Local Lidocaine Research Articles

Death from the introduction of Ceftriaxone in the presence of Lidocaine (case report)

In clinical and expert practice, pathological processes such as toxic reactions and anaphylaxis may develop following the introduction of the local anesthetic lidocaine; however, information about the death of children is limited and scattered. The morphological signs of these cases are non-specific, which leads to difficulty in interpreting the results of the study and determining the causes of death.
 This report described the death of a child following intramuscular administration of ceftriaxone in a 2% lidocaine solution. The results of the primary and commission examination of the corpse and data of repeated pathohistological examinations of a 2-year-old child are presented. The objective expert conclusion about the cause of death following the intramuscular administration of ceftriaxone in a 2% lidocaine solution was toxic effects (overdose) or anaphylactic shock, which requires assessing the sequence of the event and nature of the clinical picture, taking into account the route of drug administration, comprehensive pathohistological and morphological studies, and mandatory forensic chemical determination of the concentration of these drugs in the internal organs and blood.
 Morphological signs of an allergic reaction can be verified based on pathomorphological data, including changes in the target organs of anaphylaxis and pronounced hemocirculatory disorders. In our opinion, further in-depth study and systematization of available data are needed.

Effect of Volumes of Solutions on Intraocular Pressure During Intravitreal Injection of Low Dose Gentamicin in Horses With Recurrent Uveitis: A Randomized Controlled Study.

Horses with recurrent uveitis can be treated by intravitreal injection of low dose gentamicin under sedation and after local anesthetic techniques including the retrobulbar nerve block. Since it is reported that retinal degeneration can be secondary to an acute increase of intraocular pressure (IOP), the current randomized controlled study was carried out in order to investigate the changes in IOP following retrobulbar anesthesia, with two different volumes of local anesthetic (lidocaine) solution (10 and 5 mL), and intravitreal injection of 6 mg gentamicin in two different volumes of solution (0.3 and 0.15 mL). Multivariate regression showed that IOP was significantly lower in the pathologic eye at baseline (estimated effect size -6.1 mmHg; P=.0001) and after sedation (estimated effect size -9.4 mmHg; P < .0001). The IOP was significantly higher after a 10 mL block (P .0002) but this effect was very small (+0.5 mmHg). There was no significant difference in IOP after the injection of 0.15 or 0.3 mL solution of gentamicin. There was no significant combined effect of the volume of local anesthetic used for the block and the volume of the gentamicin solution. Since the expected anesthetic effects (desensitization and akinesia) were met in all cases, the smaller volume of 5 mL of lidocaine solution would be preferable for retrobulbar block for intravitreal injections, while intravitreal injections volumes of 0.15 and 0.30 mL can be used indifferently.

A Comparative Study between Surgical Techniques by Local Excisional debridement with a Xylocaine Block and Excisional Debridement under General Anesthesia, in Necrotizing Fasciitis

Objective: This study aimed to compare the clinical and economic outcomes between excisional debridement with a local xylocaine block (LAD) and excisional debridement under general anesthesia (GAD). Material and Methods: This retrospective medical record review was designed to review records of excisional debridement in necrotizing fasciitis (NF) at Sisaket Hospital from January 1, 2017, to December 31, 2019. Outcome measures were clinical outcomes at the preoperative time (baseline data, door-to-operating room), peri-operative time (operating time, blood loss, number of reoperations), postoperative time (mortality rate, length of stay, pain score, opioid drug use), types of NF, and direct costs of treatment by the provider’s perspective. Descriptive statistics, chi-square and Mann-Whitney U test were used. Results: The results of 245 patients showed that LAD was superior to GAD in terms of door-to-operating room time, lower operating time and blood loss, shorter length of hospital stay and lower cost of treatment. Moreover, the LAD showed a lower postoperative pain score, and less opioid drug use when compared to GAD. There were no significant differences in mortality rate, sites of infection and types of NF. Conclusion: LAD showed better clinical outcomes and lower cost of treatment when compared to GAD in the treatment of NF. Nevertheless, excisional debridement under a LAD could be a choice for small wounds at the lower extremities in hospitals with limited resources, and insufficient numbers of anesthesiologists.

Voltage sensor dynamics of a bacterial voltage-gated sodium channel NavAb reveal three conformational states

High-resolution structures of voltage-gated sodium channels (Nav) were first obtained from a prokaryotic ortholog NavAb, which provided important mechanistic insights into Na+ selectivity and voltage gating. Unlike eukaryotic Navs, the NavAb channel is formed by four identical subunits, but its ion selectivity and pharmacological profiles are very similar to eukaryotic Navs. Recently, the structures of the NavAb voltage sensor at resting and activated states were obtained by cryo-EM, but its intermediate states and transition dynamics remain unclear. In the present work, we used liposome flux assays to show that purified NavAb proteins were functional to conduct both H+ and Na+ and were blocked by the local anesthetic lidocaine. Additionally, we examined the real-time conformational dynamics of the NavAb voltage sensor using single-molecule FRET. Our single-molecule FRET measurements on the tandem NavAb channel labeled with Cy3/5 FRET fluorophore pair revealed spontaneous transitions of the NavAb S4 segment among three conformational states, which fitted well with the kinetic model developed for the S4 segment of the human voltage-gated proton channel hHv1. Interestingly, even under strong activating voltage, the NavAb S4 segment seems to adopt a conformational distribution similar to that of the hHv1 S4 segment at a deep resting state. The conformational behaviors of the NavAb voltage sensor under different voltages need to be further examined to understand the mechanisms of voltage sensing and gating in the canonical voltage-gated ion channel superfamily.

Lidocaine for Neuropathic Cancer Pain (LiCPain): study protocol for a mixed-methods pilot study

IntroductionMany patients experience unrelieved neuropathic cancer-related pain. Most current analgesic therapies have psychoactive side effects, lack efficacy data for this indication and have potential medication-related harms. The local anaesthetic lidocaine...

Evaluation of a constant rate intravenous infusion of dexmedetomidine on the duration of a femoral and sciatic nerve block using lidocaine in dogs.

This study investigated the effects of 1 μg/kg/h intravenous constant rate infusion (CRI) of dexmedetomidine on the sensory and motor blockade for femoral and sciatic nerve blocks in dogs undergoing stifle surgery. Client-owned dogs referred for stifle surgery were enrolled in this prospective, randomized, blinded study. Dogs were pre-medicated with acepromazine (0.005-0.01 mg/kg intramuscularly, IM); anesthesia was induced with propofol intravenously and maintained with isoflurane in a mixture of air and oxygen. Electrolocation-guided sciatic and femoral nerve blocks with lidocaine 2% (0.15 mL/kg) were performed using the parasacral and lateral pre-iliac approaches, respectively. After performing local block, a systemic infusion of saline solution (group C) or dexmedetomidine (group D) was started at a CRI at 1 ml/kg/h and continued until the end of surgery. Dexmedetomidine was infused at a dose of 1 μg/kg/h. Respiratory and hemodynamic variables were recorded during surgery. Sensory and motor blockade was evaluated by response to pinching the skin innervated by the sciatic/femoral nerves, with forceps and by observing the dogs' ability to walk and testing proprioception at 30, 60, 120, 180, and 240 min after extubation. Analgesia was monitored with SF-GCPS. Methadone IM was administered as rescue analgesia. Intraoperative data were analyzed by analysis of variance, while postoperative data were analyzed by the independent two-tailed t-test and a Kaplan-Meier test (p < 0.05). Twenty dogs were included in this study (10/group). A significant difference in the recovery of sensory nerve function was observed between the groups. The mean durations of the sensory blockade for femoral and sciatic nerves, respectively, was longer (p < 0.001) for group D [168 (146-191, 95% CI), 161 (143-179, 95% CI) min] than in group C [120 (96.1-144, 95% CI), 116 (90.9-142, 95% CI]. No differences in the recovery of patellar and tibial reflexes, proprioceptive function, and ability to walk were found among groups. The overall postoperative rescue analgesia requirement was significantly different (p = 0.019) between groups, with an incidence of 5/10 (50%) dogs in group D and 10/10 (100%) dogs in group C. Dexmedetomidine administered as a CRI (1 μg/kg/h) combined with local lidocaine increases the duration of the sensory component of the sciatic and femoral nerve blocks and reduces the requirement for additional analgesia during the immediate postoperative hours.

Suppressing Discomfort Caused by Electrical Stimulation Using a Local Anesthetic Cream

Electrical stimulation is one of the methods that have been developed to stimulate skin sensations, and can provide sensations such as vibration and pressure by varying the polarity of the stimulus. Such stimuli can be combined to generate a variety of tactile sensations. However, itching or painful sensations are elicited with increasing amounts of electrical current. To address this major problem, in this study, we developed a method to suppress the itching and pain caused by electrical stimulation while presenting stable pressure and vibration sensations. We applied an anesthetic cream containing the commonly used local anesthetics lidocaine and propitocaine to reduce pain and itching associated with electrical stimulation. In particular, we examined the effects of the local anesthetic cream on pain and tactile thresholds. The results showed a significant relationship between the application of the cream and the dynamic range (i.e., pain and tactile thresholds) of the stimulating current. Thus, our proposed approach considerably improved the quality of the participants’ subjective experience with electrical stimulation technology.

The impact of Lidocaine gel on TNF-α expression in surgically induced oral mucosal ulcers: an immunohistochemical analysis in rabbits

Background: Besides being a local anesthetic agent lidocaine is a promising anti-inflammatory agent with limited studies on its effect on the mucosa. Aim: Assess the anti-inflammatory effect of lidocaine following surgical induction wound in the oral mucosa as assessed by tumor necrosis factor-α (TNF-α) expression. Materials and methods: The study was conducted on 32 albino rabbits that were categorized into 2 equal groups of 16 rabbits: In the control group an oral wound was surgically induced and left without treatment and in the treatment group an oral wound was surgically induced and received topical Lidocaine gel. Euthanasia of animals was carried out on days 1, 3, 7, and 10, and sample sites were processed for histopathological and immunohistochemical staining for TNF-α. Results: In the histological observations, it was noticed that the healing process was more rapid and convenient in the test group compared to the control group. For Immunohistochemical assessment, the TNF-α started to express clearly at 1 day and gradually decreased and disappeared at 10 days with a superior effect of the lidocaine group over the control group. Conclusion: Lidocaine seems to have anti-inflammatory reactions by lowering TNF-α levels and preventing the production of pro-inflammatory cytokines.

Development and Evaluation of Combined Effect Buccal Films for Treatment of Oral Candidiasis.

Buccal film formulations, including antifungal nystatin, anti-inflammatory agent hydrocortisone acetate, and local anesthetic lidocaine hydrochloride for pain relief, were developed. Bioadhesive films were fabricated with hydrophilic polymers, hydroxyethyl cellulose (HEC), and xanthan gum (XG) and dried in the incubator. Textural, swelling, and bioadhesive properties, physicochemical and in vitro release characteristics, and antifungal activities of bioadhesive films were evaluated.Bioadhesive films significantly extended nystatin release by prolonging retention time of the target area formulation while rapidly releasing hydrocortisoneacetate and lidocaine HCl, reducing drug administration. The polymer type affected bioadhesion strength and erosion ratio, and XG formulations had more polymer suitability. Consequently, XT-O2 formulation that was prepared with xanthan gum and tween 80,was best for its highest antifungal film activity (20.00 ± 0.07mm), released nystatin (44.296% ± 1.695), and lowest erosion matrix (36.719% ± 0.249). The selected formulation can be used for compatibility, stability and in vivo studies targeted oral candidiasis infections.

892 ELECTRICAL STORM IN ISCHAEMIC HEART DISEASE: A CASE OF LEFT STELLATE GANGLION BLOCK AS BRIDGE TO URGENT PCI RESCUE

Abstract A 73 year-old man was admitted for syncope and sustained ventricular arrhythmia complicated by cardiogenic shock treated with electrical cardioversion and restoration of sinus rhythm. Former smoker, he suffered by arterial hypertension, hypercholesterolemia and known heart failure with reduced ejection fraction. In the 1995 the patient underwent aortic valve replacement surgery with a mechanical prosthetic valve. The patient underwent coronary angiography that showed multivessel coronary artery disease with functional occlusion of posterior interventricular artery (rehabilitated by hetero-coronary circles) and critical stenosis of the middle left anterior descending artery. In this angiographic framework, the indication was collegial revaluation considering other patient's comorbidities (chronic renal dysfunction, mitral moderate-severe regurgitation). The patient underwent ICD implantation for secondary prevention. Despite maximal medical therapy, the patient experienced new episodes of sustained VT complicated by hemodynamic instability. Hypokalemia, hypomagnesemia and hyperthyroidism were excluded as triggering factors for arrhythmias on laboratory investigations. In the following days due to persistent and symptomatic arrhythmias, configuring electrical storm, we decided to proceed with anatomical stellate ganglion block, guarantying a free interval from ventricular arrhythmia about six hours. The anesthetic has been injected at the C6 or C7 vertebral level with the Chassignac's tubercle, the cricoid cartilage, and the carotid artery serving as the anatomic landmarks to the procedure. An aspiration test must be done to avoid the suction of blood or cerebrospinal fluid, then a local anesthetic is injected, and the diffusion of the injectate is seen in real-time. Local anesthetic (lidocaine mixed with bupivacaine) is injected until the fluid spread along the paravertebral fascia to the stellate ganglion. The period free from VA allowed us to transfer the patient in another center in order to receive myocardial revascularization supported by ECMO. Left ganglion stellate block has a central role in the treatment of the refractory ventricular arrhythmias and may offer effective arrhythmia control giving time to rescue and/or other bridge therapy. In our case, it had a key role to perform an inter-hospital transfer and subsequent “rescue PCI therapy”. Thanks to Stellate ganglion block, the sinus rhythm was retained immediately, there were no ventricular tachycardia episodes for at least six hours allowing to perform myocardial revascularization supported by ECMO. No further ventricular arrhythmias occurred after revascularization, corroborating the ischemic trigger of electrical storm.

Apoptosis, Proliferation, and Autophagy Are Involved in Local Anesthetic-Induced Cytotoxicity of Human Breast Cancer Cells.

Breast cancer accounts for almost one quarter of all female cancers worldwide, and more than 90% of those who are diagnosed with breast cancer undergo mastectomy or breast conservation surgery. Local anesthetics effectively inhibit the invasion of cancer cells at concentrations that are used in surgical procedures. The limited treatment options for triple-negative breast cancer (TNBC) demonstrate unmet clinical needs. In this study, four local anesthetics, lidocaine, levobupivacaine, bupivacaine, and ropivacaine, were applied to two breast tumor cell types, TNBC MDA-MB-231 cells and triple-positive breast cancer BT-474 cells. In addition to the induction of apoptosis and the suppression of the cellular proliferation rate, the four local anesthetics decreased the levels of reactive oxygen species and increased the autophagy elongation indicator in both cell types. Our combination index analysis with doxorubicin showed that ropivacaine had a synergistic effect on the two cell types, and lidocaine had a synergistic effect only in MDA-MB-231 cells; the others had no synergistic effects on doxorubicin. Lidocaine contributed significantly to the formation of autophagolysosomes in a dose-dependent manner in MDA-MB-231 cells but not in BT-474 cells. Our study demonstrated that the four local anesthetics can reduce tumor growth and proliferation and promote apoptosis and autophagy.

Radiocaine: An Imaging Marker of Neuropathic Injury.

Voltage-gated sodium channels (Navs) play a crucial electrical signaling role in neurons. Nav-isoforms present in peripheral sensory neurons and dorsal root ganglia of the spinal cord are critically involved in pain perception and transmission. While these isoforms, particularly Nav1.7, are implicated in neuropathic pain disorders, changes in the functional state and expression levels of these channels have not been extensively studied in vivo. Radiocaine, a fluorine-18 radiotracer based on the local anesthetic lidocaine, a non-selective Nav blocker, has previously been used for cardiac Nav1.5 imaging using positron-emission tomography (PET). In the present study, we used Radiocaine to visualize changes in neuronal Nav expression after neuropathic injury. In rats that underwent unilateral spinal nerve ligation, PET/MR imaging demonstrated significantly higher uptake of Radiocaine into the injured sciatic nerve, as compared to the uninjured sciatic nerve, for up to 32 days post-surgery. Radiocaine, due to its high translational potential, may serve as a novel diagnostic tool for neuropathic pain conditions using PET imaging.

Efficacy of lidocaine local anesthesia on pain perception during amniocentesis: A meta-analysis of randomized controlled trials.

To evaluate the efficacy of lidocaine local analgesia on maternal pain reduction during amniocentesis. Web of Science, Scopus, PubMed, and CENTRAL databases were screened from inception and updated in July 2022. The included randomized controlled trials (RCTs) were evaluated for the risk of bias via the Cochrane tool. The primary outcome was pain perception using the 10 cm visual analog scale, and was summarized as mean difference (MD) with 95% confidence interval (CI) in a random-effects model. Subgroup analysis was performed according to the mode of administration. Meta-analysis was done via Review Manager software. We included five RCTs totaling 1004 women (lidocaine arm n=502 patients and control arm n=502 patients). Overall, there was no significant difference between both arms [MD=-0.21, 95% CI (-0.48, 0.07), p=0.80]. The pooled analysis showed homogeneity (p=0.13, I2=43%). Subgroup analysis according to the mode of administration showed that pain perception did not significantly differ between both arms when lidocaine was employed as injection [n=3 RCTs, MD=-0.26, 95% CI (-0.76, 0.23), p=0.29] or non-injection [n=2 RCTs, MD=-0.18, 95% CI (-0.55, 0.18), p=0.33]. The pooled analyses showed heterogeneity (p=0.05, I2=66%) and homogeneity (p=0.27, I2=19%), respectively. There was no noteworthy change concerning maternal pain perception between the lidocaine and control arms. Most women reported just minimal discomfort during amniocentesis. Counseling should educate patients that the pain they might experience during amniocentesis is comparable to venous blood sampling.

Naphazoline and oxymetazoline are superior to epinephrine in enhancing the cutaneous analgesia of lidocaine in rats.

This study observed the cutaneous analgesic effect of adrenergic agonists when combined with lidocaine. We aimed at the usefulness of four adrenergic agonists and epinephrine as analgesics or as tools to prolong the effect of local anesthetics using a model of cutaneous trunci muscle reflex (pinprick pain) in rats. We showed that subcutaneous four adrenergic agonists and epinephrine, as well as the local anesthetic bupivacaine and lidocaine, developed a concentration-dependent cutaneous analgesia. The rank order of the efficacy of different compounds (ED50 ; median effective dose) was epinephrine [0.013 (0.012-0.014)μmol] > oxymetazoline [0.25 (0.22-0.28) μmol] > naphazoline [0.42 (0.34-0.53)μmol] = bupivacaine [0.43 (0.37-0.50) μmol] > xylometazoline [1.34 (1.25-1.45)μmol] > lidocaine [5.86 (5.11-6.72) μmol] > tetrahydrozoline [6.76 (6.21-7.36)μmol]. The duration of full recovery caused by tetrahydrozoline, oxymetazoline, or xylometazoline was greater (P < 0.01) than that induced via epinephrine, bupivacaine, lidocaine, or naphazoline at equianesthetic doses (ED25 , ED50 , and ED75 ). Co-administration of lidocaine (ED50 ) with four adrenergic agonists or epinephrine enhanced the cutaneous analgesic effect. We observed that four adrenergic agonists and epinephrine induce analgesia by themselves, and such an effect has a longer duration than local anesthetics. Co-administration of lidocaine with the adrenergic agonist enhances the analgesic effect, and the cutaneous analgesic effect of lidocaine plus naphazoline (or oxymetazoline) is greater than that of lidocaine plus epinephrine.

Synthesis and characterization of molecularly imprinted polymers for detection of the local anesthetic lidocaine in urine

AbstractMolecularly imprinted polymers are materials that can capture target analytes using molecular recognition. These polymers can efficiently detect trace target chemical species in biological samples, such as urine and blood, containing various matrix components. We aimed to analyze the interaction of molecularly imprinted polymers with the target molecule lidocaine, which is an amino amide pharmaceutical. Lidocaine‐templated molecularly imprinted polymers were synthesized by bulk polymerization. Gas chromatography‐mass spectrometry showed there was a strong interaction between lidocaine and the recognition site in the molecularly imprinted polymers. Non‐selective adsorption of lidocaine on the molecularly imprinted polymers was confirmed and characterized by Scatchard analysis. The washing solution was optimized for the separation of lidocaine from the structurally similar anesthetics procaine and tetracaine by taking advantage of differences in binding strength. The molecularly imprinted polymers could adsorb lidocaine in urine samples and were not affected by interfering compounds. Consequently, they could be applied to the analysis of biological materials. These results suggest that the molecularly imprinted polymers can be used for separation and detection with high selectivity and could be applied in forensic and clinical analysis.

Transversus Abdominis Plane Block as a Strategy for Effective Pain Management in Patients with Pain during Laparoscopic Cholecystectomy: A Systematic Review.

Laparoscopic cholecystectomy (LC), unlike laparotomy, is an invasive surgical procedure, and some patients report mild to moderate pain after surgery. Transversus abdominis plane (TAP) block has been shown to be an appropriate method for postoperative analgesia in patients undergoing abdominal surgery. However, there have been few studies on the efficacy of TAP block after LC surgery, with unclear information on the optimal dose, long-term effects, and clinical significance, and the analgesic efficacy of various procedures, hence the need for this review. Five electronic databases (PubMed, Academic Search Premier, Web of Science, CINAHL, and Cochrane Library) were searched for eligible studies published from inception to the present. Post-mean and standard deviation values for pain assessed were extracted, and mean changes per group were calculated. Clinical significance was determined using the distribution-based approach. Four different local anesthetics (Bupivacaine, Ropivacaine, Lidocaine, and Levobupivacaine) were used at varying concentrations from 0.2% to 0.375%. Ten different drug solutions (i.e., esmolol, Dexamethasone, Magnesium Sulfate, Ketorolac, Oxycodone, Epinephrine, Sufentanil, Tropisetron, normal saline, and Dexmedetomidine) were used as adjuvants. The optimal dose of local anesthetics for LC could be 20 mL with 0.4 mL/kg for port infiltration. Various TAP procedures such as ultrasound-guided transversus abdominis plane (US-TAP) block and other strategies have been shown to be used for pain management in LC; however, TAP blockade procedures were reported to be the most effective method for analgesia compared with general anesthesia and port infiltration. Instead of 0.25% Bupivacaine, 1% Pethidine could be used for the TAP block procedures. Multimodal analgesia could be another strategy for pain management. Analgesia with TAP blockade decreases opioid consumption significantly and provides effective analgesia. Further studies should identify the long-term effects of different TAP block procedures.

Improving pain control during transarterial chemoembolization for hepatocellular carcinoma performed under local anesthesia with multimodal analgesia

PurposeThe purpose of this study was to assess the performance of a reinforced analgesic protocol (RAP) on pain control in patients undergoing conventional trans-arterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC). Materials and methodsEighty-one consecutive patients (57 men, 24 women) with a mean age of 69 ± 10 (standard deviation) years (age range: 49–92 years) underwent 103 cTACEs. Standard antalgic protocol (50 mg hydroxyzine, 10 mg oxycodone, 8 mg ondansetron, and lidocaine for local anesthesia) was prospectively compared to a RAP (standard + 40 mg 2-h infusion nefopam and 50 mg tramadol). The individual pain risk was stratified based on age, the presence of cirrhosis and alcoholic liver disease, and patients were assigned to a low-risk group (standard protocol) or high-risk group (RAP). The primary endpoint was severe periprocedural abdominal pain (SAP), defined as a visual analog scale score ≥30/100. A predefined intermediate analysis was performed to monitor the benefit-risk of the RAP. Based on the intermediate analysis, all patients were treated with the RAP. ResultsThe intermediate analysis performed after 52 cTACE showed that 2/17 (12%) high-risk patients (i.e., those receiving the RAP) experienced SAP compared to 15/35 (43%) low-risk patients (odds ratio [OR] = 0.18; 95% confidence interval [CI]: 0.02–0.98; P = 0.03). Analysis of all procedures showed that 12/67 (18%) patients in cTACE receiving the RAP experienced SAP compared to 15/36 (42%) patients who did not receive it (OR = 3.27; 95% CI: 1.32–8.14; P = 0.01). There were no statistical differences in adverse events, particularly for nausea, between groups. ConclusionReinforcing the analgesic protocol by combining non-opioid and opioid molecules reduces perioperative pain in patients undergoing cTACE for HCC.

Inflammatory diseases of the external ear: place and possibilities of topical therapy

Otitis externa (NO) is manifested by inflammatory changes in the auricle, external auditory canal and epidermal layer of the eardrum. The disease is characterized by a wide prevalence and a continuing increase in morbidity, a persistent, resistant to adequate therapy course and frequent recurrence of the pathological process. For the development of NO, the presence of an etiotropic agent and a violation of the integrity of the epidermal layer of the skin of an endogenous and exogenous nature are necessary. According to the area of distribution and the type of pathological process, limited and diffuse NO are considered. Most often, bacteria act as the causative agents of NO, with diffuse forms Pseudomonas aeruginosa is the leader. The appointment of systemic antibiotics for uncomplicated forms of NO is impractical, it is optimal to use topical combined drugs that have adequate activity against the main pathogens of NO. The advantages of topical therapy in such patients are the rapid accumulation of required active substance concentration in the area of inflammation and almost complete lack of systemic action, minimal risk of development and spread of resistant strains of microorganisms. It is required to use antimicrobial agents that have been shown to be active against the main pathogens of otitis externa. The reduction of inflammation and pain is also an important component of the management of patients with OE. A good option for topical therapy of patients with inflammatory changes in the external ear is a drug with antimicrobial and local anesthetic action containing antibacterial components: aminoglycoside neomycin sulfate and cyclic polypeptide polymyxin B sulfate, and local anesthetic lidocaine hydrochloride. Such agents have a balanced antimicrobial and local anesthetic action, high safety and can be recommended for use in patients with diffuse otitis externa.

Effect of microneedles shape on skin penetration and transdermal drug administration

Microneedle (MN) patches are highly efficient and versatile tools for transdermal drug administration, in particular for pain-free, self-medication and rapid local applications. Diffraction ultraviolet (UV) light lithography offers an advanced method in fabricating poly(ethylene glycol)-based MNs with different shapes, by changing both the UV-light exposure time and photomask design. The exposure time interval is limited at obtaining conical structures with aspect ratio < 1:3, otherwise MNs exhibit reduced fracture load and poor indentation ability, not suitable for practical application. Therefore, this work is focused on a systematic analysis of the MN's base shapes effects on the structural characteristics, skin penetration and drug delivery. Analyzing four different base shapes (circle, triangle, square and star), it has been found that the number of vertices in the polygon base heavily affects these properties. The star-like MNs reveal the most efficient skin penetration ability (equal to 40 % of -their length), due to the edges action on the skin during the perforation. Furthermore, the quantification of the drug delivered by the MNs through ex-vivo porcine skin shows that the amounts of small molecules released over 24 h by star-like MNs coated by local anesthetic (Lidocaine) and an anti-inflammatory (Diclofenac epolamine) drugs are 1.5× and 2× higher than the circular-MNs, respectively.

Pain in the hours following surgical and rubber ring castration in dairy calves: Evidence from conditioned place avoidance

Male cattle reared for beef are typically castrated. Male calves born on dairy farms are increasingly reared for beef, so a better understanding of how to humanely perform this procedure in dairy systems is now required. We studied the short-term affective responses of dairy calves to castration using a conditioned place aversion paradigm. Young Holstein bulls (16 d old, n = 30) were castrated by either rubber ring (n = 15) or surgery (n = 15), and then kept in a visually distinctive recovery pen for 6 h after the procedure. Calves acted as their own control and were sham castrated and allowed to recover for 6 h in another visually distinctive pen. During both castration and sham procedures, calves received a sedative (xylazine, 0.2 mg/kg), local anesthetic (lidocaine, 5 mL), and a nonsteroidal anti-inflammatory (meloxicam, 0.5 mg/kg). After exposure to both treatments (castration and sham), calves were tested for place aversion by providing free access to the 2 pens where they experienced the different treatments. Calves were tested for aversion 48, 72, and 96 h after their last treatment. We recorded how much time they spent in each pen and where they chose to rest. We did not find differences in time spent resting or resting location, suggesting that calves did not form a more negative memory of castration in comparison to the sham procedure. The lack of treatment effects may be due to features of our testing paradigm, including effective multimodal pain control during the 6-h conditioning period and limiting testing to the first days after the procedure.