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.

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.

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.

[Local anesthetics with elderly patients]. / Die Anwendung von Lokalanästhetika bei Patientinnen und Patienten im Alter.

When choosing local anesthetics, risk factors such as underlying diseases, use of other medications and allergies have to be taken into consideration. Systematic complications might occur if a specific limit in the plasma concentration is exceeded. Articaine and prilocaine are metabolized extrahepatically. In case of an absolute contraindication for vasoconstrictors, the use of mepivacaine, bupivacaine or articaine is recommended.

Methaemoglobinaemia in pregnancy with chronic kidney disease an uncommon case: A case report.

The development of methaemoglobinaemia due to prilocaine, which is used for local anaesthesia, is a rare, life-threatening, but well-known side effect. The development of this side-effect in a pregnant patient with chronic kidney disease can lead to foetal distress. The case presented here is of a 21-year old pregnant female with chronic kidney disease who required haemodialysis in the 22nd week of pregnancy due to the progression to end-stage kidney disease. During haemodialysis, a right jugular tunneled double-lumen catheter was inserted using prilocaine as the local anaesthetic. Prilocaine-induced methaemoglobinaemia was diagnosed. In the 24-hour follow-up, the methaemoglobin level decreased to normal with oxygen supply of 10-15 L/min, 2 units of erythrocyte suspension and accompanying haemodialysis.

Local anesthetic systemic toxicity in the pediatric patient.

Lidocaine and prilocaine are local anesthetics, a class of medications which are frequently used in clinical medicine to minimize pain in a variety of procedures. They are commonly found in over-the-counter products such as topical anesthetic creams advertised to relieve localized muscle and joint pain. While safe and well-tolerated when used appropriately, an overdose of these anesthetics increases the risk for local anesthetic systemic toxicity (LAST), which in severe cases can present with seizures, cardiac dysrhythmias, and ultimately cardiovascular collapse. The reduced muscle mass of pediatric patients puts them at an increased risk of LAST due to the depot effect of the systemically absorbed anesthetic. Methemoglobinemia may also be associated with local anesthetic toxicity. Our case involves a previously healthy 15-month-old female who presented to one of our networks' emergency departments in status epilepticus following an accidental ingestion of a tube of 2.5% lidocaine/2.5% prilocaine cream. Her seizure activity was initially resistant to intraosseous benzodiazepine administration, but ultimately resolved following administration of lipid emulsion and sodium bicarbonate. Additionally, the patient had refractory hypoxia on the monitor which resolved shortly after administration of methylene blue. After stabilization, the patient was transferred to the Pediatric ICU and ultimately made a complete recovery. LAST is a life-threatening presentation which requires early recognition by clinicians, as well as an understanding of the appropriate treatment modalities. We review the assessment and management of LAST, with special focus on the pediatric patient.

Real-life use of the eutectic mixture lidocaine/prilocaine spray in men with premature ejaculation.

Topical anaesthetics are considered a first-line therapy option in men with premature ejaculation (PE). A cross-sectional retrospective analysis was performed to evaluate the real-life use of the eutectic mixture of prilocaine/lidocaine spray (FORTACIN™) in a cohort of 198 white-European men who had been consecutively and prospectively seen at a single tertiary-referral andrology centre for self-reported PE and naive for previous PE treatments. Descriptive statistics was used to describe the whole cohort and the paired t-test was applied to investigate potential differences throughout a 12-month follow-up (baseline, 1, 3, 6 and 12 months). Overall, mean (SD) age was 37 (6.5) years. Of all, lifelong, acquired and subjective PE were reported in 101 (51%), 59 (29.8%) and 38 (19.2%) patients at baseline, respectively. FORTACIN™ use increased up to 6 months, with 184 (92.9%) and 128 (66.4%) men who had tried and regularly used the compound, respectively. At 12-month follow-up, 53 (26.8%) men reported a regular use of the compound. Mean Premature Ejaculation Diagnostic Tool score significantly decreased at 6 and 12 months compared to baseline (all p < 0.05). Conversely, mean IELT significantly improved at 6-month follow-up compared to baseline (all p ≤ 0.04). Overall, FORTACIN™ emerged to be a safe and effective treatment option in PE patients of various types, with almost one fourth of patients still under treatment after 12 months. Timing and dosing of the drug can deserve to be adjusted according to patient's needs and their sexual ecology.

Eutectic Mixture of Lidocaine and Prilocaine Decreases Movement and Propofol Requirements for Pediatric Lumbar Puncture During Deep Sedation: A Randomized, Placebo-Controlled, Double Blind Trial.

Deep sedation/general anesthesia is commonly used in pediatric oncology patients undergoing lumbar puncture (LP). Propofol is often used for sedation, with or without a narcotic. We hypothesized that eutectic mixture of lidocaine and prilocaine (EMLA) would allow for lower cumulative doses of propofol and less movement. We performed a prospective, randomized, double blind, placebo-controlled trial in children undergoing sedation for LP. Standard initial weight-based doses of propofol and fentanyl were administered, with either EMLA cream or a placebo cream applied topically. The primary outcome was the total dose of propofol administered to each patient. We also tracked patient movement and complications. Twenty-seven patients underwent 152 LPs. Patients randomized to EMLA cream (n=75) were significantly more likely to receive a lower dose of propofol (2.94 mg/kg, SE=0.25, vs. 3.22 mg/kg, SE=0.19; P=0.036) and to not require additional propofol doses (probability 0.49, SE=0.08 vs. 0.69, SE=0.06; P=0.001) compared with patients randomized to placebo cream (n=77). In addition, patients with EMLA cream were significantly less likely to demonstrate minor or major movement. EMLA cream results in less movement and less propofol administration in pediatric oncology patients undergoing sedation for LP.

[Unexplained cyanosis in two newborns: neonatal methemoglobinemia after maternal perineal infiltration of prilocaine]. / Onbegrepen cyanose bij twee neonaten.

BACKGROUND: Methemoglobinemia is a rare cause of neonatal cyanosis in the newborn. It is considered a medical emergency. Failure of recognition or appropriated treatment could result in serious disease and neonatal death. Neonatal methemoglobinemia can be caused by both hereditary and acquired factors. CASE DESCRIPTION: We present two cases of newborns who developed severe cyanosis a few hours after birth due to methemoglobinemia. This was thought to be related to the local maternal perineal infiltration of prilocaine during childbirth. Though rare, prilocaine is the most potent agent to induce methemoglobinemia compared to other local aneasthetics. After intravenous administration of methylene blue, both newborns fully recovered. CONCLUSION: Neonatal methemoglobinemia is a rare and potentially fatal complication of local anesthetics, particularly prilocaine, administered to the mother during childbirth. Midwives, obstetricians, gynecologists and pediatricians should be aware of this complication. The use of other local anesthetics, including lidocaine, should be considered.

Immediate local anesthetic reactions and diagnostic test results in pediatric patients.

BACKGROUND/OBJECTIVES: Adverse reactions to local anesthetics are relatively common, but proven IgE-mediated allergy is extremely rare. We aimed to determine the frequency of local anesthetic allergy in pediatric patients. PATIENTS AND METHODS: The medical records of 73 patients who presented to our clinic with a history of suspected allergic reaction to local anesthetics and underwent diagnostic testing between 2012 and 2020 were retrospectively analyzed. Diagnoses were based on case histories, skin tests, and subcutaneous challenge tests. RESULTS: A total of 75 test series were carried out on the 73 patients (43 boys; median [IQR] age 9.25 [7.26-14.25] years, range 3-17.8 years). The most commonly tested drugs were lidocaine (n = 38; 50.6%) and prilocaine (n = 15; 20%). Local anesthetic allergy was confirmed in one (1.3%) of the 73 patients by positive subcutaneous challenge test with mepivacaine. CONCLUSION: There are limited data in the current literature regarding local anesthetic allergies and diagnosis test results in pediatric patients. Proven local anesthetic allergy is less common than expected by society and physicians, and therefore diagnostic tests are needed for patients with no contra-indications such as severe or life-threatening reactions.

[Liposuction with consequences: what to consider when using prilocaine]. / Folgenreiche Liposuktion ­ was man im Umgang mit Prilocain beachten sollte.

Aetiologically, prilocaine-induced methaemoglobinaemia is a rare form of acquired methaemoglobinaemia, which occurs rarely in the first place. The following report highlights a potentially dangerous complication arising after application of prilocaine during liposuction.A young female visited the Accident and Emergency Department following a pre-syncopal fall. As a consequence of her fall, she experienced debilitating wrist pain and exhibited a laceration on her chin. She had undergone liposuction of the lower extremity as an outpatient approximately 12 hours earlier and received regional anaesthesia in the process. A large volume of an anaesthetic solution containing prilocaine had been injected into the tissue.The patient was normotensive and slightly tachycardic and had oxygen saturations of 90 % on room air. She was cyanotic and her lips were pale. Initial arterial blood gas analysis showed a methaemoglobin fraction, which was increased significantly to 10.9 %. Conventional radiography confirmed the presence of a minimally dislocated distal radius fracture. Following subsequent oxygen therapy over a four-hour period, the patient's methaemoglobin level dropped to 6 %, her lip cyanosis abated and her vital parameters stabilised. The laceration of her chin was sutured and her wrist immobilised in a split plaster brace. After a 12-hour hospital stay, the patient was discharged. At her six-week follow-up appointment, the fracture had healed and both the functional and cosmetic aspects of her chin wound were adequate. We hope that this report draws the attention of emergency care personnel to the possible diagnosis of prilocaine-induced methaemoglobinaemia after liposuction and encourages more general discussions around the use of prilocaine.

Comparing the Efficacy of a Compound Topical Anesthetic Versus Benzocaine: A Pilot Study.

To compare the effectiveness of a combination of 10% lidocaine, 10% prilocaine, and 4% tetracaine versus 20% benzocaine for use as a topical anesthetic agent prior to dental injections. A double-blind randomized prospective clinical trial was conducted with 26 participants receiving a topical anesthetic of 20% benzocaine (control) and 26 participants receiving a compound topical anesthetic mixture of 10% lidocaine, 10% prilocaine, and 4% tetracaine (experimental) prior to a maxillary infiltration injection. The procedure was conducted by 1 operator with the Wand® injection system. Pain was assessed directly with visual analog scale (VAS) scores and indirectly by measuring changes in heart rate at 4 different time points. Complications associated with the application of the topical anesthetics were also assessed. The experimental group had a significantly higher mean VAS score of 19.5 ± 19.7 mm versus 14.2 ± 14.6 mm for the control group (p < .001). No significant differences in heart rate at any of the 4 measured time points compared with baseline were noted for either group. The experimental group had a significantly higher incidence of complications, including tissue sloughing, when compared with the control group (p < .001). Participants in the control group reported significantly lower VAS scores than those in the experimental group. Both types of topical anesthetic showed similar impacts on alterations to heart rate. No benefits were seen with the use of 10% lidocaine, 10% prilocaine, and 4% tetracaine as a topical anesthetic prior to a maxillary infiltration of local anesthetic when compared with 20% benzocaine.

Topical anesthetics for pediatric laser treatment.

Topical anesthetic agent causes transient insensibility to pain in a limited area of skin, and provides effective anesthesia in a short onset time, short duration, with seldom local or systemic side effects on intact skin and is simple to use. Topical formulations may offer significant benefits for prevention of procedural pain. Currently, they are considered to be the most effective anesthesia for laser treatments. Unfortunately, there is no standard anesthetic technique for this procedure. Lasers are being widely used in numerous dermatological and esthetics treatments in childhood. The advancement of new knowledge in laser technology have contributed to the development of new lasers that are commonly used in a pediatric population, such as Pulsed Dye, Carbon-dioxide and Nd:YAG laser. The most commonly used topical anesthetics in young patients for minimally or moderately painful laser cutaneous procedures are Lidocaine, Prilocaine, Tetracaine gel and combinations thereof.

Transient Methemoglobinemia in three Neonates due to Maternal Pudendal Anesthesia.

Methemoglobin (MetHb) is a form of hemoglobin which contains iron in ferric state. The delivery of oxygen to tissues is impaired and cellular hypoxia develops with an increase in MetHb levels. Methemoglobinemia is a rare but potentially lethal complication of local anesthetics. In this clinical brief, three cases of transient neonatal methemoglobinemia, caused by maternal pudendal anesthesia with prilocaine, are reported.

A rare cause of cyanosis and hypoxia that should not be forgotten after implantable cardioverter defibrillator implantation.

Transvenous pacemaker or implantable cardioverter defibrillator (ICD) implantation procedures are usually performed under local anesthetic, and prilocaine is the most common agent to be used. The data regarding methemoglobinemia after cardiac device implantation are scarce. Thus, presently described is the case of a 47-year-old female patient with arrhythmogenic right ventricular cardiomyopathy/dysplasia who underwent ICD implantation for secondary prophylaxis and developed cyanosis as a result of prilocaine-associated methemoglobinemia. Prilocaine was administered during the procedure. To our knowledge, this is the second case in the literature presenting methemoglobinemia due to local anesthetic after transvenous cardiac device implantation.

Topic anaesthesia with a eutectic mixture of lidocaine/prilocaine cream after elective caesarean section: a randomised, placebo-controlled trial.

PURPOSE: Aim of the study was to investigate the topical application of a eutectic mixture of lidocaine/prilocaine (EMLA®) cream after caesarean section (CS) and its effect on postoperative pain, time to mobilisation, and time to discharge. MATERIALS AND METHODS: A total of 189 pregnant women were enrolled; full data sets were available for 139 of them, who were prospectively randomised to receive either placebo (control group) or EMLA® cream (study group) on the CS lesion directly as well as 24 h after surgery. Postoperative pain was assessed 24 and 48 h after surgery using the short form of the McGill Pain Questionnaire (SF-MPQ). Additional analgesic pain medication on demand was assessed in both groups. RESULTS: A total of 62 women were allocated randomly to the study and 77 patients to the control group before primary CS. There were no statistically significant differences regarding demographic and surgical parameters comparing both collectives. In addition, the postoperative total pain scores after 24 h [McGill total: 38.5 (0-102) vs. 50 (0-120) p = 0.0889] as well as after 48 h [24 (0-79) vs. 30.5 (0-92); p = 0.1455] showed no significant differences. Furthermore, time to mobilisation (hours) [9.68 (2.18-51.38) vs. 9.47 (4.18-41.77); p = 0.5919] and time to discharge (hours) [98.6 (54.08-170.15) vs. 98.2 (43.45-195.87); p = 0.5331] were comparable. CONCLUSION: The postoperative application of EMLA® cream after CS did not reduce postoperative pain or time to mobilisation or discharge, so that its use in this context has to be seen critically.