Characteristics of plasma NOx levels in severe sepsis: high interindividual variability and correlation with illness severity, but lack of correlation with cortisol levels

• Published in: Clinical endocrinology (Oxford) Vol. 73; no. 3; pp. 413 - 420
• Main Authors: HO, J. T, CHAPMAN, M. J, O'CONNOR, S, LAM, S, EDWARDS, J, LUDBROOK, G, LEWIS, J. G, TORPY, D. J
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01-09-2010
• Subjects: Analysis of Variance; Bacterial diseases; Bacterial sepsis; Biological and medical sciences; Corticoids; Dobutamine - therapeutic use; Endocrinopathies; Epinephrine - therapeutic use; Female; Fundamental and applied biological sciences. Psychology; Globulins; Human bacterial diseases; Humans; Hydrocortisone; Hydrocortisone - blood; Hydrocortisone - therapeutic use; Infectious diseases; Intensive Care Units; Male; Medical sciences; Metabolites; Middle Aged; Nitrates - blood; Nitric oxide; Nitric Oxide - metabolism; Nitrites - blood; Norepinephrine - therapeutic use; Prospective Studies; Renal function; Sepsis; Sepsis - blood; Sepsis - drug therapy; Sepsis - pathology; Septic shock; Severity of Illness Index; Shock, Septic - blood; Shock, Septic - drug therapy; Shock, Septic - pathology; Time Factors; Transcortin - metabolism; Vasoconstrictor Agents - therapeutic use; Vertebrates: endocrinology; Corticosteroid; Correlation; Steroid hormone; Antiinflammatory agent; Cortisol; Severity; Hydrocortisone; Glucocorticoid; Bacteremia; Blood plasma; Infection; Sepsis syndrome; Adrenal hormone; Interindividual comparison; Bacteriosis; Severe; Endocrinology
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/j.1365-2265.2010.03817.x

Objectives Nitric oxide (NO) concentrations are elevated in sepsis and their vasodilatory action may contribute to the development of hyperdynamic circulatory failure. Hydrocortisone infusion has been reported to reduce nitric oxide metabolite (NOx) concentrations and facilitate vasopressor withdrawal in septic shock. Our aim was to determine whether NOx concentrations relate to (i) protocol-driven vasopressor initiation and withdrawal and (ii) plasma cortisol concentrations, from endogenous and exogenous sources. Demonstration of a relation between NOx, cortisol and vasopressor requirement may provide an impetus towards the study of hydrocortisone-mediated NOx suppression as a tool in sepsis management. Design A prospective study of 62 patients with severe sepsis admitted to the intensive care unit. Measurements Plasma NOx, total and free cortisol, and corticosteroid-binding globulin (CBG) concentrations were measured and related to protocol-driven vasopressor use for 7 days following admission. Results Patients who developed septic shock (n = 35) had higher plasma NOx, total and free cortisol, and lower CBG concentrations than the nonseptic shock group (n = 27). Cortisol, CBG and NOx concentrations correlated with illness severity. Free cortisol, and to a lesser extent total cortisol, but not NOx concentrations, predicted septic shock. NOx concentrations were higher in nonsurvivors, and the concentrations were characteristically stable within individuals but marked interindividual differences were only partly accounted for by illness severity or renal dysfunction. NOx concentrations did not correlate with cortisol, did not relate to vasopressor requirement and did not fall after standard dose hydrocortisone, given for clinical indications. Conclusions Nitric oxide production increased with sepsis severity but did not correlate with plasma cortisol or vasopressor requirement. NOx levels were not suppressed reproducibly by hydrocortisone. High interindividual variability of NOx levels suggests that absolute NOx levels may not be a suitable target for individualized hydrocortisone therapy.