title: Bundled care for septic shock: an analysis of clinical trials.
abstract: BACKGROUND
  Sepsis bundles have been developed to improve patient outcomes by combining component therapies. Valid bundles require effective components with additive benefits. Proponents encourage evaluation of bundles, both as a whole and based on the performance of each component.
  
  
  OBJECTIVE
  Assess the association between outcome and the utilization of component therapies in studies of sepsis bundles.
  
  
  METHODS
  Database searches (January 1980 to July 2008) of PubMed, Embase, and the Cochrane Library, using the terms sepsis, bundles, guidelines, and early goal directed therapy.
  
  
  METHODS
  Inclusion required comparison of septic adults who received bundled care vs. nonprotocolized care. Survival and use rates for individual interventions were abstracted.
  
  
  RESULTS
  Eight unblinded trials, one randomized and seven with historical controls, were identified. Sepsis bundles were associated with a consistent (I2 = 0%, p = .87) and significant increase in survival (odds ratio, 1.91; 95% confidence interval, 1.49-2.45; p < .0001). For all studies reporting such data, there were consistent (I2 = 0%, p > or = .64) decreases in time to antibiotics, and increases in the appropriateness of antibiotics (p < or = .0002 for both). In contrast, significant heterogeneity was seen across trials for all other treatments (antibiotic use within a specified time period; administration of fluids, vasopressors, inotropes, and packed red blood cells titrated to hemodynamic goals; corticosteroids and human recombinant activated protein C use) (all I2 > or = 67%, p < .002). Except for antibiotics, sepsis bundle components are still being investigated for efficacy in randomized controlled trials.
  
  
  CONCLUSIONS
  Bundle use was associated with consistent and significant improvement in survival and antibiotic use. Use of other bundle components changed heterogeneously across studies, making their impact on survival uncertain. However, this analysis should be interpreted cautiously as these studies were unblinded, and only one was randomized.
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA. barochiaav@mail.nih.gov
authors.forename: Amisha V
authors.initials: AV
authors.lastname: Barochia
authors.forename: Xizhong
authors.initials: X
authors.lastname: Cui
authors.forename: David
authors.initials: D
authors.lastname: Vitberg
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Suffredini
authors.forename: Naomi P
authors.initials: NP
authors.lastname: O'Grady
authors.forename: Steven M
authors.initials: SM
authors.lastname: Banks
authors.forename: Peter
authors.initials: P
authors.lastname: Minneci
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kern
authors.forename: Robert L
authors.initials: RL
authors.lastname: Danner
authors.forename: Charles
authors.initials: C
authors.lastname: Natanson
authors.forename: Peter Q
authors.initials: PQ
authors.lastname: Eichacker
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016001:Confidence Intervals; D019983:Guideline Adherence; D006801:Humans; D016017:Odds Ratio; D017410:Practice Guidelines as Topic; D012772:Shock, Septic / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents