Elucidating the Spectrum of Disease Severity Encompassed by Sepsis

Abstract

The term sepsis commonly evokes a critically ill patient with multiorgan failure who requires immediate and aggressive lifesaving care. In the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined conceptually as "life-threatening organ dysfunction caused by a dysregulated host response to infection." 1(p801) The Sepsis-3 task force recommended operationalizing this definition as suspected infection and a concurrent increase in the Sequential Organ Failure Assessment (SOFA) score by 2 or more points. A growing body of work is making it increasingly clear, however, that these clinical criteria identify many patients with mild infections that respond quickly to treatment in addition to individuals with life-threatening critical illness. 2 Peltan and colleagues 3 reported the prevalence, characteristics, and outcomes of adult patients with sepsis who were discharged alive from the emergency departments (EDs) of 4 hospitals in Utah.The investigators used detailed electronic health record data to identify 12 333 ED patients with suspected infection (defined as the collection of a clinical culture and administration of intravenous antibiotics) and organ dysfunction (defined as an increase in SOFA score by 2 or more points higher than baseline), in accordance with Sepsis-3. 1 Peltan and colleagues 3 found that 16.1% of patients who met the sepsis criteria were discharged alive from the ED. Similar observations have previously been reported. A national study of ED visits between2009 and 2011 that defined sepsis using diagnosis codes and/or clinical criteria reported that approximately 20% of patients with sepsis did not require inpatient admission. 4 Another study reported that, among 67 733 patients with sepsis diagnosis who were admitted to 110 US hospitals, 1 in 10 were discharged alive within 3 days. 5 The analysis by Peltan and colleagues 3 expands on these studies by providing the clinical characteristics and 30-day outcomes of patients with sepsis who were discharged from the ED.These patients tended to be younger and less severely ill compared with those who were admitted to the hospital, with fewer perturbations in their vital signs, milder organ dysfunction, and higher rates of arrival by private vehicle over ambulance. Two-thirds had urinary infections, whereas those who were admitted to the hospital more commonly had pulmonary or intra-abdominal infections.The 30-day mortality rate in patients who were discharged was only 0.9% compared with 8.3% in those who were hospitalized. Although both crude and risk-adjusted 30-day mortality rates were lower in patients with sepsis who were discharged from the ED vs admitted to the hospital, Peltan and colleagues 3 recognized the massive potential for residual confounding and were careful not to overstate these findings as support for routine outpatient sepsis management. Rather, the authors concluded that most ED clinicians synthesize the entire constellation of objective and subjective clinical data to appropriately triag...

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

“…Sepsis encompasses a spectrum of illnesses with varying severities ( 16 , 17 ), raising the possibility of treating patients as a continuum. Therefore, we used diffusion maps to order the samples in our reference sets into a progression.…”

An immune dysfunction score for stratification of patients with acute infection based on whole blood gene expression

“…Interestingly, it was previously thought that systemic inflammatory response syndrome (SIRS), sepsis, and septic shock formed a continuum 17 , but evidence of different molecular processes operating in these conditions led to SIRS being removed as a diagnosis in Sepsis-3. 29,30 While this simplifies diagnostic criteria, a spectrum of severities and mechanisms of immune dysfunction exists within sepsis 19 , and it is recognised that Sepsis-3 guidelines might fail to identify individuals with lower severity 18 . SRSq transcends diagnostic conventions and provides a quantitative metric of immune dysfunction, potentially supporting clinical decision making.…”

“…Sepsis can be viewed as a spectrum of illnesses with varying severities [17][18][19] , which raises the possibility of modelling patients as a continuum. We did this by using diffusion maps (Methods), a method designed to embed samples into a low-dimensional space that reflects their original connectivity.…”

Applications of peptides in nanosystems for diagnosing and managing bacterial sepsis

“…Sepsis is a medical emergency and a life-threatening condition associated with a global disease burden [52]. Despite all experimental and clinical research efforts, sepsis remains one of the leading causes of morbidity and mortality in critically ill patients [53].…”