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

Objectives: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. Design:Prospective, interventional cohort study with a historical control comparison group. Setting:Urban, tertiary care, university hospital with 46,000 emergency department visits and 4,100 intensive care unit admissions annually. Patients:Inclusion criteria were a) emergency department patients aged ≥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. Intervention:A sepsis treatment pathway incorporating empirical antibiotics, early goal-directed therapy, drotrecogin alfa, steroids, intensive insulin therapy, and lung-protective ventilation. Measurements and Main Results: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). Conclusions: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.

[1]  Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock , 2003, Current infectious disease reports.

[2]  D. Schoenfeld,et al.  Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. , 2000, The New England journal of medicine.

[3]  J Ean,et al.  Efficacy and safety of recombinant human activated protein C for severe sepsis. , 2001, The New England journal of medicine.

[4]  Margaret M Parker,et al.  Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock , 2004, Critical care medicine.

[5]  E. Draper,et al.  APACHE II: A severity of disease classification system , 1985, Critical care medicine.

[6]  Gary Garber,et al.  The efficacy and safety of recombinant human activated protein C for the treatment of patients with severe sepsis (vol 28, pg 48, 2000) , 2001 .

[7]  David W Bates,et al.  Mortality in Emergency Department Sepsis (MEDS) score: A prospectively derived and validated clinical prediction rule* , 2003, Critical care medicine.

[8]  D. Berwick.  Disseminating innovations in health care. , 2003, JAMA.

[9]  C. Gross,et al.  Impact of randomized trial results on acute lung injury ventilator therapy in teaching hospitals. , 2003, American journal of respiratory and critical care medicine.

[10]  Daniel Talmor,et al.  A blueprint for a sepsis protocol. , 2005, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[11]  T. Clemmer,et al.  A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. , 1987, The New England journal of medicine.

[12]  J. Bartlett,et al.  Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. , 2004, Archives of internal medicine.

[13]  B. Bistrian,et al.  Intensive insulin therapy in critically ill patients. , 2002, The New England journal of medicine.

[14]  Leibovici,et al.  The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection , 1998, Journal of internal medicine.

[15]  E. Ivers,et al.  Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock , 2001 .

[16]  Michael P Young,et al.  Ventilation of patients with acute lung injury and acute respiratory distress syndrome: Has new evidence changed clinical practice?* , 2004, Critical care medicine.

[17]  J. Siegel.  Assessing the use of activated protein C in the treatment of severe sepsis. , 2002, The New England journal of medicine.

[18]  J. E. Carceller.  American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis , 1992, Critical care medicine.

[19]  J. Vincent,et al.  Has the mortality of septic shock changed with time. , 1998, Critical care medicine.

[20]  G. Clermont,et al.  Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care , 2001, Critical care medicine.

[21]  E. Rivers,et al.  Early goal-directed therapy prevents organ failure and mortality in severe sepsis and septic shock , 2003 .

[22]  N. Tritos.  Corticosteroid insufficiency in acutely ill patients. , 2003, The New England journal of medicine.

[23]  T. Calandra,et al.  Antibiotics in sepsis , 2001, Intensive Care Medicine.

[24]  W. Knaus,et al.  Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. , 1992, Chest.

[25]  D. Pittet,et al.  The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. , 1995, JAMA.

[26]  J. Garnacho-Montero,et al.  Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis* , 2003, Critical care medicine.