Background: Some older adults show exaggerated responses to drugs that act on the brain. 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 resistance to volatile anesthetics and hypothesized that low scores on it would be associated with postoperative delirium risk.
Methods: We defined the Duke Anesthesia Resistance Scale (DARS) as the average bispectral index (BIS) divided by the quantity (2.5 minus the average age-adjusted end-tidal minimum alveolar concentration [aaMAC] inhaled anesthetic fraction). The relationship between DARS and postoperative delirium was analyzed in 139 older surgical patients (age ≥65) from Duke University Medical Center (n = 69) and Mt Sinai Medical Center (n = 70). Delirium was assessed by geriatrician interview at Duke, and by research staff utilizing the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) instrument at Mt Sinai. We examined the relationship between DARS and delirium and used the Youden index to identify an optimal low DARS threshold (for delirium risk), and its associated 95% bootstrap confidence bounds. We used multivariable logistic regression to examine the relationship between low DARS and delirium risk.
Results: The relationship between DARS and delirium risk was nonlinear, with higher delirium risk at low DARS scores. A DARS threshold of 28.755 maximized the Youden index for the association between low DARS and delirium, with bootstrap 95% confidence bounds of 26.18 and 29.80. A low DARS (<28.755) was associated with increased delirium risk in multivariable models adjusting for site (odds ratio [OR] [95% confidence interval {CI}] = 4.30 [1.89-10.01]; P = .001), or site-plus-patient risk factors (OR [95% CI] = 3.79 [1.63-9.10]; P = .003). These associations with postoperative delirium risk remained significant when using the 95% bootstrap confidence bounds for the low DARS threshold (P < .05 for all). Further, a low DARS (<28.755) was associated with delirium risk after accounting for opioid, midazolam, propofol, phenylephrine, and ketamine dosage as well as site (OR [95% CI] = 4.21 [1.80-10.16]; P = .002). This association between low DARS and postoperative delirium risk after controlling for these other medications remained significant (P < .05) when using either the lower or the upper 95% bootstrap confidence bounds for the low DARS threshold.
Conclusions: These results demonstrate that an intraoperative processed EEG-based measure of lower brain anesthetic resistance (ie, low DARS) is independently associated with increased postoperative delirium risk in older surgical patients.
Trial registration: ClinicalTrials.gov NCT02650687.
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