Serum proteomic analysis in esophagectomy patients with postoperative delirium: A case-control study

Abstract

Background: Postoperative delirium occurs in up to 80% of patients undergoing esophagectomy. We performed an exploratory proteomic analysis to identify protein pathways that may be associated with delirium post-esophagectomy.

Objectives: Identify proteins associated with delirium and delirium severity in a younger and higher-risk surgical population.

Methods: We performed a case-control study using blood samples collected from patients enrolled in a negative, randomized, double-blind clinical trial. English speaking adults aged 18 years or older, undergoing esophagectomy, who had blood samples obtained were included. Cases were defined by a positive delirium screen after surgery while controls were patients with negative delirium assessments. Delirium was assessed using Richmond Agitation Sedation Scale and Confusion Assessment Method for the Intensive Care Unit, and delirium severity was assessed by Delirium Rating Scale-Revised-98. Blood samples were collected pre-operatively and on post-operative day 1, and discovery proteomic analysis was performed. Between-group differences in median abundance ratios were reported using Wilcoxon-Mann-Whitney Odds (WMWodds¹) test.

Results: 52 (26 cases, 26 controls) patients were included in the study with a mean age of 64 (SD 9.6) years, 1.9% were females and 25% were African American. The median duration of delirium was 1 day (IQR: 1-2), and the median delirium/coma duration was 2.5 days (IQR: 2-4). Two proteins with greater relative abundance ratio in patients with delirium were: Coagulation factor IX (WMWodds: 1.89 95%CI: 1.0-4.2) and mannosyl-oligosaccharide 1,2-alpha-mannosidase (WMWodds: 2.4 95%CI: 1.03-9.9). Protein abundance ratios associated with mean delirium severity at postoperative day 1 were Complement C2 (Spearman r_s = -0.31, 95%CI [-0.55, -0.02]) and Mannosyl-oligosaccharide 1,2-alpha-mannosidase (r_s = 0.61, 95%CI = [0.29, 0.81]).

Conclusions: We identified changes in proteins associated with coagulation, inflammation, and protein handling; larger, follow-up studies are needed to confirm our hypothesis-generating findings.

Keywords: Coma; Critical care; Delirium severity; Encephalopathy; Proteins.

Figure A.1.

Experimental Workflow.

Figure A.2.

Patients screened for eligibility in the study.

Figure A.3.

Co-expression of Angiotensinogen and Ceruloplasmin. AGT: Angiotensinogen, CP: Ceruloplasmin: C2: Complement C2; ITIH3: Inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3).