Incidence, Patient Characteristics, Mode of Drug Delivery, and Outcomes of Septic Shock Patients Treated With Vasopressors in the Arise Trial

Introduction: To describe the utilization of vasopressors (VP) in patients enrolled in the Australasian Resuscitation In Sepsis Evaluation (ARISE) trial, and to explore the association between time to VP and 90-day mortality. Methods: The primary exposure variable was VP use after arrival in the emergency department (ED). Vasoactive agents considered as VP included: norepinephrine, epinephrine, metaraminol, or vasopressin. Time-to-event analysis, multivariable logistic regression, and propensity-matched treatment effects modeling were used to assess the association between time to VP and 90-day mortality. Results: In total 1,102 of 1,588 patients (69%) in ARISE received VP at any point. The median [interquartile range (IQR)] time from ED presentation to commencing VP was 4.4 [2.7, 7.1] h, and 38% did so prior to central venous access. The median [IQR] volume of intravenous (i.v.) fluid administered prior to commencing VP was 3.1 [2.3, 4.3] L. Increasing age and volume of i.v. fluid therapy were associated with a lower likelihood of commencing VP early (within 4 h of ED presentation), while greater illness severity was associated with a higher likelihood, P < 0.001, respectively. In those who subsequently died within 90 days, the sub-hazard ratio (95% confidence interval) for commencing VP was 1.4 (1.20, 1.68), P < 0.001, adjusted for age, acute physiology and chronic health evaluation II score, study group, inclusion criteria, plasma lactate, i.v. fluid prior to VP, study institution, and site of infection. Discussion: 50% of the ARISE cohort commenced VP within 4.4 h of ED presentation, and many did so prior to central venous access. Earlier initiation of VP was associated with greater crude and adjusted 90-day mortality.