A panel of 19 experts convened and published a recent JAMA paper entitled, “The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).”[1]

Sepsis is a hugely important syndrome in medicine, especially in the critical care arena. However, the definitions of sepsis and septic shock had not been revised since 2001.

As per the introduction to JAMA’s paper, “These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.”

Whether you work inside an ICU setting or at a general ambulatory clinic, the information and new definitions in this paper will prove useful to you. As such, we’ve broken down the major tenets to further your knowledge on this important update to the literature on sepsis.

Not too long ago, we were indoctrinated with the idea that sepsis can be viewed as a continuum from the mild systemic inflammatory response syndrome (SIRS)[2] to the much-feared septic shock. The classic definition, released over two decades ago, was that the presence of 2 or more criteria* meant that a patient was “in SIRS.” Combine 2+ SIRS criteria with an infectious source, and the patient had sepsis. If there is superimposed evidence of end-organ failure, the condition was dubbed “severe sepsis.” And, if the patient is hypotensive and not fluid-responsive, then s/he had entered the realm of “septic shock.” The SIRS criteria were simple enough for even a first-year medical student to employ. But it left us with a lot of questions…

“If I am running a mile with adequate increase in heart rate and respiratory rate, am I in SIRS?”

“If I’m home and sick with a 102.0℉ fever and appropriate tachycardia secondary to a GI bug, does that make me septic? I sure don’t need the ICU or even hospitalization.”

“Shouldn’t all sepsis, by nature of increasing morbidity and mortality, be labeled as severe’?”

The biggest qualm the expert panel had with the SIRS septic shock continuum is that sepsis is not simply a serious infection. It is a syndrome characterized by “an aberrant or dysregulated host response and the presence of organ dysfunction.”[1] A serious infection can lead to sepsis, but can also be handled appropriately by the immune system (fulfilling SIRS criteria + infection) without evidence of organ dysfunction. This is perhaps the biggest departure from our old dogmatic SIRS approach which focused too heavily on inflammation. Sepsis is more than an inflammatory state; it must involve end-organ dysfunction and an atypical host response, thereby increasing mortality. We now enter the realm of a different scaling system focusing on organ performance, which, in an accompanying paper,[3] trumps SIRS criteria in assessing disease severity: the Sepsis-related Organ Failure Assessment (SOFA).[4]

What is SOFA?

First described in 1996, it is a specific set of criteria that scales how well different organ systems are functioning. The scale takes into account the respiratory, hematologic, hepatic, cardiovascular, renal, and central nervous systems. (SOFA scoring can be found here). The JAMA paper demonstrates that SOFA scores outperform SIRS criteria in determining hospital mortality. While SOFA doesn’t guide management, it does allow us to “clinically characterize a septic patient.” Something I found most interesting in the article is that an infected patient with a SOFA score of 2+ has a ~10% risk of mortality. What is the risk of mortality for a patient with a STEMI? A mere 8.1%.[5] Granted, cardiovascular disease is much more common than sepsis. However, sepsis is not a rare occurance, and it should be a disease manifestation that, at the very least, is on our radar with any infected patient.

How do we fine-tune this radar?

The expert panel offered up another screening tool in the monitoring of a patient who might be approaching the realm of sepsis, the qSOFA (Quick SOFA) criteria. It is a stripped-down, wildly simple screening tool that can assess patients at the bedside without the need for any laboratory testing. The three criteria are respiratory rate > 22, altered mentation, and systolic blood pressure ≤ 100. If a patient fulfills 2 or more of these criteria, then s/he is more likely to have a poor outcome. A combination of these red flag symptoms should heighten awareness for sepsis in an infected patient, or force clinicians to consider infection in a patient if they had not already.

Another important facet of the paper was the explicit definition of terms we commonly use with septic patients. “Sepsis” was defined as “a life-threatening organ dysfunction caused by a dysregulated host response to infection.” Terse and elegant. The term “severe sepsis” was deemed “redundant.” All sepsis is severe, as “sepsis” itself represents organ dysfunction. “Septic shock” was defined as “a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone.” Clinical identifiers include “vasopressor requirement to maintain a MAP  65 mmHg and serum lactate level  2 mmol/L in the absence of hypovolemia.” This is a much more pointed and precise definition than the former, subjective standard of being “hypotensive despite adequate fluid resuscitation.”

A drawback to this paper is that it offers us little in terms of the management of sepsis (although this was not the paper’s aim). Cynics might deride it as a bunch of experts in a room putting definitions on conditions that already exist. However, I don’t think that the production of expert-level consensus definitions, the development of the qSOFA score, and the push to replace SIRS with SOFA can be overlooked. The paper achieves its goal of elevating the consciousness of readers regarding new tools in the recognition and definition of sepsis.

Here are the take home messages:

Development of qSOFA criteria = 2 or more of the following:

• respiratory rate > 22
• altered mentation
• systolic blood pressure  100.

If fulfilled, explore further for signs of organ dysfunction, and consider infection if you have not already.

A push for use of SOFA criteria:

A score of 2 or more above baseline translates to a 2 to 25-fold increased risk of dying compared to scores less than 2.

New Definitions:

• Sepsis – Life-threatening organ dysfunction caused by a dysregulated host response to infection
• Severe sepsis – Considered redundant; its usage is not recommended
• Septic shock – Sepsis with profound circulatory, metabolic, and cellular abnormalities with a concomitant increase in mortality; criteria include necessity of vasopressors to maintain MAP  65 and lactate > 2 mmol/L in the absence of hypovolemia.

*Temperature > 38℃ (or < 36℃); HR > 90; RR > 20 (or pCO2 < 32); WBC > 12,000 (or < 4000) or > 10% bands

References:

1. Singer M et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).JAMA. 2016 Feb 23;315(8):801-10.

2. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit. Care Med. 1992;20(6):864874.

3. Seymour CW et al. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):762-74. doi: 10.1001/jama.2016.0288.

4. Vincent JL et al. Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med. 1996;22(7):707-710.

5. Shah RU et al. Increasing percutaneous coronary interventions for ST-segment elevation myocardial infarction in the United States: progress and opportunity. JACC Cardiovasc Interv. 2015;8(1 pt B):139-146.