Despite the challenges posed by vast geographical distances and relatively small populations (Australia: 26 million, New Zealand: 5 million), Australia and New Zealand (ANZ) are renowned for their high quality innovative pediatric intensive care research. A strong culture of partnership across units led to the formation of the ANZ Intensive Care Society Paediatric Study Group (ANZICS PSG) in 2003, which has evolved since its formation into one of the leading international pediatric intensive care trial networks, along with two in the United States (1, 2) and one in the United Kingdom (3). Here, we describe the factors leading to the growth of the ANZICS PSG, explore the current established research ecosystem, along with future plans to sustain success.

Importance Children with congenital heart defects who undergo cardiopulmonary bypass (CPB) surgery are at risk for delayed or impaired neurodevelopmental outcomes. Nitric oxide (NO) added to the CPB oxygenator may reduce systemic inflammation due to CPB and improve recovery from surgery, including improved neurodevelopmental outcomes. Objective To investigate neurodevelopment, health-related quality of life (HRQOL), and factors associated with impaired neurodevelopment at 12 months post surgery in infants who received CPB with NO or standard CPB. Design, Setting, and Participants This double-masked randomized clinical trial was conducted in 6 centers in Australia, New Zealand, and the Netherlands between July 19, 2017, and April 28, 2021, with a preplanned prospective follow-up 12 months postrandomization completed on August 5, 2022. The cohort included 1364 infants younger than 2 years who underwent open heart surgery with CPB for congenital heart disease. Interventions The intervention group received NO 20 ppm into the CPB oxygenator. The control group received standard CPB. Main Outcomes and Measures The primary outcome was neurodevelopment, defined as the Ages and Stages Questionnaire, Third Edition (ASQ-3) total score. Secondary outcomes were HRQOL and functional status as measured by Pediatric Quality of Life Inventory and modified Pediatric Overall Performance Category scores, respectively. Sensitivity analyses modeled the outcome for patients lost to follow-up. Results Of 1318 infants alive 12 months after randomization, follow-up was performed in 927, with 462 patients in the NO group and 465 in the standard care group (median [IQR] age at follow-up, 16.6 [13.7-19.8] months; median [IQR] time since randomization, 12.7 [12.1-13.9] months; 516 male [55.7%]). There were no differences between the NO and standard care groups in ASQ-3 total score (mean [SD], 196.6 [75.4] vs 198.7 [73.8], respectively; adjusted mean difference, −2.24; 95% CI, −11.84 to 7.36). There were no differences in secondary outcomes. Prematurity (gestational age <37 weeks), univentricular lesions, congenital syndromes, and longer intensive care unit length of stay were associated with lower ASQ-3 total scores in adjusted multivariable analyses. Conclusions and Relevance In this randomized clinical trial of infants with congenital heart disease, NO administered via the CPB oxygenator did not improve neurodevelopmental outcomes or HRQOL 12 months after open heart surgery. Further research should explore homogenous cohorts with higher surgical risk and higher-dose or alternative therapies. Trial Registration ANZCTR Identifier: ACTRN12617000821392

IntroductionDespite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile and the emergence of specific impairments in children with CHD entering school. The performance of standardised screening tools to predict neurodevelopmental outcomes at school age in this high-risk population remains poorly understood. The NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial randomised 1371 children <2 years of age, investigating the effect of gaseous nitric oxide applied into the cardiopulmonary bypass oxygenator during heart surgery. The NITRIC follow-up study will follow this cohort annually until 5 years of age to assess outcomes related to cognition and socioemotional behaviour at school entry, identify risk factors for adverse outcomes and evaluate the performance of screening tools.Methods and analysisApproximately 1150 children from the NITRIC trial across five sites in Australia and New Zealand will be eligible. Follow-up assessments will occur in two stages: (1) annual online screening of global neurodevelopment, socioemotional and executive functioning, health-related quality of life and parenting stress at ages 2–5 years; and (2) face-to-face assessment at age 5 years assessing intellectual ability, attention, memory and processing speed; fine motor skills; language and communication; and socioemotional outcomes. Cognitive and socioemotional outcomes and trajectories of neurodevelopment will be described and demographic, clinical, genetic and environmental predictors of these outcomes will be explored.Ethics and disseminationEthical approval has been obtained from the Children’s Health Queensland (HREC/20/QCHQ/70626) and New Zealand Health and Disability (21/NTA/83) Research Ethics Committees. The findings will inform the development of clinical decision tools and improve preventative and intervention strategies in children with CHD. Dissemination of the outcomes of the study is expected via publications in peer-reviewed journals, presentation at conferences, via social media, podcast presentations and medical education resources, and through CHD family partners.Trial registration numberThe trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as ‘Gene Expression to Predict Long-Term Neurodevelopmental Outcome in Infants from the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) Study – A Multicentre Prospective Trial’. Trial registration: ACTRN12621000904875.

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

Objective 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. Study design 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. Results 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. Conclusions 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.

Key Points Question How commonly are hyperosmolar therapies used in the management of severe traumatic brain injury in children, and which agent—mannitol or hypertonic saline solution—is associated with greater decreases in intracranial pressure (ICP) and/or increases in cerebral perfusion pressure (CPP)? Findings In this comparative effectiveness research study of 1000 consecutive children with traumatic brain injury, more than 77% of the study population received hyperosmolar therapies during the ICP treatment phase of their care, and almost 2500 bolus administrations of 3% hypertonic saline and mannitol were analyzed. Hypertonic saline was associated with decreased ICP, whereas hypertonic saline and mannitol had similar observed effectiveness for CPP. Meaning This study of children with severe traumatic brain injury found that bolus administration of hypertonic saline was associated with superior ICP and CPP outcomes.

Objectives: To describe regional differences and change over time in the degree of centralization of pediatric intensive care in Australia and New Zealand (ANZ) and to compare the characteristics and ICU mortality of children admitted to specialist PICUs and general ICUs (GICUs). Design: A retrospective cohort study using registry data for two epochs of ICU admissions, 2003-2005 and 2016-2018. Setting: Population-based study in ANZ. Patients: A total of 43,256 admissions of children aged younger than 16 years admitted to an ICU in ANZ were included. Infants aged younger than 28 days without cardiac conditions were excluded. Interventions: None. Measurements and Main Results: The primary outcome was risk-adjusted ICU mortality. Logistic regression was used to investigate the association of mortality with the exposure to ICU type, epoch, and their interaction. Compared with children admitted to GICUs, children admitted to PICUs were younger (median 25 vs 47 mo; p < 0.01) and stayed longer in ICU (median 1.6 vs 1.0 d; p < 0.01). For the study overall, 93% of admissions in Australia were to PICUs whereas in New Zealand only 63% of admissions were to PICUs. The adjusted odds of death in epoch 2 relative to epoch 1 decreased (adjusted odds ratio [AOR], 0.50; 95% CI, 0.42-0.59). There was an interaction between unit type and epoch with increased odds of death associated with care in a GICU in epoch 2 (AOR, 1.63; 95% CI, 1.05-2.53 for all admissions; 1.73, CI, 1.002-3.00 for high-risk admissions). Conclusions: Risk-adjusted mortality of children admitted to specialist PICUs decreased over a study period of 14 years; however, a similar association between time and outcome was not observed in high-risk children admitted to GICUs. The results support the continued use of a centralized model of delivering intensive care for critically ill children.

Objective: A small percentage of infants with d-loop transposition of the great ar-teries with intact intraventricular septum have life-threatening refractory hypox-emia often due to coexistent persistent pulmonary hypertension of the newborn. In this case series we describe the outcomes of a "rescue" emergency arterial switch operation (ASO).Methods: We undertook a retrospective medical record analysis of infants with d-loop transposition of the great arteries with intact intraventricular septum who underwent an ASO in New Zealand from January 1, 1996, to April 30, 2017. Data were compared for those who received an emergency ASO and those with a nonemergency ASO for descriptive purposes. An emergency ASO was defined as one that was undertaken for life-threatening refractory hypoxemia when the only alternative stabilization strategy was preoperative extracorporeal life support. Pri-mary outcome measures were 30-day postoperative mortality and abnormal neuro-developmental outcome in the survivors. Secondary outcomes were low cardiac output, arrhythmia, renal dysfunction, postoperative seizures, and length of stay. Other known risk factors for morbidity and mortality were also assessed.Results: Two hundred seventy-two infants underwent an ASO with 25 (9%) who received an emergency ASO. No infants received preoperative extracorporeal life support. The emergency group had greater 30-day postoperative mortality (8.0% vs 0.4%; P = .01) with no difference in abnormal neurodevelopmental outcome among the survivors (17.4% vs 13.8%; P = .35). The emergency group had more therapies for low cardiac output syndrome, more postoperative seizures, and a longer length of stay.Conclusions: An emergency ASO is a definitive rescue therapy that can be under-taken with acceptable mortality and neurodevelopmental outcome with consider-ation of the preoperative clinical state. (J Thorac Cardiovasc Surg 2023;166:183-90)

The Neurodevelopmental and Psychological Outcomes Working Group of the Cardiac Neurodevelopmental Outcome Collaborative was formed in 2018 through support from an R13 grant from the National Heart, Lung, and Blood Institute with the goals of identifying knowledge gaps regarding the neurodevelopmental and psychological outcomes of individuals with CHD and investigations needed to advance science, policy, clinical care, and patient/family outcomes. Accurate characterisation of neurodevelopmental and psychological outcomes in children with CHD will drive improvements in patient and family outcomes through targeted intervention. Decades of research have produced a generalised perspective about neurodevelopmental and psychological outcomes in this heterogeneous population. Future investigations need to shift towards improving methods, measurement, and analyses of outcomes to better inform early identification, prevention, and intervention. Improved definition of underlying developmental, neuropsychological, and social-emotional constructs is needed, with an emphasis on symptom networks and dimensions. Identification of clinically meaningful outcomes that are most important to key stakeholders, including patients, families, schools and providers, is essential, specifically how and which neurodevelopmental differences across the developmental trajectory impact stakeholders. A better understanding of the discontinuity and patterns of neurodevelopment across the lifespan is critical as well, with some areas being more impactful at some ages than others. Finally, the field needs to account for the impact of race/ethnicity, socio-economic status, cultural and linguistic diversity on our measurement, interpretation of data, and approach to intervention and how to improve generalisability to the larger worldwide population of patients and families living with CHD.

Severe traumatic brain injury continues to present complex management and prediction challenges for the clinician. While there is some evidence that better systems of care can improve outcome, multiple multi-centre randomised controlled trials of specific therapies have consistently failed to show benefit. In addition, clinicians are challenged in attempting to accurately predict which children will recover well and which children will have severe and persisting neurocognitive deficits. Traumatic brain injury is vastly heterogeneous and so it is not surprising that one therapy or approach, when applied to a mixed cohort of children in a clinical trial setting, has yielded disappointing results. Children with severe traumatic brain injury have vastly different brain injury pathologies of widely varying severity, in any number of anatomical locations at what may be disparate stages of brain development. This heterogeneity may also explain why clinicians are unable to accurately predict outcome. Biomarkers are objective molecular signatures of injury that are released following traumatic brain injury and may represent a way of unifying the heterogeneity of traumatic brain injury into a single biosignature. Biomarkers hold promise to diagnose brain injury severity, guide intervention selection for clinical trials, or provide vital prognostic information so that early intervention and rehabilitation can be planned much earlier in the course of a child's recovery. Serum S100B and serum NSE levels show promise as a diagnostic tool with biomarker levels significantly higher in children with severe TBI including children with inflicted and non-inflicted head injury. Serum S100B and serum NSE also show promise as a predictor of neurodevelopmental outcome. The role of biomarkers in traumatic brain injury is an evolving field with the potential for clinical application within the next few years.

Introduction/Hypothesis: Robust evidence to support conditionspecific guidelines in pediatric neurocritical care (NCC) is limited. Our objective is to describe current pediatric NCC practice patterns to inform future investigations. Methods: Secondary analysis of a prospective point prevalence study conducted at 107 centers in 23 countries over a 4-week period that included children (n=924) 1 d 17 y of age admitted to an intensive care unit with cardiac arrest (CA, 23%), stroke (9%), traumatic brain injury (TBI, 19%), status epilepticus (SE, 17%), CNS infection (CNSI, 16%), hydrocephalus (HC, 5%), mass (9%), or spinal cord injury (SCI, 3%). Monitoring and interventions during hospitalization were compared between conditions and regions (χ2). Results: Use of conventional mechanical ventilation (50%), and central venous (58%) and arterial catheters (59%) were not different among conditions. Vasoactive agents were used in 24% of patients on d1, highest in CA (45%, p<0.001). Extracorporeal membrane oxygenation support was used in 10% of patients (30% in CA, p<0.001). Intracranial pressure (ICP) monitors were placed in 16% of patients (TBI 45%, p<0.001), most commonly with an external ventricular drain (61%). ICP-directed therapy (IDT) was used in 24% of patients, 47% without an ICP monitor. Use of ICP monitors among regions was similar; however, use of any IDT was higher in South America (41%) and Asia (45%) compared to other regions (range 19-45%, p<0.001). EEG was performed in 43% of children (62% in SE, p<0.001). Seizure prophylaxis was most common in SE (57%) and TBI (49%, p<0.001). Therapeutic hypothermia was uncommon (2%), used most in CA (5%). Cranial CTs were obtained in 70% of children (92% TBI, p<0.001) and MRIs in 79% (70% SCI, p=0.006). Physical (75%) and occupational (54%) therapy (PT, OT) were prescribed most for SCI (p<0.001) patients. PT (49%, range 19-49%, p=0.002) and OT (43%, range 19-49%, p<0.001) were most frequently prescribed in the North American region. Conclusions: Practice patterns varied significantly by condition and region, supporting the need for evidence generation to create pediatric-focused NCC management guidelines. These data also serve to provide key background information to power and direct future multi-center trials targeting new global pediatric NCC interventions.

Introduction: While bronchiolitis is regarded as a viral lower respiratory tract infection, there is some evidence for the perturbation of the airway microbiota in infants with bronchiolitis. Little is known about the lower airway microbiota in children with bronchiolitis due to difficulty obtaining samples. Aim: To describe the lower airway microbiota in comparison with upper airway microbiota in infants with severe bronchiolitis needing intubation and ventilation. Methods: Infants intubated with bronchiolitis in the paediatric intensive care unit were recruited and nasal swabs and non-bronchoscopic lavage were performed. Bacterial DNA was extracted and the V3-V4 region of the 16S rRNA gene was amplified and sequenced using Illumina MiSeq. The relative abundance of taxa and alpha diversity were calculated. Results: Ten infants (median age of 3 months) were sampled. Five children had RSV bronchiolitis and five had Rhinovirus bronchiolitis. Proteobacteria were the most abundant taxa in both upper and lower airway samples. In the lower airway samples, Haemophilus was the most abundant genus (mean relative abundance 67.7%), followed by Streptococcus (15.1%) and Moraxella (5.1%). This was very similar to the upper airway samples (mean relative abundance Haemophilus 42.2% followed by Streptococcus 18.1%, Prevotella 10.5% and Moraxella 6.7%). Conclusion: In infants with severe bronchiolitis, the lower and upper airway microbiota are largely similar in bacterial composition with dominance of Proteobacteria at the Phylum level and Haemophilus at the genus level.

INTRODUCTION:Congenital heart disease (CHD) is a major cause of infant mortality. Many infants with CHD require corrective surgery with most operations requiring cardiopulmonary bypass (CPB). CPB triggers a systemic inflammatory response which is associated with low cardiac output syndrome (LCOS), postoperative morbidity and mortality. Delivery of nitric oxide (NO) into CPB circuits can provide myocardial protection and reduce bypass-induced inflammation, leading to less LCOS and improved recovery. We hypothesised that using NO during CPB increases ventilator-free days (VFD) (the number of days patients spend alive and free from invasive mechanical ventilation up until day 28) compared with standard care. Here, we describe the NITRIC trial protocol. METHODS AND ANALYSIS:The NITRIC trial is a randomised, double-blind, controlled, parallel-group, two-sided superiority trial to be conducted in six paediatric cardiac surgical centres. One thousand three-hundred and twenty infants <2 years of age undergoing cardiac surgery with CPB will be randomly assigned to NO at 20 ppm administered into the CPB oxygenator for the duration of CPB or standard care (no NO) in a 1:1 ratio with stratification by age (<6 and ≥6 weeks), single ventricle physiology (Y/N) and study centre. The primary outcome will be VFD to day 28. Secondary outcomes include a composite of LCOS, need for extracorporeal membrane oxygenation or death within 28 days of surgery; length of stay in intensive care and in hospital; and, healthcare costs. Analyses will be conducted on an intention-to-treat basis. Preplanned secondary analyses will investigate the impact of NO on host inflammatory profiles postsurgery. ETHICS AND DISSEMINATION:The study has ethical approval (HREC/17/QRCH/43, dated 26 April 2017), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617000821392) and commenced recruitment in July 2017. The primary manuscript will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER:ACTRN12617000821392.

OBJECTIVEThere is no consensus on the optimal timing and specific brain MRI sequences in the evaluation and management of severe pediatric traumatic brain injury (TBI), and information on current practices is lacking. The authors performed a survey of MRI practices among sites participating in a multicenter study of severe pediatric TBI to provide information for designing future clinical trials using MRI to assess brain injury after severe pediatric TBI.METHODSInformation on current imaging practices and resources was collected from 27 institutions participating in the Approaches and Decisions after Pediatric TBI Trial. Multiple-choice questions addressed the percentage of patients with TBI who have MRI studies, timing of MRI, MRI sequences used to investigate TBI, as well as the magnetic field strength of MR scanners used at the participating institutions and use of standardized MRI protocols for imaging after severe pediatric TBI.RESULTSOverall, the reported use of MRI in pediatric patients with severe TBI at participating sites was high, with 40% of sites indicating that they obtain MRI studies in > 95% of this patient population. Differences were observed in the frequency of MRI use between US and international sites, with the US sites obtaining MRI in a higher proportion of their pediatric patients with severe TBI (94% of US vs 44% of international sites reported MRI in at least 70% of patients with severe TBI). The reported timing and composition of MRI studies was highly variable across sites. Sixty percent of sites reported typically obtaining an MRI study within the first 7 days postinjury, with the remainder of responses distributed throughout the first 30-day postinjury period. Responses indicated that MRI sequences sensitive for diffuse axonal injury and ischemia are frequently obtained in patients with TBI, whereas perfusion imaging and spectroscopy techniques are less common.CONCLUSIONSResults from this survey suggest that despite the lack of consensus or guidelines, MRI is commonly obtained during the acute clinical setting after severe pediatric TBI. The variation in MRI practices highlights the need for additional studies to determine the utility, optimal timing, and composition of clinical MRI studies after TBI. The information in this survey describes current clinical MRI practices in children with severe TBI and identifies important challenges and objectives that should be considered when designing future studies.

OBJECTIVESNeurodevelopmental disability is the most common complication among congenital heart surgery survivors. The Bayley scales are standardized instruments to assess neurodevelopment. The most recent edition (Bayley Scales of Infant and Toddler Development 3rd Edition, Bayley-III) yields better-than-expected scores in typically developing and high-risk infants than the second edition (Bayley Scales of Infant Development 2nd Edition, BSID-II). We compared BSID-II and Bayley-III scores in infants undergoing cardiac surgery.METHODSWe evaluated 2198 infants who underwent operations with cardiopulmonary bypass between 1996 and 2009 at 26 institutions. We used propensity score matching to limit confounding by indication in a subset of patients (n = 705).RESULTSOverall, unadjusted Bayley-III motor scores were higher than BSID-II Psychomotor Development Index scores (90.7 ± 17.2 vs 77.6 ± 18.8, P < 0.001), and unadjusted Bayley-III composite cognitive and language scores were higher than BSID-II Mental Development Index scores (92.0 ± 15.4 vs 88.2 ± 16.7, P < 0.001). In the propensity-matched analysis, Bayley-III motor scores were higher than BSID-II Psychomotor Development Index scores [absolute difference 14.1, 95% confidence interval (CI) 11.7-17.6; P < 0.001] and the Bayley-III classified fewer children as having severe [odds ratio (OR) 0.24; 95% CI 0.14-0.42] or mild-to-moderate impairment (OR 0.21; 95% CI 0.14-0.32). The composite of Bayley-III cognitive and language scores was higher than BSID-II Mental Development Index scores (absolute difference 4.0, 95% CI 1.4-6.7; P = 0.003), but there was no difference between Bayley editions in the proportion of children classified as having severe cognitive and language impairment.CONCLUSIONSThe Bayley-III yielded higher scores than the BSID-II and classified fewer children as severely impaired. The systematic bias towards higher scores with the Bayley-III precludes valid comparisons between early and contemporary cardiac surgery cohorts.

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 determine if transfusing ABO compatible platelets has a greater effect on incremental change in platelet count as compared to ABO incompatible platelets in critically ill children. Design: Secondary analysis of a prospective, observational study. Transfusions were classified as either ABO compatible, major incompatibility, or minor incompatibility. The primary outcome was the incremental change in platelet count. Transfusion reactions were analyzed as a secondary outcome. Setting: Eighty-two PICUs in 16 countries. Patients: Children (3 d to 16 yr old) were enrolled if they received a platelet transfusion during one of the predefined screening weeks. Interventions: None. Measurements and Main Results: Five-hundred three children were enrolled and had complete ABO information for both donor and recipient, as well as laboratory data. Three-hundred forty-two (68%) received ABO-identical platelets, 133 (26%) received platelets with major incompatibility, and 28 (6%) received platelets with minor incompatibility. Age, weight, proportion with mechanical ventilation or underlying oncologic diagnosis did not differ between the groups. After adjustment for transfusion dose, there was no difference in the incremental change in platelet count between the groups; the median (interquartile range) change for ABO-identical transfusions was 28 × 109 cells/L (8–68 × 109 cells/L), for transfusions with major incompatibility 26 × 109 cells/L (7–74 × 109 cells/L), and for transfusions with minor incompatibility 54 × 109 cells/L (14–81 × 109 cells/L) (p = 0.37). No differences in count increment between the groups were noted for bleeding (p = 0.92) and nonbleeding patients (p = 0.29). There were also no differences observed between the groups for any transfusion reaction (p = 0.07). Conclusions: No differences were seen in the incremental change in platelet count nor in transfusion reactions when comparing major ABO incompatible platelet transfusions with ABO compatible transfusions in a large study of critically ill children. Studies in larger, prospectively enrolled cohorts should be performed to validate whether ABO matching for platelet transfusions in critically ill children is necessary.

Objectives: To describe the epidemiology of platelet transfusions in critically ill children with an underlying oncologic diagnosis and to examine effects of prophylactic versus therapeutic transfusions. Design: Subgroup analysis of a prospective, observational study. Setting: Eighty-two PICUs in 16 countries. Patients: All children (3 d to 16 yr old) who received a platelet transfusion during one of the six predefined screening weeks and had received chemotherapy in the previous 6 months or had undergone hematopoietic stem cell transplantation in the last year. Interventions: None. Measurements and Main Results: Of the 548 patients enrolled in the parent study, 237 (43%) had an underlying oncologic diagnosis. In this population, 71% (168/237) of transfusions were given prophylactically, and 59% (139/237) of transfusions were given at a total platelet count greater than 20 × 109/L, higher than the current recommendations. Those with an underlying oncologic diagnosis were significantly older, and received less support including less mechanical ventilation, fewer medications that affect platelet function, and less use of extracorporeal life support than those without an underlying oncologic diagnosis. In this subpopulation, there were no statistically significant differences in median (interquartile range) platelet transfusion thresholds when comparing bleeding or nonbleeding patients (50 × 109/L [10–50 × 109/L] and 30 × 109/L [10–50 × 109/L], respectively [p = 0.166]). The median (interquartile range) interval transfusion increment in children with an underlying oncologic diagnosis was 17 × 109/L (6–52 × 109/L). The presence of an underlying oncologic diagnosis was associated with a poor platelet increment response to platelet transfusion in this cohort (adjusted odds ratio, 0.46; 95% CI, 0.22–0.95; p = 0.035). Conclusions: Children with an underlying oncologic diagnosis receive nearly half of platelet transfusions prescribed by pediatric intensivists. Over half of these transfusions are prescribed at total platelet count greater than current recommendations. Studies must be done to clarify appropriate indications for platelet transfusions in this vulnerable population.

Aims & Objectives: Brain injury & poor neurological outcomes have been reported in as many as 50% of ECMO survivors. We systematically searched the literature so that recommendations could be made on which neuromonitoring methods accurately predict neurological outcomes. Methods A systematic search of Medline (including ‘In-Process’ and ‘Non-Indexed’), Embase and Cochrane Central Register of Controlled trials was conducted from database inception to December 2014. Results The search strategy yeilded 7503 citations of which 190 full text articles were reviewed. Of these, 144 were excluded and 4 citations were identified from hand searching reference lists. A total of 50 articles evaluating 61 neuromonitoring methods underwent data abstraction. Neuromonitoring was used to evaluate an outcome of interest in 3816 children and adults. Acute brain injury: there were 18 diagnostic studies evaluating 24 neuromonitoring methods. These were serum biomarkers (7 studies), cranial ultrasound (7 studies), electroencephalogram (3 studies), clinical examination (3 studies), cerebral blood flow velocity (3 studies) & combination (1 study). Functional & Neurodevelopmental Outcomes: There were 14 prognostic studies that evaluated 13 neuromonitoring methods in children. These included cranial ultrasound (6 studies), serum biomarkers (2 studies), electroencephalogram (2 studies), clinical examination (2 studies) & cerebral blood flow velocity (1 study). Death: There were 29 prognostic studies that evaluated 33 neuromonitoring methods. These included serum biomarkers (20 studies), clinical examination (5 studies), electrophysiology (4 studies), cranial ultrasound (3 studies) & cerebral oximetry (1 study). Conclusions The majority of studies were high or unclear bias and it is likely that a weak recommendation will be made for neuromonitoring methods currently in use.

Objectives: The role of venoarterial extracorporeal membrane oxygenation in the treatment of severe pediatric septic shock continues to be intensely debated. Our objective was to determine whether the use of venoarterial extracorporeal membrane oxygenation in severe septic shock was associated with altered patient mortality, morbidity, and/or length of ICU and hospital stay when compared with conventional therapy. Design: International multicenter, retrospective cohort study using prospectively collected data of children admitted to intensive care with a diagnosis of severe septic shock between the years 2006 and 2014. Setting: Tertiary PICUs in Australia, New Zealand, Netherlands, United Kingdom, and United States. Patients: Children greater than 30 days old and less than 18 years old. Interventions: None. Measurements and Main Results: Of 2,452 children with a diagnosis of sepsis or septic shock, 164 patients met the inclusion criteria for severe septic shock. With conventional therapy (n = 120), survival to hospital discharge was 40%. With venoarterial extracorporeal membrane oxygenation (n = 44), survival was 50% (p = 0.25; CI, –0.3 to 0.1). In children who suffered an in-hospital cardiac arrest, survival to hospital discharge was 18% with conventional therapy and 42% with venoarterial extracorporeal membrane oxygenation (Δ = 24%; p = 0.02; CI, 2.5–42%). Survival was significantly higher in patients who received high extracorporeal membrane oxygenation flows of greater than 150 mL/kg/min compared with children who received standard extracorporeal membrane oxygenation flows or no extracorporeal membrane oxygenation (82%, 43%, and 48%; p = 0.03; CI, 0.1–0.7 and p < 0.01; CI, 0.2–0.7, respectively). Lengths of ICU and hospital stay were significantly longer for children who had venoarterial extracorporeal membrane oxygenation. Conclusions: The use of venoarterial extracorporeal membrane oxygenation in severe pediatric sepsis is not by itself associated with improved survival. However, venoarterial extracorporeal membrane oxygenation significantly reduces mortality after cardiac arrest due to septic shock. Venoarterial extracorporeal membrane oxygenation flows greater than 150 mL/kg/min are associated with almost twice the survival rate of conventional therapy or standard-flow extracorporeal membrane oxygenation.