Hypothalamic-pituitary-adrenal axis dysfunction in critically ill patients with traumatic brain injury: Incidence, pathophysiology, and relationship to vasopressor dependence and peripheral interleukin-6 levels*

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Abstract
Objective To investigate hypothalamic-pituitary-adrenal axis function in patients requiring mechanical ventilation for traumatic brain injury and to assess the relation of hypothalamic-pituitary-adrenal axis abnormalities with vasopressor dependence and peripheral cytokine levels. Design Prospective study. Setting General intensive care unit in a university teaching hospital. Patients Forty patients (33 men and 7 women) with moderate to severe traumatic brain injury (mean age, 37 ± 16 yrs) were studied the day after termination of mechanical ventilation (7–60 days after trauma). Interventions First, a morning blood sample was obtained to measure baseline cortisol, corticotropin, interleukin-6, and tumor necrosis factor alpha. Subsequently, 1 μg of synthetic corticotropin was injected intravenously, and 30 mins later, a second blood sample was drawn to determine stimulated plasma cortisol. Based on data derived from healthy volunteers, patients having stimulated cortisol levels p = .02) and for a longer time interval (median, 0 vs. 293 hrs; p = .006) compared with responders. Furthermore, nonresponders had higher interleukin-6 levels compared with responders (56.03 vs. 28.04 pg/mL; p = .01), whereas tumor necrosis factor alpha concentrations were similar in the two groups (2.42 vs. 1.55 pg/mL; p = .53). Conclusions Adrenal cortisol secretion after dynamic stimulation is deficient in a subset of critically ill patients with moderate to severe head injury. This disorder is associated with prior vasopressor dependency and higher interleukin-6 levels.