Author: Bob Kronemyer
Administration of EEG-guided anesthesia does not decrease the likelihood of postoperative delirium, according to ENGAGES (Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes), a randomized clinical trial of older adults undergoing major surgery with general anesthesia.
The study found that among 1,232 adults, all of whom were at least 60 years of age, delirium during postoperative days 1 through 5 occurred in 157 of 604 patients (26.0%) in the EEG-guided group and in 140 of 608 patients (23.0%) in the group with routine anesthetic care (JAMA2019;321:473-483).
“Delirium is one of the most common complications affecting older adults undergoing major surgery, affecting approximately one out of four,” said first author Troy Wildes, MD, an associate professor of anesthesiology and the chief of the Division of Perioperative Medicine at Washington University School of Medicine in St. Louis. “Delirium is associated with increased mortality, longer hospital stays and poor long-term cognitive function.”
Dr. Wildes noted that prior research has shown a link between postoperative delirium and excessive intraoperative EEG waveform suppression. “Additionally, the ability of higher doses of anesthetics to produce EEG suppression is well described,” he said. “It has therefore been hypothesized that lower anesthetic doses may reduce the probability of postoperative delirium. However, existing clinical evidence has been mixed.”
A Surprising Result
The study authors sought to determine whether EEG monitoring to dynamically adjust the anesthetic dose could reduce EEG suppression and decrease the incidence of postoperative delirium.
“We were surprised that the treatment did not impact the incidence of postoperative delirium,” said principal investigator Michael Avidan, MBBCh, a professor of anesthesiology and the chief of the Division of Clinical and Translational Research at Washington University. “This suggests that intraoperative encephalographic suppression is more important as a predictor of delirium rather than a target for intervention, as we had hypothesized.”
The authors also were surprised by the difference in the mortality rate between the two groups. Within 30 days of surgery, four patients (0.65%) in the guided group and 19 (3.07%) in the usual care group died. “This finding deserves additional study and will be partially addressed by analysis of the one-year mortality data from our study,” Dr. Avidan said.
There are several possible explanations for the lack of a significant reduction in delirium with EEG guidance. “First, it is possible that even larger reductions in anesthetic dosing and EEG suppression are necessary to reduce delirium,” Dr. Wildes said. “However, both the lack of a trend toward such a treatment effect and our sensitivity analyses do not support this interpretation.”
Second, it is plausible that guided reduction of anesthetic-associated suppression is only helpful in specific subpopulations that were underrepresented in the study population.
“It is also possible that while EEG-guided reduction of volatile anesthetic administration does not prevent delirium, EEG guidance during total intravenous anesthesia to reduce intravenous anesthetic administration, such as propofol infusion, might be effective,” Dr. Wildes said.
Although the study authors still believe it is important to monitor the brain during general anesthesia, as it is the primary target organ of general anesthesia, “the utility of this monitor relating to postoperative delirium may be most importantly a marker of delirium risk rather than a target for intraoperative intervention,” Dr. Avidan said. “The intraoperative identification of patients more likely to experience postoperative delirium may allow subsequent targeted intervention. For example, promotion of appropriate sleeping and wakefulness intervals, support of sensory impairments, reorientation efforts and avoidance of problematic medications could all be prioritized in patients with intraoperative EEG findings predicting postoperative delirium.”
On the other hand, the authors caution that the ENGAGES study is a single study, and its results should be interpreted alongside the results of other trials, such as the ongoing ENGAGES-CANADA study.
“Continued research is also needed for other anesthetic drugs and techniques, such as total intravenous anesthesia,” Dr. Wildes said. “More widespread use of known preventative measures and increased education of clinicians in delirium recognition are required, too.”
Matthias Kreuzer, PhD, a senior researcher in the Department of Anesthesiology and Critical Care at Technische UniversitÄt MÜnchen School of Medicine, in Munich, said the study “adds some really important and interesting information to the current knowledge about the association between deep anesthetic levels and adverse outcomes. However, while this study is important for the field, I feel that the conclusion statement may be too bold, since the study focused on extensively deep levels and burst suppression, but not on other features of the EEG, like alpha oscillations, that may be important as well.”
In addition, a potentially missing piece of information is whether EEG monitoring reduced the number of patients with burst suppression. “If not, burst suppression per se, independent of duration, may be associated with post-op delirium, or the durations observed in both groups may be long enough to show an association with post-op delirium,” Dr. Kreuzer said.
Dr. Kreuzer believes a better study conclusion would have been that “although monitoring helps to decrease extensively deep levels of general anesthesia, it does not help to decrease the incidence of post-op delirium, if the purpose of using the monitor and the EEG was to prevent or, as in this case, reduce the time in the state of burst suppression.”