# Lower butyrylcholinesterase is associated with postoperative delirium in adult cardiac surgery patients: a secondary analysis of two prospective studies

## TL;DR

Lower preoperative butyrylcholinesterase activity is linked to a higher risk of delirium after cardiac surgery in older adults.

## Contribution

This study identifies butyrylcholinesterase activity as a novel predictor for postoperative delirium in cardiac surgery patients.

## Key findings

- Patients with postoperative delirium had significantly lower preoperative BChE activity.
- BChE activity was the only significant factor associated with delirium in multivariable analysis.
- Postoperative BChE activity remained lower in delirium patients, possibly due to inflammation.

## Abstract

Postoperative delirium (POD) is a serious complication after surgery and is associated with prolonged stay in the Intensive-Care-Unit (ICU), increased mortality, and cognitive decline. Older patients undergoing cardiac surgery are at higher risk for POD. Disbalance in the cholinergic pathway activity has been suggested to play an important role in the pathogenesis of POD. This secondary analysis investigates the association between butyrylcholinesterase (BChE) activity and POD in adult cardiac surgery patients.

A secondary analysis was performed using pooled data from two prospective studies including patients aged ≥ 50 years undergoing elective cardiac surgery. Preoperative cognitive baseline and BChE activity (preoperatively and on postoperative day one) were obtained as part of clinical routine care. POD was assessed by experienced clinicians using standardized diagnostic criteria (CAM-ICU, DSM-V, and medical records) up to five days after surgery. Association between BChE and POD were analyzed using multivariable logistic regression. Predictors were screened in univariate analyses (p ≤ 0.25) and included in the model using backward elimination based on Akaike’s Information Criterion.

A total of 188 patients’ datasets were included. The overall incidence of POD was 21%. Patients who developed POD had significantly lower preoperative BChE activity than those who did not (median 6.30 kU/L [IQR 5.55, 7.25] vs. median 7.70 kU/L [IQR 6.70, 8.90]; p < 0.001; d = 0.847). In multivariable logistic regression, BChE activity was the only significant factor associated with POD (OR 0.65, CI 95%: 0.48–0.86; padjusted < 0.028). Other factors did not reach statistical significance in the multivariable analysis. After surgery, BChE activity drop was significant in both groups. The median absolute value remained lower in the POD group (5.10 vs. 4.90 kU/L), though statistically non-significant.

This study confirmed that lower preoperative BChE activity is associated with higher odds of developing POD in adult patients undergoing cardiac surgery. These results suggest that BChE activity may identify patients at risk for POD. We suggest that a postoperative decrease in BChE activity is due to inflammatory processes.

“Low cholinesterase activity is a risk factor for delirium after cardiac surgery”: German Clinical Trials Registry (DRKS 00017144, registered 15.05.2019).

The online version contains supplementary material available at 10.1186/s12871-026-03662-w.