Lidocaine 70mg / Tetracaine 70mg cream

During intensive and long-lasting treatments, short-term or emergency care, children often undergo minor needle-related procedures (ie, venepuncture, venous cannulation and puncture of central venous access ports). The use of topical analgesia topical analgesia before these procedures can reduce needle-related pain. There is, however, uncertainty about the type of local anaesthetic (ie, eutectic mixture of topical analgesia (EMLA) or tetracaine-containing creams (eg, Rapydan) that should be used.Therefore, a clinical practice guideline (CPG) was developed to establish a comprehensive, evidence-based overview and provide recommendations for clinical practice.A comprehensive multidisciplinary panel was assembled, comprising 16 professionals and patient representatives in the Netherlands. A systematic literature review was performed, and after dual appraisal of all articles, results were extracted and meta-analyses were performed. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess, extract and summarise the evidence. An in-person meeting was held to discuss the evidence, complete an evidence-to-decision framework and formulate recommendations.In total, ten randomised controlled trials comprising 1808 children formed the evidence base for the recommendations. We recommend the use of EMLA in children who need to undergo a minor needle-related procedure, with minimal application duration of 60 min (strong recommendation, very low-quality evidence). We suggest the use of tetracaine-containing creams only when rapid cannulation/puncture (ie, within 30-60 min) is required (weak recommendation, very low-quality evidence).In this CPG, we provide recommendations regarding the choice of local anaesthetic for needle-induced pain during minor procedures in children. With these recommendations, we aim to reduce procedural pain and thereby contribute to improving care for children.

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Purpose: To evaluate the efficacy and safety of topical tetracaine eye drops as a preemptive skin anesthetic during botulinum toxin type A injection in blepharospasm patients. Patients and Methods: A double-blind, split-face randomized controlled trial was conducted in 17 participants diagnosed with benign essential blepharospasm between November 2023 and July 2024. Each patient received randomized treatment on opposite sides of the face: a cotton pad soaked with 5 mL of 0.5% tetracaine ophthalmic solution on one side and normal saline solution on the other, for 30 minutes. The cotton pad temperature, the injection dose, and the techniques were controlled on each side. A single neuro-ophthalmologist performed the injection. Pain scores were immediately rated after the injection, using a numeric rating scale from 0 to 10. Jankovic rating scale and complications were assessed on the day of injection, then 1 month and 3 months after injection. Results: The numeric rating scale on the side receiving topical 0.5% tetracaine eye drops was significantly lower than the side receiving topical normal saline solution (4.56 ± 2.63 vs 6.71 ± 2.54, p = 0.013). There were no significant differences in the Jankovic rating scale, cotton pad temperature, bleeding at the injection site, and other complications between the two groups. Conclusion: The application of 0.5% tetracaine ophthalmic solution as a preemptive topical skin anesthesia can decrease pain during botulinum toxin type A injection for blepharospasm patients without affecting the efficacy or producing any significant complications.

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ABSTRACT Background Effective pain management is essential for enhancing patient satisfaction and treatment compliance during facial rejuvenation procedures. Compound lidocaine cream and lidocaine–prilocaine cream are commonly used topical anesthetics in clinical practice; however, high‐quality randomized controlled trials directly comparing their analgesic efficacy and safety in facial rejuvenation remain limited. Objective This study aimed to compare the analgesic efficacy and safety of compound lidocaine cream and lidocaine–prilocaine cream in patients undergoing facial rejuvenation procedures. Methods This single‐center, prospective, randomized controlled trial enrolled 100 patients undergoing facial rejuvenation between January 2024 and June 2025. Participants were randomly assigned to receive either compound lidocaine cream ( n = 47) or lidocaine–prilocaine cream ( n = 53). The primary outcome was procedural pain intensity, assessed using a 10‐point visual analog scale (VAS). Secondary outcomes included the incidence of adverse reactions, patient satisfaction, and treatment compliance. Results Baseline characteristics were comparable between the two groups ( p > 0.05). The mean pain score was significantly lower in the compound lidocaine cream group than in the lidocaine–prilocaine cream group (2.51 ± 1.80 vs. 3.75 ± 1.74; t = −3.48, p < 0.001). Adverse reactions occurred in 4.3% (2/47) of patients in the compound lidocaine cream group and 11.3% (6/53) in the lidocaine–prilocaine cream group, with no statistically significant difference between groups (χ 2 = 1.89, p = 0.169). Conclusion Compound lidocaine cream demonstrated superior analgesic efficacy in this clinical comparison; however, differences in anesthetic concentration, application technique, and lack of participant blinding should be considered when interpreting these findings. Larger studies with standardized dosing and blinding are warranted.

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In recent years, the popularity of aesthetic and cosmetic procedures, often performed in outpatient settings, has strongly renewed interest in topical anesthetics. A number of different options are widely used, alone or in combination, in order to minimize the pain related to surgery. Moreover, interest in local anesthetics in the treatment of some painful degenerative conditions such as myofascial trigger point pain, shoulder impingement syndrome, or patellar tendinopathy is increasing. Numerous clinical trials have shown that lidocaine-tetracaine combination, recently approved for adults aged 18 or older, is effective and safe in managing pain. The present paper gives an overview of the recent literature regarding the efficacy and safety of lidocaine-tetracaine combination use.

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Neuroblastoma (NB), a neural crest-derived tumour, is one of the most common extracranial solid malignancies in children. Most patients are under 5 years old at diagnosis (median, 18 months) [1]. The main cause of death is metastasis with high-risk patients having a survival rate below 50% over 5 years. The main treatment for high-risk cases is multimodal involving surgery, chemotherapy, radiotherapy, immunotherapy and stem cell transplantation. However, despite aggressive therapy, more than 50% of children with high-risk NB relapse. Consequently, there is significant unmet need in diagnosing metastatic NB early and treating it effectively and, ideally, non-toxically [1]. Here, we aimed to elucidate the potential anti-invasive role of tetracaine. Tetracaine is a well-established blocker of voltage-gated sodium channel (VGSC) activity shown previously to promote metastatic cell behaviours in several cancers [2, 3]. It is in routine clinical use as a long-acting local anaesthetic [4]. Several human NB cell lines have been shown to express VGSCs [5, 6]. Indeed, a novel developmentally regulated (‘neonatal’) splice variant of Nav1.5 was first described in a NB cell line [5]. However, little is known about the possible pathophysiological role of VGSC expression in NB. The study adhered to the Basic and Clinical Pharmacology and Toxicology policy for experimental and clinical studies [7]. All the procedures used, except the following, have been described already [2]. Transcriptomic expression data were extracted from available databases [8, 9]. For non-normalised data, mRNA transcript abundances were normalised relative to all the detected transcripts in the sample. This was done by calculating the relative abundance of each gene transcript relative to the total amount of mRNA in each sample, accounting for the fact that the number of sequencings reads per sample may vary. For the housekeeping genes RPL9 and ELAVL1, there was less than a twofold difference in expression in the different cell lines. For the glutamate receptor associated GRINA, there was a 2.3-fold variability in expression. The expression levels were lower and more varied for all the VGSC genes, so a threshold of 0.5 was applied to determine the relative levels of expression across the NB cell lines. In a comparative approach, two of the cell lines with markedly different invasiveness were adopted: SH-EP cells, characterised as non-aggressive with low invasive potential, and SK-N-SH cells, representing a more aggressive phenotype. The cells were grown in high-glucose Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% foetal bovine serum (FBS) and 1% penicillin/streptomycin (Gibco, Thermo Scientific, USA). Cells were maintained at 37°C in a humidified 5% CO2 incubator. Tetracaine (Thermo Scientific, USA) was prepared in ethanol as a 50 mM stock solution and stored at −20°C until use. Culture media containing equimolar solvent was used as controls. Data were analysed as means ± standard errors of the mean. Statistical analyses were performed with GraphPad Prism 8 software (GraphPad Software, USA). Each experiment was performed independently three times. Significance was evaluated using one-way ANOVA for multiple comparison and two-tailed unpaired Student's t-test for two-group comparison. Significance was denoted as ‘*’ (p < 0.05) or ‘**’ (p < 0.01). Six different human NB cell lines were adopted: SH-EP, IMR-5, SH-SY5Y, KELLY, SK-N-BE and SK-N-SH. Transcriptomic profiling revealed stable expression of housekeeping genes (RPL9 and ELAVL1), validating their use in normalisation, whereas GRINA (encoding for an ionotropic glutamate receptor) displayed considerable variability. Among VGSCs, SCN8A (Nav1.6) was expressed ubiquitously (Table 1). By contrast, SCN5A (Nav1.5) expression exhibited a restricted profile. It was undetectable in SH-EP and SH-SY5Y but highly expressed in SK-N-SH cells. Thus, Nav1.5 expression could underlie a part of the heterogeneity of NB [8, 9]. Of the two contrasting cell types adopted for the experiments, the SK-N-SH cell line demonstrated an overall neuroblast phenotype (N-type). These cells had neurite-like processes, reflecting their partially differentiated neuronal characteristics. In contrast, SH-EP cells, derived from the substrate-adherent (S-type) subpopulation of SK-N-SH cells, lacked most neuronal characteristics (including neurites), displayed a flattened, epithelial-like morphology with a fibroblast-like appearance. They adhered tightly to the culture surface and grew as a monolayer. These differences made SH-EP a useful model of non-aggressive/less invasive NB, whereas SK-N-SH cells served as a model with relatively strong metastatic potential. Derived from a 4-year-old female patient's bone marrow metastasis Intrinsically non-tumourigenic; lacking processes Doubling time = 30–40 h Substrate-adherent/non-invasive Derived from a young child's untreated tumour Adherent growth Doubling time = 20–30 h Invasive Neuroblast-like thrice-clone of SK-N-SH (derived from bone marrow biopsy of a 4-year-old girl) Large, flat, epithelial-like phenotype with many short processes Exhibit immature neuronal characteristics Doubling time: 48–60 h Non-invasive Derived from the tumour of a 1-year-old female patient Adherent, capable of growth in monolayers Doubling time = 30–40 h Invasive Derived from bone marrow biopsy of a 22-month-old male patient Display variable morphology, form loosely adherent aggregates Stem cell–like properties Doubling time = 20–30 h Invasive Derived from a metastatic bone marrow aspirate Comprises two morphologically distinctive cell types, a small spiny cell and a large epithelioid cell Doubling time: 40–50 h Highly invasive Treatment of both cell lines for 24–48 h with tetracaine up to 100 μM had no effect on their viability (Figure 1A,B). Moreover, tetracaine did not exhibit any noticeable effect on the proliferation of SH-EP cells at concentrations up to 100 μM, or of SK-N-SH cells up to 50 μM (Figure 1C,D). In the following experiments, accordingly, the working concentrations of tetracaine were fixed as 50 μM for SH-EP and 25 μM for SK-N-SH cells, so as to ensure viability of the cells and no effect on proliferative activity while studying motility and invasiveness. Such limited effects of tetracaine are similar to previous observations on human breast, prostate and colon cancer cells using tetrodotoxin (TTX) as a highly specific blocker of VGSCs [2]. Two types of cell behaviour involved in the metastatic cascade were studied: lateral motility and Matrigel invasion. Lateral motility resembles early stages of metastatic cascade when the tumour cells are moving out of their primary sites, whereas Matrigel invasion represents more advanced behaviour involving both motility and proteolytic degradation of the extracellular matrix. Preliminary experiments revealed that SH-EP cells were not invasive. However, the cells were motile. Thus, in scratch assays, their motility index (MoI) increased significantly from 0.45 (24 h) to 0.87 (48 h). Treatment with tetracaine (50 μM) inhibited lateral motility, MoI falling by 10% and 35% after 24 and 48 h, respectively (Figure 2). These effects were statistically significant (p < 0.05 and < 0.01). On the other hand, SK-N-SH cells exhibited clear invasive behaviour and were tested in Matrigel-based transwell invasion assays. Following 25 μM tetracaine treatment for 48 h, invasiveness was reduced significantly by ~20% (p < 0.01; Figure 3). According to the bioinformatics, the elevated expression of Nav1.5 in SK-N-SH cells (and other invasive cell lines) is noteworthy, as this channel has been linked to metastatic behaviour in breast and colorectal cancers [2, 10]. Its expression as a developmentally regulated neonatal splice variant was demonstrated earlier in NB-1 cells [5]. Its selective enrichment in an aggressive NB cell line is consistent with a potential role in promoting tumour aggressiveness. Clinically, Nav1.5 may therefore represent both a biomarker of high-risk NB and a candidate therapeutic target, where pharmacological inhibition of its activity could help to limit metastatic progression and improve patient outcome [3]. Tetracaine is a reversible blocker of VGSC activity, binding to the Na+ pore from the intracellular side of the channel protein [4]. It has been used extensively as a local anaesthetic clinically as well as to inhibit cellular VGSC activity experimentally [4, 11]. At the maximum concentration (100 μM) of tetracaine used here, it is likely that the VGSC currents would be blocked by some 50% [4]. In the two model NB cell lines adopted (SH-EP and SK-N-SH), tetracaine had no effect on cell viability at concentrations up to 100 μM. This agrees with previous studies on NB, glioblastoma and oral squamous cell carcinoma cells showing cytotoxic effects of tetracaine only at concentrations greater than 100 μM [12]. We, therefore, adopted 50 and 25 μM of tetracaine, respectively, to study metastatic cell behaviours free from any possible effect on cell viability or proliferation over 48 h. Tetracaine inhibited the lateral motility SH-EP cells significantly by 35%. Unlike SH-EP, SK-N-SH cells were invasive and tetracaine inhibited the invasiveness by 20%. This was a true effect on invasion because, at the working concentration of tetracaine, neither proliferation nor cell viability were involved. These findings agree with previous work on multiple cancer types (especially breast, colon and prostate cancers) showing (i) that VGSC activity promotes metastatic cell behaviours and (ii) that local anaesthetics can block invasiveness [13-15]. On breast cancer MDA-MB-231 cells, for example, tetracaine had a significant suppressive effect on motility, invasion and adhesion [11]. A major mode of action of the cancer VGSC is in acidifying extracellular pH, leading to activation of proteolytic enzymes. Consistent with this, tetracaine was shown earlier to downregulate matrix metalloproteinases and upregulate tissue inhibitors of metalloproteinases [11]. VGSC activity can also affect the intracellular Ca2+ level via Na+/Ca2+ exchange (NCX) and together with the VGSC β-subunits can lead to further remodelling of the cytoskeleton including the formation of actin-rich invasive structures such as invadopodia [16]. Thus, VGSCs act as upstream regulators that integrate ionic signalling, adhesion dynamics, and gene expression to enhance migration and invasiveness of cancer cells [10]. In addition to tetracaine, several clinically approved VGSC modulators, originally developed for non-oncological indications, have gained increasing attention for their potential anticancer properties. In particular, lidocaine, a widely used local anaesthetic, and ranolazine, an antianginal agent, have both demonstrated inhibitory effects on cancer cell proliferation, migration and invasion in preclinical including human studies [15, 17]. Furthermore, human trials suggested that perioperative administration of lidocaine can be associated with reduced cancer recurrence rates and longer patient survival [18] Another interesting candidate is ranolazine, which (i) binds to the same site intracellular site within the VGSC protein as local anaesthetics and (ii) blocks selectively the channel's persistent current leading to inhibition of metastasis with real-world evidence suggesting a survival benefit [17]. Although such agents have been shown to produce anti-cancer effects through VGSC inhibition dosages need to be carefully controlled since side effects are also possible (e.g., https://www.drugs.com/ranexa.html). Our study does suffer from two main limitations. First, we have not revealed the subtype(s) of the VGSCs present in the NB cells and if these are electrophysiological active. Second, we have not elucidated the possible signalling mechanisms associated with the anti-invasive effect of tetracaine. Nevertheless, well-established insights do exist for both limitations. Several NB cell lines have indeed been shown to express functional VGSCs, and their activity can induce changes in extracellular pH and intracellular Ca2+ with wide-ranging downstream consequences, as noted in Section 4.2. We plan to probe deeper into these areas in future work. Tetracaine has anti-invasive effects on NB cells and, accordingly, may ultimately be repurposed as a safe clinical agent against NB especially its aggressive forms. This study was supported by Pro Cancer Research Fund (PCRF). We thank Prof Louis Chesler (ICR, Sutton) for supplying NB cell lines. This study was supported by Pro Cancer Research Fund (PCRF). M.B.A.D. holds shares in Celex Oncology Innovations Ltd., which aims to develop ion channel modulators as cancer drugs. The other authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.

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