Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis.
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ABSTRACT:
SUBMITTER: van den Akker EL
PROVIDER: S-EPMC2698978 | biostudies-other | 2009 Jul
REPOSITORIES: biostudies-other
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Project description:Capillary integrity continues to challenge critical care physicians worldwide when treating children with sepsis. Vascular growth factors, specifically angiopoietin-1 and angiopoietin-2, play opposing roles in capillary stabilization in patients with sepsis. We aim to determine whether pediatric patients with severe sepsis/shock have persistently high angiopoietin-2/1 ratios when compared with nonseptic PICU patients over a 7-day period.Prospective observational study. Patients were classified within 24 hours of admission into non-systemic inflammatory response syndrome, systemic inflammatory response syndrome/sepsis, or severe sepsis/shock. Plasma levels of angiopoietin-1 and angiopoietin-2 were measured via enzyme-linked immunosorbent assay. The angiopoietin-2/1 ratio was graphically plotted and determined whether patients fell into "constant" or "variable" patterns.Tertiary care center PICU.Critically ill pediatric patients with varying sepsis severity.None.Forty-five patients were enrolled (nine non-systemic inflammatory response syndrome, 19 systemic inflammatory response syndrome/sepsis, and 17 severe sepsis/shock). Gender, age, weight, comorbidities, and PICU length of stay were not significantly different between the groups. Admission pediatric risk stratification scores and net fluid ins/outs were significantly elevated in the severe sepsis/shock group when compared (all p < 0.05). Admission angiopoietin-2 levels and angiopoietin-2/1 ratios were significantly different in the severe sepsis/shock group when all groups were compared (both p < 0.05). Additionally, the latter were significantly elevated in the severe sepsis/shock group at multiple time points (all p ? 0.05) with the peak occurring on day 2 of illness. In a separate analysis, 32% of systemic inflammatory response syndrome/sepsis and 82% of severe sepsis/shock had variable angiopoietin-2/1 ratio patterns compared with none in the control group (p < 0.001).Pediatric patients with severe sepsis and septic shock possess significantly elevated angiopoietin-2/1 ratios during their first 3 days of illness, which peak at day 2 of illness. A subset of these patients demonstrated variable angiopoietin-2/1 ratio patterns.
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Project description:OBJECTIVES:Postoperative administration of corticosteroids is common practice for managing catecholamine refractory low cardiac output syndrome. Since corticosteroid activity is dependent on the glucocorticoid receptor, we sought to characterize glucocorticoid receptor levels in children undergoing cardiac surgery and examined the association between glucocorticoid receptor levels and cardiovascular dysfunction. DESIGN:Prospective observational cohort study. SETTING:Large, tertiary pediatric cardiac center. SUBJECTS:Children undergoing corrective or palliative cardiac surgery. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:A prospective observational cohort study was conducted in 83 children with congenital heart disease. Total glucocorticoid receptor levels were measured in the peripheral WBCs using flow cytometry. In addition, blood samples were collected for total cortisol levels. The primary outcome studied was the time to being inotrope free. An increase in glucocorticoid receptor level from postoperative day 1 to postoperative day 3 was associated with a longer time to being inotrope free (hazard ratio, 0.49 [0.29-0.81]; p = 0.01) in the univariate analysis. This association remained significant after adjusting for age, weight, cardiopulmonary bypass time, cross clamp time, Risk Adjustment for Congenital Heart Surgery-1 score, and postoperative steroid use (hazard ratio, 0.53 [0.29-0.99]; p = 0.05). Postoperative day 3 glucocorticoid receptor level showed a trend to have longer time to being inotrope free (hazard ratio, 0.66 [0.42-1.02]; p = 0.0.06). The cortisol levels minimally increased during the study duration and did not correlate with glucocorticoid receptor levels. CONCLUSIONS:Increasing glucocorticoid receptor levels in peripheral WBCs of children undergoing cardiac surgery are associated with a longer time to being inotrope free. Cortisol levels minimally increased during the study duration. These results suggest that exposure to high-dose perioperative corticosteroids may suppress the hypothalamic-pituitary-adrenal axis leading to increase in glucocorticoid receptor levels in response to a low cortisol environment. Further studies are required to better delineate the interplay between glucocorticoid receptor levels, cortisol levels, corticosteroid exposure, and postoperative inotropic requirements.
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