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Objectives: Describe prehospital tranexamic acid (TXA) use and appropriateness within a major trauma pediatric population, and identify the factors associated with its use., Design: Multicenter, retrospective study, 2014-2020., Setting: Data were extracted from a multicenter French trauma registry including nine trauma centers within a physician-led prehospital emergency medical services (EMS) system., Patients: Patients less than 18 years old were included. Those who did not receive prehospital intervention by a mobile medical team and those with missing data on TXA administration were excluded., Interventions: None., Measurements and Main Results: Nine-hundred thirty-four patients (median [interquartile range] age: 14 yr [9-16 yr]) were included, and 68.6% n = 639) were male. Most patients were involved in a road collision (70.2%, n = 656) and suffered a blunt trauma (96.5%; n = 900). Patients receiving TXA (36.6%; n = 342) were older (15 [13-17] vs 12 yr [6-16 yr]) compared with those who did not. Patient severity was higher in the TXA group (Injury Severity Score 14 [9-25] vs 6 [2-13]; p < 0.001). The median dosage was 16 mg/kg (13-19 mg/kg). TXA administration was found in 51.8% cases ( n = 256) among patients with criteria for appropriate use. Conversely, 32.4% of patients ( n = 11) with an isolated severe traumatic brain injury (TBI) also received TXA. Age (odds ratio [OR], 1.2; 95% CI, 1.1-1.2), A and B prehospital severity grade (OR, 7.1; 95% CI, 4.1-12.3 and OR, 4.5; 95% CI, 2.9-6.9 respectively), and year of inclusion (OR, 1.2; 95% CI, 1.1-1.3) were associated with prehospital TXA administration., Conclusions: In our physician-led prehospital EMS system, TXA is used in a third of severely injured children despite the lack of high-level of evidence. Only half of the population with greater than or equal to one criteria for appropriate TXA use received it. Conversely, TXA was administered in a third of isolated severe TBI. Further research is warranted to clarify TXA indications and to evaluate its impact on mortality and its safety profile to oversee its prescription., Competing Interests: Dr. Claustre’s institution received funding from the Regional Agency for Health. Dr. Fraticelli disclosed work for hire. Dr. Jacquet disclosed the off-label product use of Tranexamic acid. The remaining authors have disclosed that they do 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.)

Objectives: To describe and estimate the mortality rate of severe influenza-associated encephalopathy/encephalitis among children admitted to PICUs., Design: Multicenter retrospective study., Setting: Twelve French PICUs., Patients: All children admitted for influenza-associated encephalopathy/encephalitis between 2010 and 2018 with no severe preexisting chronic neurologic disorders and no coinfection potentially responsible for the disease., Intervention: None., Measurements and Main Results: We collected the clinical presentation; laboratory, electroencephalographic, and MRI findings; and treatments used in the PICU. The primary outcome was mortality. The secondary outcomes included sequelae at discharge and last follow-up. We included 41 patients with a median (interquartile range) age of 4.7 years (2.5-8.2 yr). The main reasons for admission were altered consciousness (59%) and status epilepticus (34%); 48% of patients had meningitis, and one third had acute necrotizing encephalopathy on MRI. Mechanical ventilation was required in 73% of patients and hemodynamic support in 24%. The use of specific treatments was variable; steroids were given to 49% of patients. Seven patients (17%) died in the PICU. Median (interquartile range) PICU stay length was 7 days (2-13 d), and total hospital length of stay was 23 days (7-33 d). On hospital discharge, 49% (n = 20) had neurologic sequelae, with 27% (n = 11) having severe disabilities defined by modified Rankin Score greater than or equal to 4., Conclusions: Children requiring PICU admission for influenza-associated encephalopathy/encephalitis have high mortality and morbidity rates. The management remains highly variable due to the lack of guidelines., Competing Interests: Dr. Bergounioux received funding from Aerogen medical device company (Galway, Ireland). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Major trauma in adults induces immune dysfunction, with diminished expression of human leukocyte antigen-DR on circulating monocytes. No pediatric data are available. This study described the kinetics of human leukocyte antigen-DR on circulating monocytes following major pediatric trauma and relationships between human leukocyte antigen-DR on circulating monocytes and outcomes., Design: Prospective observational study., Setting: PICU and trauma unit at a tertiary-care university hospital in South Africa., Patients: Children between 1 month and 13 years hospitalized for severe brain trauma or trauma with an Injury Severity Score greater than or equal to 16, from November 2016 to March 2017., Interventions: None., Measurements and Main Results: We included 36 children. Median (interquartile range) age and Injury Severity Score were 7 years (4.9-10.5 yr) and 25 years (22.7-30 yr), respectively. Blood samples (n = 83) for standardized human leukocyte antigen-DR on circulating monocytes measurement were collected at days 1-2, 3-4, and 8-9 after injury (D1, D3, and D8, respectively). On D1, median (interquartile range) human leukocyte antigen-DR on circulating monocytes was markedly reduced relative to normal values (7,031 [5,204-11,201] antibodies per cell). There was a significant increase in human leukocyte antigen-DR on circulating monocytes from D1 to D8. Although all patients with secondary infections (n = 8; 22%) had human leukocyte antigen-DR on circulating monocytes less than 15,000 antibodies per cell at D3, human leukocyte antigen-DR on circulating monocytes levels were not associated with the occurrence of secondary infections (p = 0.22). At D3, human leukocyte antigen-DR on circulating monocytes was significantly higher in patients discharged home (n = 21) by Day 30 after trauma compared with those who died or were still hospitalized (n = 14) (p = 0.02)., Conclusions: Pediatric severe trauma induced an early and dramatic decrease in human leukocyte antigen-DR on circulating monocytes expression. This alteration of innate immunity was not associated with the occurrence of secondary infection, possibly due to a lack of statistical power. However, human leukocyte antigen-DR on circulating monocytes at Day 3 is a potential indicator of those at high risk of secondary infection and worse outcomes., Competing Interests: Dr. Morrow’s institution received funding from National Research Foundation, and she received funding from University of Cape Town and Imperial College Press (royalties). Dr. Argent received funding from N. Kelly Attorneys and from various conferences as an invited speaker. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

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.)

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, 52 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, 49 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 determine the prevalence and risk markers of anemia at PICU discharge., Design: Bicenter retrospective cohort study., Setting: Two multidisciplinary French PICUs., Patients: All children admitted during a 5-year period, staying in the PICU for at least 2 days, and for whom a hemoglobin was available at PICU discharge., Interventions: None., Measurements and Main Results: Patient, admission, and PICU stay characteristics were retrospectively collected in the electronic medical records of each participating PICU. Anemia was defined according to the World Health Organization criteria. Among the 3,170 patients included for analysis, 1,868 (58.9%) were anemic at discharge from PICU. The proportion of anemic children differed between age categories, whereas the median hemoglobin level did not exhibit significant variations according to age. After multivariate adjustment, anemia at PICU admission was the strongest predictor of anemia at PICU discharge, and the strength of this association varied according to age (interaction). Children anemic at PICU admission had a reduced risk of anemia at PICU discharge if transfused with RBCs during the PICU stay, if less than 6 months old, or if creatinine level at PICU admission was low. Children not anemic at PICU admission had an increased risk of anemia at PICU discharge if they were thrombocytopenic at PICU admission, if they had higher C-reactive protein levels, and if they received plasma transfusion, inotropic/vasopressor support, or mechanical ventilation during the PICU stay., Conclusions: Anemia is frequent after pediatric critical illness. Anemia status at PICU admission defines different subgroups of critically ill children with specific prevalence and risk markers of anemia at PICU discharge. Further studies are required to confirm our results, to better define anemia during pediatric critical illness, and to highlight the causes of post-PICU stay anemia, its course, and its association with post-PICU outcomes.

Objectives: Malnutrition and faltering growth at PICU admission have been related to suboptimal outcomes. However, little is known about nutritional status deterioration during PICU stay, as critical illness is characterized by a profound and complex metabolism shift, which affects energy requirements and protein turnover. We aim to describe faltering growth occurrence during PICU stay., Design: Single-center prospective observational study., Setting: Twenty-three-bed general PICU, Lyon, France., Patients: All critically ill children 0-18 years old with length of stay longer than 5 days were included (September 2013-December 2015)., Interventions: Weight and height/length were measured at admission, and weight was monitored during PICU stay, in order to calculate body mass index for age z score. Faltering growth was defined as body mass index z score decline over PICU stay. Children admitted during the first year of the study and who presented with faltering growth were followed after PICU discharge for 3 months., Measurements and Main Results: We analyzed 579 admissions. Of them, 10.2% presented a body mass index z score decline greater than 1 SD and 27.8% greater than 0.5. Admission severity risk scores and prolonged PICU stay accounted for 4% of the variability in nutritional status deterioration. Follow-up of post-PICU discharge nutritional status showed recovery within 3 months in most patients., Conclusions: Nutritional deterioration is frequent and often intense in critically ill children with length of stay greater than 5 days. Future research should focus on how targeted nutritional therapies can minimize PICU faltering growth and improve post-PICU rehabilitation.

Objectives: Micronutrient supplementation in critically ill adults remains controversial. In the pediatric setting, the impact of oxidative stress on the overall micronutrient status has been poorly explored, due to the limited number of studies and to confounding factors (i.e., malnutrition or extra losses). In order to better understand this phenomenon, we aim to describe micronutrient status, focusing on seven micronutrients, in well-nourished critically ill children presenting with severe oxidative stress., Design: Prospective, transversal, observational, single-center study., Setting: PICU, and anesthesiology department, Lyon, France., Patients: Three groups of patients were clinically defined: severe oxidative stress PICU group (at least two organ dysfunctions), moderate oxidative stress PICU group (single organ dysfunction), and healthy control group (prior to elective surgery); oxidative stress intensity was controlled by measuring plasma levels of glutathione peroxidase and glutathione. Children presenting any former condition leading to micronutrient deficiency were excluded (malnutrition, external losses)., Interventions: Plasma levels of selenium, zinc, copper, vitamin A, vitamin E, vitamin C, and β-carotene were measured in PICU oxidative stress conditions and compared with those of healthy children., Measurements and Main Results: Two hundred one patients were enrolled (51, 48, and 102 in severe, moderate, and healthy control groups, respectively). Median age was 7.1 years (interquartile range, 2.1-13.8 yr). There was a significant trend (p < 0.02) toward plasma level decrease of six micronutrients (selenium, zinc, copper, vitamin E, vitamin C, and β-carotene) while oxidative stress intensity increased. Biological markers of oxidative stress (glutathione peroxidase and glutathione) were in accordance with the clinical definition of the three groups., Conclusions: A multiple micronutrient deficiency or redistribution occurs in critically ill children presenting with severe oxidative stress. These findings will help to better identify children who might benefit from micronutrient supplementation and to design adapted supplementation trials in this particular setting.

Objectives: Significant muscle wasting develops in critically ill adults, with subsequent worse outcomes. In the pediatric setting, occurrence and effects of muscle wasting are undescribed; this is in part due to a lack of validated, objective methods for assessing muscle wasting. A single measurement of quadriceps femoris thickness has failed to show consistent reproducibility. We hypothesized that averaging repeated measurements could afford good reproducibility to allow for quadriceps femoris thickness decline detection and monitoring., Design: A prospective bedside observational study., Setting: Two PICUs., Patients: Mechanically ventilated critically ill children were 15 years and younger., Interventions: Transverse and longitudinal axis measurements of quadriceps femoris anterior thickness were undertaken using bedside ultrasound. The average of four measurement values was recorded. The location of measurement was marked for consistency within subsequent measurements by the same or another trained operator, to assess intra- and interoperator repeatability and reproducibility of the technique. Where feasible, serial measurements were undertaken until the time of extubation in a group of children with prolonged PICU stay (> 5 d)., Measurements and Main Results: Seventy-three children were enrolled to assess intra- and interoperator ultrasound reliability. Their median (25-75 interquartile range) age and weight were 30 months (4.5-96) and 10 kg (5-23.5). In the intraoperator repeatability study, mean relative difference in quadriceps femoris muscle thickness was 0.36% ± 2.5% (lower and upper limits of agreement: -4.5/+5.2%). In the interoperator reproducibility study, intraclass correlation coefficient was 0.998. In the 17 children monitored over their PICU stay, quadriceps femoris thickness significantly decreased at day 5 by 9.8% (p = 0.006) and by 13.3% (< 0.001) at the last performed measurement., Conclusions: Quadriceps femoris thickness decrease, proposed as a surrogate for muscle mass, is an early, frequent, and intense phenomenon in PICU. Quadriceps femoris ultrasonography is a reliable technique to monitor this process and in future could help to guide rehabilitation and nutrition interventions.

Objectives: The cornerstone of an optimal nutrition approach in PICUs is to evaluate the nutritional status of any patient. Anthropometric measurements and nutritional indices calculation allow for nutritional status assessment, which is not often part of routine management, as it is considered difficult to perform in this setting. We designed a study to evaluate the impact of a training program by the PICU nutritional support team on the implementation of routine anthropometric measurements on our PICU., Design: A prospective study was performed over a 2-year period, which included: a baseline evaluation of nutritional assessment, knowledge, anthropometric measurements (weight, height, and head and mid upper arm circumferences), and nutritional indices calculation in patient files. This was followed by a training program to implement the newly developed nutrition assessment guidelines, which included anthropometrical measurements and also the interpretation of these. The impact of this nutritional assessment program was reviewed annually for 2 years after the implementation., Setting: PICU--Lyon, France., Patients and Subjects: PICU nursing and medical staff, and patients admitted in February 2011, 2012, and 2013., Interventions: Training program., Measurements and Main Results: Ninety-nine percent of staff (n = 145) attended the individual teaching. We found significant progress in nutritional awareness and confidence about nutritional assessment following the teaching program. In addition, an improvement in staff knowledge about undernutrition and its consequences were found. We enrolled 41, 55, and 91 patients in 2011, 2012, and 2013, respectively. There was a significant increase in anthropometric measurements during this time: 32%, 65% (p = 0.002), and 96% in 2013 (p < 0.001). Nutritional indices were calculated in 20%, 74% (p < 0.001), and 96% (p < 0.001) of cases., Conclusions: This is the first study, showing that a targeted nutritional assessment teaching program that highlights both the importance and techniques of anthropometrical measurements has successfully been implemented in a PICU. It managed to improve staff knowledge and nutritional practice.

Objective: To examine the impact of acute care management on outcome in children severely injured in road accidents., Design and Setting: Prospective follow-up study conducted in 12 French pediatric intensive care units over a 24-month period., Patients: Excluding those in refractory shock or in brain death at admission, a total of 125 children aged <17 years admitted to the pediatric intensive care unit with severe trauma (Injury Severity Score > or =16) were included., Results: Intracranial pressure (ICP) monitoring and admission into a trauma resuscitation room (TRR) were used as proxy markers for the center management aggressiveness. Centers which admitted to TRR and monitored ICP when indicated in >75% of cases were called aggressive centers. Children with an ICP monitoring indication admitted to a TRR and monitored, as well as those without an indication treated in a TRR, were judged appropriately managed. A poor outcome at pediatric intensive care unit discharge was defined as a difference between the baseline and discharge pediatric overall performance category above 3, or a hospital death. Children with traumatic brain injury appropriately managed in a less-aggressive center were more likely to have a poor outcome than those appropriately managed in an aggressive center (odds ratio 7.56, 95% confidence interval 1.5-38.4), after adjustment for severity, age, and type of road user., Conclusions: The management in a more aggressive center for children admitted to TRR and monitored for ICP, when indicated, is associated with a better outcome. This could be explained by a more extensive experience in trauma management.