How to follow the guidelines, when the appropriate fluid is missing?

Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. Recently paediatric societies have produced evidence-based practice guidelines that recommend the use of balanced isotonic fluid when prescribing IV-MFT in both acute and critical paediatric care. Unfortunately, the applicability of these guidelines could be called into question when a ready-to-use glucose-containing balanced isotonic fluid is not available. The main objective of this study was to describe the availability of glucose-containing balanced isotonic fluids in European and Middle Eastern paediatric acute and critical care settings. This work is an ancillary study of the survey dedicated to IV-MFT practices in the paediatric acute and critical care settings in Europe and Middle East, a cross-sectional electronic 27-item survey, emailed in April-May 2021 to paediatric critical care physicians across 34 European and Middle East countries. The survey was developed by an expert multi-professional panel within the European Society of Peadiatric and Neonatal Intensive Care (ESPNIC). Balanced isotonic fluid with glucose 5% was available for only 32/153 (21%) responders. Balanced isotonic fluid with glucose 5% was consistently available in the UK (90%) but not available in France, Greece, The Netherlands and Turkey.    Conclusion: Ready-to-use isotonic balanced IV solutions containing glucose in sufficient amount exist but are inconsistently available throughout Europe. National and European Medication Safety Incentives should guarantee the availability of the most appropriate and safest IV-MFT solution for all children. What is Known: • Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. • Balanced isotonic fluid is recommended when prescribing IV-MFT in both acute and critical paediatric care. What is New: • Balanced isotonic fluid with glucose 5% is available for less than 25% of the prescribers in Europe and the Middle East. Availability of balanced isotonic fluid with glucose 5% varies from one country to another but can also be inconsistent within the same country. • Clinicians who have access to a ready-to-use balanced isotonic fluid with glucose 5% are more likely to consider its use than clinicians who do not have access to such an IV solution.

Prevalence of anemia at diagnosis of pediatric chronic myeloid leukemia and prognostic impact on the disease course.

The clinical presentation of chronic myeloid leukemia (CML) at diagnosis differs in children compared to adults. At younger age, anemia appears to be frequent at diagnosis, but its prevalence and its impact on prognosis are not well known. In the International Registry of Childhood CML, we selected children and adolescents in chronic phase at diagnosis of CML and treated upfront with imatinib. We examined their hemoglobin level at diagnosis according to the WHO grades to assess the prevalence of anemia and its impact on response to tyrosine kinase inhibitors (TKIs). Data on 430 patients were included. Anemia at diagnosis was observed in 350 patients (81%), with a mean hemoglobin level of 96.4 g/l (SD 23.6). Among them, 182 patients (52%) presented with moderate anemia and 110 (31%) with severe anemia while 58 (17%) had mild anemia. Compared with mild and no anemia, moderate and severe forms were significantly associated with younger age at diagnosis, asthenia, splenomegaly, and increased leukocyte and basophil counts. Delays in achieving major and deep molecular responses were significantly increased for patients with moderate and severe anemia, and also failure of imatinib treatment was more frequent in these two sub-cohorts. However, hemoglobin level was not significantly associated with survival. Anemia at diagnosis of pediatric CML was frequent and may be considered as a prognostic factor.

Intravenous maintenance fluid therapy practice in the pediatric acute and critical care settings: a European and Middle Eastern survey.

The ideal fluid for intravenous maintenance fluid therapy (IV-MFT) in acutely and critically ill children is controversial, and evidence-based clinical practice guidelines are lacking and current prescribing practices remain unknown. We aimed to describe the current practices in prescribing IV-MFT in the context of acute and critically ill children with regard to the amount, tonicity, composition, use of balanced fluids, and prescribing strategies in various clinical contexts. A cross-sectional electronic 27-item survey was emailed in April-May 2021 to pediatric critical care physicians across European and Middle East countries. The survey instrument was developed by an expert multi-professional panel within the European Society of Pediatric and Neonatal Intensive Care (ESPNIC). A total of 154 respondents from 35 European and Middle East countries participated (response rate 64%). Respondents were physicians in charge of acute or critically ill children. All respondents indicated they routinely use a predefined formula to prescribe the amount of IV-MFT and considered fluid balance monitoring very important in the management of acute and critically ill children. The use of balanced solution was preferred if there were altered serum sodium and chloride levels or metabolic acidosis. Just under half (42%, 65/153) of respondents believed balanced solutions should always be used. Respondents considered the use of isotonic IV solutions as important for acute and critically ill children. In terms of the indication and the composition of IV-MFT prescribed, responses were heterogeneous among centers. Almost 70% (107/154) respondents believed there was a gap between current practice and what they considered ideal IV-MFT due to a lack of guidelines and inadequate training of healthcare professionals.   Conclusions: Our study showed considerable variability in clinical prescribing practice of IV-MFT in acute pediatric settings across Europe and the Middle East. There is an urgent need to develop evidence-based guidelines for IV-MFT prescription in acute and critically ill children. What is Known: • The administration of maintenance intravenous fluid therapy is a standard of care for a lot of hospitalized children • Maintenance intravenous fluid therapy prescriptions are often based on Holliday and Segar's historical guidelines even if this practice has been associated with several complications. What is New: • This study provided information on the prescribing practice regarding fluid restriction, fluid tonicity, and balance. • This study showed considerable variability in clinical prescribing practice of intravenous maintenance fluid therapy across Europe and the Middle East.

Proton Pump Inhibitor Use and Associated Infectious Complications in the PICU: Propensity Score Matching Analysis.

OBJECTIVES: We aimed to evaluate the association between proton pump inhibitor (PPI) exposure and nosocomial infection (NI) during PICU stay. DESIGN: Propensity score matched analysis of a single-center retrospective cohort from January 1, 2017, to December 31, 2018. SETTING: Tertiary medical and surgical PICU in France. PATIENTS: Patients younger than 18 years old, admitted to the PICU with a stay greater than 48 hours. INTERVENTION: Patients were retrospectively allocated into two groups and compared depending on whether they received a PPI or not. MEASUREMENTS AND MAIN RESULTS: Seven-hundred fifty-four patients were included of which 231 received a PPI (31%). PPIs were mostly used for stress ulcer prophylaxis (174/231; 75%), but upper gastrointestinal bleed risk factors were rarely present (18%). In the unadjusted analyses, the rate of NI was 8% in the PPI exposed group versus 2% in the nonexposed group. After propensity score matching ( n = 184 per group), we failed to identify an association between PPI exposure and greater odds of NI (adjusted odds ratio 2.9 [95% CI, 0.9-9.3]; p = 0.082). However, these data have not excluded the possibility that there is up to nine-fold greater odds of NI. CONCLUSIONS: This study highlights the prevalent use of PPIs in the PICU, and the potential association between PPIs and nine-fold greater odds of NI is not excluded.

Influence of implementing a protocol for an intravenously administered ammonia scavenger on the management of acute hyperammonemia in a pediatric intensive care unit.

The purpose of the study was to evaluate the influence of establishing a protocol for the use of combined sodium benzoate and sodium phenylacetate (SBSP) (Ammonul®) to treat acute hyperammonemia. This was a retrospective, single-center study in a 24-bed medical and surgical pediatric intensive care unit (PICU) in a tertiary care teaching maternal-child hospital in Canada. Inclusion criteria were age < 18 years, PICU admission between 1 January 2000 and 30 June 2016, and SBSP treatment. An SBSP delivery protocol was implemented in our hospital on 30 August 2008 in order to improve management of acute hyperammonemia. Patients were assigned to one of the two groups, without or with protocol, depending on date of admission. SBSP was ordered 34 times during the study period, and 23 orders were considered for analysis (14 with and 9 without protocol). Patient characteristics were similar between groups. The median time from diagnosis to prescription was significantly shorter in the protocol group [40 min (21-82) vs 100 min (70-150), p = 0.03)] but the median time from diagnosis to administration of the treatment was equivalent [144 min (90-220) vs 195 (143-274), (p = 0.2)]. Other clinical outcomes did not differ. This study is the first to compare two SBSP delivery strategies in the treatment of acute hyperammonemia in this PICU setting. Implementation of a delivery protocol shortened the time from diagnosis of hyperammonemia to prescription of SBSP and helped us identify other parameters that can be improved to optimize treatment delivery.

Ventilator-Associated Pneumonia and Events in Pediatric Intensive Care: A Single Center Study.

OBJECTIVES: Ventilator-associated pneumonia is the second most common nosocomial infection in pediatric intensive care. The Centers for Disease Control and Prevention recently issued diagnosis criteria for pediatric ventilator-associated pneumonia and for ventilator-associated events in adults. The objectives of this pediatric study were to determine the prevalence of ventilator-associated pneumonia using these new Centers for Disease Control and Prevention criteria, to describe the risk factors and management of ventilator-associated pneumonia, and to assess a simpler method to detect ventilator-associated pneumonia with ventilator-associated event in critically ill children. DESIGN: Retrospective, observational, single-center. SETTING: PICU in a tertiary-care university hospital. PATIENTS: Consecutive critically ill children mechanically ventilated for greater than or equal to 48 hours between November 2013 and November 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 304 patients mechanically ventilated for greater than or equal to 48 hours, 284 were included. Among them, 30 (10.6%) met clinical and radiologic Centers for Disease Control and Prevention criteria for ventilator-associated pneumonia, yielding an prevalence of 7/1,000 mechanical ventilation days. Median time from mechanical ventilation onset to ventilator-associated pneumonia diagnosis was 4 days. Semiquantitative culture of tracheal aspirates was the most common microbiological technique. Gram-negative bacteria were found in 60% of patients, with a predominance of Haemophilus influenzae and Pseudomonas aeruginosa. Antibiotic therapy complied with adult guidelines. Compared with patients without ventilator-associated pneumonia, those with ventilator-associated pneumonia had significantly longer median durations of mechanical ventilation (15 vs 6 d; p < 0.001) and PICU stay (19 vs 9 d; p < 0.001). By univariate analysis, risk factors for ventilator-associated pneumonia were younger age, reintubation, acute respiratory distress syndrome, and continuous enteral feeding. Among the 30 patients with ventilator-associated pneumonia, 17 met adult ventilator-associated event's criteria (sensitivity, 56%). CONCLUSIONS: Ventilator-associated pneumonia is associated with longer times on mechanical ventilation and in the PICU. Using the ventilator-associated event criteria is of interest to rapidly screen for ventilator-associated pneumonia in children. However, sensitivity must be improved by adapting these criteria to children.

Creating a High-Frequency Electronic Database in the PICU: The Perpetual Patient.

OBJECTIVE: Our objective was to construct a prospective high-quality and high-frequency database combining patient therapeutics and clinical variables in real time, automatically fed by the information system and network architecture available through fully electronic charting in our PICU. The purpose of this article is to describe the data acquisition process from bedside to the research electronic database. DESIGN: Descriptive report and analysis of a prospective database. SETTING: A 24-bed PICU, medical ICU, surgical ICU, and cardiac ICU in a tertiary care free-standing maternal child health center in Canada. PATIENTS: All patients less than 18 years old were included at admission to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between May 21, 2015, and December 31, 2016, 1,386 consecutive PICU stays from 1,194 patients were recorded in the database. Data were prospectively collected from admission to discharge, every 5 seconds from monitors and every 30 seconds from mechanical ventilators and infusion pumps. These data were linked to the patient's electronic medical record. The database total volume was 241 GB. The patients' median age was 2.0 years (interquartile range, 0.0-9.0). Data were available for all mechanically ventilated patients (n = 511; recorded duration, 77,678 hr), and respiratory failure was the most frequent reason for admission (n = 360). The complete pharmacologic profile was synched to database for all PICU stays. Following this implementation, a validation phase is in process and several research projects are ongoing using this high-fidelity database. CONCLUSIONS: Using the existing bedside information system and network architecture of our PICU, we implemented an ongoing high-fidelity prospectively collected electronic database, preventing the continuous loss of scientific information. This offers the opportunity to develop research on clinical decision support systems and computational models of cardiorespiratory physiology for example.

Noninvasive Estimation of Arterial CO2 From End-Tidal CO2 in Mechanically Ventilated Children: The GRAeDIENT Pilot Study.

OBJECTIVES: The aim of our pilot study was to develop a model to better predict Paco2 in mechanically ventilated children using noninvasive parameters including volumetric capnography. DESIGN: Prospective clinical pilot study. SETTING: Level III PICU. PATIENTS: Sixty-five mechanically ventilated children. INTERVENTIONS: None. MATERIALS AND METHODS: We conducted a prospective clinical pilot study that included all children admitted to the PICU (< 18 yr; weight, > 3 kg; mechanically ventilated, > 6 hr; with an arterial line). A predictive model for PaCO2 was developed using linear multivariable regression. Among the data collected in PICU patients, candidate predictors of PaCO2 were defined by a panel of experts and included end-tidal partial pressure of carbon dioxide, ventilation parameters, and data resulting from the analysis of volumetric capnogram recorded 5 minutes before an arterial blood gas. Children with tidal volume less than 30 mL were excluded because of technical limits. RESULTS: A total of 65 children (43 boys, 65%) (65 [21-150] mo old) were analyzed. By linear multivariable regression, the best model included the mean airway pressure, end-tidal partial pressure of carbon dioxide, FIO2, and the capnographic index with an R equal to 0.90, p value less than 0.001. After correction, 95% (n = 62) of children had an estimated PaCO2 at ± 5 mm Hg. CONCLUSION: Our model developed provides an accurate estimation of the PaCO2 using end-tidal CO2 and noninvasive variables. Studies are needed to validate the equation in PICUs.

Early goal-directed therapy based on endotracheal bioimpedance cardiography: a prospective, randomized controlled study in coronary surgery.

The objective was to compare the impact of an early goal-directed hemodynamic therapy based on cardiac output monitoring (Endotracheal Cardiac Output Monitor, ECOM) with a standard of care on postoperative outcome following coronary surgery. This prospective, controlled, parallel-arm trial randomized 100 elective primary coronary artery bypass grafting patients to a study group (ECOM; n = 50) or a control group (control; n = 50). In the ECOM group, hemodynamic therapy was guided by respiratory stroke volume variation and cardiac index given by the ECOM system. A standard of care was used in the control. Goal-directed therapy was started immediately after induction of anesthesia and continued until arrival in the intensive care unit (ICU). The primary endpoint was the time when patients fulfilled discharge criteria from hospital (possible hospital discharge). Secondary endpoints were the hospital discharge, the time to reach extubation, the length of stay in ICU, the number of major adverse cardiac events, and in-hospital mortality. Patients in the ECOM group received more often fluid loading and dobutamine. The time to reach extubation was reduced in the ECOM group: 510 min [360-1,110] versus 570 min [320-1,520], P = 0.005. No significant differences were found between both groups for possible hospital discharge [Hazard Ratio = 0.96 (95 % CI 0.64-1.45)] and hospital discharge [Hazard Ratio = 1.20 (95 % CI 0.79-1.81)]. A mini-invasive early goal-directed hemodynamic therapy based on ECOM can reduce the time to reach extubation but fails to significantly reduce the length of stay in hospital and the rate of major cardiac morbidity.

Withholding life support for children with severe neurological impairment: Prevalence and predictive factors prior to admission in the PICU.

BACKGROUND: Our study aimed to evaluate the prevalence and predictive factors of withholding life support for children suffering from severe neurological impairment before admission to the pediatric intensive care unit (PICU). METHOD: Children under 18 years of age with severe neurological impairment, who were hospitalized between January 2006 and December 2016, were included in this retrospective study. They were allocated to a withholding group or a control group, depending on whether life support was withheld or not, before admission to the PICU. RESULTS: Overall, 119 patients were included. At admission to the PICU, the rate of withholding life support was 10 % (n = 12). Predictive factors were: (1) a previous stay in the PICU (n = 11; 92 %, p<0.01, odds ratio [OR]: 14 [2-635], p = 0.001); (2) the need for respiratory support (n = 5; 42 %, p = 0.01, OR: 6 [1-27], p = 0.01); (3) the need for feeding support (n = 10; 83 %, p = 0.01, OR: 10 [2-100], p = 0.001); and (4) a higher functional status score (FSS: 16 [12.5-19] vs. 10 [8-13], p<0.01). CONCLUSION: The withholding of life support for children suffering from severe neurological impairment appeared limited in our pediatric department. The main predictor was at least one admission to the PICU, which raised the question of the pediatrician's role in the decision to withhold life support.

A severe pediatric life-threatening metabolic ketoacidosis.

This case report presents a 9-year-old child without underlying pathology, with a severe life-threatening non-diabetic metabolic ketoacidosis occurring less than 48 h after the onset of fasting and vomiting. The patient was admitted to the pediatric intensive care unit. He received volume expansion and maintenance fluid therapy which allowed a favorable evolution. Because of the unusual rapid onset of intense ketonemia and acidosis, a hereditary metabolic disease was investigated. The association between short fasting period and severe metabolic ketoacidosis has never been described in children outside of the neonatal period. This clinical case emphasizes urgent recognition, rigorous diagnostic and appropriate management in clinical practice.

ROX (Respiratory rate-OXygenation) index to predict early response to high-flow nasal cannula therapy in infants with viral bronchiolitis.

INTRODUCTION: High-flow nasal cannula (HFNC) is commonly used as first step respiratory support in infants with moderate-to-severe acute viral bronchiolitis (AVB). This device, however, fails to effectively manage respiratory distress in about a third of patients, and data are limited on determinants of patient response. The respiratory rate-oxygenation (ROX) index is a relevant tool to predict the risk for HFNC failure in adult patients with lower respiratory tract infections. The primary objective of this study was to assess the relationship between ROX indexes collected before and 1 h after HFNC initiation, and HFNC failure occurring in the following 48 h in infants with AVB. METHOD: This is an ancillary study to the multicenter randomized controlled trial TRAMONTANE 2, that included 286 infants of less than 6 months with moderate-to-severe AVB. Collection of physiological variables at baseline (H0), and 1 h after HFNC (H1), included heart rate (HR), respiratory rate (RR), fraction of inspired oxygen (FiO2), respiratory distress score (modified Wood's Clinical Asthma Score [mWCAS]), and pain and discomfort scale (EDIN). ROX and ROX-HR were calculated as SpO 2 FiO 2 RR $\frac{\left(\frac{{\mathrm{SpO}}_{2}}{{\mathrm{FiO}}_{2}}\right)}{\mathrm{RR}}$ and 100 × ROX HR $100\times \frac{\mathrm{ROX}}{\mathrm{HR}}$ , respectively. Predefined HFNC failure criteria included increase in respiratory distress score or RR, increase in discomfort, and severe apnea episodes. The accuracies of ROX, ROX-HR indexes and clinical variable to predict HFNC failure were assessed using receiver operating curve analysis. We analyzed predictive factors of HFNC failure using multivariate logistic regressions. RESULT: HFNC failure occurred in 111 of 286 (39%) infants, and for 56 (50% of the failure) of them within the first 6 h. The area under the curve of ROX indexes at H0 and H1 were, respectively, 0.56 (95% confidence interval [CI] 0.48-0.63, p = 0.14), 0.56 (95% CI 0.49-0.64, p = 0.09). ROX-HR performances were better but remained poorly discriminant. HFNC failure was associated with higher mWCAS score at H1 (p < 0.01) and lower decrease in EDIN scale during the first hour of HFNC delivery (p = 0.02). In the multivariate analyses, age and mWCAS score were were found to be independent factors associated with HFNC failure at H0. At H1, weight and mWCAS were associated factors. CONCLUSION: In this study, neither ROX index, nor physiological variables usually collected in infants with AVB had early discriminatory capacity to predict HFNC failure.

Severe acute respiratory syndrome coronavirus-2-related and imputable deaths in children: results from the French pediatric national registry.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for an important mortality rate worldwide. We aimed to evaluate the actual imputability of SARS-CoV-2 on the mortality rate associated with SARS-CoV-2-related illnesses in the pediatric intensive care unit (PICU). Secondary objectives were to identify risk factors for death. METHODS: This national multicenter comparative study comprised all patients under 18 years old with positive SARS-CoV-2 polymerase chain reactions (PCRs) [acute corona virus disease 2019 (COVID-19) or incidental SARS-CoV-2 infection] and/or pediatric inflammatory multisystem syndrome (PIMS) recorded in the French PICU registry (PICURe) between September 1, 2021, and August 31, 2022. Included patients were classified and compared according to their living status at the end of their PICU stay. Deceased patients were evaluated by four experts in the field of pediatric infectiology and/or pediatric intensive care. The imputability of SARS-CoV-2 as the cause of death was classified into four categories: certain, very probable, possible, or unlikely, and was defined by any of the first three categories. RESULTS: There were 948 patients included of which 43 died (4.5%). From this, 26 deaths (67%) could be attributed to SARS-CoV-2 infection, with an overall mortality rate of 2.8%. The imputability of death to SARS-CoV-2 was considered certain in only one case (0.1%). Deceased patients suffered more often from comorbidities, especially heart disease, neurological disorders, hematological disease, cancer, and obesity. None of the deceased patients were admitted for pediatric inflammatory multisystem syndrome (PIMS). Mortality risk factors were male gender, cardiac comorbidities, cancer, and acute respiratory distress syndrome. CONCLUSIONS: SARS-CoV-2 mortality in the French pediatric population was low. Even though the imputability of SARS-CoV-2 on mortality was considered in almost two-thirds of cases, this imputability was considered certain in only one case.

Intravenous maintenance fluid therapy in acutely and critically ill children: state of the evidence.

Intravenous maintenance fluid therapy (IV-MFT) is one of the most prescribed, yet one of the least studied, interventions in paediatric acute and critical care settings. IV-MFT is not typically treated in the same way as drugs with specific indications, contraindications, compositions, and associated adverse effects. In the last decade, societies in both paediatric and adult medicine have issued evidence-based practice guidelines for the use of intravenous fluids in clinical practice. The main objective of this Viewpoint is to summarise and compare the rationales on which these international expert guidelines were based and how these recommendations affect IV-MFT practices in paediatric acute and critical care. Although these guidelines recommend the use of isotonic fluids as a standard in IV-MFT, some discrepancies and uncertainties remain regarding the systematic use of balanced fluids, glucose and electrolyte requirements, and appropriate fluid volume. IV-MFT should be considered in the same way as any other prescription drug and none of the components of IV-MFT prescription should be overlooked (ie, choice of drug, dosing rate, duration of treatment, and de-escalation). Furthermore, most evidence that was used to inform the guidelines comes from high-income countries. Although some principles of IV-MFT are universal, the direct relevance to and feasibility of implementing the guidelines in low-income and middle-income countries is uncertain.

Central role of the ramAR locus in the multidrug resistance in ESBL-Enterobacterales.

The aim of this study was to evaluate the proportion of resistance to a temocillin, tigecycline, ciprofloxacin, and chloramphenicol phenotype called t2c2 that resulted from mutations within the ramAR locus among extended-spectrum ß-lactamases-Enterobacterales (ESBL-E) isolated in three intensive care units for 3 years in a French university hospital. Two parallel approaches were performed on all 443 ESBL-E included: (i) the minimal inhibitory concentrations of temocillin, tigecycline, ciprofloxacin, and chloramphenicol were determined and (ii) the genomes obtained from the Illumina sequencing platform were analyzed to determine multilocus sequence types, resistomes, and diversity of several tetR-associated genes including ramAR operon. Among the 443 ESBL-E strains included, isolates of Escherichia coli (n = 194), Klebsiella pneumoniae (n = 122), and Enterobacter cloacae complex (Ecc) (n = 127) were found. Thirty-one ESBL-E strains (7%), 16 K. pneumoniae (13.1%), and 15 Ecc (11.8%) presented the t2c2 phenotype in addition to their ESBL profile, whereas no E. coli presented these resistances. The t2c2 phenotype was invariably reversible by the addition of Phe-Arg-ß-naphthylamide, indicating a role of resistance-nodulation-division pumps in these observations. Mutations associated with the t2c2 phenotype were restricted to RamR, the ramAR intergenic region (IR), and AcrR. Mutations in RamR consisted of C- or N-terminal deletions and amino acid substitutions inside its DNA-binding domain or within key sites of protein-substrate interactions. The ramAR IR showed nucleotide substitutions involved in the RamR DNA-binding domain. This diversity of sequences suggested that RamR and the ramAR IR represent major genetic events for bacterial antimicrobial resistance.IMPORTANCEMorbimortality caused by infectious diseases is very high among patients hospitalized in intensive care units (ICUs). A part of these outcomes can be explained by antibiotic resistance, which delays the appropriate therapy. The transferable antibiotic resistance gene is a well-known mechanism to explain the high rate of multidrug resistance (MDR) bacteria in ICUs. This study describes the prevalence of chromosomal mutations, which led to additional antibiotic resistance among MDR bacteria. More than 12% of Klebsiella pneumoniae and Enterobacter cloacae complex strains presented mutations within the ramAR locus associated with a dysregulation of an efflux pump called AcrAB-TolC and a porin: OmpF. These dysregulations led to an increase in antibiotic output notably tigecycline, ciprofloxacin, and chloramphenicol associated with a decrease of input for beta-lactam, especially temocillin. Mutations within transcriptional regulators such as ramAR locus played a major role in antibiotic resistance dissemination and need to be further explored.

Post traumatic cerebral sinovenous thrombosis in children: A retrospective and multicenter study.

CONTEXT: Cerebral sinovenous thrombosis (CSVT) is a rare but life-threatening condition in the pediatric population and there is no pediatric guidelines regarding anticoagulation for post traumatic CSVT. OBJECTIVE: This study aims to describe a cohort of children with post traumatic CSVT and the use of anticoagulant therapy in this population. METHODS: A multicenter retrospective study. Patients admitted with post traumatic CSVT in the six participating Pediatric Intensive Care Unit were included. RESULTS: Overall, 29 patients (median age 8.2 years [IQR 4.8-14.6], n = 22 (76%) males) were included in the study (Table 1). CSVT was observed within the first 24 h after admission for a half of the patients (n = 14, 50%). Anticoagulation was initiated in 18 patients (62%). No patient received thrombolytic therapy or endovascular treatment. The presence of epidural hematoma was associated with the absence of anticoagulation (n = 0 versus n = 10, p = 0.003). One patient (3%) died of extracranial injury (not related with adverse event of anticoagulation) and in survivors, median Pediatric Overall Performance Category Outcome (POPC) score at discharge from PICU was 2 [IQR 2-4] (i.e., mild disability). Regarding the outcomes of patients, we found no association according to the anticoagulation status (p = 1). Overall, 23 patients (79%) had a follow-up cerebral imaging with a median delay of 42 days [IQR 6-63] after admission. CSVT was still seen in 9 patients (31%). We found no difference regarding the persistence of CSVT between patients according to the anticoagulation status (p = 0.36). The median duration of anticoagulant treatment was 58 days [IQR 44-91] and one patient (3%) experienced adverse event related to anticoagulation. CONCLUSION: There were minimal adverse events in patients with post traumatic CSVT treated with therapeutic anticoagulation. However, the effect of anticoagulation on outcomes needs to be confirmed in further studies.

Evaluation of the SIMULRESP: A simulation software of child and teenager cardiorespiratory physiology.

BACKGROUND: Mathematical models based on the physiology when programmed as a software can be used to teach cardiorespiratory physiology and to forecast the effect of various ventilatory support strategies. We developed a cardiorespiratory simulator for children called "SimulResp." The purpose of this study was to evaluate the quality of SimulResp. METHODS: SimulResp quality was evaluated on accuracy, robustness, repeatability, and reproducibility. Blood gas values (pH, PaCO2 , PaO2,  and SaO2 ) were simulated for several subjects with different characteristics and in different situations and compared to expected values available as reference. The correlation between reference and simulated data was evaluated by the coefficient of determination and Intraclass correlation coefficient. The agreement was evaluated with the Bland & Altman analysis. RESULTS: SimulResp produced healthy child physiological values within normal range (pH 7.40 ± 0.5; PaCO2 40 ± 5 mmHg; PaO2 90 ± 10 mmHg; SaO2 97 ± 3%) starting from a weight of 25-35 kg, regardless of ventilator support. SimulResp failed to simulate accurate values for subjects under 25 kg and/or affected with pulmonary disease and mechanically ventilated. Based on the repeatability was considered as excellent and the reproducibility as mild to good. SimulResp's prediction remains stable within time. CONCLUSIONS: The cardiorespiratory simulator SimulResp requires further development before future integration into a clinical decision support system.

ESPNIC clinical practice guidelines: intravenous maintenance fluid therapy in acute and critically ill children- a systematic review and meta-analysis.

PURPOSE: Intravenous maintenance fluid therapy (IV-MFT) prescribing in acute and critically ill children is very variable among pediatric health care professionals. In order to provide up to date IV-MFT guidelines, the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) undertook a systematic review to answer the following five main questions about IV-MFT: (i) the indications for use (ii) the role of isotonic fluid (iii) the role of balanced solutions (iv) IV fluid composition (calcium, magnesium, potassium, glucose and micronutrients) and v) and the optimal amount of fluid. METHODS: A multidisciplinary expert group within ESPNIC conducted this systematic review using the Scottish Intercollegiate Guidelines Network (SIGN) grading method. Five databases were searched for studies that answered these questions, in acute and critically children (from 37 weeks gestational age to 18 years), published until November 2020. The quality of evidence and risk of bias were assessed, and meta-analyses were undertaken when appropriate. A series of recommendations was derived and voted on by the expert group to achieve consensus through two voting rounds. RESULTS: 56 papers met the inclusion criteria, and 16 recommendations were produced. Outcome reporting was inconsistent among studies. Recommendations generated were based on a heterogeneous level of evidence, but consensus within the expert group was high. "Strong consensus" was reached for 11/16 (69%) and "consensus" for 5/16 (31%) of the recommendations. CONCLUSIONS: Key recommendations are to use isotonic balanced solutions providing glucose to restrict IV-MFT infusion volumes in most hospitalized children and to regularly monitor plasma electrolyte levels, serum glucose and fluid balance.