Franz E. Babl

Objective: Severe acute kidney injury (AKI) portends poor outcomes in pediatric sepsis. We evaluated the trajectory and prognostic utility of AKI biomarkers in pediatric septic shock using a subset of participants in the ongoing Pragmatic Pediatric Trial of Balanced vs. Normal Saline Fluid in Sepsis (PRoMPT BOLUS) trial, NCT04102371. We tested whether fluid volume is associated with persistent elevation of urine neutrophil gelatinase-associated lipocalin (Ur-NGAL). Methods: Prospective, non-prespecified cohort study within the PRoMPT BOLUS trial. Methods: Three children's hospitals in the United States. Methods: Four hundred seventy-eight patients aged 2 months to younger than 18 years old with septic shock. Methods: None. Results: Ur-NGAL, kidney injury molecule-1, liver fatty acid binding protein, and interleukin-18 and plasma cystatin C were collected at presentation (T1), days 2-3 (T2), and before discharge/death (T3). At presentation, 418 (88%) had no or only stage 1 AKI and 60 (12%) had stage 2/3 AKI defined using Kidney Disease Improving Global Outcomes creatinine thresholds. All biomarkers were higher with stage 2/3 compared with no/stage 1 AKI at T1 and T2, but only cystatin C remained higher at T3. Among patients with no/stage 1 AKI at presentation, those with Ur-NGAL greater than or equal to 150 vs. less than 150 ng/mL had fewer hospital-free days (21 [interquartile range (IQR) 15-24] vs. 23 d [IQR 19-25], p = 0.05). After applying inverse probability treatment weighting to balance covariates, 14% of patients who received greater than 100 mL/kg within 48 hours had persistently elevated Ur-NGAL over time compared with 6% who received 40-100 mL/kg (odds ratio 2.7 [95% CI, 1.1-6.2]). Hospital-free days were no different across fluid volume groups. Conclusions: Although kidney injury biomarkers mirrored serum creatinine in children with septic shock, elevated Ur-NGAL identified a subset with subclinical AKI with fewer hospital-free days despite no/stage 1 AKI by creatinine. Children receiving greater than 100 mL/kg fluid had greater odds of early and persistently elevated Ur-NGAL, suggesting high fluid volumes may perpetuate initial kidney damage.

Background: Paediatric cervical spine injury (CSI) is uncommon but can have devastating consequences. Many children, however, present to emergency departments (EDs) for the assessment of possible CSI. While imaging can be used to determine the presence of injuries, these tests are not without risks and costs, including exposure to radiation and associated life-time cancer risks. Clinical decision rules (CDRs) to guide imaging decisions exist, although two of the existing rules, the National Emergency X-Radiography Low Risk Criteria and the Canadian C-Spine Rule (CCR), focus on adults and a newly developed paediatric rule from the Pediatric Emergency Care Applied Research Network (PECARN) is yet to be externally validated. This study aims to externally validate these three CDRs in children. Methods: This is a multicentre prospective observational study of children younger than 16 years presenting with possible CSI following blunt trauma to 1 of 14 EDs across Australia, New Zealand and Singapore. Data will be collected on presenting features (history, injury mechanism, physical examination findings) and management (diagnostic imaging, admission, interventions, outcomes). The performance accuracy (sensitivity, specificity, negative and positive predictive values) of three existing CDRs in identifying children with study-defined CSIs and the specific CDR defined outcomes will be determined, along with multiple secondary outcomes including CSI epidemiology, investigations and management of possible CSI. Background: Ethics approval for the study was received from the Royal Children's Hospital Melbourne Human Research Ethics Committee in Australia (HREC/69436/RCHM-2020) with additional approvals from the New Zealand Human and Disability Ethics Committee and the SingHealth Centralised Institutional Review Board. Findings will be disseminated through peer-reviewed publications and future management guidelines. Background: Registration with the Australian New Zealand Clinical Trials Registry prior to the commencement of participant recruitment (ACTRN12621001050842). 50% of expected patients have been enrolled to date.

The novel Phoenix Sepsis Score and sepsis criteria were derived and validated using a multicountry dataset and proposed as a new definition for sepsis in children. To externally validate the Phoenix Sepsis Score and sepsis criteria in a cohort of children hospitalized with suspected community-acquired sepsis. This diagnostic study used data from the multicenter, multicountry Sepsis Epidemiology in Australian and New Zealand Emergency Departments (SENTINEL) study, collected from 2021 to 2023 and including 90-day follow-up. Children admitted to the hospital through 11 emergency departments in Australia and New Zealand and treated with parenteral antibiotics with either (1) a provisional diagnosis of sepsis or (2) treatment for sepsis (intravenous fluid bolus to treat poor perfusion) were included. Development of organ dysfunction over the first 24 hours of hospitalization. The main outcomes were (1) in-hospital mortality and (2) death or requirement for extracorporeal life support (ECLS) within 72 hours of hospitalization. A total of 6232 children were included in the analysis, with a median (IQR) age of 2.1 (0.3-7.1) years, 3386 (54.1%) male, in-hospital mortality of 60 (1.0%), and death or ECLS within 72 hours in 36 (0.6%). In this population, the worst Phoenix Sepsis Score calculated over the first 24 hours of hospitalization had an area under the precision recall curve of 0.17 (95% CI, 0.07-0.28) for predicting in-hospital mortality and 0.23 (95% CI, 0.11-0.36) for predicting death or ECLS within 72 hours. Overall, 306 children (4.9%) met the Phoenix sepsis criteria, of whom 33 (10.8%) died in the hospital (nearly half of the total number who died) and 28 (9.2%) died or required ECLS within 72 hours. The Phoenix sepsis criteria had a sensitivity of 55.0% (95% CI, 41.6%-67.9%) and positive predictive value (PPV) of 10.8% (95% CI, 7.6%-14.9%) for in-hospital mortality and sensitivity of 77.8% (95% CI, 60.8%-89.9%) and PPV of 9.2% (95% CI, 6.2%-13.0%) for death or ECLS within 72 hours. Coagulation data for the calculation of the Phoenix Sepsis Score were missing in more than 85% of children. In this multicenter diagnostic study of children hospitalized with suspected sepsis, the Phoenix Sepsis Score and sepsis criteria had similar performance to the original derivation and validation cohorts. The small proportion of children meeting Phoenix sepsis criteria, missingness of data, timing of application, and lack of sensitivity for in-hospital mortality limit the clinical utility of the criteria.

The Paediatric Research in Emergency Departments International Collaborative (PREDICT) has operated as an emergency research network in Australia and Aotearoa New Zealand for 20 years. A focus on both knowledge generation and, over the last decade, knowledge translation research has produced more than 200 network publications. Active research sites have increased from the original 12 sites to 47, with enhanced representation of where children with acute illness present in both countries. We outline ongoing challenges across the network, which will be relevant for those providing acute paediatric care and to other emergency clinicians interested in multicentre research collaboration.

Objective: Research in critically ill children poses challenges in acquiring prospective informed consent. International ethical guidelines generally have provisions to perform research without prior consent (RWPC) in circumstances where consent is not feasible, but there is a paucity of data regarding the community acceptance of this process. The objectives of the current study were to explore the attitudes and experiences of parents of children enrolled into trials to determine understanding and acceptability of RWPC to parents of children involved. Methods: Qualitative study of semi-structured telephone interviews in 2017 exploring themes of medical research, trial participation in RWPC. Interview transcripts underwent inductive thematic analysis with intercoder agreement, using Nvivo 14 software. Methods: Two clinical interventional trials in Australia conducted in critically ill children without prospective consent. Methods: Parents of children enrolled in critical care research. Methods: None. Results: A total of 49 interviews were conducted and analyzed. Parents of participants were supportive of processes used in the trials and RWPC. Paperwork was often not thought to contribute to improved understanding, with verbal information more valued. There was no consensus on the optimal approach of RWPC in situations when clinical outcome was poor. Conclusions: Our study in 2017 shows that parent/carer supported RWPC in two pediatric trials involving critically ill children. Parents were satisfied with existing approval methods and safeguards. Parents valued brief verbal information at the time of randomization. These historical findings support the feasibility of conducting research on time-sensitive interventions in emergency settings with RWPC, aligning with community expectations.