Effect of norepinephrine initiation timing on mortality in septic shock: a multicenter cohort study

Abstract

Background: This study aims to investigate the association between timing of norepinephrine (NE) initiation and mortality in septic shock. Methods: We conducted a retrospective study using data from a multicenter database. Adult patients with septic shock presenting to the emergency departments, who showed initial hypotension and received NE, were included. We performed multivariable regression analysis to evaluate the association between norepinephrine timing and 28-day mortality, with stratifying according to the Sepsis-3 shock definition and vasopressor requirement risk assessed by the diastolic shock index and lactate levels. Results: A total of 4,456 patients were included. In the non-Sepsis-3 shock group, no significant association was found between the timing of NE administration and 28-day mortality. However, in the Sepsis-3 shock group, a significant association was observed, with each hourly delay in NE administration increasing the risk of 28-day mortality (aOR for hourly delay: 1.07, 95% CI: 1.02-1.13, P = 0.002). Compared to the > 6-hour group, the aOR for 28-day high vasopressor requirement risk. mortality was 0.54 (95% CI: 0.35-0.81, P = 0.003) for norepinephrine administration within 1 h and 0.63 (95% CI: 0.42-0.95, P = 0.025) for the 1-3 h group. In the high-vasopressor requirement risk, hourly delay in NE administration was also associated with an increased risk of 28-day mortality (aOR for hourly delay: 1.07, 95% CI: 1.00-1.13, P = 0.027). Compared to the > 6-hour group, the aOR for 28-day mortality was 0.53 (95% CI: 0.33-0.86, P = 0.010) for within 1 h group. Conclusions: Early NE administration was associated with decreased 28-day mortality in patients who met the Sepsis-3 septic shock criteria and who had high vasopressor requirement risk.