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Extracorporeal membrane oxygenation (ECMO) may be a viable salvage therapy in selected patients with septic shock. As ECMO use increases, we studied left ventricular (LV) performance during sepsis with and without ECMO using a pressure–volume (PV) loop in a murine model and aimed to understand LV hemodynamics in septic shock with ECMO. The rats were divided into Group 1 (ECMO applied to healthy rats), Group 2 (ECMO for septic rats), Group 3 (Controls, n = 20) and Group 4 (Sepsis induction only, n = 20). The cardiac parameters include end-diastolic volume (EDV), end-systolic volume (ESV), end-diastolic pressure (EDP), and end-systolic pressure (ESP), ejection fraction (EF), end-systolic elastance (Ees), diastolic time constant (Tau) index, arterial elastance (Ea), pressure–volume area (PVA), stroke work (SW), and potential energy (PE). We compared the changes of parameters in all groups. A total of 74 rats were included in the analyses. After 2 h on ECMO, Group 2 was associated with significant increases in ESP, EDV, ESV, PVA, PE, and SW. The difference ratio of PE and PVA was significantly higher in Group 2 compared to Group 1 (P < 0.01). In conclusion, myocardial oxygen consumption was higher in septic shock with ECMO than in controls.

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.

Mitochondrial and neurogenetic diseases can present diagnostic challenges. We investigated if near infrared spectroscopy with the vascular occlusion test is able to differentiate between children with mitochondrial disease and children with neurogenetic disease or healthy controls. Prospective observational study conducted in a tertiary children's hospital. Forty-three children with mitochondrial disease (including both genetically confirmed primary mitochondrial disease and cases with biochemical evidence of mitochondrial dysfunction), 19 children with non-mitochondrial neurogenetic disease and 13 healthy controls were recruited. The delta tissue oxygen index (ΔTOI) values showed greater variability amongst children with mitochondrial disease and neurogenetic disease than healthy controls despite the median ΔTOI being similar (median 14.1 and 18.8, t-test, p = 0.16). A low ΔTOI identifies cases with a higher probability of mitochondrial disease or neurogenetic disease compared to healthy controls (positive likelihood ratio: 3.67; 95%CI:1.01-13). A high ΔTOI with the near infrared spectroscopy with vascular occlusion test identifies cases with a lower probability of having a disease (negative likelihood ratio: 0.51; 95%CI:0.36-0.74). Near infrared spectroscopy with vascular occlusion test might be able to discriminate children with mitochondrial disease and neurogenetic disease from healthy controls.

Acute fulminant myocarditis (AFM) occurs as an inflammatory response to an initial myocardial insult. Its rapid and deadly progression calls for prompt diagnosis with aggressive treatment measures. The demonstration of its excellent recovery potential has led to increasing use of mechanical circulatory support, especially extracorporeal membrane oxygenation (ECMO). Arrhythmias, organ failure, elevated cardiac biomarkers, and decreased ventricular function at presentation predict requirement for ECMO. In these patients, ECMO should be considered earlier as the clinical course of AFM can be unpredictable and can lead to rapid haemodynamic collapse. Key uncertainties that clinicians face when managing children with AFM such as timing of initiation of ECMO and left ventricular decompression need further investigation.

IntroductionIntravenous fluid therapy is the most common intervention in critically ill children. There is an increasing body of evidence questioning the safety of high-volume intravenous fluid administration in these patients. To date, the optimal fluid management strategy remains unclear. We aimed to test the feasibility of a pragmatic randomised controlled trial comparing a restrictive with a standard (liberal) fluid management strategy in critically ill children.Methods and analysisMulticentre, binational pilot, randomised, controlled, open-label, pragmatic trial. Patients <18 years admitted to paediatric intensive care unit and mechanically ventilated at the time of screening are eligible. Patients with tumour lysis syndrome, diabetic ketoacidosis or postorgan transplant are excluded. Interventions: 1:1 random assignment of 154 individual patients into two groups—restrictive versus standard, liberal, fluid strategy—stratified by primary diagnosis (cardiac/non-cardiac). The intervention consists of a restrictive fluid bundle, including lower maintenance fluid allowance, limiting fluid boluses, reducing volumes of drug delivery and initiating diuretics or peritoneal dialysis earlier. The intervention is applied for 48 hours postrandomisation or until discharge (whichever is earlier). Endpoints: The number of patients recruited per month and proportion of recruited to eligible patients are feasibility endpoints. New-onset acute kidney injury and the incidence of clinically relevant central venous thrombosis are safety endpoints. Fluid balance at 48 hours after randomisation is the efficacy endpoint. Survival free of paediatric intensive care censored at 28 days is the clinical endpoint.Ethics and disseminationEthics approval was gained from the Children’s Health Queensland Human Research Ethics Committee (HREC/21/QCHQ/77514, date: 1 September 2021), and University of Zurich (2021-02447, date: 17 March 2023). The trial is registered with the Australia New Zealand Clinical Trials Registry (ACTRN12621001311842). Open-access publication in high impact peer-reviewed journals will be sought. Modern information dissemination strategies will also be used including social media to disseminate the outcomes of the study.Trial registration numberACTRN12621001311842.Protocol version/dateV5/23 May 2023.

ObjectivesBeta-lactams and vancomycin often require extended or continuous infusion strategies for antibiotic optimisation in the paediatric intensive care unit (PICU). Simultaneous administration of multiple drugs through a single lumen via a Y-site connector is utilised with uncertainty due to limited intravenous access and the common need for sedative-analgesic infusions in critical illness. The compatibility data supporting antibiotics and sedative-analgesics co-administration is lacking. This study describes the physicochemical compatibility between antibiotics and sedative-analgesics commonly prescribed in the PICU.MethodsAdmixtures of cefotaxime, meropenem, piperacillin-tazobactam and vancomycin with fentanyl, midazolam and morphine were examined for physicochemical compatibility at 6 hours after mixing. Fifty drug combinations at different nominal concentrations and two mixing ratios were analysed in triplicates against standards set out by the UK National Health Service Yellow Cover Document and the European Pharmacopoeia. Physical compatibility was assessed by visual inspection and subvisible particle counting, and chemical compatibility using pH measurements and content by ultra-high-performance liquid chromatography. Deviation of drug concentrations after mixing (assayed vs nominal) within 10% was defined as chemically compatible. Overall compatibility was described as ‘compatible’ when all criteria were met, and as ‘incompatible’ when at least one criterion was not met.ResultsY-site compatibility was demonstrated across all concentrations of fentanyl (10 to 50 μg/mL) and morphine (0.1 to 1 mg/mL) with the study antibiotics. Concentration-dependent compatibility of midazolam with cefotaxime, meropenem and piperacillin-tazobactam was observed. Compatibility was exhibited at a midazolam concentration of 0.2 mg/mL but not at concentrations of 1 and 2.5 mg/L. Vancomycin was compatible across the midazolam concentration range.ConclusionsThis study describes the favourable compatibility of fentanyl, morphine and vancomycin admixtures with the study drugs. It highlights the incompatibility of midazolam when co-infused with beta-lactam antibiotics. Clinicians must exercise caution when co-administering prolonged infusions of antibiotics to minimise the risk of antibiotic ineffectiveness.

Background: Pediatric oropharyngeal dysphagia screening protocols remain limited in acute and critical care settings due to the lack of psychometrically valid and reliable tools. Objectives: The eDelphi methodology was employed to establish content validity for the Children’s Oral Feeding Screener (COFS), a novel, nurse-led oropharyngeal dysphagia screening tool for hospitalized children in acute and critical care (0–16 years). Methods: The two-round eDelphi study was completed using Qualtrics®. A multidisciplinary, international steering-group guided tool conceptualization, elements for rating in the eDelphi, and oversaw consensus decisions. Experienced speech pathologists in pediatric acute and/or critical care were invited as panelists and rated tool content regarding (a) clinical presentations requiring immediate referral for dysphagia assessment; (b) oral trial component/s; and (c) signs observed during oral trials suggesting dysphagia. Items were rated on a 10-point Likert scale, and panelists could give open-ended feedback. Items not reaching pre-defined consensus (>75%) were re-presented in round two. Results: Fifty panelists participated in round one and 41 in round two, primarily from Australia (n = 19; 46%) and the United Kingdom (n = 13; 34%). Half (n = 22; 54%) had >10 years’ experience. Based on consensus scores, panelists’ qualitative feedback, and steering group decision, final items included eight clinical presentations, three oral trial elements (cup, bottle, breastfeeding) with three associated oral trial protocols, and fourteen signs suggestive of dysphagia. Other feedback led to changes to headings and the format of the COFS layout. Conclusions: Content validity for items in the three components of the COFS was established. Further work is now required to explore other psychometric properties (construct validity, sensitivity/specificity, and feasibility) in clinical settings.

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.

Introduction Shock-induced endotheliopathy (SHINE), defined as a profound sympathoadrenal hyperactivation in shock states leading to endothelial activation, glycocalyx damage, and eventual compromise of end-organ perfusion, was first described in 2017. The aggressive resuscitation therapies utilised in treating shock states could potentially lead to further worsening endothelial activation and end-organ dysfunction. Objective This study aimed to systematically review the literature on resuscitation-associated and resuscitation-induced endotheliopathy. Methods A predetermined structured search of literature published over an 11-year and 6-month period (1 January 2011 to 31 July 2023) was performed in two indexed databases (PubMed/MEDLINE and Embase) per PRISMA guidelines. Inclusion was restricted to original studies published in English (or with English translation) reporting on endothelial dysfunction in critically ill human subjects undergoing resuscitation interventions. Reviews or studies conducted in animals were excluded. Qualitative synthesis of studies meeting the inclusion criteria was performed. Studies reporting comparable biomarkers of endothelial dysfunction post-resuscitation were included in the quantitative meta-analysis. Results Thirty-two studies met the inclusion criteria and were included in the final qualitative synthesis. Most of these studies (47%) reported on a combination of mediators released from endothelial cells and biomarkers of glycocalyx breakdown, while only 22% reported on microvascular flow changes. Only ten individual studies were included in the quantitative meta-analysis based on the comparability of the parameters assessed. Eight studies measured syndecan-1, with a heterogeneity index, I 2  = 75.85% (pooled effect size, mean = 0.27; 95% CI  − 0.07 to 0.60; p  = 0.12). Thrombomodulin was measured in four comparable studies ( I 2  = 78.93%; mean = 0.41; 95% CI  − 0.10 to 0.92; p  = 0.12). Three studies measured E-selectin ( I 2  = 50.29%; mean =  − 0.15; 95% CI  − 0.64 to 0.33; p  = 0.53), and only two were comparable for the microvascular flow index, MFI ( I 2  = 0%; mean =  − 0.80; 95% CI  − 1.35 to − 0.26; p  < 0.01). Conclusion Resuscitation-associated endotheliopathy (RAsE) refers to worsening endothelial dysfunction resulting from acute resuscitative therapies administered in shock states. In the included studies, syndecan-1 had the highest frequency of assessment in the post-resuscitation period, and changes in concentrations showed a statistically significant effect of the resuscitation. There are inadequate data available in this area, and further research and standardisation of the ideal assessment and panel of biomarkers are urgently needed.