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The exposure to intense physical and psychological stress during intensive care can result in posttraumatic stress disorder (PTSD) in survivors. Cortisol is a biological stress mediator that can have a protective effect during severe stress. The administration of stress doses of hydrocortisone during treatment in the intensive care unit could theoretically result in a lower incidence of PTSD. We tested this hypothesis in survivors of septic shock.A retrospective case-controlled analysis.A 20-bed multidisciplinary intensive care unit of a tertiary-care university hospital.We identified 27 patients who received standard therapy for septic shock. These patients served as controls and were compared with an equal number of patients who received hydrocortisone in addition to standard treatment. These patients were selected from our database with regard to age (±4 yrs), gender, and cause of septic shock to be as similar as possible with control patients.Patients from the hydrocortisone group had received stress doses of hydrocortisone (100 mg bolus, followed by 0.18 mg/kg/hr) in addition to standard treatment. Patients from the control group received standard protocol-driven treatment only. PTSD was diagnosed with the Posttraumatic Stress Syndrome-10 inventory, a self-report scale for diagnosis of PTSD. Health-related quality of life was measured using the Medical Outcomes Study Short-Form Survey (Medical Outcomes Trust, Boston, MA), which consists of 36 questions.Patients who received hydrocortisone during septic shock had a significantly lower incidence of PTSD than patients who received standard treatment only (5 of 27 vs. 16 of 27; p = .01) and had significantly higher scores on the mental health index of the Medical Outcomes Study Short-Form health-related quality-of-life questionnaire (68 vs. 44 points; p = .009).Data from this study support the hypothesis that the administration of stress doses of hydrocortisone in doses equivalent to the maximal endocrine secretion rate during septic shock reduces the incidence of PTSD and improves emotional well-being in survivors. This hypothesis should be tested in a prospective randomized trial.