Predictive value of microcirculation for pediatric extracorporeal membrane oxygenation weaning test: A monocentric prospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is widely used for children treated for refractory respiratory failures or refractory cardiogenic shock. Its duration depends on organ functions recovery. Weaning is decided using macro-circulatory tools, but microcirculation is not well evaluated. Sidestream dark-field video imaging is used to assess the perfusion of the sublingual microvascular vessels. The aim of this study was to assess the predictive value of microcirculatory indices in ECMO weaning. METHODS: This prospective monocentric study examined pediatric patients at Trousseau Hospital between March 2017 and December 2020. The study included all patients from 35 weeks of gestational age to 18 years old who were treated with ECMO. Children were divided into two groups: one with stability after weaning and the other with instability after weaning. We collected clinical and biological data, ventilation parameters, extracorporeal membrane oxygenation parameters, and drugs used at admission and after the weaning test. Microcirculations videos were taken after weaning trials with echocardiography and blood gas monitoring. RESULTS: The study included 30 patients with a median age of 29 days (range: 1-770 days) at admission, including 18 patients who received venoarterial ECMO (60%). There were 19 children in the stability group and 11 in the instability group. Macrocirculatory and microcirculatory indices showed no differences between groups. The microvascular flow index was subnormal in both groups (2.3 (1.8-2.4) and 2.3 (2.3-2.6), respectively; p = 0.24). The microvascular indices were similar between cases of venovenous and venoarterial ECMO and between age groups. CONCLUSION: Microcirculation monitoring at the weaning phase did not predict the failure of ECMO weaning.

Pao2 and Mortality in Neonatal Extracorporeal Membrane Oxygenation: Retrospective Analysis of the Extracorporeal Life Support Organization Registry, 2015-2020.

OBJECTIVES: Extracorporeal life support can lead to rapid reversal of hypoxemia but the benefits and harms of different oxygenation targets in severely ill patients are unclear. Our primary objective was to investigate the association between the Pao2 after extracorporeal membrane oxygenation (ECMO) initiation and mortality in neonates treated for respiratory failure. DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization (ELSO) Registry data, 2015-2020. PATIENTS: Newborns supported by ECMO for respiratory indication were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pao2 24 hours after ECMO initiation (H24 Pao2) was reported. The primary outcome was 28-day mortality. We identified 3533 newborns (median age 1 d [interquartile range (IQR), 1-3]; median weight 3.2 kg [IQR, 2.8-3.6]) from 198 ELSO centers, who were placed on ECMO. By 28 days of life, 731 (20.7%) had died. The median H24 Pao2 was 85 mm Hg (IQR, 60-142). We found that both hypoxia (Pao2 < 60 mm Hg) and moderate hyperoxia (Pao2 201-300 mm Hg) were associated with greater adjusted odds ratio (aOR [95% CI]) of 28-day mortality, respectively: aOR 1.44 (95% CI, 1.08-1.93), p = 0.016, and aOR 1.49 (95% CI, 1.01-2.19), p value equals to 0.045. CONCLUSIONS: Early hypoxia or moderate hyperoxia after ECMO initiation are each associated with greater odds of 28-day mortality among neonates requiring ECMO for respiratory failure.

Lung biopsies in infants and children in critical care situation.

INTRODUCTION: Lung biopsy is considered as the last step investigation for diagnosing lung diseases; however, its indication must be carefully balanced with its invasiveness. The present study aims to evaluate the diagnostic yield of lung biopsy in critically ill patients hospitalized in the pediatric intensive care unit (ICU). MATERIAL AND METHODS: Children who underwent a lung biopsy in the ICU between 1995 and 2022 were included. Biopsies performed in the operating room and post-mortem biopsies were excluded. RESULTS: Thirty-one patients were included, with a median age of 18 days (2 days to 10.8 years); 21 (67.7%) were newborns. All patients required invasive mechanical ventilation, 26 (89.7%) had a pulmonary hypertension, and 22 (70.9%) were placed under extracorporeal membrane oxygenation (ECMO). The lung biopsy led to a diagnosis in 81% of the patients. The diagnostic reliability seemed to decrease with age (95% in newborns, 71% in 1 month to 2 years and 0/3 patients aged over 2 years old). Diffuse developmental disorders of the lung accounted for 15 (49%) patients, primarily alveolar capillary dysplasia, followed by surfactant disorders in 5 (16%) patients. Complications occurred in 9/31 (29%) patients including eight under ECMO, with massive hemorrhages in seven cases. DISCUSSION AND CONCLUSION: In critical situations, lung biopsy should be performed. Lung biopsy is a reliable diagnostic procedure for neonates in critical situation when a diffuse developmental disorder of the lung is suspected. The majority of lung biopsy complication was associated with the use of ECMO. The prospective evaluation of the complications of such procedure under ECMO, and particularly over 10 days of ECMO and in children over 2-year-old remains to be ascertained.

Adaptation of Autoencoder for Sparsity Reduction From Clinical Notes Representation Learning.

When dealing with clinical text classification on a small dataset, recent studies have confirmed that a well-tuned multilayer perceptron outperforms other generative classifiers, including deep learning ones. To increase the performance of the neural network classifier, feature selection for the learning representation can effectively be used. However, most feature selection methods only estimate the degree of linear dependency between variables and select the best features based on univariate statistical tests. Furthermore, the sparsity of the feature space involved in the learning representation is ignored. GOAL: Our aim is, therefore, to access an alternative approach to tackle the sparsity by compressing the clinical representation feature space, where limited French clinical notes can also be dealt with effectively. METHODS: This study proposed an autoencoder learning algorithm to take advantage of sparsity reduction in clinical note representation. The motivation was to determine how to compress sparse, high-dimensional data by reducing the dimension of the clinical note representation feature space. The classification performance of the classifiers was then evaluated in the trained and compressed feature space. RESULTS: The proposed approach provided overall performance gains of up to 3% for each test set evaluation. Finally, the classifier achieved 92% accuracy, 91% recall, 91% precision, and 91% f1-score in detecting the patient's condition. Furthermore, the compression working mechanism and the autoencoder prediction process were demonstrated by applying the theoretic information bottleneck framework. Clinical and Translational Impact Statement- An autoencoder learning algorithm effectively tackles the problem of sparsity in the representation feature space from a small clinical narrative dataset. Significantly, it can learn the best representation of the training data because of its lossless compression capacity compared to other approaches. Consequently, its downstream classification ability can be significantly improved, which cannot be done using deep learning models.

Clinical Decision Support System to Detect the Occurrence of Ventilator-Associated Pneumonia in Pediatric Intensive Care.

OBJECTIVES: Ventilator-associated pneumonia (VAP) is a severe care-related disease. The Centers for Disease Control defined the diagnosis criteria; however, the pediatric criteria are mainly subjective and retrospective. Clinical decision support systems have recently been developed in healthcare to help the physician to be more accurate for the early detection of severe pathology. We aimed at developing a predictive model to provide early diagnosis of VAP at the bedside in a pediatric intensive care unit (PICU). METHODS: We performed a retrospective single-center study at a tertiary-care pediatric teaching hospital. All patients treated by invasive mechanical ventilation between September 2013 and October 2019 were included. Data were collected in the PICU electronic medical record and high-resolution research database. Development of the clinical decision support was then performed using open-access R software (Version 3.6.1®). MEASUREMENTS AND MAIN RESULTS: In total, 2077 children were mechanically ventilated. We identified 827 episodes with almost 48 h of mechanical invasive ventilation and 77 patients who suffered from at least one VAP event. We split our database at the patient level in a training set of 461 patients free of VAP and 45 patients with VAP and in a testing set of 199 patients free of VAP and 20 patients with VAP. The Imbalanced Random Forest model was considered as the best fit with an area under the ROC curve from fitting the Imbalanced Random Forest model on the testing set being 0.82 (95% CI: (0.71, 0.93)). An optimal threshold of 0.41 gave a sensitivity of 79.7% and a specificity of 72.7%, with a positive predictive value (PPV) of 9% and a negative predictive value of 99%, and with an accuracy of 79.5% (95% CI: (0.77, 0.82)). CONCLUSIONS: Using machine learning, we developed a clinical predictive algorithm based on clinical data stored prospectively in a database. The next step will be to implement the algorithm in PICUs to provide early, automatic detection of ventilator-associated pneumonia.

Association between pediatric intensive care mortality and mechanical ventilation settings during extracorporeal membrane oxygenation for pediatric acute respiratory distress syndrome.

The main objective of this study was to describe the current mechanical ventilation (MV) settings during extracorporeal membrane oxygenation (ECMO) for pediatric acute respiratory distress syndrome (P-ARDS) in six European centers. This is a retrospective observational cohort study performed in six European centers from January 2009 to December 2019. Children > 1 month to 18 years supported with ECMO for refractory P-ARDS were included. Collected data were as follows: patients' pre-ECMO medical condition, pre-ECMO adjunctive therapies for P-ARDS, pre-ECMO and during ECMO MV settings on day (D) 1, D3, D7, and D14 of ECMO, use of adjunctive therapies during ECMO, duration of ECMO, pediatric intensive care unit length of stay, and survival. A total of 255 patients with P-ARDS were included. The multivariate analysis showed that PEEP on D1 (OR = 1.13, 95% CI [1.03-1.24], p = 0.01); D3 (OR = 1.17, 95% CI [1.06-1.29], p = 0.001); and D14 (OR = 1.21, 95% CI [1.05-1.43], p = 0.02) and DP on D7 were significantly associated with higher odds of mortality (OR = 0.82, 95% CI [0.71-0.92], p = 0.001). Moreover, DP on D1 above 15 cmH2O (OR 2.23, 95% CI (1.09-4.71), p = 0.03) and native lung FiO2 above 60% on D14 (OR 10.36, 95% CI (1.51-116.15), p = 0.03) were significantly associated with higher odds of mortality.   Conclusion: MV settings during ECMO for P-ARDS varied among centers; however, use of high PEEP levels during ECMO was associated with higher odds of mortality as well as a DP above 15 cmH2O and a native lung FiO2 above 60% on D14 of ECMO. What is Known: • Invasive ventilation settings are well defined for pediatric acute respiratory distress syndrome; however, once the children required an extracorporeal respiratory support, there is no recommendation how to set the mechanical ventilator. • Impact of invasive ventilator during extracorporeal respiratory support ad only been during the first days of this support but the effects of these settings later in the assistance are not described. What is New: • It seems to be essential to early decrease FiO2 on native lung once the ECMO flow allows an efficient oxygenation. • Tight control to limit the driving pressure at 15 cmH20 during ECMO run seems to be associated with better survival rate.

A Web-Based Platform for the Automatic Stratification of ARDS Severity.

Acute respiratory distress syndrome (ARDS), including severe pulmonary COVID infection, is associated with a high mortality rate. It is crucial to detect ARDS early, as a late diagnosis may lead to serious complications in treatment. One of the challenges in ARDS diagnosis is chest X-ray (CXR) interpretation. ARDS causes diffuse infiltrates through the lungs that must be identified using chest radiography. In this paper, we present a web-based platform leveraging artificial intelligence (AI) to automatically assess pediatric ARDS (PARDS) using CXR images. Our system computes a severity score to identify and grade ARDS in CXR images. Moreover, the platform provides an image highlighting the lung fields, which can be utilized for prospective AI-based systems. A deep learning (DL) approach is employed to analyze the input data. A novel DL model, named Dense-Ynet, is trained using a CXR dataset in which clinical specialists previously labelled the two halves (upper and lower) of each lung. The assessment results show that our platform achieves a recall rate of 95.25% and a precision of 88.02%. The web platform, named PARDS-CxR, assigns severity scores to input CXR images that are compatible with current definitions of ARDS and PARDS. Once it has undergone external validation, PARDS-CxR will serve as an essential component in a clinical AI framework for diagnosing ARDS.

Risk of Admission to the Pediatric Intensive Care Unit for SARS-CoV-2 Delta and Omicron Infections.

BACKGROUND: The severity of SARS-CoV-2-related diseases in children remains unclear. This study aimed to describe the incidence of French pediatric intensive care units (PICUs) admissions with acute COVID-19, incidental positive SARS-CoV-2 test result, and multisystem inflammatory syndrome in children (MIS-C) during the delta and omicron variant periods. METHODS: This study used the French PICU registry to obtain data on all patients admitted to 41 French PICUs diagnosed with acute COVID-19, incidental positive SARS-CoV-2 test result, or MIS-C between August 30, 2021 and April 20, 2022. Data regarding the total number of positive SARS-CoV-2 polymerase chain reaction results according to the type of variants were obtained from the French National Public Health Agency. RESULTS: Of 745 children, 244 (32.8%) were admitted for acute COVID-19, 246 (33.0%) for incidental positive SARS-CoV-2 test results, and 255 (34.2%) for MIS-C. The incidence of each group was higher with delta than with omicron. The incidence rate ratios with the delta variant were 7.47 (95% CI, 4.22-13.26) for acute COVID-19, 4·78 (95% CI, 2.30-9.94) for incidental positive SARS-CoV-2 test results, and 10.46 (95% CI, 5.98-18.31) for MIS-C compared to the omicron variant. The median age was 66 (7.7-126.8) months; 314 (42%) patients had comorbidities. Patients with acute COVID-19 and incidental positive SARS-CoV-2 test results had similar proportions of comorbidities. No patient with MIS-C died, whereas the mortality rates in the acute COVID-19 and incidental positive SARS-CoV-2 test results groups were 6.8% and 3.8%, respectively. CONCLUSIONS: The incidence of acute COVID-19, incidental positive SARS-CoV-2 test results, and MIS-C admitted to the PICU were significantly higher with the delta variant than with the omicron variant.

Association Between Early Change in Arterial Carbon Dioxide Tension and Outcomes in Neonates Treated by Extracorporeal Membrane Oxygenation.

The primary objective was to investigate the association between partial pressure of carbon dioxide (PaCO 2 ) change after extracorporeal membrane oxygenation (ECMO) initiation and neurologic outcome in neonates treated for respiratory failure. A retrospective analysis of the Extracorporeal Life Support Organization (ELSO) database including newborns supported by ECMO for respiratory indication during 2015-2020. The closest Pre-ECMO (Pre-ECMO PaCO 2 ) and at 24 hours after ECMO initiation (H24 PaCO 2 ) PaCO 2 values allowed to calculate the relative change in PaCO 2 (Rel Δ PaCO 2 = [H24 PaCO 2 - Pre-ECMO PaCO 2 ]/Pre-ECMO PaCO 2 ). The primary outcome was the onset of any acute neurologic event (ANE), defined as cerebral bleeding, ischemic stroke, clinical or electrical seizure, or brain death during ECMO. We included 3,583 newborns (median age 1 day [interquartile range {IQR}, 1-3], median weight 3.2 kg [IQR, 2.8-3.6]) from 198 ELSO centers. The median Rel Δ PaCO 2 value was -29.9% [IQR, -46.2 to -8.5]. Six hundred nine (17%) of them had ANE (405 cerebral bleedings, 111 ischemic strokes, 225 seizures, and 6 brain deaths). Patients with a decrease of PaCO 2 > 50% were more likely to develop ANE than others (odds ratio [OR] 1.78, 95% confidence interval [CI], 1.31-2.42, p < 0.001). This was still observed after adjustment for all clinically relevant confounding factors (adjusted OR 1.94, 95% CI, 1.29-2.92, p = 0.001). A significant decrease in PaCO 2 after ECMO start is associated with ANE among neonates requiring ECMO for respiratory failure. Cautious PaCO 2 decrease should be considered after start of ECMO therapy.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

Extracorporeal Membrane Oxygenation in Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: To systematically review and assimilate literature on children receiving extracorporeal membrane oxygenation (ECMO) support in pediatric acute respiratory distress syndrome (PARDS) with the goal of developing an update to the Pediatric Acute Lung Injury Consensus Conference recommendations and statements about clinical practice and research. DATA SOURCES: Electronic searches of MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: The search used a medical subject heading terms and text words to capture studies of ECMO in PARDS or acute respiratory failure. Studies using animal models and case reports were excluded from our review. DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. There were 18 studies identified for full-text extraction. When pediatric data was lacking, adult and neonatal data from randomized clinical trials and observational studies were considered. Six clinical recommendations were generated related to ECMO indications, initiation, and management in PARDS. There were three good practice statements generated related to ECMO indications, initiation, and follow-up in PARDS. Two policy statements were generated involving the impact of ECMO team organization and training in PARDS. Last, there was one research statement. CONCLUSIONS: Based on a systematic literature review, we propose clinical management, good practice and policy statements within the domains of ECMO indications, initiation, team organization, team training, management, and follow-up as they relate to PARDS.

Clinical practice guidelines: management of severe bronchiolitis in infants under 12 months old admitted to a pediatric critical care unit.

PURPOSE: We present guidelines for the management of infants under 12 months of age with severe bronchiolitis with the aim of creating a series of pragmatic recommendations for a patient subgroup that is poorly individualized in national and international guidelines. METHODS: Twenty-five French-speaking experts, all members of the Groupe Francophone de Réanimation et Urgence Pédiatriques (French-speaking group of paediatric intensive and emergency care; GFRUP) (Algeria, Belgium, Canada, France, Switzerland), collaborated from 2021 to 2022 through teleconferences and face-to-face meetings. The guidelines cover five areas: (1) criteria for admission to a pediatric critical care unit, (2) environment and monitoring, (3) feeding and hydration, (4) ventilatory support and (5) adjuvant therapies. The questions were written in the Patient-Intervention-Comparison-Outcome (PICO) format. An extensive Anglophone and Francophone literature search indexed in the MEDLINE database via PubMed, Web of Science, Cochrane and Embase was performed using pre-established keywords. The texts were analyzed and classified according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. When this method did not apply, an expert opinion was given. Each of these recommendations was voted on by all the experts according to the Delphi methodology. RESULTS: This group proposes 40 recommendations. The GRADE methodology could be applied for 17 of them (3 strong, 14 conditional) and an expert opinion was given for the remaining 23. All received strong approval during the first round of voting. CONCLUSION: These guidelines cover the different aspects in the management of severe bronchiolitis in infants admitted to pediatric critical care units. Compared to the different ways to manage patients with severe bronchiolitis described in the literature, our original work proposes an overall less invasive approach in terms of monitoring and treatment.

Acute care for patients exposed to a chemical attack: protocol for an international multicentric observational study.

INTRODUCTION: The use of weapons of mass destruction against civilian populations is of serious concern to public health authorities. Chemical weapons are of particular concern. A few studies have investigated medical responses in prehospital settings in the immediate aftermath of a chemical attack, and they were limited by the paucity of clinical data. This study aims to describe the acute management of patients exposed to a chemical attack from the incident site until their transfer to a medical facility. METHODS AND ANALYSIS: This international multicentric observational study addresses the period from 1970 to 2036. An online electronic case report form was created to collect data; it will be hosted on the Biomedical Telematics Laboratory Platform of the Quebec Respiratory Health Research Network. Participating medical centres and their clinicians are being asked to provide contextual and clinical information, including the use of protective equipment and decontamination capabilities for the medical evacuation of the patient from the incident site of the chemical attack to the moment of admission at the medical facility. In brief, variables are categorised as follows: (1) chemical exposure (threat); (2) prehospital and hospital/medical facility capabilities (staffing, first aid, protection, decontamination, disaster plans and medical guidelines); (3) clinical interventions before hospital admission, including the use of protection and decontamination and (4) outcomes (survivability vs mortality rates). Judgement criteria focus on decontamination drills applied to any of the patient's conditions. ETHICS AND DISSEMINATION: The Sainte-Justine Research Centre Ethics Committee approved this multicentric study and is acting as the main evaluating centre. Study results will be disseminated through various means, including conferences, indexed publications in medical databases and social media. TRIAL REGISTRATION NUMBER: NCT05026645.

HEAD AND THORAX ELEVATION PREVENTS THE RISE OF INTRACRANIAL PRESSURE DURING EXTRACORPOREAL RESUSCITATION IN SWINE.

Aim: Head and thorax elevation during cardiopulmonary resuscitation improves cerebral hemodynamics and ultimate neurological outcome after cardiac arrest. Its effect during extracorporeal cardiopulmonary resuscitation (E-CPR) is unknown. We tested whether this procedure could improve hemodynamics in swine treated by E-CPR. Methods and Results: Pigs were anesthetized and submitted to 15 minutes of untreated ventricular fibrillation followed by E-CPR. Animals randomly remained in flat position (flat group) or underwent head and thorax elevation since E-CPR institution (head-up group). Electric shocks were delivered after 30 minutes until the return of spontaneous circulation (ROSC). They were followed during 120 minutes after ROSC. After 30 minutes of E-CPR, ROSC was achieved in all animals, with no difference regarding blood pressure, heart rate, and extracorporeal membrane of oxygenation flow among groups. The head-up group had an attenuated increase in ICP as compared with the flat group after cardiac arrest (13 ± 1 vs. 26 ± 2 mm Hg at the end of the follow-up, respectively). Cerebral perfusion pressure tended to be higher in the head-up versus flat group despite not achieving statistical difference (66 ± 1 vs 46 ± 1 mm Hg at the end of the follow-up). Carotid blood flow and cerebral oxygen saturation were not significantly different among groups. Conclusion: During E-CPR, head and thorax elevation prevents ICP increase. Whether it could improve the ultimate neurological outcome in this situation deserves further investigation.

Cefepime population pharmacokinetics and dosing regimen optimization in critically ill children with different renal function.

OBJECTIVE: Cefepime is commonly used in pediatric intensive care units, where unpredictable variations in the patients' pharmacokinetic (PK) variables may require drug dose adjustments. The objectives of the present study were to build a population PK model for cefepime in critically ill children and to optimize individual initial dosing regimens. METHODS: Children (aged from 1 month to 18 years; body weight >3 kg) receiving cefepime were included. Cefepime total plasma concentrations were measured using high performance liquid chromatography. Data were modelled using nonlinear, mixed-effect modeling software, and Monte Carlo simulations were performed with a PK target of 100% fT > MIC. RESULTS: Fifty-nine patients (median (range) age: 13.5 months (1.1 months to 17.6 years)) and 129 cefepime concentration measurements were included. The cefepime concentration data were best fitted by a one-compartment model. The selected covariates were body weight with allometric scaling and estimated glomerular filtration rate on clearance. Mean population values for clearance and volume were 1.21 L/h and 4.8 L, respectively. According to the simulations, a regimen of 100 mg/kg/d q12 h over 30 min or 100 mg/kg/d as a continuous infusion was more likely to achieve the PK target in patients with renal failure and in patients with normal or augmented renal clearance, respectively. DISCUSSION: Appropriate cefepime dosing regimens should take renal function into account. Continuous infusions are required in critically ill children with normal or augmented renal clearance, while intermittent infusions are adequate for children with acute renal failure. Close therapeutic drug monitoring is mandatory, given cefepime's narrow therapeutic window.

Antifungal combination therapy for invasive fungal infections in a paediatric oncology and haematology department: A retrospective analysis of practice.

BACKGROUND: Invasive fungal infections (IFI) are an important cause of morbidity and mortality in children with leukaemia. International guidelines recommend a monotherapy for most IFI. The use of antifungal combination therapy (ACT) has been reported, but clinical data supporting these combinations are scarce, particularly in paediatrics. OBJECTIVE: To describe, among patients treated in our department, the situations in which an ACT was used. RESULTS: Between January 2017 and December 2020, 239 patients (406 hospital stays) benefited from systemic antifungals. Among them, ACT was prescribed for 14 (5.9%) patients (13 leukaemia, 1 aplastic anaemia) corresponding to 16 (3.9%) hospital stays. IFI cases treated with ACT were mainly proven (n=9) or probable (n=4). Seven cases required admission to the intensive care unit. The most commonly used antifungal agents were liposomal amphotericin B (n=13), caspofungin (n=12) and voriconazole (n=9). In 13 cases, monotherapy was prescribed as first-line therapy and changed to an ACT for an uncontrolled infection. But in 3 cases, the ACT was started immediately. The response at 12 weeks after diagnosis of proven/probable IFI was successful in 12 cases (92.3%). The only IFI-related death was attributed to disseminated mucormycosis. ACT were generally well tolerated. In 4 cases, adverse events led to the discontinuation of the offending antifungal agent. CONCLUSION: This retrospective analysis of practices shows that the use of ACT in our paediatric haemato-oncology department is rare, and concerns the most severe cases and/or those not responding to the first line treatment. In most cases, ACT was efficient and well tolerated.

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.

Usefulness of implementation of a protective mechanical ventilation bundle during extracorporeal membrane oxygenation for pediatric acute respiratory distress syndrome.

OBJECTIVE: Defining the best ventilatory settings under ECMO remains a challenging question. Despite a well-defined ARDS treatment before ECMO initiation, there is no recommendation on how to ventilate a patient under ECMO for P-ARDS. Only a few descriptive studies are available on ventilatory settings during respiratory ECMO. We aim at evaluating the usefulness of a protective ventilation bundle under ECMO and its capacity to reduce the ventilatory pressure in our ECMO center. METHODS: We performed a monocentric retrospective study from January 2007 to December 2018. All children aged from 1 month to 18 years old and requiring an extracorporeal membrane oxygenation for a refractory acute respiratory distress syndrome were included. A protective mechanical ventilation under ECMO bundle has been developed in 2014. We compare the period 1 (before 2014) to the period 2 (after 2014). RESULTS: Eighty-three patient had been included during the study. We reported a significant increase of PEEP and mean pressure respectively at day 3, day 7 and day 14 of ECMO during the period 2. Conversely, the driving pressure were significantly lower in the period 2 at day 3 (p: 0.009), day 7 (p:0.001) and day 14 (p: 0.001). We also shown a strong increase in the use of prone positioning during ECMO in the period 2 (p: 0.01). There was no significant effect of our bundle on the length of mechanical ventilation, of hospitalization and on the survival rate. CONCLUSIONS: The implementation of a protective mechanical ventilation bundle during ECMO is usefulness to apply for lower ventilatory pressure and higher use of prone positioning. Nonetheless, the lack of power of our study prevents us from showing its efficacy on outcome criteria.