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Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.

OBJECTIVE: To report longitudinal differences in baseline characteristics, treatment, and outcomes in patients with coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) between the first and second waves of COVID-19 in Australia. DESIGN, SETTING AND PARTICIPANTS: SPRINT-SARI Australia is a multicentre, inception cohort study enrolling adult patients with COVID-19 admitted to participating ICUs. The first wave of COVID-19 was from 27 February to 30 June 2020, and the second wave was from 1 July to 22 October 2020. RESULTS: A total of 461 patients were recruited in 53 ICUs across Australia; a higher number were admitted to the ICU during the second wave compared with the first: 255 (55.3%) versus 206 (44.7%). Patients admitted to the ICU in the second wave were younger (58.0 v 64.0 years; P = 0.001) and less commonly male (68.9% v 60.0%; P = 0.045), although Acute Physiology and Chronic Health Evaluation (APACHE) II scores were similar (14 v 14; P = 0.998). High flow oxygen use (75.2% v 43.4%; P < 0.001) and non-invasive ventilation (16.5% v 7.1%; P = 0.002) were more common in the second wave, as was steroid use (95.0% v 30.3%; P < 0.001). ICU length of stay was shorter (6.0 v 8.4 days; P = 0.003). In-hospital mortality was similar (12.2% v 14.6%; P = 0.452), but observed mortality decreased over time and patients were more likely to be discharged alive earlier in their ICU admission (hazard ratio, 1.43; 95% CI, 1.13–1.79; P = 0.002). CONCLUSION: During the second wave of COVID-19 in Australia, ICU length of stay and observed mortality decreased over time. Multiple factors were associated with this, including changes in clinical management, the adoption of new evidence-based treatments, and changes in patient demographic characteristics but not illness severity.

OBJECTIVE: Most interventions in paediatric critical care lack high grade evidence. We aimed to identify the key research priorities and key clinical outcome measures pertinent to research in paediatric intensive care patients. DESIGN: Modified three-stage Delphi study combining staged online surveys, followed by a face-to-face discussion and final voting. SETTING: Paediatric intensive care units in Australia and New Zealand. PARTICIPANTS: Medical and nursing staff working in intensive care. MAIN OUTCOME MEASUREMENTS: Self-reported priorities for research. RESULTS: 193 respondents provided a total of 267 research questions and 234 outcomes. In Stage 3, the top 56 research questions and 50 outcomes were discussed face to face, which allowed the identification of the top 20 research questions with the Hanlon prioritisation score and the top 20 outcomes. Topics centred on the use of intravenous fluids (restrictive v liberal fluids, use of fluid resuscitation bolus, early inotrope use, type of intravenous fluid, and assessment of fluid responsiveness), and patient- and family-centred outcomes (health-related quality of life, liberation) emerged as priorities. While mortality, length of stay, and organ support/organ dysfunction were considered important and the most feasible outcomes, long term quality of life and neurodevelopmental measures were rated highly in terms of their importance. CONCLUSIONS: Using a modified Delphi method, this study provides guidance towards prioritisation of research topics in paediatric critical care in Australia and New Zealand, and identifies study outcomes of key relevance to clinicians and experts in the field.

Although extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly utilized in the pediatric critical care environment, our understanding regarding pediatric candidacy for ECPR remains unknown. Our objective is to explore current practice and indications for pediatric ECPR. Scenario-based, self-administered, online survey, evaluating clinical determinants that may impact pediatric ECPR initiation with respect to four scenarios: postoperative cardiac surgery, cardiac failure secondary to myocarditis, septic shock, and chronic respiratory failure in a former preterm child. Responders are pediatric critical care physicians from four societies. 249 physicians, mostly from North America, answered the survey. In cardiac scenarios, 40% of the responders would initiate ECPR, irrespective of CPR duration, compared with less than 20% in noncardiac scenarios. Nearly 33% of responders would consider ECPR if CPR duration was less than 60 minutes in noncardiac scenarios. Factors strongly decreasing the likelihood to initiate ECPR were out-of-hospital unwitnessed cardiac arrest and blood pH6.60. Additional factors reducing this likelihood were multiple organ failure, pre-existing neurologic delay,10 doses of adrenaline, poor CPR quality, and lactate18 mmol/l. Pediatric intensive care unit location for cardiac arrest, good CPR quality, 24/7 in-house extracorporeal membrane oxygenation (ECMO) team moderately increase the likelihood of initiating ECPR. This international survey of pediatric ECPR initiation practices reveals significant differences regarding ECPR candidacy based on patient category, location of arrest, duration of CPR, witness status, and last blood pH. Further research identifying prognostic factors measurable before ECMO initiation should help define the optimal ECPR initiation strategy.

Internationally, diabetes mellitus is recognised as a risk factor for severe COVID-19. The relationship between diabetes mellitus and severe COVID-19 has not been reported in the Australian population.The objective of this study was to determine the prevalence of and outcomes for patients with diabetes admitted to Australian intensive care units (ICUs) with COVID-19.This is a nested cohort study of four ICUs in Melbourne participating in the Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) Australia project. All adult patients admitted to the ICU with COVID-19 from 20 February 2020 to 27 February 2021 were included. Blood glucose and glycated haemoglobin (HbA1c) data were retrospectively collected. Diabetes was diagnosed from medical history or an HbA1c ≥6.5% (48 mmol/mol). Hospital mortality was assessed using logistic regression.There were 136 patients with median age 58 years [48-68] and median Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 14 [11-19]. Fifty-eight patients had diabetes (43%), 46 patients had stress-induced hyperglycaemia (34%), and 32 patients had normoglycaemia (23%). Patients with diabetes were older, were with higher APACHE II scores, had greater glycaemic variability than patients with normoglycaemia, and had longer hospital length of stay. Overall hospital mortality was 16% (22/136), including nine patients with diabetes, nine patients with stress-induced hyperglycaemia, and two patients with normoglycaemia.Diabetes is prevalent in patients admitted to Australian ICUs with severe COVID-19, highlighting the need for prevention strategies in this vulnerable population.

Objectives: Gestational age at birth is declining, probably because more deliveries are being induced. Gestational age is an important modifiable risk factor for neonatal mortality and morbidity. We aimed to investigate the association between gestational age and mortality in hospital for term-born neonates (>= 37 wk') admitted to PICUs in Australia and New Zealand. Design: Observational multicenter cohort study. Setting: PICUs in Australia and New Zealand. Patients: Term-born neonates (>= 37 wk) admitted to PICUs. Interventions: None Measurements and Main Results: We studied 5,073 infants born with a gestational age greater than or equal to 37 weeks and were less than 28 days old when admitted to a PICU in Australia or New Zealand between 2007 and 2016. The association between gestational age and mortality was estimated using a multivariable logistic regression model, adjusting for age, sex, indigenous status, Pediatric Index of Mortality version 2, and site. The median gestational age was 39.1 weeks (interquartile range, 38.2-40 wk) and mortality in hospital was 6.6%. Risk of mortality declined log-linearly with gestational age. The adjusted analysis showed a 20% (95% CI, 11-28%) relative reduction in mortality for each extra week of gestation beyond 37 weeks. The effect of gestation was stronger among those who received extracorporeal life support: each extra week of gestation was associated with a 44% (95% CI, 25-57%) relative reduction in mortality. Longer gestation was also associated with reduced length of stay in hospital: each week increase in gestation, the average length of stay decreased by 4% (95% CI, 2-6%). Conclusions: Among neonates born at "term" who are admitted to a PICU, increasing gestational age at birth is associated with a substantial reduction in the risk of dying in hospital. The maturational influence on outcome was more strongly noted in the sickest neonates, such as those requiring extracorporeal life support. This information is important in view of the increasing proportion of planned births in both high- and low-/middle-income countries.

To determine whether the combination of systemic corticosteroids and nebulized epinephrine, compared with standard care, reduces the duration of positive pressure support in children with bronchiolitis admitted to intensive care.We performed a pragmatic, multicenter, open-label, randomized trial between July 2013 and November 2019 in children younger than 18 months old with a clinical diagnosis of bronchiolitis. The intervention group received the equivalent of 13 mg/kg prednisolone over 3 days, then 1 mg/kg daily for 3 days, plus 0.05 mL/kg of nebulized 1% epinephrine made up to 6 ml with 0.9% saline via jet nebulizer and mask using oxygen at 12 l/min every 30 minutes for 5 doses, then 1-4 hourly for 3 days, then as required for 3 days. The primary outcome was clinician-managed duration of positive pressure support in intensive care defined as high-flow nasal-prong oxygen, nasopharyngeal continuous positive airway pressure, or mechanical ventilation.In total, 210 children received positive pressure support. In the corticosteroid-epinephrine group, 107 children received positive pressure support for a geometric mean of 26 (95% CI, 22-32) hours compared with 40 (95% CI 34-47) hours in 103 controls, adjusted ratio 0.66 (95% CI 0.51-0.84), P = .001. In the intervention group, 41 (38%) children experienced at least 1 adverse event, compared with 39 (38%) in the control group.In children with severe bronchiolitis, the duration of clinician-managed pressure support was reduced by regular treatment with systemic corticosteroids and inhaled epinephrine compared with standard care.Australian Clinical Trials Research Network: ACTRN12613000316707.

CONTEXT Respiratory dysfunction is a component of every organ failure scoring system developed, reflecting the significance of the lung in multiple organ dysfunction syndrome. However, existing systems do not reflect current practice and are not consistently evidence based. OBJECTIVE We aimed to review the literature to identify the components of respiratory failure associated with outcomes in children, with the purpose of developing an operational and evidence-based definition of respiratory dysfunction. DATA SOURCES Electronic searches of PubMed and Embase were conducted from 1992 to January 2020 by using a combination of medical subject heading terms and text words to define respiratory dysfunction, critical illness, and outcomes. STUDY SELECTION We included studies of critically ill children with respiratory dysfunction that evaluated the performance of metrics of respiratory dysfunction and their association with patient-centered outcomes. Studies in adults, studies in premature infants (≤36 weeks’ gestational age), animal studies, reviews and commentaries, case series with sample sizes ≤10, and studies not published in English in which we were unable to determine eligibility criteria were excluded. DATA EXTRACTION Data were abstracted into a standard data extraction form. RESULTS We provided binary (no or yes) and graded (no, nonsevere, or severe) definitions of respiratory dysfunction, prioritizing oxygenation and respiratory support. The proposed criteria were approved by 82% of members in the first round, with a score of 8 of 9 (interquartile range 7–8). LIMITATIONS Exclusion of non-English publications, heterogeneity across the pediatric age range, small sample sizes, and incomplete handling of confounders are limitations. CONCLUSIONS We propose definitions for respiratory dysfunction in critically ill children after an exhaustive literature review.

OBJECTIVES: To describe the characteristics and outcomes of patients with COVID-19 admitted to intensive care units (ICUs) during the initial months of the pandemic in Australia. DESIGN, SETTING: Prospective, observational cohort study in 77 ICUs across Australia. PARTICIPANTS: Patients admitted to participating ICUs with laboratory-confirmed COVID-19 during 27 February - 30 June 2020. MAIN OUTCOME MEASURES: ICU mortality and resource use (ICU length of stay, peak bed occupancy). RESULTS: The median age of the 204 patients with COVID-19 admitted to intensive care was 63.5 years (IQR, 53-72 years); 140 were men (69%). The most frequent comorbid conditions were obesity (40% of patients), diabetes (28%), hypertension treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (24%), and chronic cardiac disease (20%); 73 patients (36%) reported no comorbidity. The most frequent source of infection was overseas travel (114 patients, 56%). Median peak ICU bed occupancy was 14% (IQR, 9-16%). Invasive ventilation was provided for 119 patients (58%). Median length of ICU stay was greater for invasively ventilated patients than for non-ventilated patients (16 days; IQR, 9-28 days v 3 days; IQR, 2-5 days), as was ICU mortality (26 deaths, 22%; 95% CI, 15-31% v four deaths, 5%; 95% CI, 1-12%). Higher Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores on ICU day 1 (adjusted hazard ratio [aHR], 1.15; 95% CI, 1.09-1.21) and chronic cardiac disease (aHR, 3.38; 95% CI, 1.46-7.83) were each associated with higher ICU mortality. CONCLUSION: Until the end of June 2020, mortality among patients with COVID-19 who required invasive ventilation in Australian ICUs was lower and their ICU stay longer than reported overseas. Our findings highlight the importance of ensuring adequate local ICU capacity, particularly as the pandemic has not yet ended.

Introduction The epidemiology and clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection are different in children and adolescents compared with adults. Although coronavirus disease 2019 (COVID‐19) appears to be less common in children, with milder disease overall, severe complications may occur, including paediatric inflammatory multisystem syndrome (PIMS‐TS). Recognising the distinct needs of this population, the National COVID‐19 Clinical Evidence Taskforce formed a Paediatric and Adolescent Care Panel to provide living guidelines for Australian clinicians to manage children and adolescents with COVID‐19 and COVID‐19 complications. Living guidelines mean that these evidence‐based recommendations are updated in near real time to give reliable, contemporaneous advice to Australian clinicians providing paediatric care. Main recommendations To date, the Taskforce has made 20 specific recommendations for children and adolescents, including definitions of disease severity, recommendations for therapy, respiratory support, and venous thromboembolism prophylaxis for COVID‐19 and for the management of PIMS‐TS. Changes in management as a result of the guidelines The Taskforce currently recommends corticosteroids as first line treatment for acute COVID‐19 in children and adolescents who require oxygen. Tocilizumab could be considered, and remdesivir should not be administered routinely in this population. Non‐invasive ventilation or high flow nasal cannulae should be considered in children and adolescents with hypoxaemia or respiratory distress unresponsive to low flow oxygen if appropriate infection control measures can be used. Children and adolescents with PIMS‐TS should be managed by a multidisciplinary team. Intravenous immunoglobulin and corticosteroids, with concomitant aspirin and thromboprophylaxis, should be considered for the treatment of PIMS‐TS. The latest updates and full recommendations are available at www.covid19evidence.net.au.

To the Editor: The global coronavirus disease (COVID-19) pandemic has seen a significant increase in the use of preprint services to enable the widespread dissemination of research findings (1). However, whether such facilities influence practice change is currently unknown. Here, we describe the impact of the preprint release and eventual publication of the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial (2) on corticosteroid use in clinical practice in Australian ICUs. The RECOVERY trial tested the efficacy of dexamethasone (6 mg by mouth or intravenously for up to 10 d) in hospitalized patients with clinically suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and demonstrated a reduction in 28-day mortality, particularly in those receiving either mechanical ventilation or oxygen. Before these results, the Australian and New Zealand Intensive Care Society COVID-19 guidelines recommended against the routine use of corticosteroids (3).

OBJECTIVES: To assess the feasibility, safety, and efficacy of a sedation protocol using dexmedetomidine as the primary sedative in mechanically ventilated critically ill children. DESIGN: Open-label, pilot, prospective, multicenter, randomized, controlled trial. The primary outcome was the proportion of sedation scores in the target sedation range in the first 48 hours. Safety outcomes included device removal, adverse events, and vasopressor use. Feasibility outcomes included time to randomization and protocol fidelity. SETTING: Six tertiary PICUs in Australia and New Zealand. PATIENTS: Critically ill children, younger than 16 years old, requiring intubation and mechanical ventilation and expected to be mechanically ventilated for at least 24 hours. INTERVENTIONS: Children randomized to dexmedetomidine received a dexmedetomidine-based algorithm targeted to light sedation (State Behavioral Scale -1 to +1). Children randomized to usual care received sedation as determined by the treating clinician (but not dexmedetomidine), also targeted to light sedation. MEASUREMENTS AND MAIN RESULTS: Sedation with dexmedetomidine as the primary sedative resulted in a greater proportion of sedation measurements in the light sedation range (State Behavioral Scale -1 to +1) over the first 48 hours (229/325 [71%] vs 181/331 [58%]; p = 0.04) and the first 24 hours (66/103 [64%] vs 48/116 [41%]; p < 0.001) compared with usual care. Cumulative midazolam dosage was significantly reduced in the dexmedetomidine arm compared with usual care (p = 0.002).There were more episodes of hypotension and bradycardia with dexmedetomidine (including one serious adverse event) but no difference in vasopressor requirements. Median time to randomization after intubation was 6.0 hours (interquartile range, 2.0-9.0 hr) in the dexmedetomidine arm compared with 3.0 hours (interquartile range, 1.0-7.0 hr) in the usual care arm (p = 0.24). CONCLUSIONS: A sedation protocol using dexmedetomidine as the primary sedative was feasible, appeared safe, achieved early, light sedation, and reduced midazolam requirements. The findings of this pilot study justify further studies of sedative agents in critically ill children.

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.

Objectives: To describe the incidence and mortality of invasive infections in Indigenous children admitted to paediatric and general intensive care units (ICUs) in Australia. Design: Retrospective multi-centre cohort study of Australian and New Zealand Paediatric Intensive Care Registry data. Participants: All children under 16 years of age admitted to an ICU in Australia, 1 January 2002 e 31 December 2013. Indigenous children were defined as those identified as Aboriginal and/or Torres Strait Islander in a mandatory admissions dataset. Main outcomes: Population-based ICU mortality and admission rates. Results: Invasive infections accounted for 23.0% of non-elective ICU admissions of Indigenous children (726 of 3150), resulting in an admission rate of 47.6 per 100 000 children per year. Staphylococcus aureus was the leading pathogen identified in children with sepsis/septic shock (incidence, 4.42 per 100 000 Indigenous children per year; 0.57 per 100 000 non-Indigenous children per year; incidence rate ratio 7.7; 95% CI, 5.8-10.1; P < 0.001). While crude and risk-adjusted ICU mortality related to invasive infections was not significantly different for Indigenous and non-Indigenous children (odds ratio, 0.75; 95% CI, 0.53-1.07; P = 0.12), the estimated population-based age-standardised mortality rate for invasive infections was significantly higher for Indigenous children (2.67 per 100 000 per year v 1.04 per 100 000 per year; crude incidence rate ratio, 2.65; 95% CI, 1.88e3.64; P < 0.001). Conclusions: The ICU admission rate for severe infections was several times higher for Indigenous than for non-Indigenous children, particularly for S. aureus infections. While ICU case fatality rates were similar, the population-based mortality was more than twice as high for Indigenous children. Our study highlights an important area of inequality in health care for Indigenous children in a high income country that needs urgent attention.

Background Outcomes for pediatric cardiac surgery are commonly reported from international databases compiled from voluntary data submissions. Surgical outcomes for all children in a country or region are less commonly reported. We aimed to describe the bi‐national population‐based outcome for children undergoing cardiac surgery in Australia and New Zealand and determine whether the Risk Adjustment for Congenital Heart Surgery ( RACHS ) classification could be used to create a model that accurately predicts in‐hospital mortality in this population. Methods and Results The study was conducted in all children's hospitals performing cardiac surgery in Australia and New Zealand between January 2007 and December 2015. The performance of the original RACHS ‐1 model was assessed and compared with an alternative RACHS ‐ ANZ (Australia and New Zealand) model, developed balancing discrimination with parsimonious variable selection. A total of 14 324 hospital admissions were analyzed. The overall hospital mortality was 2.3%, ranging from 0.5% for RACHS category 1 procedures, to 17.0% for RACHS category 5 or 6 procedures. The original RACHS ‐1 model was poorly calibrated with death overpredicted (1161 deaths predicted, 289 deaths observed). The RACHS ‐ ANZ model had better performance in this population with excellent discrimination (Az‐ ROC of 0.830) and acceptable Hosmer and Lemeshow goodness‐of‐fit ( P =0.216). Conclusions The original RACHS ‐1 model overpredicts mortality in children undergoing heart surgery in the current era. The RACHS ‐ ANZ model requires only 3 risk variables in addition to the RACHS procedure category, can be applied to a wider range of patients than RACHS ‐1, and is suitable to use to monitor regional pediatric cardiac surgery outcomes.

Objectives To compare the prevalence of infection applying the proposed pediatric ventilator-associated events criteria versus clinician-diagnosed ventilator-associated infection to subjects in the pediatric ventilator-associated infection study. Design Analysis of prospectively collected data from the pediatric ventilator-associated infection study. Setting PICUs of 47 hospitals in the United States, Canada, and Australia. Patients Two-hundred twenty-nine children ventilated for greater than 48 hours who had respiratory secretion cultures performed to evaluate for suspected ventilator-associated infection. Interventions None. Measurements and main results Applying the proposed pediatric ventilator-associated event criteria, 15 of 229 subjects in the ventilator-associated infection study qualified as "ventilator-associated condition" and five of 229 (2%) met criteria for "infection-related ventilator-associated complication." This was compared with 89 of 229 (39%) diagnosed as clinical ventilator-associated infection (Kappa = 0.068). Ten of 15 subjects identified as ventilator-associated condition did not meet criteria for infection-related ventilator-associated complication primarily because they did not receive 4 days of antibiotics. Ventilator-associated condition subjects were similar demographically to nonventilator-associated condition subjects and had similar mortality (13% vs 10%), PICU-free days (6.9 ± 7.7; interquartile range, 0-14 vs 9.8 ± 9.6; interquartile range, 0-19; p = 0.25), but fewer ventilator-free days (6.6 ± 9.3; interquartile range, 1-15 vs 12.4 ± 10.7; interquartile range, 0-22; p = 0.04). The clinical ventilator-associated infection diagnosis in the ventilator-associated infection study was associated with fewer PICU-free days but no difference in mortality or ventilator-free days. Conclusions The ventilator-associated event criteria appear to be insensitive to the clinical diagnosis of ventilator-associated infection. Differentiation between ventilator-associated condition and infection-related ventilator-associated complication was primarily determined by the clinician decision to treat with antibiotics rather than clinical signs and symptoms. The utility of the proposed pediatric ventilator-associated event criteria as a surrogate for ventilator-associated infection criteria is unclear.

Summary Background Paediatric acute respiratory distress syndrome (PARDS) is associated with high mortality in children, but until recently no paediatric-specific diagnostic criteria existed. The Pediatric Acute Lung Injury Consensus Conference (PALICC) definition was developed to overcome limitations of the Berlin definition, which was designed and validated for adults. We aimed to determine the incidence and outcomes of children who meet the PALICC definition of PARDS. Methods In this international, prospective, cross-sectional, observational study, 145 paediatric intensive care units (PICUs) from 27 countries were recruited, and over a continuous 5 day period across 10 weeks all patients were screened for enrolment. Patients were included if they had a new diagnosis of PARDS that met PALICC criteria during the study week. Exclusion criteria included meeting PARDS criteria more than 24 h before screening, cyanotic heart disease, active perinatal lung disease, and preparation or recovery from a cardiac intervention. Data were collected on the PICU characteristics, patient demographics, and elements of PARDS (ie, PARDS risk factors, hypoxaemia severity metrics, type of ventilation), comorbidities, chest imaging, arterial blood gas measurements, and pulse oximetry. The primary outcome was PICU mortality. Secondary outcomes included 90 day mortality, duration of invasive mechanical and non-invasive ventilation, and cause of death. Findings Between May 9, 2016, and June 16, 2017, during the 10 study weeks, 23 280 patients were admitted to participating PICUs, of whom 744 (3·2%) were identified as having PARDS. 95% (708 of 744) of patients had complete data for analysis, with 17% (121 of 708; 95% CI 14–20) mortality, whereas only 32% (230 of 708) of patients met Berlin criteria with 27% (61 of 230) mortality. Based on hypoxaemia severity at PARDS diagnosis, mortality was similar among those who were non-invasively ventilated and with mild or moderate PARDS (10–15%), but higher for those with severe PARDS (33% [54 of 165; 95% CI 26–41]). 50% (80 of 160) of non-invasively ventilated patients with PARDS were subsequently intubated, with 25% (20 of 80; 95% CI 16–36) mortality. By use of PALICC PARDS definition, severity of PARDS at 6 h after initial diagnosis (area under the curve [AUC] 0·69, 95% CI 0·62–0·76) discriminates PICU mortality better than severity at PARDS diagnosis (AUC 0·64, 0·58–0·71), and outperforms Berlin severity groups at 6 h (0·64, 0·58–0·70; p=0·01). Interpretation The PALICC definition identified more children as having PARDS than the Berlin definition, and PALICC PARDS severity groupings improved the stratification of mortality risk, particularly when applied 6 h after PARDS diagnosis. The PALICC PARDS framework should be considered for use in future epidemiological and therapeutic research among children with PARDS. Funding University of Southern California Clinical Translational Science Institute, Sainte Justine Children's Hospital, University of Montreal, Canada, Reseau en Sante Respiratoire du Fonds de Recherche Quebec-Sante, and Children's Hospital Los Angeles, Department of Anesthesiology and Critical Care Medicine.

Fluid bolus therapy (FBT) is a widely used intervention in paediatric critical illness. The aim of this study was to describe the attitudes and practices towards FBT of paediatric intensive care doctors in Australia and New Zealand.An internet-based survey of paediatric intensive care doctors in Australia and New Zealand between 7 and 30 November 2016.Paediatric intensive care units with greater than 400 admissions annually.Paediatric intensive care specialists and junior medical staff.Preferences for FBT and markers of fluid responsiveness.There were 106/175 respondents (61%); 0.9% saline and 4% albumin are used frequently or almost always by 86% and 57% of respondents respectively. The preferred volume and duration were 10 mL/kg in less than 10 minutes. The highest rated markers of fluid responsiveness were heart rate and blood pressure - rated as "good" or "very good" by 75% and 58% of respondents respectively. Central venous saturations and serum lactate were the highest rated biochemical markers. The most frequently expected magnitude of change for heart rate and blood pressure was 6-15% by 89% and 76% of respondents respectively. The preferred fluid composition for sepsis, trauma, traumatic brain injury and acute lung injury was 0.9% saline, and 4% albumin for post-operative cardiac surgery.Paediatric intensive care doctors prefer 0.9% saline and 4% albumin for FBT. Heart rate and blood pressure are the most preferred markers to assess fluid responsiveness. Preferences for FBT in specific conditions exist.

Objective: Outcomes for children with chronic critical illness are not defined. We examined the long-term survival of these children in Australia and New Zealand.

Objectives:Although there are similarities in the pathophysiology of acute respiratory distress syndrome in adults and children, pediatric-specific practice patterns, comorbidities, and differences in outcome necessitate a pediatric-specific definition. We sought to create such a definition.Design:A

Purpose Requiring PaO2/FiO2 ratio (PF) to define ARDS may bias towards children with cardiovascular dysfunction and hypoxemia. We sought to evaluate (1) the Berlin definition of ARDS in children using PF; (2) the effect of substituting SpO2/FiO2(SF) ratio; (3) differences between patients with and without arterial blood gases; and (4) the ability of SpO2 and PaO2 indices to discriminate ICU mortality.

Suspected ventilator-associated infection is the most common reason for antibiotics in the PICU. We sought to characterize the clinical variables associated with continuing antibiotics after initial evaluation for suspected ventilator-associated infection and to determine whether clinical variables or antibiotic treatment influenced outcomes.Prospective, observational cohort study conducted in 47 PICUs in the United States, Canada, and Australia. Two hundred twenty-nine pediatric patients ventilated more than 48 hours undergoing respiratory secretion cultures were enrolled as "suspected ventilator-associated infection" in a prospective cohort study, those receiving antibiotics of less than or equal to 3 days were categorized as "evaluation only," and greater than 3 days as "treated." Demographics, diagnoses, comorbidities, culture results, and clinical data were compared between evaluation only and treated subjects and between subjects with positive versus negative cultures.PICUs in 47 hospitals in the United States, Canada, and Australia.All patients undergoing respiratory secretion cultures during the 6 study periods.None.Treated subjects differed from evaluation-only subjects only in frequency of positive cultures (79% vs 36%; p0.0001). Subjects with positive cultures were more likely to have chronic lung disease, tracheostomy, and shorter PICU stay, but there were no differences in ventilator days or mortality. Outcomes were similar in subjects with positive or negative cultures irrespective of antibiotic treatment. Immunocompromise and higher Pediatric Logistic Organ Dysfunction scores were the only variables associated with mortality in the overall population, but treated subjects with endotracheal tubes had significantly lower mortality.Positive respiratory cultures were the primary determinant of continued antibiotic treatment in children with suspected ventilator-associated infection. Positive cultures were not associated with worse outcomes irrespective of antibiotic treatment although the lower mortality in treated subjects with endotracheal tubes is notable. The necessity of continuing antibiotics for a positive respiratory culture in suspected ventilator-associated infection requires further study.

BACKGROUND: Organ dysfunction scores, based on physiological parameters, have been created to describe organ failure. In a general pediatric intensive care unit (PICU) population, the PEdiatric Logistic Organ Dysfunction-2 score (PELOD-2) score had both a good discrimination and calibration, allowing to describe the clinical outcome of critically ill children throughout their stay. This score is increasingly used in clinical trials in specific subpopulation. Our objective was to assess the performance of the PELOD-2 score in a subpopulation of critically ill children requiring plasma transfusions.METHODS: This was an ancillary study of a prospective observational study on plasma transfusions over a 6-week period, in 101 PICUs in 21 countries. All critically ill children who received at least one plasma transfusion during the observation period were included. PELOD-2 scores were measured on days 1, 2, 5, 8, and 12 after plasma transfusion. Performance of the score was assessed by the determination of the discrimination (area under the ROC curve: AUC) and the calibration (Hosmer-Lemeshow test).RESULTS: Four hundred and forty-three patients were enrolled in the study (median age and weight: 1 year and 9.1 kg, respectively). Observed mortality rate was 26.9 % (119/443). For PELOD-2 on day 1, the AUC was 0.76 (95 % CI 0.71-0.81) and the Hosmer-Lemeshow test was p = 0.76. The serial evaluation of the changes in the daily PELOD-2 scores from day 1 demonstrated a significant association with death, adjusted for the PELOD-2 score on day 1.CONCLUSIONS: In a subpopulation of critically ill children requiring plasma transfusion, the PELOD-2 score has a lower but acceptable discrimination than in an entire population. This score should therefore be used cautiously in this specific subpopulation.

OBJECTIVE: To describe in detail the pediatric intensive care experience of influenza A, particularly pandemic H1N1-09, in Australia and New Zealand during the 2009 Southern Hemisphere winter and to compare the pediatric experience with that of adults. METHOD: This was an inception-cohort study of all children who were admitted to intensive care with confirmed influenza A during winter 2009 at all general ICUs and PICUs in Australia and New Zealand. RESULTS: From June 1 through August 31, 2009, 107 children (20.0 per million [95% confidence interval: 16.1–23.8]) with influenza A, including 83 (15.5 per million [95% confidence interval: 12.1–18.9]) with H1N1-09 were admitted to ICUs. Fifty-two percent (39 of 75) of children with H1N1-09 had 1 or more comorbidity, most commonly neurologic (20%). Most (48 of 83 [58%]) presented with pneumonia. Thirteen of 83 (16%) had neurologic presentations. Eighty percent of the children with H1N1-09 required ventilation. Mortality was lower than in adults: 6 of 83 (7%) vs 114 of 668 (17%) (P = .02). The median length of stay for children with H1N1-09 was 5 days. Children with H1N1-09 occupied 773 bed-days (147 per million children) and 5.8% of specialist PICU beds. Presentation with septic shock or after cardiac arrest and the presence of 1 or more comorbidities were risk factors for severe disease. CONCLUSIONS: H1N1-09 caused a substantial burden on pediatric intensive care services in Australia and New Zealand. Compared with adults, children more commonly had nonrespiratory presentations and required ventilation more often but had a lower mortality rate.

ObjectivesWe hypothesised that sildenafil would improve hemodynamics in children with pulmonary hypertension and attenuate rebound pulmonary hypertension after inhaled nitric oxide withdrawal.Patients and methodsWe undertook an open-label, single-drug study of sildenafil in patients under 5 years of age with either symptomatic or rebound pulmonary hypertension following inhaled nitric oxide withdrawal.ResultsWe recruited 25 patients (median age 180 days, 10–1790) to receive sildenafil. The median right ventricular to systemic systolic blood pressure ratio before sildenafil therapy was 1.0 (0.5–1.4) and decreased to 0.5 (with a range from 0.3 to 1.3; p = 0.0002). In five patients the baseline pulmonary vascular resistance index was 10 (7.1–13.6) Wood units metre square and decreased to 5.8 (2.7–15.6) Wood units metre square (p = 0.04) at 6 months. Ten patients were treated with sildenafil for a median of 34 days (9–499) until resolution of pulmonary artery hypertension and continue to do well. Six patients continued sildenafil therapy for a median of 1002 days (384–1574) with improvement but without resolution of pulmonary hypertension. There was no change in serum creatinine, urea, liver function tests, or platelet count. In 15 patients sildenafil abolished rebound pulmonary artery hypertension following withdrawal of inhaled nitric oxide. Median right ventricular pressure to systemic systolic pressure ratio decreased from 1.0 (0.8–1.4) during nitric oxide withdrawal to 0.4 (0.3–0.8) p = 0.006 after pre-treatment with sildenafil.ConclusionIn children under 5 years of age with severe pulmonary hypertension, sildenafil therapy resulted in prolonged hemodynamic improvements without adverse effects. Sildenafil attenuated rebound pulmonary hypertension after withdrawal of inhaled nitric oxide.

Bronchiolitis represents the most common cause of non-elective admission to paediatric intensive care units (ICUs).We assessed changes in admission rate, respiratory support, and outcomes of infants During the study period, bronchiolitis was responsible for 9628 (27.6%) of 34 829 non-elective ICU admissions. The estimated population-based ICU admission rate due to bronchiolitis increased by 11.76 per 100 000 each year (95% CI 8.11–15.41). The proportion of bronchiolitis patients requiring intubation decreased from 36.8% in 2002, to 10.8% in 2014 (adjusted OR 0.35, 95% CI 0.27–0.46), whilst a dramatic increase in high-flow nasal cannula therapy use to 72.6% was observed (pWe observed an increasing healthcare burden due to severe bronchiolitis, with a major change in practice in the management from invasive to non-invasive support that suggests thresholds to admittance of bronchiolitis patients to ICU have changed. Future studies should assess strategies for management of bronchiolitis outside ICUs.

To determine whether aminophylline reduced the duration of respiratory support in children admitted to intensive care with bronchiolitis.A multicentre, randomised, double-blind, placebo controlled trial.Paediatric intensive care units in teaching hospitals.Forty-five children with severe bronchiolitis.Patients were randomly assigned to receive an infusion of aminophylline (23) or placebo (22). The primary outcome measure was the number of hours of respiratory support required in the 120 hours after randomisation; respiratory support was defined as either nasal continuous positive airways pressure or mechanical ventilation.The trial was stopped early due to poor recruitment. Respiratory support was required for a median of only 1.5 days (interquartile range [IQR], 0.4-3.5 days) in the aminophylline group compared with 1.9 days (IQR, 0.3-3.5) days in the placebo group. However, more patients in the placebo group were receiving respiratory support at the time of randomisation and, after adjustment for this, there was no suggestion of a beneficial effect of aminophylline among the small number of patients studied (P=0.54, exact log-rank test stratified by respiratory support at the time of randomisation and censored at the time of death in one child in the aminophylline group).Not enough children were recruited for the study to test the hypothesis that aminophylline reduces the need for respiratory support in severe bronchiolitis. Consequently, the role of aminophylline in the management of severe bronchiolitis remains unknown.

Oceania traditionally comprises Australia, New Zealand, Polynesia, Melanesia, and Micronesia. This includes diverse geography from sparsely populated desert inland with communities living hundreds of kilometers from each other, to densely populated cities with significant infrastructure and congestion problems. Isolated islands with rudimentary intensive care services share the region with sophisticated neonatal and pediatric intensive care units. While Australia and New Zealand are fortunate to have well-organized and well-resourced intensive care units with efficient transport systems, services providing intensive care to babies and children in countries such as Papua New Guinea, Fiji, and smaller islands are much more limited. Interactions between different regions in Oceania are also complicated, and many critical care services, such as cardiac surgery, are provided to many countries in Oceania by volunteer groups and Australian and New Zealand government aid. Provision of critical care in Australia and New Zealand is in some ways indistinguishable from those provided in Europe and North America, while those available to children in Polynesia, Melanesia, and Micronesia may be more akin to those in sub-Saharan Africa.

ObjectivesWe investigated the effects of different CO2tensions on oxygenation, pulmonary blood flow (Qp), cerebral blood flow, and systemic blood flow (Qs) after the bidirectional superior cavopulmonary anastomosis (BCPA).BackgroundHypoxemia refractory to management of a high pulmonary vascular resistance index (PVRI) may complicate recovery from the BCPA.MethodsAfter BCPA, CO2was added to the inspired gas of mechanically ventilated patients. The Qp, Qs, PVRI, and systemic vascular resistance index (SVRI) were calculated from oxygen consumption, intravascular pressures, and oxygen saturations. Cerebral blood flow was estimated by near infrared spectroscopy and transcranial Doppler.ResultsIn nine patients (median age 7.1, range 2 to 23 months), arterial oxygen tension increased significantly (p < 0.005) from 36 ± 6 mm Hg to 44 ± 6 to 50 ± 7 mm Hg at arterial carbon dioxide tensions (PaCO2) of 35, 45, and 55 mm Hg, respectively and decreased to 40 ± 8 mm Hg at PaCO240 mm Hg. At a PaCO2of 55 and 45 compared with 35 mm Hg, Qp, cerebral blood flow, and Qs increased significantly, PVRI, Qp/Qs, and the ratio of Qp to inferior vena caval blood flow were unchanged, but SVRI decreased.ConclusionsWe have demonstrated that after the BCPA, systemic oxygenation, Qp, Qs, and cerebral blood flow increased and SVRI decreased at CO2tensions of 45 and 55 mm Hg compared with 35 mm Hg. We suggest that hypoxemia after the BCPA is ameliorated by a higher PaCO2and that low PaCO2or alkalosis may be detrimental. Hypercarbic management strategies may allow earlier progression to the BCPA, which may contribute to reducing the interval morbidity in patients with a functional single ventricle.

During the 2009 H1N1 pandemic, large numbers of patients had severe respiratory failure. High frequency oscillation ventilation was used as a salvage technique for profound hypoxaemia. Our aim was to compare this experience with high frequency oscillation ventilation during the 2009 H1N1 pandemic with the same period in 2008 by performing a three-month period prevalence study in Australian and New Zealand intensive care units. The main study end-points were clinical demographics, care delivery and survival. Nine intensive care units contributed data. During 2009 there were 22 H1N1 patients (17 adults, five children) and 10 non-H1N1 patients (five adults, five children), while in 2008, 18 patients (two adults, 16 children) received high frequency oscillation ventilation. The principal non-H1N1 high frequency oscillation ventilation indication was bacterial or viral pneumonia (56%). For H1N1 patients, the median duration of high frequency oscillation ventilation was 3.7 days (interquartile range 1.8 to 5) with concomitant therapies including recruitment manoeuvres (22%), prone ventilation (41%), inhaled prostacyclins (18%) and inhaled nitric oxide (36%). Seven patients received extracorporeal membrane oxygenation, six having H1N1. Three patients had extracorporeal membrane oxygenation concurrently, two as salvage therapy following the commencement of high frequency oscillation ventilation. In 2008, no high frequency oscillation ventilation patient received extracorporeal membrane oxygenation. Overall hospital survival was 77% in H1N1 patients, while survival in patients having adjunctive extracorporeal membrane oxygenation was similar to those receiving high frequency oscillation ventilation alone (65% compared to 71%, P=1.00). Survival rates were comparable to published extracorporeal membrane oxygenation outcomes. high frequency oscillation ventilation was used successfully as a rescue therapy for severe respiratory failure. high frequency oscillation ventilation was only available in a limited number of intensive care units during the H1N1 pandemic.

Background: The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. Objective: To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses. Stata scripts for analyses have been prepared alongside this statistical analysis plan. Methods: The statistical analysis plan was designed collaboratively by the chief investigators and trial statistician and builds on the previously published study protocol. All authors remain blinded to treatment allocation. Detail is provided on statistical analyses including cohort description, analysis of primary and secondary outcomes and adverse events. Statistical methods to compare outcomes are planned in detail to ensure methods are verifiable and reproducible. Results: The statistical analysis plan developed provides the trial outline, list of mock tables, and analysis scripts. The plan describes statistical analyses on cohort and baseline description, primary and secondary outcome analyses, process of care measures, physiological descriptors, and safety and adverse event reporting. We define the pre-specified subgroup analyses and the respective statistical tests used to compare subgroups. Conclusion: The statistical analysis plan for the NITRIC trial establishes detailed pre-planned analyses alongside Stata scripts to analyse the largest trial in the field of neonatal and paediatric heart surgery. The plan ensures standards for trial analysis validity aiming to minimise bias of analyses. Trial registration: ACTRN12617000821392

International audience; Severe acute respiratory infections (SARI) remain one of the leading causes of mortality around the world in all age groups. There is large global variation in epidemiology, clinical management and outcomes, including mortality. We performed a short period observational data collection in critical care units distributed globally during regional peak SARI seasons from 1 January 2016 until 31 August 2017, using standardised data collection tools. Data were collected for 1 week on all admitted patients who met the inclusion criteria for SARI, with follow-up to hospital discharge. Proportions of patients across regions were compared for microbiology, management strategies and outcomes. Regions were divided geographically and economically according to World Bank definitions. Data were collected for 682 patients from 95 hospitals and 23 countries. The overall mortality was 9.5%. Of the patients, 21.7% were children, with case fatality proportions of 1% for those less than 5 years. The highest mortality was in those above 60 years, at 18.6%. Case fatality varied by region: East Asia and Pacific 10.2% (21 of 206), Sub-Saharan Africa 4.3% (8 of 188), South Asia 0% (0 of 35), North America 13.6% (25 of 184), and Europe and Central Asia 14.3% (9 of 63). Mortality in low-income and low-middle-income countries combined was 4% as compared with 14% in high-income countries. Organ dysfunction scores calculated on presentation in 560 patients where full data were available revealed Sequential Organ Failure Assessment (SOFA) scores on presentation were significantly associated with mortality and hospital length of stay. Patients in East Asia and Pacific (48%) and North America (24%) had the highest SOFA scores of >12. Multivariable analysis demonstrated that initial SOFA score and age were independent predictors of hospital survival. There was variability across regions and income groupings for the critical care management and outcomes of SARI. Intensive care unit-specific factors, geography and management features were less reliable than baseline severity for predicting ultimate outcome. These findings may help in planning future outbreak severity assessments, but more globally representative data are required.