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1.
J Laryngol Otol ; 138(3): 338-340, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37649262

ABSTRACT

OBJECTIVE: Out-patient channelled endoscopic local anaesthetic biopsy reduces the time to diagnosis and wider use may improve cancer pathway times. This study aimed to assess the practice of ENT surgeons using channelled local anaesthetic biopsy. METHOD: A survey was distributed nationally, containing questions about out-patient local anaesthetic biopsy. RESULTS: In total, 58 responses were returned; only 12 per cent of respondents (n = 7) used general anaesthetic biopsy. The advantages of local anaesthetic biopsy were: the avoidance of general anaesthetic for patients with poor performance scores (95 per cent, n = 55) and faster cancer pathway times (91 per cent, n = 53). Disadvantages were: clinics running late (29 per cent, n = 17) and complications (24 per cent, n = 14). The main barrier to using local anaesthetic was access to channelled flexible endoscopy (38 per cent, n = 22), with 43 per cent (n = 25) reporting they were not using out-patient channelled endoscopes but would be interested in using them. CONCLUSION: Surgeons are interested in using channelled endoscopic local anaesthetic biopsy, but they are limited by access to equipment. Increased use of channelled endoscopes may improve national cancer pathway times and avoid challenging general anaesthetics.


Subject(s)
Anesthetics, General , Head and Neck Neoplasms , Humans , Anesthetics, Local , Anesthesia, Local , Biopsy
2.
Molecules ; 28(15)2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37570703

ABSTRACT

Six new sesquiterpene coumarin ethers, namely turcicanol A (1), turcicanol A acetate (2), turcicanol B (3), turcica ketone (4), 11'-dehydrokaratavicinol (5), and galbanaldehyde (6), and one new sulfur-containing compound, namely turcicasulphide (7), along with thirty-two known secondary metabolites were isolated from the root of the endemic species Ferula turcica Akalin, Miski, & Tuncay through a bioassay-guided isolation approach. The structures of the new compounds were elucidated by spectroscopic analysis and comparison with the literature. Cell growth inhibition of colon cancer cell lines (COLO205 and HCT116) and kidney cancer cell lines (UO31 and A498) was used to guide isolation. Seventeen of the compounds showed significant activity against the cell lines.


Subject(s)
Anesthetics, General , Antineoplastic Agents, Phytogenic , Antineoplastic Agents , Ferula , Sesquiterpenes , Ferula/chemistry , Sulfur Compounds/analysis , Molecular Structure , Ethers , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents/analysis , Coumarins/chemistry , Sesquiterpenes/chemistry , Sulfur/analysis , Plant Roots/chemistry
3.
Neuroendocrinology ; 113(10): 1008-1023, 2023.
Article in English | MEDLINE | ID: mdl-37271138

ABSTRACT

INTRODUCTION: Despite the widespread use of general anaesthetics, the mechanisms mediating their effects are still not understood. Although suppressed in most parts of the brain, neuronal activity, as measured by FOS activation, is increased in the hypothalamic supraoptic nucleus (SON) by numerous general anaesthetics, and evidence points to this brain region being involved in the induction of general anaesthesia (GA) and natural sleep. Posttranslational modifications of proteins, including changes in phosphorylation, enable fast modulation of protein function which could be underlying the rapid effects of GA. In order to identify potential phosphorylation events in the brain-mediating GA effects, we have explored the phosphoproteome responses in the rat SON and compared these to cingulate cortex (CC) which displays no FOS activation in response to general anaesthetics. METHODS: Adult Sprague-Dawley rats were treated with isoflurane for 15 min. Proteins from the CC and SON were extracted and processed for nano-LC mass spectrometry (LC-MS/MS). Phosphoproteomic determinations were performed by LC-MS/MS. RESULTS: We found many changes in the phosphoproteomes of both the CC and SON in response to 15 min of isoflurane exposure. Pathway analysis indicated that proteins undergoing phosphorylation adaptations are involved in cytoskeleton remodelling and synaptic signalling events. Importantly, changes in protein phosphorylation appeared to be brain region specific suggesting that differential phosphorylation adaptations might underlie the different neuronal activity responses to GA between the CC and SON. CONCLUSION: In summary, these data suggest that rapid posttranslational modifications in proteins involved in cytoskeleton remodelling and synaptic signalling events might mediate the central mechanisms mediating GA.


Subject(s)
Anesthetics, General , Isoflurane , Rats , Animals , Supraoptic Nucleus/metabolism , Isoflurane/pharmacology , Isoflurane/metabolism , Chromatography, Liquid , Rats, Sprague-Dawley , Proto-Oncogene Proteins c-fos/metabolism , Tandem Mass Spectrometry , Hypothalamus/metabolism , Anesthetics, General/metabolism , Anesthetics, General/pharmacology , Paraventricular Hypothalamic Nucleus/metabolism
4.
J Oral Rehabil ; 50(9): 902-913, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37247258

ABSTRACT

BACKGROUND: Temporomandibular disorders (TMDs) have multiple aetiological factors. Although some evidence suggests invasive and lengthy dental procedures may contribute towards TMD development, there is a relative paucity in the literature regarding an association between elements of paediatric dental general anaesthesia (pDGA) and TMDs. This review aims to consider the impact of dental rehabilitation (and its constituent elements) performed under general anaesthesia on the development of TMDs in childhood and adolescence and identify theories and/or gaps in knowledge which may benefit from future research. METHODS: Due to the need to preliminarily examine the nature and extent of the current evidence base, a scoping review approach was chosen. The review was conducted based on the framework provided by the methodological working group of the Joanna Briggs Institute (JBI) for conducting systematic scoping reviews. Electronic databases MEDLINE, Embase, Scopus, Web of Science and Cochrane Library were searched as well as the grey literature using OpenGrey, Nexis, Ethos, Google Scholar and ProQuest, with eligible studies uploaded onto Zotero (Mac Version 5.0.96.2). RESULTS: A total of 810 records were identified. After removing duplicates and those not available in English, 260 were identified for title and abstract screening. Seventy-six records underwent full-text review of which only one met the broad inclusion criteria. The most common reasons for exclusion were no specific relation to general anaesthesia, not specifically relating to dental treatment and only being concerned with TMD management. The included study found that while development of TMDs following dental rehabilitation under GA did occur in children, whether the problems caused by treatment were exacerbated by other elements of the pDGA process remains unknown. CONCLUSION: This review has confirmed a distinct paucity of research in this field. While there is no current tangible scientific evidence that common and routine dental procedures lead to TMD, the literature shows that alterations to any one or a combination of critical factors can contribute to TMD development, which may be collectively exacerbated by iatrogenic macrotrauma during the pDGA process. We have highlighted elements of pre-, peri- and post-operative pDGA, alongside biopsychosocial factors, which may contribute to TMD development in childhood and adolescence and may benefit from future research.


Subject(s)
Anesthetics, General , Temporomandibular Joint Disorders , Humans , Child , Adolescent , Anesthesia, General/adverse effects , Anesthesia, General/methods , Temporomandibular Joint Disorders/etiology , Temporomandibular Joint Disorders/therapy
5.
Eur Arch Otorhinolaryngol ; 280(5): 2237-2245, 2023 May.
Article in English | MEDLINE | ID: mdl-36376527

ABSTRACT

AIMS: To assess all available data and determine the success rates and tolerability of local anaesthetic myringoplasty in comparison with those undertaken under general anaesthetic myringoplasty. MATERIALS AND METHODS: The study was designed following a PRISMA-P protocol and registered with the PROSPERO database. MEDLINE, Cochrane Library (CDSR/Central), EMBASE and CINHAL-were directly searched for studies, which met the inclusion criteria. OBJECTIVES: Primary objective was to compare perforation closure rates between patients undergoing myringoplasty under local anaesthetic and those under general anaesthetic from all available published data. Secondary outcomes include complications, such as 'any minor complications', infection rates in the first 6 month post-op, facial nerve weakness, dysgeusia and patient satisfaction. RESULTS: 27 studies were included in the final analysis and found that myringoplasty had an overall perforation closure rate of 89%. The pooled proportion of closures after myringoplasty under local anesthesia was 87% and for myringoplasties under general anesthesia was 91%. Analysis of myringoplasty under local anaesthesia focusing on 'in-office' performed procedures only, found a closure rate of 88%. CONCLUSIONS: There is no significant difference in the success rate of myringoplasty surgery when performed under local or general anaesthetic as measured by perforation closure rates. However, there are other factors, which can drive choosing local anaesthetic surgery, such as minimising anaesthetic risks, reducing costs and reducing environmental impact.


Subject(s)
Anesthetics, General , Tympanic Membrane Perforation , Humans , Anesthesia, General/adverse effects , Anesthesia, Local/adverse effects , Anesthetics, Local , Myringoplasty/methods , Retrospective Studies , Treatment Outcome , Tympanic Membrane Perforation/surgery , Tympanic Membrane Perforation/etiology
6.
Hand (N Y) ; 18(6): 918-924, 2023 09.
Article in English | MEDLINE | ID: mdl-35249406

ABSTRACT

BACKGROUND: Patient return-to-driving following minor hand surgery is unknown. Through daily text message surveys, we sought to determine return-to-driving after minor hand surgery and the factors that influence return-to-driving. METHODS: One hundred five subjects undergoing minor hand surgery received daily text messaging surveys postoperatively to assess: (1) if they drove the day before and if so; (2) whether they wore a cast, sling, or splint. Additional patient-, procedure-, and driving-related data were collected. RESULTS: More than half of subjects, 54 out of 105, returned to driving by the end of postoperative day #1. While patient-related factors had no effect on return-to-driving, significant differences were seen in anesthesia type, procedure laterality, driving assistance, and distance. Return-to-driving was significantly later for subjects who had general anesthetic compared to wide awake local anesthetic with no tourniquet (4 ± 4 days vs 1 ± 3 days, P = 0.020), as well as for bilateral procedures versus unilateral procedures (5 ± 5 days vs 1 ± 3 days, P = 0.046). Lack of another driver and driving on highways led to earlier return-to-driving (P = 0.040 and, P = 0.005, respectively). CONCLUSIONS: Most patients rapidly return to driving after minor hand surgery. Use of general anesthetic and bilateral procedures may delay return-to-driving. Confidential real-time text-based surveys can provide valuable information on postoperative return-to-driving and other patient behaviors.


Subject(s)
Anesthetics, General , Carpal Tunnel Syndrome , Humans , Hand/surgery , Carpal Tunnel Syndrome/surgery , Upper Extremity , Anesthesia, Local/methods
7.
Am J Otolaryngol ; 43(5): 103547, 2022.
Article in English | MEDLINE | ID: mdl-35914452

ABSTRACT

PURPOSE: Tonsillectomy under general anesthesia may be viewed preferentially to local anesthesia, due to mitigation of potential airway compromise secondary to intraoperative hemorrhage, patient discomfort and anxiety. However, this is offset by risk of increased trauma (via the endotracheal tube and gag), adverse medication reactions and cost. Here we evaluated the case for use of local anesthesia in tonsillectomy using the BiZact™ (Medtronic) device by comparing surgical outcomes and cost factors across patients where either local or general anesthesia was employed. MATERIALS AND METHODS: Retrospective cohort study of 59 BiZact™ tonsillectomy patients (38 under local anesthetic, and 21 under general anesthetic) from a single surgeon at Tauranga Hospital (public) and Grace Hospital (private) in New Zealand; March 2018 to June 2021. RESULTS: Neither patient group had any primary postoperative hemorrhage and there was comparable incidence of secondary hemorrhage (one case in each cohort). Local anesthetic tonsillectomy was well tolerated with only 2 patients requiring conversion to general anesthetic secondary to anxiety. Local anesthetic proved to be cost-effective, with a halving of hospital length of stay and significant associated overall cost saving, and did not add significantly to operating or total theatre time. Local anesthetic tonsillectomies where perioperative sedation was not required were associated with additional reductions in recovery and overall hospital stay, and cost. CONCLUSIONS: Local anesthetic BiZact™ tonsillectomy is evidently safe and cost-effective.


Subject(s)
Anesthetics, General , Tonsillectomy , Anesthesia, General , Anesthesia, Local , Anesthetics, Local , Humans , Postoperative Hemorrhage/epidemiology , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/prevention & control , Retrospective Studies , Tonsillectomy/adverse effects
8.
Int J Med Sci ; 18(3): 652-659, 2021.
Article in English | MEDLINE | ID: mdl-33437200

ABSTRACT

Objective: Different anesthetics have distinct effects on the interstitial fluid (ISF) drainage in the extracellular space (ECS) of the superficial rat brain, while their effects on ISF drainage in the ECS of the deep rat brain still remain unknown. Herein, we attempt to investigate and compare the effects of propofol and isoflurane on ECS structure and ISF drainage in the caudate-putamen (CPu) and thalamus (Tha) of the deep rat brain. Methods: Adult Sprague-Dawley rats were anesthetized with propofol or isoflurane, respectively. Twenty-four anesthetized rats were randomly divided into the propofol-CPu, isoflurane-CPu, propofol-Tha, and isoflurane-Tha groups. Tracer-based magnetic resonance imaging (MRI) and fluorescent-labeled tracer assay were utilized to quantify ISF drainage in the deep brain. Results: The half-life of ISF in the propofol-CPu and propofol-Tha groups was shorter than that in the isoflurane-CPu and isoflurane-Tha groups, respectively. The ECS volume fraction in the propofol-CPu and propofol-Tha groups was much higher than that in the isoflurane-CPu and isoflurane-Tha groups, respectively. However, the ECS tortuosity in the propofol-CPu and propofol-Tha groups was much smaller than that in isoflurane-CPu and isoflurane-Tha groups, respectively. Conclusions: Our results demonstrate that propofol rather than isoflurane accelerates the ISF drainage in the deep rat brain, which provides novel insights into the selective control of ISF drainage and guides selection of anesthetic agents in different clinical settings, and unravels the mechanism of how general anesthetics function.


Subject(s)
Anesthetics, General/administration & dosage , Caudate Nucleus/drug effects , Extracellular Fluid/metabolism , Putamen/drug effects , Thalamus/drug effects , Administration, Inhalation , Animals , Caudate Nucleus/cytology , Caudate Nucleus/diagnostic imaging , Caudate Nucleus/metabolism , Extracellular Space/drug effects , Extracellular Space/metabolism , Gadolinium DTPA/administration & dosage , Infusions, Parenteral , Isoflurane/administration & dosage , Magnetic Resonance Imaging/methods , Models, Animal , Propofol/administration & dosage , Putamen/cytology , Putamen/diagnostic imaging , Putamen/metabolism , Rats , Rats, Sprague-Dawley , Thalamus/cytology , Thalamus/diagnostic imaging , Thalamus/metabolism
9.
Cell ; 180(4): 666-676.e13, 2020 02 20.
Article in English | MEDLINE | ID: mdl-32084339

ABSTRACT

The mystery of general anesthesia is that it specifically suppresses consciousness by disrupting feedback signaling in the brain, even when feedforward signaling and basic neuronal function are left relatively unchanged. The mechanism for such selectiveness is unknown. Here we show that three different anesthetics have the same disruptive influence on signaling along apical dendrites in cortical layer 5 pyramidal neurons in mice. We found that optogenetic depolarization of the distal apical dendrites caused robust spiking at the cell body under awake conditions that was blocked by anesthesia. Moreover, we found that blocking metabotropic glutamate and cholinergic receptors had the same effect on apical dendrite decoupling as anesthesia or inactivation of the higher-order thalamus. If feedback signaling occurs predominantly through apical dendrites, the cellular mechanism we found would explain not only how anesthesia selectively blocks this signaling but also why conscious perception depends on both cortico-cortical and thalamo-cortical connectivity.


Subject(s)
Anesthetics, General/pharmacology , Cerebral Cortex/drug effects , Pyramidal Cells/drug effects , Animals , Cerebral Cortex/cytology , Cerebral Cortex/physiology , Cholinergic Antagonists/pharmacology , Consciousness , Dendrites/drug effects , Dendrites/physiology , Excitatory Amino Acid Antagonists/pharmacology , Feedback, Physiological , Female , Male , Mice , Pyramidal Cells/physiology , Synaptic Transmission , Thalamus/cytology , Thalamus/drug effects , Thalamus/physiology
10.
ACS Chem Neurosci ; 10(12): 4787-4799, 2019 12 18.
Article in English | MEDLINE | ID: mdl-31697472

ABSTRACT

Previously, we designed, synthesized, and evaluated a series of quinolone-benzofuran derivatives as multitargeted anti-Alzheimer's disease (anti-AD) compounds, and we discovered that WBQ5187 possesses superior anti-AD bioactivity. In this work, we investigated the pharmacokinetics of this new molecule, as well as its therapeutic efficacy in restoring cognition and neuropathology, in the APP/PS1 mouse model of AD. Pharmacokinetic analyses demonstrated that WBQ5187 possessed rational oral bioavailability, metabolic stability, and excellent blood-brain barrier (BBB) permeability. Pharmacodynamics studies indicated that a 12-week treatment with the lead compound at doses of 40 mg/kg or higher significantly enhanced the learning and memory performance of the APP/PS1 transgenic mice, and the effect was more potent than that of clioquinol (CQ). Furthermore, WBQ5187 notably reduced cerebral ß-amyloid pathology, gliosis, and neuronal cell loss and increased the levels of cAMP in the hippocampus of these mice. The surrogate measures of emesis indicated that WBQ5187 had no effect at its cognitive effective doses. Overall, our results demonstrated that this compound markedly improves cognitive and spatial memory functions in AD mice and represents a promising pharmaceutical agent with potential for the treatment of AD.


Subject(s)
Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Benzofurans/therapeutic use , Brain Chemistry/drug effects , Clioquinol/analogs & derivatives , Neuroprotective Agents/therapeutic use , Phosphodiesterase 4 Inhibitors/therapeutic use , Resorcinols/therapeutic use , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Anesthetics, General/toxicity , Animals , Benzofurans/chemistry , Benzofurans/pharmacokinetics , Biological Availability , Blood-Brain Barrier , Clioquinol/chemistry , Clioquinol/pharmacokinetics , Clioquinol/therapeutic use , Cyclic AMP/metabolism , Disease Models, Animal , Drug Evaluation, Preclinical , Gliosis/drug therapy , Gliosis/prevention & control , Hippocampus/drug effects , Hippocampus/metabolism , Male , Maze Learning/drug effects , Memory Disorders/drug therapy , Memory Disorders/genetics , Mice , Mice, Inbred C57BL , Mice, Transgenic , Nausea/chemically induced , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacokinetics , Phosphodiesterase 4 Inhibitors/chemistry , Phosphodiesterase 4 Inhibitors/pharmacokinetics , Phosphodiesterase 4 Inhibitors/toxicity , Resorcinols/chemistry , Resorcinols/pharmacokinetics , Second Messenger Systems/drug effects , Vomiting/chemically induced
11.
Neuron ; 102(5): 1053-1065.e4, 2019 06 05.
Article in English | MEDLINE | ID: mdl-31006556

ABSTRACT

How general anesthesia (GA) induces loss of consciousness remains unclear, and whether diverse anesthetic drugs and sleep share a common neural pathway is unknown. Previous studies have revealed that many GA drugs inhibit neural activity through targeting GABA receptors. Here, using Fos staining, ex vivo brain slice recording, and in vivo multi-channel electrophysiology, we discovered a core ensemble of hypothalamic neurons in and near the supraoptic nucleus, consisting primarily of neuroendocrine cells, which are persistently and commonly activated by multiple classes of GA drugs. Remarkably, chemogenetic or brief optogenetic activations of these anesthesia-activated neurons (AANs) strongly promote slow-wave sleep and potentiates GA, whereas conditional ablation or inhibition of AANs led to diminished slow-wave oscillation, significant loss of sleep, and shortened durations of GA. These findings identify a common neural substrate underlying diverse GA drugs and natural sleep and reveal a crucial role of the neuroendocrine system in regulating global brain states. VIDEO ABSTRACT.


Subject(s)
Anesthetics, General/pharmacology , Hypnotics and Sedatives/pharmacology , Neuroendocrine Cells/drug effects , Sleep, Slow-Wave/drug effects , Supraoptic Nucleus/drug effects , Anesthesia, General , Animals , Dexmedetomidine/pharmacology , Electroencephalography , Electromyography , Electrophysiological Phenomena , Hypothalamus/cytology , Hypothalamus/drug effects , Hypothalamus/metabolism , Isoflurane/pharmacology , Ketamine/pharmacology , Mice , Neuroendocrine Cells/metabolism , Neurons/drug effects , Neurons/metabolism , Optogenetics , Patch-Clamp Techniques , Propofol/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Sleep/drug effects , Sleep/physiology , Sleep, Slow-Wave/physiology , Supraoptic Nucleus/cytology , Supraoptic Nucleus/metabolism
13.
J Anesth Hist ; 4(3): 177-181, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30217390

ABSTRACT

According to the Chinese historical books, Records of the Three Kingdoms () and Book of the Later Han (), Hua Tuo (, 140 - 208), a Traditional Chinese medicine (TCM) physician invented Mafeisan, an oral herbal general anesthetic, more than 1800 years ago during Eastern Han Dynasty. However, no written record of ingredients of the original Mafeisan has been found anywhere so far although there have been several similar anesthetic prescriptions published in TCM books later. There has been controversy over the existence of Mafeisan and even Hua Tuo in Chinese literature. We did extensive literature search and analysis, and believe that there indeed was Mafeisan in Hua Tuo's time.


Subject(s)
Anesthetics, General/history , Anesthetics/history , Drugs, Chinese Herbal/history , Medicine, Chinese Traditional/history , Anesthetics/analysis , Anesthetics, General/analysis , China , Drugs, Chinese Herbal/analysis , History, Ancient
14.
J Neurosci ; 38(39): 8441-8452, 2018 09 26.
Article in English | MEDLINE | ID: mdl-30126970

ABSTRACT

The systems-level mechanisms underlying loss of consciousness (LOC) under anesthesia remain unclear. General anesthetics suppress sensory responses within higher-order cortex and feedback connections, both critical elements of predictive coding hypotheses of conscious perception. Responses to auditory novelty may offer promise as biomarkers for consciousness. This study examined anesthesia-induced changes in auditory novelty responses over short (local deviant [LD]) and long (global deviant [GD]) time scales, envisioned to engage preattentive and conscious levels of processing, respectively. Electrocorticographic recordings were obtained in human neurosurgical patients (3 male, 3 female) from four hierarchical processing levels: core auditory cortex, non-core auditory cortex, auditory-related, and PFC. Stimuli were vowel patterns incorporating deviants within and across stimuli (LD and GD). Subjects were presented with stimuli while awake, and during sedation (responsive) and following LOC (unresponsive) under propofol anesthesia. LD and GD effects were assayed as the averaged evoked potential and high gamma (70-150 Hz) activity. In the awake state, LD and GD effects were present in all recorded regions, with averaged evoked potential effects more broadly distributed than high gamma activity. Under sedation, LD effects were preserved in all regions, except PFC. LOC was accompanied by loss of LD effects outside of auditory cortex. By contrast, GD effects were markedly suppressed under sedation in all regions and were absent following LOC. Thus, although the presence of GD effects is indicative of being awake, its absence is not indicative of LOC. Loss of LD effects in higher-order cortical areas may constitute an alternative biomarker of LOC.SIGNIFICANCE STATEMENT Development of a biomarker that indexes changes in the brain upon loss of consciousness (LOC) under general anesthesia has broad implications for elucidating the neural basis of awareness and clinical relevance to mechanisms of sleep, coma, and disorders of consciousness. Using intracranial recordings from neurosurgery patients, we investigated changes in the activation of cortical networks involved in auditory novelty detection over short (local deviance) and long (global deviance) time scales associated with sedation and LOC under propofol anesthesia. Our results indicate that, whereas the presence of global deviance effects can index awareness, their loss cannot serve as a biomarker for LOC. The dramatic reduction of local deviance effects in areas beyond auditory cortex may constitute an alternative biomarker of LOC.


Subject(s)
Anesthesia, General , Auditory Cortex/physiology , Auditory Perception/physiology , Awareness/physiology , Prefrontal Cortex/physiology , Acoustic Stimulation , Adult , Anesthetics, General/administration & dosage , Auditory Cortex/drug effects , Auditory Perception/drug effects , Awareness/drug effects , Brain Waves , Electrocorticography , Evoked Potentials, Auditory/drug effects , Female , Humans , Male , Prefrontal Cortex/drug effects , Young Adult
15.
Br J Anaesth ; 121(3): 605-615, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30115259

ABSTRACT

BACKGROUND: Current concepts suggest that impaired representation of information in cortical networks contributes to loss of consciousness under anaesthesia. We tested this idea in rat auditory cortex using information theory analysis of multiunit responses recorded under three anaesthetic agents with different molecular targets: isoflurane, propofol, and dexmedetomidine. We reasoned that if changes in the representation of sensory stimuli are causal for loss of consciousness, they should occur regardless of the specific anaesthetic agent. METHODS: Spiking responses were recorded with chronically implanted microwire arrays in response to acoustic stimuli incorporating varied temporal and spectral dynamics. Experiments consisted of four drug conditions: awake (pre-drug), sedation (i.e. intact righting reflex), loss of consciousness (a dose just sufficient to cause loss of righting reflex), and recovery. Measures of firing rate, spike timing, and mutual information were analysed as a function of drug condition. RESULTS: All three drugs decreased spontaneous and evoked spiking activity and modulated spike timing. However, changes in mutual information were inconsistent with altered stimulus representation being causal for loss of consciousness. First, direction of change in mutual information was agent-specific, increasing under dexmedetomidine and decreasing under isoflurane and propofol. Second, mutual information did not decrease at the transition between sedation and LOC for any agent. Changes in mutual information under anaesthesia correlated strongly with changes in precision and reliability of spike timing, consistent with the importance of temporal stimulus features in driving auditory cortical activity. CONCLUSIONS: The primary sensory cortex is not the locus for changes in representation of information causal for loss of consciousness under anaesthesia.


Subject(s)
Anesthesia, General/methods , Anesthetics, General/pharmacology , Auditory Cortex/drug effects , Consciousness/drug effects , Acoustic Stimulation/methods , Anesthetics, Inhalation/pharmacology , Anesthetics, Intravenous/pharmacology , Animals , Auditory Cortex/physiology , Consciousness/physiology , Dexmedetomidine/pharmacology , Electroencephalography/drug effects , Female , Hypnotics and Sedatives/pharmacology , Isoflurane/pharmacology , Propofol/pharmacology , Rats, Inbred ACI , Reaction Time/drug effects , Reflex, Righting/drug effects , Reflex, Righting/physiology
16.
Front Neural Circuits ; 12: 50, 2018.
Article in English | MEDLINE | ID: mdl-30013465

ABSTRACT

It has been argued that general anesthetics suppress the level of consciousness, or the contents of consciousness, or both. The distinction between level and content is important because, in addition to clarifying the mechanisms of anesthesia, it may help clarify the neural bases of consciousness. We assess these arguments in the light of evidence that both the level and the content of consciousness depend upon the contribution of apical input to the information processing capabilities of neocortical pyramidal cells which selectively amplify relevant signals. We summarize research suggesting that what neocortical pyramidal cells transmit information about can be distinguished from levels of arousal controlled by sub-cortical nuclei and from levels of prioritization specified by interactions within the thalamocortical system. Put simply, on the basis of the observations reviewed, we hypothesize that when conscious we have particular, directly experienced, percepts, thoughts, feelings and intentions, and that general anesthetics affect consciousness by interfering with the subcellular processes by which particular activities are selectively amplified when relevant to the current context.


Subject(s)
Anesthetics, General/pharmacology , Arousal , Consciousness , Neocortex , Pyramidal Cells , Signal Transduction , Thalamus , Animals , Arousal/drug effects , Arousal/physiology , Consciousness/drug effects , Consciousness/physiology , Humans , Neocortex/drug effects , Neocortex/physiology , Pyramidal Cells/drug effects , Pyramidal Cells/physiology , Signal Transduction/drug effects , Signal Transduction/physiology , Thalamus/drug effects , Thalamus/physiology
17.
Br J Anaesth ; 119(4): 685-696, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-29121295

ABSTRACT

BACKGROUND: Actions of general anaesthetics on activity in the cortico-thalamic network likely contribute to loss of consciousness and disconnection from the environment. Previously, we showed that the general anaesthetic isoflurane preferentially suppresses cortically evoked synaptic responses compared with thalamically evoked synaptic responses, but how this differential sensitivity translates into changes in network activity is unclear. METHODS: We investigated isoflurane disruption of spontaneous and stimulus-induced cortical network activity using multichannel recordings in murine auditory thalamo-cortical brain slices. RESULTS: Under control conditions, afferent stimulation elicited short latency, presumably monosynaptically driven, spiking responses, as well as long latency network bursts that propagated horizontally through the cortex. Isoflurane (0.05-0.6 mM) suppressed spiking activity overall, but had a far greater effect on network bursts than on early spiking responses. At isoflurane concentrations >0.3 mM, network bursts were almost entirely blocked, even with increased stimulation intensity and in response to paired (thalamo-cortical + cortical layer 1) stimulation, while early spiking responses were <50% blocked. Isoflurane increased the threshold for eliciting bursts, decreased their propagation speed and prevented layer 1 afferents from facilitating burst induction by thalamo-cortical afferents. CONCLUSIONS: Disruption of horizontal activity spread and of layer 1 facilitation of thalamo-cortical responses likely contribute to the mechanism by which suppression of cortical feedback connections disrupts sensory awareness under anaesthesia.


Subject(s)
Anesthetics, General/pharmacology , Anesthetics, Inhalation/pharmacology , Cerebral Cortex/drug effects , Electrodiagnosis/methods , Isoflurane/pharmacology , Thalamus/drug effects , Animals , Cerebral Cortex/physiology , Consciousness/drug effects , Female , Male , Models, Animal , Thalamus/physiology
18.
Neurochem Res ; 41(12): 3181-3191, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27561291

ABSTRACT

Although accumulative evidence indicates that the thalamocortical system is an important target for general anesthetics, the underlying mechanisms of anesthetic action on thalamocortical neurotransmission are not fully understood. The aim of the study is to explore the action of etomidate on glutamatergic and GABAergic transmission in rat thalamocortical slices by using whole cell patch-clamp recording. We found that etomidate mainly prolonged the decay time of spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs), without changing the frequency. Furthermore, etomidate not only prolonged the decay time of miniature inhibitory postsynaptic currents (mIPSCs) but also increased the amplitude. On the other hand, etomidate significantly decreased the frequency of spontaneous glutamatergic excitatory postsynaptic currents (sEPSCs), without altering the amplitude or decay time in the absence of bicuculline. When GABAA receptors were blocked using bicuculline, the effects of etomidate on sEPSCs were mostly eliminated. These results suggest that etomidate enhances GABAergic transmission mainly through postsynaptic mechanism in thalamocortical neuronal network. Etomidate attenuates glutamatergic transmission predominantly through presynaptic action and requires presynaptic GABAA receptors involvement.


Subject(s)
Anesthetics, General/pharmacology , Cerebral Cortex/drug effects , Etomidate/pharmacology , Glutamic Acid/physiology , Thalamus/drug effects , gamma-Aminobutyric Acid/physiology , Animals , Bicuculline/pharmacology , Cerebral Cortex/physiology , Excitatory Postsynaptic Potentials/drug effects , GABA-A Receptor Antagonists/pharmacology , In Vitro Techniques , Inhibitory Postsynaptic Potentials/drug effects , Miniature Postsynaptic Potentials/drug effects , Rats, Sprague-Dawley , Receptors, GABA-A/physiology , Receptors, Presynaptic/physiology , Synaptic Transmission/drug effects , Thalamus/physiology
19.
Burns ; 42(6): 1241-56, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27156791

ABSTRACT

INTRODUCTION: There is a paucity of evidence guiding management of small area partial thickness paediatric scalds. This has prevented the development of national management guidelines for these injuries. This research aimed to investigate whether a lack of evidence for national guidelines has resulted in variations in both management and outcomes of paediatric small area scalds across England and Wales (E&W). METHODS: A national survey of initial management of paediatric scalds ≤5% Total Body Surface Area (%TBSA) was sent to 14 burns services in E&W. Skin graft rates of anonymised burns services over seven years were collected from the international Burns Injury Database (iBID). Average skin grafting rates across services were compared. Length of stay and proportion of patients receiving general anaesthesia for dressing application at each service were also compared. RESULTS: All 14 burns services responded to the survey. Only 50% of services had a protocol in place for the management of small area burns. All protocols varied in how partial thickness paediatrics scalds ≤5% TBSA should be managed. There was no consensus as to which scalds should be treated using biosynthetic dressings. Data from iBID for 11,917 patients showed that the average reported skin grafting rate across all burns services was 2.3% (95% CI 2.1, 2.6) but varied from 0.3% to 7.1% (P<0.001). Service provider remained associated with likelihood of skin grafting when variations in the %TBSA case mix seen by each service were controlled for (χ(2)=87.3, P<0.001). The use of general anaesthetics across services varied between 0.6 and 35.5% (P<0.001). The median length of stay across services varied from 1 to 3 days (P<0.001). DISCUSSION: A lack of evidence guiding management of small-area paediatric scalds has resulted in variation in management of these injuries across E&W. There is also significant variation in outcomes for these injuries. Further research is indicated to determine if care pathways and outcomes are linked. An evidence-based national policy for the management of small area paediatric scalds would ensure that high quality, standardised care is delivered throughout E&W and variations in outcome are reduced.


Subject(s)
Anesthetics, General/therapeutic use , Bandages , Burns/therapy , Critical Pathways , Practice Patterns, Physicians'/statistics & numerical data , Skin Transplantation , Body Surface Area , Child, Preschool , Disease Management , England , Female , Humans , Infant , Infant, Newborn , Length of Stay , Male , Reference Standards , Trauma Severity Indices , United Kingdom , Wales
20.
Ther Umsch ; 73(2): 61-6, 2016.
Article in German | MEDLINE | ID: mdl-26982643

ABSTRACT

The majority of ophthalmic interventions can be done today under locoregional anesthesia using "Monitored Anesthesia Care" (MAC). General anesthesia techniques are mostly reserved for the pediatric segment and for patients with specific comorbidity and/or lengthy procedure. Cataract surgery in predominantly geriatric patients belongs to the field of the so-called "high volume-surgery": Given the low perioperative risk in this patient group, adapted and optimized processes are indicated. A focused premedication and informing these patients ensures good perioperative compliance. Preoperative tests are be conducted in this patient population only as a function of relevant comorbidity. Premedication usually takes place as a classical anesthesia consultation, but new methods such as an internet-based premedication for healthy patients offers a new option. The intraoperative anesthesia method depends on the needs of the surgeon and the expectations and possibilities of cooperation of the patient.


Subject(s)
Anesthesia, General/methods , Anesthesia, Local/methods , Anesthetics, General/administration & dosage , Anesthetics, Local/administration & dosage , Ophthalmologic Surgical Procedures/methods , Preanesthetic Medication/methods , Humans
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