Compliance with antibiotic therapy guidelines in french paediatric intensive care units: a multicentre observational study.

BACKGROUND: Bacterial infections (BIs) are widespread in ICUs. The aims of this study were to assess compliance with antibiotic recommendations and factors associated with non-compliance. METHODS: We conducted an observational study in eight French Paediatric and Neonatal ICUs with an antimicrobial stewardship programme (ASP) organised once a week for the most part. All children receiving antibiotics for a suspected or proven BI were evaluated. Newborns < 72 h old, neonates < 37 weeks, age ≥ 18 years and children under surgical antimicrobial prophylaxis were excluded. RESULTS: 139 suspected (or proven) BI episodes in 134 children were prospectively included during six separate time-periods over one year. The final diagnosis was 26.6% with no BI, 40.3% presumed (i.e., not documented) BI and 35.3% documented BI. Non-compliance with antibiotic recommendations occurred in 51.1%. The main reasons for non-compliance were inappropriate choice of antimicrobials (27.3%), duration of one or more antimicrobials (26.3%) and length of antibiotic therapy (18.0%). In multivariate analyses, the main independent risk factors for non-compliance were prescribing ≥ 2 antibiotics (OR 4.06, 95%CI 1.69-9.74, p = 0.0017), duration of broad-spectrum antibiotic therapy ≥ 4 days (OR 2.59, 95%CI 1.16-5.78, p = 0.0199), neurologic compromise at ICU admission (OR 3.41, 95%CI 1.04-11.20, p = 0.0431), suspected catheter-related bacteraemia (ORs 3.70 and 5.42, 95%CIs 1.32 to 15.07, p < 0.02), a BI site classified as "other" (ORs 3.29 and 15.88, 95%CIs 1.16 to 104.76, p < 0.03), sepsis with ≥ 2 organ dysfunctions (OR 4.21, 95%CI 1.42-12.55, p = 0.0098), late-onset ventilator-associated pneumonia (OR 6.30, 95%CI 1.15-34.44, p = 0.0338) and ≥ 1 risk factor for extended-spectrum ß-lactamase-producing Enterobacteriaceae (OR 2.56, 95%CI 1.07-6.14, p = 0.0353). Main independent factors for compliance were using antibiotic therapy protocols (OR 0.42, 95%CI 0.19-0.92, p = 0.0313), respiratory failure at ICU admission (OR 0.36, 95%CI 0.14-0.90, p = 0.0281) and aspiration pneumonia (OR 0.37, 95%CI 0.14-0.99, p = 0.0486). CONCLUSIONS: Half of antibiotic prescriptions remain non-compliant with guidelines. Intensivists should reassess on a day-to-day basis the benefit of using several antimicrobials or any broad-spectrum antibiotics and stop antibiotics that are no longer indicated. Developing consensus about treating specific illnesses and using department protocols seem necessary to reduce non-compliance. A daily ASP could also improve compliance in these situations. TRIAL REGISTRATION: ClinicalTrials.gov: number NCT04642560. The date of first trial registration was 24/11/2020.

[Paediatric Life Support]. / Lebensrettende Maßnahmen bei Kindern (Paediatric Life Support, PLS): Leitlinien des European Resuscitation Council 2021.

The European Resuscitation Council (ERC) Paediatric Life Support (PLS) guidelines are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations of the International Liaison Committee on Resuscitation (ILCOR). This section provides guidelines on the management of critically ill or injured infants, children and adolescents before, during and after respiratory/cardiac arrest.

Outcome of children with Shiga toxin-associated haemolytic uraemic syndrome treated with eculizumab: a matched cohort study.

BACKGROUND: Treatment with eculizumab in Shiga toxin-associated haemolytic and uraemic syndrome (STEC-HUS) remains controversial despite its increasing utilization. The aim of our study was to evaluate the outcomes of children treated with eculizumab for STEC-HUS in a single-centre matched cohort study. METHODS: Data were retrospectively collected from medical records of children diagnosed with STEC-HUS. The outcomes of patients treated with eculizumab for STEC-HUS were compared with those of a control group of untreated patients matched for age, sex and severity of acute kidney injury with a 1:2 matching scheme. RESULTS: Eighteen children (median age 40.6 months) with STEC-HUS treated with eculizumab were compared with 36 matched control patients (median age 36.4 months) who did not receive eculizumab. All patients survived in the two groups. Within 1 month of HUS onset, the evolution of haematological and renal parameters did not differ between the two groups. At 12 months of follow-up, renal outcome was not significantly different between the two groups. At the last follow-up, the prevalence of decreased glomerular filtration rate in the eculizumab group (27%) was not statistically different from that in controls (38%), as was the prevalence of proteinuria and high blood pressure. Children who received eculizumab more often had extrarenal sequelae during follow-up. Eculizumab treatment appeared to be safe in children with STEC-HUS. CONCLUSION: The benefit of eculizumab on renal and extrarenal outcomes in STEC-HUS could not be established based on our findings. However, efficacy and safety are not best assessed by the observational design and small sample size of our study. Randomized controlled trials are thus required to determine the efficacy of eculizumab in this indication.

SHADOWS: a spectro-gonio radiometer for bidirectional reflectance studies of dark meteorites and terrestrial analogs: design, calibrations, and performances on challenging surfaces.

We have developed a new spectro-gonio radiometer, SHADOWS, to study in the laboratory the bidirectional reflectance distribution function of dark and precious samples. The instrument operates over a wide spectral range from the visible to the near-infrared (350-5000 nm) and is installed in a cold room to operate at a temperature as low as -20°C. The high flux monochromatic beam is focused on the sample, resulting in an illumination spot of about 5.2 mm in diameter. The reflected light is measured by two detectors with high sensitivity (down to 0.005% in reflectance) and absolute accuracy of 1%. The illumination and observations angles, including azimuth, can be varied over wide ranges. This paper presents the scientific and technical constraints of the spectro-gonio radiometer, its design and additional capabilities, as well as the performances and limitations of the instrument.

[The emotions of caregivers in neonatal and paediatric intensive care]. / Les émotions des soignants en réanimation néonatale et pédiatrique.

When treating a child hospitalised in a neonatal or paediatric unit, the emotions of the child's parents are of particular concern for the caregivers. The emotional experience of the nursing teams, however, is rarely taken into account, despite it having an impact on the quality of the support. Group discussion and individual reflection around professionals' emotions is essential.

[The role of the psychologist with a death in neonatal and paediatric intensive care]. / Le rôle du psychologue lors d'un dêcès en réanimation néonatale et pédiatrique.

The psychologist within a neonatal and paediatric intensive care unit intervenes in accordance with the condition of the patient and those at whom their services are aimed. The psychological practice in this particular context comprises certain specificities. As the child nears the end of life the psychologist must find his place within the unit and adapt his care to the needs expressed.

Pediatric intensive care unit follow-up: Thinking before acting.

OBJECTIVE: It is now well established that post-intensive care syndrome is frequent in critically ill children after discharge from the pediatric intensive care unit (PICU). Nevertheless, post-intensive care follow-up is highly heterogenous worldwide and is not considered routine care in many countries. The purpose of this viewpoint was to report the reflections of the French PICU society working group on how to implement post-PICU follow-up. METHODS: A working group was set up within the Groupe Francophone de Reanimation et d'Urgences Pédiatriques (GFRUP) to provide conceptual and practical guidance for developing post-PICU follow-up. The working group included psychologists, PICU physicians, physiotherapists, and nurses, from different French PICUs. Five virtual meetings have been held. RESULTS: First, we described in this work the objectives of the follow-up program and the population to be targeted. We also provided a framework to implement post-PICU follow-up in clinical practice. Finally, we detailed the potential obstacles and challenges to consider. CONCLUSION: Although implementing a post-PICU follow-up program is a challenge, the benefits could be significant for both patient and relatives, as well as for the health care professionals involved.

Neuroprotective effects of dexmedetomidine against glutamate agonist-induced neuronal cell death are related to increased astrocyte brain-derived neurotrophic factor expression.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a prominent role in neuroprotection against perinatal brain injury. Dexmedetomidine, a selective agonist of α2-adrenergic receptors, also provides neuroprotection against glutamate-induced damage. Because adrenergic receptor agonists can modulate BDNF expression, our goal was to examine whether dexmedetomidine's neuroprotective effects are mediated by BDNF modulation in mouse perinatal brain injury. METHODS: The protective effects against glutamate-induced injury of BDNF and dexmedetomidine alone or in combination with either a neutralizing BDNF antibody or an inhibitor of the extracellular signal-regulated kinase pathway (PD098059) were compared in perinatal ibotenate-induced cortical lesions (n = 10-20 pups/groups) and in mouse neuronal cultures (300 µM of ibotenate for 6 h). The effect of dexmedetomidine on BDNF expression was examined in vivo and in vitro with cortical neuronal and astrocyte isolated cultures. RESULTS: Both BDNF and dexmedetomidine produced a significant neuroprotective effect in vivo and in vitro. Dexmedetomidine enhanced Bdnf4 and Bdnf5 transcription and BDNF protein cortical expression in vivo. Dexmedetomidine also enhanced Bdnf4 and Bdnf5 transcription and increased BDNF media concentration in isolated astrocyte cultures but not in neuronal cultures. Dexmedetomidine's protective effect was inhibited with BDNF antibody (mean lesion size ± SD: 577 ± 148 µm vs. 1028 ± 213 µm, n = 14-20, P < 0.001) and PD098059 in vivo but not in isolated neuron cultures. Finally, PD098059 inhibited the increased release of BDNF induced by dexmedetomidine in astrocyte cultures. CONCLUSION: These results suggest that dexmedetomidine increased astrocyte expression of BDNF through an extracellular signal-regulated kinase-dependent pathway, inducing subsequent neuroprotective effects.

Diagnostic value of polymerase chain reaction analysis of skin biopsies in purpura fulminans.

Even though prompt diagnosis and treatment of purpura fulminans (PF) is essential to reduce mortality, early administration of antibiotics may preclude identification of the causative agent by standard bacterial cultures and thus render definitive diagnosis impossible. Here we present a case of an infant with PF and negative bacterial cultures for whom polymerase chain reaction (PCR) analysis of a cutaneous biopsy specimen obtained 4 days after initiation of antibiotics identified the genomic sequence of Neisseria meningitidis genogroup C. When bacterial cultures fail to provide useful information, PCR of skin biopsy specimens can be a valuable diagnostic tool in PF.

Pulmonary hypertension among preterm infants born at 22 through 32 weeks gestation in France: Prevalence, survival, morbidity and management in the EPIPAGE-2 cohort study.

OBJECTIVE: To determine the prevalence, short-term prognosis and pharmacologic management of pulmonary hypertension (PH) among very preterm infants born before 32 weeks gestation (WG). STUDY DESIGN: In the EPIPAGE-2 French national prospective population-based cohort of preterm infants born in 2011, those presenting with PH were identified and prevalence was estimated using multiple imputation. The primary outcome was survival without severe morbidity at discharge and was compared between infants with or without PH after adjusting for confounders, using generalized estimating equations models. Subgroup analysis was performed according to gestational age (GA) groups. RESULTS: Among 3383 eligible infants, 3222 were analyzed. The prevalence of PH was 6.0 % (95 % CI, 5.2-6.9), 14.5 % in infants born at 22-27+6 WG vs 2.7 % in infants born at 28-31+6 WG (P < .001). The primary outcome (survival without severe morbidity at discharge) occurred in 30.2 % of infants with PH vs 80.2 % of infants without PH (P < .001). Adjusted incidence rate ratios for survival without severe morbidity among infants with PH were 0.42 (0.32-0.57) and 0.52 (0.39-0.69) in infants born at 22-27+6 weeks gestation and those born at 28-31+6 weeks, respectively. Among infants with PH, 92.2 % (95 % CI, 87.7-95.2) received sedation and/or analgesia, 63.5 % (95 % CI, 56.6-69.9) received inhaled NO and 57.6 % (95 % CI, 50.9-64.0) received hemodynamic treatments. CONCLUSION: In this population-based cohort of very preterm infants, the prevalence of PH was 6 %. PH was associated with a significant decrease of survival without severe morbidity in this population.

Fluid bolus therapy in pediatric sepsis: a narrative review.

Leading cause of death in children under five, pediatric sepsis remains a significant global health threat. The 2020 Surviving Sepsis Campaign guidelines revised the management of septic shock and sepsis-associated organ dysfunction in children. In addition to empiric broad-spectrum antibiotics, fluid bolus therapy is one of the cornerstones of management, due to theoretical improvement of cardiac output, oxygen delivery and organ perfusion. Despite a very low level of evidence, the possible benefit of balanced crystalloids in sepsis resuscitation has led to discussion on their position as the ideal fluid. However, the latest adult data are not consistent with this, and the debate is still ongoing in pediatrics. We provide here the current state of knowledge on fluid bolus therapy in pediatric sepsis with emphasis on balanced crystalloids.

In-hospital Outcomes and Early Hemodynamic Management According to Echocardiography Use in Hypotensive Preterm Infants: A National Propensity-Matched Cohort Study.

Background: Hypotension is a common condition during the first postnatal days of very preterm infants and has been associated with an increased risk of adverse outcomes but its management remains controversial. There is a consensus to promote the use of neonatologist-performed echocardiography (NPE) in hypotensive very preterm infants, although no clinical trial ever assessed this practice. Methods: We conducted a retrospective analysis of prospectively collected data from the French national EPIPAGE-2 cohort to evaluate the association of NPE with survival, severe morbidity, and therapeutic management in very preterm infants with early hypotension. Reasons for administering antihypotensive treatments were also analyzed. We included infants born before 30 weeks of gestation with hypotension within 72 h of birth. Infants managed with (NPE group) or without (no-NPE group) NPE use were compared after matching on gestational age and a propensity score, reflecting each patient's probability of having an NPE based on his/her baseline covariates. This matching procedure intended to control for the indication bias of NPE. Results: Among 966 eligible infants, 809 were included (NPE group, n = 320; no-NPE group, n = 489), and 229 from each group could be matched. The NPE group did not differ significantly from the no-NPE group for survival (OR 1.01, 95% CI 0.64 to 1.60; p = 0.95) or survival without severe morbidity at discharge (OR 0.92, 95% CI 0.63 to 1.34; p = 0.66), but received more antihypotensive treatments [144/229 (62.9%) vs. 99/229 (43.0%), p < 0.001]. Isolated hypotension was the main reason for treatment in both groups. Among treated infants, volume expansion was administered at equal rates to the NPE and no-NPE groups [118/144 (82.1%) vs. 79/99 (80.1%), p = 0.67], but the NPE group received inotropic drugs more often [77/144 (53.7%) vs. 37/99 (37.8%), p = 0.023]. Conclusion: NPE use in hypotensive preterm infants was not associated with in-hospital outcomes and had little influence on the nature of and reasons for antihypotensive treatments. These results suggest the need to optimize NPE use.

Simulation-based summative assessment in healthcare: an overview of key principles for practice.

BACKGROUND: Healthcare curricula need summative assessments relevant to and representative of clinical situations to best select and train learners. Simulation provides multiple benefits with a growing literature base proving its utility for training in a formative context. Advancing to the next step, "the use of simulation for summative assessment" requires rigorous and evidence-based development because any summative assessment is high stakes for participants, trainers, and programs. The first step of this process is to identify the baseline from which we can start. METHODS: First, using a modified nominal group technique, a task force of 34 panelists defined topics to clarify the why, how, what, when, and who for using simulation-based summative assessment (SBSA). Second, each topic was explored by a group of panelists based on state-of-the-art literature reviews technique with a snowball method to identify further references. Our goal was to identify current knowledge and potential recommendations for future directions. Results were cross-checked among groups and reviewed by an independent expert committee. RESULTS: Seven topics were selected by the task force: "What can be assessed in simulation?", "Assessment tools for SBSA", "Consequences of undergoing the SBSA process", "Scenarios for SBSA", "Debriefing, video, and research for SBSA", "Trainers for SBSA", and "Implementation of SBSA in healthcare". Together, these seven explorations provide an overview of what is known and can be done with relative certainty, and what is unknown and probably needs further investigation. Based on this work, we highlighted the trustworthiness of different summative assessment-related conclusions, the remaining important problems and questions, and their consequences for participants and institutions of how SBSA is conducted. CONCLUSION: Our results identified among the seven topics one area with robust evidence in the literature ("What can be assessed in simulation?"), three areas with evidence that require guidance by expert opinion ("Assessment tools for SBSA", "Scenarios for SBSA", "Implementation of SBSA in healthcare"), and three areas with weak or emerging evidence ("Consequences of undergoing the SBSA process", "Debriefing for SBSA", "Trainers for SBSA"). Using SBSA holds much promise, with increasing demand for this application. Due to the important stakes involved, it must be rigorously conducted and supervised. Guidelines for good practice should be formalized to help with conduct and implementation. We believe this baseline can direct future investigation and the development of guidelines.

Severe transient ADAMTS13 deficiency in pneumococcal-associated hemolytic uremic syndrome.

Thrombotic microangiopathies comprise different entities, including hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and several other conditions. TTP is characterized by hemolytic anemia, thrombocytopenia, and multiorgan failure. TTP is the result of severe von Willebrand factor multimer cleaving protease (ADAMTS13) deficiency that is either inherited or the result of acquired autoantibodies. We report a critically ill 2-year-old girl with invasive pneumococcal disease associated HUS (p-HUS) whose condition was complicated by severe ADAMTS13 deficiency, without detectable inhibitor, in a context of multiple organ failure. The patient recovered with supportive treatment, and ADAMTS13 activity normalized without plasmatherapy. Severe ADAMTS13 deficiency appears to be a manifestation of transient endothelial cell injury in the context of severe sepsis, including invasive p-HUS. The choice of appropriate therapy should not be based on this finding.

Successful treatment with rituximab for acute refractory thrombotic thrombocytopenic purpura related to acquired ADAMTS13 deficiency: a pediatric report and literature review.

OBJECTIVE: To report the case of a child with severe autoimmune thrombotic thrombocytopenic purpura (TTP) resistant to plasma exchange and steroids who was successfully treated with rituximab. DESIGN: Case report and review of the literature on pediatric acquired TTP. The report was approved by an independent local ethics committee. SETTING: Pediatric intensive care unit in a tertiary care children's hospital. PATIENT: A 10-yr-old boy was referred to the emergency unit with fever, vomiting, confusion, hemolytic anemia, thrombocytopenia, and mild acute renal failure. An atypical hemolytic uremic syndrome was suspected, and plasma exchange was started urgently. The patient was refractory to plasma therapy and presented critical complications. After a diagnosis of acquired TTP attributable to anti-ADAMTS13 autoantibodies had been made, he was treated with rituximab, which resulted in a stable clinical remission. INTERVENTIONS: Rituximab therapy. MEASUREMENTS AND MAIN RESULTS: Clinical remission. CONCLUSIONS: TTP is a rare but life-threatening condition in children that is characterized by hemolytic anemia, thrombocytopenia, and signs of ischemic organ dysfunction. If renal involvement is present, TTP may be misdiagnosed as hemolytic uremic syndrome, but reliable screening for ADAMTS13 activity and anti-ADAMTS autoantibodies allow us to distinguish the two entities and provide adequate therapy.

Patent ductus arteriosus in the preterm infant: a survey of clinical practices in French neonatal intensive care units.

Patent ductus arteriosus (PDA) is one of the most common problems in the care of premature infants, especially the extremely premature. There is no real consensus regarding the diagnostic criteria or treatment of a hemodynamically significant PDA. Its diagnosis, assessment, and treatment still remain challenges. Therefore, we investigated clinical practices in French tertiary neonatology centers regarding the management of PDA to compare their similarities and differences. We sent a questionnaire by email to the PDA specialist in every French tertiary neonatal intensive care unit. It contained 27 items regarding the unit's structure, method of diagnosing PDA, and treatment choices. The completed questionnaire were returned via email and analyzed blindly. The questionnaire response rate was 87.5%, which allowed us to draw some conclusions regarding French clinical practices in the care of neonates with PDA. Although the diagnostic criteria are quite similar, the therapeutic practices are rather different across neonatal care units. We highlight the great variability in French clinical practices when it comes to treating PDA and underscore the necessity for harmonization of these practices, which could be achieved using multicenter, randomized studies to identify the advantages of one approach compared with another.

A Rodent Model of Mild Neonatal Hypoxic Ischemic Encephalopathy.

In the brain of full-term newborns, Hypoxic Ischemic Encephalopathy (HIE), a consequence of severe hypoxia and ischemia due to low cardiac output, is frequently observed and results in cerebral injuries with dramatic consequences for life. To investigate the physiopathology of HIE, several animal models have been developed, but none closely replicate human cases, mostly because they are based on a single carotid ligation protocol. In the present study we aimed to develop a novel and more accurate HIE model in juvenile (post-natal days (PND) 14-16) rats. For this, we induced a 9 min hypoxic cardiac arrest (CA) by stopping mechanical ventilation of intubated, ventilated and curarized rats followed by a cardiopulmonary resuscitation. To evaluate the consequences of the CA we performed radiological (cerebral MRI), behavioral (Open Field, Elevated Plus Maze, Fear Conditioning), and histological (Cresyl Violet and Fluoro-Jade B) testing on treated animals. We found that rats in the CA group developed an anxiolytic-like behavioral profile in adulthood without any locomotor impairment, nor memory deficits. However, MRI investigation performed early after CA failed to reveal any change in apparent diffusion coefficient (ADC) in brain tissue (including the hippocampus, striatum, and thalamus), suggesting no massive anatomical lesion had occurred. In contrast, signs of neurodegeneration were found in the Dentate Gyrus and the CA1 region of the hippocampus at day 1 post-CA, suggesting that the anxiolytic-like phenotype observed in adulthood could be related to an abnormal degeneration of this brain region beginning immediately after CA. Thus, our model, despite not representing a severe condition of HIE, nonetheless constitutes a potential model for studying mild, yet persistent and region-specific cerebral injury resulting from an acute oxygen deprivation.

Brain MRI after therapeutic hypothermia in asphyxiated newborns: Predictive value at one year of imaging features.

PURPOSE: To compare early brain MRI using a composite imaging score and outcome at one year in asphyxiated newborns treated by hypothermia. METHODS: This retrospective study included for two years consecutive asphyxiated term newborns treated by hypothermia for hypoxic-ischemic encephalopathy, and who had brain MRI before day 8. Therapeutic hypothermia was initiated within the first 6 h of life and continued for 72 h. Imaging protocol included T1 and T2 sequences, diffusion-weighted imaging (DWI), evaluated with a specific composite score, and spectroscopy. Clinical evaluation was performed at one year of age, outcome was classified as favorable/unfavorable. The primary endpoint was the correlation between our MRI score and outcome with the definition of a threshold. The secondary endpoints were to find the most relevant criteria within the score and to evaluate objective signal measurements to support subjective criteria. RESULTS: Among the 33 included patients, 9 died during the first days of life, 20 had a favorable outcome, 4 an unfavorable one. MRI score was correlated to a poor clinical outcome (p < 0.001). Most of the criteria within the score and spectroscopy results were relevant (p < 0.05). Cerebral edema was objectively assessed by the signal intensity ratio of white matter compared to cerebrospinal fluid (CSF) on T2-weighted images (p < 0.001). CONCLUSION: MRI score was predictive of neurodevelopmental outcome at one year. The most relevant criteria within the score were DWI abnormalities in basal ganglia and thalami and loss of white-cortical grey matter differentiation. Signal intensity ratio between white matter and CSF higher than 0.75 supports the presence of edema.

European Resuscitation Council Guidelines 2021: Paediatric Life Support.

These European Resuscitation Council Paediatric Life Support (PLS) guidelines, are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. This section provides guidelines on the management of critically ill infants and children, before, during and after cardiac arrest.