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.

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.

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.

[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.

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.

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.

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.

Ammonium salts are a reservoir of nitrogen on a cometary nucleus and possibly on some asteroids.

The measured nitrogen-to-carbon ratio in comets is lower than for the Sun, a discrepancy which could be alleviated if there is an unknown reservoir of nitrogen in comets. The nucleus of comet 67P/Churyumov-Gerasimenko exhibits an unidentified broad spectral reflectance feature around 3.2 micrometers, which is ubiquitous across its surface. On the basis of laboratory experiments, we attribute this absorption band to ammonium salts mixed with dust on the surface. The depth of the band indicates that semivolatile ammonium salts are a substantial reservoir of nitrogen in the comet, potentially dominating over refractory organic matter and more volatile species. Similar absorption features appear in the spectra of some asteroids, implying a compositional link between asteroids, comets, and the parent interstellar cloud.

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.

Brief summary of French guidelines for the prevention, diagnosis and treatment of hospital-acquired pneumonia in ICU.

BACKGROUND: The French Society of Anaesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit. The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists. RESULTS: The guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, post-operative and paediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases. CONCLUSIONS: HAP should be prevented by a standardised multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram-negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.

A multicenter randomized controlled trial of a 3-L/kg/min versus 2-L/kg/min high-flow nasal cannula flow rate in young infants with severe viral bronchiolitis (TRAMONTANE 2).

PURPOSE: High-flow nasal cannula (HFNC) therapy is increasingly proposed as first-line respiratory support for infants with acute viral bronchiolitis (AVB). Most teams use 2 L/kg/min, but no study compared different flow rates in this setting. We hypothesized that 3 L/kg/min would be more efficient for the initial management of these patients. METHODS: A randomized controlled trial was performed in 16 pediatric intensive care units (PICUs) to compare these two flow rates in infants up to 6 months old with moderate to severe AVB and treated with HFNC. The primary endpoint was the percentage of failure within 48 h of randomization, using prespecified criteria of worsening respiratory distress and discomfort. RESULTS: From November 2016 to March 2017, 142 infants were allocated to the 2-L/kg/min (2L) flow rate and 144 to the 3-L/kg/min (3L) flow rate. Failure rate was comparable between groups: 38.7% (2L) vs. 38.9% (3L; p = 0.98). Worsening respiratory distress was the most common cause of failure in both groups: 49% (2L) vs. 39% (3L; p = 0.45). In the 3L group, discomfort was more frequent (43% vs. 16%, p = 0.002) and PICU stays were longer (6.4 vs. 5.3 days, p = 0.048). The intubation rates [2.8% (2L) vs. 6.9% (3L), p = 0.17] and durations of invasive [0.2 (2L) vs. 0.5 (3L) days, p = 0.10] and noninvasive [1.4 (2L) vs. 1.6 (3L) days, p = 0.97] ventilation were comparable. No patient had air leak syndrome or died. CONCLUSION: In young infants with AVB supported with HFNC, 3 L/kg/min did not reduce the risk of failure compared with 2 L/kg/min. This clinical trial was recorded on the National Library of Medicine registry (NCT02824744).

Targeted temperature management in the ICU: Guidelines from a French expert panel.

Over the recent period, the use of induced hypothermia has gained an increasing interest for critically ill patients, in particular in brain-injured patients. The term "targeted temperature management" (TTM) has now emerged as the most appropriate when referring to interventions used to reach and maintain a specific level temperature for each individual. TTM may be used to prevent fever, to maintain normothermia, or to lower core temperature. This treatment is widely used in intensive care units, mostly as a primary neuroprotective method. Indications are, however, associated with variable levels of evidence based on inhomogeneous or even contradictory literature. Our aim was to conduct a systematic analysis of the published data in order to provide guidelines. We present herein recommendations for the use of TTM in adult and paediatric critically ill patients developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. These guidelines were conducted by a group of experts from the French Intensive Care Society (Société de réanimation de langue française [SRLF]) and the French Society of Anesthesia and Intensive Care Medicine (Société francaise d'anesthésie réanimation [SFAR]) with the participation of the French Emergency Medicine Association (Société française de médecine d'urgence [SFMU]), the French Group for Pediatric Intensive Care and Emergencies (Groupe francophone de réanimation et urgences pédiatriques [GFRUP]), the French National Association of Neuro-Anesthesiology and Critical Care (Association nationale de neuro-anesthésie réanimation française [ANARLF]), and the French Neurovascular Society (Société française neurovasculaire [SFNV]). Fifteen experts and two coordinators agreed to consider questions concerning TTM and its practical implementation in five clinical situations: cardiac arrest, traumatic brain injury, stroke, other brain injuries, and shock. This resulted in 30 recommendations: 3 recommendations were strong (Grade 1), 13 were weak (Grade 2), and 14 were experts' opinions. After two rounds of rating and various amendments, a strong agreement from voting participants was obtained for all 30 (100%) recommendations, which are exposed in the present article.

Hospital-acquired pneumonia in ICU.

The French Society of Anesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit (ICU). The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists. The guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, postoperative and pediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases. HAP should be prevented by a standardized multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.

Targeted temperature management in the ICU: guidelines from a French expert panel.

Over the recent period, the use of induced hypothermia has gained an increasing interest for critically ill patients, in particular in brain-injured patients. The term "targeted temperature management" (TTM) has now emerged as the most appropriate when referring to interventions used to reach and maintain a specific level temperature for each individual. TTM may be used to prevent fever, to maintain normothermia, or to lower core temperature. This treatment is widely used in intensive care units, mostly as a primary neuroprotective method. Indications are, however, associated with variable levels of evidence based on inhomogeneous or even contradictory literature. Our aim was to conduct a systematic analysis of the published data in order to provide guidelines. We present herein recommendations for the use of TTM in adult and paediatric critically ill patients developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. These guidelines were conducted by a group of experts from the French Intensive Care Society (Société de Réanimation de Langue Française [SRLF]) and the French Society of Anesthesia and Intensive Care Medicine (Société Francaise d'Anesthésie Réanimation [SFAR]) with the participation of the French Emergency Medicine Association (Société Française de Médecine d'Urgence [SFMU]), the French Group for Pediatric Intensive Care and Emergencies (Groupe Francophone de Réanimation et Urgences Pédiatriques [GFRUP]), the French National Association of Neuro-Anesthesiology and Critical Care (Association Nationale de Neuro-Anesthésie Réanimation Française [ANARLF]), and the French Neurovascular Society (Société Française Neurovasculaire [SFNV]). Fifteen experts and two coordinators agreed to consider questions concerning TTM and its practical implementation in five clinical situations: cardiac arrest, traumatic brain injury, stroke, other brain injuries, and shock. This resulted in 30 recommendations: 3 recommendations were strong (Grade 1), 13 were weak (Grade 2), and 14 were experts' opinions. After two rounds of rating and various amendments, a strong agreement from voting participants was obtained for all 30 (100%) recommendations, which are exposed in the present article.