Effect of early parenteral nutrition on the HPA axis and on treatment with corticosteroids in ICU patients

Nutrition can affect the hypothalamus-pituitary-adrenal axis. We hypothesized that early administration of parenteral nutrition (PN) during critical illness reduces plasma ACTH and cortisol concentrations and hereby increases the use of corticosteroids. This is a preplanned substudy of a randomized controlled trial (EPaNIC) which compared early PN with late PN in 4640 critically ill patients. We investigated the impact of early versus late PN on any steroid treatment and on treatment for ≥5 days to capture patients with clinical suspicion of adrenal insufficiency, and assessed whether this was related to an effect on septic shock. Also, in a propensity score matched subgroup (n=174) of patients not receiving steroids, plasma ACTH and (free) cortisol were quantified. As compared with late PN, more patients on early PN received treatment with corticosteroids (26.2% vs. 23.8%; p=0.05) and with corticosteroids for ≥5 days (14.0% vs. 11.9%; p=0.03). However, plasma ACTH and (free) cortisol concentrations were unaffected and thus could not explain the higher use of corticosteroids with early PN. Instead, more patients developed new septic shock with early PN (17.0%) than with late PN (14.2%) (p=0.01). In multivariate logistic regression analysis, new septic shock was an independent determinant for ≥5 days steroid treatment (OR 6.25; 95% CI 4.93-7.94; p