Document resource
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.