-oxygen required escalation (risk-difference -7.7% percentage points; 95% confidence interval -14.3, -1.1); in children with non-obstructive disease no difference was observed. Neither difference in ICU admissions nor any difference in length of hospital stay was observed. Sixty percent of children who failed standard-oxygen responded to rescue high-flow. CONCLUSION: High-flow outside ICU appears to be feasible in children with AHRF and the required proportion of escalation was lower compared to standard-oxygen. The trial design can be applied in a future large randomised controlled trial.

Background Pulse oximetry (SpO 2 ) is used to monitor oxygen saturation levels to avoid hypoxaemia in children. Sensor manufacturers claim high sensitivity, specificity and accuracy. Few studies have evaluated accuracy and precision of SpO 2 in children. Methods This prospective, observational study was conducted in a 36-bed mixed medical/surgical paediatric intensive care unit. All children

AIM: Bronchiolitis is the most common lower respiratory tract disorder in infants aged less than 12 months, and research has demonstrated that there is substantial variation in practice patterns despite treatment being well defined. In order to align and improve the consistency of the management of bronchiolitis, an evidence-based guideline was developed for the Australasian population. METHODS: The guideline development committee included representation from emergency and paediatric specialty medical and nursing personnel in addition to geographical representation across Australia and New Zealand - rural, remote and metropolitan. Formulation of the guideline included identification of population, intervention, comparator, outcomes and time questions and was associated with an extensive literature search from 2000 to 2015. Evidence was summarised and graded using the National Health and Medical Research Council and Grading of Recommendations Assessment, Development and Evaluation methodology, and consensus within the guideline group was sought using nominal group technique principles to formulate the clinical practice recommendations. The guideline was reviewed and endorsed by key paediatric health bodies. RESULTS: The guideline consists of a usable clinical interface for bedside functionality supported by evidence summary and tables. The Grading of Recommendations Assessment, Development and Evaluation and National Health and Medical Research Council processes provided a systematic and transparent process to review and assess the literature, resulting in a guideline that is relevant to the management of bronchiolitis in the Australasian setting. CONCLUSION: This is the first robust Australasian acute paediatric guideline and provides clear guidance for the management of the vast majority of patients seen in Australasian emergency departments and general paediatric wards with bronchiolitis.

Item does not contain fulltext OBJECTIVES: Duplicative institutional review board/research ethics committee review for multicenter studies may impose administrative burdens and inefficiencies affecting study implementation and quality. Understanding variability in site-specific institutional review board/research ethics committee assessment and barriers to using a single review committee (an increasingly proposed solution) can inform a more efficient process. We provide needed data about the regulatory oversight process for the Sepsis PRevalence, OUtcomes, and Therapies multicenter point prevalence study. DESIGN: Survey. SETTING: Sites invited to participate in Sepsis PRevalence, OUtcomes, and Therapies. SUBJECTS: Investigators at sites that expressed interest and/or participated in Sepsis PRevalence, OUtcomes, and Therapies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using an electronic survey, we collected data about 1) logistics of protocol submission, 2) institutional review board/research ethics committee requested modifications, and 3) use of a single institutional review board (for U.S. sites). We collected surveys from 104 of 167 sites (62%). Of the 97 sites that submitted the protocol for institutional review board/research ethics committee review, 34% conducted full board review, 54% expedited review, and 4% considered the study exempt. Time to institutional review board/research ethics committee approval required a median of 34 (range 3-186) days, which took longer at sites that required protocol modifications (median [interquartile range] 50 d [35-131 d] vs 32 d [14-54 d)]; p = 0.02). Enrollment was delayed at eight sites due to prolonged (> 50 d) time to approval. Of 49 U.S. sites, 43% considered using a single institutional review board, but only 18% utilized this option. Time to final approval for U.S. sites using the single institutional review board was 62 days (interquartile range, 34-70 d) compared with 34 days (interquartile range, 15-54 d) for nonsingle institutional review board sites (p = 0.16). CONCLUSIONS: Variability in regulatory oversight was evident for this minimal-risk observational research study, most notably in the category of type of review conducted. Duplicative review prolonged time to protocol approval at some sites. Use of a single institutional review board for U.S. sites was rare and did not improve efficiency of protocol approval. Suggestions for minimizing these challenges are provided.

The definitions of sepsis and septic shock have recently been revised in adults, but contemporary data are needed to inform similar approaches in children.Multicenter cohort study including children16 years admitted with sepsis or septic shock to ICUs in Australia and New Zealand in the period 2012-2015. We assessed septic shock criteria at ICU admission to define sepsis severity, using 30-day mortality as outcome. Through multivariable logistic regression, a pediatric sepsis score was derived using variables available within 60 min of ICU admission.Of 42,523 pediatric admissions, 4403 children were admitted with invasive infection, including 1697 diagnosed as having sepsis/septic shock on admission. Mortality was 8.5% (144/1697) and 50.7% of deaths occurred within 48 h of admission. The presence of septic shock as defined by the 2005 consensus was sensitive but not specific in predicting mortality (AUC = 0.69; 95% CI 0.65-0.72). Combinations of hypotension, vasopressor therapy, and lactate2 mmol/l discriminated poorly (AUC0.60). Multivariate models showed that oxygenation markers, ventilatory support, hypotension, cardiac arrest, serum lactate, pupil responsiveness, and immunosuppression were the best-performing predictors (0.843; 0.811-0.875). We derived a pediatric sepsis score (0.817; 0.779-0.855), and every one-point increase was associated with a 28.5% (23.8-33.2%) increase in the odds of death. Children with a score ≥6 had 19.8% mortality and accounted for 74.3% of deaths. The sepsis score performed comparably when applied to all children admitted with invasive infection (0.810; 0.781-0.840).We observed mortality patterns specific to pediatric sepsis that support the need for specialized definitions of sepsis severity in children. We demonstrated the importance of lactate, cardiovascular, and respiratory derangements at ICU admission for the identification of children with substantially higher risk of sepsis mortality.

IntroductionAcute hypoxaemic respiratory failure (AHRF) in children is the most frequent reason for non-elective hospital admission. During the initial phase, AHRF is a clinical syndrome defined for the purpose of this study by an oxygen requirement and caused by pneumonia, lower respiratory tract infections, asthma or bronchiolitis. Up to 20% of these children with AHRF can rapidly deteriorate requiring non-invasive or invasive ventilation. Nasal high-flow (NHF) therapy has been used by clinicians for oxygen therapy outside intensive care settings to prevent escalation of care. A recent randomised trial in infants with bronchiolitis has shown that NHF therapy reduces the need to escalate therapy. No similar data is available in the older children presenting with AHRF. In this study we aim to investigate in children aged 1 to 4 years presenting with AHRF if early NHF therapy compared with standard-oxygen therapy reduces hospital length of stay and if this is cost-effective compared with standard treatment.Methods and analysisThe study design is an open-labelled randomised multicentre trial comparing early NHF and standard-oxygen therapy and will be stratified by sites and into obstructive and non-obstructive groups. Children aged 1 to 4 years (n=1512) presenting with AHRF to one of the participating emergency departments will be randomly allocated to NHF or standard-oxygen therapy once the eligibility criteria have been met (oxygen requirement with transcutaneous saturation Ethics and disseminationEthics approval has been obtained in Australia (HREC/15/QRCH/159) and New Zealand (HDEC 17/NTA/135). The trial commenced recruitment in December 2017. The study findings will be submitted for publication in a peer-reviewed journal and presented at relevant conferences. Authorship of all publications will be decided by mutual consensus of the research team.Trial registration numberACTRN12618000210279

Aim: Nasal high-flow oxygen therapy is increasingly used in infants for supportive respiratory therapy in bronchiolitis. It is unclear whether enteral hydration is safe in children receiving high-flow. Methods: We performed a planned secondary analysis of a multi-centre, randomised controlled trial of infants aged

Objective To assess the effect of nasal high flow (NHF) cannula on end‐expiratory level (EEL), continuous distending pressure (CDP) and regional ventilation distribution in preterm infants. Design A prospective observational clinical study with randomly applied NHF rates. Patients and Setting Preterm infants requiring continuous positive airway pressure (CPAP) respiratory support in a Neonatal Intensive Care Unit. Interventions Infants were measured on randomly applied flow rates at 2, 4, and 6 L/min of NHF and compared with bubble CPAP. Measurements and Results Regional ventilation distribution and EEL were measured using electrical impedance tomography (EIT) and respiratory inductance plethysmography (RIP) in 24 preterm infants (31.19 ± 1.17 weeks corrected age). Changes in CDP were measured from the esophagus via the nasogastric tube. Physiological variables were also recorded. There were no differences in ventilation distribution, EEL or CDP between CPAP and NHF (P > .05). However, the physiological variables of FiO2 (P = .01) and SpO2/FiO2 (P

Background: High-flow oxygen-therapy is increasingly used in children with acute hypoxic respiratory failure (AHRF), despite limited high-quality evidence of efficacy outside intensive care units. Methods: An open labelled RCT feasibility design was used in emergency departments and general wards of two tertiary children's hospitals. Over a period of 1-year, children aged 0-16 years with AHRF were randomised (1:1) to either high-flow or standard-oxygen. Children on the standard-oxygen could receive rescue high-flow in the general wards if their conditions met treatment failure criteria. The primary efficiency-endpoints were feasibility, recruitment rates and safety followed by the efficacy-endpoints measuring the proportion escalation of care. We measured the duration of hospital stay, duration of oxygen therapy and rates of ICU admission. Findings: Of 563 randomised, 283 received high-flow and 280 standard-oxygen with no adverse events. The proportion of children receiving escalation of care was 11.7% (32/283 children) on the high-flow and 18.1% (50/280 infants) on standard-oxygen (risk difference -6.4 percentage points; 95% CI -12.4%, -0.5%; p=0.04). In children with obstructive airway disease 9.7% on high-flow and 17.4% on standard-oxygen required escalation (risk difference -7.7% percentage points; 95% CI -14.3%, -1.1%; p=0.03), whereas in children with non-obstructive disease no difference was observed. No difference in length of hospital stay was observed. 40% of children who failed standard-oxygen responded to rescue high-flow. Interpretation: High-flow outside ICU appears to be safe in children with AHRF and the required proportion of escalation was lower compared to standard-oxygen. The trial design can be applied in a future large RCT. Trial Registration: The study protocol was registered with the Australian and New Zealand Clinical Trials Registry. (ACTRN12615001305516). Funding Statement: The study was supported by a grant provided by Thrasher Research Fund and a project grant provided by the National Health and Medical Research Council. The high-flow equipment and consumables for both trial sites were donated by Fisher & Paykel Healthcare, which had no involvement in the design and conduct of the trial, the analysis of the data, or in the preparation of the manuscript. Declaration of Interests: DF and AS report financial support for travel and accommodation provided by Fisher&Paykel Healthcare, Auckland, New Zealand Ethics Approval Statement: The study was approved by Children’s Health Queensland Human Research Ethics Committee (HREC/15/QRCH/159) and the authors used a consent to continue process.

Objective To investigate the relationship between applied flows of nasal high flow (NHF) and physiological outcomes and work of breathing (WOB), to identify an optimal delivery flow which results in reduced WOB in preterm infants. Design A prospective observational clinical study with randomly applied NHF rates. Patients and Setting Preterm infants within 72 hours of commencement of NHF respiratory support. Interventions Infants were initially placed on 8 L/min of NHF and flows of 2, 4, and 6 L/min were then applied in random order. Measurements and Results WOB was measured using transcutaneous electromyography and respiratory inductance plethysmography. Physiological variables were also recorded. Measurements taken 10 minutes after each flow change were compared with 8 L/min. Sixteen infants with a median gestational age of 28 (range 24-31) weeks and postnatal age of 14 (2-55) days were included in the study. The median flow rate before the study was 6 (4-8) L/min and a fraction of inspired oxygen (FiO2) was 0.21 (0.21-0.26). Changes in flow resulted in changes in activity in the front diaphragm (P = .027) and intercostals (P = .034). The electrical activity of the front diaphragm at 8 L/min was significantly lower than that at 2 L/min (P = .016). Respiratory rate was lowest at 6 L/min (P = .002) and SpO2/FiO2 was highest at 8 L/min (P