Search Results (433)

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

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

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

This umbrella review summarized evidence from systematic reviews of randomized clinical trials regarding the efficacy of systemic and local premedication on anesthetic success in nonsurgical root canal treatment of teeth with symptomatic irreversible pulpitis. Searches were conducted in PubMed, Scopus, Web of Science, Cochrane Library, EMBASE, LILACS/BBO, and gray literature sources up to February 2025. Methodological quality was assessed using AMSTAR-2. The risk of bias was evaluated using the ROBIS tool. The Corrected Covered Area (CCA) was calculated to quantify the primary study overlap. Data regarding risk ratios and anesthetic success rates were synthesized qualitatively. Sixteen systematic reviews were included. The narrative synthesis suggests that oral NSAIDs (particularly ibuprofen > 400 mg and ketorolac 10–20 mg) and corticosteroids (dexamethasone) are associated with increased anesthetic success compared to placebo, with no significant difference between systemic and local administration. However, the reliability of these findings is impacted by the quality of the primary evidence: according to the appraisal, 13 reviews presented a high overall risk of bias/low methodological quality, while only three were classified as having low risk of bias. Furthermore, the CCA was 19.5%, indicating a high degree of redundancy among reviews. Consequently, while premedication appears effective, these conclusions must be interpreted with caution due to the substantial overlap and predominantly high risk of bias in the available literature. 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

Neutrophil extracellular traps (NETs)—webs of DNA and granular proteins expelled by neutrophils—have been implicated in hepatocellular carcinoma (HCC) progression. NETs promote tumor angiogenesis, facilitate invasion/metastasis, and enable immune evasion. Recent data suggest that perioperative factors, including anesthetic techniques, may modulate NET formation (NETosis), thus potentially influencing oncologic outcomes. We conducted a literature review of experimental and clinical studies on NETosis pathophysiology and involvement in HCC and how anesthetic techniques may modulate NET formation and, implicitly, cancer outcomes. NET biomarkers such as citrullinated histone H3 (CitH3), cell-free DNA (cfDNA), and myeloperoxidase–DNA complexes (MPO-DNA) are elevated in HCC patients and correlate with tumor spread, showing diagnostic and prognostic potential. Perioperative anesthetic choices may influence NET activity and immune function. Regional anesthesia and local anesthetics (e.g., lidocaine infusion) attenuate the surgical stress response and preserve anti-tumor immunity. Notably, lidocaine may modulate NET formation and, in a few studies published so far, was shown to reduce postoperative NET markers and other pro-metastatic factors (MMP-9, VEGF) in cancer surgery. In conclusion, NETosis is a process that is strongly implicated in HCC biology. Data published so far suggest that the clinical significance of NETosis may lie in its potential as a marker for disease evaluation and progression, including during the perioperative period. Preliminary results suggest that lidocaine may have a role in decreasing NETosis. Future large randomized trials are needed to exactly quantify these effects. Targeting NETs may be another way to influence HCC outcomes. Full article

Background/Objectives: Spinal anesthesia (SA) for cesarean section and epidural analgesia (EA) for vaginal delivery induce hemodynamic changes that may compromise maternal and fetal safety. In this observational, hypothesis-generating study, we used impedance cardiography (ICG) to characterize maternal hemodynamic responses to EA for labor versus SA for cesarean delivery and to describe hemodynamic profiles associated with commonly used local anesthetic and vasopressor regimens. Methods: In this observational study, 132 women at term were included (52 with epidural analgesia (EA), 80 with spinal anesthesia (SA)). Hemodynamic parameters were measured using the ICON electrical cardiometry monitor (Osypka Medical GmbH). ICON and oscillometric blood pressure (BP) monitoring captured cardiac index (CI), stroke volume (SV), heart rate (HR), systemic vascular resistance index (SVRI), and thoracic fluid content (TFC) at T0 (baseline), approximately 5 and approximately 10 min, skin incision, delivery, and oxytocin administration. Results: CI remained stable and comparable between EA and SA (3.9 ± 0.6 vs. 3.9 ± 0.6 L/min/m²; p = 0.530). SV was higher in EA (85.1 ± 11.3 vs. 78.1 ± 9.7 mL; p < 0.001), whereas HR was higher in SA (92.2 ± 12.9 vs. 85.8 ± 12.5 bpm; p = 0.009). In EA, ropivacaine and bupivacaine showed similar hemodynamic profiles. Within the SA cohort, women managed with phenylephrine infusion had lower CI and HR but higher MAP and SVRI compared with those receiving ephedrine boluses, consistent with the expected pharmacodynamic profiles of these agents. Conclusions: ICG was feasible and provided dynamic, noninvasive estimates of maternal cardiovascular adaptation during obstetric anesthesia. In this non-randomized, exploratory cohort, descriptive differences in hemodynamic profiles between vasopressor strategies were more pronounced than between local anesthetics. Phenylephrine-based management showed a pattern of higher BP and SVRI but lower CI and HR, whereas ephedrine-based management tended to preserve CI through chronotropic effects. Full article

Damage-associated molecular patterns (DAMPs) are endogenous molecules released during cellular stress or injury that trigger sterile inflammation. In perioperative settings, common triggers include surgical trauma, ischemia–reperfusion injury, cardiopulmonary bypass, blood transfusion, and mechanical ventilation. When released extracellularly, DAMPs activate innate immune receptors such as Toll-like receptors (TLRs) and the receptor for advanced glycation end products (RAGE), initiating signaling cascades that amplify inflammation, disrupt endothelial integrity, and promote coagulation and metabolic imbalance. This sterile inflammatory response may extend local tissue injury into systemic organ dysfunction, manifesting clinically as acute lung injury, acute kidney injury, myocardial dysfunction, disseminated intravascular coagulation, and perioperative neurocognitive disorders. Recognizing the central role of DAMPs reframes these complications as predictable consequences of endogenous danger signaling rather than solely as results of infection or hemodynamic instability. This understanding supports the use of established strategies such as protective ventilation and restrictive transfusion to minimize DAMP release. Emerging evidence also suggests that anesthetic agents may influence DAMP-mediated inflammation: propofol and dexmedetomidine appear to exert anti-inflammatory effects, whereas volatile anesthetics show variable results. Although clinical data remain limited, anesthetic choice and perioperative management may significantly affect systemic inflammatory burden and recovery. Future research validating DAMPs as biomarkers and therapeutic targets may inform precision anesthetic strategies aimed at modulating sterile inflammation, ultimately enhancing perioperative outcome. Full article

Background: Preventing postoperative infections in hand surgery is an important factor for achieving sustainable results of surgical procedures. To prevent infections, especially when implants are used, preoperative prophylactic antibiotics are applied in adherence to predominantly national guidelines, which are not specifically tailored to hand surgery. However, several studies related to elective soft tissue hand surgery indicate that the preoperative use of antibiotics does not reduce the incidence of postoperative infections. Evidence regarding their efficacy in osteosynthesis of the hand and wrist remains limited. Methods: In this retrospective study, we analyzed 542 adult patients who underwent hand or wrist osteosynthesis between 2016 and 2019 at our university center. They were enrolled in an antibiotic treatment group and a control group without antibiotic treatment. The prophylaxis group (P) underwent surgery in the main operating theater under intravenous anesthesia, whereas the non-prophylaxis group (NP) was treated under WALANT (Wide Awake Local Anesthetic No Tourniquet) in an outpatient operating theater without receiving preoperative antibiotics. Theater construction and installation were otherwise similar, and both were classified as grade 1 theaters. We applied propensity modeling and inverse probability of treatment weighting (IPTW) to achieve balanced treatment groups with respect to risk factors for infection, and we calculated the odds ratio of prophylaxis and infection. Inclusion factors for risk of infection were age, female sex, smoking, diabetes, metabolic disease, inflammatory disease, substance abuse, cardiovascular disease, hepatopathy, renal disease, polytrauma, open fracture, being a manual worker, and occupational accidents. To assess the severity of the cases, we considered whether the fractures were intraarticular, multi-fragmentary, or open, and we collected data on the types of surgical implants that were used. Results: No significant association was found between antibiotic prophylaxis and postoperative infection rate (infection rate P: 3.86%; NP: 3.27%; unadjusted OR: 1.19; adjusted OR after IPTW: 1.09). In terms of risk factors, there was an insignificant trend of higher infection rates in the subgroups smoking, cardiovascular disease, open fracture, occupational accident, and open fixations. Conclusions: In this cohort, routine use of preoperative antibiotics in hand osteosynthesis did not reduce infection rates. The effectiveness of the widespread standardized application of prophylactic antibiotics to reduce the risk of postoperative infections in osteosynthesis of the hand and wrist remains debatable. Our findings set the basis for further prospective studies aiming at clearer guidelines for evidence-based perioperative patient care. Full article

Background and Objectives: We performed a systematic review and meta-analysis using trial sequential analysis (TSA) to investigate the potential preventive postoperative antiadhesive effects of local anesthetics (LA). Materials and Methods: A comprehensive search was conducted using Ovid-MEDLINE, Ovid-EMBASE, Web of Science, and Google Scholar to identify animal studies that explored the postoperative antiadhesive effect of LA applied in the surgical area. The primary outcome was the macroscopic adhesion score, including adhesion quality, quantity, and total adhesion score, whereas the secondary outcome was the microscopic adhesion score, including adhesion severity, inflammation, and fibrosis. Certainty of evidence was assessed using a GRADE-adapted framework for animal studies. Results: The comprehensive analysis involved 227 rats across 6 animal studies, with 158 rats subjected to LA and the remaining 69 administered a placebo or received no treatment. For macroscopic adhesion score, LA were associated with reductions in the total adhesion score (standardized mean difference (SMD) −1.528; 95% confidence interval (CI) −2.081 to −0.976; I² = 30.0%) and adhesion quality (SMD: −0.996; 95% CI −1.906 to −0.085; I² = 72.6%), while no significant difference was observed in adhesion quantity (SMD −0.544; 95% CI −1.452 to 0.365; I² = 77.6%). For the microscopic adhesion score, LA appeared to reduce adhesion severity (SMD −1.304; 95% CI −1.862 to −0.746; I² = 31.7%) and fibrosis (SMD: −2.373; 95% CI −3.400 to −1.346; I² = 60.4%), whereas the effect on inflammation was inconsistent. Across all macroscopic outcomes, TSA demonstrated that the accrued sample size was far below the required information size, and the certainty of evidence remained low to very low. Most included studies had unclear or high risks of bias, which reduces confidence in the synthesized estimates. Conclusions: LA may have a potential association with reduced postoperative adhesion formation; however, the certainty of evidence was low to very low, and TSA indicated insufficient required information size to draw firm conclusions. Full article

Orthopedic and lower limb fracture surgeries are among the most frequent emergency procedures and are commonly performed under general anesthesia (GA). Background and clinical significance: Epidemiologically, postoperative coma after GA is rare (0.005–0.08%), but delayed awakening (2–4%) and postoperative delirium or postoperative cognitive dysfunction (POCD) (15–40%) remain significant. These neurological complications increase markedly in vulnerable brain patients with psychiatric, cerebrovascular, or neurodegenerative disorders. Methods: This mechanistic narrative review synthesizes evidence from clinical and experimental studies (1990–2025) comparing the effects of general versus Regional (RA)/local (LA) or spinal anesthesia in vulnerable neuropsychiatric populations “with pre-existing brain illness” undergoing orthopedic surgery. Domains analyzed include neuropsychiatric medications effects and interactions with the GA process and with general anesthetic agents, alongside alterations in neurotransmitter modulation, cerebrovascular autoregulation, mitochondrial dysfunction, oxidative stress, redox imbalance, and neuroinflammatory activation. The review summarizes evidence on how the choice of anesthesia type influences postoperative brain outcomes in patients with known neurological conditions. Results: From previous studies, patients with psychiatric and/or chronic brain illness have a 3–5-fold increased risk of delayed emergence and up to 60% incidence of postoperative delirium. Pathophysiological mechanisms involve GABAergic overinhibition, impaired perfusion, mitochondrial energy failure, and inflammatory amplification. Regional/local and spinal anesthesia may offer physiological advantages, preserve cerebral perfusion, and lower neurological complication rates. Conclusions: General anesthesia may exacerbate pre-existing brain vulnerability, converting reversible neural suppression into irreversible dysfunction. Therefore, whenever possible, regional/local or spinal anesthesia with or without sedation should be prioritized in those neurologically vulnerable patients to reduce the length of hospital stay (LOS) and to lower postoperative neurological complications and risks in psychiatric and neurologically unstable patients. Full article

Background/Objectives: The pericapsular nerve group (PENG) block is increasingly used as part of multimodal analgesia for total hip arthroplasty (THA). However, standard high-volume local anesthetic regimens may impair motor function. The addition of perineural dexamethasone could allow for volume reduction while maintaining analgesic efficacy and minimizing quadriceps weakness. This study evaluated whether adding dexamethasone to a low-volume PENG block prolongs analgesia, reduces opioid consumption, maintains pain control, and preserves motor function compared to a standard-volume PENG block. Materials and Methods: In this randomized controlled trial (NCT06470334), 60 adult patients undergoing THA via the direct superior approach received either a standard-volume PENG block with 20 mL of 0.2% ropivacaine (PENG group) or a low-volume block with 10 mL of 0.2% ropivacaine plus 4 mg of perineural dexamethasone (PENG + DEX group). The primary outcome was time to first rescue opioid. Secondary outcomes included total 48-h opioid consumption (oral morphine equivalents), pain scores (numeric rating scale, NRS) at rest and during movement, and quadriceps muscle strength at predefined postoperative intervals. Results: The PENG + DEX group demonstrated a significantly longer time to first opioid administration (15.0 ± 1.5 h vs. 9.1 ± 1.7 h; p < 0.0001) and reduced total opioid consumption within 48 h (2.3 ± 3.1 mEQ vs. 5.0 ± 4.4 mEQ; p = 0.0120). Pain scores were similar at 4 h but significantly lower in the PENG + DEX group at 8, 12, and 24 h postoperatively (all p < 0.01). Quadriceps strength was fully preserved in both groups at all assessed timepoints (p > 0.9999). Conclusions: The addition of perineural dexamethasone to a low-volume PENG block provides longer-lasting analgesia and reduces opioid requirements without compromising pain control or quadriceps function. This approach may improve the safety and efficacy of regional anesthesia in THA. Full article

This pilot study evaluated the feasibility and preliminary outcomes of computer-guided intraosseous anesthesia for oral surgery and dental implantology. Background/Objectives: The inferior alveolar nerve block (IANB) is widely used for dental anesthesia; however, issues such as anatomical variation and inflammation can hinder effective pain control. Alternatives have been studied primarily in irreversible pulpitis, with limited data available for other procedures. Methods: In a retrospective analysis, data from 85 patients who underwent implantation, root resection, or osteotomy using QuickSleeper^® intraosseous anesthesia (IO), infiltration (INF), or IANB were assessed. Results: IO, IANB, and INF produced similar pain levels during administration, procedure, and recovery; blood pressure and heart rate were comparable. IO and INF led to less lip numbness after 15 min and required less anesthetic. IO had a significantly shorter latency than IANB, allowing earlier surgery. Conclusions: Computer-guided IO is a viable alternative to IANB for implantation, root resection, and osteotomy, offering equal pain control, shorter latency, earlier surgery, and reduced injection volume. Within the limitations of this pilot study, the findings should be considered preliminary and require confirmation in larger prospective studies. Given the exploratory pilot design, no formal sample size calculation was performed; the sample size was defined by feasibility considerations. Full article

Postoperative pain following pediatric tonsillectomy remains a significant clinical challenge. Inadequate management leads to delayed recovery, dehydration, and increased healthcare utilization. Multimodal analgesia, including combining systemic analgesics, local anesthetic techniques, and adjunctive medications, has emerged as the standard of care. This review highlights current perioperative pain management strategies, including recent evidence on multimodal and opioid-sparing approaches. Local infiltration and nerve blocks provide site-specific pain relief, reducing opioid requirements and improving patient comfort. A comprehensive understanding and careful selection of analgesic regimens are crucial for enhancing outcomes in this population. Full article