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ObjectiveThe Surviving Sepsis Campaign recommends systematic screening for sepsis. Although many sepsis screening tools include parent or healthcare professional concern, there remains a lack of evidence to support this practice. We aimed to test the diagnostic accuracy of parent and healthcare professional concern in relation to illness severity, to diagnose sepsis in children.DesignThis prospective multicenter study measured the level of concern for illness severity as perceived by the parent, treating nurse and doctor using a cross-sectional survey. The primary outcome was sepsis, defined as a pSOFA score >0. The unadjusted area under receiver-operating characteristic curves (AUC) and adjusted Odds Ratios (aOR) were calculated.SettingTwo specialised pediatric Emergency Departments in QueenslandPatientsChildren aged 30 days to 18 years old that were evaluated for sepsisInterventionNoneMain Results492 children were included in the study, of which 118 (23.9%) had sepsis. Parent concern was not associated with sepsis (AUC 0.53, 95% CI: 0.46–0.61, aOR: 1.18; 0.89–1.58) but was for PICU admission (OR: 1.88, 95% CI: 1.17–3.19) and bacterial infection (aOR: 1.47, 95% CI: 1.14–1.92). Healthcare professional concern was associated with sepsis in both unadjusted and adjusted models (nurses: AUC 0.57, 95% CI-0.50, 0.63, aOR: 1.29, 95% CI: 1.02–1.63; doctors: AUC 0.63, 95% CI: 0.55, 0.70, aOR: 1.61, 95% CI: 1.14–2.19).ConclusionsWhile our study does not support the broad use of parent or healthcare professional concern in isolation as a pediatric sepsis screening tool, measures of concern may be valuable as an adjunct in combination with other clinical data to support sepsis recognition.Clinical Trial RegistrationACTRN12620001340921.

Paediatric sepsis remains a leading cause of childhood death. Morbidity is high, with up to one third of children affected developing ongoing, sometimes lifelong sequelae. To address the major burden of sepsis on child health, there is need for a unified approach to care, as outlined in the Australian National Action Plan for sepsis. While the Surviving Sepsis Campaign 2020 guidelines provided evidence-based recommendations for sepsis management in hospital, additional emphasis on families, pre-hospital recognition and post-sepsis care incorporating the multidisciplinary team is paramount to achieve quality patient outcomes. The role of families, paramedics and nurses in recognising and managing paediatric sepsis remains an under-represented area in current literature. The aim of this paper is to critically discuss key challenges surrounding the journey of paediatric sepsis, drawing on contemporary literature to highlight key areas pertinent to recognition and management of sepsis in children. Application of a holistic, patient-centred focus will provide an overview of paediatric sepsis, aiming to inform future development for enhanced healthcare delivery and identify critical areas for further research.

Major postintensive care sequelae affect up to one in three adult survivors of critical illness. Large cohorts on educational outcomes after pediatric intensive care are lacking. We assessed primary school educational outcomes in a statewide cohort of children who survived PICU during childhood.Multicenter population-based study on children less than 5 years admitted to PICU. Using the National Assessment Program-Literacy and Numeracy database, the primary outcome was educational achievement below the National Minimum Standard (NMS) in year 3 of primary school. Cases were compared with controls matched for calendar year, grade, birth cohort, sex, socioeconomic status, Aboriginal and Torres Strait Islander status, and school. Multivariable logistic regression models to predict educational outcomes were derived.Tertiary PICUs and mixed ICUs in Queensland, Australia.Children less than 5 years admitted to PICU between 1998 and 2016.Not applicable.Year 3 primary school data were available for 5,017 PICU survivors (median age, 8.0 mo at first PICU admission; interquartile range, 1.9-25.2). PICU survivors scored significantly lower than controls across each domain (p0.001); 14.03% of PICU survivors did not meet the NMS compared with 8.96% of matched controls (p0.001). In multivariate analyses, socioeconomic status (odds ratio, 2.14; 95% CI, 1.67-2.74), weight (0.94; 0.90-0.97), logit of Pediatric Index of Mortality-2 score (1.11; 1.03-1.19), presence of a syndrome (11.58; 8.87-15.11), prematurity (1.54; 1.09-2.19), chronic neurologic conditions (4.38; 3.27-5.87), chronic respiratory conditions (1.65; 1.24-2.19), and continuous renal replacement therapy (4.20; 1.40-12.55) were independently associated with a higher risk of not meeting the NMS.In this population-based study of childhood PICU survivors, 14.03% did not meet NMSs in the standardized primary school assessment. Socioeconomic status, underlying diseases, and severity on presentation allow risk-stratification to identify children most likely to benefit from individual follow-up and support.

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.

Background A novel human parechovirus 3 Australian recombinant (HPeV3-AR) strain emerged in 2013 and coincided with biennial outbreaks of sepsis-like illnesses in infants. We evaluated the molecular evolution of the HPeV3-AR strain and its association with severe HPeV infections. Methods HPeV3-positive samples collected from hospitalized infants aged 5–252 days in 2 Australian states (2013–2020) and from a community-based birth cohort (2010–2014) were sequenced. Coding regions were used to conduct phylogenetic and evolutionary analyses. A recombinant-specific polymerase chain reaction was designed and utilized to screen all clinical and community HPeV3-positive samples. Results Complete coding regions of 54 cases were obtained, which showed the HPeV3-AR strain progressively evolving, particularly in the 3′ end of the nonstructural genes. The HPeV3-AR strain was not detected in the community birth cohort until the initial outbreak in late 2013. High-throughput screening showed that most (>75%) hospitalized HPeV3 cases involved the AR strain in the first 3 clinical outbreaks, with declining prevalence in the 2019–2020 season. The AR strain was not statistically associated with increased clinical severity among hospitalized infants. Conclusions HPeV3-AR was the dominant strain during the study period. Increased hospital admissions may have been from a temporary fitness advantage and/or increased virulence.

Supplemental Digital Content is available in the text., Objective: To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020. Study Selection: Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms “sepsis,” “septicemia,” or “septic shock” in the title or abstract. Data Extraction: Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed. Data Synthesis: One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001). Conclusions: Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.

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

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

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.

Intensified treatment protocols have improved survival of pediatric oncology patients. However, these treatment protocols are associated with increased treatment-related morbidity requiring admission to pediatric intensive care unit (PICU). We aimed to describe the organizational characteristics and processes of care for this patient group across PICUs in Europe.A web-based survey was sent to PICU directors or representative physicians between February and June 2021.Responses were obtained from 77 PICUs of 12 European countries. Organizational characteristics were similar across the different countries of Europe. The median number of PICU beds was 12 (IQR 8-16). The majority of the PICUs was staffed by pediatric intensivists and had a 24/7 intensivist coverage. Most PICUs had a nurse-to-patient ratio of 1:1 or 1:2. The median numbers of yearly planned and unplanned PICU admissions of pediatric cancer patients were 20 (IQR 10-45) and 10 (IQR 10-30, respectively. Oncology specific practices within PICU were less common in participating centres. This included implementation of oncology protocols in PICU (30%), daily rounds of PICU physicians on the wards (13%), joint mortality and morbidity meetings or complex patients' discussions (30% and 40%, respectively) and participation of parents during clinical rounds (40%).Our survey provides an overview on the delivery of critical care for oncology patients in PICU across European countries. Multidisciplinary care for these vulnerable and challenging patients remains complex and challenging. Future studies need to determine the effects of differences in PICU organization and processes of care on patients' outcome.

OBJECTIVES: In children, coronavirus disease 2019 is usually mild but can develop severe hypoxemic failure or a severe multisystem inflammatory syndrome, the latter considered to be a postinfectious syndrome, with cardiac involvement alone or together with a toxic shock like-presentation. Given the novelty of severe acute respiratory syndrome coronavirus 2, the causative agent of the recent coronavirus disease 2019 pandemic, little is known about the pathophysiology and phenotypic expressions of this new infectious disease nor the optimal treatment approach.STUDY SELECTION: From inception to July 10, 2020, repeated PubMed and open Web searches have been done by the scientific section collaborative group members of the European Society of Pediatric and Neonatal Intensive Care.DATA EXTRACTION: There is little in the way of clinical research in children affected by coronavirus disease 2019, apart from descriptive data and epidemiology.DATA SYNTHESIS: Even though basic treatment and organ support considerations seem not to differ much from other critical illness, such as pediatric septic shock and multiple organ failure, seen in PICUs, some specific issues must be considered when caring for children with severe coronavirus disease 2019 disease.CONCLUSIONS: In this clinical guidance article, we review the current clinical knowledge of coronavirus disease 2019 disease in critically ill children and discuss some specific treatment concepts based mainly on expert opinion based on limited experience and the lack of any completed controlled trials in children at this time.

We validated an adapted form of the Pediatric Sepsis Score (aPSS), a disease-specific severity score available within 60 min of PICU admission, in children with invasive infection. aPSS consist of all components of PSS except lactate. aPSS predicted mortality in children with invasive infection (n = 4096; AUC 0.70 (95% CI 0.67-0.73)) and in children with sepsis (n = 1690; AUC 0.71 (0.67-0.76)). aPSS can be an adequate tool to predict outcome in children admitted to PICU with invasive infection or sepsis, especially in situations where lactate is not available within 60 min.

Background: Current strategies for risk stratification and prediction of neonatal early-onset sepsis (EOS) are inefficient and lack diagnostic performance. The aim of this study was to use machine learning to analyze the diagnostic accuracy of risk factors (RFs), clinical signs and biomarkers and to develop a prediction model for culture-proven EOS. We hypothesized that the contribution to diagnostic accuracy of biomarkers is higher than of RFs or clinical signs.Study Design: Secondary analysis of the prospective international multicenter NeoPInS study. Neonates born after completed 34 weeks of gestation with antibiotic therapy due to suspected EOS within the first 72 hours of life participated. Primary outcome was defined as predictive performance for culture-proven EOS with variables known at the start of antibiotic therapy. Machine learning was used in form of a random forest classifier.Results: One thousand six hundred eighty-five neonates treated for suspected infection were analyzed. Biomarkers were superior to clinical signs and RFs for prediction of culture-proven EOS. C-reactive protein and white blood cells were most important for the prediction of the culture result. Our full model achieved an area-under-the-receiver-operating-characteristic-curve of 83.41% (±8.8%) and an area-under-the-precision-recall-curve of 28.42% (±11.5%). The predictive performance of the model with RFs alone was comparable with random.Conclusions: Biomarkers have to be considered in algorithms for the management of neonates suspected of EOS. A 2-step approach with a screening tool for all neonates in combination with our model in the preselected population with an increased risk for EOS may have the potential to reduce the start of unnecessary antibiotics.

AIM: To evaluate the frequency and predictors of poor outcome in febrile children presenting to the Emergency Department. METHODS: Retrospective observational study from the Emergency Department of The Royal Children's Hospital, Melbourne, Australia. All children with presenting complaint of fever or triage temperature >38°C over a 6-month period were included. Poor outcome was defined as: new organ dysfunction or the requirement for organ support therapy (inotrope infusion, mechanical ventilation, renal replacement therapy and extra-corporeal life support). Predictors evaluated were as follows: initial vital signs, blood tests and clinical scores. Odds ratio, sensitivity, specificity and area under the receiver-operating characteristics curve were calculated for each predictor variable. RESULTS: Between Jan-June 2019, 6217 children met inclusion criteria. Twenty-seven (0.4%) developed new organ dysfunction, 10 (0.2%) required organ support therapy (inotrope infusion in 5, mechanical ventilation in 6, renal replacement therapy in 1, extra-corporeal life support in 1). Odds of new organ dysfunction, requirement for inotropic support and mechanical ventilation were higher with abnormal initial vital signs, blood tests and clinical scores, though overall test characteristics were poor due to infrequency. CONCLUSION: Poor outcomes were uncommon among febrile children presenting to the Emergency Department. Vital signs, blood tests and clinical scores were poor predictors.

Neonatal group B streptococcal sepsis remains a leading cause of neonatal sepsis globally and is characterized by unique epidemiologic features. Extracorporeal membrane oxygenation has been recommended for neonatal septic shock refractory to conventional management, but data on extracorporeal membrane oxygenation in group B streptococcal sepsis are scarce. We aimed to assess outcomes of extracorporeal membrane oxygenation in neonates with group B streptococcal sepsis.Retrospective study of the international registry of the Extracorporeal Life Support Organization.Extracorporeal membrane oxygenation centers contributing to Extracorporeal Life Support Organization registry.Patients less than or equal to 30 days treated with extracorporeal membrane oxygenation and a diagnostic code of group B streptococcal sepsis between January 1, 2007, and December 31, 2016.None.In-hospital mortality was the primary outcome. Univariable and multivariable logistic regression models to predict mortality were established. One hundred ninety-two runs in 191 neonates were identified meeting eligibility criteria, of which 55 of 191 (29%) died. One hundred thirty-seven (71%) were treated with venoarterial extracorporeal membrane oxygenation. One hundred sixty-nine runs (88%) occurred during the first week of life for early-onset sepsis and 23 (12%) after 7 days of life. The in-hospital mortality for extracorporeal membrane oxygenation used after 7 days of life was significantly higher compared with early-onset sepsis (65% vs 24%; p0.01). In addition, lower weight, lower pH, lower bicarbonate, and surfactant administration precannulation were significantly associated with mortality (p0.05). Adjusted analyses confirmed that age greater than 7 days, lower weight, and lower pH were associated with higher mortality (p0.05). One hundred fifty-one of 192 runs (79%) experienced a major complication. The number of major complications during extracorporeal membrane oxygenation was associated significantly with mortality (p0.001; adjusted odds ratio, 1.27 [1.08-1.49; p = 0.004]).This large registry-based study indicates that treatment with extracorporeal membrane oxygenation for neonatal group B streptococcal sepsis is associated with survival in the majority of patients. Future quality improvement interventions should aim to reduce the burden of major extracorporeal membrane oxygenation-associated complications which affected four out of five neonatal group B streptococcal sepsis extracorporeal membrane oxygenation patients.

Introduction: Peripheral arterial catheters (PAC) are used for haemodynamic monitoring and blood sampling in paediatric critical care. Limited data are available regarding PAC insertion and management practices, and how they relate to device function and failure. This information is necessary to inform future interventional research. Objectives: The primary objective of this study was to describe PAC insertion and management practices, and associated complications. Secondary objectives were to determine patient and clinical characteristics associated with risk of PAC successful insertion and failure. Methods: A prospective, observational study was conducted in the anaesthetic department and paediatric intensive care unit of a tertiary paediatric facility. Data were collected on PAC insertion, PAC management and PAC removal. Standard incidence and prevalence were calculated per 1,000 device days. Risk factors for multiple insertions and PAC failure were identified using Cox regression. Results: A total of 100 catheters in 89 children were examined capturing 472 device days. PACs were primarily inserted for blood sampling (78%) in the radial artery (78%) using ultrasound guidance (67%), with 31% inserted on first attempt. Heparin saline solution was used in 82% of devices. Median catheter dwell was 50.6 hours (IQR 24.0 – 158.0), with PAC failure occurring in 19 devices (20%), at a rate of 40.2 per 1000 catheter days (95% CI 25.7 - 63.1). Arm board immobilisation (HR 2.9; 95% CI 1.02-8.02; p = 0.05), higher PIM3 score (HR 1.06; 95% CI 1.03-1.09; p < 0.01) was associated with an increased the risk of PAC failure, and non-2% chlorhexidine antisepsis was associated with a decrease in PAC failure (HR 0.32; 95% CI 0.11-0.96; p = 0.04), in univariate analysis. Conclusions: PAC insertion is challenging, and failure is common. Prospective clinical trial data is needed to identify high risk patient groups and to develop interventions which optimise practices, thereby reducing failure.

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.

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

OBJECTIVES: Extracorporeal membrane oxygenation is increasingly used in critically ill patients with refractory cardiopulmonary failure. Nosocomial infection acquired during extracorporeal membrane oxygenation represents one of the most frequent complications but the available evidence on the risk of infection and its association with outcomes has not been comprehensively analyzed. We performed a narrative review examining the epidemiology of nosocomial infection during extracorporeal membrane oxygenation, association with clinical outcomes, and preventive strategies. DATA SOURCES: We searched PubMed, Web of Science, EMBASE, and the Cochrane Library between 1972 and June 2018. STUDY SELECTION: We included any article which detailed nosocomial infection during extracorporeal membrane oxygenation. Articles were excluded if they were not written in English, detailed extracorporeal membrane oxygenation use for infections acquired prior to extracorporeal membrane oxygenation, or used other forms of extracorporeal support such as ventricular assist devices. DATA EXTRACTION: Two reviewers independently assessed eligibility and extracted data. We screened 984 abstracts and included 59 articles in the final review. DATA SYNTHESIS: The reported risk of nosocomial infection among patients receiving extracorporeal membrane oxygenation ranged from 3.5% to 64% per extracorporeal membrane oxygenation run, while the incidence of infection ranged from 10.1 to 116.2/1,000 extracorporeal membrane oxygenation days. Nosocomial infections during extracorporeal membrane oxygenation were consistently associated with longer duration of extracorporeal membrane oxygenation and, in several large multicenter studies, with increased mortality. Risk factors for nosocomial infection included duration of extracorporeal membrane oxygenation, mechanical and hemorrhagic complications on extracorporeal membrane oxygenation, and use of venoarterial and central extracorporeal membrane oxygenation. Biomarkers had low specificity for infection in this population. Few studies examined strategies on how to prevent nosocomial infection on extracorporeal membrane oxygenation. CONCLUSIONS: Nosocomial infections in extracorporeal membrane oxygenation patients are common and associated with worse outcomes. There is substantial variation in the rates of reported infection, and thus, it is possible that some may be preventable. The evidence for current diagnostic, preventive, and therapeutic strategies for infection during extracorporeal membrane oxygenation is limited and requires further investigation.

IntroductionPeripheral intravenous catheters (PIVCs) frequently fail during therapy administration, resulting in infusates pooling in the surrounding tissue. These extravasation injuries can cause significant pain, tissue destruction and scarring. ivWatch is a biosensor that uses visible and near-infrared light to measure tissue changes surrounding the PIVC and alert clinicians when extravasation may occur. The effectiveness of ivWatch, in comparison to clinical observation, in decreasing injury severity is unknown. The present study aims to investigate whether using ivWatch may potentially detect injury earlier and decrease the severity of PIVC extravasation injuries.Methods and analysisA single centre, parallel group, open-label superiority randomised controlled trial comparing (a) standard care (clinical observation) to (b) ivWatch monitoring in addition to standard care, to decrease the severity of extravasation injuries. 200 children with PIVCs inserted in the distal half of the limb, receiving intermediate-risk to high-risk infusates for ≥24 hours, will be consecutively recruited at a paediatric intensive care unit in Queensland, Australia. The primary outcome is extravasation severity, measured by the Cincinnati Children’s Extravasation Harm Scale. Secondary outcomes include severity assessed with three-dimensional camera imaging, extravasation volume, treatment sequelae, the number of PIVCs used and dwell time, quality of life and healthcare costs. The between treatment difference in extravasation severity will be compared using ordinal logistic regression, with the treatment group included as the main effect, and reported with corresponding 95% CIs. Estimates of value will be presented as net monetary benefits and cost per reduction in extravasation injury severity, both presented with corresponding 95% credible intervals.Ethics and disseminationThis study received approval from the Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) (reference number: HREC/20/QCHQ/60867) and the Griffith University HREC (reference number: 2020/310) and will be disseminated via peer-reviewed publications and conference presentations.Trial registration numberACTRN12620000317998.

Since its introduction into the medical literature in the 1970s, the term multiple organ dysfunction syndrome (or some variant) has been applied broadly to any patient with >1 concurrent organ dysfunction. However, the epidemiology, mechanisms, time course, and outcomes among children with multiple organ dysfunction vary substantially. We posit that the term pediatric multiple organ dysfunction syndrome (or MODS) should be reserved for patients with a systemic pathologic state resulting from a common mechanism (or mechanisms) that affects numerous organ systems simultaneously. In contrast, children in whom organ injuries are attributable to distinct mechanisms should be considered to have additive organ system dysfunctions but not the syndrome of MODS. Although such differentiation may not always be possible with current scientific knowledge, we make the case for how attempts to differentiate multiple organ dysfunction from other states of additive organ dysfunctions can help to evolve clinical and research priorities in diagnosis, monitoring, and therapy from largely organ-specific to more holistic strategies.

CONTEXT Multiple scores exist to characterize organ dysfunction in children. OBJECTIVE To review the literature on multiple organ dysfunction (MOD) scoring systems to estimate severity of illness and to characterize the performance characteristics of currently used scoring tools and clinical assessments for organ dysfunction in critically ill children. DATA SOURCES Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020. STUDY SELECTION Studies were included if they evaluated critically ill children with MOD, evaluated the performance characteristics of scoring tools for MOD, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. DATA EXTRACTION Data were abstracted into a standard data extraction form by a task force member. RESULTS Of 1152 unique abstracts screened, 156 full text studies were assessed including a total of 54 eligible studies. The most commonly reported scores were the Pediatric Logistic Organ Dysfunction Score (PELOD), pediatric Sequential Organ Failure Assessment score (pSOFA), Pediatric Index of Mortality (PIM), PRISM, and counts of organ dysfunction using the International Pediatric Sepsis Definition Consensus Conference. Cut-offs for specific organ dysfunction criteria, diagnostic elements included, and use of counts versus weighting varied substantially. LIMITATIONS While scores demonstrated an increase in mortality associated with the severity and number of organ dysfunctions, the performance ranged widely. CONCLUSIONS The multitude of scores on organ dysfunction to assess severity of illness indicates a need for unified and data-driven organ dysfunction criteria, derived and validated in large, heterogenous international databases of critically ill children.

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

ObjectiveThe Surviving Sepsis Campaign guidelines recommend the implementation of systematic screening for sepsis. We aimed to validate a paediatric sepsis screening tool and derive a simplified screening tool.DesignProspective multicentre study conducted between August 2018 and December 2019. We assessed the performance of the paediatric sepsis screening tool using stepwise multiple logistic regression analyses with 10-fold cross-validation and evaluated the final model at defined risk thresholds.SettingTwelve emergency departments (EDs) in Queensland, Australia.Participants3473 children screened for sepsis, of which 523 (15.1%) were diagnosed with sepsis.InterventionsA 32-item paediatric sepsis screening tool including rapidly available information from triage, risk factors and targeted physical examination.Primary outcome measureSenior medical officer-diagnosed sepsis combined with the administration of intravenous antibiotics in the ED.ResultsThe 32-item paediatric sepsis screening tool had good predictive performance (area under the receiver operating characteristic curve (AUC) 0.80, 95% CI 0.78 to 0.82). A simplified tool containing 16 of 32 criteria had comparable performance and retained an AUC of 0.80 (95% CI 0.78 to 0.82). To reach a sensitivity of 90% (95% CI 87% to 92%), the final model achieved a specificity of 51% (95% CI 49% to 53%). Sensitivity analyses using the outcomes of sepsis-associated organ dysfunction (AUC 0.84, 95% CI 0.81 to 0.87) and septic shock (AUC 0.84, 95% CI 0.81 to 0.88) confirmed the main results.ConclusionsA simplified paediatric sepsis screening tool performed well to identify children with sepsis in the ED. Implementation of sepsis screening tools may improve the timely recognition and treatment of sepsis.

BackgroundThe surviving sepsis campaign recommends consideration for extracorporeal membrane oxygenation (ECMO) in refractory septic shock. We aimed to define the benefit threshold of ECMO in pediatric septic shock.MethodsRetrospective binational multicenter cohort study of all ICUs contributing to the Australian and New Zealand Paediatric Intensive Care Registry. We included patients ResultsFive thousand sixty-two children with sepsis and septic shock met eligibility criteria, of which 80 (1.6%) were treated with veno-arterial ECMO. A model based on 12 clinical variables predicted mortality with an AUROC of 0.879 (95% CI 0.864–0.895). The benefit threshold was calculated as 47.1% predicted risk of mortality. The observed mortality for children treated with ECMO below the threshold was 41.8% (23 deaths), compared to a predicted mortality of 30.0% as per the baseline model (16.5 deaths; standardized mortality rate 1.40, 95% CI 0.89–2.09). Among patients above the benefit threshold, the observed mortality was 52.0% (13 deaths) compared to 68.2% as per the baseline model (16.5 deaths; standardized mortality rate 0.61, 95% CI 0.39–0.92). Multivariable analyses identified lower lactate, the absence of cardiac arrest prior to ECMO, and the central cannulation (OR 0.31, 95% CI 0.10–0.98,p = 0.046) as significant predictors of survival for those treated with VA-ECMO.ConclusionsThis binational study demonstrates that a rapidly available sepsis mortality prediction model can define thresholds for survival benefit in children with septic shock considered for ECMO. Survival on ECMO was associated with central cannulation. Our findings suggest that a fully powered RCT on ECMO in sepsis is unlikely to be feasible.

We examined systems-level costs before and after the implementation of an emergency department paediatric sepsis screening, recognition and treatment pathway. Aggregated hospital admissions for all children aged

BackgroundInfections represent one of the most common complications in patients managed on Extracorporeal Membrane Oxygenation (ECMO) and are associated with poorer outcomes. Clinical signs of infection in patients on ECMO are non-specific. We assessed the diagnostic accuracy of Procalcitonin (PCT), C-reactive protein (CRP) and White cell count (WCC) to diagnose infection on ECMO.MethodsRetrospective single center observational study including neonates and children ResultsSixty-five ECMO runs in 58 patients were assessed. CRP had the best accuracy with an area under the ROC curve (AUC) of 0.79 (95%-CI 0.66–0.92) to diagnose confirmed infection and an AUC of 0.72 (0.61–0.84) to diagnose confirmed and suspected infection. Abnormal WCC performed slightly worse with an AUC of 0.70 (0.59–0.81) for confirmed and AUC of 0.66 (0.57–0.75) for confirmed and suspected infections. PCT was non-discriminatory.ConclusionThe diagnosis of infections acquired during ECMO remains challenging. Larger prospective studies are needed that also include novel infection markers to improve recognition of infection in patients on ECMO.

Antibiotic therapy represents one of the most common interventions in pediatric intensive care units (PICUs). This study aims to describe current antimicrobial stewardship programs (ASP) in European PICUs. A cross-sectional survey distributed to European pediatric intensive care physicians through the European Society of Neonatal and Pediatric Intensive Care (ESPNIC) Infection, Inflammation, and Sepsis Section, to members of the Spanish Society of Pediatric Intensive Care, of the Pediatric Reanimation and Emergency Care French Group, and to European physicians known to be involved in antimicrobial stewardship programs. Responses from 60 PICUs across 12 countries were analyzed. Fifty three (88%) stated that ASP was implemented. The main interventions considered as ASP were the pharmacokinetic monitoring of antimicrobials (n = 41, 77%) and the development of facility-specific clinical practice guidelines (n = 40, 75%). The most common team composition of antimicrobial stewardship program included a pediatric infectious disease physician, a pharmacist, and a microbiologist (n = 11, 21%). Although ASP practices were reported to be widely implemented across European PICUs, this survey observed a large heterogeneity in terms of activities and modalities of intervention.• Antibiotic therapy represents one of the most common interventions in pediatric intensive care units. • The role and subsequent success of antimicrobial stewardship programs has largely been reported in the adult population but scarcely in the pediatric population.• Antimicrobial stewardship programs were reported to be widely implemented across European pediatric intensive care units. • We observed a large heterogeneity in terms of activities and modalities of intervention.

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

Backgrounds The large, international, randomized controlled NeoPInS trial showed that procalcitonin (PCT)-guided decision making was superior to standard care in reducing the duration of antibiotic therapy and hospitalization in neonates suspected of early-onset sepsis (EOS), without increased adverse events. This study aimed to perform a cost-minimization study of the NeoPInS trial, comparing health care costs of standard care and PCT-guided decision making based on the NeoPInS algorithm, and to analyze subgroups based on country, risk category and gestational age. Methods Data from the NeoPInS trial in neonates born after 34 weeks of gestational age with suspected EOS in the first 72 h of life requiring antibiotic therapy were used. We performed a cost-minimization study of health care costs, comparing standard care to PCT-guided decision making. Results In total, 1489 neonates were included in the study, of which 754 were treated according to PCT-guided decision making and 735 received standard care. Mean health care costs of PCT-guided decision making were not significantly different from costs of standard care (€3649 vs. €3616). Considering subgroups, we found a significant reduction in health care costs of PCT-guided decision making for risk category ‘infection unlikely’ and for gestational age ≥ 37 weeks in the Netherlands, Switzerland and the Czech Republic, and for gestational age Conclusions Health care costs of PCT-guided decision making of term and late-preterm neonates with suspected EOS are not significantly different from costs of standard care. Significant cost reduction was found for risk category ‘infection unlikely,’ and is affected by both the price of PCT-testing and (prolonged) hospitalization due to SAEs.

Objective: Sepsis is responsible for a massive burden of disease, with a global estimate of 48.9 million cases resulting in approximately 11 million deaths annually. Survivors of sepsis may also experience long-term impairments that can persist for years after hospital discharge. These cognitive, physical and/or psychosocial deficits may contribute to a lower health related quality of life and represent a significant ongoing burden to the individual, the community and the health care system. We aim to systematically review the available evidence on long-term functional and quality of life outcomes after sepsis in children and adults.Data Sources: Medline, EMBASE, and CINAHL will be searched for eligible studies.Study Selection: Studies of adult and pediatric survivors of sepsis who had required admission to intensive care will be included. A minimum 6 month prospective follow up will be required. Accepted outcomes will be any validated measure of health-related quality of life (HRQoL) or functional deficits, using the Post-Intensive Care Syndrome (PICS) framework of cognitive, physical or psychosocial outcomes.Data Extraction: Data extraction will include information related to study characteristics, population characteristics, clinical criteria and outcomes.Data Synthesis: Studies meeting the inclusion criteria will be presented descriptively separated for pediatric and adult age groups. Meta-analysis will be attempted if sufficient primary data from several studies applying the same tests and outcomes are available. The primary outcome is HRQoL after sepsis; secondary outcomes include the functional status at follow-up.Conclusions: This systematic review will define the long-term impact of sepsis survivorship. The data will contribute to informing patient, clinician and stakeholder decisions and guide further research and resource management.