The 2001 International Sepsis Definitions Conference involved five medical professional societies. A stratification system, similar to cancer staging, was developed predominantly to predict therapy response rather than predict mortality.15 Components of the PIRO model were predisposition (baseline factors influencing survival, etc.), insult (infecting pathogens, source control, etc.), response (physiologic response, SIRS, etc.), and organ dysfunction (number of failing organs). However, the model was complex and difficult to standardize and quantify, and it was never universally applied. Both of the early definitions were based primarily on consensus of expert opinion.
The Sepsis-3 definition focused primarily on infection and end-organ dysfunction. Sepsis became infection and worsening or new end-organ dysfunction based upon the Sequential Organ Failure Assessment (SOFA) scale or quick SOFA. Sepsis includes vasopressor-dependent hypotension and excludes lactate. Septic shock was defined as vasopressor-dependent hypotension with lactate elevation. The Sepsis-3 process made several important advancements. It would be the first definition conference to: 1) employ data analytics in conjunction with clinical expertise rather than solely relying on expert opinion, 2) attempt a standardized process, and 3) acknowledge continued refinement as science and our understanding evolves.16 However, the Sepsis-3 definitions have not been universally adopted by emergency medicine, critical care, and low- and middle-income countries.17–24 The Surviving Sepsis Campaign (SSC) ultimately decided upon an intermediate definition, where sepsis was defined by the previous severe sepsis definition (not including persistent hypotension) and septic shock remained any vasopressor-dependent hypotension. Henning et al did an excellent job illustrating implications of the different definitions.25
Unfortunately, sepsis continues to be an elusive entity, recognized by most and unmistakably defined by none.
“There are two great shocks for every emergency medicine resident: one, not every patient is sick, and two, many patients are much sicker than they first appear.” —Peter Rosen1
Definition usefulness is based upon the purpose for which it is derived, combined with the ability to effectively operationalize it within a target environment. Purpose is based upon the context of value and prioritization.16 Effective operationalization involves pragmatic implementation within the environment to which it is applied.
“Emergency medicine is in the business of sensitivity.” —Donald Yealy
Importance of Perspective
When working in the ICU, the intensivist is concerned about specificity. There are limited resources appropriately reserved for the most acutely ill. If intensivist assessment of a patient denied ICU admission is incorrect, the patient is invariably still in a hospital-based, monitored setting. With unexpected deterioration, accommodations can be made and resources leveraged. In the emergency department, the physician is concerned about sensitivity, or who could be missed. An incorrect assessment of a patient who decompensates after being discharged home is not afforded the same accommodations and may have significant consequences. For example, when the SSC data from the septic shock manuscript were divided into hypotension and normal lactate or normotension and lactate >4 mmol/L, the mortality was essentially the same at 30 percent. Hypotension was included in the definition of sepsis, and lactate was not. Although the authors never dissuaded using lactate because, from their perspective, lactate added no additional predictive validity for mortality or ICU resources, it was only retained during hypotension. From an emergency medicine perspective, a quick point-of-care test that identifies a patient at risk is of great value. If mortality and a prolonged ICU stay are averted, it could signal a job well-done through early identification and treatment rather than unnecessary information.