Risk factors for intensive care admission in children with severe acute asthma in the Netherlands:a prospective multicentre study

Rationale: Severe 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). Objectives: To 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. Methods: A 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 results: 110 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. Conclusions: Children 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

Single nucleotide polymorphisms in genes of circulatory homeostasis in surviving pediatric intensive care patients with meningococcal infection

Objective: In the course of a meningococcal infection, invasive and severe disease occurs in a restricted number of individuals. The predominant mechanism of death in case of meningococcal septic shock is circulatory failure. Inotropic requirements between patients vary widely. We investigated whether polymorphisms in genes regulating the hemodynamic response influence the amount of inotropics required or the susceptibility to severe meningococcal disease. Design: Retrospective case control study. Setting: Single-center pediatric intensive care unit (PICU). Patients: Fifty-six cases (all consecutive patients admitted to the PICU between 1993 and 2001 with a proven meningococcal infection) and 136 controls. Patients were divided into two groups according to their inotropic requirements. Intervention: DNA analysis was performed to determine the polymorphisms of the beta-adrenergic receptor gene-1, beta-adrenergic receptor gene-2, alpha-adducin, angiotensin converting enzyme, and angiotensin II type-1 receptor-1 genes. Results: For the alpha-adducin gene a significant difference of the genotype distribution was found between the cases and controls. The odds ratio for admission to the PICU with meningococcal sepsis with or without meningitis, for carriers of the variant allele (Gly460Trp or Trp460Trp) was 2.1 (95% confidence interval 1.11-4.04; p <0.02). Cases, homozygote for the wildtype allele of the beta-1 adrenergic receptor at locus 389, were more likely to have a low pediatric risk of mortality score on admission (odds ratio 3.6, 95% confidence interval 1.11-11.76). No difference was found in the distribution of the beta-adrenergic receptor gene-1, beta-adrenergic receptor gene-2, angiotensin converting enzyme, and angiotensin II type-1 receptor-1 polymorphisms between the two groups of patients or between cases and controls. Conclusions: Among patients admitted to the PICU with a meningococcal infection, the variant allele of the alpha-adducin gene was more prevalent compared with controls. Patients with the variant allele of the beta-adrenergic receptor gene-1 at locus 389 were more likely to have a high pediatric risk of mortality score on admission. The mechanism and clinical relevance of these findings is unclear. (Pediatr Crit Care Med 2008; 9:517-523

Neurocognitive, Psychosocial, and Quality of Life Outcomes After Multisystem Inflammatory Syndrome in Children Admitted to the PICU

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.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