Sevoflurane Sedation with AnaConDa-S Device for a Child Undergoing Extracorporeal Membrane Oxygenation

International audienceBackground: Deep sedation in critically ill children undergoing extracorporeal membrane oxygenation (ECMO) can be challenging. Volatile anesthetics like sevoflurane can be a good alternative for patients hospitalized in pediatric intensive care units, in whom adequate sedation is difficult to obtain.Case description: We report here the first pediatric case of a patient under extracorporeal membrane oxygenation receiving sedation by sevoflurane using the AnaConDa-S device. This 2-year-old girl, suffering from congenital diaphragmatic hernia, was put on extracorporeal membrane oxygenation due to a persistent pulmonary hypertension following metapneumovirus infection. Despite high doses of drugs, neither satisfactory sedation nor analgesia could be reached. Sevoflurane allowed her to be released and we were able to wean her from certain drugs. Her physiological parameters and the indicators of pain and sedation improved.Conclusion: Anesthesia using sevoflurane with the AnaConDa-S device is efficient for children under ECMO.Clinical significance: This is the first pediatric report on anesthesia with sevoflurane under ECMO

Reduced Sufentanil Doses are Effective for Postoperative Analgesia After Ductal Closure in Extremely Premature Infants: A 10 Years Retrospective Cohort Study

International audienceObjectives: The objective of the study was to assess the efficacy of reduced sufentanil doses for postoperative analgesia following surgical ductal closure in extremely premature infants.Methods: This was a retrospective, single-center, cohort study comparing 2 sufentanil dosing regimens used between 2001 and 2010 and included all infants born at <28 weeks of gestation with surgical ductal closure. Sufentanil doses were reduced in 2007 as a standard of care. Time was divided into 3 epochs to distinguish the effects of practice changes over time from the effects of sufentanil dose change: epoch 1 (2001 to 2004), epoch 2 (May 2005 to 2007), and epoch 3 (June 2007 to 2010).Results: A total of 109 of 114 eligible infants were analyzed (mean [±SD], gestational age: 25.1 [±1.1] wk; mean [±SD], birth weight: 756 [±144] g). Median sufentanil doses were significantly higher during epochs 1 and 2 (0.1 to 0.2 µg/kg/h) than during epoch 3 (0.03 to 0.04 µg/kg/h) (P<0.0001). EDIN (Echelle de Douleur et d'Inconfort du Nouveau-né) pain scores were mostly ≤4 throughout the study period and their changes over time were not contemporaneous with the reduction in sufentanil doses; they were lower during epoch 1 versus epochs 2 and 3 (P<0.0001) and comparable between epochs 2 and 3. Midazolam doses and paracetamol use were not higher during epoch 3 as compared with epochs 1 and 2. No difference in opioid-related adverse events was observed between the 3 epochs.Conclusion: Our study supports the use of low continuous intravenous sufentanil doses, consistent with morphine doses currently recommended in this population

Dysplasie acineuse associée à un variant de NKX2.1 chez un nouveau-né à terme

National audienc

Hidden Harlequin syndrome in neonatal and pediatric VA-ECMO

International audienc

Acinar dysplasia in a full-term newborn with a NKX2.1 variant

International audienceAcinar dysplasia (AcDys) is one of the three main diffuse developmental disorders of the lung. The transcription factor NK2 homeobox 1 (NKX2.1) partly controls the synthesis of surfactant proteins by type 2 alveolar epithelial cells (AEC2), and germline mutations are known to be associated with brain-lung thyroid syndrome. We report the case of a full-term neonate who developed refractory respiratory failure with pulmonary hypertension requiring veno-arterial extracorporeal membrane oxygenation (ECMO). Histological examination of the lung biopsy specimen was consistent with the diagnosis of AcDys. Molecular analyses led to the identification of the missense heterozygous variant in NKX2.1 (NM_001079668) c.731A>G p.(Tyr244Cys), which is predicted to be pathogenic. After five weeks, because AcDys is a fatal disorder and the patient’s status worsened, life-sustaining therapies were withdrawn, and she died after a few hours. This study is the first to extend the phenotype of NKX2.1 pathogenic variant, to a fatal form of AcDys

Polymicrogyria with Dysmorphic Neurons in a Patient with SNCA2 Mutation

International audienc

Halogenated volatile anaesthetics for prolonged sedation in pediatric intensive care unit: first experience in two French pediatric intensive care units

International audienceObjective Sedation is necessary for patients to achieve comfort and safety, but prolonged sedation can lead to the need for increased doses, resulting in withdrawal syndrome and delayed extubation. Inhaled anaesthetics (IAs) may cause less withdrawal syndrome while providing similar sedative effects to intravenous agents. This study aims to describe the efficacy of halogenated IAs during prolonged sedation and identify any adverse effects on the PICU. Design This is a retrospective, bicentric cohort study. Setting The study was conducted at two PICUs in university hospitals in Paris between January 2018 and December 2020. Patients The study included 50 children (aged 2.2 years, [0.8-7.2]) who received prolonged sedation (> 72 h) and were sedated with volatile anaesthetics for at least 24 h. Interventions No interventions were performed. Measurements and main results The study found a statistically significant reduction in benzodiazepine dosages (μg/kg/h) (118 [62.5; 200] vs 80.0 [32.5; 120], p < 0.01). Similar results were observed for other hypnotics (ketamine 2.00 [1.00; 2.00] vs 1.50 [1.00; 2.00], p = 0.036, mg/kg/h; clonidine: 0.55 [0.35; 1.27] vs 0.20 [0.12; 0.43], p = 0.036, μg/ kg/h). For opioids (μg/kg/h), no significant reduction in doses was observed 24 h after IA introduction (4 [1.00; 8.00] vs 4.00 [1.00; 6.70], p = 0.7). No major adverse effects were reported, although 26% of patients developed withdrawal syndrome. Conclusions Halogenated IAs appear to be a promising therapy to reduce the dosages of hypnotics and opioids used during prolonged sedations

SP-A restaure l’oligomérisation et la sécrétion de mutants de SFTPA1 et SFTPA2

National audienceIntroductionLa protéine A du surfactant (SP)-A est composée de SP-A1 et SP-A2 (codés respectivement par SFTPA1 et SFTPA2) oligomérisées en hexamères de SP-A1 et SP-A2. Les variants hétérozygotes de SFTPA1 et SFTPA2 sont associés à des fibroses et des adénocarcinomes pulmonaires. Cette étude a pour but d’analyser l’effet des variants de SFTPA1 et SFTPA2 sur la localisation subcellulaire, l’oligomérisation et la sécrétion de SP-A.MéthodesDes cellules HEK293T ont été co-transfectées de façon transitoire avec des vecteurs d’expression des ADNc de SFTPA1 ou SFTPA2 normaux (wt), mutés (m) ou vecteur vide (vv) selon les combinaisons suivantes : [SFTPA1_wt + vv], [SFTPA2_wt + vv], [SFTPA1_m + vv], [SFTPA2_m + vv], [SFTPA1_wt + SFTPA2_wt], [SFTPA1_wt + SFTPA1_m], [SFTPA1_wt + SFTPA2_m], [SFTPA2_wt + SFTPA2_m] ou [SFTPA2_wt + SFTPA1_m]. Plusieurs variants ont été testés. La localisation subcellulaire des protéines exprimées a été analysée par immunofluorescence (IF) après transfection dans des cellules HEK293. Le profil d’oligomérisation et la sécrétion ont été évalués par western blot (WB) des protéines du lysat cellulaire et du surnageant. La spécificité des interactions entre SP-A1 et SP-A2 a été vérifiée par co-immunoprécipitation (co-IP). Pour chaque expérience, des Tags différents ont été introduits dans les protéines recombinantes pour identifier les isoformes en jeu. RésultatsEn IF, les protéines SP-A2_wt sont décelables dans des vésicules de sécrétion alors que le marquage cellulaire associé aux protéines SP-A2_m est diffus dans le cytoplasme sans marquage vésiculaire. Cette observation confirme l’absence de sécrétion de SP-A2_m que nous avions précédemment rapportée. En WB, le profil d’oligomérisation de SP-A2_m est anormal avec la formation de tétramères sans hexamères décelables, et la sécrétion de SP-A2_m est absente. La co-transfection [SFTPA2_wt + SFTPA2_m] conduit à l’augmentation de l’expression de SP-A2_m, à la restauration des hexamères et d’une sécrétion pour deux des trois variants testés. Les mêmes résultats ont été retrouvés avec la co-transfection [SFTPA2_wt + SFTPA1_m]. La co-transfection [SFTPA1_wt + SFTPA2_m] conduit aussi à l’augmentation de l’expression de SP-A2_m, sans toutefois restaurer la formation des hexamères ni une sécrétion significative de SP-A2_m. Les mêmes résultats ont été retrouvés avec la co-transfection [SFTPA1_wt + SFTPA1_m]. Les expériences de co-IP ont par ailleurs confirmé la spécificité des interactions SP-A1/SP-A2. ConclusionCette étude révèle une interaction spécifique de SP-A1 et SP-A2 associée, lors de la co-expression avec SP-A2_wt, à une augmentation de l’expression de SP-A1_m ou SP-A2_m, mais aussi à la restauration d’un profil d’oligomérisation en hexamères et à une sécrétion de protéines du surfactant. Dans une perspective thérapeutique, ces résultats permettent d’envisager l’adjonction de SP-A2 exogène dans des modèles cellulaires surexprimant SP-A1_m ou SP-A2_m

Acinar Dysplasia in a Full-Term Newborn with a NKX2.1 Variant

International audienceAcinar dysplasia (AcDys) is one of the three main diffuse developmental disorders of the lung. The transcription factor NK2 homeobox 1 (NKX2.1) partly controls the synthesis of surfactant proteins by type 2 alveolar epithelial cells (AEC2), and germline mutations are known to be associated with brain-lung thyroid syndrome. We report the case of a full-term neonate who developed refractory respiratory failure with pulmonary hypertension requiring venoarterial extracorporeal membrane oxygenation. Histological examination of the lung biopsy specimen was consistent with the diagnosis of AcDys. Molecular analyses led to the identification of the missense heterozygous variant in NKX2.1 (NM_001079668) c.731A&gt;G p.(Tyr244Cys), which is predicted to be pathogenic. After 5 weeks, because AcDys is a fatal disorder and the patient's status worsened, life-sustaining therapies were withdrawn, and she died after a few hours. This study is the first to extend the phenotype of NKX2.1 pathogenic variant, to a fatal form of AcDys

Small for Gestational Age Preterm Neonates Exhibit Defective GH/IGF1 Signaling Pathway

International audienceTo investigate the impact of fetal growth restriction (FGR) on hormonal regulation of post-natal growth and glucose metabolism [via insulin and growth hormone (GH)/Insulin-like Growth factor 1 (IGF1) axis pathways] in small for gestational age (SGA) neonates. We conducted a monocentric observational prospective comparative study on 73 singleton babies born with a weight inferior to 2,000 g. We analyzed auxological (weight, height and head circumference), and hormonal (GH, IGF1, and insulin plasma concentrations) data comparing SGA and appropriate for gestational age (AGA) neonates, between day 1 and 60.One third (23/73) of the neonates were SGA. Twenty-five percent (18/73) required insulin for idiopathic hyperglycemia of prematurity and were smaller in weight and head circumference at discharge. In the SGA group compared with the AGA group, GH plasma concentrations were higher at day 3 (70.1 vs. 38.0 mIU/L) and IGF1 plasma concentrations were higher at day 10 (29.0 vs. 18.7 ng/ml). SGA neonates displayed resistance to GH and IGF1, concomitant to insulin resistance. This could partially explain the initial defective catch-up growth and, later in life, the higher prevalence of metabolic syndrome in this population