Bundled care for septic shock: an analysis of clinical trials

Abstract

Context: 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.

Data source: 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.

Data extraction: Inclusion required comparison of septic adults who received bundled care vs. nonprotocolized care. Survival and use rates for individual interventions were abstracted.

Main 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.

Conclusion: 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.

Figure 1

Study selection.

Figure 2

Effect of bundled care on the odds ratio of survival (95% confidence interval [CI]) for the seven studies analyzed and overall.

Figure 3

Effect of bundled care on antibiotic therapy including: A, antibiotics within a prespecified time period; B, mean time to antibiotics; and C, percentage of patients receiving appropriate antibiotics. CI, confidence interval.

Figure 4

Effect of bundled care on therapies based on set central venous pressure, mean arterial blood pressure, and central venous oxygen saturation goals including: A, total crystalloid use; and B–D, the percentage of patients receiving vasopressors, inotropes, and packed red blood cells (PRBC), respectively. CI, confidence interval.

Figure 5

Effect of bundled care on the percentage of patients administered (A) corticosteroids and (B) recombinant human activated protein C. CI, confidence interval.