Comparison of Proparacaine, Tetracaine, and Oxybuprocaine in Corneal Sensitivity Measurement.

Purpose: This study aimed to determine the onset and duration of action of 3 commercially available topical anesthetic solutions in Brazil, using the Cochet-Bonnet esthesiometer (Luneau®, Paris, France) and to quantitatively assess patient-reported discomfort during application. Methods: A prospective, randomized, masked, and double-blind study was conducted, involving 40 eyes from 21 patients. Patients were administered each one of the topical anesthetics weekly, and corneal sensitivity was measured using the Cochet-Bonnet esthesiometer's corneal touch threshold (CTT). Patients rated the burning sensation using a visual analogue scale (VAS). Results: Among the 21 patients (42.9% male), with a mean age of 31.95 years (±standard deviation = 10.17, range = 22.0-58.0), corneal sensitivity significantly decreased 30 s after application, returning to baseline after 30 min for all groups (P < 0.0001). Significant differences in CTT were observed at 5 min, with proparacaine exhibiting a superior anesthetic effect (P = 0.0003), at 10 min, where tetracaine displayed the most substantial anesthetic effect (P = 0.0135), and at 20 min, where tetracaine demonstrated the highest anesthetic efficacy (P < 0.0001). VAS scores indicated the most intense burning sensation with tetracaine (P < 0.0001). Men reported experiencing more discomfort during instillation compared with women (P = 0.0168). Conclusions: Proparacaine exhibited the fastest onset of action among the 3 topical anesthetics and provided a more comfortable eye sensation during instillation. However, tetracaine demonstrated the longest duration of action despite causing more discomfort.

A comparative evaluation of peppermint oil and lignocaine spray as topical anesthetic agents prior to local anesthesia in children: a randomized clinical trial.

Background: In pediatric dentistry, fear and anxiety are common among children. Local anesthetics (LA) are widely used to control pain and reduce discomfort in children during dental treatment. Topical anesthetics play a vital role in reducing pain and the unpleasant sensation of a needle puncture in children. Peppermint oil has been extensively used for various diseases. However, its anesthetic properties remain unknown. Peppermint oil, used in mouthwashes, toothpastes, and other topical preparations has analgesic, anesthetic, and antiseptic properties. This study aimed to compare and evaluate pain perception following the topical application of peppermint oil versus lignocaine spray before an intraoral injection in children, aged 8-13 years. Method: Fifty-two children, aged between 8-13 years, who required local anesthesia for dental treatment were divided into two groups of 26 each by simple random sampling (Group 1: 0.2% peppermint oil and Group 2: lignocaine spray). In both groups, physiological measurements (e.g., heart rate) were recorded using pulse oximetry before, during, and after the procedure. Objective pain measurement (Sound Eye Motor (SEM) scale) during administration and subjective measuremeant (Wong-Baker Faces Pain Rating Scale (WBFPRS)) after LA administration were recorded. This was followed by the required treatment of the child.Physiological parameters were compared between the two groups using an independent t-test for intergroup assessment and a paired t-test and repeated-measures ANOVA for intragroup comparisons. The Mann-Whitney U test was used to analyze the pain scores. Results: Intragroup mean heart rates, before, during, and after treatment were statistically significantly different (P < 0.05). However, the intergroup mean pulse rates did not differ significantly between the two groups. The mean WBFPS score in the lignocaine spray group was 4.133 ± 2.06 was statistically different from that of the peppermint oil group (0.933 ± 1.03; P < 0.001*). The mean SEM score was significantly lower in the peppermint oil group than that in the lignocaine spray group (P = 0.006). No negative effects were observed in this study. Conclusion: 0.2% peppermint oil was effective in reducing pain perception.

Efficacy of sucrose application in minimizing pain perception related to dental injection in children aged 3 to 9 years: a randomized control trial.

Background: Dental fear and anxiety are significant challenges in managing behavior in children. Oral administration of sucrose or sweet-tasting solutions has shown effectiveness in reducing procedural pain in infants and neonates. This study aimed to investigate whether pre-application of sucrose solution had an effect on minimizing pain perception during injection and to assess the potential impact of the child's age and sweet preference. Methods: A randomized control clinical trial was conducted on 60 children aged 3-9 years requiring buccal infiltration injections. Following parental consent, demographic data of the children were recorded. Sweet preferences was assessed using a modified forced-choice test. Children were equally and randomly allocated into study (sucrose) and control groups using a lottery method. Sucrose solution or distilled water, respectively, was applied to the lateral surface of the tongue for 2 min. Topical anesthetic was applied at the site of injection, followed by local anesthesia administration. The children rinsed their mouths thrice with water immediately after anesthetic injection. A video was recorded during injection which was then scored by three blinded examiners on the Sound Eye Motor (SEM) scale. The children also self-evaluated using Wong-Baker Faces Pain Rating Scale (WBFPS). Results: The mean SEM scores and WBFPS scores were analyzed using the Kruskall-Wallis test. The mean SEM score in the study group was 1.37 ± 0.61, compared to 3.17 ± 0.87 in the control group, showing a statistically significant difference (P < 0.001). Mean pain scores assessed by WBFPS in the study group were 0.60 ± 1.4, while in the control group, they were 6.27 ± 2.33, also showing a statistically significant difference (P < 0.001). Children with a sweet preference demonstrated a subjective reduction in pain perception. Conclusion: Application of sucrose before dental injections in children helps to minimize pain upon injection across all age groups.

Effectiveness of pre-injection use of cryoanesthesia as compared to topical anesthetic gel in reducing pain perception during palatal injections: a randomized controlled trial.

Background: Palatal injections are often painful. We aimed to compare topical ice and 20% benzocaine gel for pre-injection anesthesia before greater palatine nerve block (GPNB) injections. Methods: A randomized split-mouth clinical trial was conducted among patients aged 15-60-years needing bilateral GPNB injections. A total of 120 palatal sites from 60 patients were randomly allocated to Group A (topical ice) or Group B (20% benzocaine gel). Pain was evaluated using sound, eye, motor (SEM), and the visual analog scale (VAS) in both groups. Inferential analysis was performed using the Mann-Whitney U test. Results: The mean age of the participants was 20.5 ± 3.9 years. The median VAS score for group A was 11 (Q1 - Q3: 5.25 - 21.75), which was slightly higher than the 10 (Q1 - Q3: 4.0 - 26.75) reported in group B. However, the difference was not statistically significant (P = 0.955). The median SEM score for group A and group B was 3.5 (Q1 - Q3: 3.0 - 4.0) and 4.0 (Q1 - Q3: 3.0 - 4.0), respectively, which was statistically insignificant (P = 0.869). Conclusion: Using ice as a form of topical anesthetic for achieving pre-injection anesthesia before GPNB was as effective as 20% benzocaine gel.

Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia.

Apart from being a significant line of defense in the host defense system, neutrophils have many immunological functions. Although there are not many publications that accurately present the functions of neutrophils in relation to oncological pathology, their activity and implications have been studied a lot recently. This review aims to extensively describe neutrophils functions'; their clinical implications, especially in tumor pathology; the value of clinical markers related to neutrophils; and the implications of neutrophils in onco-anesthesia. This review also aims to describe current evidence on the influence of anesthetic drugs on neutrophils' functions and their potential influence on perioperative outcomes.

Periarticular Infiltration Compared to Single Femoral Nerve Block in Total Knee Arthroplasty: A Prospective Randomized Study.

Objective To compare patients undergoing total knee arthroplasty (TKA) under spinal anesthesia and single femoral nerve block (FNB) with subjects undergoing TKA under spinal anesthesia and periarticular infiltration (PAI). Materials and Methods A total of 100 patients undergoing primary TKA were randomized into two groups. Group 1 included patients undergoing surgery under FNB associated with spinal anesthesia, while group 2 included patients undergoing TKA under IPA and spinal anesthesia. The assessment of these subjects in the early postoperative period included pain, active flexion, active extension, elevation of the extended limb, and morphine use. Results There was no significant difference in the types of analgesia concerning pain, the elevation of the extended limb, and morphine use. Active flexion and extension were better in the PAI group ( p = 0.04 and p = 0.02 respectively). Conclusion We conclude that the techniques are similar regarding pain control, limb elevation, and morphine use. The use of IPA provided better active flexion and extension during the hospital stay compared to single FNB in patients undergoing TKA.

Sustained release local anesthetics for pain management: relevance and formulation approaches.

This review attempted to ascertain the rationale for the formulation of sustained-release local anesthetics and summarize the various formulation approaches designed to date to achieve sustained and localized local analgesic effects. The incidence of pain, which is the concern of patients as well as health care professionals, is increasing due to accidents, surgical procedures, and other diseases. Local anesthetics can be used for the management of moderate to severe acute and chronic pain. They also allow regional analgesia, in situations where the cause and source of the pain are limited to a particular site or region, without the need for loss of consciousness or systemic administration of other analgesics thereby decreasing the risk of potential toxicities. Though they have an interesting antipain efficacy, the short duration of action of local anesthetics makes the need for their multiple injections or opioid adjuvants mandatory. To overcome this problem, different formulations are being designed that help achieve prolonged analgesia with a single dose of administration. Combination with adjuvants, liposomal formulations, lipid-based nanoparticles, thermo-responsive nanogels, microspheres, microcapsules, complexation with multivalent counterions and HP-ß-CD, lipid-based nanoparticles, and bio-adhesive films, and polymeric matrices are among the approaches. Further safety studies are required to ensure the safe and effective utilization of sustained-release local anesthetics. Moreover, the release kinetics of the various formulations should be adequately established.

Local anesthetics inhibit muscarinic acetylcholine receptor-mediated calcium responses and the recruitment of ß-arrestin in HSY human parotid cells.

OBJECTIVES: Local anesthetics act on G protein-coupled receptors (GPCRs); thus, their potential as allosteric modulators of GPCRs has attracted attention. Intracellular signaling via GPCRs involves both G-protein- and ß-arrestin-mediated pathways. To determine the effects of local anesthetics on muscarinic acetylcholine receptors (mAChR), a family of GPCRs, we analyzed the effects of local anesthetics on mAChR-mediated Ca2+ responses and formation of receptor-ß-arrestin complexes in the HSY human parotid cell line. METHODS: Ca2+ responses were monitored by fura-2 spectrofluorimetry. Ligand-induced interactions between mAChR and ß-arrestin were examined using a ß-arrestin GPCR assay kit. RESULTS: Lidocaine reduced mAChR-mediated Ca2+ responses but did not change the intracellular Ca2+ concentration in non-stimulated cells. The membrane-impermeant lidocaine analog QX314 and procaine inhibited mAChR-mediated Ca2+ responses, with EC50 values of 48.0 and 20.4 µM, respectively, for 50 µM carbachol-stimulated Ca2+ responses. In the absence of extracellular Ca2+, the pretreatment of cells with QX314 reduced carbachol-induced Ca2+ release, indicating that QX314 reduced Ca2+ release from intracellular stores. Lidocaine and QX314 did not affect store-operated Ca2+ entry as they did not alter the thapsigargin-induced Ca2+ response. QX314 and procaine reduced the carbachol-mediated recruitment of ß-arrestin, and administration of procaine suppressed pilocarpine-induced salivary secretion in mice. CONCLUSION: Local anesthetics, including QX314, act on mAChR to reduce carbachol-induced Ca2+ release from intracellular stores and the recruitment of ß-arrestin. These findings support the notion that local anesthetics and their derivatives are starting points for the development of functional allosteric modulators of mAChR.

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.

Transversus Abdominis Plane Block versus Epidural Anesthesia for Pain Management Post-Caesarean Delivery: A Pilot Study.

Background: Effective post-operative analgesia profoundly influences patient recovery and outcomes after caesarean delivery. The Transversus Abdominis Plane (TAP) block represents a potential alternative, potentially offering greater effectiveness than epidural analgesia while causing fewer adverse effects. Objective: To assess if the abdominal transverse block provides superior postoperative pain relief in patients undergoing caesarean delivery compared to epidural analgesia. Methods: Participants were divided into parallel groups: an experimental group receiving TAP block (n=25) and a control group receiving epidural analgesia (n=24). All patients received a 10 mg dose of hyoscine at the end of the surgery. Experimental Group received a total of 20 mL of 0.2% ropivacaine. In Epidural group received 0.2% ropivacaine at 4 mL/h for 24 hours. All participants were administered combined with neuroaxial block anesthesia. The patients selected for epidural analgesia received the mentioned dose, while the other group block had the epidural catheter removed after the cesarean section. The primary outcome was post-caesarean pain, evaluated using the Visual Analog Scale (VAS) at four intervals (0, 6, 12, and 24 hours). Also, surgical bleeding and residual motor were evaluated. VAS pain scores between the groups were compared using the Friedman test and Generalized Linear Model (GLM) for non-normally distributed data. The effect size was estimated with Eta Square ([Formula: see text]), considering values ≥0.38 as indicative of large effects. A two-tailed p-value < 0.05 was deemed statistically significant. Results: Statistically significant differences in pain scores were noted at 0 and 6 hours post-surgery (p<0.01). The TAP block group reported lower pain scores at 0 hours (mean=0.04) and 6 hours (mean=1.16) compared to the epidural group, reflecting a substantial effect size. Conclusion: The TAP block proves advantageous in mitigating postoperative pain for women post-caesarean delivery, particularly in the initial 6 postpartum hours. This relief promotes early mother-infant bonding and facilitates breastfeeding.

AG-920 (Articaine) Ophthalmic Solution: A Masked, Active-Controlled Evaluation of Its Local Anesthetic Efficacy and Safety in Pediatric Patients.

Purpose: The safety and efficacy of a novel topical ocular anesthetic (AG-920 sterile ophthalmic solution, 8%) was previously evaluated in adults. For both clinical and regulatory purposes, this new agent was evaluated in children. Methods: This was a Phase 3, randomized, active-controlled, single-masked, parallel-group design study in healthy pediatric subjects performed at a private practice retina clinic in the United States. The safety and anesthetic efficacy of AG-920 was compared with proparacaine hydrochloride ophthalmic solution 0.5% in 60 children undergoing ophthalmic examinations. The primary efficacy endpoint was whether the investigator was able to perform the eye examination. Results: In all subjects in each treatment group, the investigator was able to perform the eye examination without additional local anesthetic. There were no adverse events reported in this study. In both the study eye and fellow eye, there were no notable changes after dosing, and both treatment groups were similar. All external eye exams in all subjects in both treatment groups were normal. Conclusions: In this pediatric population aged 7 months to >11 years, AG-920 was therapeutically equivalent to marketed proparacaine with respect to having an ophthalmic examination performed without needing additional local anesthetic. Further, AG-920 was well tolerated, and there were no clinically significant safety findings.

Voltage Gated Ion Channels: Structure, Pharmacology and Photopharmacology.

Voltage-gated ion channels are transmembrane proteins responsible for the generation and propagation of action potentials in excitable cells. In the past few years, crystal structures of ion channels have become accessible and, when combined with mutagenesis data, have aided in the discovery of drugs that can modulate ion conduction. However, many traditional drugs lack selectivity and come with adverse side effects. The emergence of photopharmacology has provided an orthogonal way of controlling the activity of compounds, enabling the regulation of ion conduction with light. In this review, we explore the central pore region of voltage-gated sodium and potassium channels, providing insights from both structural and pharmacological perspectives. We discuss the different binding modes of synthetic compounds that can physically occlude the pore and, therefore, block the ion conduction. Moreover, we examine recent advances in the photopharmacology of voltage-gated ion channels, introducing molecular approaches aimed at controlling their activity by using photosensitive drugs.

Effect of Sevoflurane, Isoflurane, and Desflurane on the Random Blood Glucose Levels in Non-diabetic Patients Undergoing General Anesthesia: A Randomized, Single-Blind Study.

BACKGROUND: Volatile anesthetic agents like sevoflurane, isoflurane, and desflurane are widely used for maintaining general anesthesia (GA). Their effect on the autonomic system is different and can impact the blood sugar homeostasis. This study compares the intraoperative blood glucose levels in non-diabetic patients undergoing non-cardiac surgery under GA with the three volatile agents. METHODS: A randomized, single-blind, parallel-arm study recruited 105 non-diabetic patients into three groups. GA induction and maintenance were standardized except for the volatile agent. Capillary blood sugar levels were measured at different time points and compared between and within the groups. A p-value of <0.05 was considered significant. RESULTS: Entire participants completed the study, and their baseline characteristics were statistically indifferent. Intraoperative blood glucose rise and variation were the highest in the desflurane group and the lowest in the isoflurane group; the differences were statistically significant at 15, 30, and 45 minutes. The highest blood sugar level was noted at 60 minutes in all groups; after that, the level started falling. However, none of the raises were beyond 140 mg% to categorize them as hyperglycemia. CONCLUSION: Intraoperative glycemic variation was evident with isoflurane, sevoflurane, and desflurane. The maximum increase from the pre-induction level was noted at 60 minutes. However, none of the readings reached the hyperglycemia level. The rise was significantly higher in desflurane-based anesthesia than in isoflurane. This study was, however, conducted in non-diabetic patients; hence, results might not be extrapolated to diabetic patients.

Trial watch: local anesthetics in cancer therapy.

Preclinical evidence indicates potent antitumor properties of local anesthetics. Numerous underlying mechanisms explaining such anticancer effects have been identified, suggesting direct cytotoxic as well as indirect immunemediated effects that together reduce the proliferative, invasive and migratory potential of malignant cells. Although some retrospective and correlative studies support these findings, prospective randomized controlled trials have not yet fully confirmed the antineoplastic activity of local anesthetics, likely due to the intricate methodology required for mitigating confounding factors. This trial watch aims at compiling all published preclinical and clinical research, along with completed and ongoing trials, that explore the potential antitumor effects of local anesthetics.

The Effects of Low Viscosity Preservative-Free Chloroprocaine Ophthalmic Gel 3% versus BAK-Containing Tetracaine 0.5% on the Bactericidal Action of Povidone-Iodine.

Purpose: To evaluate if chloroprocaine ophthalmic gel 3% acts as a barrier to the bactericidal actions of povidone-iodine (PVI) which has been seen in other higher viscosity gel anesthetics. Methods: This was a single site, prospective, randomized, patient-masked study evaluating the effects of preservative-free chloroprocaine ophthalmic gel 3% (IHEEZO®, Harrow, Nashville, TN) compared with tetracaine ophthalmic solution 0.5% and their effects on the bactericidal action of povidone-iodine 5%. The study comprised 82 patients who had both eyes cultured before and after application of randomized treatment and povidone-iodine. Results: In terms of mean percent reduction in colony forming units, chloroprocaine with povidone-iodine was non-inferior to tetracaine with povidone-iodine, with a higher mean percent reduction in colony forming units in the chloroprocaine group (change [∆] = -7.2; 90% CI, -13.56 to 3.28). Conclusion: Data collected in this study suggest that preservative-free chloroprocaine ophthalmic gel 3% does not act as a barrier to the bactericidal actions of povidone-iodine 5% and that the reduction in CFU from PVI is similar when compared with tetracaine 0.5% ophthalmic solution with PVI.

Depth of anesthesia monitoring in Norway-A web-based survey.

BACKGROUND: The bispectral index (BIS) monitor is the most frequently used electroencephalogram (EEG)-based depth of anesthesia (DoA) technology in Norwegian hospitals. However, there is limited knowledge regarding the extent and clinical impact of its use and how anesthesiologists and nurse anesthetists use the information provided by the DoA monitors in their clinical practice. METHODS: This cross-sectional survey on the use of DoA monitors in Norway used a web-based questionnaire distributed to anesthesia personnel in all hospitals in Norway. Participation was voluntary and anonymized, and the web form could not track IP sources or respondents' locations. RESULTS: Three hundred and ninety-one nurse anesthetists (n = 324) and anesthesiologists (n = 67) responded. Among the EEG-based DoA monitoring tools, BIS was most often used to observe and assess patients' DoA (98%). Raw EEG waveform analysis (10%), EEG-spectrogram (9%), and suppression rate (10%) were seldom used. Twenty-seven percent of the anesthesia personnel were able to recognize a burst suppression pattern on EEG and its significance. Fifty-eight percent of the respondents considered clinical observations more reliable than BIS. Almost all respondents reported adjusting anesthetic dosage based on the BIS index values (80%). However, the anesthetic dose was more often increased (90%) because of high BIS index values than lowered (55%) because of low BIS index values. CONCLUSION: Despite our respondents' extensive use of DoA monitoring, the anesthesia personnel in our survey did not use all the information and the potential to guide the titration of anesthetics the DoA monitors provide. Thus, anesthesia personnel could generally benefit from increased knowledge of how EEG-based DoA monitoring can be used to assess and determine individual patients' need for anesthetic medication.

Early sevoflurane sedation in severe COVID-19-related lung injury patients. A pilot randomized controlled trial.

BACKGROUND: This study aimed to assess a potential organ protective effect of volatile sedation in a scenario of severe inflammation with an early cytokine storm (in particular IL-6 elevation) in patients suffering from COVID-19-related lung injury with invasive mechanical ventilation and sedation. METHODS: This is a small-scale pilot multicenter randomized controlled trial from four tertiary hospitals in Switzerland, conducted between April 2020 and May 2021. 60 patients requiring mechanical ventilation due to severe COVID-19-related lung injury were included and randomized to 48-hour sedation with sevoflurane vs. continuous intravenous sedation (= control) within 24 h after intubation. The primary composite outcome was determined as mortality or persistent organ dysfunction (POD), defined as the need for mechanical ventilation, vasopressors, or renal replacement therapy at day 28. Secondary outcomes were the length of ICU and hospital stay, adverse events, routine laboratory parameters (creatinine, urea), and plasma inflammatory mediators. RESULTS: 28 patients were randomized to sevoflurane, 32 to the control arm. The intention-to-treat analysis revealed no difference in the primary endpoint with 11 (39%) sevoflurane and 13 (41%) control patients (p = 0.916) reaching the primary outcome. Five patients died within 28 days in each group (16% vs. 18%, p = 0.817). Of the 28-day survivors, 6 (26%) and 8 (30%) presented with POD (p = 0.781). There was a significant difference regarding the need for vasopressors (1 (4%) patient in the sevoflurane arm, 7 (26%) in the control one (p = 0.028)). Length of ICU stay, hospital stay, and registered adverse events within 28 days were comparable, except for acute kidney injury (AKI), with 11 (39%) sevoflurane vs. 2 (6%) control patients (p = 0.001). The blood levels of IL-6 in the first few days after the onset of the lung injury were less distinctly elevated than expected. CONCLUSIONS: No evident benefits were observed with short sevoflurane sedation on mortality and POD. Unexpectedly low blood levels of IL-6 might indicate a moderate injury with therefore limited improvement options of sevoflurane. Acute renal issues suggest caution in using sevoflurane for sedation in COVID-19. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (NCT04355962) on 2020/04/21.

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.

Cognitive trajectories after surgery: Guideline hints for assessment and treatment.

Elderly patients who undergo major surgery (not-neurosurgical) under general anaesthesia frequently complain about cognitive difficulties, especially during the first weeks after surgical "trauma". Although recovery usually occurs within a month, about one out of four patients develops full-blown postoperative Neurocognitive disorders (NCD) which compromise quality of life or daily autonomy. Mild/Major NCD affect approximately 10% of patients from three months to one year after major surgery. Neuroinflammation has emerged to have a critical role in the postoperative NCDs pathogenesis, through microglial activation and the release of pro-inflammatory cytokines which increase blood-brain-barrier permeability, enhance movement of leukocytes into the central nervous system (CNS) and favour the neuronal damage. Moreover, pre-existing Mild Cognitive Impairment, alcohol or drugs consumption, depression and other factors, together with several intraoperative and post-operative sequelae, can exacerbate the severity and duration of NCDs. In this context it is crucial rely on current progresses in serum and CSF biomarker analysis to frame neuroinflammation levels, along with establishing standard protocol for neuropsychological assessment (with specific set of tools) and to apply cognitive training or neuromodulation techniques to reduce the incidence of postoperative NCDs when required. It is recommended to identify those patients who would need such preventive intervention early, by including them in pre-operative and post-operative comprehensive evaluation and prevent the development of a full-blown dementia after surgery. This contribution reports all the recent progresses in the NCDs diagnostic classification, pathogenesis discoveries and possible treatments, with the aim to systematize current evidences and provide guidelines for multidisciplinary care.

Impact of anesthetics on rat hippocampus and neocortex: A comprehensive proteomic study based on label-free mass spectrometry.

Anesthesia is regarded as an important milestone in medicine. However, the negative effect on memory and learning has been observed. In addition, the impact of anesthetics on postoperative cognitive functions is still discussed. In this work, in vivo experiment simulating a general anesthesia and ICU sedation was designed to assess the impact of two intravenous (midazolam, dexmedetomidine) and two inhalational (isoflurane, desflurane) agents on neuronal centers for cognition (neocortex), learning, and memory (hippocampus). More than 3600 proteins were quantified across both neocortex and hippocampus. Proteomic study revealed relatively mild effects of anesthetics, nevertheless, protein dysregulation uncovered possible different effect of isoflurane (and midazolam) compared to desflurane (and dexmedetomidine) to neocortical and hippocampal proteins. Isoflurane induced the upregulation of hippocampal NMDAR and other proteins of postsynaptic density and downregulation of GABA signaling, whereas desflurane and dexmedetomidine rather targeted mitochondrial VDAC isoforms and protein regulating apoptotic activity.