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Over the past two decades, pediatric intensive care research networks have been formed across North America, Europe, Asia, and Australia/New Zealand. The U.K. Paediatric Critical Care Society Study Group (PCCS-SG) has over a 20-year tradition of fostering collaborative research, leading to the design and successful conduct of randomized clinical trials (RCTs). To date, the PCCS-SG network has delivered 13 different multicenter RCTs, covering a spectrum of study designs, methodologies, and scale. Lessons from the early years have led PCCS-SG to now focus on the entire process needed for developing an RCT, starting from robust preparatory steps such as surveys, data analysis, and feasibility work through to a definitive RCT. Pilot RCTs have been an important part of this process as well. Facilitators of successful research have included the presence of a national registry to facilitate efficient data collection; close partnerships with established Clinical Trials Units to bring together clinicians, methodologists, statisticians, and trial managers; greater involvement of transport teams to recruit patients early in trials of time-sensitive interventions; and the funded infrastructure of clinical research staff within the National Health Service to integrate research within the clinical service. The informal nature of PCCS-SG has encouraged buy-in from clinicians. Greater international collaboration and development of embedded trial platforms to speed up the generation and dissemination of trial findings are two key future strategic goals for the PCCS-SG research network., Competing Interests: Dr. Peters’ institution received funding from the National Institute of Health Research Health Technology Assessment grants; he received support for article research from the U.K. National Institute of Health and Social Care Research. Dr. Ramnarayan received funding from Sanofi. Dr. Tasker received funding from Society of Critical Care Medicine as the Editor-in-Chief of Pediatric Critical Care Medicine and from Oxford University Press, Up-to-Date, and Walters Kluwer. Dr. Scholefield is supported on a National Institute of Health and Social Care Research Clinician Scientist Fellowship. Dr. Tume has disclosed that he does not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Purpose: Intravenous maintenance fluid therapy (IV-MFT) prescribing in acute and critically ill children is very variable among pediatric health care professionals. In order to provide up to date IV-MFT guidelines, the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) undertook a systematic review to answer the following five main questions about IV-MFT: (i) the indications for use (ii) the role of isotonic fluid (iii) the role of balanced solutions (iv) IV fluid composition (calcium, magnesium, potassium, glucose and micronutrients) and v) and the optimal amount of fluid., Methods: A multidisciplinary expert group within ESPNIC conducted this systematic review using the Scottish Intercollegiate Guidelines Network (SIGN) grading method. Five databases were searched for studies that answered these questions, in acute and critically children (from 37 weeks gestational age to 18 years), published until November 2020. The quality of evidence and risk of bias were assessed, and meta-analyses were undertaken when appropriate. A series of recommendations was derived and voted on by the expert group to achieve consensus through two voting rounds., Results: 56 papers met the inclusion criteria, and 16 recommendations were produced. Outcome reporting was inconsistent among studies. Recommendations generated were based on a heterogeneous level of evidence, but consensus within the expert group was high. "Strong consensus" was reached for 11/16 (69%) and "consensus" for 5/16 (31%) of the recommendations., Conclusions: Key recommendations are to use isotonic balanced solutions providing glucose to restrict IV-MFT infusion volumes in most hospitalized children and to regularly monitor plasma electrolyte levels, serum glucose and fluid balance., (© 2022. The Author(s).)

The ideal fluid for intravenous maintenance fluid therapy (IV-MFT) in acutely and critically ill children is controversial, and evidence-based clinical practice guidelines are lacking and current prescribing practices remain unknown. We aimed to describe the current practices in prescribing IV-MFT in the context of acute and critically ill children with regard to the amount, tonicity, composition, use of balanced fluids, and prescribing strategies in various clinical contexts. A cross-sectional electronic 27-item survey was emailed in April-May 2021 to pediatric critical care physicians across European and Middle East countries. The survey instrument was developed by an expert multi-professional panel within the European Society of Pediatric and Neonatal Intensive Care (ESPNIC). A total of 154 respondents from 35 European and Middle East countries participated (response rate 64%). Respondents were physicians in charge of acute or critically ill children. All respondents indicated they routinely use a predefined formula to prescribe the amount of IV-MFT and considered fluid balance monitoring very important in the management of acute and critically ill children. The use of balanced solution was preferred if there were altered serum sodium and chloride levels or metabolic acidosis. Just under half (42%, 65/153) of respondents believed balanced solutions should always be used. Respondents considered the use of isotonic IV solutions as important for acute and critically ill children. In terms of the indication and the composition of IV-MFT prescribed, responses were heterogeneous among centers. Almost 70% (107/154) respondents believed there was a gap between current practice and what they considered ideal IV-MFT due to a lack of guidelines and inadequate training of healthcare professionals.   Conclusions: Our study showed considerable variability in clinical prescribing practice of IV-MFT in acute pediatric settings across Europe and the Middle East. There is an urgent need to develop evidence-based guidelines for IV-MFT prescription in acute and critically ill children. What is Known: • The administration of maintenance intravenous fluid therapy is a standard of care for a lot of hospitalized children • Maintenance intravenous fluid therapy prescriptions are often based on Holliday and Segar's historical guidelines even if this practice has been associated with several complications. What is New: • This study provided information on the prescribing practice regarding fluid restriction, fluid tonicity, and balance. • This study showed considerable variability in clinical prescribing practice of intravenous maintenance fluid therapy across Europe and the Middle East., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To determine research priorities in PICU nutrition, which represent the shared priorities of patients, parents, carers, and PICU healthcare professionals within the United Kingdom., Design: A national multiphase priority setting methodology in partnership with the James Lind Alliance delivered over 16 months (June 2020-September 2021). Part 1: a national scoping survey asked respondents to submit their research uncertainties related to PICU nutrition. Part 2: summarizing and evidence-checking the submitted uncertainties. Part 3: interim prioritization survey. Part 4: consensus workshop., Setting: PICU., Participants: Patients, parents, and carers of patients who had been admitted to PICU, and PICU healthcare professionals involved in the treatment of these patients within the United Kingdom., Interventions: None., Measurements and Main Results: A national scoping survey asked respondents to submit their research uncertainties related to PICU nutrition. In the first survey, 165 topic ideas were suggested (12% by parents/carers and 88% by PICU healthcare professionals). These were categorized into 57 summary questions. The existing evidence was searched to ensure that the proposed summary questions had not already been answered. Forty were judged to be true uncertainties following a systematic literature review. These 40 uncertainties were grouped into eight themes for the second interim survey, which asked respondents to prioritize their top research questions. One hundred and forty participants contributed to this second interim survey. A final shortlist of 25 questions was derived, with the top 18 questions taken to a multistakeholder workshop where a consensus was reached on the top 10 priorities., Conclusions: This research identified important research gaps in the management of patients in PICU. Areas that need to be addressed as a priority include energy requirements in ventilated neonates, nutritional supplementation of probiotics to manage and prevent sepsis, the impact of postintensive care syndrome on nutrition and growth, and when to commence parenteral (IV) nutrition. The challenge now is to refine and deliver answers to these research priorities., Competing Interests: This work was led from Great Ormond Street Hospital. Dr. O’Connor secured financial support for the study from the British Dietetic Association. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: The European Society of Pediatric and Neonatal Intensive Care (ESPNIC) published 32 clinical recommendations around supporting nutrition in critically ill children following an extensive review of the literature online in January 2020. The challenge now is to engage with paediatric intensive care unit teams to implement these into their practice., Objective: This practical implementation guide uses a recognised implementation model to guide pediatric intensive care professionals to implement these evidence-based clinical recommendations into clinical practice., Results and Conclusions: We use the Pronovost implementation of evidence into practice model to provide a practical framework with associated documents to facilitate PICU healthcare professional's implementation of these clinical recommendations into PICU practice. The paper is structured around the four steps in this model: summarising the evidence, identifying local barriers to implementation, measuring performance and ensuring all patients receive the intervention and useful checklists for implementation and compliance monitoring are provided, in addition to tables outlining key professional roles and responsibilities around nutrition in the paediatric Intensive care Unit., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Routine measurement of gastric residual volume (GRV) to guide feeding in neonatal and paediatric intensive care is widespread. However, this practice is not evidence based and may cause harm. As part of a feasibility study, we explored parent and practitioner views on the acceptability of a trial comparing GRV measurement or no GRV measurement., Methods: A mixed-methods study involving interviews and focus groups with practitioners and interviews with parents with experience of tube feeding in neonatal and/or paediatric intensive care. A voting system recorded closed question responses during practitioner data collection, enabling the collection of quantitative and qualitative data. Data were analysed using thematic analysis and descriptive statistics., Results: We interviewed 31 parents and nine practitioners and ran five practitioner focus groups (n=42). Participants described how the research question was logical, and the intervention would not be invasive and potential benefits of not withholding the child's feeds. However, both groups held concerns about the potential risk of not measuring GRV, including delayed diagnosis of infection and gut problems, increased risk of vomiting into lungs and causing discomfort or pain. Parent's views on GRV measurement and consent decision making were influenced by their views on the importance of feeding in the ICU, their child's prognosis and associated comorbidities or complications., Conclusions: The majority of parents and practitioners viewed the proposed trial as acceptable. Potential concerns and preferences were identified that will need careful consideration to inform the development of the proposed trial protocol and staff training.

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., Competing Interests: Dr. Rimensberger has received a research grant from the European Union’s Horizon Research and Innovation Program (grant no 668259) through the Swiss State Secretariat for Education, Research, and Innovation (grant no 15.0342-1), 2016–2019 and research support by Getinge, SLE Ltd, and Stephan GmbH in 2013 and from ImtMedical in 2017. Dr. Jourdain had received a travel grant from Chiesi in 2015 and an accommodation grant by Teleflex in 2017. Dr. Pons-Odena’s institution received funding from Maquet, Philips, Fisher & Paykel, and Resmed, and he has been speaker for Maquet, Fisher & Paykel, and ResMed. Dr. Scholefield disclosed that he is funded by a National Institute for Health Research (Clinician Scientist) Fellowship award. Dr Terheggen has received a research grant by the Swiss National Foundation in 2016 and support for speaker activity from Hamilton, and he has received a nonrestricted grant from Nutricia Research. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: The FIRST-ABC trial comprises of two pragmatic, multicentre, parallel groups, non-inferiority randomised clinical trials designed to evaluate the clinical non-inferiority of first-line use of high flow nasal cannula (HFNC) to continuous positive airway pressure (CPAP) in critically ill children who require non-invasive respiratory support (NRS)., Objectives: To describe the pre-specified statistical and health economic analysis for the FIRST-ABC trial before completion of patient recruitment and data collection., Methods: The statistical analysis plan was designed by the chief investigators and statisticians. We define the primary and secondary outcomes, summarise methods for data collection and safety monitoring, and present a detailed description of the planned statistical and health economic analysis., Results: The primary clinical outcome is time to liberation from respiratory support. The primary effect estimate will be the adjusted hazard ratio, reported with a 95% confidence interval. As a sensitivity analysis, the primary analysis will be repeated using time to start weaning of NRS. Subgroup analyses will be performed to test for interactions between the effect of allocated treatment group and pre-specified baseline covariates. The health economic analysis will follow the intention-to-treat principle and report the mean (95% confidence interval) incremental costs, quality-adjusted life years (QALYs) and cost-effectiveness up to 6 months. All analyses will be performed separately for each of the two trials, and any results will not be combined., Conclusion: The FIRST-ABC trial will assess the non-inferiority of HFNC compared to CPAP in two parallel trials with shared infrastructure (step-up RCT and step-down RCT). We have developed a pre-specified statistical and health economics analysis plan for the FIRST-ABC study before trial completion to minimise analytical bias., Trial Registration: ISRCTN ISRCTN60048867 . Registered on 19 June 2019.

Background: Generating robust evidence within pediatric intensive care (PIC) can be challenging because of low patient numbers and patient heterogeneity. Systematic reviews may overcome small study biases but are limited by lack of standardization in outcome measures and their definition. Trials of nutrition interventions in PIC are increasing; thus, we wanted to examine the outcome measures being used in these trials., Objective: Our objective was to systematically describe outcome measures used when a nutrition intervention has been evaluated in a PIC randomized controlled trial., Methods: A systematic literature review of all studies involving a PIC trial of a nutrition intervention was undertaken from January 1, 1996, until February 20, 2018., Results: Twenty-nine trials met the criteria and were reviewed. They included a total of 3226 patients across all trials. Thirty-seven primary outcomes and 83 secondary outcomes were found. These were categorized into PIC-related outcomes (infection, intensive care dependency, organ dysfunction, and mortality) and nutrition outcomes (energy targets, nutrition parameters, and feeding tolerance). We found large variation in the outcome measures used. Outcome domains of energy targets, feeding tolerance, and infection were not adequately defined., Conclusions: Considerable variation in the outcome measures chosen and their definitions exist within PIC nutrition trials. Optimal nutrition outcomes for PIC must be agreed upon and defined, specifically domains of nutrition efficiency, nutrition tolerance, and non-nutrition PIC outcomes. The next step is to conduct an international Delphi study to gain expert consensus and develop a core outcome set to be reported in future pediatric nutrition trials., (© 2020 American Society for Parenteral and Enteral Nutrition.)

Background: Nutritional support is considered essential for the outcome of paediatric critical illness. There is a lack of methodologically sound trials to provide evidence-based guidelines leading to diverse practices in PICUs worldwide. Acknowledging these limitations, we aimed to summarize the available literature and provide practical guidance for the paediatric critical care clinicians around important clinical questions many of which are not covered by previous guidelines., Objective: To provide an ESPNIC position statement and make clinical recommendations for the assessment and nutritional support in critically ill infants and children., Design: The metabolism, endocrine and nutrition (MEN) section of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) generated 15 clinical questions regarding different aspects of nutrition in critically ill children. After a systematic literature search, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was applied to assess the quality of the evidence, conducting meta-analyses where possible, to generate statements and clinical recommendations, which were then voted on electronically. Strong consensus (> 95% agreement) and consensus (> 75% agreement) on these statements and recommendations was measured through modified Delphi voting rounds., Results: The final 15 clinical questions generated a total of 7261 abstracts, of which 142 publications were identified relevant to develop 32 recommendations. A strong consensus was reached in 21 (66%) and consensus was reached in 11 (34%) of the recommendations. Only 11 meta-analyses could be performed on 5 questions., Conclusions: We present a position statement and clinical practice recommendations. The general level of evidence of the available literature was low. We have summarised this and provided a practical guidance for the paediatric critical care clinicians around important clinical questions.

Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction., Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process., Methods: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate., Results: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified., Conclusions: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

Objective: To identify the core components of successful early warning systems for detecting and initiating action in response to clinical deterioration in paediatric inpatients., Methods: A hermeneutic systematic literature review informed by translational mobilisation theory and normalisation process theory was used to synthesise 82 studies of paediatric and adult early warning systems and interventions to support the detection of clinical deterioration and escalation of care. This method, which is designed to develop understanding, enabled the development of a propositional model of an optimal afferent component early warning system., Results: Detecting deterioration and initiating action in response to clinical deterioration in paediatric inpatients involves several challenges, and the potential failure points in early warning systems are well documented. Track and trigger tools (TTT) are commonly used and have value in supporting key mechanisms of action but depend on certain preconditions for successful integration into practice. Several supplementary interventions have been proposed to improve the effectiveness of early warning systems but there is limited evidence to recommend their wider use, due to the weight and quality of the evidence; the extent to which systems are conditioned by the local clinical context; and the need to attend to system component relationships, which do not work in isolation. While it was not possible to make empirical recommendations for practice, the review methodology generated theoretical inferences about the core components of an optimal system for early warning systems. These are presented as a propositional model conceptualised as three subsystems: detection, planning and action., Conclusions: There is a growing consensus of the need to think beyond TTTs in improving action to detect and respond to clinical deterioration. Clinical teams wishing to improve early warning systems can use the model to consider systematically the constellation of factors necessary to support detection, planning and action and consider how these arrangements can be implemented in their local context., Prospero Registration Number: CRD42015015326., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Feeding difficulties are common in young infants presenting with acute bronchiolitis, but limited data is available to guide clinicians adapting nutritional management. We aimed to assess paediatricians' nutritional practices among Western Europe French speaking countries. A survey was disseminated to describe advice given to parents for at home nutritional support, in hospital nutritional management, and preferred methods for enteral nutrition and for intravenous fluid management. A documentary search of international guidelines was concomitantly conducted. Ninety-three (66%) contacted physicians responded. Feeding difficulties were a common indication for infants' admission. Written protocols were rarely available. Enteral nutrition was favoured most of the time when oral nutrition was insufficient and might be withheld in case of severe dyspnoea to decrease respiratory workload. Half of physicians were aware of hyponatremia risk and pathophysiology, and isotonic intravenous solutions were used in less than 15% of centres. International guideline search (23 countries) showed a lack of detailed nutritional management recommendations in most of them.Conclusion: practices were inconsistent among physicians. Guidelines detailed nutritional management poorly. Awareness of hyponatremia risk in relation to intravenous hypotonic fluids and of the safety of enteral hydration and nutrition is insufficient. New guidelines including detailed nutritional management recommendations are urgently needed. What is Known? • Infants presenting with acute bronchiolitis face feeding difficulties. • Underfeeding may promote undernutrition, and intravenous hydration with hypotonic fluids may induce hyponatremia. What is New? • Physicians' nutritional practices are inconsistent and awareness of hyponatremia risk and pathophysiology is insufficient among physicians. • Awareness of hyponatremia risk and pathophysiology is insufficient among physicians. • The reasons for enteral nutrition withholding in bronchiolitis infants are not evidence based, and national guidelines of acute bronchiolitis across the world are elusive regarding nutritional management. • National guidelines of acute bronchiolitis across the world are elusive regarding nutritional management.

Ensuring optimal nutrition is vital in critically ill children and enteral feeding is the main route of delivery in intensive care. Feeding intolerance is the most commonly cited reason amongst pediatric intensive care unit healthcare professionals for stopping or withholding enteral nutrition, yet the definition for this remains inconsistent, nebulous, and entirely arbitrary. Not only does this pose problems clinically, but research in this field frequently uses feeding intolerance as an endpoint and the heterogeneity in this definition makes the comparison of studies difficult and meta-analysis impossible. We reviewed the use of, and definitions of, the term feed intolerance in pediatric intensive care research papers in the last 20 years. Gastric residual volume remains the most common factor used to define feed intolerance, despite the lack of evidence for this. Healthcare professionals would benefit from further education to improve their awareness of the limitations of the markers to define feeding intolerance, and the international PICU community needs to agree a consistent definition of this phenomenon to improve consistency in both practice and research.Conclusion: This paper will provide a narrative review of the definitions of, evidence for, and markers of feeding intolerance in critically ill children. What is Known?: • Feeding intolerance is a commonly cited reason amongst pediatric intensive care unit healthcare professionals for stopping or withholding enteral nutrition. • There is no agreed definition for feeding intolerance in critically ill children. What is New?: • This paper provides an up to date review of the definitions of, evidence for, and markers of feeding intolerance in critically ill children. • Despite no evidence, gastric residual volume continues to drive clinical bedside decisions about enteral feeding and feeding tolerance.