EEG dynamics in children from preanesthetic awake state, under general anaesthesia until regain of consciousness

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Devices have been developed for adult patients, and validation in this young patient population is often lacking. However, young children are particularly vulnerable to anaesthesia, and the effects of anaesthetics on brain development are uncertain. The purpose of this study was to characterise perioperative frontal EEGs in young children younger than 8 years. Methods A total of 147 frontal EEGs from children ranging from 1 month to 8 years of age were recorded prospectively under general anaesthesia at Charité - Campus Virchow Klinik (CVK). For data acquisition, the Narcotrend Monitor was used, and the raw EEG files were further analysed in their frequency bands. The patient cohort was divided into four age groups (0–5 months, 6–11 months, 12–23 months, and > 24 months), and EEG signatures were compared between the age groups. Results Delta activity is the predominant frequency in all age groups already in the awake state before induction of anaesthesia, with a step increase at loss of consciousness, which is more pronounced in older children. Intraoperatively, alpha- and beta-activity emerges at the age of six months and is greater in the older age groups. Infants (0–5 months) remain with a high amount of Delta activity intraoperatively. With the return of consciousness, the faster frequencies gradually decrease, and the EEG is characterised again by a predominant delta-activity in all age groups. Conclusion In this study, we characterised differences in the perioperative EEG signatures of children from 1 month to 8 years from the preoperative awake state during induction and general anaesthesia until they regained consciousness from general anaesthesia. The EEG readouts differ across age groups, and age-adapted monitoring systems are needed to protect this vulnerable patient group from over- and undersedation. Trial Registration This study was approval from the Charité – University Medicine Berlin's ethics committee (EA2/027/15) and was registered at clinicaltrials.gov (23rd of June 2015/NCT02481999). paediatric anaesthesia EEG neuromonitoring Figures Figure 1 Figure 2 Keywords 1. Children <6 months of age show only minimal changes in EEG dynamics from preanaesthetic state, under general anaesthesia until regain of consciousness. 2. Delta activity is the predominant frequency throughout general anaesthesia from awake state until regain of consciousness in all age groups. 3. Activation of faster frequencies (alpha and beta) under general anaesthesia can only be observed from 6 months onwards. 1. Introduction General anaesthesia is administered to children for surgical procedures every day across the globe. While it is essential for pain-free surgery, concerns regarding its potential impact on the developing brain have been growing. Although these effects are not immediately observable, evidence from preclinical studies and emerging clinical data suggests that general anaesthetics may have long-term consequences for the central nervous system ( 1 , 2 ). Preclinical studies have demonstrated that anaesthetic agents disrupt neurodevelopment through dual receptor-mediated mechanisms. Potentiation of GABA_A receptors induces paradoxical excitatory depolarisation in immature neurons due to elevated intracellular chloride, triggering calcium overload and excitotoxicity ( 3 , 4 ). NMDA receptor inhibition suppresses glutamate-mediated trophic signalling, impairing dendritic maturation and synaptic refinement ( 3 , 5 , 6 ). This receptor imbalance amplifies mitochondrial apoptotic pathways, which are characterised by Bax translocation, cytochrome C release, and caspase-3 activation ( 3 , 6 ). Combined GABAergic and NMDA antagonist exposure synergistically exacerbates neurodegeneration, with animal models showing dose-dependent reductions in hippocampal neurogenesis and persistent deficits in learning and social behaviour ( 3 , 5 ). The FDA’s 2017 warning-updated in 2022-highlights prolonged or repeated exposures as higher-risk scenarios, reflecting preclinical evidence of dendritic spine loss and glial dysfunction ( 7 , 8 ). The FDA advised healthcare providers to consider delaying nonurgent procedures in this age group when medically appropriate ( 9 ). This warning was grounded in animal studies, where exposure to general anaesthetics led to neurodegeneration, underlining the vulnerability of the developing brain ( 10 – 12 ). The translation of these findings into clinical outcomes remains complex. Smaller clinical studies suggest that a single brief exposure to general anaesthesia does not result in long-term neurodevelopmental impairment ( 13 ). However, multiple exposures have been associated with deficits in various cognitive domains, including executive function, memory, learning, language skills, visual perception, and behaviour ( 13 ). Larger, more rigorous studies provide nuanced insights. The GAS trial, which compared general anaesthesia with spinal anaesthesia in infants, reported no evidence of harm from a single exposure of less than one hour ( 14 ). Similarly, the PANDA and MASK trials reported no significant neurocognitive effects from single brief exposures ( 15 , 16 ). However, the MASK trial also indicated that multiple exposures may be associated with subtle neurodevelopmental deficits, although confounding factors such as preexisting medical conditions limit definitive conclusions. An emerging approach to optimise anaesthetic care and possibly mitigate risk is EEG-based neuromonitoring, which provides real-time information about brain activity and anaesthesia depth. While this technique is increasingly used in adult and elderly populations—to prevent oversedation and postoperative delirium ( 17 )—its application in paediatrics remains underexplored. Bong et al. (2023) reported that EEG patterns in young children differ significantly from those in adults and that current evidence-based guidance for its use in paediatric anaesthesia is lacking ( 18 ). Aim of the Study The aim of this study was to characterise EEG signals in children during the perioperative period—from the preanaesthetic awake state, induction of anaesthesia, and intraoperative general anaesthesia through emergence from general anaesthesia—to improve our understanding of paediatric brain responses under general anaesthesia and to develop future EEG neuromonitoring algorithms. 2. Methods 2.1 Data collection and participant demographics In this prospective clinical observational study, electroencephalogram (EEG) data were recorded from children with approval from the Charité – University Medicine Berlin's ethics committee (EA2/027/15). The study was registered at clinicaltrials.gov under the number: NCT02481999. The data were collected at the Campus Virchow Klinik (CVK) of the Charité – Universitätsmedizin Berlin, which spans from 08.09.2015--24.05.2017. Inclusion criteria: male or female children aged 0.5--8 years planned elective surgery informed consent by both parents if both parents have joint custody No planned operation in the next three months No operation in the last half year before study inclusion Exclusion criteria: known neurological or psychiatric precondition (disease) inability of the parents to speak and/or read German Indications for the isolation of patients with multiresistant bacteria lack of willingness to save and hand out pseudonymized data within the clinical study contact allergy to silver or silver chloride participation in another prospective interventional clinical study As shown in Figure 1, a total of 412 patients were screened during the study. A total of 112 parents refused to participate in the study. Furthermore, 109 patients did not fulfil the inclusion criteria, of whom 58 were diagnosed with neurological or psychiatric preconditions, 20 parents were unable to communicate sufficiently in German, 12 were planning for very short operations, seven were not allowed to have intraoperative EEG data, seven were isolated due to multidrug-resistant bacteria, three exceeded the age limit, and two patients were already participating in a different prospective study. Therefore, 197 patients were enrolled in the study. Fifty patients were further excluded because of cancelled operations (n=17) or incomplete EEG data (n=27), parents of four children changed their minds, and two patients were later shown that they did not fulfil the inclusion criteria. The EEG data of 147 patients were analysed, and these patients were divided into 4 age groups: 0–5 months (n=6), 6–11 months (n=18), 12–23 months (n=29) and ≥24 months (n=94). EEG data from infants (Clinicaltrials.gov Registration: NCT04093661) were collected from 2018 until 2019 with the same inclusion and exclusion criteria with approval from the Charité–University Medicine Berlin ethics committee (EA2/115/19). Both patient cohorts were combined for further EEG processing and final analysis. In line with our institution's standard operating procedures, frontal EEG recordings during surgery were performed via Narcotrend Monitor (MT Monitor Technik GmbH & Co. KG, Bad Bramstedt, Germany; Software version 4.0). To ensure low impedance levels, the skin was prepared with alcohol prior to electrode placement. EEG electrodes (Ambu BlueSensor N, Bad Nauheim, Germany) were positioned at the Fz, F7, and F8 locations, with Fp2 used as the reference point. The impedance at each electrode site was maintained below 5 kΩ, with the disparity between any two electrodes remaining under 3.5 kΩ. Recordings were captured at a sampling rate of 128 Hz, employing a bandpass filter that restricted the frequency range to 0.5–45 Hz. Using EEG-Viewer software (MT Monitor Technik, Bad Bramstedt, Germany, Version 6.1), a two-minute segment devoid of artifacts was selected by manual inspection for each time point. Data were exported as CSV files from the EEG viewer, and analyses were conducted to ascertain the mean total power (0.5--45 Hz), along with the mean absolute and relative powers of the β (12.5--30 Hz), α (7.5--12.5 Hz), θ (3.5--7.5 Hz), and δ (0.5--3.5 Hz) frequency bands for the designated two-minute epochs. The continuous EEGs were subsegmented into 2-minute intervals at four time points: Baseline : This interval was shortly before the induction of anaesthesia. During this time interval, the children were awake. Loss of consciousness (LOC) : This time, together with the attending anaesthetist, the child no longer reacted, and the airway was secured afterwards. Intraop : The interval was at least 15 min after surgical incision. During this period, anaesthesia was maintained, and a stable course was observed. Return of consciousness (ROC) : At this time, the child opened his or her eyes, or movement was observed. 2.2 Statistical analysis: The EEG frequency band power perioperatively over the four time points was analysed and compared across the four age groups. We used the Kruskal‒Wallis test to compare EEG frequency band power among the four age groups at a single time point, as the data were not normally distributed. This nonparametric test is appropriate for detecting differences between independent groups when the assumption of normality is violated. When the Kruskal‒Wallis test indicated significant group differences, we performed post hoc pairwise comparisons between age groups. To control for multiple testing and reduce the risk of Type I error, p values were adjusted via the Bonferroni correction. The data are presented as the means and 95% confidence intervals. Statistical testing was performed in SPSS © (Version 29, Chicago, Illinois, USA). For better visualisation, the statistical program R (Version 4.3.3 Vienna, Austria) was used to plot the diagrams via the emmeans and ggplot packages. 3. Results We included 147 children in total, with six aged 0–5 months, 18 aged 6–11 months, 29 aged 12–23 months and 94 > 24 months. Patient characteristics are presented in Table 1. In the infant age group (0–5 months), a higher American Society of Anesthesiologists (ASA) score was observed than in the older group, where the ASA status was evenly distributed. The duration of anaesthesia was longer for 6–11-month-old children because mostly cleft lip or cleft palate surgeries, which usually have long operating times, were performed. Premedication with p.o. midazolam was not prescribed for children < 6 months of age according to our hospital’s standard operating procedures. From 6 months, almost all the children received premedication with midazolam at a similar dosage ranging from 0.59 mg/kg body weight (>24 months) to 0.77 mg/kg body weight (12–23 months). Induction of anaesthesia was performed inhalative for children <6 months. In older children, induction changed from inhalation with sevoflurane to intravenous induction with propofol. From 24 months onwards, children mainly received i.v. induction. For maintenance of anaesthesia, mainly sevoflurane was used for up to 23 months. Afterward, in children >24 months, both sevoflurane (52,9%) and total intravenous anaesthesia (TIVA) (44,7%) were used for maintenance of anaesthesia. 3.1 Baseline EEG In the preoperative baseline EEG, the dominant frequency in all age groups was in the δ range. It expands from 1181 µV² (95% CI: 347; 2016 µV²) in 0–5-month-old children to 4978 µV² (95% CI: 4039; 5917 µV²) in children > 24 months. θ-frequencies and β-frequencies are present in all age groups, whereas α-band power remains markedly low during the preoperative baseline period. Specifically, α-power ranges from 16 µV² (95% CI: 1; 30 µV²) in the youngest group to 31 µV² (95% CI: 27; 35 µV²) in children over 24 months, indicating a minimal contribution of α-activity in the resting state across the examined age spectrum (Figure 2). 3.2 Loss of consciousness After the induction of anaesthesia, the EEG is characterised by an increase in δ-activity. In the baseline EEG, the power in the δ-frequency band was similar across all age groups; however, after induction of anaesthesia, the power of the δ-activity increased sharply in all age groups, most markedly in the group of 24-month-old children, with a 2.1-fold increase. Owing to this difference, the absolute power in the δ-frequency band now differs significantly (0–5 months: 4240 µV² (95% CI: -4134; 12614 µV²) and in >24 months 10467 µV² (95% CI: 8711; 12223 µV²) post hoc analysis with Bonferoni correction p=0,019) (Figure 2). Children > 6 months show a steep increase in β-activity, α-activity and θ-activity from baseline to loss of consciousness. In contrast, young children <6 months present minimal β-, α-, and θ-activity at loss of consciousness and, importantly, are now dynamic from baseline (Figure 2). 3.3 Intraoperative EEG Intraoperative EEG is dominated by δ-activity, but the high amplitudes after the induction of anaesthesia decrease back to the baseline level. For children > 6 months, the intraoperative EEG showed further increases in β-activity and α-activity from baseline and loss of consciousness, with increases in β- and α-power with age. In young children <6 months, β-, α-, and θ-activities remain minimal and do not change from baseline, resulting in a loss of consciousness to intraoperative recording. 3.4 Return of consciousness With the return of consciousness, δ-activity again remains the dominant rhythm in all age groups. The β-activity, α-activity and θ-activity observed in children > 6 months after loss of consciousness and during maintenance of anaesthesia decreased again back to their preoperative baseline levels (Figure 2). 4. Discussion In our analysis of perioperative EEG neuromonitoring data, we observed predominant δ-activity across all age groups from the preoperative awake state until the patients regained consciousness. Following induction of anaesthesia, δ-activity increased from baseline through loss of consciousness and remained elevated during the maintenance phase. At the end of general anaesthesia, δ-activity decreased and returned to baseline levels as the patient regained consciousness. Children older than 6 months exhibited a marked age-related increase in α- and β-activity at the time of loss of consciousness, followed by a further increase during intraoperative maintenance. These faster frequencies subsequently declined to baseline levels upon the return of consciousness. In contrast, this perioperative dynamic of α- and β-activity was not observed in children younger than 6 months. Using full-montage EEG, Cornelissen et al. extensively studied children under general anaesthesia. In a 2015 study, they reported that δ-activity is present in awake children aged 0–6 months and represents the dominant rhythm. Furthermore, the absolute δ-power remains relatively constant when comparing preoperative to intraoperative values. Faster frequencies (θ- and α-activity) begin to emerge at approximately 4 months of age during anaesthesia maintenance ( 19 ). Our findings align with these results, confirming that δ-activity remains the dominant frequency both preoperatively and intraoperatively. Faster frequencies were minimal in children younger than 6 months. Since our youngest subgroup includes infants up to 5 months of age—an age at which faster frequencies are just beginning to emerge—the separation of frequency bands is less pronounced. In a separate study conducted at our institution involving newborns and infants aged 0–12 months, α- and β-band activity was first observed at 4 months of age ( 20 ). These findings support the hypothesis that GABAergic synaptogenesis in children under 6 months of age is still developing and therefore does not yet support the generation of characteristic α-oscillations ( 19 ). Beekoo et al. (2019) analysed EEG patterns in patients ranging in age from 1 month to 80 years under general anaesthesia with 1 MAC of sevoflurane. In this deeply anaesthetised state, no fast frequencies were observed in any age group. This aligns with our findings for children under 6 months, where intraoperative EEG recordings were dominated by δ-activity. However, in children older than 6 months, faster frequencies were observed, and with increasing age, α-power increased significantly. These findings suggest that α-activity may serve as a useful marker of adequate anaesthetic depth in more mature paediatric patients ( 21 ). In a randomised controlled trial by Long et al. (2020), 200 children aged 1–6 years received intraoperative sevoflurane titration guided either by EEG neuromonitoring or by standard care. EEG guidance was based on maintaining slow δ-oscillations in the unprocessed raw EEG as a marker of appropriate anaesthetic depth. This approach led to a significant reduction in the sevoflurane concentration—by 88% during induction and 15% during maintenance ( 22 ). Our data show that δ-oscillations are indeed the dominant frequency in the preoperative state across all age groups. While δ-power increases during loss of consciousness, the intraoperative values are comparable to the baseline values. This highlights a challenge: if δ-power is already high in the awake state, it may be difficult to use it reliably as an indicator of anaesthetic depth. A prospective randomised trial by Sullivan et al. at the Children’s Hospital in Boston evaluated whether neuromonitoring via the bispectral index (BIS) in children aged 2–12 years can improve guidance and thereby reduce the sevoflurane concentration intraoperatively. They concluded that the BIS index does not reduce the amount of sevoflurane used intraoperatively and that they do not consider the BIS monitor as a “useful monitor” in the paediatric population ( 23 ). These results are consistent with the results of Tokuwaka et al., in which the BIS value did not fall below the index value of 50 even if the dosage was titrated up to 4.8% sevoflurane; thus, a measurement of the intraoperative anaesthesia depth in children between 1 and 2 years of age does not appear valid ( 24 ). In an observational study from Lee et al., 97 children aged 0–21 years were studied, and raw EEG oscillations were analysed. Interestingly, power was not observed in the very specific alpha range (8–13 Hz) and instead showed a broader span with power at faster frequencies ranging from 12–25 Hz ( 4 ). In an observational study by Cornelissen et al., 95 raw EEGs from children aged 0 to 3 years were recorded during the emergence of anaesthesia. α-Activity was present in all children older than 3 months at an end-expiratory sevoflurane concentration of 2% during surgery. With decreasing sevoflurane concentration, the α-activity decreased until it disappeared. In almost all patients, body movement occurs within 5 minutes after the loss of α-oscillations ( 25 ). This finding is in line with our results, which revealed prominent α-activity during the maintenance of anaesthesia and only minimal values at the emergence of anaesthesia for children older than 6 months. Infants with initially low alpha-band EEG activity are more likely to develop burst suppression patterns during the maintenance phase of anaesthesia ( 26 ). In neonates undergoing cardiac surgery, the presence of burst suppression has been inversely associated with communication outcomes at five years of age, and those with prolonged burst suppression episodes—lasting over 90 minutes—demonstrated the poorest behavioral outcomes postoperatively ( 27 ). Despite these findings, there are currently no established guidelines specifying how to reliably measure anaesthetic depth or how to optimise it in neonates and infants. However, certain institutions, such as the Department of Women’s and Children’s Hospital in Singapore, have implemented specialised training for anaesthesiologists in interpreting intraoperative EEG patterns in paediatric patients. This targeted education aims to reduce the risk of both over- and undersedation, thereby minimising the potential for anaesthesia-related neurotoxicity in this vulnerable population ( 18 ). Limitations The administration of anaesthetics was not controlled by a uniform drug protocol, which allows different dosages for each individual patient. The anaesthesiologist in charge adhered to the standard operating procedures of our clinic; however, a controlled drug protocol with fixed dosages would ease the comparison between age groups. Unfortunately, ethical reasons make it difficult to perform those studies in these young age groups. Furthermore, the administration of midazolam was not equal across all groups on the basis of our clinical standard operating procedure, especially with no administration in young children aged 0–5 months. However, a prior study by our group revealed that premedication with midazolam increases the intraoperative α-power in adult patients ( 28 ). The group size is inhomogeneous, with a particularly large number of children in the oldest age group. This is because young children are vulnerable to anaesthetics, and the indication for surgery is determined strictly. A larger patient cohort could have increased the reliability of our results and clarified group differences. 5. Conclusion In this study, we aimed to characterise perioperative EEG dynamics in children aged 1 month to 8 years to better understand age-specific EEG signatures and ultimately reduce the risk of anaesthetic over- or underdosing in this vulnerable population. Our findings demonstrate fundamental differences from adult EEG dynamics: notably, delta activity consistently remains the dominant rhythm across all perioperative phases in children, including during wakefulness—a pattern distinctly different from that in adults. Furthermore, intraoperative activation of faster frequency bands, such as the alpha and beta bands, is strongly age dependent, becoming evident only from approximately 6 months of age onwards. These developmental differences underscore the importance of age-adjusted EEG monitoring during paediatric anaesthesia. Declarations Ethics approval and consent to participate In this prospective clinical observational study, electroencephalogram (EEG) data were recorded from children with approval from the Charité University Medicine Berlin ethics committee (EA2/027/15). The study was registered at clinicaltrials.gov under the number: NCT02481999. The data were collected at the Campus Virchow Klinik (CVK) of the Charité – Universitätsmedizin Berlin, which spans from 08.09.2015--24.05.2017. EEG data from infants (Clinicaltrials.gov Registration: NCT04093661) were collected from 2018 until 2019 with the same inclusion and exclusion criteria with approval from the Charité–University Medicine Berlin ethics committee (EA2/115/19). Both patient cohorts were combined for further EEG processing and final analysis. The study adhered to the Declaration of Helsinki. The consent for participation of the patients was obtained from their parents. Consent for publication Not applicable Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request. Competing interests CS received grants or contracts and nonfinancial support from the German Research Society, German Aerospace Center, Einstein Foundation Berlin, Federal Joint Committee (G-BA), Inner University Grants, Project Management Agency, Non-Profit Society Promoting Science and Education, European Society of Anaesthesiology and Intensive Care, BMWI – Federal Ministry for Economic Affairs and Climate Action, Georg Thieme Verlag, Dr. F. Köhler Chemie GmbH, Sintetica GmbH, Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., Stifterverband für die deutsche Wissenschaft e.V., Metronic, Philips Electronics Nederland BV, BMBF (Federal Ministry of Education and Research, RKI, The European Commission Horizont Europa, Prothor, Takeda Pharmaceutical Company Limited, Association of the Scientific Medical Societies in Germany, German Research Foundation, German National Academy of Sciences – Leopoldina, Berliner Medizinische Gesellschaft, European Society of Intensive Care Medicine, European Society of Anaesthesiology and Intensive Care, German Society of Anaesthesiology and Intensive Care Medicine, German Interdisciplinary Association for Intensive Care and Emergency Medicine, German Sepsis Foundation and holds various international patents; these holdings have not affected any decisions regarding his research or this study. SK was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Society) – Project number KO 4249/3-1), she is an inventor on patents, sold to Medtronic. She received speakers’ fee from Medtronic, and personal fees from Georg Thieme Verlag and Springer Verlag. All remaining authors declare that they have no conflict of interest. Funding None Authors' contributions Design of the study: CS, SK, MM, Contribution to the materials/tools: CS, SK Data Collection: FP, SK Data Analyzation: FP, MM, SK Writing manuscript: MM, FP, SK All authors read and approved of the final manuscript Acknowledgements Prior Presentations: An abstract of this project has been presented at the Euroanaesthesia Congress 2025 in Lisbon. Authors' information (optional) References Brown RE, Jr. Safety considerations of anesthetic drugs in children. Expert Opin Drug Saf. 2017;16(4):445-54. Jevtovic-Todorovic V. Exposure of Developing Brain to General Anesthesia: What Is the Animal Evidence? 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Beekoo D, Yuan K, Dai S, Chen L, Di M, Wang S, et al. Analyzing Electroencephalography (EEG) Waves Provides a Reliable Tool to Assess the Depth of Sevoflurane Anesthesia in Pediatric Patients. Med Sci Monit. 2019;25:4035-40. Long MHY, Lim EHL, Balanza GA, Allen JC, Jr., Purdon PL, Bong CL. Sevoflurane requirements during electroencephalogram (EEG)-guided vs standard anesthesia Care in Children: A randomized controlled trial. J Clin Anesth. 2022;81:110913. Sullivan CA, Egbuta C, Park RS, Lukovits K, Cavanaugh D, Mason KP. The Use of Bispectral Index Monitoring Does Not Change Intraoperative Exposure to Volatile Anesthetics in Children. J Clin Med. 2020;9(8). Tokuwaka J, Satsumae T, Mizutani T, Yamada K, Inomata S, Tanaka M. The relationship between age and minimum alveolar concentration of sevoflurane for maintaining bispectral index below 50 in children. Anaesthesia. 2015;70(3):318-22. Cornelissen L, Kim SE, Lee JM, Brown EN, Purdon PL, Berde CB. Electroencephalographic markers of brain development during sevoflurane anaesthesia in children up to 3 years old. Br J Anaesth. 2018;120(6):1274-86. Chao JY, Gutierrez R, Legatt AD, Yozawitz EG, Lo Y, Adams DC, et al. Decreased Electroencephalographic Alpha Power During Anesthesia Induction Is Associated With EEG Discontinuity in Human Infants. Anesth Analg. 2022;135(6):1207-16. Seltzer L, Swartz MF, Kwon J, Burchfiel J, Cholette JM, Wang H, et al. Neurodevelopmental outcomes after neonatal cardiac surgery: Role of cortical isoelectric activity. J Thorac Cardiovasc Surg. 2016;151(4):1137-42. Windmann V, Spies C, Brown EN, Kishnan D, Lichtner G, Koch S. Influence of midazolam premedication on intraoperative EEG signatures in elderly patients. Clin Neurophysiol. 2019;130(9):1673-81. Table 1 Table 1 Patient characteristics 0-5 months (n=6) 6-11 months (n=18) 12-23 months (n=29) >24 months (n=94) Age Months, median (IQR) 3 (2-4) 9 (8-9) 16 (15-20) 67 (63-74) Weight Mean kg (SD) 5.3 (0.5) 8.9 (0.3) 10.5 (0.4) 20.1 (0.7) ASA ASA I (%) 33.3% 70.6% 69% 77.6% ASA II (%) 50% 29.4% 31% 18.8% ASA III (%) 16.7% 3.5% Anaesthesia duration Duration (mean min, SD) 152 (34) 222 (25) 156 (23) 80 (8) Premedication Midazolam received 0% 94.4% 100% 97.6% Dosage (mean mg/kg bw + SD) 0.69 (0.06) 0.77 (0.01) 0.59 (0.02) Induction of Anaesthesia Inhalative with Sevoflurane 100% 66.7% 61.5% 24.1% i.v. with Propofol 33.3% 38.5% 75.9% Maintenance of Anaesthesia Sevoflurane 100% 94.1% 89.3% 52.9% Sevoflurane (mean % (SD) 2.17 (0.18) 2.32 (0.07) 2.36 (0.17) 2.29 (0.06) TIVA 5.9% 7.1% 44.7% TIVA mg/kg/h (mean + (SD)) 8 7.7 (1.7) 8.8 (0.3) Mixed 3.6% 2.4% Classification of Surgery Eye surgery 1 (3.8%) 14 (17.1%) Cleft lip/Cleft palate 1 (16.7%) 10 (66.7%) 11 (42.3%) 2 (2.4%) ENT-surgery 1 (3.8%) 16 (19.5%) Tumor surgery 1 (6.7%) 1 (1.2%) Smaller operations 4h 2 (33.3%) 2 (13.3%) 2 (7.7%) 2 (2.4%) Bronchoscopy 1 (16.7%) Additional Declarations Competing interest reported. CS received grants or contracts and nonfinancial support from the German Research Society, German Aerospace Center, Einstein Foundation Berlin, Federal Joint Committee (G-BA), Inner University Grants, Project Management Agency, Non-Profit Society Promoting Science and Education, European Society of Anaesthesiology and Intensive Care, BMWI – Federal Ministry for Economic Affairs and Climate Action, Georg Thieme Verlag, Dr. F. Köhler Chemie GmbH, Sintetica GmbH, Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., Stifterverband für die deutsche Wissenschaft e.V., Metronic, Philips Electronics Nederland BV, BMBF (Federal Ministry of Education and Research, RKI, The European Commission Horizont Europa, Prothor, Takeda Pharmaceutical Company Limited, Association of the Scientific Medical Societies in Germany, German Research Foundation, German National Academy of Sciences – Leopoldina, Berliner Medizinische Gesellschaft, European Society of Intensive Care Medicine, European Society of Anaesthesiology and Intensive Care, German Society of Anaesthesiology and Intensive Care Medicine, German Interdisciplinary Association for Intensive Care and Emergency Medicine, German Sepsis Foundation and holds various international patents; these holdings have not affected any decisions regarding his research or this study. SK was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Society) – Project number KO 4249/3-1), she is an inventor on patents, sold to Medtronic. She received speakers’ fee from Medtronic, and personal fees from Georg Thieme Verlag and Springer Verlag. All remaining authors declare that they have no conflict of interest. Supplementary Files NarkokidsSupplement.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6696965","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":472488329,"identity":"8b2ad212-b7ae-4c06-9a55-6899a987e759","order_by":0,"name":"Maximilian Markus","email":"data:image/png;base64,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","orcid":"","institution":"Charité - Universitätsmedizin Berlin","correspondingAuthor":true,"prefix":"","firstName":"Maximilian","middleName":"","lastName":"Markus","suffix":""},{"id":472488330,"identity":"20d0c751-4b06-44ce-a29f-d4a078ad88e6","order_by":1,"name":"Feidias Panagiotou","email":"","orcid":"","institution":"Charité - Universitätsmedizin Berlin","correspondingAuthor":false,"prefix":"","firstName":"Feidias","middleName":"","lastName":"Panagiotou","suffix":""},{"id":472488331,"identity":"15710840-a7ba-435b-b33d-7def2b3a7b14","order_by":2,"name":"Claudia Spies","email":"","orcid":"","institution":"Charité - Universitätsmedizin Berlin","correspondingAuthor":false,"prefix":"","firstName":"Claudia","middleName":"","lastName":"Spies","suffix":""},{"id":472488332,"identity":"9491ff63-1e14-4310-9738-660a214d0f08","order_by":3,"name":"Susanne Koch","email":"","orcid":"","institution":"Charité - Universitätsmedizin Berlin","correspondingAuthor":false,"prefix":"","firstName":"Susanne","middleName":"","lastName":"Koch","suffix":""}],"badges":[],"createdAt":"2025-05-19 08:53:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6696965/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6696965/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85364098,"identity":"b91c7b4e-e4a9-49c2-b3f1-33762078583c","added_by":"auto","created_at":"2025-06-25 06:27:09","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":561805,"visible":true,"origin":"","legend":"\u003cp\u003eInclusion and exclusion diagram with 412 patients screened and 147 patients included in the final analysis.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6696965/v1/b6b78d65997c8494705d2ca1.jpg"},{"id":85364094,"identity":"43c0e281-0912-4a54-968d-d6e4f35b3cb2","added_by":"auto","created_at":"2025-06-25 06:27:09","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":171524,"visible":true,"origin":"","legend":"\u003cp\u003eEEG characteristics for each age group. Figure 2a: Total Power, Figure 2b: Delta-Power, Figure 2c: Alpha-Power, Figure 2d: Beta-Power. Delta activity was the dominant rhythm at all 4 time points. After the induction of anaesthesia, faster frequencies can be observed in children \u0026gt; than 6 months. In infants \u0026lt; 6 months, delta activity characterises the EEG, and faster frequencies (alpha and beta) are not observed. (PreOP: Preoperative, LOC: Loss of consciousness, intraOP: maintenance of anaesthesia, ROC: Return of consciousness.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6696965/v1/6db645f467ade6aadd3a6685.jpg"},{"id":86023183,"identity":"e6ebc10d-328f-4694-8c98-8b97a39a10ba","added_by":"auto","created_at":"2025-07-04 12:25:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1361429,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6696965/v1/ffb856be-5f61-4c6f-afde-eed2d451893c.pdf"},{"id":85364641,"identity":"cc17f700-ade6-4b7b-872b-515ea1d39a8d","added_by":"auto","created_at":"2025-06-25 06:35:09","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":21502,"visible":true,"origin":"","legend":"","description":"","filename":"NarkokidsSupplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-6696965/v1/de4d2ec4ede8d33a91f0f6a4.docx"}],"financialInterests":"Competing interest reported. CS received grants or contracts and nonfinancial support from the German Research Society, German Aerospace Center, Einstein Foundation Berlin, Federal Joint Committee (G-BA), Inner University Grants, Project Management Agency, Non-Profit Society Promoting Science and Education, European Society of Anaesthesiology and Intensive Care, BMWI – Federal Ministry for Economic Affairs and Climate Action, Georg Thieme Verlag, Dr. F. Köhler Chemie GmbH, Sintetica GmbH, Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., Stifterverband für die deutsche Wissenschaft e.V., Metronic, Philips Electronics Nederland BV, BMBF (Federal Ministry of Education and Research, RKI, The European Commission Horizont Europa, Prothor, Takeda Pharmaceutical Company Limited, Association of the Scientific Medical Societies in Germany, German Research Foundation, German National Academy of Sciences – Leopoldina, Berliner Medizinische Gesellschaft, European Society of Intensive Care Medicine, European Society of Anaesthesiology and Intensive Care, German Society of Anaesthesiology and Intensive Care Medicine, German Interdisciplinary Association for Intensive Care and Emergency Medicine, German Sepsis Foundation and holds various international patents; these holdings have not affected any decisions regarding his research or this study.\nSK was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Society) – Project number KO 4249/3-1), she is an inventor on patents, sold to Medtronic. She received speakers’ fee from Medtronic, and personal fees from Georg Thieme Verlag and Springer Verlag.\nAll remaining authors declare that they have no conflict of interest.","formattedTitle":"EEG dynamics in children from preanesthetic awake state, under general anaesthesia until regain of consciousness","fulltext":[{"header":"Keywords","content":"\u003cp\u003e1. Children \u0026lt;6 months of age show only minimal changes in EEG dynamics from preanaesthetic state, under general anaesthesia until regain of consciousness.\u003c/p\u003e\n\u003cp\u003e2. Delta activity is the predominant frequency throughout general anaesthesia from awake state until regain of consciousness in all age groups.\u003c/p\u003e\n\u003cp\u003e3. Activation of faster frequencies (alpha and beta) under general anaesthesia can only be observed from 6 months onwards.\u003c/p\u003e"},{"header":"1. Introduction","content":"\u003cp\u003eGeneral anaesthesia is administered to children for surgical procedures every day across the globe. While it is essential for pain-free surgery, concerns regarding its potential impact on the developing brain have been growing. Although these effects are not immediately observable, evidence from preclinical studies and emerging clinical data suggests that general anaesthetics may have long-term consequences for the central nervous system (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePreclinical studies have demonstrated that anaesthetic agents disrupt neurodevelopment through dual receptor-mediated mechanisms. Potentiation of GABA_A receptors induces paradoxical excitatory depolarisation in immature neurons due to elevated intracellular chloride, triggering calcium overload and excitotoxicity (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). NMDA receptor inhibition suppresses glutamate-mediated trophic signalling, impairing dendritic maturation and synaptic refinement (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). This receptor imbalance amplifies mitochondrial apoptotic pathways, which are characterised by Bax translocation, cytochrome C release, and caspase-3 activation (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Combined GABAergic and NMDA antagonist exposure synergistically exacerbates neurodegeneration, with animal models showing dose-dependent reductions in hippocampal neurogenesis and persistent deficits in learning and social behaviour (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe FDA\u0026rsquo;s 2017 warning-updated in 2022-highlights prolonged or repeated exposures as higher-risk scenarios, reflecting preclinical evidence of dendritic spine loss and glial dysfunction (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). The FDA advised healthcare providers to consider delaying nonurgent procedures in this age group when medically appropriate (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). This warning was grounded in animal studies, where exposure to general anaesthetics led to neurodegeneration, underlining the vulnerability of the developing brain (\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe translation of these findings into clinical outcomes remains complex. Smaller clinical studies suggest that a single brief exposure to general anaesthesia does not result in long-term neurodevelopmental impairment (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). However, multiple exposures have been associated with deficits in various cognitive domains, including executive function, memory, learning, language skills, visual perception, and behaviour (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eLarger, more rigorous studies provide nuanced insights. The GAS trial, which compared general anaesthesia with spinal anaesthesia in infants, reported no evidence of harm from a single exposure of less than one hour (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Similarly, the PANDA and MASK trials reported no significant neurocognitive effects from single brief exposures (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). However, the MASK trial also indicated that multiple exposures may be associated with subtle neurodevelopmental deficits, although confounding factors such as preexisting medical conditions limit definitive conclusions.\u003c/p\u003e \u003cp\u003eAn emerging approach to optimise anaesthetic care and possibly mitigate risk is EEG-based neuromonitoring, which provides real-time information about brain activity and anaesthesia depth. While this technique is increasingly used in adult and elderly populations\u0026mdash;to prevent oversedation and postoperative delirium (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u0026mdash;its application in paediatrics remains underexplored. Bong et al. (2023) reported that EEG patterns in young children differ significantly from those in adults and that current evidence-based guidance for its use in paediatric anaesthesia is lacking (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003eAim of the Study\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe aim of this study was to characterise EEG signals in children during the perioperative period\u0026mdash;from the preanaesthetic awake state, induction of anaesthesia, and intraoperative general anaesthesia through emergence from general anaesthesia\u0026mdash;to improve our understanding of paediatric brain responses under general anaesthesia and to develop future EEG neuromonitoring algorithms.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003ch2\u003e2.1 Data collection and participant demographics\u003c/h2\u003e\n\u003cp\u003eIn this prospective clinical observational study, electroencephalogram (EEG) data were recorded from children with approval from the Charit\u0026eacute; \u0026ndash; University Medicine Berlin\u0026apos;s ethics committee (EA2/027/15). The study was registered at clinicaltrials.gov under the number: NCT02481999. The data were collected at the Campus Virchow Klinik (CVK) of the Charit\u0026eacute; \u0026ndash; Universit\u0026auml;tsmedizin Berlin, which spans from 08.09.2015--24.05.2017.\u003c/p\u003e\n\u003cp\u003eInclusion criteria:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003emale or female children aged 0.5--8 years\u003c/li\u003e\n \u003cli\u003eplanned elective surgery\u003c/li\u003e\n \u003cli\u003einformed consent by both parents if both parents have joint custody\u003c/li\u003e\n \u003cli\u003eNo planned operation in the next three months\u003c/li\u003e\n \u003cli\u003eNo operation in the last half year before study inclusion\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eExclusion criteria:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eknown neurological or psychiatric precondition (disease)\u003c/li\u003e\n \u003cli\u003einability of the parents to speak and/or read German\u003c/li\u003e\n \u003cli\u003eIndications for the isolation of patients with multiresistant bacteria\u003c/li\u003e\n \u003cli\u003elack of willingness to save and hand out pseudonymized data within the clinical study\u003c/li\u003e\n \u003cli\u003econtact allergy to silver or silver chloride\u003c/li\u003e\n \u003cli\u003eparticipation in another prospective interventional clinical study\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAs shown in Figure 1, a total of 412 patients were screened during the study. A total of 112 parents refused to participate in the study. Furthermore, 109 patients did not fulfil the inclusion criteria, of whom 58 were diagnosed with neurological or psychiatric preconditions, 20 parents were unable to communicate sufficiently in German, 12 were planning for very short operations, seven were not allowed to have intraoperative EEG data, seven were isolated due to multidrug-resistant bacteria, three exceeded the age limit, and two patients were already participating in a different prospective study. Therefore, 197 patients were enrolled in the study. Fifty patients were further excluded because of cancelled operations (n=17) or incomplete EEG data (n=27), parents of four children changed their minds, and two patients were later shown that they did not fulfil the inclusion criteria. The EEG data of 147 patients were analysed, and these patients were divided into 4 age groups: 0\u0026ndash;5 months (n=6), 6\u0026ndash;11 months (n=18), 12\u0026ndash;23 months (n=29) and \u0026ge;24 months (n=94).\u003c/p\u003e\n\u003cp\u003eEEG data from infants (Clinicaltrials.gov Registration: NCT04093661) were collected from 2018 until 2019 with the same inclusion and exclusion criteria with approval from the Charit\u0026eacute;\u0026ndash;University Medicine Berlin ethics committee (EA2/115/19). Both patient cohorts were combined for further EEG processing and final analysis.\u003c/p\u003e\n\u003cp\u003eIn line with our institution\u0026apos;s standard operating procedures, frontal EEG recordings during surgery were performed via Narcotrend Monitor (MT Monitor Technik GmbH \u0026amp; Co. KG, Bad Bramstedt, Germany; Software version 4.0). To ensure low impedance levels, the skin was prepared with alcohol prior to electrode placement. EEG electrodes (Ambu BlueSensor N, Bad Nauheim, Germany) were positioned at the Fz, F7, and F8 locations, with Fp2 used as the reference point. The impedance at each electrode site was maintained below 5 kΩ, with the disparity between any two electrodes remaining under 3.5 kΩ.\u003c/p\u003e\n\u003cp\u003eRecordings were captured at a sampling rate of 128 Hz, employing a bandpass filter that restricted the frequency range to 0.5\u0026ndash;45 Hz. Using EEG-Viewer software (MT Monitor Technik, Bad Bramstedt, Germany, Version 6.1), a two-minute segment devoid of artifacts was selected by manual inspection for each time point.\u003c/p\u003e\n\u003cp\u003eData were exported as CSV files from the EEG viewer, and analyses were conducted to ascertain the mean total power (0.5--45 Hz), along with the mean absolute and relative powers of the \u0026beta; (12.5--30 Hz), \u0026alpha; (7.5--12.5 Hz), \u0026theta; (3.5--7.5 Hz), and \u0026delta; (0.5--3.5 Hz) frequency bands for the designated two-minute epochs.\u003c/p\u003e\n\u003cp\u003eThe continuous EEGs were subsegmented into 2-minute intervals at four time points: \u003cstrong\u003eBaseline\u003c/strong\u003e: This interval was shortly before the induction of anaesthesia. During this time interval, the children were awake. \u003cstrong\u003eLoss of consciousness (LOC)\u003c/strong\u003e: This time, together with the attending anaesthetist, the child no longer reacted, and the airway was secured afterwards. \u003cstrong\u003eIntraop\u003c/strong\u003e: The interval was at least 15 min after surgical incision. During this period, anaesthesia was maintained, and a stable course was observed. \u003cstrong\u003eReturn of consciousness (ROC)\u003c/strong\u003e: At this time, the child opened his or her eyes, or movement was observed.\u003c/p\u003e\n\u003ch2\u003e2.2 Statistical analysis:\u003c/h2\u003e\n\u003cp\u003eThe EEG frequency band power perioperatively over the four time points was analysed and compared across the four age groups. We used the Kruskal‒Wallis test to compare EEG frequency band power among the four age groups at a single time point, as the data were not normally distributed. This nonparametric test is appropriate for detecting differences between independent groups when the assumption of normality is violated. When the Kruskal‒Wallis test indicated significant group differences, we performed post hoc pairwise comparisons between age groups. To control for multiple testing and reduce the risk of Type I error, p values were adjusted via the Bonferroni correction. The data are presented as the means and 95% confidence intervals. Statistical testing was performed in SPSS \u0026copy; (Version 29, Chicago, Illinois, USA). For better visualisation, the statistical program R (Version 4.3.3 Vienna, Austria) was used to plot the diagrams via the emmeans and ggplot packages.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eWe included 147 children in total, with six aged 0\u0026ndash;5 months, 18 aged 6\u0026ndash;11 months, 29 aged 12\u0026ndash;23 months and 94 \u003cu\u003e\u0026gt;\u003c/u\u003e 24 months. Patient characteristics are presented in Table 1. In the infant age group (0\u0026ndash;5 months), a higher American Society of Anesthesiologists (ASA) score was observed than in the older group, where the ASA status was evenly distributed. The duration of anaesthesia was longer for 6\u0026ndash;11-month-old children because mostly cleft lip or cleft palate surgeries, which usually have long operating times, were performed. Premedication with p.o. midazolam was not prescribed for children \u0026lt; 6 months of age according to our hospital\u0026rsquo;s standard operating procedures. From 6 months, almost all the children received premedication with midazolam at a similar dosage ranging from 0.59 mg/kg body weight (\u0026gt;24 months) to 0.77 mg/kg body weight (12\u0026ndash;23 months). Induction of anaesthesia was performed inhalative for children \u0026lt;6 months. In older children, induction changed from inhalation with sevoflurane to intravenous induction with propofol. From 24 months onwards, children mainly received i.v. induction. For maintenance of anaesthesia, mainly sevoflurane was used for up to 23 months. Afterward, in children \u0026gt;24 months, both sevoflurane (52,9%) and total intravenous anaesthesia (TIVA) (44,7%) were used for maintenance of anaesthesia.\u003c/p\u003e\n\u003ch2\u003e3.1 Baseline EEG\u003c/h2\u003e\n\u003cp\u003eIn the preoperative baseline EEG, the dominant frequency in all age groups was in the \u0026delta; range. It expands from 1181 \u0026micro;V\u0026sup2; (95% CI: 347; 2016 \u0026micro;V\u0026sup2;) in 0\u0026ndash;5-month-old children to 4978 \u0026micro;V\u0026sup2; (95% CI: 4039; 5917 \u0026micro;V\u0026sup2;) in children \u003cu\u003e\u0026gt;\u003c/u\u003e 24 months. \u0026theta;-frequencies and \u0026beta;-frequencies are present in all age groups, whereas \u0026alpha;-band power remains markedly low during the preoperative baseline period. Specifically, \u0026alpha;-power ranges from 16 \u0026micro;V\u0026sup2; (95% CI: 1; 30 \u0026micro;V\u0026sup2;) in the youngest group to 31 \u0026micro;V\u0026sup2; (95% CI: 27; 35 \u0026micro;V\u0026sup2;) in children over 24 months, indicating a minimal contribution of \u0026alpha;-activity in the resting state across the examined age spectrum (Figure 2).\u003c/p\u003e\n\u003ch2\u003e3.2 Loss of consciousness\u003c/h2\u003e\n\u003cp\u003eAfter the induction of anaesthesia, the EEG is characterised by an increase in\u0026nbsp;\u0026delta;-activity. In the baseline EEG, the power in the\u0026nbsp;\u0026delta;-frequency band was similar across all age groups; however, after induction of anaesthesia, the power of the\u0026nbsp;\u0026delta;-activity increased sharply in all age groups, most markedly in the group of 24-month-old children, with a 2.1-fold increase. Owing to this difference, the absolute power in the\u0026nbsp;\u0026delta;-frequency band now differs significantly (0\u0026ndash;5 months: 4240 \u0026micro;V\u0026sup2; (95% CI: -4134; 12614 \u0026micro;V\u0026sup2;) and in \u0026gt;24 months 10467 \u0026micro;V\u0026sup2; (95% CI: 8711; 12223 \u0026micro;V\u0026sup2;) post hoc analysis with Bonferoni correction p=0,019) (Figure 2).\u003c/p\u003e\n\u003cp\u003eChildren \u003cu\u003e\u0026gt;\u003c/u\u003e6 months show a steep increase in\u0026nbsp;\u0026beta;-activity,\u0026nbsp;\u0026alpha;-activity and \u0026theta;-activity\u0026nbsp;from baseline to loss of consciousness. In contrast, young children \u0026lt;6 months present minimal\u0026nbsp;\u0026beta;-,\u0026nbsp;\u0026alpha;-, and\u0026nbsp;\u0026theta;-activity at loss of consciousness and, importantly, are now dynamic from baseline (Figure 2).\u003c/p\u003e\n\u003ch2\u003e3.3 Intraoperative EEG\u003c/h2\u003e\n\u003cp\u003eIntraoperative EEG is dominated by\u0026nbsp;\u0026delta;-activity, but the high amplitudes after the induction of anaesthesia decrease back to the baseline level. For children \u003cu\u003e\u0026gt;\u003c/u\u003e 6 months, the intraoperative EEG showed further increases in\u0026nbsp;\u0026beta;-activity and\u0026nbsp;\u0026alpha;-activity from baseline and loss of consciousness, with increases in\u0026nbsp;\u0026beta;-\u0026nbsp;and\u0026nbsp;\u0026alpha;-power with age. In young children \u0026lt;6 months,\u0026nbsp;\u0026beta;-,\u0026nbsp;\u0026alpha;-,\u0026nbsp;and \u0026theta;-activities remain minimal and do not change from baseline, resulting in a loss of consciousness to intraoperative recording.\u003c/p\u003e\n\u003ch2\u003e3.4 Return of consciousness\u003c/h2\u003e\n\u003cp\u003eWith the return of consciousness,\u0026nbsp;\u0026delta;-activity again remains the dominant rhythm in all age groups. The\u0026nbsp;\u0026beta;-activity,\u0026nbsp;\u0026alpha;-activity and\u0026nbsp;\u0026theta;-activity\u0026nbsp;observed in children \u003cu\u003e\u0026gt;\u003c/u\u003e 6 months after loss of consciousness and during maintenance of anaesthesia decreased again back to their preoperative baseline levels (Figure 2).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn our analysis of perioperative EEG neuromonitoring data, we observed predominant δ-activity across all age groups from the preoperative awake state until the patients regained consciousness. Following induction of anaesthesia, δ-activity increased from baseline through loss of consciousness and remained elevated during the maintenance phase. At the end of general anaesthesia, δ-activity decreased and returned to baseline levels as the patient regained consciousness.\u003c/p\u003e \u003cp\u003eChildren older than 6 months exhibited a marked age-related increase in α- and β-activity at the time of loss of consciousness, followed by a further increase during intraoperative maintenance. These faster frequencies subsequently declined to baseline levels upon the return of consciousness. In contrast, this perioperative dynamic of α- and β-activity was not observed in children younger than 6 months.\u003c/p\u003e \u003cp\u003eUsing full-montage EEG, Cornelissen et al. extensively studied children under general anaesthesia. In a 2015 study, they reported that δ-activity is present in awake children aged 0\u0026ndash;6 months and represents the dominant rhythm. Furthermore, the absolute δ-power remains relatively constant when comparing preoperative to intraoperative values. Faster frequencies (θ- and α-activity) begin to emerge at approximately 4 months of age during anaesthesia maintenance (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Our findings align with these results, confirming that δ-activity remains the dominant frequency both preoperatively and intraoperatively. Faster frequencies were minimal in children younger than 6 months. Since our youngest subgroup includes infants up to 5 months of age\u0026mdash;an age at which faster frequencies are just beginning to emerge\u0026mdash;the separation of frequency bands is less pronounced.\u003c/p\u003e \u003cp\u003eIn a separate study conducted at our institution involving newborns and infants aged 0\u0026ndash;12 months, α- and β-band activity was first observed at 4 months of age (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). These findings support the hypothesis that GABAergic synaptogenesis in children under 6 months of age is still developing and therefore does not yet support the generation of characteristic α-oscillations (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBeekoo et al. (2019) analysed EEG patterns in patients ranging in age from 1 month to 80 years under general anaesthesia with 1 MAC of sevoflurane. In this deeply anaesthetised state, no fast frequencies were observed in any age group. This aligns with our findings for children under 6 months, where intraoperative EEG recordings were dominated by δ-activity. However, in children older than 6 months, faster frequencies were observed, and with increasing age, α-power increased significantly. These findings suggest that α-activity may serve as a useful marker of adequate anaesthetic depth in more mature paediatric patients (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn a randomised controlled trial by Long et al. (2020), 200 children aged 1\u0026ndash;6 years received intraoperative sevoflurane titration guided either by EEG neuromonitoring or by standard care. EEG guidance was based on maintaining slow δ-oscillations in the unprocessed raw EEG as a marker of appropriate anaesthetic depth. This approach led to a significant reduction in the sevoflurane concentration\u0026mdash;by 88% during induction and 15% during maintenance (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Our data show that δ-oscillations are indeed the dominant frequency in the preoperative state across all age groups. While δ-power increases during loss of consciousness, the intraoperative values are comparable to the baseline values. This highlights a challenge: if δ-power is already high in the awake state, it may be difficult to use it reliably as an indicator of anaesthetic depth.\u003c/p\u003e \u003cp\u003eA prospective randomised trial by Sullivan et al. at the Children\u0026rsquo;s Hospital in Boston evaluated whether neuromonitoring via the bispectral index (BIS) in children aged 2\u0026ndash;12 years can improve guidance and thereby reduce the sevoflurane concentration intraoperatively. They concluded that the BIS index does not reduce the amount of sevoflurane used intraoperatively and that they do not consider the BIS monitor as a \u0026ldquo;useful monitor\u0026rdquo; in the paediatric population (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). These results are consistent with the results of Tokuwaka et al., in which the BIS value did not fall below the index value of 50 even if the dosage was titrated up to 4.8% sevoflurane; thus, a measurement of the intraoperative anaesthesia depth in children between 1 and 2 years of age does not appear valid (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn an observational study from Lee et al., 97 children aged 0\u0026ndash;21 years were studied, and raw EEG oscillations were analysed. Interestingly, power was not observed in the very specific alpha range (8\u0026ndash;13 Hz) and instead showed a broader span with power at faster frequencies ranging from 12\u0026ndash;25 Hz (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn an observational study by Cornelissen et al., 95 raw EEGs from children aged 0 to 3 years were recorded during the emergence of anaesthesia. α-Activity was present in all children older than 3 months at an end-expiratory sevoflurane concentration of 2% during surgery. With decreasing sevoflurane concentration, the α-activity decreased until it disappeared. In almost all patients, body movement occurs within 5 minutes after the loss of α-oscillations (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). This finding is in line with our results, which revealed prominent α-activity during the maintenance of anaesthesia and only minimal values at the emergence of anaesthesia for children older than 6 months.\u003c/p\u003e \u003cp\u003eInfants with initially low alpha-band EEG activity are more likely to develop burst suppression patterns during the maintenance phase of anaesthesia (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). In neonates undergoing cardiac surgery, the presence of burst suppression has been inversely associated with communication outcomes at five years of age, and those with prolonged burst suppression episodes\u0026mdash;lasting over 90 minutes\u0026mdash;demonstrated the poorest behavioral outcomes postoperatively (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Despite these findings, there are currently no established guidelines specifying how to reliably measure anaesthetic depth or how to optimise it in neonates and infants. However, certain institutions, such as the Department of Women\u0026rsquo;s and Children\u0026rsquo;s Hospital in Singapore, have implemented specialised training for anaesthesiologists in interpreting intraoperative EEG patterns in paediatric patients. This targeted education aims to reduce the risk of both over- and undersedation, thereby minimising the potential for anaesthesia-related neurotoxicity in this vulnerable population (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003eLimitations\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe administration of anaesthetics was not controlled by a uniform drug protocol, which allows different dosages for each individual patient. The anaesthesiologist in charge adhered to the standard operating procedures of our clinic; however, a controlled drug protocol with fixed dosages would ease the comparison between age groups. Unfortunately, ethical reasons make it difficult to perform those studies in these young age groups. Furthermore, the administration of midazolam was not equal across all groups on the basis of our clinical standard operating procedure, especially with no administration in young children aged 0\u0026ndash;5 months. However, a prior study by our group revealed that premedication with midazolam increases the intraoperative α-power in adult patients (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). The group size is inhomogeneous, with a particularly large number of children in the oldest age group. This is because young children are vulnerable to anaesthetics, and the indication for surgery is determined strictly. A larger patient cohort could have increased the reliability of our results and clarified group differences.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn this study, we aimed to characterise perioperative EEG dynamics in children aged 1 month to 8 years to better understand age-specific EEG signatures and ultimately reduce the risk of anaesthetic over- or underdosing in this vulnerable population. Our findings demonstrate fundamental differences from adult EEG dynamics: notably, delta activity consistently remains the dominant rhythm across all perioperative phases in children, including during wakefulness\u0026mdash;a pattern distinctly different from that in adults. Furthermore, intraoperative activation of faster frequency bands, such as the alpha and beta bands, is strongly age dependent, becoming evident only from approximately 6 months of age onwards. These developmental differences underscore the importance of age-adjusted EEG monitoring during paediatric anaesthesia.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eIn this prospective clinical observational study, electroencephalogram (EEG) data were recorded from children with approval from the Charit\u0026eacute; University Medicine Berlin ethics committee (EA2/027/15). The study was registered at clinicaltrials.gov under the number: NCT02481999. The data were collected at the Campus Virchow Klinik (CVK) of the Charit\u0026eacute; \u0026ndash; Universit\u0026auml;tsmedizin Berlin, which spans from 08.09.2015--24.05.2017.\u0026nbsp;EEG data from infants (Clinicaltrials.gov Registration:\u0026nbsp;NCT04093661) were collected from 2018 until 2019 with the same inclusion and exclusion criteria with approval from the\u0026nbsp;Charit\u0026eacute;\u0026ndash;University Medicine Berlin ethics committee (EA2/115/19). Both patient cohorts were combined for further EEG processing and final analysis. The study adhered to the Declaration of Helsinki. The consent for participation of the patients was obtained from their parents.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eCS received grants or contracts and nonfinancial support from the German Research Society, German Aerospace Center, Einstein Foundation Berlin, Federal Joint Committee (G-BA), Inner University Grants, Project Management Agency, Non-Profit Society Promoting Science and Education, European Society of Anaesthesiology and Intensive Care, BMWI \u0026ndash; Federal Ministry for Economic Affairs and Climate Action, Georg Thieme Verlag, Dr. F. K\u0026ouml;hler Chemie GmbH, Sintetica GmbH, Max-Planck-Gesellschaft zur F\u0026ouml;rderung der Wissenschaften e.V., Stifterverband f\u0026uuml;r die deutsche Wissenschaft e.V., Metronic, Philips Electronics Nederland BV, BMBF (Federal Ministry of Education and Research, RKI, The European Commission Horizont Europa, Prothor, Takeda Pharmaceutical Company Limited, Association of the Scientific Medical Societies in Germany, German Research Foundation, German National Academy of Sciences \u0026ndash; Leopoldina, Berliner Medizinische Gesellschaft, European Society of Intensive Care Medicine, European Society of Anaesthesiology and Intensive Care, German Society of Anaesthesiology and Intensive Care Medicine, German Interdisciplinary Association for Intensive Care and Emergency Medicine, German Sepsis Foundation and holds various international patents; these holdings have not affected any decisions regarding his research or this study.\u003c/p\u003e\n\u003cp\u003eSK was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Society) \u0026ndash; Project number KO 4249/3-1), she is an inventor on patents, sold to Medtronic. She received speakers\u0026rsquo; fee from Medtronic, and personal fees from Georg Thieme Verlag and Springer Verlag.\u003c/p\u003e\n\u003cp\u003eAll remaining authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions\u003c/p\u003e\n\u003cp\u003eDesign of the study: CS, SK, MM,\u003c/p\u003e\n\u003cp\u003eContribution to the materials/tools: CS, SK\u003c/p\u003e\n\u003cp\u003eData Collection: FP, SK\u003c/p\u003e\n\u003cp\u003eData Analyzation: FP, MM, SK\u003c/p\u003e\n\u003cp\u003eWriting manuscript: MM, FP, SK\u003c/p\u003e\n\u003cp\u003eAll authors read and approved of the final manuscript\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003ePrior Presentations: An abstract of this project has been presented at the Euroanaesthesia Congress 2025 in Lisbon.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; information (optional)\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBrown RE, Jr. Safety considerations of anesthetic drugs in children. Expert Opin Drug Saf. 2017;16(4):445-54.\u003c/li\u003e\n\u003cli\u003eJevtovic-Todorovic V. Exposure of Developing Brain to General Anesthesia: What Is the Animal Evidence? Anesthesiology. 2018;128(4):832-9.\u003c/li\u003e\n\u003cli\u003eDurga P, Yalamanchili V. Basic cellular and molecular mechanisms of anesthetic-induced developmental neurotoxicity: Potential strategies for alleviation. Journal of Neuroanaesthesiology and Critical Care. 2018;03(01):015-24.\u003c/li\u003e\n\u003cli\u003eLee JM, Akeju O, Terzakis K, Pavone KJ, Deng H, Houle TT, et al. A Prospective Study of Age-dependent Changes in Propofol-induced Electroencephalogram Oscillations in Children. Anesthesiology. 2017;127(2):293-306.\u003c/li\u003e\n\u003cli\u003eXiao A, Feng Y, Yu S, Xu C, Chen J, Wang T, et al. General anesthesia in children and long-term neurodevelopmental deficits: A systematic review. Front Mol Neurosci. 2022;15:972025.\u003c/li\u003e\n\u003cli\u003eLei X, Guo Q, Zhang J. Mechanistic insights into neurotoxicity induced by anesthetics in the developing brain. Int J Mol Sci. 2012;13(6):6772-99.\u003c/li\u003e\n\u003cli\u003eZhou P, Zhang C, Huang G, Hu Y, Ma W, Yu C. The effect of sevoflurane anesthesia for dental procedure on neurocognition in children: a prospective, equivalence, controlled trial. BMC Pediatr. 2021;21(1):177.\u003c/li\u003e\n\u003cli\u003eBriner A, De Roo M, Dayer A, Muller D, Habre W, Vutskits L. Volatile Anesthetics Rapidly Increase Dendritic Spine Density in the Rat Medial Prefrontal Cortex during Synaptogenesis. Anesthesiology. 2010;112(3):546-56.\u003c/li\u003e\n\u003cli\u003eFDA. FDA Drug Safety Communication: FDA approves label changes for use of general anesthetic and sedation drugs in young children 2017 [\u003c/li\u003e\n\u003cli\u003eBrambrink AM, Back SA, Riddle A, Gong X, Moravec MD, Dissen GA, et al. Isoflurane‐induced apoptosis of oligodendrocytes in the neonatal primate brain. Annals of Neurology. 2012;72(4):525-35.\u003c/li\u003e\n\u003cli\u003eCreeley C, Dikranian K, Dissen G, Martin L, Olney J, Brambrink A. Propofol-induced apoptosis of neurones and oligodendrocytes in fetal and neonatal rhesus macaque brain. British Journal of Anaesthesia. 2013;110:i29-i38.\u003c/li\u003e\n\u003cli\u003eJevtovic-Todorovic V, Hartman RE, Izumi Y, Benshoff ND, Dikranian K, Zorumski CF, et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci. 2003;23(3):876-82.\u003c/li\u003e\n\u003cli\u003eBorzage MT, Peterson BS. A Scoping Review of the Mechanisms Underlying Developmental Anesthetic Neurotoxicity. Anesth Analg. 2025;140(2):409-26.\u003c/li\u003e\n\u003cli\u003eMcCann ME, de Graaff JC, Dorris L, Disma N, Withington D, Bell G, et al. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial. Lancet. 2019;393(10172):664-77.\u003c/li\u003e\n\u003cli\u003eWarner DO, Zaccariello MJ, Katusic SK, Schroeder DR, Hanson AC, Schulte PJ, et al. Neuropsychological and Behavioral Outcomes after Exposure of Young Children to Procedures Requiring General Anesthesia: The Mayo Anesthesia Safety in Kids (MASK) Study. Anesthesiology. 2018;129(1):89-105.\u003c/li\u003e\n\u003cli\u003eSun LS, Li G, Miller TL, Salorio C, Byrne MW, Bellinger DC, et al. Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood. JAMA. 2016;315(21):2312-20.\u003c/li\u003e\n\u003cli\u003eAldecoa C, Bettelli G, Bilotta F, Sanders RD, Aceto P, Audisio R, et al. Update of the European Society of Anaesthesiology and Intensive Care Medicine evidence-based and consensus-based guideline on postoperative delirium in adult patients. Eur J Anaesthesiol. 2024;41(2):81-108.\u003c/li\u003e\n\u003cli\u003eBong CL, Balanza GA, Khoo CE, Tan JS, Desel T, Purdon PL. A Narrative Review Illustrating the Clinical Utility of Electroencephalogram-Guided Anesthesia Care in Children. Anesth Analg. 2023;137(1):108-23.\u003c/li\u003e\n\u003cli\u003eCornelissen L, Kim SE, Purdon PL, Brown EN, Berde CB. Age-dependent electroencephalogram (EEG) patterns during sevoflurane general anesthesia in infants. Elife. 2015;4:e06513.\u003c/li\u003e\n\u003cli\u003eMarkus M, Nagelsmann H, Schneider M, Rupp L, Spies C, Koch S. Peri- and intraoperative EEG signatures in newborns and infants. Clinical Neurophysiology. 2021;132(12):2959-64.\u003c/li\u003e\n\u003cli\u003eBeekoo D, Yuan K, Dai S, Chen L, Di M, Wang S, et al. Analyzing Electroencephalography (EEG) Waves Provides a Reliable Tool to Assess the Depth of Sevoflurane Anesthesia in Pediatric Patients. Med Sci Monit. 2019;25:4035-40.\u003c/li\u003e\n\u003cli\u003eLong MHY, Lim EHL, Balanza GA, Allen JC, Jr., Purdon PL, Bong CL. Sevoflurane requirements during electroencephalogram (EEG)-guided vs standard anesthesia Care in Children: A randomized controlled trial. J Clin Anesth. 2022;81:110913.\u003c/li\u003e\n\u003cli\u003eSullivan CA, Egbuta C, Park RS, Lukovits K, Cavanaugh D, Mason KP. The Use of Bispectral Index Monitoring Does Not Change Intraoperative Exposure to Volatile Anesthetics in Children. J Clin Med. 2020;9(8).\u003c/li\u003e\n\u003cli\u003eTokuwaka J, Satsumae T, Mizutani T, Yamada K, Inomata S, Tanaka M. The relationship between age and minimum alveolar concentration of sevoflurane for maintaining bispectral index below 50 in children. Anaesthesia. 2015;70(3):318-22.\u003c/li\u003e\n\u003cli\u003eCornelissen L, Kim SE, Lee JM, Brown EN, Purdon PL, Berde CB. Electroencephalographic markers of brain development during sevoflurane anaesthesia in children up to 3 years old. Br J Anaesth. 2018;120(6):1274-86.\u003c/li\u003e\n\u003cli\u003eChao JY, Gutierrez R, Legatt AD, Yozawitz EG, Lo Y, Adams DC, et al. Decreased Electroencephalographic Alpha Power During Anesthesia Induction Is Associated With EEG Discontinuity in Human Infants. Anesth Analg. 2022;135(6):1207-16.\u003c/li\u003e\n\u003cli\u003eSeltzer L, Swartz MF, Kwon J, Burchfiel J, Cholette JM, Wang H, et al. Neurodevelopmental outcomes after neonatal cardiac surgery: Role of cortical isoelectric activity. J Thorac Cardiovasc Surg. 2016;151(4):1137-42.\u003c/li\u003e\n\u003cli\u003eWindmann V, Spies C, Brown EN, Kishnan D, Lichtner G, Koch S. Influence of midazolam premedication on intraoperative EEG signatures in elderly patients. Clin Neurophysiol. 2019;130(9):1673-81.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"649\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 213px;\"\u003e\n \u003cp\u003eTable 1\u003c/p\u003e\n \u003cp\u003ePatient characteristics\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0-5 months\u003c/p\u003e\n \u003cp\u003e(n=6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e6-11 months\u003c/p\u003e\n \u003cp\u003e(n=18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e12-23 months\u003c/p\u003e\n \u003cp\u003e(n=29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026gt;24 months\u003c/p\u003e\n \u003cp\u003e(n=94)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 649px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eMonths, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e3 (2-4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e9 (8-9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e16 (15-20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e67 (63-74)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 649px;\"\u003e\n \u003cp\u003eWeight\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eMean kg (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e5.3 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e8.9 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e10.5 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e20.1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 649px;\"\u003e\n \u003cp\u003eASA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eASA I (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e33.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e70.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e69%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e77.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eASA II (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e50%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e29.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e31%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e18.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eASA III (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e16.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e3.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 649px;\"\u003e\n \u003cp\u003eAnaesthesia duration\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eDuration (mean min, SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e152 (34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e222 (25)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e156 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e80 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 649px;\"\u003e\n \u003cp\u003ePremedication\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eMidazolam received\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e94.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e97.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eDosage (mean mg/kg bw + SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e0.69 (0.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.77 (0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.59 (0.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 649px;\"\u003e\n \u003cp\u003eInduction of Anaesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eInhalative with Sevoflurane\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e66.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e61.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e24.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003ei.v. with Propofol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e33.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e38.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e75.9%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 649px;\"\u003e\n \u003cp\u003eMaintenance of Anaesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eSevoflurane\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e100%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e94.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e89.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e52.9%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eSevoflurane (mean % (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2.17 (0.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e2.32 (0.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e2.36 (0.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2.29 (0.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eTIVA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e5.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e7.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e44.7%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eTIVA mg/kg/h (mean + (SD))\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e7.7 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e8.8 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e3.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 649px;\"\u003e\n \u003cp\u003eClassification of Surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eEye surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e1 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e14 (17.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eCleft lip/Cleft palate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e1 (16.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e10 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e11 (42.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2 (2.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eENT-surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e1 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e16 (19.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eTumor surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e1 (6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e1 (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eSmaller operations \u0026lt;1,5h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e2 (13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e11 (42.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e47 (57.3%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eLarger operations \u0026gt;4h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e2 (13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e2 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e2 (2.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 213px;\"\u003e\n \u003cp\u003eBronchoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e1 (16.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"paediatric anaesthesia, EEG, neuromonitoring","lastPublishedDoi":"10.21203/rs.3.rs-6696965/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6696965/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eLittle is known about electroencephalographic (EEG) neuromonitoring in young children during anaesthesia and their specific EEG characteristics. Devices have been developed for adult patients, and validation in this young patient population is often lacking. However, young children are particularly vulnerable to anaesthesia, and the effects of anaesthetics on brain development are uncertain. The purpose of this study was to characterise perioperative frontal EEGs in young children younger than 8 years.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e \u003cb\u003eA total of\u003c/b\u003e 147 frontal EEGs from children ranging from 1 month to 8 years of age were recorded prospectively under general anaesthesia at Charit\u0026eacute; - Campus Virchow Klinik (CVK). For data acquisition, the Narcotrend Monitor was used, and the raw EEG files were further analysed in their frequency bands. The patient cohort was divided into four age groups (0\u0026ndash;5 months, 6\u0026ndash;11 months, 12\u0026ndash;23 months, and \u0026gt;\u0026thinsp;24 months), and EEG signatures were compared between the age groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eDelta activity is the predominant frequency in all age groups already in the awake state before induction of anaesthesia, with a step increase at loss of consciousness, which is more pronounced in older children. Intraoperatively, alpha- and beta-activity emerges at the age of six months and is greater in the older age groups. Infants (0\u0026ndash;5 months) remain with a high amount of Delta activity intraoperatively. With the return of consciousness, the faster frequencies gradually decrease, and the EEG is characterised again by a predominant delta-activity in all age groups.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn this study, we characterised differences in the perioperative EEG signatures of children from 1 month to 8 years from the preoperative awake state during induction and general anaesthesia until they regained consciousness from general anaesthesia. The EEG readouts differ across age groups, and age-adapted monitoring systems are needed to protect this vulnerable patient group from over- and undersedation.\u003c/p\u003e\u003ch2\u003eTrial Registration\u003c/h2\u003e \u003cp\u003e This study was approval from the Charit\u0026eacute; \u0026ndash; University Medicine Berlin's ethics committee (EA2/027/15) and was registered at clinicaltrials.gov (23rd of June 2015/NCT02481999).\u003c/p\u003e","manuscriptTitle":"EEG dynamics in children from preanesthetic awake state, under general anaesthesia until regain of consciousness","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-25 06:27:04","doi":"10.21203/rs.3.rs-6696965/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"001459bd-a70d-4c02-8943-b42efc34ac84","owner":[],"postedDate":"June 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-04T11:53:34+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-25 06:27:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6696965","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6696965","identity":"rs-6696965","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}