Search Results (350)

This review examines and hypothesizes cytoprotection as a conceptual therapeutic criterion for antiarrhythmic drugs, referring to the possibility of suppressing arrhythmias while avoiding adverse electrophysiological or systemic effects. Toward a theoretically complete cytoprotective profile—preserving benefits and eliminating toxicity—the criterion was the degree of counteraction of arrhythmias (i.e., bradycardia, tachycardia, atrioventricular (AV) block, ventricular tachycardia (VT), ST-segment changes, prolonged P, PR, QRS, and QT/QTc intervals, and repolarization). Conventional and new antiarrhythmics share class I–IV ≈ partial cytoprotection/narrow range; late INa inhibitors, IKs enhancers, RyR2 stabilizers, gap junction modulators, and atrial-selective antiarrhythmics ≈ partial cytoprotection/more extended range. Still predominantly in preclinical models, stable gastric pentadecapeptide BPC 157, in the clinic, has not demonstrated adverse effects in available human trials (non-cardiac) to date. As a prominent cytoprotection mediator (LD1 not achieved in toxicology studies), it demonstrates well-matched cytoprotective–antiarrhythmic effects, BPC 157 ≈ full cytoprotection/wide-range homeostasis. In vivo, this was across models of hypo-/hyperkalemia, hypermagnesemia, ischemia–reperfusion, myocardial infarction, drug-induced arrhythmias (including local anesthetics), and vascular occlusion. BPC 157 restores sinus rhythm, normalizes P/QRS/QT intervals, prevents AV block, suppresses VT, attenuates ST-segment changes, and stabilizes heart rate, even when insults are advanced. In vitro, HEK293 studies confirm direct membrane-stabilizing actions: BPC 157 prevents hypokalemia-induced hyperpolarization, reduces hyperkalemia- and hypermagnesemia-induced depolarization, and mitigates local anesthetic-induced Na⁺/Ca²⁺ dysregulation, reflecting bidirectional homeostatic modulation of membrane potential. Thus, to confirm the hypothesis, these BPC 157 conditional, not constitutive effects, in rodent models or in vitro systems (HEK293 cells), mandate expansion of now limited clinical data and mechanisms in human investigated as a translational cytoprotective strategy for complex arrhythmias. Full article

Personalized anesthesia has emerged as a key direction in modern perioperative medicine, driven by advances in molecular biology, analytical technologies, and digital monitoring. Traditional physiological parameters often fail to detect early stages of organ dysfunction, whereas molecular biomarkers provide earlier and more sensitive insight into inflammation, oxidative stress, neurotoxicity, and renal or hepatic injury. Inflammatory markers such as IL-6, CRP, and PCT indicate early immune activation, while oxidative stress biomarkers, including 8-isoprostanes and malondialdehyde, quantify metabolic imbalance and ischemia–reperfusion injury. Neurotoxicity biomarkers such as S100β, NSE, and GFAP allow early detection of subclinical cerebral injury, whereas kynurenine-pathway metabolites reflect neuroinflammation and the risk of postoperative cognitive dysfunction. Renal biomarkers such as NGAL, KIM-1, and cystatin C detect acute kidney injury significantly earlier than creatinine, and miR-122 holds strong potential as an early marker of hepatocellular injury. Genetic and epigenetic biomarkers—including polymorphisms in CYP2D6, CYP3A4/5, RYR1, OPRM1, and COMT, as well as microRNA-based signatures—enable individualized drug dosing and optimization of anesthetic strategies. Meanwhile, digital biomarkers such as EEG-derived indices, HRV, and NIRS provide continuous real-time physiological monitoring and can integrate with AI-based algorithms for predictive, adaptive anesthesia management. Although no single biomarker meets all criteria for an ideal clinical indicator, combining molecular, genetic, and digital biomarkers represents the most promising pathway toward fully personalized, safe, and outcome-optimized perioperative care. Full article

Maintaining cardiovascular stability during anesthesia is essential, yet the routine use of atropine to prevent vagally induced low heart rate may impose additional stress on the heart. This randomized, controlled, observer-blinded, clinical study aimed to evaluate whether ondansetron, a selective 5-HT₃ receptor antagonist, could serve as an alternative anesthetic adjuvant to modulate autonomic activity while maintaining cardiovascular stability in dogs. A total of 66 female dogs, with a mean age of 1.5 years and a mean weight of 16–18 kg ASA I, undergoing elective surgery were assigned to three study groups to receive atropine, ondansetron, or no autonomic-modulating drug. Heart rate, arterial pressure, respiratory rate, and NT-proBNP were recorded before, during, and after anesthesia. Dogs treated with ondansetron maintained stable cardiovascular values throughout the procedure, with no episodes of low heart rate or excessive increases in heart rate. In contrast, atropine induced marked and sustained elevation in heart rate and higher arterial pressures. Concentrations of the cardiac biomarker NT-proBNP increased significantly 48 h after surgery in the atropine group but remained unchanged in the ondansetron group, indicating the absence of additional myocardial stress. These findings suggest that ondansetron may help preserve autonomic balance during anesthesia while minimizing myocardial stress. Ondansetron could represent a useful component of multimodal anesthetic protocols, particularly in dogs in which excessive cardiac stimulation should be avoided. Full article

Dissolvable microneedles (DMNs) represent an innovative approach to patient-friendly drug delivery, eliminating the need for conventional hypodermic injections. This study reports on the fabrication, Confocal Laser Scanning Microscopy (CLSM)-based optical visualization of drug distribution, and mechanical characterization of maltose-based DMNs impregnated with lignocaine, a local anesthetic. Microneedles were fabricated using a micro-molding technique and dried for nine hours. Structural integrity was evaluated using Field Emission Scanning Electron Microscopy (FESEM); drug distribution was examined via CLSM; and mechanical strength was assessed using nanoindentation. The FESEM results showed uniform microneedle formation with sharp tips and smooth surfaces, averaging 435 µm in height and 116 µm in width, with no significant dimensional variability (p > 0.5). CLSM analysis indicated even distribution of lignocaine throughout the matrix. Mechanical testing showed that each microneedle withstood 0.6 N, surpassing the 0.1 N threshold required for skin insertion. These results support the viability of maltose-based DMNs for local anesthetic delivery, with implications for outpatient, pediatric, and self-administered care settings. Future investigations will include Franz diffusion and in vitro dissolution studies to examine release kinetics. Full article

Lidocaine, an amide-type regional anesthetic, has been an important medication in the field of anesthesia since its clinical approval. Recently, lidocaine has emerged as a powerful immunomodulatory agent beyond its classical anesthetic properties. This review has summarized the recent basic and clinical studies with sufficient evidence on the multifaceted effects of lidocaine on both innate and adaptive immune cells, including macrophages, neutrophils, eosinophils, basophils, natural killer (NK) cells, mast cells, dendritic cells (DCs), monocytes, and T lymphocytes. We have also detailed how lidocaine affects critical cellular processes, such as cellular polarization, cytokine production, phagocytosis, and apoptosis, through multiple signaling pathways, including NF-κB, TLR4/p38 MAPK, voltage-sensitive sodium channels, HIF1α, TGF-β/Smad3, AMPK-SOCS3, TBK1-IRF7, and G protein-coupled receptors. These immunoregulatory effects of lidocaine are dependent on its concentration, duration of action, and the microenvironment. The immunomodulatory actions of lidocaine may contribute to its potential therapeutic value in various settings of diseases, such as cancer, sepsis, acute lung injury, asthma, organ transplantation, ischemia–reperfusion injury (IRI), and diabetes. We propose that lidocaine can be repurposed as an immunomodulator for treating immune-mediated inflammatory diseases. However, future research should define optimal dosing strategies, validate its mechanisms of action in clinical trials, and explore its novel clinical applications as a complementary immunotherapy. Full article

Background: Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) for clavicle fracture pain management carry significant adverse effect and allergic reaction risks. This study assessed ultrasound-guided nerve block (USNB) efficacy for acute clavicle fracture pain in emergency department (ED) patients, providing an alternative to NSAIDs and opioids with fewer adverse effects. Methods: This retrospective, single-center observational study was conducted in accordance with Methods of Medical Record Review Studies in Emergency Medicine Research guidelines. Adult patients (≥20 years) who presented to the ED with traumatic clavicle fractures between 1 January 2015 and 30 November 2023 were included. Of the 343 eligible patients, 12 received ultrasound-guided nerve blocks (USNB) and 331 received standard care. To improve exchangeability, 1:10 matching with replacement was performed according to patients’ characteristics, such as age, sex, initial pain score, and comorbidities. The primary outcome was pain relief, assessed via the pain intensity difference (PID) on the Numerical Rating Scale within 360 min post-intervention. Meaningful pain relief was defined as a PID ≥ 4. Secondary outcomes included rescue opioid use, ED length of stay, hospital length of stay, and USNB-associated complications, such as vascular puncture, nerve injury, or local anesthetic systemic toxicity. Data were analyzed using time-course, time-to-event (time to meaningful pain relief), and linear regression analyses. Results: A total of 12 patients in the USNB group and 85 matched patients in the standard care group were analyzed after baseline characteristics matching with replacement. Compared to standard care, USNB was associated with significantly greater pain relief (p < 0.001). In the time-to-event analysis, USNB led to a 3.41-fold faster achievement of meaningful pain relief compared with that achieved with standard care (HR = 3.41; 95% CI, 1.47–7.90; p = 0.004). No significant differences were observed between groups in rescue opioid use, ED length of stay, or hospital length of stay. No USNB-associated complication developed in the USNB group. Conclusions: In patients with traumatic clavicle fractures, USNB provides more rapid and sustained pain relief than standard analgesic care in the ED, without increasing the ED length of stay. Large prospective studies are needed to confirm these findings. Full article

The buccal micronucleus cytome assay (BMCyt) is a validated, non-invasive biomonitoring method used to detect early genotoxic and cytotoxic changes linked to environmental and occupational exposures. Healthcare workers, especially nurses and dentists, are routinely exposed to genotoxic agents such as anesthetic gases, cytotoxic drugs, ionizing radiation, and heavy metals. This study compared seven cytological biomarkers in exfoliated buccal cells from female nurses, dentists, and teachers to assess multivariate cytogenetic differences and potential occupational influences. Samples were collected from 32 nurses, 41 dentists, and 47 teachers, and 3000 cells per participant were evaluated for micronuclei (MN) and six additional nuclear abnormalities. Group differences were examined using MANOVA and permutation MANOVA, followed by pairwise tests, and visualized with Principal Component Analysis (PCA). Significant multivariate differences were found between nurses and both dentists and teachers (p = 0.003), supported by permutation tests, while dentists and teachers did not differ. PCA explained 56% of the variance and showed apparent clustering of nurses. Chromatin condensation and MN were the main contributors to group separation. Nurses had significantly higher MN (p ≤ 0.001) and karyorrhexis (p ≤ 0.0004) than dentist and teachers. Overall, nurses showed a distinct cytogenetic profile consistent with greater genotoxic susceptibility. Full article

Background/Objectives: Accurate drug dosage calculation in pediatric dentistry represents an essential component of everyday clinical practice. However, manual calculation methods, reliance on memory, and inconsistent pharmacological education often lead to uncertainty among practitioners. Methods: To support clinicians in this process, a mobile application—Dent.IN CALC—was developed as a rapid, evidence-based, and user-friendly tool. The app allows the input of age and weight to instantly generate recommended and maximum safe dosages of commonly prescribed antibiotics, analgesics, and local anesthetics. Additionally, it includes a list of corresponding pharmaceutical preparations available on the local market. A preliminary evaluation among sixty dentists revealed significant variability in dosage knowledge and confirmed the need for digital tools that facilitate accurate and efficient prescribing. Results: Most users rated the app as intuitive, time-saving, and highly beneficial for daily practice (mean satisfaction score 4.7 ± 0.4; 95% would recommend the app). Conclusions: The Dent.IN CALC app shows strong user acceptance and demonstrates how digital solutions can streamline workflow and support clinicians in routine pediatric pharmacological decision-making. Full article

Background: Lidocaine, classified as an amide-type agent, and tetracaine, designated as an ester-type agent, are frequently co-formulated for dermatologic procedures. Despite the extensive literature on the pharmacokinetics (PK) of these substances, there is a paucity of head-to-head comparisons of intravenous (IV) and topical administration in the same preclinical model. Absolute bioavailability (F%) is imperative for optimizing formulation design and safety. Methods: A single-dose, single-sequence, three-period pilot study was performed in male Göttingen mini-pigs. The first period of the study involved the intravenous bolus administration of lidocaine HCl and tetracaine HCl, with a dosage of 1 mg/kg for each agent. In Period 2, the topical application of Pliaglis (a combination of 7% lidocaine and 7% tetracaine, with a concentration of 10 g/100 cm² and a duration of 60 min) was utilized. In Period 3, the pharmacokinetic profile of Z4T4L4 (a formulation comprising 4% lidocaine HCl and 4% tetracaine HCl) was assessed under the same experimental conditions. Blood samples were collected up to 24 h after the administration of the drug; skin biopsies were obtained 90 min after the application of the test substance. Plasma and skin concentrations were measured by means of validated liquid chromatography–tandem mass spectrometry (LC–MS/MS). PK parameters were derived using a noncompartmental analysis approach, while F% was calculated through AUC comparison with IV dosing. Results: Subsequent to intravenous administration, the mean elimination half-lives of lidocaine and tetracaine were determined to be 1.62 h and 1.85 h, respectively. Pliaglis demonstrated higher skin concentrations of lidocaine (358 μg/g) and tetracaine (465 μg/g) compared to Z4T4L4 (33.6 μg/g and 46.1 μg/g, respectively). Despite lower skin levels, Z4T4L4 produced higher F% (lidocaine: 1.98% vs. 1.41%; tetracaine: 3.34% vs. 1.26%). The time to maximum plasma concentration (T_max) for lidocaine was found to be 2–4 h (Pliaglis) and 2–8 h (Z4T4L4), while for tetracaine, it was 1–8 h (Pliaglis) and 2–8 h (Z4T4L4). Conclusions: In this preliminary study, which included three subjects, Z4T4L4 exhibited a numerical tendency towards increased systemic bioavailability in comparison with Pliaglis. This observation was noted despite the fact that Z4T4L4 resulted in markedly lower skin concentrations. Due to the exploratory nature of the pilot study (n = 3), observed differences are reported as numerical trends. The data suggest that Z4T4L4 may enhance systemic absorption while reducing skin retention, highlighting a potential formulation-dependent dissociation between local concentration and systemic bioavailability. These preliminary findings provide in vivo evidence of a divergence between eutectic-based tissue retention and enhancer-driven systemic flux. This highlights that formulation design fundamentally dictates the safety profile of local anesthetics, necessitating a balance between local efficacy and systemic safety. Full article

Gel-based depots are increasingly recognized as platforms to extend the intratissue residence of local anesthetics (LAs) while reducing systemic exposure. Hydrogels, organogels, and emerging bigels represent three distinct architectures defined by their continuous phases and drug–matrix interactions. Hydrogels provide hydrated polymer networks with predictable injectability, tunable degradation, and diffusion- or stimulus-responsive release, enabling sustained analgesia in perineural, peri-incisional, intra-articular, and implant-adjacent settings. Organogels, formed by supramolecular assembly of low-molecular-weight gelators in lipids or semi-polar solvents, strongly solubilize lipophilic LA bases and enhance barrier partitioning, making them suitable for dermal, transdermal, and mucosal applications in outpatient or chronic pain care. Bigels integrate aqueous and lipid domains within biphasic matrices, improving rheology, spreadability, and dual-solubilization capacity, although their use in LA delivery remains at the formulation stage, with no validated in vivo pharmacology. This narrative review synthesizes the design principles, release mechanisms, and translational evidence across these platforms, highlighting domain-specific advantages and barriers related to mechanical robustness, sterilization, reproducibility, and regulatory feasibility. We propose a platform-level framework in which depot selection is aligned with LA chemistry, anatomical context, and clinical objectives to guide the development of workflow-compatible next-generation LA depots. Full article

Dexmedetomidine is a commonly used sedative because it has minimal adverse effects on respiratory function. Nevertheless, its cardiovascular safety profile, particularly bradycardia risk and drug–drug interactions (DDIs), remains incompletely understood. Additionally, current studies, including our previous analysis using the FDA adverse event reporting system (FAERS), hold several limitations. In this study, the electronic health record (EHR) platform TriNetX was utilized for pharmacovigilance analyses of dexmedetomidine. The significantly elevated incidence of bradycardia in dexmedetomidine-treated patients was demonstrated compared to other prevalent anesthetics. Age-stratified analyses revealed pronounced susceptibility in geriatric patients, while a slightly increased susceptibility in male patients was observed. In addition, elevated DDIs of dexmedetomidine with risperidone and albuterol were identified using disproportionality analysis with propensity score matching. Finally, to investigate molecular mechanisms of dexmedetomidine-associated bradycardia, analyses were conducted on a public microarray dataset, and nine differentially expressed miRNAs were identified following dexmedetomidine administration. Gene Ontology (GO) analysis of target genes of all five up-regulated miRNAs revealed rhythmic process and muscle tissue development as potential explanations. Notably, the target genes of the up-regulated miRNAs miR-26a-5p and miR-30c-5p were significantly enriched in GO terms associated with bradycardia. Together, this study identified bradycardia as a significant adverse drug event (ADE) of dexmedetomidine administration, observed possible clinically meaningful DDIs with dexmedetomidine, demonstrated a greater risk in elderly patients, and provided transcriptomic evidence that miRNA-mediated pathway dysregulation may contribute to dexmedetomidine-associated bradycardia. Full article

Background: Perinatal hypoxia is a leading cause of early mortality in canine neonates and accounts for over 90% of early deaths in canine neonates. Respiratory depression may result from dystocia, prolonged labor, or anesthetic protocols used during cesarean delivery, requiring rapid pharmacological support. This study evaluated the effects of aminophylline, caffeine, and doxapram on clinical and biochemical viability parameters in hypoxic neonatal dogs. Methods: Forty-five puppies born via elective or emergency cesarean section were included, of which 35 exhibiting cardiorespiratory depression (heart rate ≤ 180 bpm, respiratory rate < 15 movements per minute, Apgar score < 7, and reflex score < 3) were randomly allocated into aminophylline group (AG; n = 12), caffeine group (CafG; n = 11), or doxapram group (DG; n = 12). Ten clinically healthy neonates constituted the physiological control group (CG). Apgar score, neonatal reflexes, lactate, blood glucose, oxygen saturation, blood gas parameters, and cardiac troponin I (cTnI) were evaluated immediately after birth (M1) and 10 min following treatment (M10). Results: No significant differences were observed in laboratory parameters among groups (p > 0.05). Although all evaluated drugs improved clinical status by increasing heart rate, respiratory rate, and reflex scores, caffeine produced the greatest enhancement in vitality. The Δ Apgar score showed a significant difference between CafG and DG (p = 0.0095), while no statistical differences were detected between AG and CafG (p = 0.08) or between AG and GD (p = 0.60). Conclusions: Aminophylline, caffeine, and doxapram supported postnatal resuscitation in hypoxic neonatal puppies; however, caffeine demonstrated superior improvement in Apgar recovery, suggesting its potential as a preferred pharmacological adjunct in neonatal canine resuscitation protocols. Full article

Background/Objectives: The quality of trial data reporting within the field of anesthesiology has, to date, been insufficiently examined. This study aims to investigate the consistency of reporting for WHO Data Set Items, trial outcomes, and adverse events between the data reported in ClinicalTrials.gov and the corresponding peer-reviewed publications in a cohort of anesthetic-related randomized controlled trials (RCTs) subject to the FDAAA. Methods: In a cross-sectional study, we investigated RCTs performed on 29 drugs in anesthesiology. We examined data reporting for eight categories, including the results and outcome probability measures, adverse events, all-cause mortality, study size, study outcome, study arm, selection criteria, and date of enrollment. We also examined compliance with the ClinicalTrials.gov registration deadline. Using descriptive statistics, we described the reporting reliability in both trial registration and corresponding publication data. Differences in the frequencies of discrepant or inadequate data reporting between selected subgroups were analyzed. Results: We identified 258 trials from 2009 to 2022 from ClinicalTrials.gov with corresponding publications. Of these, 28.7% were retrospectively registered. Discrepancies in reporting results occurred in 33.3% of the trials, with serious adverse events in 62.4% and other adverse events in 67.4% of the trials. Primary outcomes were reported much more consistently than secondary ones (77.5% vs. 27.9%). The selection criteria (24%) and enrollment date (29.5%) were the least consistently reported data categories. The only data item with improved reporting over time was all-cause mortality. Conclusions: Trial data in anesthesiology clinical trials continue to be misreported. Responsible parties involved in the peer-review process should consider using trial data registration forms as valuable sources for validating the integrity of trial data. Additionally, discrepancies along manuscript progression from submission to publication raise the question about the reliability of both registered and published data as sources for clinical decisions and meta-research. Full article

Anesthesia in older patients is challenging and requires a range of skills in various techniques, both during surgery and in the post-operative period. Post-operative delirium is one of the most common cognitive dysfunctions after surgery, and elderly patients are at the highest risk. The pathophysiology of post-operative delirium remains incompletely understood. Several mechanisms (vascular, neurodegenerative, neuroimmune, neuroinflammation, drug-induced, stress-induced, and monoaminergic) have been considered to play a role. The type of anesthesia—general (gas, total intravenous), regional, or combined—was identified as a predictive factor. However, numerous prospective and retrospective studies have failed to determine which anesthetic technique is the best for preventing post-operative delirium. The type of surgery appears to be more critical than the type of anesthesia. However, the development of post-operative cognitive dysfunction could be linked to the depth of anesthesia. Dexmedetomidine displayed promising therapeutic potential for the efficient prevention or treatment of hyperactive post-operative delirium. The management of hypoactive post-operative delirium still requires further investigations, particularly in elderly patients. Full article

Pain management remains a major clinical challenge, as conventional opioids and local anesthetics suffer from short analgesic duration, systemic toxicity, and dependence risks. Advanced drug delivery systems, particularly hydrogels and liposomal bupivacaine, have emerged as promising solutions to address these limitations. Hydrogels, composed of cross-linked hydrophilic polymer networks, enable biocompatible, biodegradable, and sustained drug release, while liposomal bupivacaine encapsulates the anesthetic within lipid vesicles to prolong local analgesia and minimize systemic toxicity. The combination of these systems offers synergistic benefits, including extended drug retention, enhanced efficacy, and reduced opioid reliance. However, clinical translation remains constrained by formulation instability, high production costs, variable patient responses, and stringent regulatory requirements. This review provides a comprehensive overview of current advances in hydrogel and liposomal bupivacaine technologies, highlighting their clinical potential, ongoing challenges, and future directions toward safer, more effective, and personalized pain management strategies. Full article