After Sepsis Hospitalization, Elevated Biomarkers Linked to Readmission and Death May Persist

Two-thirds of sepsis survivors were found to have persistent elevated circulating biomarkers for both inflammation and immunosuppression, with a higher risk of readmission and mortality—particularly due to cardiovascular disease and cancer—compared with patients with normal biomarkers in the year following the index hospitalization, according to a report in JAMA Network Open.

“Persistent elevation of inflammation and immunosuppression biomarkers is common up to a year ... and may be associated with poor long-term outcomes.”-Sachin Yende, MD, MS, Deputy Chief of Staff, Veterans Affairs Pittsburgh Healthcare System

“The dysregulated host immune response activated during sepsis may persist up to one year,” write the authors. “Our findings suggest that long-term immunomodulation strategies should be explored in patients hospitalized with sepsis.”

Investigators analyzed data collected via bedside assessments, home interviews, and medical records on 483 adults (mean age, 60.5 years; male, 54.9%; white, 82.2%) hospitalized for sepsis in one of 12 U.S. hospitals across eight states from 2012 to 2017.

Post-discharge follow-up included measurements at three, six, and 12 months of circulating biomarkers of pathways activated during sepsis: inflammation, immunosuppression, hemostasis, endothelial dysfunction, and oxidative stress.

Overall

• 77.8% of sepsis patients had at least one chronic disease.
• 88.4% were discharged to home; 11.6%, to a long-term care facility.
• 42.5% were readmitted during the following year, with 31.7% of those being readmitted ≥ 3 times. Median time to first readmission was 63 days.
• 8.9% had died by three months; 11.6%, by six months; 17.6%, by 12 months.
• Common causes of death included cancer (46.4%), infection (23.2%), and cardiovascular disease (17.4%).

Key Findings: Biomarkers

• Elevated inflammation markers were observed in 25.8% of patients at three months; in 30.2% at six months; and in 25.6% at 12 months.
• Elevated immunosuppression markers were seen in 46.4% of patients at three months; in 44.9% at six months; and in 49.4% at 12 months.
• Based on these trajectories, two common phenotypes were identified: hyperinflammation and immunosuppression phenotype (68.3% of patients) and normal phenotype (29.6%).

Patients with the hyperinflammation and immunosuppression phenotype had similar clinical characteristics, in-hospital course, age, chronic disease burden, and illness severity compared with patients with the normal phenotype.

Phenotypes and Outcomes

Compared with normal phenotype, patients with the hyperinflammation and immunosuppression phenotype had higher:

• One-year mortality (odds ratio [OR], 8.26; 95% confidence interval [CI], 3.45 to 21.69; P < 0.001)
• Six-month all-cause readmission or mortality (hazard ratio [HR],1.53; 95% CI, 1.10 to 2.13; P = 0.01)
• Six-month readmission or mortality attributable to cardiovascular disease (HR, 5.07; 95% CI, 1.18 to 21.84; P = 0.02)
• Six-month readmission or mortality attributable to cancer (HR, 5.15; 95% CI, 1.25 to 21.18; P = 0.02)

Source: Yende, S., et al. (2010). Long-term host immune response trajectories among hospitalized patients with sepsis. JAMA Network Open, 2(8):e198686. DOI: 10.1001/jamanetworkopen.2019.8686. Veterans Affairs Pittsburgh Healthcare System; Clinical Research, Investigation, and Systems Modeling of Acute Illness Center; and Center for Critical Nephrology, Department of Critical Care Medicine, University of Pittsburgh, all in Pittsburgh, PA.