Current practices in children with severe acute asthma across European PICUs: an ESPNIC survey

Most pediatric asthma guidelines offer evidence-based or best practice approaches to the management of asthma exacerbations but struggle with evidence-based approaches for severe acute asthma (SAA). We aimed to investigate current practices in children with SAA admitted to European pediatric intensive care units (PICUs), in particular, adjunct therapies, use of an asthma severity score, and availability of a SAA guideline. We designed a cross-sectional electronic survey across European PICUs. Thirty-seven PICUs from 11 European countries responded. In 8 PICUs (22%), a guideline for SAA management was unavailable. Inhaled beta-agonists and anticholinergics, combined with systemic steroids and IV MgSO4 was central in SAA treatment. Seven PICUs (30%) used a loading dose of a short-acting beta-agonist. Eighteen PICUs (49%) used an asthma severity score, with 8 different scores applied. Seventeen PICUs (46%) observed an increasing trend in SAA admissions. Conclusion: Variations in the treatment of children with SAA mainly existed in the use of adjunct therapies and asthma severity scores. Importantl

Daily interruption of sedation in critically ill children: Study protocol for a randomized controlled trial

Background: In adult patients who are critically ill and mechanically ventilated, daily interruption of sedation (DSI) is an effective method of improving sedation management, resulting in a decrease of the duration of mechanical ventilation, the length of stay in the intensive care unit (ICU) and the length of stay in the hospital. It is a safe and effective approach and is common practice in adult ICUs. For critically ill children it is unknown if DSI is effective and feasible. The aim of this multicenter randomized controlled trial is to evaluate the safety and

Epidemiology and Outcome of Critically Ill Pediatric Cancer and Hematopoietic Stem Cell Transplant Patients Requiring Continuous Renal Replacement Therapy: A Retrospective Nationwide Cohort Study

Objective: Acute kidney injury requiring continuous renal replacement therapy is a serious treatment-related complication in pediatric cancer and hematopoietic stem cell transplant patients. The purpose of this study was to assess epidemiology and outcome of these patients requiring continuous renal replacement therapy in the PICU. Design: A nationwide, multicenter, retrospective, observational study. Setting: Eight PICUs of a tertiary care hospitals in the Netherlands. Patients: Pediatric cancer and hematopoietic stem cell transplan

Validation of the SOS-PD scale for assessment of pediatric delirium: a multicenter study

BACKGROUNDS: Reports of increasing incidence rates of delirium in critically ill children are reason for concern. We evaluated the measurement properties of the pediatric delirium component (PD-scale) of the Sophia Observation Withdrawal Symptoms scale Pediatric Delirium scale (SOS-PD scale). METHODS: In a multicenter prospective observational study in four Dutch pediatric ICUs (PICUs), patients aged ≥ 3 months and admitted for ≥ 48 h were assessed with the PD-scale thrice daily. Criterion validity was assessed: if the PD-scale score was ≥ 4, a child psychiatrist clinically assessed the presence or absence of PD according to the Diagnostic and statistical manual of mental disorders (DSM)-IV. In addition, the child psychiatrist assessed a randomly selected group to establish the false-negative rate. The construct validity was assessed by calculating the Pearson coefficient (rp) for correlation between the PD-scale and Cornell Assessment Pediatric Delirium (CAP-D) scores. Interrater reliability was determined by comparing paired nurse-researcher PD-scale assessments and calculating the intraclass correlation coefficient (ICC). RESULTS: Four hundred eighty-five patients with a median age of 27.0 months (IQR 8-102) were included, of whom 48 patients were diagnosed with delirium by the child psychiatrist. The PD-scale had overall sensitivity of 92.3% and specificity of 96.5% compared to the psychiatrist diagnosis for a cutoff score ≥4 points. The rp between the PD-scale and the CAP-D was 0.89 (CI 95%, 0.82-0.93; p < 0.001). The ICC of 75 paired nurse-researcher observations was 0.99 (95% CI, 0.98-0.99). CONCLUSIONS: The PD-scale has good reliability and validity for early screening of PD in critically ill children. It can be validly and reliably used by nurses to this aim

Intravenous morphine versus intravenous paracetamol after cardiac surgery in neonates and infants

Background: Morphine is worldwide the analgesic of first choice after cardiac surgery in children. Morphine has unwanted hemodynamic and respiratory side effects. Therefore, post-cardiac surgery patients may potentially benefit from a non-opioid drug for pain relief. A previous study has shown that intravenous (IV) paracetamol is effective and opioid-sparing in children after major non-cardiac surgery. The aim of the study is to test the hypothesis that intermittent IV paracetamol administration in children after cardiac surgery will result in a reduction of at least 30% of the cumulative morphine requirement. Methods: This is a prospective, multi-center, randomized controlled trial at four level-3 pediatric intensive care units (ICUs) in the Netherlands and Belgium. Children who are 0-36months old will be randomly assigned to receive either intermittent IV paracetamol or continuous IV morphine up to 48h post-operatively. Morphine will be available as rescue medication for both groups. Validated pain and sedation assessment tools will be used to monitor patients. The sample size (n=208, 104 per arm) was calculated in order to detect a 30% reduction in morphine dose; two-sided significance level was 5% and power was 95%. Discussion: This study will focus on the reduction, or replacement, of morphine by IV paracetamol in children (0-36months old) after cardiac surgery. The results of this study will form the basis of a new pain management algorithm and will be implemented at the participating ICUs, resulting in an evidence-based guideline on post-operative pain after cardiac surgery in infants who are 0-36months old

Retrospective cohort study on factors associated with mortality in high-risk pediatric critical care patients in the Netherlands

Background: High-risk patients in the pediatric intensive care unit (PICU) contribute substantially to PICU-mortality. Complex chronic conditions (CCCs) are associated with death. However, it is unknown whether CCCs also increase mortality in the high-risk PICU-patient. The objective of this study is to determine if CCCs or other factors are associated with mortality in this group. Methods: Retrospective cohort study from a national PICU-database (2006-2012, n = 30,778). High-risk PICU-patients, defined as patients 30% according to either the recalibrated Pediatric Risk of Mortality-II (PRISM) or the Paediatric Index of Mortality 2 (PIM2), were included. Patients with a cardiac arrest before PICU-admission were excluded. Results: In total, 492 high-risk PICU patients with mean predicted risk of 24.8% (SD 22.8%) according to recalibrated PIM2 and 40.0% (SD 23.8%) according to recalibrated PRISM were included of which 39.6% died. No association was found between CCCs and non-survival (odds ratio 0.99; 95% CI 0.62-1.59). Higher Glasgow coma scale at PICU admission was associated with lower mortality (odds ratio 0.91; 95% CI 0.87-0.96). Conclusio

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes