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Corticosteroid-Binding Globulin Deficiency Independently Predicts Mortality in Septic Shock
Emily Jane Meyer1,2,3, Marni Anne Nenke1,2,3, Michael Laurence Davies4
1Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.
Insights
Severely deficient corticosteroid-binding globulin (CBG) levels in septic shock patients predict higher mortality. CBG concentration was the only directly reversible independent mortality risk factor, highlighting its potential therapeutic target.
Area of Science:
- Endocrinology
- Critical Care Medicine
- Biochemistry
Background:
- Corticosteroid-binding globulin (CBG) transports cortisol and is depleted in septic shock, yet its role in mortality remains controversial.
- Hydrocortisone administration in septic shock is a debated therapeutic strategy.
Purpose of the Study:
- To investigate if severely deficient serum CBG (<200 nmol/L) independently predicts mortality in septic shock patients.
- To analyze the association between CBG levels and other clinical outcomes.
Main Methods:
- A prospective observational study included 135 septic shock patients.
- Patients were grouped by mean plasma CBG concentrations (<200 nmol/L vs. ≥200 nmol/L) and nadir CBG levels.
- Primary outcome was intensive care unit (ICU) mortality; secondary outcomes included 28- and 90-day mortality and treatment requirements.
Main Results:
- ICU mortality was significantly higher in patients with CBG <200 nmol/L (32.4% vs. 13.9%).
- Independent predictors of ICU mortality included low CBG (<200 nmol/L), high APACHE II score, elevated SOFA liver score, and renal replacement therapy.
- Lower nadir CBG levels correlated with increased norepinephrine requirements and duration.
Conclusions:
- Septic shock patients with CBG <200 nmol/L exhibit increased norepinephrine needs and a 3.2-fold higher ICU mortality risk.
- CBG concentration emerged as the sole directly reversible independent risk factor for mortality in this cohort.
Context:
Hydrocortisone administration in septic shock remains controversial. Corticosteroid-binding globulin (CBG) transports cortisol to inflammatory sites and is depleted in septic shock.
Objective:
To determine whether severely deficient serum CBG < 200 nmol/L (reference range 269-641 nmol/L) independently predicts septic shock mortality.
Methods:
A prospective observational study in patients with septic shock. Patients were categorized into 2 groups: mean plasma CBG concentrations <200 nmol/L and ≥200 nmol/L (day 1/2), with additional categorization by nadir CBG. Primary outcome was intensive care unit (ICU) mortality. Secondary outcomes were 28- and 90-day mortality, norepinephrine requirements, renal replacement therapy, and clinician-instituted hydrocortisone.
Results:
135 patients were included. Mortality rates in ICU were higher in the CBG < 200 nmol/L vs the CBG ≥ 200 nmol/L group: 32.4% vs 13.9% [odds ratio (OR) 2.97 (95% CI 1.19, 7.41); P = 0.02] with 28-day mortality OR 2.25 (95% CI 0.99, 5.11) and 90-day mortality OR 2.21 (95% CI 0.99, 4.91). Multivariate analysis revealed 4 factors independently associated with ICU mortality: CBG < 200 nmol/L (adjusted OR 3.23, 95% CI 1.06, 9.88), Acute Physiology and Chronic Health Evaluation II > 25 (adjusted OR 3.58, 95% CI 1.20, 10.68), Sequential Organ Failure Assessment (SOFA) liver score (adjusted OR 1.98, 95% CI 1.04, 3.72), and renal replacement therapy (adjusted OR 6.59, 95% CI 2.17, 20.01). Nadir CBG levels were associated with higher SOFA cardiovascular scores and norepinephrine total dose (μg; P < 0.01) and duration (days; P < 0.01). Plasma cortisol concentrations and hydrocortisone administration did not relate to ICU mortality.
Conclusion:
Septic shock patients with CBG < 200 nmol/L had higher norepinephrine requirements and 3.2-fold higher ICU mortality. CBG concentration was the only directly reversible independent mortality risk factor.
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