Ketamine is typically used by anesthesiologists as an adjunct for general anesthesia and as a nonopioid analgesic. It has been explored for prevention of postoperative delirium, although results have been contradictory. In this study, we investigated the association of ketamine with postoperative delirium and specific encephalographic signatures. Furthermore, we examined these associations in the context of baseline neurocognition as measured by a validated assessment.
We conducted a prospective observational study from January 2019 to December 2020. Ninety-eight patients aged ≥65 years and undergoing spine surgery scheduled for ≥3 hours were included in the study. All participants who completed the University of California San Francisco (UCSF) Brain Health Assessment preoperatively and postoperatively were assessed with the confusion assessment method for intensive care unit (CAM-ICU) and/or the Nursing Delirium Screening Scale (NuDESC). Patients had frontal electroencephalogram (EEG) recordings (SedLine Root, Masimo, Corp) quantitatively analyzed. We used 60 seconds of artifact-free EEG (without burst suppression) extracted from the middle of the maintenance period to calculate the normalized power spectral density (PSD). Comparisons were made between those who did or did not receive ketamine and according to results from neurocognitive assessments.
Ninety-eight patients (of a total of 155, enrolled and consented) had EEG of sufficient quality for analysis (42 women). Overall, we found a significant increase in the EEG power in the moderate frequency range (10-20 Hz) in patients that received ketamine. When the patients were divided by their preoperative cognitive status, this result in the ketamine group only held true for the cognitively normal patients. Patients that were cognitively impaired at baseline did not demonstrate a significant change in EEG characteristics based on ketamine administration, but impaired patients that received ketamine had a significantly higher rate of postoperative delirium (52% ketamine versus 20% no ketamine) (odds ratio [OR], 4.36; confidence interval [CI], 1.02-18.22; P = .048). In patients determined to be preoperatively cognitively normal, the incidence of postoperative delirium was not significantly associated with ketamine administration (19% ketamine versus 17% no ketamine) (OR, 1.10; CI, 0.30-4.04; P = .5833).
Ketamine-related changes in EEG are observed in a heterogeneous group of patients receiving spine surgery. This result was driven primarily by the effect of ketamine on cognitively normal patients and not observed in patients that were cognitively impaired at baseline. Furthermore, patients who were cognitively impaired at baseline and who had received ketamine were more likely to develop postoperative delirium, suggesting that cognitive vulnerability might be predicted by the lack of a neurophysiologic response to ketamine.

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