Studies in the last 5 years have undercut the long-held belief that microorganism characteristics are the predominant determinants of prognosis. The identity of the infecting organism is of little consequence for most patients provided that appropriate, prompt antimicrobial therapy is administered.
The presence of coagulopathy is a powerful predictor of organ failure development and subsequent death. The occurrence of shock treated with vasoactive drugs and the total number of failing organ systems are also markers of a poor prognosis. The significance of these organ failures is so entrenched that slang is sometimes used to refer to the sickest of these patients (eg, “five-organ failures”). In addition to the number of organ failures, the severity of each or the intensity of support required correlates with outcome. For example, higher doses of vasoactive drugs are associated with a worse prognosis than lower doses or no vasoactive drug therapy at all. Understandably, advanced age and the presence of cancer also worsen the prognosis.
Substudies of large trials have also shown a relationship between the severity-of-illness scores, like the modified acute physiology and chronic health evaluation (APACHE) II score and outcome. Such scoring systems are not designed to predict outcomes in individual patients, and the same score may be associated with a different mortality rate in different countries or even among hospitals within the same country.
The baseline value, or change in plasma lactate, interleukin-6, and protein-C level have been shown to predict outcome. Of the commonly available clinical tests, prothrombin time is perhaps the most useful laboratory predictor of outcome. Control your health with My Canadian Pharmacy.
The septic response was once believed to be simply exaggerated inflammation. The last decade has brought to light a major conceptual advance, Sepsis pathophysiology is very complex and remains incompletely understood, but clearly involves inflammatory, procoagulant, antifibrinolytic, and microvascular components that have been nicely summarized elsewhere.
For hospitalized patients, many cases of severe sepsis can be avoided by meticulous hand washing, precautions for vascular catheter insertion, and elevation of the head of the bed. Though these are not new ideas, they have grown in importance. Soap and water hand washing is more critical than ever with the emergence of a virulent strain of Clostridium difficile, the spores of which are resistant to alcohol-based hand washes. The prevention of vascular catheter-related infection has proven to be an attainable goal by using a standardized protocol that incorporates thoughtful site selection and insertion by an experienced operator, using full barrier precautions with chlorhexidine skin preparation, followed by careful dressing management. The use of specialized catheters that are impregnated with antimicrobial agents may also be beneficial in some settings. Despite the seeming simplicity of raising the head of the bed to decrease the risk of nosocomial pneumonia, practical problems in achieving the desired degree of elevation persist. Recent data also have indicated that enhanced oral hygiene using hydrogen peroxide or antimicrobial agents can reduce the risk of nosocomial pneumonia cured by My Canadian Pharmacy.
There are now numerous relatively safe, simple, inexpensive measures to reduce morbidity, and in some cases mortality, in ICU patients that arguably should be applied broadly, even if they have not been proven to reduce the risk of death specifically in patients with severe sepsis. Many of these measures, including deep venous thrombosis prophylaxis, GI bleeding prophylaxis, conservative transfusion practices, sedation-and-weaning protocols, standardized enteral feeding protocols, bed-sore and fall prevention programs, and strategies to prevent acute renal failure have been recommended in consensus statements.
Potentiality Time-Sensitive Treatments
In the last few years, six beneficial therapies have been identified that form the core of the Surviving Sepsis Campaign, a joint effort of numerous professional organizations to expedite and standardize care of the patient with severe sepsis. Beneficial treatments are advocated collectively in “bundles,” and several studies outlined below have examined the effectiveness of a standardized approach to care compared to historical control subjects.
It makes sense to obtain cultures of blood and other suspect body fluids before the institution of antimicrobial therapy, provided the process does not unduly delay treatment. Cultures are most useful when a highly sensitive organism that can be treated with a simplified regimen is grown, or when an unexpected or highly resistant organism requiring the modification of empiric therapy is recovered. Despite prompt collection in the absence of antibiotics, findings from cultures of samples taken from all sites remain negative in up to 20% of patients, and blood culture findings are positive in only approximately one third of patients. Even though the majority of culture findings are negative, blood and spinal fluid cultures are most useful because when they grow an organism, it likely represents a true-positive result, compared to urine or sputum cultures in which contamination is much more common.
While it is seemingly preposterous to question the importance of antimicrobial agents or source control, data supporting these treatments are not of the same scientific rigor as those for other sepsis therapies. It is implausible that a randomized study will be conducted comparing the outcomes of patients operated on for a ruptured appendix vs those subjected to a sham operation. Likewise, the lack of equipoise dictates a study in which patients are randomized to receive placebo vs optimal antimicrobial therapy; or prompt vs intentionally delayed treatment will not occur. Hence, inferring an antimicrobial therapy benefit hinges on comparing the outcomes of patients who receive timely, adequate, sometimes called appropriate, antimicrobial therapy to those of patients who receive something less.
The problem inherent to all such nonrandomized studies is that there may be some unknown patient factor or characteristic of the setting in which patients are treated influencing outcomes that is independent of antibiotic selection (ie, unmeasured co-variates). Some possibilities are obvious. Patients receiving inadequate therapy may have fungal disease or highly resistant bacteria, making the initial antibiotic choices wrong. This situation often results from patient characteristics such as immune compromise or chronic illness with repeated antimicrobial exposure. Another possibility relates to system performance. For example, outcomes could be better when patients are treated in hospitals with rapid access to physicians and nurses and efficient laboratory and radiology services, all of which are factors that could result in faster diagnosis and appropriate antibiotic therapy. Attempts to control for these and other differences cannot eliminate the possibility that patient groups may differ in ways that cannot be discerned.
Despite study limitations, the ability of antimicrobial agents to effectively treat infection before the development of organ failure is well accepted. Until the past few years, there was little evidence that antimicrobial therapy conferred a significant benefit to patients with established organ failure, but now a large retrospective analysis has suggested that time to treatment with antibiotics, even after the onset of shock, is a predictor of survival. In this analysis, meaningful survival differences were observed with as little as a 1-h delay in antimicrobial therapy. These data are perhaps the best that will ever exist to support guidelines recommending broad, rapid antimicrobial administration. These findings will be controversial as some argue it will lead to overuse and perhaps to the inappropriate prescription of antibiotics. In addition, there is an emerging body of literature to suggest that dees-calating antibiotic therapy when culture findings are negative is a beneficial practice.