Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study.

INTRODUCTION: Current sepsis guidelines recommend antimicrobial treatment (AT) within one hour after onset of sepsis-related organ dysfunction (OD) and surgical source control within 12 hours. The objective of this study was to explore the association between initial infection management according to sepsis treatment recommendations and patient outcome. METHODS: In a prospective observational multi-center cohort study in 44 German ICUs, we studied 1,011 patients with severe sepsis or septic shock regarding times to AT, source control, and adequacy of AT. Primary outcome was 28-day mortality. RESULTS: Median time to AT was 2.1 (IQR 0.8 - 6.0) hours and 3 hours (-0.1 - 13.7) to surgical source control. Only 370 (36.6%) patients received AT within one hour after OD in compliance with recommendation. Among 422 patients receiving surgical or interventional source control, those who received source control later than 6 hours after onset of OD had a significantly higher 28-day mortality than patients with earlier source control (42.9% versus 26.7%, P <0.001). Time to AT was significantly longer in ICU and hospital non-survivors; no linear relationship was found between time to AT and 28-day mortality. Regardless of timing, 28-day mortality rate was lower in patients with adequate than non-adequate AT (30.3% versus 40.9%, P < 0.001). CONCLUSIONS: A delay in source control beyond 6 hours may have a major impact on patient mortality. Adequate AT is associated with improved patient outcome but compliance with guideline recommendation requires improvement. There was only indirect evidence about the impact of timing of AT on sepsis mortality.

Immunoglobulins in adult sepsis and septic shock.

For more than 30 years, intravenously administered immunoglobulins (ivIG) have been used to treat primary and secondary syndromes of immune deficiency. Increasing insight into pathomechanisms of severe sepsis and septic shock have led to the implementation of ivIG therapy in the strategies for adjunctive therapy in sepsis in both adults and children. Direct antitoxic effects, as well as indirect immunomodulatory mechanisms of ivIG have been described in the literature and were the basis for the rationale to use these substances in life-threatening infections and hyperinflammatory states. Several clinical trials have been performed, most of them as minor, investigator-initiated protocols. This review summarizes the results of clinical investigations and systematic meta-analyses that have implications for the development of therapeutic strategies, and international guidelines for the management of severe sepsis and septic shock in adult patients.

Sensitive, specific, predictive statistical basics: how to use biomarkers.

Biomarkers are frequently used in critically ill patients, especially during inflammatory and/or infectious diseases such as severe sepsis and septic shock. The rationale of when to measure laboratory parameters, which marker may be useful, and how to interpret the results is not well defined. Terms like sensitive, predictive, or significant to describe the capabilities of specific markers are often mixed up or misused, which may have fatal consequences regarding diagnosis and treatment. This review reflects some statistical basics with clinical examples, showing possibilities as well as limitations of how data for biomarkers may be used in critically ill patients.

Managing septic shock.

Although several successful clinical trials in the last 2-3 years have been greeted with enthusiasm by intensivists, severe sepsis and septic shock still have increasing incidence and more or less unchanged mortality. Within the last few years, the progress in sepsis research covering definitions, epidemiology, pathophysiology, diagnosis, and standard and adjunctive therapy as well as general measures such as treatment bundles is encouraging. In this report, a small selection of recent publications, focusing on the current discussion of activated protein C as well as the relevance of the Surviving Sepsis Campaign bundle therapy, is presented and the possible impact on clinical routine is discussed.

[Clinical value of the sepsis bundles and modes of implementation]. / Sepsis - Klinischer Stellenwert der Sepsisbündel und Möglichkeiten der Implementierung.

The sepsis bundles comprise the most important steps that have to be made in the first 24 hours following the sepsis diagnosis. Being comprehensive and manageable, they can be implemented in every ICU and in every hospital, and wherever this happens, more patients suffering from severe sepsis or septic shock survive. The ideal mode of implementation has yet to be found. Education and both financial and human resources play an important role for success, and so does the strong wish for improvement among the individual doctor, and among all responsible individuals within an institution or a scientific society caring for critically ill patients.

'Relation, association, attribution ...' - the multiple faces of death in critical care medicine.

Mortality is one of the most important quality markers in critical care, and there have been many epidemiological studies trying to identify risk factors to better understand the mechanisms leading to death in this complex disease. One of the major problems is that there are multiple factors contributing to fatal outcome of septic patients, and it is difficult to distinguish between those that are independent from the acute disease (comorbidities and 'risk factors') and those that are directly involved in the pathomechanisms of sepsis, thus leading to the 'sepsis-attributable' mortality. In this short commentary, some examples of different approaches of how to analyze data on mortality are presented.

Organ failure in sepsis.

The development of organ failure determines the course and prognosis of the septic patient. Although several successful clinical trials in recent years have raised the enthusiasm of intensivists, severe sepsis and septic shock still have an increasing incidence with more or less unchanged mortality. Recent sepsis research, including progress made in definitions, epidemiology, pathophysiology, diagnosis, standard and adjunctive therapy, and experimental approaches, is encouraging. This includes genomic information for stratifying subgroups of patients, a broader field of laboratory diagnostics due to clinical studies, and basic research on the cellular mechanisms of inflammation and organ dysfunction. Furthermore, new findings in pathogenesis and therapeutic approaches to organ failure merit attention. In this review, state-of-the-art publications are presented to elucidate the possible impact of sepsis-induced organ failure on clinical routine.

Between prediction, education, and quality control: simulation models in critical care.

Today, computer-aided strategies in social sciences are an indispensable component of teaching programs. In recent years, microsimulation modeling has gained attention in its ability to represent predicted physiological developments visually, thus providing the user with a full understanding of the impacts of a proposed scheme. There are several microsimulation models in human medicine, and they can be either dynamic or static. If the model is dynamic the course of variables changes over time; in contrast, in the static case time constancy is assumed. In critical care there have been several approaches to implement microsimulation models to predict outcome. This commentary describes current approaches for predicting disease progression by using dynamic microsimulation in pneumonia-related sepsis.