Characterization of the glucocorticoid receptor in children undergoing cardiac surgery
Open accessAbstract
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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Reported incidences of LCOS in the pediatric population are between 17 and 67%.
“In the pediatric population reported incidences are between 17 and 67% (9–11).”
From Definitions of low cardiac output syndrome after cardiac surgery and their effect on the incidence of intraoperative LCOS: A literature review and cohort study (2022) · cites this paper as [9]
The Introduction describes LCOS as a prevalent complication after pediatric cardiac surgery, but gives no incidence range. The Results discuss LCOS severity rather than population incidence; searches for 17%, 67%, and LCOS incidence found no passage verifying the claimed figures. (LLM, conf=0.74)
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Schoonen, A., van Klei, W. A., van Wolfswinkel, L., & van Loon, K. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.926957 · Cited by 74 · see citing works
“In five of these articles multiple definitions were used (5 (15), 5 (9), 2 (22), 3 (23) and 2 (24), respectively), initially resulting in a total of 262 definitions.”
Iliopoulos, I., Alder, M. N., Cooper, D. S., Villarreal, E. G., Loomba, R., Sahay, R. D., Fei, L., Steele, P. E., & Flores, S. (2020) · Cardiology in the Young · doi:10.1017/s1047951120000487 · Cited by 34 · see citing works
Self-citation
- Authors
- Flores, S., Cooper, D. S., Opoka, A. M., Iliopoulos, I., Pluckebaum, S., Alder, M. N., Krallman, K. A., Sahay, R. D., Fei, L., & Wong, H. R.
- Affiliations
- Department of Pediatrics, Section of Critical Care Medicine, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX.
- Cincinnati Children's Hospital Medical Center (US)
- ORCID
- Venue
- Pediatric Critical Care Medicine
- Published
- 2018-08
- Volume
- 19
- Issue
- 8
- Pages
- 705-712
- ISSN
- 1529-7535 (ISSN-L)
- PMC
- PMC6086750
- OpenAlex
- W2801015882
- Cited by
- 7
- References
- 41
- Citations by year
- 2025: 1 · 2022: 1 · 2020: 4 · 2018: 1
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pediatric Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM108025)
- Topics
- Health Sciences › Medicine › Epidemiology › Congenital Heart Disease Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Surgery › Cardiac and Coronary Surgery Techniques
- Keywords
- glucocorticoid receptor, pediatric cardiac surgery, low cardiac output syndrome, postoperative corticosteroids, inotrope requirement, cortisol, hypothalamic-pituitary-adrenal axis, peripheral blood leukocytes, congenital heart disease
- MeSH terms
- Cardiac Output, Low, Child, Preschool, Female, Flow Cytometry, Glucocorticoids, Heart Defects, Congenital, Humans, Hydrocortisone, Infant, Male, Methylprednisolone, Postoperative Period, Prospective Studies, Receptors, Glucocorticoid, Intensive Care Units, Pediatric, Proportional Hazards Models, Kaplan-Meier Estimate, Preoperative Period
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