Perioperative Epidural Use and Risk of Delirium in Surgical Patients: A Secondary Analysis of the PODCAST Trial.

BACKGROUND: Postoperative delirium is an important public health concern without effective prevention strategies. This study tested the hypothesis that perioperative epidural use would be associated with decreased risk of delirium through postoperative day 3. METHODS: This was a secondary, observational, nonrandomized analysis of data from The Prevention of Delirium and Complications Associated With Surgical Treatments Trial (PODCAST; NCT01690988). The primary outcome of the current study was the incidence of delirium (ie, any positive delirium screen, postanesthesia care unit through postoperative day 3) in surgical patients (gastrointestinal, hepatobiliary-pancreatic, gynecologic, and urologic) receiving postoperative epidural analgesia compared to those without an epidural. As a secondary outcome, all delirium assessments were then longitudinally analyzed in relation to epidural use throughout the follow-up period. Given the potential relevance to delirium, postoperative pain, opioid consumption, sleep disturbances, and symptoms of depression were also analyzed as secondary outcomes. A semiparsimonious multivariable logistic regression model was used to test the association between postoperative epidural use and delirium incidence, and generalized estimating equations were used to test associations with secondary outcomes described. Models included relevant covariates to adjust for confounding. RESULTS: In total, 263 patients were included for analysis. Epidural use was not independently associated with reduced delirium incidence (adjusted odds ratio, 0.65 [95% CI, 0.32-1.35]; P = .247). However, when analyzing all assessments over the follow-up period, epidural patients were 64% less likely to experience an episode of delirium (adjusted odds ratio, 0.36 [95% CI, 0.17-0.78]; P = .009). Adjusted pain scores (visual analog scale, 0-100 mm) were significantly lower in the epidural group on postoperative day 1 (morning, -16 [95% CI, -26 to -7], P < .001; afternoon, -15 [95% CI, -25 to -5], P < .01) and postoperative day 3 (morning, -13 [95% CI, -20 to -5], P < .01). Adjusted mean oral and IV morphine equivalents were also significantly lower on postoperative day 1 in the epidural group (74% lower [95% CI, 55%-85%]; P < .0001). Finally, postoperative epidural use was not significantly associated with new sleep disturbances or changes in depression symptoms. CONCLUSIONS: Postoperative epidural use was not associated with a reduced overall incidence of delirium. However, longitudinal analysis revealed reduced adjusted odds of experiencing an episode of delirium in the epidural group. Epidural use was also associated with reduced postoperative pain and opioid consumption. An appropriately designed follow-up study is warranted to further analyze the relationship among epidural use, postoperative delirium, and related outcomes.

Neurophysiologic Correlates of Ketamine Sedation and Anesthesia: A High-density Electroencephalography Study in Healthy Volunteers.

BACKGROUND: Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although discrepant findings might relate to differences in doses studied, brain regions analyzed, coadministration of other anesthetic medications, and resolution of the electroencephalograph. The objective of this study was to characterize the dose-dependent effects of ketamine on cortical oscillations and functional connectivity. METHODS: Ten healthy human volunteers were recruited for study participation. The data were recorded using a 128-channel electroencephalograph during baseline consciousness, subanesthetic dosing (0.5 mg/kg over 40 min), anesthetic dosing (1.5 mg/kg bolus), and recovery. No other sedative or anesthetic medications were administered. Spectrograms, topomaps, and functional connectivity (weighted and directed phase lag index) were computed and analyzed. RESULTS: Frontal theta bandwidth power increased most dramatically during ketamine anesthesia (mean power ± SD, 4.25 ± 1.90 dB) compared to the baseline (0.64 ± 0.28 dB), subanesthetic (0.60 ± 0.30 dB), and recovery (0.68 ± 0.41 dB) states; P < 0.001. Gamma power also increased during ketamine anesthesia. Weighted phase lag index demonstrated theta phase locking within anterior regions (0.2349 ± 0.1170, P < 0.001) and between anterior and posterior regions (0.2159 ± 0.1538, P < 0.01) during ketamine anesthesia. Alpha power gradually decreased with subanesthetic ketamine, and anterior-to-posterior directed connectivity was maximally reduced (0.0282 ± 0.0772) during ketamine anesthesia compared to all other states (P < 0.05). CONCLUSIONS: Ketamine anesthesia correlates most clearly with distinct changes in the theta bandwidth, including increased power and functional connectivity. Anterior-to-posterior connectivity in the alpha bandwidth becomes maximally depressed with anesthetic ketamine administration, suggesting a dose-dependent effect.