Neuronal Networks during Burst Suppression as Revealed by Source Analysis

Introduction

Burst-suppression (BS) is an electroencephalography (EEG) pattern consisting of alternant periods of slow waves of high amplitude (burst) and periods of so called flat EEG (suppression). It is generally associated with coma of various etiologies (hypoxia, drug-related intoxication, hypothermia, and childhood encephalopathies, but also anesthesia). Animal studies suggest that both the cortex and the thalamus are involved in the generation of BS. However, very little is known about mechanisms of BS in humans. The aim of this study was to identify the neuronal network underlying both burst and suppression phases using source reconstruction and analysis of functional and effective connectivity in EEG.

Material/Methods

Dynamic imaging of coherent sources (DICS) was applied to EEG segments of 13 neonates and infants with burst and suppression EEG pattern. The brain area with the strongest power in the analyzed frequency (1–4 Hz) range was defined as the reference region. DICS was used to compute the coherence between this reference region and the entire brain. The renormalized partial directed coherence (RPDC) was used to describe the informational flow between the identified sources.

Results/Conclusion

Delta activity during the burst phases was associated with coherent sources in the thalamus and brainstem as well as bilateral sources in cortical regions mainly frontal and parietal, whereas suppression phases were associated with coherent sources only in cortical regions. Results of the RPDC analyses showed an upwards informational flow from the brainstem towards the thalamus and from the thalamus to cortical regions, which was absent during the suppression phases. These findings may support the theory that a “cortical deafferentiation” between the cortex and sub-cortical structures exists especially in suppression phases compared to burst phases in burst suppression EEGs. Such a deafferentiation may play a role in the poor neurological outcome of children with these encephalopathies.     

Pediatric Anesthesia Monitoring with the Help of EEG and ECG

This paper presents research regarding the monitoring of the brain and the adequacy of anesthesia during surgery. Particular variables are derived from EEG and ECG signals and are correlated to anesthetic gas (sevoflurane) concentration, in pediatric anesthesia. The methods used for parameter extraction are based on change detection theory and time-frequency representation. Preliminary results show that the expired anesthetic gas concentration modulates both the heart rate variability and the duration of the burst suppression. Monitors of the central nervous system and autonomic nervous system activities can be expected to be based on these variables.     

Quantification of transient quadratic phase couplings within EEG burst patterns in sedated patients during electroencephalic burst-suppression period

The time dynamics of the quadratic phase coupling within burst patterns during electroencephalic burst-suppression has been quantified. It can be shown that a transient quadratic phase coupling (QPC) exists between the frequency ranges 0 to 2.5 and 3 to 7.5 Hz and between the frequency ranges 0 to 2.5 and 8 to 12 Hz. The QPC can be explained by an amplitude modulation, where the slow rhythm modulates the rhythmic activities with a higher frequency. By means of time-variant bicoherence analysis, a strong phase-locking between the modulating and the modulated component can be identified. The phase-locking is demonstrable within the first 250 ms after the burst onset and comes up to the maximum between 750 and 1250 ms. The effect is maintained over the whole first part of the burst (2 s) with a decreasing tendency after 1250 ms. All these effects cannot be found in the EEG before entering the burst suppression period (BSP). The transient coupling phenomena in the EEG bursts during BSP can be regarded as indicators for short-term interrelations between the underlying electrophysiologic processes.     

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.     

Motor imaginary-based brain–machine interface design using programmable logic controllers for the disabled

Aiming at the implementation of brain–machine interfaces (BMI) for the aid of disabled people, this paper presents a system design for real-time communication between the BMI and programmable logic controllers (PLCs) to control an electrical actuator that could be used in devices to help the disabled. Motor imaginary signals extracted from the brain's motor cortex using an electroencephalogram (EEG) were used as a control signal. The EEG signals were pre-processed by means of adaptive recursive band-pass filtrations (ARBF) and classified using simplified fuzzy adaptive resonance theory mapping (ARTMAP) in which the classified signals are then translated into control signals used for machine control via the PLC. A real-time test system was designed using MATLAB for signal processing, KEP-Ware V4 OLE for process control (OPC), a wireless local area network router, an Omron Sysmac CPM1 PLC and a 5 V/0.3 A motor. This paper explains the signal processing techniques, the PLC's hardware configuration, OPC configuration and real-time data exchange between MATLAB and PLC using the MATLAB OPC toolbox. The test results indicate that the function of exchanging real-time data can be attained between the BMI and PLC through OPC server and proves that it is an effective and feasible method to be applied to devices such as wheelchairs or electronic equipment.     

Cerebral Oxidative Metabolism and Blood Flow During Acute Hypoglycemia and Recovery in Unanesthetized Rats

Abstract: Progressive neurological depression leading to coma was produced in unanesthetized rats at a constant level of hypoglycemia induced by insulin. High-energy phosphate concentrations in brain remained normal during hypoglycemic lethargy, but ATP declined by 6% during stupor and by 40% during coma that was characterized by an isoelectric EEG. Cerebral blood flow (CBF) remained normal during hypoglycemia whereas the cerebral metabolic rates for oxygen (CMRo₂) and glucose (CMR_glucose) decreased by 45 and 73%, respectively, indicating oxidation of nonglucose fuels. A plot of CMRo₂ and CMR_glucose versus plasma glucose indicated increasing oxidation of alternate substrates (elevated CMRo²/CMR_glucose) at plasma glucose concentrations below 2.5 mm . The cerebral uptake of β-hydroxybutyrate increased during hypoglycemic stupor and its complete oxidation could account for the CMRo₂ in excess of glucose utilization. Brain ammonia, a byproduct of amino acid metabolism, reached a level during hypoglycemic coma sufficient to produce coma in normoglycemic animals. The rate and degree of recovery after glucose administration depended on the duration of hypoglycemia and the pretreatment neurological state of the animal. Following 10 min of glucose infusion, ATP levels that were modestly depressed in stuporous rats recovered fully, paralleling the animals' apparently full neurological recovery. Rats that had been in hypoglycemic coma for 1 min or less fully recovered high-energy phosphate concentrations in brain. However, when normalization of plasma glucose was delayed for more than 1 min of coma, the CMRo₂ remained depressed, CBF decreased to 40% of control, and high-energy substrates failed to normalize. In keeping with the depression of oxidative metabolism and blood flow, neurological function and the EEG remained abnormal even after 1 h of glucose infusion. The findings suggest that irreversible brain injury may develop within the first minutes of hypoglycemic coma.     

不同麻醉方法对腹腔镜子宫全切2型糖尿病患者血流动力学、血糖水平及补体C3、C4的影响

摘要 目的：探讨不同麻醉方法对行腹腔镜子宫全切2型糖尿病（T2DM）患者血流动力学、血糖水平及补体C3、C4的影响。方法：前瞻性选择2016年1月至2019年1月期间我院收治的120例拟行腹腔镜子宫全切术的T2DM患者,采用随机数字表法将患者分为两组,A组（60例）采用靶控输注丙泊酚、瑞芬太尼全麻,B组（60例）采用靶控输注丙泊酚、瑞芬太尼复合吸入七氟醚全麻。观察两组围手术期血流动力学、血糖、胰岛素、胰高血糖素、C肽及补体C3、C4水平变化和差异,对比两组麻醉效果。结果：B组苏醒时间、拔管时间短于A 组（P＜0.05）,苏醒后视觉模拟评分法（VAS）评分低于A组（P＜0.05）。B组建立气腹前（T1）、建立气腹后1.5 h（T2）、手术结束时(T3)、苏醒时(T4) 观测点平均动脉压（MAP）高于A组（P＜0.05）。建立气腹前（M1）、建立气腹后1.5 h（M2）、术后第1 d（M3）、术后第3 d（M4）观测点胰岛素、C肽水平低于A组（P＜0.05）。M1-M4观测点血糖高于A组（P＜0.05）,M2-M4观测点胰高血糖素水平高于A组（P＜0.05）。M1-M4观测点补体C3、C4水平高于A组（P＜0.05）。结论：靶控输注丙泊酚、瑞芬太尼复合七氟醚全麻麻醉效果更好,且有助于维持腹腔镜子宫全切T2DM患者血流动力学稳定,改善补体C3、C4水平,而靶控输注丙泊酚、瑞芬太尼全麻可维持血糖水平稳定,临床应根据患者情况选择合适的麻醉方案。     

Implementation of Neural Networks to Frontal Electroencephalography for the Identification of the Transition Responsiveness/Unresponsiveness During Induction of General Anesthesia

ObjectiveGeneral anesthesia is a reversible drug-induced state of altered arousal characterized by loss of responsiveness (LOR) due to brainstem inactivation. Precise identification of the LOR during the induction of general anesthesia is extremely important to provide personalized information on anesthetic requirements and could help maintain an adequate level of anesthesia throughout surgery, ensuring safe and effective care and balancing the avoidance of intraoperative awareness and overdose. So, main objective of this paper was to investigate whether a Convolutional Neural Network (CNN) applied to bilateral frontal electroencephalography (EEG) dataset recorded from patients during opioid-propofol anesthetic procedures identified the exact moment of LOR.Material and methodsA clinical protocol was designed to allow for the characterization of different clinical endpoints throughout the transition to unresponsiveness. Fifty (50) patients were enrolled in the study and data from all was included in the final dataset analysis. While under a constant estimated effect-site concentration of 2.5 ng/mL of remifentanil, an 1% propofol infusion was started at 3.3 mL//h until LOR. The level of responsiveness was assessed by an anesthesiologist every six seconds using a modified version of the Richmond Agitation-Sedation Scale (aRASS). The frontal EEG was acquired using a bilateral bispectral (BIS VISTA™ v2.0, Medtronic, Ireland) sensor. EEG data was then split into 5-second epochs, and for each epoch, the anesthesiologist's classification was used to label it as responsiveness (no-LOR) or unresponsiveness (LOR). All 5-second epochs were then used as inputs for the CNN model to classify the untrained segment as no-LOR or LOR.ResultsThe CNN model was able to identify the transition from no-LOR to LOR successfully, achieving 97.90±0.07% accuracy on the cross-validation set.ConclusionThe obtained results showed that the proposed CNN model was quite efficient in the responsiveness/unresponsiveness classification. We consider our approach constitutes an additional technique to the current methods used in the daily clinical setting where LOR is identified by the loss of response to verbal commands or mechanical stimulus. We therefore hypothesized that automated EEG analysis could be a useful tool to detect the moment of LOR, especially using machine learning approaches.     

Cerebral Polyamine Metabolism in Reversible Hypoglycemia of Rat: Relationship to Energy Metabolites and Calcium

Thirty minutes of insulin-induced reversible hypoglycemic coma (defined in terms of cessation of EEG activity) was produced in anesthetized rats. At the end of the hypoglycemic coma or after recovery for 3, 24, or 72 h induced by glucose infusion, the animals were reanesthetized and their brains frozen in situ. Two control groups were used: untreated controls without prior manipulations, and insulin controls, which received injections of insulin followed by glucose infusion to maintain blood glucose within the physiological range. The brains of these latter animals were frozen 3, 24, or 72 h after glucose infusion. Tissue samples from the cortex, striatum, hippocampus, and thalamus were taken to measure ornithine decarboxylase (ODC) activity, and putrescine and spermidine levels, as well as phosphocreatine (PCr), ATP, glucose, and lactate content. In addition, 20-microns thick coronal sections taken from the striatum and dorsal hippocampus were used for histological evaluation of cell damage and also stained for calcium. Insulin in the absence of hypoglycemia produced a significant increase in ODC activity and putrescine level but had no effect on the profiles of energy metabolites or spermidine. During hypoglycemic coma, brain PCr, ATP, glucose, and lactate levels were sharply reduced, as expected. Energy metabolites normalized after 3 h of recovery. In the striatum, significant secondary decreases in PCr and ATP contents and rises in glucose and lactate levels were observed after 24 h of recovery. ODC activity, and putrescine and spermidine levels were unchanged during hypoglycemic coma. After 3 h of recovery, ODC activity increased markedly throughout the brain, except in the striatum. After 24 h of recovery, ODC activity decreased and approached control values 2 days later. Putrescine levels increased significantly throughout the brain after reversible hypoglycemic coma, the highest values observed after 24 h of recovery (p less than or equal to 0.001, compared with controls). After 72 h of recovery, putrescine levels decreased, but still significantly exceeded control values. Reversible hypoglycemic coma did not produce significant changes in regional spermidine levels except in the striatum, where an approximately 30% increase was observed after 3 and 72 h of recovery (p less than or equal to 0.01 and p less than or equal to 0.05, respectively). Twenty-four hours after hypoglycemic coma, intense calcium staining was apparent in layer III of the cerebral cortex, the lateral striatum, and the crest of the dentate gyrus. After 72 h of recovery, the intense calcium staining included also cortical layer II, the septal nuclei, the subiculum, and the hippocampal CA1-subfield.(ABSTRACT TRUNCATED AT 400 WORDS)     

The anaesthetic agent propofol interacts with GABA(B)-receptors: an electrophysiological study in rat

The mode of action by which propofol induces anaesthesia is not fully understood, although several studies suggest that the compound acts via potentiation of brain GABA(A)-receptors. The aim of the present study is to investigate a putative GABA(B)-receptor agonistic action of propofol. For this purpose the action of propofol on a GABA-receptor mediated regulation of dopamine neurons was analyzed with extracellular single unit recordings of dopaminergic neurons of the substantia nigra in chloral hydrate anaesthetized rats.Intravenous administration of propofol (1-16 mg/kg) was found to dose-dependently decrease the firing rate and burst firing activity of nigral DA neurons. These effects by propofol were effectively antagonized by pretreatment with the selective GABA(B)-receptor antagonist CGP 35348 (200 mg/kg, i.v.) but not by pretreatment with the GABA(A)-receptor antagonist picrotoxin (4.5 mg/kg, i.v.).It is proposed that an activation of central GABA(B)-receptors may, at least partially, contribute to the anesthetic properties of propofol.     

Evoked response potential markers for anesthetic and behavioral states

The rodent whisker sensory system is a commonly used model of cortical processing; however, anesthetics cause profound differences in the shape and timing of evoked responses. Evoked response studies, especially those that use spatial mapping techniques, such as fMRI or optical imaging, will thus show significantly different results depending on the anesthesia used. To describe the effect of behavioral states and commonly used anesthetics, we characterized the early surface-evoked response potentials (ERPs) components (first ERP peak: gamma band 25-45 Hz; fast oscillation: 200-400 Hz; and very fast oscillation: 400-600 Hz) using a 25-channel electrode array on the somatosensory cortex during whisker stimulation. We found significant differences in the ERP shape when ketamine/xylazine, urethane, propofol, isoflurane, and pentobarbital sodium were administered and during sleep and wake states. The highest ERP amplitudes were observed under propofol anesthesia and during quiet sleep. Under isoflurane, the ERP was nearly absent, except for a very late component, which was concombinant with burst synchronization. The slowest responses were seen under urethane and propofol anesthesia. Spatial mapping experiments that use electrical, NMR, or optical techniques must consider the anesthetic dependency of these signals, especially when stimulation protocols or electrical and metabolic responses are compared.     

Influence of time of day on propofol pharmacokinetics and pharmacodynamics in rabbits

This study evaluates the administration time-of-day effects on propofol pharmacokinetics and sedative response in rabbits. Nine rabbits were sedated with 5?mg/kg propofol at three local clock times: 10:00, 16:00, and 22:00?h. Each rabbit served as its own control by being given a single infusion at the three different times of day on three separate occasions. Ten arterial blood samples were collected during each clock-time experiment for propofol assay. A two-compartment model was used to describe propofol pharmacokinetics, and the pedal withdrawal reflex was used as the sedation pharmacodynamic response. The categorical data comprising the presence or absence of pedal withdrawal reflex was described by a logistic model. The typical volume of the central compartment equaled 7.67?L and depended on rabbit body weight. The elimination rate constant depended on drug administration time; it was lowest at 10:00?h, highest at 16:00?h, and intermediate at 22:00?h. Delay of the anesthetic effect, with respect to plasma concentrations, was described by the effect compartment, with the rate constant for the distribution to the effector compartment equal to 0.335?min(-1). Drug concentration had a large effect on the probability of anesthesia. The degree of anesthesia was largest at 10:00?h, lowest at 16:00?h, and intermediate at 22:00?h. In summary, both the pharmacokinetics and pharmacodynamics of propofol in rabbits depended on administration time. The developed population approach may be used to assess chronopharmacokinetics and chronopharmacodynamics of medications in animals and humans.     

Human mediotemporal EEG characteristics during propofol anesthesia

Evidence for a response-control-related kind of declarative memory during deep propofol anesthesia has recently been reported. Connectivity within the mediotemporal lobe (MTL), and in particular rhinal–hippocampal synchronization within the gamma band, has been shown to be crucial for declarative memory formation. Thus, we analyzed EEG recordings obtained from the scalp, as well as directly from within the hippocampus and from the anterior parahippocampal gyrus, which is covered by rhinal cortex, in patients with unilateral temporal lobe epilepsy during propofol anesthesia, which preceded electrode explantation. For the gamma band a power decrease starting with induction of anesthesia was observed at scalp position Cz, but a power increase was detected at MTL locations. In contrast to prior results for sleep recordings, rhinal–hippocampal coherence did not decrease within the gamma band at deeper levels of anesthesia. These findings may represent an indirect electrophysiological correlate of partially intact declarative memory formation during deep propofol sedation. Furthermore, we investigated how well the plasma propofol level, as well as different stages of anesthesia including the burst suppression phase, could be monitored by different spectral as well as by nonlinear EEG measures. We observed that conventional spectral power measures, most prominently those recorded from mediotemporal locations, are most closely correlated with the plasma propofol level, whereas different stages of anesthesia can be distinguished best by nonconventional spectral as well as nonlinear measures.     

Guanosine Exerts Neuroprotective Effect in an Experimental Model of Acute Ammonia Intoxication

The nucleoside guanosine (GUO) increases glutamate uptake by astrocytes and acts as antioxidant, thereby providing neuroprotection against glutamatergic excitotoxicity, as we have recently demonstrated in an animal model of chronic hepatic encephalopathy. Here, we investigated the neuroprotective effect of GUO in an acute ammonia intoxication model. Adult male Wistar rats received an intraperitoneal (i.p.) injection of vehicle or GUO 60 mg/kg, followed 20 min later by an i.p. injection of vehicle or 550 mg/kg of ammonium acetate. Afterwards, animals were observed for 45 min, being evaluated as normal, coma (i.e., absence of corneal reflex), or death status. In a second cohort of rats, video-electroencephalogram (EEG) recordings were performed. In a third cohort of rats, the following were measured: (i) plasma levels of glucose, transaminases, and urea; (ii) cerebrospinal fluid (CSF) levels of ammonia, glutamine, glutamate, and alanine; (iii) glutamate uptake in brain slices; and (iv) brain redox status and glutamine synthetase activity in cerebral cortex. GUO drastically reduced the lethality rate and the duration of coma. Animals treated with GUO had improved EEG traces, decreased CSF levels of glutamate and alanine, lowered oxidative stress in the cerebral cortex, and increased glutamate uptake by astrocytes in brain slices compared with animals that received vehicle prior to ammonium acetate administration. This study provides new evidence on mechanisms of guanine-derived purines in their potential modulation of glutamatergic system, contributing to GUO neuroprotective effects in a rodent model of by acute ammonia intoxication.     

Auditory Evoked Bursts in Mouse Visual Cortex during Isoflurane Anesthesia

General anesthesia is not a uniform state of the brain. Ongoing activity differs between light and deep anesthesia and cortical response properties are modulated in dependence of anesthetic dosage. We investigated how anesthesia level affects cross-modal interactions in primary sensory cortex. To examine this, we continuously measured the effects of visual and auditory stimulation during increasing and decreasing isoflurane level in the mouse visual cortex and the subiculum (from baseline at 0.7 to 2.5 vol % and reverse). Auditory evoked burst activity occurred in visual cortex after a transition during increase of anesthesia level. At the same time, auditory and visual evoked bursts occurred in the subiculum, even though the subiculum was unresponsive to both stimuli previous to the transition. This altered sensory excitability was linked to the presence of burst suppression activity in cortex, and to a regular slow burst suppression rhythm (∼0.2 Hz) in the subiculum. The effect disappeared during return to light anesthesia. The results show that pseudo-heteromodal sensory burst responses can appear in brain structures as an effect of an anesthesia induced state change.     

Restoration of whole body movement: toward a noninvasive brain-machine interface system

This article highlights recent advances in the design of noninvasive neural interfaces based on the scalp electroencephalogram (EEG). The simplest of physical tasks, such as turning the page to read this article, requires an intense burst of brain activity. It happens in milliseconds and requires little conscious thought. But for amputees and stroke victims with diminished motor-sensory skills, this process can be difficult or impossible. Our team at the University of Maryland, in conjunction with the Johns Hopkins Applied Physics Laboratory (APL) and the University of Maryland School of Medicine, hopes to offer these people newfound mobility and dexterity. In separate research thrusts, were using data gleaned from scalp EEG to develop reliable brainmachine interface (BMI) systems that could soon control modern devices such as prosthetic limbs or powered robotic exoskeletons.     

Brain cooling maintenance with cooling cap following induction with intracarotid cold saline infusion: a quantitative model

Intracarotid cold saline infusion (ICSI) is potentially much faster than whole-body cooling and more effective than cooling caps in inducing therapeutic brain cooling. One drawback of ICSI is hemodilution and volume loading. We hypothesized that cooling caps could enhance brain cooling with ICSI and minimize hemodilution and volume loading. Six-hour-long simulations were performed in a 3D mathematical brain model. The Pennes bioheat equation was used to propagate brain temperature. Convective heat transfer through jugular venous return and the circle of Willis was simulated. Hemodilution and volume loading were modeled using a two-compartment saline infusion model. A feedback method of local brain temperature control was developed where ICSI flow rate was varied based on the rate of temperature change and the deviation of temperature to a target (32 °C) within a voxel in the treated region of brain. The simulations confirmed the inability of cooling caps alone to induce hypothermia. In the ICSI and the combination models (ICSI and cap), the control algorithm guided ICSI to quickly achieve and maintain the target temperature. The combination model had lower ICSI flow rates than the ICSI model resulting in a 55% reduction of infusion volume over a 6 h period and higher hematocrit values compared to the ICSI model. Moreover, in the combination model, the ICSI flow rate decreased to zero after 4 h, and hypothermia was subsequently maintained solely by the cooling cap. This is the first study supporting a role of cooling caps in therapeutic hypothermia in adults.     

丙泊酚靶控输注复合瑞芬太尼对腹腔镜直肠癌根治术患者血流动力学及术后认知功能的影响

摘要 目的：探讨丙泊酚靶控输注复合瑞芬太尼对腹腔镜直肠癌根治术患者血流动力学及术后认知功能的影响。方法：选取2017年4月~2019年4月期间我院收治的行腹腔镜直肠癌根治术患者101例,根据随机数字表法将患者分为对照组（n=50,静吸复合麻醉）和研究组（n=51,丙泊酚靶控输注复合瑞芬太尼麻醉）,比较两组围术期指标、血流动力学、术后认知功能及不良反应情况。结果：研究组麻醉诱导时间、拔管时间、清醒时间、自主呼吸恢复时间均较对照组缩短,丙泊酚使用剂量、瑞芬太尼使用剂量均少于对照组（P<0.05）。两组患者麻醉诱导后（T2）~手术结束时（T5）时间点心率(HR)呈先升高再下降的趋势（P<0.05）,平均动脉压(MAP)呈持续升高趋势（P<0.05）;研究组T2时间点HR高于对照组,插管即刻（T3）~手术开始时（T4）时间点HR则低于对照组（P<0.05）;研究组T2~T5时间点MAP均高于对照组（P<0.05）。两组拔管时的简易智能精神状态量表（MMSE）评分均降低,但研究组高于对照组（P<0.05）。两组不良反应发生率比较无统计学差异（P>0.05）。结论：腹腔镜直肠癌根治术中使用丙泊酚靶控输注复合瑞芬太尼麻醉,可有效改善围术期指标,减轻血流动力学波动,对患者术后的认知功能影响较轻。     

Influence of Time of Day on Propofol Pharmacokinetics and Pharmacodynamics in Rabbits

This study evaluates the administration time-of-day effects on propofol pharmacokinetics and sedative response in rabbits. Nine rabbits were sedated with 5?mg/kg propofol at three local clock times: 10:00, 16:00, and 22:00?h. Each rabbit served as its own control by being given a single infusion at the three different times of day on three separate occasions. Ten arterial blood samples were collected during each clock-time experiment for propofol assay. A two-compartment model was used to describe propofol pharmacokinetics, and the pedal withdrawal reflex was used as the sedation pharmacodynamic response. The categorical data comprising the presence or absence of pedal withdrawal reflex was described by a logistic model. The typical volume of the central compartment equaled 7.67?L and depended on rabbit body weight. The elimination rate constant depended on drug administration time; it was lowest at 10:00?h, highest at 16:00?h, and intermediate at 22:00?h. Delay of the anesthetic effect, with respect to plasma concentrations, was described by the effect compartment, with the rate constant for the distribution to the effector compartment equal to 0.335?min^?1. Drug concentration had a large effect on the probability of anesthesia. The degree of anesthesia was largest at 10:00?h, lowest at 16:00?h, and intermediate at 22:00?h. In summary, both the pharmacokinetics and pharmacodynamics of propofol in rabbits depended on administration time. The developed population approach may be used to assess chronopharmacokinetics and chronopharmacodynamics of medications in animals and humans. (Author correspondence: agnbienert@op.pl)