Background: Cognitive abilities decline with aging, leading to a higher risk for the development of postoperative delirium or postoperative neurocognitive disorders after general anesthesia. Since frontal α-band power is known to be highly correlated with cognitive function in general, we

BACKGROUND: Intraoperative electroencephalography (EEG) signatures related to the development of postoperative delirium (POD) in older patients are frequently studied. However, a broad analysis of the EEG dynamics including preoperative, postinduction, intraoperative and postoperative scenarios and its correlation to POD development is still lacking. We explored the relationship between perioperative EEG spectra-derived parameters and POD development, aiming to ascertain the diagnostic utility of these parameters to detect patients developing POD. METHODS: Patients aged ≥65 years undergoing elective surgeries that were expected to last more than 60 minutes were included in this prospective, observational single center study (Biomarker Development for Postoperative Cognitive Impairment [BioCog] study). Frontal EEGs were recorded, starting before induction of anesthesia and lasting until recovery of consciousness. EEG data were analyzed based on raw EEG files and downloaded excel data files. We performed multitaper spectral analyses of relevant EEG epochs and further used multitaper spectral estimate to calculate a corresponding spectral parameter. POD assessments were performed twice daily up to the seventh postoperative day. Our primary aim was to analyze the relation between the perioperative spectral edge frequency (SEF) and the development of POD. RESULTS: Of the 237 included patients, 41 (17%) patients developed POD. The preoperative EEG in POD patients was associated with lower values in both SEF (POD 13.1 ± 4.6 Hz versus no postoperative delirium [NoPOD] 17.4 ± 6.9 Hz; P = .002) and corresponding γ-band power (POD −24.33 ± 2.8 dB versus NoPOD −17.9 ± 4.81 dB), as well as reduced postinduction absolute α-band power (POD −7.37 ± 4.52 dB versus NoPOD −5 ± 5.03 dB). The ratio of SEF from the preoperative to postinduction state (SEF ratio) was ~1 in POD patients, whereas NoPOD patients showed a SEF ratio >1, thus indicating a slowing of EEG with loss of unconscious. Preoperative SEF, preoperative γ-band power, and SEF ratio were independently associated with POD (P = .025; odds ratio [OR] = 0.892, 95% confidence interval [CI], 0.808-0.986; P = .029; OR = 0.568, 95% CI, 0.342-0.944; and P = .009; OR = 0.108, 95% CI, 0.021-0.568, respectively). CONCLUSIONS: Lower preoperative SEF, absence of slowing in EEG while transitioning from preoperative state to unconscious state, and lower EEG power in relevant frequency bands in both these states are related to POD development. These findings may suggest an underlying pathophysiology and might be used as EEG-based marker for early identification of patients at risk to develop POD. (Anesth Analg XXX;XXX:00-00) KEY POINTS• Question: Are characteristic perioperative electroencephalography (EEG) patterns related to the development of postoperative delirium (POD) in older patients? • Findings: Lower preoperative spectral edge frequency (SEF) based on reduced γ-band power and absence of change in SEF with loss of consciousness (LOC) and lower intraoperative αband power are rela...

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BACKGROUNDː Dysglycemia is associated with adverse outcome including increased morbidity and mortality in surgical patients. Acute insulin resistance due to the surgical stress response is seen as a major cause of so-called stress hyperglycemia. However, understanding of factors determining blood glucose (BG) during surgery is limited. Therefore, we investigated risk factors contributing to intraoperative dysglycemia. METHODSː In this subgroup investigation of the BIOCOG study, we analyzed 87 patients of ≥ 65 years with tight intraoperative BG measurement every 20 min during elective surgery. Dysglycemia was defined as at least one intraoperative BG measurement outside the recommended target range of 80-150 mg/dL. Additionally, all postoperative BG measurements in the ICU were obtained. Multivariable logistic regression analysis adjusted for age, sex, American Society of Anesthesiologists (ASA) status, diabetes, type and duration of surgery, minimum Hemoglobin (Hb) and mean intraoperative norepinephrine use was performed to identify risk factors of intraoperative dysglycemia. RESULTSː 46 (52.9%) out of 87 patients developed intraoperative dysglycemia. 31.8% of all intraoperative BG measurements were detected outside the target range . Diabetes [OR 9.263 (95% CI 2.492, 34.433); p=0.001] and duration of surgery [OR 1.005 (1.000, 1.010); p=0.036] were independently associated with the development of intraoperative dysglycemia. Patients who experienced intraoperative dysglycemia had significantly elevated postoperative mean (p<0.001) and maximum BG levels (p=0.001). Length of ICU (p=0.007) as well as hospital stay (p=0.012) were longer in patients with dysglycemia. CONCLUSIONSː Diabetes and duration of surgery were confirmed as independent risk factors for intraoperative dysglycemia, which was associated with adverse outcome. These patients, therefore, might require intensified glycemic control. Increased awareness and management of intraoperative dysglycemia is warranted.

Background Cerebral microbleeds (CMB) occur in the context of cerebral small vessel disease. Other brain MRI markers of cerebral small vessel disease are associated with the occurrence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), but for CMB this is unknown. We aimed to study the association between CMB and the occurrence of POD and POCD in older individuals. Methods The current study consists of 65 patients (72±5 years) from the BIOCOG study, which is a prospective, observational study of patients who underwent an elective surgery of at least 60 minutes. Patients in the current study received a preoperative cerebral MRI scan including a 3D susceptibility-weighted imaging sequence to detect CMB. The occurrence of POD was screened for twice a day until postoperative day 7 by using the DSM-5, NuDesc, CAM, and CAM-ICU. The occurrence of POCD was determined by the reliable change index model at 7 days after surgery or discharge, respectively, and 3 months after surgery. Statistical analyses consisted of logistic regression adjusted for age and gender. Results A total of 39 CMB were detected in 17 patients (26%) prior to surgery. POD occurred in 14 out of 65 patients (22%). POCD at 7 days after surgery occurred in 11 out of 54 patients (20%) and in 3 out of 40 patients at the 3 month follow-up (8%). Preoperative CMB were not associated with the occurrence of POD (OR (95%-CI): 0.28 (0.05, 1.57); p = 0.147) or POCD at 7 days after surgery (0.76 (0.16, 3.54); p = 0.727) or at 3 months follow-up (0.61 (0.03, 11.64); p = 0.740). Conclusion We did not find an association between preoperative CMB and the occurrence of POD or POCD. Trial registration clinicaltrials.gov ( NCT02265263 ) on 23 September 2014.

BackgroundPostoperative Delirium (POD) is the most frequent neurocognitive complication after general anesthesia in older patients. The development of POD is associated with prolonged periods of burst suppression activity in the intraoperative electroencephalogram (EEG). The risk to present burst suppression activity depends not only on the age of the patient but is also more frequent during propofol anesthesia as compared to inhalative anesthesia. The aim of our study is to determine, if the risk to develop POD differs depending on the anesthetic agent given and if this correlates with a longer duration of intraoperative burst suppression.MethodsIn this secondary analysis of the SuDoCo trail [ISRCTN 36437985] 1277 patients, older than 60 years undergoing general anesthesia were included. We preprocessed and analyzed the raw EEG files from each patient and evaluated the intraoperative burst suppression duration. In a logistic regression analysis, we assessed the impact of burst suppression duration and anesthetic agent used for maintenance on the risk to develop POD.Results18.7% of patients developed POD. Burst suppression duration was prolonged in POD patients (POD 27.5 min ± 21.3 min vs. NoPOD 21.4 ± 16.2 min, p &lt; 0.001), for each minute of prolonged intraoperative burst suppression activity the risk to develop POD increased by 1.1% (OR 1.011, CI 95% 1.000–1.022, p =  0.046). Burst suppression duration was prolonged under propofol anesthesia as compared to sevoflurane and desflurane anesthesia (propofol 32.5 ± 20.3 min, sevoflurane 17.1 ± 12.6 min and desflurane 20.1 ± 16.0 min, p &lt; 0.001). However, patients receiving desflurane anesthesia had a 1.8fold higher risk to develop POD, as compared to propofol anesthesia (OR 1.766, CI 95% 1.049–2.974, p =  0.032).ConclusionWe found a significantly increased risk to develop POD after desflurane anesthesia in older patients, even though burst suppression duration was shorter under desflurane anesthesia as compared to propofol anesthesia. Our finding might help to explain some discrepancies in studies analyzing the impact of burst suppression duration and EEG-guided anesthesia on the risk to develop POD.

To investigate the influence of midazolam premedication on the EEG-spectrum before and during general anesthesia in elderly patients. Methods Patients aged ≥65 years, undergoing elective surgery were included in this prospective observational study. A continuous pre-and intraoperative frontal EEG was recorded in patients who received premedication with midazolam (Mid, n = 15) and patients who did not (noMid, n = 30). Absolute power within the delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta (12-25 Hz) frequency-bands was analyzed in EEG-sections before (preinduction), and after induction of anesthesia with propofol (post-induction), as well as during general anesthesia with either propofol or volatile-anesthetics (intra-operative). Results Pre-induction, α-power of Mid patients was lower compared with noMid-patients (α-power: Mid: −10.75 dB vs. noMid: −9.20 dB; p = 0.036). After induction of anesthesia Mid-patients displayed a stronger increase of frontal α-power resulting in higher absolute α-power at post-induction state, (α-power: Mid −3.56 dB vs. noMid: −6.69 dB; p = 0.004), which remained higher intraoperatively (α-power: Mid: −2.12 dB vs. noMid: −6.10 dB; p = 0.024). Conclusion Midazolam premedication alters the intraoperative EEG-spectrum in elderly patients. This prospective, observational cohort study was performed as a subproject of the BioCog Study at the university hospital Charité-Universitätsmedizin Berlin Campus Charité Mitte and Campus Virchow-Klinikum, Germany (NCT02265263). Ethics approval was obtained from the institutional review board (EA2/092/14). While inclusion of patients for the BioCog study took place from October 2014 until April 2017, patients for this subproject were examined between February 2015 and April 2017 after written informed consent from each patient was obtained. Intraoperative EEG measurements were performed at the study center Charité-Universitätsmedizin Berlin. Patients were eligible if they were aged 65 years or older, undergoing elective surgery under general anesthesia with an expected operating time of at least 60 minutes. Exclusion criteria comprised preoperative Mini-Mental-State-Examination (MMSE) < 24 points, neuropsychiatric morbidity that limited conduction of neurocognitive testing, and proposed neurological surgery, maxillofacial surgery or surgery in prone position were not included, as an abundance of EEG artefacts could be expected. Patients receiving oral premedication with midazolam prior to induction (Mid group) were compared to an age-matched group of patients not receiving oral premedication (noMid group). Dosage and time of administration Significance This finding provides further evidence for the role of GABAergic activation in the induction of elevated, frontal α-power during general anesthesia.

BACKGROUND AND PURPOSE In hyperglycemic patients, who succumbed to septic shock, an increased rate of apoptosis of microglial cells and damaged neurons of the hippocampus were found. However, the influence of perioperative glucose levels on hippocampal brain structures has not yet been investigated. METHODS As part of the ongoing BIOCOG project, a subgroup of N = 65 elderly nondemented patients were analyzed who underwent elective surgery of ≥60 minutes. In these patients, at least one intraoperative blood glucose (BG) measurement was available from the medical charts. Intraoperative glucose maximum was determined in each patient. Preoperatively and at 3 months follow‐up, structural neuroimaging was performed with T1‐weighted magnetization prepared rapid gradient‐echo sequence (MP‐Rage) and a dedicated high‐resolution hippocampus magnetic resonance imaging (MRI). The MRI scans were analyzed to assess pre‐ or postoperative volume changes of the hippocampus as a whole and hippocampal subfields. We also assessed changes of frontal lobe volume and cortical thickness. RESULTS Overall, 173 intraoperative BG levels were obtained in 65 patients (median 2 per patient). A total of 18 patients showed intraoperative hyperglycemia (glucose maximum ≥150 mg/dL). Controlling for age and diabetes status, no significant impact of intraoperative hyperglycemia was found on the pre–post volume change of the hippocampus as a whole, hippocampal subfields, frontal lobe, and frontal cortical thickness. CONCLUSIONS This study found no effect of intraoperative hyperglycemia on postoperative brain structures and volumes including volumes of hippocampus and hippocampal subfields, frontal lobe, and frontal cortical thickness. Further studies investigating the impact of intraoperatively elevated glucose levels should consider a tighter or even continuous glycemic measurement and the determination of central microglial activation.