Effects Of Local Anesthetics Research Articles

Clinical Efficacy and Safety of Lidocaine Tape for Topical Anesthesia of the Oral Mucosa: A Preliminary Controlled Trial.

Local anesthesia is administered to reduce pain-induced stress during dental treatment. However, local anesthetic injections are extremely painful; thus, methods to minimize this pain should be developed. Clinical studies on the pain-relieving effects of dental topical anesthetics have shown that few topical anesthetics provide fast and adequate pain relief without harming the oral mucosa. We examined the efficacy and safety of lidocaine tape, which has a potent topical anesthetic effect. Lidocaine tape was applied to the oral mucosa of 14 healthy participants, and its suppression effect was assessed by examining the pain intensity at the non-lidocaine tape-applied site using the visual analog evaluation scale and the verbal evaluation scale. Lidocaine tape application significantly reduced visual analog scale (VAS) scores during mucosal puncture compared to non-application (p < 0.01). Moreover, lidocaine tape application significantly reduced VAS scores during local anesthetic injection compared to non-application (p < 0.001). Adverse events were evaluated using the Common Terminology Criteria for Adverse Events, version 5.0. No adverse events attributed to the application of lidocaine tape were observed in any participant. The findings in this study suggest that the application of lidocaine tape before infiltration anesthesia can reduce patient distress.

Development of a Predictive Statistical Pharmacological Model for Local Anesthetic Agent Effects with Bayesian Hierarchical Model Parameter Estimation.

As an alternative to animal use, computer simulations are useful for predicting pharmacokinetics and cardiovascular activities. For this purpose, we constructed a statistical model to simulate the effects of local anesthetic agents. To train the model, animal experiments were performed on 6-week-old male Hartley guinea pigs. Firstly, the guinea pigs' backs were shaved, then local anesthetic agents were subcutaneously injected, with subsequent stimulation of the anesthetized site with a needle six times at regular intervals. The number of reactions (score value) was counted. In this statistical model, the probability of reacting to needle stimulation was calculated using the elapsed time, type of local anesthetic agent, and presence or absence of adrenaline. Score values were assumed to follow a binomial distribution at the calculated probability. Parameters were estimated using the Bayesian hierarchical model and Hamiltonian Monte Carlo method. The predicted curves using the estimated parameters fitted well the observed animal values. When score values were predicted using randomly generated parameters, the median of duration was similar between animal experiments and simulations (Procaine: 55 min vs. 50 min, Lidocaine: both 60 min, and Mepivacaine: both 85 min). This approach effectively modeled the effects of local anesthetic agents. It is possible to create the simulator using the parameter values estimated in this study.

The condition of newborns after the conversion of epidural analgesia to anesthesia during cesarean section: a prospective randomized study

INTRODUCTION: When performing epidural analgesia in childbirth, if surgical delivery is necessary, the question arises about the choice of further tactics of regional anesthesia. The article discusses the peculiarities of the effect of local anesthetics on the condition of a newborn during the conversion of epidural analgesia into anesthesia when caesarean section is necessary, depending on the local anesthetic used. OBJECTIVE: To assess the condition of a newborn baby during the conversion of epidural analgesia in childbirth through the natural birth canal into anesthesia during cesarean section, depending on the local anesthetic used. MATERIALS AND METHODS: A prospective randomized study of 143 children born to mothers who underwent the conversion of epidural analgesia into anesthesia for operative delivery by caesarean section was conducted. Depending on the local anesthetic used, the patients were divided into three groups, in the first group 20.0 ml of 2 % lidocaine in combination with 0.1 mg of epinephrine was injected into the epidural space, in the second group — 20.0 ml of 0.5 % bupivacaine, in the third — 20.0 ml of 0.75 % ropivacaine. The assessment of the condition of newborns was carried out on the Apgar scale at the 1st and 5th minutes of life and on the NACS scale in the first 15 minutes, 2, 24 and 72 hours after birth. RESULTS: The assessment of newborns on the Apgar scale, regardless of the local anesthetic used during epidural anesthesia at the first and fifth minutes, corresponded to 7 or more points (p &gt; 0.05). The neuropsychiatric state of newborns when assessed on the NACS scale did not differ statistically significantly in all groups and at all stages of the study. Within each group, between the study stages, the average values of the NACS scores increased statistically significantly compared to the previous one. CONCLUSIONS: The conversion of epidural analgesia in childbirth through the natural birth canal into anesthesia during cesarean section is safe for the fetus and newborn when using 20.0 ml of 2 % lidocaine in combination with 0.1 mg of epinephrine or 20.0 ml of 0.5 % bupivacaine, or 0.75 % ropivacaine in a volume of 20.0 ml.

Cryotherapy: A new paragon in the field of endodontics

The discussion on cryotherapy mechanism, its physiological effects, and many uses in the field of endodontics was motive of this review study. The chosen articles were limited to those which were published in English by using few specific keywords. An electronic search of research papers was conducted on the complete PubMed database using certain keywords. Using combinations of the pre-defined keywords, the last access was in January 2021. According to studies, using the intracanal cryotherapy approach in combination with irrigation under negative pressure relieves post-endodontic discomfort. It was also seen that DCT (deep cryogenic treatment) had successfully raised the cyclic fatigue resistance with 24-hour soaking time by 13% and with 6-hour only 1%. Anyhow, soaking time does not influence cutting efficiency. When combined with local anaesthesia, cryotherapy has a local anaesthetic effect by lowering the nociceptors activation threshold and the conduction velocity of pain signals. Therefore, in case of symptomatic apical periodontitis, cryotherapy is a straightforward and affordable adjunctive approach for reducing postoperative discomfort and for managing pulpal hemorrhage during critical pulp therapy. Also, unquestionably an essential step in treating edoema and discomfort following endodontic surgery.

Determination of Scalp Vascular Topography by Laser Doppler Flowmetry and Comparison of Vascular Damage by Different Blades in Hair Transplantation.

Although necrosis is a rare complication in hair transplantation, it is extremely traumatic for both the patient and surgeon and also has potential medicolegal consequence. Studies have shown that ischemia in the recipient bed is related to tissue damage caused by the instruments used and the number of grafts per cm². We aimed to measure the effects of different instruments on circulation by dividing the recipient area of hair grafts of the same person into 2 sides as right and left. Sapphire percutaneous blade was used on the right side, and a handmade razor slit was used on the left side in 12 male patients with consent. Subsequently, vascularity was evaluated with laser Doppler flowmetry. Scalp vascularity has so far only been evaluated with macroanatomic studies in the literature. First, the authors evaluated the effect of local anesthesia and adrenaline-containing swelling fluids on vascularity with a Laser Doppler Flowmeter. Afterward, the tissue damage caused by sapphire percutaneous blades and handmade blades (obtained from razor blades) were quantitatively analyzed and compared with each other. Our results showed that handmade razor blades caused significantly less tissue damage.

The use of articaine for anesthetic support in geriatric patients with degenerative-dystrophic hand and forearm conditions: results of a randomized trial

Aim. To conduct a comparative analysis of the effectiveness of local anesthetics used for regional anesthesia.Methods. An open randomized study was conducted to assess the effiacy and safety of Articaine-Binergia 20 mg/ml and Lidocaine as local anaesthetics for anaesthesia at two levels (axillary and wrist) during surgical procedures on the upper limbs of geriatric patients with degenerative-dystrophic hand and forearm conditions.Results. The results of the study convincingly proved the advantage of Articaine-Binergia 20 mg/ml in terms of effiacy and safety. A notable advantage observed was the shorter latency period, which translates into reduced patient time in the operating room and increased operational effiiency.Conclusions. Based on the study fidings, Articaine-Binergia is recommended for anaesthesia in traumatology-orthopedics involving upper limb procedures, especially for patient groups at higher risk of systemic toxicity.

Development of a Dosage form for a Photoswitchable Local Anesthetic Ethercaine.

The toxicity of local anesthetics is a serious problem, given their widespread use. One of the main causes of the side effects of local anesthetics is their non-selectivity of action in the body. A possible way to increase the selectivity of the action of drugs is to use the photopharmacology approach. Previously, we described the light-controlled local anesthetic ethercaine, the biological effect of which can be controlled using light, thereby increasing its selectivity of action. An important limitation of ethercaine was its low solubility in water, limiting the potential of this compound. In this work, we developed a dosage form of ethercaine, which allowed us to increase its solubility from 0.6% to 2% or more. The resulting 1% solution of ethercaine hydrochloride in 4% Kolliphor ELP had high biological activity on the surface anesthesia model, while demonstrating low acute toxicity in mice with intravenous administration (4-5 times less than that of lidocaine).

Effect of local anesthetics on renal function: An animal study in Iran

Effect of local anesthetics on renal function: An animal study in Iran

Lipid Emulsion for Spinal Anaesthesia Reversal - A Therapeutic Option

High spinal anaesthesia is also one of the commonly faced problems, with a low incidence of a complete spinal block; which is one of the life-threatening complications unless immediately identified and treated. Up to now, its management has relied mainly on intensive means such as respiratory and circulatory assistance. Intravenous lipid emulsions have an established position in the management of local anesthetic toxicity. After the success in this area, ILE has been used under clinical conditions for various kinds of overdose. At present, ILEs are expanding into a new field, that of reversing the effects of local anesthesia on peripheral nerves and neuraxial anesthesia. We report two cases of patients operated at our department, the first for genital prolapse under perimedullary anaesthesia, complicated by high spinal anaesthesia. The second case was a patient who underwent Caesarean section under spinal anaesthesia, intubated mid-operatively and presented with postoperative delayed awakening. Both complications were resolved by intralipid injection. We then reviewed the literature concerning similar cases and the different means used to resolve the problem.

СОЕДИНЕНИЕ N-АЦЕТИЛ-6-АМИНОГЕКСАНОВОЙ КИСЛОТЫ ПОДАВЛЯЕТ НЕРВНУЮ ПРОВОДИМОСТЬ

Local anesthetic effect of N-acetyl-6-aminohexanoate salt (compound LHT-9-17) in the form of a substance with a purity of 99.8% was studied and also assessed the effect of the substance on the conductivity of single sodium channels and the conductivity of the nerve conductor at normal pH values and against the background of acidosis. Experimental ligature periodontitis was modeled in 20 laboratories male Wistar rats weighing 200-220 g. Local anesthetic effects of 2% LHT-9-17 and 2% lidocaine hydrochloride solution induced by infraorbital administration was assessed at day 12 of the pathology development. Conduction of single Na-channels was assessed by patch-clamp method on isolated giant neurons of Limnea stagnalis. Registration of the action potential of Rana radibunda isolated sciatic nerve was carried out in perfusion chamber contained 0.00001 to 0.01 μM LCT-9-17. Experiments included increasing the force of stimulating incentives until the maximum response. Compound LHT-9-17 has local anesthetic activity, including during the inflammatory process. The analgesic effect is due to the suppression of the conductivity of Na-channels of nerve conductors. The activity kept under inflammatory conditions may be due to the action of substances against the inflammatory state.

Pharmacological interventions for the management of pain and discomfort during lumbar puncture in newborn infants.

Lumbar puncture (LP) is a common invasive procedure, most frequently performed to diagnose infection. Physicians perform LP in newborn infants with the help of an assistant using a strict aseptic technique; it is important to monitor the infant during all the steps of the procedure. Without adequate analgesia, LP can cause considerable pain and discomfort. As newborns have increased sensitivity to pain, it is crucial to adequately manage the procedural pain of LP in this population. To assess the benefits and harms, including pain, discomfort, and success rate, of any pharmacological intervention during lumbar puncture in newborn infants, compared to placebo, no intervention, non-pharmacological interventions, or other pharmacological interventions. We searched CENTRAL, PubMed, Embase, and three trial registries in December 2022. We also screened the reference lists of included studies and related systematic reviews for studies not identified by the database searches. We included randomized controlled trials (RCTs) and quasi-RCTs comparing drugs used for pain management, sedation, or both, during LP. We considered the following drugs suitable for inclusion. • Topical anesthetics (e.g. eutectic mixture of local anesthetics [EMLA], lidocaine) • Opioids (e.g. morphine, fentanyl) • Alpha-2 agonists (e.g. clonidine, dexmedetomidine) • N-Methyl-D-aspartate (NMDA) receptor antagonists (e.g. ketamine) • Other analgesics (e.g. paracetamol) • Sedatives (e.g. benzodiazepines such as midazolam) DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We used the fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD) or standardized mean difference (SMD) for continuous data, with their 95% confidence intervals (CIs). Our main outcomes were successful LP on first attempt, total number of LP attempts, episodes of bradycardia, pain assessed with validated scales, episodes of desaturation, number of episodes of apnea, and number of infants with one or more episodes of apnea. We used the GRADE approach to evaluate the certainty of the evidence. We included three studies (two RCTs and one quasi-RCT) that enrolled 206 newborns. One study included only term infants. All studies assessed topical treatment versus placebo or no intervention. The topical anesthetics were lidocaine 4%, lidocaine 1%, and EMLA. We identified no completed studies on opioids, non-steroidal anti-inflammatory drugs, alpha-2 agonists, NMDA receptor antagonists, other analgesics, sedatives, or head-to-head comparisons (drug A versus drug B). Based on very low-certainty evidence from one quasi-RCT of 100 LPs in 76 infants, we are unsure if topical anesthetics (lidocaine), compared to no anesthesia, has an effect on the following outcomes. • Successful LP on first attempt (first-attempts success in 48% of LPs in the lidocaine group and 42% of LPs in the control group) • Number of attempts per LP (mean 1.9 attempts, [standard error of the mean 0.2] in the lidocaine group, and mean 2.1 attempts [standard error of the mean 2.1] in the control group) • Episodes of bradycardia (0% of LPs in the lidocaine group and 4% of LPs in the control group) • Episodes of desaturation (0% of LPs in the lidocaine group and 8% of LPs in the control group) • Occurrence of apnea (RR 3.24, 95% CI 0.14 to 77.79; risk difference [RD] 0.02, 95% CI -0.03 to 0.08). Topical anesthetics compared to placebo may reduce pain assessed with the Neonatal Facial Coding System (NFCS) score (SMD -1.00 standard deviation (SD), 95% CI -1.47 to -0.53; I² = 98%; 2 RCTs, 112 infants; low-certainty evidence). No studies in this comparison reported total number of episodes of apnea. We identified three ongoing studies, which will assess the effects of EMLA, lidocaine, and fentanyl. Three studies are awaiting classification. The evidence is very uncertain about the effect of topical anesthetics (lidocaine) compared to no anesthesia on successful lumbar puncture on first attempt, the number of attempts per lumbar puncture, episodes of bradycardia, episodes of desaturation, and occurrence of apnea. Compared to placebo, topical anesthetics (lidocaine or EMLA) may reduce pain assessed with the NFCS score. One ongoing study will assess the effects of systemic treatment.

The Correlation between Trigeminal Neuralgia and Local Anesthetics Neurotoxicity Associated with Acute Inflammation: A Cross-sectional Study

Background: Trigeminal neuralgia (TN) represents a subject of importance in oral medicine due to the large number of patients complaining of TN who are aware that the orofacial pain has a dental origin and therefore seek initial care from the dentist. The reasons for the majority of TN cases remain controversial, but nearly 10% of patients have an obvious pathological condition, such as intracranial pathology. Aim: This study aimed to assess the correlation between idiopathic trigeminal neuralgia and local anesthetic overdose and/or repeated injections caused by dental malpractice. Patients and Methods: An adequate sample of thirty-four patients was selected from the teaching clinic of oral medicine in the College of Dentistry, the University of Karbala, Iraq. All patients were fit for the inclusion criteria and subjected to a thorough oral examination to exclude any organic diseases that cause orofacial pain. Also, they were subjected to a medical examination by multiple neurologists using magnetic resonance imaging and other medical investigations to ensure that all patients did not suffer from intracranial pathology. Results: The patients were statistically distributed by their ages into two sub-groups. The first group (25-48 years old) represented 52.94% of all patients, and the second group (49-72 years old) included 47.06%. The percentage of disease according to sex was 79.4% in males and 20.6% in females. 3-6 dental carpules containing lidocaine (2%) with epinephrine were given to patients. The data of the studied sample were analyzed by using the statistical package of social sciences (SPSS) version 25. The chi-square test was used to test the effect of the type of dental procedure before pain in the two age groups and the two sex groups. For the age group, the difference was significant (p-value &lt; 0.05), which indicated an increased incidence of nerve damage caused by local anesthesia in older patients. For the sex group, the chi-square test exhibited a value of 2.45, with no significant difference (p-value &gt; 0.05). The main theory suggested for the occurrence of local neuropathies and the initiation of TN was the demyelination of nerve, which may be due to the neurotoxic effects of local anesthesia administered at high concentrations and for prolonged exposure times (repeated injections at the site of the dental infection after failure of LA) that may activate the intrinsic pathway of apoptosis through cytochrome C release. The local anesthetic-related neurotoxicity has thus been found to have harmful effects on the nerve tissue, including demyelination and axonal degeneration. Conclusion: The malpractice of local anesthesia in dentistry may lead to dysesthesia, allodynia, and trigeminal neuralgia with different degrees and severity due to the neurotoxicity of the peripheral nerve fiber. The nerve damage may occur in many forms, such as demyelination, apoptosis, axonal degeneration, and hypoxia due to thrombosis. So, dentists should recognize the risk of repeated injections or high dose solution (4%) of LA in the inflamed tissues when inducing analgesia for their dental operations that might initiate the primary trigeminal neuralgia.

Comparison of Systemic Extended-release Buprenorphine and Local Extended-release Bupivacaine-Meloxicam as Analgesics for Laparotomy in Mice.

Extended-release (ER) local anesthetics can be used in multi-modal analgesia or in situations in which systemic analgesics may alter animal physiology and thus introduce interpretational confounds. In this study, we compared the analgesic efficacy of an ER buprenorphine formulation with that of a synergistic combination of ER bupivacaine and meloxicam. Female and male CD1 mice were randomly assigned to receive subcutaneous buprenorphine (3.25mg/kg) preemptively, subcutaneous infiltration of bupivacaine???meloxicam (0.03mL at incision closure (bupivacaine, 35mg/kg; meloxicam, 1mg/kg), or saline (10mL/kg SC) after induction of anesthesia. After laparotomy, mice were assessed for changes in daily body weight, rearing frequency, nest consolidation scores, time-to-integrate-nest test (TINT), and response to von Frey testing at 4, 8, 24, 48, and 72h after surgery. Daily weight, nest consolidation scores and rearing frequency were not significantly different among the 3 groups. TINT had fallen significantly response at 24 and 48h after injection in the ER buprenorphine group as compared with the saline and ER bupivacaine-meloxicam groups. Nociceptive thresholds, as assessed with von Frey testing, differed between saline controls and both analgesic groups at 4, 8, 24, 48, and 72 h after surgery. None of the mice in the bupivacaine???meloxicam group developed signs of neurotoxicity, a potential side effect of high-dose local anesthetics. This study demonstrates that local ER bupivacaine???meloxicam may be a useful alternative to systemic, ER buprenorphine for the relief of pain after laparotomy in mice.

Magnesium Sulfate in Pediatric Abdominal Cancer Surgery: Safety and Efficacy in Ultrasound-Guided Transversus Abdominis Plane (US-TAP) Block in Conjugation with Levobupivacaine.

Magnesium sulfate (MgSO4) may enhance the effects of local anesthetics when used as an adjuvant in peripheral nerve blocks. Our objective was to evaluate efficiency and safety of utilizing MgSO4 alongside levobupivacaine in bilateral ultrasound-guided transversus abdominis plane (US-TAP) block for postoperative pain in pediatric cancer patients who underwent abdominal surgery. A randomized double-blinded controlled trial at South Egypt Cancer Institute, Assiut University, Assiut, Egypt, included that 40 pediatric patients with Wilms' tumor or neuroblastoma were randomly allocated to get bilateral (US-TAP) block and divided into two groups; M group: received US-TAP with 0.6 mL/kg levobupivacaine 0.25% + 2 mg/kg MgSO4 and C group: received with 0.6 mL/kg levobupivacaine 0.25% only. FLACC scores (Face, Leg, Activity, Cry, Consolability) were used to evaluate post-operative pain, first analgesic request, total analgesic consumption, adverse effects, as well as hemodynamics were monitored for 24 h and recorded at time points (2, 4, 6, 8, 12, 18, and 24h). Parent's satisfaction at discharge, also, was evaluated. FLACC score in M group was significantly lower than in C group from 4 h to 24 h with the first analgesic request being longer (15.95 ± 1.99 vs 7.70 ± 0.80 (h); p < 0.001) and lower total analgesic consumption (231.75 ± 36.57 vs 576.00 ± 170.71 (mg); p < 0.001) when comparing M group to C group, respectively. Both groups had insignificant differences regarding hemodynamics, parent satisfaction, postoperative agitation, and side effects except vomiting occurred in two patients in the C group and one patient in the M group. We conclude that adding magnesium sulphate as an adjuvant to local anaesthetic in US-TAP block for pain management in pediatric abdominal cancer surgeries resulted in better and longer analgesia, with less consumption of rescue analgesics with no serious side effects.

EFFECT OF PROPOLIS ON WOUND HEALING: A CLINICAL AND HISTOMORPHOMETRIC STUDY IN RATS

Background: Propolis is known to have antioxidant, antiinflammatory, antibacterial, antiviral, immunostimulant and local anesthetic effects. The aim of the present study was to investigate the clinical and histomorphometric effects of propolis on the healing of excisional palatal wounds in rats. &#x0D; Materials and methods: Sixty male Wistar rats were used for the study. Six animals were sacrificed at beginning of the study as initial wound (0 day). The rats were divided into three groups: Propolis (P), Chlorhexidine (CHX) and Control (C). Subjects in all three groups were randomly selected to form nine subgroups of six rats each. Under anesthesia, circular excision wounds with a diameter of 3 mm were formed in the middle of the palate of the rats by punching. The mucoperiosteal part was removed with sharp dissection, and the area on the open bone surface was left to heal the secondary wound. Propolis was administered locally at a rate of 1 ml/day. The rats were sacrificed on days 7, 14, and 21, and pictures of the wound area were taken. Each photograph was transferred to a dedicated program to measure the defect area. Histological sections were taken and the presence of inflammatory cells, epithelialization, and degree of healing were assessed.&#x0D; Results: The average wound area between epithelial margins decreased significantly over time in all groups (p

The effect of local anesthetics against planktonic forms and film formation of S. aureus strains and its dependence on antiseptics activity.

Today surgical site infections (SSIs) remain the second among hospital acquired infections in Europe and the USA. Staphylococcus aureus as a pathogen of nosocomial infections occur more frequently in surgical hospitals. The work was aimed to establish the effect of local anesthetics against planktonic forms and biofilm-formation of S. aureus clinical strains and the relationship between the sensitivity of S. aureus strains to local anesthetics and antiseptics in vitro. The antimicrobial activity of local anesthetics (0.5%, bupivacaine, 2.0% lidocaine, 0.375% ropivacaine) and antiseptics (decamethoxine 0.02%, chlorhexidine 0.05%) against clinical strains of S. aureus was observed and studied their ability to produce biofilms. The antimicrobial effect of local anesthetics was lower compared to antiseptics, but we observed inhibition of growth and reproduction of S. aureus in their presence. The ropivacaine solution and the lidocaine solution demonstrated almost the same activity against the studied microorganism isolates. Along with this, bupivacaine solution had the highest activity against the studied microorganisms. The minimal inhibitory concentration of bupivacaine for S. aureus was 2.2 times lower than the minimal inhibitory concentration of lidocaine and 2.1 times lower than the minimal inhibitory concentration of ropivacaine significantly (p < 0.05). Scientific research on various aspects of the formation of bacterial biofilms is a relevant area that will change approaches to the prophylaxis and treatment of a number of infections, including SSIs.

Stability of Lidocaine Solutions Following Sodium Bicarbonate Alkalinization

(Reg Anesth Pain Med 2022;47:773–774) It is known that the effectiveness of local anesthesia can be increased by alkalinization using sodium bicarbonate by increasing the fraction of the drug that is undissociated. There is a research gap, however, in examining the degree of alkalinization in different concentrations of lidocaine, its pharmacological stability, and bacterial contamination. This study aimed to fill that gap by examining changes in the amount of unaltered lidocaine according to pH in different concentrations, and by assessing its stability and the incidence of bacterial contamination during preparation.

The effect of local anaesthetics on apoptosis and NETosis of human neutrophils in vitro: comparison between lidocaine and ropivacaine

There are immunological consequences to the method by which neutrophils undergo cell death. Neutrophil apoptosis, called silent death, leads to the resolution of inflammation, while NETosis deepens and prolongs the inflammatory response and is associated with a worse prognosis of severe infections, e.g., sepsis. Besides nociceptive inhibition, local anaesthetics modulate leukocyte functions, even at low, clinically relevant concentrations. There is currently no data on ropivacaine NETosis, and this study aimed to evaluate the impact of clinical concentrations of ropivacaine (0.0007, 0.007 and 1.4 mmol/L) and lidocaine (0.002, 0.02 and 4 mmol/L) on apoptosis and NETosis of adult peripheral blood neutrophils after 2 h of incubation. Neutrophil identification, apoptosis and NETosis were evaluated by flow cytometry using forward and side scatter characteristics and fluorescent labelling: CD15 for neutrophils identification; Annexin V and propidium iodide for apoptosis and citrullinated histone H3 and myeloperoxidase for NETosis. Lidocaine (4 mmol/L) and ropivacaine (1.4 mmol/L) induced early apoptosis in resting but not in stimulated neutrophils. Low doses of ropivacaine (0.0007 and 0.007 mmol/L) decreased the number of late apoptotic neutrophils, and the lowest dose slightly increased their viability. None of the drugs induced NETosis in resting neutrophils but decreased NETosis at clinical concentrations compared to PMA-stimulated 4 mM lidocaine, PMA-stimulated control, and 1.4 mM ropivacaine. The effect of lidocaine and ropivacaine on apoptosis and NETosis depended on neutrophil stimulation and drug concentrations. Ropivacaine tends to be cytoprotective at concentrations observed in plasma under local anaesthesia. Lidocaine enhanced NETosis at high concentration only in stimulated neutrophils. Thus, both drugs have the ability to change the course of inflammation.

Topical Anesthetics and Premature Ejaculation: A Systematic Review and Meta-Analysis.

This meta-analysis was conducted to assess the effectiveness of topical anesthetics in preventing premature ejaculation. We conducted an online database searchfor original studies comparing topical anesthetic agents with placebo in patients with premature ejaculation. After selecting relevant articles, we extracted data on baseline characteristics and predetermined endpoints. Intravaginal ejaculatory latency time (IELT) was the primary outcome for efficacy. Mean differences and corresponding 95% confidence intervals were used to present continuous data. A random-effects model was used to pool the data, and subgroup analysis was performed based on the type of anesthetic agent used. Eleven randomized controlled trials were examined, involving a total of 2008 participants. After analyzing the combined results, it was found that Severance Secret (SS) cream (CJ CheilJedang Corporation, Seoul, South Korea) demonstrated significantly higher effectiveness than a placebo in increasing IELT (P = 0.001). Similarly, the topical eutectic mixture for premature ejaculation (TEMPE), lidocaine, and the eutectic mixture of local anesthetics (EMLA) were significantly more efficient than a placebo (P<0.00001; P = 0.0001; P<0.00001). Additionally, it was found that lidocaine gel was more efficient than paroxetine or sildenafil (P = 0.04; P<0.00001). In conclusion, topical anesthetics increase IELT in men with premature ejaculation more effectively than placebo, sildenafil, tadalafil, paroxetine, and dapoxetine.

The Effect of Local Anesthetics on Neutrophils in the Context of Different Isolation Techniques.

Various functions of polymorphonuclear neutrophils (PMNs) are related to diseases and postoperative plasma changes. The influence of some local anesthetics (LAs) on PMNs obtained by conventional isolation methods and their functions has already been demonstrated. This study investigates the effect of selected LAs on PMNs, comparing a new isolation method with conventional ones. To obtain the PMNs, we performed either gelafundin sedimentation, hypotonic lysis or density gradient centrifugation. Subsequently, PMNs were mixed with different concentrations of bupivacaine, levobupivacaine, lidocaine or ropivacaine. Live cell imaging and flow cytometry were performed to quantify the migration, ROS production, NETosis and antigen expression of PMNs. We found the inhibition of chemotaxis and ROS production by LAs. PMNs showed a strong reduction in time to half maximal NETosis in response to bupivacaine and lidocaine, but not to levobupivacaine and ropivacaine. We also found distinct differences in survival time and migration duration between the isolation methods. This suggests that the careful selection of LAs has a short-term impact on in vitro PMNs.