The number of children requiring pediatric intensive care unit (PICU) admission for severe acute asthma (SAA) around the world has increased.ObjectivesWe investigated whether this trend in SAA PICU admissions is present in the Netherlands.MethodsA 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.ResultsIn 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]).ConclusionsThe 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.

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 posttraumatic stress (PTS) and asthma-related QoL in the parents. Methods: A preplanned follow-up of 3 to 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 and 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 = .001). Parents in the PICU group reported more PTS symptoms (intrusion P = .01, avoidance P = .01, arousal P = .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, to timely provide appropriate interventions.

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 MgSO 4 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. Importantly, in 22% of the PICUs, a SAA guideline was unavailable. Standardizing SAA guidelines across PICUs in Europe may improve quality of care. However, the limited number of PICUs represented and the data compilation method are constraining our findings. What is Known: • Recent reports demonstrate increasing numbers of children with SAA requiring PICU admission in several countries across the world. • Most pediatric guidelines offer evidence-based approaches to the management of asthma exacerbations, but struggle with evidence-based approaches for SAA beyond these initial steps. What is New: • A large arsenal of adjunct therapies and 8 different asthma scores were used. • In a large number of PICUs, a written guideline for SAA management is lacking.

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. Nienke J. Vet and Brenda C. M. de Winter contributed equally to this work.In this prospective study, we developed a population pharmacokinetic model of intravenous R-and S-salbutamol in children with status asthmaticus admitted to the intensive care unit.The model described the data well and showed that a loading dose seems valid to reach higher initial R-salbutamol concentrations with a possible therapeutic advantage.This model can be used to evaluate the pharmacokinetic-pharmacodynamic relationship of intravenous salbutamol.

RationaleSevere acute asthma (SAA) can be fatal, but is often preventable. We previously observed in a retrospective cohort study, a three-fold increase in SAA paediatric intensive care (PICU) admissions between 2003 and 2013 in the Netherlands, with a significant increase during those years of numbers of children without treatment of inhaled corticosteroids (ICS).ObjectivesTo determine whether steroid-naïve children are at higher risk of PICU admission among those hospitalised for SAA. Furthermore, we included the secondary risk factors tobacco smoke exposure, allergic sensitisation, previous admissions and viral infections.MethodsA prospective, nationwide multicentre study of children with SAA (2–18 years) admitted to all Dutch PICUs and four general wards between 2016 and 2018. Potential risk factors for PICU admission were assessed using logistic regression analyses.Measurements and main results110 PICU and 111 general ward patients were included. The proportion of steroid-naïve children did not differ significantly between PICU and ward patients. PICU children were significantly older and more exposed to tobacco smoke, with symptoms >1 week prior to admission. Viral susceptibility was not a significant risk factor for PICU admission.ConclusionsChildren with SAA admitted to a PICU were comparable to those admitted to a general ward with respect to ICS treatment prior to admission. Preventable risk factors for PICU admission were >7 days of symptoms without adjustment of therapy and exposure to tobacco smoke. Physicians who treat children with asthma must be aware of these risk factors.