Point-of-care hemostasis in children with congenital heart disease, the POCHEMO study : baseline reference values of thromboelastometry and impedance aggregometry

: Viscoelastic tests and impedance aggregometry allow coagulation evaluation at the bedside, but reference values are scarce in pediatrics. The aim of this study was to establish reference values of thromboelastometry and impedance aggregometry for this population and compare it between age groups. This prospective, single-center, observational study evaluates viscoelastic tests and impedance aggregometry in children with congenital heart disease. A total of 204 children were included with a median age of 3.6 years old. We provide references values for this population with median, percentile 2.5 and percentile 97.5. Infants demonstrate for extrinsic activity a shorter coagulation time (52 [49-55] vs. 56 [51-62] s, P = 0.007) and clot formation time (90 [71-118] vs. 113 [93-146] s, P < 0.0001) so as for intrinsic activity a shorter clot formation time (53 [44-69] vs. 75 [59-92] s, P < 0.0001). The maximal clot firmness was significantly stronger in infants for extrinsic (65 [61-69] vs. 59 [54-63] mm, P < 0.0001), intrinsic (68 [64-70] vs. 61 [57-65] mm, P < 0.0001), and fibrinogen (12 [9-16] vs. 10 [8-13] mm, P = 0.02) activities. Platelet aggregation was significantly higher in infants with an amplitude at 6 min of 28 [23-34] vs. 22 [15-27] Ω, P less than 0.0001, a maximum speed of 11 [9-13] vs. 7 [5-10] Ω/min, P less than 0.0001, and an area under the curve of 120 [92-135] vs. 86 [59-112] Ω min, P less than 0.0001. We provided the first reference values for impedance aggregometry and thromboelastometry in children with congenital heart disease. We showed that these infants tend to have accelerated coagulation and stronger clot firmness compared with older children, but this finding may have only minimal relevance when treating a bleeding child. Trial registration number: ClinicalTrials.gov (clinicaltrials.gov/ct2/show/NCT02387944)

Use of levosimendan in post-operative setting after surgical repair of congenital heart disease in children

Contexte : Le bas débit cardiaque est une des complications les plus fréquentes après la chirurgie cardiaque. Le levosimendan, nouvel agent inotrope, a démontré être efficace chez les adultes en bas débit cardiaque lorsque le traitement classique par catécholamine a échoué. Le but de cette étude est d'évaluer l'effet du levosimendan sur les paramètres du débit cardiaque chez les enfants. Méthodes : Analyse rétrospective de 62 enfants hospitalisés dans notre unité de soins intensifs pédiatriques en bas débit cardiaque après chirurgie cardiaque, sans réponse aux catécholamines et ayant reçu un traitement par levosimendan. Les paramètres de bas débit (diurèse, saturation veineuse centrale (Sv02), différence de C02 artério-veineuse (ÀavC02) et lactate plasmique) ont été comparés avant le traitement et à 3, 6, 12 et 24 heures après le début de la perfusion. Nous avons également analysé l'effet sur le score d'aminé, les effets indésirables et la mortalité. Résultats : Après le début de la perfusion, la diurèse (1,1 ml / kg / h vs 3,5 ml / kg / h, p = 0,001) et la Sv02 (59,5% vs 63,3%, p = 0,026) ont augmenté de façon significative au cours des 24 heures. Dans le même temps, le lactate plasmatique (2,3 vs 1,3 mmol /1, p <0,001) a diminué. La différence de C02 artério-veineuse (10,8 vs 9,4 mmHg, p = 0,21) et le score d'amine (44,5 vs 22,5, p = 0,143) ont également diminué, non significativement. Aucun effet secondaire n'a été observé, la mortalité représentant 16%. Conclusion : Le levosimendan est efficace chez les enfants présentant un bas débit cardiaque après une chirurgie cardiaque congénitale. Notre étude confirme l'amélioration du débit cardiaque déjà démontrée dans d'autres études pédiatriques, sans effets indésirables

Quality of clinical practice guidelines and recommendations for the management of pain, sedation, delirium and iatrogenic withdrawal in pediatric intensive care: a systematic review protocol

Introduction Inadequate management of pain and sedation in critically ill children can cause unnecessary suffering and agitation, but also delirium and iatrogenic withdrawal. It is, therefore, important to address these four interrelated conditions together. Some clinical practice guidelines (CPGs) are available for the management of pain and sedation, and a few for delirium and iatrogenic withdrawal in the paediatric intensive care unit; none address the four conditions altogether. Critical appraisal of the quality of CPGs is necessary for their recommendations to be adopted into clinical practice. The aim of this systematic review is to identify and appraise the quality of CPGs and recommendations for management of either pain, sedation, delirium and iatrogenic withdrawal. Methods and analysis Researchers will conduct a systematic review in electronic databases (Medline ALL (Ovid), Embase.com, CINAHL with Full Text (EBSCO), JBI EBP Database (Ovid)), guideline repositories and websites of professional societies to identify CPGs published from 2010 to date. They will then combine index and free terms describing CPGs with pain, sedation, delirium and withdrawal. The researchers will include CPGs if they can be applied in the paediatric intensive care population (newborns to 18 years old) and include recommendation(s) for assessment of at least one of the four conditions. Two independent reviewers will screen for eligibility, complete data extraction and quality assessments using the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the AGREE Recommendation Excellence instruments. Researchers will report characteristics, content and recommendations from CPGs in tabulated forms. Ethics and dissemination Ethical approval is not required for this systematic review. Results will be published in a peer-reviewed journal. PROSPERO registration number CRD42021274364

Suspected Case of Drug-Induced Acute Respiratory Distress Syndrome following Trimethoprim-Sulfamethoxazole Treatment

In this article, we reported the case of a child patient who was admitted to our PICU for severe acute respiratory distress syndrome (ARDS) while being treated with trimethoprim-sulfamethoxazole (TMP-SMX) for osteomyelitis. Based on the timing of exposure, lack of alternative explanations, and clinical course similar to previously described cases, we suspect that TMP-SMX may have triggered ARDS. Despite meeting criteria for extracorporeal membrane oxygenation cannulation, conservative management and lung recruitment with high-frequency percussive ventilation could avoid the latter

Cardiac assessment and inflammatory markers in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV2 (PIMS-TS) treated with methylprednisolone versus intravenous immunoglobulins: 6-month follow-up outcomes of the randomised controlled Swissped RECOVERY trialResearch in context

Summary: Background: Previous findings from the Swissped RECOVERY trial showed that patients with Pediatric Inflammatory Multisystem Syndrome–Temporally Associated with SARS-CoV-2 (PIMS-TS) who were randomly assigned to intravenous immunoglobulins or methylprednisolone have a comparable length of hospital stay. Here, we report the 6-month follow-up outcomes of cardiac pathologies and normalisation of clinical or laboratory signs of inflammation from this study population. Methods: This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). Findings: Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2–12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI) −0.05 to 1.0; p = 0.39). Interpretation: Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes. Funding: NOMIS, Vontobel, and Gaydoul Foundation

Performance of the PEdiatric Logistic Organ Dysfunction-2 score in critically ill children requiring plasma transfusions

BackgroundOrgan dysfunction scores, based on physiological parameters, have been created to describe organ failure. In a general pediatric intensive care unit (PICU) population, the PEdiatric Logistic Organ Dysfunction-2 score (PELOD-2) score had both a good discrimination and calibration, allowing to describe the clinical outcome of critically ill children throughout their stay. This score is increasingly used in clinical trials in specific subpopulation. Our objective was to assess the performance of the PELOD-2 score in a subpopulation of critically ill children requiring plasma transfusions.MethodsThis was an ancillary study of a prospective observational study on plasma transfusions over a 6-week period, in 101 PICUs in 21 countries. All critically ill children who received at least one plasma transfusion during the observation period were included. PELOD-2 scores were measured on days 1, 2, 5, 8, and 12 after plasma transfusion. Performance of the score was assessed by the determination of the discrimination (area under the ROC curve: AUC) and the calibration (Hosmer–Lemeshow test).ResultsFour hundred and forty-three patients were enrolled in the study (median age and weight: 1 year and 9.1 kg, respectively). Observed mortality rate was 26.9 % (119/443). For PELOD-2 on day 1, the AUC was 0.76 (95 % CI 0.71–0.81) and the Hosmer–Lemeshow test was p = 0.76. The serial evaluation of the changes in the daily PELOD-2 scores from day 1 demonstrated a significant association with death, adjusted for the PELOD-2 score on day 1.ConclusionsIn a subpopulation of critically ill children requiring plasma transfusion, the PELOD-2 score has a lower but acceptable discrimination than in an entire population. This score should therefore be used cautiously in this specific subpopulation.</p

Factors influencing plasma transfusion practices in paediatric intensive care units around the world

Background and Objectives Plasma transfusions are a frequent treatment worldwide, but many studies have reported a wide variation in the indications to transfuse. Recently, an international paediatric study also showed wide variation in frequency in the use of plasma transfusions: 25% of the centres transfused plasma to >5% of their patients, whereas another 25% transfused plasma to <1% of their patients. The objective of this study was to explore the factors associated with different plasma transfusion practices in these centres. Materials and Methods Online survey sent to the local investigators of the 101 participating centres, in February 2016. Four areas were explored: beliefs regarding plasma transfusion, patients’ case‐mix in each unit, unit's characteristics, and local blood product transfusion policies and processes. Results The response rate was 82% (83/101). 43% of the respondents believed that plasma transfusions can arrest bleeding, whereas 27% believe that plasma transfusion can prevent bleeding. Centres with the highest plasma transfusion rate were more likely to think that hypovolaemia and mildly abnormal coagulation tests are appropriate indications for plasma transfusions (P = 0·02 and P = 0·04, respectively). Case‐mix, centre characteristics or local transfusion services were not identified as significant relevant factors. Conclusion Factors influencing plasma transfusion practices reflect beliefs about indications and the efficacy of transfusion in the prevention and management of bleeding as well as effects on coagulation tests. Educational and other initiatives to target these beliefs should be the focus of research