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Background: As the primary Ca 2+ release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in type 1 ryanodine receptor (RyR1) or its binding partners underlie a constellation of muscle disorders, including malignant hyperthermia (MH). In patients with MH mutations, triggering agents including halogenated volatile anaesthetics bias RyR1 to an open state resulting in uncontrolled Ca 2+ release, increased sarcomere tension, and heat production. Propofol does not trigger MH and is commonly used for patients at risk of MH. The atomic-level interactions of any anaesthetic with RyR1 are unknown., Methods: RyR1 opening was measured by [ 3 H]ryanodine binding in heavy SR vesicles (wild type) and single-channel recordings of MH mutant R615C RyR1 in planar lipid bilayers, each exposed to propofol or the photoaffinity ligand analogue m-azipropofol (AziPm). Activator-mediated wild-type RyR1 opening as a function of propofol concentration was measured by Fura-2 Ca 2+ imaging of human skeletal myotubes. AziPm binding sites, reflecting propofol binding, were identified on RyR1 using photoaffinity labelling. Propofol binding affinity to a photoadducted site was predicted using molecular dynamics (MD) simulation., Results: Both propofol and AziPm decreased RyR1 opening in planar lipid bilayers (P<0.01) and heavy SR vesicles, and inhibited activator-induced Ca 2+ release from human skeletal myotube SR. Several putative propofol binding sites on RyR1 were photoadducted by AziPm. MD simulation predicted propofol K D values of 55.8 μM and 1.4 μM in the V4828 pocket in open and closed RyR1, respectively., Conclusions: Propofol demonstrated direct binding and inhibition of RyR1 at clinically plausible concentrations, consistent with the hypothesis that propofol partially mitigates malignant hyperthermia by inhibition of induced Ca 2+ flux through RyR1., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate cardiopulmonary, arterial blood gas and propofol-sparing effects of magnesium sulfate (MgSO 4 ) constant rate infusion (CRI) in mechanically ventilated dogs maintained under total intravenous anesthesia with propofol., Study Design: Blinded, randomized, clinical trial., Animals: A total of 24 healthy adult dogs., Methods: Dogs were premedicated with intramuscular acepromazine (0.05 mg kg -1 ) and morphine (0.5 mg kg -1 ), followed by an intravenous (IV) bolus of saline or MgSO 4 (50 mg kg -1 over 15 minutes) and propofol (given to effect to induce anesthesia). Anesthesia was maintained with an IV propofol infusion (beginning at 0.3 mg kg -1 minute -1 , adjusted as necessary). Concurrently, one of three IV infusions were administered: GS (0.9% NaCl), GM30 (MgSO 4 , 30 mg kg -1 hour -1 ) or GM80 (MgSO 4 , 80 mg kg -1 hour -1 ). Propofol induction and maintenance doses were recorded. The following variables were recorded at baseline (T0), after bolus treatment (T1), after beginning mechanical ventilation (T5) and every 15 minutes until the end of the procedure (T15-T120): mean arterial pressure, heart rate, peripheral oxygen saturation, end-tidal partial pressure of CO 2 , temperature, blood gas variables, indirect calorimetry and extubation time. Values of p < 0.05 were considered significant., Results: Propofol induction bolus dose was lower in GM30 (31.2%, p = 0.04) and GM80 (38.9%, p = 0.003) than in GS. The maintenance propofol infusion rate in GM80 was 16.9% lower (p = 0.03), resulting in fewer propofol CRI rescues during the perioperative period. GM30 and GM80 exhibited faster extubation times than GS (46.2%, p = 0.002 and 48.9%, p = 0.001, respectively)., Conclusions and Clinical Relevance: Infusion of a 50 mg kg -1 bolus, followed by CRI of MgSO 4 (30 and 80 mg kg -1 hour -1 ), reduces the propofol induction and maintenance (CRI) requirement, maintaining cardiorespiratory stability and reducing the time required to extubation., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Background: The Eleveld pharmacokinetic-pharmacodynamic model for propofol predicts bispectral index (BIS) processed electroencephalogram values from estimated effect-site concentrations. We investigated agreement between measured and predicted BIS values during total intravenous anaesthesia (TIVA)., Methods: Forty participants undergoing lower limb surgery received TIVA using remifentanil target-controlled infusions and propofol by manually controlled, target-guided infusions based upon the Eleveld model and directed by two pharmacokinetic computer simulation applications: PKPD Tools and StelSim. We evaluated the predictive performance of the Eleveld model by calculating median prediction errors (BIS units) and by Bland-Altman analyses. We also performed |Bland-Altman analysis of supplementary data provided by the authors of the Eleveld model., Results: Whereas median prediction errors were small (MDPE -1.9, MDAPE 10), the ranges were wide (-18.5 to 24.3 and 1.7 to 24.3). The proportion of MDAPE >10 BIS units was 47.8%. Bland-Altman analysis showed a small mean bias (-0.52 BIS units) with wide limits of agreement (-27.7 to 26.2). Each participant's limits of agreement did not meet the requirements for declaring interchangeability between the two measurements. The measurement differences depended on the BIS values, as indicated by the positive slopes of the differences vs BIS values. Bland-Altman analysis of the Eleveld model supplementary data revealed similar results., Conclusion: BIS predictions by the Eleveld model should be interpreted with caution. In spite of the acceptable MDPE and MDAPE, there are unacceptable degrees of both within-subject and between-subject variation during propofol target-controlled infusions. This limits the use of adjusting targeted concentrations to achieve desired simulated BIS values with confidence., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Previous research has demonstrated that basal forebrain (BF) regulates arousal during propofol anesthesia. However, as the BF comprises cholinergic neurons alongside two other types of neurons, the specific role of cholinergic neurons has not been definitively elucidated. In our study, calcium signal imaging was utilized to monitor the real-time activities of cholinergic neurons in the BF during propofol anesthesia. Additionally, we selectively stimulated these neurons to investigate EEG and behavioral responses during propofol anesthesia. Furthermore, we specifically lesioned cholinergic neurons in the BF to investigate the sensitivity to propofol and the induction time. The results revealed that propofol suppressed calcium signals of cholinergic neurons within the BF following intraperitoneal injection. Notably, upon recovery of the righting reflex, the calcium signals partially recovered. Spectral analysis of the EEG elucidated that optical stimulation of cholinergic neurons led to a decrease in δ power underlie propofol anesthesia. Conversely, depletion of cholinergic neurons in the BF enhanced sensitivity to propofol and shortened the induction time. These findings clarify the role of cholinergic neurons in the anesthesia-arousal process, as well as the depth and the sensitivity of propofol anesthesia., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the propofol-sparing and hemodynamic effects of guaifenesin administered for co-induction of anesthesia in sheep., Study Design: Prospective, blinded, two-way crossover experimental study., Animals: Thirteen healthy adult female sheep., Methods: Anesthesia was induced without premedication with intravenous (IV) guaifenesin 5% at 100 mg kg -1 (GGE) or an equivalent volume of physiologic saline (SAL), followed by IV propofol at a controlled rate (1 mg kg -1 min -1 ). Heart rate (HR), respiratory rate and oscillometric noninvasive arterial blood pressure (NIBP) were recorded at baseline after co-induction administration, following endotracheal intubation and every 2 minutes thereafter for 10 minutes. Propofol doses required to achieve intubation after each co-induction treatment were compared by independent Student's t-test. Values of p < 0.05 were considered statistically significant., Results: The propofol dose required (mean ± standard deviation) to achieve intubation was significantly lower (p = 0.001) in the GGE treatment (3.40 ± 0.74 mg kg -1 ) than in the SAL treatment (5.94 ± 1.09 mg kg -1 ). HR was increased after anesthetic induction compared with baseline in both treatments. HR was generally lower in the GGE treatment than in the SAL treatment. NIBP did not vary between GGE and SAL treatments., Conclusions and Clinical Relevance: Guaifenesin, when administered as a co-induction agent with propofol in sheep, reduces propofol dose requirements and maintains hemodynamic variables within a clinically acceptable range., (Published by Elsevier Ltd.)

Objective: To compare the effects of propofol, ketamine-propofol and isoflurane, at similar anesthetic depth, on cardiopulmonary variables in unpremedictated chickens., Study Design: Prospective, randomized, crossover experimental trial., Animals: A total of 10 male Leghorn domestic chickens, aged 3 months and body mass 1.4-2.0 kg., Methods: Birds were randomly assigned to each of three anesthetic protocols, 7 days apart: intravenous propofol, intravenous ketamine-propofol or isoflurane. Anesthesia was induced (indicated by loss of righting reflex and tracheal intubation) and maintained with propofol (10 mg kg -1 minute -1 , then 1.1 mg kg -1 minute -1 ), ketamine-propofol (5 mg mL -1 ketamine and 5 mg mL -1 propofol combined; 10 mg kg -1 minute -1 , then 1.1 mg kg -1 minute -1 ) or isoflurane [5% vaporizer setting initially, then end-tidal concentration (Fe'Iso) of 2%] for 65 minutes. Anesthesia was maintained at a similar anesthetic depth based upon positive or negative responses to toe pinch. Heart rate (HR), respiratory rate (f R ), noninvasive arterial blood pressure and arterial blood gases were measured during anesthesia. Propofol or ketamine-propofol infusion rates and Fe'Iso required to prevent movement in response to a noxious stimulus and recovery times were recorded., Results: Anesthesia induction dose was 9.0 ± 0.8 (mean ± SD) and 12.2 ± 0.3 mg kg -1 for propofol and ketamine-propofol, respectively. Propofol and ketamine-propofol infusion rates and Fe'Iso required to prevent movement in response to the noxious stimulus were 0.88 ± 0.14 mg kg -1 minute -1 , 0.92 ± 0.14 mg kg -1 minute -1 and 1.45 ± 0.28%, respectively. Cardiopulmonary variables remained clinically acceptable, but ketamine-propofol was associated with a significantly higher HR (p = 0.0001) and lower f R (p = 0.0001). Time to extubation did not differ among treatments., Conclusions and Clinical Relevance: Cardiovascular and respiratory variables were maintained within normal ranges in all treatments. Coadministration of ketamine with propofol significantly reduced the induction and maintenance dose of propofol., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Phosphatidylinositol 4,5-bisphosphate (PIP 2 ), as well as other anionic phospholipids, play a pivotal role in various cellular processes, including ion channel regulation, receptor trafficking, and intracellular signaling pathways. The binding of volatile anesthetics and propofol to PIP 2 leads to alterations in PIP 2 -mediated signaling causing modulation of ion channels such as ɣ-aminobutyric acid type A (GABA A ) receptors, voltage-gated calcium channels, and potassium channels through various mechanisms. Additionally, the interaction between anionic phospholipids and G protein-coupled receptors plays a critical role in various anesthetic pathways, with these anesthetic-induced changes impacting PIP 2 levels which cause cascading effects on receptor trafficking, including GABA A receptor internalization. This comprehensive review of various mechanisms of interaction provides insights into the intricate interplay between PIP 2 signaling and anesthetic-induced changes, shedding light on the molecular mechanisms underlying anesthesia., (Published by Elsevier Inc.)

Electroconvulsive shock (ECS) is utilized to treat depression but may cause learning/memory impairments, which may be ameliorated by anesthetics through the modulation of hippocampal synaptic plasticity. Given that synaptic plasticity is governed by aerobic glycolysis, it remains unclear whether anesthetics modulate aerobic glycolysis to enhance learning and memory function. Depression-like behavior in rats was induced by chronic mild unpredictable stress (CUMS), with anhedonia assessed via sucrose preference test (SPT). Depressive-like behaviors and spatial learning/memory were assessed with forced swim test (FST), open field test (OFT), and Morris water maze (MWM) test. Changes in aerobic glycolysis and synaptic plasticity in the hippocampal region of depressive-like rats post-ECS were documented using immunofluorescence analysis, Western blot, Lactate Assay Kit and transmission electron microscopy. Both the OFT and FST indicated that ECS was effective in alleviating depressive-like behaviors. The MWM test demonstrated that anesthetics were capable of attenuating ECS-induced learning and memory deficits. Immunofluorescence analysis, Western blot, Lactate Assay Kit and transmission electron microscopy revealed that the decline in learning and memory abilities in ECS-induced depressive-like rats was correlated with decreased aerobic glycolysis, and that the additional use of ciprofol or propofol ameliorated these alterations. Adding the glycolysis inhibitor 2-DG diminished the ameliorative effects of the anesthetic. No significant difference was observed between ciprofol and propofol in enhancing aerobic glycolysis in astrocytes and synaptic plasticity after ECS. These findings may contribute to understanding the mechanisms by which anesthetic drugs modulate learning and memory impairment after ECS in depressive-like behavior rats., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Sleep disruption is a common occurrence during medical care and is detrimental to patient recovery. Long-term sedation in the critical care setting is a modifiable factor that affects sleep, but the impact of different sedative-hypnotics on sleep homeostasis is not clear., Methods: We conducted a systematic comparison of the effects of prolonged sedation (8 h) with i.v. and inhalational agents on sleep homeostasis. Adult Sprague-Dawley rats (n=10) received dexmedetomidine or midazolam on separate days. Another group (n=9) received propofol or sevoflurane on separate days. A third group (n=12) received coadministration of dexmedetomidine and sevoflurane. Wakefulness (wake), slow-wave sleep (SWS), and rapid eye movement (REM) sleep were quantified during the 48-h post-sedation period, during which we also assessed wake-associated neural dynamics using two electroencephalographic measures: theta-high gamma phase-amplitude coupling and high gamma weighted phase-lag index., Results: Dexmedetomidine-, midazolam-, or propofol-induced sedation increased wake and decreased SWS and REM sleep (P<0.0001) during the 48-h post-sedation period. Sevoflurane produced no change in SWS, decreased wake for 3 h, and increased REM sleep for 6 h (P<0.02) post-sedation. Coadministration of dexmedetomidine and sevoflurane induced no change in wake (P>0.05), increased SWS for 3 h, and decreased REM sleep for 9 h (P<0.02) post-sedation. Dexmedetomidine, midazolam, and coadministration of dexmedetomidine with sevoflurane reduced wake-associated phase-amplitude coupling (P≤0.01). All sedatives except sevoflurane decreased wake-associated high gamma weighted phase-lag index (P<0.01)., Conclusions: In contrast to i.v. drugs, prolonged sevoflurane sedation produced minimal changes in sleep homeostasis and neural dynamics. Further studies are warranted to assess inhalational agents for long-term sedation and sleep homeostasis., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: We compared the effective networks derived from Single Pulse Electrical Stimulation (SPES) in intracranial electrocorticography (ECoG) of awake epilepsy patients and while under general propofol-anesthesia to investigate the effect of propofol on these brain networks., Methods: We included nine patients who underwent ECoG for epilepsy surgery evaluation. We performed SPES when the patient was awake (SPES-clinical) and repeated this under propofol-anesthesia during the surgery in which the ECoG grids were removed (SPES-propofol). We detected the cortico-cortical evoked potentials (CCEPs) with an automatic detector. We constructed two effective networks derived from SPES-clinical and SPES-propofol. We compared three network measures (indegree, outdegree and betweenness centrality), the N1-peak-latency and amplitude of CCEPs between the two effective networks., Results: Fewer CCEPs were observed during SPES-propofol (median: 6.0, range: 0-29) compared to SPES-clinical (median: 10.0, range: 0-36). We found a significant correlation for the indegree, outdegree and betweenness centrality between SPES-clinical and SPES-propofol (respectively r s  = 0.77, r s  = 0.70, r s  = 0.55, p < 0.001). The median N1-peak-latency increased from 22.0 ms during SPES-clinical to 26.4 ms during SPES-propofol., Conclusions: Our findings suggest that the number of effective network connections decreases, but network measures are only marginally affected., Significance: The primary network topology is preserved under propofol., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate cardiovascular effects of oral tasipimidine on propofol-isoflurane anaesthesia with or without methadone and dexmedetomidine at equianaesthetic levels., Study Design: Prospective, placebo-controlled, blinded, experimental trial., Animals: A group of seven adult Beagle dogs weighing (mean ± standard deviation) 12.4 ± 2.6 kg and a mean age of 20.6 ± 1 months., Methods: The dogs underwent four treatments 60 minutes before induction of anaesthesia with propofol. PP: placebo orally and placebo (NaCl 0.9%) intravenously (IV); TP: tasipimidine 30 μg kg -1 orally and placebo IV; TMP: tasipimidine 30 μg kg -1 orally and methadone 0.2 mg kg -1 IV; and TMPD: tasipimidine 30 μg kg -1 orally with methadone 0.2 mg kg -1 and dexmedetomidine 1 μg kg -1 IV followed by 1 μg kg -1 hour -1 . Isoflurane in oxygen was maintained for 120 minutes at 1.2 individual minimum alveolar concentration preventing motor movement. Cardiac output (CO), tissue blood flow (tbf), tissue oxygen saturation (stO 2 ) and relative haemoglobin content were determined. Arterial and mixed venous blood gases, arterial and pulmonary artery pressures and heart rate (HR) were measured at baseline; 60 minutes after oral premedication; 5 minutes after IV premedication; 15, 30, 60, 90 and 120 minutes after propofol injection; and 30 minutes after switching the vaporiser off. Data were analysed by two-way anova for repeated measures; p < 0.05., Results: Tasipimidine induced a significant 20-30% reduction in HR and CO with decreases in MAP (10-15%), tbf (40%) and stO 2 (43%). Blood pressure and oxygenation variables were mainly influenced by propofol-isoflurane-oxygen anaesthesia, preceded by short-lived alterations related to IV methadone and dexmedetomidine., Conclusions and Clinical Relevance: Tasipimidine induced mild to moderate cardiovascular depression. It can be incorporated into a common anaesthetic protocol without detrimental effects in healthy dogs, when anaesthetics are administered to effect and cardiorespiratory function is monitored., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the effect of oral tasipimidine on dog handling, ease of catheter placement and propofol and isoflurane requirements for anaesthesia., Study Design: Placebo-controlled, randomized, blinded, experimental trial., Animals: A group of seven adult Beagle dogs weighing (mean ± standard deviation) 13.1 ± 2.7 kg with a mean age of 18.6 ± 1 months., Methods: The dogs underwent four treatments before induction of anaesthesia with propofol. PP: placebo orally (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) intravenously (IV). TP: tasipimidine 30 μg kg -1 (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) IV. TMP: tasipimidine 30 μg kg -1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg -1 IV. TMPD: tasipimidine 30 μg kg -1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg -1 and dexmedetomidine 1 μg kg -1 IV followed by a dexmedetomidine constant rate infusion of 1 μg kg -1 hour -1 . Sedation, response to catheter placement, intubation quality, time to loss of consciousness, time to intubation, required dose of propofol and minimum alveolar isoflurane concentration preventing motor movement (MAC NM ) were determined. A mixed-model analysis or the Friedman and Mann-Whitney test were used; p-value < 0.05., Results: Response to catheter placement did not differ between treatments. Tasipimidine alone reduced the propofol dose by 30%. Addition of methadone or methadone and dexmedetomidine reduced the propofol dose by 48% and 50%, respectively. Isoflurane MAC NM was reduced by 19% in tasipimidine-medicated dogs, whereas in combination with methadone or methadone and dexmedetomidine, isoflurane MAC NM was reduced by 35%., Conclusions and Clinical Relevance: An anxiolytic dose of tasipimidine induced mild signs of sedation in dogs and reduced propofol and isoflurane requirements to induce and maintain anaesthesia, which needs to be considered in an anaesthetic plan., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Information integration and network science are important theories for quantifying consciousness. However, whether these theories propose drug- or conscious state-related changes in EEG during anaesthesia-induced unresponsiveness remains unknown., Methods: A total of 72 participants were randomised to receive i.v. infusion of propofol, dexmedetomidine, or ketamine at a constant infusion rate until loss of responsiveness. High-density EEG was recorded during the consciousness transition from the eye-closed baseline to the unresponsiveness state and then to the recovery of the responsiveness state. Permutation cross mutual information (PCMI) and PCMI-based brain networks in broadband (0.1-45 Hz) and sub-band frequencies were used to analyse drug- and state-related EEG signature changes., Results: PCMI and brain networks exhibited state-related changes in certain brain regions and frequency bands. The within-area PCMI of the frontal, parietal, and occipital regions, and the between-area PCMI of the parietal-occipital region (median [inter-quartile ranges]), baseline vs unresponsive were as follows: 0.54 (0.46-0.58) vs 0.46 (0.40-0.50), 0.58 (0.52-0.60) vs 0.48 (0.44-0.53), 0.54 (0.49-0.59) vs 0.47 (0.42-0.52) decreased during anaesthesia for three drugs (P<0.05). Alpha PCMI in the frontal region, and gamma PCMI in the posterior area significantly decreased in the unresponsive state (P<0.05). The frontal, parietal, and occipital nodal clustering coefficients and parietal nodal efficiency decreased in the unresponsive state (P<0.05). The increased normalised path length in delta, theta, and gamma bands indicated impaired global integration (P<0.05)., Conclusions: The three anaesthetics caused changes in information integration patterns and network functions. Thus, it is possible to build a quantifying framework for anaesthesia-induced conscious state changes on the EEG scale using PCMI and network science., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Clarifying the mechanisms of loss and recovery of consciousness in the brain is a major challenge in neuroscience, and research on the spatiotemporal organization of rhythms at the brain region scale at different levels of consciousness remains scarce. By applying computational neuroscience, an extended corticothalamic network model was developed in this study to simulate the altered states of consciousness induced by different concentration levels of propofol. The cortex area containing oscillation spread from posterior to anterior in four successive time stages, defining four groups of brain regions. A quantitative analysis showed that hierarchical rhythm propagation was mainly due to heterogeneity in the inter-brain region connections. These results indicate that the proposed model is an anatomically data-driven testbed and a simulation platform with millisecond resolution. It facilitates understanding of activity coordination across multiple areas of the conscious brain and the mechanisms of action of anesthetics in terms of brain regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Understanding the neural correlates of consciousness has important ramifications for the theoretical understanding of consciousness and for clinical anaesthesia. A major limitation of prior studies is the use of responsiveness as an index of consciousness. We identified a collection of measures derived from unresponsive subjects and more specifically their association with consciousness (any subjective experience) or connectedness (specific experience of environmental stimuli)., Methods: Using published data generated through the UNderstanding Consciousness Connectedness and Intra-Operative Unresponsiveness Study (NCT03284307), we evaluated 10 previously published resting-state EEG-based measures that were derived using unresponsiveness as a proxy for unconsciousness. Measures were tested across dexmedetomidine and propofol sedation and natural sleep. These markers represent the complexity, connectivity, cross-frequency coupling, graph theory, and power spectrum measures., Results: Although many of the proposed markers were associated with consciousness per se (reported subjective experience), none were specific to consciousness alone; rather, each was also associated with connectedness (i.e. awareness of the environment). In addition, multiple markers showed no association with consciousness and were associated only with connectedness. Of the markers tested, loss of normalised-symbolic transfer entropy (front to back) was associated with connectedness across all three experimental conditions, whereas the transition from disconnected consciousness to unconsciousness was associated with significant decreases in permutation entropy and spectral exponent (P<0.05 for all conditions)., Conclusions: None of the proposed EEG-based neural correlates of unresponsiveness corresponded solely to consciousness, highlighting the need for a more conservative use of the term (un)consciousness when assessing unresponsive participants., Clinical Trial Registration: NCT03284307., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Emergency Department (ED) propofol sedation is widely used to facilitate reduction of fractures and dislocations, but little is known about patient and staff perceptions of the practice. Better understanding of these aspects may improve patient care., Methods: A qualitative exploratory study involving semi-structured patient interviews and ED healthcare professional focus groups. Interviews with adult patients (≥16 years) >1 hour after their sedation episode were audio-recorded, anonymised and transcribed verbatim to an electronic database. Thematic analysis using a general inductive method led to development of codes and themes. ED focus groups recordings were similarly transcribed and triangulated to patient interview outcomes., Results: Data saturation was reached after 16 patient interviews. Emergent central themes from a patient perspective were: 'fear of the unknown' and 'expressed relief that the procedure was comfortable.' Key themes included 'trust in the clinical team,' 'efficacy of pain management prior to sedation' and 'quality of the information delivered to patients.' Focus group discussions around patient interview outcomes identified triage, analgesia delivery, communication, and consideration of the environment as areas for improvement., Conclusions: ED procedural sedation with propofol is generally very well accepted by patients and clinical staff but there is scope to improve patient-focus and increase satisfaction., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DMP, SS, LMYK and JGC report no conflicts of interest. JGC is supported by NHS Research Scotland., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background: Procedural sedation is commonly practiced by emergency physicians to facilitate patient care in the emergency department (ED). Although various guidelines have modernized our approach to procedural sedation, many procedural sedation guidelines and practices still often require that patients be discharged into the care of a responsible adult., Discussion: Such requirement for discharge often cannot be met by underserved and undomiciled patients. Benzodiazepines, opioids, propofol, ketamine, "ketofol," etomidate, and methohexital have all been utilized for procedural sedation in the ED. For patients who may require discharge without the presence of an accompanying responsible adult, ketamine, propofol, methohexital, "ketofol," and etomidate are ideal agents for procedural sedation given rapid onsets, short durations of action, and rapid recovery times in patients without renal or hepatic impairment. Proper pre- and postprocedure protocols should be utilized when performing procedural sedation to ensure patient safety. Through the use of appropriate medications and observation protocols, patients can safely be discharged 2 to 4 h postprocedure., Conclusion: There is no pharmacodynamic or pharmacokinetic basis to require discharge in the care of a responsible adult after procedural sedation. Thoughtful medication selection and the use of evidence-based pre- and postprocedure protocols in the ED can help circumvent this requirement, which likely disproportionally impacts patients who are of low socioeconomic status or undomiciled., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to delare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Sleep disorders can profoundly affect neurological function. We investigated changes in social and anxiety-related brain functional connectivity induced by sleep deprivation, and the potential therapeutic effects of the general anaesthetics propofol and sevoflurane in rats., Methods: Twelve-week-old male Sprague-Dawley rats were subjected to sleep deprivation for 20 h per day (from 14:00 to 10:00 the next day) for 4 consecutive weeks. They were free from sleep deprivation for the remaining 4 h during which they received propofol (40 mg kg -1 i.p.) or sevoflurane (2% for 2 h) per day or no treatment. These cohorts were instrumented for EEG/EMG recordings on days 2, 14, and 28. Different cohorts were used for open field and three-chambered social behavioural tests, functional MRI, nuclear magnetic resonance spectroscopy, and positron emission tomography imaging 48 h after 4 weeks of sleep deprivation., Results: Propofol protected against sleep deprivation-induced anxiety behaviours with more time (44.7 [8.9] s vs 24.2 [4.1] s for the sleep-deprivation controls; P<0.001) spent in the central area of the open field test and improved social preference index by 30% (all P<0.01). Compared with the sleep-deprived rats, propofol treatment enhanced overall functional connectivity by 74% (P<0.05) and overall glucose metabolism by 30% (P<0.01), and improved glutamate kinetics by 20% (P<0.05). In contrast, these effects were not found after sevoflurane treatment., Conclusions: Unlike sevoflurane, propofol reduced sleep deprivation-induced social and anxiety-related behaviours. Propofol might be superior to sevoflurane for patients with sleep disorders who receive anaesthesia, which should be studied in clinical studies., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Slow wave sleep (SWS), characterized by large electroencephalographic oscillations, facilitates crucial physiologic processes that maintain synaptic plasticity and overall brain health. Deficiency in older adults is associated with depression and cognitive dysfunction, such that enhancing sleep slow waves has emerged as a promising target for novel therapies. Enhancement of SWS has been noted after infusions of propofol, a commonly used anesthetic that induces electroencephalographic patterns resembling non-rapid eye movement sleep. This paper 1) reviews the scientific premise underlying the hypothesis that sleep slow waves are a novel therapeutic target for improving cognitive and psychiatric outcomes in older adults, and 2) presents a case series of two patients with late-life depression who each received two propofol infusions. One participant, a 71-year-old woman, had a mean of 2.8 minutes of evening SWS prior to infusions (0.7% of total sleep time). SWS increased on the night after each infusion, to 12.5 minutes (5.3% of total sleep time) and 24 minutes (10.6% of total sleep time), respectively. Her depression symptoms improved, reflected by a reduction in her Montgomery-Asberg Depression Rating Scale (MADRS) score from 26 to 7. In contrast, the other participant, a 77-year-old man, exhibited no SWS at baseline and only modest enhancement after the second infusion (3 minutes, 1.3% of total sleep time). His MADRS score increased from 13 to 19, indicating a lack of improvement in his depression. These cases provide proof-of-concept that propofol can enhance SWS and improve depression for some individuals, motivating an ongoing clinical trial (ClinicalTrials.gov NCT04680910)., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Propofol and remifentanil are frequently combined for the induction and maintenance of general anaesthesia. Both propofol and remifentanil cause vasodilation and potentially reduce arterial BP. We aimed to develop a mechanism-based model that characterises the haemodynamic interactions between remifentanil and propofol., Methods: Data from two clinical trials in healthy volunteers were analysed using remifentanil-alone, propofol-alone, and combination groups. We evaluated remifentanil effects on haemodynamics using a previously developed mechanism-based haemodynamic model of propofol. The interaction between propofol and remifentanil was explored using the principles of the general pharmacodynamic interaction (GPDI) model., Results: Remifentanil alone increased the dissipation rate of total peripheral resistance by 50% at 3.0 ng ml -1 . Additionally, the dissipation rates of HR and stroke volume were attenuated by 4.8% and 4.9% per 1 ng ml -1 increase in remifentanil concentration, respectively. The maximal effect of propofol alone in decreasing the production rate of total peripheral resistance was 78%, which decreased to 32% when combined with remifentanil 4 ng ml -1 . The effects of remifentanil on HR and stroke volume were attenuated by propofol with maximum decreases of 11.9% and 21.2%, respectively. Goodness-of-fit plots and prediction-corrected visual predictive check plots showed good predictive performance of the models., Conclusions: The structure of the previous mechanism-based haemodynamic model for propofol was able to describe the effects of remifentanil alone on haemodynamic variables. The GPDI model provided a good framework for characterising the pharmacodynamic interaction between remifentanil and propofol on haemodynamic properties., Clinical Trial Registration: NCT02043938; NCT03143972., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Animal studies have shown that isoflurane and propofol have differential effects on Alzheimer's disease (AD) pathology and memory, although it is unclear whether this occurs in humans., Methods: This was a nested randomised controlled trial within a prospective cohort study; patients age ≥60 yr undergoing noncardiac/non-neurological surgery were randomised to isoflurane or propofol for anaesthetic maintenance. Cerebrospinal fluid (CSF) was collected via lumbar puncture before, 24 h, and 6 weeks after surgery. Cognitive testing was performed before and 6 weeks after surgery. Nonparametric methods and linear regression were used to evaluate CSF biomarkers and cognitive function, respectively., Results: There were 107 subjects (54 randomised to isoflurane and 53 to propofol) who completed the 6-week follow-up and were included in the analysis. There was no significant effect of anaesthetic treatment group, time, or group-by-time interaction for CSF amyloid-beta (Aβ), tau, or phospho-tau 181p levels, or on the tau/Aβ or p-tau 181p /Aβ ratios (all P>0.05 after Bonferroni correction). In multivariable-adjusted intention-to-treat analyses, there were no significant differences between the isoflurane and propofol groups in 6-week postoperative change in overall cognition (mean difference [95% confidence interval]: 0.01 [-0.12 to 0.13]; P=0.89) or individual cognitive domains (P>0.05 for each). Results remained consistent across as-treated and per-protocol analyses., Conclusions: Intraoperative anaesthetic maintenance with isoflurane vs propofol had no significant effect on postoperative cognition or CSF Alzheimer's disease-related biomarkers within 6 weeks after noncardiac, non-neurological surgery in older adults., Clinical Trial Registration: NCT01993836., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Although sex differences in anaesthetic sensitivity have been reported, what underlies these differences is unknown. In rodents, one source of variability in females is the oestrous cycle. Here we test the hypothesis that the oestrous cycle impacts emergence from general anaesthesia., Methods: Time to emergence was measured after isoflurane (2 vol% for 1 h), sevoflurane (3 vol% for 20 min), dexmedetomidine (50 μg kg -1 i.v., infused over 10 min), or propofol (10 mg kg -1 i.v. bolus) during proestrus, oestrus, early dioestrus, and late dioestrus in female Sprague-Dawley rats (n=24). EEG recordings were taken during each test for power spectral analysis. Serum was analysed for 17β-oestradiol and progesterone concentrations. The effect of oestrous cycle stage on return of righting latency was assessed using a mixed model. The association between righting latency and serum hormone concentration was tested by linear regression. Mean arterial blood pressure and arterial blood gases were assessed in a subset of rats after dexmedetomidine and compared in a mixed model., Results: Oestrous cycle did not affect righting latency after isoflurane, sevoflurane, or propofol. When in the early dioestrus stage, rats emerged more rapidly from dexmedetomidine than in the proestrus (P=0.0042) or late dioestrus (P=0.0230) stage and showed reduced overall power in frontal EEG spectra 30 min after dexmedetomidine (P=0.0049). 17β-Oestradiol and progesterone serum concentrations did not correlate with righting latency. Oestrous cycle did not affect mean arterial blood pressure or blood gases during dexmedetomidine., Conclusions: In female rats, the oestrous cycle significantly impacts emergence from dexmedetomidine-induced unconsciousness. However, 17β-oestradiol and progesterone serum concentrations do not correlate with the observed changes., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe ketamine-propofol total intravenous anaesthesia (TIVA) following premedication with acepromazine and either medetomidine, midazolam or morphine in rabbits., Study Design: Randomized, crossover experimental study., Animals: A total of six healthy female New Zealand White rabbits (2.2 ± 0.3 kg)., Methods: Rabbits were anaesthetized on four occasions, each separated by 7 days: an intramuscular injection of saline alone (treatment Saline) or acepromazine (0.5 mg kg -1 ) in combination with medetomidine (0.1 mg kg -1 ), midazolam (1 mg kg -1 ) or morphine (1 mg kg -1 ), treatments AME, AMI or AMO, respectively, in random order. Anaesthesia was induced and maintained with a mixture containing ketamine (5 mg mL -1 ) and propofol (5 mg mL -1 ) (ketofol). Each trachea was intubated and the rabbit administered oxygen during spontaneous ventilation. Ketofol infusion rate was initially 0.4 mg kg -1 minute -1 (0.2 mg kg -1 minute -1 of each drug) and was adjusted to maintain adequate anaesthetic depth based on clinical assessment. Ketofol dose and physiological variables were recorded every 5 minutes. Quality of sedation, intubation and recovery times were recorded., Results: Ketofol induction doses decreased significantly in treatments AME (7.9 ± 2.3) and AMI (8.9 ± 4.0) compared with treatment Saline (16.8 ± 3.2 mg kg -1 ) (p < 0.05). The total ketofol dose to maintain anaesthesia was significantly lower in treatments AME, AMI and AMO (0.6 ± 0.1, 0.6 ± 0.2 and 0.6 ± 0.1 mg kg -1 minute -1 , respectively) than in treatment Saline (1.2 ± 0.2 mg kg -1 minute -1 ) (p < 0.05). Cardiovascular variables remained at clinically acceptable values, but all treatments caused some degree of hypoventilation., Conclusions and Clinical Relevance: Premedication with AME, AMI and AMO, at the doses studied, significantly decreased the maintenance dose of ketofol infusion in rabbits. Ketofol was determined to be a clinically acceptable combination for TIVA in premedicated rabbits., (Copyright © 2023 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: Regional techniques minimize anesthetic requirements and their effects may be beneficial. There is a lack of consensus and evidence concerning alternative analgesia strategies for cranial neurosurgery. This study was designed to evaluate the effect of scalp block with or without dexmedetomidine combined with general anesthesia on hemodynamic stability, opioid consumption and postoperative pain in patients undergoing elective craniotomy., Methods: One hundred five patients undergoing elective craniotomy for tumor dissection were randomly divided into three groups to receive scalp block as an adjuvant to general anesthesia: with either 40 ml ropivacaine 0.5 % (Group R), 40 ml ropivacaine 0.5 % plus dexmedetomidine 1 μg/kg (Group RD) or 40 ml saline as a placebo (Group C). After a standard induction sequence using propofol, fentanyl and a single dose of rocuronium, patients were intubated. Bilateral scalp block was given immediately after induction. Anesthesia was maintained with propofol and remifentanil infusion. Five minutes before head pinning scalp block was performed by blocking the supraorbital, supratrochlear, auriculotemporal, occipital, and postauricular branches of the greater auricular nerves. All patients were monitored with electrocardiogram, invasive blood pressure, pulse oximetry and BIS monitoring. Primary outcomes measures were overall hemodynamic variables during surgery and intravenous fentanyl and remifentanil consumption. Mean arterial pressure (MAP) and heart rate (HR) were recorded at seven time-points: scalp block (T1-baseline), pin fixation (T2), skin incision (T3), drilling (T4), dura matter incision (T5), dura matter closure (T6) and skin closure (T7). For all time points it was recorded the mean value after 3 consecutive measures with 5 min interval. Secondary outcome was postoperative pain intensity using visual analog scale 24 and 48 h after surgery. VAS scores, fentanyl and remifentanil were evaluated using Kruskal-Wallis test. MAP and HR were compared by One-Way repeated measures Anova (GLMM) using time as random efect and by One-Way Anova using time as fxed efect., Results: Mean arterial pressure was significant lower at skin closure compared to baseline in group R (p < 0,001) and in group RD (p < 0,001). Patients in group RD showed significant lower heart rate at dura matter incision, dura matter closure and skin closure compared to baseline, pin fixation and skin incision time points (p < 0,001) and reported significantly less heart rate than group C (p < 0,001) and group R (p < 0,001) during dura matter incision, dura matter closure and skin closure time points. Patients in group RD receive significant lower fentanyl than group R (p < 0,01). The intraoperative consumption of remifentanil was significant higher in control group compared to group R (p < 0,01) and to group RD (p < 0,001). Additionally, remifentanil consumption was significant lower in group RD as compared to group R (p < 0,001). Postoperative pain had no statistically differences between the three groups at 24 h and 48 h after craniotomy (Preop VAS: p = 0,915, VAS 24: p = 0,284, VAS 48, p = 0,385). No adverse effects were noted., Conclusion: Our study indicated that addition of dexmedetomidine to scalp block with ropivacaine 0.5% provided significantly better perioperative hemodynamic stability during elective craniotomy. Moreover, scalp block with or without dexmedetomidine reduced fentanyl and remifentanil consumption, but it didn't significantly prolonged analgesia in patients undergoing elective craniotomy., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality. Propofol functions as a tumor-inhibitor drug by regulating microRNAs (miRNAs). The primary objective of this study is to explore the functional mechanism of propofol in cisplatin (Cis) resistance of NSCLC cells by regulating the miR-744-5p/miR-615-3p axis. Cis-resistant NSCLC cell lines were cultured and chemotherapy-resistance (CR) to Cis of NSCLC cells to Cis was confirmed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, flow cytometry, and colony formation assay. Ferroptosis was evaluated by measurement of iron content, ferroptosis-related proteins (GPX4/ ACSL4/SLC7A11) and lipid peroxidation (SOD/GSH/MDA) through Western blot analysis and assay kits. After the dual-luciferase reporter assay to testify gene interactions, the functional rescue experiments and nude mouse tumor formation assay were performed. Based on results, propofol reduced IC50 value and CR of NSCLC cells to Cis and induced ferroptosis. Propofol upregulated miR-744-5p/miR-615-3p to inhibit GPX4 transcription. Upregulation of GPX4 or downregulation of miR-744-5p/miR-615-3p attenuated the inhibitory effect of propofol on CR to Cis. In vivo, propofol inhibited tumor growth and CR to Cis by upregulating miR-744-5p/miR-615-3p and inhibiting GPX4 to induce ferroptosis. In summary, propofol inhibited GPX4-mediated ferroptosis and reduces CR of NSCLC cells to Cis through the miR-744-5p/miR-615-3p axis. SIGNIFICANCE: To study the effect of propofol on chemoresistance of non-small cell lung cancer (NSCLC), and to provide a new theoretical basis for the treatment of NSCLC., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To evaluate effects of repeated alfaxalone or propofol administration on haematological and serum biochemical variables in cats undergoing radiotherapy., Study Design: Prospective, block-randomized, clinical trial., Animals: A group of 39 client-owned cats., Methods: After butorphanol (0.2 mg kg -1 ) and midazolam (0.1 mg kg -1 ) sedation, cats were randomly assigned to receive either alfaxalone or propofol for induction of anaesthesia and sevoflurane maintenance. Cats were anaesthetized daily with the same induction agent for 10-12 days. Complete blood counts, reticulocytes, Heinz body score and serum biochemistry were performed before the first treatment (T1), at T6, T10 and 3 weeks after the final treatment (T21). Cumulative induction agent dose for each cat at each time point was evaluated for an effect on Heinz body score. Data are shown as mean ± standard deviation; p < 0.05., Results: At baseline there were no significant differences in signalment or blood variables between groups. A significant decrease in haematocrit of 2.3% ± 0.77 (p = 0.02) between T1-T6 and T1-T10 [mean 4.1% (± 0.78, p < 0.0001)] was detected, with a significant increase in haematocrit of 2.1% ± 0.80 (p = 0.046) between T6-T21 and 4.0% ± 0.8 (p < 0.001) between T10-T21. Heinz body score significantly increased by 1.86 ± 0.616 (p = 0.013) between T1-T10. In the propofol group, reticulocytes increased significantly between T1-T6 [mean 23,090 μL -1 ± 7670 (p = 0.02)] and T1-T10 [mean 27,440 μL -1 ± 7990 (p = 0.007)]. Mean cumulative dose at T10 was 19.65 mg kg -1 ± 5.3 and 43.4 mg kg -1 ± 14.4 for alfaxalone and propofol, respectively, with no significant effect on Heinz body formation at any time point., Conclusions and Clinical Relevance: Haematocrit decreased in both groups with recovery after 3 weeks. Repeated alfaxalone and propofol administration was not associated with marked haematological or serum biochemistry changes., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the sedative effects and characteristics of cardiac rhythm with intravenous (IV) premedication of medetomidine, butorphanol and ketamine in dogs., Study Design: Prospective, blinded, randomized clinical trial., Animals: A total of 116 client-owned healthy dogs undergoing elective surgery., Methods: Dogs were randomly allocated one of four groups: group M, medetomidine 5 μg kg -1 ; group B, butorphanol 0.2 mg kg -1 ; group MB, medetomidine 5 μg kg -1 and butorphanol 0.2 mg kg -1 ; or group MBK, medetomidine 5 μg kg -1 , butorphanol 0.2 mg kg -1 and ketamine 1 mg kg -1 IV. Sedation was assessed using a numerical descriptive scale. Heart rate (HR) and rhythm were monitored; propofol dose (mg kg -1 IV) to allow orotracheal intubation was documented. Data were analysed using anova, accounting for multiple testing with the Tukey honest significant difference test., Results: Sedation scores varied significantly between all groups at all time points, except between groups MB and MBK at four time points. HR decreased in all groups: most in groups M and MB, least in group B. HR was initially higher in group MBK than in groups M and MB. Arrhythmias occurred in all groups: group B showed second-degree atrioventricular blocks occasionally, all other groups showed additionally ventricular escape complexes and bundle branch blocks. Dose of propofol required for orotracheal intubation was significantly higher in group B (5.0 ± 2.0 mg kg -1 ) than in group M (2.6 ± 0.6 mg kg -1 ). Although no difference could be demonstrated between groups MB (1.4 ± 0.6 mg kg -1 ) and MBK (0.9 ± 0.8 mg kg -1 ), both groups required significantly less propofol than group M., Conclusion and Clinical Relevance: Medetomidine-based premedication protocols led to various bradyarrhythmias. Addition of subanaesthetic doses of ketamine to medetomidine-based protocols resulted in higher HRs, fewer bradyarrhythmias and fewer animals that required propofol for intubation without causing side effects in healthy dogs., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine if the administration of atropine would reduce the measured minimum anaesthetic concentration of isoflurane (MAC isoflurane ) in freshwater turtles - the yellow-bellied slider (Trachemys scripta scripta)., Study Design: Paired, blinded, randomized, prospective studies of 1) the effect of atropine in isoflurane anaesthetized freshwater turtles (T. scripta scripta) and 2) the effect of atropine in yellow-bellied sliders in which anaesthesia was induced with propofol and maintained with isoflurane., Animals: T. scripta scripta (n = 8), female, adult., Methods: Atropine (2 mg kg -1 ) or an isovolumetric control injection of saline was administered intraperitoneally 15 minutes prior to induction of anaesthesia with isoflurane. Individual MAC isoflurane was then determined by end-tidal gas analysis in a bracketing design by an experimenter blinded to the administered drug, with a 2 week washout period. The experiment was repeated, with atropine (2 mg kg -1 ) or saline administered intravascularly in combination with propofol for anaesthetic induction. Linear mixed modelling was used to determine the effects of atropine and propofol on the individual MAC isoflurane . Data are presented as mean ± standard deviation., Results: Premedication with atropine significantly reduced MAC isoflurane (p = 0.0039). In isoflurane-induced T. scripta scripta, MAC isoflurane decreased from 4.2 ± 0.4% to 3.3 ± 0.8% when atropine had been administered. Propofol as an induction agent had a MAC-sparing effect (p < 0.001) such that MAC isoflurane following propofol and a control injection of saline was 2.3 ± 1.0%, which decreased further to 1.5 ± 0.8% when propofol was combined with atropine., Conclusions and Clinical Relevance: Atropine, presumably by inhibiting parasympathetically mediated pulmonary artery constriction, decreases right-to-left cardiac shunting and the MAC isoflurane in yellow-bellied sliders, and thereby may facilitate control of inhalant anaesthesia. Propofol can be used for induction of anaesthesia and reduces the required concentration of inhaled anaesthesia assessed 1.5 hours following induction., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The safety of anaesthesia has improved as a result of better control of anaesthetic depth. However, conventional monitoring does not inform on the nature of nociceptive processes during unconsciousness. A means of inferring the quality of potentially painful experiences could derive from analysis of brain activity using neuroimaging. We have evaluated the dose effects of remifentanil on brain response to noxious stimuli during deep sedation and spontaneous breathing., Methods: Optimal data were obtained in 26 healthy subjects. Pressure stimulation that proved to be moderately painful before the experiment was applied to the thumbnail. Functional MRI was acquired in 4-min periods at low (0.5 ng ml -1 ), medium (1 ng ml -1 ), and high (1.5 ng ml -1 ) target plasma concentrations of remifentanil at a stable background infusion of propofol adjusted to induce a state of light unconsciousness., Results: At low remifentanil doses, we observed partial activation in brain areas processing sensory-discriminative and emotional-affective aspects of pain. At medium doses, relevant changes were identified in structures highly sensitive to general brain arousal, including the brainstem, cerebellum, thalamus, auditory and visual cortices, and the frontal lobe. At high doses, no significant activation was observed., Conclusions: The response to moderately intense focal pressure in pain-related brain networks is effectively eliminated with safe remifentanil doses. However, the safety margin in deep sedation-analgesia would be narrowed in minimising not only nociceptive responses, but also arousal-related biological stress., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To compare the ease of endoscopic duodenal intubation (EDI) in dogs during maintenance of general anaesthesia with isoflurane or propofol infusion., Study Design: Prospective, randomized, partially blinded clinical trial., Animals: A total of 22 dogs undergoing upper gastrointestinal tract endoscopy to include EDI were recruited., Methods: Dogs were randomly assigned isoflurane (ISO; n = 10) or propofol (PROP; n = 11) for maintenance of general anaesthesia. Following anaesthetic premedication with intramuscular medetomidine (0.005 mg kg -1 ) and butorphanol (0.2 mg kg -1 ), general anaesthesia was induced with propofol, to effect, maintained with 1.5% (vaporizer setting) isoflurane in 100% oxygen or 0.2 mg kg -1 minute -1 propofol. The dose of both agents was adjusted to maintain general anaesthesia adequate for the procedure. Degree of sedation 20 minutes post-anaesthetic premedication, propofol induction dose, anaesthetist and endoscopist training grade, animal's response to endoscopy, presence of gastro-oesophageal and duodenal-gastric reflux, spontaneous opening of the lower oesophageal and pyloric sphincters, antral movement and time to achieve EDI were recorded. EDI was scored 1 (immediate entry with minimal manoeuvring) to 4 (no entry after 120 seconds) by the endoscopist, blinded to the agent in use. Data were tested for normality (Shapiro-Wilk test) and differences between groups analysed using independent t test, Mann-Whitney U test and Fisher's exact test as appropriate., Results: There were no significant differences between groups for EDI score [median (interquartile range): 2 (3) ISO, 2 (3) PROP] or time to achieve EDI [mean ± standard deviation: 52.50 ± 107.00 seconds (ISO), 70.00 ± 196.00 seconds (PROP)]. Significantly more dogs responded to passage of the endoscope into the oesophagus in group PROP compared with group ISO (p = 0.01)., Conclusions and Clinical Relevance: Maintenance of general anaesthesia with either isoflurane or propofol did not affect EDI score or time to achieve EDI., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To compare a propofol continuous rate infusion (CRI) with a target-controlled infusion (TCI) in dogs., Study Design: Randomized prospective double-blinded clinical study., Animals: A total of 38 healthy client-owned dogs., Methods: Dogs premedicated intramuscularly with acepromazine (0.03 mg kg -1 ) and an opioid (pethidine 3 mg kg -1 , morphine 0.2 mg kg -1 or methadone 0.2 mg kg -1 ) were allocated to P-CRI group (propofol 4 mg kg -1 intravenously followed by CRI at 0.2 mg kg -1 minute -1 ), or P-TCI group [propofol predicted plasma concentration (Cp) of 3.5 μg mL -1 for induction and maintenance of anaesthesia via TCI]. Plane of anaesthesia, heart rate, respiratory rate, invasive blood pressure, oxygen haemoglobin saturation, end-tidal carbon dioxide and body temperature were monitored by an anaesthetist blinded to the group. Numerical data were analysed by unpaired t test or Mann-Whitney U test, one-way analysis of variance and Dunnett's post hoc test. Categorical data were analysed with Fisher's exact test. Significance was set for p < 0.005., Results: Overall, propofol induced a significant incidence of relative hypotension (mean arterial pressure 20% below baseline, 45%), apnoea (71%) and haemoglobin desaturation (65%) at induction of anaesthesia, with a higher incidence of hypotension and apnoea in the P-CRI than P-TCI group (68% versus 21%, p = 0.008; 84% versus 58%, p = 0.0151, respectively). Propofol Cp was significantly higher at intubation in the P-CRI than P-TCI group (4.83 versus 3.5 μg mL -1 , p < 0.0001), but decreased during infusion, while Cp remained steady in the P-TCI group. Total propofol administered was similar between groups., Conclusions and Clinical Relevance: Both techniques provided a smooth induction of anaesthesia but caused a high incidence of side effects. Titration of anaesthesia with TCI caused fewer fluctuations in Cp and lower risk of hypotension compared with CRI., (Copyright © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. All rights reserved.)

Objective: To compare the effect of propofol, alfaxalone and ketamine on intraocular pressure (IOP) in cats., Study Design: Prospective, masked, randomized clinical trial., Animals: A total of 43 ophthalmologically normal cats scheduled to undergo general anesthesia for various procedures., Methods: Following baseline IOP measurements using applanation tonometry, anesthesia was induced with propofol (n = 15), alfaxalone (n = 14) or ketamine (n = 14) administered intravenously to effect. Then, midazolam (0.3 mg kg -1 ) was administered intravenously and endotracheal intubation was performed without application of topical anesthesia. The IOP was measured following each intervention. Data was analyzed using one-way anova and repeated-measures mixed design with post hoc analysis. A p-value <0.05 was considered significant., Results: Mean ± standard error IOP at baseline was not different among groups (propofol, 18 ± 0.6; alfaxalone, 18 ± 0.7; ketamine, 17 ± 0.5 mmHg). Following induction of anesthesia, IOP increased significantly compared with baseline in the propofol (20 ± 0.7 mmHg), but not in the alfaxalone (19 ± 0.8 mmHg) or ketamine (16 ± 0.7 mmHg) groups. Midazolam administration resulted in significant decrease from the previous measurement in the alfaxalone group (16 ± 0.7 mmHg), but not in the propofol group (19 ± 0.7 mmHg) or the ketamine (16 ± 0.8 mmHg) group. A further decrease was measured after intubation in the alfaxalone group (15 ± 0.9 mmHg)., Conclusions and Clinical Relevance: Propofol should be used with caution in cats predisposed to perforation or glaucoma, as any increase in IOP should be avoided., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the heart rate (HR) and systemic arterial pressure (sAP) effects, and propofol induction dose requirements in healthy dogs administered propofol with or without guaifenesin for the induction of anesthesia., Study Design: Prospective blinded crossover experimental study., Animals: A total of 10 healthy adult female Beagle dogs., Methods: Dogs were premedicated with intravenous (IV) butorphanol (0.4 mg kg -1 ) and administered guaifenesin 5% at 50 mg kg -1 (treatment G50), 100 mg kg -1 (treatment G100) or saline (treatment saline) IV prior to anesthetic induction with propofol. HR, invasive sAP and respiratory rate (f R ) were recorded after butorphanol administration, after guaifenesin administration and after propofol and endotracheal intubation. Propofol doses for intubation were recorded. Repeated measures analysis of variance (anova) was used to determine differences in propofol dose requirements among treatments, and differences in cardiopulmonary values over time and among treatments with p < 0.05 considered statistically significant., Results: Propofol doses (mean ± standard deviation) for treatments saline, G50 and G100 were 3.3 ± 1.0, 2.7 ± 0.7 and 2.1 ± 0.8 mg kg -1 , respectively. Propofol administered was significantly lower in treatment G100 than in treatment saline (p = 0.04). In treatments G50 and G100, HR increased following induction of anesthesia and intubation compared with baseline measurements. HR was higher in treatment G100 than in treatments G50 and saline following induction of anesthesia. In all treatments, sAP decreased following intubation compared with baseline values. There were no significant differences in sAP among treatments. f R was lower following intubation than baseline and post co-induction values and did not differ significantly among treatments., Conclusions and Clinical Relevance: When administered as a co-induction agent in dogs, guaifenesin reduced propofol requirements for tracheal intubation. HR increased and sAP and f R decreased, but mean values remained clinically acceptable., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. All rights reserved.)

Background: Post-induction hypotension, a common complication after propofol-based induction regimen, is a life-threatening challenge for anesthesiologists especially when unexpected pre-induction hypertension characterized by angiotensin release and increased vascular tone was presented by the same patient. Gap junctions (GJs) composed of connexin 43 (Cx43) have been considered a key factor in regulating vascular contraction and dilation. We aimed to explore the role of Cx43-GJs during peri-induction blood pressure fluctuation and elucidate the underlying mechanisms., Methods: Human umbilical arterial smooth muscle cells (HUASMCs) were pretreated by short-term Angiotensin Ⅱ (Ang Ⅱ) with or without subsequent propofol treatment to simulate transient contraction and dilation of vascular smooth muscle cells during anesthesia induction. F-actin polymerization, a classic indicator of HUASMCs constriction, was determined by F-actin staining assay. Both the function and expression of Cx43-GJs during transient contraction and dilation of HUASMCs, and their potential regulation of downstream Ca 2+ /RhoA/LIMK2/Cofilin signaling pathway were explored via different targeting inhibitors and siRNAs., Results: Ang Ⅱ pretreatment significantly induced F-actin polymerization that indicate cell contraction, accompanied by enhanced GJs function on HUASMCs. With the inhibition of Cx43 GJs by the specific inhibitor, Gap26, and Cx43-siRNA, Ang Ⅱ-induced F-actin polymerization was reversed accompanied with the decrease of intracellular Ca 2+ mobility and the RhoA/LIMK2/Cofilin signaling pathway activity. We also noticed that propofol application could inhibit GJs function, the same as Gap26. Simultaneously, intracellular Ca 2+ mobility and RhoA/LIMK2/Cofilin signaling pathway activity on HUASMCs were both downregulated, finally resulting in downstream reduction of F-actin polymerization., Conclusion: The function of Cx43-GJs lies in the center of Ang Ⅱ-induced contraction of HUASMCs, which potentially regulates intracellular Ca 2+ mobility as well as RhoA/LIMK2/Cofilin signaling pathway activity. Propofol can reverse this effect induced by Ang Ⅱ through suppressing the function of Cx43-GJs., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The aim of this systematic review is to summarize outcomes of studies focused on the effects of opioids, injectable sedative and anaesthetic drugs and inhalant anaesthetics on tear production in dogs. This manuscript complements the systematic review describing the effect of anaesthetics on intraocular pressure in dogs (Pierce-Tomlin et al. 2020). Databases used A detailed search of scientific references has been performed. PubMed, Web of Science, Science Direct and Google Scholar databases were used to search for sources using free text terms 'Dog' or 'Canine', 'Anaesthesia' or 'Anaesthetic' or 'Sedative' or 'Opioid' or the name of used opioids, sedative and anaesthetic drugs and 'Tear' or 'Schirmer' or 'Lacrimation'. The time frame searched was from 1960 to October 2021. Any published manuscripts that were concerned with sedative or anaesthetic drugs administered systemically in the dog and tear production were evaluated., Conclusions: Low doses of α 2 -adrenoceptor agonists, neuroleptics, benzodiazepines, opioids, propofol or alfaxalone administered alone have no clinically significant effect on aqueous tear production in healthy dogs measured by the Schirmer tear test I (STT-I). Intramuscular injection of ketamine increases STT-I values. Higher doses of α 2 -adrenoceptor agonists and combinations of anaesthetics, including inhaled anaesthetics, always clinically significantly decrease tear production., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Techniques grounded on the simultaneous utilization of Tiecks' second order differential equations and spontaneous variability of mean arterial pressure (MAP) and mean cerebral blood flow velocity (MCBFV), recorded from middle cerebral arteries through a transcranial Doppler device, provide a characterization of cerebral autoregulation (CA) via the autoregulation index (ARI). These methods exploit two metrics for comparing the measured MCBFV series with the version predicted by Tiecks' model: normalized mean square prediction error (NMSPE) and normalized correlation ρ. The aim of this study is to assess the two metrics for ARI computation in 13 healthy subjects (age: 27 ± 8 yrs., 5 males) at rest in supine position (REST) and during 60° head-up tilt (HUT) and in 19 patients (age: 64 ± 8 yrs., all males), scheduled for coronary artery bypass grafting, before (PRE) and after (POST) propofol general anesthesia induction. Analyses were carried out over the original MAP and MCBFV pairs and surrogate unmatched couples built individually via time-shifting procedure. We found that: i) NMSPE and ρ metrics exhibited similar performances in passing individual surrogate test; ii) the two metrics could lead to different ARI estimates; iii) CA was not different during HUT or POST compared to baseline and this conclusion held regardless of the technique and metric for ARI estimation. Results suggest a limited impact of the sympathetic control on CA., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Propofol, an intravenous short-acting anesthetic, has the potential to induce craving and relapse. Accumulated evidence demonstrates that extracellular signal-regulated kinase (ERK) plays an essential role in drug reward and relapse. In the previous study, we demonstrated that the ERK signaling pathways in the Nucleus accumbens (NAc) were involved in propofol reward. However, the role of the ERK signaling pathways in propofol relapse is still unknown. We first trained rats to self-administer propofol for 14 days, then evaluated propofol-seeking behavior of relapse induced by a contextual cues and conditioned cues after 14-day withdrawal. Meanwhile, MEK inhibitor U0126 was used to investigate the role of the ERK signal pathways in propofol-seeking behavior induced by contextual cues and conditioned cues. Results showed that the number of active nose-poke responses in propofol-seeking behavior induced by conditioned cues was much higher compared to contextual cues. U0126 (5.0 μg/side, Lateral Ventricle (LV)) pretreatment significantly decreased the active responses induced by conditioned cues, which was associated with a large decline in the expression of p-ERK in the NAc. Moreover, microinjectionofU0126 (2.0 μg/side) in the NAc also attenuated the active responses of propofol-seeking behavior. Additionally, microinjections with U0126 in the LV (5.0 μg/side) or NAc (2.0 μg/side) both failed to alter sucrose self-administration or locomotor activity of rats. Therefore, we conclude that ERK phosphorylation in the NAc maybe involved in propofol relapse., Competing Interests: Declaration of competing interest The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the effects of three recruitment airway pressures (RP aw ) on lung aeration and volumes in mechanically ventilated dogs during propofol anesthesia., Study Design: Prospective, crossover randomized experimental study., Animals: A total of eight healthy anesthetized experimental Beagle dogs in dorsal recumbency., Methods: Dogs were mechanically ventilated with a tidal volume of 15 mL kg -1 and zero positive end-expiratory pressure and 100% oxygen. Three maneuvers consisting of a 30 second inspiration at RP aw s of 15 (RP aw 15), 25 (RP aw 25) and 35 (RP aw 35) cmH 2 O were performed randomly, 15 minutes apart. Changes in lung aeration and lung deformation were compared with end-expiratory baseline (before the application of each RP aw ) and between-RP aw s using computed tomography scans and calculations of global lung strain. Between-group comparisons were performed with one-way anova for repeated measures followed by Tukey test for multiple comparisons. A p value < 0.05 was considered significant., Results: The amount of nonaeration was minimal (<1%) at baseline and not different with the application of the RP aw s. The amount of hypoaeration and normoaeration during baseline decreased with all RP aw s (p < 0.001). There was no difference between RP aw s regarding hypoaeration (all p > 0.999), whereas normoaeration was higher at RP aw 15 than RP aw 25 and RP aw 35 (p < 0.009). Compared with baseline, the fraction of hyperaerated alveoli increased with each RP aw (p < 0.001) and was lower during RP aw 15 than RP aw 25 and RP aw 35 (both p ≤ 0.007). Global lung strain was lower during RP aw 15 than at higher RP aw (p < 0.001)., Conclusions and Clinical Relevance: A RP aw of 15 cmH 2 O for 30 seconds was the recommended RP aw because it was as effective at reversing hypoaeration as RP aw s of 25 and 35 cmH 2 O but with less hyperaeration and potential for overdistension of the lungs in this particular population of dogs with negligible atelectasis., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the effects of intramuscularly administered acepromazine or dexmedetomidine on buccal mucosa microcirculation in Beagle dogs., Study Design: Experimental, blinded, crossover study., Animals: A group of seven Beagle dogs aged 7.5 ± 1.4 years (mean ± standard deviation)., Methods: Microcirculation was assessed on buccal mucosa using sidestream dark field videomicroscopy. After baseline measurements, 5 μg kg -1 dexmedetomidine or 30 μg kg -1 acepromazine were administered intramuscularly. After 10, 20 and 30 minutes, measurements were repeated. At 40 minutes after premedication, anaesthesia was induced with propofol intravenously and maintained with isoflurane. Measurements were repeated 50, 60 and 65 minutes after the injection of the investigated drugs. Analysed microcirculatory variables were: Perfused de Backer density, Perfused de Backer density of vessels < 20 μm, Proportion of perfused vessels and Proportion of perfused vessels < 20 μm. Heart rate (HR), systolic, diastolic (DAP) and mean (MAP) arterial pressures were recorded at the same time points. Macro- and microcirculatory variables were analysed using a linear mixed model with baseline as a covariate, treatment, trial period and repetition as fixed effects and time and dog as random effect. Results are presented as effect size and confidence interval; p values < 0.05 were considered significant., Results: After acepromazine, Perfused de Backer density was greater during sedation and anaesthesia [3.71 (1.93-5.48 mm mm -2 , p < 0.0001) and 2.3 (0.86-3.75 mm mm -2 , p < 0.003)], respectively, than after dexmedetomidine. HR was significantly lower, whereas MAP and DAP were significantly higher with dexmedetomidine during sedation and anaesthesia (p < 0.0001 for all) compared with acepromazine., Conclusions and Clinical Relevance: The sedative drugs tested exerted a significant effect on buccal mucosal microcirculation with a higher Perfused de Backer density after the administration of acepromazine compared with dexmedetomidine. This should be considered when microcirculation is evaluated using these drugs., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Background: General anaesthetics have marked effects on synaptic transmission, but their neuronal and circuit-level effects remain unclear. The volatile anaesthetic isoflurane differentially inhibits synaptic vesicle exocytosis in specific neuronal subtypes, but whether other common anaesthetics also have neurone-subtype-specific actions is unknown., Methods: We used the genetically encoded fluorescent Ca 2+ sensor GCaMP6f to compare the pharmacological effects of isoflurane, sevoflurane, propofol, and ketamine on presynaptic excitability in hippocampal glutamatergic neurones and in hippocampal parvalbumin-, somatostatin-, and vasoactive intestinal peptide-expressing (PV + , SST + , and VIP + , respectively) GABAergic interneurones., Results: Isoflurane and sevoflurane depressed activity-driven presynaptic Ca 2+ transients in a neurone-type-specific manner, with greater potency for inhibition of glutamate and SST + compared with PV + and VIP + neurone presynaptic activation. In contrast, clinical concentrations of propofol (1 μM) or ketamine (15 μM) had no significant effects on presynaptic activation. Propofol potentiated evoked Ca 2+ entry in PV + interneurones but only at a supraclinical concentration (3 μM)., Conclusions: Anaesthetic-agent-selective effects on presynaptic Ca 2+ entry have functional implications for hippocampal circuit function during i.v. or volatile anaesthetic-mediated anaesthesia. Hippocampal interneurones have distinct subtype-specific sensitivities to volatile anaesthetic actions on presynaptic Ca 2+ , which are similar between isoflurane and sevoflurane., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: How conscious experience becomes disconnected from the environment, or disappears, across arousal states is unknown. We sought to identify the neural correlates of sensory disconnection and unconsciousness using a novel serial awakening paradigm., Methods: Volunteers were recruited for sedation with dexmedetomidine i.v., propofol i.v., or natural sleep with high-density EEG monitoring and serial awakenings to establish whether subjects were in states of disconnected consciousness or unconsciousness in the preceding 20 s. The primary outcome was classification of conscious states by occipital delta power (0.5-4 Hz). Secondary analyses included derivation (dexmedetomidine) and validation (sleep/propofol) studies of EEG signatures of conscious states., Results: Occipital delta power differentiated disconnected and unconscious states for dexmedetomidine (area under the curve [AUC] for receiver operating characteristic 0.605 [95% confidence interval {CI}: 0.516; 0.694]) but not for sleep/propofol (AUC 0.512 [95% CI: 0.380; 0.645]). Distinct source localised signatures of sensory disconnection (AUC 0.999 [95% CI: 0.9954; 1.0000]) and unconsciousness (AUC 0.972 [95% CI: 0.9507; 0.9879]) were identified using support vector machine classification of dexmedetomidine data. These findings generalised to sleep/propofol (validation data set: sensory disconnection [AUC 0.743 {95% CI: 0.6784; 0.8050}]) and unconsciousness (AUC 0.622 [95% CI: 0.5176; 0.7238]). We identified that sensory disconnection was associated with broad spatial and spectral changes. In contrast, unconsciousness was associated with focal decreases in activity in anterior and posterior cingulate cortices., Conclusions: These findings may enable novel monitors of the anaesthetic state that can distinguish sensory disconnection and unconsciousness, and these may provide novel insights into the biology of arousal., Clinical Trial Registration: NCT03284307., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: Most anesthetic drugs used for electroconvulsive therapy (ECT) have dose-dependent anticonvulsive effects, counter-acting seizure induction, lowering seizure quality. However, a consummate drug for ECT anesthesia has not yet been established. Therefore, in this study, we aimed to investigate the effects of etomidate, thiopental, propofol and co-administration of ketamine-propofol (ketofol) on seizure quality and hemodynamic safety., Methods: Registries of 121 patients (1077 sessions) were retrospectively evaluated. The effects of anesthetics on ECT-related parameters (stimulation charge, central seizure duration, number of failed stimulation trials, mean arterial pressure, and peak heart rate) were analyzed via linear mixed-effects models., Results: Overall, the seizure duration decreased, and the stimulation charge increased in time with continuing sessions within a course of ECT. The decrease in seizure duration and the increase in required stimulation charge was significantly lower with etomidate and ketofol. Additionally, ketofol was significantly related to a lower number of failed stimulation trials compared to propofol. Ketofol and propofol use was associated with a significantly lower postictal mean arterial pressure., Conclusion: Ketofol and etomidate were equivalently superior in the rate of decrease in seizure duration and the required elevation in stimulus charge, which would interpret into valuable clinical guidance, especially for "seizure resistant" patients, and their use may potentially lower ECT related cognitive side effects., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Propofol (2,6-diisopropylphenol) is frequently used as intravenous anesthetic agent, especially in its injectable form (Diprivan), to initiate and maintain sedative state during surgery or in intensive care units. Numerous studies have reported the antioxidant and anti-inflammatory effect of propofol. The oxidant enzyme myeloperoxidase (MPO), released from activated neutrophils, plays a key role in host defense. An increase of the circulating MPO concentration has been observed in patients admitted in intensive care unit and presenting a systemic inflammatory response related to septic shock or trauma., Methods: This study investigates the immunomodulatory action of propofol and Diprivan as inhibitor of the oxidant activity of MPO. The understanding of the redox action mechanism of propofol and Diprivan on the myeloperoxidase chlorination and peroxidase activities has been refined using the combination of fluorescence and absorption spectroscopies with docking and cyclic voltammetry., Results: Propofol acts as a reversible MPO inhibitor. The molecule interacts as a reducing substrate in the peroxidase cycle and promotes the accumulation of compound II. At acidic pH (5.5), propofol and Diprivan do not inhibit the chlorination activity, but their action increases at physiological pH (7.4). The main inhibitory action of Diprivan could be attributed to its HOCl scavenging property., General Significance: Propofol can act as a reversible MPO inhibitor at clinical concentrations. This property could, in addition to other previously proven anti-inflammatory actions, induce an immunomodulatory action, beneficial during clinical use, particularly in the treatment of systemic inflammation response syndrome., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Porcine animal models are used in biomedical research due to anatomical and physiological similarities with human patients. The study aimed to validate telemetric systemic blood pressure (BP) and heart rate (HR) monitoring in Göttingen Minipigs, and in addition to study the effects of three different anaesthesia protocols on telemetric BP and HR measurements., Methods: Eight female Göttingen Minipigs had telemetry transmitters implanted in the right carotid artery. Over ten weeks, systemic 24-h BP and HR monitoring were repeated four times, each ending with an angiotensin II stimulation test. In addition, systemic BP and HR evaluated by telemetry, intra-arterial catheter (IAC) and oscillometric tail-cuff were compared before and after the 10-weeks period. Furthermore, changes in telemetric systemic BP and HR were monitored during anaesthesia in a cross-over design using three different protocols of general anaesthesia: Midazolam/ketamine (MK), propofol, and a combination of tiletamine, zolazepam, xylazine, ketamine and butorphanol (Zoletil-mix)., Results: One minipig was excluded and some data were missing due to central-venous catheter issues. The coefficient of variation was below 10% for the 24-h BP and HR measurements, but higher during angiotensin II stimulation. There was a disagreement between the tail-cuff measurement and telemetry/IAC, however the differences were independent of the BP and HR level. All anaesthesia protocols numerically influenced BP and HR, but only propofol statistically significantly decreased the BP., Conclusion: The study showed acceptable reproducibility of telemetric measurement of BP and HR over ten weeks in freely moving Göttingen Minipigs. There was a disagreement between direct and indirect BP measurement, and BP and HR were influenced by all anaesthesia protocols., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to compare the effects of different coinduction agents on the duration and dose of propofol in healthy cats. Six cats aged 4.8 ± 1.0 years and weighing 4.4 ± 1.1 kg participated in 4 treatment groups of propofol combined with: saline or control group (TC); ketamine 2 mg/kg (Tket); fentanyl 1 µg/kg (Tfen); or midazolam 0.3 mg/kg (Tmid). Twenty minutes following premedication with dexmedetomidine at 10 µg/kg, induction followed the same protocol in all groups, starting with a propofol bolus of 1 mg/kg over 1 minute followed by an adjuvant, then propofol again at 1 mg/kg/minute for orotracheal intubation. Variables recorded were (in minutes): time of extubation, time to return of palpebral reflex, eye recentralization, recovery of consciousness, quadrupedal position and total propofol dose used (mg/kg). A comparison between the 4 groups was performed by analysis of variance followed by Dunnett test under 5% significance. There was no significant difference in any of the times evaluated during anesthetic recovery between the groups. The propofol dose used to allow orotracheal intubation was significantly lower in all groups compared to TC (P < .05). Ketamine, midazolam, and fentanyl are indicated as suitable choices for coinduction with propofol in cats., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The choice of anaesthetic may influence regulation of renal perfusion and function. We investigated renal function in patients anaesthetised with propofol or sevoflurane before surgery and postoperatively., Methods: Patients with ASA physical status 1-2 planned for spinal surgery were randomised to propofol or sevoflurane anaesthesia. Blood and urine were collected before anaesthesia, during anaesthesia (before surgery), during postoperative care, and the day after surgery., Results: Twenty-seven patients completed the study protocol (average age, 51 yr; average BMI, 28 kg m -2 ) and 11 were women. Urine output and sodium excretion were lower during sevoflurane anaesthesia (n=14) than during propofol anaesthesia (n=13) (0.3 vs 1.1 ml kg -1 h -1 [P=0.01] and 2.6 vs 6.0 mmol h -1 [P=0.04], respectively). Urinary potassium excretion was lower during anaesthesia than after, without intergroup difference (2.3 vs 5.7 mmol h -1 , P<0.001). Sevoflurane anaesthesia increased plasma renin compared with baseline (138 vs 23 mIU L -1 , P<0.001) and propofol anaesthesia (138 vs 27 mIU L -1 , P=0.008). Plasma arginine-vasopressin did not change significantly during anaesthesia, but was elevated postoperatively compared with baseline irrespective of anaesthetic (21 vs 12 ng L -1 , P=0.02). Sevoflurane caused higher postoperative plasma creatinine than propofol (83 vs 66 mmol L -1 , P=0.01). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin did not change significantly in either group., Conclusions: Sevoflurane anaesthesia reduced urine output and sodium excretion and increased plasma renin compared with propofol anaesthesia. The impact of this on acute kidney injury and fluid resuscitation during surgery warrants further investigation., Clinical Trial Registration: EudraCT: 2017-001646-10; Clinicaltrials.gov: NCT0333680., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine an optimum infusion rate of propofol that permitted rapid tracheal intubation while minimizing the duration of postinduction apnoea., Study Design: Prospective, randomized, blinded clinical trial., Animals: A total of 60 client-owned dogs presented for elective neutering and radiography., Methods: Dogs were randomly allocated to one of five groups (groups A-E) to have propofol at an infusion rate of 0.5, 1, 2, 3, or 4 mg kg -1 minute -1 , respectively, following intramuscular premedication with methadone 0.5 mg kg -1 and dexmedetomidine 5 μg kg -1 . Propofol administration was stopped when adequate conditions for tracheal intubation were identified. Time to tracheal intubation and duration of apnoea were recorded. If oxygen haemoglobin saturation decreased to < 90%, manual ventilation was initiated. A one-way analysis of covariance was conducted to compare the effect of propofol infusion rate on duration of apnoea and intubation time whilst controlling for covariates, followed by post hoc tests. The significance level was set at p < 0.05., Results: Propofol infusion rate had a significant effect on duration of apnoea (p = 0.004) and intubation time (p < 0.001) after controlling for bodyweight and sedation scores, respectively. The adjusted means (± standard error) of duration of apnoea were significantly shorter in groups A and B (49 ± 39 and 67 ± 37 seconds, respectively) than in groups C, D and E (207 ± 34, 192 ± 36 and 196 ± 34 seconds, respectively). Group B (115 ± 10 seconds) had a significantly shorter intubation time than group A (201 ± 10 seconds, p < 0.001)., Conclusions and Clinical Relevance: An infusion rate of 1.0 mg kg -1 minute -1 (group B) appears to offer the optimal compromise between speed of induction and duration of postinduction apnoea., (Copyright © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)