Early initiation of low-dose corticosteroid therapy in the management of septic shock: a retrospective observational study

Abstract

Introduction: The 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.

Methods: We 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.

Results: The 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).

Conclusions: Early initiation of low-dose corticosteroid therapy was significantly associated with decreased mortality.

Figure 1

Trend of 28-day mortality rate according to the time to initiation of low-dose corticosteroid therapy in quintiles (1^st quintile, 0 to 3.0 hours; 2^nd quintile, 3.1 to 6.3 hours; 3^rd quintile, 6.4 to 11.3 hours; 4^th quintile 11.4 to 24.5 hours; 5^th quintile, ≥ 24.6 h) (P = 0.0107, test for trend).

Figure 2

Kaplan-Meier survival analysis comparing patients treated with low-dose corticosteroid therapy within six hours after development of septic shock and those treated later (solid line represents the early therapy group, who received the therapy within six hours; dotted line represents the late therapy group, who received the therapy after six hours).