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OBJECTIVES: To assess the effect of administration of sodium bicarbonate on carbon dioxide levels in children with life-threatening asthma (LTA) and to evaluate the clinical effect of this treatment.Study DESIGN: Retrospective study. SETTING: A pediatric ICU (PICU) of a tertiary care university hospital. PATIENTS: Seventeen children with LTA who received sodium bicarbonate. MEASUREMENTS AND RESULTS: In January 1999, a new protocol for the treatment of LTA was initiated in our institution, incorporating the use of IV sodium bicarbonate in acidotic patients (pH < 7.15) with refractory status asthmaticus. Since January 1999, sodium bicarbonate was administered to 17 patients; 5 patients received two or three doses of sodium bicarbonate. In three patients, sodium bicarbonate was administered after intubation. Intubation and mechanical ventilation were performed in five patients before admission to the PICU, and in one patient during admission. There was a significant decrease of Pco(2) after sodium bicarbonate infusion (p = 0.007). An improvement of respiratory distress in all but one patient was seen as well. CONCLUSIONS: Administration of sodium bicarbonate in 17 children with LTA was associated with a significant decrease in Pco(2) and an improvement of respiratory distress. The possible benefits of sodium bicarbonate in LTA deserve further study in a controlled, prospective design. [ABSTRACT FROM AUTHOR]

Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024. Published by Elsevier Inc.)

Long-term outcome studies after pediatric cardiac arrest (CA) are few. They require a CA registry and dedicated outcome teams. Learning about the long-term outcomes is very important for developing prognostication guidelines, improving post-cardiac care, counseling caregivers about the future of their child, and creating opportunities for therapeutic intervention studies to improve outcomes. Few PICUs worldwide provide a multidisciplinary follow-up program as routine practice at an outpatient clinic with standardized measurements, using validated instruments including neuropsychological assessments by psychologists. The primary goal of such a follow-up program should be to provide excellent care to children and their caregivers, thereby resulting in a high attendance. Pediatric psychologists, neurologists and pediatricians/pediatric intensivists should ideally be involved to screen for delayed development and psychosocial problems and offer appropriate care at the same time. Preferably, outcomes should consist of evaluation of morbidity (physical and neuropsychological), functional health and Health Related Quality Of Life (QoL) of the patient and their caregivers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Aim: This study aimed to investigate trends over time in pre-hospital factors for pediatric out-of-hospital cardiac arrest (pOHCA) and long-term neurological and neuropsychological outcomes. These have not been described before in large populations., Methods: Non-traumatic arrest patients, 1 day-17 years old, presented to the Sophia Children's Hospital from January 2002 to December 2020, were eligible for inclusion. Favorable neurological outcome was defined as Pediatric Cerebral Performance Categories (PCPC) 1-2 or no difference with pre-arrest baseline. The trend over time was tested with multivariable logistic and linear regression models with year of event as independent variable., Findings: Over a nineteen-year study period, the annual rate of long-term favorable neurological outcome, assessed at a median 2.5 years follow-up, increased significantly (OR 1.10, 95%-CI 1.03-1.19), adjusted for confounders. Concurrently, annual automated external defibrillator (AED) use and, among adolescents, initial shockable rhythm increased significantly (OR 1.21, 95% CI 1.10-1.33 and OR 1.15, 95% CI 1.02-1.29, respectively), adjusted for confounders. For generalizability purposes, only the total intelligence quotient (IQ) was considered for trend analysis of all tested domains. Total IQ scores and bystander basic life support (BLS) rate did not change significantly over time., Interpretation: Long-term favorable neurological outcome, assessed at a median 2.5 years follow-up, improved significantly over the study period. Total IQ scores did not significantly change over time. Furthermore, AED use (OR 1.21, 95%CI 1.10-1.33) and shockable rhythms among adolescents (OR1.15, 95%CI 1.02-1.29) increased over time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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 < 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 > 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%)., (© 2023. The Author(s).)

Background: SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data., Methods: This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity., Results: We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curaçao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies., Conclusions: Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Neuroprognostication in severe traumatic brain injury (sTBI) is challenging and occurs in critical care settings to determine withdrawal of life-sustaining therapies (WLST). However, formal pediatric sTBI neuroprognostication guidelines are lacking, brain death criteria vary, and dilemmas regarding WLST persist, which lead to institutional differences. We studied WLST practice and outcome in pediatric sTBI to provide insight into WLST-associated factors and survivor recovery trajectory ≥1 year post-sTBI. This retrospective, single center observational study included patients <18 years admitted to the pediatric intensive care unit (PICU) of Erasmus MC-Sophia (a tertiary university hospital) between 2012 and 2020 with sTBI defined as a Glasgow Coma Scale (GCS) ≤8 and requiring intracranial pressure (ICP) monitoring. Clinical, neuroimaging, and electroencephalogram data were reviewed. Multi-disciplinary follow-up included the Pediatric Cerebral Performance Category (PCPC) score, educational level, and commonly cited complaints. Seventy-eight children with sTBI were included (median age 10.5 years; interquartile range [IQR] 5.0-14.1; 56% male; 67% traffic-related accidents). Median ICP monitoring was 5 days (IQR 3-8), 19 (24%) underwent decompressive craniectomy. PICU mortality was 21% (16/78): clinical brain death (5/16), WLST due to poor neurological prognosis (WLST&#95;neuro, 11/16). Significant differences ( p  < 0.001) between survivors and non-survivors: first GCS score, first pupillary reaction and first lactate, Injury Severity Score, pre-hospital cardiopulmonary resuscitation, and Rotterdam CT (computed tomography) score. WLST&#95;neuro decision timing ranged from 0 to 31 days (median 2 days, IQR 0-5). WLST&#95;neuro decision ( n  = 11) was based on neurologic examination (100%), brain imaging (100%) and refractory intracranial hypertension (5/11; 45%). WLST discussions were multi-disciplinary with 100% agreement. Immediate agreement between medical team and caregivers was 81%. The majority (42/62, 68%) of survivors were poor outcome (PCPC score 3 to 5) at PICU discharge, of which 12 (19%) in a vegetative state. One year post-injury, no patients were in a vegetative state and the median PCPC score had improved to 2 (IQR 2-3). No patients died after PICU discharge. Twenty percent of survivors could not attend school 2 years post-injury. Survivors requiring an adjusted educational level increased to 45% within this timeframe. Chronic complaints were headache, behavioral problems, and sleeping problems. In conclusion, two-thirds of sTBI PICU mortality was secondary to WLST&#95;neuro and occurred early post-injury. Median survivor PCPC score improved from 4 to 2 with no vegetative patients 1 year post-sTBI. Our findings show the WLST decision process was multi-disciplinary and guided by specific clinical features at presentation, clinical course, and (serial) neurological diagnostic modalities, of which the testing combination was determined by case-to-case variation. This stresses the need for international guidelines to provide accurate neuroprognostication within an appropriate timeframe whereby overall survivor outcome data provides valuable context and guidance in the acute phase decision process.

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Objectives: To investigate neurocognitive, psychosocial, and quality of life (QoL) outcomes in children with Multisystem Inflammatory Syndrome in Children (MIS-C) seen 3-6 months after PICU admission., Design: National prospective cohort study March 2020 to November 2021., Setting: Seven PICUs in the Netherlands., Patients: Children with MIS-C (0-17 yr) admitted to a PICU., Interventions: None., Measurements and Main Results: Children and/or parents were seen median (interquartile range [IQR] 4 mo [3-5 mo]) after PICU admission. Testing included assessment of neurocognitive, psychosocial, and QoL outcomes with reference to Dutch pre-COVID-19 general population norms. Effect sizes (Hedges' g ) were used to indicate the strengths and clinical relevance of differences: 0.2 small, 0.5 medium, and 0.8 and above large. Of 69 children with MIS-C, 49 (median age 11.6 yr [IQR 9.3-15.6 yr]) attended follow-up. General intelligence and verbal memory scores were normal compared with population norms. Twenty-nine of the 49 followed-up (59%) underwent extensive testing with worse function in domains such as visual memory, g = 1.0 (95% CI, 0.6-1.4), sustained attention, g = 2.0 (95% CI 1.4-2.4), and planning, g = 0.5 (95% CI, 0.1-0.9). The children also had more emotional and behavioral problems, g = 0.4 (95% CI 0.1-0.7), and had lower QoL scores in domains such as physical functioning g = 1.3 (95% CI 0.9-1.6), school functioning g = 1.1 (95% CI 0.7-1.4), and increased fatigue g = 0.5 (95% CI 0.1-0.9) compared with population norms. Elevated risk for posttraumatic stress disorder (PTSD) was seen in 10 of 30 children (33%) with MIS-C. Last, in the 32 parents, no elevated risk for PTSD was found., Conclusions: Children with MIS-C requiring PICU admission had normal overall intelligence 4 months after PICU discharge. Nevertheless, these children reported more emotional and behavioral problems, more PTSD, and worse QoL compared with general population norms. In a subset undergoing more extensive testing, we also identified irregularities in neurocognitive functions. Whether these impairments are caused by the viral or inflammatory response, the PICU admission, or COVID-19 restrictions remains to be investigated., Competing Interests: Dr. Buddingh’s institution received funding from Leids Universitair Fonds/ Bontiusstichting and ZonMw. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

The optimal dose regimen for intravenous (IV) treatment in children with severe acute asthma (SAA) is still a matter of debate. We assessed the efficacy of adding a salbutamol loading dose to continuous infusion with salbutamol in children admitted to a pediatric intensive care unit (PICU) with SAA. This multicentre, placebo-controlled randomized trial in the PICUs of four tertiary care children's hospitals included children (2-18 years) with SAA admitted between 2017 and 2019. Children were randomized to receive either a loading dose IV salbutamol (15 mcg/kg, max. 750 mcg) or normal saline while on continuous salbutamol infusion. The primary outcome was the asthma score (Qureshi) 1 h after the intervention. Analysis of covariance models was used to evaluate sensitivity to change in asthma scores. Serum concentrations of salbutamol were obtained. Fifty-eight children were included (29 in the intervention group). Median baseline asthma score was 12 (IQR 10-13) in the intervention group and 11 (9-12) in the control group (p = 0.032). The asthma score 1 h after the intervention did not differ significantly between the groups (p = 0.508, β-coefficient = 0.283). The median increase in salbutamol plasma levels 10 min after the intervention was 13 μg/L (IQR 5-24) in the intervention group and 4 μg/L (IQR 0-7) in the control group (p = 0.001). Side effects were comparable between both groups., Conclusion: We found no clinical benefit of adding a loading dose IV salbutamol to continuous infusion of salbutamol, in children admitted to the PICU with SAA. Clinically significant side effects from the loading dose were not encountered., What Is Known: • Pediatric asthma guidelines struggle with an evidence-based approach for the treatment of SAA beyond the initial steps of oxygen suppletion, repetitive administration of inhaled β2-agonists, and systemic steroids. • During an SAA episode, effective delivery of inhaled drugs is unpredictable due to severe airway obstruction., What Is New: • This study found no beneficial effect of an additional loading dose IV salbutamol in children admitted to the PICU. • This study found no clinically significant side effects from the loading dose., (© 2022. The Author(s).)

Importance: Oxygen supplementation is a cornerstone treatment in pediatric critical care. Accumulating evidence suggests that overzealous use of oxygen, leading to hyperoxia, is associated with worse outcomes compared with patients with normoxia., Objectives: To evaluate the association of arterial hyperoxia with clinical outcome in critically ill children among studies using varied definitions of hyperoxia., Data Sources: A systematic search of EMBASE, MEDLINE, Cochrane Library, and ClinicalTrials.gov from inception to February 1, 2021, was conducted., Study Selection: Clinical trials or observational studies of children admitted to the pediatric intensive care unit that examined hyperoxia, by any definition, and described at least 1 outcome of interest. No language restrictions were applied., Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology guideline and Newcastle-Ottawa Scale for study quality assessment were used. The review process was performed independently by 2 reviewers. Data were pooled with a random-effects model., Main Outcomes and Measures: The primary outcome was 28-day mortality; this time was converted to mortality at the longest follow-up owing to insufficient studies reporting the initial primary outcome. Secondary outcomes included length of stay, ventilator-related outcomes, extracorporeal organ support, and functional performance., Results: In this systematic review, 16 studies (27 555 patients) were included. All, except 1 randomized clinical pilot trial, were observational cohort studies. Study populations included were post-cardiac arrest (n = 6), traumatic brain injury (n = 1), extracorporeal membrane oxygenation (n = 2), and general critical care (n = 7). Definitions and assessment of hyperoxia differed among included studies. Partial pressure of arterial oxygen was most frequently used to define hyperoxia and mainly by categorical cutoff. In total, 11 studies (23 204 patients) were pooled for meta-analysis. Hyperoxia, by any definition, showed an odds ratio of 1.59 (95% CI, 1.00-2.51; after Hartung-Knapp adjustment, 95% CI, 1.05-2.38) for mortality with substantial between-study heterogeneity (I2 = 92%). This association was also found in less heterogeneous subsets. A signal of harm was observed at higher thresholds of arterial oxygen levels when grouped by definition of hyperoxia. Secondary outcomes were inadequate for meta-analysis., Conclusions and Relevance: These results suggest that, despite methodologic limitations of the studies, hyperoxia is associated with mortality in critically ill children. This finding identifies the further need for prospective observational studies and importance to address the clinical implications of hyperoxia in critically ill children.

Introduction: Shockable rhythm following pediatric out-of-hospital cardiac arrest (pOHCA) is consistently associated with hospital and short-term survival. Little is known about the relationship between shockable rhythm and long-term outcomes (>1 year) after pOHCA. The aim was to investigate the association between first documented rhythm and long-term outcomes in a pOHCA cohort over 18 years., Methods: All children aged 1 day-18 years who experienced non-traumatic pOHCA between 2002-2019 and were subsequently admitted to the emergency department (ED) or pediatric intensive care unit (PICU) of Erasmus MC-Sophia Children's Hospital were included. Data was abstracted retrospectively from patient files, (ground) ambulance and Helicopter Emergency Medical Service (HEMS) records, and follow-up clinics. Long-term outcome was determined using a Pediatric Cerebral Performance Category (PCPC) score at the longest available follow-up interval through august 2020. The primary outcome measure was survival with favorable neurologic outcome, defined as PCPC 1-2 or no difference between pre- and post-arrest PCPC. The association between first documented rhythm and the primary outcome was calculated in a multivariable regression model., Results: 369 children were admitted, nine children were lost to follow-up. Median age at arrest was age 3.4 (IQR 0.8-9.9) years, 63% were male and 14% had a shockable rhythm (66% non-shockable, 20% unknown or return of spontaneous circulation (ROSC) before emergency medical service (EMS) arrival). In adolescents (aged 12-18 years), 39% had shockable rhythm. 142 (39%) of children survived to hospital discharge. On median follow-up interval of 25 months (IQR 5.1-49.6), 115/142 (81%) of hospital survivors had favorable neurologic outcome. In multivariable analysis, shockable rhythm was associated with survival with favorable long-term neurologic outcome (OR 8.9 [95%CI 3.1-25.9])., Conclusion: In children with pOHCA admitted to ED or PICU shockable rhythm had significantly higher odds of survival with long-term favorable neurologic outcome compared to non-shockable rhythm. Survival to hospital discharge after pOHCA was 39% over the 18-year study period. Of survivors to discharge, 81% had favorable long-term (median 25 months, IQR 5.1-49.6) neurologic outcome. Efforts for improving outcome of pOHCA should focus on early recognition and treatment of shockable pOHCA at scene., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Studies of pediatric cardiac arrest use inconsistent outcomes, including return of spontaneous circulation and short-term survival, and basic assessments of functional and neurological status. In 2018, the International Liaison Committee on Resuscitation sponsored the COSCA initiative (Core Outcome Set After Cardiac Arrest) to improve consistency in reported outcomes of clinical trials of adult cardiac arrest survivors and supported this P-COSCA initiative (Pediatric COSCA). The P-COSCA Steering Committee generated a list of potential survival, life impact, and economic impact outcomes and assessment time points that were prioritized by a multidisciplinary group of healthcare providers, researchers, and parents/caregivers of children who survived cardiac arrest. Then expert panel discussions achieved consensus on the core outcomes, the methods to measure those core outcomes, and the timing of the measurements. The P-COSCA includes assessment of survival, brain function, cognitive function, physical function, and basic daily life skills. Survival and brain function are assessed at discharge or 30 days (or both if possible) and between 6 and 12 months after arrest. Cognitive function, physical function, and basic daily life skills are assessed between 6 and 12 months after cardiac arrest. Because many children have prearrest comorbidities, the P-COSCA also includes documentation of baseline (ie, prearrest) brain function and calculation of changes after cardiac arrest. Supplementary outcomes of survival, brain function, cognitive function, physical function, and basic daily life skills are assessed at 3 months and beyond 1 year after cardiac arrest if resources are available., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: To determine timing and cause of death in children admitted to the PICU following return of circulation after out-of-hospital cardiac arrest., Design: Retrospective observational study., Setting: Single-center observational cohort study at the PICU of a tertiary-care hospital (Erasmus MC-Sophia, Rotterdam, The Netherlands) between 2012 and 2017., Patients: Children younger than 18 years old with out-of-hospital cardiac arrest and return of circulation admitted to the PICU., Measurements and Results: Data included general, cardiopulmonary resuscitation and postreturn of circulation characteristics. The primary outcome was defined as survival to hospital discharge. Modes of death were classified as brain death, withdrawal of life-sustaining therapies due to poor neurologic prognosis, withdrawal of life-sustaining therapies due to refractory circulatory and/or respiratory failure, and recurrent cardiac arrest without return of circulation. One hundred thirteen children with out-of-hospital cardiac arrest were admitted to the PICU following return of circulation (median age 53 months, 64% male, most common cause of out-of-hospital cardiac arrest drowning [21%]). In these 113 children, there was 44% survival to hospital discharge and 56% nonsurvival to hospital discharge (brain death 29%, withdrawal of life-sustaining therapies due to poor neurologic prognosis 67%, withdrawal of life-sustaining therapies due to refractory circulatory and/or respiratory failure 2%, and recurrent cardiac arrest 2%). Compared with nonsurvivors, more survivors had witnessed arrest (p = 0.007), initial shockable rhythm (p < 0.001), shorter cardiopulmonary resuscitation duration (p < 0.001), and more favorable clinical neurologic examination within 24 hours after admission. Basic cardiopulmonary resuscitation event and postreturn of circulation (except for the number of extracorporeal membrane oxygenation) characteristics did not significantly differ between the withdrawal of life-sustaining therapies due to poor neurologic prognosis and brain death patients. Timing of decision-making to withdrawal of life-sustaining therapies due to poor neurologic prognosis ranged from 0 to 18 days (median: 0 d; interquartile range, 0-3) after cardiopulmonary resuscitation. The decision to withdrawal of life-sustaining therapies was based on neurologic examination (100%), electroencephalography (44%), and/or brain imaging (35%)., Conclusions: More than half of children who achieve return of circulation after out-of-hospital cardiac arrest died after PICU admission. Of these deaths, two thirds (67%) underwent withdrawal of life-sustaining therapies based on an expected poor neurologic prognosis and did so early after return of circulation. There is a need for international guidelines for accurate neuroprognostication in children after cardiac arrest., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Studies of pediatric cardiac arrest use inconsistent outcomes, including return of spontaneous circulation and short-term survival, and basic assessments of functional and neurological status. In 2018, the International Liaison Committee on Resuscitation sponsored the COSCA initiative (Core Outcome Set After Cardiac Arrest) to improve consistency in reported outcomes of clinical trials of adult cardiac arrest survivors and supported this P-COSCA initiative (Pediatric COSCA). The P-COSCA Steering Committee generated a list of potential survival, life impact, and economic impact outcomes and assessment time points that were prioritized by a multidisciplinary group of healthcare providers, researchers, and parents/caregivers of children who survived cardiac arrest. Then expert panel discussions achieved consensus on the core outcomes, the methods to measure those core outcomes, and the timing of the measurements. The P-COSCA includes assessment of survival, brain function, cognitive function, physical function, and basic daily life skills. Survival and brain function are assessed at discharge or 30 days (or both if possible) and between 6 and 12 months after arrest. Cognitive function, physical function, and basic daily life skills are assessed between 6 and 12 months after cardiac arrest. Because many children have prearrest comorbidities, the P-COSCA also includes documentation of baseline (ie, prearrest) brain function and calculation of changes after cardiac arrest. Supplementary outcomes of survival, brain function, cognitive function, physical function, and basic daily life skills are assessed at 3 months and beyond 1 year after cardiac arrest if resources are available.

Purpose: To describe current practices in European Paediatric Intensive Care Units (PICUs) regarding neuro-prognostication in comatose children after cardiac arrest (CA)., Methods: An anonymous online survey was conducted among members of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) and the European Paediatric Neurology Society (EPNS) throughout January and February 2019. The survey consisted of 49 questions divided into 4 sections: general information, cardiac arrest, neuro-prognostication and follow-up., Results: The survey was sent to 1310 EPNS and 611 ESPNIC members. Of the 108 respondents, 71 (66%) (23 countries, 45 PICUs) completed the "neuro-prognostication" section. Eight PICUs (20%) had a local neuro-prognostication guideline. The 3 methods considered as most useful were neurological examination (92%), magnetic resonance imaging (MRI) (82%) and continuous electroencephalography (cEEG) (45%). In 50% a Pediatric Cerebral Performance Category (PCPC) score ≥ 4 was considered as poor neurological outcome. In 63% timing of determining neurological prognosis was based on the individual patient. Once decided that neurological prognosis was futile, 55% indicated that withdrawing life-sustaining therapy (WLST) was (one of) the options, whereas 44% continued PICU treatment (with or without restrictions). In 28 PICUs (68%) CA-survivors were scheduled for follow-up visits., Conclusion: Local guidelines for neuro-prognostication in comatose children after CA are uncommon. Methods to assess neurological outcome were mainly neurological examination, MRI and cEEG. Consequences of poor outcome differed between respondents. Inaccuracies in neuro-prognostication can result in premature WLST, thereby biasing outcome research and creating a self-fulfilling cycle. Further research is needed to develop scientifically based international guidelines for neuro-prognostication in comatose children after CA., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Objectives: To prospectively evaluate quality of life (QoL) and psychosocial outcomes in children with severe acute asthma (SAA) after pediatric intensive care (PICU) admission compared to children with SAA who were admitted to a general ward (GW). In addition, we assessed post-traumatic stress (PTS) and asthma-related QoL in the parents., Methods: A preplanned follow-up of 3-9 months of our nationwide prospective multicenter study, in which children with SAA admitted to a Dutch PICU (n=110) or GW (n=111) were enrolled between 2016-2018. Asthma-related QoL, PTS symptoms, emotional and behavioral problems, and social impact in children and/or parents were assessed with validated web-based questionnaires., Results: We included 100 children after PICU and 103 after GW admission, with a response rate of 50% for the questionnaires. Median time to follow-up was 5 months (range 1-12 months). Time to reach full schooldays after admission was significantly longer in the PICU group (mean of 10 vs 4 days, p=0.001). Parents in the PICU group reported more PTS symptoms (intrusion p=0.01, avoidance p=0.01, arousal p=0.02) compared to the GW group., Conclusion: No significant differences were found between PICU and GW children on self-reported outcome domains, except for the time to reach full schooldays. PICU parents reported PTS symptoms more often than the GW group. Therefore, monitoring asthma symptoms and psychosocial screening of children and parents after PICU admission should both be part of standard care after SAA. This should identify those who are at risk for developing PTSD, in order to timely provide appropriate interventions. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Objective: Hyperoxia is associated with adverse outcome in severe traumatic brain injury (TBI). This study explored differences in patient classification of oxygen exposure by PaO 2 cutoff and cumulative area-under-the-curve (AUC) analysis., Methods: Retrospective, explorative study including children (<18 years) with accidental severe TBI (2002-2015). Oxygen exposure analysis used three PaO 2 cutoff values and four PaO 2 AUC categories during the first 24 hours of Pediatric Intensive Care Unit (PICU) admission., Results: Seventy-one patients were included (median age 8.9 years [IQR 4.6-12.9]), mortality 18.3% (n = 13). Patient hyperoxia classification differed depending on PaO 2 cutoff vs AUC analysis: 52% vs. 26%, respectively, were classified in the highest hyperoxia category. Eleven patients (17%) classified as 'intermediate oxygen exposure' based on cumulative PaO 2 analysis whereby they did not exceed the 200 mmHg PaO2 cutoff threshold. Patient classification variability was reflected by Pearson correlation coefficient of 0.40 ( p -value 0.001)., Conclusions: Hyperoxia classification in pediatric severe TBI during the first 24 hours of PICU admission differed depending on PaO 2 cutoff or cumulative AUC analysis. We consider PaO 2 cumulative (AUC) better approximates (patho-)physiological circumstances due to its time- and dose-dependent approach. Prospective studies exploring the association between cumulative PaO 2 , physiological parameters (e.g. ICP, PbtO 2 ) and outcome are warranted as different patient classifications of oxygen exposure influences how its relationship to outcome is interpreted.

Background: Intravenous salbutamol is used to treat children with refractory status asthmaticus, however insufficient pharmacokinetic data are available to guide initial and subsequent dosing recommendations for its intravenous use. The pharmacologic activity of salbutamol resides predominantly in the (R)-enantiomer, with little or no activity and even concerns of adverse reactions attributed to the (S)-enantiomer., Objective: Our aim was to develop a population pharmacokinetic model to characterize the pharmacokinetic profile for intravenous salbutamol in children with status asthmaticus admitted to the pediatric intensive care unit (PICU), and to use this model to study the effect of different dosing schemes with and without a loading dose., Methods: From 19 children (median age 4.9 years [range 9 months-15.3 years], median weight 18 kg [range 7.8-70 kg]) treated with continuous intravenous salbutamol at the PICU, plasma samples for R- and S-salbutamol concentrations (111 samples), as well as asthma scores, were collected prospectively at the same time points. Possible adverse reactions and patients' clinical data (age, sex, weight, drug doses, liver and kidney function) were recorded. With these data, a population pharmacokinetic model was developed using NONMEM 7.2. After validation, the model was used for simulations to evaluate the effect of different dosing regimens with or without a loading dose., Results: A two-compartment model with separate clearance for R- and S-salbutamol (16.3 L/h and 8.8 L/h, respectively) best described the data. Weight was found to be a significant covariate for clearance and volume of distribution. No other covariates were identified. Simulations showed that a loading dose can result in higher R-salbutamol concentrations in the early phase after the start of infusion therapy, preventing accumulation of S-salbutamol., Conclusions: The pharmacokinetic model of intravenous R- and S-salbutamol described the data well and showed that a loading dose should be considered in children. This model can be used to evaluate the pharmacokinetic-pharmacodynamic relationship of intravenous salbutamol in children, and, as a next step, the effectiveness and tolerability of intravenous salbutamol in children with severe asthma.

The number of children requiring pediatric intensive care unit (PICU) admission for severe acute asthma (SAA) around the world has increased., Objectives: We investigated whether this trend in SAA PICU admissions is present in the Netherlands., Methods: A multicenter retrospective cohort study across all tertiary care PICUs in the Netherlands. Inclusion criteria were children (2-18 years) hospitalized for SAA between 2003 and 2013. Data included demographic data, asthma diagnosis, treatment, and mortality., Results: In the 11-year study period 590 children (660 admissions) were admitted to a PICU with a threefold increase in the number of admissions per year over time. The severity of SAA seemed unchanged, based on the first blood gas, length of stay and mortality rate (0.6%). More children received highflow nasal cannula (P < 0.001) and fewer children needed invasive ventilation (P < 0.001). In 58% of the patients the maximal intravenous (IV) salbutamol infusion rate during PICU admission was 1 mcg/kg/min. However, the number of patients treated with IV salbutamol in the referring hospitals increased significantly over time (P = 0.005). The proportion of steroid-naïve patients increased from 35% to 54% (P = 0.004), with a significant increase in both age groups (2-4 years [P = 0.026] and 5-17 years [P = 0.036])., Conclusions: The number of children requiring PICU admission for SAA in the Netherlands has increased. We speculate that this threefold increase is explained by an increasing number of steroid-naïve children, in conjunction with a lowered threshold for PICU admission, possibly caused by earlier use of salbutamol IV in the referring hospitals., (© 2018 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc.)