Bundled care for septic shock: An analysis of clinical trials

Care bundles or protocols that combine several medical practices have been proposed as tools to promote rapid adoption of proven therapies, benchmark performance, and improve patient outcomes (1). Reports that several practices instituted together could reduce the prevalence of catheter-related infection or mortality in mechanically ventilated patients supported this approach (2, 3). Care bundles have also been proposed based on the holistic principle that the whole is greater than the sum of its parts (4). Based on this therapeutic approach, the Institute for Healthcare Improvement and the Centers for Medicare and Medicaid Services recently proposed instituting “all or none” performance measures (5, 6). Hospital performance, and possibly re-imbursement in the future, may be based on the frequency with which all elements of a care bundle were administered together (7, 8). The Joint Commission and Institute for Healthcare Improvement have recommended that components of a bundle should individually have proven benefit and wide acceptance, and together have even greater benefit (1, 9, 10). Importantly, bundle proponents encourage determination that individual components add to aggregate beneficial effects on outcome (6). However, there is currently no consensus on methods and standards for the development and testing of valid care bundles. Although promising, care bundles pose challenges. Several care bundles posted on the Internet have not undergone rigorous peer review (11, 12). Some bundles addressing the same problem—sepsis—differ in content and compliance rates (13). Many bundles lack strong evidence for the efficacy of one or more of their individual components (14). Importantly, adoption of all bundle elements as a single intervention limits the ability to test the interdependent and independent efficacy of individual components (15). Therefore, the introduction of care bundles may mandate changes in standard care without the ability to fully monitor the impact of component parts. Resolving these issues has become critical as care bundles have evolved from preventing complications (e.g., catheter-related infections) to treating life-threatening conditions (e.g., sepsis). As bundle development and application lack clear standards but are increasing in frequency, we examined this approach for the treatment of sepsis. We performed a meta-analysis of clinical trials, testing the impact of sepsis bundles compared with nonprotocolized care. Component therapies of interest were adopted from two widely instituted sepsis bundles, i.e., a 6-hr acute bundle and a 24-hr management bundle (Table 1) that were based on guidelines originally developed by the Surviving Sepsis Campaign and available at the time of these clinical trials (12, 16). Our goals were to examine the effect of bundle institution on survival and the application of individual bundle components. Table 1 Components in two sepsis bundles formulated by the Surviving Sepsis Campaign (12, 16)