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  1. Alcamo AM, Weiss SL, Fitzgerald JC, Kirschen MP, Loftis LL, Tang SF, et al.
    Pediatr Crit Care Med, 2022 Aug 01;23(8):593-605.
    PMID: 36165937 DOI: 10.1097/PCC.0000000000002979
    OBJECTIVES: To compare outcomes associated with timing-early versus late-of any neurologic dysfunction during pediatric sepsis.

    DESIGN: Secondary analysis of a cross-sectional point prevalence study.

    SETTING: A total of 128 PICUs in 26 countries.

    PATIENTS: Less than 18 years with severe sepsis on 5 separate days (2013-2014).

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: Patients were categorized as having either no neurologic dysfunction or neurologic dysfunction (i.e., present at or after sepsis recognition), which was defined as Glasgow Coma Scale score less than 5 and/or fixed dilated pupils. Our primary outcome was death or new moderate disability (i.e., Pediatric Overall [or Cerebral] Performance Category score ≥3 and change ≥1 from baseline) at hospital discharge, and 87 of 567 severe sepsis patients (15%) had neurologic dysfunction within 7 days of sepsis recognition (61 at sepsis recognition and 26 after sepsis recognition). Primary site of infection varied based on presence of neurologic dysfunction. Death or new moderate disability occurred in 161 of 480 (34%) without neurologic dysfunction, 45 of 61 (74%) with neurologic dysfunction at sepsis recognition, and 21 of 26 (81%) with neurologic dysfunction after sepsis recognition (p < 0.001 across all groups). On multivariable analysis, in comparison with those without neurologic dysfunction, neurologic dysfunction whether at sepsis recognition or after was associated with increased odds of death or new moderate disability (adjusted odds ratio, 4.9 [95% CI, 2.3-10.1] and 10.7 [95% CI, 3.8-30.5], respectively). We failed to identify a difference between these adjusted odds ratios of death or new moderate disability that would indicate a differential risk of outcome based on timing of neurologic dysfunction (p = 0.20).

    CONCLUSIONS: In this severe sepsis international cohort, the presence of neurologic dysfunction during sepsis is associated with worse outcomes at hospital discharge. The impact of early versus late onset of neurologic dysfunction in sepsis on outcome remains unknown, and further work is needed to better understand timing of neurologic dysfunction onset in pediatric sepsis.

  2. Weiss SL, Fitzgerald JC, Maffei FA, Kane JM, Rodriguez-Nunez A, Hsing DD, et al.
    Crit Care, 2015;19:325.
    PMID: 26373923 DOI: 10.1186/s13054-015-1055-x
    Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs).
  3. Giuliano JS, Markovitz BP, Brierley J, Levin R, Williams G, Lum LC, et al.
    Pediatr Crit Care Med, 2016 06;17(6):522-30.
    PMID: 27124566 DOI: 10.1097/PCC.0000000000000760
    OBJECTIVES: Pediatric severe sepsis remains a significant global health problem without new therapies despite many multicenter clinical trials. We compared children managed with severe sepsis in European and U.S. PICUs to identify geographic variation, which may improve the design of future international studies.

    DESIGN: We conducted a secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies study. Data about PICU characteristics, patient demographics, therapies, and outcomes were compared. Multivariable regression models were used to determine adjusted differences in morbidity and mortality.

    SETTING: European and U.S. PICUs.

    PATIENTS: Children with severe sepsis managed in European and U.S. PICUs enrolled in the Sepsis PRevalence, OUtcomes, and Therapies study.

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: European PICUs had fewer beds (median, 11 vs 24; p < 0.001). European patients were younger (median, 1 vs 6 yr; p < 0.001), had higher severity of illness (median Pediatric Index of Mortality-3, 5.0 vs 3.8; p = 0.02), and were more often admitted from the ward (37% vs 24%). Invasive mechanical ventilation, central venous access, and vasoactive infusions were used more frequently in European patients (85% vs 68%, p = 0.002; 91% vs 82%, p = 0.05; and 71% vs 50%; p < 0.001, respectively). Raw morbidity and mortality outcomes were worse for European compared with U.S. patients, but after adjusting for patient characteristics, there were no significant differences in mortality, multiple organ dysfunction, disability at discharge, length of stay, or ventilator/vasoactive-free days.

    CONCLUSIONS: Children with severe sepsis admitted to European PICUs have higher severity of illness, are more likely to be admitted from hospital wards, and receive more intensive care therapies than in the United States. The lack of significant differences in morbidity and mortality after adjusting for patient characteristics suggests that the approach to care between regions, perhaps related to PICU bed availability, needs to be considered in the design of future international clinical trials in pediatric severe sepsis.

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