The Impact of Different Anesthetics on the Distribution and Cytotoxic Function of NK Cell Subpopulations: An In Vitro Study.

Only some subpopulations of natural killer (NK) cells have cytotoxic functionality, and the effects of anesthetics on these subpopulations are unknown. This study aimed to evaluate the in vitro effects of various anesthetics, both alone and in combination, on the distribution and cytotoxic function of NK cells and their subpopulations. Peripheral blood mononuclear cells (PBMCs) from eight healthy volunteers were treated for 4 h in vitro with dexmedetomidine, remifentanil, lidocaine, propofol, sevoflurane, and combinations in clinically relevant concentrations or left untreated. Flow cytometry was used to quantify the percentage of sampled NK cells and evaluate their distribution (CD56brightCD16neg, CD56brightCD16dim, CD56dimCD16neg, CD56dimCD16bright, and CD56negCD16bright) and cytotoxicity (Granzyme B (GrzB) and perforin) of NK cell subpopulations. Although the percentage of total NK cells did not change following exposure to anesthesia, the most important cytotoxic subpopulation (CD56dimCD16bright NK cells) decreased after exposure to both propofol (-3.58%, p = 0.045) and sevoflurane (-16.10%, p = 0.008) alone, and most combinations, especially in combination with lidocaine (propofol with lidocaine (-9.66%, p = 0.002) and sevoflurane with lidocaine (-21.90%, p < 0.001)). Dexmedetomidine and remifentanil had no effect on CD56dimCD16bright NK cells. Furthermore, no anesthetic regimen or combination altered the expression of GrzB and perforin in NK cells or NK cell subpopulations. In short, propofol and sevoflurane suppressed the highly cytotoxic phenotype (CD56dimCD16bright) of NK cells, with those exposed to sevoflurane combinations showing greater reductions. Immunosuppression was intensified with the inclusion of lidocaine in the anesthetic regimen.

Perioperative anaesthetic complications in healthy cats undergoing anaesthesia for neutering in first opinion practice.

OBJECTIVES: The aim of the present study was to identify the incidence of common perioperative anaesthetic complications in cats undergoing anaesthesia for neutering in three UK first opinion practices. METHODS: A retrospective anaesthetic record analysis was performed on cats anaesthetised for neutering at practices 1 and 2 between 9 December 2017 and 2 February 2021 and practice 3 between 9 March 2020 and 7 January 2021. A search of the practice management system identified all cats that had undergone neutering in the selected timeframe. Data from 1019 cats were included in the study. Information relating to patient characteristics and data from the anaesthesia session were extracted from electronic patient records and anaesthesia record charts and entered into an Excel spreadsheet. A definition of the complications was created after reviewing the literature and their incidence determined from the data set. Comparisons between different groups of cats in the study were made using a χ2 test for homogeneity or Fisher's exact tests to identify factors associated with increased incidence of complications. RESULTS: The anaesthetic-related mortality was 1/1019 (0.10%). The most common complications were hypotension (22.6%), bradycardia (16.7%) and hypothermia (13.8%). Less common complications were hypocapnia (12.7%), hypercapnia (8.7%), tachycardia (6.6%), apnoea (3.1%), hyperthermia (1.7%), hypertension (1.4%), endotracheal tube obstruction (1.1%), hypoxia (0.3%), undesirable recovery (0.6%) and cardiac arrhythmia (0.2%). Factors associated with increased risk of hypotension were acepromazine pre-anaesthetic medication, higher maximum isoflurane dose, longer anaesthetic duration and lower body weight. Factors associated with increased risk of bradycardia were medetomidine pre-anaesthetic medication, longer anaesthetic duration and higher body weight. Factors associated with increased risk of hypothermia were higher maximum isoflurane dose, increased anaesthetic duration and lower body weight. CONCLUSIONS AND RELEVANCE: This study showed that anaesthetic complications were frequently observed, with complications documented in 53.4% of the cats in the study. The information in this study may help to guide prioritisation of monitoring in feline anaesthesia.

Preoperative echocardiography and anesthetic drugs as predictors of post-induction hypotension during general anesthesia: a prospective observational study.

Post-induction hypotension (PIH) during general anesthesia is a serious concern due to its high incidence and association with adverse postoperative outcomes and prognosis. We prospectively enrolled consecutive 1,603 patients scheduled for non-cardiac and cardiac surgery under general anesthesia. The primary outcome was defined as the lowest mean blood pressure from induction of general anesthesia to the start of surgery: post-induction blood pressure (PIB). Multivariable regression analysis was used to investigate the relationships between PIB and preoperative echocardiographic measurements, types and doses of anesthetic agents, and preoperative comorbidities and oral medication. Left ventricle regional wall motion abnormality (RWMA) and lower estimated glomerular filtration rate significantly associated lower PIB. Factors significantly associated with higher PIB were high BMI, beta blockers, high pre-induction mean blood pressure, and starting induction in the afternoon. Sevoflurane and prophylactic norepinephrine use were associated with higher PIB as anesthetic interventions. Significant interactions were found between sevoflurane and RWMA (P for interaction: 0.01). This is the first study to demonstrate the feasibility of intervening in the selection of anesthetic agents based on echocardiographic findings and to recommend the use of sevoflurane and prophylactic norepinephrine for the prevention of PIH, especially in patients with RWMA.

Systematized Serendipity: Fishing Expeditions for Anesthetic Drugs and Targets.

Most of science involves making observations, forming hypotheses, and testing those hypotheses, to form valid conclusions. However, a distinct, longstanding, and very productive scientific approach does not follow this paradigm; rather, it begins with a screen through a random collection of drugs or genetic variations for a particular effect or phenotype. Subsequently, the identity of the drug or gene is determined, and only then are hypotheses formed and the more standard scientific method employed. This alternative approach is called forward screening and includes methods such as genetic mutant screens, small molecule screens, metabolomics, proteomics, and transcriptomics. This review explains the rational for forward screening approaches and uses examples of screens for mutants with altered anesthetic sensitivities and for novel anesthetics to illustrate the methods and impact of the approach. Forward screening approaches are becoming even more powerful with advances in bioinformatics aided by artificial intelligence.

Design, synthesis, and activity evaluation of water-soluble propofol derivatives as anesthetic drugs.

In this work, two series of water-soluble derivatives were designed and synthesized based on the structure of propofol as the lead compound. Furthermore, the anesthetic activities of the synthesized compounds were evaluated in vivo against mice, and the in vitro propofol release rate from five target compounds was determined. The findings of this study have shown that series II compounds which possess the structure feature of propofol + Î³-hydroxybutyric acid + α-aminoacetate or γ-aminobutyrate have higher therapeutic index than that of series I compounds which possess the structure feature of propofol + α-aminoacetate or ß-aminopropionate. In addition, the rate of propofol released from series II compounds was significantly better than that of series I compounds. Among series II compounds, compound II-20 had a therapeutic index of 5.6 (propofol = 2.7), a duration time of 571 s (propofol = 57 s), and no significant toxicity was observed in vivo, which made it valuable for further development.

Influence of Anesthetic Regimes on Extracellular Vesicles following Remote Ischemic Preconditioning in Coronary Artery Disease.

Remote ischemic preconditioning (RIPC) reduces ischemia-reperfusion injury in aortocoronary bypass surgery, potentially via extracellular vesicles (EVs) and their micro-RNA content. Clinical data implicate that propofol might inhibit the cardioprotective RIPC effect. This prospective, randomized study investigated the influence of different anesthetic regimes on RIPC efficacy and EV micro-RNA signatures. We also assessed the impact of propofol on cell protection after hypoxic conditioning and EV-mediated RIPC in vitro. H9c2 rat cardiomyoblasts were subjected to hypoxia, with or without propofol, and subsequent simulated ischemia-reperfusion injury. Apoptosis was measured by flow cytometry. Blood samples of 64 patients receiving anesthetic maintenance with propofol or isoflurane, along with RIPC or sham procedures, were analyzed, and EVs were enriched using a polymer-based method. Propofol administration corresponded with increased Troponin T levels (4669 ± 435.6 pg/mL), suggesting an inhibition of the cardioprotective RIPC effect. RIPC leads to a notable rise in miR-21 concentrations in the group receiving propofol anesthesia (fold change 7.22 ± 6.6). In vitro experiments showed that apoptosis reduction was compromised with propofol and only occurred in an EV-enriched preconditioning medium, not in an EV-depleted medium. Our study could clinically and experimentally confirm propofol inhibition of RIPC protection. Increased miR-21 expression could provide evidence for a possible inhibitory mechanism.

Correlation between anesthetic concentration and low Apgar scores in neonates born via Cesarean sections under general anesthesia.

OBJECTIVES: This study aimed to compare plasma concentrations of anesthetic drugs administered during Cesarean section with low Apgar score in neonates deliveried under general anesthesia and analyze associated risk factors. METHODS: Data from 76 neonates undergoing Cesarean section under general anesthesia with blood concentrations of anesthetic drugs were analyzed. A low Apgar score was defined as ≤ 7. Perioperative maternal and neonatal data were collected and analyzed. Neonates were divided into a control group (Group CON, n = 65) and a low Apgar score group (Group LAS, n = 11) based on Apgar score. RESULTS: There were no significant differences in the plasma concentrations of anesthetic drugs in maternal artery, umbilical vein or umbilical artery blood between the two groups. Risk factors for neonatal low Apgar scores during Cesarean section under general anesthesia were premature delivery (aOR 10.2, 95% CI = 1.8-56.9) and preoperative fetal distress (aOR 9.6, 95% CI = 1.3-69.0). The prediction model was: probability = 1/(e­Y), Y= -4.607 + 2.318× (premature delivery) + 2.261× (fetal distress) (yes = 1, no = 0). The Hosmer-Lemeshow test showed χ²= 9.587, P = 0.213, and the area under the curve (AUC) was 0.850 (0.670 ~ 1.000). With a cutoff value of 0.695, sensitivity and specificity were 81.8% and 87.7%, respectively. CONCLUSIONS: There was no correlation between blood concentration of general anesthetic drugs and Apgar score or occurrence of neonatal low Apgar scores. Premature delivery and preoperative fetal distress were identified as independent risk factors for neonatal low Apgar scores after Cesarean section under general anesthesia.

Since the COVID-19 pandemic, approximately 90% of elective anesthetics have been ambulatory: A retrospective analysis of statewide data in Florida from 2010 through 2022.

BACKGROUND: When the vast majority (e.g., ≈90%) of a specialty's elective (scheduled) care is ambulatory (i.e., length of stay 0 or 1 night), the administrative, clinical, and economic policy implications are profound. We examined the progressive shift of elective anesthetics in Florida from inpatient to ambulatory, from the first quarter of 2010 through the fourth quarter of 2022. We were particularly interested in the most recent data following the lifting of COVID-19 restrictions on elective surgery in the state. METHODS: This retrospective cohort study included major therapeutic and major diagnostic procedures with >0 American Society of Anesthesiologists base units in the state of Florida inpatient and ambulatory surgery databases. The last 8 quarters of these operating room anesthetic data corresponded to the end of restrictions on elective surgery in Florida due to the COVID-19 pandemic. Our goal was to determine whether the overall mean percentage of cases with 0- or 1-day lengths of stay has reached 90% since the lifting of pandemic restrictions. Numbers of cases over periods of at least four weeks tend to follow normal distributions. Therefore, we analyzed the N = 8 quarters of cases from 2021 to 2022 using Student's t-test. The study was performed when there were N = 8 quarters available from the Florida healthcare databases. RESULTS: There were overall 22,584,752 surgical cases studied. The percentages of elective anesthetics with length of stay ≤1-day increased progressively from 2010 through 2020. Among the eight successive quarters since the end of pandemic-related elective surgery restrictions, the percentage of elective cases with length of stay 0- or 1 day was stable, averaging 90% (95% two-sided confidence interval 89.4% to 90.3%). CONCLUSION: Since the COVID-19 pandemic, the mean quarterly percentage of elective surgery cases with anesthesia in Florida that were ambulatory has been reliably ≈90%. Implications include value in expecting overnight post-anesthesia care unit stay in ambulatory surgery centers and scheduling and sequencing cases based on post-anesthesia care unit capacity. Furthermore, because the vast majority (i.e., ≈90%) of cases would be excluded (i.e., not involve hospital admission for at least 2 midnights), there is a minimal role that risk-adjusted hospital length of stay and mortality can have in evaluating anesthesia department overall quality and economic effectiveness.

The efficient method to get better raw brain signal on rat anesthetics experiment.

This paper introduces an efficient methodology for conducting rat anesthesia experiments, aimed at enhancing the quality of raw brain signals obtained. The proposed approach enables the acquisition of animal brain signals during experiments without the confounding influence of muscle noise. Initially, the use of alpha-chloralose (a-c) in conjunction with Isoflurane is introduced to induce anesthesia in rats. Subsequently, Dexdomitor is administered to prevent muscular movements during the collection of brain signals, further refining the signal quality. Experimental outcomes conclusively demonstrate that our anesthesia method produces cleaner raw signals and exhibits improved robustness during data acquisition, outperforming existing methods that rely solely on Isoflurane or the Ketamine-Xylazine combination. Notably, this improved performance is achieved with minimal alterations to vital physiological parameters, including body temperature, respiration, and heart rates. Moreover, the efficacy of a-c in maintaining anesthesia for up to 7 h stands in contrast to the shorter durations achievable with continuous Isoflurane administration or the 30-min window offered by Ketamine-Xylazine, highlighting the practical advantages of our proposed method. Finally, post-experiment observations confirmed that the animals gradually returned to normal behavior without any signs of distress or adverse effects, indicating that our method was both effective and safe.

Comprehensive review of perioperative factors influencing ferroptosis.

The perioperative period encompasses all phases of patient care from the decision to perform surgery until full recovery. Ferroptosis, a newly identified type of regulated cell death, influences a wide array of diseases, including those affecting the prognosis and regression of surgical patients, such as ischemia-reperfusion injury and perioperative cognitive dysfunction. This review systematically examines perioperative factors impacting ferroptosis such as surgical trauma-induced stress, tissue hypoxia, anesthetics, hypothermia, and blood transfusion. By analyzing their intrinsic relationships, we aim to improve intraoperative management, enhance perioperative safety, prevent complications, and support high-quality postoperative recovery, ultimately improving patient outcomes.

Unveiling the hidden dangers: a review of non-apoptotic programmed cell death in anesthetic-induced developmental neurotoxicity.

Anesthetic-induced developmental neurotoxicity (AIDN) can arise due to various factors, among which aberrant nerve cell death is a prominent risk factor. Animal studies have reported that repeated or prolonged anesthetic exposure can cause significant neuroapoptosis in the developing brain. Lately, non-apoptotic programmed cell deaths (PCDs), characterized by inflammation and oxidative stress, have gained increasing attention. Substantial evidence suggests that non-apoptotic PCDs are essential for neuronal cell death in AIDN compared to apoptosis. This article examines relevant publications in the PubMed database until April 2024. Only original articles in English that investigated the potential manifestations of non-apoptotic PCD in AIDN were analysed. Specifically, it investigates necroptosis, pyroptosis, ferroptosis, and parthanatos, elucidating the signaling mechanisms associated with each form. Furthermore, this study explores the potential relevance of these non-apoptotic PCDs pathways to the pathological mechanisms underlying AIDN, drawing upon their distinctive characteristics. Despite the considerable challenges involved in translating fundamental scientific knowledge into clinical therapeutic interventions, this comprehensive review offers a theoretical foundation for developing innovative preventive and treatment strategies targeting non-apoptotic PCDs in the context of AIDN.

[Impacts of different anesthetic protocols on the speed and quality of postoperative resuscitation in patients undergoing painless gastroscopy].

Objective: To estimate the impacts of different anesthetic protocols on the speed and quality of postoperative resuscitation in patients undergoing painless gastroscopy. Methods: This was a prospectively designed randomized control study that included 150 patients who underwent painless gastroscopy in Hainan Cancer Hospital affiliated to Hainan Medical College between April and December of 2023. All the patients, classified as American Society of Aneshesiologists (ASA) Grade Ⅰ or Ⅱ, were randomly divided into three groups with different anesthetic protocols, including propofol group (group P), remimazolam group (group R) and remimazolam with flumazenil group (group RF). There were eventually 50 patients in each group. The three groups of patients were compared for their resuscitation time and the time that they stayed in the resuscitation room (addressed as"room time"below). At 10 min and 20 min after resuscitation, each patient was tested for recognition ability (orientation score), walking ability and fine motor skill (including reaction speed, quick-click ability and visual memory), respectively, with possible adverse reactions recorded spontaneously, such as hypotension, dizziness, nausea and vomitus. Results: There were 29 males and 21 females in group P with an average age of (34±6) years, 27 males and 23 females in group R with an average age of (36±8) years, and 26 males and 24 females in group RF with an average age of (33±7) years, respectively. All examinations for each patient were successfully completed with no interruptions. The resuscitation time and room time of group RF were (47±15) s and (26±5) min,respectively, which were both shorter than those in either group R [(489±92) s and (35±6) min] or group P [(196±61) s and (31±7) min] (all P<0.05). The orientation score of patients in group RF at 10 min after resuscitation was (79.0±10.5), which was significantly higher than that in group R (70.0±11.7) (P<0.05). The patients' walking ability score of group RF at 10 min and 20 min after resuscitation were [(23.6±10.8), (48.0±4.5)], which were better than those in group R[(15.4±11.1), (47.6±4.8)] (both P<0.05). The patients' reaction speed and quick-click scores of group RF were [(851.0±150.9), (547.0±114.0) ms] and [(758.0±73.2), (629.0±128.9) ms], which were better than those in either group R [(1 151.0±206.0), (732.0±135.1) ms], [(893.0±110.9), (765.8±125.8) ms] or group P [(985.0±225.3), (613.0±123.2) ms], [(831.0±87.7), (691.0±115.8) ms] (all P<0.05). The incidence rate of hypotension in group P was 18% (9/50), higher than that in either Group R [4% (2/50)] or group RF [2% (1/50)] (all P<0.05). The incidence rates of dizziness, nausea and vomitus were comparable among all the three groups with no statistical differences (all P>0.05). Conclusion: In patients undergoing anesthesia with remazolam, the use of flumazenil can not only shorten the resuscitation time and the time that the patients need to stay in the resuscitation room, but also speed up the recovery of the patients' recognition, walking and fine motor skill abilities.

Etomidate as an anesthetic in Colossoma macropomum: Behavioral and electrophysiological data complement each other as a tool to assess anesthetic safety.

The use of anesthetic agents in the management of fish in fish farming or ornamental fish breeding aims to minimize stress and promote animal welfare. Therefore, this study aims to investigate behavioral, electrocardiographic, and ventilatory characteristics of tambaquis exposed to anesthetic baths with etomidate. The study was conducted with juvenile tambaquis (27.38 ± 3.5g) n = 99, at etomidate concentrations of 2-4 mg.L -1, analyzing induction and anesthetic recovery behavior (experiment I), electrocardiogram (experiment II), and opercular movement (experiment III). Fish exposed to high concentrations of etomidate reached the stage of general anesthesia faster, however, the recovery time was longer, characterizing a dose-dependent relationship. Cardiorespiratory analyzes demonstrated a reduction in heart rate (69.19%) and respiratory rate (40.70%) depending on the concentration of etomidate used during anesthetic induction. During the recovery period, there was cardiorespiratory reversibility to normality. Therefore, etomidate proved to be safe as an anesthetic agent for this species at concentrations of 2 to 3 mg.L -1 for short-term anesthesia, but at higher doses the animals showed slow reversibility of anesthesia in a gradual manner and without excitability. The hemodynamic effect due to the rapid decrease in heart rate includes a negative factor of using higher concentrations of etomidate for Colossome macropomum anesthesia.

Toxic and signaling effects of the anaesthetic lidocaine on rice cultured cells.

Most studies on anesthesia focus on the nervous system of mammals due to their interest in medicine. The fact that any life form can be anaesthetised is often overlooked although anesthesia targets ion channel activities that exist in all living beings. This study examines the impact of lidocaine on rice (Oryza sativa). It reveals that the cellular responses observed in rice are analogous to those documented in animals, encompassing direct effects, the inhibition of cellular responses, and the long-distance transmission of electrical signals. We show that in rice cells, lidocaine has a cytotoxic effect at a concentration of 1%, since it induces programmed reactive oxygen species (ROS) and caspase-like-dependent cell death, as already demonstrated in animal cells. Additionally, lidocaine causes changes in membrane ion conductance and induces a sharp reduction in electrical long-distance signaling following seedlings leaves burning. Finally, lidocaine was shown to inhibit osmotic stress-induced cell death and the regulation of Ca2+ homeostasis. Thus, lidocaine treatment in rice and tobacco (Nicotiana benthamiana) seedlings induces not only cellular but also systemic effects similar to those induced in mammals.

Existence of multiple transitions of the critical state due to anesthetics.

Scale-free statistics of coordinated neuronal activity, suggesting a universal operating mechanism across spatio-temporal scales, have been proposed as a necessary condition of healthy resting-state brain activity. Recent studies have focused on anesthetic agents to induce distinct neural states in which consciousness is altered to understand the importance of critical dynamics. However, variation in experimental techniques, species, and anesthetics, have made comparisons across studies difficult. Here we conduct a survey of several common anesthetics (isoflurane, pentobarbital, ketamine) at multiple dosages, using calcium wide-field optical imaging of the mouse cortex. We show that while low-dose anesthesia largely preserves scale-free statistics, surgical plane anesthesia induces multiple dynamical modes, most of which do not maintain critical avalanche dynamics. Our findings indicate multiple pathways away from default critical dynamics associated with quiet wakefulness, not only reflecting differences between these common anesthetics but also showing significant variations in individual responses. This is suggestive of a non-trivial relationship between criticality and the underlying state of the subject.

Drug administration errors among anaesthesia providers in South Africa: a cross-sectional descriptive study.

BACKGROUND: Drug administration errors (DAEs) in anaesthesia are common, the aetiology multifactorial and though mostly inconsequential, some lead to substantial harm. The extend of DAEs remain poorly quantified and effective implementation of prevention strategies sparse. METHOD: A cross-sectional descriptive study was conducted using a peer-reviewed survey questionnaire, circulated to 2217 anaesthetists via a national communication platform. The aim was to determine the self-reported frequency, nature, contributing factors and reporting patterns of DAEs among anaesthesia providers in South Africa. RESULTS: Our cohort had a response rate was 18.9%, with 420 individuals populating the questionnaire. 92.5% of surveyed participants have made a DAE and 89.2% a near-miss. Incorrect route of administration, potentially resulting in serious harm, accounted for 8.2% (n = 23/N = 279) of these errors. DAEs mostly reported in cases involving adult patients (80.5%, n = 243/N = 302), receiving a general anaesthetic (71.8%, n = 216/N = 301), where the drug-administrator prepared the drugs themselves (78.7%, n = 218/N = 277), during normal daytime hours (69.9%, n = 202/N = 289) with good lightning conditions (93.0%, n = 265/N = 285). 26% (n = 80/N = 305) of DAEs involved ampoule misidentification, whilst syringe identification error reported in 51.6% (n = 150/N = 291) of cases. DAEs are often not reported (40.3%, n = 114/N = 283), with knowledge of correct reporting procedures lacking. 70.5% (n = 198/N = 281) of DAEs were never discussed with the patient. CONCLUSIONS: DAEs in anaesthesia remain prevalent. Known error traps continue to drive these incidents. Implementation of system based preventative strategies are paramount to guard against human error. Efforts should be made to encourage scrupulous reporting and training of anaesthesia providers, with the aim of rendering them proficient and resilient to handle these events.