Abstract
IntroductionThe use of low-dose steroid therapy in the management of septic shock has been extensively studied. However, the association between the timing of low-dose steroid therapy and the outcome has not been evaluated. Therefore, we evaluated whether early initiation of low-dose steroid therapy is associated with mortality in patients with septic shock.MethodsWe retrospectively analyzed the clinical data of 178 patients who received low-dose corticosteroid therapy for septic shock between January 2008 and December 2009. Time-dependent Cox regression models were used to adjust for potential confounding factors in the association between the time to initiation of low-dose corticosteroid therapy and in-hospital mortality.ResultsThe study population consisted of 107 men and 71 women with a median age of 66 (interquartile range, 54 to 71) years. The 28-day mortality was 44% and low-dose corticosteroid therapy was initiated within a median of 8.5 (3.8 to 19.1) hours after onset of septic shock-related hypotension. Median time to initiation of low-dose corticosteroid therapy was significantly shorter in survivors than in non-survivors (6.5 hours versus 10.4 hours; P = 0.0135). The mortality rates increased significantly with increasing quintiles of time to initiation of low-dose corticosteroid therapy (P = 0.0107 for trend). Other factors associated with 28-day mortality were higher Simplified Acute Physiology Score (SAPS) 3 (P < 0.0001) and Sequential Organ Failure Assessment (SOFA) scores (P = 0.0007), dose of vasopressor at the time of initiation of low-dose corticosteroid therapy (P < 0.0001), need for mechanical ventilation (P = 0.0001) and renal replacement therapy (P < 0.0001), while the impaired adrenal reserve did not affect 28-day mortality (81% versus 82%; P = 0.8679). After adjusting for potential confounding factors, the time to initiation of low-dose corticosteroid therapy was still significantly associated with 28-day mortality (adjusted odds ratio (OR) 1.025, 95% confidence interval (CI) 1.007 to 1.044, P = 0.0075). The early therapy group (administered within 6 hours after the onset of septic shock, n = 66) had a 37% lower mortality rate than the late therapy group (administered more than 6 hours after the onset of septic shock, n = 112) (32% versus 51%, P = 0.0132).ConclusionsEarly initiation of low-dose corticosteroid therapy was significantly associated with decreased mortality.
Highlights
The use of low-dose steroid therapy in the management of septic shock has been extensively studied
adrenocorticotropic hormone (ACTH) stimulation tests were performed in 96 (54%) patients, and corticosteroid insufficiency (CIRCI) was diagnosed in 78 patients
The number of patients with relative adrenal insufficiency defined by a delta serum cortisol level of < 9 μg/dL after ACTH administration was 71 (91% of patients with CIRCI)
Summary
The use of low-dose steroid therapy in the management of septic shock has been extensively studied. We evaluated whether early initiation of low-dose steroid therapy is associated with mortality in patients with septic shock. Annane et al initially enrolled patients in the study within three hours of the onset of shock, and this time window from the onset of septic shock to randomization was increased to eight hours [9]. In the CORTICUS study, patients were required to undergo randomization within 24 hours after the onset of septic shock, and this time window was subsequently increased to 72 hours [10]. There have been no reports regarding the association between the timing of corticosteroid therapy and mortality in patients with septic shock. We performed a retrospective analysis of the clinical data from patients who received low-dose corticosteroid therapy for septic shock to determine whether early initiation of this therapy is associated with decreased mortality in such cases
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