Preoperative Midazolam and Patient-Centered Outcomes of Older Patients: The I-PROMOTE Randomized Clinical Trial.

Importance: The effect of oral midazolam premedication on patient satisfaction in older patients undergoing surgery is unclear, despite its widespread use. Objective: To determine the differences in global perioperative satisfaction in patients with preoperative administration of oral midazolam compared with placebo. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial was conducted in 9 German hospitals between October 2017 and May 2019 (last follow-up, June 24, 2019). Eligible patients aged 65 to 80 years who were scheduled for elective inpatient surgery for at least 30 minutes under general anesthesia and with planned extubation were enrolled. Data were analyzed from November 2019 to December 2020. Interventions: Patients were randomized to receive oral midazolam, 3.75 mg (n = 309), or placebo (n = 307) 30 to 45 minutes prior to anesthesia induction. Main Outcomes and Measures: The primary outcome was global patient satisfaction evaluated using the self-reported Evaluation du Vécu de l'Anesthésie Generale (EVAN-G) questionnaire on the first postoperative day. Key secondary outcomes included sensitivity and subgroup analyses of the primary outcome, perioperative patient vital data, adverse events, serious complications, and cognitive and functional recovery up to 30 days postoperatively. Results: Among 616 randomized patients, 607 were included in the primary analysis. Of these, 377 (62.1%) were male, and the mean (SD) age was 71.9 (4.4) years. The mean (SD) global index of patient satisfaction did not differ between the midazolam and placebo groups (69.5 [10.7] vs 69.6 [10.8], respectively; mean difference, -0.2; 95% CI, -1.9 to 1.6; P = .85). Sensitivity (per-protocol population, multiple imputation) and subgroup analyses (anxiety, frailty, sex, and previous surgical experience) did not alter the primary results. Secondary outcomes did not differ, except for a higher proportion of patients with hypertension (systolic blood pressure ≥160 mm Hg) at anesthesia induction in the placebo group. Conclusion and Relevance: A single low dose of oral midazolam premedication did not alter the global perioperative patient satisfaction of older patients undergoing surgery or that of patients with anxiety. These results may be affected by the low dose of oral midazolam. Further trials-including a wider population with commonplace low-dose intravenous midazolam and plasma level measurements-are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03052660.

Preoperative characterization of baseline EEG recordings for risk stratification of post-anesthesia care unit delirium.

STUDY OBJECTIVE: Delirium in the post-anesthesia care unit (PACU-D) presents a serious condition with a high medical and socioeconomic impact. In particular, PACU-D is among common postoperative complications of elderly patients. As PACU-D may be associated with postoperative delirium, early detection of at-risk patients and strategies to prevent PACU-D are important. We characterized EEG baseline signatures of patients who developed PACU-D following surgery and general anesthesia and patients who did not. DESIGN AND SETTING: We conducted a post-hoc analysis of preoperative EEG recordings between patients with and without PACU-D, as indicated by positive bCAM scores post general anesthesia and surgery. PATIENTS AND MEASUREMENTS: Preoperative baseline EEG recordings from 89 patients were recorded at controlled eyes-open (focused wakefulness) and eyes-closed (relaxed wakefulness) conditions. We computed power spectral densities, permutation entropy, spectral entropy and spectral edge frequency to see if these parameters can reflect potential baseline EEG differences between PACU-D (31.5%) and noPACU-D (68.5%) patients. Wilcoxon's Rank Sum Test as well as AUC values were used to determine statistical significance. MAIN RESULTS: Baseline EEG recordings showed significant differences between PACU-D and noPACU-D patients preoperatively. Compared to the noPACU-D group, PACU-D patients presented with lower power in higher frequencies during relaxed and focused wakefulness alike. These differences in power led to AUC values of 0.73 [0.59;0.85] (permutation entropy) and 0.72 [0.61;0.83] (spectral edge frequency) indicative of a "fair" performance to separate patients with and without PACU-D. CONCLUSIONS: The baseline EEG of relaxed wakefulness as well as focused wakefulness may be used to assess the risk of developing PACU-D following surgery under general anesthesia. Moreover, routinely used monitoring parameters capture these differences as well, potentially allowing an easy transfer to clinical settings. CLINICAL TRIAL NUMBER: NCT03775356.

Always Assess the Raw Electroencephalogram: Why Automated Burst Suppression Detection May Not Detect All Episodes.

BACKGROUND: Electroencephalogram (EEG)-based monitors of anesthesia are used to assess patients' level of sedation and hypnosis as well as to detect burst suppression during surgery. One of these monitors, the Entropy module, uses an algorithm to calculate the burst suppression ratio (BSR) that reflects the percentage of suppressed EEG. Automated burst suppression detection monitors may not reliably detect this EEG pattern. Hence, we evaluated the detection accuracy of BSR and investigated the EEG features leading to errors in the identification of burst suppression. METHODS: With our study, we were able to compare the performance of the BSR to the visual burst suppression detection in the raw EEG and obtain insights on the architecture of the unrecognized burst suppression phases. RESULTS: We showed that the BSR did not detect burst suppression in 13 of 90 (14%) patients. Furthermore, the time comparison between the visually identified burst suppression duration and elevated BSR values strongly depended on the BSR value being used as a cutoff. A possible factor for unrecognized burst suppression by the BSR may be a significantly higher suppression amplitude ( P = .002). Six of the 13 patients with undetected burst suppression by BSR showed intraoperative state entropy values >80, indicating a risk of awareness while being in burst suppression. CONCLUSIONS: Our results complement previous results regarding the underestimation of burst suppression by other automated detection modules and highlight the importance of not relying solely on the processed index, but to assess the native EEG during anesthesia.

Targeted Interventions to Increase Blood Pressure and Decrease Anaesthetic Concentrations Reduce Intraoperative Burst Suppression: A Randomised, Interventional Clinical Trial.

Background: It has been suggested that intraoperative electroencephalographic (EEG) burst suppression (BSupp) may be associated with post-operative neurocognitive disorders in the elderly, and EEG-guided anaesthesia may help to reduce BSupp. Despite of this suggestion, a standard treatment does not exist, as we have yet to fully understand the phenomenon and its underlying pathomechanism. This study was designed to address two underlying phenomena-cerebral hypoperfusion and individual anaesthetic overdose. Objectives: We aimed to demonstrate that targeted anaesthetic interventions-treating intraoperative hypotension and/or reducing the anaesthetic concentration-reduce BSupp. Methods: We randomly assigned patients to receive EEG-based interventions during anaesthesia or EEG-blinded standard anaesthesia. If BSupp was detected, defined as burst suppression ratio (BSR) > 0, the primary intervention aimed to adjust the mean arterial blood pressure to patient baseline (MAP intervention) followed by reduction of anaesthetic concentration (MAC intervention). Results: EEG-based intervention significantly reduced total cumulative BSR, BSR duration, and maximum BSR. MAP intervention caused a significant MAP increase at the end of a BSR > 0 episode compared to the control group. Coincidentally, the maximum BSR decreased significantly; in 55% of all MAP interventions, the BSR decreased to 0% without any further action. In the remaining events, additional MAC intervention was required. Conclusion: Our results show that targeted interventions (MAC/MAP) reduce total cumulative amount, duration, and maximum BSR > 0 in the elderly undergoing general anaesthesia. Haemodynamic intervention already interrupted or reduced BSupp, strengthening the current reflections that hypotension-induced cerebral hypoperfusion may be seen as potential pathomechanism of intraoperative BSupp. Clinical Trial Registration: NCT03775356 [ClinicalTrials.gov], DRKS00015839 [German Clinical Trials Register (Deutsches Register klinischer Studien, DRKS)].

State entropy and burst suppression ratio can show contradictory information: A retrospective study.

BACKGROUND: Burst suppression is a characteristic electroencephalographic (EEG) pattern that reflects very deep levels of general anaesthesia and may correlate with increased risk of adverse outcomes such as postoperative delirium. EEG-based monitors such as the Entropy Module estimate the level of anaesthesia (state entropy) and provide another index reflecting the occurrence of burst suppression, that is the ratio of burst and suppression (BSR). In the Entropy Module, state entropy and BSR are not interconnected, as they are in the bispectral index (BIS). Hence, state entropy and BSR may provide contradicting information regarding the level of anaesthesia. OBJECTIVES: We aimed to describe the frequency and characteristics of contradicting state entropy and BSR and to present possible strategies of how to act in these situations. METHODS: We based our analyses on state entropy and BSR trend recordings from 2551 patients older than 59 years that showed BSR was > 0 throughout their intervention under general anaesthesia. We determined the maximum state entropy when BSR was > 0, the minimum state entropy with BSR = 0 and the duration of high state entropy with BSR > 0. Further, we selected four exemplar patients to present details of how state entropy and BSR can contradict each other during anaesthesia. RESULTS: We observed a wide range of state entropy values with BSR > 0. The median [IQR] of the maximum state entropy with BSR > 0 was 53 [45 to 61] and the median of the minimum state entropy without BSR was 21 [15 to 26]. Contradictory BSR and state entropy could persist over several minutes. The presented cases highlight these contradictory BSR and state entropy situations. CONCLUSIONS: Our results illustrate contradictory state entropy and BSR indices that may be relevant for anaesthesia navigation. Longer-lasting episodes may lead to incorrect titration of the depth of the hypnotic component of anaesthesia. Hence, our results demonstrate the necessity to monitor and check the raw EEG or EEG parameters that are less processed than the commercially available indices to safely navigate anaesthesia.