Repurposing electroencephalogram monitoring of general anaesthesia for building biomarkers of brain ageing: an exploratory study.

Background: Electroencephalography (EEG) is increasingly used for monitoring the depth of general anaesthesia, but EEG data from general anaesthesia monitoring are rarely reused for research. Here, we explored repurposing EEG monitoring from general anaesthesia for brain-age modelling using machine learning. We hypothesised that brain age estimated from EEG during general anaesthesia is associated with perioperative risk. Methods: We reanalysed four-electrode EEGs of 323 patients under stable propofol or sevoflurane anaesthesia to study four EEG signatures (95% of EEG power <8-13 Hz) for age prediction: total power, alpha-band power (8-13 Hz), power spectrum, and spatial patterns in frequency bands. We constructed age-prediction models from EEGs of a healthy reference group (ASA 1 or 2) during propofol anaesthesia. Although all signatures were informative, state-of-the-art age-prediction performance was unlocked by parsing spatial patterns across electrodes along the entire power spectrum (mean absolute error=8.2 yr; R2=0.65). Results: Clinical exploration in ASA 1 or 2 patients revealed that brain age was positively correlated with intraoperative burst suppression, a risk factor for general anaesthesia complications. Surprisingly, brain age was negatively correlated with burst suppression in patients with higher ASA scores, suggesting hidden confounders. Secondary analyses revealed that age-related EEG signatures were specific to propofol anaesthesia, reflected by limited model generalisation to anaesthesia maintained with sevoflurane. Conclusions: Although EEG from general anaesthesia may enable state-of-the-art age prediction, differences between anaesthetic drugs can impact the effectiveness and validity of brain-age models. To unleash the dormant potential of EEG monitoring for clinical research, larger datasets from heterogeneous populations with precisely documented drug dosage will be essential.

Association of sleep and anaesthesia EEG biomarkers with preoperative MoCA score: A pilot study.

INTRODUCTION: Preoperative cognitive impairments increase the risk of postoperative complications. The electroencephalogram (EEG) could provide information on cognitive vulnerability. The feasibility and clinical relevance of sleep EEG (EEGsleep ) compared to intraoperative EEG (EEGintraop ) in cognitive risk stratification remains to be explored. We investigated similarities between EEGsleep and EEGintraop vis-a-vis preoperative cognitive impairments. METHODS: Pilot study including 27 patients (63 year old [53.5, 70.0]) to whom Montreal cognitive assessment (MoCA) and EEGsleep were administered 1 day before a propofol-based general anaesthesia, in addition to EEGintraop acquisition from depth-of-anaesthesia monitors. Sleep spindles on EEGsleep and intraoperative alpha-band power on EEGintraop were particularly explored. RESULTS: In total, 11 (41%) patients had a MoCA <25 points. These patients had a significantly lower sleep spindle power on EEGsleep (25 vs. 40 µv2 /Hz, p = .035) and had a weaker intraoperative alpha-band power on EEGintraop (85 vs. 150 µv2 /Hz, p = .001) compared to patients with normal MoCA. Correlation between sleep spindle and intraoperative alpha-band power was positive and significant (r = 0.544, p = .003). CONCLUSION: Preoperative cognitive impairment appears to be detectable by both EEGsleep and EEGintraop . Preoperative sleep EEG to assess perioperative cognitive risk is feasible but more data are needed to demonstrate its benefit compared to intraoperative EEG.

Impact of impaired cerebral blood flow autoregulation on electroencephalogram signals in adults undergoing propofol anaesthesia: a pilot study.

Background: Cerebral autoregulation actively maintains cerebral blood flow over a range of MAPs. During general anaesthesia, this mechanism may not compensate for reductions in MAP leading to brain hypoperfusion. Cerebral autoregulation can be assessed using the mean flow index derived from Doppler measurements of average blood velocity in the middle cerebral artery, but this is impractical for routine monitoring within the operating room. Here, we investigate the possibility of using the EEG as a proxy measure for a loss of cerebral autoregulation, determined by the mean flow index. Methods: Thirty-six patients (57.5 [44.25; 66.5] yr; 38.9% women, non-emergency neuroradiology surgery) anaesthetised using propofol were prospectively studied. Continuous recordings of MAP, average blood velocity in the middle cerebral artery, EEG, and regional cerebral oxygen saturation were made. Poor cerebral autoregulation was defined as a mean flow index greater than 0.3. Results: Eighteen patients had preserved cerebral autoregulation, and 18 had altered cerebral autoregulation. The two groups had similar ages, MAPs, and average blood velocities in the middle cerebral artery. Patients with altered cerebral autoregulation exhibited a significantly slower alpha peak frequency (9.4 [9.0, 9.9] Hz vs 10.5 [10.1, 10.9] Hz, P<0.001), which persisted after adjusting for age, norepinephrine infusion rate, and ASA class (odds ratio=0.038 [confidence interval, 0.004, 0.409]; P=0.007). Conclusion: In this pilot study, we found that loss of cerebral autoregulation was associated with a slower alpha peak frequency, independent of age. This work suggests that impaired cerebral autoregulation could be monitored in the operating room using the existing EEG setup. Clinical trial registration: NCT03769142.

Simplified frontal EEG in adults under veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: EEG-based prognostication studies in intensive care units often rely on a standard 21-electrode montage (stdEEG) requiring substantial human, technical, and financial resources. We here evaluate whether a simplified 4-frontal electrode montage (4-frontEEG) can detect EEG patterns associated with poor outcomes in adult patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: We conducted a reanalysis of EEG data from a prospective cohort on 118 adult patients under VA-ECMO, in whom EEG was performed on admission to intensive care. EEG patterns of interest included background rhythm, discontinuity, reactivity, and the Synek's score. They were all reassessed by an intensivist on a 4-frontEEG montage, whose analysis was then compared to an expert's interpretation made on stdEEG recordings. The main outcome measure was the degree of correlation between 4-frontEEG and stdEEG montages to identify EEG patterns of interest. The performance of the Synek scores calculated on 4-frontEEG and stdEEG montage to predict outcomes (i.e., 28-day mortality and 90-day Rankin score [Formula: see text]) was investigated in a secondary exploratory analysis. RESULTS: The detection of EEG patterns using 4-frontEEG was statistically similar to that of stdEEG for background rhythm (Spearman rank test, ρ = 0.66, p < 0.001), discontinuity (Cohen's kappa, [Formula: see text] = 0.955), reactivity ([Formula: see text] = 0.739) and the Synek's score (ρ = 0.794, p < 0.001). Using the Synek classification, we found similar performances between 4-frontEEG and stdEEG montages in predicting 28-day mortality (AUC 4-frontEEG 0.71, AUC stdEEG 0.68) and for 90-day poor neurologic outcome (AUC 4-frontEEG 0.71, AUC stdEEG 0.66). An exploratory analysis confirmed that the Synek scores determined by 4 or 21 electrodes were independently associated with 28-day mortality and poor 90-day functional outcome. CONCLUSION: In adult patients under VA-ECMO, a simplified 4-frontal electrode EEG montage interpreted by an intensivist, detected common EEG patterns associated with poor outcomes, with a performance similar to that of a standard EEG montage interpreted by expert neurophysiologists. This simplified montage could be implemented as part of a multimodal evaluation for bedside prognostication.

Propofol Requirement and EEG Alpha Band Power During General Anesthesia Provide Complementary Views on Preoperative Cognitive Decline.

Background: Although cognitive decline (CD) is associated with increased post-operative morbidity and mortality, routinely screening patients remains difficult. The main objective of this prospective study is to use the EEG response to a Propofol-based general anesthesia (GA) to reveal CD. Methods: 42 patients with collected EEG and Propofol target concentration infusion (TCI) during GA had a preoperative cognitive assessment using MoCA. We evaluated the performance of three variables to detect CD (MoCA < 25 points): age, Propofol requirement to induce unconsciousness (TCI at SEF95: 8-13 Hz) and the frontal alpha band power (AP at SEF95: 8-13 Hz). Results: The 17 patients (40%) with CD were significantly older (p < 0.001), had lower TCI (p < 0.001), and AP (p < 0.001). We found using logistic models that TCI and AP were the best set of variables associated with CD (AUC: 0.89) and performed better than age (p < 0.05). Propofol TCI had a greater impact on CD probability compared to AP, although both were complementary in detecting CD. Conclusion: TCI and AP contribute additively to reveal patient with preoperative cognitive decline. Further research on post-operative cognitive trajectory are necessary to confirm the interest of intra operative variables in addition or as a substitute to cognitive evaluation.

Influence of noninvasive central blood pressure devices for afterload monitoring with aortic velocity-pressure Loop in anesthetized patients.

BACKGROUND: Global afterload angle (GALA) is a parameter derived from velocity-pressure loop (VP Loop), for continuous assessment of cardiac afterload in the operating room. It has been validated with invasive measure of central pressure. The aim of this study was to evaluate the feasibility of noninvasive VP Loop obtained with central pressure measured with two different noninvasive tonometers. METHODS: A prospective, observational, monocentric study was conducted in 51 patients under general anesthesia. Invasive central pressure (cPINV) was measured with a fulfilled intravascular catheter, and noninvasive central pressure signals were obtained with two applanation tonometry devices: radial artery tonometry (cPSHYG: Sphygmocor tonometer) and carotid tonometry (cPCOMP: Complior tonometer). Three VP Loops were built: VP LoopINV, VP LoopSPHYG and VP LoopCOMP. Patients were separated according to cardiovascular risk factors. RESULTS: In the 51 patients under general anesthesia, cPSHYG was adequately obtained in 48 patients (89%) but, compared to cPINV, SBP was underestimated (-4 ± 6 mmHg, P < 0.0001), augmentation index (AIXSPHYG) and a GALASPHYG were overestimated (+13 ± 19%, P = 0.0077 and +4 ± 8°, P = 0.0024, respectively) with large limit of agreement (LOA) (-21 to 47% and -13 to 21° for AIXSPHYG and GALASPHYG, respectively). With the Complior, the failure rate of measurement for cPCOMP was 41%. SBP was similar (3 ± 17 mmHg, P = 0.32), AIXCOMP was underestimated (-11 ± 19%, P = 0.0046) and GALACOMP was similar but with large LOA (-50 to 26% and -20 to 18° for AIXCOMP and GALACOMP, respectively). CONCLUSION: In anesthetized patient, the reliability of noninvasive central pressure monitoring by tonometry seems too limited to monitor cardiac afterload with VP Loop.

Impact of hypotension on cerebral perfusion during general anesthesia induction: A prospective observational study in adults.

INTRODUCTION: During anesthesia, decreases in mean arterial pressure (MAP) are common but the impact on possible cerebral hypoperfusion remains a matter of debate. We evaluated cerebral perfusion in patients with or without cardiovascular comorbidities (Hi-risk vs Lo-risk) during induction of general anesthesia and during hypotensive episodes. METHODS: Patients scheduled for neuroradiology procedure using standardized target-controlled Propofol-Remifentanil infusion were prospectively included. Monitoring included Transcranial Doppler (TCD) measuring mean blood velocity of the middle cerebral artery (Vm), Bispectral Index with burst suppression ratio (SR) and cerebral Near-Infrared Spectroscopy (NIRS). Hypotensive episodes were treated with a 10 µg bolus of Norepinephrine. RESULTS: Eighty-one patients were included, 37 Hi-risk and 44 Lo-risk. During induction of anesthesia, MAP and Vm decreased in all patients, with greater changes observed in Hi-risk patients compared to Lo-risk patients (-34 [38-29]% vs -17 [25-8]%, P < .001 and -39 [45-29]% vs -28 [34-19]%, P < .01 respectively). In Hi-risk patients, the MAP-decrease correlated with the Vm-decrease (r = .48, P < .01), and was associated with more frequent occurrences of SR (21 vs 5 patients, P < .01 for Hi-risk vs Lo-risk). For the MAP-increase induced by norepinephrine, the Vm-increase was greater in Hi-risk than in Lo-risk patients (+15 [8-21]% vs +4 [1-11]%, P < .01). During induction and norepinephrine boluses, NIRS values did not follow acute changes of Vm. CONCLUSION: Our results showed that Hi-risk patients had a higher decrease in MAP and Vm, and a higher occurrence of SR during induction of anesthesia than Lo-risk patients. Correction of MAP with norepinephrine increased Vm mainly in Hi-rik patients.

Alpha rhythm collapse predicts iso-electric suppressions during anesthesia.

Could an overly deep sedation be anticipated from ElectroEncephaloGram (EEG) patterns? We report here motifs hidden in the EEG signal that predict the appearance of Iso-Electric Suppressions (IES), observed during epileptic encephalopathies, drug intoxications, comatose, brain death or during anesthetic over-dosage that are considered to be detrimental. To show that IES occurrences can be predicted from EEG traces dynamics, we focus on transient suppression of the alpha rhythm (8-14 Hz) recorded for 80 patients, that had a Propofol target controlled infusion of 5 µg/ml during a general anesthesia. We found that the first time of appearance as well as changes in duration of these Alpha-Suppressions (αS) are two parameters that anticipate the appearance of IES. Using machine learning, we predicted IES appearance from the first 10 min of EEG (AUC of 0.93). To conclude, transient motifs in the alpha rhythm predict IES during anesthesia and can be used to identify patients, with higher risks of post-operative complications.

EEG power spectral density under Propofol and its association with burst suppression, a marker of cerebral fragility.

OBJECTIVE: Under General Anesthesia (GA), age and Burst Suppression (BS) are associated with cognitive postoperative complications, yet how these parameters are related to per-operative EEG and hypnotic doses is unclear. In this prospective study, we address this question comparing age and BS occurrences with a new score (BPTIVA) based on Propofol doses, EEG and alpha-band power spectral densities, evaluated for SEF95 = 8-13 Hz. METHODS: 59 patients (55 [34-67] yr, 67% female) undergoing neuroradiology or orthopedic surgery were included. Total IntraVenous Anesthesia was used for Propofol and analgesics infusion. Cerebral activity was monitored from a frontal electrodes montage EEG. RESULTS: BPTIVA was inversely correlated with age (Pearson r = -0.78, p < 0.001), and was significantly lower (p < 0.001) when BS occurred during the GA first minutes (induction). Additionally, the age-free BPTIVA score was better associated with BS at induction than age (AUC = 0.94 versus 0.82, p < 0.05). CONCLUSION: We designed BPTIVA score based on hypnotics and EEG. It was correlated with age yet was better associated to BS occurring during GA induction, the latter being a cerebral fragility sign. SIGNIFICANCE: This advocate for an approach based on evaluating the cerebral physiological age («brain age¼) to predict postoperative cognitive evolution.

Predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation.

BACKGROUND: Amikacin infusion requires targeting a peak serum concentration (Cmax) 8-10 times the minimal inhibitory concentration, corresponding to a Cmax of 60-80 mg/L for the least susceptible bacteria to theoretically prevent therapeutic failure. Because drug pharmacokinetics on extracorporeal membrane oxygenation (ECMO) are challenging, we undertook this study to assess the frequency of insufficient amikacin Cmax in critically ill patients on ECMO and to identify relative risk factors. METHODS: This was a prospective, observational, monocentric study in a university hospital. Patients on ECMO who received an amikacin loading dose for suspected Gram-negative infections were included. The amikacin loading dose of 25 mg/kg total body weight was administered intravenously and Cmax was measured 30 min after the end of the infusion. Independent predicators of Cmax < 60 mg/L after the first amikacin infusion were identified with mixed-model multivariable analyses. Various dosing simulations were performed to assess the probability of reaching 60 mg/L < Cmax < 80 mg/L. RESULTS: A total of 106 patients on venoarterial ECMO (VA-ECMO) (68%) or venovenous-ECMO (32%) were included. At inclusion, their median (1st; 3rd quartile) Sequential Organ-Failure Assessment score was 15 (12; 18) and 54 patients (51%) were on renal replacement therapy. Overall ICU mortality was 54%. Cmax was < 60 mg/L in 41 patients (39%). Independent risk factors for amikacin under-dosing were body mass index (BMI) < 22 kg/m2 and a positive 24-h fluid balance. Using dosing simulation, increasing the amikacin dosing regimen to 30 mg/kg and 35 mg/kg of body weight when the 24-h fluid balance is positive and the BMI is ≥ 22 kg/m2 or < 22 kg/m2 (Table 3), respectively, would have potentially led to the therapeutic target being reached in 42% of patients while reducing under-dosing to 23% of patients. CONCLUSIONS: ECMO-treated patients were under-dosed for amikacin in one third of cases. Increasing the dose to 35 mg/kg of body weight in low-BMI patients and those with positive 24-h fluid balance on ECMO to reach adequate targeted concentrations should be investigated.