Persistent Inflammation and Risk of Mortality among Sepsis Survivors

Individuals with increased levels of inflammation after 1 year were associated higher rates of all-cause mortality and mortality attributable to cardiovascular disease and cancer.

A new study has found evidence that suggests persistent inflammation could be an indication sepsis patients are at a greater risk of dying or being readmitted to the hospital. 



Results of the study, which was led by investigators from the University of Pittsburgh School of Medicine, revealed that two-thirds of sepsis patients had persistent elevation of inflammation and immunosuppression biomarkers — investigators also found that inflammation increased a patient’s risk of mortality or readmission due to cardiovascular disease or cancer. 



“Patients discharged from the hospital aren’t out of the woods yet. Approximately 1 out of every 3 sepsis survivors will die in the following year,” said lead investigator Sachin Yende, MD, MS, of the University of Pittsburgh and vice president of critical care and deputy chief of staff at the Veterans Affairs Pittsburgh Healthcare System. “Our new findings about chronic inflammation post-discharge suggest that addressing this condition may be important to improve patients’ long-term outcomes.”

In an effort to guide future treatments and improve outcomes for sepsis survivors, investigators conducted a prospective, multicenter study that included 483 patients who had survived a hospitalization for spas between January 10, 2012 and May 25, 2017. Patients were recruited from 12 sites across the US and, for inclusion in the study, needed to have a sepsis infection and at least 1 organ dysfunction.

The mean age of the patients was 60.5 years and 54.9% (265) of the group was male. Investigators noted that 378 (77.8%) patients had at least 1 chronic disease and their mean Sequential Organ Failure Assessment score was 4.2. 



Assessments were performed a total of 5 times during the study period — twice during index hospitalization and again at 3, 6, and 12 months. During those assessments, investigators measured multiple inflammation and immunosuppression biomarkers as well as endothelial dysfunction, hemostasis, and oxidative stress.

The full list of biomarkers assessed includes IL-6, high-sensitivity C-reactive protein (hs-CRP), soluble programmed death liana 1 (sPD-L1), plasminogen activator inhibitor 1, D-dimer, E-selectin, intercellular adhesion molecule, vascular cell adhesion molecule 1, and nitrates.

During the study period, investigators identified 485 readmission among 205 (42.5%) patients. At 3 months, 43 (8.9%) of patients had died, 56 (11.6%) had died at 6 months, and 85 (17.6%) had died at the 12-month mark.

Investigators noted elevated hs-CRP levels among 23 (25.8%) patients at 3 months, 26 (25.6%) patients at 6 months, and 23 (25.6%) patients at 12 months. Additionally, elevated sPD-L1 levels were observed in in 45 patients (46.4%) at 3 months, 40 patients (44.9%) at 6 months, and 44 patients (49.4%) at 12 months.

Based on their observations, investigators created 2 phenotypes based on whether a patient had high or normal hs-CRP and sPD-L1 levels. 



After adjusting for multiple confounding factors, investigators found that those with the hyperinflammation and immunosuppression phenotype had higher 1-year mortality (OR, 8.26; 95% CI: 3.45 - 21.69; P<.001) and 6-month all-cause readmission or mortality (HR, 1.53; 95% CI: 1.10 - 2.13; P=.01). Additionally, investigators found that hyperinflammation and immunosuppression was associated with an increase in 6-month readmission or mortality attributable to cardiovascular disease (HR 5.07; 95% CI: 1.18 - 21.84; P=.02) or cancer (HR, 5.15; 95% CI: 1.25 - 21.18; P=.02). &#8232;&#8232;

Sepsis increases risk of heart disease and stroke, and, for the first time, we’ve linked these adverse outcomes to persistent inflammation,” said Derek Angus, MD, MPH, professor and chair of the University of Pittsburgh’s Department of Critical Care Medicine. “This opens the door to future studies into why high levels of inflammation persist for at least a year after hospital discharge and the development of treatments aimed at modifying the inflammation with the hope that will improve health.”

This study, “Long-term Host Immune Response Trajectories Among Hospitalized Patients With Sepsis,” was published online in JAMA Network Open.