The Influence of Acid-Base Balance on Anesthetic Muscle Relaxants: A Comprehensive Review on Clinical Applications and Mechanisms.

Muscle relaxants have broad application in anesthesiology. They can be used for safe intubation, preparing the patient for surgery, or improving mechanical ventilation. Muscle relaxants can be classified based on their mechanism of action into depolarizing and non-depolarizing muscle relaxants and centrally acting muscle relaxants. Non-depolarizing neuromuscular blocking drugs (NMBDs) (eg, tubocurarine, atracurium, pipecuronium, mivacurium, pancuronium, rocuronium, vecuronium) act as competitive antagonists of nicotine receptors. By doing so, these drugs hinder the depolarizing effect of acetylcholine, thereby eliminating the potential stimulation of muscle fibers. Depolarizing drugs like succinylcholine and decamethonium induce an initial activation (depolarization) of the receptor followed by a sustained and steady blockade. These drugs do not act as competitive antagonists; instead, they function as more enduring agonists compared to acetylcholine itself. Many factors can influence the duration of action of these drugs. Among them, electrolyte disturbances and disruptions in acid-base balance can have an impact. Acidosis increases the potency of non-depolarizing muscle relaxants, while alkalosis induces resistance to their effects. In depolarizing drugs, acidosis and alkalosis produce opposite effects. The results of studies on the impact of acid-base balance disturbances on non-depolarizing relaxants have been conflicting. This work is based on the available literature and the authors' experience. This article aimed to review the use of anesthetic muscle relaxants in patients with acid-base disturbances.

Anaesthetic mortality in cats: A worldwide analysis and risk assessment.

BACKGROUND: Patient safety is essential in small animal anaesthesia. This study aimed to assess anaesthesia-related deaths in cats worldwide, identify risk and protective factors and provide insights for clinical practice. METHODS: A prospective multicentre cohort study of 14,962 cats from 198 veterinary centres across different countries was conducted. Data on anaesthesia-related deaths, from premedication up to 48 hours postextubation, were collected. Logistic regression was used to analyse patient demographics, American Society of Anesthesiologists (ASA) classification, procedure type and anaesthetic drugs. RESULTS: The anaesthesia-related mortality was 0.63%, with 74.5% of deaths occurring postoperatively. Cats with cachexia, a higher ASA status or who underwent abdominal, orthopaedic/neurosurgical or thoracic procedures exhibited elevated mortality. Mechanical ventilation use was associated with increased mortality. Mortality odds were reduced by the use of alpha2-agonist sedatives, pure opioids in premedication and locoregional techniques. LIMITATIONS: Limitations include non-randomised sampling, potential biases, unquantified response rates, subjective death cause classification and limited variable analysis. CONCLUSIONS: Anaesthetic mortality in cats is significant, predominantly postoperative. Risk factors include cachexia, higher ASA status, specific procedures and mechanical ventilation. Protective factors include alpha2-agonist sedatives, pure opioids and locoregional techniques. These findings can help improve anaesthesia safety and outcomes. However, further research is required to improve protocols, enhance data quality and minimise risks.

Anesthetics drug wastage and preventive strategies: Systematic review.

BACKGROUND: Surgical Patients and hospitals are now facing financial strain due to direct anesthetic demand as a result of the development of new anesthetic drugs, equipment, and techniques. Up to 15% of a hospital's pharmacy budget is currently allocated to anesthetic drug expenses. Drug wastage during anesthesia practice is a widespread hidden source of healthcare waste that leads to anesthetic drug shortages as well as poor operating room efficiency. On the other hand, despite the fact that it is preventable in the vast majority of cases, it is well described that drug wastage is routinely observed, including in developing countries where the consequences significantly affect both hospitals and patients. METHODS: This review aims to review the prevalence of anesthetic drug waste across the world and systematically formulate and describe preventive strategies. Relevant publications were identified using systematic searches on databases including Google Scholar, Medline (PubMed), the Cochrane Library, and Embase. In addition, papers were detected and then selected through the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria guidelines and the inclusion and exclusion criteria. Using the predetermined terms and dates from the searching databases, a total of 504 articles were identified. Based on the screening criteria, 16 papers were considered eligible and included in the final review. In addition, the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis was used for evaluating the quality of selected articles. This study is registered on PROSPERO, number CRD42024497044. RESULTS: Of the sixteen publications from eleven different nations that were considered suitable for inclusion, only two of them addressed the waste of inhalational anesthetics. In more than half of eligible articles, propofol was the frequently wasted drug that contributed to increased financial loss through drug waste. The first most significant factor contributing to the waste of intravenous and inhalational anesthetics was the disposal of multidrug vials following their use for a single patient and high fresh gas flow, respectively. CONCLUSION: Anesthetic medication waste is a common occurrence worldwide, despite the fact that it is expensive and has a significant negative impact on operating room efficiency. Because the majority of drug waste is avoidable, preventive measures may lower drug waste and improve patient and hospital efficiency.

Antimicrobial and Anesthetic Niosomal Formulations Based on Amino Acid-Derived Surfactants.

BACKGROUND: This work proposes the development of new vesicular systems based on anesthetic compounds (lidocaine (LID) and capsaicin (CA)) and antimicrobial agents (amino acid-based surfactants from phenylalanine), with a focus on physicochemical characterization and the evaluation of antimicrobial and cytotoxic properties. METHOD: Phenylalanine surfactants were characterized via high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Different niosomal systems based on capsaicin, lidocaine, cationic phenylalanine surfactants, and dipalmitoyl phosphatidylcholine (DPPC) were characterized in terms of size, polydispersion index (PI), zeta potential, and encapsulation efficiency using dynamic light scattering (DLS), transmitted light microscopy (TEM), and small-angle X-ray scattering (SAXS). Furthermore, the interaction of the pure compounds used to prepare the niosomal formulations with DPPC monolayers was determined using a Langmuir balance. The antibacterial activity of the vesicular systems and their biocompatibility were evaluated, and molecular docking studies were carried out to obtain information about the mechanism by which these compounds interact with bacteria. RESULTS: The stability and reduced size of the analyzed niosomal formulations demonstrate their potential in pharmaceutical applications. The nanosystems exhibit promising antimicrobial activity, marking a significant advancement in pharmaceutical delivery systems with dual therapeutic properties. The biocompatibility of some formulations underscores their viability. CONCLUSIONS: The proposed niosomal formulations could constitute an important advance in the pharmaceutical field, offering delivery systems for combined therapies thanks to the pharmacological properties of the individual components.

The drug titration paradox: a control engineering perspective.

PURPOSE OF REVIEW: The drug titration paradox describes that, from a population standpoint, drug doses appear to have a negative correlation with its clinical effect. This paradox is a relatively modern discovery in anesthetic pharmacology derived from large clinical data sets. This review will interpret the paradox using a control engineering perspective. RECENT FINDINGS: Drug titration is a challenging endeavor, and the medication delivery systems used in everyday clinical practice, including infusion pumps and vaporizers, typically do not allow for rapid or robust titration of medication being delivered. In addition, clinicians may be reluctant to deviate from a predetermined plan or may be content to manage patients within fixed goal boundaries. SUMMARY: This drug titration paradox describes the constraints of how the average clinician will dose a patient with an unknown clinical response. While our understanding of the paradox is still in its infancy, it remains unclear how alternative dosing schemes, such as through automation, may exceed the boundaries of the paradox and potentially affect its conclusions.

Environmental impact of anesthetic drugs.

PURPOSE OF REVIEW: The environmental impact of anesthesia far exceeds that of other medical specialties due to our use of inhaled anesthetic agents (which are potent greenhouse gases) and many intravenous medications. RECENT FINDINGS: Calls for reducing the carbon footprint of anesthesia are ubiquitous in the anesthesia societies of developed nations and are appearing in proposed changes for hospital accreditation and funding in the United States. The body of research on atmospheric, land and water impacts of anesthetic pharmaceuticals is growing and generally reinforces existing recommendations to reduce the greenhouse gas emissions of anesthesia care. SUMMARY: The environmental impact of anesthesia care should factor into our clinical decisions. The onus is on clinicians to safely care for our patients in ways that contribute the least harm to the environment. Intravenous anesthesia and regional techniques have less environmental impact than the use of inhaled agents; efforts to reduce and properly dispose of pharmaceutical waste are central to reducing environmental burden; desflurane should not be used; nitrous oxide should be avoided except where clinically necessary; central nitrous pipelines should be abandoned; low fresh gas flows should be utilized whenever inhaled agents are used.

Effective concentration of herbal anaesthetics Origanum vulgare L. oil and its effects on stress parameters in Nile tilapia (Oreochromis niloticus).

BACKGROUND: Using anaesthetics is an important application in aquaculture especially where the fish transportation, vaccination, grading, sorting activities and many other handling operations have been conducted during the different stages of production periods in the farms or hatcheries. OBJECTIVES: This study aimed to evaluate the efficacy of oregano essential oil (OO) as an anaesthetic for Nile tilapia and to determine the optimal concentration and post-application stress effects compared to clove oil (CO). METHODS: Nile tilapia juveniles were exposed to different concentrations of OO (20-40-60-80-100 mg L-1) and CO (50 mg L-1) for different time periods to determine the optimal concentration and exposure time. After the effective concentration of OO was determined, in the second experiment, stress parameters (glucose, plasma cortisol) were analysed after 0, 2, 6, 12 and 24 h of application. The results compared to the control group and CO results. RESULTS: The study found that OO which has carvacrol compound higher than 78% was an efficient anaesthetic for Nile tilapia, and the effective concentration was found to be 60 mg L-1. No significant differences were found between opercular beats in any concentration of OO and CO. Basal glucose level in blood without anaesthesia application and recorded at 39.33 mg dL-1 and significantly lower than OO and CO at first two sampling points, 0 and 2 h (p < 0.05). According to plasma cortisol level results, although CO experimental group showed secondary stress response at 12 h (17.91 ± 4.21 ng mL-1), OO and CO group cortisol levels decreased at 24 h after anaesthesia application 7.13 ± 0.14and 7.01 ± 0.54 ng mL-1, respectively, below the control group cortisol concentration (12.28 ± 1.81 ng mL-1). CONCLUSIONS: These findings have important implications for the aquaculture industry as the use of OO as an anaesthetic could reduce the stress and mortality associated with traditional anaesthetics. Further research is needed to evaluate the efficacy of OO as an anaesthetic agent for other fish species and to determine the optimal concentration and exposure time for different species.

Uncovering essential anesthetics-induced exosomal miRNAs related to hepatocellular carcinoma progression: a bioinformatic investigation.

BACKGROUND: Anesthetic drugs may alter exosomal microRNA (miRNA) contents and mediate cancer progression and tumor microenvironment remodeling. Our study aims to explore how the anesthetics (sevoflurane and propofol) impact the miRNA makeup within exosomes in hepatocellular carcinoma (HCC), alongside the interconnected signaling pathways linked to the tumor immune microenvironment. METHODS: In this prospective study, we collected plasma exosomes from two groups of HCC patients (n = 5 each) treated with either propofol or sevoflurane, both before anesthesia and after hepatectomy. Exosomal miRNA profiles were assessed using next-generation sequencing (NGS). Furthermore, the expression data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) was used to pinpoint the differentially expressed exosomal miRNAs (DEmiRNAs) attributed to the influence of propofol or sevoflurane in the context of HCC. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to dissect the signaling pathways and biological activities associated with the identified DEmiRNAs and their corresponding target genes. RESULTS: A total of 35 distinct DEmiRNAs were exclusively regulated by either propofol (n = 9) or sevoflurane (n = 26). Through TCGA-LIHC database analysis, 8 DEmiRNAs were associated with HCC. These included propofol-triggered miR-452-5p and let-7c-5p, as well as sevoflurane-induced miR-24-1-5p, miR-122-5p, miR-200a-3p, miR-4686, miR-214-3p, and miR-511-5p. Analyses revealed that among these 8 DEmiRNAs, the upregulation of miR-24-1-5p consistently demonstrated a significant association with lower histological grades (p < 0.0001), early-stage tumors (p < 0.05) and higher survival (p = 0.029). Further analyses using GSEA and GSVA indicated that miR-24-1-5p, along with its target genes, were involved in governing the tumor immune microenvironment and potentially inhibiting tumor progression in HCC. CONCLUSIONS: This study provided bioinformatics evidence suggesting that sevoflurane-induced plasma exosomal miRNAs may have a potential impact on the immune microenvironment of HCC. These findings established a foundation for future research into mechanistic outcomes in cancer patients.

TILETAMINE-ZOLAZEPAM-XYLAZINE ANESTHESIA IN EX SITU BLACK-HANDED SPIDER MONKEYS (ATELES GEOFFROYI SSP.).

Black-handed spider monkeys (Ateles geoffroyi ssp.) are endangered in Mexico. Safe anesthetic protocols are important for in situ and ex situ conservation problems. Such protocols are scarce in the literature; nor have safety and physiologic responses been reported. High doses and volume are a counter side for field immobilizations. We tested an anesthetic protocol with a combination of tiletamine-zolazepam (5 mg/kg) plus xylazine (1 mg/kg) in 14 black-handed spider monkeys under human care from two facilities in Mexico. Physiological parameters such as HR, RR, T, SPO2, systolic arterial pressure (), diastolic arterial pressure (DAP), and median arterial pressure (MAP) were obtained. HR and RR decreased over time, but T increased significantly during the anesthetic time for the whole group; RR and T decreased for juveniles only. Variation between individuals was observed for HR, RR, and DAP. Volume reduction of drugs was achieved compared to previously reported anesthesia protocols. Induction time was fast (6.2 ± 10.4 min) and no tail prehension was seen. Recovery was prolonged (mean and SD). Physiologic parameters remained stable throughout. The protocol proved to be safe for the chemical immobilization of black-handed spider monkeys.

Congenital Sub-Mitral Aneurysm: Anesthetics and Surgical Management.

ABSTRACT: A sub-mitral left ventricular aneurysm is a rare condition. It is a congenital outpouching of the left ventricular wall, invariably occurring adjacent to the posterior mitral leaflet. Sub-mitral aneurysm (SMA) has usually been reported as a consequence of myocardial ischemia (MI), rheumatic heart disease, tuberculosis, and infective endocarditis. Nevertheless, there have been few case reports of congenital SMA in India. It usually presents with symptoms of heart failure. We report a rare case of congenital SMA in a 27-year-old young Indian and its successful management through a trans-aneurysmal approach.

Anaesthetics reduce the viability of adipose-derived stem cells.

Adipose-derived stem cells (ADSCs) are characterized by their low immunogenicity and unique immunosuppressive properties, providing many opportunities for autologous transplantation in regenerative medicine and plastic surgery. These methods are characterized by low rejection rates and intense stimulation of tissue regeneration. However, procedures during which fat tissue is harvested occur under local anaesthesia. To better understand the effects and mechanisms of anaesthetic compounds in cosmetic and therapeutic procedures, the present study used a mixture of these compounds (0.1% epinephrine, 8.4% sodium bicarbonate, and 4% articaine) and examined their impact on a human adipose-derived stem cell line. The results showed anesthetics' negative, dose-dependent effect on cell viability and proliferation, especially during the first 24 h of incubation. After extending the exposure to 48 and 72 h of incubation, cells adapted to new culture conditions. In contrast, no significant changes were observed in immunophenotype, cell cycle progression, and apoptosis. The results obtained from this study provide information on the effect of the selected mixture of anaesthetics on the characteristics and function of ASC52telo cells. The undesirable changes in the metabolic activity of cells suggest the need to search for new drugs to harvest cells with unaltered properties and higher efficacy in aesthetic medicine treatments.

Combining melatonin with dexmedetomidine improves anesthesia in rats.

Melatonin (ML) and dexmedetomidine (DM) are used separately as anesthetic premedication or as an anesthetic in humans and laboratory animals. In this study, we aimed to investigate the anesthetic properties of both drugs combined. The anesthetic effects of several combinations of ML (50 and 100 mg/kg) and DM (50 and 100 µg/kg) were evaluated in rats by observing behavioral manifestations and recording the duration and depth of anesthesia. Five anesthetic intervals were established according to the loss and recovery of reflexes. While each individual drug did not induce an appropriate anesthetic effect at the tested doses, ML50 + DM100, ML100 + DM50 and ML100 + DM100 combinations resulted in surgical anesthesia intervals of 60 to 360 min. Together, our results point that the use of ML allows to decrease the dose of DM, reducing the unwanted anesthetic effects of this α2-agonist.

Recovery of the baroreflex and autonomic modulation after anesthesia with MS-222 in bullfrogs.

The time course for recovery after anesthesia is poorly described for tricaine methanesulfonate (MS-222). We suggest that the baroreflex and the heart rate variability (HRV) could be used to index the recovery of the autonomic modulation after anesthesia. We analyzed the recovery profile of behavioral and physiological parameters over time to analyze the progression of recovery after anesthesia of American bullfrogs with MS-222. Mean heart rate stabilized after 17 h, whereas the baroreflex efficiency index took 23 h and the baroreflex operating gain, 29 h. Mean arterial pressure recovered after 26 h. Power spectral density peaked at 23 h and again after 40 h. Baroreflex was a relevant component of the first phase of HRV, while autonomic modulation for resting may take longer than 40 h. We suggest that physiological recovery is a complex phenomenon with multiple progressive phases, and the baroreflex may be a useful tool to observe the first substantial recovery of post-instrumentation capacity for autonomic modulation.

O-GlcNAcylation levels remain stable regardless of the anaesthesia in healthy rats.

Anaesthetics are used daily in human and veterinary medicine as well as in scientific research. Anaesthetics have an impact on cell homeostasis especially through modulation of protein post-translational modifications. O-GlcNAcylation, a ubiquitous post-translational modification, plays a role in many biological processes. The aims of this study were to evaluate whether (1) anaesthesia influences O-GlcNAcylation and (2) its stimulation affects physiological parameters. Male Wistar rats (n = 38) were anaesthetized with ketamine-xylazine or isoflurane. They randomly received either an intravenous injection of Ringer's lactate or NButGT (10mg/kg) in order to increase O-GlcNAcylation levels. One hour after induction of anaesthesia, haemodynamic parameters and plasmatic markers were evaluated. Heart, brain and lungs were harvested and O-GlcNAcylation levels and O-GlcNAc-related enzymes were evaluated by western blot. Cardiac and pulmonary O-GlcNAcylation levels and cardiac, cerebral and pulmonary O-GlcNAc associated enzyme expression were not impacted with anaesthesia. Compared with ketamine-xylazine, isoflurane had a lower impact on blood pressure, heart rate and glycaemia. Pharmacological stimulation of O-GlcNAcylation by NButGT did not affect the physiological parameters. This study offers unprecedented insights into the regulation of O-GlcNAcylation and O-GlcNAc related enzymes during anaesthesia. Pharmacological stimulation of O-GlcNAcylation over a 1-h period did not disrupt the physiological balance in healthy anaesthetized rats.

Efficacy of fennel (Foeniculum vulgare) and anise (Pimpinella anisum) essential oils as anaesthesics in common carp (Cyprinus carpio L. 1758).

In this study, the anaesthetic effects of fennel and anise essential oils were investigated on common carp. Fish (10 ± 0.45 g) were exposed to nine concentrations of essential oils (5, 10, 20, 50, 100, 200, 300, 400 and 500 mg L-1). Additionally, the histopathological effects on the fish tissues including gill, skin and hepatopancreas and physiological effects on some blood parameters (Na+, K+, Ca+2, Cl-, total plasma protein and glucose) of essential oils were investigated in carp. At the end of the experiment, fennel oil showed an anaesthetic effect at a concentration of 500 mg L-1 in carp (anaesthesia induction and recovery times were 308 and 472 s, respectively). Anise essential oil showed deep anaesthesia at a concentration of 100 mg L-1, but anaesthesia induction time was found to be very long (20 min). In addition, anise oil at concentrations above 100 mg L-1 caused 10% mortality in fish. Blood parameters except glucose level in both essential oils were unchanged during deep anaesthesia in carp. However, plasma glucose levels were found lower in fish anaesthetized with anise oil than control and fennel groups (P < 0.05). At the histopathological examination, no pathological findings were observed in any organ of fish in the fennel group. However, severe hyperemia and inflammatory cell infiltrations in gills, erosive lesions in the skin and slight inflammatory reactions in the skin were observed in the anise group. The present study demonstrated that fennel essential oil at 500 mg L-1 concentration can be used as an effective and safe anaesthetic in common carp, but anise essential oil is not suitable.

Is there a future for nitrous oxide in anaesthetic practice?

Although nitrous oxide is widely used for analgesia and anxiolysis, its use is under scrutiny because of concerns about its environmental impact and potential implications for mental health. This article discusses the advantages and disadvantages of this agent.

Comparison Between the Protective Effect of Isoflurane and Propofol on Myocardium During Coronary Artery Bypass Grafting: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Intravenous non-volatile anaesthetics like propofol are commonly used in cardiac surgeries across several countries. Volatile anaesthetics like isoflurane may help in protecting the myocardium and minimize ischaemia-reperfusion injury. Hence, we did this review to compare the cardioprotective effect of isoflurane and propofol among patients undergoing coronary artery bypass grafting (CABG). METHODS: We conducted a search in the databases Medical Literature Analysis and Retrieval System Online (or MEDLINE), Embase, PubMed Central®, ScienceDirect, Google Scholar, and Cochrane Library from inception until April 2021. We carried out a meta-analysis with random-effects model and reported pooled risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) depending on the type of outcome. RESULTS: We analysed 13 studies including 808 participants. Almost all were low-quality studies. For cardiac index, the pooled SMD was 0.14 (95% CI: -0.22 to 0.50); for cardiac troponin I, pooled SMD was 0.10 (95% CI: -0.28 to 0.48). For mortality, the RR was 3.00 (95% CI: 0.32 to 28.43); for MI, pooled RR was 1.58 (95% CI: 0.59 to 4.20); and for inotropic drug use, pooled RR was 1.04 (95% CI: 0.90 to 1.21). For length of intensive care unit stay, the pooled SMD was 0.13 (95% CI: -0.29 to 0.55), while pooled SMD for mechanical ventilation time was -0.02 (95% CI: -0.54 to 0.51). CONCLUSION: Isoflurane did not have significant cardioprotective effect compared to propofol following CABG. Hence, the anaesthetists need to check some viable alternatives to manage these patients and reduce the rate of postoperative complications.