Objective:Several studies have shown septic shock developing later during the hospital stay are associated with greater mortality. However, the precise point at which time from hospital admission to the onset of septic shock (admission-shock-onset-time) becomes an independent prognostic marker of mortality remains unknown. This study aimed to evaluate the association between admission-shock-onset-time and in-hospital mortality among patients with septic shock, as well as the optimal cut-off

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... period to categorize early and late-onset septic shock.Method: We conducted a single-center retrospective, observational cohort study at a quaternary academic hospital comprising adult patients with septic shock admitted to a medical intensive care unit (ICU) from 01/2011 to 12/2020. A multivariable Cox regression model was developed to assess if log-transformed admission-shock-onset-time was associated with in-hospital mortality. A multivariable additive logistic regression was performed to estimate the odds ratio for mortality using the log-transformed admission-shock-onset-time. The thin plate spline function was used to describe the nonlinear relationship between the log-transformed admission-shock-onset-time and in-hospital mortality.The primary outcome was in-hospital mortality and the secondary outcome was ICU mortality.Results:A total of 2,520 patients met the inclusion criteria with an overall in-hospital mortality of 37.3%. The log-transformed admission-shock-onset-time was associated with higher in-hospital mortality [Hazard ratio (HR): 1.08, 95% confidence interval (CI): 1.05-1.11, p< 0.001] and ICU mortality (HR: 1.06, 95%CI: 1.03-1.10, p<0.001). This association remained significant after adjusting for clinical variables. The odds ratio for in-hospital mortality continued to increase throughout the observation period.Conclusion:In-hospital mortality continued to rise as admission-shock-onset-time increased in septic shock. No clear dichotomization between early and late septic shock can be ascertained and this categorization may limit our understanding of the temporal relationship of shock onset to mortality.Trial RegistrationThis study was approved by Cleveland Clinic Institutional Review Board (IRB 15-1233).