Implementation and outcomes of the Multiple Urgent Sepsis Therapies (MUST) protocol*

TLDR

The study evaluates the implementation and outcomes of a comprehensive sepsis protocol, comparing mortality and therapies in septic shock patients to historical controls. A prospective, interventional cohort study at a tertiary university hospital enrolled adults with suspected infection and lactate ≥ 4 mmol/L or septic shock, applying a sepsis pathway that included empirical antibiotics, early goal‑directed therapy, drotrecogin alfa, steroids, intensive insulin therapy, and lung‑protective ventilation, with historical controls from 2000‑2001. Protocol patients received more fluid, earlier antibiotics, better empirical coverage, increased vasopressor use, tighter glucose control, and more adrenal function assessment, yet 28‑day mortality (20.3% vs 29.4%) was not significantly reduced, indicating feasibility but no proven mortality benefit.

Abstract

To describe the effectiveness of a comprehensive, interdisciplinary sepsis treatment protocol with regard to both implementation and outcomes and to compare the mortality rates and therapies of patients with septic shock with similar historical controls.Prospective, interventional cohort study with a historical control comparison group.Urban, tertiary care, university hospital with 46,000 emergency department visits and 4,100 intensive care unit admissions annually.Inclusion criteria were a) emergency department patients aged > or =18 yrs, b) suspected infection, and c) lactate of >4 mmol/L or septic shock. Exclusion criteria were a) emergent operation, b) prehospital cardiac arrest, and c) comfort measures only. Time period: protocol, November 10, 2003, through November 9, 2004; historical controls, February 1, 2000, through January 31, 2001.A sepsis treatment pathway incorporating empirical antibiotics, early goal-directed therapy, drotrecogin alfa, steroids, intensive insulin therapy, and lung-protective ventilation.There were 116 protocol patients, with a mortality rate of 18% (11-25%), of which 79 patients had septic shock. Comparing these patients with 51 historical controls, protocol patients received more fluid (4.0 vs. 2.5 L crystalloid, p < .001), earlier antibiotics (90 vs. 120 mins, p < .013), more appropriate empirical coverage (97% vs. 88%, p < .05), more vasopressors in the first 6 hrs (80% vs. 45%, p < .001), tighter glucose control (mean morning glucose, 123 vs. 140, p < .001), and more frequent assessment of adrenal function (82% vs. 10%, p < .001), with a nonstatistically significant increase in dobutamine use (14% vs. 4%, p = .06) and red blood cell transfusions (30% vs. 18%, p = .07) in the first 24 hrs. For protocol patients with septic shock, 28-day in-hospital mortality was 20.3% compared with 29.4% for historical controls (p = .3).Clinical implementation of a comprehensive sepsis treatment protocol is feasible and is associated with changes in therapies such as time to antibiotics, intravenous fluid delivery, and vasopressor use in the first 6 hrs. No statistically significant decrease in mortality was demonstrated, as this trial was not sufficiently powered to assess mortality benefits.