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Redefining Sepsis

Amesh A. Adalja, MD, FACP, FACEP, FIDSA March 4, 2016

Sepsis is often the final common pathway of infectious diseases of all types that ultimately lead to morbidity and mortality. However, the concept of sepsis is, to many physicians, a nebulous idea that lacks clear distinguishing characteristics. To standardize the meaning of the concept, essential for research, clinical care, and epidemiology, a consensus process was used in 1991 and 2001 to generate definitions. These definitions, which included such terms as “systemic inflammatory response syndrome (SIRS)” and “severe sepsis,” were important steps in refining the concept of sepsis. A new definition, which reflects increased understanding of the pathophysiology underlying the sepsis process, was recently announced at the meeting of the Society of Critical Care Medicine (SCCM), and several companion pieces on the topic were published in JAMA. University of Pittsburgh Critical Care Medicine Chairman Derek Angus and Assistant Professor Christopher Seymour were instrumental in the development of the new definitions.


Organ Dysfunction Key

The prior definition of sepsis—SIRS caused by suspected infection—had increasingly been noted to be less useful, as it often captured mild illness (eg, streptococcal pharyngitis) and missed others. Also, by focusing attention on inflammation, it failed to account for the anti-inflammatory changes that occur during sepsis.

The new definition of sepsis, derived from studying 13 million electronic medical records at UPMC, is “life-threatening organ dysfunction caused by a dysregulated host response to infection,” which places the focus on infections that are severe enough to lead to organ dysfunction or death.


Emphasis on SOFA Scoring

The cornerstone for the detection of sepsis involves the employment of the Sequential Organ Failure Assessment score (SOFA). The SOFA score involves measuring parameters of oxygenation, liver function, kidney function, blood clotting, level of consciousness, and blood pressure. When a SOFA score changes by 2 from a person’s baseline level and infection is suspected, the sepsis threshold has been crossed. In order to simplify the process, and obviate the need to draw blood and perform laboratory tests, a quick SOFA (qSOFA) was developed; it involves assessing the patient’s respiratory rate (≥22), Glasgow Coma Scale (GCS) score (≤13), and systolic blood pressure (≤100 mm Hg). If 2 of these are abnormal in the context of suspected infection, sepsis should be suspected.

The category of severe sepsis (sepsis with organ dysfunction) was discarded. Septic shock is defined as a subset of sepsis “in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.”


Importance of the New Definition

The new definition of sepsis represents an important achievement because it reflects a deepening understanding of an extremely important process that may result from infection. As sepsis is understood as a cascading process that begins with aberrant host reactions to an infecting organism, it will lend itself to better recognition and treatment. In the future, as more is discovered about sepsis and its heterogeneity, the definition may evolve to facilitate a more nuanced approach to the septic patient, with much more specific targeting of therapies toward the aspect of host response that is dysregulated in a given patient at a given time.



Sepsis/septic shock. JAMA. Accessed March 1, 2016.