标题: New Developments in Sepsis（有翻译） [打印本页] 作者: wangmax 时间: 2007-1-8 09:47 标题: New Developments in Sepsis（有翻译） Defining Sepsis
The current definitions and classification for the sepsis syndromes date back to the landmark expert panel conference convened in 1991 by Roger Bone under the auspices of the American College of Chest Physicians and the Society of Critical Care Medicine.[1] The major objectives of the conference were two-fold: (1) to provide simple, widely accepted, and clinically applicable definitions to categorize patients for clinical studies and therapeutic trials in sepsis; and (2) to help better identify patients at high risk of poor outcome who would potentially benefit from early interventions and new adjuvant therapies for sepsis. The paradigm adopted was that clinical sepsis was the expression of the host response to infection and could present in various stages of severity, evolving from the least to the most severe, depending on the characteristics of infection and host factors.
Of note, the expert panel promulgated definitions for a few clinical conditions, which together help our understanding of sepsis. The systemic inflammatory response syndrome (SIRS) represents physiological derangements that are nonspecific but are expected to be present in patients with sepsis. Sepsis was then defined as present for patients in whom infection was accompanied by at least 2 SIRS criteria. Also of note, severe sepsis was defined as the intersection of sepsis and acute organ dysfunction, such as renal failure, respiratory failure, disseminated intravascular coagulation, or shock. Thus, septic shock (sepsis with refractory hypotension despite fluid replacement) is effectively a form of severe sepsis. Although these definitions were imperfect, they provided a useful framework for subsequent pathophysiologic and epidemiologic studies, as well as for the conduct of successful clinical trials in the field in the ensuing 15 years.
However, it was soon recognized that some patients with clinically overt sepsis did not fulfill the definition for SIRS; conversely, the SIRS criteria lacked specificity in intensive care unit (ICU) patients and had a poor discriminating power to identify patients at high risk for sepsis from other patients having a nonspecific inflammatory response to various insults. Clinical symptoms characterizing the systemic inflammatory response are present at some point in time in a large proportion of acutely ill patients. Surveys of high-risk hospitalized patients have found that criteria for SIRS were met for between 44%[2] and 68%[3] of subjects. In these studies, infection was documented (ie, sepsis) in less than 50% of cases. Furthermore, the occurrence of SIRS is even more common in postoperative and trauma patients, irrespective of the presence of infection. Therefore, the SIRS criteria are not specific for infection or sepsis. Similarly, surveys of critically ill patients find that SIRS are not sensitive indicators of sepsis either. Studies conducted in various ICUs have shown that between 10% and 43% of sepsis patients do not meet the SIRS criteria.[4,5] In addition, accumulated knowledge suggested that addition of predisposing factors to sepsis, or of biological markers, might be useful to complement the sepsis definitions with the aim to identify high-risk patients, and that organ dysfunctions could be identified using a broader range of clinical and biological markers than originally defined.
These definitions were thus revisited in 2001 by an enlarged expert panel, in an attempt to resolve some of the problems with the original definitions.[6] The conclusions from this panel were that the original definitions remained valid for practical purposes (and especially for enrollment into clinical trials), although several additions could be considered to better characterize or stratify patients in clinical studies. Included in this concept were biomarkers (such as C-reactive protein, procalcitonin, or cytokines) to either differentiate infection from noninfectious SIRS or to prognosticate clinical outcomes; as well as other measurable markers of clinical risk (such as genetic predisposition) or readily apparent clinical variables such as host-specific variables (eg, comorbidities) or infection-specific variables (eg, type or source of infection). This approach generated the PIRO concept (Predisposition, Infection, host Response, Organ dysfunction), which is hoped to better characterize and stratify patients into different risk groups, much as tumor staging is conducted in oncology.
未完待续。