A Processed EEG based Brain Anesthetic Resistance Index Predicts Postoperative Delirium in Older Adults: A Dual Center Study

Cooter, M.; Bunning, T.; Eleswarpu, S. S.; Heflin, M. T.; McDonald, S.; Lagoo-Deenadalayan, S.; Whitson, H.; Deiner, S. G.; Berger, M.

Background: Some older adults show exaggerated responses to drugs that act on the brain, such as increased delirium risk in response to anticholinergic drugs. The brain's response to anesthetic drugs is often measured clinically by processed electroencephalogram (EEG) indices. Thus, we developed a processed EEG based-measure of the brain's neurophysiologic resistance to anesthetic dose-related changes, and hypothesized that it would predict postoperative delirium. Methods: We defined the Duke Anesthesia Resistance Scale (DARS) as the average BIS index divided by the quantity 2.5 minus the average age-adjusted end-tidal MAC (aaMAC) inhaled anesthetic fraction. The relationship between DARS and postoperative delirium was analyzed in derivation (Duke; N=69), validation (Mt Sinai; N=70), and combined estimation cohorts (N=139) of older surgical patients (age >/= 65). In the derivation cohort, we identified a threshold relationship between DARS and for delirium and identified an optimal cut point for prediction. Results: In the derivation cohort, the optimal DARS threshold for predicting delirium was 27.0. The delirium rate was 11/49 (22.5%) vs 11/20 (55.0%) and 7/57 (12.3%) vs 6/13 (46.2%) for those with DARS >/= 27 vs those with DARS < 27 in the derivation and validation cohorts respectively. In the combined estimation cohort, multivariable analysis found a significant association of DARS <27.0 with postoperative delirium (OR=4.7; 95% CI: 1.87, 12.0; p=0.001). In the derivation cohort, the DARS had an AUC of 0.63 with sensitivity of 50%, specificity of 81%, positive predictive value of 0.55, and negative predictive value of 0.78. The DARS remained a significant predictor of delirium after accounting for opioid, midazolam, propofol, non-depolarizing neuromuscular blocker, phenylephrine and ketamine dosage, and for nitrous oxide and epidural usage. Conclusions: These results, if confirmed by larger future studies, suggest than an intraoperative processed EEG-based measure of lower brain anesthetic resistance (i.e. DARS <27) could be used in older surgical patients as an independent predictor of postoperative delirium risk.