Resuscitation With Early Adrenaline Infusion for Children With Septic Shock: A Randomized Pilot Trial.

OBJECTIVES: In children with septic shock, guidelines recommend resuscitation with 40-60 mL/kg of fluid boluses, yet there is a lack of evidence to support this practice. We aimed to determine the feasibility of a randomized trial comparing early adrenaline infusion with standard fluid resuscitation in children with septic shock. DESIGN: Open-label parallel randomized controlled, multicenter pilot study. The primary end point was feasibility; the exploratory clinical endpoint was survival free of organ dysfunction by 28 days. SETTING: Four pediatric Emergency Departments in Queensland, Australia. PATIENTS: Children between 28 days and 18 years old with septic shock. INTERVENTIONS: Patients were assigned 1:1 to receive a continuous adrenaline infusion after 20 mL/kg fluid bolus resuscitation (n = 17), or standard care fluid resuscitation defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to inotrope commencement (n = 23). MEASUREMENTS AND MAIN RESULTS: Forty of 58 eligible patients (69%) were consented with a median age of 3.7 years (interquartile range [IQR], 0.9-12.1 yr). The median time from randomization to inotropes was 16 minutes (IQR, 12-26 min) in the intervention group, and 49 minutes (IQR, 29-63 min) in the standard care group. The median amount of fluid delivered during the first 24 hours was 0 mL/kg (IQR, 0-10.0 mL/kg) in the intervention group, and 20.0 mL/kg (14.6-28.6 mL/kg) in the standard group (difference, -20.0; 95% CI, -28.0 to -12.0). The number of days alive and free of organ dysfunction did not differ between the intervention and standard care groups, with a median of 27 days (IQR, 26-27 d) versus 26 days (IQR, 25-27 d). There were no adverse events reported associated with the intervention. CONCLUSIONS: In children with septic shock, a protocol comparing early administration of adrenaline versus standard care achieved separation between the study arms in relation to inotrope and fluid bolus use.

Knowledge translation following the implementation of a state-wide Paediatric Sepsis Pathway in the emergency department- a multi-centre survey study.

BACKGROUND: Several health care systems internationally have implemented protocolised sepsis recognition and treatment bundles for children to improve outcomes, as recommended by the Surviving Sepsis Campaign. Successful implementation of clinical pathways is challenging and dependent on nurse engagement. There is limited data on knowledge translation during implementation of sepsis quality improvement programs. METHODS: This cross-sectional, multicentre observational survey study evaluated knowledge and perceptions of Emergency Department nurses in relation to the recognition, escalation and management of paediatric sepsis following implementation of a sepsis pathway. The study was conducted between September 2019 and March 2020 across 14 Emergency Departments in Queensland, Australia. The primary outcome was a sepsis knowledge score. An exploratory factor analysis was conducted to identify factors impacting nurses' perceptions of recognition, escalation and management of paediatric sepsis and their association with knowledge. Using a logistic mixed effects model we explored associations between knowledge, identified factors and other clinical, demographic and hospital site variables. RESULTS: In total, 676 nurses responded to the survey and 534 were included in the analysis. The median knowledge score was 57.1% (IQR = 46.7-66.7), with considerable variation observed between sites. The exploratory factor analysis identified five factors contributing to paediatric sepsis recognition, escalation and management, categorised as 1) knowledge and beliefs, 2) social influences, 3) beliefs about capability and skills delivering treatment, 4) beliefs about capability and behaviour and 5) environmental context. Nurses reported strong agreement with statements measuring four of the five factors, responding lowest to the factor pertaining to capability and skills delivering treatment for paediatric sepsis. The factors knowledge and beliefs, capability and skills, and environmental context were positively associated with a higher knowledge score. Years of paediatric experience and dedicated nurse funding for the sepsis quality improvement initiative were also associated with a higher knowledge score. CONCLUSION: Translation of evidence to practice such as successful implementation of a sepsis care bundle, relies on effective education of staff and sustained uptake of protocols in daily practice. Our survey findings identify key elements associated with enhanced knowledge including dedicated funding for hospitals to target paediatric sepsis quality improvement projects.

Cross-sectional study of a United Kingdom cohort of neonatal vein of galen malformation.

OBJECTIVE: Describe the course and outcomes in a UK national cohort of neonates with vein of Galen malformation identified before 28 days of life. METHODS: Neonates with angiographically confirmed vein of Galen malformation presenting to 1 of 2 UK treatment centers (2006-2016) were included; those surviving were invited to participate in neurocognitive assessment. Results in each domain were dichotomized into "good" and "poor" categories. Cross-sectional and angiographic brain imaging studies were systematically interrogated. Logistic regression was used to explore potential outcome predictors. RESULTS: Of 85 children with neonatal vein of Galen malformation, 51 had survived. Thirty-four participated in neurocognitive assessment. Outcomes were approximately evenly split between "good" and "poor" categories across all domains, namely, neurological status, general cognition, neuromotor skills, adaptive behavior, and emotional and behavioral development. Important predictors of poor cognitive outcome were initial Bicêtre score ≤ 12 and presence of brain injury, specifically white matter injury, on initial imaging; in multivariate analysis, only Bicêtre score ≤ 12 remained significant. INTERPRETATION: Despite modern supportive and endovascular treatment, more than one-third of unselected newborns with vein of Galen malformation did not survive. Outcome was good in around half of survivors. The importance of white matter injury suggests that abnormalities of venous as well as arterial circulation are important in the pathophysiology of brain injury. Ann Neurol 2018;84:547-555.

FIRST-line support for Assistance in Breathing in Children (FIRST-ABC): a multicentre pilot randomised controlled trial of high-flow nasal cannula therapy versus continuous positive airway pressure in paediatric critical care.

BACKGROUND: Although high-flow nasal cannula therapy (HFNC) has become a popular mode of non-invasive respiratory support (NRS) in critically ill children, there are no randomised controlled trials (RCTs) comparing it with continuous positive airway pressure (CPAP). We performed a pilot RCT to explore the feasibility, and inform the design and conduct, of a future large pragmatic RCT comparing HFNC and CPAP in paediatric critical care. METHODS: In this multi-centre pilot RCT, eligible patients were recruited to either Group A (step-up NRS) or Group B (step-down NRS). Participants were randomised (1:1) using sealed opaque envelopes to either CPAP or HFNC as their first-line mode of NRS. Consent was sought after randomisation in emergency situations. The primary study outcomes were related to feasibility (number of eligible patients in each group, proportion of eligible patients randomised, consent rate, and measures of adherence to study algorithms). Data were collected on safety and a range of patient outcomes in order to inform the choice of a primary outcome measure for the future RCT. RESULTS: Overall, 121/254 eligible patients (47.6%) were randomised (Group A 60%, Group B 44.2%) over a 10-month period (recruitment rate for Group A, 1 patient/site/month; Group B, 2.8 patients/site/month). In Group A, consent was obtained in 29/33 parents/guardians approached (87.9%), while in Group B 84/118 consented (71.2%). Intention-to-treat analysis included 113 patients (HFNC 59, CPAP 54). Most reported adverse events were mild/moderate (HFNC 8/59, CPAP 9/54). More patients switched treatment from HFNC to CPAP (Group A: 7/16, 44%; Group B: 9/43, 21%) than from CPAP to HFNC (Group A: 3/13, 23%; Group B: 5/41, 12%). Intubation occurred within 72 h in 15/59 (25.4%) of HFNC patients and 10/54 (18.5%) of CPAP patients (p = 0.38). HFNC patients experienced fewer ventilator-free days at day 28 (Group A: 19.6 vs. 23.5; Group B: 21.8 vs. 22.2). CONCLUSIONS: Our pilot trial confirms that, following minor changes to consent procedures and treatment algorithms, it is feasible to conduct a large national RCT of non-invasive respiratory support in the paediatric critical care setting in both step-up and step-down NRS patients. TRIAL REGISTRATION: clinicaltrials.gov, NCT02612415 . Registered on 23 November 2015.

Can capillary microsampling facilitate a clinical pharmacokinetics study of cefazolin in critically ill children?

Aim: Pharmacokinetic studies in children are limited, in part due to challenges in blood sampling. We compare the use of capillary microsampling and conventional sampling techniques in pediatric patients to show results that can be used in the pharmacokinetic analysis of Cefazolin.Patients & Methods: Paired blood samples (n = 48) were collected from 12 patients (median age/weight 49 months/18 kg).Results: The United States Federal Drug Administration incurred sample reanalysis acceptance criteria was used and identified 79% of paired samples achieved a difference of less than 20% in magnitude with a capillary microsampling bias of -10% (SD 20%). With exclusion of PK outliers, this rose to 88%.Conclusion: Capillary microsampling is reliable, meets acceptance criteria and can be used in pharmacokinetic studies.ACTRN: 12618001469202.

What is this article about? This study assesses a novel method of blood sample collection (capillary microsampling) for the analysis of a common antibiotic, cefazolin. In this study, we compare the results from samples collected using this method to blood tests taken in the traditional way.Capillary microsampling collects a very small volume of blood (about a drop of blood or 0.05 ml) taken from a skin prick and collected in a capillary tube. Traditional blood sampling collects a larger volume of blood (typically from 1 to 3 ml) taken from an artery or a vein. In this study, the patients (10 male and 2 female) had a mean age of 49 months and a mean weight of 18 kg. The amount of cefazolin in the blood samples were analyzed using the same methodology and results compared with assess the variability and reliability of the capillary microsampling method.What were the results? The results showed that difference of the two sample types is within the accepted criteria of the United States Federal Drug Administration and the European Medicines Agency, meaning the results are reliable.What do the results of the study mean? Blood samples for cefazolin can be small and easily obtained from a skin prick as a capillary microsample and can give reliable results. This greatly aids the ability to study the metabolism of cefazolin in children, particularly those that are not able to give a large amount of blood.

Validation of a paediatric sepsis screening tool to identify children with sepsis in the emergency department: a statewide prospective cohort study in Queensland, Australia.

OBJECTIVE: The Surviving Sepsis Campaign guidelines recommend the implementation of systematic screening for sepsis. We aimed to validate a paediatric sepsis screening tool and derive a simplified screening tool. DESIGN: Prospective multicentre study conducted between August 2018 and December 2019. We assessed the performance of the paediatric sepsis screening tool using stepwise multiple logistic regression analyses with 10-fold cross-validation and evaluated the final model at defined risk thresholds. SETTING: Twelve emergency departments (EDs) in Queensland, Australia. PARTICIPANTS: 3473 children screened for sepsis, of which 523 (15.1%) were diagnosed with sepsis. INTERVENTIONS: A 32-item paediatric sepsis screening tool including rapidly available information from triage, risk factors and targeted physical examination. PRIMARY OUTCOME MEASURE: Senior medical officer-diagnosed sepsis combined with the administration of intravenous antibiotics in the ED. RESULTS: The 32-item paediatric sepsis screening tool had good predictive performance (area under the receiver operating characteristic curve (AUC) 0.80, 95% CI 0.78 to 0.82). A simplified tool containing 16 of 32 criteria had comparable performance and retained an AUC of 0.80 (95% CI 0.78 to 0.82). To reach a sensitivity of 90% (95% CI 87% to 92%), the final model achieved a specificity of 51% (95% CI 49% to 53%). Sensitivity analyses using the outcomes of sepsis-associated organ dysfunction (AUC 0.84, 95% CI 0.81 to 0.87) and septic shock (AUC 0.84, 95% CI 0.81 to 0.88) confirmed the main results. CONCLUSIONS: A simplified paediatric sepsis screening tool performed well to identify children with sepsis in the ED. Implementation of sepsis screening tools may improve the timely recognition and treatment of sepsis.

Patient and economic impact of implementing a paediatric sepsis pathway in emergency departments in Queensland, Australia.

We examined systems-level costs before and after the implementation of an emergency department paediatric sepsis screening, recognition and treatment pathway. Aggregated hospital admissions for all children aged < 18y with a diagnosis code of sepsis upon admission in Queensland, Australia were compared for 16 participating and 32 non-participating hospitals before and after pathway implementation. Monte Carlo simulation was used to generate uncertainty intervals. Policy impacts were estimated using difference-in-difference analysis comparing observed and expected results. We compared 1055 patient episodes before (77.6% in-pathway) and 1504 after (80.5% in-pathway) implementation. Reductions were likely for non-intensive length of stay (- 20.8 h [- 36.1, - 8.0]) but not intensive care (-9.4 h [- 24.4, 5.0]). Non-pathway utilisation was likely unchanged for interhospital transfers (+ 3.2% [- 5.0%, 11.4%]), non-intensive (- 4.5 h [- 19.0, 9.8]) and intensive (+ 7.7 h, [- 20.9, 37.7]) care length of stay. After difference-in-difference adjustment, estimated savings were 596 [277, 942] non-intensive and 172 [148, 222] intensive care days. The program was cost-saving in 63.4% of simulations, with a mean value of $97,019 [- $857,273, $1,654,925] over 24 months. A paediatric sepsis pathway in Queensland emergency departments was associated with potential reductions in hospital utilisation and costs.

Impact of 1-hour and 3-hour sepsis time bundles on patient outcomes and antimicrobial use: A before and after cohort study.

BACKGROUND: Sepsis bundles, promulgated by Surviving Sepsis Campaign have not been widely adopted because of variability in sepsis identification strategies, implementation challenges, concerns about excess antimicrobial use, and limited evidence of benefit. METHODS: A 1-hour septic shock and a 3-hour sepsis bundle were implemented using a Breakthrough Series Collaborative in 14 public hospitals in Queensland, Australia. A before (baseline) and after (post-intervention) study evaluated its impact on outcomes and antimicrobial prescription in patients with confirmed bacteremia and sepsis. FINDINGS: Between 01 July 2017 to 31 March 2020, of 6976 adults presenting to the Emergency Departments and had a blood culture taken, 1802 patients (732 baseline, 1070 post-intervention) met inclusion criteria. Time to antibiotics in 1-hour 73.7% vs 85.1% (OR 1.9 [95%CI 1.1-3.6]) and the 3-hour bundle compliance (48.2% to 63.3%, OR 1.7, [95%CI 1.4 to 2.1]) improved post-intervention, accompanied by a significant reduction in Intensive Care Unit (ICU) admission rates (26.5% vs 17.5% (OR 0.5, [95%CI 0.4 to 0.7]). There were no significant differences in-hospital and 30-day post discharge mortality between the two phases. In a post-hoc analysis of the post-intervention phase, sepsis pathway compliance was associated with lower in-hospital mortality (9.7% vs 14.9%, OR 0.6, 95%CI 0.4 to 0.8). The proportions of appropriate antimicrobial prescription at baseline and post-intervention respectively were 55.4% vs 64.1%, (OR 1.4 [95%CI 0.9 to 2.1]). INTERPRETATION: Implementing 1-hour and 3-hour sepsis bundles for patients presenting with bacteremia resulted in improved bundle compliance and a reduced need for ICU admission without adversely influencing antimicrobial prescription.

Effectiveness-implementation hybrid-2 randomised trial of a collaborative Shared Care Model for Detecting Neurodevelopmental Impairments after Critical Illness in Young Children (DAISY): pilot study protocol.

INTRODUCTION: In Australia, while paediatric intensive care unit (PICU) mortality has dropped to 2.2%, one in three survivors experience long-term neurodevelopmental impairment, limiting their life-course opportunities. Unlike other high-risk paediatric populations, standardised routine neurodevelopmental follow-up of PICU survivors is rare, and there is limited knowledge regarding the best methods. The present study intends to pilot a combined multidisciplinary, online screening platform and general practitioner (GP) shared care neurodevelopmental follow-up model to determine feasibility of a larger, future study. We will also assess the difference between neurodevelopmental vulnerability and parental stress in two intervention groups and the impact of child, parent, sociodemographic and illness/treatment risk factors on child and parent outcomes. METHODS AND ANALYSIS: Single-centre randomised effectiveness-implementation (hybrid-2 design) pilot trial for parents of children aged ≥2 months and <4 years discharged from PICU after critical illness or injury. One intervention group will receive 6 months of collaborative shared care follow-up with GPs (supported by online outcome monitoring), and the other will be offered self-directed screening and education about post-intensive care syndrome and child development. Participants will be followed up at 1, 3 and 6 months post-PICU discharge. The primary outcome is feasibility. Secondary outcomes include neurodevelopmental vulnerability and parental stress. An implementation evaluation will analyse barriers to and facilitators of the intervention. ETHICS AND DISSEMINATION: The study is expected to lead to a full trial, which will provide much-needed guidance about the clinical effectiveness and implementation of follow-up models of care for children after critical illness or injury. The Children's Health Queensland Human Research Ethics Committee approved this study. Dissemination of the outcomes of the study is expected via publication in a peer-reviewed journal, presentation at relevant conferences, and via social media, podcast presentations and open-access medical education resources. REGISTRATION DETAILS: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as 'Pilot testing of a collaborative Shared Care Model for Detecting Neurodevelopmental Impairments after Critical Illness in Young Children' (the DAISY Pilot Study). TRIAL REGISTRATION NUMBER: ACTRN12621000799853.

Chemical, Biological, Radiological, or Nuclear Response in Queensland Emergency Services: A Multisite Study.

A disaster overwhelms the normal operating capacity of a health service. Minimal research exists regarding Australian hospitals' capacity to respond to chemical, biological, radiological, or nuclear (CBRN) disasters. This article, and the research supporting it, begins to fill that research gap. We conducted a descriptive quantitative study with 5 tertiary hospitals and 1 rural hospital in Queensland, Australia. The study population was the hospitals' clinical leaders for disaster preparedness. The 25-item survey consisted of questions relating to each hospital's current response capacity, physical surge capacity, and human surge capacity in response to a CBRN disaster. Data were analyzed using descriptive statistics. The survey data indicated that over the previous 12 months, each site reached operational capacity on average 66 times and that capacity to respond and create additional emergency, intensive care, or surgical beds varied greatly across the sites. In the previous 12 months, only 2 sites reported undertaking specific hospital-wide training to manage a CBRN disaster, and 3 sites reported having suitable personal protective equipment required for hazardous materials. There was a noted shortfall in all the hospitals' capacity to respond to a radiological disaster in particular. Queensland hospitals are crucial to CBRN disaster response, and they have areas for improvement in their response and capacity to surge when compared with international preparedness benchmarks. CBRN-focused education and training must be prioritized using evidence-based training approaches to better prepare hospitals to respond following a disaster event.

Does triage to critical care during a pandemic necessarily result in more survivors?

OBJECTIVE: The 2009 H1N1 pandemic reinforced the need for a planned response to increased demand for critical care. Triage protocols have been proposed incorporating the exclusion of specified subgroups of patients from critical care. There have been no studies that explore the theoretical underpinning of triage at referral, and it is not clear under what circumstances triage would confer the intended benefits. We sought to explore the mechanisms whereby triage could lead to fewer deaths across a critical care population in the context of a pandemic. DESIGN: We constructed a mathematical model based on queuing theory to compare the estimated short-term survival achieved by using a critical care service with and without triage at referral. Illustrative scenarios concerning a hypothetical critical care population were constructed to explore the roles of length of stay and critical care survival in determining the impact of triage and to identify "tipping points" of demand at which triage would result in more survivors. SETTING: Not applicable as this was a data-free mathematical modeling exercise. MAIN RESULTS: We identified circumstances in which triage would be expected to result in more survivors and circumstances in which it would not. In some scenarios, excluding patient groups solely on the basis of anticipated length of stay could be effective due to a more efficient use of critical care bed days. CONCLUSIONS: The impact of triage is dependent on the level of demand and on the scale of achievable differences between included and excluded groups in terms of anticipated length of stay and critical care survival. It cannot be assumed that triage can or will result in fewer deaths. It should be remembered that there are considerations other than population-level short-term survival when determining the objectives of triage and its ethical implementation.

Designing Support Structures Post Sepsis in Children: Perspectives of the Queensland Paediatric Sepsis Program.

Introduction: Paediatric post sepsis syndrome is poorly defined and causes physical, neurocognitive, psychosocial morbidity, and family dysfunction. Families of sepsis survivors report unmet needs during care. Worldwide, the provision of post sepsis care is in its infancy with limited evidence to design clinical support pathways. Perspective: The Queensland Paediatric Sepsis Program (QPSP) developed a family support structure (FSS) to improve care during all stages of childhood sepsis. It was designed in partnership with consumers guided by information from consumers and it is partly delivered by consumers. Key areas include online, multimodal education for families and the ability to connect with other families affected by sepsis. The FSS is delivered by a multidisciplinary team (MDT) acting with clinicians local to the child. Families can join the FSS registry at any stage of their sepsis journey which connects them to our MDT team and opens opportunities to participate in future research and other initiatives. Improving public awareness is a critical outcome for our consumers and they have co-designed media and digital campaigns. Discussion: The ideal FSS for post sepsis syndrome management is a clinical pathway designed in partnership with consumers of interventions proven to improve outcomes from sepsis that meets their requirements. The QPSP FSS is novel as it is co-designed with, and partly delivered by, consumers with interventions aimed to improve the entire spectrum of morbidities suffered by survivors and their families, not just physical sequelae. Evaluation is embedded in the program and outcomes will guide evolution of the FSS.

Queensland Pediatric Sepsis Breakthrough Collaborative: Multicenter Observational Study to Evaluate the Implementation of a Pediatric Sepsis Pathway Within the Emergency Department.

OBJECTIVES: To evaluate the implementation of a pediatric sepsis pathway in the emergency department as part of a statewide quality improvement initiative in Queensland, Australia. DESIGN: Multicenter observational prospective cohort study. SETTING: Twelve emergency departments in Queensland, Australia. PATIENTS: Children less than 18 years evaluated for sepsis in the emergency department. Patients with signs of shock, nonshocked patients with signs of organ dysfunction, and patients without organ dysfunction were assessed. INTERVENTIONS: Introduction of a pediatric sepsis pathway. MEASUREMENTS AND MAIN RESULTS: Process measures included compliance with and timeliness of the sepsis bundle, and bundle components. Process and outcome measures of children admitted to the ICU with sepsis were compared with a baseline cohort. Five-hundred twenty-three children were treated for sepsis including 291 with suspected sepsis without organ dysfunction, 86 with sepsis-associated organ dysfunction, and 146 with septic shock. Twenty-four (5%) were admitted to ICU, and three (1%) died. The median time from sepsis recognition to bundle commencement for children with septic shock was 56 minutes (interquartile range, 36-99 min) and 47 minutes (interquartile range, 34-76 min) for children with sepsis-associated organ dysfunction without shock; 30% (n = 44) and 40% (n = 34), respectively, received the bundle within the target timeframe. In comparison with the baseline ICU cohort, bundle compliance improved from 27% (n = 45) to 58% (n = 14) within 60 minutes of recognition and from 47% (n = 78/167) to 75% (n = 18) within 180 minutes of recognition (p < 0.05). CONCLUSIONS: Our findings on the introduction of protocolized care in a large and diverse state demonstrate ongoing variability in sepsis bundle compliance. Although bundle compliance improved compared with a baseline cohort, continued efforts are required to ensure guideline targets and sustainability are achieved.

WITHDRAWN. Inhaled steroids for neonatal chronic lung disease.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic disorder associated with prematurity. Systemic steroids induce at least a temporary improvement in respiratory function, but are associated with adverse side effects. Inhaled steroids have fewer side effects. OBJECTIVES: To determine if inhaled corticosteroids are effective in alleviating the morbidity of bronchopulmonary dysplasia (BPD) compared to placebo. SEARCH STRATEGY: We identified randomised, controlled trials (RCT) within the Cochrane Database, references from retrieved trials, hand searches of journals and contact with pharmaceutical companies and experts in this field. SELECTION CRITERIA: Only randomised controlled trials involving infants with chronic lung disease of prematurity and treated with inhaled steroids versus placebo were included. Patients receiving systemic corticosteroids were excluded. Co-interventions included antenatal systemic steroids, routine neonatal intensive care, ventilatory support, surfactant replacement therapy, diuretics and bronchodilators. DATA COLLECTION AND ANALYSIS: Four of the seven included trials were of good methodological quality. There were five parallel-group trials in ventilated infants. These were comparable in terms of population, co-interventions and need for increased inspired oxygen concentration. They differed in terms of type, dose and duration (7-28 days) of inhaled steroids. Two cross-over trials were performed in non-ventilated patients. An update search was conducted in June 2002, which identified an additional excluded study. MAIN RESULTS: The inability to extubate during treatment was markedly reduced in infants treated with inhaled steroids; Peto Odds Ratio (OR) 0.12, 95% Confidence Interval (CI) 0.03 to 0.43. There was heterogeneity in this finding, however, with one study that contributed 30% of the total number of patients reporting no successful extubations in either treatment arm over one week. The risk of sepsis appeared similar between the two groups (N=3, OR=0.72, 95%CI: 0.21 to 2.43). The small number of trials precluded analysis to examine the effect of differences in drug, duration of therapy, delivery system, co-interventions, and disease severity. Reduced oxygen requirements were reported in one of the two trials performed in non-ventilated infants, but inadequate data reporting precluded pooling of data. AUTHORS' CONCLUSIONS: In ventilated infants with BPD, inhaled steroids administered for 1 to 4 weeks improved the rate of extubation with no apparent increase in the risk of sepsis. No firm conclusion could be derived with regard to the efficacy of inhaled steroids in non-ventilated infants.

ANZICS guiding principles for complex decision making during the COVID-19 pandemic.

The global 2019 coronavirus disease (COVID-19) pandemic has led to major challenges in clinical decision making when the demand for intensive care exceeds local capacity. In order to promote consistent, transparent, objective and ethical decision making, the Australian and New Zealand Intensive Care Society (ANZICS) formed a committee to urgently develop guidelines outlining key principles that should be utilised during the pandemic. This guidance is intended to support the practice of intensive care specialists during the COVID-19 pandemic and to promote the development of local admission policies that should be endorsed by health care organisations and relevant local authorities.

Effects of blood sample volume on hematocrit in critically ill children and neonates.

BACKGROUND: There are no studies correlating the volume of blood taken from children and hematocrit (Hct) stability, relating those changes to duration of stay, severity of illness or weight. Earlier studies in neonates suggest that repeated sampling results in a drop in Hct. AIM: To characterize the changes in Hct in children of all ages admitted to intensive care over a 5-day period following routine blood volume sampling. METHODS: We undertook an open prospective observational study. Eligible children were recruited sequentially and data recorded for 5 days following admission. The bedside nurse recorded the daily volume of blood samples taken and transfusions given. Daily Hct was noted from the routine full blood count. The relationship between changes in Hct and blood sample volume and transfusion requirement was studied. RESULTS: There were no differences in mean Hct on admission at end of the study (P = 0.69, n = 30) nor in the median blood volume sampled between transfused and nontransfused groups (7.5 ml.kg(-1) vs 7.9 ml.kg(-1), P = 0.88). The largest blood sample volumes were taken on admission and from the smallest patients. CONCLUSION: We have quantitated the change in Hct and size of blood volume taken for routine laboratory studies. We suggest that children can tolerate 0.25 ml.kg(-1).day(-1) blood sampling without a fall in Hct and sampling can be tailored to the individual child according to the admission Hct.

Characteristics and mortality risk of children with life-threatening influenza infection admitted to paediatric intensive care in England 2003-2015.

BACKGROUND: Information is lacking about the severity of complications in children with influenza admitted to paediatric intensive care units (PICU) in the UK. In this study, we report risk factors for mortality, invasive ventilation and use of vasoactive drugs for children admitted to PICU with influenza. METHODS: We evaluated all admissions to PICUs in England for resident children with a recorded influenza diagnosis between September 2003 and March 2015. We used the Paediatric Intensive Care Audit Network (PICANet) database linked to hospital admission records to identify influenza cases, and high-risk comorbidities among admitted children. We used mixed effects logistic regression models to determine risk factors for mortality, use of invasive ventilation and vasoactive drugs. RESULTS: We identified 1961 influenza-related PICU admissions in 1778 children. Children with high-risk conditions accounted for 1540 admissions (78.5%). The odds of mortality were significantly higher for girls than boys (adjusted odds ratio 1.91; 95% confidence interval 1.31, 2.79), children from Asian/Asian British (2.70; 1.74, 4.20) or other minority ethnic groups (3.95; 1.65, 9.42) compared to white British children, and significantly increased before and during the A(H1N1)pdm 2009 pandemic compared to the post-pandemic period. Children required invasive ventilation in 1588 admissions (81.0%), and received vasoactive drugs in 586 admissions (29.9%). CONCLUSIONS: Nearly four fifths of influenza-related PICU admissions occurred in children with high-risk conditions, highlighting the burden of severe influenza in this vulnerable population Further research is required to explain sex and ethnic group differences in PICU mortality among children admitted with influenza.

Development of a short course on management of critically ill patients with acute respiratory infection and impact on clinician knowledge in resource-limited intensive care units.

BACKGROUND: The 2009 influenza A (H1N1) pandemic caused surges of patients in intensive care units (ICUs) in resource-limited settings. Several Ministries of Health requested clinical management guidance from the World Health Organization (WHO), which had not previously developed guidance regarding critically ill patients. OBJECTIVE: To assess the acceptability and impact on knowledge of a short course about the management of critically ill patients with acute respiratory infections complicated by sepsis or acute respiratory distress syndrome delivered to clinicians in resource-limited ICUs. METHODS: Over 4 years (2009-2013), WHO led the development, piloting, implementation and preliminary evaluation of a 3-day course that emphasized patient management based on evidence-based guidelines and used interactive adult-learner teaching methodology. International content experts (n = 35) and instructional designers contributed to development. We assessed participants' satisfaction and content knowledge before and after the course. RESULTS: The course was piloted among clinicians in Trinidad and Tobago (n = 29), Indonesia (n = 38) and Vietnam (n = 86); feedback from these courses contributed to the final version. In 2013, inaugural national courses were delivered in Tajikistan (n = 28), Uzbekistan (n = 39) and Azerbaijan (n = 30). Participants rated the course highly and demonstrated increased immediate content knowledge after (vs before) course completion (P < .001). CONCLUSIONS: We found that it was feasible to create and deliver a focused critical care short course to clinicians in low- and middle-income countries. Collaboration between WHO, clinical experts, instructional designers, Ministries of Health and local clinician-leaders facilitated course delivery. Future work should assess its impact on longer-term knowledge retention and on processes and outcomes of care.

Impact of the introduction of a universal childhood influenza vaccination programme on influenza-related admissions to paediatric intensive care units in England.

INTRODUCTION: A universal childhood influenza vaccination programme was introduced in the UK in September 2013. We examine the impact of the gradual introduction of this programme on influenza-related paediatric intensive care unit (PICU) admission rates in England. METHODS: We extracted data on all influenza-related admissions to PICUs in England in resident children aged 0-15 years old between October 2003 and March 2017 from the Paediatric Intensive Care Audit Network (PICANet) database. We estimated influenza-associated PICU admission rates per 100 000 children by age group, sex and winter season (October to March), and used Poisson regression models to estimate incidence rate ratios (IRRs) in the winter seasons since the introduction of universal childhood vaccination compared with the two winters before the introduction of the programme (2011-2013). RESULTS: We identified 929 influenza-related PICU admissions among 873 children. 48.3% of admissions were among children aged less than 2 years old. The influenza-associated PICU admission rate was 1.32 per 100 000 children (95% CI 1.23 to 1.40). We identified a significant increase in influenza PICU admissions in the winters following the introduction of the universal childhood vaccination programme compared with the winters of 2010/2011-2012/2013 among children aged <5 years old: IRR 1.58 (1.05, 2.37) in children <1 year, 2.71 (1.43, 5.17) in 1 year-olds and 1.98 (1.18, 3.31) in children 2-4 years old. No significant difference was found among children aged 5-15 years. CONCLUSION: The universal childhood influenza vaccination has not yet reduced the influenza-associated burden on PICUs in England during its early phase of introduction. Monitoring of influenza PICU admission rates needs to continue in England to assess the long-term impact of universal paediatric influenza vaccination. Linkage between PICANet and national infection surveillance databases would better enable such monitoring.