Electroencephalographic and Cardiovascular Assessments of Isoflurane-Anesthetized Dogs.

This study investigated the use of frontal electroencephalography (EEG) to monitor varying levels of isoflurane anesthesia in dogs. The patient state index (PSI), burst suppression ratio (SR), and waveforms, were continuously recorded while mean arterial blood pressure (MBP), heart rate, responses to electric stimuli, and subjective anesthetic "depth" were assessed every 3 min. At deep anesthesia (2.5× MAC - 3.2%), the PSI (6.5 ± 10.8) and MBP (45.6 ± 16.4 mmHg) were the lowest, and SR was the highest (78.3 ± 24.0%). At 1× MAC (1.3%), the PSI and MBP increased significantly to 47.8 ± 12.6 and 99.8 ± 13.2, respectively, and SR decreased to 0.5 ± 2.5%. The EEG was predominantly isoelectric at 2×-2.5× MAC, indicating unconsciousness and unresponsiveness. As anesthesia lightened, waveforms transitioned to flatter and faster activity patterns with a response to noxious stimuli, suggesting regained consciousness. The PSI and MBP exhibited a stronger correlation (ρ = 0.8098, p = 0.001) than the relationship of PSI with heart rate (ρ = -0.2089, p = 0.249). Five of the six dogs experienced rough recovery, possibly due to high SR and low MBP. These findings suggest that EEG monitoring in dogs can be a valuable tool for the real-time tracking of brain states and can be used to guide the management of isoflurane anesthesia.

Overcoming age: Slow anesthesia induction may prevent geriatric patients from developing burst suppression and help developing intraoperative EEG signatures of a younger brain.

Elderly patients are prone to develop postoperative neurocognitive deficits potentially precipitated by inadequate anesthetic management. To investigate the potential of EEG-guided individualized anesthetic titration we evaluated the effect of the patient's age on the spectral composition of the EEG during slow propofol induction. Twenty-six young (<65 years) and 25 old (≥65 years) patients received propofol until loss of responsiveness (LOR). After LOR, we switched from a flow rate-based to a target-controlled infusion mode keeping the calculated effect-site concentration at LOR stable. We recorded a frontal EEG and calculated the power spectral density (PSD) and the band powers. For the comparison of the spectral composition of old and young patients, we used an effect size, the area under the receiver operating characteristic curve. The older patients received significantly less propofol (p < 0.001). No patient showed a burst suppression pattern. Whereas the absolute power in all frequency bands decreased significantly with the patient's age, the spectral composition did not change throughout the extended induction period. Slow anesthesia induction may be a suitable approach for geriatric patients to preserve spectral composition patterns typically found in younger brains and to individually identify anesthetic requirements reducing the risk of excessive anesthetic effects.

Intrafamilial neurological phenotypic variability due to either biallelic or monoallelic pathogenic variants in CACNA1A.

Pathogenic heterozygous variants in CACNA1A are associated with familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia type 6, and more recently, neurodevelopmental disorders. We describe a severe, early-onset phenotype including severe muscular hypotonia, early-onset epileptic seizures, apnoea, optic atrophy and dysphagia in three siblings carrying compound heterozygous frameshift variants in CACNA1A. Two male patients died at the age of 5 or 14 months of suspected SIDS or severe developmental epileptic encephalopathy (DEE) with refractory seizures and apnoea. A male child (index patient) developed severe early-onset DEE including seizures and ictal apnoea at the age of 4 weeks. Another male child developed generalized epilepsy and mild intellectual impairment in late infancy, and his mother and his maternal uncle were identified as carriers of a known CACNA1A pathogenic variant [c.2602delG heterozygous, p. (Ala868Profs*24)] with a diagnosis of episodic ataxia type 2. This maternal pathogenic variant c.2602delG was detected in the index patient and child 2. Trio-Exome sequencing identified an additional heterozygous pathogenic variant in the CACNA1A gene, c.5476delC, p.(His1826Thrfs*30) in the index patient and child 2, which was inherited from the asymptomatic father. In conclusion, the novel compound heterozygosity for two frameshift pathogenic variants, maternally [c.2602delG, p.(Ala868Profs*24)] and paternally [c.5476delC, p.(His1826Thrfs*3)] is associated with a severe phenotype of early-onset DEE. This observation highlights the necessity of additional analyses to clarify unusual phenotypes even if a pathogenic variant has already been identified, and expands the clinical spectrum of CACNA1A-related disorders.

Optimizing anesthesia management based on early identification of electroencephalogram burst suppression risk in non-cardiac surgery patients: a visualized dynamic nomogram.

BACKGROUND: Burst suppression (BS) is a specific electroencephalogram (EEG) pattern that may contribute to postoperative delirium and negative outcomes. Few prediction models of BS are available and some factors such as frailty and intraoperative hypotension (IOH) which have been reported to promote the occurrence of BS were not included. Therefore, we look forward to creating a straightforward, precise, and clinically useful prediction model by incorporating new factors, such as frailty and IOH. MATERIALS AND METHODS: We retrospectively collected 540 patients and analyzed the data from 418 patients. Univariate analysis and backward stepwise logistic regression were used to select risk factors to develop a dynamic nomogram model, and then we developed a web calculator to visualize the process of prediction. The performance of the nomogram was evaluated in terms of discrimination, calibration, and clinical utility. RESULTS: According to the receiver operating characteristic (ROC) analysis, the nomogram showed good discriminative ability (AUC = 0.933) and the Hosmer-Lemeshow goodness-of-fit test demonstrated the nomogram had good calibration (p = 0.0718). Age, Clinical Frailty Scale (CFS) score, midazolam dose, propofol induction dose, total area under the hypotensive threshold of mean arterial pressure (MAP_AUT), and cerebrovascular diseases were the independent risk predictors of BS and used to construct nomogram. The web-based dynamic nomogram calculator was accessible by clicking on the URL: https://eegbsnomogram.shinyapps.io/dynnomapp/ or scanning a converted Quick Response (QR) code. CONCLUSIONS: Incorporating two distinctive new risk factors, frailty and IOH, we firstly developed a visualized nomogram for accurately predicting BS in non-cardiac surgery patients. The model is expected to guide clinical decision-making and optimize anesthesia management.

We firstly developed a dynamic nomogram to accurately predict the risk of burst suppression (BS) in non-cardiac surgery, and provided a Quick Response (QR) code based on a web calculator to visualize it.The accuracy of the model is enhanced by the inclusion of frailty and intraoperative hypotension (IOH).Our model aims to help clinicians effectively identify the risk of BS, thus guiding clinical decision-making and optimizing anesthesia management.

Use of ketamine in Super Refractory Status Epilepticus: a systematic review.

OBJECTIVE: This review specifically investigates ketamine's role in SRSE management. METHODS: PubMed, EMBASE, and Google Scholar databases were searched from inception to May 1st, 2023, for English-language literature. Inclusion criteria encompassed studies on SRSE in humans of all ages and genders treated with ketamine. RESULTS: In this systematic review encompassing 19 studies with 336 participants, age ranged from 9 months to 86 years. Infections, anoxia, and metabolic issues emerged as the common causes of SRSE, while some cases had unknown origins, termed as NORSE (New Onset RSE) or FIRESs (Febrile Infection-Related Epilepsy Syndrome). Most studies categorized SRSE cases into convulsive (N = 105) and non-convulsive (N = 197). Ketamine was used after failed antiepileptics and anesthetics in 17 studies, while in others, it was a first or second line of treatment. Dosages varied from 0.5 mg/kg (bolus) and 0.2-15 mg/kg/hour (maintenance) in adults and 1-3 mg/kg (bolus) and 0.5-3 mg/kg/hour (maintenance) in pediatrics, lasting one to 30 days. Ketamine was concurrently used with other drugs in 40-100% of cases, most frequently propofol and midazolam. Seizure resolution rate varied from 53.3 to 91% and 40-100% in larger (N = 42-68) and smaller case series (N = 5-20) respectively. Seizure resolution occurred in every case of case report except in one in which the patient died. Burst suppression in EEG was reported in 12 patients from two case series and two case reports. Recurrence was reported in 11 patients from five studies. The reported all-cause mortality varied from 38.8 to 59.5% and 0-36.4% in larger and smaller case series., unrelated directly to ketamine dosage or duration. SIGNIFICANCE: Ketamine demonstrates safety and effectiveness in SRSE, offering advantages over GABAergic drugs by acting on NMDA receptors, providing neuroprotection, and reducing vasopressor requirement.

Intraoperative electroencephalogram patterns as predictors of postoperative delirium in older patients: a systematic review and meta-analysis.

Background: Postoperative delirium (POD) significantly affects patient outcomes after surgery, leading to increased morbidity, extended hospital stays, and potential long-term cognitive decline. This study assessed the predictive value of intraoperative electroencephalography (EEG) patterns for POD in adults. Methods: This systematic review and meta-analysis followed the PRISMA and Cochrane Handbook guidelines. A thorough literature search was conducted using PubMed, Medline, and CENTRAL databases focusing on intraoperative native EEG signal analysis in adult patients. The primary outcome was the relationship between the burst suppression EEG pattern and POD development. Results: From the initial 435 articles identified, 19 studies with a total of 7,229 patients were included in the systematic review, with 10 included in the meta-analysis (3,705 patients). In patients exhibiting burst suppression, the POD incidence was 22.1% vs. 13.4% in those without this EEG pattern (p=0.015). Furthermore, an extended burst suppression duration associated with a higher likelihood of POD occurrence (p = 0.016). Interestingly, the burst suppression ratio showed no significant association with POD. Conclusions: This study revealed a 41% increase in the relative risk of developing POD in cases where a burst suppression pattern was present. These results underscore the clinical relevance of intraoperative EEG monitoring in predicting POD in older patients, suggesting its potential role in preventive strategies. Systematic Review Registration: This study was registered on International Platform for Registered Protocols for Systematic Reviews and Meta-Analyses: INPLASY202420001, https://doi.org/10.37766/inplasy2024.2.0001.

[Updated ESAIC guidelines on postoperative delirium in adults]. / Aktualisierte ESAIC-Leitlinie zum postoperativen Delir beim Erwachsenen.

The updated ESAIC guideline on postoperative delirium (POD) comprises a total of 13 recommendations, including five with the recommendation grade "strong": 1.) The assessment of preoperative POD risk factors, 2.) the optimisation of the preoperative condition, 3.) the discussion of prevention strategies, 4) the implementation of a non-pharmacological multicomponent intervention in patients at risk of POD and 5.) the risk-benefit assessment of the prophylactic administration of dexmedetomidine. The latter applies in particular due to the partly contradictory data situation and different areas of application (cardiac surgery versus non-cardiac surgery patients). Index-based EEG monitoring of the depth of anaesthesia is also recommended, whereby other parameters such as burst suppression and density spectral array should also be included. If non-pharmacological measures fail, POD should be treated with haloperidol. In contrast, the use of benzodiazepines is not recommended.

Continuity with caveats in anesthesia: state and response entropy of the EEG.

The growing use of neuromonitoring in general anesthesia provides detailed insights into the effects of anesthetics on the brain. Our study focuses on the processed EEG indices State Entropy (SE), Response Entropy (RE), and Burst Suppression Ratio (BSR) of the GE EntropyTM Module, which serve as surrogate measures for estimating the level of anesthesia. While retrospectively analyzing SE and RE index values from patient records, we encountered a technical anomaly with a conspicuous distribution of index values. In this single-center, retrospective study, we analyzed processed intraoperative electroencephalographic (EEG) data from 15,608 patients who underwent general anesthesia. We employed various data visualization techniques, including histograms and heat maps, and fitted custom non-Gaussian curves. Individual patients' anesthetic periods were evaluated in detail. To compare distributions, we utilized the Kolmogorov-Smirnov test and Kullback-Leibler divergence. The analysis also included the influence of the BSR on the distribution of SE and RE values. We identified distinct pillar indices for both SE and RE, i.e., index values with a higher probability of occurrence than others. These pillar index values were not age-dependent and followed a non-equidistant distribution pattern. This phenomenon occurs independently of the BSR distribution. SE and RE index values do not adhere to a continuous distribution, instead displaying prominent pillar indices with a consistent pattern of occurrence across all age groups. The specific features of the underlying algorithm responsible for this pattern remain elusive.

Early onset epileptic and developmental encephalopathy and MOGS variants: a new diagnosis in the whole exome sequencing (WES) ERA : Report of a new patient and review of the literature.

Mannosyl-oligosaccharide glucosidase - congenital disorder of glycosylation (MOGS-CDG) is determined by biallelic mutations in the mannosyl-oligosaccharide glucosidase (glucosidase I) gene. MOGS-CDG is a rare disorder affecting the processing of N-Glycans (CDG type II) and is characterized by prominent neurological involvement including hypotonia, developmental delay, seizures and movement disorders. To the best of our knowledge, 30 patients with MOGS-CDG have been published so far. We described a child who is compound heterozygous for two novel variants in the MOGS gene. He presented Early Infantile Developmental and Epileptic Encephalopathy (EI-DEE) in the absence of other specific systemic involvement and unrevealing first-line biochemical findings. In addition to the previously described features, the patient presented a Hirschprung disease, never reported before in individuals with MOGS-CDG.

Utility and limitations of EEG in the diagnosis and management of ALDH7A1-related pyridoxine-dependent epilepsy. A retrospective observational study.

Purpose: Pyridoxine-dependent epilepsy due to ALDH7A1 variants (PDE-ALDH7A1) is a rare disorder, presenting typically with severe neonatal, epileptic encephalopathy. Early diagnosis is imperative to prevent uncontrolled seizures. We have explored the role of EEG in the diagnosis and management of PDE. Methods: A total of 13 Norwegian patients with PDE-ALDH7A1 were identified, of whom five had reached adult age. Altogether 163 EEG recordings were assessed, 101 from the 1st year of life. Results: Median age at seizure onset was 9 h (IQR 41), range 1 h-6 days. Median delay from first seizure to first pyridoxine injection was 2 days (IQR 5.5). An EEG burst suppression pattern was seen in eight patients (62%) during the first 5 days of life. Eleven patients had recordings during pyridoxine injections: in three, immediate EEG improvement correlated with seizure control, whereas in six, no change of epileptiform activity occurred. Of these six, one had prompt clinical effect, one had delayed effect (< 1 day), one had no effect, one had uncertain effect, and another had more seizures. A patient without seizures at time of pyridoxine trial remained seizure free for 6 days. Two patients with prompt clinical effect had increased paroxysmal activity, one as a conversion to burst suppression. Autonomic seizures in the form of apnoea appeared to promote respiratory distress and were documented by EEG in one patient. EEG follow-up in adult age did not show signs of progressing encephalopathy. Conclusion: A neonatal burst suppression EEG pattern should raise the suspicion of PDE-ALDH7A1. Respiratory distress is common; isolated apnoeic seizures may contribute. EEG responses during pyridoxine trials are diverse, often with poor correlation to immediate clinical effect. Reliance on single trials may lead to under-recognition of this treatable condition. Pyridoxine should be continued until results from biomarkers and genetic testing are available.

Effect of remimazolam on electroencephalogram burst suppression in elderly patients undergoing cardiac surgery: Protocol for a randomized controlled noninferiority trial.

Background: Postoperative delirium (POD) is a common complication following cardiac surgery and increases postoperative morbidity and mortality. Intraoperative electroencephalogram (EEG) burst suppression suggests excessively deep anesthesia and predicts POD. Use of remimazolam provides a stable hemodynamic status and an appropriate depth of anesthesia. We aim to assess remimazolam administered for anesthesia and sedation in elderly patients having cardiac surgery. Methods: This is a randomized controlled clinical trial with noninferiority design. A total of 260 elderly patients aged equal to or greater than 60 years undergoing cardiac surgery will be randomly allocated to receive remimazolam or propofol (1:1) for general anesthesia and postoperative sedation until extubation. The primary outcome is the cumulative time with EEG burst suppression which is obtained from the SedLine system. The noninferiority margin is 2.0 min. The secondary outcomes include the POD occurrence within the first 5 days postoperatively and the duration of perioperative hypotension. Discussion: This noninferiority trial is the first to evaluate the effect of perioperative remimazolam administration on EEG burst suppression, POD occurrence, and duration of hypotension in elderly patients who undergo cardiac surgery. Trial registration: Chinese Clinical Trial Registry (ChiCTR2200056353).

A Retrospective Study of the Patient State Index During General Anesthesia in Infants and Young Children.

This study described electroencephalogram (EEG) parameters in children under general anesthesia, which could monitor patient-specific brain responses to anesthetics and assess the effects of anesthesia. The objective was to detect the patient state index (PSI) and associated factors. We analyzed EEG parameters in patients in the age range 1 to 36 months. Patients were stratified into 2 groups as those aged 1 to 12 months and 13 to 36 months. Sixty-two patients were involved. Spectral edge frequency (SEF), PSI, and blood pressure were lower, and burst suppression rate (BSR) and heart rate were higher in the 1 to 12 months group. The SEF was associated with PSI in both groups. Age and blood pressure were positively associated with PSI, and BSR was negatively related to PSI in children under 1 year of age. Blood pressure was not associated with PSI in the 13 to 36 months age group. We found that the PSI levels did not accurately assess the depth of anesthesia in children under 1 year of age.

Prevalence of nonconvulsive seizures and nonconvulsive status epilepticus in dogs and cats with a history of cluster seizures: A retrospective study.

BACKGROUND: Nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE) are frequently observed in human patients. Diagnosis of NCS and NCSE only can be achieved by the use of electroencephalography (EEG). Electroencephalographic monitoring is rare in veterinary medicine and consequently there is limited data on frequency of NCS and NCSE. OBJECTIVES: Determine the prevalence of NCS and NCSE in dogs and cats with a history of cluster seizures. ANIMALS: Twenty-six dogs and 12 cats. METHODS: Retrospective study. Medical records of dogs and cats with cluster seizures were reviewed. Electroencephalography was performed in order to identify electrographic seizure activity after the apparent cessation of convulsive seizure activity. RESULTS: Nonconvulsive seizures were detected in 9 dogs and 2 cats out of the 38 patients (29%). Nonconvulsive status epilepticus was detected in 4 dogs and 2 cats (16%). Five patients had both NCS and NCSE. A decreased level of consciousness was evident in 6/11 patients with NCS, 3/6 also had NCSE. Mortality rate for patients with NCS (73%) and NCSE (67%) was much higher than that for patients with no seizure activity on EEG (27%). CONCLUSION AND CLINICAL IMPORTANCE: Prevalence of NCS and NCSE is high in dogs and cats with a history of cluster seizures. Nonconvulsive seizures and NCSE are difficult to detect clinically and are associated with higher in hospital mortality rates. Results indicate that prompt EEG monitoring should be performed in dogs and cats with cluster seizures.

The dosage of thiopental as pharmacological cerebral protection during non-shunt carotid endarterectomy: A retrospective study.

Background: Thiopental has been used as a pharmacological cerebral protection strategy during carotid endarterectomy surgeries. However, the optimal dosage required to induce burst suppression on the electroencephalogram (EEG) remains unknown. This retrospective study aimed to determine the optimal dosage of thiopental required to induce burst suppression during non-shunt carotid endarterectomy. Methods: The Neurological Institute of Thailand Review Board approved the study. Data were collected from 2009 to 2019 for all non-shunt carotid endarterectomy patients who received thiopental for pharmacological cerebral protection and had intraoperative EEG monitoring. Demographic information, carotid stenosis severity, intraoperative EEG parameters, thiopental dosage, carotid clamp time, intraoperative events, and patient outcomes were abstracted. Results: The study included 57 patients. Among them, 24 patients (42%) achieved EEG burst suppression pattern with a thiopental dosage of 26.3±10.1 mg/kg/hr. There were no significant differences in perioperative events between patients who achieved burst suppression and those who did not. After surgery, 33.3% of patients who achieved burst suppression were extubated and awakened. One patient in the non-burst suppression group experienced mild neurological deficits. No deaths occurred within one month postoperative. Conclusions: The optimal dosage of thiopental required to achieve burst suppression on intraoperative EEG during non-shunt carotid endarterectomy was 26.3±10.1 mg/kg/hr.

Electric Field Effects on Brain Activity: Implications for Epilepsy and Burst Suppression.

Electric fields are now considered a major mechanism of epileptiform activity. However, it is not clear if another electrophysiological phenomenon, burst suppression, utilizes the same mechanism for its bursting phase. Thus, the purpose of this study was to compare the role of ephaptic coupling-the recruitment of neighboring cells via electric fields-in generating bursts in epilepsy and burst suppression. We used local injections of the GABA-antagonist picrotoxin to elicit epileptic activity and a general anesthetic, sevoflurane, to elicit burst suppression in rabbits. Then, we applied an established computational model of pyramidal cells to simulate neuronal activity in a 3-dimensional grid, with an additional parameter to trigger a suppression phase based on extra-cellular calcium dynamics. We discovered that coupling via electric fields was sufficient to produce bursting in scenarios where inhibitory control of excitatory neurons was sufficiently low. Under anesthesia conditions, bursting occurs with lower neuronal recruitment in comparison to seizures. Our model predicts that due to the effect of electric fields, the magnitude of bursts during seizures should be roughly 2-3 times the magnitude of bursts that occur during burst suppression, which is consistent with our in vivo experimental results. The resulting difference in magnitude between bursts during anesthesia and epileptiform bursts reflects the strength of the electric field effect, which suggests that burst suppression and epilepsy share the same ephaptic coupling mechanism.

EEG pre-burst suppression: characterization and inverse association with preoperative cognitive function in older adults.

The most common complication in older surgical patients is postoperative delirium (POD). POD is associated with preoperative cognitive impairment and longer durations of intraoperative burst suppression (BSup) - electroencephalography (EEG) with repeated periods of suppression (very low-voltage brain activity). However, BSup has modest sensitivity for predicting POD. We hypothesized that a brain state of lowered EEG power immediately precedes BSup, which we have termed "pre-burst suppression" (preBSup). Further, we hypothesized that even patients without BSup experience these preBSup transient reductions in EEG power, and that preBSup (like BSup) would be associated with preoperative cognitive function and delirium risk. Data included 83 32-channel intraoperative EEG recordings of the first hour of surgery from 2 prospective cohort studies of patients ≥age 60 scheduled for ≥2-h non-cardiac, non-neurologic surgery under general anesthesia (maintained with a potent inhaled anesthetic or a propofol infusion). Among patients with BSup, we defined preBSup as the difference in 3-35 Hz power (dB) during the 1-s preceding BSup relative to the average 3-35 Hz power of their intraoperative EEG recording. We then recorded the percentage of time that each patient spent in preBSup, including those without BSup. Next, we characterized the association between percentage of time in preBSup and (1) percentage of time in BSup, (2) preoperative cognitive function, and (3) POD incidence. The percentage of time in preBSup and BSup were correlated (Spearman's ρ [95% CI]: 0.52 [0.34, 0.66], p < 0.001). The percentage of time in BSup, preBSup, or their combination were each inversely associated with preoperative cognitive function (ß [95% CI]: -0.10 [-0.19, -0.01], p = 0.024; -0.04 [-0.06, -0.01], p = 0.009; -0.04 [-0.06, -0.01], p = 0.003, respectively). Consistent with prior literature, BSup was significantly associated with POD (odds ratio [95% CI]: 1.34 [1.01, 1.78], p = 0.043), though this association did not hold for preBSup (odds ratio [95% CI]: 1.04 [0.95, 1.14], p = 0.421). While all patients had ≥1 preBSup instance, only 20.5% of patients had ≥1 BSup instance. These exploratory findings suggest that future studies are warranted to further study the extent to which preBSup, even in the absence of BSup, can identify patients with impaired preoperative cognition and/or POD risk.

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.

Modulatory dynamics mark the transition between anesthetic states of unconsciousness.

Unconsciousness maintained by GABAergic anesthetics, such as propofol and sevoflurane, is characterized by slow-delta oscillations (0.3 to 4 Hz) and alpha oscillations (8 to 14 Hz) that are readily visible in the electroencephalogram. At higher doses, these slow-delta-alpha (SDA) oscillations transition into burst suppression. This is a marker of a state of profound brain inactivation during which isoelectric (flatline) periods alternate with periods of the SDA patterns present at lower doses. While the SDA and burst suppression patterns have been analyzed separately, the transition from one to the other has not. Using state-space methods, we characterize the dynamic evolution of brain activity from SDA to burst suppression and back during unconsciousness maintained with propofol or sevoflurane in volunteer subjects and surgical patients. We uncover two dynamical processes that continuously modulate the SDA oscillations: alpha-wave amplitude and slow-wave frequency modulation. We present an alpha modulation index and a slow modulation index which characterize how these processes track the transition from SDA oscillations to burst suppression and back to SDA oscillations as a function of increasing and decreasing anesthetic doses, respectively. Our biophysical model reveals that these dynamics track the combined evolution of the neurophysiological and metabolic effects of a GABAergic anesthetic on brain circuits. Our characterization of the modulatory dynamics mediated by GABAergic anesthetics offers insights into the mechanisms of these agents and strategies for monitoring and precisely controlling the level of unconsciousness in patients under general anesthesia.

Analysis of the relationship between EEG burst suppression and poor prognosis in children under general anaesthesia: study protocol for a prospective, observational, single-centre study.

BACKGROUND: Emergence delirium (ED) in children refers to the immediate postoperative period when children experience decreased perception of their surroundings, accompanied by disorientation and altered perception. Burst suppression (BS) is recognised as periods longer than 0.50 s during which the EEG does not exceed approximately + 5.0 mV, which is an electroencephalographic state associated with profound inactivation of the brain. Our primary objective was to determine the association between BS on electroencephalogram (EEG) under general anaesthesia with postoperative wake-up delirium and multiple adverse outcomes, such as prolonged awakening and extubation. METHODS: In this prospective, observational cohort study at Beijing Children's Hospital, Capital Medical University, Beijing, China, children aged 6 months to 9 years who underwent surgery under general anaesthesia and underwent EEG monitoring between January 2022 and January 2023 were included. Patients' prefrontal EEGs were recorded intraoperatively as well as analysed for the occurrence and duration of BS and scored postoperatively for delirium by the PAED scale, with a score of no less than 10 considered as having developed wake-up delirium. DISCUSSION: This study identified a relationship between EEG BS and postoperative awakening delirium under general anaesthesia in children and provides a novel preventive strategy for postoperative awakening delirium and multiple adverse outcomes in paediatric patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055256. Registered on January 5, 2022.