What question did this study set out to answer?

This study investigates the relationship between the timing of norepinephrine initiation and 28-day mortality in sepsis patients.

June 11, 2026

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

Key Points

This study investigates the relationship between the timing of norepinephrine initiation and 28-day mortality in sepsis patients.
Conducted a prospective multicenter study involving 138 patients with sepsis.
Recorded norepinephrine initiation time, 28-day mortality, mean arterial pressure (MAP), net fluid balance, and lactate clearance for analysis.
Utilized Cox regression analysis to determine associations between parameters and mortality.
Non-survivors had a median norepinephrine initiation time of 98.5 minutes compared to 49.5 minutes for survivors (p<0.001).
Longer time to reach target MAP was observed in non-survivors (80 minutes vs 60 minutes, p=0.013).
Norepinephrine initiation time over 1 hour increased the risk of 28-day mortality (adjusted HR=2.60, 95% CI 1.40 to 4.84, p=0.003).

Abstract

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.

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