Altered gene expression associated with postoperative delirium in patients undergoing surgery and anesthesia

Postoperative delirium is a severe complication associated with poor overall and especially neurocognitive prognosis after anesthesia and surgery. As a systemic phenomenon, peripheral immune response to surgical trauma may play a central role. Although analysis of differential gene expression in peripheral immune cells could provide insights into immune dysregulation in postoperative delirium (POD), no such analysis has been conducted yet in a sufficiently sized prospective cohort.

We performed gene expression analysis in N=599 cognitively healthy male and female patients ≥65 years who provided blood samples for microarray-based transcriptomics before major elective surgery and on the first postoperative day. Patients were followed up for delirium until the seventh postoperative day. We identified differentially expressed genes in POD using a multivariable linear regression framework adjusted for sex, age, body mass index, preoperative physical status, duration of anesthesia and operative procedure.

Preoperative gene expression was not significantly different in patients who were later diagnosed with POD. However, we identified a total of 1063 unique significantly associated genes which differed in baseline-corrected mRNA abundance among POD patients after surgery (n=394 positively, n=681 inversely). This set was significantly enriched for genes related to cellular and humoral immune response, RNA metabolism and platelet function.

Post-, but not preoperative gene expression in peripheral immune cells has been found to be altered in patients with POD. Whereas most enriched pathways were related to immune response and acute phase reaction, few molecular alterations were found, which may reflect nervous system alterations and need further clarification.

HIGHLIGHTS

• Postoperative delirium (POD) is a common severe complication in older surgical patients

• Systemic inflammation has been considered a major hallmark of POD

• We describe immune cell gene expression in a large prospective cohort of surgical patients

• POD is associated with postoperative, but no preoperative alteration in gene expression

• Differentially expressed genes are involved in immune, platelet, but also neuronal function