CARPEDIEM® for continuous kidney replacement therapy in neonates and small infants: a French multicenter retrospective study.

BACKGROUND: The Cardio-Renal Pediatric Dialysis Emergency Machine (CA.R.P.E.D.I.E.M.®) device is a continuous kidney replacement therapy (CKRT) equipment dedicated to neonates and small infants. This study aimed to assess the effectiveness, feasibility, outcomes, and technical considerations relating to CARPEDIEM® use. METHODS: This retrospective multicenter study included 19 newborns and six infants receiving CARPEDIEM® in five French pediatric and neonatal intensive care units. Laboratory parameters were collected at the initiation and end of the first CARPEDIEM® session. Results are presented as median [IQR] (range). RESULTS: At initiation, age was 4 days [2-13] (1-1134) with a body weight of 3.3 kg [2.5-4] (1.3-11.1). Overall, 131 sessions and 2125 h of treatment were performed. Treatment duration per patient was 42 h [24-91] (8-557). Continuous veno-venous hemofiltration (CVVH) was performed in 20 children. Blood flow rate was 8 mL/kg/min [6-9] (3-16). The effluent flow rate for CVVH was 74 mL/kg/h [43-99] (28-125) and net ultrafiltration (UF) 6 mL/kg/h [2-8] (1-12). In the five children treated by hemodialysis, the blood and dialysate flow rates were 6 mL/kg/min [5-7] (4-7) and 600 mL/h [300-600] (120-600), respectively, while session duration was 8 h [6-12] (2-24). Most infants required a catheter between 4.5 and 6.5 French. Hemodynamic instability with a need for volume replacement occurred in 31 sessions (23%). Thrombocytopenia was observed in 29 sessions (22%). No hemorrhage occurred; all the patients survived the sessions, but only eight patients (32%) were alive at hospital discharge. CONCLUSIONS: These data confirm that the use of CARPEDIEM® is safe and effective in critically ill neonates and infants. A higher resolution version of the Graphical abstract is available as Supplementary information.

Type-I Interferon assessment in 45 minutes using the FilmArray® PCR platform in SARS-CoV-2 and other viral infections.

Low concentrations of type-I interferon (IFN) in blood seem to be associated with more severe forms of Coronavirus disease 2019 (COVID-19). However, following the type-I interferon response (IR) in early stage disease is a major challenge. We evaluated detection of a molecular interferon signature on a FilmArray® system, which includes PCR assays for four interferon stimulated genes. We analyzed three types of patient populations: (i) children admitted to a pediatric emergency unit for fever and suspected infection, (ii) ICU-admitted patients with severe COVID-19, and (iii) healthcare workers with mild COVID-19. The results were compared to the reference tools, that is, molecular signature assessed with Nanostring® and IFN-α2 quantification by SIMOA® (Single MOlecule Array). A strong correlation was observed between the IR measured by the FilmArray®, Nanostring®, and SIMOA® platforms (r-Spearman 0.996 and 0.838, respectively). The FilmArray® panel could be used in the COVID-19 pandemic to evaluate the IR in 45-min with 2 min hand-on-time at hospitalization and to monitor the IR in future clinical trials.

Cardiac involvement in pediatric hemolytic uremic syndrome.

BACKGROUND: Cardiac involvement is a known but rare complication of pediatric hemolytic uremic syndrome (HUS). We conducted a nationwide observational, retrospective case-control study describing factors associated with the occurrence of myocarditis among HUS patients. METHODS: Cases were defined as hospitalized children affected by any form of HUS with co-existent myocarditis in 8 French Pediatric Intensive Care Units (PICU) between January 2007 and December 2018. Control subjects were children, consecutively admitted with any form of HUS without coexistent myocarditis, at a single PICU in Lyon, France, during the same time period. RESULTS: A total of 20 cases of myocarditis were reported among 8 PICUs, with a mean age of 34.3 ± 31.9 months; 66 controls were identified. There were no differences between the two groups concerning the season and the typical, Shiga toxin-producing Escherichia coli (STEC-HUS), or atypical HUS (aHUS). Maximal leukocyte count was higher in the myocarditis group (29.1 ± 16.3G/L versus 21.0 ± 9.9G/L, p = 0.04). The median time between admission and first cardiac symptoms was of 3 days (range 0-19 days), and 4 patients displayed myocarditis at admission. The fatality rate in the myocarditis group was higher than in the control group (40.0% versus 1.5%, p < 0.001). Thirteen (65%) children from the myocarditis group received platelet transfusion compared to 19 (29%) in the control group (p = 0.03). CONCLUSION: Our study confirms that myocarditis is potentially lethal and identifies higher leukocyte count and platelet transfusion as possible risk factors of myocarditis. A higher resolution version of the Graphical abstract is available as Supplementary information.

Antimicrobial stewardship programs in European pediatric intensive care units: an international survey of practices.

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

Prehospital Tranexamic Acid in Major Pediatric Trauma Within a Physician-Led Emergency Medical Services System: A Multicenter Retrospective Study.

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.

Renal Replacement Therapy for Acute Kidney Injury in French Intensive Care Units: A Nationwide Survey of Practices.

BACKGROUND: The frequency of acute kidney injury (AKI) can be as high as 50% in the intensive care unit (ICU). Despite the publication of national guidelines in France in 2015 for the use of RRT, there are no data describing the implementation of these recommendations in real-life. METHODS: We performed a nationwide survey of practices from November 15, 2019, to January 24, 2020, in France. An electronic questionnaire based on the items recommended in the national guidelines was sent using an online survey platform, to the chiefs of all ICUs in France. The questionnaire comprised a section for the Department Chief about local organization and facilities, and a second section destined for individual physicians about their personal practices. RESULTS: We contacted the Department Chief in 356 eligible ICUs, of whom 88 (24.7%) responded regarding their ICU organization. From these 88 ICUs, 232/285 physicians (82%) completed the questionnaire regarding individual practices. The practices reported by respondent physicians were as follows: intermittent RRT was first-line choice in >75% in a patient with single organ (kidney) failure at the acute phase, whereas continuous RRT was predominant (>75%) in patients with septic shock or multi-organ failure. Blood and dialysate flow for intermittent RRT were 200-300 mL/min and 400-600 mL/min, respectively. The dose of dialysis for continuous RRT was 25-35 mL/kg/h (65%). Insertion of the dialysis catheter was mainly performed by the resident under echographic guidance, in the right internal jugular vein. The most commonly used catheter lock was citrate (53%). The most frequently cited criterion for weaning from RRT was diuresis, followed by a drop in urinary markers (urea and creatinine). CONCLUSION: This study shows a satisfactory level of reported compliance with French guidelines and recent scientific evidence among ICU physicians regarding initiation of RRT for AKI in the ICU.

Capillary refill time for the management of acute circulatory failure: a survey among pediatric and adult intensivists.

INTRODUCTION: Recent studies have shown the prognostic value of capillary refill time (CRT) and suggested that resuscitation management guided by CRT may reduce morbidity and mortality in patients with septic shock. However, little is known about the current use of CRT in routine clinical practice. This study aimed to assess the modalities of CRT use among French adult and pediatric intensivists. METHODS: A cross-sectional survey exploring CRT practices in acute circulatory failure was performed. The targeted population was French adult and pediatric intensivists (SFAR and GFRUP networks). An individual invitation letter including a survey of 32 questions was emailed twice. Descriptive and analytical statistics were performed. RESULTS: Among the 6071 physicians who received the letter, 418 (7%) completed the survey. Among all respondents, 82% reported using CRT in routine clinical practice, mainly to diagnose acute circulatory failure, but 45% did not think CRT had any prognostic value. Perfusion goal-directed therapy based on CRT was viewed as likely to improve patient outcome by 37% of respondents. The measurement of CRT was not standardized as the use of a chronometer was rare (3%) and the average of multiple measurements rarely performed (46%). Compared to adult intensivists, pediatric intensivists used CRT more frequently (99% versus 76%) and were more confident in its diagnostic value and its ability to guide treatment. CONCLUSION: CRT measurement is widely used by intensivists in patients with acute circulatory failure but most often in a non-standardized way. This may lead to a misunderstanding of CRT reliability and clinical usefulness.

Occurrence and risk factors associated with seizures in infants with severe bronchiolitis.

Neurological morbidity is a growing concern in children with severe bronchiolitis. The aim of the study was to evaluate the frequency of occurrence and the factors associated with seizures in very young infants < 3 months of age, admitted to a pediatric intensive care unit (PICU) for severe bronchiolitis. We performed a single center retrospective cohort study evaluating occurrence of seizures in infants admitted to the PICU between 2010 and 2018 for severe bronchiolitis. We described characteristics of the patients, laboratory test, brain imaging, and electroencephalogram results, as well as the treatment used. We conducted a multivariable logistic regression to identify factors associated with the occurrence of seizures. A p value < 0.05 was considered significant. A total of 805 patients were included in the study; 722 (89.6%) were mechanically ventilated. Twenty-six infants (3.2%, 95% confidence interval, 95% CI [2.1%; 4.7%]) had seizures shortly prior to admission or during PICU stay. In the multivariable analysis, hyponatremia (odds ratio, OR: 4.6, 95%CI [1.86; 11.43], p = 0.001) and invasive ventilation (OR: 2.6, 95% CI [1.14; 5.9], p < 0.001) were associated with an increased likelihood of seizures occurrence.Conclusion: Seizures occur in at least 3% of very young infants with severe bronchiolitis, and the characteristics of these are different to those experienced by older infants, but they shared the same risk factors (hyponatremia and mechanical ventilation). This highlights the extrapulmonary morbidity associated with bronchiolitis in this population. What is Known: • Bronchiolitis is the leading cause of pediatric intensive care admission and use of mechanical ventilation in infants. • Neurological morbidities have to be investigated in this population at risk of neurological complications. What is New: • Seizure is a complication in at least 3% of very young infants with severe bronchiolitis. • Seizure characteristics are different, but the main risk factors are the same than in older infants (hyponatremia and mechanical ventilation).

Mortality and Neurologic Sequelae in Influenza-Associated Encephalopathy: Retrospective Multicenter PICU Cohort in France.

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.

Decreased Human Leukocyte Antigen DR on Circulating Monocytes Expression After Severe Pediatric Trauma: An Exploratory Report.

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.

Caring for Critically Ill Children With Suspected or Proven Coronavirus Disease 2019 Infection: Recommendations by the Scientific Sections' Collaborative of the European Society of Pediatric and Neonatal Intensive Care.

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.

Review: Neonatal dialysis is technically feasible but ethical and global issues need to be addressed.

AIM: Our aim was to look at the technical, ethical and global issues related to neonatal dialysis. METHODS: We performed a PubMed research on manuscripts published from March 2010 to March 2020 and retrospectively reviewed all neonates who received dialysis in our French paediatric and neonatal intensive care units from April 2009 to March 2019. RESULTS: Dialysis is performed on neonates with pre-existing renal diseases, acute kidney injuries or inborn errors of metabolism. It is required in 0.5%-1% of neonates admitted to the neonatal intensive care units. Peritoneal dialysis and extracorporeal blood purification are both feasible, with more complications, but the results are close to those obtained in older infants, at least in children without multi-organ dysfunction. Novel haemodialysis machines are being evaluated. Ethical issues are a major concern. Multidisciplinary teams should consider associated comorbidities, risks of permanent end-stage renal disease and provide parents with full and neutral information. These should drive decisions about whether dialysis is in child's best interests. CONCLUSION: Neonatal dialysis is technically feasible, but ethically challenging, and short-term and long-term data remain limited. Prospective studies and dialysis registries would improve global management and quality of life of these patients at risk of chronic kidney disease.

Characteristics of the delayed respiratory syncytial virus epidemic, 2020/2021, Rhône Loire, France.

The Rhône-Loire metropolitan areas' 2020/21 respiratory syncytial virus (RSV) epidemic was delayed following the implementation of non-pharmaceutical interventions (NPI), compared with previous seasons. Very severe lower respiratory tract infection incidence among infants ≤ 3 months decreased twofold, the proportion of cases among children aged > 3 months to 5 years increased, and cases among adults > 65 years were markedly reduced. NPI appeared to reduce the RSV burden among at-risk groups, and should be promoted to minimise impact of future RSV outbreaks.

Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.

Type I Interferon in Children with Viral or Bacterial Infections.

BACKGROUND: Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians' decisions and limit antibiotic overuse. METHODS: Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. RESULTS: Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001). IFN-α concentrations and IFN score were significantly higher in viral compared to bacterial infection (P < 0.001). There was a strong correlation between serum IFN-α concentrations and IFN score (p-pearson = 0.83). Both serum IFN-α concentration and IFN score robustly discriminated (Area Under the Curve >0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). CONCLUSIONS: IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov (NCT03163628).

Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children.

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.

SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020.

End of April 2020, French clinicians observed an increase in cases presenting with paediatric inflammatory multisystem syndrome (PIMS). Nationwide surveillance was set up and demonstrated temporospatial association with the coronavirus disease (COVID-19) epidemic for 156 reported cases as at 17 May: 108 were classified as confirmed (n = 79), probable (n = 16) or possible (n = 13) post-COVID-19 PIMS cases. A continuum of clinical features from Kawasaki-like disease to myocarditis was observed, requiring intensive care in 67% of cases.

Physiological Effect of Prone Position in Children with Severe Bronchiolitis: A Randomized Cross-Over Study (BRONCHIO-DV).

OBJECTIVE: To assess the effect of the prone position on physiological measures, including inspiratory effort, metabolic cost of breathing, and neural drive to the diaphragm as compared with the supine position in infants with severe bronchiolitis requiring noninvasive ventilation. STUDY DESIGN: Fourteen infants, median age 33 days (IQR [first and third quartiles], 25-58) were randomized to receive 7 cmH2O continuous positive airway pressure for 1 hour in the prone position or in the supine position, which was followed by cross-over to the supine position and the prone position for 1 hour, respectively. Flow, esophageal, airway, gastric, and transdiaphragmatic pressures, as well as electrical activity of the diaphragm were simultaneously recorded. The modified Wood clinical asthma score was also assessed. RESULTS: Median esophageal pressure-time product per minute was significantly lower in the prone position than in the supine position (227 cmH2O*s/minute [IQR, 156-282] cmH2O*s/minute vs 353 cmH2O*s/minute [IQR, 249-386 cmH2O*s/minute]; P = .048), as were the modified Wood clinical asthma score (P = .033) and electrical activity of the diaphragm (P = .006). The neuromechanical efficiency of the diaphragm, as assessed by transdiaphramagtic pressure to electrical activity of the diaphragm swing ratio, was significantly higher in the prone position than in the supine position (1.1 cmH2O/µV [IQR, 0.9-1.3 cmH2O/µV] vs 0.7 cmH2O/µV [IQR, 0.6-1.2 cmH2O/µV], respectively; P = .022). CONCLUSIONS: This study suggests a benefit of the prone position for infants with severe bronchiolitis requiring noninvasive ventilation by significantly decreasing the inspiratory effort and the metabolic cost of breathing. Further studies are needed to evaluate the potential impact of these physiological findings in a larger population. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02602678.

Escherichia coli-associated hemolytic uremic syndrome and severe chronic hepatocellular cholestasis: complication or side effect of eculizumab?

BACKGROUND: Liver lesions of hemolytic uremic syndrome due to Shiga-toxin-producing Escherichia coli (STEC-HUS) are uncommon. CASE-DIAGNOSIS/TREATMENT: We report three observations of severe STEC-HUS with delayed hepatic involvement. They presented with multiple organ failure and received eculizumab; 15 days after the onset of STEC-HUS, cholestasis appeared and cytolysis worsened. Abdominal ultrasonography showed vesicular sludge. Liver biopsy performed 3 to 6 months after the STEC-HUS found cholangiolar proliferation and inflammatory portal fibrosis. Despite renal recovery, cholestasis persisted and worsened in two cases, leading to biliary cirrhosis and subsequent liver transplantation. Pathological examination of one native liver found thrombotic microangiopathy. CONCLUSIONS: Even though the pathological examination performed on one native liver demonstrated areas of thrombotic microangiopathy, we cannot completely rule out that eculizumab may have worsened the liver lesions. Before the efficacy of eculizumab in STEC-HUS is formally demonstrated, physicians should stay cautious in its use.