title: Early goal-directed therapy in the treatment of severe sepsis and septic shock.
abstract: BACKGROUND
  Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit.
  
  
  METHODS
  We randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), end points with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups.
  
  
  RESULTS
  Of the 263 enrolled patients, 130 were randomly assigned to early goal-directed therapy and 133 to standard therapy; there were no significant differences between the groups with respect to base-line characteristics. In-hospital mortality was 30.5 percent in the group assigned to early goal-directed therapy, as compared with 46.5 percent in the group assigned to standard therapy (P = 0.009). During the interval from 7 to 72 hours, the patients assigned to early goal-directed therapy had a significantly higher mean (+/-SD) central venous oxygen saturation (70.4+/-10.7 percent vs. 65.3+/-11.4 percent), a lower lactate concentration (3.0+/-4.4 vs. 3.9+/-4.4 mmol per liter), a lower base deficit (2.0+/-6.6 vs. 5.1+/-6.7 mmol per liter), and a higher pH (7.40+/-0.12 vs. 7.36+/-0.12) than the patients assigned to standard therapy (P < or = 0.02 for all comparisons). During the same period, mean APACHE II scores were significantly lower, indicating less severe organ dysfunction, in the patients assigned to early goal-directed therapy than in those assigned to standard therapy (13.0+/-6.3 vs. 15.9+/-6.4, P < 0.001).
  
  
  CONCLUSIONS
  Early goal-directed therapy provides significant benefits with respect to outcome in patients with severe sepsis and septic shock.
authors.affiliation: Department of Emergency Medicine, Henry Ford Health Systems, Case Western Reserve University, Detroit, MI 48202, USA. erivers1@hfhs.org
authors.forename: E
authors.initials: E
authors.lastname: Rivers
authors.forename: B
authors.initials: B
authors.lastname: Nguyen
authors.forename: S
authors.initials: S
authors.lastname: Havstad
authors.forename: J
authors.initials: J
authors.lastname: Ressler
authors.forename: A
authors.initials: A
authors.lastname: Muzzin
authors.forename: B
authors.initials: B
authors.lastname: Knoblich
authors.forename: E
authors.initials: E
authors.lastname: Peterson
authors.forename: M
authors.initials: M
authors.lastname: Tomlanovich
mesh_terms: D018806:APACHE; D000368:Aged; D000465:Algorithms; D001794:Blood Pressure; D002317:Cardiovascular Agents / Q000627:therapeutic use; D004636:Emergency Service, Hospital; D017707:Erythrocyte Transfusion; D005260:Female; D005440:Fluid Therapy; D006295:Health Resources / Q000706:statistics & numerical data; D006439:Hemodynamics; D017052:Hospital Mortality; D006786:Hospitals, Urban; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010100:Oxygen / Q000097:blood; D011446:Prospective Studies; D018805:Sepsis / Q000503:physiopathology / Q000628:therapy*; D012772:Shock, Septic / Q000503:physiopathology / Q000628:therapy; D016037:Single-Blind Method; D018746:Systemic Inflammatory Response Syndrome / Q000503:physiopathology / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D010100:Oxygen