The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors

Abstract

Background: Exposure to intense physical and psychological stress during septic shock can result in posttraumatic stress disorder in survivors. Patients with chronic posttraumatic stress disorder often show sustained reductions in serum cortisol concentration. This investigation examines whether increasing serum cortisol levels with hydrocortisone treatment during septic shock reduces the incidence of posttraumatic stress disorder in survivors.

Methods: Patients (n = 20) were recruited from a prospective, randomized double-blind study on the hemodynamic effects of hydrocortisone during septic shock. Eleven patients had received placebo and nine stress doses of hydrocortisone. Posttraumatic stress disorder was diagnosed 31 months (median) after intensive care unit discharge using SCID-IV (DSM-IV-criteria). Furthermore, the number of categories of traumatic memory from ICU treatment was determined in both groups at that time.

Results: Only one of nine patients from the hydrocortisone group developed posttraumatic stress disorder, compared with seven of 11 patients in the placebo group (p = .02). There was no significant difference with regard to the number of categories of traumatic memory between the hydrocortisone and placebo groups.

Conclusions: The administration of hydrocortisone during septic shock in a dosage similar to the endogenous maximal production rate was associated with a lower incidence of posttraumatic stress disorder in long-term survivors, which seems to be independent of the number of categories of traumatic memory.

Introduction

Patients with septic shock face a 50% risk of death in the intensive care unit (ICU) (Matthay 2001) and are exposed to extensive physical and emotional stress, which is the combined result of severe systemic infection, multiple organ dysfunction, and the intensive care treatment itself. In addition, many survivors of septic shock or acute pulmonary failure report emotionally traumatic episodes such as anxiety, pain, respiratory distress, or nightmares from their stay in the ICU Eddleston et al 2000, Hayden 1994, Schelling et al 1998. Due to this combined exposure to maximal physical and psychological stress, patients may develop long-term emotional sequelae such as posttraumatic stress disorder (PTSD) after ICU treatment Jones et al 2001, Schelling et al 1998.

In addition to a characteristic pattern of emotional symptoms, neuroendocrine system alterations such as lower plasma (Yehuda et al 1991) or urinary cortisol levels (Mason et al 1986) and high noradrenergic activity Mason et al 1988, Mellman et al 1995 are often found in patients with chronic PTSD. In a recent case-control study, we reported that patients who received hydrocortisone during septic shock and had increased serum cortisol levels in the ICU had a significantly lower risk of developing PTSD (Schelling et al 1999). Hydrocortisone was given to these patients because two prospective randomized studies have demonstrated a reduction in dosage and duration of norepinephrine requirements, which resulted in a significant shortening of the shock phase Bollaert et al 1998, Briegel et al 1999. This effect of stress doses of hydrocortisone may be due, at least in part, to a down regulation of the severe systemic inflammatory response typically found during sepsis.

In addition, the aforementioned case-control study (Schelling et al 1999) suggested a possible role for lower cortisol levels during severe stress exposure as a co-factor for the development of PTSD. The design of this study was retrospective, however, because we had selected patients with septic shock from our database and matched patients with hydrocortisone with those with standard therapy (Schelling et al 1999). Hydrocortisone administration was not randomized in this study and, theoretically, patients in the hydrocortisone group could have been sicker and could have received more intensive sedation, thus resulting in a lower incidence of PTSD. Furthermore, sedation was not standardized in the matched case study, different drugs were used during different phases of the investigations, and no data were available regarding the duration of the shock phase, exposure to norepinephrine, the duration of hydrocortisone administration, or serum cortisol levels. Because of an increased understanding of how these variables might influence the development of PTSD, we decided to evaluate a subgroup of critically ill patients in whom data on stress hormone dosages, degree of sedation, or duration of the shock phase were prospectively recorded, and came up with patients from a prospective randomized study on hydrocortisone during septic shock that has been performed at our institution. Some data of 14 patients from this study had already been included in the previous report (mainly hydrocortisone yes/no, PTSD scores, and data on disease severity) (Schelling et al 1999), but the reevaluation of these data (together with data from six other patients from the original septic shock study) now evaluates two groups which are truly comparable with regard to other variables such as traumatic memories, level of sedation, or norepinephrine dosage, which are known to have possible additional effects on PTSD.