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)

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.

Quantification of systemic o-toluidine after intrathecal administration of hyperbaric prilocaine in humans: a prospective cohort study.

Hyperbaric 2% prilocaine is increasingly used for spinal anesthesia. It is the only local anesthetic metabolized to o-toluidine, a human bladder carcinogen. Increase of o-toluidine hemoglobin adducts, a marker of o-toluidine ability to modify the DNA structure, was described following subcutaneous injection. In this prospective cohort study we aimed to assess and quantify o-toluidine hemoglobin adducts and urinary o-toluidine after a single intrathecal dose of hyperbaric prilocaine.10 patients undergoing surgery received 50 mg of hyperbaric prilocaine intrathecally. Blood and urine samples were collected before injection and up to 24 h later (Hospital Braine l'Alleud-Waterloo, Braine l'Alleud, Belgium). Urinary o-toluidine and o-toluidine hemoglobin adducts were measured by tandem mass-spectrometry after gas-chromatographic separation (Institute of the Ruhr-Universität, Bochum Germany). The trial was registered to ClinicalTrials.gov (NCT03642301; 22-08-2018)Intrathecal administration of 50 mg of hyperbaric prilocaine leads to a significant increase of o-toluidine hemoglobin adducts (0.1 ± 0.02-11.9 ± 1.9 ng/g Hb after 24 h, p = 0.001). Peak of urinary o-toluidine was observed after 8 h (0.1 ± 0.1-460.5 ± 352.8 µg/L, p = 0.001) and declined to 98 ± 66.8 µg/L after 24 h (mean ± SD)Single intrathecal administration of hyperbaric prilocaine leads to a systemic burden with o-toluidine and o-toluidine hemoglobin adducts. O-toluidine-induced modifications of DNA should be examined and intrathecal hyperbaric prilocaine should not be proposed to patients chronically exposed to o-toluidine.Clinical trial number and registry URL NCT03642301.

Effectiveness of lidocaine/prilocaine cream on cardiovascular reactions from endotracheal intubation and cough events during recovery period of older patients under general anesthesia: prospective, randomized placebo-controlled study.

BACKGROUND: Endotracheal intubation is known to pose significant physiological, pharmacokinetic, and dynamic changes and postoperative respiratory complications in patients under general anesthesia. METHOD: An RCT trial was organized by the Third Affiliated Hospital at Sun Yat-sen University, China. Patients were eligible for inclusion in the trial if they were over 60 years old and had upper-abdominal surgery during the induction of anesthesia and had enrolled in endotracheal intubations. The primary end point included cardiovascular reactions during the induction of anesthesia and endotracheal intubations and cough events during the recovery period. In the test group, 2 g of lidocaine/prilocaine cream (and in the control group, 2 g of Vaseline) were laid over the surface of the tracheal tube cuff. RESULTS: The systolic blood pressure (F value = 62.271, p < 0.001), diastolic blood pressure (F value = 150.875, p < 0.001), and heart rate (F value = 75.627, p < 0.001) of the test group were significantly lower than the control group. Cough events during the recovery period in the test group were better (spontaneous cough, χ2 value = 10.591, p < 0.001; induced cough, χ2 value =10.806, p < 0.001). CONCLUSION: In older patients, coughing and cardiovascular reactions under anesthesia and endotracheal intubations were reduced, as a result of using lidocaine/prilocaine cream on the surface of the tracheal tube cuff. TRIAL REGISTRATION: International Clinical Trials Network NCT02017392, 2013-12-16.

Topical lidocaine-prilocaine cream versus rectal meloxicam suppository for relief of post-episiotomy pain in primigravidae: A randomized clinical trial.

OBJECTIVES: To compare the analgesic effect of topical lidocaine-prilocaine (LP) cream and rectal meloxicam suppository on the post-episiotomy pain in primigravidae. PATIENTS AND METHODS: A randomized open-label clinical trial included primigravidae delivered vaginally with episiotomy. Eligible women were recruited and randomized to topical LP cream on the episiotomy line or rectal meloxicam suppository 15 mg. The intensity of the perineal pain was assessed using a visual analog scale (VAS) immediately, at 6, 12 h and after 5 days post-episiotomy. RESULTS: One hundred ninety women were enrolled (n = 95 in each arm). No difference between both groups in the VAS scores immediately (mean ± SD: 8.54 ± 1.35 vs. 8.33 ± 1.50, p = 0.419) and 6 h after episiotomy (p = 0.859). However, women in the LP arm were more likely to report lower VAS scores at 12 h and 5 days post-episiotomy (mean ± SD: 1.20 ± 0.50 vs. 5.65 ± 1.65, p = 0.0001; 1.19 ± 0.49 vs. 2.64 ± 1.73, p < 0.001; respectively). CONCLUSION: Application of topical LP cream after repair of episiotomy in primigravidae seems to substantially alleviate the induced pain with subsequent less need for additional analgesia and more patients' satisfaction.

Sustained delivery of prilocaine and lidocaine using depot microemulsion system: in vitro, ex vivo and in vivo animal studies.

Topical drug delivery for local anesthetics has been an interesting area of research for formulators considering the resistance and barrier properties of skin and high clearance rate of drugs like prilocaine and lidocaine (duration of action < 2.5 h). In this study, efforts have been made to sustain the release of prilocaine and lidocaine by using depot microemulsion system. Drug loaded microemulsions were formulated using Capmul MCM, Pluronic F127, polyethylene glycol 200 (PEG 200) and water from pseudo-ternary diagrams. The Smix at 1:4 ratio showed larger microemulsion area in comparison to 1:2 ratio. The ex-vivo studies indicate sustained release of prilocaine and lidocaine from the microemulsion up to 8 h, in comparison to 4 h with ointments. Skin irritation study on rabbits confirmed the safety of drug loaded microemulsions for local drug delivery. The improved ex vivo data is reflected in the in vivo studies, were radiant heat tail-flick test and sciatic nerve model showed prolong duration of action for both prilocaine and lidocaine microemulsions in comparison to ointment. The in vitro and in vivo efficacy of prilocaine and lidocaine was non-significant. The improved efficacy was due to high penetration of microemulsion and depot effect due to local precipitation (destabilization of microemulsion) of drug in the skin layer. The sustained local anesthetic effect is highly desirable for the treatment of skin irritation due to skin burns and pre- and post-operative pain.

Liposomal anesthetic gel for pain control during periodontal therapy in adults: a placebo-controlled RCT.

INTRODUCTION: Periodontal therapy usually requires local anesthesia. If effective, a non-invasive, liposomal anesthetic gel could increase the levels of acceptance of patients in relation to periodontal therapy. OBJECTIVE: This study investigated the efficacy of liposomal anesthetic gel for pain control during periodontal therapy. METHODOLOGY: Forty volunteers with moderate to severe chronic periodontitis were recruited, of which at least three sextants required periodontal therapy. At least one of the selected teeth had one site with a probing depth of ≥4 mm. The volunteers received the following three gels: a placebo, lidocaine/prilocaine (Oraqix®), or a liposomal lidocaine/prilocaine, which were applied to different sextants. Pain frequency was registered during treatment and the volunteers received a digital counter to register any painful or uncomfortable experiences. At the end of each session, the volunteers indicated their pain intensity using rating scales (NRS-101 and VRS-4). The volunteers had their hemodynamic parameters measured by a non-invasive digital monitor. RESULTS: Pain frequency/intensity did not show statistical difference between intervention groups. The tested gels did not interfere with the hemodynamic indices. Dental anxiety, suppuration and probing depth could influence pain during periodontal therapy. CONCLUSION: Our results suggest limited indications for the use of non-invasive anesthesia when used for scaling and root planing. Intra-pocket anesthetic gel could be a good option for anxious patients, or those who have a fear of needles.

Liposomal anesthetic gel for pain control during periodontal therapy in adults: a placebo-controlled RCT

Abstract Periodontal therapy usually requires local anesthesia. If effective, a non-invasive, liposomal anesthetic gel could increase the levels of acceptance of patients in relation to periodontal therapy. Objective: This study investigated the efficacy of liposomal anesthetic gel for pain control during periodontal therapy. Methodology: Forty volunteers with moderate to severe chronic periodontitis were recruited, of which at least three sextants required periodontal therapy. At least one of the selected teeth had one site with a probing depth of ≥4 mm. The volunteers received the following three gels: a placebo, lidocaine/prilocaine (Oraqix®), or a liposomal lidocaine/prilocaine, which were applied to different sextants. Pain frequency was registered during treatment and the volunteers received a digital counter to register any painful or uncomfortable experiences. At the end of each session, the volunteers indicated their pain intensity using rating scales (NRS-101 and VRS-4). The volunteers had their hemodynamic parameters measured by a non-invasive digital monitor. Results: Pain frequency/intensity did not show statistical difference between intervention groups. The tested gels did not interfere with the hemodynamic indices. Dental anxiety, suppuration and probing depth could influence pain during periodontal therapy. Conclusion: Our results suggest limited indications for the use of non-invasive anesthesia when used for scaling and root planing. Intra-pocket anesthetic gel could be a good option for anxious patients, or those who have a fear of needles.

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.

[The use of neurostimulation with ultrasound-guided brachial plexus block: Does it increase success?] / Ultrasonografi esliginde brakial pleksus blogunda nörostimülasyonun kullanilmasi: Basariyi arttiriyor mu?

OBJECTIVES: Infraclavicular brachial plexus blockade is an anesthetic technique used for operations of the hand, wrist, and elbow. Ultrasound (US)-guidance is a recent addition to the surgical technique. The aim of this study was to compare the use of US alone and US with a nerve stimulator in an infraclavicular brachial plexus blockade in terms of the performance time, successful blockade rate, and the quality of sensory block. METHODS: A total of 40 patients who were scheduled for hand, wrist, or elbow surgery were included in the study. The patients were divided into 2 groups: US and USSS (ultrasonography + neurostimulation). A dose of 40 mL, containing 100 mg bupivacaine and 200 mg prilocaine was administered with the guidance of US or USSS in the infraclavicular regions. Performance time was measured and recorded. Motor and sensory blockade was assessed within 30 minutes after the block. RESULTS: The mean performance time for Group US and Group USSS was 6.68+-0.75 and 6.9+-1.02 minutes, respectively, without significant difference between groups (p>0.05, p=0.62, respectively). A complete blockade was seen in 16/20 patients in Group US and in 14/20 patients in Group USSS in 20 minutes, which did not yield a significant difference. During the surgery, local anesthetic infiltration was required in 2/20 patients in Group US and in 1/20 patients in Group USSS. CONCLUSION: The results of this study revealed no additional benefit to USSS in block success in comparison with US alone. Considering the feeling of discomfort and pain due to nerve stimulation, it was concluded that use of US alone may be preferred to combination use.

Is prilocaine safe and potent enough for use in the oral surgery of medically compromised patients.

OBJECTIVES: To investigate the potency and speed of action of 2% lidocaine and 3% prilocaine for upper teeth extractions. METHODS: This prospective clinical study was conducted from November 2016 to May 2017. Ninety-six patients, aged between 16 to 70 years old were recruited in this study. Two regimens were randomly administered over one visit. Patients, treatment group I, received 2% lidocaine with 1:00.000 adrenaline. Patients treatment group II received prilocaine 3% and felypressin 0.03 I.U. per ml. The efficacy of pulp anesthesia was determined by electronic pulp testing. At any point of trial (10 minutes), the anesthetized tooth becomes unresponsive for maximal pulp stimulation (64 reading), the extraction was carried out.  Results: There were no significant differences in the mean onset time of pulpal anesthesia and extraction between the prilocaine and lidocaine buccal infiltration groups (p=0.28). However, clinically, the patients in prilocaine group recorded faster onset time of anesthesia and teeth extraction than those in lidocaine group. Conclusion: Prilocaine has a better clinical performance in terms of providing rapid dental anesthesia and earlier teeth extraction than lidocaine but the differences were not significant. Prilocaine with felypressin could be a good choice for patients who have contraindication to the use of lidocaine with adrenaline.

Hybrid Hydrogel Composed of Polymeric Nanocapsules Co-Loading Lidocaine and Prilocaine for Topical Intraoral Anesthesia.

This study reports the development of nanostructured hydrogels for the sustained release of the eutectic mixture of lidocaine and prilocaine (both at 2.5%) for intraoral topical use. The local anesthetics, free or encapsulated in poly(ε-caprolactone) nanocapsules, were incorporated into CARBOPOL hydrogel. The nanoparticle suspensions were characterized in vitro in terms of particle size, polydispersity, and surface charge, using dynamic light scattering measurements. The nanoparticle concentrations were determined by nanoparticle tracking analysis. Evaluation was made of physicochemical stability, structural features, encapsulation efficiency, and in vitro release kinetics. The CARBOPOL hydrogels were submitted to rheological, accelerated stability, and in vitro release tests, as well as determination of mechanical and mucoadhesive properties, in vitro cytotoxicity towards FGH and HaCaT cells, and in vitro permeation across buccal and palatal mucosa. Anesthetic efficacy was evaluated using Wistar rats. Nanocapsules were successfully developed that presented desirable physicochemical properties and a sustained release profile. The hydrogel formulations were stable for up to 6 months under critical conditions and exhibited non-Newtonian pseudoplastic flows, satisfactory mucoadhesive strength, non-cytotoxicity, and slow permeation across oral mucosa. In vivo assays revealed higher anesthetic efficacy in tail-flick tests, compared to a commercially available product. In conclusion, the proposed hydrogel has potential for provision of effective and longer-lasting superficial anesthesia at oral mucosa during medical and dental procedures. These results open perspectives for future clinical trials.

The clinical efficacy of EMLA cream for intravenous catheter placement in client-owned dogs.

OBJECTIVE: To assess the reaction of client-owned dogs to intravenous (IV) catheter placement after applying a local anaesthetic (EMLA) or placebo cream for either 30 or 60 minutes. STUDY DESIGN: Prospective, randomized, blinded, placebo-controlled, clinical trial. ANIMALS: A total of 202 client-owned dogs of various breeds. METHODS: With owner consent, dogs were randomly allocated to one of four treatment groups: EMLA 60 minutes, EMLA 30 minutes, Placebo 60 minutes and Placebo 30 minutes. After the cream was applied for the allocated time, an IV catheter was placed and the behavioural reaction of the dog was scored. The reaction score was analysed using a Kruskal-Wallis test followed by Mann-Whitney U tests of the multiple pairwise comparisons, with Bonferroni correction. RESULTS: A large number of dogs, even in the placebo groups, did not react to IV catheter placement. However, the Kruskal-Wallis test showed an overall difference between treatment groups (χ2 = 11.029, df = 3, p = 0.012). The pairwise comparisons showed a lower overall reaction score in the EMLA 60 group than in the EMLA 30 and Placebo 60 groups (adjusted p = 0.018 and adjusted p = 0.044, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: This study shows that EMLA cream applied for 60 minutes reduces the behavioural reaction of dogs to IV catheter placement; therefore, this intervention can be advocated for routine use in veterinary medicine to enhance the welfare of dogs undergoing IV catheter placement.

Effects of local anesthetics on wound healing / Efeitos dos anestésicos locais na cicatrização de feridas

Abstract Introduction Local anesthetic infiltration is used widely for post-operative analgesia in many situations. However the effects of local anesthetics on wound healing are not demonstrated clearly. This study planned to evaluate the effects of lidocaine, prilocaine, bupivacaine and levobupivacaine on wound healing, primarily on wound tensile strength and on collagen ultrastructure. Methods This study was conducted on male Sprague Dawley rats. On days 0, 8th, 15th, and 21st, all animals were weighed and received a preincisional subcutaneous infiltration of 3 mL of a solution according the group. Control saline (C), lidocaine (L) 7 mg.kg-1, prilocaine (P) 2 mg.kg-1, bupivacaine (B) 2 mg.kg-1 and levobupivacaine (LVB) 2.5 mg.kg-1. The infiltrations were done at the back region 1.5 cm where incision would be performed at the upper, middle and lower part along the midline, under general anesthesia. Wound tensile strengths were measured after 0.7 cm × 2 cm of cutaneous and subcutaneous tissue samples were obtained vertical to incision from infiltrated regions. Tissue samples were also obtained for electron microscopic examination. Evaluations were on the 8th, 15th and 21st days after infiltration. Results There was no difference between groups in the weights of the rats at the 0th, 8th, 15th and 21st days. The collagen maturation was no statistically different between groups at the 8th and 15th days. The maturation scores of the B and L groups at the 21st day was significantly lower than the Group C (1.40, 1.64 and 3.56; respectively). The wound tensile strength was no statistically different between groups at the 8th and 15th days but at the 21st day the Groups B and LVB had significantly lower value than Group C (5.42, 5.54 and 6.75; respectively). Conclusion Lidocaine and prilocaine do not affect wound healing and, bupivacaine and levobupivacaine affect negatively especially at the late period.

Resumo Introdução A infiltração de anestésico local é amplamente usada para analgesia pós-operatória em muitas situações. No entanto, os efeitos dos anestésicos locais na cicatrização de feridas não foram demonstrados claramente. Neste estudo planejamos avaliar os efeitos de lidocaína, prilocaína, bupivacaína e levobupivacaína sobre a cicatrização de feridas, principalmente sobre a força tênsil da ferida e a ultraestrutura do colágeno. Métodos Este estudo foi feito em ratos machos da linhagem Sprague Dawley. Nos dias 0, 8, 15 e 21, todos os animais foram pesados e receberam uma infiltração subcutânea pré-incisional de 3 mL de uma solução, de acordo com a designação dos grupos: Grupo C recebeu salina (controle); Grupo L recebeu lidocaína (7 mg.kg-1); Grupo P recebeu prilocaína (2 mg.kg-1); Grupo B recebeu bupivacaína (2 mg.kg-1); Grupo LVB recebeu levobupivacaína (2,5 mg.kg-1). As infiltrações foram feitas na região posterior a 1,5 cm de onde a incisão seria feita na parte superior, média e inferior ao longo da linha média, sob anestesia geral. A força tênsil da ferida foi medida após amostras de 0,7 × 2 cm de tecido cutâneo e subcutâneo serem obtidas das regiões infiltradas, verticalmente à incisão. Amostras de tecido também foram obtidas para exame microscópico eletrônico. As avaliações foram feitas nos dias 8, 15 e 21 após a infiltração. Resultados Não houve diferença entre os grupos em relação ao peso dos ratos nos dias 0, 8, 15 e 21. A maturação do colágeno não foi estatisticamente diferente entre os grupos nos dias 8 e 15. Os escores de maturação dos grupos B e L no dia 21 foram significativamente inferiores aos do Grupo C (1,40, 1,64 e 3,56, respectivamente). A força tênsil da ferida não foi estatisticamente diferente entre os grupos nos dias 8 e 15, mas no dia 21 os grupos B e LVB apresentaram valores significativamente menores que o Grupo C (5,42, 5,54 e 6,75, respectivamente). Conclusão Lidocaína e prilocaína não afetam a cicatrização de feridas, enquanto bupivacaína e levobupivacaína afetam negativamente, especialmente no período tardio.

Improving the therapeutic efficacy of prilocaine by PLGA microparticles: Preparation, characterization and in vivo evaluation.

A delivery system based on poly(lactic-co-glycolic acid) polymer (PLGA) microparticles has been developed for parenteral administration of the local anesthetic prilocaine in its free base form. Both drug-free and drug-loaded microparticles, prepared by a double-emulsion-evaporation method, were characterized for mean size by Laser Diffraction Analysis, while their morphology was investigated by scanning electron microscopy. The preparation technique allowed obtainment of homogeneous microparticles of about 25 µm diameter, suitable for subcutaneous administration. The encapsulation efficiency, determined by both direct and indirect methods, was around 36-38%. Differential Scanning Calorimetry was used to characterize the solid state of the raw materials, assess drug-polymer compatibility and miscibility and highlight possible modifications of the components induced by the preparation method. In vitro release studies showed a sustained release profile, with about 80% of drug released after the first 24 h. The anesthetic effect of the formulation was evaluated in vivo on rats, according to the test of cutaneous trunci muscle reflex. Administration of prilocaine base as PLGA microparticles allowed to significantly enhance both extent (60% AUC increase) and duration (100% increase) of the anesthetic effect in the animal model, in comparison with the equivalent dose of prilocaine hydrochloride aqueous solution.

A Randomized Clinical Trial Evaluating Rubber Dam Clamp Pain Reduction from a New Topical Liposomal Anesthetic Gel.

PURPOSE: Discomfort during rubber dam clamp often occurs in pediatric dentistry. The purpose of this randomized, triple-blind, clinical trial was to evaluate the effect of pain reduction using a new topical liposomal thermo-sensitive gel (TLTG) or a placebo gel during rubber dam clamp isolation for sealants in children. METHODS: Eighty-one children (eight to 12 years old) had LTSG or the placebo gel with random assignment placed around the gingival tissue of their permanent mandibular first molars. A clamp was placed after two minutes on the teeth, and intensity of pain was registered using a Wong-Baker FACES scale and an 11-point numerical scale. The data were evaluated using McNemar's test and Wilcoxon signed rank test. RESULTS: The odds ratio for pain (OR equals 0.7; 95 percent confidence interval equals 0.3 to 1.8) was not statistically significant (P=0.52). However, there was a small difference in the pain intensity between liposomal and placebo groups for both scales (P<0.05). CONCLUSION: The liposomal thermo-sensitive anesthetic gel may reduce, to a small extent, the pain intensity in children submitted to rubber dam isolation before resin sealant placement.

Efficacy of anesthetic rice nanogel on pain reduction in human oral cavity.

The aim of this study was to determine the efficacy of two local anesthetic rice nanogels (RNG) on pain reduction from needle insertion in oral cavity. Nanogel base was prepared using modified rice as gelling agent. The average particle size of RNG determined by photon correlation spectrophotometer was 485 ± 70 nm. Lidocaine hydrochloride (LH) and prilocaine hydrochloride (PH) were incorporated into RNG to obtain anesthetic RNG containing 5% and 20% LH or PH. Clinical efficacy test of each gel was performed in oral cavity of 100 healthy volunteers (25-60 years old). Evaluation was done by recording different pain measurements after inserting a needle into buccal mucosa after applying 5% and 20% anesthetic RNG. RNG base (placebo) and commercial anesthetic gels were used as negative and positive controls, respectively. It was found that the pain level in the negative control group was significantly higher than those of the anesthetic groups. Moreover, the pain level of the anesthetic RNG groups were lower than that of the commercial groups, especially in 20% anesthetic groups. For patient's satisfaction, most of the volunteers were appreciated with the anesthetic RNG as well as the commercial gels. They preferred to use high drug content RNG more than those with low drug content or placebo. It can be concluded that the anesthetic RNG has potential clinical efficacy in pain reduction during needle insertion in oral cavity.

Anesthetic Efficacy of a Combination of 4% Prilocaine/2% Lidocaine with Epinephrine for the Inferior Alveolar Nerve Block: A Prospective, Randomized, Double-blind Study.

INTRODUCTION: Prilocaine plain has a high pH and concentration (4%), which could decrease the pain of injection and increase success. The purpose of this study was to compare pain associated with anesthetic solution deposition and the degree of pulpal anesthesia obtained with the combination of prilocaine and lidocaine versus a lidocaine and lidocaine combination when used for inferior alveolar nerve blocks (IANBs). METHODS: One hundred eighteen asymptomatic subjects were randomly given a combination of 1 cartridge of 4% prilocaine plain plus 1 cartridge of 2% lidocaine with 1:100,000 epinephrine or a combination of 2 cartridges of 2% lidocaine with 1:100,000 epinephrine for the IANB at 2 separate appointments. Subjects rated the pain associated with anesthetic solution deposition of injection. Mandibular teeth were tested with an electric pulp tester every 4 minutes for 57 minutes. Anesthesia was considered successful when 2 consecutive 80 readings were obtained within 17 minutes and the 80 reading was continuously sustained for 57 minutes. Comparisons for anesthetic success were analyzed using the exact McNemar test, and pain ratings associated with anesthetic solution deposition were analyzed using multiple Wilcoxon matched pairs signed rank tests; both were adjusted using the step-down Bonferroni method of Holm. RESULTS: Four percent prilocaine plain was significantly less painful upon anesthetic solution deposition. Pulpal anesthetic success was not significantly different between the 2 combinations. CONCLUSIONS: The combination of 4% prilocaine plain plus 2% lidocaine with 1:100,000 epinephrine did not increase pulpal anesthetic success for IANBs compared with a combination of 2 cartridges of 2% lidocaine with 1:100,000 epinephrine. Pain associated with anesthetic solution deposition from the first cartridge of 4% prilocaine plain was significantly less when compared with the first cartridge of 2% lidocaine with 1:100,000 epinephrine.

Effects of transdermal lidocaine or lidocaine with prilocaine or tetracaine on mechanical superficial sensation and nociceptive thermal thresholds in horses.

OBJECTIVE: To evaluate the transdermal local anaesthetic effect of lidocaine or lidocaine combined with prilocaine or tetracaine in horses. STUDY DESIGN: Experimental, randomized study. ANIMALS: A total of five healthy adult warmblood horses. METHODS: Horses were clipped bilaterally at the withers, cranial saddle area and caudal saddle area. Baseline measurements for mechanical superficial sensation via von Frey filaments and nociceptive thermal thresholds were performed. A 5% lidocaine patch (12 hour exposure, treatment L), a lidocaine/prilocaine cream (each 2.5%, treatment LP) and a lidocaine/tetracaine cream (each 7%, treatment LT) were applied (both 2 hour exposure). The same product was applied at the same location bilaterally, but on the right side an epidermal micro-perforation (dermaroller, 1200 needles) was performed prior to application. A total of five more measurements were performed at each location, immediately at the end of exposure time followed by hourly measurements. Thermal thresholds normalized to thermal excursion were analysed. One- or two-way anova and the Wilcoxon signed-rank test were used for statistical analysis with p<0.05 considered significant. RESULTS: Epidermal micro-perforation had no enhancing effect. Treatments L, LP, and LT resulted in increased thermal excursion (%) immediately (84.7±12.9; 100.0±0.0; 100.0±0.0) and 1 hour (81.7±66; 86.0±17.7; 87.7±14.4) after the removal of the respective product compared to baseline (66.1±9.3; 69.9±8.3; 76.5±7.8). Superficial mechanical sensation was decreased by the lidocaine-and-tetracaine cream at all time points, and by the lidocaine patch and lidocaine-and-prilocaine cream for three measurements. CONCLUSIONS AND CLINICAL RELEVANCE: Eutectic mixtures of lidocaine with either prilocaine or tetracaine led to a reduction in thermal nociception and mechanical sensation for up to 2 hours.