Amide naphthotube as a novel supramolecular sequestration agent for tetracaine and decamethonium.

RATIONALE: Anesthetics are widely used for optimizing surgical conditions, postoperative pain management, and treating various chronic pain conditions. Tetracaine and decamethonium are representative drugs of local anesthetics and neuromuscular blocking agents, respectively. However, overdose and toxicity of the drugs always lead to serious adverse events. Thus, there is a strong demand for effective antidotes. METHODS: The binding interactions of amide naphthotubes with tetracaine and decamethonium were systematically studied using 1H NMR, ITC, and DFT calculations. The antidotal effects of amide naphthotube to tetracaine toxicity were assessed in vitro and in vivo, and the mechanism of detoxification was explored at a cellular level. Additionally, mouse models were established to evaluate the reversal activities of amide naphthotube on decamethonium-induced mortality and muscle relaxation, and the reversal mechanism was investigated through pharmacokinetic experiments. RESULTS: We have demonstrated that the anti-isomer of amide naphthotube exhibits significant binding affinities towards tetracaine (K a = 1.89×107 M-1) and decamethonium (K a = 1.01×107 M-1) in water. The host displayed good biocompatibility both in vitro and in vivo. The administration of amide naphthotube following tetracaine overdose in mouse models notably increased the overall survival rate, indicating its effective antidotal properties. The host could reverse the tetracaine-induced Na+ channels blockage at the cellular level. Moreover, the injection of amide naphthotube also reversed the mortality and paralysis induced by decamethonium in mouse models following a pharmacokinetic mechanism. CONCLUSION: An emerging artificial receptor, amide naphthotube, has strong binding affinities towards tetracaine and decamethonium. It functions as a supramolecular antidote for tetracaine poisoning and a reversal agent for decamethonium by selectively sequestering these compounds in vivo.

Comparative efficacy of topical lidocaine, tetracaine, and articaine for post-tonsillectomy pain management in children: a prospective, placebo-controlled study.

BACKGROUND: The most important problem in tonsillectomy is pain in the early postoperative period. OBJECTIVE: We purposed to compare the effects of lidocaine, tetracaine, and articaine application to the peritonsillar bed on post-tonsillectomy pain in children. METHODS: The prospective, placebo-controlled study included 80 patients, ages 3-14, who were scheduled for elective tonsillectomy. Patients were randomly divided into four groups. Group 1 received 0.9% NaCl; group 2 received 2% lidocaine; group 3 received 2% tetracaine; and group 4 received 4% articaine to the tonsillary bed for 5 min just after the operation. All patients were evaluated in terms of pain and pain-related adverse events in the postoperative 24 h. RESULTS: All groups that used local anesthetics had significantly lower pain levels than the control group in the first eight hours (p < .001). Furthermore, the articaine group had a lower pain score than the tetracaine group at the eighth hour (p < .05). The articaine group had a lower pain score at the 16th hour than both the control and tetracaine groups (p < .05). There was no significant difference between the groups at the 24th hour (p > .05). CONCLUSION AND SIGNIFICANCE: We recommend the immediate application of topical articaine to the tonsillar bed following the procedure to enhance postoperative pain management.

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.

Comparison of Proparacaine, Tetracaine, and Oxybuprocaine in Corneal Sensitivity Measurement.

Purpose: This study aimed to determine the onset and duration of action of 3 commercially available topical anesthetic solutions in Brazil, using the Cochet-Bonnet esthesiometer (Luneau®, Paris, France) and to quantitatively assess patient-reported discomfort during application. Methods: A prospective, randomized, masked, and double-blind study was conducted, involving 40 eyes from 21 patients. Patients were administered each one of the topical anesthetics weekly, and corneal sensitivity was measured using the Cochet-Bonnet esthesiometer's corneal touch threshold (CTT). Patients rated the burning sensation using a visual analogue scale (VAS). Results: Among the 21 patients (42.9% male), with a mean age of 31.95 years (±standard deviation = 10.17, range = 22.0-58.0), corneal sensitivity significantly decreased 30 s after application, returning to baseline after 30 min for all groups (P < 0.0001). Significant differences in CTT were observed at 5 min, with proparacaine exhibiting a superior anesthetic effect (P = 0.0003), at 10 min, where tetracaine displayed the most substantial anesthetic effect (P = 0.0135), and at 20 min, where tetracaine demonstrated the highest anesthetic efficacy (P < 0.0001). VAS scores indicated the most intense burning sensation with tetracaine (P < 0.0001). Men reported experiencing more discomfort during instillation compared with women (P = 0.0168). Conclusions: Proparacaine exhibited the fastest onset of action among the 3 topical anesthetics and provided a more comfortable eye sensation during instillation. However, tetracaine demonstrated the longest duration of action despite causing more discomfort.

Influence of Pre- and Intraoperative Local Anaesthetic in Strabismus Surgery under General Anaesthesia in Adults.

BACKGROUND: As studies have shown a reduction in the occurrence of the oculocardiac reflex with the addition of local anaesthesia, we changed our care regime accordingly a few years ago. To promote and establish better patient care, we retrospectively analysed the files of our patients who underwent strabismus surgery from 2013 to 2021 in order to compare strabismus surgery under general anaesthesia with and without local anaesthetics in a routine clinical setting. PATIENTS AND METHODS: Data from 238 adult patients who had undergone strabismus surgery could be extracted from the files: G1: n = 102, only general anaesthesia; G2: n = 136, preoperative application of tetracaine eye drops and intraoperative subtenon lidocaine/levobupivacaine in addition to general anaesthesia. We compared the two groups in regard to the frequency of oculocardiac reflex, the amount of atropine needed to treat, as well as the amount of antiemetic and analgesic medication given, and time spent in the recovery room. RESULTS: Mean age of G1 was 50 years and 52 years in G2. There was no significant difference between the kind of surgeries (recessions/resections), the number of patients who had undergone a reoperation, or the duration of the operations. Adding local anaesthetics resulted in significantly less occurrence of oculocardiac reflex (p = 0.009), a reduction in the need for atropine, analgesic, or antiemetic medication, as well as reduced time in the recovery room. CONCLUSION: As this increases patient safety and comfort and is cost-effective (less time in the recovery room), we recommend adding perioperative local anaesthesia to strabismus surgery performed under general anaesthesia.

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.

Eutectic mixture of local anesthetics and amethocaine as topical anesthetics in pediatrics: a meta-analysis.

BACKGROUND: Pediatric patients often receive topical anesthesia before skin procedures in the Emergency Department, with EMLA cream and amethocaine gel being common choices. The most effective option remains a subject of debate. OBJECTIVE: Our goal was to compare EMLA cream with amethocaine gel in pediatric patients undergoing topical anesthesia, focusing on outcomes: first-attempt cannulation success, child-reported visual analogue scale (VAS) score, parent-reported VAS score, observed pain score, child-reported absence of pain, and child-reported acceptable anesthesia. METHODS: A database search for studies comparing EMLA cream and amethocaine gel in pediatric topical anesthesia was conducted. Two reviewers extracted and cross-verified data, with a third ensuring accuracy. Using R software, a pairwise meta-analysis was performed via the Mantel-Haenszel method. Outcomes were pooled as risk ratios or standard mean differences with 95% confidence intervals using the random-effects model. RESULTS: Amethocaine gel surpasses EMLA cream in child-reported pain absence and first cannulation success. No significant differences were found in child-reported acceptable anesthesia or observed pain scores. Similarly, child- and parent-reported VAS scores showed no variations between EMLA and amethocaine. CONCLUSION: This analysis favors amethocaine gel for pediatric topical anesthesia. Further large randomized trials comparing EMLA cream and amethocaine gel in pediatric patients are warranted. IMPACT: Procedural pain is a major concern for pediatric patients, their families, and physicians. Topical anesthesia is routinely given prior to children undergoing skin-related procedures in the Emergency Department. In pediatric patients, topical anesthetics such as eutectic mixture of local anesthetics cream and amethocaine gel have proved to be pioneering in pain reduction, but the most effective method is often disputed. Presently, this is the most comprehensive pooled analysis of trials comparing EMLA cream and amethocaine gel in pediatric patients undergoing topical anesthesia. Amethocaine performed better with regards to child-reported absence of pain and first attempt cannulation success.

Use of Topical Anesthetics in the Management of Patients With Simple Corneal Abrasions: Consensus Guidelines From the American College of Emergency Physicians.

The management of corneal abrasions has largely excluded dispensing topical local anesthetics for home use due to concern for corneal toxicity. We have reviewed and critically appraised the available literature evidence regarding the use of topical anesthetics in patients with simple corneal abrasions. Using sequential Delphi review, we have developed these clinical guidelines. Herein are evidentiary summaries and consensus recommendations for 8 specific relevant questions. Our key observation is that for only simple corneal abrasions, as diagnosed and treated in accordance with the full protocol described herein, it appears safe to prescribe or otherwise provide a commercial topical anesthetic (ie, proparacaine, tetracaine, oxybuprocaine) for use up to every 30 minutes as needed during the first 24 hours after presentation, as long as no more than 1.5 to 2 mL total (an expected 24-hour supply) is dispensed and any remainder is discarded after 24 hours. Importantly, although published findings suggest absent harm for short courses, more rigorous studies with a greater cumulative sample size and ophthalmologic follow-up are needed.

Topical anaesthesia and decongestion in rhinology.

Topical anaesthesia and decongestion of the sinonasal mucosa are used commonly in rhinology practice to facilitate nasal endoscopy, as well as debridement and biopsies. Topical agents used for sinonasal anaesthesia include lignocaine, tetracaine and cocaine. Unlike lignocaine and tetracaine, cocaine also has a decongestant effect. Phenylephrine, oxymetazoline, xylometazoline or adrenaline are usually added to lignocaine and tetracaine to provide decongestion. Several studies have been performed seeking to identify the optimal nasal preparation for nasal endoscopy in the clinic setting. However, there remains no clear consensus in the literature resulting in ongoing wide variation between anaesthetic-decongestant preparations used in clinical practice. Indeed, some authors have argued that no anaesthetic is required at all for flexible nasendoscopy despite the apparent consensus that nasal instrumentation is generally uncomfortable, inferred by the persistence of ongoing research in this area. This review provides a practical summary of local anaesthetic and decongestant pharmacology as it relates to rhinologic practice and summarises the literature to date, with the goal of identifying current gaps in the literature and guiding future research efforts.

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.

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.

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".

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.

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.

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.