Influence of time from admission to norepinephrine administration and volume of fluids received on outcomes of patients meeting sepsis-3 criteria: a retrospective study using the MIMIC-IV database

OBJECTIVES: Vasopressors are a cornerstone in the management of sepsis, marked by distributive shock often unresponsive to fluid resuscitation. Prior research and clinician surveys have suggested that earlier usage of vasopressors corresponds to improved outcomes. METHODS: A retrospective cohort was constructed using patient data contained within the Medical Information Mart for Intensive Care-IV database. Analytic cohort included a total of 2079 patients meeting sepsis-3 criteria with a ≥2-point rise in Sequential Organ Failure Assessment score and administered norepinephrine (NE) as first-line vasopressor within 24 hours of admission to the intensive care unit (ICU). Patients receiving other vasopressors or missing documented fluid resuscitation information were excluded. Primary end points included mortality, use of invasive mechanical ventilation and length of stay which were analyzed in a multivariate logistic regression model for the primary effect of time from ICU admission to NE administration using covariates. RESULTS: Time to NE use was defined as either early, using <6 hours from time of ICU admission or late using >6 hours to ≤24 hours. Patients who received early NE had significantly lower adjusted odds of mortality (0.75, 95% CI 0.57 to 0.97, p=0.026), higher adjusted odds of invasive mechanical ventilation (1.48, 95% CI 1.01 to 2.16, p=0.045), no significant difference in hospital length of stay (difference in days 0.6 (95% CI −3.24 to 2.04)) and lower ICU length of stay (difference in days −0.9 (95% CI −1.74 to –0.01)), as compared with the late NE group. CONCLUSION: Among patients admitted to the ICU for sepsis, early use of NE was associated with significantly lower odds of mortality but higher odds of mechanical ventilation, and no significant difference in length of hospital stay but less time in the ICU. Furthermore, the volume of fluids received prior to NE use may have a significant impact on optimal NE timing. LEVEL OF EVIDENCE: Level IV—therapeutic care/management.