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The relationship between adrenocortical candidate gene expression and clinical response to hydrocortisone in patients with septic shock
- Source :
- Intensive Care Medicine. 47:974-983
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- To determine if adrenocortical gene expression is associated with clinical outcomes or response to corticosteroid treatment in septic shock. A pre-specified nested cohort study of a randomised controlled trial of hydrocortisone compared to placebo in septic shock. Blood was collected for RNAseq analysis prior to treatment with hydrocortisone or placebo. The expression of adrenocortical candidate genes related to pituitary releasing hormones, mineralocorticoid and glucocorticoid receptors, intracellular glucocorticoid metabolism and transport proteins was measured. From May 2014 to April 2017, 671 patients were enrolled in the nested cohort study, from which 494 samples were available for analysis. We found no evidence of an association between candidate gene expression levels and either 90-day mortality, 28-day mortality or time to shock reversal. We observed evidence of a significant interaction between expression and treatment group for time to shock reversal in two genes; GLCCI1 (HR 3.81, 95%CI 0.57–25.47 vs. HR 0.64, 95%CI 0.13–3.07 for hydrocortisone and placebo respectively, p for interaction 0.008) and BHSD1 (HR 0.55, 95%CI 0.28–1.09 vs. HR 1.32 95%CI 0.67–2.60, p for interaction 0.01). In patients with septic shock, there is no association between adrenocortical candidate gene expression and mortality. Patients with higher expression of GLCCI1 who received hydrocortisone achieved shock resolution faster than those receiving placebo; conversely, patients who had higher expression of BHSD1 who received hydrocortisone achieved shock resolution slower than those who received placebo. Variation in gene expression may be a mechanism for heterogeneity of treatment response to corticosteroids in septic shock.
- Subjects :
- medicine.medical_specialty
Candidate gene
business.industry
Septic shock
medicine.drug_class
030208 emergency & critical care medicine
Critical Care and Intensive Care Medicine
medicine.disease
Placebo
Sepsis
03 medical and health sciences
0302 clinical medicine
Endocrinology
Glucocorticoid receptor
030228 respiratory system
Mineralocorticoid
Shock (circulatory)
Internal medicine
Medicine
medicine.symptom
business
Hydrocortisone
medicine.drug
Subjects
Details
- ISSN :
- 14321238 and 03424642
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- Intensive Care Medicine
- Accession number :
- edsair.doi...........fe981234ec64e12be1dd8e700c4b91e9