Bundled care for septic shock: an analysis of clinical trials.
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.
Barochia
Amisha V
AV
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA. barochiaav@mail.nih.gov
Cui
Xizhong
X
Vitberg
David
D
Suffredini
Anthony F
AF
O'Grady
Naomi P
NP
Banks
Steven M
SM
Minneci
Peter
P
Kern
Steven J
SJ
Danner
Robert L
RL
Natanson
Charles
C
Eichacker
Peter Q
PQ
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
D000900:Anti-Bacterial Agents