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

Abstract

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. 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. 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. 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.