Evaluation of Anesthetic Specific EEG Dynamics during State Transitions between Loss and Return of Responsiveness

Purpose: electroencephalographic (EEG) information is used to monitor the level of cortical depression of a patient undergoing surgical intervention under general anesthesia. The dynamic state transitions into and out of anesthetic-induced loss and return of responsiveness (LOR, ROR) present a possibility to evaluate the dynamics of the EEG induced by different substances. We evaluated changes in the EEG power spectrum during anesthesia emergence for three different anesthetic regimens. We also assessed the possible impact of these changes on processed EEG parameters such as the permutation entropy (PeEn) and the cerebral state index (CSI). Methods: we analyzed the EEG from 45 patients, equally assigned to three groups. All patients were induced with propofol and the groups differed by the maintenance anesthetic regimen, i.e., sevoflurane, isoflurane, or propofol. We evaluated the EEG and parameter dynamics during LOR and ROR. For the emergence period, we focused on possible differences in the EEG dynamics in the different groups. Results: depending on the substance, the EEG emergence patterns showed significant differences that led to a substance-specific early activation of higher frequencies as indicated by the “wake” CSI values that occurred minutes before ROR in the inhalational anesthetic groups. Conclusion: our results highlight substance-specific differences in the emergence from anesthesia that can influence the EEG-based monitoring that probably have to be considered in order to improve neuromonitoring during general anesthesia.

Sevoflurane Promotes Neurodegeneration Through Inflammasome Formation in APP/PS1 Mice

Sevoflurane (SEVO) is a highly fluorinated methyl isopropyl ether used as an inhalational anesthetic for general anesthesia. Previous studies have shown that SEVO may induce impaired memory and recognition ability and may be associated with neurodegenerative disease, e.g., Alzheimer’s disease (AD). However, the underlying mechanism remains unknown. Here, we used a mouse AD model, APP/PS1, to study the effects of SEVO on neurodegeneration occurring in AD. We found that SEVO exposure significantly impaired the spatial reference memory, sensorimotor, and cognitive function of the mice. Mechanistically, we found that SEVO induced formation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and its downstream caspase 1-mediated production of IL-1β and IL-18, which subsequently deactivated brain-derived neurotrophic factor (BDNF) to promote neurodegeneration. Together, these data suggest that NLRP3 inflammasome is essential for SEVO-induced AD.

Sevoflurane anesthesia: impact on postoperative cognitive dysfunction

Background: Sevoflurane is the inhalational anesthetic agent that is used widely in operating room. It is currently the most commonly used inhalation anesthetic in operating rooms. A series of studies on animal and human model detected the association of intraoperative use of sevoflurane and postoperative cognitive dysfunction (POCD) manifestation. On the other hand other studies demonstrate the same POCD associated with intravenous agents. Relevant multicentric trials got the reasons to suspect other key factors in developing postoperative cognitive dysfunction. Conclusions: The intra-anesthetic use of sevoflurane has been associated for a long time with the higher incidence of POCD. The mechanism was not identified, and the theory of neuroinflammation remained the main key of pathophysiological reaction that leads to cognitive dysfunction. Recent multicentre trial gives reliable information that the use of intravenous anesthetic agents is associated with the same POCD. Neuroinflammation remains to be the mediator of cognitive disorders, and apparently IL-6 keeps a major role in them. Future studies are needed to be conducted to identify the role of anesthetic agents in determining the neuroinflammation.

Vital signs of Cavia porcellus (Guinea pig) diagnosed with malignant hyperthermia using sevoflurane gas

Malignant hyperthermia (MH) is a life-threatening clinical syndrome of hypermetabolism involving the skeletal muscle. It is triggered in susceptible individuals primarily by volatile inhalational anesthetic agents and the muscle relaxant succinylcholine. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include A dramatic rise in body temperature, rigid or painful muscles, especially in the jaw, flushed skin, sweating, an abnormally rapid or irregular heartbeat, rapid breathing or uncomfortable breathing, brown or cola-colored urine, very low blood pressure (shock), confusion and muscle weakness or swelling after the event. The syndrome is likely to be fatal if untreated. This study therefore assessed the effects of sevoflurane gas on the vital signs of Cavia porcellus with malignant hyperthermia. For the determination of malignant hyperthermia, 50, 15 day-old weaned kits of Peru breed were placed in an anesthesia chamber for 5 minutes and subjected to a mixture of air with 3% sevoflurane gas. Only 6% of them reacted positively, while most of them, 94%, were negative. The average body temperature of the positive kits was 38.9ºC, oscillating between 38.7 and 39.1 ° C, while the negative ones averaged 37.9 ° C. The positive kits had an average of 142.3 breaths per minute compared to the negative ones, which was determined to be 83.7. The number of heart beats per minute in the kits with a positive reaction to sevoflurane averaged 205 and the negative ones 119.5. Muscle tremors were observed throughout the body during exposure of the positive kits to sevoflurane gas. It is concluded that for every 16 guinea pigs, 1 will react to the sevoflurane gas exposure positive due to the result obtained from the vital sign. Only the positive ones presented muscle tremors. L'hyperthermie maligne (HM) est un syndrome clinique d'hypermétabolisme mettant en jeu le pronostic vital impliquant le muscle squelettique. Elle est déclenchée chez les individus sensibles principalement par des agents anesthésiques volatils par inhalation et le relaxant musculaire succinylcholine. MH affecte les humains, certaines races de porcs, les chiens, les chevaux et probablement d'autres animaux. Les signes classiques de MH comprennent une augmentation spectaculaire de la température corporelle, des muscles rigides ou douloureux, en particulier dans la mâchoire, une peau rougeoyante, une transpiration, un rythme cardiaque anormalement rapide ou irrégulier, une respiration rapide ou une respiration inconfortable, une urine brune ou de couleur cola, très faible tension artérielle (choc), confusion et faiblesse ou gonflement musculaire après l'événement. Le syndrome estsusceptible d'être fatal s'il n'est pas traité. Cette étude a donc évalué les effets du gaz sévoflurane sur les signes vitaux de Cavia porcellus avec hyperthermie maligne. Pour la détermination de l'hyperthermie maligne, 50 chatons sevrés de 15 jours de race Pérou ont été placés dans une chambre d'anesthésie pendant 5 minutes et soumis à un mélange d'air avec 3% de sévoflurane. Seuls 6 % d'entre eux ont réagi positivement, alors que la plupart d'entre eux, 94 %, ont été négatifs. La température corporelle moyenne des kits positifs était de 38,9 ° C, oscillant entre 38,7 et 39,1 ° C, tandis que les kits négatifs étaient en moyenne de 37,9 ° C. Les kits positifs avaient une moyenne de 142,3 respirations par minute par rapport aux négatifs, ce qui a été déterminé à être 83,7. Le nombre de battements cardiaques par minute dans les kits avec une réaction positive au sévoflurane était en moyenne de 205 et ceux négatifs de 119,5. Des tremblements musculaires ont été observés dans tout le corps pendant l'exposition des kits positifs au sévoflurane. Il est conclu que pour 16 cobayes, 1 réagira positivement à l'exposition au gaz sévoflurane en raison du résultat obtenu à partir du signe vital. Seuls les positifs présentaient des tremblements musculaires.

Efficiency and safety of use of the extemporal inhalation anesthetic “Sevoflurane Chemoteka” for anesthetic management in abdominal surgery

Sevoflurane is the most widely used modern inhalational anesthetic in the world. Sevoflurane is the “gold standard” for anesthetic management now. The article discusses the modern possibilities of using inhalation anesthesia, and the experience of using the domestic inhalational anesthetic “Sevoflurane Chemoteka” by the authors from the point of view of its effectiveness and safety.

Volatile Anesthetic Sevoflurane Precursor 1,1,1,3,3,3-Hexafluoro-2-Propanol (HFIP) Exerts an Anti-Prion Activity in Prion-Infected Culture Cells

Prion disease is a neurodegenerative disorder with progressive neurologic symptoms and accelerated cognitive decline. The causative protein of prion disease is the prion protein (PrP), and structural transition of PrP from the normal helix rich form (PrPC) to the abnormal β-sheet rich form (PrPSc) occurs in prion disease. While so far numerous therapeutic agents for prion diseases have been developed, none of them are still useful. A fluorinated alcohol, hexafluoro isopropanol (HFIP), is a precursor to the inhalational anesthetic sevoflurane and its metabolites. HFIP is also known as a robust α-helix inducer and is widely used as a solvent for highly aggregated peptides. Here we show that the α-helix-inducing activity of HFIP caused the conformational transformation of the fibrous structure of PrP into amorphous aggregates in vitro. HFIP added to the ScN2a cell medium, which continuously expresses PrPSc, reduced PrPSc protease resistance after 24-h incubation. It was also clarified that ScN2a cells are more susceptible to HFIP than any of the cells being compared. Based on these findings, HFIP is expected to develop as a therapeutic agent for prion disease.

Analgesic Effectiveness and Improvement in Quality of Life after Using Topical Sevoflurane for an Extremely Painful Anal Fissure

Painful anal fissures could be distressing conditions that severely impair the patients' quality of life. The analgesic effectiveness of topical drugs, such as calcium-antagonists and nitrates is quite variable. The inhalational anesthetic sevoflurane is being repurposed as a topical analgesic for painful chronic wounds. We report a pioneer experience treating a painful chronic anal fissure with topical sevoflurane. A young adult male was suffering from an extremely painful chronic anal fissure, which severely affected his quality of life. The topical treatment with nitroglycerine and diltiazem gels failed. The patient agreed to the treatement with topical sevoflurane as an off-label medication, and it produced an immediate, intense, and long-lasting analgesic effect. An intense but rapidly transient burning sensation, as well as persistent but well-tolerated flatulence were the only adverse effects. The quality of life was greatly improved, and the cost of the treatment was affordable. Therefore, the off-label use of topical sevoflurane appears to be an effective alternative for the symptomatic treatment of painful anal fissures.

Involvement of Mitochondrial Dynamics and Mitophagy in Sevoflurane-Induced Cell Toxicity

General anesthesia is a powerful and indispensable tool to ensure the accomplishment of surgical procedures or clinical examinations. Sevoflurane as an inhalational anesthetic without unpleasant odor is commonly used in clinical practice, especially for pediatric surgery. However, the toxicity caused by sevoflurane has gained growing attention. Mitochondria play a key role in maintaining cellular metabolism and survival. To maintain the stability of mitochondrial homeostasis, they are constantly going through fusion and fission. Also, damaged mitochondria need to be degraded by autophagy, termed as mitophagy. Accumulating evidence proves that sevoflurane exposure in young age could lead to cell toxicity by triggering the mitochondrial pathway of apoptosis, inducing the abnormalities of mitochondrial dynamics and mitophagy. In the present review, we focus on the current understanding of mitochondrial apoptosis, dynamics and mitophagy in cell function, the implications for cell toxicity in response to sevoflurane, and their underlying potential mechanisms.