Objectives: To investigate the agreement between the calculated free cortisol levels according to widely applied Coolens and adjusted Södergård equations with measured levels in the critically ill.
Design and methods: A prospective study in a mixed intensive care unit. We consecutively included 103 patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250μg) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin and albumin were assessed. Free cortisol was estimated by the Coolens method (C) and two adjusted Södergård (S1 and S2) equations. Bland Altman plots were made.
Results: The bias for absolute (t=0, 30 and 60min after ACTH injection) cortisol levels was 38, -24, 41nmol/L when the C, S1 and S2 equations were used, with 95% limits of agreement between -65-142, -182-135, and -57-139nmol/L and percentage errors of 66, 85, and 64%, respectively. Bias for delta (peak-baseline) cortisol was 14, -31 and 16nmol/L, with 95% limits of agreement between -80-108, -157-95, and -74-105nmol/L, and percentage errors of 107, 114, and 100% for C, S1 and S2 equations, respectively.
Conclusions: Calculated free cortisol levels have too high bias and imprecision to allow for acceptable use in the critically ill.
Keywords: Affinity constants; Coolens method; Cortisol-binding globulin; Critical illness related corticosteroid insufficiency; Equilibrium dialysis; Free cortisol; Relative adrenal insufficiency; Södergard equation.
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