Evaluation of the Initiation Timing of Hydrocortisone in Adult Patients With Septic Shock.

INTRODUCTION: Clinical studies evaluating the use of hydrocortisone in patients with septic shock are heterogeneous in design with conflicting results. The appropriate time in which to initiate hydrocortisone after shock onset is unknown. This study sought to compare clinical outcomes including vasopressor duration and mortality in patients with septic shock who received hydrocortisone based on timing of initiation after shock onset.

METHODS: Retrospective cohort study of patients between 2011 and 2017 admitted to 10 medical, surgical, and neurosciences intensive care units (ICUs) at a large, tertiary care academic medical center. Adult patients with vasopressor-dependent septic shock who received hydrocortisone were included. Patients were divided into five timing cohorts based on time after shock onset: 0-6, 6-12, 12-24, 24-48, or >48 h. The primary outcome was days alive and free from vasopressors.

RESULTS: One thousand four hundred seventy patients were included: 567 (38.6%) received hydrocortisone between 0 and 6 h, 231 (15.7%) 6 and 12 h, 260 (17.7%) 12 and 24 h, 195 (13.3%) 24 and 48 h, and 217 (14.8%) >48 h after shock onset. Patients who received hydrocortisone earlier were sicker at baseline with higher APACHE III scores, lactate concentrations, and norepinephrine requirements. On univariate analysis, days alive and free from vasopressors did not significantly differ amongst the timing groups (median 3.3 days for 0-6 h; 1.9 for 6-12 h; 1.9 for 12-24 h; 0 for 24-48 h; 0 for >48 h; P = 0.39); similarly, ICU mortality did not differ. On multivariable linear regression, timing of hydrocortisone was independently associated with more days alive and free from vasopressors when comparing initiation within 0 to 6 h with >48 h (beta-coefficient 2.8 days [95% CI 0.8-4.7]), 6-12 h with >48 h (2.5 days [95% CI 0.2-4.7]), and 12-24 h with >48 h (2.3 days [95% CI 0.2-4.5]). On multivariable logistic regression, timing of hydrocortisone was associated with reduced ICU mortality when comparing receipt within 0 to 6 h of shock onset to >48 h after shock onset (OR 0.6, 95% CI 0.4-0.8).

CONCLUSIONS: In patients in whom hydrocortisone is prescribed for vasopressor-dependent septic shock, timing is crucial and hydrocortisone should be started within the first 12 h after shock onset.