Richard K. Ellerkmann

BACKGROUND: Postoperative delirium (POD) occurs frequently after cardiac surgery and is associated with increased morbidity and mortality. We analysed whether perioperative bilateral BIS monitoring may detect abnormalities before the onset of POD in cardiac surgery patients. METHODS: In a prospective observational study, 81 patients undergoing cardiac surgery were included. Bilateral Bispectral Index (BIS)-monitoring was applied during the pre-, intra- and postoperative period, and BIS, EEG Asymmetry (ASYM), and Burst Suppression Ratio (BSR) were recorded. POD was diagnosed according to the Confusion Assessment Method for the Intensive Care Unit, and patients were divided into a delirium and non-delirium group. RESULTS: POD was detected in 26 patients (32%). A trend towards a lower ASYM was observed in the delirium group as compared to the non-delirium group on the preoperative day (ASYM = 48.2 ± 3.6% versus 50.0 ± 4.7%, mean ± sd, p = 0.087) as well as before induction of anaesthesia, with oral midazolam anxiolysis (median ASYM = 49.5%, IQR [47.4;51.5] versus 50.6%, IQR [49.1;54.2], p = 0.081). Delirious patients remained significantly (p = 0.018) longer in a burst suppression state intraoperatively (107 minutes, IQR [47;170] versus 44 minutes, IQR [11;120]) than non-delirious patients. Receiver operating analysis revealed burst suppression duration (area under the curve = 0.73, p = 0.001) and BSR (AUC = 0.68, p = 0.009) as predictors of POD. CONCLUSIONS: Intraoperative assessment of BSR may identify patients at risk of POD and should be investigated in further studies. So far it remains unknown whether there is a causal relationship or rather an association between intraoperative burst suppression and the development of POD. TRIAL REGISTRATION: clinicaltrials.gov NCT01048775.

BACKGROUND: There is an urgent need to rapidly distinguish COVID-19 from other respiratory conditions, including influenza, at first-presentation. Point-of-care tests not requiring laboratory- support will speed diagnosis and protect health-care staff. We studied the feasibility of using breath-analysis to distinguish these conditions with near-patient gas chromatography-ion mobility spectrometry (GC-IMS). METHODS: Independent observational prevalence studies at Edinburgh, UK, and Dortmund, Germany, recruited adult patients with possible COVID-19 at hospital presentation. Participants gave a single breath-sample for VOC analysis by GC-IMS. COVID-19 infection was identified by transcription polymerase chain reaction (RT- qPCR) of oral/nasal swabs together with clinical-review. Following correction for environmental contaminants, potential COVID-19 breath-biomarkers were identified by multi-variate analysis and comparison to GC-IMS databases. A COVID-19 breath-score based on the relative abundance of a panel of volatile organic compounds was proposed and tested against the cohort data. FINDINGS: Ninety-eight patients were recruited, of whom 21/33 (63.6%) and 10/65 (15.4%) had COVID-19 in Edinburgh and Dortmund, respectively. Other diagnoses included asthma, COPD, bacterial pneumonia, and cardiac conditions. Multivariate analysis identified aldehydes (ethanal, octanal), ketones (acetone, butanone), and methanol that discriminated COVID-19 from other conditions. An unidentified-feature with significant predictive power for severity/death was isolated in Edinburgh, while heptanal was identified in Dortmund. Differentiation of patients with definite diagnosis (25 and 65) of COVID-19 from non-COVID-19 was possible with 80% and 81.5% accuracy in Edinburgh and Dortmund respectively (sensitivity/specificity 82.4%/75%; area-under-the-receiver- operator-characteristic [AUROC] 0.87 95% CI 0.67 to 1) and Dortmund (sensitivity / specificity 90%/80%; AUROC 0.91 95% CI 0.87 to 1). INTERPRETATION: These two studies independently indicate that patients with COVID-19 can be rapidly distinguished from patients with other conditions at first healthcare contact. The identity of the marker compounds is consistent with COVID-19 derangement of breath-biochemistry by ketosis, gastrointestinal effects, and inflammatory processes. Development and validation of this approach may allow rapid diagnosis of COVID-19 in the coming endemic flu seasons. FUNDING: MR was supported by an NHS Research Scotland Career Researcher Clinician award. DMR was supported by the University of Edinburgh ref COV_29.

Background Recently, entropy algorithms have been proposed as electroencephalographic measures of anesthetic drug effects. Datex-Ohmeda (Helsinki, Finland) introduced the Entropy Module, a new electroencephalographic monitor designed for measuring depth of anesthesia. The monitor calculates a state entropy (SE) computed over the frequency range of 0.8-32 Hz and a response entropy (RE) computed over the frequency range of 0.8-47 Hz. The authors investigated the dose-response relation of SE and RE during sevoflurane anesthesia in comparison with the Bispectral Index (BIS). Methods Sixteen patients were studied without surgical stimulus. Anesthesia was induced by sevoflurane inhalation with a tight-fitting facemask. Sevoflurane concentrations were increased and subsequently decreased and increased two to four times until the measurement was stopped and patients were intubated for surgery. The performances of SE, RE, and BIS to predict the estimated sevoflurane effect site concentration, obtained by simultaneous pharmacokinetic and pharmacodynamic modeling, were compared by calculating the correlation coefficients and the prediction probability. Results State entropy, RE, and BIS values decreased continuously over the observed concentration range of sevoflurane. Correlation coefficients were slightly but not significantly better for entropy parameters (0.87 +/- 0.09 and 0.86 +/- 0.10 for SE and RE, respectively) than for BIS (0.85 +/- 0.12). Calculating the prediction probability confirmed these results with a prediction probability of 0.84 +/- 0.05 and 0.82 +/- 0.06 for SE and RE, respectively, and 0.80 +/- 0.06 for BIS. Conclusion State entropy and RE seem to be useful electroencephalographic measures of sevoflurane drug effect.

BACKGROUND: The Bispectral Index (BIS) and the Patient State Index (PSI) quantify depth of anesthesia by analyzing the electroencephalogram. The authors examined the response of BIS and PSI to sevoflurane anesthesia. METHODS: In 22 patients, sevoflurane anesthesia was induced by inhalation with a tight-fitting facemask and was maintained via a laryngeal mask. Sevoflurane concentrations were increased until burst suppression occurred and subsequently decreased until BIS recovered to values above 60. This procedure was repeated twice until patients underwent intubation for subsequent surgery. End-tidal sevoflurane concentrations, BIS, and PSI were recorded simultaneously. The performance of PSI and BIS to predict the estimated sevoflurane effect site concentration, as derived from simultaneous pharmacokinetic and pharmacodynamic modeling, was compared by determination coefficients (rho(2)) and prediction probabilities (P(K)). RESULTS: A significant (P < 0.001) correlation between BIS and PSI was found (r(2) = 0.75), and a close sigmoid relation between sevoflurane effect site concentration and both BIS (rho(2) = 0.84 +/- 0.09) and PSI (rho(2) = 0.85 +/- 0.15) was observed. The maximum sevoflurane electroencephalographic effect resulted in PSI values (1.3 +/- 4.3) that were significantly (P = 0.019) lower than BIS values (7.9 +/- 12.1), and the effect site efflux constant k(e0) was significantly smaller (P = 0.001) for PSI (0.13 +/- 0.08 min(-1)) than for BIS (0.24 +/- 0.15 min(-1)). The probability of BIS (P(K) = 0.80 +/- 0.11) to predict sevoflurane effect site concentration did not differ (P = 0.76) from that of PSI (P(K) = 0.79 +/- 0.09). CONCLUSIONS: The BIS reacted faster to changes in sevoflurane concentrations, whereas the PSI made better use of the predefined index range. However, despite major differences in their algorithms and minor differences in their dose-response relations, both PSI and BIS predicted depth of sevoflurane anesthesia equally well.