Ketamine Associated Intraoperative Electroencephalographic Signatures of Elderly Patients With and Without Preoperative Cognitive Impairment

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. (Anesth Analg 2022;135:683-92) KEY POINTS• Question: How does ketamine affect the electroencephalog...

Intraoperative Anesthetic Probes of Brain Health: Ketamine as a Canary in the Coal Mine?

“…Chang et al 2 analyzed differences in ketamine’s effects on delirium incidence and frontal EEG power across the frequency spectrum in 98 patients age ≥65 undergoing spine surgery for at least 3 hours. Preoperative cognition was assessed in these patients via the Brain Health Assessment (BHA), a 10-minute digital battery that covers 4 cognitive domains: associative memory, executive function and processing speed, visuospatial skills, and language.…”

“…Since preoperative cognitive impairment is one of the biggest risk factors for postoperative delirium (along with age and frailty), this raises the question of whether patients with preoperative cognitive impairment (or other patient subgroups) may be differentially sensitive to the effects of ketamine on postoperative delirium rates. In this issue, Chang et al 2 present a timely initial answer to this question by studying the effects of ketamine on both delirium risk and brain electroencephalographic (EEG) activity in patients with versus without baseline cognitive impairment.…”

A novel approach for the detection of cognitive impairment and delirium risk in older patients undergoing spine surgery

“…The study was approved by the UCSF Committee on Human Research (IRB 18‐26716), and participants provided written informed consent. Details of the study have been published elsewhere 22 . Inclusion criteria included age 65 years and older; undergoing spine surgery for 3 h or longer, and ability to understand and sign an informed consent.…”

“…Details of the study have been published elsewhere. 22 Inclusion criteria included age 65 years and older; undergoing spine surgery for 3 h or longer, and ability to understand and sign an informed consent. Exclusion criteria included an inability to read, understand, or speak English.…”

Development of Postanesthesia Care Unit Delirium Is Associated with Differences in Aperiodic and Periodic Alpha Parameters of the Electroencephalogram during Emergence from General Anesthesia: Results from a Prospective Observational Cohort Study

“…Delirium occurring in the PACU is associated with a longer hospital stay, 12,37 and there is some evidence that it is associated with perioperative complications. 12,38 However, this area of research is rapidly evolving. Additionally, CAM-ICU was performed only by a single observer, so we cannot provide any data about the reliability of the assessment such as inter-rater agreement for example.…”