Association between the time to norepinephrine initiation and mortality in patients with sepsis

BACKGROUND: The optimal timing for initiating norepinephrine in sepsis remains unclear. This study aimed to assess the link between the timing of norepinephrine initiation (NE time) and the 28-day all-cause mortality in sepsis. METHODS: We conducted a prospective multicentre study. We recorded NE time, the 28-day all-cause mortality rate, the time to achieve a mean arterial pressure (MAP) >65 mm Hg, net fluid balance and lactate clearance. These parameters were compared between survivors and non-survivors. Cox regression analysis was used to determine their association with mortality. RESULTS: A total of 138 patients were included in the study. Non-survivors had a longer median NE time (98.5 min (IQR 60.0-131) vs 49.5 min (IQR 25.5-75.0), p<0.001) and a longer duration to reach the target MAP (80 min (IQR 30.0-217.5) vs 60 min (IQR 25.0-117.5), p=0.013) compared with survivors. In the multivariable Cox regression analysis, NE time remained a predictor of 28-day all-cause mortality (adjusted HR=1.335, 95% CI 1.034 to 1.722, p=0.026). NE time exceeding 1 hour (adjusted HR=2.60, 95% CI 1.40 to 4.84, p=0.003) and 2 hours (adjusted HR=2.96, 95% CI 1.49 to 5.87, p=0.002) associated with increasing the risk of 28-day mortality. CONCLUSION: NE time was associated with the 28-day all-cause mortality in sepsis patients. Commencing NE therapy within the first 60 min following the onset of hypotension was associated with a reduced risk of 28-day all-cause mortality. TRIAL REGISTRATION NUMBER: TCTR20221103005.