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Lower Anesthesia May Not Reduce Post-Op Delirium

Lower amounts of anesthesia in surgical patients monitored by intraoperative electroencephalography (EEG) did not reduce the incidence of postoperative delirium, the ENGAGES randomized clinical trial found.

Delirium in days 1 through 5 after surgery occurred in 26% of a group of older adults who had EEG-guided anesthesia, compared with 23% in a usual care group (difference 3.0%, 95% CI −2.0% to 8.0%, P=0.22), reported Michael Avidan, MBBCh, of the Washington University School of Medicine in St. Louis, and colleagues in JAMA.

But in an unexpected finding, patients who had EEG monitoring during surgery had lower 30-day mortality: four patients (0.65%) in the guided group died, compared with 19 (3.07%) in the usual care group.

“When older adults have major surgery, one in four of them experiences delirium,” Avidan said in a statement. “If there is a way to change that, it would have a major impact on public health.” Because delirium has been linked to longer ICU and hospital stays and a higher risk of death, a number of organizations — including the NIH, the American Geriatric Society, the American Society of Anesthesiologists, and the American Geriatric Society — have identified delirium prevention as a public health priority.

In contrast to the outcomes of this study, meta-analyses of controlled trials have reported that EEG-guided anesthesia reduced the incidence of postoperative delirium by one-third to one-half, perhaps due to the avoidance of burst suppression, an EEG pattern that suggests excessively deep anesthesia.

“The thought has been that at certain levels of anesthesia, brain activity is suppressed, and that is what mediates these problems,” said co-author Troy Wildes, MD, also of Washington University. “But we found that preventing suppression by closely monitoring and then adjusting doses of anesthesia made delirium no less likely.”

The ENGAGES trial studied 1,232 adults, ages ≥60, who had major surgery with general volatile anesthesia at three facilities of a single center, Barnes-Jewish Hospital in St. Louis, from 2015 to 2018. Patients were randomized 1:1 to receive EEG-guided anesthetic administration (n=614) or usual anesthetic care (n=618). The median age in each group was about 69 and 54% of each group were men.

Each patient had a bispectral EEG sensor applied to the forehead. The device used a proprietary algorithm to display anesthetic depth on a scale of 0 to 100, with values <40 suggesting excessive depth. In the EEG-guided group, clinicians were encouraged to minimize periods of low EEG activity and periods where the bispectral index was <40.

The researchers used the Confusion Assessment Method (CAM) and CAM-ICU scales to evaluate delirium daily for 5 days after surgery. Because delirium often manifests at night, these assessments were supplemented with medical record review.

In the EEG-guided group, the median dose of the anesthetic agent was significantly lower (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), but more phenylephrine was administered in the usual care group. Undesirable movement occurred in 22.3% of the guided and 15.4% of the usual care group, but no patients reported intraoperative awareness.

Existing evidence supporting EEG-guided anesthesia is controversial, especially about preventing unintentional awareness, observed Thomas Abbott, PhD, and Rupert Pearse, MD, both of Queen Mary University in London, in an accompanying editorial.

Overall, the ENGAGES findings contrast with those found in meta-analyses, but previous studies of EEG-guided anesthesia have been criticized for their methods and small sample sizes, they noted. While it’s unusual for a general medical journal like JAMA to publish a single-center clinical effectiveness trial, “the ENGAGES trial was robustly designed and well conducted, leading to a low risk of bias, and focuses on an important question, particularly given the number of procedures performed worldwide,” they added.

Still, the study has several limitations, Abbott and Pearse noted. Anesthesiologists in this study exclusively used volatile anesthetic agents to maintain general anesthesia, which may not reflect practices in some hospitals. And it’s unclear whether device manufacturers have made changes to the bispectral index and other proprietary algorithms over time, making it difficult to compare ENGAGES with previous studies.

Importantly, delirium is a fluctuating disorder that can be hard to diagnose, and some patients in the study may have been misclassified, Avidan and colleagues pointed out. The lower 30-day mortality in the EEG-guided group warrants further investigation, they added.

The study was funded by the NIH.

Researchers disclosed relevant relationships with Takeda, Alkermes, Aptinyx, Janssen, the Barnes Jewish Foundation, the Taylor Family Institute for Innovative Psychiatric Research, Lundbeck, the Dr. Seymour and Rose T. Brown Endowed Chair, the McDonnell Foundation for Neuroscience, and the Canadian Institutes of Health Research.

Pearse disclosed relevant relationships with GlaxoSmithkline, B. Braun Medical, Intersurgical, and Edwards Lifesciences.