Propofol For Induction Of General Anesthesia Research Articles

The effect of esketamine combined with propofol-induced general anesthesia on cerebral blood flow velocity: a randomized clinical trial

BackgroundEsketamine is increasingly used in clinical anesthesia. The effect of esketamine on the blood flow velocity of the middle cerebral artery has a clinical guiding effect. To investigate the effect of esketamine combined with propofol-induced general anesthesia for endotracheal intubation on the blood flow velocity of middle cerebral artery and hemodynamics during the induction period.MethodsThe randomized clinical trial included 80 patients aged 20-65 years who would undergo non-intracranial elective surgery under general anesthesia in our hospital from May 2022 to May 2023. The participants were divided into two groups based on anesthesia drugs: sufentanil 0.5μg/kg (group C) or 1.5mg/kg esketamine (group E). The primary outcome was variation value in average cerebral blood velocity. The secondary outcomes included cerebral blood flow velocities (CBFV), blood pressure (BP) and heart rate (HR) at four different time points: before induction of general anesthesia (T0), 1 min after the induction drug injected (T1), before endotracheal intubation (T2), and 1min after endotracheal intubation (T3). The occurrence of hypotension, hypertension, tearing and choking during induction was also documented.ResultsThe variation of average CBFV from time T0 to T2(ΔVm1) and the variation from time T3 to T0 (ΔVm2) were not obviously different. The median consumption of intraoperative sufentanil in group C was obviously lower than that in group E. At T1, the mean HR of group E was significantly higher than that of group C. At T2 and T3, the BP and HR of group E were obviously higher than that of group C. At T2, the CBFV in the group E were obviously higher than those in the group C. The incidence of hypotension was significantly reduced in the group E compared with the group C. There were no differences in the other outcomes.ConclusionsThe induction of esketamine combined with propofol does not increase the blood flow velocity of middle cerebral artery. Esketamine is advantageous in maintaining hemodynamic stability during induction. Furthermore, the administration of esketamine did not result in an increased incidence of adverse effects.Trial Registration15/06/2023 clinicaltrials.gov ChiCTR2300072518 https://www.chictr.org.cn/bin/project/edit?pid=176675.

Differential cortical network engagement during states of un/consciousness in humans

What happens in the human brain when we are unconscious? Despite substantial work, we are still unsure which brain regions are involved and how they are impacted when consciousness is disrupted. Using intracranial recordings and direct electrical stimulation, we mapped global, network, and regional involvement during wake vs. arousable unconsciousness (sleep) vs. non-arousable unconsciousness (propofol-induced general anesthesia). Information integration and complex processing we`re reduced, while variability increased in any type of unconscious state. These changes were more pronounced during anesthesia than sleep and involved different cortical engagement. During sleep, changes were mostly uniformly distributed across the brain, whereas during anesthesia, the prefrontal cortex was the most disrupted, suggesting that the lack of arousability during anesthesia results not from just altered overall physiology but from a disconnection between the prefrontal and other brain areas. These findings provide direct evidence for different neural dynamics during loss of consciousness compared with loss of arousability.

Kendall transfer entropy: a novel measure for estimating information transfer in complex systems

Objective. Transfer entropy (TE) has been widely used to infer causal relationships among dynamical systems, especially in neuroscience. Kendall transformation provides a novel quantization method for estimating information-theoretic measures and shows potential advantages for small-sample neural signals. But it has yet to be introduced into the framework of TE estimation, which commonly suffers from the limitation of small sample sizes. This paper aims to introduce the idea of Kendall correlation into TE estimation and verify its effect. Approach. We proposed the Kendall TE (KTE) which combines the improved Kendall transformation and the TE estimation. To confirm its effectiveness, we compared KTE with two common TE estimation techniques: the adaptive partitioning algorithm (D-V partitioning) and the symbolic TE. Their performances were estimated by simulation experiments which included linear, nonlinear, linear + nonlinear models and neural mass models. Moreover, the KTE was also applied to real electroencephalography (EEG) recordings to quantify the directional connectivity between frontal and parietal regions with propofol-induced general anesthesia. Main results. The simulation results showed that the KTE outperformed the other two methods by many measures: (1) identifying the coupling direction under a small sample size; (2) the sensitivity to coupling strength; (3) noise resistance; and (4) the sensitivity to time-dependent coupling changes. For real EEG recordings, the KTE clearly detected the disrupted frontal-to-parietal connectivity in propofol-induced unconsciousness, which is in agreement with previous findings. Significance. We reveal that the proposed KTE method is a robust and powerful tool for estimating TE, and is particularly suitable for small sample sizes. The KTE also provides an innovative form of quantizing continuous time series for information-theoretic measures.

GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol.

The mechanism underlying the hypnosis effect of propofol is still not fully understood. In essence, the nucleus accumbens (NAc) is crucial for regulating wakefulness and may be directly engaged in the principle of general anesthesia. However, the role of NAc in the process of propofol-induced anesthesia is still unknown. We used immunofluorescence, western blotting, and patch-clamp to access the activities of NAc GABAergic neurons during propofol anesthesia, and then we utilized chemogenetic and optogenetic methods to explore the role of NAc GABAergic neurons in regulating propofol-induced general anesthesia states. Moreover, we also conducted behavioral tests to analyze anesthetic induction and emergence. We found out that c-Fos expression was considerably dropped in NAc GABAergic neurons after propofol injection. Meanwhile, patch-clamp recording of brain slices showed that firing frequency induced by step currents in NAc GABAergic neurons significantly decreased after propofol perfusion. Notably, chemically selective stimulation of NAc GABAergic neurons during propofol anesthesia lowered propofol sensitivity, prolonged the induction of propofol anesthesia, and facilitated recovery; the inhibition of NAc GABAergic neurons exerted opposite effects. Furthermore, optogenetic activation of NAc GABAergic neurons promoted emergence whereas the result of optogenetic inhibition was the opposite. Our results demonstrate that NAc GABAergic neurons modulate propofol anesthesia induction and emergence.

Propofol disrupts alpha dynamics in functionally distinct thalamocortical networks during loss of consciousness

During propofol-induced general anesthesia, alpha rhythms measured using electroencephalography undergo a striking shift from posterior to anterior, termed anteriorization, where the ubiquitous waking alpha is lost and a frontal alpha emerges. The functional significance of alpha anteriorization and the precise brain regions contributing to the phenomenon are a mystery. While posterior alpha is thought to be generated by thalamocortical circuits connecting nuclei of the sensory thalamus with their cortical partners, the thalamic origins of the propofol-induced alpha remain poorly understood. Here, we used human intracranial recordings to identify regions in sensory cortices where propofol attenuates a coherent alpha network, distinct from those in the frontal cortex where it amplifies coherent alpha and beta activities. We then performed diffusion tractography between these identified regions and individual thalamic nuclei to show that the opposing dynamics of anteriorization occur within two distinct thalamocortical networks. We found that propofol disrupted a posterior alpha network structurally connected with nuclei in the sensory and sensory associational regions of the thalamus. At the same time, propofol induced a coherent alpha oscillation within prefrontal cortical areas that were connected with thalamic nuclei involved in cognition, such as the mediodorsal nucleus. The cortical and thalamic anatomy involved, as well as their known functional roles, suggests multiple means by which propofol dismantles sensory and cognitive processes to achieve loss of consciousness.

Journal-related Activities and Other Special Activities at the 2022 American Society of Anesthesiologists Meeting

Journal-related Activities and Other Special Activities at the 2022 American Society of Anesthesiologists Meeting

Effects of propofol on sleep architecture and sleep–wake systems in rats

Previous studies have shown that the synchronization of electroencephalogram (EEG) signals is found during propofol-induced general anesthesia, which is similar to that of slow-wave sleep (SWS). However, a complete understanding is lacking in terms of the characteristics of EEG changes in rats after propofol administration and whether propofol acts through natural sleep circuits. Here, we examined the characteristics of EEG patterns induced by intraperitoneal injection of propofol in rats. We found that high (10 mg/kg) and medium (5 mg/kg) doses of propofol induced a cortical EEG of low-frequency, high-amplitude activity with rare electromyographic activity and markedly shortened sleep latency. The high dose of propofol increased deep slow-wave sleep (SWS2) to 4 h, as well as the number of large SWS2 bouts (>480 s), their mean duration and the peak of the power density curve in the delta range of 0.75–3.25 Hz. After the medium dose of propofol, the total number of wakefulness, light slow-wave sleep (SWS1) and SWS2 episodes increased, whereas the mean duration of wakefulness decreased. The high dose of propofol significantly increased c-fos expression in the ventrolateral preoptic nucleus (VLPO) sleep center and decreased the number of c-fos-immunoreactive neurons in wake-related systems including the tuberomammillary nucleus (TMN), perifornical nucleus (PeF), lateral hypothalamic nucleus (LH), ventrolateral periaqueductal gray (vPAG) and supramammillary region (SuM). These results indicated that the high dose of propofol produced high-quality sleep by increasing SWS2, whereas the medium dose produced fragmented and low-quality sleep by disrupting the continuity of wakefulness. Furthermore, sleep-promoting effects of propofol are correlated with activation of the VLPO cluster and inhibition of the TMN, PeF, LH, vPAG and SuM.

Pharmacodynamic modeling of propofol-induced general anesthesia in young adults.

Target controlled infusion (TCI) of intraveneous anesthetics can assist clinical practitioners to provide improved care for General Anesthesia (GA). Pharmacokinetic/Pharmacodynamic (PK/PD) models help in relating the anesthetic drug infusion to observed brain activity inferred from electroencephalogram (EEG) signals. The parameters in popular population PK/PD models for propofol-induced GA (Marsh and Schnider models) are either verified based on proprietary functions of the EEG signal which are difficult to correlate with the neurophysiological models of anesthesia, or the marker itself needs to be estimated simultaneously with the PD model. Both these factors make these existing paradigms challenging to apply in real-time context where a patient-specific tuning of parameters is desired. In this work, we propose a simpler EEG marker from frequency domain description of EEG and develop two corresponding PK/PD modeling approaches which differ in whether they use existing population-level PK models (approach 1) or not (approach 2). We use a simple deterministic parameter estimation approach to identify the unknown PK/PD model parameters from an existing human EEG data-set. We infer that both approaches 1 and 2 yield similar and reasonably good fits to the marker data. This work can be useful in developing patient-specific TCI strategies to induce GA.

A Pharmacokinetics-Neural Mass Model (PK-NMM) for the Simulation of EEG Activity during Propofol Anesthesia.

Modeling the effects of anesthetic drugs on brain activity is very helpful in understanding anesthesia mechanisms. The aim of this study was to set up a combined model to relate actual drug levels to EEG dynamics and behavioral states during propofol-induced anesthesia. We proposed a new combined theoretical model based on a pharmacokinetics (PK) model and a neural mass model (NMM), which we termed PK-NMM—with the aim of simulating electroencephalogram (EEG) activity during propofol-induced general anesthesia. The PK model was used to derive propofol effect-site drug concentrations (C eff) based on the actual drug infusion regimen. The NMM model took C eff as the control parameter to produce simulated EEG-like (sEEG) data. For comparison, we used real prefrontal EEG (rEEG) data of nine volunteers undergoing propofol anesthesia from a previous experiment. To see how well the sEEG could describe the dynamic changes of neural activity during anesthesia, the rEEG data and the sEEG data were compared with respect to: power-frequency plots; nonlinear exponent (permutation entropy (PE)); and bispectral SynchFastSlow (SFS) parameters. We found that the PK-NMM model was able to reproduce anesthesia EEG-like signals based on the estimated drug concentration and patients’ condition. The frequency spectrum indicated that the frequency power peak of the sEEG moved towards the low frequency band as anesthesia deepened. Different anesthetic states could be differentiated by the PE index. The correlation coefficient of PE was 0.80±0.13 (mean±standard deviation) between rEEG and sEEG for all subjects. Additionally, SFS could track the depth of anesthesia and the SFS of rEEG and sEEG were highly correlated with a correlation coefficient of 0.77±0.13. The PK-NMM model could simulate EEG activity and might be a useful tool for understanding the action of propofol on brain activity.

EEG slow-wave mediates the fragmentation and coupling of cortical networks in propofol-induced general anesthesia

Electroencephalogram (EEG) recorded from propofol-induced general anesthesia is characterized by large amplitude slow-waves (0.1--1.5 Hz). Clinically, these lowest frequency components of the EEG signal become dominant over other higher frequency components during and after loss of consciousness [1]. However, it remains unclear how these slow oscillations are produced and to what extent they reflect changes in cortical network connectivity. Modeling anesthesia as a moderate reduction in interneuronal gap-junction coupling, a recent theoretical work by Steyn-Ross et al [2] predicts emergence of anesthetic slow-waves with chaotic dynamics. In the modeled anesthesia state, the weakened gap-junction coupling supports a codimension-2 bifurcation point where competing Turing (space) and Hopf (time) dynamics coexist, signifying spontaneous symmetry-breaking instabilities in the firing behavior of cortical neurons. Further, these chaotic slow-waves are found to perturb the neuronal coupling across the cortex, leading to a dramatic drop in global phase-coherence compared to its high level during consciousness. In this study, we analyze clinically-recorded EEG data to examine the model prediction for changes in phase-coherence between pairs of EEG channels in the sub-delta band during propofol anesthetic induction. Our study finds a coherence decrease in the frontal and occipital regions (see left panel of Figure ​Figure1),1), as well in the connection between them. Concomitantly, more strongly coupled neuronal activities are disclosed in the temporal-frontal, temporal-occipital and left-right temporal regions (right panel). Our clinical observation of reduced EEG coherence is consonant with cortical model predictions. However, our EEG study indicates that the coherence alternation is regional in nature, while the cortical model describes a spatially-uniform trend. Moreover, we did not find any theoretical prediction for the left- and right-temporal increased-coherence patterns. As the cortical model by Steyn-Ross et al. is spatially homogenous, i.e., there are no explicit front-to-back or right-to-left directionality, it is unable to produce regional coherence changes. It appears that the Steyn-Ross cortical model best represents the cortical dynamics in the frontal region. Figure 1 Correlation representations showing electrode pairs with significantly reduced (left, blue) or increased (right, pink) phase-coherence for sub-delta band (0.05-1.5 Hz) EEG induced by propofol anesthesia. Only electrode pairs (from 128 scalp electrodes) ...

General anesthesia reduces the information exchange between heart and circulation.

The study demonstrates the ability of an information-theoretic measure, such as the transfer entropy (TE), in detecting the depression of the cardiac baroreflex control and circulatory-cardio mechanical feedforward link during propofol-induced general anesthesia. TE was computed from spontaneous variability of heart period (HP) and systolic arterial pressure (SAP) in patients undergoing coronary artery bypass graft (CABG). TE from SAP to HP and from HP to SAP were evaluated by accounting for the confounding effect of respiration (R) affecting both HP and SAP (i.e. TESAP→HP|R and TEHP→SAP|R respectively). Both TESAP→HP|R and TEHP→SAP|R decreased during general anesthesia, thus suggesting that the strength of the causal relation diminished over both arms of the closed loop HP-SAP control. The squared coherence function between HP and SAP confirmed the decreased HP-SAP coupling during general anesthesia, even though it could not distinguish directionality.

Ephedrine and propofol for induction of general anesthesia can decrease intraoperative hypothermia in patients undergoing plastic and breast surgery: a randomized, controlled trial

Background: Ephedrine has vasoconstrictive and mild ?-adrenergic agonist effects that may be able to decrease intraoperative core temperature hypothermia. However, its efficacy is still unclear. Objectives: To determine the efficacy of ephedrine given during induction to maintain core temperature during plastic and breast surgery under general anesthesia. Materials and Methods: A prospective, randomized, double-blinded study was approved by our Institutional Review Board and registered with the Thai Clinical Trials Registry as TCTR20141212002. We randomly assigned 30 patients to receive mixture of propofol and ephedrine (ephedrine group, n = 15) or a mixture of propofol and normal saline (control group, n = 15) for induction of general anesthesia. The tympanic temperature (core temperature before intubation), esophageal temperature (core temperature after intubation), index temperature (peripheral temperature), systolic and diastolic blood pressure were compared between groups and baselines. Results: During surgery, patients in ephedrine group showed better esophageal temperature maintenance than those in the control group. Whereas systolic blood pressure in ephedrine group was significantly higher than in the control group in early phase after induction. Conclusions: A bolus dose of ephedrine given during induction can decrease core temperature loss during plastic and breast surgery under general anesthesia. Keywords: Ephedrine, general anesthesia, hypothermia, temperature

EEG slow-wave coherence changes in propofol-induced general anesthesia: experiment and theory.

The electroencephalogram (EEG) patterns recorded during general anesthetic-induced coma are closely similar to those seen during slow-wave sleep, the deepest stage of natural sleep; both states show patterns dominated by large amplitude slow waves. Slow oscillations are believed to be important for memory consolidation during natural sleep. Tracking the emergence of slow-wave oscillations during transition to unconsciousness may help us to identify drug-induced alterations of the underlying brain state, and provide insight into the mechanisms of general anesthesia. Although cellular-based mechanisms have been proposed, the origin of the slow oscillation has not yet been unambiguously established. A recent theoretical study by Steyn-Ross et al. (2013) proposes that the slow oscillation is a network, rather than cellular phenomenon. Modeling anesthesia as a moderate reduction in gap-junction interneuronal coupling, they predict an unconscious state signposted by emergent low-frequency oscillations with chaotic dynamics in space and time. They suggest that anesthetic slow-waves arise from a competitive interaction between symmetry-breaking instabilities in space (Turing) and time (Hopf), modulated by gap-junction coupling strength. A significant prediction of their model is that EEG phase coherence will decrease as the cortex transits from Turing–Hopf balance (wake) to Hopf-dominated chaotic slow-waves (unconsciousness). Here, we investigate changes in phase coherence during induction of general anesthesia. After examining 128-channel EEG traces recorded from five volunteers undergoing propofol anesthesia, we report a significant drop in sub-delta band (0.05–1.5 Hz) slow-wave coherence between frontal, occipital, and frontal–occipital electrode pairs, with the most pronounced wake-vs.-unconscious coherence changes occurring at the frontal cortex.

Bursting suppression in propofol-induced general anesthesia as bi-stability in a non-linear neural mass model

Bursting activity suppression, a phenomenon characterized by sequences of alternating quiescent (’down’) and bursting (’up’) states, is ubiquitously present during deep sedation in general anesthesia and can be observed in LFPs and in EEG recordings as well [1,2]. However, the dynamical principles underlying such phenomena are unclear. Prevailing theoretical approaches to this problem suggest that such bi-stable dynamics could be explained by the existence of notable non-linearities in the neuronal membrane potential as a function of the anesthetic agent, with frequent noise-induced transitions between two stable (attracting) branches. Nevertheless, the mathematical tractability of those models is rather limited due to the dimensionality (2D) of the phase-space (see Figure ​Figure1).1). It has been shown for a neural-mass version of the model proposed in [3], that the 2D-trajectory likely escapes to the other attractor trough a limited section of the saddle-line separating the attractions basins [4]. This prediction is here supported by numerical simulations, permitting the simplification of the dynamics to a simpler two-state trace. Relevant statistics can then be extracted, including histograms of the duration of the visit in each state that may support future analytical calculations of the EEG power spectrum following renewal theory [5]. Interestingly, it is found that only the average waiting time in the 'up' states is a non-linear decreasing function of p, differently to the residence time in the ’down’ state that behaves linearly in p and in the synaptic time-scale (1/α) direction as well. Figure 1 Bi-stability in a simplified neural-mass version of the Hutt & Longtin model [3], with neuron firing rates functions of Heaviside kind. A. 2D phase-portrait in the PSPs membrane potentials, showing the vector field (arrows) and sample free-noise ...

Reproduction of EEG power spectrum over frontal region during the propofol-induced general anesthesia

The present work aims to reproduce certain changes observed experimentally in the EEG power spectrum over the frontal head region during general anesthesia induced by propofol. These observations include increased delta (0-4 Hz) and alpha (8-12 Hz) activities [1]. We extend a previous cortical model [2] and study a neuronal population model of a single thalamo-cortical module consisting of three different populations of neurons, namely cortical excitatory neurons, thalamocortical relay neurons and inhibitory thalamic reticular neurons (Fig. ​(Fig.1).1). Each module obeys a neural mass model. The cortical inhibitory population is neglected in our model to reveal the effect of propofol action in the thalamus. Our model describes well the characteristic spectral changes observed experimentally within the delta- and alpha- frequency bands in frontal and occipital electrodes with increasing concentration of propofol. Figure 1 Schematic of a thalamocortical module. The blue and red lines indicate excitatory and inhibitory connections, respectively. The solid lines represent connections associated with the same delay and the dotted lines denote connections without delay. This shows that neglecting inhibitory action in the cortex but considering thalamic GABAergic action suffices to reproduce the data. From a modeling point of view, our reduced mathematical model is low dimensional and remains analytically treatable while still being adequate to reproduce observed changes in EEG rhythms. Moreover, it is shown that the propofol concentration acts as a control parameter of the system and that propofol-induced changes in the stationary states of the model system lead to changes in the corresponding nonlinear gain function that result in EEG power modulation: increases of power over the frontal region can be caused by an increase in the gain function of thalamocortical network. The results suggest that intra-thalamic inhibition from reticular neurons to relay cells plays an important role in the generation of the characteristic EEG patterns seen during general anesthesia.

Meanfield modeling of propofol-induced changes in spontaneous EEG rhythms

During the maintenance period of propofol-induced general anesthesia, specific changes in spontaneous EEG rhythms can be observed. These comprise increased delta and theta power and the emergence of alpha oscillations over frontal regions. In this study we use a meanfield model of the thalamo-cortical system to reproduce these changes and to elucidate the underlying mechanisms. The model is able to reproduce the most dominant changes in the EEG and suggests that they are caused by the amplification of resonances within the thalamo-cortical system. Specifically, while observed increases in delta and alpha power are reflections of amplified resonances in the respective frequency bands, increases in theta power are caused indirectly by spectral power leakage from delta and alpha bands. The model suggests that these changes are brought about through increased inhibition within local cortical interneuron circuits. These results are encouraging and motivate more extensive use of neural meanfield models in elucidating the physiological mechanisms underlying the effects of pharmacological agents on macroscopic brain dynamics.

Persistent Seizure after Propofol-Induced General Anesthesia in Recovery Room: A Case Report

Persistent Seizure after Propofol-Induced General Anesthesia in Recovery Room: A Case Report

Endoscopic Argon Plasma Trimming of Biliary and Gastrointestinal Metallic Stents

The aim of this study was to assess the feasibility and efficiency of plasma argon trimming of gastrointestinal and biliary metallic stents. A total of 31 patients underwent plasma argon trimming of their metallic stents (14 women, 17 men; mean +/- SD age 73 +/- 12.2 years, range 46 - 96 years). Of these 31 patients, 24 had had covered or noncovered Unistep Wallstents placed in the biliary tract (13 patients with pancreatic neoplasms, five patients with Vater ampulloma, five patients with biliary tract carcinoma and one patient with chronic calcifiying pancreatitis); three patients had noncovered Enteral Unistep Wallstents (pyloroduodenal); two patients with obstructive colorectal carcinoma had a noncovered Bard Memotherm stent inserted; and two patients had noncovered Ultraflex stents placed for esophageal carcinoma. Endoscopic trimming of the stents was performed under propofol-induced general anesthesia, with the power set at 70 - 80 watts and an argon flow of 0.8 liters/minute. Complete and satisfactory trimming of the stents was possible, without complications (mean follow-up 15.8 months), in all patients except one, a patient with a covered biliary Wallstent. In 13 patients with biliary or Enteral Wallstents the trimming procedure was preventive. In eight patients with ulceration and/or hemorrhage (duodenal or rectal), healing was achieved after stent trimming and epinephrine (adrenaline) injection followed by electrocoagulation. Stent trimming restored patency of the duodenal lumen in six patients and of the esophageal lumen in two patients, and was done to allow insertion of a biliary stent in one patient whose duodenal stent was covering the papilla. In one patient with rectal tenesmus, stent shortening resulted in complete resolution of symptoms. Endsocopic plasma argon trimming of metallic stents is an efficient procedure which allows easy, reproducible and well-tolerated correction of complications that arise due to these prostheses.