Background: The article describes a case of methemoglobinemia in a 4-year-old child with nephrotic syndrome with simultaneous use of therapeutic doses of three drugs that cause methemoglobinemia: lidocaine (topically), benzocaine (topically), and co-trimoxazole (systemically). An increase in the level of methemoglobin in the blood to 47.6% led to the development of respiratory failure. To correct the child's condition, high-flow oxygen therapy was performed and ascorbic acid was administered. During the day, there was a positive trend, the level of methemoglobin decreased to 1.5%. Toxicological examination of urine showed the presence of lidocaine, benzocaine, and trimethoprim. Thus, in conditions of polypragmasia in a child with comorbidity, the simultaneous use of three drugs with the potential of methemoglobinemia caused a significant increase in the level of methemoglobin and the development of respiratory failure, which required hospitalization in the intensive care unit. After 2 days, the patient's condition stabilized and he was transferred to a specialized department. As far as we know, this is the first documented case of methemoglobinemia in a child with polypragmasia.

Methemoglobinemia is a rare, potentially life-threatening disorder caused by oxidation of hemoglobin iron from the ferric (Fe[3+]) to the ferrous (Fe[2+]) state, impairing oxygen delivery to tissues. Although most cases of methemoglobinemia that are documented are reported after procedural use of benzocaine sprays, those occurring from over-the-counter benzocaine gel are uncommon and often underrecognized. We report a case of an elderly woman with multiple comorbidities who developed significant methemoglobinemia after prolonged Benzocaine use for oral discomfort. She presented with refractory hypoxemia unresponsive to escalating supplemental oxygen. Arterial blood gas analysis revealed elevated methemoglobin levels. Timely recognition and administration of methylene blue resulted in rapid resolution of symptoms. This case highlights the importance of considering methemoglobinemia in patients presenting with unexplained refractory hypoxia, especially in patients who report the use of local anesthetics.

Cocaine is the second most popular traditional illicit drug in the European Union, after cannabis, and its high potential for addiction makes it a significant public health concern. Therefore, monitoring trends in the content and purity of street samples can provide valuable information to support harm reduction strategies. This study analysed a selection of 160 street cocaine samples collected at a large British summer festival between 2014 and 2024. A comparison between a low-cost, transportable 60 MHz benchtop nuclear magnetic resonance (NMR) instrument and a more expensive, larger laboratory-based 400 MHz NMR device was used to assess variations in composition and purity levels. Despite a lower signal-to-noise ratio and signal overlap causing some differences in values, the benchtop NMR produced almost identical results to those of the 400 MHz system. Until 2014, cocaine samples were highly adulterated; their purity increased sharply from 2015 onwards, with levels ranging from 80% to 98%, before showing a downward trend in 2024. The most commonly detected cutting agents were benzocaine, levamisole, caffeine, phenacetin, and lactose. Overall, this work demonstrates that low-field NMR can be effectively used to quantify cocaine in street samples. This could be especially beneficial on-site for guiding and enhancing harm reduction services and law enforcement.

Local anesthetics are fundamental to dermatologic practice, yet their safety profile requires nuanced understanding in high-risk contexts including end-arterial sites, barrier-compromised skin, and scenarios predisposing to systemic toxicity. This narrative review synthesizes contemporary evidence across these three interacting domains to provide an integrated, risk-stratified framework for clinical decision-making. Regarding end-arterial territories, over two decades of clinical evidence encompassing more than 200,000 digital and acral injections has effectively dismantled the historical dogma against epinephrine use in digits, nose, ear, and penis, demonstrating an excellent safety profile when dilute concentrations are used in patients with adequate perfusion, with phentolamine providing reliable rescue for rare, prolonged vasoconstriction. In barrier-compromised skin (e.g. burns, ulcers, and inflammatory dermatoses) topical anesthetics function as absorption amplifiers, with dramatically accelerated systemic uptake that can precipitate local anesthetic systemic toxicity or prilocaine- and benzocaine-induced methemoglobinemia, particularly in infants and frail elderly patients. For large, denuded areas, dilute tumescent infiltration offers a pharmacokinetically safer alternative to high-dose topical therapy. The review details systemic toxicity risk factors, recognition, and management, emphasizing that intravenous lipid emulsion therapy has transformed severe toxicity from an often-fatal event to a manageable emergency. Special considerations for pediatric and geriatric populations, drug interactions, and cumulative dosing across modalities are addressed. The overarching conclusion is that context-sensitive risk stratification which includes integrating vascular status, barrier integrity, and host pharmacokinetics combined with office preparedness including phentolamine and lipid emulsion, enables safe local anesthesia even in traditionally high-risk dermatologic scenarios.

Despite the growing popularity of aesthetic procedures, procedural pain remains a major concern among patients. Topical numbing cream and local anesthetic injection are widely used to manage discomfort and reduce pain; however, their relative effectiveness in cannula-based facial treatments remains a subject of ongoing debate. The aim of the study was to compare the anesthetic efficacy of BLT cream (benzocaine 20%, lidocaine 10%, and tetracaine 4%) and 1% lidocaine local injection in patients undergoing cannula-based facial aesthetic treatments. Retrospectively, 29 females underwent 2 separate treatment sessions, each using a different anesthetic method. Pain intensity was assessed using a self-reported numerical pain rating scale, and patients were asked to indicate their preferred method upon completion of the second treatment session. Mean pain scores were compared using paired samples t-test, and patient preference was analyzed using frequency and percentage distributions. A P-value of <.05 was considered statistically significant. Of the 29 patients enrolled, 28 patients were included in the final analysis. The mean pain score with BLT cream was 5.07 ± 0.40 (95% CI, 4.24-5.90), compared with 3.04 ± 0.32 (95% CI, 2.38-3.69) with 1% lidocaine injection. The difference was statistically significant (P = .0001), with a mean difference of 2.03. Most patients reported a preference for 1% lidocaine injection over topical cream for future treatments. In this preliminary study, local injection of 1% lidocaine provides significantly better pain control than BLT cream during cannula-based facial treatments, with higher patient preference. Injectable anesthesia may be a more effective option for enhancing patient comfort in aesthetic practice. Level of Evidence: 3 (Therapeutic).

Benzocaine (BC) (ethyl 4-aminobenzoate) is an ester-type local anesthetic extensively used in topical, oral, and dermatological formulations for rapid, localized pain relief. Despite its widespread application, accurate quantification remains challenging due to poor aqueous solubility, susceptibility to hydrolysis into para-aminobenzoic acid (PABA), and the risk of methemoglobinemia associated with improper exposure. This review presents a critical and comparative evaluation of chromatographic, electrochemical, and spectroscopic methods for determining BC and its metabolites, integrating analytical performance, matrix applicability, and methodological evolution within a unified framework. Evidence was synthesized from major scientific databases, including Scopus, Web of Science, ScienceDirect, PubMed, and Google Scholar. High-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography (UPLC) remain gold-standard techniques, offering high selectivity, precision, and stability-indicating capability for trace-level analysis. Electrochemical and voltammetric approaches using advanced electrodes, such as boron-doped diamond and carbon nanocomposites, provide excellent sensitivity with low detection limits and improved environmental sustainability. UV-Vis and fluorescence spectrophotometry continue to support routine quality control, particularly when combined with chemometric tools. Ongoing challenges include analyte instability and complex matrices. Future perspectives highlight nanomaterial-based sensors, hybrid analytical platforms, and artificial intelligence integration for sensitive, automated BC monitoring.

Needle-insertion pain during dental local anesthesia remains one of the strongest triggers of dental anxiety. Conventional topical anesthetics show limited penetration through the thick palatal mucosa and often provide insufficient suppression of insertion pain. Microneedle (MN) patches have emerged as a minimally invasive drug-delivery platform capable of enhancing transmucosal permeability and topical anesthetic efficacy. This randomized, double-blind, crossover clinical trial evaluated the efficacy and safety of a benzocaine-loaded MN patch applied to the palatal mucosa prior to local anesthesia. Twenty adult patients requiring bilateral maxillary premolar scaling and root planing received MN or placebo patches in two study periods separated by a one-week washout. The primary outcome was the presence or absence of needle-insertion pain. Secondary outcomes included injection-phase pain assessed using a 100-mm visual analogue scale (VAS), numbness or discomfort at the application site, vital signs, and adverse events. Needle-insertion pain was reported in 2 of 20 cases (10%) under the MN patch condition, compared with 14 of 20 cases (70%) under the placebo patch condition, demonstrating a significantly lower incidence with the MN patch (p = 0.00049). In contrast, VAS scores for injection-phase pain did not differ significantly between conditions. No clinically relevant numbness, mucosal irritation, or MN-related adverse events were observed, and vital signs remained stable throughout both study periods. The benzocaine-loaded MN patch selectively attenuated superficial needle-insertion pain while maintaining an excellent safety profile. The absence of an effect on deeper injection-phase pain is likely attributable to the substantial thickness of the palatal mucosa. These findings support the clinical utility of MN-assisted transmucosal anesthesia as a novel drug-delivery modality in dentistry and provide a foundation for the development of minimally invasive analgesic systems.

Abstracts: Background: Hair dye-related allergic contact dermatitis (ACD) is a common problem among both consumers and professionals. The main sensitizers are aromatic amines such as para-phenylenediamine (PPD) and toluene-2,5-diamine (TDA), which can also cross-react with chemically related compounds.Objective: To analyze patch-test results from patients with suspected hair dye-related ACD, focusing on the prevalence of sensitization to hair dye allergens, cross-reactivity patterns, and occupational differences.Methods: We retrospectively reviewed 666 patients patch-tested between 2005 and 2023 at the Patch Test Clinic of Andreas Sygros Hospital, Athens, Greece. All patients were tested with the European baseline and extended hairdresser series. Results were evaluated according to the International Contact Dermatitis Research Group and European Society of Contact Dermatitis criteria. Logistic regression was used to calculate odds ratios for co-sensitization, adjusted for sex and age.Results: Overall, 82.4% of patients reacted to at least 1 allergen, with a median of 3 positive reactions. PPD was the most frequent allergen (47.9%), followed by TDA (35.9%) and nickel (41.1%). Significant co-sensitization was observed between PPD and several chemically related compounds, including 4-aminophenol, 3-aminophenol, benzocaine, textile dyes, hydroquinone, and pyrogallol (P < 0.001). Similar associations were observed for TDA. Hairdressers were younger (mean 32.2 vs 40.7 years, P < 0.001) and had predominantly hand dermatitis (62.9%). Patients reacting to multiple hair dye components were significantly more likely to be sensitized to PPD. Co-sensitization between PPD and cocamidopropyl betaine likely reflected cosmetic co-exposure rather than structural cross-reactivity.Conclusions: PPD and TDA remain the dominant sensitizers in hair dye-related ACD, with strong cross-reactivity to aminophenols, benzocaine, and textile dyes. Extended patch testing is essential for accurate diagnosis, as 7% of para-amino-compound-sensitized patients would be missed by PPD testing alone. Occupational exposure and multi-allergen sensitization highlight the need for safer formulations and preventive strategies in hair dye use.

The binding of local anesthetics (LAs) to cell membranes is required for LAs to reach the target ion channels, but lipid interactions may also play a role in a purely membrane-mediated mode of activity. Here, we used solid-state NMR and further biophysical techniques to characterize the effect of six LAs covering a wide range of structures and properties (benzocaine, bupivacaine, mepivacaine, lidocaine, procaine, QX-314) on membranes. Membrane partitioning log D values (between 2.1 and 3.7) varied little with pH, in contrast to octanol partitioning. Membrane thinning was induced by most LAs, except for benzocaine. A conformational change in the lipid headgroup was observed, with a pronounced dependence on the protonation state, indicating the importance of the positive charge that is maintained by most membrane-bound LAs. We found stabilization of negative membrane curvature in the case of benzocaine, and of positive curvature in the case of bupivacaine, procaine, mepivacaine and, most pronouncedly, for QX-314. Comparing the LAs with respect of their influence on membranes as observed in the different experiments, benzocaine and QX-314 were always found at either extreme of the scale, with bupivacaine and lidocaine closer in their effect to benzocaine. This order of influence correlates with the depth of membrane insertion and with the protonation state, both of which were identified as key factors for LA behavior. Finally, we found indications that LAs are able to alter the activity of bacterial mechanosensitive channels without any expected LA binding sites, thus supporting a membrane-mediated activity of LAs.

Anaesthesia is a cornerstone of modern aquaculture practice playing a crucial role in routine fish husbandry procedures and research activities. The present review discusses about anaesthetic use in fish, including commonly used synthetic agents such as MS-222, benzocaine, metomidate, quinaldine, 2-phenoxyethanol, and propofol, together with emerging plant-derived anaesthetics, especially clove oil and other essential oils that have reduced environmental impact. Attention is drawn to the physiological basis of anaesthesia in relation to fish welfare, inclusive of both sedation and general anaesthesia, emphasizing their role in mitigating stress. The review outlines the classical stages of anaesthesia in fish and summarizes important physiological and biochemical responses associated with the use of various anaesthetics. Pharmacokinetic processes, including absorption, primarily across the gills, tissue distribution, metabolism, and excretion are also discussed. Regulatory regimes governing approved anaesthetics are summarized to highlight compliance requirements in aquaculture settings. Particular attention is paid to the use of anaesthetics during transport, where light sedation is shown to effectively decrease metabolic rate thereby significantly improving fish welfare. Finally, the review points towards emerging future directions including the development of eco-friendly plant-based anaesthetics and nanotechnology-enhanced formulations aimed at improving solubility, stability, and efficacy of anaesthetic agents.