Efficacy and Clinical Value of Commonly Used Ingredients in Pain Management Compounds: A Literature Review.

The need for continued improvement in pain management is growing. This review is aimed towards identifying the literature regarding clinical and therapeutic value of the commonly used ingredients in pain management compounds: lidocaine, tetracaine, ketoprofen, ketamine, and gabapentin. Prospectively, future studies should be conducted to identify the exact benefits and side effects of compounded pain management therapies, such that these compounds can be effectively utilized when deemed appropriate.

Chloroprocaine 3% Gel as a Novel Ocular Topical Anesthetic: Results from a Multicenter, Randomized Clinical Trial in Patients Undergoing Cataract Surgery.

Purpose: To compare the efficacy and safety of a novel ophthalmic anesthetic, chloroprocaine 3% gel to tetracaine 0.5% eye drops in patients undergoing cataract surgery with phacoemulsification. Methods: This was a prospective, randomized, multicenter, active-controlled, masked-observer, parallel group competitive equivalence study. The study comprised 338 patients having routine cataract extraction by clear corneal phacoemulsification, randomized to receive 3 drops of chloroprocaine gel (n = 166) or tetracaine eye drops (n = 172) before surgery. The primary objective of the study was to assess the equivalence of chloroprocaine gel to tetracaine eye drops as proportion of patients with successful ocular surface anesthesia, without any supplementation just before intraocular lens implantation. Safety measurements were pain, irritation, burning, stinging, photophobia, and foreign body sensation, graded by the patient and objective ocular signs. Results: Equivalence was demonstrated, with a somewhat higher success rate of chloroprocaine gel: 152/166 (92.0%) chloroprocaine versus 153/172 (90.5%) tetracaine patients achieved ocular surface anesthesia with no supplementation. Difference in proportions was 1.5% confidence interval [95% CI: (-3.6 to 6.6)] and 90% CI fell within (-10 to 10). Mean onset of anesthesia was 1.35 ± 0.87 min for chloroprocaine and 1.57 ± 1.85 for tetracaine (P = 0.083). Mean duration of anesthesia was 21.57 ± 12.26 min for chloroprocaine and 22.04 ± 12.58 for tetracaine (P = 0.574). No treatment emergent adverse events related to chloroprocaine were reported and no relevant findings related to local tolerance or vital signs were observed in both arms. Conclusions: Results obtained from the present cataract study demonstrated that chloroprocaine 3% ophthalmic gel is safe and effective, representing a valid alternative in ocular topical anesthesia. Clinical Trial Registration number: NCT04685538.

Effect of superior laryngeal nerve block in alleviating sore throat after application of i-gel supraglottic airway: a randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a common complaint after supraglottic airway device (SAD) application. Internal branch of the superior laryngeal nerve (iSLN) block has the potential to alleviate POST. The aim of this trial was to explore the effect of iSLN block in alleviating sore throat, as well as to identify the potential risk factors for POST after SAD insertion. METHODS: One hundred thirty-four patients scheduled for elective gynecological surgery were randomized to either group T: tetracaine syrup (1%) for local lubrication on i-gel supraglottic device (n = 67) or group B: i-gel insertion with water based lubricant on it and followed by bilateral iSLN block (ropivacaine, 0.375%, 2 ml for each side) (n = 67). Under ultrasound guidance, iSLN was exposed below thyrohyoid membrane. The primary outcome was the intensity of sore throat at 6 h after surgery. In addition, POST score at 0.5 h and 24 h, the severity of postoperative swallowing discomfort, acoustic analysis and complications were measured. RESULTS: Compared with tetracaine syrup for local lubrication, iSLN block resulted in a reduced intensity of POST at 0.5 h (P = 0.044, OR = 1.99, 95%CI 1.02 to 3.88) and 6 h (P < 0.001, OR = 5.07, 95%CI 2.53 to 10.14) after surgery, as well as less severity of swallowing discomfort (P < 0.001, OR = 2.21, 95%CI 1.63 to 2.99) and cough (P = 0.039, OR = 1.97, 95%CI 1.04 to 3.73). The patients after iSLN block presented lower jitter and shimmer value in acoustic analysis at 6 h after surgery (P < 0.001). CONCLUSIONS: iSLN block was effective in alleviating POST, improving voice function, as well as reducing postoperative swallowing discomfort and coughing. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000037974) on 8th Sept 2020.

Tetracaine downregulates matrix metalloproteinase activity and inhibits invasiveness of strongly metastatic MDA-MB-231 human breast cancer cells.

Tetracaine, a long-acting amino ester-type local anesthetic, prevents the initiation and propagation of action potentials by reversibly blocking voltage-gated sodium channels (VGSCs). These channels, which are highly expressed in several carcinomas (e.g. breast, prostate, colon and lung cancers) have been implicated in promoting metastatic behaviours. Recent evidence suggests that local anesthetics can suppress cancer progression. In this paper, we aimed to explore whether tetracaine would reduce the invasive characteristics of breast cancer cells. In a comparative approach, we used two cell lines of contracting metastatic potential: MDA-MB-231 (strongly metastatic) and MCF-7 (weakly metastatic). Tetracaine (50 µM and 75 µM) did not affect the proliferation of both MDA-MB-231 and MCF-7 cells. Importantly, tetracaine suppressed the migratory, invasive, and adhesive capacities of MDA-MB-231 cells; there was no effect on the motility of MCF-7 cells. Tetracaine treatment also significantly decreased the expression and activity levels of MMP-2 and MMP-9, whilst increasing TIMP-2 expression in MDA-MB-231 cells. On the other hand, VGSC α/Nav1.5 and VGSC-ß1 mRNA and protein expression levels were not affected. We conclude that tetracaine has anti-invasive effects on breast cancer cells and may be exploited clinically, for example, in surgery and/or in combination therapies.

Efficacy of tetracaine eye drops in strabismus surgery: a systematic review and meta-analysis of randomized controlled trials.

AIM: To comprehensively evaluate the efficacy and safety profile of tetracaine eye drops as a local anesthetic agent among pediatric patients undergoing for strabismus surgery. METHODS: We systemically searched four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Library) from inception until April 2023. We included randomized controlled trials (RCTs) comparing tetracaine and placebo or no intervention for intraoperative and postoperative outcomes in strabismus surgery patients. We used the Cochrane risk of bias-2 tool for the risk of bias assessment. Continuous variables were pooled as mean difference (MD) or standardized mean difference (SMD), and categorical variables were pooled as risk ratio (RR) with a 95% confidence interval (CI). RESULTS: Six RCTs were included in the meta-analysis, with a total of 326 patients. There was no significant difference between the tetracaine and the control groups regarding the mean operative time (MD = -0.10 minutes, 95% CI [-3.79, 3.59], p = .96), the mean time to first analgesia (MD = -0.87 minutes, 95% CI [-11.15, 9.40], P = .87), the mean behavior score (SMD = -S0.48, 95% CI [-1.24, 0.28], p = .22), the rate of postoperative vomiting (RR = 1.27, 95% CI [0.62, 2.61], p = .52), or the number of additional analgesia (RR = 0.55, 95% CI [0.27, 1.13], p = .10). CONCLUSION: Our systematic review and meta-analysis found no significant differences in the safety and efficacy of tetracaine eye drops for strabismus surgery when compared to placebo or no intervention. Further investigation is needed to establish the best local anesthetic for strabismus surgery.

Topical application of local anesthetics to melanoma increases the efficacy of anti-PD-1 therapy.

Experimental and clinical data have shown that the nervous system can significantly stimulate the initiation and progression of melanoma. In support of this, approaches that reduce the transmission of signals from peripheral nerves to effector tissues reduce the recurrence of melanoma. Therefore, we investigated the effect of topical application of the local anesthetic Pliaglis (7% lidocaine and 7% tetracaine) on the growth of melanoma induced by intradermal application of B16F0 cells in mice without treatment and in mice treated with the anti-PD-1 antibody. We found that application of Pliaglis to melanoma significantly reduced its growth and this effect was even pronounced in mice treated with the anti-PD-1 antibody. To determine the mechanisms and pathways responsible for the observed effect, the in vitro effect of incubating melanoma cells with lidocaine and/or tetracaine and the in vivo gene expression of cancer and immune-related factors, percentage of immune cells, gene expression of selected neurotransmitter receptors and nerve growth factors in melanoma tissue were studied. We found that lidocaine and tetracaine significantly reduced the viability of B16F0 cells in vitro. In mice with melanoma, Pliaglis potentiated the effect of anti-PD-1 antibody on gene expression of COX-2, IL-1ß, IL-6, CCL11, F4/80, CD206, and NCR1. In addition, Pliaglis increased the gene expression of α9nACHR and 5-HT2a receptors and decreased the gene expression of nerve growth factor receptor (p75NTR) and p53. We also observed Pliaglis-mediated changes in myeloid populations. Topical application of this local anesthetic cream decreased the CD11b+Gr1- population and increased the CD11b+Gr1high population. Our data suggest that Pliaglis reduces melanoma growth through a direct effect on melanoma cells as well as through modulation of the immune response. The involvement of nervous system-related signaling in the inhibitory effect of Pliaglis on melanoma is inconclusive from our data.

Compound lidocaine/prilocaine cream combined with tetracaine prevents cough caused by extubation after general anaesthesia: a randomised controlled trial.

BACKGROUND: Coughing caused by tracheal extubation is common following general anaesthesia. Heavy aerosol production by coughing during recovery from general anaesthesia in patients with respiratory infections (especially COVID-19) may be one of the highest risk factors for infection in healthcare workers. The application of local anaesthetics to the endotracheal tube is an effective method to reduce coughing. The most commonly used anaesthetics are compound lidocaine/prilocaine cream and tetracaine spray. However, coughing still occurs when the two anaesthetics are used alone. We speculated that the application of compound lidocaine/prilocaine combined with tetracaine spray would better prevent coughing caused by tracheal extubation. METHODS: Patients scheduled for laparoscopic cholecystectomy or cholecystectomy combined with common bile duct exploration under general anaesthesia were randomly assigned to Group C (saline spray), Group L (2 g compound lidocaine/prilocaine cream contains 5 mg of lidocaine and 5 mg prilocaine)), Group T (tetracaine) and Group F (compound lidocaine/prilocaine cream combined with tetracaine). The incidence of coughing, the endotracheal tube tolerance assessment, the incidence of agitation, the active extubation rate, the incidence of postoperative pharyngeal pain and the incidence of postoperative cough were recorded and analysed. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and the plasma concentrations of epinephrine and norepinephrine were measured immediately before extubation and 1 min after extubation. RESULTS: A total of 211 patients were randomly assigned to Group C (53 cases), Group L (52 cases), Group T (52 cases) and Group F (54 cases). The primary result is assessment of the incidence of cough. The patients emerged from general anaesthesia, 96% of Group C had cough, which was significantly reduced in Group L (61.5%, P < 0.001), Group T (75%, P < 0.05) and Group F (22.2%, P < 0.001). Group F had a significantly reduced incidence of cough compared to Group L and Group T (P < 0.05 or P < 0.01, respectively). The secondary results were assessed. The endotracheal tube tolerance score in Group C ((1, 3) 4, P < 0.001) was higher than Group L ((0, 1) 2), Group T ((0, 1.25) 3) and Group F ((0, 0) 1). Group F had a significantly lower score than Group L and Group T (P < 0.05, P < 0.01, respectively). The incidence of agitation and the active extubation rate were also higher in Group C (96.2% and 71.7%, respectively, P < 0.001) than Group L (48.1% and 15.4%, respectively), Group T (61.5% and 26.9%, respectively) and Group F (17.3% and 7.7%, respectively). Blood pressure, HR and plasma concentrations of epinephrine and norepinephrine were significantly higher in Group C than in all other groups at the time of extubation and 1 min after extubation (P < 0.001). Group F exhibited significantly reduced blood pressure, heart rate and plasma concentrations of epinephrine and norepinephrine compared to Group L and Group T (P < 0.05, P < 0.01 or P < 0.001, respectively). The incidence of postoperative pharyngeal pain and the incidence of postoperative cough were not significantly different among the groups. CONCLUSIONS: Compound lidocaine/prilocaine cream combined with tetracaine may be a more effective approach for preventing coughing and stabilising circulation during extubation following general anaesthesia. This may play an important role in preventing medical staff from contracting respiratory infectious diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200058429 (registration date: 09-04-2022) "retrospectively registered".

Topical Anesthetics for Analgesia in Acute Corneal Abrasion: Eye Care Providers Survey.

STUDY OBJECTIVES: To evaluate the current attitudes of ophthalmologists and optometrists regarding topical anesthetic (TA) use in the emergency department (ED) for analgesia in corneal abrasions. METHODS: A survey was distributed through email to ophthalmologists and optometrists, and their responses were deidentified. Three scenarios were presented involving the addition of tetracaine in addition to usual care in the setting of uncomplicated corneal abrasion. A 250-character space for comments and demographic questionnaire followed. A chi-square test, Fisher exact test, or sign test, at a significance level of 0.05, was used. RESULTS: Of the 978 individuals surveyed, 486 responded (MD/DOs: 47.1% and ODs: 52.9%). Topical anesthetic favorability significantly decreased with shorter practice length when the patient was only examined by an ED provider. Topical anesthetic favorability was significantly impacted by respondents' degree type. When respondents were posed with using TAs if the respondents were the patient, the respondents were 22.6% more likely to use TA when compared with their answers in the scenario where the ED provider examined the patient and 20.0% more likely when compared with the scenario where a MD/OD examined the patient. Most did not support tetracaine use. CONCLUSIONS: Although treating pain is associated with improved quality of life, most respondents did not support TA use in the ED. Practice length and degree type significantly impacted responses. Respondents were more inclined to use TAs when the respondents were the patient. Results suggest that eye care providers need additional research data supporting safety before routine use in the ED, given the potential for adverse events with TAs.

Factors Associated With Low Procedural Pain Scores Among 1- to 5-Year-Old Patients Undergoing Facial Laceration Repair.

OBJECTIVES: Our objectives were to quantify pain experienced by young children undergoing facial laceration repair and identify factors associated with low procedural pain scores. METHODS: We conducted a prospective cohort study of children's distress among a convenience sample of children aged 1 to 5 years undergoing facial or scalp laceration repair in 2 pediatric emergency departments. We reviewed video recordings and documented pain scores at 15-second intervals using the Face, Leg, Activity, Cry, Consolability-Revised (FLACC-r) scale. We dichotomized FLACC-r into low/high scores (≤3 and >3) to evaluate practice variables. RESULTS: We included 11,474 FLACC-r observations from 258 procedures in the analysis. Two-thirds of 3- to 5-year-olds completed their laceration repair without the use of restraint, sedation, or anxiolytics. Mean distress scores were low (≤2.5 out of 10) across all procedure phases for 2- to 5-year-old patients. One-year-old patients experienced significantly more distress than their older counterparts (mean ≤4.2 out of 10). Odds of having low FLACC scores (≤3) were greater for patients with an expert clinician (adjusted odds ratio [aOR]: 1.72; 95% confidence interval [CI], 1.05-2.84). Wound infiltration (aOR, 0.35; 95% CI, 0.13-0.93), patient observation of a needle (aOR, 0.21; 95% CI, 0.14-0.33), and restraint (aOR, 0.04; 95% CI, 0.02-0.06) were negatively associated with low FLACC score. CONCLUSION: The majority of 3- to 5-year-old patients were able to undergo facial laceration repair without restraint, sedation, or anxiolytics and with low mean distress scores. Our findings suggest that children's risk of experiencing moderate and severe distress during facial and scalp laceration repair may be reduced by prioritizing wound closure by expert-level clinicians, ensuring effective lidocaine-epinephrine-tetracaine application, avoiding restraint, and concealing needles from patient view.

Fluidized or not fluidized? Biophysical characterization of biohybrid lipid/protein/polymer liposomes and their interaction with tetracaine.

BACKGROUND: Nanomedicine and the pharmaceutical industry demand the investigation of new biomaterials to improve drug therapies. Combinations of lipids, proteins, and polymers represent innovative platforms for drug delivery. However, little is known about the interactions between such compounds and this knowledge is key to prepare successful drug delivery systems. METHODS: Biophysical properties of biohybrid vesicles (BhVs) composed of phospholipids, proteins, and amphiphilic block copolymers, assembled without using organic solvents, were investigated by differential scanning calorimetry and dynamic light scattering. We studied four biohybrid systems; two of them included the effect of incorporating tetracaine. Thermal changes of phospholipids and proteins when interacting with the amphiphilic block copolymers and tetracaine were analyzed. RESULTS: Lysozyme and the copolymers adsorb onto the lipid bilayer modifying the phase transition temperature, enthalpy change, and cooperativity. Dynamic light scattering investigations revealed relevant changes in the size and zeta potential of the BhVs. Interestingly, tetracaine, a membrane-active drug, can fluidize or rigidize BhVs. CONCLUSIONS: We conclude that positively charged regions of lysozyme are necessary to incorporate the block copolymer chains into the lipid membrane, turning the bilayer into a more rigid system. Electrostatic properties and the hydrophilic-lipophilic balance are determinant for the stability of biohybrid membranes. GENERAL SIGNIFICANCE: This investigation provides fundamental information associated with the performance of biohybrid drug delivery systems and can be of practical significance for designing more efficient drug nanocarriers.

Characterization of seven new related impurities and forced degradation products of tetracaine hydrochloride and proposal of degradation pathway by UHPLC-Q-TOF-MS.

A rapid and highly sensitive method was developed for separation and identification of the related impurities and degradation products in tetracaine hydrochloride by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). The chromatographic separation was achieved on an Agilent Infinity Lab Poroshell 120 EC-C18 column (4.6 ×100 mm, 2.7 µm) using gradient elution with mobiles phase of A (10 mM ammonium acetate buffer containing 0.1% formic acid) and B (acetonitrile) at a flow rate of 1.0 mL/min. Forced degradation experiments were also performed under acidic, alkaline, thermal, photolytic, and oxidative stress conditions following ICH guidance. The result revealed that tetracaine hydrochloride is extremely sensitive to oxidation condition and highly sensitive to alkaline/acidic hydrolysis, and susceptible to light condition. In total, five related impurities and seven degradation products were successfully detected in the positive mode of electrospray ionization. The structures of all these impurities were characterized based on the high-resolution MS data and manufacture process, and the fragmentation pathways of tetracaine and these impurities were constructed and discussed. Seven of them have not been reported before, and two of them were specified impurities described in various pharmacopoeias. The fragmentation pathways and plausible mechanisms for the formation of these impurities were proposed.

Effects of local anesthetics on compound action potentials generated from the frog sciatic nerve.

The frog sciatic nerve provides a robust physiological preparation students may conveniently use to investigate the properties of compound action potentials. Electrical stimulation with standard physiology teaching equipment elicits compound action potentials that are easily recorded by upper-level undergraduate students. The amplitude of compound action potentials increases with greater stimulation voltages, up until a maximum response is achieved. Plotting action potential size as a function of stimulating voltage produces a curve that illustrates the responsiveness of a nerve. In the present study, several local anesthetics (MS-222, procaine, lidocaine, benzocaine, and tetracaine) were used to reversibly suppress compound action potentials within a time frame consistent with the limitations of teaching labs. Highly responsive nerves generate steep response curves that reach asymptotes at relatively low stimulating voltages. Less active nerves require higher stimulating voltages and appear "right-shifted." Anesthetized response curves may also appear "flatter," exhibiting lower peak amplitude, when compared to fully active nerves. The magnitude of action potential suppression and time course of recovery depended upon the specific anesthetic applied. Nerves anesthetized with MS-222 were the fastest to recover, reaching their original responsiveness within 20 min. Tetracaine had the most dramatic effects, with nerves typically requiring more than a day to fully recover physiological responses. Carefully dissected nerves maintained their physiological responses for many days when stored in Ringer solution at 4°C, making this preparation particularly useful for undergraduate lab experiences. Quantitative analyses may be performed on the data collected, providing students with opportunities to design and implement their own experiments.NEW & NOTEWORTHY The frog sciatic nerve preparation represents a "classical" physiology lab for demonstrating principles of action potentials. Local anesthetics provide an inexpensive tool to manipulate the physiological activity of nerves and other excitable tissues. Isolated nerves retain their physiological activity for up to several days when kept in Ringer solution at 4°C. Quantitative data analysis from this robust nerve preparation should present students with many opportunities for designing their own experiments with anesthetics.

[Effects of topical anesthesia with 1% tetracaine on hemodynamic responses in microlaryngosurgery].

Objective: To observe the effects of topical anesthesia with 1% tetracaine on hemodynamic responses in general anesthesia patients undergoing microlaryngosurgery. Methods: From October 2021 to December 2021, 92 patients (46 males and 46 females) in Beijing Tongren Hospital, with a median age [M (Q1, Q3)] of 51 (42, 57) years who scheduled for microlaryngosurgery under general anesthesia, were divided into two groups (n=46 in each group) using the random number table method. Group T received topical anesthesia with 1% tetracaine at the root of the tongue and epiglottis and glottis on the basis of general intravenous anesthesia induction, with 0.5 ml at each position, while the control group (group C) received equal volume of normal saline. Heart rate (HR) and mean arterial pressure (MAP) were recorded at the time of patients entering the operating room (baseline), after induction, after intubation, immediately after suspending laryngoscopy, 1 min after suspending laryngoscopy, 3 min after suspending laryngoscopy, 5 min after suspending laryngoscopy and immediately after extubation. The recovery profiles, including time to recover breathing, time to open eyes, time to extubation and adverse reactions were evaluated during recovery period. Results: The MAP of patients in group T at baseline, after induction, after intubation, immediately after suspending laryngoscopy, 1 min after suspending laryngoscopy, 3 min after suspending laryngoscopy, 5 min after suspending laryngoscopy and immediately after extubation were (99.4±12.9), (78.5±8.8), (79.2±10.2), (100.6±17.0), (101.9±14.7), (100.8±13.9), (97.4±12.1), (107.3±16.8) mmHg (1 mmH=0.133 kPa), respectively, while in group C were (99.5±11.6), (80.9±12.8), (90.5±16.0), (109.5±20.4), (108.0±18.9), (103.7±15.5), (100.1±13.3), (114.2±17.3) mmHg, respectively. The two critical time points of MAP after intubation and immediately suspending laryngoscopy in group C were significantly higher than group T (P<0.05).The HR of patients in group T at baseline, after induction, after intubation, immediately after suspending laryngoscopy, 1 min after suspending laryngoscopy, 3 min after suspending laryngoscopy, 5 min after suspending laryngoscopy and immediately after extubation was (71.3±10.6), (66.0±10.1), (69.5±11.4), (61.3±14.2), (69.8±9.8), (71.0±10.6), (70.6±11.0), (78.8±11.6) bmp, respectively, while in group C were (73.1±10.9), (67.8±9.9), (79.5±12.9), (57.1±18.1), (69.2±12.8), (71.4±11.7), (70.7±11.5), (85.3±13.0) bmp, respectively. The two critical time points of HR after intubation and after extubation in group C were significantly higher than that of group T (P<0.05). The time to recover breathing in the two groups was (11.8±3.5) min and (11.3±4.6) min, respectively. The time to open eyes was (12.0±3.3) min and (11.5±5.0) min, respectively. The time to extubation was (13.2±3.7) min and (12.6±4.9) min, respectively. There were no statistically significant difference in time to recovery between the two groups (P>0.05). Likewise, there were no toxic reactions to local anesthetics, respiratory depression, hypoxemia, laryngospasm and cough occurred in either group. Conclusion: Topical anesthesia with 1% tetracaine can effectively reduce the hemodynamic changes without influencing patient's recovery, and does not increase the incidence of adverse reactions.

Kovanaze Intranasal Spray vs Traditional Injected Anesthetics: a Study of Pulpal Blood Flow Utilizing Laser Doppler Flowmetry.

OBJECTIVE: An ideal local anesthetic would be effective, minimally reduce pulpal blood flow (PBF), and not require injection. This study compared the effects of 3% tetracaine plus 0.05% oxymetazoline nasal spray (Kovanaze; KNS) and injections using 2% lidocaine with 1:100,000 epinephrine (LE) or 3% mepivacaine plain (MP) on PBF, anesthetic efficacy, and participant preference. METHODS: In a double-blind cross-over design, 20 subjects randomly received a test anesthetic and placebo at each of 3 visits (KNS/mock infiltration; mock nasal spray/LE; or mock nasal spray/MP). Nasal sprays and infiltration apical to a maxillary central incisor were delivered ipsilaterally. PBF was evaluated by laser Doppler flowmetry, and local anesthetic success was assessed with electric pulp testing. Postoperative pain levels, participant preference, and adverse events were also assessed. RESULTS: LE injections demonstrated significant reductions in PBF at all time intervals compared with baseline (P < .05), whereas KNS and MP did not. Pulpal anesthesia success rates were higher for LE (85%) compared with MP (35%) and KNS (5%). Participants reported significantly higher postoperative pain levels for KNS compared with LE and MP. Additionally, KNS was the least preferred of the anesthetics administered and resulted in more reported adverse events. CONCLUSION: Although KNS showed no significant effect on PBF, it was not effective in achieving pulpal anesthesia as used in this study.

Rapid and sensitive simultaneous separation and electrochemical detection of tetracaine hydrochloride and oxymetazoline hydrochloride in pharmaceutical formulations via core-shell reversed-phase liquid chromatography.

Tetracaine hydrochloride (TCH) is a nasal anesthetic and oxymetazoline hydrochloride (OZH) is a nasal decongestant. A moderate to acute overdosage of OZH and TCH can lead to mydriasis, nausea, cyanosis, tachycardia, dyspnoea, cardiovascular failure, disorientation, seizures, and even death. Liquid chromatography (LC) has been mainly utilized for the individual determination of either TCH or OZH; however, there is a need for rapid and efficient methods for simultaneous analysis in pharmaceutical formulations and aqueous samples. This study highlights the use of the fast and efficient separation capabilities of core-shell silica particles in liquid chromatography (LC) for the simultaneous determination of TCH and OZH using UV detection and the enhanced selectivity afforded by electrochemical detection at a boron-doped diamond (BDD) electrode. Rapid reversed-phase (RP) separation and detection of OZH and TCH in nasal spray and eye drops was achieved within 45 s using a poroshell 120 EC-C18 column, by adjusting the ratio of organic solvent, mobile phase pH, detection potential and mobile phase flow rate. Sensitivity was compared using ultraviolet (UV) detection at 280 nm, and ECD at + 1.3 V with detection limits of 40 and 70 nM for TCH and OZH, respectively. The developed rapid method was utilized successfully in the analysis of pharmaceutical formulations, where the estimated levels of TCH and OZH in these formulations are in agreement with the specified values outlined by the manufacturers.

Triple Versus Single Application of Lidocaine, Epinephrine, and Tetracaine for Laceration Repair in Children.

OBJECTIVE: Lidocaine (4%), epinephrine (0.1%), and tetracaine (0.5%) topical gel (LET) is a safe and effective method of providing anesthesia for laceration repair. Some patients, however, require additional infiltrated local anesthetic. We sought to determine if 3 applications of LET 10 minutes apart (triple LET) result in lower pain scores with suturing than one application for 30 minutes (single LET). METHODS: We performed a randomized single-blind controlled trial of pediatric emergency department patients 7 to 17 years old with simple lacerations requiring sutures. Patients received either triple or single LET, and the first suture was placed or attempted within 15 minutes of removing the LET. Visual analog pain score on a 100-mm scale was obtained by a blinded nurse. Pain scores between groups were compared using the Wilcoxon rank sum test. RESULTS: Forty-eight patients were enrolled: 21 for single LET and 27 for triple LET. Mean visual analog pain scale (VAS) score for single LET patients was 16 (SD, 17; range, 0-48), and that for triple LET patients was 16 (SD, 24; range, 0-95), with the difference not significant at 0.37 (95% confidence interval, -11.9 to 12.6). There was no significant difference in requirement for additional anesthesia between single LET (4 of 21 [19%]) and triple LET (5 of 27 [19%]) patients. CONCLUSIONS: Lidocaine (4%), epinephrine (0.1%), and tetracaine (0.5%) topical gel every 10 minutes for 3 applications was not superior in anesthetic efficacy to applying it once for 30 minutes.

Real-life experience of a lidocaine/tetracaine self-occluding topical anesthetic for dermatological procedures.

BACKGROUND: Pliaglis® is a self-occluding topical anesthetic containing a eutectic mixture of 7% lidocaine and 7% tetracaine, with proven efficacy and safety in several trials. AIMS: To evaluate the effectiveness and safety of Pliaglis® for different dermatological procedures in real-life clinical practice. METHODS: This retrospective, multicenter study included 35 patients treated with Pliaglis® prior to five dermatological procedures (pulsed dyed laser, picosecond laser, non-ablative fractional laser, radiofrequency microneedling, and photodynamic therapy). The primary endpoint was to assess the pain during the procedure with a visual analogue score (VAS) from 0 (no pain) to 10 (most severe pain). Secondary endpoints were the global effectiveness and tolerability (from 0 = very low to 10 = excellent), and the adverse events (AEs) after Pliaglis® removal, classified according to intensity (1-3). RESULTS: The median and mean pain VAS reported by patients was 2 (range 0-9) and 2.9 (±2.3), respectively. More than 65% of the patients had a VAS score ≤3. The effectiveness reported by investigators was "very good" (median 8 [range 2-10], mean 7.5 [±1.9]), which was strongly correlated with the pain VAS reported by patients (Spearman coefficient = - 0.9; p < 0.001). Forty-five percent of patients reported AEs and they were transient and mostly mild, with a mean intensity score of 1.5 (range 1-3). Tolerability of Pliaglis® was reported by investigators as "excellent" (median 10 [range 1-10], mean 9 [±1.8]). CONCLUSIONS: Pliaglis® is an effective topical anesthetic for several dermatological procedures, with an excellent safety and tolerability profile.

Tetracaine hydrochloride induces cell cycle arrest in melanoma by downregulating hnRNPA1.

Recent evidence suggests potential benefits of applying local anesthetics in cancer patients. Specifically, tetracaine has a potent antitumor effect in diverse cancers, including neuroblastoma, breast cancer, and melanoma; however, the underlying molecular mechanisms remain unclear. Here, we reported that tetracaine hydrochloride inhibited the growth of melanoma cells and arrested melanoma cells in the G0/G1 phase. Tetracaine hydrochloride treatment resulted in translocation of hnRNPA1 from the nucleoplasm to the nuclear envelope and reduced the protein stability of hnRNPA1 possibly by disrupting the dynamic balance of ubiquitination and neddylation. Elevated hnRNPA1 upregulated cyclin D1 to promote cell cycle in melanoma. The hnRNPA1 overexpression attenuated the effect of tetracaine hydrochloride on melanoma cell growth suppression and cell cycle arrest. Furthermore, melanoma homograft experiments demonstrated that tetracaine hydrochloride suppressed melanoma growth, while hnRNPA1 overexpression alleviated tetracaine's antitumor effect on melanoma. Taken together, our findings suggest that tetracaine hydrochloride exerts a potent antitumor effect on melanoma both in vitro and in vivo, and the effect involves cell cycle arrest induction via downregulation of hnRNPA1.