Distinguishing between 4 different subtypes of sepsis sets the stage for individualised treatment

Prof. Christopher Seymour (University of Pittsburgh School of Medicine, USA) presented data showing that 4 clinical sepsis phenotypes correlate with host-response patterns and clinical outcomes [1]. This work was simultaneously published in JAMA [2].

Successful treatment of sepsis has been more than vexing, and the reason for this, according to Prof. Seymour, is the existence of 4 different phenotypes. The 4 novel sepsis phenotypes -alpha (α), beta (β), gamma (γ), and delta (δ)- have different demographics, laboratory values, and patterns of organ dysfunction. Furthermore, they correlate with specific biomarkers and mortality. Their analysis also identified a subtype of patients at high risk of liver dysfunction and shock, who had the highest in-hospital death rates.

Prof. Seymour and colleagues examined 29 specific variables recorded in the electronic health record system of >20,000 patients identified with sepsis at 12 Pennsylvania hospitals from 2010 to 2012 (derivation cohort). Reproducibility of the findings was measured in a second dataset involving 43,000 patient arrivals at the Pennsylvania hospitals from 2013 to 2014 (validation cohort). Both cohorts were comparable with regard to mean age, gender distribution, and mean maximum 24-hour Sequential Organ Failure Assessment score.

The 4 sepsis subtypes are distinct in the following features:

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  • alpha (α): identified in ±33% patients; characterised by having the fewest abnormal laboratory test results, the least organ dysfunction, and the lowest in-hospital death rate (23%);
  • beta (β): identified in 27% of patients; defining characteristics including older age, more chronic illness, and kidney dysfunction;
  • gamma (γ): identified in ±25% patients; distinguished from β by association with elevated inflammation and primary pulmonary dysfunction; and
  • delta (δ): identified in 13% of patients is the least common and most deadly phenotype; characterised by liver dysfunction and shock, and the highest in-hospital mortality (32%).

Consistent differences by phenotype were seen. In the derivation cohort, cumulative 28-day mortality was 5% in the α phenotype, 13% in the β phenotype, 24% in the γ phenotype, and 40% in the δ phenotype. Across all cohorts and trials, 28-day and 365-day mortality were highest among the δ phenotype vs the other 3 phenotypes (P<0.001). Prof. Seymour concluded that a key goal is delivering targeted treatments to patients with sepsis in the way that treatment is now delivered for many cancers.

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   1. De Merle K, et al. A7470, ATS 2019, 17-22 May, Dallas, USA.
   2. Seymour CW, et al. JAMA. 2019;321(20):2003-2017.

Posted on 23 July, 201923 March, 2021