Introduction: The use of low-dose steroid therapy in the management of septic shock has been extensively\r\nstudied. However, the association between the timing of low-dose steroid therapy and the outcome has not been\r\nevaluated. Therefore, we evaluated whether early initiation of low-dose steroid therapy is associated with mortality\r\nin patients with septic shock.\r\nMethods: We retrospectively analyzed the clinical data of 178 patients who received low-dose corticosteroid\r\ntherapy for septic shock between January 2008 and December 2009. Time-dependent Cox regression models were\r\nused to adjust for potential confounding factors in the association between the time to initiation of low-dose\r\ncorticosteroid therapy and in-hospital mortality.\r\nResults: The study population consisted of 107 men and 71 women with a median age of 66 (interquartile range,\r\n54 to 71) years. The 28-day mortality was 44% and low-dose corticosteroid therapy was initiated within a median\r\nof 8.5 (3.8 to 19.1) hours after onset of septic shock-related hypotension. Median time to initiation of low-dose\r\ncorticosteroid therapy was significantly shorter in survivors than in non-survivors (6.5 hours versus 10.4 hours; P =\r\n0.0135). The mortality rates increased significantly with increasing quintiles of time to initiation of low-dose\r\ncorticosteroid therapy (P = 0.0107 for trend). Other factors associated with 28-day mortality were higher Simplified\r\nAcute Physiology Score (SAPS) 3 (P < 0.0001) and Sequential Organ Failure Assessment (SOFA) scores (P = 0.0007),\r\ndose of vasopressor at the time of initiation of low-dose corticosteroid therapy (P < 0.0001), need for mechanical\r\nventilation (P = 0.0001) and renal replacement therapy (P < 0.0001), while the impaired adrenal reserve did not\r\naffect 28-day mortality (81% versus 82%; P = 0.8679). After adjusting for potential confounding factors, the time to\r\ninitiation of low-dose corticosteroid therapy was still significantly associated with 28-day mortality (adjusted odds\r\nratio (OR) 1.025, 95% confidence interval (CI) 1.007 to 1.044, P = 0.0075). The early therapy group (administered\r\nwithin 6 hours after the onset of septic shock, n = 66) had a 37% lower mortality rate than the late therapy group\r\n(administered more than 6 hours after the onset of septic shock, n = 112) (32% versus 51%, P = 0.0132).\r\nConclusions: Early initiation of low-dose corticosteroid therapy was significantly associated with decreased mortali
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