Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial

Abstract

Importance: Intraoperative electroencephalogram (EEG) waveform suppression, often suggesting excessive general anesthesia, has been associated with postoperative delirium.

Objective: To assess whether EEG-guided anesthetic administration decreases the incidence of postoperative delirium.

Design, setting, and participants: Randomized clinical trial of 1232 adults aged 60 years and older undergoing major surgery and receiving general anesthesia at Barnes-Jewish Hospital in St Louis. Recruitment was from January 2015 to May 2018, with follow-up until July 2018.

Interventions: Patients were randomized 1:1 (stratified by cardiac vs noncardiac surgery and positive vs negative recent fall history) to receive EEG-guided anesthetic administration (n = 614) or usual anesthetic care (n = 618).

Main outcomes and measures: The primary outcome was incident delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration, EEG suppression, and hypotension. Adverse events included undesirable intraoperative movement, intraoperative awareness with recall, postoperative nausea and vomiting, medical complications, and death.

Results: Of the 1232 randomized patients (median age, 69 years [range, 60 to 95]; 563 women [45.7%]), 1213 (98.5%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 157 of 604 patients (26.0%) in the guided group and 140 of 609 patients (23.0%) in the usual care group (difference, 3.0% [95% CI, -2.0% to 8.0%]; P = .22). Median end-tidal volatile anesthetic concentration was significantly lower in the guided group than the usual care group (0.69 vs 0.80 minimum alveolar concentration; difference, -0.11 [95% CI, -0.13 to -0.10), and median cumulative time with EEG suppression was significantly less (7 vs 13 minutes; difference, -6.0 [95% CI, -9.9 to -2.1]). There was no significant difference between groups in the median cumulative time with mean arterial pressure below 60 mm Hg (7 vs 7 minutes; difference, 0.0 [95% CI, -1.7 to 1.7]). Undesirable movement occurred in 137 patients (22.3%) in the guided and 95 (15.4%) in the usual care group. No patients reported intraoperative awareness. Postoperative nausea and vomiting was reported in 48 patients (7.8%) in the guided and 55 patients (8.9%) in the usual care group. Serious adverse events were reported in 124 patients (20.2%) in the guided and 130 (21.0%) in the usual care group. Within 30 days of surgery, 4 patients (0.65%) in the guided group and 19 (3.07%) in the usual care group died.

Conclusions and relevance: Among older adults undergoing major surgery, EEG-guided anesthetic administration, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support the use of EEG-guided anesthetic administration for this indication.

Trial registration: ClinicalTrials.gov Identifier: NCT02241655.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Wildes reported grants from National Institute on Aging (NIA) during the conduct of the study and grants from National Institutes of Health (NIH) outside the submitted work. Ms Mickle reported grants from NIA during the conduct of the study. Dr Ben Abdallah reported grants from NIA during the conduct of the study. Ms Maybrier reported grants from NIA during the conduct of the study. Mr Oberhaus reported grants from NIA during the conduct of the study. Dr Budelier reported grants from NIA during the conduct of the study. Mr Kronzer reported grants from the Agency for Healthcare Research and Quality and the National Science Foundation outside the submitted work. Ms McKinnon reported grants from NIA during the conduct of the study and grants from the Agency for Healthcare Research and Quality and the National Science Foundation outside the submitted work. Mr Park reported grants from NIA during the conduct of the study. Dr Palanca reported grants from NIA outside the submitted work during the conduct of the study. Dr Goswami reported grants from the National Science Foundation outside the submitted work. Dr Jordan reports grants from NIA and NIH during the conduct of the study. Dr Lin reported grants from NIA during the conduct of the study. Dr Fritz reported grants from NIH outside the submitted work during the conduct of the study. Dr Jacobsohn reported grants from Canadian Institutes of Health Research outside the submitted work during the conduct of the study. Dr Schmitt reported grants from NIA during the conduct of the study. Dr Inouye reported grants from NIA during the conduct of the study. Dr Stark reported grants from NIA during the conduct of the study. Dr Lenze reported grants from NIA, grants from NIH, grants from FDA and grants from PCORI, personal fees from Takeda, personal fees and nonfinancial support from Alkermes, personal fees from Aptinyx, personal fees and nonfinancial support from Janssen, personal fees from Barnes Jewish Foundation, personal fees from Taylor Family Institute for Innovative Psychiatric Research, personal fees from Lundbeck, and personal fees from McKnight Brain Research Foundation outside the submitted work. Dr Avidan reported grants from NIA and funds from the Dr Seymour and Rose T. Brown Endowed Professorship during the conduct of this study, and grants from other NIH institutes, the Agency for Healthcare Research and Quality, the National Science Foundation, the McDonnell Foundation for Neuroscience, and the Canadian Institutes of Health Research outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Recruitment, Randomization, and Patient Flow Diagram for the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes Trial

Figure 2.. Time With Electroencephalogram (EEG) Suppression and Low Bispectral Index (BIS)

The box-and-whisker plots show the medians (thick horizontal lines) and interquartile ranges (IQRs; boundaries of the box) and ranges. Whisker boundaries are set at 1.5 × IQR. Outliers 3 x IQR. The suppression time plots depict the cumulative times in each of the study groups during which the electroencephalogram suppression ratio was >1%. There was no imputation of missing suppression ratio or BIS data. Suppression ratio and BIS data were excluded when the EEG signal quality index was P < .001). These comparisons between the groups were assessed with the Mann-Whitney U test.