Preoperative Cognitive Abnormality, Intraoperative Electroencephalogram Suppression, and Postoperative Delirium: A Mediation Analysis

Abstract

Background: Postoperative delirium is a common complication that hinders recovery after surgery. Intraoperative electroencephalogram suppression has been linked to postoperative delirium, but it is unknown if this relationship is causal or if electroencephalogram suppression is merely a marker of underlying cognitive abnormalities. The hypothesis of this study was that intraoperative electroencephalogram suppression mediates a nonzero portion of the effect between preoperative abnormal cognition and postoperative delirium.

Methods: This is a prespecified secondary analysis of the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized trial, which enrolled patients age 60 yr or older undergoing surgery with general anesthesia at a single academic medical center between January 2015 and May 2018. Patients were randomized to electroencephalogram-guided anesthesia or usual care. Preoperative abnormal cognition was defined as a composite of previous delirium, Short Blessed Test cognitive score greater than 4 points, or Eight Item Interview to Differentiate Aging and Dementia score greater than 1 point. Duration of intraoperative electroencephalogram suppression was defined as number of minutes with suppression ratio greater than 1%. Postoperative delirium was detected via Confusion Assessment Method or chart review on postoperative days 1 to 5.

Results: Among 1,113 patients, 430 patients showed evidence of preoperative abnormal cognition. These patients had an increased incidence of postoperative delirium (151 of 430 [35%] vs.123 of 683 [18%], P < 0.001). Of this 17.2% total effect size (99.5% CI, 9.3 to 25.1%), an absolute 2.4% (99.5% CI, 0.6 to 4.8%) was an indirect effect mediated by electroencephalogram suppression, while an absolute 14.8% (99.5% CI, 7.2 to 22.5%) was a direct effect of preoperative abnormal cognition. Randomization to electroencephalogram-guided anesthesia did not change the mediated effect size (P = 0.078 for moderation).

Conclusions: A small portion of the total effect of preoperative abnormal cognition on postoperative delirium was mediated by electroencephalogram suppression. Study precision was too low to determine if the intervention changed the mediated effect.

Figure 1.. Relationship among Abnormal Cognition, Electroencephalogram Suppression, and Postoperative Delirium

The direct effect represents the expected change in delirium if preoperative abnormal cognition changes, but electroencephalogram suppression remains artificially fixed. The indirect effect represents the expected change in delirium if preoperative abnormal cognition remains artificially fixed, but electroencephalogram suppression changes to the degree it would have changed if abnormal cognition were not fixed.

Figure 2.. Flow Diagram

The number of patients included at each stage of the analysis is shown.

Figure 3.. Contributions to Delirium Incidence in Unadjusted Analysis

Within each cohort, the incidence of delirium among patients with preoperative abnormal cognition (gray bar) should be equal to the sum of the incidence without preoperative abnormal cognition (green bar), the absolute incidence increase associated with the direct effect of preoperative abnormal cognition (blue bar), and the absolute incidence increase associated with the indirect effect of abnormal cognition mediated by electroencephalogram suppression (red bar). Error bars represent 99.5% confidence intervals around incidence rates (gray and green) or 99.5% confidence intervals around effect sizes (blue and red).

Figure 4.. Sensitivity Analyses of Mediation Effect

Percentage of the total effect of preoperative abnormal cognition on postoperative delirium that is mediated by intraoperative electroencephalogram suppression. (Equal to indirect effect size divided by total effect size)