Anesthetic Agent Propofol Research Articles

Tracheal intubation in paediatric surgeries without muscle relaxation using magnesium sulphate as an adjuvant

Background Tracheal intubation under deep inhalational anaesthesia is a common practice in paediatrics; however, since the introduction of short-acting opioids, intubation has become more successful when these drugs are used in combination with propofol, avoiding the use of neuromuscular blocking agents with their unwanted side effects. Several techniques and adjuvants have been used to improve intubating conditions. We studied the interaction between magnesium sulphate and the anaesthetic agent's propofol and fentanyl to facilitate intubation in paediatrics. Patients and methods A total of 40 preschool and school-aged patients scheduled for short urogenital procedures were randomly assigned in a double-blind study to be administered either a 5-min infusion of magnesium sulphate (30 mg/kg) in 0.9% saline 5 ml/kg (magnesium group, n = 20), or the same volume of saline (control group, n = 20). Anaesthesia was induced (1 μg/kg) fentanyl followed by propofol (2.5 mg/kg). Intubating conditions were assessed by Copenhagen score. Blood pressure, heart rate, respiratory rate and EtCO 2 were recorded. Serum magnesium was measured, and Aldrete recovery score was assessed. Results The two groups were comparable regarding demographic data. Intubating conditions were better in the magnesium group than in the control group (0 vs. 60%). There were no differences between both groups regarding haemodynamic variables. The duration of intubation was insignificantly shorter in the magnesium group. Aldrete recovery score showed no difference between both groups. Serum magnesium increased from 1.92 to 3.18 mg/dl in the magnesium group, but with no signs of hypermagnesemia. Conclusion Adding magnesium sulphate to propofol and fentanyl improves intubating conditions without the use of muscle relaxants during the start of procedures in paediatrics.

Epileptic high‐frequency oscillations in intraoperative electrocorticography: The effect of propofol

Epileptic high-frequency oscillations (HFOs; 80-500 Hz) may be used to guide neurosurgeons during epilepsy surgery to identify epileptogenic tissue. We studied the effect of the anesthetic agent propofol on the occurrence of HFOs in intraoperative electrocorticography (ECoG). We selected patients who were undergoing surgery for temporal lobe epilepsy with a standardized electrode grid placement. Intraoperative ECoG was recorded at 2,048 Hz following cessation of propofol. The number and distribution of interictal spikes, ripples (R [80-250 Hz]), and fast ripples (FRs; 250-500 Hz) were analyzed. The amount of events on mesiotemporal channels and lateral neocortical channels were compared between patients with a suspected mesiotemporal and lateral epileptogenic area (Student's t-test), and HFOs were compared with the irritative zone, using correlation between amounts of events per channel, to provide evidence for the epileptic nature of the HFOs. Next, the amount of events within the first minute and the last minute were compared to each other and the change in events over the entire epochs was analyzed using correlation analyses of 10 epochs during the emergence periods (Spearman rank test). We studied whether the duration of HFOs changed over time. The change in events within presumed epileptogenic area was compared to the change outside this area (Student's t-test). Periods of burst suppression and continuous background activity were compared between and within patients (t-test). Twelve patients were included: five with suspected mesiotemporal epileptogenic area and three with suspected lateral epileptogenic area (and four were "other"). Spikes, ripples, and FRs were related to the suspected epileptogenic areas, and HFO zones were related to the irritative zones. Ripples and FRs increased during emergence from propofol anesthesia (mean number of ripples from first minute-last minute: 61.5-73.0, R = 0.46, p < 0.01; FRs: 3.1-5.7, R = 0.30, p < 0.01) and spikes remained unchanged (80.1-79.9, R = -0.05, p = 0.59). There was a decrease in number of channels with spikes (R = -0.18, p = 0.05), but no change in ripples (R = -0.13, p = 0.16) or FRs (R = 0.11, p = 0.45). There was no change in the durations of HFOs. The amount of HFOs in the presumed epileptogenic areas did not change more than the amount outside the presumed epileptogenic area, whereas spikes paradoxically decreased more within the suspected epileptogenic area. Six patients showing burst-suppression had lower rates of ripples than six other patients with continuous background activity (p = 0.02). No significant difference was found between burst suppression and continuous background activity in four patients, but there was a trend toward showing more ripples during continuous background activity (p = 0.16). Propofol, known for its antiepileptic effects, reduces the number of epileptic HFOs, but has no effect on spikes. This enforces the hypothesis that, in epilepsy, HFOs mirror the disease activity and HFOs might be useful for monitoring antiepileptic drug treatment. It is feasible to record HFOs during surgery, but propofol infusion should be interrupted for some minutes to improve detection.

Comparative canine Pharmacokinetics–Pharmacodynamics of Fospropofol Disodium Injection, Propofol Eemulsion, and Cyclodextrin-Enabled Propofol Solution Following Bolus Parenteral Administration

The pharmacokinetics and pharmacodynamics of fospropofol (FP) disodium injection, propofol emulsion (PE), and cyclodextrin-enabled propofol (CDP) solution following bolus parenteral administration in dogs was evaluated. Three healthy male beagle dogs were treated in a three-way cross-over study (14 day washout period) with 6 mg/kg propofol equivalents. Blood samples were collected predose and at 16 points postdose through 1440 min and analyzed for propofol and FP, when appropriate. From 5 min predose to 30 min postdose, brain electrical activity [electroencephalography (EEG)] was recorded and analyzed by power spectrum analysis techniques. Each formulation appeared to be well tolerated with transient discomfort observed in the PE and CDP animals and minor excitability in the FP animals prior to loss of consciousness. Blood propofol followed three-compartment pharmacokinetic behavior and derived parameters were not statistically different except for elimination half-life from the CDP formulation and onset, and duration of anesthesia from the FP formulation. The effect site concentrations at 50% the maximum EEG effect for the FP and CDP formulations were approximately one-half that of the PE formulation. Onset and duration of anesthesia are correlated with modeled effect site propofol concentrations. The implications of formulation on pain on injection and propofol activity are discussed.

Optical Detection of the Anesthetic Agent Propofol in the Gas Phase

The anesthetic agent propofol (2,6-diisopropylphenol) is the most widely used intravenously administered drug in general anesthesia. However, a viable online capability to monitor metabolized levels of propofol in patients does not currently exist. Here we show for the first time that optical spectroscopy has good potential to detect metabolized propofol from patients' exhaled breath. We present quantitative absorption measurements of gas phase propofol both in the ultraviolet and middle-infrared spectral regions. We demonstrate that a detection limit in the subparts-per-billion concentration range can be reached with photoacoustic spectroscopy in the UV spectral region, paving the way for the development of future optical monitors.

Neuroadaptive Output Feedback Control for Automated Anesthesia With Noisy EEG Measurements

Critical care patients, whether undergoing surgery or recovering in intensive care units, require drug administration to regulate physiological variables such as blood pressure, cardiac output, heart rate, and degree of consciousness. The rate of infusion of each administered drug is critical, requiring constant monitoring and frequent adjustments. Nonnegative and compartmental models provide a broad framework for biological and physiological systems, including clinical pharmacology, and are well suited for developing models for closed-loop control of drug administration. In this paper, we develop a neuroadaptive output feedback control framework for nonlinear uncertain nonnegative and compartmental systems with nonnegative control inputs and noisy measurements. The proposed framework is Lyapunov-based and guarantees ultimate boundedness of the error signals. In addition, the neuroadaptive controller guarantees that the physical system states remain in the nonnegative orthant of the state space. Finally, the proposed approach is used to control the infusion of the anesthetic drug propofol for maintaining a desired constant level of depth of anesthesia for surgery in the face of noisy electroencephalographic (EEG) measurements. Clinical trials demonstrate excellent regulation of unconsciousness allowing for a safe and effective administration of the anesthetic agent propofol.

Individual Differences in Pharmacokinetics and Pharmacodynamics of Anesthetic Agent Propofol with Regard to CYP2B6 and UGT1A9 Genotype and Patient Age

Propofol (2,6-diisopropylphenol) is administered intravenously for induction and maintenance of anesthesia; however, cases of progressive myocardial failure (propofol syndrome) related to the use of propofol have been reported. In the present study, the individual differences in pharmacokinetics and/or pharmacodynamics of propofol were investigated in patients who were genotyped for CYP2B6 and UGT1A9. Fifty-one patients treated with propofol in St. Marianna University Hospital were recruited for this study and provided written informed consent. The following parameters were analyzed: awakening time as a pharmacodynamic parameter, duration of propofol infusion, drug concentration in plasma after treatment, genotypes of CYP2B6 and UGT1A9, and age (42-84 years, mean of 65 years). Propofol was rapidly cleared from the blood of the subjects as a result of distribution and elimination. The awakening time after stopping propofol infusion was significantly correlated with the duration of infusion and the maximum concentration of propofol in these subjects. The maximum plasma concentration of propofol after normalizing with the duration of infusion was affected by the CYP2B6 G516T variant (related to impaired function) and was significantly affected by a propofol risk index score that incorporated CYP2B6 G516T and UGT1A9 I399C>T (high expression) genotypes and advanced age. These results provide important information indicating that the genotypes of the two enzymes studied and advanced age are combinative determinant factors of the pharmacokinetics and/or pharmacodynamics of propofol.

Changes in Resting Neural Connectivity during Propofol Sedation

BackgroundThe default mode network consists of a set of functionally connected brain regions (posterior cingulate, medial prefrontal cortex and bilateral parietal cortex) maximally active in functional imaging studies under “no task” conditions. It has been argued that the posterior cingulate is important in consciousness/awareness, but previous investigations of resting interactions between the posterior cingulate cortex and other brain regions during sedation and anesthesia have produced inconsistent results.Methodology/Principal FindingsWe examined the connectivity of the posterior cingulate at different levels of consciousness. “No task” fMRI (BOLD) data were collected from healthy volunteers while awake and at low and moderate levels of sedation, induced by the anesthetic agent propofol. Our data show that connectivity of the posterior cingulate changes during sedation to include areas that are not traditionally considered to be part of the default mode network, such as the motor/somatosensory cortices, the anterior thalamic nuclei, and the reticular activating system.Conclusions/SignificanceThis neuroanatomical signature resembles that of non-REM sleep, and may be evidence for a system that reduces its discriminable states and switches into more stereotypic patterns of firing under sedation.

State of the Art Review: Intravenous Fat Emulsions: Current Applications, Safety Profile, and Clinical Implications

To review the current state of the science regarding intravenous fat emulsions (IVFEs), with an emphasis on their safety profile. Articles were identified via a search of the MEDLINE database, including publications from 1979 to December 2009, using a search string that included the terms parenteral nutrition, lipid emulsion, fat emulsion, IVFE, safety, adverse effect, neonate intralipid, and terms describing a range of specific adverse events (AEs) such as pancreatitis. We selected articles that allowed us to compare the results of clinical trials involving delivery of medications via IVFEs with the historical use and effects of IVFEs in parenteral nutrition, with an emphasis on AEs. We focused on 2 drugs in current use that are administered intravenously in lipid emulsions: propofol and clevidipine. Clearance of the fat particles in IVFEs is mediated by the enzyme lipoprotein lipase. AEs are more likely if the rate or duration of IVFE administration exceeds the enzyme's clearance capacity. AEs are also more likely after administration of a 10% IVFE formulation than a 20% formulation, because the higher concentration of free phospholipid in the 10% formulation interferes with lipoprotein lipase activity. AEs can be reduced by administering IVFEs at a dosage < or = 2.5 g/kg/day and at a rate < or = 0.11 g/kg/h. The anesthetic agent propofol, which is formulated in a 10% IVFE, has been used clinically for 25 years. Typical AEs associated with propofol use include infection, high plasma triglyceride concentrations, and pancreatitis. Recent clinical trials involving clevidipine, which is formulated in a 20% IVFE, have demonstrated a low rate of lipid-related AEs. The results of this review demonstrate that IVFEs are well tolerated when administered in accordance with guideline recommendations.

Effects of the anesthetic agent propofol on neural populations.

The neuronal mechanisms of general anesthesia are still poorly understood. Besides several characteristic features of anesthesia observed in experiments, a prominent effect is the bi-phasic change of power in the observed electroencephalogram (EEG), i.e. the initial increase and subsequent decrease of the EEG-power in several frequency bands while increasing the concentration of the anaesthetic agent. The present work aims to derive analytical conditions for this bi-phasic spectral behavior by the study of a neural population model. This model describes mathematically the effective membrane potential and involves excitatory and inhibitory synapses, excitatory and inhibitory cells, nonlocal spatial interactions and a finite axonal conduction speed. The work derives conditions for synaptic time constants based on experimental results and gives conditions on the resting state stability. Further the power spectrum of Local Field Potentials and EEG generated by the neural activity is derived analytically and allow for the detailed study of bi-spectral power changes. We find bi-phasic power changes both in monostable and bistable system regime, affirming the omnipresence of bi-spectral power changes in anesthesia. Further the work gives conditions for the strong increase of power in the δ-frequency band for large propofol concentrations as observed in experiments.

Sedation with propofol for interventional endoscopy by trained nurses in high-risk octogenarians: a prospective, randomized, controlled study

Sedation with the short-acting anesthetic agent propofol has shown several advantages, particularly in interventional endoscopy. So far, however, there are no valid data on the safety of nurse-administered propofol sedation (NAPS) during interventional endoscopy in elderly high-risk patients. A total of 150 patients aged > 80 years with high comorbidity were randomized to receive midazolam plus meperidine (n = 75) or propofol alone (n = 76) for sedation during endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS), or double-balloon endoscopy (DBE). Sedation was supervised by a trained nurse and a trained physician both of whom were not involved in the endoscopic procedure. Vital signs were continuously monitored as well as patient cooperation and tolerance. Mortality and morbidity at 30 days was analyzed. The overall cardiopulmonary complication rate was 16 % in the midazolam group and 23.7 % in the propofol group ( P > 0.05). The mean decline in oxygen saturation (initial vs. lowest O (2) saturation) and the mean decline of blood pressure (initial vs. lowest blood pressure) were significantly greater with propofol (7 % +/- 3 % vs. 4 % +/- 2 % [ P < 0.05] and 10 % +/- 2 % vs. 8 % +/- 2 %, respectively [ P < 0.05]). No procedure had to be interrupted due to serious adverse events. Patient cooperation was statistically significantly better in the propofol group (7 +/- 2 vs. 5 +/- 2 points). Patients sedated with propofol showed a significantly lower oxygen saturation rate during recovery time (8 % vs. 28 %; P < or = 0.01). NAPS during interventional endoscopy is as safe as midazolam/pethidine sedation even in high-risk patients aged > 80 years.

Propofol: neuroprotection in an in vitro model of traumatic brain injury

IntroductionThe anaesthetic agent propofol (2,6-diisopropylphenol) has been shown to be an effective neuroprotective agent in different in vitro models of brain injury induced by oxygen and glucose deprivation. We examined its neuroprotective properties in an in vitro model of traumatic brain injury.MethodsIn this controlled laboratory study organotypic hippocampal brain-slice cultures were gained from six- to eight-day-old mice pups. After 14 days in culture, hippocampal brain slices were subjected to a focal mechanical trauma and subsequently treated with different molar concentrations of propofol under both normo- and hypothermic conditions. After 72 hours of incubation, tissue injury assessment was performed using propidium iodide (PI), a staining agent that becomes fluorescent only when it enters damaged cells via perforated cell membranes. Inside the cell, PI forms a fluorescent complex with nuclear DNA.ResultsA dose-dependent reduction of both total and secondary tissue injury could be observed in the presence of propofol under both normo- and hypothermic conditions. This effect was further amplified when the slices were incubated at 32°C after trauma.ConclusionsWhen used in combination, the dose-dependent neuroprotective effect of propofol is additive to the neuroprotective effect of hypothermia in an in vitro model of traumatic brain injury.

Recovery and long-term renal excretion of propofol, its glucuronide, and two di-isopropylquinol glucuronides after propofol infusion during surgery

BackgroundThe metabolism of the short-acting anaesthetic agent propofol has been described over the first 24 h. However, the long-term disposition of propofol and its metabolites is unclear. We describe the pharmacokinetics (renal excretion rates and renal clearance) of propofol and its metabolites over 60 h. MethodsTen patients undergoing lung surgery were included in the study. They received anaesthesia with continuous i.v. propofol at an average rate of 10 mg min−1. During surgery and 60 h thereafter, we sampled blood and urine. Propofol and its metabolites were measured using gradient high performance liquid chromatography (HPLC). ResultsIn nine patients, propofol and its glucuronides were found in the plasma over the first 15 h. In the urine, however, even after 60 h, propofol and its quinol glucuronides were still detectable. One patient had a markedly different pharmacokinetic profile, showing a limited renal excretion or absorption of 12% of the dose. ConclusionsAfter an infusion of propofol, patients excrete propofol and its metabolites in the urine over a period in excess of 60 h. We hypothesize that (re)absorption of propofol and its metabolites by the kidney is a major process in elimination and that the reabsorbed compounds are gradually conjugated in the kidney and excreted in the urine. One patient showed a different pharmacokinetic profile for which we currently have no explanation.

Reaction between the anesthetic agent propofol and the free radical DPPH˙ in semiaqueous media: Kinetics and characterization of the products

The reaction of the free radical diphenylpicrylhydrazyl (DPPH˙) with the anesthetic agent 2,6-diisopropylphenol (propofol, PPF) was investigated in buffered hydroalcoholic media. The kinetics was followed using a stopped-flow system. DPPH˙ was reduced to the hydrazine analogue DPPH–H with a measured stoichiometry (DPPH˙/PPF) of 2. The main product of the reaction, 3,5,3′,5′-tetraisopropyl-(4,4′)-diphenoquinone (PPFDQ) was isolated by chromatography and its structure was fully characterized. The reaction mechanism was inferred from the stoichiometry, kinetics, and product identification. The first step, which primarily determines the kinetics, is the reaction of DPPH˙ with PPF to produce DPPH–H and the PPF radical. The rate constant was found to be 31.8, 207, and 908 M − 1 s − 1 at pH 6.4, 7.4, and 8.4, respectively. The pH dependence is indicative of a higher reactivity of the phenolate form of PPF. Then, PPF radicals combine to form dipropofol, which is quickly oxidized to PPFDQ by the remaining DPPH˙. This reaction scheme is corroborated by numerical simulations of the kinetics. In the course of this study we also disclosed an unexpected effect, the photochemical degradation of PPFDQ. The need to compare antioxidants on a kinetics basis is again emphasized. In our hands, PPF presents a significantly weaker reactivity than Trolox.

Anesthesia with propofol slows atrial fibrillation dominant frequencies

The mechanisms responsible for the maintenance of atrial fibrillation (AF) are not completely understood yet. It has been demonstrated that AF can be modulated by several cardiac diseases, the autonomic nervous system and even drugs with purportedly no antiarrhythmic properties. We evaluated the effects of a widely used anaesthetic agent (propofol) in the fibrillation patterns. Spectral analysis was performed over atrial electrograms at baseline and immediately after a propofol bolus. Only after performing principal component analysis (PCA), we were able to significantly detect that propofol slows AF.

Anesthetic-Induced Transitions by Propofol Modeled by Nonlocal Neural Populations Involving Two Neuron Types

The present work derives the spatiotemporal field equation of neural populations considering two types of neurons. The model considers pyramidal cells, which may excite or inhibit other neurons, and GABAergic interneurons inhibiting terminal neurons. Additionally, taking into account excitatory and inhibitory synapses, the neural population obeys a vector-field equation involving nonlocal spatial interactions. The work studies the effect of the anesthetic agent propofol, which increases the decay time of inhibitory synapses. In addition, it explains the bifurcation mechanism in some detail and finds a saddle-node bifurcation subject to the propofol concentration. This bifurcation may model the transition between consciousness and nonconsciousness and vice versa during the administration of general anesthetics in medicine.

Modulation of AMPA receptor GluR1 subunit phosphorylation in neurons by the intravenous anaesthetic propofol

BackgroundThe ionotropic glutamate receptor is a potential molecular site in the central nervous system that general anaesthetics may interact with to produce some of their biological actions. Protein phosphorylation has been well documented to occur in the intracellular C-terminal domain of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of glutamate receptors, which represents a pivotal mechanism for the post-translational modulation of AMPA receptor functions. In this study, we investigated a possible influence of an i.v. anaesthetic agent propofol on the phosphorylation of AMPA receptor GluR1 subunits in cultured neurons. MethodsThe effect of propofol on phosphorylation of GluR1 subunits at serine 831 and 845 was assayed in cultured rat striatal and cortical neurons by western blot with phospho- and site-specific antibodies. ResultsPropofol consistently elevated phosphorylation of GluR1 subunits at the C-terminal serine 845 site in both striatal and cortical neurons. The elevation in phosphorylation was concentration-dependent and started at a low concentration (3 μM). This increase in serine 845 phosphorylation was rapid and sustained during the entire course of propofol exposure. In contrast to serine 845, phosphorylation of GluR1 at serine 831 was not altered by propofol in striatal and cortical neurons. Total GluR1 abundance remained unchanged in response to propofol incubation. ConclusionsThese data indicate that propofol possesses the ability to upregulate AMPA receptor GluR1 subunit phosphorylation at a specific serine 845 site in neurons and provide evidence supporting the AMPA receptor as a molecular target for general anaesthetics.

Breakdown of consciousness: Neuronal oscillations during distinct levels of human anesthesia

Event Abstract Back to Event Breakdown of consciousness: Neuronal oscillations during distinct levels of human anesthesia Gernot G. Supp1*, M. Siegel2, M. Hauck1, G. N. Schmidt3 and A.K Engel1 1 University Medical Center Hamburg-Eppendorf, Department of Neurophysiology and Pathophysiology, Germany 2 Massachusetts Institute of Technology, Picower Institute for Learning and Memory, Department of Brain and Cognitive Science, United States 3 Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Germany A primary goal of clinical anesthesia is to suppress consciousness. Although anesthesia has become standard clinical procedure, the neural mechanisms underlying the concomitant loss of consciousness remain poorly understood on the system-level. We thus investigated changes in macroscopic brain signals during the loss of consciousness under step-wise anesthesia. We recorded the 128-channel EEG in 10 healthy male volunteers during intravenous application of the short-acting anesthetic agent propofol (target-controlled infusions of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 5.0 μg/ml). During each period, subjects received median nerve stimulation at their left wrist and electric intracutaneous pain stimulation at the tip of their left middle finger. We continuously measured vital parameters, subjective pain ratings, vigilance and sedation level. We classified periods for which subjects were able or not able to verbally rate painfulness as “conscious” or “unconscious”, respectively. We found that propofol anesthesia profoundly altered ongoing neural activity and stimulus-related cortical oscillations. For ongoing neural activity, propofol anesthesia induced strong 8-18 Hz (peak: 13 Hz) oscillations that increased in a dose-dependent manner up to 1000 % relative to the pre-medication baseline. Distributed source reconstruction revealed that this activity originated bilaterally from prefrontal and temporal cortical regions. Median nerve stimulation elicited an early (20-50 ms) power increase in the gamma band (> 30 Hz) that originated from contralateral primary somatosensory cortex and remained unchanged during increasing levels of propofol anesthesia. In addition, propofol induced a late (100-500 ms) decrease of gamma-band activity during the post-stimulation interval. This late decrease in gamma power was located in the left and right prefrontal gyrus, and the right superior and middle frontal gyrus. Directly contrasting conscious and unconscious periods, we found a stronger gamma decrease for unconscious periods in left prefrontal brain areas, especially in the left medial frontal and cingulate cortex. Our results indicate that propofol anesthesia alters the global processing mode of the brain by inducing spindle-like low-frequency oscillations similar to those observed during regular sleep. Additionally, our data suggest that anesthesia affects somatosensory processing in a stage-specific manner. While during anesthesia, sensory processing in primary somatosensory cortex was preserved, processing at later stages presumably was impaired. This suggests that anesthesia may specifically block the routing of sensory information from primary to subsequent cortical processing stages. Furthermore, during unconscious somatosensory processing activation of the anterior parts of the medial frontal cortex was reduced, which may reflect a blocked transmission of sensory input to cortical parts of the limbic system. Conference: 10th International Conference on Cognitive Neuroscience, Bodrum, Türkiye, 1 Sep - 5 Sep, 2008. Presentation Type: Oral Presentation Topic: Symposium 12: Gamma-band responses in the brain: A general Mechanism subserving cortical information processing? Citation: Supp GG, Siegel M, Hauck M, Schmidt GN and Engel A (2008). Breakdown of consciousness: Neuronal oscillations during distinct levels of human anesthesia. Conference Abstract: 10th International Conference on Cognitive Neuroscience. doi: 10.3389/conf.neuro.09.2009.01.055 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Nov 2008; Published Online: 28 Nov 2008. * Correspondence: Gernot G Supp, University Medical Center Hamburg-Eppendorf, Department of Neurophysiology and Pathophysiology, Geneva, Germany, g.supp@uke.uni-hamburg.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Gernot G Supp M. Siegel M. Hauck G. N Schmidt A.K Engel Google Gernot G Supp M. Siegel M. Hauck G. N Schmidt A.K Engel Google Scholar Gernot G Supp M. Siegel M. Hauck G. 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Dissociating speech perception and comprehension at reduced levels of awareness.

We used functional MRI and the anesthetic agent propofol to assess the relationship among neural responses to speech, successful comprehension, and conscious awareness. Volunteers were scanned while listening to sentences containing ambiguous words, matched sentences without ambiguous words, and signal-correlated noise (SCN). During three scanning sessions, participants were nonsedated (awake), lightly sedated (a slowed response to conversation), and deeply sedated (no conversational response, rousable by loud command). Bilateral temporal-lobe responses for sentences compared with signal-correlated noise were observed at all three levels of sedation, although prefrontal and premotor responses to speech were absent at the deepest level of sedation. Additional inferior frontal and posterior temporal responses to ambiguous sentences provide a neural correlate of semantic processes critical for comprehending sentences containing ambiguous words. However, this additional response was absent during light sedation, suggesting a marked impairment of sentence comprehension. A significant decline in postscan recognition memory for sentences also suggests that sedation impaired encoding of sentences into memory, with left inferior frontal and temporal lobe responses during light sedation predicting subsequent recognition memory. These findings suggest a graded degradation of cognitive function in response to sedation such that "higher-level" semantic and mnemonic processes can be impaired at relatively low levels of sedation, whereas perceptual processing of speech remains resilient even during deep sedation. These results have important implications for understanding the relationship between speech comprehension and awareness in the healthy brain in patients receiving sedation and in patients with disorders of consciousness.

Fourier transformed steady-state flash evoked potentials for continuous monitoring of visual pathway function

Monitoring of somatosensory, motor and auditory pathway function by evoked potentials is routine in surgery placing these pathways at risk. However, visual pathway function remains yet inaccessible to a reliable monitoring. For this study, a method of continuous recordings was developed and tested. Steady-state visual evoked potentials were elicited by flash stimulation at 16 Hz and analysed using discrete Fourier transform. Amplitude and phase of the fundamental response were dynamically averaged and continuously plotted in a trend graph. The method was applied on awake individuals with normal vision and on patients undergoing neurosurgery. In most individuals it was possible to continuously record significant responses. Surprisingly, characteristic time-courses of amplitude and phase were observed in several subjects. These findings were attributed mainly to flicker-adaptation. During anesthesia, amplitude and signal-to-noise ratio were markedly smaller. Signal recognition was facilitated when potentials were recorded with a subdural electrode placed directly at the occipital pole. The anesthetic agent propofol had a major impact on the recordings.

Time course and attenuation of ischaemia-reperfusion induced oxidative injury by propofol in human renal transplantation

Ischaemia-reperfusion injury resulting from interruption and restoration of blood flow might be related to free radical mediated oxidative stress and inflammation, and subsequently to post-surgery related complications. We studied the impact of renal transplantation on oxidative stress and inflammation by measuring F2-isoprostanes and prostaglandin F2α, respectively, during transplantation and post-surgery. Additionally, due to earlier observations, two dissimilar anaesthetic agents (thiopentone and propofol) were compared to determine their antioxidative capacity rather than their anaesthetic properties. Blood samples were collected before, post-intubation, immediately, 30, 60,120, 240 min, and 12 and 24 h after reperfusion. Oxidative stress and inflammatory response were detected by measuring 8-iso-PGF2α (a major F2-isoprostane and a biomarker of oxidative stress) and 15-keto-dihydro-PGF2α (a major metabolite of PGF2α and a biomarker of COX-mediated inflammatory response), respectively. Reperfusion of the transplanted graft significantly increased plasma levels of 8-iso-PGF2α. PGF2α metabolite levels, although elevated, did not reach statistical significance. In addition, significantly lower levels of 8-iso-PGF2a were observed in the propofol group compared to the thiopentone group. Together, these findings underline an augmented oxidative stress activity following an inflammatory response after human renal transplantation. Furthermore, propofol a well-known anaesthetic, counteracted oxidative stress by lowering the formation of a major F2-isoprostane.