Substance specific EEG patterns in mice undergoing slow anesthesia induction.

The exact mechanisms and the neural circuits involved in anesthesia induced unconsciousness are still not fully understood. To elucidate them valid animal models are necessary. Since the most commonly used species in neuroscience are mice, we established a murine model for commonly used anesthetics/sedatives and evaluated the epidural electroencephalographic (EEG) patterns during slow anesthesia induction and emergence. Forty-four mice underwent surgery in which we inserted a central venous catheter and implanted nine intracranial electrodes above the prefrontal, motor, sensory, and visual cortex. After at least one week of recovery, mice were anesthetized either by inhalational sevoflurane or intravenous propofol, ketamine, or dexmedetomidine. We evaluated the loss and return of righting reflex (LORR/RORR) and recorded the electrocorticogram. For spectral analysis we focused on the prefrontal and visual cortex. In addition to analyzing the power spectral density at specific time points we evaluated the changes in the spectral power distribution longitudinally. The median time to LORR after start anesthesia ranged from 1080 [1st quartile: 960; 3rd quartile: 1080]s under sevoflurane anesthesia to 1541 [1455; 1890]s with ketamine. Around LORR sevoflurane as well as propofol induced a decrease in the theta/alpha band and an increase in the beta/gamma band. Dexmedetomidine infusion resulted in a shift towards lower frequencies with an increase in the delta range. Ketamine induced stronger activity in the higher frequencies. Our results showed substance-specific changes in EEG patterns during slow anesthesia induction. These patterns were partially identical to previous observations in humans, but also included significant differences, especially in the low frequencies. Our study emphasizes strengths and limitations of murine models in neuroscience and provides an important basis for future studies investigating complex neurophysiological mechanisms.

Nicardipine constant rate infusion alleviates the cardiovascular effects of dexmedetomidine infusions without affecting the minimal alveolar concentration in sevoflurane-anesthetized dogs.

Two randomized crossover trials evaluated the effects of nicardipine constant rate infusion (CRI) on 1) the anesthetic potency of sevoflurane and 2) the ability to attenuate dexmedetomidine-induced cardiovascular depression in anesthetized dogs. First, six healthy Beagle dogs weighing 11.7 ± 0.9 kg were allocated to one of three treatments that administered a CRI of carrier (saline) or dexmedetomidine 0.5 or 3.0 µg/kg/h following a loading dose. The minimum alveolar concentration (MAC) of sevoflurane was determined utilizing electric stimuli before and after the loading dose of nicardipine (20 µg/kg intravenously for 10 min), followed by CRI at 40 µg/kg/h with 60 min of equilibration. Subsequently, cardiovascular and blood gas variables were evaluated in another trial under sevoflurane anesthesia at the individual 1.5 MAC. After baseline measurements, the dogs were assigned to two treatments (dexmedetomidine CRI at 0.5 or 3.0 µg/kg/h following a loading dose) with sevoflurane doses adjusted to 1.5 times of MAC equivalent, and the measurements were repeated every 15 min for 120 min. After 60 min, nicardipine CRI at 40 µg/kg/h with a loading dose was added to the dexmedetomidine CRI. Dexmedetomidine infusions significantly decreased the sevoflurane MAC but nicardipine did not significantly alter the MAC either with or without dexmedetomidine CRI in dogs. Dexmedetomidine dose-dependently decreased the cardiac index and increased the systemic vascular resistance index; these effects were fully counteracted by concomitant nicardipine CRI. Nicardipine CRI can be useful for controlling the cardiovascular depression elicited by dexmedetomidine in anesthetized dogs without affecting the anesthetic potency of sevoflurane.

Lidocaine effects on neutrophil extracellular trapping and angiogenesis biomarkers in postoperative breast cancer patients with different anesthesia methods: a prospective, randomized trial.

BACKGROUND: Anesthesia techniques and drug selection may influence tumor recurrence and metastasis. Neutrophil extracellular trapping (NETosis), an immunological process, has been linked to an increased susceptibility to metastasis in individuals with tumors. Furthermore, recurrence may be associated with vascular endothelial growth factor A (VEGF-A), a mediator of angiogenesis. This study investigates the impact of lidocaine (combined with sevoflurane or propofol anesthesia ) during breast cancer surgery inhibits the expression of biomarkers associated with metastasis and recurrence (specifically H3Cit, NE, MPO, MMP-9 and VEGF-A). METHODS: We randomly assigned 120 women undergoing primary or invasive breast tumor resection to receive one of four anesthetics: sevoflurane (S), sevoflurane plus i.v. lidocaine (SL), propofol (P), and propofol plus i.v. lidocaine (PL). Blood samples were collected before induction and 3 h after the operation. Biomarkers associated with NETosis (citrullinated histone H3 [H3Cit], myeloperoxidase [MPO], and neutrophil elastase [NE]) and angiogenesis were quantified using enzyme-linked immunosorbent assays. RESULTS: Patient and breast tumor characteristics, along with perioperative management, did not differ between study groups. In intra-group comparisons, S and P groups demonstrated a statistically significant increase in post-operative MPO (S group: 10.39[6.89-17.22] vs. 14.31[8.55-20.87] ng ml-1, P = 0.032; P group: 9.45[6.73-17.37] vs. 14.34[9.87-19.75] ng ml-1, P = 0.035)and NE(S group: 182.70[85.66-285.85] vs. 226.20[91.85-391.65] ng ml-1, P = 0.045; P group: 154.22[97.31-325.30] vs. 308.66[132.36-483.57] ng ml-1, P = 0.037) concentrations compared to pre-operative measurements, whereas SL and PL groups did not display a similar increase. H3Cit, MMP-9, and VEGF-A concentrations were not significantly influenced by the anesthesia techniques and drugs. CONCLUSIONS: Regardless of the specific technique employed for general anesthesia, there was no increase in the postoperative serum concentrations of MPO and NE after perioperative lidocaine infusion compared to preoperative serum concentrations. This supports the hypothesis that intravenous lidocaine during cancer surgery aimed at achieving a cure may potentially decrease the likelihood of recurrence. Further interpretation and discussion of clinical implications are warranted, emphasizing the significance of these findings in the context of cancer surgery and recurrence prevention. CLINICAL TRIAL REGISTRATION: ChiCTR2300068563.

Application Value of Sevoflurane Combined with Brachial Plexus Block in Children with Humeral Fracture Surgery and its Effect on Hemodynamics: A Clinical and Anatomical Study

SUMMARY: To observe the effect of sevoflurane combined with brachial plexus block (BPB) in children with humeral fracture surgery and its effect on hemodynamics. 84 children who received surgical treatment of humeral fracture in our hospital from September 2019 to September 2022 were selected. According to different anesthesia methods, the children were divided into control group and study group. The control group only received laryngeal mask sevoflurane; the study group received laryngeal mask sevoflurane combined with BPB. The operation situation, hemodynamic indexes, stress level, pain and adverse reactions of children was observed. The postoperative awakening time in the study group was lower than control group, the postoperative pain onset time in the study group was higher than control group (P0.05). Postoperative 2h, the levels of serum cortisol, b-endorpin, norepinephrine and epinephrine in the study group were lower than control group (P0.05). Sevoflurane combined with BPB is helpful to shorten the postoperative awakening time of children with humeral fracture, reduce the degree of postoperative pain, improve hemodynamics, and reduce stress response, and has good safety.

El objetivo fue observar el efecto del sevoflurano combinado con bloqueo del plexo braquial (BPB) en niños con cirugía de fractura de húmero y su efecto sobre la hemodinámica. Se seleccionaron 84 niños que recibieron tratamiento quirúrgico de fractura de húmero en nuestro hospital desde septiembre de 2019 hasta septiembre de 2022. Según diferentes métodos de anestesia, los niños se dividieron en grupo control y grupo de estudio. El grupo control solo recibió sevoflurano en mascarilla laríngea; el grupo de estudio recibió sevoflurano con mascarilla laríngea combinado con BPB. Se observó la situación operatoria, índices hemodinámicos, nivel de estrés, dolor y reacciones adversas de los niños. El tiempo hasta el despertar postoperatorio en el grupo de estudio fue menor que el del grupo control, el tiempo de aparición del dolor postoperatorio en el grupo de estudio fue mayor que el del grupo control (P0,05). A las 2 horas postoperatorias, los niveles séricos de cortisol, β-endorfina, norepinefrina y epinefrina en el grupo de estudio fueron más bajos que los del grupo control (P 0,05). El sevoflurano combinado con BPB es útil para acortar el tiempo de despertar del posoperatorio de los niños con fractura de húmero, reduce el grado de dolor postoperatorio, mejora la hemodinámica y reduce la respuesta al estrés, además de tener buena seguridad.

Plasma cytokine levels in spinal surgery with sevoflurane or total intravenous propofol anesthesia - A post hoc analysis of a randomized controlled trial.

Surgical tissue trauma stimulates an inflammatory response resulting in increased levels of cytokines which could contribute to acute kidney injury (AKI). It is not clear if anesthetic modality affects this response. We aimed to investigate the role of anesthesia in a healthy surgical population on the inflammatory response and the correlation to plasma creatinine. This study is a post hoc analysis of a published randomized clinical trial. We analyzed plasma from patients who underwent elective spinal surgery randomized to either total intravenous propofol anesthesia (n = 12) or sevoflurane anesthesia (n = 10). The plasma samples were collected before anesthesia, during anesthesia, and 1 h after surgery. Plasma cytokine levels after surgery were analyzed for correlations with duration of surgical insult and change in plasma creatinine concentration. The cytokine interleukin-6 (IL-6) was increased after surgery compared with preoperatively. IL-6 was higher in the sevoflurane group than the propofol group after surgery. No patient developed AKI, but plasma creatinine was increased postoperatively in the sevoflurane group. There was a significant association between surgical time and plasma IL-6 postoperatively. No significant correlation between change in plasma creatinine and IL-6 was detected. The cytokines IL-4, IL-13, Eotaxin, Interferon γ-Induced Protein 10 (IP-10), Granulocyte Colony-Stimulating Factor (G-CSF), Macrophage Inflammatory Protein-1ß (MIP-1ß), and Monocyte Chemoattractant Protein 1 (MCP-1) were lower postoperatively than before surgery independent of anesthetic modality. This post hoc analysis revealed that plasma IL-6 was increased after surgery and more so in the sevoflurane group than the propofol group. Postoperative plasma IL-6 concentration was associated with surgical time.

Effects of intra-operative administration of subanesthetic s-ketamine on emergence from sevoflurane anesthesia: a randomized double-blind placebo-controlled study.

BACKGROUND: Ketamine is administered in the perioperative period for its benefits in analgesia, anti-agitation and anti-depression when administered at a small dose. However, it is not clear whether the intra-operative administration of ketamine would affect emergence under sevoflurane anesthesia. To investigate this effect, we designed this trial. METHODS: In this randomized, double-blind, placebo-controlled study, we enrolled 44 female patients aged 18-60 who were scheduled to elective laparoscopic gynecological surgeries. All patients were randomly assigned to saline or s-ketamine group. In s-ketamine group, patients received 0.125 mg/kg s-ketamine 30 min after the start of surgery. In saline group, patients were administered the same volume of saline. Sevoflurane and remifentanil were used to maintain general anesthesia. The primary outcome was emergence time. We also assessed postoperative agitation, cognitive function, and delirium. In addition, we collected and analyzed prefrontal electroencephalogram (EEG) during and after general anesthesia. RESULTS: There were no significant differences in emergence time between s-ketamine group and saline group (10.80 ± 3.77 min vs. 10.00 ± 2.78 min, P = 0.457). Neither postoperative agitation (4 [3, 4] vs. 4 [3, 4], P = 0.835) nor cognitive function (25.84 ± 2.69 vs. 25.55 ± 2.19, P = 0.412) differed between groups. No postoperative delirium was observed in either group. Subanesthetic s-ketamine resulted in active EEG with decreased power of slow (-0.35 ± 1.13 dB vs. -1.63 ± 1.03 dB, P = 0.003), delta (-0.22 ± 1.11 dB vs. -1.32 ± 1.09 dB, P = 0.011) and alpha (-0.31 ± 0.71 dB vs. -1.71 ± 1.34 dB, P = 0.0003) waves and increased power of beta-gamma bands (-0.30 ± 0.89 dB vs. 4.20 ± 2.08 dB, P < 0.0001) during sevoflurane anesthesia, as well as an increased alpha peak frequency (-0.16 ± 0.48 Hz vs. 0.31 ± 0.73 Hz, P = 0.026). EEG patterns did not differ during the recovery period after emergence between groups. CONCLUSION: Ketamine administered during sevoflurane anesthesia had no apparent influence on emergence time in young and middle-aged female patients undergoing laparoscopic surgery. Subanesthetic s-ketamine induced an active prefrontal EEG pattern during sevoflurane anesthesia but did not raise neurological side effects after surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100046479 (date: 16/05/2021).

Sevoflurane Exposure of Clinical Doses in Pregnant Rats Induces Vcan Changes without Significant Neural Apoptosis in the Offspring.

Background and Objectives: Sevoflurane is a commonly used inhalational anaesthetic in clinics. Prolonged exposure to sevoflurane can induce significant changes in lipid metabolism and neuronal damage in the developing brain. However, the effect of exposure of pregnant rats to clinical doses of sevoflurane remains unclear. Materials and Methods: Twenty-eight pregnant rats were randomly and equally divided into sevoflurane exposure (S) group, control (C) and a blank group at gestational day (G) 18; Rats in S group received 2% sevoflurane with 98% oxygen for 6 h in an anesthetizing chamber, while C group received 100% oxygen at an identical flow rate for 6 h in an identical chamber. Partial least squares discriminant analysis (PLS-DA), ultra performance liquid chromatography/time-of-flight mass spectrometry(UPLC/TOF-MS) and MetaboAnalyst were used to analysis acquire metabolomics profiles, and immunohistochemical changes of neuronalapoptosis in hippocampus and cortex of neonatal rats were also analyzed. Results: This study aimed to explore lipidomics and transcriptomics changes related to 2% sevoflurane exposure for 6 h in the developing brains of newborn offspring rats. Ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) and RNA sequencing (RNA-seq) analyses were used to acquire metabolomics and transcriptomics profiles. We used RNA-seq to analyse the expression of the coding and non-coding transcripts in neural cells of the cerebral cortex. No significant differences in arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), or arterial blood gas were found between the groups. The relative standard deviation (RSD) of retention times was <1.53%, and the RSDs of peak areas ranged from 2.13% to 8.51%. Base peak chromatogram (BPC) profiles showed no differences between the groups. We evaluated the partial least square-discriminant analysis (PLS-DA) model. In negative ion mode, R2X was over 70%, R2Y was over 93%, and Q2 (cum) was over 80%. Cell apoptosis was not remarkably enhanced by TUNEL and haematoxylin and eosin (HE) staining in the sevoflurane-exposed group compared to the control group (p > 0.05). Glycerophospholipid (GP) and sphingolipid metabolism disturbances might adversely influence neurodevelopment in offspring. The expression of mRNAs (Vcan gene, related to neuronal development, function and repair) of the sevoflurane group was significantly increased in the differential genes by qRT-PCR verification. Conclusions: GP and sphingolipid metabolism homeostasis may be potential therapeutic approaches against inhalational anaesthetic-induced neurodegenerative disorders. Meanwhile, sevoflurane-induced Vcan changes indicated some lipidomic and transcriptomic changes, even if neural cell apoptosis was not significantly changed in the usual clinical dose of sevoflurane exposure.

Sevoflurane consumption pattern by individual anaesthesiologists varies widely despite using the same high-end workstations in the same hospital.

Volatile anaesthetics are potent greenhouse gasses but contemporary workstations enable considerable savings while improving patient safety. Institutions may provide this technology to reduce the ecological footprint but proper training and motivation is required to maximize their ecologic and financial benefit. This study aims to compare the sevoflurane consumption of 22 anaesthesiologists in a medium sized hospital 4 years after flow-i workstations (Getinge, Sweden) entered into service, in three airway approaches: intubated patients, laryngeal mask ventilation, and mask anaesthesia. Typical sevoflurane consumption for each anaesthesiologist was defined as the mean cumulative consumption in the chronologically first 50 cases meeting the inclusion criteria for each airway group in 2019. The potential savings, if everyone were to adopt the approach of the more economical anaesthesiologists (15th percentile), was calculated. The CO2 equivalent emissions were calculated using a GWP20 of 702 and a GWP100 of 195. The median [range] consumption after 45 min was 10.9 [7.5-18.4] ml in intubated patients and 9.0 [7.4-15.3] ml in patients with laryngeal mask, and 9.9 [3.4-20.9] ml after 8 min with mask ventilation. This corresponds to a double to six fold consumption between the least and most wasteful approach. The typical CO2 equivalent emissions (GWP20) per anaesthesiologist varied between 8.0 and 19.6 kg/45 min in intubated airways, between 7.9 and 16.3 kg/45 min in LMA, and between 3.6 and 22.3 kg/8 min in mask ventilation. Despite using the same workstations in the same hospital, the typical sevoflurane consumption differed dramatically between 22 anaesthesiologists. In addition to providing advanced workstations, proper education is required to achieve the behavior change needed to reduce the pollution and financial waste associated with volatile anaesthetics.

Sevoflurane attenuates myocardial ischemia/reperfusion injury by up-regulating microRNA-99a and down-regulating BRD4

Purpose: It has been explored that sevoflurane (Sevo) is cardioprotective in myocardial ischemia/reperfusion injury (MI/RI) and mediates microRNA (miRNA) expression that control various physiological systems. Enlightened by that, the work was programmed to decode the mechanism of Sevo and miR-99a with the participation of bromodomain-containing protein 4 (BRD4). Methods: MI/RImodel was established on mice. MI/RI modeled mice were exposed to Sevo or injected with miR-99a or BRD4-related vectors to identify their functions in cardiac function, pathological injury, cardiomyocyte apoptosis, inflammation, and oxidative stress in MI/RI mice. MiR-99a and BRD4 expression in myocardial tissues were tested, and their relation was further validated. Results: MiR-99a was down-regulated, and BRD4 was up-regulated in MI/RI mice. Sevo up-regulated miR-99a to inhibit BRD4 expression in myocardial tissues of MI/RI mice. Sevo improved cardiac function, relieved myocardial injury, repressed cardiomyocyte apoptosis, and alleviated inflammation and oxidative stress in mice with MI/RI. MiR-99a restoration further enhanced the positive effects of Sevo on mice with MI/RI. Overexpression of BRD4 reversed up-regulation of miR-99a-induced attenuation of MI/RI in mice. Conclusions: The work delineated that Sevo up-regulates miR-99a to attenuate MI/RI by inhibiting BRD4.

miRNA-384-3p alleviates sevoflurane-induced nerve injury by inhibiting Aak1 kinase in neonatal rats.

OBJECTIVE: Sevoflurane is a common anesthetic and is widely used in pediatric clinical surgery to induce and maintain anesthesia through inhalation. Increasing studies have revealed that sevoflurane has neurotoxic effects on neurons, apoptosis, and memory impairment. miR-384 is involved in the process of neurological diseases. However, the role of miRNA-384-3p in sevoflurane-induced nerve injury is not clear. This study focused on exploring the roles and mechanisms of miRNA-384-3p in sevoflurane-induced nerve injury. METHODS: Seven-day-old rats were exposed to 2.3% sevoflurane to induce nerve injury. The morphological changes in neurons in the hippocampal CA1 region were detected by HE staining and Nissl staining. Neuronal apoptosis was detected by TUNEL and Western blot assays. Spatial memory and learning ability were detected by the Morris water maze assay. The target gene of miRNA-384-3p was verified through a luciferase reporter assay. A rescue experiment was used to confirm the miRNA-384-3p pathway in sevoflurane-induced nerve injury. RESULTS: Sevoflurane reduced miRNA-384-3p expression in the rat hippocampus. miRNA-384-3p alleviated sevoflurane-induced morphological changes in hippocampal neurons and apoptosis of neurons in the hippocampal CA1 region. Meanwhile, miRNA-384-3p attenuated the decline in spatial memory and learning ability induced by sevoflurane. miRNA-384-3p alleviated sevoflurane-induced nerve injury by inhibiting the expression of adaptor-associated kinase 1 (Aak1). CONCLUSION: Our findings revealed the role and mechanism of miRNA-384-3p in sevoflurane-induced nerve injury, suggesting that miRNA-384-3p could be a novel and promising strategy for reducing sevoflurane-induced neurotoxicity.

Ethanol reduces the minimum alveolar concentration of sevoflurane in rats.

A high number of trauma patients are under the influence of alcohol. Since many of them need immediate surgical procedures, it is imperative to be aware of the interaction of alcohol with general anesthesia. To counter challenges that arise from clinical studies, we designed an animal experiment in which 48 adult Wistar rats either received 1 g · kg-1 ethanol, 2 g · kg-1 ethanol or placebo via intraperitoneal application. Subsequently, they were anesthetized with an individual concentration of sevoflurane. The minimum alveolar concentration (MAC) of the different groups was assessed using Dixon's up-and-down design and isotonic regression methods. The bootstrap estimate of the MAC of sevoflurane in the placebo group was 2.24 vol% (95% CI 1.97-2.94 vol%). In the low dose ethanol group, the bootstrap estimate was 1.65 vol% (95% CI 1.40-1.98 vol%), and in the high dose ethanol group, it was 1.08 vol% (95% CI 0.73-1.42 vol%). We therefore report that intraperitoneal application of 1 g · kg-1 or 2 g · kg-1 ethanol both resulted in a significant reduction of the MAC of sevoflurane in adult Wistar rats: by 26.3% and 51.8% respectively as compared to placebo.

Phosphoinositide-3-Kinase/Akt-Endothelial Nitric Oxide Synthase Signaling Pathway Mediates the Neuroprotective Effect of Sevoflurane Postconditioning in a Rat Model of Hemorrhagic Shock and Resuscitation.

BACKGROUND: Although extensive reports have demonstrated the neuroprotection of sevoflurane postconditioning in cases of focal and global cerebral ischemia/reperfusion, the underlying mechanisms are not completely elucidated. This study investigated whether this effect is related to endothelial nitric oxide synthase (eNOS) and mediated by the phosphoinositide-3-kinase pathway in a rat model of hemorrhagic shock and resuscitation. METHODS: Adult male Sprague Dawley rats were subjected to hemorrhagic shock for 60 minutes and then resuscitation for 30 minutes in experimental groups. Sevoflurane postconditioning was performed at the beginning of resuscitation to completion. At 24 hours after resuscitation, the brain infarct volume was evaluated by 2,3,5-triphenyltetrazolium chloride staining. The neuronal morphological changes and apoptosis were determined by hematoxylin and eosin staining and immunohistochemistry analysis, respectively. The activity of phosphorylated Akt and eNOS was evaluated by Western blot analysis. RESULTS: Brain injuries such as the cerebral infarct volume and pathological neuronal changes as well as cell apoptosis were observed in the hippocampus after hemorrhagic shock and resuscitation. Postconditioning with 2.4% sevoflurane significantly attenuated brain injuries. Wortmannin prevented the improvements of neuronal characteristics elicited by sevoflurane postconditioning as well as the hyperactivity of eNOS and phosphorylated Akt. CONCLUSIONS: Sevoflurane postconditioning could attenuate brain injury induced by hemorrhagic shock and resuscitation, and this neuroprotective effect may be partly by upregulation of eNOS through the phosphoinositide-3-kinase/Akt signaling pathway.

Lateralisation of subcortical functional connectivity during and after general anaesthesia.

BACKGROUND: Arousal and awareness are two important components of consciousness states. Functional neuroimaging has furthered our understanding of cortical and thalamocortical mechanisms of awareness. Investigating the relationship between subcortical functional connectivity and arousal has been challenging owing to the relatively small size of brainstem structures and thalamic nuclei, and their depth in the brain. METHODS: Resting state functional MRI scans of 72 healthy volunteers were acquired before, during, 1 h after, and 1 day after sevoflurane general anaesthesia. Functional connectivity of subcortical regions of interest vs whole brain and homotopic functional connectivity for assessment of left-right symmetry analyses of both cortical and subcortical regions of interest were performed. Both analyses used high resolution atlases generated from deep brain stimulation applications. RESULTS: Functional connectivity in subcortical loci within the thalamus and of the ascending reticular activating system was sharply restricted under anaesthesia, featuring a general lateralisation of connectivity. Similarly, left-right homology was sharply reduced under anaesthesia. Subcortical bilateral functional connectivity was not fully restored after emergence from anaesthesia, although greater restoration was seen between ascending reticular activating system loci and specific thalamic nuclei thought to be involved in promoting and maintaining arousal. Functional connectivity was fully restored to baseline by the following day. CONCLUSIONS: Functional connectivity in the subcortex is sharply restricted and lateralised under general anaesthesia. This restriction may play a part in loss and return of consciousness. CLINICAL TRIAL REGISTRATION: NCT02275026.

Prophylactic progesterone prevents adverse behavioural and neurocognitive effects of neonatal anaesthesia exposure in rat.

BACKGROUND: Evidence from animal models and human studies suggests an association between early general anaesthesia exposure and development of long-lasting neurocognitive problems including learning and memory impairments and an anxious phenotype. Because millions of children each year undergo procedures that require anaesthesia, it is important to investigate ways to protect the vulnerable developing brain. We evaluated whether progesterone treatment administered before general anaesthesia exposure could prevent long-term anaesthesia-induced neurocognitive and behavioural changes. METHODS: Female and male Long-Evans rat pups were repeatedly exposed to 2 h of sevoflurane or control procedures at postnatal days 7, 10, and 13. Subcutaneous injections of progesterone or vehicle were administered immediately before general anaesthesia exposure or control procedures. Neurobehavioural and cognitive outcomes were evaluated using elevated plus maze and Morris water maze tests. RESULTS: Prophylactic progesterone treatment attenuated the chemokine (C-X-C motif) ligand 1 (CXCL1) response to sevoflurane exposure. Rats given vehicle treatment with general anaesthesia exposure exhibited increased anxiety on the elevated plus maze and learning and memory impairments on the Morris water maze. However, rats treated with progesterone before general anaesthesia lacked these impairments and performed in a similar manner to controls on both tasks. CONCLUSIONS: Progesterone attenuated the anaesthesia-induced, acute peripheral inflammatory response and prevented cognitive and behavioural alterations associated with early repeated general anaesthesia exposure. Importantly, our results suggest that progesterone treatments given before general anaesthesia may help to protect the developing brain.

Sevoflurane-based enhancement of phase-amplitude coupling and localization of the epileptogenic zone.

OBJECTIVE: Phase-amplitude coupling between high-frequency (≥150 Hz) and delta (3-4 Hz) oscillations - modulation index (MI) - is a promising, objective biomarker of epileptogenicity. We determined whether sevoflurane anesthesia preferentially enhances this metric within the epileptogenic zone. METHODS: This is an observational study of intraoperative electrocorticography data from 621 electrodes chronically implanted into eight patients with drug-resistant, focal epilepsy. All patients were anesthetized with sevoflurane during resective surgery, which subsequently resulted in seizure control. We classified 'removed' and 'retained' brain sites as epileptogenic and non-epileptogenic, respectively. Mixed model analysis determined which anesthetic stage optimized MI-based classification of epileptogenic sites. RESULTS: MI increased as a function of anesthetic stage, ranging from baseline (i.e., oxygen alone) to 2.0 minimum alveolar concentration (MAC) of sevoflurane, preferentially at sites showing higher initial MI values. This phenomenon was accentuated just prior to sevoflurane reaching 2.0 MAC, at which time, the odds of a site being classified as epileptogenic were enhanced by 86.6 times for every increase of 1.0 MI. CONCLUSIONS: Intraoperative MI best localized the epileptogenic zone immediately before sevoflurane reaching 2.0 MAC in this small cohort of patients. SIGNIFICANCE: Prospective, large cohort studies are warranted to determine whether sevoflurane anesthesia can reduce the need for extraoperative, invasive evaluation.

Cognitive Recovery by Decade in Healthy 40- to 80-Year-Old Volunteers After Anesthesia Without Surgery.

BACKGROUND: Postoperative delirium and postoperative cognitive dysfunction are the most common complications for older surgical patients. General anesthesia may contribute to the development of these conditions, but there are little data on the association of age with cognitive recovery from anesthesia in the absence of surgery or underlying medical condition. METHODS: We performed a single-center cohort study of healthy adult volunteers 40 to 80 years old (N = 71, mean age 58.5 years, and 44% women) with no underlying cognitive dysfunction. Volunteers underwent cognitive testing before and at multiple time points after 2 hours of general anesthesia consisting of propofol induction and sevoflurane maintenance, akin to a general anesthetic for a surgical procedure, although no procedure was performed. The primary outcome was time to recovery to cognitive baseline on the Postoperative Quality of Recovery Scale (PQRS) within 30 days of anesthesia. Secondary cognitive outcomes were time to recovery on in-depth neuropsychological batteries, including the National Institutes of Health Toolbox and well-validated paper-and-pencil tests. The primary hypothesis is that time to recovery of cognitive function after general anesthesia increases across decades from 40 to 80 years of age. We examined this with discrete-time logit regression (for the primary outcome) and linear mixed models for interactions of age decade with time postanesthesia (for secondary outcomes). RESULTS: There was no association between age group and recovery to baseline on the PQRS; 36 of 69 (52%) recovered within 60-minute postanesthesia and 63 of 69 (91%) by day 1. Hazard ratios (95% confidence interval) for each decade compared to 40- to 49-year olds were: 50 to 59 years, 1.41 (0.50-4.03); 60 to 69 years, 1.03 (0.35-3.00); and 70 to 80 years, 0.69 (0.25-1.88). There were no significant differences between older decades relative to the 40- to 49-year reference decade in recovery to baseline on secondary cognitive measures. CONCLUSIONS: Recovery of cognitive function to baseline was rapid and did not differ between age decades of participants, although the number in each decade was small. These results suggest that anesthesia alone may not be associated with cognitive recovery in healthy adults of any age decade.

Sleep quality and emergence delirium in children undergoing strabismus surgery: a comparison between preschool- and school-age patients.

BACKGROUND: Emergence delirium (ED) is common in pediatric patients undergoing general anesthesia with sevoflurane. Preoperative sleep quality is associated with the risk factors for ED. However, research on the relationship between sleep quality and ED is limited. We aimed to investigate the relationship between ED and preoperative sleep quality in pediatric patients undergoing strabismus surgery. METHODS: This clinical trial included pediatric patients aged 4-12 years who underwent elective strabismus surgery. The patients and their parents were questioned about the patients' preoperative sleep quality using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. For anesthesia induction, thiopental (5 mg/kg) and rocuronium (0.6 mg/kg) were used, and anesthesia was maintained with sevoflurane (minimum alveolar concentration, 1-1.5). After administration of a reversal drug, extubation was performed, and the patients were transferred to a post-anesthesia recovery unit. At 10 min after extubation, the degree of ED was measured using the pediatric anesthesia emergence delirium (PAED) and Watcha scale scores. RESULTS: Of the 62 enrolled patients, three pediatric patients were excluded. The overall incidence of ED was 22%. A total of 59 patients were divided into the two groups. The ED group and the non-ED group comprised 13 and 46 patients. Age, height and weight were significantly lower in the ED group than in the non-ED group. Preoperative PSQI and Watcha scale score were significantly higher in the ED group than in the non-ED group. Multivariate analysis showed that age (adjusted OR [95% CI]: 0.490 [0.290-0.828], p = 0.008) and preoperative PSQI score (adjusted OR [95% CI]: 2.149[1.224-3.771], p = 0.008) was associated with ED. In sub-group analysis, PAED scale and Watcha scale scores showed a moderate correlation with preoperative sleep quality in preschool-age patients. CONCLUSION: In conclusion, the incidence of ED tended to be higher in younger age and poorer preoperative sleep quality in pediatric patients. In particular, the poorer sleep quality score was associated with higher incidence of ED in the preschool-age. Large-scale clinical studies and long-term follow-up studies on ED and sleep quality are required. TRIAL REGISTRATION: This study was registered with Clinicaltrials.gov ( NCT03332407 ) at November 5th 2017.

Effect of Global Ventilation to Perfusion Ratio, for Normal Lungs, on Desflurane and Sevoflurane Elimination Kinetics.

BACKGROUND: Kinetics of the uptake of inhaled anesthetics have been well studied, but the kinetics of elimination might be of more practical importance. The objective of the authors' study was to assess the effect of the overall ventilation/perfusion ratio (VA/Q), for normal lungs, on elimination kinetics of desflurane and sevoflurane. METHODS: The authors developed a mathematical model of inhaled anesthetic elimination that explicitly relates the terminal washout time constant to the global lung VA/Q ratio. Assumptions and results of the model were tested with experimental data from a recent study, where desflurane and sevoflurane elimination were observed for three different VA/Q conditions: normal, low, and high. RESULTS: The mathematical model predicts that the global VA/Q ratio, for normal lungs, modifies the time constant for tissue anesthetic washout throughout the entire elimination. For all three VA/Q conditions, the ratio of arterial to mixed venous anesthetic partial pressure Part/Pmv reached a constant value after 5 min of elimination, as predicted by the retention equation. The time constant corrected for incomplete lung clearance was a better predictor of late-stage kinetics than the intrinsic tissue time constant. CONCLUSIONS: In addition to the well-known role of the lungs in the early phases of inhaled anesthetic washout, the lungs play a long-overlooked role in modulating the kinetics of tissue washout during the later stages of inhaled anesthetic elimination. The VA/Q ratio influences the kinetics of desflurane and sevoflurane elimination throughout the entire elimination, with more pronounced slowing of tissue washout at lower VA/Q ratios.

Arterial and Mixed Venous Kinetics of Desflurane and Sevoflurane, Administered Simultaneously, at Three Different Global Ventilation to Perfusion Ratios in Piglets with Normal Lungs.

BACKGROUND: Previous studies have established the role of various tissue compartments in the kinetics of inhaled anesthetic uptake and elimination. The role of normal lungs in inhaled anesthetic kinetics is less understood. In juvenile pigs with normal lungs, the authors measured desflurane and sevoflurane washin and washout kinetics at three different ratios of alveolar minute ventilation to cardiac output value. The main hypothesis was that the ventilation/perfusion ratio (VA/Q) of normal lungs influences the kinetics of inhaled anesthetics. METHODS: Seven healthy pigs were anesthetized with intravenous anesthetics and mechanically ventilated. Each animal was studied under three different VA/Q conditions: normal, low, and high. For each VA/Q condition, desflurane and sevoflurane were administered at a constant, subanesthetic inspired partial pressure (0.15 volume% for sevoflurane and 0.5 volume% for desflurane) for 45 min. Pulmonary arterial and systemic arterial blood samples were collected at eight time points during uptake, and then at these same times during elimination, for measurement of desflurane and sevoflurane partial pressures. The authors also assessed the effect of VA/Q on paired differences in arterial and mixed venous partial pressures. RESULTS: For desflurane washin, the scaled arterial partial pressure differences between 5 and 0 min were 0.70 ± 0.10, 0.93 ± 0.08, and 0.82 ± 0.07 for the low, normal, and high VA/Q conditions (means, 95% CI). Equivalent measurements for sevoflurane were 0.55 ± 0.06, 0.77 ± 0.04, and 0.75 ± 0.08. For desflurane washout, the scaled arterial partial pressure differences between 0 and 5 min were 0.76 ± 0.04, 0.88 ± 0.02, and 0.92 ± 0.01 for the low, normal, and high VA/Q conditions. Equivalent measurements for sevoflurane were 0.79 ± 0.05, 0.85 ± 0.03, and 0.90 ± 0.03. CONCLUSIONS: Kinetics of inhaled anesthetic washin and washout are substantially altered by changes in the global VA/Q ratio for normal lungs.

Monitoring of Anesthesia by Bispectral Analysis of EEG Signals.

BACKGROUND: In intensive care, monitoring the depth of anesthesia during surgical procedures is a key element in the success of the medical operation and postoperative recovery. However, despite the development of anesthesia thanks to technological and pharmacological advances, its side effects such as underdose or overdose of hypnotics remain a major problem. Observation and monitoring must combine clinical observations (loss of consciousness and reactivity) with tools for real-time measurement of changes in the depth of anesthesia. Methodology. In this work, we will develop a noninvasive method for calculating, monitoring, and controlling the depth of general anesthesia during surgery. The objective is to reduce the effects of pharmacological usage of hypnotics and to ensure better quality recovery. Thanks to the overall activity of sets of neurons in the brain, we have developed a BIS technique based on bispectral analysis of the electroencephalographic signal EEG. Discussion. By collecting the electrical voltages from the brain, we distinguish light sleep from deep sleep according to the values of the BIS indicator (ranging from 0 : sleep to 100 : wake) and also control it by acting on the dosage of propofol and sevoflurane. We showed that the BIS value must be maintained during the operation and the anesthesia at a value greater than 60. CONCLUSION: This study showed that the BIS technology led to an optimization of the anesthetic management, the adequacy of the hypnotic dosage, and a better postoperative recovery.