Sudden cardiac arrest in infants and children:proposal for a diagnostic workup to identify the etiology. An 18-year multicenter evaluation in the Netherlands

Sudden cardiac arrest (SCA) studies are often population-based, limited to sudden cardiac death, and excluding infants. To guide prevention opportunities, it is essential to be informed of pediatric SCA etiologies. Unfortunately, etiologies frequently remain unresolved. The objectives of this study were to determine paediatric SCA etiology, and to evaluate the extent of post-SCA investigations and to assess the performance of previous cardiac evaluation in detecting conditions predisposing to SCA. In a retrospective cohort (2002–2019), all children 0–18 years with out-of-hospital cardiac arrest (OHCA) referred to Erasmus MC Sophia Children's Hospital or the Amsterdam UMC (tertiary-care university hospitals), with cardiac or unresolved etiologies were eligible for inclusion. SCA etiologies, cardiac and family history and etiologic investigations in unresolved cases were assessed. The etiology of arrest could be determined in 52% of 172 cases. Predominant etiologies in children ≥ 1 year (n = 99) were primary arrhythmogenic disorders (34%), cardiomyopathies (22%) and unresolved (32%). Events in children &lt; 1 year (n = 73) were largely unresolved (70%) or caused by cardiomyopathy (8%), congenital heart anomaly (8%) or myocarditis (7%). Of 83 children with unresolved etiology a family history was performed in 51%, an autopsy in 51% and genetic testing in 15%. Pre-existing cardiac conditions presumably causative for SCA were diagnosed in 9%, and remained unrecognized despite prior evaluation in 13%. Conclusion: SCA etiology remained unresolved in 83 of 172 cases (48%) and essential diagnostic investigations were often not performed. Over one-fifth of SCA patients underwent prior cardiac evaluation, which did not lead to recognition of a cardiac condition predisposing to SCA in all of them. The diagnostic post-SCA approach should be improved and the proposed standardized pediatric post-SCA diagnostics protocol may ensure a consistent and systematic evaluation process increasing the diagnostic yield. What is Known: • Arrests in infants remain unresolved in most cases. In children &gt; 1 year, predominant etiologies are primary arrhythmia disorders, cardiomyopathy and myocarditis. • Studies investigating sudden cardiac arrest are often limited to sudden cardiac death (SCD) in 1 to 40 year old persons, excluding infants and successfully resuscitated children. What is New: • In patients with unresolved SCA events, the diagnostic work up was often incompletely performed. • Over one fifth of victims had prior cardiac evaluation before the arrest, with either a diagnosed cardiac condition (9%) or an unrecognized cardiac condition (13%). Graphical Abstract: [Figure not available: see fulltext.].</p

Healthcare costs related to respiratory syncytial virus in paediatric intensive care units in the Netherlands:a nationwide prospective observational study (the BRICK study)

Background: The implementation of the approved respiratory syncytial virus (RSV) preventive interventions in immunisation programmes is advancing rapidly. Insight into healthcare costs of RSV-related paediatric intensive care unit (PICU) admissions is lacking, but of great importance to evaluate the impact of implementation. Therefore, this study aimed to determine the total annual RSV-related paediatric intensive care healthcare costs in the Netherlands. Methods: A nationwide prospective, observational, multicenter study was performed from September 2021 until June 2023. The total annual RSV-related healthcare costs on PICUs in the Netherlands were calculated using RSV-related costs (subgroup I) and consequential costs (subgroup II and III). Subgroup I comprised all PICU admitted infants ≤12 months of age with laboratory-confirmed RSV infection. Subgroup II and III consisted of postponed elective PICU admissions and refused acute PICU admissions due to RSV-related lack of PICU capacity.Findings: A total of 424 infants with RSV-related PICU admission were included. Median age at PICU admission was 46 days (IQR 25–89). The median length of PICU admission was 5 days (IQR 3–8). The total RSV-related PICU costs are € 3,826,386 in 2021–2022, and € 3,183,888 in 2022–2023. Potential costs averted by RSV preventive interventions is € 1.9 to € 2.6 million depending on season, and the duration of protection. Interpretation: RSV-related PICU admissions cost €3.1 to €3.8 million in the Netherlands during one season. The introduction of new RSV preventive interventions into the Dutch immunisation programme will generate significant cost-savings on PICUs and decreases the admission burden of PICUs. </p

Healthcare costs related to respiratory syncytial virus in paediatric intensive care units in the Netherlands: a nationwide prospective observational study (the BRICK study)

Background: The implementation of the approved respiratory syncytial virus (RSV) preventive interventions in immunisation programmes is advancing rapidly. Insight into healthcare costs of RSV-related paediatric intensive care unit (PICU) admissions is lacking, but of great importance to evaluate the impact of implementation. Therefore, this study aimed to determine the total annual RSV-related paediatric intensive care healthcare costs in the Netherlands. Methods: A nationwide prospective, observational, multicenter study was performed from September 2021 until June 2023. The total annual RSV-related healthcare costs on PICUs in the Netherlands were calculated using RSV-related costs (subgroup I) and consequential costs (subgroup II and III). Subgroup I comprised all PICU admitted infants ≤12 months of age with laboratory-confirmed RSV infection. Subgroup II and III consisted of postponed elective PICU admissions and refused acute PICU admissions due to RSV-related lack of PICU capacity. Findings: A total of 424 infants with RSV-related PICU admission were included. Median age at PICU admission was 46 days (IQR 25–89). The median length of PICU admission was 5 days (IQR 3–8). The total RSV-related PICU costs are € 3,826,386 in 2021–2022, and € 3,183,888 in 2022–2023. Potential costs averted by RSV preventive interventions is € 1.9 to € 2.6 million depending on season, and the duration of protection. Interpretation: RSV-related PICU admissions cost €3.1 to €3.8 million in the Netherlands during one season. The introduction of new RSV preventive interventions into the Dutch immunisation programme will generate significant cost-savings on PICUs and decreases the admission burden of PICUs. Funding: None

Imaging sublingual microcirculatory perfusion in pediatric patients receiving procedural sedation with propofol: A pilot study

Objective: Procedural sedation with propofol is widely used in the pediatric population. A well-known side effect of propofol is a decrease in peripheral vascular resistance resulting in hypotension, but little is known about the effects on microcirculation in humans. We aimed to evaluate the effects of propofol on the sublingual microcirculatory perfusion by continuous video imaging in pediatric patients undergoing procedural sedation. Methods: Patients admitted to the Pediatric Intensive Care Unit for procedural sedation were recruited. Oral microcirculation was measured employing a continuous monitoring strategy with incident dark-field illumination imaging. Measurements were obtained before and 3 minutes after propofol induction. Total and perfused vessel densities, proportion of perfused vessels, microvascular flow index, blood vessel diameter (Øbv), and systemic hemodynamics were analyzed. Results: Continuous measurements were achieved in seven patients. Three minutes after propofol induction mean arterial pressure decreased (P = 0.028) and total and perfused vessel densities increased by 12% (P = 0.018) and 16% (P = 0.018), respectively. MFI was unaltered and mean Øbv increased but not significantly. Conclusions: Propofol induction induces a reduction in mean arterial pressure and a rise in sublingual microvascular perfusion. The observed effects of propofol on the sublingual microcirculation may be due to a decrease in microvascular resistance

Use of [13C]bicarbonate for metabolic studies in preterm infants: intragastric versus intravenous administration

The metabolic fate of substrates in humans can be examined by the use of stable isotopes, one of which, [13C]bicarbonate, may serve to estimate CO2 production rate. In view of minimizing the burden of metabolic studies for preterm infants, the authors determined whether intragastric and intravenous infusions of [13C]bicarbonate would achieve the same 13CO2 enrichment in expired air during steady state. A second aim of this study was to determine the minimum time required to reach steady state during intragastric infusion. Ten preterm infants received a primed continuous [13C]bicarbonate infusion intragastrically, followed by an intravenous infusion the next day. Breath samples were obtained every 30 min by the direct sampling method. 13CO2 isotopic enrichment, expressed as atom percent excess, was measured by isotopic ratio mass spectrometry. Two-tailed t tests were used to detect statistically significant differences between the infusion routes. The isotopic enrichment at plateau did not differ between intragastric and intravenous infusion. A steady state of 13CO2 enrichment was achieved after 60 min of intravenous infusion and after 120 min of intragastric infusion. In conclusion, intragastric infusion of [13C]bicarbonate may serve to estimate the whole-body CO2 production rate in preterm infants. To reach 13CO2 steady state, a minimum of 120 min of bicarbonate administration is require

Splanchnic oxidation is the major metabolic fate of dietary glutamate in enterally fed preterm infants

The intestine is a major site of amino acid metabolism, especially in neonates. The energy needed for the metabolic processes in neonatal animals is derived from dietary glucose and amino acids. No data are available showing that dietary amino acids function as intestinal fuel source in human neonates as well. We hypothesized that preterm infants show a high splanchnic first-pass glutamate metabolism and the primary metabolic fate of glutamate is oxidation. Five preterm infants (birth weight 1.2+/-0.2 kg, gestational age 29+/-1 wk) were studied by dual tracer ([U-(13)C]glutamate and [D3]glutamate) techniques on two study days (within postnatal d 14-19). Splanchnic and whole-body glutamate kinetics were assessed by plasma isotopic enrichment of [U-(13)C]glutamate and [D3]glutamate and breath CO2 enrichment. Fractional first-pass glutamate uptake was 77+/-18% on d 1, and 70+/-7% on d 2, mean 74+/-13%. Almost all (86+/-7%) of the glutamate used in the first pass is directed toward oxidation. There is a high splanchnic fractional first-pass uptake and a high oxidation rate of glutamate in preterm infants. Glutamate is an important source of energy for the splanchnic tissues in preterm infants receiving full enteral feedin

Development of entrustable professional activities for paediatric intensive care fellows: A national modified Delphi study

Entrustable professional activities (EPAs), as a focus of learner assessment, are supported by validity evidence. An EPA is a unit of professional practice requiring proficiency in multiple competencies simultaneously, that can be entrusted to a sufficiently competent learner. Taken collectively, a set of EPAs define and inform the curriculum of a specialty training. The goal of this study was to develop a set of EPAs for Dutch PICU fellows. A multistage methodology was employed incorporating sequential input from task force members, a medical education expert, PICU fellowship program directors, and PICU physicians and fellows via a modified three-round Delphi study. In the first modified Delphi round, experts rated indispensability and clarity of preliminary EPAs. In the subsequent rounds, aggregated scores for each EPA and group comments were provided. In round two, respondents rated indispensability and clarity of revised EPAs. Round three was used to gain explicit confirmation of suitability to implement these EPAs. Based on median ratings and content validity index (CVI) analysis for indispensability in the first two rounds, all nine preliminary EPAs covered activities that were deemed essential to the clinical practice of PICU physicians. Based on median ratings and CVI analysis for clarity however, four EPAs needed revision. With an agreement percentage of 93–100% for all individual EPAs as well as the set as a whole, a high degree of consensus among experts was reached in the third round. The resulting nine PICU EPAs provide a succinct overview of the core tasks of Dutch PICU physicians. These EPAs were created as an essential first step towards developing an assessment system for PICU fellows, grounded in core professional activities. The robust methodology used, may have broad applicability for other (sub)specialty training programs aiming to develop specialty specific EPAs

Adverse Events in Pediatric Critical Care Nonsurvivors With a Low Predicted Mortality Risk: A Multicenter Case Control Study

OBJECTIVES: Some patients with a low predicted mortality risk in the PICU die. The contribution of adverse events to mortality in this group is unknown. The aim of this study was to estimate the occurrence of adverse events in low-risk nonsurvivors (LN), compared with low-risk survivors (LS) and high-risk PICU survivors and nonsurvivors, and the contribution of adverse events to mortality. DESIGN: Case control study. Admissions were selected from the national Dutch PICU registry, containing 53,789 PICU admissions between 2006 and 2017, in seven PICUs. PICU admissions were stratified into four groups, based on mortality risk (low/high) and outcome (death/survival). Random samples were selected from the four groups. Cases were "LN." Control groups were as follows: "LS," "high-risk nonsurvivors" (HN), and "high-risk survivors" (HS). Adverse events were identified using the validated trigger tool method. SETTING: Patient chart review study. PATIENTS: Children admitted to the PICU with either a low predicted mortality risk (< 1%) or high predicted mortality risk (≥ 30%). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 419 patients were included (102 LN, 107 LS, 104 HN, and 106 HS). LN had more complex chronic conditions (93.1%) than LS (72.9%; p < 0.01), HN (49.0%; p < 0.001), and HS (48.1%; p < 0.001). The occurrence of adverse events in LN (76.5%) was higher than in LS (13.1%) and HN (47.1%) ( p < 0.001). The most frequent adverse events in LN were hospital-acquired infections and drug/fluid-related adverse events. LN suffered from more severe adverse events compared with LS and HS ( p < 0.001). In 30.4% of LN, an adverse event contributed to death. In 8.8%, this adverse event was considered preventable. CONCLUSIONS: Significant and preventable adverse events were found in low-risk PICU nonsurvivors. 76.5% of LN had one or more adverse events. In 30.4% of LN, an adverse event contributed to mortality

Adverse Events in Pediatric Critical Care Nonsurvivors with a Low Predicted Mortality Risk: A Multicenter Case Control Study

OBJECTIVES: Some patients with a low predicted mortality risk in the PICU die. The contribution of adverse events to mortality in this group is unknown. The aim of this study was to estimate the occurrence of adverse events in low-risk nonsurvivors (LN), compared with low-risk survivors (LS) and high-risk PICU survivors and nonsurvivors, and the contribution of adverse events to mortality. DESIGN: Case control study. Admissions were selected from the national Dutch PICU registry, containing 53,789 PICU admissions between 2006 and 2017, in seven PICUs. PICU admissions were stratified into four groups, based on mortality risk (low/high) and outcome (death/survival). Random samples were selected from the four groups. Cases were "LN." Control groups were as follows: "LS," "high-risk nonsurvivors" (HN), and "high-risk survivors" (HS). Adverse events were identified using the validated trigger tool method. SETTING: Patient chart review study. PATIENTS: Children admitted to the PICU with either a low predicted mortality risk (< 1%) or high predicted mortality risk (≥ 30%). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 419 patients were included (102 LN, 107 LS, 104 HN, and 106 HS). LN had more complex chronic conditions (93.1%) than LS (72.9%; p < 0.01), HN (49.0%; p < 0.001), and HS (48.1%; p < 0.001). The occurrence of adverse events in LN (76.5%) was higher than in LS (13.1%) and HN (47.1%) (p < 0.001). The most frequent adverse events in LN were hospital-acquired infections and drug/fluid-related adverse events. LN suffered from more severe adverse events compared with LS and HS (p < 0.001). In 30.4% of LN, an adverse event contributed to death. In 8.8%, this adverse event was considered preventable. CONCLUSIONS: Significant and preventable adverse events were found in low-risk PICU nonsurvivors. 76.5% of LN had one or more adverse events. In 30.4% of LN, an adverse event contributed to mortality

Cysteine: a conditionally essential amino acid in low-birth-weight preterm infants?

Cyst(e)ine can be synthesized de novo from methionine and serine and is, therefore, a nonessential amino acid in human adults. Several studies have suggested that cyst(e)ine might be a conditionally essential amino acid in preterm infants because of biochemical immaturity. No data are available on cyst(e)ine requirements in low-birth-weight (LBW) preterm infants. The aim was to determine cyst(e)ine requirements in LBW infants with gestational ages from 32 to 34 wk, measured 1 mo after birth with the use of the indicator amino acid oxidation technique. LBW infants were randomly assigned to 1 or 2 of the 5 formulas containing graded cystine concentrations (11, 22, 32, 43, or 65 mg cyst(e)ine/100 mL) and generous amounts of methionine. After 24-h adaptation, cyst(e)ine requirement was determined by (13)CO(2) release from [1-(13)C]phenylalanine in expired breath. (13)CO(2) enrichment was measured by isotopic ratio mass spectrometry. Cyst(e)ine requirement was determined in 25 LBW infants with a mean (+/-SD) gestational age of 33 +/- 1 wk and birth weight of 1.78 +/- 0.32 kg. Fractional oxidation of [1-(13)C]phenylalanine did not differ between the 5 groups. There is no evidence for limited endogenous cyst(e)ine synthesis in 4-wk-old LBW preterm infants born at gestational ages from 32 to 34 wk. It is safe to conclude that the cyst(e)ine requirement is <18 mg kg(-1) d(-1) providing generous amounts of methionine and that cyst(e)ine is probably not a conditionally essential amino acid in fully enterally fed LBW preterm infants born at 32-34 w