Anesthesia,Anesthetics,and Postoperative Cognitive Dysfunction in Elderly Patients

Postoperative cognitive dysfunction(POCD)remains a major issue that worsens the prognosis of elderly surgery patients.This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients,aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols,ultimately reducing the incidence of POCD in elderly surgery patients.

Inhaled volatile anesthetics in the intensive care unit

The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th century.Recently,a paradigm shift is observed as volatile anesthetics extend beyond traditional confines of the operating theatres,finding diverse applications in intensive care settings.In the dynamic landscape of intensive care,volatile anesthetics emerge as a promising avenue for addressing complex sedation requirements,managing refractory lung pathologies including acute respiratory distress syndrome and status asthmaticus,conditions of high sedative requirements including burns,high opioid or alcohol use and neurological conditions such as status epilepticus.Volatile anesthetics can be administered through either inhaled route via anesthetic machines/devices or through extracorporeal membrane oxygenation circuitry,providing intensivists with multiple options to tailor therapy.Furthermore,their unique pharmacokinetic profiles render them titratable and empower clinicians to individualize management with heightened accuracy,mitigating risks associated with conventional sedation modalities.Despite the amounting enthusiasm for the use of these therapies,barriers to widespread utilization include expanding equipment availability,staff familiarity and training of safe use.This article delves into the realm of applying inhaled volatile anesthetics in the intensive care unit through discussing their pharmacology,administration considerations in intensive care settings,complication considerations,and listing indications and evidence of the use of volatile anesthetics in the critically ill patient population.

Comparative studies on the binding site of anesthetics to GABA a receptors using in silico docking methods

Although the GABAA receptor(GABAAR)has been proposed as the main action site for sevoflurane,isoflurane,halothane,enflurane,propofol,and benzodiazepines(BZDs),binding of these anesthetics with high-resolution structures of the GABAAR have been rarely examined by comparative docking analyses.Moreover,various combinations of ligands on more GABAARs with various subtypes need to be analyzed to understand the elaborate action mechanism of GABAARs better because some GABAA ligands showed specificity toward the distinct subtypes of the GABAAR.Methods:We performed in silico docking analysis to compare the binding modes of sevoflurane,isoflurane,halothane,enflurane,propofol,and BZDs to the GABAAR based on one of the most recently provided 3D structures.We performed the docking analysis and the affinity-based ranking of the binding sites.Results:Our docking studies revealed that isoflurane,halothane,and enflurane docked in an extracellular domain(ECD)on GABAARs,in contrast to sevoflurane.Conclusion:Our results supported a multi-site mechanism for the allosteric modulation of propofol.Propofol was bound to the pore or favored various subsites in the transmembrane domain(TMD).Our result confirmed that different chemically related BZD ligands interact via distinct binding modes rather than by using a common binding mode,as previously suggested.

Adjuvants to local anesthetics: Current understanding and future trends

Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids(dexamethasone), anti-inflammatory agents(parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action(tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability(liposomal, microspheres and cyclodextrin systems) and further studies with other drugs(adenosine, neuromuscular blockers, dextrans).

Protective effects of intravenous anesthetics on kidney tissue in obstructive jaundice

AIM: To evaluate the protective effects on kidney tissue of frequently used intravenous anesthetics (ketamine, propofol, thiopental, and fentanyl) in rats with obstructive jaundice.

Effect of Inhalational Anesthetics on Cytotoxicity and Intracellular Calcium Differently in Rat Pheochromocytoma Cells (PC12)

Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in rat pheochromocytoma cells （PC12） in a concentration- and time-dependent manner with unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum （ER） via activation of inositol 1,4,5-trisphosphate （IP3） receptors. Alzheimer＇s presenilin-1 （PS 1） mutation increased activity of IP3 receptors and therefore rendered cells vulnerable to isoflurane-induced cytotoxicity. Sevoflurane and desflurane had less ability to disrupt intracellular calcium homeostasis and thus being less potent pared the cytotoxic effects of various inhaled to cause cytotoxicity. This study examined and com-anesthetics on PC12 cells transfected with the Alzheimer＇s mutated PS 1 （L286V） and the disruption of intracellular calcium homeostasis. PC 12 cells transfected with wild type （WT） and mutated PS 1 （L286V） were treated with equivalent of 1 MAC of isoflurane, sevoflurane and desflurane for 12 h. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in cytosolic space （[Ca^2＋]c） were determined after exposing different types of cells to various inhalational anesthetics. The effects of IP3 receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in L286V PC12 cells were also determined. The results showed that isoflurane at 1 MAC for 12 h induced cytoxicity in L286V but not WT PC12 cells, which was also associated with greater and faster elevation of peak [Ca^2＋]c in L286V than in the WT cells. Xestospongin C significantly ameliorated isoflurane cytotoxicity in L286V cells, as well as inhibited the calcium release from the ER in L286V cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar cytotoxicity or elevation of peak [Ca^2＋]c in L286V PC 12 cells. These results suggested that isoflurane induced cytoxicity by partially causing abnormal calcium release from the ER via activation of IP3 receptors in L286V PC12 cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar elevation of [Ca^2＋]c or neurotoxicity in PC 12 cells transfected with the Alzheimer＇s PS 1 mutation.

Why Labor Epidural Causes Fever and Why Lidocaine Burns on Injection? Role of TRPV 1 Receptor in Hyperthermia: Possible Explanation of Mechanism of Hyperthermia during Labor Epidural and Burning Sensation on Injection of Local Anesthetics

The mechanisms of epidural-associated fever remain incompletely understood [1-3]. We propose that action of local anesthetic on TPRV1. The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor can explain this effect and explain mechanism of burning sensation on local anesthetic injected subcutaneously or intramuscular. Role of TRPV1 receptor was not discussed previously in Obstetric Anesthesia literature. Based on available data, we propose that Local Anesthetics work as agonist/antagonist on TPRV1 receptors. Antagonist action may cause hyperthermia through modifying thermoregulation [4], agonist action may cause hyperthermia thru release of IL-6 and other mediators of inflammation [5-10]. Agonist action may explain burning sensation on injection of Local Anesthetics. Burning sensation can be diminished by increasing pH of Local Anesthetic solution, because vanillin receptors are stimulated by acidification through lower pH [11,12].

Anesthetic Action of Volatile Anesthetics by Using Paramecium as a Model

Although empirically well understood in their clinical administration, volatile anesthetics are not yet well comprehended in their mechanism studies. A major conundrum emerging from these studies is that there is no validated model to assess the presumed candidate sites of the anesthetics. We undertook this study to test the hypothesis that the single-celled Paramecium could be anesthetized and served as a model organism in the study of anesthetics. We assessed the motion of Paramecium cells with Expert Vision system and the chemoresponse of Paramecium cells with T-maze assays in the presence of four different volatile anesthetics, including isoflurane, sevoflurane, enflurane and ether. Each of those volatiles was dissolved in buffers to give drug concentrations equal to 0.8, 1.0, and 1.2 EC50, respectively, in clinical practice. We could see that after application of volatile anesthetics, the swimming of the Paramecium cells was accelerated and then suppressed, or even stopped eventually, and the index of the chemoresponse of the Paramecium cells （denoted as Iche） was decreased. All of the above impacts were found in a concentration-dependent fashion. The biphasic effects of the clinical concentrations of volatile anesthetics on Paramecium simulated the situation of high species in anesthesia, and the inhibition of the chemoresponse also indicated anesthetized. In conclusion, the findings in our studies suggested that the single-celled Paramecium could be anesthetized with clinical concentrations of volatile anesthetics and therefore be utilized as a model organism to study the mechanisms of volatile anesthetics.

Analysis of the Effect of Anesthetics Comprising of Remifentanil Combined with Propofol During Thyroidectomy

Objective:To analyze the anesthetic effect of remifentanil combined with propofol during thyroidectomy.Methods:A total of 70 patients who underwent thyroidectomy during November 2018 to November 2019 in Chongqing Eleventh People’s Hospital were selected and recruited.These patients were divided into control group and observation group by random number table method.Each group consisted of 35 patients.The patients in the control group was given intravenous anesthesia comprising of propofol combined with intermittent fentanyl anesthesia,whereas the patients in the observation group was given intravenous anesthesia comprising of remifentanil combined with propofol.Results:The heart rate and mean arterial pressure of the observation group after anesthesia for 30 minutes were lower than those of the control group,and the differences were statistically significant(P<0.05).The total incidence of adverse reactions in the observation group was lower than that of the control group,and the differences were statistically significant(P<0.05).Conclusion:Remifentanil combined with propofol is effective in thyroidectomy.This combination can reduce the risk of adverse reactions and maintain stable hemodynamic parameters.

Effectiveness of Disinfection of Anesthetics Tubes in Oral Surgery -An in Vitro Study

Context： Anesthetic tubes are always on the surgical table, for this reason, it＇s necessary to perform its disinfection, generally by chemicals. Aim： Was to analyze the effectiveness of tubes decontamination made by disinfectant substances used in a clinical setting and to identify the microorganisms found on their surface. Materials and Methods： 14 anesthetic tubes were collected from dental clinic, on 5 groups. 01 plastic and 01 glass tubes that were not submitted to any disinfection process composed the control group and they had been sown in Agar Blood. Experimental groups underwent immersion and fixation with the proposed chemicals for 1 minute, laminar flow hood was used to seed it in Agar Blood and then it was transferred to incubator for 24 hours at 37℃. Tests were used to identify the main Gram positive pathogenic genera. Gram-negative pathogenic colonies isolated were seeded in biochemical means of identification. Results： It was possible to identify the presence of Staphylococcus coagulase negative, Staphylococcus aureus, Streptococcus viridans, Staphylococcus saprophyticus, Escherichia coli and Acinetobacter spp, as well as the effectiveness of chemical solutions proposed in this study. Conclusions： All chemical solutions proposed in this study were effective for the surface disinfection process of anesthetic tubes.

Neuroendocrine,epigenetic,and intergenerational effects of general anesthetics

The progress of modern medicine would be impossible without the use of general anesthetics(GAs).Despite advancements in refining anesthesia approaches,the effects of GAs are not fully reversible upon GA withdrawal.Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly.Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research,but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects.The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents,which are far more extensively studied than any other species.Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated.Specifically,we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities(somatic effects),but also epigenetic reprogramming of germ cells(germ cell effects).The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring,who may be affected even at levels of anesthesia that are not harmful to the exposed parents.The large number of patients who require general anesthesia,the even larger number of their future unexposed offspring whose health may be affected,and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs.In this mini review,we discuss emerging experimental findings on neuroendocrine,epigenetic,and intergenerational effects of GAs.

Different Volumes of Local Anesthetics in Ultrasound-Guided Combined Interscalene-Supraclavicular Block for Traumatic Humeral Fracture

Background: Procedures that require anesthesia of entire length of the arm should have combined Interscalene block (ISB) and Supraclavicular block (SCB) to ensure adequate block. However, dual block requires high dose of local anesthetic (LA). We examined if Ultrasound (U/S) guided block helps to decrease the required volume of LA by visualizing trunks, so we only need injection of LA toward cervical nerve roots C5 and C6 aiming to block branches escaped from supraclavicular block. Patients and methods: Ninety-three patients were randomly allocated into one of three equal groups, each included 31 patients. All patients received SCB 20 ml (10 ml Bupivacaine 0.5% plus 10 ml lidocaine 2%) and ISB with different volumes of LA according to the group as follow: group A: 20 ml, group B: 15 ml, and group C: 10 ml. Result: No significant difference in onset of block (sensory and motor) and duration of block (motor only) between the three groups (P value > 0.05). The duration of sensory block was significantly longer in group A (760.65 ± 30.87 minutes) than in either group B (740.48 ± 21.15 minutes, P value P value P value P value P value P value < 0.001). Conclusion: A reduced volume of LA can be used in ultra sound guided ISB in combined with SCB to give satisfactory level of anesthesia to entire length of the arm, but the sensory block duration and duration of post-operative analgesia will be decreased significantly with decreasing the volume.

Toxic keratopathy associated with abuse of topical anesthetics and amniotic membrane transplantation for treatment

AIMTo evaluate the clinical findings of toxic keratopathy associated with abuse of topical anesthetics and the treatment efficacy of amniotic membrane transplantation (AMT).METHODSFifteen eyes of 10 patients with abuse of topical anesthetics were included in this study. The data collected included patients' demographic information, initial best corrected visual acuity (BCVA), clinical findings, time to AMT, duration of epithelization, additional treatments, posttreatment BCVA, and the results of psychiatric examination.RESULTSAll patients were male, with the mean age of 37.9&#x000b1;5.4y. The patients had received 0.5% proparacaine hydrochloride due to pain resulting from foreign bodies, such as welding flash burns and car battery explosions, for a mean of 18.2&#x000b1;12.4d. The mean initial BCVA of the patients was 0.069&#x000b1;0.100. All patients had persistent epithelial defects, stromal infiltration, ring ulcer, and corneal edema. Initially, medical treatment was attempted in all cases. Because of severe pain, persistent epithelial defects and progressing stromal thinning did not improve with medical treatment, thus, the patients underwent AMT. The mean posttreatment BCVA of the patients was 0.33&#x000b1;0.27. All of them, except for two patients, showed improved visual acuity. One patient underwent evisceration for corneal melting and endophthalmitis in another center, and one patient underwent evisceration for severe pain of unknown origin. All 5 patients who consented to a psychiatric examination had depression, had personality disorder, and used tobacco.CONCLUSIONAMT appears to be an effective method for pain relief, rapid epithelial and stromal healing; however, visual prognosis is still poor despite medical and surgical interventions.

Designing General Anesthetics That Have a Better Safety Profile

General anesthetics constitute some of the most important and widely-used therapeutic drugs in the pharmacotherapeutic armamentarium. They are routinely used effectively and with adequate precaution-safety throughout the world for a multitude of clinical applications, predominantly as adjunctive agents for surgical procedures. Nevertheless, they have potential adverse effects (such as a drop in blood pressure and the inhibition of steroid production), particularly in vulnerable populations such as the very young and the frail elderly. It would be desirable therefore to have alternative agents that are just as efficacious, but have a better safety profile in a broader spectrum of patients. Toward this end, an anesthetic based on a unique chemical core (viz., an N-arylpyrrole derivative) has been reported in preclinical models to produce anesthetic effects without hemodynamic suppression. This lead could pave the way for new general anesthetics that are safer and easier to use.

Study of physisorption of volatile anesthetics on phos-pholipid monolayers using a highly sensitive quartz crystal microbalance (HS-QCM)

We have investigated the interactions between phospholipid monolayers and volatile anest-hatics. Two monolayers (dihexadecyl phosphate (DHP) and dipalmitoyl phosphatidyl choline (DPPC) and two anesthetics (halothane and enflurane) were used to observe these interac-tions using a highly sensitive quartz crystal microbalance (HS-QCM). The concentration of each anesthetic in aqueous solution was kept at 4 mM. The frequency of QCM showed no change when halothane was added to the DHP monolayer, however, it responded and de-creased when interaction occurred with DPPC monolayer. In case of enflurane addition the frequency decreased in both the monolayers of DHP and DPPC. The frequency change followed the following order of monolayer-anesthetic interactions: DHP-halothane <DPPC-halothane <DHP-enflurane <DPPC-enflurane. These re-sults showed that the response of anesthetics to the monolayers i.e. the physisorption not only depends on the anesthetic structure, the type of anesthetic hydrate formed, but also the hydrophilic polar group structure of the monolayer or the monolayer/water interface had an important role in physisorption.

Combined effect of hypothermia and crystalloid hemodilution on the solubility of volatile anesthetics in human blood

OBJECTIVE: To determine the combined effect of hypothermia and crystalloid hemodilution on blood solubility of volatile anesthetics. METHODS: Two hundred and thirty ml blood samples obtained from each of twelve healthy male volunteers were adjusted to a hematocrit of 40% and then diluted with normal saline to hematocrits of 36%, 32%, 28%, 24%, and 20%. Blood/gas partition coefficients of desflurane, sevoflurane, isoflurane, enflurane and halothane were measured at 37 degrees C,33 degrees C, 29 degrees C, 25 degrees C, 21 degrees C and 17 degrees C using a two-stage headspace double equilibration method. RESULTS: As the temperature decreased, the logarithm of the blood/gas partition coefficient increased linearly (P

The effects of local anesthetics on intracellular Ca2+ release from ryanod ine-sensitive Ca2+ stores in gerbil hippocampal neurons

OBJECTIVE: To examine the effects of procaine and lidocaine on intracellular Ca(2+) release from sarcoplasmic reticulum ryanodine-sensitive Ca(2+) stores. METHODS: The experiment was performed on hippocampal slices from 60-80 g male Mongolian gerbils. Levels of intracellular Ca(2+) concentration in the slices were measured by microfluorometry. The slices were perfused with 50 mmol/L KCl containing medium for 30 seconds. Then, the medium was switched to physiological medium. After 5 min of incubation, the slice was perfused with 20 mmol/L caffeine containing physiology medium for 2 min. Following incubation, the slice was superfused with physiological medium until the end of the experiment. The effects of procaine and lidocanin (100 micro mol/L) on caffeine-evoked Ca(2+) release were evaluated by adding them to the medium after high K(+) medium perfusion. RESULTS: Caffeine induced a marked increase in intracellular Ca(2+) concentration which was then decreased 12% upon the addition of procaine (P

Impact of propofol and sevoflurane anesthesia on cognition and emotion in gastric cancer patients undergoing radical resection

BACKGROUND Propofol and sevoflurane are commonly used anesthetic agents for maintenance anesthesia during radical resection of gastric cancer.However,there is a debate concerning their differential effects on cognitive function,anxiety,and depression in patients undergoing this procedure.AIM To compare the effects of propofol and sevoflurane anesthesia on postoperative cognitive function,anxiety,depression,and organ function in patients undergoing radical resection of gastric cancer.METHODS A total of 80 patients were involved in this research.The subjects were divided into two groups:Propofol group and sevoflurane group.The evaluation scale for cognitive function was the Loewenstein occupational therapy cognitive assessment(LOTCA),and anxiety and depression were assessed with the aid of the self-rating anxiety scale(SAS)and self-rating depression scale(SDS).Hemodynamic indicators,oxidative stress levels,and pulmonary function were also measured.RESULTS The LOTCA score at 1 d after surgery was significantly lower in the propofol group than in the sevoflurane group.Additionally,the SAS and SDS scores of the sevoflurane group were significantly lower than those of the propofol group.The sevoflurane group showed greater stability in heart rate as well as the mean arterial pressure compared to the propofol group.Moreover,the sevoflurane group displayed better pulmonary function and less lung injury than the propofol group.CONCLUSION Both propofol and sevoflurane could be utilized as maintenance anesthesia during radical resection of gastric cancer.Propofol anesthesia has a minimal effect on patients'pulmonary function,consequently enhancing their postoperative recovery.Sevoflurane anesthesia causes less impairment on patients'cognitive function and mitigates negative emotions,leading to an improved postoperative mental state.Therefore,the selection of anesthetic agents should be based on the individual patient's specific circumstances.

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells.Oligodendrocytes perform essential roles in the central nervous system,including myelin sheath formation,axonal metabolism,and neuroplasticity regulation.They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation,and apoptosis.Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes.These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways,but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function.In this review,we summarize the effects of general anesthetic agents on oligodendrocytes.We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

General anesthetic agents induce neurotoxicity through astrocytes

Neuroscientists have recognized the importance of astrocytes in regulating neurological function and their influence on the release of glial transmitters.Few studies,however,have focused on the effects of general anesthetic agents on neuroglia or astrocytes.Astrocytes can also be an important target of general anesthetic agents as they exert not only sedative,analgesic,and amnesic effects but also mediate general anesthetic-induced neurotoxicity and postoperative cognitive dysfunction.Here,we analyzed recent advances in understanding the mechanism of general anesthetic agents on astrocytes,and found that exposure to general anesthetic agents will destroy the morphology and proliferation of astrocytes,in addition to acting on the receptors on their surface,which not only affect Ca^(2+)signaling,inhibit the release of brain-derived neurotrophic factor and lactate from astrocytes,but are even involved in the regulation of the pro-and anti-inflammatory processes of astrocytes.These would obviously affect the communication between astrocytes as well as between astrocytes and neighboring neurons,other neuroglia,and vascular cells.In this review,we summarize how general anesthetic agents act on neurons via astrocytes,and explore potential mechanisms of action of general anesthetic agents on the nervous system.We hope that this review will provide a new direction for mitigating the neurotoxicity of general anesthetic agents.