Clinical Context

Sepsis is a major public health concern. It accounts for more than $20 billion (5.2%) of total US hospital costs in 2011, with long-term physical, psychological, and cognitive disabilities creating major healthcare and social burdens. The incidence of sepsis is increasing, in part because of aging populations with more comorbid conditions, as well as greater recognition.

Since 2001, when definitions of sepsis and septic shock were last revised, there has been significant progress in the underlying pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology. The Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) convened a task force of 19 experts in sepsis pathobiology, clinical trials, and epidemiology to assess and update definitions for sepsis and septic shock.

Study Synopsis and Perspective

The definitions of sepsis and septic shock have been updated by an international task force for the first time in 15 years. New criteria for septic shock have been added, and standards for the rapid recognition of sepsis-related organ failure have been simplified.

"There are more than 2 million hospitalizations for sepsis in the United States each year, and it accounts for about 5% of the healthcare budget. It's an enormous public health burden," said Christopher W. Seymour, MD, MSc, from the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, who is a member of the Third International Consensus Definitions Task Force.

"Our care in sepsis is focused on prompt recognition and early treatment. We hope that the new criteria and definitions will be used by clinicians to find patients faster and get treatment started right away," Dr Seymour told Medscape Medical News.

The new definitions were presented here at the SCCM's 45th Critical Care Congress and were published in the February 23 issue of JAMA.^[1]

Quick Identification Key to Saving Lives

In the new criteria, the quick Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score is used to assess just 3 symptoms in patients with suspected sepsis: altered mental status, fast respiratory rate, and low blood pressure. Blood tests are not required.

"If patients with infection show two of the three criteria, they should be considered likely to be septic," said Dr Seymour, who led team that developed the score.^[2]

He and his group analyzed more than 800,000 encounters recorded in electronic health records at 177 hospitals around the world, including academic, community, public, private, and federal hospitals.

"This is one of the largest collaborative studies ever conducted in the field of critical care medicine. It is also one of the first studies of electronic health records in our field. We focused primarily on patients in the intensive care unit [ICU] who were receiving antibiotics and fluid cultures, as those were the patients who were thought to be infected," he explained.

The team analyzed 148,907 patients with suspected infection, and evaluated how well the existing and the new criteria predicted sepsis mortality in these patients.

Organ Failure Check Best in the ICU, Quick Score Better Elsewhere

In the old criteria for sepsis, the systemic inflammatory response syndrome score was a measure of respiratory rate, white blood cell count, heart rate, and fever.

The SOFA score and the logistic organ dysfunction system score are criteria that are more recent.

Dr Seymour and his colleagues looked at how well these existing scores for inflammation and organ dysfunction predicted mortality compared with the quick score.

"The quick sepsis-related organ failure assessment score has a range from 0 to 3, with 1 point each for systolic hypotension of 100 mm Hg or below, tachypnea of at least 22 breaths/min, and altered mental state," Dr Seymour reported.

His team used the area under the receiver operating characteristic curve (AUROC) to assess the predictive validity of the different scores. The quick score was a better predictor of hospital mortality for patients with suspected infection who were not in the ICU than for those in the ICU.

Table. Predictive Validity for Death

AUROC = area under the receiver operating characteristic curve; ICU = intensive care unit.

"The sequential organ failure assessment score found patients more likely to be septic both in and out of the ICU. But it involves the use of many lab tests and is a bit complex," Dr Seymour explained. For patients not in the ICU, the performance of quick sepsis-related organ failure assessment score was similar to that of the sequential organ failure assessment score, he added.

"This is what was recommended by the task force as the new criteria for sepsis: infection plus two or more sequential organ failure assessment points, and the use of quick sepsis-related organ failure assessment score as a prompt to identify patients likely to be septic early on," he said.

Redefining Septic Shock

Dr Seymour was also part of the team that developed the new criteria for assessing septic shock.^[3]

"For a decade, clinicians and researchers have classified patients with shock in very different ways -- one group may find that among patients with shock, only one in five die, whereas other groups may find that four of five die -- so there is wide variability. The task force wanted to bring some clarity to how we define shock," he said.

"The new definition for septic shock is the administration of vasopressors or vasoactive medication to maintain mean arterial blood pressure of 65 mm Hg or higher after adequate fluid resuscitation, with the presence of a high lactate (more than 2 mmol/L). It is a new criterion that shock requires a high lactate. This is in particular to identify a very sick group," Dr Seymour said.

New Criteria More Effective in Recognizing Sepsis

"We now have a scientifically based classification that will give the clinician at the bedside new and more effective ways to recognize the septic patient and the severely septic patient so as to afford the earliest possible intervention," said Timothy Buchman, MD, from Emory University in Atlanta, Georgia, who is past president of the Society of Critical Care Medicine and editor-in-chief of Critical Care Medicine.

"We expect that, as a result of these definitions, we will have the right population recognized, we will be able to apply a suite of proven interventions and, by providing the right care, right now, and doing that every time, we will see significant improvements in the recovery from this very lethal state," Dr Buchman told Medscape Medical News.

These studies were funded by the National Institutes of Health, the Department of Veterans Affairs, the Permanente Medical Group, the German Federal Ministry of Education and Research, the ESICM, and the SCCM. Dr Seymour discloses receiving personal fees from Beckman Coulter. Dr Buchman is the editor-in-chief of Critical Care Medicine, the official journal of the SCCM.

Society of Critical Care Medicine's (SCCM) 45th Critical Care Congress. Presented February 22, 2016.

Clinical Implications

• The updated SCCM/ESICM definition of sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection.
• The updated SCCM/ESICM definition of septic shock is a subset of sepsis with greater mortality risk than with sepsis alone because of particularly severe circulatory, cellular, and metabolic abnormalities.
• Implications for the Healthcare Team: Members of the healthcare team should be aware that these updated definitions should improve consistency across epidemiologic studies and clinical trials and allow earlier diagnosis and intervention for patients with sepsis or at risk for the development of sepsis.

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