[The quantitative EEG in electroencephalogram-based brain monitoring during general anesthesia]. / Das quantifizierte EEG im elektroenzephalogrammbasierten Monitoring während Allgemeinanästhesie.

The electroencephalogram (EEG) is increasingly being used in the clinical routine of anesthesia in German-speaking countries. In over 90% of patients the frontal EEG changes somewhat predictably in response to administration of the normally used anesthetic agents (propofol and volatile gasses). An adequate depth of anesthesia and appropriate concentrations of anesthetics in the brain generate mostly frontal oscillations between 8 and 12 Hz as well as slow delta waves between 0.5 and 4 Hz. The frontal EEG channel is well-suited for avoidance of insufficient depth of anesthesia and excessive administration of anesthetics. This article explains the clinical interpretation of the most important EEG patterns and the biophysical background. Also discussed are important limitations and pitfalls for the clinical routine, which the anesthetist should know in order to utilize the EEG as an admittedly incomplete but clinically extremely important parameter for the level of consciousness.

The relationship between obstructive sleep apnoea and postoperative delirium and pain: an observational study of a surgical cohort.

Patients with obstructive sleep apnoea are at increased risk of adverse postoperative outcomes, such as cardiac and respiratory complications. It has been hypothesised that obstructive sleep apnoea also increases the risk for postoperative delirium and acute postoperative pain. We conducted a retrospective, observational study investigating the relationship of obstructive sleep apnoea with postoperative delirium and acute postoperative pain severity. Patients were classified as being at high risk for obstructive sleep apnoea if they had been diagnosed with this condition, or if they were positive for more than four factors using the 'STOP-BANG' screening tool. Adjusted logistic regression was used to investigate the association between obstructive sleep apnoea and postoperative delirium, and multivariable linear regression to study the relationship between obstructive sleep apnoea and postoperative pain severity. The incidence of postoperative delirium was 307 in 1441 patients (21.3%; 95%CI 19.2-23.5%). In unadjusted analysis, high risk for obstructive sleep apnoea was associated with delirium, with an odds ratio (95%CI) of 1.77 (1.22-2.57; p = 0.003). After adjustment for pre-specified variables, the association was not statistically significant with odds ratio 1.34 (0.80-2.23; p = 0.27). The mean (SD) maximum pain (resting or provoked) reported for the entire cohort was 63.8 (27.9) mm on a 0-100 mm visual analogue scale. High risk for obstructive sleep apnoea was not associated with postoperative pain severity (ß-coefficient 2.82; 95%CI, -2.34-7.97; p = 0.28). These findings suggest that obstructive sleep apnoea is unlikely to be a strong risk factor for postoperative delirium or acute postoperative pain severity.

Duration of EEG suppression does not predict recovery time or degree of cognitive impairment after general anaesthesia in human volunteers.

BACKGROUND: Burst suppression occurs in the EEG during coma and under general anaesthesia. It has been assumed that burst suppression represents a deeper state of anaesthesia from which it is more difficult to recover. This has not been directly demonstrated, however. Here, we test this hypothesis directly by assessing relationships between EEG suppression in human volunteers and recovery of consciousness. METHODS: We recorded the EEG of 27 healthy humans (nine women/18 men) anaesthetised with isoflurane 1.3 minimum alveolar concentration (MAC) for 3 h. Periods of EEG suppression and non-suppression were separated using principal component analysis of the spectrogram. After emergence, participants completed the digit symbol substitution test and the psychomotor vigilance test. RESULTS: Volunteers demonstrated marked variability in multiple features of the suppressed EEG. In order to test the hypothesis that, for an individual subject, inclusion of features of suppression would improve accuracy of a model built to predict time of emergence, two types of models were constructed: one with a suppression-related feature included and one without. Contrary to our hypothesis, Akaike information criterion demonstrated that the addition of a suppression-related feature did not improve the ability of the model to predict time to emergence. Furthermore, the amounts of EEG suppression and decrements in cognitive task performance relative to pre-anaesthesia baseline were not significantly correlated. CONCLUSIONS: These findings suggest that, in contrast to current assumptions, EEG suppression in and of itself is not an important determinant of recovery time or the degree of cognitive impairment upon emergence from anaesthesia in healthy adults.

Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial.

BACKGROUND: Ketamine is a general anaesthetic with anti-depressant effects at subanaesthetic doses. We hypothesised that intraoperative administration of ketamine would prevent or mitigate postoperative depressive symptoms in surgical patients. METHODS: We conducted an international, randomised clinical trial testing the effects of intraoperative administration of ketamine [0.5 mg kg-1 (Lo-K) or 1.0 mg kg-1 (Hi-K)] vs control [saline placebo (P)] in patients ≥60 yr old undergoing major surgery with general anaesthesia. We administered the Patient Health Questionnaire-8 before the operation, on postoperative day (POD) 3 (primary outcome), and on POD30 to assess depressive symptoms, a secondary outcome of the original trial. RESULTS: There was no significant difference on POD3 in the proportion of patients with symptoms suggestive of depression between the placebo [23/156 (14.7%)] and combined ketamine (Lo-K plus Hi-K) [61/349 (17.5%)] groups [difference = -2.7%; 95% confidence interval (CI), 5.0% to -9.4%; P=0.446]. Of the total cohort, 9.6% (64/670; 95% CI, 7.6-12.0%) had symptoms suggestive of depression before operation, which increased to 16.6% (84/505; 95% CI, 13.6-20.1%) on POD3, and decreased to 11.9% (47/395; 95% CI, 9.1-15.5%) on POD30. Of the patients with depressive symptoms on POD3 and POD30, 51% and 49%, respectively, had no prior history of depression or depressive symptoms. CONCLUSIONS: Major surgery is associated with new-onset symptoms suggestive of depression in patients ≥60 yr old. Intraoperative administration of subanaesthetic ketamine does not appear to prevent or improve depressive symptoms. CLINICAL TRIALS REGISTRATION: NCT01690988.

Intraoperative electroencephalogram suppression at lower volatile anaesthetic concentrations predicts postoperative delirium occurring in the intensive care unit.

BACKGROUND: Postoperative delirium is a common complication associated with increased morbidity and mortality. A recently-reported association between intraoperative electroencephalogram suppression and postoperative delirium might be mediated in some patients by a heightened sensitivity to volatile anaesthetics. METHODS: This retrospective cohort study included 618 elective surgery patients with planned intensive care unit admission, who also received intraoperative electroencephalogram monitoring and had delirium assessments documented in the medical record. Sensitivity to volatile anaesthetics was assessed using a mixed effects model predicting the likelihood of electroencephalogram suppression at each time point based on the current end-tidal anaesthetic concentration. Patients with a random intercept above the population median (electroencephalogram suppression at lower anaesthetic concentrations) were classified as having heightened sensitivity to volatile anaesthetics. Delirium was defined as a positive Confusion Assessment Method for the Intensive Care Unit assessment anytime in the first five postoperative days. RESULTS: Postoperative delirium was observed in 162 of 618 patients (26%). Patients who experienced electroencephalogram suppression at lower volatile anaesthetic concentrations had a higher incidence of postoperative delirium [109/309 (35%)] than other patients [53/309 (17%)] [unadjusted odds ratio 2.63; 95% confidence interval (CI), 1.81-3.84, P<0.001]. This association remained significant after adjusting for patient characteristics, surgical variables, and duration of electroencephalogram suppression (adjusted odds ratio 2.13; 95% CI 1.24-3.65, P=0.006). CONCLUSIONS: These data support the hypothesis that patients with electroencephalogram suppression at lower volatile anaesthetic concentrations have an increased incidence of postoperative delirium. Such patients appear to exhibit a phenotype of anaesthetic sensitivity, which might predispose them to adverse cognitive outcomes.

Human neural correlates of sevoflurane-induced unconsciousness.

Sevoflurane, a volatile anaesthetic agent well-tolerated for inhalation induction, provides a useful opportunity to elucidate the processes whereby halogenated ethers disrupt consciousness and cognition. Multiple molecular targets of sevoflurane have been identified, complementing imaging and electrophysiologic markers for the mechanistically obscure progression from wakefulness to unconsciousness. Recent investigations have more precisely detailed scalp EEG activity during this transition, with practical clinical implications. The relative timing of scalp potentials in frontal and parietal EEG signals suggests that sevoflurane might perturb the propagation of neural information between underlying cortical regions. Spatially distributed brain activity during general anaesthesia has been further investigated with positron emission tomography (PET) and resting-state functional magnetic resonance imaging (fMRI). Combined EEG and PET investigations have identified changes in cerebral blood flow and metabolic activity in frontal, parietal, and thalamic regions during sevoflurane-induced loss of consciousness. More recent fMRI investigations have revealed that sevoflurane weakens the signal correlations among brain regions that share functionality and specialization during wakefulness. In particular, two such resting-state networks have shown progressive breakdown in intracortical and thalamocortical connectivity with increasing anaesthetic concentrations: the Default Mode Network (introspection and episodic memory) and the Ventral Attention Network (orienting of attention to salient feature of the external world). These data support the hypotheses that perturbations in temporally correlated activity across brain regions contribute to the transition between states of sevoflurane sedation and general anaesthesia.

Electroencephalography and delirium in the postoperative period.

Delirium commonly manifests in the postoperative period as a clinical syndrome resulting from acute brain dysfunction or encephalopathy. Delirium is characterized by acute and often fluctuating changes in attention and cognition. Emergence delirium typically presents and resolves within minutes to hours after termination of general anaesthesia. Postoperative delirium hours to days after an invasive procedure can herald poor outcomes. Easily recognized when patients are hyperactive or agitated, delirium often evades diagnosis as it most frequently presents with hypoactivity and somnolence. EEG offers objective measurements to complement clinical assessment of this complex fluctuating disorder. Although EEG features of delirium in the postoperative period remain incompletely characterized, a shift of EEG power into low frequencies is a typical finding shared among encephalopathies that manifest with delirium. In aggregate, existing data suggest that serial or continuous EEG in the postoperative period facilitates monitoring of delirium development and severity and assists in detecting epileptic aetiologies. Future studies are needed to clarify the precise EEG features that can reliably predict or diagnose delirium in the postoperative period, and to provide mechanistic insights into this pathologically diverse neurological disorder.

Review of perioperative falls.

Falls are a known public health problem, and there is increasing recognition of the importance of perioperative falls for risk prediction and quality assessment. Our objective was to review existing literature regarding the occurrence, injuries, and risk factors of preoperative and postoperative falls. A systematized search of PubMed entries between 1947 and November 2015 produced 24 articles that met inclusion criteria. Most studied orthopaedic surgery patients older than 65 yr. Four were rated 'good' quality. Interrater reliability for the quality assessment was moderate (κ = 0.77). In the 3-12 months before surgery, the proportion of preoperative patients who fell ranged from 24 to 48%. Injuries were common (70%). The rate of postoperative falls ranged from 0.8 to 16.3 per 1000 person-days, with a gradual decline in the months after surgery. Injuries from postoperative falls occurred in 10-70% of fallers, and 5-20% experienced a severe injury. Risk factors were not well studied. Prospective studies reported a higher percentage of falls and fall-related injuries than retrospective studies, suggesting that there may be underdetection of falls and injuries with retrospective studies. Perioperative falls were more common than falls reported in the general community, even up to 12 months after surgery. Surgery-related falls may therefore occur beyond the hospitalization period. Future studies should use a prospective design, validated definitions, and broader populations to study perioperative falls. In particular, investigations of risk factors and follow-up after hospitalization are needed. REGISTRY NUMBER: PROSPERO registration number CRD42015029971.

Protocol for the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) study: a pragmatic, randomised clinical trial.

INTRODUCTION: Postoperative delirium, arbitrarily defined as occurring within 5 days of surgery, affects up to 50% of patients older than 60 after a major operation. This geriatric syndrome is associated with longer intensive care unit and hospital stay, readmission, persistent cognitive deterioration and mortality. No effective preventive methods have been identified, but preliminary evidence suggests that EEG monitoring during general anaesthesia, by facilitating reduced anaesthetic exposure and EEG suppression, might decrease incident postoperative delirium. This study hypothesises that EEG-guidance of anaesthetic administration prevents postoperative delirium and downstream sequelae, including falls and decreased quality of life. METHODS AND ANALYSIS: This is a 1232 patient, block-randomised, double-blinded, comparative effectiveness trial. Patients older than 60, undergoing volatile agent-based general anaesthesia for major surgery, are eligible. Patients are randomised to 1 of 2 anaesthetic approaches. One group receives general anaesthesia with clinicians blinded to EEG monitoring. The other group receives EEG-guidance of anaesthetic agent administration. The outcomes of postoperative delirium (≤5 days), falls at 1 and 12 months and health-related quality of life at 1 and 12 months will be compared between groups. Postoperative delirium is assessed with the confusion assessment method, falls with ProFaNE consensus questions and quality of life with the Veteran's RAND 12-item Health Survey. The intention-to-treat principle will be followed for all analyses. Differences between groups will be presented with 95% CIs and will be considered statistically significant at a two-sided p<0.05. ETHICS AND DISSEMINATION: Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) is approved by the ethics board at Washington University. Recruitment began in January 2015. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media. TRIAL REGISTRATION NUMBER: NCT02241655; Pre-results.