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This review aims to: (1) describe the rationale of pleural (PPL) and transpulmonary (PL) pressure measurements in children during mechanical ventilation (MV); (2) discuss its usefulness and limitations as a guide for protective MV; (3) propose future directions for paediatric research. We conducted a scoping review on PLin critically ill children using PubMed and Embase search engines. We included peer-reviewed studies using oesophageal (PES) and PLmeasurements in the paediatric intensive care unit (PICU) published until September 2021, and excluded studies in neonates and patients treated with non-invasive ventilation. PLcorresponds to the difference between airway pressure and PPL. Oesophageal manometry allows measurement of PES, a good surrogate of PPL, to estimate PLdirectly at the bedside. Lung stress is the PL, while strain corresponds to the lung deformation induced by the changing volume during insufflation. Lung stress and strain are the main determinants of MV-related injuries with PLand PPLbeing key components. PL-targeted therapies allow tailoring of MV: (1) Positive end-expiratory pressure (PEEP) titration based on end-expiratory PL(direct measurement) may be used to avoid lung collapse in the lung surrounding the oesophagus. The clinical benefit of such strategy has not been demonstrated yet. This approach should consider the degree of recruitable lung, and may be limited to patients in which PEEP is set to achieve an end-expiratory PLvalue close to zero; (2) Protective ventilation based on end-inspiratory PL(derived from the ratio of lung and respiratory system elastances), might be used to limit overdistention and volutrauma by targeting lung stress values < 20–25 cmH2O; (3) PPLmay be set to target a physiological respiratory effort in order to avoid both self-induced lung injury and ventilator-induced diaphragm dysfunction; (4) PPLor PLmeasurements may contribute to a better understanding of cardiopulmonary interactions. The growing cardiorespiratory system makes children theoretically more susceptible to atelectrauma, myotrauma and right ventricle failure. In children with acute respiratory distress, PPLand PLmeasurements may help to characterise how changes in PEEP affect PPLand potentially haemodynamics. In the PICU, PPLmeasurement to estimate respiratory effort is useful during weaning and ventilator liberation. Finally, the use of PPLtracings may improve the detection of patient ventilator asynchronies, which are frequent in children. Despite these numerous theoritcal benefits in children, PESmeasurement is rarely performed in routine paediatric practice. While the lack of robust clincal data partially explains this observation, important limitations of the existing methods to estimate PPLin children, such as their invasiveness and technical limitations, associated with the lack of reference values for lung and chest wall elastances may also play a role. PPLand PLmonitoring have numerous potential clinical applications in the PICU to tailor protective MV, but its usefulness is counterbalanced by technical limitations. Paediatric evidence seems currently too weak to consider oesophageal manometry as a routine respiratory monitoring. The development and validation of a noninvasive estimation of PLand multimodal respiratory monitoring may be worth to be evaluated in the future.

Background Intensive care units (ICUs) have seen a spike in the use of noninvasive ventilation (NIV) for many medical conditions. We sought to investigate the attitudes and clinical practice regarding the management of acute chest syndrome (ACS) with a focus on NIV in pediatric ICUs. Method Members of the French Group for Pediatric Intensive Care Emergencies (GFRUP) were asked to complete an online survey on physicians’ attitudes toward children with ACS admitted to the PICU during 2015. Results The survey was answered by teams from 17 PICUs (240 beds). In total, 15 centers (88%) had a local transfusion unit and 14 (82%) worked in connection with a sickle cell disease (SCD) reference center. During 2015, 360 patients with SCD were managed (median: 7 per center; 21) of whom 137 (38%) for an ACS (median: 4 ACS per center; 8). The median length of PICU stay for ACS was 5 days (3.1). Among the 137 patients who presented with ACS, 73 (53%) received simple blood transfusion and 16 (12%) received exchange transfusion. For patients who required noninvasive ventilatory support, NIV with bilevel pressure (BiPAP) was the most frequent method (n = 68, 50%), followed by continuous positive airway pressure (CPAP) (n = 23, 17%) and high-flow oxygen (n = 21, 15%). The proportion of patients on BiPAP was up to 71% in the centers most frequently managing ACS patients. Conclusion BiPAP is commonly used in PICUs for SCD patients with ACS, especially in trained centers. Future physiological studies and randomized controlled trials might help to choose the best ventilatory support for ACS.

We aimed to develop a piperacillin population pharmacokinetic (PK) model in critically ill children receiving continuous renal replacement therapy (CRRT) and to optimize dosing regimens. The piperacillin plasma concentration was quantified by high-performance liquid chromatography. Piperacillin PK was investigated using a nonlinear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration according to the target of 100% interdose interval time in which concentration is one to four times above the MIC (100% fT > 1 to 4× MIC). A total of 32 children with a median (interquartile range [IQR]) postnatal age of 2 years (0 to 11), body weight (BW) of 15 kg (6 to 38), and receiving CRRT were included. Concentration-time courses were best described by a one-compartment model with first-order elimination. BW and residual diuresis (Q(u)) explained some between-subject variabilities on volume of distribution (V), where [Image: see text] , and clearance (CL), where [Image: see text] , where CL(pop) and V(pop) are 6.78 L/h and 55.0 L, respectively, normalized to a 70-kg subject and median residual diuresis of 0.06 mL/kg/h. Simulations with intermittent and continuous administrations for 4 typical patients with different rates of residual diuresis (0, 0.1, 0.25, and 0.5 mL/kg/h) showed that continuous infusions were appropriate to attain the PK target for patients with residual diuresis higher than 0.1 mL/kg/h according to BW and MIC, while for anuric patients, less frequent intermittent doses were mandatory to avoid accumulation. Optimal exposure to piperacillin in critically ill children on CRRT should be achieved by using continuous infusions with escalating doses for high-MIC bacteria, except for anuric patients who require less frequent intermittent doses.

We aimed to develop a meropenem population pharmacokinetic model in critically ill children receiving continuous renal replacement therapy and simulate dosing regimens to optimize patient exposure.Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem pharmacokinetics was investigated using a non-linear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration, according to the target of a 100% inter-dose interval time in which concentration is one to four times above the minimum inhibitory concentration (100% fT1-4×MIC).A total of 27 patients with a median age of 4 [interquartile range 0-11] years, a median body weight of 16 [range 7-35] kg receiving continuous renal replacement therapy were included. Concentration-time courses were best described by a one-compartment model with first-order elimination. Body weight (BW) produced significant effects on volume of distribution (V) and BW and continuous renal replacement therapy effluent flow rate (QMeropenem exposure in critically ill children receiving continuous renal replacement therapy needs dosing adjustments to the minimum inhibitory concentration that take into account body weight and the continuous renal replacement therapy effluent flow rate.

This study aimed to assess the incidence of amikacin plasma peak concentration (Cmax) below 60 mg·L−1 in critically ill children receiving an amikacin dosing regimen of 30 mg kg−1·day−1. Secondary objectives were to identify factors associated with low Cmax and to assess the incidence of acute kidney injury (AKI). A retrospective observational study was performed in two French pediatric intensive care units. All admitted children who received 30 mg·kg−1 amikacin and had a Cmax measurement were eligible. Clinical and biological data, amikacin dose, and concentrations were collected. In total, 30 patients were included, aged from 3 weeks to 7 years. They received a median amikacin dosage of 30 mg kg−1·day−1 (range 29–33) based on admission body weight (BW), corresponding to 27 mg kg−1·day−1 (range 24–30) based on actual BW. Cmax was 8. Univariate analysis showed that factors associated with Cmax

Dans une moindre mesure que les réanimations adultes, les réanimations pédiatriques ont dû faire face à la pandémie du SARS-CoV-2. Les pédiatres réanimateurs ont été confrontés (i) à la prise en charge d’enfants atteints d’une primo-infection grave puis dans un 2ème temps à ceux présentant des atteintes inflammatoires systémiques post infectieuses et (ii) tandis que d’autres ont été sollicités pour aider à la prise en charge d’adulte atteints d’une forme sévère de SARS-CoV-2. Ils ont ainsi dû faire preuve d’adaptation en un temps record. Nous rapportons dans cette mise au point (i) les données de la littérature de ces deux formes sévères pédiatriques, la primo infection et les manifestations inflammatoires systémiques liées au SARS-CoV-2 ; (ii) l’expérience d’un service de réanimation pédiatrique à la prise en charge d’adultes atteints du SARS-CoV-2 et (iii) et l’impact de la pandémie sur la place des familles des enfants en situation critique dans les services de réanimation pédiatrique.

Supplemental Digital Content is available in the text., TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5–11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35–45%), 261 ng/mL (131–390 ng/mL), and 3.2 mmol/L (2–4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5–28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814–11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987–192,499 pg/mL]), von Willebrand factor antigen (344% [288–378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472–1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.

The population pharmacokinetics of amiodarone and its active metabolite, N-desethylamiodarone (DEA) were investigated in paediatric patients with arrhythmias, mainly supraventricular tachycardias. A total of 55 patients from the Department of Pediatric Intensive Care and Pediatric Cardiology at Necker-Enfants malades Hospital (Paris, France) provided 72 concentrations for both amiodarone and DEA following repeated oral or intravenous administration. Blood samples drawn for biological analyses were used for drug concentrations. Plasma amiodarone concentrations were measured by a liquid chromatography method coupled with mass spectrometry and the data were modelled using the software Monolix 2019R2. Parent pharmacokinetics was described with a 2-compartment open model and the metabolite formation was connected to the central parent compartment. Parameter estimates scaled allometrically on bodyweight (normalized to 70 kg) were, respectively (% relative standard errors, RSEs), 6.32 (31%) and 7.14 L/h (26%) for elimination (CL) and intercompartmental clearances and 167 (31%) and 3930 (32%) L for V

International audience; BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is the most severe clinical entity associated with pediatric SARS-CoV-2 infection with a putative role of the spike protein into the immune system activation. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown. We aimed to assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children. METHODS: We conducted a post-authorization national population-based surveillance using the French enhanced pharmacovigilance surveillance system for COVID-19 vaccines. All cases of suspected hyper-inflammatory syndrome following COVID-19 mRNA vaccine in 12-17-year-old children between June 15(th), 2021 and January 1(st), 2022, were reported. Cases were reviewed according to WHO criteria for MIS-C. The reporting rate of this syndrome was compared to the MIS-C rate per 1,000,000 12-17-year-old children infected by SARS-CoV-2. FINDINGS: Up to January 2022, 8,113,058 COVID-19 mRNA vaccine doses were administered to 4,079,234 12-17-year-old children. Among them, 12 presented a hyper-inflammatory syndrome with multisystemic involvement. Main clinical features included male predominance (10/12, 83%), cardiac involvement (10/12, 83%), digestive symptoms (10/12, 83%), coagulopathy (7/12, 58%), cytolytic hepatitis (6/12, 50%), and shock (5/12, 42%). 4/12 (33%) required intensive care unit transfer, and 3/12 (25%) hemodynamic support. All cases recovered. In eight cases, no evidence of previous SARS-CoV-2 infection was found. The reporting rate was 1.5 (95%CI [0.8; 2.6]) per 1,000,000 doses injected, i.e. 2.9 (95%CI [1.5; 5.1]) per 1,000,000 12-17-year-old vaccinated children. As a comparison, 113 MIS-C (95%CI [95; 135]) occurred per 1,000,000 12-17-year-old children infected by SARS-CoV-2. INTERPRETATION: Very few cases of hyper-inflammatory syndrome with multi-organ involvement occurred following COVID-19 mRNA vaccine in 12-17-year-old children. The low reporting rate of this syndrome, compared to the rate of post-SARS-CoV-2 MIS-C in the same age-group, largely supports the vaccination in a context of an important circulation of SARS-CoV-2. FUNDING: ESPID Fellowship Award; Grandir-Fonds de Solidarité Pour L'enfance.

Acute brain injury (ABI) is a frequent complication of pediatric extracorporeal membrane oxygenation (ECMO) that could be detected by continuous neuromonitoring. Cerebral near-infrared spectroscopy (NIRS) allows monitoring of cerebral oxygenation. To assess whether an impaired cerebral oxygenation was associated with short-term outcome during pediatric ECMO. We conducted a single-center retrospective study in a pediatric intensive care unit. Children under 18 years old were included if receiving veno-venous or veno-arterial ECMO with concurrent NIRS monitoring. Cerebral saturation impairment was defined as rScO2 under 50% or 20% from the baseline for desaturation, and above 80%. Cerebral imaging (magnetic resonance imaging or CT scan) was performed in case of neurological concern. A radiologist blinded for patient history identified ABI as any hemorragic or ischemic lesion, then classified as major or minor. Primary endpoint was the outcome at hospital discharge. Poor outcome was defined as death or survival with a pediatric cerebral performance category scale (PCPC) score ≥ 3 and/or a major ABI. Good outcome was defined as survival with a PCPC score ≤ 2 and/or a minor or no ABI. Secondary endpoint was mortality before PICU discharge. Sixty-three patients met inclusion criteria; 48 (76%) had veno-arterial ECMO. Mortality rate was 51%. Forty-eight of sixty-three patients (76%) evolved with a poor outcome, including 20 major ABI. Mean rScO2 in the right/left hemisphere was 73 ± 9%/75 ± 9%. Cerebral desaturation and decline of rScO2 below 20% from the baseline, regardless of side, were each associated with poor outcome (multivariable-adjusted odds ratio (OR), 4 [95%CI 1.2; 15.1], p = 0.03, and 3.9 [95%CI 1.1; 14.9], p = 0.04, respectively), as well as a mean right rScO2 80% seemed to be protective. NIRS monitoring might be included within multimodal neuromonitoring to assess the risk of the brain injury related to pediatric ECMO.

Background Admission to hospital with bronchiolitis may adversely affect breastfeeding. Correct advice and support have been pointed out as a determining factor. Objectives We conducted a telephone survey to evaluate a set of actions to promote breastfeeding during hospitalization for acute bronchiolitis. Methods Population: All patients 6 months of age or younger hospitalized with acute bronchiolitis and receiving at least partial breastfeeding were eligible for the study. Patients discharged home whose parents accepted to be contacted by phone were also included. Intervention We established a set of actions to promote breastfeeding (posters, flyers, staff training, and equipment) in all pediatric wards attending to these patients. Comparison This was a cross-sectional study conducted during two epidemic seasons of bronchiolitis in a tertiary care hospital. Data on continued breastfeeding at 3 months (0.5–6; median, range) postdischarge were collected by telephone and compared with the same set of data collected from patients with bronchiolitis in the same setting the year before the intervention. Outcome We conducted a telephone survey to evaluate whether some actions regarding breastfeeding might diminish the risk of unwanted weaning during hospitalization for bronchiolitis. The primary outcome was the proportion of stopped or reduced breastfeeding at discharge. Secondary objectives were to evaluate whether there were factors associated with breastfeeding modification. Results The results of the evaluation before intervention (phase 1) are published by Heilbronner et al. In Phase 1 of our study, 84 patients were included and 43 mothers (51%) reported that breastfeeding was modified by hospitalization of their child: 20.4% stopped, 14% switched to partial breastfeeding, and 16.6% reduced breastfeeding. These mothers stated that causes of breastfeeding disturbances were lack of support and advice (63%), followed by severity of the child's respiratory disease (32%), logistical hospital difficulties (30%), and personal organizational issues (9.3%). The intervention took place in September. After the intervention, 50 patients could be included in the study between October 1and December 31, 2016. Among them, 40 (80%) mothers kept breastfeeding as before, four (8%) stopped, four (8%) switched to partial breastfeeding, and two (4%) reduced breastfeeding without stopping. Bronchiolitis was more severe among patients with altered breastfeeding in terms of ventilatory support. Conclusion Bronchiolitis is a high-risk event for breastfeeding disruption but interventions to promote breastfeeding might help to prevent the risk of unwanted weaning. More severe bronchiolitis probably poses the highest risk of weaning and the need for supplementary nutrition.

Early administration of appropriate antibiotic therapy with adequate concentration is the cornerstone of the severe sepsis and septic shock's treatment. We aim to describe the plasma concentration of the most used β-lactams in critically ill children, to describe the rate of patients with suboptimal exposure, and associated clinical and biological factors.From January 2016 to May 2017, children less than 18 years old with severe sepsis or septic shock were included. Samples were collected in pediatric intensive care unit for children with severe sepsis or septic shock. β-lactam plasma concentrations were analysed using high performance liquid chromatography.Among the 37 enrolled patients, 24 (64.9%) had insufficient concentration [cefotaxime 7/14 (43%); piperacillin-tazobactam, 10/13 (77%); amoxicillin 6/7 (86%); meropenem 3/6 (50%), cefazolin 1/4 (25%), imipenem 0/2 (0%); ceftazidime 0/1 (0%)]. Insufficient concentrations were associated with early measurements [72hours from the sepsis' onset (P=0.035) and an increased creatinine clearance (P=0.01)].β-lactams current dosing in critically ill septic children could be suboptimal.

BackgroundLung involvement in childhood Langerhans cell histiocytosis (LCH) is infrequent and rarely life threatening, but occasionally, severe presentations are observed.MethodsAmong 1482 children (ResultsThe median age was 1.3 years at the first ICU hospitalization. Of the 17 patients, 14 presented with lung involvement at the LCH diagnosis, and 7 patients (41%) had concomitant involvement of risk-organ (hematologic, spleen, or liver). Thirty-five ICU hospitalizations were analysed. Among these, 22 (63%) were secondary to a pneumothorax, 5 (14%) were associated with important cystic lesions without pneumothorax, and 8 (23%) included a diffuse micronodular lung infiltration in the context of multisystem disease.First-line vinblastine–corticosteroid combination therapy was administered to 16 patients; 12 patients required a second-line therapy (cladribine:n = 7; etoposide-aracytine:n = 3; targeted therapyn = 2). A total of 6 children (35%) died (repeated pneumothorax:n = 3; diffuse micronodular lung infiltration in the context of multisystem disease:n = 2; following lung transplantation:n = 1). For survivors, the median follow-up after ICU was 11.2 years. Among these, 9 patients remain asymptomatic despite abnormal chest imaging.ConclusionsSevere lung involvement is unusual in childhood LCH, but it is associated with high mortality. Treatment guidelines should be improved for this group of patients: viral infection prophylaxis and early administration of a new LCH therapy, such as targeted therapy.

After liver transplantation (LT), synthesis of coagulation factors by the graft recovers faster for pro thrombotic than anti thrombotic factors, resulting in a potential pro thrombotic imbalance. We studied the thrombotic and hemorrhagic complications in our pediatric LT series, providing supplementation of fresh frozen plasma (FFP) and/or antithrombin (AT) in the prophylactic antithrombotic regimen.This was a retrospective observational single center study. All isolated pediatric LTs performed between 1/11/2009 and 31/12/2019 (n = 181) were included. Postoperatively, in addition to low molecular weight heparin, 22 patients (12%) received FFP (10 ml/kg twice daily for 10 days), 27 patients (15%) were given FFP (reduced duration) and AT (50-100 IU/kg/day if AT activity remained70%), and 132 (73%) received AT only. Complications, outcome, and coagulation profiles in postoperative days 0-10 were analyzed.In all three treatment groups, AT activity normalized by day 4 while prothrombin remained70% of normal until day 9. Hepatic artery thrombosis (HAT), portal vein thrombosis (PVT), and hemorrhagic complications occurred in 2.8%, 3.3%, and 3.9% of LTs. One- and 5-year patient and graft survival were 88% (±2.4% Standard Error) and 84% (±2.5%), and 86% (±2.6%) and 84% (±2.7%), respectively, without difference between groups. HAT were associated with low AT on days 0 and 1, and PVT with low AT on day 0.Low antithrombin activity after LT was associated with postoperative thromboses. FFP and/or AT supplementation allowed early normalization of AT activity, while thrombotic or hemorrhagic complications were rare, suggesting efficient and safe management of post-LT coagulopathy.

Aim : To assess the diagnostic performance of a simplified lung point-of-care ultrasound (POCUS) to confirm the correct positioning of an endotracheal tube (ETT) in a pediatric intensive care unit (PICU) used to chest radiography (CXR), and to compare the time to obtain the ETT position between POCUS and CXR. Methods : We conducted a single-center prospective study in critically ill children requiring urgent endotracheal intubation. Esophageal tube malposition was first avoided using auscultation and end-tidal CO2. The ETT position was assessed with CXR and lung POCUS using the lung sliding sign on a pleural window. All of the investigators had to read guidelines and received 1-h training on the technical aspects of lung sliding. The primary objective was the accuracy of POCUS in confirming correct nonselective endotracheal intubation as compared with CXR. Results : A total of 71 patients were included from December 2016 to November 2018. CXR identified proper nonselective ETT placement in 43 of 71 (61%) patients, while the rate for selective intubation was 39%. The sensitivity and specificity of POCUS as compared with CXR were 77% and 68%, respectively. Median time to POCUS was significantly shorter than CXR (2 min to perform POCUS, 10 min to obtain radiographs, p Conclusion : Pleural ultrasound, although faster than CXR, appears to be inadequate for identifying selective ETT after urgent intubation in a PICU less accustomed to this kind of ultrasound. In this heterogeneous and fragile population, timely POCUS may remain useful at the bedside as compared with auscultation, aiming at guiding optimal ETT placement and reducing respiratory complications, provided by trained physicians.

Background Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention. Methods Over a 2-month period, contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Results Thirty-five children were identified and included in the study. Median age at admission was 10 years (range, 2–16 years). Comorbidities were present in 28%, including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was

The best protocol for severe inaugural diabetic ketoacidosis (DKA) in children remains unclear. We compared two protocols by assessing effects during the first 24 h on osmolality, serum sodium, and glucose variations, which are associated with the risk of cerebral oedema, the most dreaded complication of DKA. We also recorded complications. We retrospectively included children aged 28 days to 18 years and admitted for severe DKA to either of two paediatric intensive care units (PICUs) in Paris (France). The two protocols differed regarding hydration volume, glucose intake, and sodium intake. From 17 June 2010 to 17 June 2015, 93 patients were included, 29 at one PICU, and 64 at the other. We compared severe glycaemic drops ( 5.5 mmol/L/h), mean glycaemia variations, serum sodium, serum osmolality, and the occurrence of cerebral oedema (CE) during the first 24 h after PICU admission. Severe glycaemic drops occurred in 70% of patients, with no between-group difference. Blood glucose, serum sodium, and serum osmolality variations were comparable. Seven (7.5%) patients were treated for suspected CE, (4 [10.3%)] and 3 [6.3%]) in each PICU; none had major residual impairments. The two paediatric DKA-management protocols differing in terms of fluid-volume, glucose, and sodium intakes had comparable effects on clinical and laboratory-test changes within 24 h. Major drops in glycaemia and osmolality were common with both protocols. No patients had residual neurological impairments.• Cerebral oedema is the most severe complication of diabteic ketoacidosis in children.The risk of cerebral oedema is dependant on both patient related and treatment-related factors. • The optimal protocol for managing severe inaugural diabetic ketoacidosis in children remains unclear, and few studies have targeted this specific population.• Two management protocols that complied with ISPAD guidelines but differed regarding the amounts of fluids, glucose, and sodium administered produced similar outcomes in children with severe inaugural diabetic ketoacidosis. • Cerebral oedema was rare with both protocols and caused no lasting impairments.

INTRODUCTION Therapeutic plasma exchange (TPE) is acknowledged to be an effective treatment in life-threatening pediatric disorders. Apheresis for pediatric diseases has been poorly investigated, and most studies to date featured small numbers of patients and lacked control groups. The objective of the present study was to evaluate the tolerance of TPE in pediatric patients. MATERIALS AND METHODS A retrospective cohort study via a web-based electronic case report form including pediatric patients referred for TPE between January 2005 and December 2014. RESULTS A total of 78 patients (median [range] age: 9.8 [0.53-17.93]) and 731 TPE procedures were analyzed. The indications were antibody-mediated rejection (n = 33; 42%) and desensitization therapy (n = 5; 6%) after solid organ or hematopoietic stem cell transplantation, thrombotic microangiopathy (n = 17; 22%), pediatric inflammatory diseases (n = 16; 21%), kidney diseases (n = 6; 8%), and hyperviscosity syndrome (n = 1; 1%). On average, each patient underwent six procedures during the first session [range: 1-19]. In the 2 weeks following the start of a session, 72 patients (92%) presented a total of 311 adverse events (AEs) potentially related to TPE. The risk of AEs was not related to the indication for TPE, the intensity of care, venous access, plasma substitute use, or body weight. None of the deaths was related to the TPE. CONCLUSION We studied one of the largest retrospective pediatric cohorts described to date. Our experience of TPE children's TPE feasibility concerned specific, life-threatening conditions and otherwise treatment-refractory diseases.

We aimed to develop a meropenem population pharmacokinetic (PK) model in critically ill children and simulate dosing regimens in order to optimize patient exposure. Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem PK was investigated using a non-linear mixed-effect modeling approach. Forty patients with an age of 16.8 (1.4–187.2) months, weight of 9.1 (3.8–59) kg, and estimated glomerular filtration rate (eGFR) of 151 (19–440) mL/min/1.73 m2 were included. Eleven patients received continuous replacement renal therapy (CRRT). Concentration-time courses were best described by a two-compartment model with first-order elimination. Body weight (BW), eGFR, and CRRT were covariates explaining the between-subject variabilities on central/peripheral volume of distribution (V1/V2), inter-compartment clearance (Q), and clearance (CL): V1i = V1pop × (BW/70)1, Qi = Qpop × (BW/70)0.75, V2i = V2pop × (BW/70)1, CLi = (CLpop × (BW/70)0.75) × (eGFR/100)0.378) for patients without CRRT and CLi = (CLpop × (BW/70)0.75) × 0.9 for patients with CRRT, where CLpop, V1pop, Qpop, and V2pop are 6.82 L/h, 40.6 L, 1 L/h, and 9.2 L respectively normalized to a 70-kg subject. Continuous infusion, 60 and 120 mg/kg per day, is the most adequate dosing regimen to attain the target of 50% fT > MIC and 100% fT > MIC for patients infected by bacteria with high minimum inhibitory concentration (MIC) value (> 4 mg/L) without risk of accumulation except in children with severe renal failure. Continuous infusion allows reaching the fT > MIC targets safely in children with normal or increased renal clearance.

Resume Recemment, l’utilisation de l’hypothermie induite a suscite un regain d’interet pour les patients de reanimation, en particulier chez les cerebroleses. Le terme « controle cible de la temperature » (CCT) s’est maintenant impose comme le plus approprie, s’agissant des interventions utilisees pour atteindre et maintenir un niveau specifique de temperature pour chaque individu. Le CCT peut etre utilise pour prevenir la fievre, maintenir la normothermie ou baisser la temperature centrale. Ce traitement est largement utilise dans les services de reanimation, principalement comme methode de neuroprotection primaire. Les indications sont cependant associees a des niveaux de preuve variables fondes sur une litterature inhomogene ou meme contradictoire. Notre but a ete de proceder a une analyse systematique des donnees publiees dans le but de produire des recommandations. Nous presentons ici les recommandations pour l’utilisation du CCT chez l’adulte et l’enfant en reanimation, developpee selon la methode Grading of Recommendations Assessment, Development, and Evaluation (the GRADE). Ces recommandations ont ete realisees par un groupe d’experts de la Societe de reanimation de langue francaise (SRLF), et de la Societe francaise d’anesthesie reanimation (SFAR), avec la participation de la Societe francaise de medecine d’urgence (SFMU), du Groupe francophone de reanimation et urgences pediatriques (GFRUP), de l’Association nationale de neuro-anesthesie reanimation francaise (ANARLF) et de la Societe francaise neurovasculaire (SFNV). Quinze experts et deux coordinateurs se sont mis d’accord pour aborder le CCT et sa mise en pratique dans cinq situations cliniques : l’arret cardiaque, le traumatisme crânien, l’accident vasculaire cerebral, les autres agressions cerebrales et l’etat de choc. Cela a permis de produire 30 recommandations : 3 recommandations sont fortes (grade 1), 13 sont faibles (grade 2) et 14 sont des opinions d’experts. Apres deux tours de vote et plusieurs amendements, un accord fort des participants a ete obtenu pour la totalite des 30 (100 %) des recommandations, qui sont exposees dans le present article.

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.

* Abbreviation: COVID-19 — : coronavirus disease Acute bronchiolitis, a viral seasonal infection of the lower respiratory tract, affects nearly 20% of all children and leads to the hospitalization of 2% to 3% of all children younger than 12 months every year.1,2 Approximately 2% to 6% of hospitalized children require admission to the PICU.1 Acute bronchiolitis may account for as much as 13% of PICU admissions,3 and it is responsible for the death of ∼3 of 100 000 children under 12 months each year4 (eg, nearly 20 and 100 infants annually in England4 and the United States,5 respectively). Bronchiolitis epidemic has a predictable seasonal pattern, and in France, it starts in September, peaks in November to December, and ends in February. Although children have been relatively spared by the coronavirus disease (COVID-19) pandemic, the impact that the overlap of the second wave of this pandemic and of the associated public measures have … Address correspondence to Ricardo Carbajal, MD, PhD, Pediatric Emergency Department, APHP Hopital Armand Trousseau, 26, av du Dr Netter, 75012 Paris, France. E-mail: ricardo.carbajal{at}aphp.fr

Sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) are the most prevalent monogenic disorders worldwide. Trial HGB-205 ( NCT02151526 ) aimed at evaluating gene therapy by autologous CD34

Background: Cardiac injury and myocarditis have been described in adults with coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is typically minimally symptomatic. We report a series of febrile pediatric patients with acute heart failure potentially associated with SARS-CoV-2 infection and the multisystem inflammatory syndrome in children as defined by the US Centers for Disease Control and Prevention. Methods: Over a 2-month period, contemporary with the SARS-CoV-2 pandemic in France and Switzerland, we retrospectively collected clinical, biological, therapeutic, and early outcomes data in children who were admitted to pediatric intensive care units in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Results: Thirty-five children were identified and included in the study. Median age at admission was 10 years (range, 2–16 years). Comorbidities were present in 28%, including asthma and overweight. Gastrointestinal symptoms were prominent. Left ventricular ejection fraction was Conclusions: Children may experience an acute cardiac decompensation caused by severe inflammatory state after SARS-CoV-2 infection (multisystem inflammatory syndrome in children). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

Objectives The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. Methods This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. Results We analyzed the data of 27 children. Comorbidities (n = 19, 70%) were mainly neurological (n = 7), respiratory, (n = 4), or sickle cell disease (n = 4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n = 9), catecholamine (n = 4), erythropheresis (n = 4), renal replacement therapy (n = 1), and extracorporeal membrane oxygenation (n = 1). Five children died, of whom three were without past medical history. Conclusion This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children.

Concern has been raised on sickle cell disease (SCD) patients and the new viral infection with SARS‐COV‐2 since SCD patients are particularly prone to infectious diseases and acute chest syndrome (ACS). Although case reports have been published to describe COVID‐19 related ACS in adult patients (1–4), pediatric data are lacking.

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.

Background A recent increase in children admitted with hypotensive shock and fever in the context of the COVID-19 outbreak requires an urgent characterization and assessment of the involvement of SARS-CoV-2 infection. This is a case series performed at 4 academic tertiary care centers in Paris of all the children admitted to the pediatric intensive care unit (PICU) with shock, fever and suspected SARS-CoV-2 infection between April 15th and April 27th, 2020. Results 20 critically ill children admitted for shock had an acute myocarditis (left ventricular ejection fraction, 35% (25–55); troponin, 269 ng/mL (31–4607)), and arterial hypotension with mainly vasoplegic clinical presentation. The first symptoms before PICU admission were intense abdominal pain and fever for 6 days (1–10). All children had highly elevated C-reactive protein (> 94 mg/L) and procalcitonin (> 1.6 ng/mL) without microbial cause. At least one feature of Kawasaki disease was found in all children (fever, n = 20, skin rash, n = 10; conjunctivitis, n = 6; cheilitis, n = 5; adenitis, n = 2), but none had the typical form. SARS-CoV-2 PCR and serology were positive for 10 and 15 children, respectively. One child had both negative SARS-CoV-2 PCR and serology, but had a typical SARS-CoV-2 chest tomography scan. All children but one needed an inotropic/vasoactive drug support (epinephrine, n = 12; milrinone, n = 10; dobutamine, n = 6, norepinephrine, n = 4) and 8 were intubated. All children received intravenous immunoglobulin (2 g per kilogram) with adjuvant corticosteroids (n = 2), IL 1 receptor antagonist (n = 1) or a monoclonal antibody against IL-6 receptor (n = 1). All children survived and were afebrile with a full left ventricular function recovery at PICU discharge. Conclusions Acute myocarditis with intense systemic inflammation and atypical Kawasaki disease is an emerging severe pediatric disease following SARS-CoV-2 infection. Early recognition of this disease is needed and referral to an expert center is recommended. A delayed and inappropriate host immunological response is suspected. While underlying mechanisms remain unclear, further investigations are required to target an optimal treatment.

Aims Glomerular filtration rate (GFR) is difficult to assess in critically ill children using gold standard method and alternatives are needed. This study aimed to determine the most accurate GFR estimation formula for assessing piperacillin clearance in critically ill children, using a published piperacillin pharmacokinetics (PK) population model. Methods All children hospitalized in the paediatric intensive care unit of a single institution who were receiving piperacillin were included. PK were described using the nonlinear mixed effect modelling software MONOLIX. In the initial PK model, GFR was estimated according to the Schwartz 1976 formula. We evaluated a set of 12 additional validated formulas, developed using plasma creatinine and/or cystatin C concentrations, in the building model to assess the lowest between-subject variability for piperacillin clearance. Results We included 20 children with a median (range) postnatal age of 1.9 (0.1-19) years, body weight of 12.5 (3.5-69) kg. Estimated GFR according to the Schwartz 1976 formula was 160.5 (38-315) mL min-1 1.73 m-2 . Piperacillin clearance was best predicted by the Bouvet combined formula. Conclusion The combined Bouvet formula was the most accurate GFR estimation formula for assessing piperacillin clearance in critically ill children.