Annals for Hospitalists Inpatient Notes - Sepsis-3 for HospitalistsSepsis Without SIRS

Spurred by inconsistent clinical recognition of sepsis, significant mortality, and lack of reliability of the current definition, the Sepsis-3 Task Force recently published a new approach to sepsis (1). Sepsis was once believed to be the direct toxic effect of pathogens. The Sepsis-1 (1992) and -2 (2001) Task Forces argued, instead, that infection often kills through the body's inflammatory response. Coupled to this reframing was the hope that systemic inflammatory response syndrome (SIRS) criteria would identify patients with such a response. For 20 years, we have taught that the diagnosis of sepsis is based on having 2 or more SIRS criteria with an infectious source. Alas, research on the SIRS hypothesis did not validate this hope. Among patients with infection and organ dysfunction in the intensive care unit (ICU), data suggest that 12% do not meet SIRS criteria (2). Further, nearly all hospitalized patients eventually meet SIRS criteria, regardless of sepsis status, if they stay long enough (3). Because SIRS lacks discriminant and convergent validity, the Sepsis-3 Task Force abandoned the use of SIRS and changed the recommended clinical approach to sepsis. The Sepsis-3 Task Force thus sought to identify characteristics that could raise clinical suspicion of sepsis among patients who were suspected or confirmed to be infected. Several scores, signs, and symptoms were evaluated in a cohort of 1.3 million medical records. Confirmatory analysis was done in 4 data sets of 706 399 encounters. Among infected patients in the ICU, the Sequential Organ Failure Assessment (SOFA) score most effectively identified patients who would die. Therefore, the Sepsis-3 Task Force recommended that the SOFA score be used to assist in identifying sepsis in critically ill patents, with an increase of 2 SOFA points (above baseline) raising probability of the diagnosis among infected patients. For infected patients outside the ICU, the novel and simpler quick SOFA (qSOFA) score was developed. This score assigns 1 point for each of the following characteristics: systolic blood pressure under 100 mm Hg, altered mental status (formally, Glasgow Coma Scale score of 15 or less, but practically any degree of acute alteration), or respiratory rate of 22 breaths/min or greater. For patients outside the ICU, qSOFA is superior to SIRS at predicting mortality (area under the receiver-operating characteristic curve, 0.81 vs. 0.76; P < 0.001) and noninferior to the more complex SOFA score (4). To be clear: qSOFA does not define sepsis outside the ICUrather, it is a warning of increased risk for death among those who are infected. Likewise, the absence of qSOFA points does not exclude sepsis, but it lowers the likelihood of a poor outcome. Progress aside, the response to the updated sepsis definition has not been uniformly positive (5). Some have called into question whether change was really necessary: SIRS positivity identifies nearly 88% of patients with sepsis, and sepsis mortality is decreasing worldwide with the current model. Concerns have also been raised about the interaction between the new definition and prior clinical experience and studies, as well as its generalizability given the relative lack of gender and geographic diversity in both the Sepsis-3 Task Force and data used in the development of these scores. Whether the Sepsis-3 definition will improve patient outcomes is an empirical question that needs further investigation. However, hospitalists should focus on the conceptual shift in transitioning from Sepsis-2 to Sepsis-3. The latter approach reinforces the primacy of a clinical definition of sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. Using SOFA and qSOFA, clinicians are able to monitor organ dysfunction among infected patients that then informs the suspicion of sepsis and consequent risk for mortality. This differs from the Sepsis-2 paradigm in which sepsis is ruled in or out simply by counting SIRS criteria. It must be emphasized that our current understanding of sepsis precludes a simple check-box approach and perhaps even a dichotomous categorization of a patient as either septic or not septic. Instead, patients exhibit varying degrees of maladaptive dysregulation. The reality remains that all hospitalized patients are at risk for sepsis. Without a gold-standard definition, hospitalists must remain vigilant for the clinical features of the sepsis syndrome and make treatment decisions on the basis of the level and trajectory of suspicion. Sepsis-3 emphasizes clinical judgment in this diagnosis but also calls for additional research on sepsis to guide more reliable clinical definitions. We hope that these efforts will ultimately reduce sepsis mortality as well as the long-term morbidity that plagues its survivors.