Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis

Seymour CW, Kennedy JN, Wang S, et al. JAMA. 2019 May 19. [CrossRef] [PubMed]

Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care. The authors derived sepsis phenotypes from 20,189 total who met Sepsis-3 criteria within 6 hours of hospital presentation at 12 Pennsylvania hospitals (2010-2012) using consensus k means clustering applied to 29 variables. Reproducibility and correlation with biological parameters and clinical outcomes were assessed in a second database (2013-2014; n = 43 086 total patients), in a prospective cohort study of sepsis due to pneumonia. Of the 4 derived phenotypes, the α phenotype was the most common (n = 6625; 33%) and included patients with the lowest administration of a vasopressor; in the β phenotype (n = 5512; 27%), patients were older and had more chronic illness and renal dysfunction; in the γ phenotype (n = 5385; 27%), patients had more inflammation and pulmonary dysfunction; and in the δ phenotype (n = 2667; 13%), patients had more liver dysfunction and septic shock. Phenotype distributions were similar in the validation cohort. The 28-day and 365-day mortality were highest among the δ phenotype vs the other 3 phenotypes (P < .001). This study shows that older sicker patients with sepsis are more likely to die. The authors conclude that further research is needed to determine the utility of these phenotypes in clinical care.