RESUMO
This study aimed to investigate and compare the neurophysiological impacts of two widely used anesthetic agents, Fentanyl and Ketamine, on EEG power spectra during different stages of anesthesia in adult patients undergoing minimally invasive surgery. EEG data were collected from patients undergoing anesthesia with either Fentanyl or Ketamine. The data were analyzed for relative power spectrum and fast-to-slow wave power ratios, alongside Spectral Edge Frequency 95% (SEF95), at 3 key stages: pre-anesthesia, during stable anesthesia, and post-anesthesia. EEG Relative Power Spectrum: Initially, both groups exhibited similar EEG spectral profiles, establishing a uniform baseline (Pâ >â .05). Upon anesthesia induction, the Fentanyl group showed a substantial increase in delta band power (Pâ <â .05), suggesting deeper anesthesia, while the Ketamine group maintained higher alpha and beta band activity (Pâ <â .05), indicative of a lighter sedative effect. Fast and Slow Wave Power Ratios: The Fentanyl group exhibited a marked reduction in the fast-to-slow wave power ratio during anesthesia (Pâ <â .05), persisting post-anesthesia (Pâ <â .05) and indicating a lingering effect on brain activity. Conversely, the Ketamine group demonstrated a more stable ratio (Pâ >â .05), conducive to settings requiring rapid cognitive recovery. Spectral Edge Frequency 95% (SEF95): Analysis showed a significant decrease in SEF95 values for the Fentanyl group during anesthesia (Pâ <â .05), reflecting a shift towards lower frequency power. The Ketamine group experienced a less pronounced decrease (Pâ >â .05), maintaining a higher SEF95 value that suggested a lighter level of sedation. The study highlighted the distinct impacts of Fentanyl and Ketamine on EEG power spectra, with Fentanyl inducing deeper anesthesia as evidenced by shifts towards lower frequency activity and a significant decrease in SEF95 values. In contrast, Ketamine's preservation of higher frequency activity and more stable SEF95 values suggests a lighter, more dissociative anesthetic state. These findings emphasize the importance of EEG monitoring in anesthesia for tailoring anesthetic protocols to individual patient needs and optimizing postoperative outcomes.
Assuntos
Eletroencefalografia , Fentanila , Ketamina , Procedimentos Cirúrgicos Minimamente Invasivos , Humanos , Ketamina/administração & dosagem , Fentanila/administração & dosagem , Masculino , Feminino , Adulto , Eletroencefalografia/métodos , Eletroencefalografia/efeitos dos fármacos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Ondas Encefálicas/efeitos dos fármacos , Anestésicos Intravenosos/administração & dosagem , Anestésicos Dissociativos/administração & dosagemRESUMO
This paper introduces an efficient methodology for conducting rat anesthesia experiments, aimed at enhancing the quality of raw brain signals obtained. The proposed approach enables the acquisition of animal brain signals during experiments without the confounding influence of muscle noise. Initially, the use of alpha-chloralose (a-c) in conjunction with Isoflurane is introduced to induce anesthesia in rats. Subsequently, Dexdomitor is administered to prevent muscular movements during the collection of brain signals, further refining the signal quality. Experimental outcomes conclusively demonstrate that our anesthesia method produces cleaner raw signals and exhibits improved robustness during data acquisition, outperforming existing methods that rely solely on Isoflurane or the Ketamine-Xylazine combination. Notably, this improved performance is achieved with minimal alterations to vital physiological parameters, including body temperature, respiration, and heart rates. Moreover, the efficacy of a-c in maintaining anesthesia for up to 7 h stands in contrast to the shorter durations achievable with continuous Isoflurane administration or the 30-min window offered by Ketamine-Xylazine, highlighting the practical advantages of our proposed method. Finally, post-experiment observations confirmed that the animals gradually returned to normal behavior without any signs of distress or adverse effects, indicating that our method was both effective and safe.
Assuntos
Encéfalo , Isoflurano , Ketamina , Xilazina , Animais , Ratos , Isoflurano/farmacologia , Isoflurano/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Masculino , Xilazina/farmacologia , Ketamina/farmacologia , Ketamina/administração & dosagem , Cloralose/farmacologia , Anestesia/métodos , Anestésicos Inalatórios/farmacologia , Anestésicos Inalatórios/administração & dosagem , Ratos Sprague-Dawley , Anestésicos/farmacologia , Anestésicos/administração & dosagem , Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Dexmedetomidina/farmacologia , Eletroencefalografia/métodos , Eletroencefalografia/efeitos dos fármacosRESUMO
Objective.Monotherapy with antiepileptic drugs (AEDs) is the preferred strategy for the initial treatment of epilepsy. However, an inadequate response to the initially prescribed AED is a significant indicator of a poor long-term prognosis, emphasizing the importance of precise prediction of treatment outcomes with the initial AED regimen in patients with epilepsy.Approach. We introduce OxcarNet, an end-to-end neural network framework developed to predict treatment outcomes in patients undergoing oxcarbazepine monotherapy. The proposed predictive model adopts a Sinc Module in its initial layers for adaptive identification of discriminative frequency bands. The derived feature maps are then processed through a Spatial Module, which characterizes the scalp distribution patterns of the electroencephalography (EEG) signals. Subsequently, these features are fed into an attention-enhanced Temporal Module to capture temporal dynamics and discrepancies. A channel module with an attention mechanism is employed to reveal inter-channel dependencies within the output of the Temporal Module, ultimately achieving response prediction. OxcarNet was rigorously evaluated using a proprietary dataset of retrospectively collected EEG data from newly diagnosed epilepsy patients at Nanjing Drum Tower Hospital. This dataset included patients who underwent long-term EEG monitoring in a clinical inpatient setting.Main results.OxcarNet demonstrated exceptional accuracy in predicting treatment outcomes for patients undergoing Oxcarbazepine monotherapy. In the ten-fold cross-validation, the model achieved an accuracy of 97.27%, and in the validation involving unseen patient data, it maintained an accuracy of 89.17%, outperforming six conventional machine learning methods and three generic neural decoding networks. These findings underscore the model's effectiveness in accurately predicting the treatment responses in patients with newly diagnosed epilepsy. The analysis of features extracted by the Sinc filters revealed a predominant concentration of predictive frequencies in the high-frequency range of the gamma band.Significance. The findings of our study offer substantial support and new insights into tailoring early AED selection, enhancing the prediction accuracy for the responses of AEDs.
Assuntos
Anticonvulsivantes , Eletroencefalografia , Epilepsia , Redes Neurais de Computação , Oxcarbazepina , Humanos , Oxcarbazepina/administração & dosagem , Epilepsia/tratamento farmacológico , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Eletroencefalografia/métodos , Eletroencefalografia/efeitos dos fármacos , Masculino , Feminino , Resultado do Tratamento , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto Jovem , Atenção/efeitos dos fármacos , Atenção/fisiologiaRESUMO
BACKGROUND: "Metacontrol" describes the ability to maintain an optimal balance between cognitive control styles that are either more persistent or more flexible. Recent studies have shown a link between metacontrol and aperiodic EEG patterns. The present study aimed to gain more insight into the neurobiological underpinnings of metacontrol by using methylphenidate (MPH), a compound known to increase postsynaptic catecholamine levels and modulate cortical noise. METHODS: In a double-blind, randomized, placebo-controlled study design, we investigated the effect of MPH (0.5 mg/kg) on aperiodic EEG activity during a flanker task in a sample of n = 25 neurotypical adults. To quantify cortical noise, we employed the fitting oscillations and one over f algorithm. RESULTS: Compared with placebo, MPH increased the aperiodic exponent, suggesting that it reduces cortical noise in 2 ways. First, it did so in a state-like fashion, as the main effect of the drug was visible and significant in both pre-trial and within-trial periods. Second, the electrode-specific analyses showed that the drug also affects specific processes by dampening the downregulation of noise in conditions requiring more control. CONCLUSIONS: Our findings suggest that the aperiodic exponent provides a neural marker of metacontrol states and changes therein. Further, we propose that the effectiveness of medications targeting catecholaminergic signaling can be evaluated by studying changes of cortical noise, fostering the idea of using the quantification of cortical noise as an indicator in pharmacological treatment.
Assuntos
Eletroencefalografia , Metilfenidato , Humanos , Método Duplo-Cego , Metilfenidato/farmacologia , Masculino , Adulto , Feminino , Eletroencefalografia/efeitos dos fármacos , Adulto Jovem , Estimulantes do Sistema Nervoso Central/farmacologia , Catecolaminas/metabolismo , Ondas Encefálicas/efeitos dos fármacosRESUMO
BACKGROUND: The Eleveld pharmacokinetic-pharmacodynamic model for propofol predicts bispectral index (BIS) processed electroencephalogram values from estimated effect-site concentrations. We investigated agreement between measured and predicted BIS values during total intravenous anaesthesia (TIVA). METHODS: Forty participants undergoing lower limb surgery received TIVA using remifentanil target-controlled infusions and propofol by manually controlled, target-guided infusions based upon the Eleveld model and directed by two pharmacokinetic computer simulation applications: PKPD Tools and StelSim. We evaluated the predictive performance of the Eleveld model by calculating median prediction errors (BIS units) and by Bland-Altman analyses. We also performed |Bland-Altman analysis of supplementary data provided by the authors of the Eleveld model. RESULTS: Whereas median prediction errors were small (MDPE -1.9, MDAPE 10), the ranges were wide (-18.5 to 24.3 and 1.7 to 24.3). The proportion of MDAPE >10 BIS units was 47.8%. Bland-Altman analysis showed a small mean bias (-0.52 BIS units) with wide limits of agreement (-27.7 to 26.2). Each participant's limits of agreement did not meet the requirements for declaring interchangeability between the two measurements. The measurement differences depended on the BIS values, as indicated by the positive slopes of the differences vs BIS values. Bland-Altman analysis of the Eleveld model supplementary data revealed similar results. CONCLUSION: BIS predictions by the Eleveld model should be interpreted with caution. In spite of the acceptable MDPE and MDAPE, there are unacceptable degrees of both within-subject and between-subject variation during propofol target-controlled infusions. This limits the use of adjusting targeted concentrations to achieve desired simulated BIS values with confidence.
Assuntos
Anestésicos Intravenosos , Eletroencefalografia , Propofol , Propofol/farmacocinética , Propofol/administração & dosagem , Propofol/farmacologia , Humanos , Anestésicos Intravenosos/farmacocinética , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/farmacologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Monitores de Consciência , Simulação por Computador , Idoso , Modelos Biológicos , Anestesia Intravenosa/métodos , Adulto Jovem , Extremidade Inferior/cirurgia , Monitorização Intraoperatória/métodosRESUMO
Status epilepticus (SE) is a medical emergency associated with high mortality and morbidity. Na+, K+-ATPase, is a promising therapeutic target for SE, given its critical role in regulation of neuron excitability and cellular homeostasis. We investigated the effects of a Na+, K+-ATPase-activating antibody (DRRSAb) on short-term electrophysiological and behavioral consequences of pilocarpine-induced SE. Rats were submitted to pilocarpine-induced SE, followed by intranasal administration (2 µg/nostril). The antibody increased EEG activity following SE, namely, EEG power in theta, beta, and gamma frequency bands, assessed by quantitative analysis of EEG power spectra. One week later, DRRSAb-treated animals displayed less behavioral hyperreactivity in pick-up tests and better performance in novel object recognition tests, indicating that the intranasal administration of this Na+, K+-ATPase activator immediately after SE improves behavioral outcomes at a later time point. These results suggest that Na+, K+-ATPase activation warrants further investigation as an adjunctive therapeutic strategy for SE.
Assuntos
Administração Intranasal , Eletroencefalografia , Pilocarpina , ATPase Trocadora de Sódio-Potássio , Estado Epiléptico , Animais , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , ATPase Trocadora de Sódio-Potássio/metabolismo , Masculino , Pilocarpina/farmacologia , Eletroencefalografia/métodos , Eletroencefalografia/efeitos dos fármacos , Ratos , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Ratos Wistar , Anticorpos/farmacologia , Anticorpos/administração & dosagemRESUMO
Epilepsy, a chronic neurological disorder characterized by recurrent unprovoked seizures, presents a substantial challenge in approximately one-third of cases exhibiting resistance to conventional pharmacological treatments. This study investigated the effect of 4-allyl-2,6-dimethoxyphenol, a phenolic compound derived from various natural sources, in different models of induced seizures and its impact on animal electroencephalographic (EEG) recordings. Adult male Swiss albino mice were pre-treated (i.p.) with a dose curve of 4-allyl-2,6-dimethoxyphenol (50, 100, or 200â¯mg/kg), its vehicle (Tween), or standard antiepileptic drug (Diazepam; or Phenytoin). Subsequently, the mice were subjected to different seizure-inducing models - pentylenetetrazole (PTZ), 3-mercaptopropionic acid (3-MPA), pilocarpine (PILO), or maximal electroshock seizure (MES). EEG analysis was performed on other animals surgically implanted with electrodes to evaluate brain activity. Significant results revealed that animals treated with 4-allyl-2,6-dimethoxyphenol exhibited increased latency to the first myoclonic jerk in the PTZ and PILO models; prolonged latency to the first tonic-clonic seizure in the PTZ, 3-MPA, and PILO models; reduced total duration of tonic-clonic seizures in the PTZ and PILO models; decreased intensity of convulsive seizures in the PTZ and 3-MPA models; and diminished mortality in the 3-MPA, PILO, and MES models. EEG analysis indicated an increase in the percentage of total power attributed to beta waves following 4-allyl-2,6-dimethoxyphenol administration. Notably, the substance protected from behavioral and electrographic seizures in the PTZ model, preventing increases in the average amplitude of recording signals while also inducing an increase in the participation of theta and gamma waves. These findings suggest promising outcomes for the tested phenolic compound across diverse pre-clinical seizure models, highlighting the need for further comprehensive studies to elucidate its underlying mechanisms and validate its clinical relevance in epilepsy management.
Assuntos
Anticonvulsivantes , Modelos Animais de Doenças , Eletroencefalografia , Eletrochoque , Pentilenotetrazol , Convulsões , Animais , Masculino , Convulsões/tratamento farmacológico , Convulsões/induzido quimicamente , Convulsões/fisiopatologia , Camundongos , Anticonvulsivantes/farmacologia , Pentilenotetrazol/toxicidade , Eletroencefalografia/efeitos dos fármacos , Anisóis/farmacologia , Relação Dose-Resposta a Droga , Pilocarpina/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Ácido 3-Mercaptopropiônico/farmacologia , Convulsivantes/toxicidadeRESUMO
The fragmentation of the functional brain network has been identified through the functional connectivity (FC) analysis in studies investigating anesthesia-induced loss of consciousness (LOC). However, it remains unclear whether mild sedation of anesthesia can cause similar effects. This paper aims to explore the changes in local-global brain network topology during mild anesthesia, to better understand the macroscopic neural mechanism underlying anesthesia sedation. We analyzed high-density EEG from 20 participants undergoing mild and moderate sedation of propofol anesthesia. By employing a local-global brain parcellation in EEG source analysis, we established binary functional brain networks for each participant. Furthermore, we investigated the global-scale properties of brain networks by estimating global efficiency and modularity, and examined the changes in meso-scale properties of brain networks by quantifying the distribution of high-degree and high-betweenness hubs and their corresponding rich-club coefficients. It is evident from the results that the mild sedation of anesthesia does not cause a significant change in the global-scale properties of brain networks. However, network components centered on SomMot L show a significant decrease, while those centered on Default L, Vis L and Limbic L exhibit a significant increase during the transition from wakefulness to mild sedation (p<0.05). Compared to the baseline state, mild sedation almost doubled the number of high-degree hubs in Vis L, DorsAttn L, Limbic L, Cont L, and reduced by half the number of high-degree hubs in SomMot R, DorsAttn R, SalVentAttn R. Further, mild sedation almost doubled the number of high-betweenness hubs in Vis L, Vis R, Limbic R, Cont R, and reduced by half the number of high-betweenness hubs in SomMot L, SalVentAttn L, Default L, and SomMot R. Our results indicate that mild anesthesia cannot affect the global integration and segregation of brain networks, but influence meso-scale function for integrating different resting-state systems involved in various segregation processes. Our findings suggest that the meso-scale brain network reorganization, situated between global integration and local segregation, could reflect the autonomic compensation of the brain for drug effects. As a direct response and adjustment of the brain network system to drug administration, this spontaneous reorganization of the brain network aims at maintaining consciousness in the case of sedation.
Assuntos
Encéfalo , Eletroencefalografia , Hipnóticos e Sedativos , Rede Nervosa , Propofol , Humanos , Propofol/administração & dosagem , Adulto , Masculino , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Feminino , Encéfalo/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Eletroencefalografia/métodos , Eletroencefalografia/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Adulto Jovem , Anestésicos Intravenosos/administração & dosagem , Conectoma/métodosRESUMO
OBJECTIVE: In this pilot prospective cohort study, we aimed to evaluate, using high-density electroencephalography (HD-EEG), the longitudinal changes in functional connectivity (FC) in patients with chronic migraine (CM) treated with onabotulinumtoxinA (OBTA). BACKGROUND: OBTA is a treatment for CM. Several studies have shown the modulatory action of OBTA on the central nervous system; however, research on migraine is limited. METHODS: This study was conducted at the Neurology Unit of "Policlinico Tor Vergata," Rome, Italy, and included 12 adult patients with CM treated with OBTA and 15 healthy controls (HC). Patients underwent clinical scales at enrollment (T0) and 3 months (T1) from the start of treatment. HD-EEG was recorded using a 64-channel system in patients with CM at T0 and T1. A source reconstruction method was used to identify brain activity. FC in δ-θ-α-ß-low-γ bands was analyzed using the weighted phase-lag index. FC changes between HCs and CM at T0 and T1 were assessed using cross-validation methods to estimate the results' reliability. RESULTS: Compared to HCs at T0, patients with CM showed hyperconnected networks in δ (p = 0.046, area under the receiver operating characteristic curve [AUC: 0.76-0.98], Cohen's κ [0.65-0.93]) and ß (p = 0.031, AUC [0.68-0.95], Cohen's κ [0.51-0.84]), mainly involving orbitofrontal, occipital, temporal pole and orbitofrontal, superior temporal, occipital, cingulate areas, and hypoconnected networks in α band (p = 0.029, AUC [0.80-0.99], Cohen's κ [0.42-0.77]), predominantly involving cingulate, temporal pole, and precuneus. Patients with CM at T1, compared to T0, showed hypoconnected networks in δ band (p = 0.032, AUC [0.73-0.99], Cohen's κ [0.53-0.90]) and hyperconnected networks in α band (p = 0.048, AUC [0.58-0.93], Cohen's κ [0.37-0.78]), involving the sensorimotor, orbitofrontal, cingulate, and temporal cortex. CONCLUSION: These preliminary results showed that patients with CM presented disrupted EEG-FC compared to controls restored by a single session of OBTA treatment, suggesting a primary central modulatory action of OBTA.
Assuntos
Toxinas Botulínicas Tipo A , Eletroencefalografia , Transtornos de Enxaqueca , Humanos , Toxinas Botulínicas Tipo A/farmacologia , Toxinas Botulínicas Tipo A/administração & dosagem , Projetos Piloto , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/fisiopatologia , Feminino , Masculino , Adulto , Eletroencefalografia/efeitos dos fármacos , Pessoa de Meia-Idade , Doença Crônica , Estudos Prospectivos , Fármacos Neuromusculares/farmacologia , Fármacos Neuromusculares/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagemAssuntos
Antibacterianos , Cefepima , Eletroencefalografia , Síndromes Neurotóxicas , Humanos , Cefepima/efeitos adversos , Eletroencefalografia/efeitos dos fármacos , Antibacterianos/efeitos adversos , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Masculino , Cefalosporinas/efeitos adversos , FemininoRESUMO
OBJECTIVES: To confirm that levetiracetam (LEV) demonstrates predictable pharmacokinetics(PK) at higher doses and to study the pharmacodynamics(PD) of LEV. DESIGN: Pharmacokinetic data from the NEOLEV1 and NEOLEV2 trials were analysed using a non-linear mixed effects modelling approach. A post hoc analysis of the effect of LEV on seizure burden was conducted. SETTING: Neonatal intensive care unit. PATIENTS: Term neonates with electrographically confirmed seizures. INTERVENTIONS: In NEOLEV1, neonates with seizures persisting following phenobarbital (PHB) received LEV 20 or 40 mg/kg bolus followed by 5 or 10 mg/kg maintenance dose(MD) daily. In NEOLEV2, patients received a 40 mg/kg intravenous LEV load, followed by 10 mg/kg doses 8 hourly. If seizures persisted, a further 20 mg/kg intravenous load was given. If seizures persisted, PHB was given. PK data were collected from 16 NEOLEV1 patients and 33 NEOLEV2 patients. cEEG data from 48 NEOLEV2 patients were analysed to investigate onset of action and seizure burden reduction. MAIN OUTCOME MEASURES: Clearance (CL) and volume of distribution (Vd) were determined. Covariates that significantly affected LEV disposition were identified. RESULTS: Primary outcome: The median initial LEV level was 57 µg/mL (range 19-107) after the first loading dose and at least 12 µg/mL at 48 hours in all infants. CL and Vd were estimated to be 0.0538 L/hour and 0.832 L, respectively. A direct relationship between postnatal age and CL was observed. The final population pharmacokinetic(PopPK) model described the observed data well without significant biases. CL and Vd were described as CL (L/hour)=0.0538×(weight in kg/3.34)0.75×(postnatal age in days/5.5) 0.402 and Vd (L)=0.832×(weight in kg/3.34).Seizure burden reduced within 30 min of LEV administration. 28% of patients were completely seizure free after LEV. In an additional 25% of patients, seizure burden reduced by 50%. CONCLUSIONS: LEV pharmacokinetics remained predictable at higher doses. Very high-dose LEV can now be studied in neonates. TRIAL REGISTRATION NUMBER: NCT01720667.
Assuntos
Anticonvulsivantes , Relação Dose-Resposta a Droga , Levetiracetam , Convulsões , Humanos , Levetiracetam/farmacocinética , Levetiracetam/administração & dosagem , Levetiracetam/uso terapêutico , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Recém-Nascido , Convulsões/tratamento farmacológico , Masculino , Feminino , Piracetam/análogos & derivados , Piracetam/farmacocinética , Piracetam/administração & dosagem , Eletroencefalografia/efeitos dos fármacos , Fenobarbital/farmacocinética , Fenobarbital/administração & dosagem , Fenobarbital/uso terapêutico , Unidades de Terapia Intensiva Neonatal , Resultado do TratamentoRESUMO
BACKGROUND: Unlike expired sevoflurane concentration, propofol lacks a biomarker for its brain effect site concentration, leading to dosing imprecision particularly in infants. Electroencephalography monitoring can serve as a biomarker for propofol effect site concentration, yet proprietary electroencephalography indices are not validated in infants. The authors evaluated spectral edge frequency (SEF95) as a propofol anesthesia biomarker in infants. It was hypothesized that the SEF95 targets will vary for different clinical stimuli and an inverse relationship existed between SEF95 and propofol plasma concentration. METHODS: This prospective study enrolled infants (3 to 12 months) to determine the SEF95 ranges for three clinical endpoints of anesthesia (consciousness-pacifier placement, pain-electrical nerve stimulation, and intubation-laryngoscopy) and correlation between SEF95 and propofol plasma concentration at steady state. Dixon's up-down method was used to determine target SEF95 for each clinical endpoint. Centered isotonic regression determined the dose-response function of SEF95 where 50% and 90% of infants (ED50 and ED90) did not respond to the clinical endpoint. Linear mixed-effect model determined the association of propofol plasma concentration and SEF95. RESULTS: Of 49 enrolled infants, 44 evaluable (90%) showed distinct SEF95 for endpoints: pacifier (ED50, 21.4 Hz; ED90, 19.3 Hz), electrical stimulation (ED50, 12.6 Hz; ED90, 10.4 Hz), and laryngoscopy (ED50, 8.5 Hz; ED90, 5.2 Hz). From propofol 0.5 to 6 µg/ml, a 1-Hz SEF95 increase was linearly correlated to a 0.24 (95% CI, 0.19 to 0.29; P < 0.001) µg/ml decrease in plasma propofol concentration (marginal R2 = 0.55). CONCLUSIONS: SEF95 can be a biomarker for propofol anesthesia depth in infants, potentially improving dosing accuracy and utilization of propofol anesthesia in this population.
Assuntos
Anestésicos Intravenosos , Eletroencefalografia , Propofol , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/sangue , Biomarcadores/sangue , Humanos , Relação Dose-Resposta a Droga , Propofol/administração & dosagem , Propofol/sangue , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Masculino , Feminino , Lactente , Determinação de Ponto FinalRESUMO
BACKGROUND: Although effects of general anesthesia on neuronal activity in the human neonatal brain are incompletely understood, electroencephalography provides some insight and may identify age-dependent differences. METHODS: A systematic search (MEDLINE, Embase, PubMed, and Cochrane Library to November 2023) retrieved English language publications reporting electroencephalography during general anesthesia for cardiac or noncardiac surgery in term neonates (37 to 44 weeks postmenstrual age). Data were extracted, and risk of bias (ROBINS-I Cochrane tool) and quality of evidence (Grading of Recommendations Assessment, Development, and Evaluation [GRADE] checklist) were assessed. RESULTS: From 1,155 abstracts, 9 publications (140 neonates; 55% male) fulfilled eligibility criteria. Data were limited, and study quality was very low. The occurrence of discontinuity, a characteristic pattern of alternating higher and lower amplitude electroencephalography segments, was reported with general anesthesia (94 of 119 neonates, 6 publications) and with hypothermia (23 of 23 neonates, 2 publications). Decreased power in the delta (0.5 to 4 Hz) frequency range was also reported with increasing anesthetic dose (22 neonates; 3 publications). CONCLUSION: Although evidence gaps were identified, both increasing sevoflurane concentration and decreasing temperature are associated with increasing discontinuity.
Assuntos
Anestesia Geral , Eletroencefalografia , Humanos , Eletroencefalografia/métodos , Eletroencefalografia/efeitos dos fármacos , Anestesia Geral/métodos , Recém-Nascido , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologiaRESUMO
The exact mechanisms and the neural circuits involved in anesthesia induced unconsciousness are still not fully understood. To elucidate them valid animal models are necessary. Since the most commonly used species in neuroscience are mice, we established a murine model for commonly used anesthetics/sedatives and evaluated the epidural electroencephalographic (EEG) patterns during slow anesthesia induction and emergence. Forty-four mice underwent surgery in which we inserted a central venous catheter and implanted nine intracranial electrodes above the prefrontal, motor, sensory, and visual cortex. After at least one week of recovery, mice were anesthetized either by inhalational sevoflurane or intravenous propofol, ketamine, or dexmedetomidine. We evaluated the loss and return of righting reflex (LORR/RORR) and recorded the electrocorticogram. For spectral analysis we focused on the prefrontal and visual cortex. In addition to analyzing the power spectral density at specific time points we evaluated the changes in the spectral power distribution longitudinally. The median time to LORR after start anesthesia ranged from 1080 [1st quartile: 960; 3rd quartile: 1080]s under sevoflurane anesthesia to 1541 [1455; 1890]s with ketamine. Around LORR sevoflurane as well as propofol induced a decrease in the theta/alpha band and an increase in the beta/gamma band. Dexmedetomidine infusion resulted in a shift towards lower frequencies with an increase in the delta range. Ketamine induced stronger activity in the higher frequencies. Our results showed substance-specific changes in EEG patterns during slow anesthesia induction. These patterns were partially identical to previous observations in humans, but also included significant differences, especially in the low frequencies. Our study emphasizes strengths and limitations of murine models in neuroscience and provides an important basis for future studies investigating complex neurophysiological mechanisms.
Assuntos
Anestésicos Inalatórios , Dexmedetomidina , Eletroencefalografia , Ketamina , Propofol , Sevoflurano , Animais , Camundongos , Ketamina/farmacologia , Ketamina/administração & dosagem , Sevoflurano/farmacologia , Sevoflurano/administração & dosagem , Dexmedetomidina/farmacologia , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Propofol/farmacologia , Propofol/administração & dosagem , Masculino , Anestésicos Inalatórios/farmacologia , Anestésicos Inalatórios/administração & dosagem , Reflexo de Endireitamento/efeitos dos fármacos , Reflexo de Endireitamento/fisiologia , Camundongos Endogâmicos C57BL , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/administração & dosagem , Anestésicos Intravenosos/farmacologia , Anestésicos Intravenosos/administração & dosagem , Anestesia/métodosRESUMO
Background: N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased pain perception and the prevention of epileptic seizures. Nevertheless, its relationship with sleep-inducing effects remains unreported. Objective: The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp). Methods: The test of the righting reflex was used to identify the appropriate concentrations of Alp and NEM for inducing sleep-promoting effects in mice. Total sleep duration and sleep quality were evaluated through EEG/EMG analysis. The neural mechanism underlying the sleep-promoting effect was examined through c-fos immunoreactivity in the brain using immunofluorescence. Furthermore, potential CNS-side effects of the combination Alp and NEM were assessed using LABORAS automated home-cage behavioral phenotyping. Results: Combination administration of Alp (1.84 mg/kg) and NEM (1.0 mg/kg) significantly decreased sleep latency and increased sleep duration in comparison to administering 1.84 mg/kg Alp alone. This effect was characterized by a notable increase in REM duration. The findings from c-fos immunoreactivity indicated that NEM significantly suppressed neuron activation in brain regions associated with wakefulness. Additionally, combination administration of Alp and NEM showed no effects on mouse neural behaviors during automated home cage monitoring. Conclusions: This study is the first to propose and demonstrate a combination therapy involving Alp and NEM that not only enhances the hypnotic effect but also mitigates potential CNS side effects, suggesting its potential application in treating insomnia.
Assuntos
Alprazolam , Sinergismo Farmacológico , Sono , Animais , Alprazolam/farmacologia , Alprazolam/administração & dosagem , Camundongos , Masculino , Sono/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Reflexo de Endireitamento/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/administração & dosagemRESUMO
Soman produces excitotoxic effects by inhibiting acetylcholinesterase in the cholinergic synapses and neuromuscular junctions, resulting in soman-induced sustained status epilepticus (SSE). Our previous work showed delayed intramuscular (i.m.) treatment with A1 adenosine receptor agonist N-bicyclo-[2.2.1]-hept-2-yl-5'-chloro-5'-deoxyadenosine (ENBA) alone suppressed soman-induced SSE and prevented neuropathology. Using this same rat soman seizure model, we tested if delayed therapy with ENBA (60 mg/kg, i.m.) would terminate seizure, protect neuropathology, and aid in survival when given in conjunction with current standard medical countermeasures (MCMs): atropine sulfate, 2-PAM, and midazolam (MDZ). Either 15- or 30-min following soman-induced SSE onset, male rats received atropine and 2-PAM plus either MDZ or MDZ + ENBA. Electroencephalographic (EEG) activity, physiologic parameters, and motor function were recorded. Either 2- or 14-days following exposure surviving rats were euthanized and perfused for histology. All animals treated with MDZ + ENBA at both time points had 100% EEG seizure termination and reduced total neuropathology compared to animals treated with MDZ (2-day, p = 0.015 for 15-min, p = 0.002 for 30-min; 14-day, p < 0.001 for 15-min, p = 0.006 for 30-min), showing ENBA enhanced MDZ's anticonvulsant and neuroprotectant efficacy. However, combined MDZ + ENBA treatment, when compared to MDZ treatment groups, had a reduction in the 14-day survival rate regardless of treatment time, indicating possible enhancement of MDZ's neuronal inhibitory effects by ENBA. Based on our findings, ENBA shows promise as an anticonvulsant and neuroprotectant in a combined treatment regimen following soman exposure; when given as an adjunct to standard MCMs, the dose of ENBA needs to be adjusted.
Assuntos
Agonistas do Receptor A1 de Adenosina , Ratos Sprague-Dawley , Convulsões , Soman , Animais , Soman/toxicidade , Masculino , Agonistas do Receptor A1 de Adenosina/farmacologia , Ratos , Injeções Intramusculares , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Anticonvulsivantes/administração & dosagem , Eletroencefalografia/efeitos dos fármacos , Adenosina/análogos & derivados , Adenosina/administração & dosagem , Adenosina/farmacologia , Atropina/farmacologia , Atropina/administração & dosagem , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Midazolam/farmacologia , Midazolam/uso terapêuticoRESUMO
OBJECTIVE: Brivaracetam (BRV) is a recent antiseizure medication (ASM) approved as an add-on therapy for people with focal epilepsy. BRV has a good efficacy and safety profile compared to other ASMs. However, its specific effects on resting-state EEG activity and connectivity are unknown. The aim of this study is to evaluate quantitative EEG changes induced by BRV therapy in a population of adult people with drug-resistant epilepsy (PwE) compared to healthy controls (HC). METHODS: We performed a longitudinal, retrospective, pharmaco-EEG study on a population of 23 PwE and a group of 25 HC. Clinical outcome was dichotomized into drug-responders (i.e., >50% reduction in seizures' frequency; RES) and non-responders (N-RES) after two years of BRV. EEG parameters were compared between PwE and HC at baseline (pre-BRV) and after three months of BRV therapy (post-BRV). We investigated BRV-related variations in EEG connectivity using the phase locking value (PLV). RESULTS: BRV therapy did not induce modifications in power spectrum density across different frequency bands. PwE presented lower PLV connectivity values compared to HC in all frequency bands. RES exhibited lower theta PLV connectivity compared to HC before initiating BRV and experienced an increase after BRV, eliminating the significant difference from HC. CONCLUSIONS: This study shows that BRV does not alter the EEG power spectrum in PwE, supporting its favourable neuropsychiatric side-effect profile, and induces the disappearance of EEG connectivity differences between PwE and HC. SIGNIFICANCE: The integration of EEG quantitative analysis in epilepsy can provide insights into the efficacy, mechanism of action, and side effects of ASMs.
Assuntos
Anticonvulsivantes , Epilepsia Resistente a Medicamentos , Eletroencefalografia , Pirrolidinonas , Humanos , Masculino , Feminino , Adulto , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/fisiopatologia , Pirrolidinonas/uso terapêutico , Pirrolidinonas/efeitos adversos , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/farmacologia , Anticonvulsivantes/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos Longitudinais , Adulto JovemRESUMO
Objectives.The purpose of this study is to investigate the age dependence of bilateral frontal electroencephalogram (EEG) coupling characteristics, and find potential age-independent depth of anesthesia monitoring indicators for the elderlies.Approach.We recorded bilateral forehead EEG data from 41 patients (ranged in 19-82 years old), and separated into three age groups: 18-40 years (n= 12); 40-65 years (n= 14), >65 years (n= 15). All these patients underwent desflurane maintained general anesthesia (GA). We analyzed the age-related EEG spectra, phase amplitude coupling (PAC), coherence and phase lag index (PLI) of EEG data in the states of awake, GA, and recovery.Main results.The frontal alpha power shows age dependence in the state of GA maintained by desflurane. Modulation index in slow oscillation-alpha and delta-alpha bands showed age dependence and state dependence in varying degrees, the PAC pattern also became less pronounced with increasing age. In the awake state, the coherence in delta, theta and alpha frequency bands were all significantly higher in the >65 years age group than in the 18-40 years age group (p< 0.05 for three frequency bands). The coherence in alpha-band was significantly enhanced in all age groups in GA (p< 0.01) and then decreased in recovery state. Notably, the PLI in the alpha band was able to significantly distinguish the three states of awake, GA and recovery (p< 0.01) and the results of PLI in delta and theta frequency bands had similar changes to those of coherence.Significance.We found the EEG coupling and synchronization between bilateral forehead are age-dependent. The PAC, coherence and PLI portray this age-dependence. The PLI and coherence based on bilateral frontal EEG functional connectivity measures and PAC based on frontal single-channel are closely associated with anesthesia-induced unconsciousness.
Assuntos
Desflurano , Eletroencefalografia , Humanos , Desflurano/farmacologia , Adulto , Pessoa de Meia-Idade , Idoso , Eletroencefalografia/efeitos dos fármacos , Adulto Jovem , Masculino , Feminino , Idoso de 80 Anos ou mais , Adolescente , Envelhecimento/fisiologia , Envelhecimento/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/fisiologia , Isoflurano/análogos & derivados , Isoflurano/farmacologia , Anestésicos Inalatórios/farmacologia , Anestesia GeralRESUMO
STUDY OBJECTIVE: Processed electroencephalography (pEEG) may help clinicians optimize depth of general anesthesia. Avoiding excessive depth of anesthesia may reduce intraoperative hypotension and the need for vasopressors. We tested the hypothesis that pEEG-guided - compared to non-pEEG-guided - general anesthesia reduces the amount of norepinephrine needed to keep intraoperative mean arterial pressure above 65 mmHg in patients having vascular surgery. DESIGN: Randomized controlled clinical trial. SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany. PATIENTS: 110 patients having vascular surgery. INTERVENTIONS: pEEG-guided general anesthesia. MEASUREMENTS: Our primary endpoint was the average norepinephrine infusion rate from the beginning of induction of anesthesia until the end of surgery. MAIN RESULT: 96 patients were analyzed. The mean ± standard deviation average norepinephrine infusion rate was 0.08 ± 0.04 µg kg-1 min-1 in patients assigned to pEEG-guided and 0.12 ± 0.09 µg kg-1 min-1 in patients assigned to non-pEEG-guided general anesthesia (mean difference 0.04 µg kg-1 min-1, 95% confidence interval 0.01 to 0.07 µg kg-1 min-1, p = 0.004). Patients assigned to pEEG-guided versus non-pEEG-guided general anesthesia, had a median time-weighted minimum alveolar concentration of 0.7 (0.6, 0.8) versus 0.8 (0.7, 0.8) (p = 0.006) and a median percentage of time Patient State Index was <25 of 12 (1, 41) % versus 23 (3, 49) % (p = 0.279). CONCLUSION: pEEG-guided - compared to non-pEEG-guided - general anesthesia reduced the amount of norepinephrine needed to keep mean arterial pressure above 65 mmHg by about a third in patients having vascular surgery. Whether reduced intraoperative norepinephrine requirements resulting from pEEG-guided general anesthesia translate into improved patient-centered outcomes remains to be determined in larger trials.