Immunological risk factors for sepsis-associated delirium and mortality in ICU patients

Abstract

BackgroundA major challenge in intervention of critical patients, especially sepsis-associated delirium (SAD) intervention, is the lack of predictive risk factors. As sepsis and SAD are heavily entangled with inflammatory and immunological processes, to identify the risk factors of SAD and mortality in the intensive care unit (ICU) and determine the underlying molecular mechanisms, the peripheral immune profiles of patients in the ICU were characterized.MethodsThis study contains a cohort of 52 critical patients who were admitted to the ICU of the First Affiliated Hospital of Jinan University. Comorbidity, including sepsis and SAD, of this cohort was diagnosed and recorded. Furthermore, peripheral blood samples were collected on days 1, 3, and 5 of admission for peripheral immune profiling with blood routine examination, flow cytometry, ELISA, RNA-seq, and qPCR.ResultsThe patients with SAD had higher mortality during ICU admission and within 28 days of discharge. Compared with survivors, nonsurvivors had higher neutrophilic granulocyte percentage, higher CRP concentration, lower monocyte count, lower monocyte percentage, lower C3 complement level, higher CD14loCD16+ monocytes percentage, and higher levels of IL-6 and TNFα. The CD14hiCD16- monocyte percentage manifested favorable prediction values for the occurrence of SAD. Differentially expressed genes between the nonsurvival and survival groups were mainly associated with immune response and metabolism process. The longitudinal expression pattern of SLC2A1 and STIMATE were different between nonsurvivors and survivors, which were validated by qPCR.ConclusionsNonsurvival critical patients have a distinct immune profile when compared with survival patients. CD14hiCD16- monocyte prevalence and expression levels of SLC2A1 and STIMATE may be predictors of SAD and 28-day mortality in ICU patients.

High Mobility Group Box 1 (HMGB1): Potential Target in Sepsis-Associated Encephalopathy

“…Jin et al (2022) suggested that chronic obstructive pulmonary disease (COPD) in an elderly study population (age > 60 years; n = 222) was associated with a lower risk of SAE (16.4% SAE vs. 27.8% non-SAE; p -value = 0.047) and lower mortality in the SAE cohort (20% survival vs. 13.9% non-survival; p -value = 0.008) [ 89 ]. This finding is inconsistent with other results described in Table 2 [ 37 , 91 , 92 , 96 ].…”

“…Several studies suggest that increasing age might be an independent risk factor for severe sepsis and SAE development (see Table 1 ) [ 37 , 89 , 90 , 91 , 92 ]. Roughly 60% of ~200,000 septic patients were older than 65 years with 80% case fatality [ 93 ].…”

“…Some studies investigated whether pre-existing cardiovascular disease (e.g., arterial hypertension, coronary artery disease (CAD), congestive heart failure (CHF), arrhythmias) significantly increase the risk of SAE. While Jin et al (2022) found pre-existing CAD to be a risk factor for SAE development [ 85 ], other studies were not able to confirm this [ 91 , 96 ].…”

“…Similarly, discrepancies remain whether hypertension, by itself, can be considered to be a risk factor [ 37 , 89 , 90 , 91 , 96 ].…”

“…Some studies have pointed out that patients at risk for SAE have more chronic liver disease (CLD) and alcohol abuse history [ 37 ], although this remains inconsistent with other studies [ 89 , 91 , 92 ]. Of note, CLD was associated with a higher mortality rate (HR 1.92; 95% CI: 1.54–2.39; p -value < 0.01) in patients suffering from SAE [ 37 ] ( Table 2 ).…”