Search

Background In the past decade, molecular diagnostic syndromic arrays incorporating a range of bacterial and viral pathogens have been described. It is unclear how paediatric intensive care unit (PICU) staff diagnose lower respiratory tract infection (LRTI) and integrate diagnostic array results into antimicrobial decision-making. Methods An online survey with eleven questions was distributed throughout paediatric intensive care societies in the UK, continental Europe, and Australasia. Participants were asked to rate the clinical factors and investigations they used when prescribing for LRTI. Semi-structured interviews were undertaken with staff who participated in a single-centre observational study of a 52-pathogen diagnostic array. Results Seventy-two survey responses were received; most were from senior doctors. Whilst diagnostic arrays were used less frequently than routine investigations (i.e. microbiological culture), they were of comparable perceived utility when making antimicrobial decisions. Prescribers reported that for arrays to be clinically impactful, they would need to deliver results within six hours for stable patients and within one hour for unstable patients to inform their immediate decision to prescribe antimicrobials. From 16 staff interviews, we identified that arrays were helpful for the diagnosis and screening of bacterial LRTI. Staff reported it could be challenging to interpret results in some cases due to the high sensitivity of the test. Therefore, results were considered within the context of the patient and discussed within the multidisciplinary team. Conclusions Diagnostic arrays were considered of comparable value to microbiological investigations by PICU prescribers. Our findings support the need for further clinical and economic evaluation of diagnostic arrays in a randomised control trial. Trial registration Clinicaltrials.gov, NCT04233268, https://clinicaltrials.gov/ct2/show/NCT04233268. Registered 18 January 2020.

Summary Background In April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Methods We did a multicentre observational study of children (aged

Background: Broad-spectrum antimicrobial therapy is a key driver of antimicrobial resistance. Here, we aimed to review indications for antimicrobial therapy, determine the proportion of suspected bacterial infections that are confirmed by culture, and assess the time taken for microbiology test results to become available in the paediatric intensive care unit (PICU). Methods: A single-centre prospective observational cohort study of 100 consecutive general PICU admissions from 30 October 2019 to 19 February 2020. Data were collected from the hospital medical record and entered into a study database prior to statistical analysis using standard methods. Results: Of all episodes of suspected infection, 22% of lower respiratory tract infection, 43% of bloodstream and 0% of central nervous system infection were associated with growth on microbiology culture. 90% of children received antimicrobial therapy. Hospital-acquired infection occurred less commonly than primary infection, but an organism was grown in a greater proportion (64%) of cultures. Final laboratory reports for negative cultures were issued at a median of 120.3 hours for blood cultures and 55.5 hours for endotracheal tube aspirate cultures. Conclusions: Despite most critically children receiving antimicrobial therapy, infection was often not microbiologically confirmed. Novel molecular diagnostics may improve rationalisation of treatment in this population.

Background Broad-spectrum antimicrobial therapy is a key driver of antimicrobial resistance. Here, we aimed to review indications for antimicrobial therapy, determine the proportion of suspected bacterial infections that are confirmed by culture, and assess the time taken for microbiology test results to become available in the paediatric ICU (PICU). Methods A single-centre prospective observational cohort study of 100 consecutive general PICU admissions from 30 October 2019 to 19 February 2020. Data were collected from the hospital medical record and entered into a study database prior to statistical analysis using standard methods. Results Of all episodes of suspected infection, 22% of lower respiratory tract infection, 43% of bloodstream and 0% of central nervous system infection were associated with growth on microbiology culture. Ninety percent of children received antimicrobial therapy. Hospital-acquired infection occurred less commonly than primary infection, but an organism was grown in a greater proportion (64%) of cultures. Final laboratory reports for negative cultures were issued at a median of 120.3 h for blood cultures and 55.5 h for endotracheal tube aspirate cultures. Conclusions Despite most critically children receiving antimicrobial therapy, infection was often not microbiologically confirmed. Novel molecular diagnostics may improve rationalization of treatment in this population.

IntroductionLower respiratory tract infection (LRTI) is the most commonly treated infection in critically ill children. Pathogens are infrequently identified on routine respiratory culture, and this is a time-consuming process. A syndromic approach to rapid molecular testing that includes a wide range of bacterial and fungal targets has the potential to aid clinical decision making and reduce unnecessary broad spectrum antimicrobial prescribing. Here, we describe a single-centre prospective cohort study investigating the use of a 52-pathogen TaqMan array card (TAC) for LRTI in the paediatric intensive care unit (PICU).Methods and analysisCritically ill children with suspected LRTI will be enrolled to this 100 patient single-centre prospective observational study in a PICU in the East of England. Samples will be obtained via routine non-bronchoscopic bronchoalveolar lavage which will be sent for standard microbiology culture in addition to TAC. A blood draw will be obtained via any existing vascular access device. The primary outcomes of the study will be (1) concordance of TAC result with routine culture and 16S rRNA gene sequencing and (2) time of diagnostic result from TAC versus routine culture. Secondary outcomes will include impact of the test on total antimicrobial prescriptions, a description of the inflammatory profile of the lung and blood in response to pneumonia and a description of the clinical experience of medical and nursing staff using TAC.Ethics and disseminationThis study has been approved by the Yorkshire and the Humber-Bradford Leeds Research Ethics Committee (REC reference 20/YH/0089). Informed consent will be obtained from all participants. Results will be published in peer-reviewed publications and international conferences.Trial registration numberNCT04233268.

Background Acute kidney injury (AKI) in pediatric critical care patients is diagnosed using elevated serum creatinine, which occurs only after kidney impairment. There are no treatments other than supportive care for AKI once it has developed, so it is important to identify patients at risk to prevent injury. This study develops a machine learning model to learn pre-disease patterns of physiological measurements and predict pediatric AKI up to 48 h earlier than the currently established diagnostic guidelines. Methods EHR data from 16,863 pediatric critical care patients between 1 month to 21 years of age from three independent institutions were used to develop a single machine learning model for early prediction of creatinine-based AKI using intelligently engineered predictors, such as creatinine rate of change, to automatically assess real-time AKI risk. The primary outcome is prediction of moderate to severe AKI (Stage 2/3), and secondary outcomes are prediction of any AKI (Stage 1/2/3) and requirement of renal replacement therapy (RRT). Predictions generate alerts allowing fast assessment and reduction of AKI risk, such as: “patient has 90% risk of developing AKI in the next 48 h” along with contextual information and suggested response such as “patient on aminoglycosides, suggest check level and review dose and indication”. Results The model was successful in predicting Stage 2/3 AKI prior to detection by conventional criteria with a median lead-time of 30 h at AUROC of 0.89. The model predicted 70% of subsequent RRT episodes, 58% of Stage 2/3 episodes, and 41% of any AKI episodes. The ratio of false to true alerts of any AKI episodes was approximately one-to-one (PPV 47%). Among patients predicted, 79% received potentially nephrotoxic medication after being identified by the model but before development of AKI. Conclusions As the first multi-center validated AKI prediction model for all pediatric critical care patients, the machine learning model described in this study accurately predicts moderate to severe AKI up to 48 h in advance of AKI onset. The model may improve outcome of pediatric AKI by providing early alerting and actionable feedback, potentially preventing or reducing AKI by implementing early measures such as medication adjustment.

Neisseria meningitidis, the causative agent of meningococcal disease (MD), evades complement-mediated clearance upon infection by ‘hijacking’ the human complement regulator factor H (FH). The FH protein family also comprises the homologous FH-related (FHR) proteins, hypothesized to act as antagonists of FH, and FHR-3 has recently been implicated to play a major role in MD susceptibility. Here, we show that, next to FH and FHR-3, the circulating levels of all FH family proteins are equally decreased during pediatric MD. We did not observe a specific consumption of FH or FHR-3 by N. meningitidis during the first days of infection and the levels recovered over time. MD severity associated predominantly with a loss of FH. Strikingly, loss of FH and FHRs associated strongly with renal failure, suggesting insufficient protection of host tissue by the FH protein family. Retaining higher levels of FH family proteins may thus limit tissue injury during MD.

Severe acute respiratory syndrome coronavirus 2 is a novel cause of organ dysfunction in children, presenting as either coronavirus disease 2019 with sepsis and/or respiratory failure or a hyperinflammatory shock syndrome. Clinicians must now consider these diagnoses when evaluating children for septic shock and sepsis-associated organ dysfunction. The Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children provide an appropriate framework for the early recognition and initial resuscitation of children with sepsis or septic shock caused by all pathogens, including severe acute respiratory syndrome coronavirus 2. However, the potential benefits of select adjunctive therapies may differ from non-coronavirus disease 2019 sepsis.

The international scope of critical neurologic insults in children is unknown. Our objective was to assess the prevalence and outcomes of children admitted to PICUs with acute neurologic insults. Prospective study. Multicenter (n = 107 PICUs) and multinational (23 countries, 79% in North America and Europe). Children 7 days to 17 years old admitted to the ICU with new traumatic brain injury, stroke, cardiac arrest, CNS infection or inflammation, status epilepticus, spinal cord injury, hydrocephalus, or brain mass. None. We evaluated the prevalence and outcomes of children with predetermined acute neurologic insults. Child and center characteristics were recorded. Unfavorable outcome was defined as change in pre-post insult Pediatric Cerebral Performance Category score greater than or equal to 2 or death at hospital discharge or 3 months, whichever came first. Screening data yielded overall prevalence of 16.2%. Of 924 children with acute neurologic insults, cardiac arrest (23%) and traumatic brain injury (19%) were the most common. All-cause mortality at hospital discharge was 12%. Cardiac arrest subjects had highest mortality (24%), and traumatic brain injury subjects had the most unfavorable outcomes (49%). The most common neurologic insult was infection/inflammation in South America, Asia, and the single African site but cardiac arrest in the remaining regions. Neurologic insults are a significant pediatric international health issue. They are frequent and contribute substantial morbidity and mortality. These data suggest a need for an increased focus on acute critical neurologic diseases in infants and children including additional research, enhanced availability of clinical resources, and the development of new therapies.

In 2001, the Surviving Sepsis Campaign (SSC) began to develop evidence-based guidelines and recommendations for the resuscitation and management of patients with sepsis. With the 2016 edition, the Society of Critical Care Medicine and European Society of Intensive Care Medicine recommended a separate task force be dedicated to guideline formulation for children. The objective of the “Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children” is to provide guidance for the care of infants, children, and adolescents with septic shock and other sepsis-associated organ dysfunction. Recommendations are intended to guide “best practice” rather than to establish a treatment algorithm or to define standard of care and cannot replace the clinician's decision-making capability when presented with a patient's unique set of clinical variables.

Contains fulltext : 230013.pdf (Publisher’s version ) (Closed access) 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. 01 februari 2020

ObjectiveTo determine the prevalence of work-related psychological distress in staff working in UK paediatric intensive care units (PICU).DesignOnline (Qualtrics) staff questionnaire, conducted April to May 2018.SettingStaff working in 29 PICUs and 10 PICU transport services were invited to participate.Participants1656 staff completed the survey: 1194 nurses, 270 physicians and 192 others. 234 (14%) respondents were male. Median age was 35 (IQR 28–44).Main outcome measuresThe Moral Distress Scale-Revised (MDS-R) was used to look at moral distress, the abbreviated Maslach Burnout Inventory to examine the depersonalisation and emotional exhaustion domains of burnout, and the Trauma Screening Questionnaire (TSQ) to assess risk of post-traumatic stress disorder (PTSD).Results435/1194 (36%) nurses, 48/270 (18%) physicians and 19/192 (10%) other staff scored above the study threshold for moral distress (≥90 on MDS-R) (χ2 test, p2 test, p=0.0004). 366/1194 (31%) nurses, 42/270 (16%) physicians and 21/192 (11%) other staff scored at risk for PTSD (χ2 test, pConclusionsThese results suggest that UK PICU staff are experiencing work-related distress. Further studies are needed to understand causation and to develop strategies for prevention and treatment.

Objective To identify parents’ prioritised outcomes by combining qualitative findings from two trial feasibility studies of interventions for paediatric suspected severe infection. Design Qualitative synthesis combining parent interview data from the Fluids in Shock (FiSh) and Fever feasibility studies. Parents had experience of their child being admitted to a UK emergency department or intensive care unit with a suspected infection. Participants n=: 85 parents. FiSh study: n=41 parents, 37 mothers, 4 fathers, 7 were bereaved. Fever study: n=44 parents, 33 mothers, 11 fathers, 7 were bereaved. Results In addition to survival, parents prioritised short-term outcomes including: organ and physiological functioning (eg, heart rate, breathing rate and temperature); their child looking and/or behaving more like their normal self; and length of time on treatments or mechanical support. Longer term prioritised outcomes included effects of illness on child health and development. We found that parents’ prioritisation of outcomes was influenced by their experience of their child’s illness, survival and the point at which they are asked about outcomes of importance in the course of their child’s illness. Conclusions Findings provide insight into parent prioritised outcomes to inform the design of future trials investigating treatments for paediatric suspected or proven severe infection as well as core outcome set development work. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made.

Aims Working in a Paediatric intensive care unit (PICU) is stressful. Staff may be at risk of post-traumatic stress disorder (PTSD), burnout and moral distress. These impact on staff well-being, staff retention and patient care. The aim of this study was to determine the prevalence of these conditions in healthcare professionals across the UK PICU community. Methods Staff with regular patient contact from UK PICUs and PICU transport services were invited to participate. Moral Distress Scale (Revised) (MDS-R) was used to look at moral distress, Trauma Screening Questionnaire (TSQ) to assess risk of PTSD and abbreviated Maslach Burnout Inventory (aMBI) to examine depersonalisation (DP) and emotional exhaustion (EE) domains of burnout. Participation was via an online (Qualtrics LLC) questionnaire over a 6 week period (April – May 2018). Differences between the groups were assessed using appropriate non-parametric statistical tests. Results 1656 staff from 27 PICUs and 10 PICU retrieval services completed the survey; 1183 nurses, 269 physicians and 204 other members of staff. Nurses had a higher MDS-R score (median 75, IQR 48–106) than physicians (53, 31–78) and others (31, 8–61), p Conclusion These results suggest that UK PICU staff are experiencing work-related distress. Further studies are needed to understand the reasons why, to develop strategies for prevention and to help those affected, and to determine the risk in PICU staff compared to health care workers in other acute care settings.

Background: Broad-spectrum antimicrobial therapy is a key driver of antimicrobial resistance. Here, we aimed to review indications for antimicrobial therapy, determine the proportion of suspected bacterial infections that are confirmed by culture, and assess the time taken for microbiology test results to become available in the paediatric intensive care unit (PICU). Methods: A single-centre prospective observational cohort study of 100 consecutive general PICU admissions from 30 October 2019 to 19 February 2020. Data were collected from the hospital medical record and entered into a study database prior to statistical analysis using standard methods. Results: Of all episodes of suspected infection, 22% of lower respiratory tract infection, 43% of bloodstream and 0% of central nervous system infection were associated with growth on microbiology culture. 90% of children received antimicrobial therapy. Hospital-acquired infection occurred less commonly than primary infection, but an organism was grown in a greater proportion (64%) of cultures. Final laboratory reports for negative cultures were issued at a median of 120.3 hours for blood cultures and 55.5 hours for endotracheal tube aspirate cultures. Conclusions: Despite most critically children receiving antimicrobial therapy, infection was often not microbiologically confirmed. Novel molecular diagnostics may improve rationalisation of treatment in this population.

© 2017 International Society of Blood Transfusion Background and Objectives: Plasma transfusions are a frequent treatment worldwide, but many studies have reported a wide variation in the indications to transfuse. Recently, an international paediatric study also showed wide variation in frequency in the use of plasma transfusions: 25% of the centres transfused plasma to > 5% of their patients, whereas another 25% transfused plasma to < 1% of their patients. The objective of this study was to explore the factors associated with different plasma transfusion practices in these centres. Materials and Methods: Online survey sent to the local investigators of the 101 participating centres, in February 2016. Four areas were explored: beliefs regarding plasma transfusion, patients’ case-mix in each unit, unit’s characteristics, and local blood product transfusion policies and processes. Results: The response rate was 82% (83/101). 43% of the respondents believed that plasma transfusions can arrest bleeding, whereas 27% believe that plasma transfusion can prevent bleeding. Centres with the highest plasma transfusion rate were more likely to think that hypovolaemia and mildly abnormal coagulation tests are appropriate indications for plasma transfusions (P = 0·02 and P = 0·04, respectively). Case-mix, centre characteristics or local transfusion services were not identified as significant relevant factors. Conclusion: Factors influencing plasma transfusion practices reflect beliefs about indications and the efficacy of transfusion in the prevention and management of bleeding as well as effects on coagulation tests. Educational and other initiatives to target these beliefs should be the focus of research.

The role played by fever in the outcome of critical illness in children is unclear. This survey of medical and nursing staff in 35 paediatric intensive care units and transport teams in the United Kingdom and Ireland established attitudes towards the management of children with fever. Four hundred sixty-two medical and nursing staff responded to a web-based survey request. Respondents answered eight questions regarding thresholds for temperature control in usual clinical practice, indications for paracetamol use, and readiness to participate in a clinical trial of permissive temperature control. The median reported threshold for treating fever in clinical practice was 38 °C (IQR 38-38.5 °C). Paracetamol was reported to be used as an analgesic and antipyretic but also for non-specific comfort indications. There was a widespread support for a clinical trial of a permissive versus a conservative approach to fever in paediatric intensive care units. Within a trial, 58% of the respondents considered a temperature of 39 °C acceptable without treatment.Staff on paediatric intensive care units in the United Kingdom and Ireland tends to treat temperatures within the febrile range. There was a willingness to conduct a randomized controlled trial of treatment of fever. What is known: • The effect of fever on the outcome in paediatric critical illness is unknown. • Paediatricians have traditionally been reluctant to allow fever in sick children. What is new: • Paediatric intensive care staff report a tendency towards treating fever, with a median reported treatment threshold of 38 °C. • There is widespread support amongst PICU staff in the UK for a randomized controlled trial of temperature in critically ill children. • Within a trial setting, PICU staff attitudes to fever are more permissive than in clinical practice.

Each year approximately 20,000 children are admitted to PICUs across the United Kingdom. It is highlighted in several international studies that 40-70% of children admitted to PICUs have at least one chronic health condition that leads to increased length of stay and higher mortality rates. The prevalence of chronic health conditions in children admitted to U.K. PICUs is unknown. The purpose of this study was to use existing clinical data to explore the prevalence and impact of chronic health conditions on length of stay and mortality in a tertiary U.K. PICU.Single-centre retrospective observational cohort study.Single, tertiary referral PICU.One thousand one hundred ninety-seven children 0-18 years old admitted between March 1, 2009, and February 28, 2013.None.Data were derived from the unit's data submitted to the Paediatric Intensive Care Audit Network, the U.K. national PICU dataset. Data included demographics, diagnosis, Pediatric Index of Mortality-2 score, PICU interventions, PICU outcomes, chronic health condition etiologies, admission, and discharge dates and times. In total, 554 of 1,197 (46.3%) had at least one chronic health condition. Of 554, 371 patients (67.1%) presented with a single chronic health condition, 126 (22.6%) with two chronic health conditions, and 57 (10.3%) with at least three chronic health conditions to a maximum of four chronic health conditions. There was a statistically significant difference in length of stay in those with a chronic health condition compared with those without (medians, 4 vs 3 d [interquartile range, 1-7 d]; Mann-Whitney U test, p0.001). The length of stay also increased significantly according to the number of chronic health conditions (Kruskal-Wallis test, p0.001). Mortality was significantly different between those with and without chronic health conditions (8.8% vs 5.4%; chi-square test, p = 0.024). Having two or at least three chronic health conditions significantly increased mortality compared with no chronic health conditions (odds ratio, 2.3 [CI, 1.2-4.55]; p = 0.013 and 2.95 [CI, 1.28-6.8]; p = 0.011), respectively.The increasing number of chronic healthcare conditions is associated with length of stay and mortality.

Respiratory Syncytial Virus (RSV) is a common cause of bronchiolitis. Although there are a number of recognized complications, pulmonary hemorrhage has not been reported previously. A retrospective case notes review was performed through an electronic search of a Pediatric Intensive Care Unit's medical records. Seven patients with RSV infection and pulmonary hemorrhage were identified and included in this case series. Six of the seven patients were born prematurely (30-36 weeks gestation). All patients required blood transfusion. The pulmonary hemorrhage events all occurred after a period of mechanical ventilation and following extubation. All of the patients required reintubation with a mean of 5 further days of mechanical ventilation. Pulmonary hemorrhage is an uncommon complication of RSV infection, which has not been reported previously in the literature. Further studies are required to determine incidence, pathogenesis, and outcome. Pediatr Pulmonol. 2017;52:E32-E36. © 2016 Wiley Periodicals, Inc.

Summary Background Paediatric acute respiratory distress syndrome (PARDS) is associated with high mortality in children, but until recently no paediatric-specific diagnostic criteria existed. The Pediatric Acute Lung Injury Consensus Conference (PALICC) definition was developed to overcome limitations of the Berlin definition, which was designed and validated for adults. We aimed to determine the incidence and outcomes of children who meet the PALICC definition of PARDS. Methods In this international, prospective, cross-sectional, observational study, 145 paediatric intensive care units (PICUs) from 27 countries were recruited, and over a continuous 5 day period across 10 weeks all patients were screened for enrolment. Patients were included if they had a new diagnosis of PARDS that met PALICC criteria during the study week. Exclusion criteria included meeting PARDS criteria more than 24 h before screening, cyanotic heart disease, active perinatal lung disease, and preparation or recovery from a cardiac intervention. Data were collected on the PICU characteristics, patient demographics, and elements of PARDS (ie, PARDS risk factors, hypoxaemia severity metrics, type of ventilation), comorbidities, chest imaging, arterial blood gas measurements, and pulse oximetry. The primary outcome was PICU mortality. Secondary outcomes included 90 day mortality, duration of invasive mechanical and non-invasive ventilation, and cause of death. Findings Between May 9, 2016, and June 16, 2017, during the 10 study weeks, 23 280 patients were admitted to participating PICUs, of whom 744 (3·2%) were identified as having PARDS. 95% (708 of 744) of patients had complete data for analysis, with 17% (121 of 708; 95% CI 14–20) mortality, whereas only 32% (230 of 708) of patients met Berlin criteria with 27% (61 of 230) mortality. Based on hypoxaemia severity at PARDS diagnosis, mortality was similar among those who were non-invasively ventilated and with mild or moderate PARDS (10–15%), but higher for those with severe PARDS (33% [54 of 165; 95% CI 26–41]). 50% (80 of 160) of non-invasively ventilated patients with PARDS were subsequently intubated, with 25% (20 of 80; 95% CI 16–36) mortality. By use of PALICC PARDS definition, severity of PARDS at 6 h after initial diagnosis (area under the curve [AUC] 0·69, 95% CI 0·62–0·76) discriminates PICU mortality better than severity at PARDS diagnosis (AUC 0·64, 0·58–0·71), and outperforms Berlin severity groups at 6 h (0·64, 0·58–0·70; p=0·01). Interpretation The PALICC definition identified more children as having PARDS than the Berlin definition, and PALICC PARDS severity groupings improved the stratification of mortality risk, particularly when applied 6 h after PARDS diagnosis. The PALICC PARDS framework should be considered for use in future epidemiological and therapeutic research among children with PARDS. Funding University of Southern California Clinical Translational Science Institute, Sainte Justine Children's Hospital, University of Montreal, Canada, Reseau en Sante Respiratoire du Fonds de Recherche Quebec-Sante, and Children's Hospital Los Angeles, Department of Anesthesiology and Critical Care Medicine.

Background: Sepsis is one of the main reasons for non-elective admission to pediatric intensive care units (PICUs), but little is known about determinants influencing outcome. We characterized children admitted with community-acquired sepsis to European PICUs and studied risk factors for mortality and disability.Methods: Data were collected within the collaborative Seventh Framework Programme (FP7)-funded EUCLIDS study, which is a prospective multicenter cohort study aiming to evaluate genetic determinants of susceptibility and/or severity in sepsis. This report includes 795 children admitted with community-acquired sepsis to 52 PICUs from seven European countries between July 2012 and January 2016. The primary outcome measure was in-hospital death. Secondary outcome measures were PICU-free days censured at day 28, hospital length of stay, and disability. Independent predictors were identified by multivariate regression analysis.Results: Patients most commonly presented clinically with sepsis without a source (n = 278, 35%), meningitis/encephalitis (n = 182, 23%), or pneumonia (n = 149, 19%). Of 428 (54%) patients with confirmed bacterial infection, Neisseria meningitidis (n = 131, 31%) and Streptococcus pneumoniae (n = 78, 18%) were the main pathogens. Mortality was 6% (51/795), increasing to 10% in the presence of septic shock (45/466). Of the survivors, 31% were discharged with disability, including 24% of previously healthy children who survived with disability. Mortality and disability were independently associated with S. pneumoniae infections (mortality OR 4.1, 95% CI 1.1–16.0, P = 0.04; disability OR 5.4, 95% CI 1.8–15.8, P P P Conclusions: Despite widespread immunization campaigns, invasive bacterial disease remains responsible for substantial morbidity and mortality in critically ill children in high-income countries. Almost one third of sepsis survivors admitted to the PICU were discharged with some disability. More research is required to delineate the long-term outcome of pediatric sepsis and to identify interventional targets. Our findings emphasize the importance of improved early sepsis-recognition programs to address the high burden of disease.

Background: Oxygen saturation monitoring for children receiving respiratory support is standard worldwide. No randomised clinical trials have compared peripheral oxygen saturation (SpO2) targets for critically ill children. The harm of interventions to raise SpO2 to > 94% may exceed their benefits. Methods: We undertook an open, parallel-group randomised trial of children > 38 weeks completed gestation and < 16 years of age receiving invasive or non-invasive respiratory support and supplemental oxygen who were admitted urgently to one of three paediatric intensive care units. A ‘research without prior consent’ approach was employed. Children were randomly assigned to a liberal oxygenation group (SpO2 targets > 94%) or a conservative oxygenation group (SpO2 = 88–92% inclusive). Outcomes were measures of feasibility: recruitment rate, protocol adherence and acceptability, between-group separation of SpO2 and safety. The Oxy-PICU trial was registered before recruitment: ClinicalTrials.gov identifier NCT03040570. Results: A total of 159 children met the inclusion criteria, of whom 119 (75%) were randomised between April and July 2017, representing a rate of 10 patients per month per site. The mean time to randomisation from first contact with an intensive care team was 1.9 (SD 2.2) h. Consent to continue in the study was obtained in 107 cases (90%); the children’s parents/legal representatives were supportive of the consent process. The median (interquartile range, IQR) of time-weighted individual mean SpO2 was 94.9% (92.6–97.1) in the conservative oxygenation group and 97.5% (96.2–98.4) in the liberal group [difference 2.7%, 95% confidence interval (95% CI) 1.3–4.0%, p < 0.001]. Median (IQR) time-weighted individual mean FiO2 was 0.28 (0.24–0.37) in the conservative group and 0.37 (0.30–0.42) in the liberal group (difference 0.08, 95% CI 0.03–0.13, p < 0.001). There were no significant between-group differences in length of stay, duration of organ support or mortality. Two prespecified serious adverse events (cardiac arrests) occurred, both in the liberal oxygenation group. Conclusion: A definitive clinical trial of peripheral oxygen saturation targets is feasible in critically ill children.

The authors of the article entitled "Paediatric Intensive Care admission blood pressure and risk of death in 30,334 children" inform that due to an error in their database extraction, the following corrections to the data published should be notified.

Recent evidence suggests that fluid overload may be deleterious to critically ill children. The purpose of this study was to investigate the association of early fluid overload with respiratory morbidity and mortality in patients admitted to a general PICU.Retrospective cohort study.Single, tertiary referral PICU.patients aged 0-16 years invasively ventilated at 48 hours post admission, admitted between April 1, 2009, and March 31, 2013.Data collected included demographics, diagnosis, Pediatric Index of Mortality 2 score, and fluid overload percent at 48 hours from admission. Fluid overload percent was calculated as (cumulative fluid in - cumulative fluid out (L))/hospital admission weight (kg) × 100%. Outcome measures were oxygenation index at 48 hours from admission, death, and invasive ventilation days in survivors. Data are reported as median (interquartile range) and were analyzed using nonparametric tests. The median age was 1.05 years (0.3-4.2 yr). Fifty-three patients (8%) died. Median duration of ventilation in survivors was 5 days (3-8 d). Fluid overload percent correlated significantly with oxygenation index (Spearman ρ, 0.318; p0.0001) and with invasive ventilation days in survivors (Spearman ρ, 0.274; p0.0001). There was no significant difference in fluid overload percent between survivors and nonsurvivors. Regression analysis demonstrated that fluid overload percent was a significant predictor of both oxygenation index at 48 hours (p0.001) and invasive ventilation days (p = 0.002).Fluid overload at 48 hours was associated with oxygenation index at 48 hours and invasive ventilation days in survivors in a general PICU population. There was no association of fluid overload at 48 hours with mortality.

Background Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe. Methods The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) was a prospective, multicentre, cohort study done in six countries in Europe. Patients aged 1 month to 18 years with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 participating hospitals in the UK, Austria, Germany, Lithuania, Spain, and the Netherlands were prospectively recruited between July 1, 2012, and Dec 31, 2015. To assess disease burden and outcomes, we collected demographic and clinical data using a secured web-based platform and obtained microbiological data using locally available clinical diagnostic procedures. Findings 2844 patients were recruited and included in the analysis. 1512 (53·2%) of 2841 patients were male and median age was 39·1 months (IQR 12·4–93·9). 1229 (43·2%) patients had sepsis and 1615 (56·8%) had severe focal infections. Patients diagnosed with sepsis had a median age of 27·6 months (IQR 9·0–80·2), whereas those diagnosed with severe focal infections had a median age of 46·5 months (15·8–100·4; pInterpretation Mortality in children admitted to hospital for sepsis or severe focal infections is low in Europe. The disease burden is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections. Despite the availability and application of clinical procedures for microbiological diagnosis, the causative organism remained unidentified in approximately 50% of patients.

Background There has been no randomised controlled trial (RCT) of fluid bolus therapy in paediatric sepsis in the developed world despite evidence that excess fluid may be associated with harm. Objectives To determine the feasibility of the Fluids in Shock (FiSh) trial – a RCT comparing restricted fluid bolus (10 ml/kg) with current practice (20 ml/kg) in children with septic shock in the UK. Design (1) Qualitative feasibility study exploring parents’ views about the pilot RCT. (2) Pilot RCT over a 9-month period, including integrated parental and staff perspectives study. Setting (1) Recruitment took place across four NHS hospitals in England and on social media. (2) Recruitment took place across 13 NHS hospitals in England. Participants (1) Parents of children admitted to a UK hospital with presumed septic shock in the previous 3 years. (2) Children presenting to an emergency department with clinical suspicion of infection and shock after 20 ml/kg of fluid. Exclusion criteria were receipt of > 20 ml/kg of fluid, conditions requiring fluid restriction and the patient not for full active treatment (i.e. palliative care plan in place). Site staff and parents of children in the pilot were recruited to the perspectives study. Interventions (1) None. (2) Children were randomly allocated (1 : 1) to 10- or 20-ml/kg fluid boluses every 15 minutes for 4 hours if in shock. Main outcome measures (1) Acceptability of FiSh trial, proposed consent model and potential outcome measures. (2) Outcomes were based on progression criteria, including recruitment and retention rates, protocol adherence and separation between the groups, and collection and distribution of potential outcome measures. Results (1) Twenty-one parents were interviewed. All would have consented for the pilot study. (2) Seventy-five children were randomised, 40 to the 10-ml/kg fluid bolus group and 35 to the 20-ml/kg fluid bolus group. Two children were withdrawn. Although the anticipated recruitment rate was achieved, there was variability across the sites. Fifty-nine per cent of children in the 10-ml/kg fluid bolus group and 74% in the 20-ml/kg fluid bolus group required only a single trial bolus before shock resolved. The volume of fluid (in ml/kg) was 35% lower in the first hour and 44% lower over the 4-hour period in the 10-ml/kg fluid bolus group. Fluid boluses were delivered per protocol (volume and timing) for 79% of participants in the 10-ml/kg fluid bolus group and for 55% in the 20-ml/kg fluid bolus group, mainly as a result of delivery not being completed within 15 minutes. There were no deaths. Length of hospital stay, paediatric intensive care unit (PICU) transfers, and days alive and PICU free did not differ significantly between the groups. Two adverse events were reported in each group. A questionnaire was completed by 45 parents, 20 families and seven staff were interviewed and 20 staff participated in focus groups. Although a minority of site staff lacked equipoise in favour of more restricted boluses, all supported the trial. Conclusions Even though a successful feasibility and pilot RCT were conducted, participants were not as unwell as expected. A larger trial is not feasible in its current design in the UK. Future work Further observational work is required to determine the epidemiology of severe childhood infection in the UK in the postvaccine era. Trial registration Current Controlled Trials ISRCTN15244462. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 51. See the NIHR Journals Library website for further project information.

Infectious diseases remain a major cause of mortality and morbidity in the developed world, accounting for more than 25 % of deaths in children under the age of 5 years in Europe [1]. Even with improved recognition and management serious morbidity in survivors is high. As a pediatric critical care community we have often blamed inadequate fluid resuscitation for this finding, a consequence of failing to follow guidelines recommending aggressive fluid resuscitation, which we have seen as ‘‘acute medicine’s great triumph for children’’ [2]. In an article recently published in Intensive CareMedicineBhaskar et al. [3] bring to our attention the problem of early fluid accumulation in children treated for shock and its association with pediatric intensive care unit (PICU) mortality. As a concept, intolerable excess of fluid and tissue storage by inundation, is not new—Walter Cannon introduced it at the same time as he defined homeostasis [4]—but it is worth reviewing the current article in the context of where we have come from and where we should be going with fluid management.

BACKGROUND Whether an insulin infusion should be used for tight control of hyperglycemia in critically ill children remains unclear. METHODS We randomly assigned children (≤16 years of age) who were admitted to the pedi atric intensive care unit (ICU) and were expected to require mechanical ventilation and vasoactive drugs for at least 12 hours to either tight glycemic control, with a target blood glucose range of 72 to 126 mg per deciliter (4.0 to 7.0 mmol per liter), or conventional glycemic control, with a target level below 216 mg per deciliter (12.0 mmol per liter). The primary outcome was the number of days alive and free from mechanical ventilation at 30 days after randomization. The main prespecified subgroup analysis compared children who had undergone cardiac surgery with those who had not. We also assessed costs of hospital and community health services. RESULTS A total of 1369 patients at 13 centers in England underwent randomization: 694 to tight glycemic control and 675 to conventional glycemic control; 60% had undergone cardiac surgery. The mean between-group difference in the number of days alive and free from mechanical ventilation at 30 days was 0.36 days (95% confidence interval [CI], −0.42 to 1.14); the effects did not differ according to subgroup. Severe hypogly cemia (blood glucose

OBJECTIVE: To determine if the use of fresh frozen plasma/frozen plasma 24 hours compared to solvent detergent plasma is associated with international normalized ratio reduction or ICU mortality in critically ill children.DESIGN: This is an a priori secondary analysis of a prospective, observational study. Study groups were defined as those transfused with either fresh frozen plasma/frozen plasma 24 hours or solvent detergent plasma. Outcomes were international normalized ratio reduction and ICU mortality. Multivariable logistic regression was used to determine independent associations.SETTING: One hundred one PICUs in 21 countries.PATIENTS: All critically ill children admitted to a participating unit were included if they received at least one plasma unit during six predefined 1-week (Monday to Friday) periods. All children were exclusively transfused with either fresh frozen plasma/frozen plasma 24 hours or solvent detergent plasma.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: There were 443 patients enrolled in the study. Twenty-four patients (5%) were excluded because no plasma type was recorded; the remaining 419 patients were analyzed. Fresh frozen plasma/frozen plasma 24 hours group included 357 patients, and the solvent detergent plasma group included 62 patients. The median (interquartile range) age and weight were 1 year (0.2-6.4) and 9.4 kg (4.0-21.1), respectively. There was no difference in reason for admission, severity of illness score, pretransfusion international normalized ratio, or lactate values; however, there was a difference in primary indication for plasma transfusion (p < 0.001). There was no difference in median (interquartile range) international normalized ratio reduction, between fresh frozen plasma/frozen plasma 24 hours and solvent detergent plasma study groups, -0.2 (-0.4 to 0) and -0.2 (-0.3 to 0), respectively (p = 0.80). ICU mortality was lower in the solvent detergent plasma versus fresh frozen plasma/frozen plasma 24 hours groups, 14.5% versus 29.1%%, respectively (p = 0.02). Upon adjusted analysis, solvent detergent plasma transfusion was independently associated with reduced ICU mortality (odds ratio, 0.40; 95% CI, 0.16-0.99; p = 0.05).CONCLUSIONS: Solvent detergent plasma use in critically ill children may be associated with improved survival. This hypothesis-generating data support a randomized controlled trial comparing solvent detergent plasma to fresh frozen plasma/frozen plasma 24 hours.

Objectives & Background There is increasing evidence that fluid overload may be associated with harm in paediatric critical illness. Fluids in Shock (FiSH) is a combined feasibility and pilot randomised controlled trial (RCT) to determine if restrictive fluid bolus therapy (10 ml/kg) is more beneficial than current recommended fluid bolus therapy (20 ml/kg) in the resuscitation of children with presumed septic shock. This qualitative feasibility study aims to explore: acceptability of the proposed pilot RCT, including the prospect of research without prior consent (RWPC); other potential barriers to conduct of the pilot RCT; participant information; parental decision-making; and patientcentred outcome measures. Methods Qualitative interview study involving 21 parents (18 mothers, 3 fathers, 7 were bereaved) with children admitted to a UK emergency department with presumed septic shock in the last three years. Results All parents would have provided permission for the use of their child’s data in the FiSh pilot RCT. The majority of parents were unfamiliar with RWPC, yet supported its use in FiSh and in other RCTs aiming to help improve treatments for critically ill children. Parents were concerned about the change from currently recommended treatment; yet were reassured by an explanation of the current evidence base, fluid bolus therapy and monitoring procedures. Parents made recommendations about the timing of the discussion regarding permission for use of data and the patient information materials. Bereaved parents stated that recruiters should not attempt to discuss the RCT immediately after a child’s death, but supported a personalised postal ‘opt out’ approach to RWPC for FiSh. Parents prioritised outcome measures such as survival, time in hospital, time spent on machines and time to their child ‘looking or behaving more like themselves’. Conclusion Our qualitative feasibility study findings support the proposed FiSh pilot RCT, including the use of RWPC, amongst parents whose child has experienced septic shock. Our findings will inform the FiSh RCT including selection of a patient centred outcome measure, as well as inform development of participant information materials and site initiation training.

BACKGROUND: Organ dysfunction scores, based on physiological parameters, have been created to describe organ failure. In a general pediatric intensive care unit (PICU) population, the PEdiatric Logistic Organ Dysfunction-2 score (PELOD-2) score had both a good discrimination and calibration, allowing to describe the clinical outcome of critically ill children throughout their stay. This score is increasingly used in clinical trials in specific subpopulation. Our objective was to assess the performance of the PELOD-2 score in a subpopulation of critically ill children requiring plasma transfusions.METHODS: This was an ancillary study of a prospective observational study on plasma transfusions over a 6-week period, in 101 PICUs in 21 countries. All critically ill children who received at least one plasma transfusion during the observation period were included. PELOD-2 scores were measured on days 1, 2, 5, 8, and 12 after plasma transfusion. Performance of the score was assessed by the determination of the discrimination (area under the ROC curve: AUC) and the calibration (Hosmer-Lemeshow test).RESULTS: Four hundred and forty-three patients were enrolled in the study (median age and weight: 1 year and 9.1 kg, respectively). Observed mortality rate was 26.9 % (119/443). For PELOD-2 on day 1, the AUC was 0.76 (95 % CI 0.71-0.81) and the Hosmer-Lemeshow test was p = 0.76. The serial evaluation of the changes in the daily PELOD-2 scores from day 1 demonstrated a significant association with death, adjusted for the PELOD-2 score on day 1.CONCLUSIONS: In a subpopulation of critically ill children requiring plasma transfusion, the PELOD-2 score has a lower but acceptable discrimination than in an entire population. This score should therefore be used cautiously in this specific subpopulation.

Current paediatric sepsis guidelines suggest that resuscitation is titrated against clinical markers of hypovolaemia and end organ perfusion [1], including blood pressure (BP), heart rate and capillary refill time (CRT). BP is used both as a defining feature of shock and as a target for therapy. This paper will focus on the measurement of BP, the definition of hypotension and on the target BP for therapy in children with sepsis.

Objectives Assessment of whether admission plasma troponin I level is associated with mortality or requirement for vasoactive drugs in pediatric intensive care. Design Retrospective cohort study. Setting Single centre, tertiary referral general PICU, without a cardiac surgical program. Patients Three hundred and nineteen patients 0-18 years old in two cohorts. Cohort 1 was admitted between January 2009 and September 2012 and the cohort 2 between April 2014 and April 2015. Interventions None. Measurements and main results Plasma troponin I was measured in patients in cohort 1 only if the attending physician ordered the test due to clinical concern regarding myocardial injury. The second cohort had plasma troponin I routinely measured at admission. The primary outcome was death during PICU admission, and the secondary outcome was maximum inotrope requirement during PICU stay, measured by Vasoactive Inotrope Score. Plasma troponin I was a discriminator for mortality in both cohorts (area under the receiver-operating characteristic curve of 0.73 and 0.86 in cohorts 1 and 2, respectively). In an adjusted analysis using Cox regression, accounting for Pediatric Index of Mortality 2 risk of mortality and age, elevated plasma troponin I was significantly associated with death in both cohorts (hazard ratio, 4.99; p = 0.033; hazard ratio, 10.5; p = 0.026 in cohorts 1 and 2, respectively). Elevated plasma troponin I was only associated with increased Vasoactive Inotrope Score following multivariate analysis in the cohort 2. Conclusions Detectable plasma troponin I at admission to PICU is independently associated with death. The utility of troponin I as a stratification biomarker requires further evaluation.

Shock index (SI) (heart rate [HR]/systolic blood pressure [SBP]) has been used to predict outcome in both adult and pediatric sepsis within the intensive care unit (ICU). We aimed to evaluate the utility of SI before pediatric ICU (PICU) admission.We conducted a retrospective observational study of children referred to a pediatric intensive care transport service (PICTS) between 2005 and 2011. The predictive value of SI, HR, and blood pressure at three prespecified time points (at referral to PICTS, at PICTS arrival at the referring hospital, and at PICU admission) and changes in SI between the time points were evaluated. Death within the first 48 h of ICU admission (early death) was the primary outcome variable.Over the 7-year period, 633 children with sepsis were referred to the PICTS. Thirty-nine children died before transport to a PICU, whereas 474 were transported alive. Adjusting for age, time points, and time duration in a multilevel regression analysis, SI was significantly higher in those who died early. There was a significant improvement in SI with the transport team in survivors but not in nonsurvivors. However, the predictive value of a change in SI for mortality was no better than either a change in HR or blood pressure.The absolute or change in SI does not predict early death any more than HR and SBP individually in children with sepsis.