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

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Summary 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.
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Document Type: Research Article

Affiliations: 1: Intensive Care Unit 2: Department of Anaesthesia, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia 3: Canterbury Health Laboratories, Christchurch, New Zealand

Publication date: September 1, 2010

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