DOI: 10.1097/CCM.0b013e3182148c03

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PMID: 21610584

Issn Print: 0090-3493

Publication Date: 2011/05/01


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“Sepsis—It ain't so much what you don't know that gets you into trouble, it's what you know for sure that just ain't so.”—with apologies to Mark Twain*

I. Alan Fein

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Excerpt

Volumes have been written about sepsis, especially in the pages of this journal, and rightly so. Sepsis continues to be the problem child of medicine: unwanted, persistent, ubiquitous, mysterious, and maddeningly difficult to manage. Although the mortality rate has decreased somewhat in recent decades, the number of sepsis-related deaths continues to spiral higher, accounting for over 9% of all deaths in the United States (1). Sepsis is involved in some 2% of all hospitalizations, accounts for 20% of all admissions to intensive care units, and is the leading cause of deaths in noncardiac intensive care units. The concepts of sepsis and a sepsis syndrome have been with us since the days of Hippocrates (2) and have begged for clarification ever since. Of course, when astute clinicians have had flashes of insight that could not only move science forward but save innumerable lives as well, the medical community has historically been less than receptive. Witness the response to Semmelweiss' observations regarding puerperal sepsis and handwashing. Oblivious to the fact that Semmelweiss reduced the mortality rate on his maternity ward from >18% to <3%, he was fired from his position and ridiculed mercilessly by his contemporaries. In America, the obstetrician Charles Meigs famously proclaimed that “Doctors are gentlemen, and gentlemen's hands are clean.” Meigs was the acknowledged leader of obstetrics in America and was also a lifelong opponent of obstetrical anesthesia, believing it to be morally dubious. Semmelweiss died impoverished in an insane asylum a few years later (3).
More than a century ago, Osler (4) was the first to recognize that there was more to sepsis than just infection, noting that “except on few occasions, the patient appears to die of the body's response to infection rather than from the infection.” The 1991 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference belatedly sought to define the terminology of sepsis and provide guidance for treatment (5). In 2002 the European Society of Intensive Care Medicine and the Society of Critical Care Medicine initiated the Surviving Sepsis Campaign, an ongoing effort to develop and propagate evidence-based guidelines for the management of sepsis. This effort was updated in 2008, with the involvement and endorsement of 18 professional societies and organizations (6). In spite of these efforts, the level of “sepsis literacy” remains low not only among the lay public (7) but, surprisingly, among physicians and intensivists as well (8). Nevertheless, the Surviving Sepsis Campaign has proven to be dramatically successful in academic and community hospitals alike when guideline bundles are followed (9).
In this issue of Critical Care Medicine, Vincent and colleagues (10) present evidence that challenges an untested assumption of conventional wisdom: persistent rather than worsening organ failure as measured by the Sequential Organ Failure Assessment (SOFA) score is the most common presentation of septic patients before death in the intensive care unit. This study mined data accumulated in the fairly robust INDEPTH database, which pooled information from five industry-sponsored clinical trials of over 4,000 patients with severe sepsis. The goal of these trials was to assess the impact of treatment with activated protein C and a secretory phospholipase A2 inhibitor. The authors openly admit to several major limitations in this study, including the following: the initial studies comprising the database were not designed to explore the cause of death in severe sepsis, there is inadequate information relating to end-of-life practices, and there were no independent determinations of the cause of death. Most patients died of multiple-organ failure, with fairly stable SOFA scores in the days before death.

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