Surviving Sepsis Guidelines and Scientific Evidence?

Abstract

Evidence-based medicine is defined as the conscientious, explicit, and judicious use of the best current scientific evidence in making decisions about the care of individual patients. The practice of evidence-based medicine means integrating clinical acumen with the best available external evidence from systematic research. With MEDLINE adding more than 600 000 new articles a year and ‘‘medical knowledge’’ doubling every 4 years it is nearly impossible for any physician to keep abreast of all the relevant evidence from the existing literature. Clinical practice guidelines aim to bridge the gap between research and practice. Clinical practice guidelines embrace evidence-based medicine by rigorously distilling the highest level of evidence from the literature in an effort to help physicians provide the best possible care to their patients. The principle construct of the guideline development process is that they should be evidence-based and not opinion based, be fully transparent, and that the developers and sponsoring organization/organizations should be free of significant conflict of interest. Unfortunately the methodological quality of clinical practice guidelines developed by different organizations varies considerably, thereby impacting the confidence that we can place in their recommendations. In this issue of the Journal, Stoneking and coauthors using the ‘‘Surviving Sepsis Campaign International Guidelines for Management of Severe Sepsis and Septic Shock’’ as a model, explore physician adherence to guidelines and propose strategies to improve guideline compliance. It is regrettable that the authors used the Surviving Sepsis Campaign Guidelines to explore this topic, as these guidelines fail the most basic test of guideline validity. The major elements of the ‘‘6-hour resuscitation bundle’’ of the Surviving Sepsis Campaign Guidelines include fluid resuscitation to achieve a central venous pressure (CVP) of greater than 8 cm H2O and a central venous oxygen saturation (ScvO2) above 70%, with the use of blood and inotropic agents. While the concept of early resuscitation (as compared to delayed resuscitation) is a scientifically sound concept, there is now increasing recognition that the major elements of the ‘‘6-hour resuscitation bundle’’ are not supported by scientific evidence. Remarkably, the major elements of the 6-hour resuscitation bundle are based on a small (n 1⁄4 263), nonblinded, single-center study (the River’s Early GoalDirected Therapy [EGDT] study), in which the lead author had significant undisclosed conflicts of interest and where the validly of the data has come into question. Barochia and colleagues performed a systemic review of the association between the component therapies of the 6-hour resuscitation bundle and outcome. These authors concluded that the ‘‘current sepsis bundles may force physicians to provide unproven or even harmful care. As administered and studied to date, only antibiotics meet the stated criteria of proof for bundle inclusion.’’ Furthermore, it is noteworthy that the reported hospital mortality of the standard therapy group in the River’s EGDT study was 46%; this compares to 17% in a recent randomized controlled study which evaluated the outcomes of the 6-hour resuscitation bundle. Of significant concern is the fact that these flawed guidelines have been turned into performance measures. The Joint Commission and the Institute of Healthcare Improvement have used adherence to these guidelines (using checklists) as an indicator of quality of care delivered. Checklists are fine if you are a pilot, however, they can become dangerous when providing bed-side care to complex critically ill patients. While aggressive early fluid resuscitation followed by vasoactive agents (in those with persistent hypotension) remains the cornerstone of the management of patients with severe sepsis and septic shock, the end points of resuscitation should be based on validated physiologic variables that are individualized based on each patients’ comorbidities and unique clinical circumstances. The optimal approach to the management of patients with septic shock remains to be determined. It is unlikely that a ‘‘one-size fits all’’ approach will be appropriate for all patients. A number of multicenter, randomized controlled studies (ProCESS, ARISE) are currently