We did not reproduce the results of previous studies that reported a lower incidence of anesthesia awareness with BIS monitoring, and the use of the BIS protocol was not associated with reduced administration of volatile anesthetic gases. Anesthesia awareness occurred even when BIS values and ETAG concentrations were within the target ranges. Our findings do not support routine BIS monitoring as part of standard practice. (ClinicalTrials.gov number, NCT00281489 [ClinicalTrials.gov].).

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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 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. RESULTSOf 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. 40. Muhlhofer WG, Zak R, Kamal T, et al. Burst-suppression ratio underestimates absolute duration of electroencephalogram suppression compared with visual analysis of intraoperative electroencephalogram.

Background Delirium and pain are common and serious postoperative complications. Subanaesthetic ketamine is often administered intraoperatively for postoperative analgesia and to spare postoperative opioids. Some evidence also suggests that ketamine prevents delirium. The primary purpose of this trial was to evaluate the effectiveness of ketamine in preventing postoperative delirium in older adults after major surgery. Secondary outcomes, viewed as strongly related to delirium, were postoperative pain and opioid consumption. Methods This was a multicentre, international, randomised trial that enrolled adults older than 60 undergoing major cardiac and noncardiac surgery under general anaesthesia. Participants were enrolled prior to surgery and gave written informed consent. We used a computer-generated randomisation sequence. Patients at study sites were randomised to one of three study groups in blocks of 15 to receive intraoperative administration of (i) placebo (intravenous normal saline), (ii) low dose ketamine (0.5 mg/kg) or (iii) high dose ketamine (1 mg/kg). Study drug was administered following induction of anaesthesia, prior to surgical incision. Participants, clinicians, and investigators were all masked to group assignment. Delirium and pain were assessed twice daily in the first three postoperative days using the Confusion Assessment Method and Visual Analog Scale, respectively. Postoperative opioid use was recorded, and hallucinations and nightmares were assessed. Analyses were performed by intention-to-treat and adverse events were evaluated. The Prevention of Delirium and Complications Associated with Surgical Treatments [PODCAST] trial is registered in clinicaltrials.gov; NCT01690988 Findings Between February 6, 2014 and June 26, 2016, 1360 patients assessed and 672 were randomised, with 222 in the placebo group, 227 in the low dose ketamine group, and 223 in the high dose ketamine group. There was no difference in postoperative delirium incidence between those in the combined ketamine groups and those who received placebo (19.45% vs. 19.82%, respectively; absolute difference, 0.36%; 95% CI, −6.07% to 7.38%; p=0.92). There were no significant differences among the three groups in maximum pain scores (p=0.88) or median opioid consumption (p=0.47) over time. There were more postoperative hallucinations (p=0.01) and nightmares (p=0.03) with escalating doses of ketamine. Adverse events (cardiovascular, renal, infectious, gastrointestinal, bleeding), whether viewed individually (P value for each >0.40) or collectively (82/222 [36.9%] in placebo group, 90/227 [39.6%] in low dose ketamine group, 91/223 in high dose ketamine group [40.8%]; P=0.69), did not differ significantly across the three groups. Interpretation The administration of a single subanaesthetic dose of ketamine to older adults during major surgery did not show evidence of reducing postoperative delirium, pain, or opioid consumption, and might cause harm by inducing negative experiences. Given current evidence and guidelines related...

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