Comparación entre dosis bajas de bupivacaína y prilocaína en cirugía perianal ambulatoria / Comparison between low doses of bupivacaine and prilocaine in ambulatory perianal surgery

La cirugía perianal ambulatoria se caracteriza por necesitar un plano anestésico profundo durante un periodo de tiempo corto. El bloqueo subaracnoideo en silla de montar consigue una anestesia sensitiva intensa sin apenas bloqueo motor asociado. Los anestésicos locales de larga duración, como la bupivacaína, permiten en dosis bajas la realización del procedimiento y el alta hospitalaria en un tiempo acorde con la dinámica de la unidad cirugía mayor ambulatoria (UCMA). La prilocaína es un anestésico local de vida media intermedia que se caracteriza por su bajo riesgo de síntomas neurológicos transitorios y que se puede usar a dosis de 10 mg en anestesia espinal en silla de montar para la realización de cirugía perianal de menos de 45 min de duración. La hipótesis planteada es que la prilocaína, al ser un anestésico de vida media más corta que la bupivacaína, proporciona un bloqueo suficiente para la realización de un procedimiento estándar de cirugía anorrectal, acortando la estancia en la UCMA. Este estudio prospectivo, a doble ciego de 100 pacientes ASA I-III, divididos en 2 grupos aleatorios: Grupo P (10 mg de prilocaína hiperbárica 20 % + 10 μg de fentanilo) y grupo B (2,5 mg bupivacaina hiperbárica 0,5 % + 10 μg de fentanilo), donde medimos como objetivo principal el tiempo desde la realización de la técnica anestésica hasta el alta hospitalaria. Y como secundarios: el éxito del bloqueo, el tiempo desde el final de la cirugía hasta el alta hospitalaria, el tiempo de regresión del bloqueo sensitivo/motor, el tiempo hasta deambulación, la retención de orina y los efectos adversos.(AU)

Ambulatory perianal surgery is characterized by the need for a deep anesthetic plane for a short period of time. The subarachnoid saddle block achieves intense sensory anesthesia with almost no associated motor blockade. Long-acting local anesthetics, such as bupivacaine, allow the procedure to be performed at low doses and discharge from the hospital in a time that is consistent with the dynamics of the major outpatient surgery unit (MOSU). Prilocaine is a local anesthetic with an intermediate half-life that is characterized by its low risk of transient neurological symptoms and can be used at a dose of 10 mg in saddle spinal anesthesia for perianal surgery of less than 45 min duration. The hypothesis put forward is that prilocaine, being a shorter half-life anesthetic than bupivacaine, provides sufficient blockade for the performance of a standard anorectal surgery procedure, shortening the stay in the AMCU. This prospective, double-blind study of 100 ASA I-III patients, divided into 2 randomized groups: group P (10 mg hyperbaric prilocaine 20 % + 10 μg of fentanyl) and group B (2.5 mg hyperbaric bupivacaine 0.5 % + 10 μg of fentanyl), where we measured as primary objective the time from the performance ofthe anesthetic technique to hospital discharge. And as secondary objectives: success of the block, time from the end of surgery to hospital discharge, time of regression of the sensory/motor block, time to ambulation, urine retention and adverse effects.(AU)

Local anesthetics allergy in children: Evaluation of diagnostic tests with Real-Life data.

BACKGROUND: Local anesthetic (LA) drugs are commonly used in clinical practice to provide effective analgesia, including in dentistry and minor surgical procedures. The perception of a high risk of allergy in daily applications leads to the referral of atopic patients and those with other drug allergies to allergy clinics for the evaluation of allergic reactions to LA. The aim of this study was to determine who should be referred to the allergy clinic for LA allergy testing, assess the frequency of LA allergy in pediatric patients, and identify the negative predictive value of skin tests in diagnosis. METHODS: January 2017-July 2023, the clinical and laboratory data, as well as the results of drug allergy tests, of patients referred to our pediatric allergy clinic by dentists and physicians performing minor surgical procedures with suspected LA allergy were retrospectively evaluated. RESULTS: Our study included a total of 153 patients, comprising 84 girls (54.9%) and 69 boys (45.1%), with a mean age of 8.9 (±3.3) years. The most common reason for referral was a history of non-LA drug allergies (n = 66, 43.2%), followed by asthma (n = 25, 16.3%). Hypersensitivity reactions (HRs) with LA were most commonly associated with articaine (n = 7, 4.8%), followed by lidocaine (n = 6, 4.1%). When intradermal tests were evaluated, 17 patients (11.1%) had a positive test result. The positivity for lidocaine was 70.6% (n = 12), and prilocaine was 29.4% (n = 5). Subcutaneous provocation was administered to 109 patients (71.2%), and one patient exhibited local erythema and swelling with prilocaine. CONCLUSION: Although LA allergy is a rare occurrence, consultations of this nature are frequently requested from allergy clinics in real life. Considering the negative predictive value of skin tests performed with LA drugs, the reaction rate appears to be low in patients with atopy or other drug allergies. It is crucial for all relevant healthcare professionals to be knowledgeable about the appropriate approach to suspected LA allergies to avoid unnecessary tests. To the best of our knowledge, our study is the most comprehensive work in the literature that evaluates the results of diagnostic tests in children referred with a suspicion of LA allergy.

Molecular interactions of hydrated co-amorphous systems of prilocaine and lidocaine.

It is generally accepted that water as a plasticizer can decrease the glass transition temperatures (Tgs) of amorphous drugs and drug excipient systems. However, previous studies suggest that water, as an anti-plasticizer, can increase the Tgs of co-amorphous systems of prilocaine (PRL) and lidocaine (LID). In order to investigate the intermolecular interactions between water and co-amorphous PRL-LID systems, Fourier transform infrared spectroscopy (FTIR) and principal component analysis (PCA) were conducted. Water was found to bind with the carbonyl groups of PRL and LID molecularly evenly in the hydrated co-amorphous PRL-LID systems. Quantum chemical simulations visually confirmed the interactions between water and co-amorphous PRL-LID systems. Furthermore, the physical stability of hydrated co-amorphous PRL-LID systems was improved due to the anti-plasticizing effect of water, compared with the anhydrous samples. The preference of water to interact with the carbonyl groups of PRL and LID as binding sites could be associated with the anti-plasticizing effect of water on the co-amorphous PRL-LID systems.

Efficacy of Buzzy Device Versus EMLA Cream for Reducing Pain During Needle-Related Procedures in Children: A Randomized Controlled Trial.

OBJECTIVES: Several pain management tools exist but with limitations in their efficacy or applicability. The EMLA (eutectic mixture of local anesthetics) cream is currently used for pain relief for needle-related procedures; however, it needs a minimum of 30 to 45 minutes to be effective. The Buzzy is a device that generates vibrations with cold leading to quicker pain relief. Our aim was to evaluate the effect of the Buzzy device in pain and anxiety reduction compared with EMLA cream in children requiring intravenous cannulation or venepuncture. METHODS: This was a randomized clinical trial comparing pain and anxiety reduction by Buzzy device with the standard care (EMLA cream) in children aged 2 to 14 years who required blood extraction or intravenous cannulation based on their clinical needs. Eligible patients were randomized to either Buzzy device as the intervention or EMLA cream as the control. The outcome measures were the degree of pain scores and anxiety ratings at different stages of the needle-related procedures. RESULTS: A total of 300 patients with a mean age of 6.5 ± 3.1 years were enrolled. Baseline characteristics were similar between the Buzzy device and EMLA cream groups. The observed pain scores by research nurses and a parent were significantly lower in the EMLA group compared with the Buzzy device group; however, the pain scores by the self-assessment scale were not statistically significant with mean difference of -0.332, 95% confidence interval, -0.635 to -0.028 ( P = 0.062). The level of anxiety was significantly lower in EMLA compared with Buzzy device ( P = 0. 0.0001). Both staff and parents' satisfaction, success rate of cannulation, type of blood tests, and comment on the physician on the results were similar in both groups. CONCLUSIONS: Pain and anxiety relief using the Buzzy device is not as effective as EMLA cream in children requiring venepuncture. However, rapid onset of action of the Buzzy device is valuable in decreasing waiting time in a busy emergency department. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT05354739.

Applying Topical Anesthetic on Pediatric Lacerations in the Emergency Department: A Quality Improvement Project.

OBJECTIVES: Caring for pediatric lacerations in the emergency department (ED) is typically painful because of irrigation and suturing. To improve this painful experience, we aimed to increase the use of a topical anesthetic, Eutectic Mixture of Local Anesthetics (EMLA) on eligible pediatric lacerations with an attainable, sustainable, and measurable goal of 60%. The baseline rate of applying topical anesthetic to eligible lacerations was 23% in our ED. We aimed to increase the use of topical anesthetics on eligible pediatric lacerations to a measurable goal of 60% within 3 months of implementing our intervention. METHODS: We conducted a prospective, single-center, interrupted time series, ED quality improvement project from November 2019 to July 2020. A multidisciplinary team of physicians and nurses performed a cause-and-effect analysis identifying 2 key drivers: early placement of EMLA and physician buy-in on which we built our Plan, Do, Study, and Act (PDSA) cycles. We collected data on number of eligible patients receiving EMLA, as well as patient and physician feedback via phone calls within 2 days after encounter. Balancing measures included ED length of stay (LOS), patient and physician satisfaction with EMLA, and adverse effects of EMLA. RESULTS: We needed 3 PDSA cycles to reach our goal of 60% in 3 months, which was also maintained for 5 months. The PDSA cycles used educational interventions, direct provider feedback about noncompliance, and patient satisfaction results obtained via phone calls. Balancing measures were minimally impacted: 75% good patient satisfaction, no adverse events but an increase in LOS of patients who received EMLA compared with those who did not (1.79 ± 0.66 vs 1.41 ± 0.83 hours, P < 0.001). The main reasons for dissatisfaction for physicians were the increased LOS and the preference for procedural sedation or intranasal medications. CONCLUSIONS: With a few simple interventions, our aim of applying EMLA to 60% of eligible pediatric lacerations was attained and maintained.

Molecular dynamics study of the mechanical properties of drug loaded model systems: A comparison of a polymersome with a bilayer.

In this work we implement a new methodology to study structural and mechanical properties of systems having spherical and planar symmetries throughout Molecular Dynamics simulations. This methodology is applied here to a drug delivery system based in polymersomes, as an example. The chosen model drug was the local anesthetic prilocaine due to previous parameterization within the used coarse grain scheme. In our approach, mass density profiles (MDPs) are used to obtain key structural parameters of the systems, and pressure profiles are used to estimate the curvature elastic parameters. The calculation of pressure profiles and radial MPDs required the development of specific methods, which were implemented in an in-house built version of the GROMACS 2018 code. The methodology presented in this work is applied to characterize poly(ethylene oxide)-poly(butadiene) polymersomes and bilayers loaded with the model drug prilocaine. Our results show that structural properties of the polymersome membrane could be obtained from bilayer simulations, with significantly lower computational cost compared to whole polymersome simulations, but the bilayer simulations are insufficient to get insights on their mechanical aspects, since the elastic parameters are canceled out for the complete bilayer (as consequence of the symmetry). The simulations of entire polymersomes, although more complex, offer a complementary approach to get insights on the mechanical behavior of the systems.

Effects of epinephrine, lidocaine, and prilocaine on viability and differentiation capacity of human adipose stem cells.

INTRODUCTION: Local anesthetics (LAs) are routinely administered in plastic and reconstructive surgery, e.g., as tumescent anesthesia adjunct in liposuction. Historically, these substances were assumed to act cytotoxically. Thus, the application of LA was avoided when handling adipose stem cells (ASCs). We recently determined that most LAs are not cytotoxic when ASCs are exposed to concentrations used for tumescent liposuction. However, there is limited information when combining LA with epinephrine and about the effects of prilocaine on ASCs. METHODS: We analyzed the effects of prilocaine or lidocaine in co-exposure with epinephrine on the viability of primary human ASCs, i.e., proliferation, metabolic activity, and cytotoxicity, using crystal violet-staining, PrestoBlue®-, and WST-1 assay. We quantified the impact of short-term incubation of lidocaine and epinephrine on the differentiation of ASCs into the adipogenic, chondrogenic, and osteogenic lineage. RESULTS: After 2 h, prilocaine (10 mM) significantly reduced metabolic activity and cell numbers, whereas lidocaine only inhibited metabolic activity. After 6 h, prilocaine (10 mM) and lidocaine significantly decreased metabolic activity as well as cell numbers. The application of high concentrations of epinephrine did not affect cell numbers but diminished metabolic activity. Combining lidocaine with epinephrine had no additional cytotoxic effect. Differentiation into the chondrogenic lineage was significantly inhibited by epinephrine. CONCLUSIONS: Deducing from our data, neither lidocaine combined with epinephrine nor prilocaine has a cytotoxic impact on ASCs in vitro at concentrations equivalent to those in tumescent anesthesia and has no long-lasting effect on the differentiation capacity of ASCs into the osteogenic and adipogenic lineage.

Dermal effects and pharmacokinetic evaluation of the lidocaine/prilocaine cream in healthy Chinese volunteers.

BACKGROUND: EMLA cream is a local anesthetic. The pharmacokinetics and dermal effects of a topical anesthetic formulation has not been evaluated in healthy Chinese volunteers. MATERIALS AND METHODS: The Pharmacokinetics of the lidocaine/prilocaine test (T) or reference (R, EMLA) cream were evaluated in a fasting, single-dose, two-period crossover bioequivalent study conducted in 40 healthy Chinese volunteers. Meanwhile, the dermal effects including blanching, erythema, temperature sensation, edema, and skin rash were also evaluated during the study. RESULTS: After applied 15 g of the cream for 4 h to a 100 cm2 area under plastic occlusive film on the skin of the thigh of healthy volunteers, the results of the pharmacokinetic study showed that the active components absorbed in skin from topical products was relatively low compared with most system absorption drugs. After the removal of the residual anesthetic cream, there was a vascular biphasic response with initial transient blanching which reaches a peak at 4.5 h and later more persisting period erythema. The change of temperature sensory sensitivity reached the peak value at 4.5-6 h.There was no statistically significant difference of the changes after application the lidocaine/prilocaine T or R cream in subjects. In general, the lidocaine/prilocaine T or R cream was well tolerated. CONCLUSION: The method described a model for investigations of pharmacokinetics and pharmacodynamics of topical lidocaine/prilocaine cream. Except the plasma drug level indicator, these pharmacodynamics data should also be evaluated in the anesthetic transdermal pharmacokinetics study. CLINICAL TRIAL REGISTRATION: CTR20211544; registered in http://www.chinadrugtrials.org.cn/ at September 2021.

Pain associated with intravascular instrumentation reduces orthostatic tolerance and predisposes to vasovagal reactions in healthy young adults without needle phobia: a randomised controlled study.

PURPOSE: Vasovagal syncope (VVS), or fainting, is frequently triggered by pain, fear, or emotional distress, especially with blood-injection-injury stimuli. We aimed to examine the impact of intravenous (IV) instrumentation on orthostatic tolerance (OT; fainting susceptibility) in healthy young adults. We hypothesized that pain associated with IV procedures would reduce OT. METHODS: In this randomised, double-blind, placebo-controlled, cross-over study, participants (N = 23; 14 women; age 24.2 ± 4.4 years) underwent head-up tilt with combined lower body negative pressure to presyncope on three separate days: (1) IV cannulation with local anaesthetic cream (EMLA) (IV + EMLA); (2) IV cannulation with placebo cream (IV + Placebo); (3) sham IV cannulation with local anaesthetic cream (Sham + EMLA). Participants rated pain associated with IV procedures on a 1-5 scale. Cardiovascular (finger plethysmography and electrocardiogram; Finometer Pro), and forearm vascular resistance (FVR; brachial Doppler) responses were recorded continuously and non-invasively. RESULTS: Compared to Sham + EMLA (27.8 ± 2.4 min), OT was reduced in IV + Placebo (23.0 ± 2.8 min; p = 0.026), but not in IV + EMLA (26.2 ± 2.2 min; p = 0.185). Pain was increased in IV + Placebo (2.8 ± 0.2) compared to IV + EMLA (2.0 ± 2.2; p = 0.002) and Sham + EMLA (1.1 ± 0.1; p < 0.001). Orthostatic heart rate responses were lower in IV + Placebo (84.4 ± 3.1 bpm) than IV + EMLA (87.3 ± 3.1 bpm; p = 0.007) and Sham + EMLA (87.7 ± 3.1 bpm; p = 0.001). Maximal FVR responses were reduced in IV + Placebo (+ 140.7 ± 19.0%) compared to IV + EMLA (+ 221.2 ± 25.9%; p < 0.001) and Sham + EMLA (+ 190.6 ± 17.0%; p = 0.017). CONCLUSIONS: Pain plays a key role in predisposing to VVS following venipuncture, and our data suggest this effect is mediated through reduced capacity to achieve maximal sympathetic activation during orthostatic stress. Topical anaesthetics, such as EMLA, may reduce the frequency and severity of VVS during procedures requiring needles and intravascular instrumentation.

Inflammatory signal transduction pathways induced by prilocaine toxicity in cultured ARPE-19 cells.

Prilocaine (PRL) is a common local anesthetic. Despite the successful use of regional anesthesia for intraocular surgery, there are associated side effects that may affect the retina in case of accidental intravitreal injection. This study examined the signal transduction pathways activated by PRL toxicity and determined the protective role of nitric oxide synthase-2 (NOS2) inhibition in cultured human-derived retinal pigment epithelial cells (ARPE-19). Toxicity analysis was performed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay to detect the toxic dose of PRL and protective effectiveness of asperglaucide (ASP), an NOS2 inhibitor. Nuclear factor kappa B p65 (NF-κB p65), phosphorylated NF-κB p65, phospho-protein kinase B (AKT), NOS2, nitrotyrosine, and cleaved caspase-3 protein levels were evaluated by immunofluorescence staining and/or western blot analysis. Interleukin-6 (IL-6) and nitrated protein levels were quantified using an immunoassay, whereas caspase-3 activity and nitrite/nitrate levels were measured using a fluorometric method. A significant increase in NF-κB p65, and phosphorylated NF-κB p65 and AKT levels due to PRL toxicity was observed. Similarly, IL-6, NOS2, nitrite/nitrate, and nitrotyrosine levels were significantly higher in PRL-treated cells than in control cells. Application of ASP to PRL-treated cells reduced NF-κB p65, and phosphorylated NF-κB p65 and AKT to basal levels. IL-6, NOS2, nitrite/nitrate, and nitrotyrosine levels also considerably decreased following ASP treatment in cells experiencing PRL-induced toxicity. Moreover, the caspase-3-dependent apoptotic pathway was not activated. Our results indicate that ASP could ameliorate PRL-induced activation of NF-κB p65 that led to inflammation in cultured ARPE-19 cells.

Safety and Pharmacokinetics of PSD502 in Healthy Chinese Male and Female Volunteers: Two Randomized, Double-Blind, Placebo-Controlled, Phase I Trials.

BACKGROUND AND OBJECTIVE: PSD502 is a metered-dose spray for premature ejaculation. The two trials aimed to evaluate the safety and pharmacokinetics of PSD502 in healthy Chinese male and female individuals. METHODS: Two phase I, randomized, double-blind, placebo-controlled trials were conducted in men (Trial 1) and women (Trial 2). The participants were randomized 3:1 to receive PSD502 (7.5 mg of lidocaine and 2.5 mg of prilocaine per spray) or a placebo. For male individuals, a single dose (three sprays) once daily was applied to the glans penis for 21 days except for nine sprays (three doses) on days 7 and 14, 4 h apart for each dose. For female individuals, two sprays were applied to the vagina and one to the cervix once daily for 7 days. The primary endpoint was safety. Pharmacokinetics analysis was also performed. RESULTS: Twenty-four male and 24 female individuals were recruited. Treatment-emergent adverse events occurred in 38.9% (7/18) of male individuals and 66.7% (12/18) of female individuals in the PSD502 group, respectively. Both trials reported 50.0% (3/6) treatment-emergent adverse events for the placebo. No grade ≥ 3 treatment-emergent adverse events, serious adverse events, or treatment-emergent adverse events leading to early withdrawal or discontinuation occurred. After consecutive applications, lidocaine and prilocaine cleared rapidly in both trials. Plasma concentrations exhibited high inter-individual variability. The maximum plasma concentrations of active ingredients were far below the anticipated minimum toxic concentrations. The area under the plasma concentration-time curve of metabolites were ≤ 20% of the parent drugs. No clinically significant accumulations were observed in the two trials. CONCLUSIONS: PSD502 was well tolerated and showed low plasma concentrations in healthy Chinese male and female individuals.

The effects of intrathecal morphine on urinary bladder function and recovery in patients having a cesarean delivery - A randomized clinical trial.

INTRODUCTION: Spinal anesthesia with intrathecal morphine (ITM) is a common anesthesia technique for cesarean delivery. The hypothesis was that the addition of ITM will delay micturition in women undergoing cesarean delivery. METHODS: Fifty-six ASA physical status I and II women scheduled to undergo elective cesarean delivery under spinal anesthesia were randomized to the PSM group (50 mg prilocaine + 2.5 mcg sufentanil + 100 mcg morphine; n = 30) or PS group (50 mg prilocaine + 2.5 mcg sufentanil; n = 24). The patients in the PS group received a bilateral transverse abdominal plane (TAP) block. The primary outcome was the effect of ITM on the time to micturition and the secondary outcome was the need for bladder re-catheterization. RESULTS: The time to first urge to urinate (8 [6-10] hours in the PSM group versus 6 [4-6] hours in the PS group) and the time to first micturition (10 [8-12] hours in the PSM group versus 6 [6-8] hours in the PS group) were significantly (p < 0.001) prolonged in the PSM group. Two patients in the PSM group met the 800 mL criterium for urinary catheterization after 6 and 8 h respectively. CONCLUSION: This study is the first randomized trial to demonstrate that the addition of ITM to the standardized mixture of prilocaine and sufentanil significantly delayed micturition.

Topical Anesthetic versus Lidocaine Mixture for Pain Relief During Keloid Treatment: A Prospective, Split Study.

BACKGROUND: The most common typical symptoms of keloids can be pain and itchiness. Intralesional corticosteroid administration is generally the first-line conservative treatment. Minimizing pain during intralesional corticosteroid injections into keloids should be aimed, as the treatment is often painful. There has yet to be a report on which local anesthetic technique is superior in keloid treatment between topical anesthetic versus lidocaine mixture injection. METHODS: This was a single-center prospective study. The study included 100 patients with painful multiple/multifocal keloids aged 18 to 85 years and was performed between May 2021 and December 2022. Among multiple keloid lesions in a single patient, we assigned the keloids pretreated with topical cream application versus local injection. Then, subjects received 40 mg of intralesional corticosteroid injections into the keloids with a 26G needle to treat keloids. Patients rated the pain intensity of each lesion pretreated with two different anesthetic techniques on an 11-point numeric rating scale. A separate direct question of "Which technique would you recommend if you had to be injected again?" was given. RESULTS: One-hundred patients with painful multiple/multifocal keloids were included in the study. Data on pain intensity numeric rating scale (NRS) revealed that injection techniques relieved the pain statistically significantly more than topical creams. ( P <0.001) 63% of the participants (n=63) preferred the injection technique, while 25% preferred topical anesthetics. In total, 12% of patients responded that there was no difference between the two techniques. CONCLUSION: When comparing with topical lidocaine/prilocaine (EMLA) cream, a 1:1 mixture of 1% lidocaine and epinephrine significantly alleviated pain during and after the corticosteroid injection.

Crystallization of short-acting and intermediate-acting local anesthetics when mixed with adjuvants: a semiquantitative light microscopy analysis.

INTRODUCTION: The addition of adjuvants to short-acting local anesthetics (LA) is common practice in clinical routine to speed up block onset and decrease pain on injection. In a previous study, we observed the development of microscopic crystal precipitations after bupivacaine or ropivacaine were mixed with adjuvants; this follow-up study is intended to clarify whether crystallization (A) also occurs in short-acting or intermediate-acting LA-adjuvant mixtures, (B) changes over time, and (C) is associated with the solutions' pH. METHODS: Lidocaine 2%, prilocaine 2%, mepivacaine 2%, procaine 2% and chloroprocaine 2% were individually mixed with clonidine, dexamethasone, dexmedetomidine, epinephrine, fentanyl, morphine or sodium bicarbonate 8.4% in clinically established ratios. For each mixture, we measured initial pH and recorded crystallization patterns at 0, 15, 30 and 60 min using a standardized, semiquantitative light microscopy approach. RESULTS: Lidocaine 2% and mepivacaine 2% plus sodium bicarbonate 8.4%, and mepivacaine 2% plus dexamethasone developed delayed grade 5 crystallization over 1 hour. Prilocaine-based, procaine-based and chloroprocaine-based mixtures showed much less pronounced crystallization, with a maximum of grade 2. Initial pH and grade of crystallization showed weak monotonic relationships at time points t0, t15 and t30 (ρ=-0.17, 0.31 and 0.32, (all p>0.05)) and a moderate relationship time point t60 (ρ=0.57 (p=0.0003)) CONCLUSIONS: Our study revealed high grades of crystallization in lidocaine/mepivacaine-bicarbonate and mepivacaine-dexamethasone mixtures, although these were previously considered safe for local, perineural or neuraxial use. Our findings cast particular doubt on the safety of preparing these formulations for later use.

Thermal investigation on hydrated co-amorphous systems of nicotinamide and prilocaine.

It is generally recognized that water, acting as a plasticizer, increases molecular mobility, leading to a decrease of the glass transition temperature (Tg) in amorphous systems. However, an anti-plasticizing effect of water was recently observed on prilocaine (PRL). This effect might be used in co-amorphous systems to moderate the plasticizing effect of water. Nicotinamide (NIC) can form co-amorphous systems with PRL. In order to investigate the effect of water on these co-amorphous systems, the Tgs and molecular mobility of hydrated co-amorphous NIC-PRL systems were compared with those of the respective anhydrous systems. Molecular mobility was estimated by considering the enthalpic recovery at the Tg using the Kohlrausch-Williams-Watts (KWW) equation. At molar ratios of NIC above 0.2, a plasticizing effect of water on co-amorphous NIC-PRL systems was observed with increasing the NIC concentration. In contrast, at molar ratios of NIC of 0.2 and below, water had an anti-plasticizing effect on the co-amorphous NIC-PRL systems, with increased Tgs and reduced mobility upon hydration.

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".

Prilocaine/lidocaine spray for the treatment of premature ejaculation: a dose- and time-finding study for clinical practice use.

A eutectic mixture of prilocaine/lidocaine spray (Fortacin™, Recordati, Milan, Italy) has been approved for the management of patients affected by life-long premature ejaculation (PE), but to date, there is a lack of dose- or time-finding studies in the literature that indicate the best method of intake to optimize treatment outcomes. In this multicentre, randomized, two-phase study, we aimed to compare, in terms of treatment effectiveness (primary objective) and safety (secondary objective), different treatment regimens (various doses and times of drug delivery) of Fortacin™ in 91 patients affected with lifelong PE who were recruited at four different centres and randomized (1:1:1 ratio) into three different groups. The study included two phases: during the first phase (focused on time-finding), the same drug dose (three sprays) was taken at different intervals before intercourse (5, 15, 30 min). In the second phase (focused on dose finding), different drug doses (1, 3, 5 sprays) were taken at the same interval before intercourse (5 min). The main outcome measure instruments were self-measured intravaginal ejaculation latency time (sm-IELT), the premature ejaculation diagnostic tool (PEDT), and the International Index of Erectile Function-5 (IIEF-5). Furthermore, patients were asked to report any side effects that appeared during the study period. Our main study findings showed that the treatment regimen with three sprays of Fortacin™ administered 5 min before sexual intercourse showed the best results in terms of ejaculation time and control (Phase I, IELT 221 ± 3.4, PEDT 7.7 ± 0.3; Phase II, IELT 213 ± 4.9, PEDT 7.8 ± 0.4) with a safety profile that was identical to other treatment regimens. Based on these data, patients who are prescribed Fortacin™ should stick to this regimen to optimize treatment results.

Comparative effectiveness of ice packs versus topical lidocaine-prilocaine mixture for pain control in laser hair removal of the axilla: A rater-blinded randomized controlled trial.

BACKGROUND: Laser hair removal is associated with moderate acute pain. OBJECTIVE: To compare effectiveness of ice pack to topical lidocaine-prilocaine for pain reduction during axillary laser hair removal. METHODS: Participants were randomly assigned to receive topical anesthetic to one axilla and ice packs to the other before each of 3, monthly 810 nm diode laser sessions. The primary endpoint was participant-reported pain on the visual analog scale (VAS) immediately following and 5 minutes after laser session. Posttreatment erythema, overall edema, and perifollicular edema were assessed by 2 blinded photoraters. Skin temperatures, patient preferences, and adverse events were recorded. RESULTS: Eighty-eight of 90 (98%) planned laser treatments were delivered and randomized. Participants reported higher VAS scores immediately after laser treatment with lidocaine-prilocaine compared to ice (P = .03). Five minutes after, participants reported higher VAS scores with ice (P = .03). After 53 of the 88 treatments (60.2%), participants reported preferring ice (P = .055). No serious adverse events were reported. LIMITATIONS: All participants were Caucasian or Asian with Fitzpatrick skin type I to III and coarse dark axillary hair, which may limit generalizability. CONCLUSIONS: While pain control with ice and topical anesthesia is associated with time after treatment, the 2 modalities do not differ in terms of degree of pain reduction associated with axillary laser hair removal.

A Randomized Controlled Trial Comparing Two Different Local Intraurethral Anesthetics in Optical Internal Urethrotomy at the Outpatient Clinic.

OBJECTIVE: To assess feasibility and efficacy of local topical urethral anesthesia at optical internal urethrotomy (OIU) in patients with anterior and posterior urethral strictures at outpatient clinic. METHODS: One hundred and twenty eight patients were prospectively randomized to perform OIU with intraurethral prilocaine solution (group 1 = 64 patients) or intraurethral lidocaine gel (group 2 = 64 patients). Visual analog scale was used for procedure related pain evaluation at the beginning, during, and one hour after the procedure. All patients had follow-ups for a minimum of 12 months. Treatment failure was defined as Qmax < 12ml/sec at uroflowmetry and observed urethral stricture on cystoscopy. RESULTS: The overall success rate of the OIU was 75.8%. The intraoperative mean visual analogue score in group 2 (5,1 ± 1,77) was significantly higher than the group 1 (3.7 ± 1.9) (P = 0.0001). The median time to stricture recurrence was 9.2 months (range 1-13 months). Stricture recurrences were noted in 15 patients in Group 1 and 16 patients in Group 2 during the follow-up period. CONCLUSION: Prilocaine solution as a local anesthetic is a better option than intraurethral lidocaine gel in the OIU procedure and allows successful OIU to be performed in outpatient clinic. It can be preferred as a local anesthetic for OIU, particularly in unfit patients for general/regional anesthesia. Although it provides successful pain relief, it still cannot prevent experiencing moderate or severe pain in a group of patients. More studies about more effective local anesthetics for pain relief during OIU at the outpatient clinic are required.

Methemoglobinemia Induced by Prilocaine in a Child With Noonan Syndrome.

Limited information is currently available on methemoglobinemia caused by the administration of prilocaine in children undergoing dental procedures in Japan. This case report presents the development of methemoglobinemia due to prilocaine overdose. The patient was a female aged 5 years 8 months with Noonan syndrome who also had pulmonary valve stenosis and hypertrophic cardiomyopathy. She presented with severe dental caries affecting 12 total teeth and required general anesthesia due to a lack of cooperation during dental treatment. General anesthesia was performed, during which 3% prilocaine with 0.03 IU/mL felypressin was administered intraoperatively via infiltration. Her SpO2 gradually decreased after 30 minutes, and cyanosis was observed postoperatively. Several assessments including a 12-lead electrocardiogram, an anteroposterior chest radiograph, and venous blood gas analysis were performed to identify potential causes. However, there were no indications of acute respiratory or cardiovascular abnormalities. It was noted that a total of 192 mg prilocaine was administered during the procedure, and methemoglobinemia was suspected to have developed because of overdose. Further testing revealed an elevated serum methemoglobin of 6.9%, supporting methemoglobinemia as the cause of her decreased SpO2. In dental procedures that require the use of prilocaine to treat multiple teeth, particularly for pediatric patients, it is important to carefully manage prilocaine dosing, as an overdose may lead to methemoglobinemia.