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Benzocaine is well-known for its role as an anesthetic agent and largely used in oral ulcers, ear pain and dental complications. Along with lidocaine and other local anesthetics, benzocaine has marked it as an anesthetic agent in surgical procedures and as Na+ channels blocker, as well. Analogues of benzocaine have been found to possess biological potentials including antibacterial, antifungal and anti-cancer. Some derivatives were found to have conspicuous action against tuberculosis. The current review focuses to explore the century-long potential of the molecule and its analogs that have appeared in the literature. Furthermore, highlighting the biological potential of benzocaine and its analogues shall open-up new dimensions of future research to design more potent analogues., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The aim of this multi-centre, randomised, double-blind, placebo-controlled trial was to compare the efficacy and safety of the fixed combination of 0.5 mg tyrothricin, 1.0 mg benzalkonium chloride, and 1.5 mg benzocaine (study drug marketed as Dorithricin ® ) in repeat dosing for 3 days to match placebo lozenges in the treatment of acute pharyngitis in adults., Methods: Patients (pts, aged ≥18 years) with acute pharyngitis, ie, non-streptococcal sore throat and moderate-to-severe pain (intensity NRS ≥ 7; VAS ≥ 50) were assigned to study drug (n = 160) or matching placebo (n = 161). Efficacy was assessed by investigator for 2 hours post initial dose (p.i.d.), and 3 days later (Visit 2). Primary efficacy endpoint was the complete resolution of throat pain and difficulty in swallowing at Visit 2 (3 days p.i.d.). Safety and local tolerability were also assessed., Results: Seventy-two hours (p.i.d.), complete resolution of throat pain and difficulty in swallowing were achieved by 44.6% patients on study drug compared with 27.2% patients on placebo (difference 17.4% (CI [5.8%; 29.7%]; 64% improvement [GEE, P = 0.0022]). Until 2 hours p.i.d., reduction in symptoms was better with study drug (P < 0.005). Treatment satisfaction was higher with study drug (patients'/investigators' assessment (78.9%/78.9% vs 55.0%/55.6% for placebo) and was well tolerated, overall safety profile was comparable to placebo., Conclusion: The strength of this randomised controlled trial lies in the endpoint of complete remission after 3 days p.i.d., especially in the light of other trials addressing acute pharyngitis. The results of this study show a significant benefit of the study drug over placebo in the treatment of acute pharyngitis. Local treatment with the fixed combination (0.5 mg tyrothricin, 1.0 mg benzalkonium chloride, and 1.5 mg benzocaine) provides a rapid analgesic effect and is effective in relieving both severe throat pain as well as difficulty in swallowing associated with acute pharyngitis leading to a 64% improved complete remission within 72 hours. The triple active combination is a suitable treatment option for patients in the self-management of acute pharyngitis and sore throat., Clinical Trial Registration: ClinicalTrials.gov, NCT03323528., (© 2018 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.)

Background: Ear wax (cerumen) is a normal bodily secretion that can become a problem when it obstructs the ear canal. Symptoms attributed to wax (such as deafness and pain) are among the commonest reasons for patients to present to primary care with ear trouble.Wax is part of the ear's self-cleaning mechanism and is usually naturally expelled from the ear canal without causing problems. When this mechanism fails, wax is retained in the canal and may become impacted; interventions to encourage its removal may then be needed. Application of ear drops is one of these methods. Liquids used to remove and soften wax are of several kinds: oil-based compounds (e.g. olive or almond oil); water-based compounds (e.g. sodium bicarbonate or water itself); a combination of the above or non-water, non-oil-based solutions, such as carbamide peroxide (a hydrogen peroxide-urea compound) and glycerol., Objectives: To assess the effects of ear drops (or sprays) to remove or aid the removal of ear wax in adults and children., Search Methods: We searched the Cochrane ENT Trials Register; Cochrane Register of Studies; PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 23 March 2018., Selection Criteria: Randomised controlled trials (RCTs) in which a 'cerumenolytic' was compared with no treatment, water or saline, an alternative liquid treatment (oil or almond oil) or another 'cerumenolytic' in adults or children with obstructing or impacted ear wax., Data Collection and Analysis: We used the standard methodological procedures expected by Cochrane. The primary outcomes were 1) the proportion of patients (or ears) with complete clearance of ear wax and 2) adverse effects (discomfort, irritation or pain). Secondary outcomes were: extent of wax clearance; proportion of people (or ears) with relief of symptoms due to wax; proportion of people (or ears) requiring further intervention to remove wax; success of mechanical removal of residual wax following treatment; any other adverse effects recorded and cost. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics., Main Results: We included 10 studies, with 623 participants (900 ears). Interventions included: oil-based treatments (triethanolamine polypeptide, almond oil, benzocaine, chlorobutanol), water-based treatments (docusate sodium, carbamide peroxide, phenazone, choline salicylate, urea peroxide, potassium carbonate), other active comparators (e.g. saline or water alone) and no treatment. Nine of the studies were more than 15 years old.The overall risk of bias across the 10 included studies was low or unclear., Primary Outcome: proportion of patients (or ears) with complete clearance of ear waxSix studies (360 participants; 491 ears) contributed quantitative data and were included in our meta-analyses.Active treatment versus no treatmentOnly one study addressed this comparison. The proportion of ears with complete clearance of ear wax was higher in the active treatment group (22%) compared with the no treatment group (5%) after five days of treatment (risk ratio (RR) 4.09, 95% confidence interval (CI) 1.00 to 16.80); one study; 117 ears; NNTB = 8) (low-quality evidence).Active treatment versus water or salineWe found no evidence of a difference in the proportion of patients (or ears) with complete clearance of ear wax when the active treatment group was compared to the water or saline group (RR 1.47, 95% CI 0.79 to 2.75; three studies; 213 participants; 257 ears) (low-quality evidence). Two studies applied drops for five days, but one study only applied the drops for 15 minutes. When we excluded this study in a sensitivity analysis it did not change the result.Water or saline versus no treatmentThis comparison was only addressed in the single study cited above (active versus no treatment) and there was no evidence of a difference in the proportion of ears with complete wax clearance when comparing water or saline with no treatment after five days of treatment (RR 4.00, 95% CI 0.91 to 17.62; one study; 76 ears) (low-quality evidence).Active treatment A versus active treatment BSeveral single studies evaluated 'head-to-head' comparisons between two active treatments. We found no evidence to show that one was superior to any other.Subgroup analysis of oil-based active treatments versus non-oil based active treatmentsWe found no evidence of a difference in this outcome when oil-based treatments were compared with non-oil-based active treatments., Primary Outcome: adverse effects: discomfort, irritation or painOnly seven studies planned to measure and did report this outcome. Only two (141 participants;176 ears) provided useable data. There was no evidence of a significant difference in the number of adverse effects between the types of ear drops in these two studies. We summarised the remaining five studies narratively. All events were mild and reported in fewer than 30 participants across the seven studies (low-quality evidence).Secondary outcomesThree studies reported 'other' adverse effects (how many studies planned to report these is unclear). The available information was limited and included occasional reports of dizziness, unpleasant smell, tinnitus and hearing loss. No significant differences between groups were reported. There were no emergencies or serious adverse effects reported in any of the 10 studies.There was very limited or no information available on our remaining secondary outcomes., Authors' Conclusions: Although a number of studies aimed to evaluate whether or not one type of cerumenolytic is more effective than another, there is no high-quality evidence to allow a firm conclusion to be drawn and the answer remains uncertain.A single study suggests that applying ear drops for five days may result in a greater likelihood of complete wax clearance than no treatment at all. However, we cannot conclude whether one type of active treatment is more effective than another and there was no evidence of a difference in efficacy between oil-based and water-based active treatments.There is no evidence to show that using saline or water alone is better or worse than commercially produced cerumenolytics. Equally, there is also no evidence to show that using saline or water alone is better than no treatment.

Objectives: In 2011, the Food and Drug Administration issued a warning to avoid the use of any benzocaine-containing products for infant teething treatment owing to a risk of methemoglobinemia. Several benzocaine-containing products targeted for infant teething are currently available over the counter. Pharmacists are commonly asked for medical advice in the community, and there is no current literature evaluating what pharmacists are recommending for infant teething. The objectives of this study were to evaluate what pharmacists are currently recommending for infant teething treatment and assess what percentage would inappropriately recommend a benzocaine-containing product., Methods: From March to June 2016, a 16-item in-person paper-and-pen questionnaire was administered to 200 pharmacists in the San Francisco Bay area at 115 outpatient over-the-counter pharmacies. Questions included demographic information, work and educational background, infant teething recommendations, and preferred educational resources., Results: The overall response rate was 94.3%. One-half (50.5%) of the pharmacists' approaches to infant teething treatment was to recommend a nondrug option first and then, if needed, an over-the-counter medication. A majority (63.0%) of the pharmacists surveyed would inappropriately select a benzocaine-containing product., Conclusion: Despite warnings, the majority of pharmacists would still inappropriately recommend a benzocaine-containing product for treatment of infant teething. Further education is warranted to ensure that all pharmacists, health care providers, and consumers are aware of the potential harm of benzocaine use in infants., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Pain control is an important outcome measure for successful periodontal therapy. Injected local anesthesia has been used to secure anesthesia for scaling and root planing (SRP) and continues to be the anesthetic of choice for pain control. Alternatively, intra-pocket anesthetic gel has been used as an anesthetic during SRP. Hence, this clinical trial was done to compare the effectiveness of intra-pocket anesthetic gel and injected local anesthesia during SRP and also to assess the influence of intra-pocket anesthetic gel on treatment outcomes in chronic periodontitis patients., Materials and Methods: Fifteen systemically healthy chronic periodontitis patients were recruited. The dental quadrants on right side received either intra-pocket 20% benzocaine gel (Gel group) or infiltration/block by 2% lidocaine with 1:80,000 adrenaline (injection group). Quadrants on the left side received the alternative. Pain perception and patients preference for the type of anesthesia was recorded. Clinical parameters: plaque index, modified gingival index, modified sulcular bleeding index, probing pocket depth, and clinical attachment level were recorded at baseline and 1 month after treatment., Results: No difference was observed in visual analog scale (P > 0.05) and verbal rating scale (P > 0.05) pain perception between gel group and injection group. A slightly increased preference to gel as anesthesia (53% vs. 47%) was observed. The treatment outcome after SRP did not show a significant difference between gel and injection group (P > 0.05)., Conclusion: Intra-pocket administration of 20% benzocaine gel may be effective for pain control during SRP and may offer an alternative to conventional injection anesthesia.

Objective: To examine the comparative effectiveness of two topical anesthetics in controlling the pain associated with tongue-tie release (frenotomy) in young infants., Design: Randomized trial., Setting: A Pediatric Craniofacial Clinic., Subjects: Forty-two infants who were referred for frenotomy were randomly allocated to receive the topical anesthetic gel 2% tetracaine or 20% benzocaine applied prior to frenotomy. Frenotomies were videotaped. The primary outcome measure was the Neonatal Facial Coding System (NFCS) score. Secondary outcome measures included cry duration and a visual analog scale (VAS) assessed by the parents., Results: The two groups were comparable with regard to weight, age, gender, previous painful experience, and last feeding time. Median NFCS scores prior to frenotomy in the tetracaine and the benzocaine groups were 4.5 (IQR: 0.75–10.2) and 3.5 (IQR: 0–9.5), respectively (P = 0.89, 95% CI −3 to 4). During frenotomy, median NFCS score increased to 28 (IQR: 24.5–30.25) in the tetracaine group (P < 0.0001, median difference −22, 95% CI −24.5 to −19), and to 28 (IQR: 26–30) in the benzocaine group (P < 0.0001, median difference −23, 95% CI −27 to −17). Mean cry durations in the tetracaine and the benzocaine groups were 69.4 seconds and 63.9 seconds, respectively (P = 0.32, 95% CI −47 to 15), and mean VAS scores were 57.2 and 58.2, respectively (P = 0.89, 95% CI −15.2 to 13.4)., Conclusions: These topical anesthetics seem ineffective in controlling the pain associated with frenotomy. Clinicians should continue to search for an effective treatment for this procedure.

Aim: To compare the effectiveness of 5% benzocaine gel and placebo gel on reducing pain caused by fixed orthodontic appliance activation., Setting and Sample Population: Thirty subjects (15-25 years) undergoing fixed orthodontics., Methods and Materials: A randomized, double-blind, placebo-controlled and cross-over clinical trial study was conducted. Subjects were asked to apply a placebo gel and 5% benzocaine gel, exchangeable in two consecutive appointments, twice a day for 3 days and mark their level of pain on a VAS scale. The pain severity was evaluated by means of Mann-Whitney U-test for comparing two gel groups, Kruskal-Wallis nonparametric test for overall differences and post hoc test of Dunnett for paired multiple comparisons. p-value was assigned <0.05., Results: The overall mean value of pain intensity for benzocaine and placebo gels was 0.89 and 1.15, respectively. The Mann-Whitney U-test indicated that there was no significant difference between overall pain in both groups (mean difference = 0.258 p ˂ 0.21). For both groups, pain intensity was significantly lower at 2, 6 and 24 h compared with pain experienced at days 2, 3 and 7., Conclusion: Benzocaine gel caused a decrease in pain perception at 2 h compared with placebo gel. Peak pain intensity was at 2 h for placebo gel and at 6 h for benzocaine gel, followed by a decline in pain perception from that point to day 7 for both gels., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To investigate the effectiveness of topical anesthetic, 20% benzocaine in relieving pain and stress in patients following deep cavity restoration and extraction of teeth under local anesthesia (LA)., Methods: A prospective clinical trial was conducted from October 2014 until April 2015 at Taibah University, Al Madinah Al Munawarah, Kingdom of Saudi Arabia. Forty-five patients were included in the 20% benzocaine group, and 46 in the normal saline group. Evaluation of the dental stress was made pre-operatively and immediately post-operative treatment using the visual analogue scale (VAS). Furthermore, discomfort of the injections were recorded by the patients after each treatment on standard 100 mm VAS, tagged at the endpoints with "no pain" (0 mm) and "unbearable pain" (100 mm)., Results: There were statistically significant differences between the mean stress scores for patients in the benzocaine and normal saline groups post-operatively (p=0.002). There were significant differences between the mean pain scores for patients in the post buccal injection (p=0.001), post palatal injection (p=0.01), and the post inferior alveolar nerve block groups (p=0.02). Buccal, palatal, and inferior alveolar nerve block injections were more painful for patients in the normal saline group than the benzocaine group., Conclusion: This investigation has demonstrated that post-operative stress associated with deep cavity restoration and dental extractions under LA can be reduced by the application of topical anesthetic (20% benzocaine) at the operative site for intra-oral injections.

Although the use of injectable anesthesia prior to subgingival scaling and root planing (SRP) reduces pain, many patients report fear and prolonged numbness of adjacent tissues. The aim of the present study was to compare the effects of a eutectic mixture containing 25 mg/g of lidocaine and 25 mg/g of prilocaine, injectable 2% lidocaine, topical 2% benzocaine and a placebo substance on reducing pain during SRP. In this randomized, split-mouth, masked clinical trial, thirty-two patients presenting more than two teeth with probing depth and clinical attachment level ≥ 5 mm in at least 4 sextants were randomly allocated to four groups: EMLA(r); injectable 2% lidocaine; topical 2% benzocaine and placebo. Pain and discomfort were measured using a visual analogue scale (VAS) and verbal scale (VS). Repeated-measures analysis of variance and Poisson regression were used for analysis. Patient satisfaction with the anesthesia was determined at the end of each treatment session. VAS and VS scores did not differ between injectable 2% lidocaine and EMLA (p > 0.05) and both substances showed significantly better pain control compared to 2% benzocaine and placebo (p < 0.05). 93.7% and 81.2% of the individuals were satisfied with the injectable anesthetic and EMLA, respectively (p = 0.158). Dissatisfaction with benzocaine and placebo was approximately 10 times greater than injectable anesthesia (p = 0.001). In conclusion, EMLA showed an equivalent effect on pain control when compared to the injectable anesthesia and performed better than 2% benzocaine in SRP. Thus, EMLA is a viable anesthetic option during scaling and root planning, despite the frequent need for second application.

Many women experience pain during hysterosalpingogram (HSG). This prospective, randomized, double-blinded, placebo-controlled study assessed whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, parity, pre-procedure oral analgesic use and history of dysmenorrhoea and/or chronic pelvic pain. Median change in pain score from baseline to procedure was 50.6mm (-7.4 to 98.8mm) in the benzocaine group and 70.4mm (19.8 to 100mm) in the placebo group. There was no difference between groups after adjusting for history of dysmenorrhoea. There was no difference in resolution of pain in benzocaine versus placebo groups at 5 min post procedure--median pain score difference -11.1 (-90.1 to 18.5) versus -37.0 (-100 to 1.2)--or at 30 min post procedure. Satisfaction scores did not differ by treatment and did not correlate with pain score during the procedure (rho=0.005). The use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain. Many women experience pain during hysterosalpingogram (HSG), which is a test used to evaluate the uterine cavity and fallopian tube. We conducted a prospective, randomized, double-blinded, placebo-controlled study to assess whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, previous pregnancies, pre-procedure oral analgesic use and history of dysmenorrhoea (painful periods) and/or chronic pelvic pain. There was no difference in pain scores or resolution of pain between the two groups. Satisfaction scores did not differ by treatment group and did not correlate with the pain score during the procedure. We conclude that the use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: The plasma skin regeneration (PSR) device delivers thermal energy to the skin by converting nitrogen gas to plasma. Prior to treatment, hydration of the skin is recommended as it is thought to limit the zone of thermal damage. However, there is limited data on optimal hydration time. This pilot study aims to determine the effect of topical anesthetic application time on the depth of thermal injury from a PSR device using histology., Study Design/materials and Methods: PSR (1.8 and 3.5 J) was performed after 0, 30, or 60 minutes of topical anesthetic application. Rhytidectomy was then performed and skin was fixed for histologic analysis. Four patients (two control and four treatment sites per patient) undergoing rhytidectomy were recruited for the study. Each patient served as his/her own control (no hydration). A scoring system for tissue injury was developed. Epidermal injury, the presence of vacuolization, blistering, damage to adnexal structures, and depth of dermal collagen changes were evaluated in over 1,400 high-power microscopy fields., Results: There was a significant difference in the average thermal injury score, depth of thermal damage, and epidermal injury when comparing controls to 30 minutes of hydration (P = 0.012, 0.012, 0.017, respectively). There was no statistical difference between controls and 60 minutes of hydration or between 30 and 60 minutes of hydration. Epidermal vacuolization at low energy and patchy distribution of thermal injury was also observed., Conclusion: Topical hydration influences the amount of thermal damage when applied to skin for 30 minutes prior to treatment with the PSR device. There was a trend toward decreasing thermal damage at 60 minutes, and there was no difference between treatment for 30 or 60 minutes. The data suggest that application of topical anesthetic for a short period of time prior to treatment with the PSR device is cost-effective, safe, and may be clinically beneficial., (© 2013 Wiley Periodicals, Inc.)

This clinical case and the literature review show possible development of methemoglobinemia due to the use of local anesthetics, included in drugs for the gastrointestinal diseases treatment, in particular benzocaine, which is the methaemoglobin forming agent. These drugs are common and often taken by the patients themselves without any control. The aim of our paper is to draw the attention of physicians to the risk of the widely known drug administration which can be purchased without a prescription.

Objectives: To study the effect of benzocaine mucoadhesive patches (20%) on orthodontic pain caused by elastomeric separators., Subjects and Methods: A split-mouth design was used in 30 patients (12 female, 18 male, aged 23 ± 3.75 years). They were instructed to apply benzocaine and placebo patches randomly for right or left first permanent molars of maxillary/mandibular arches for 20 min and repeat this procedure every 6 h with a similar type patch. A 10 cm Visual Analogue Scale (VAS) was used for pain perception assessment in patients who were given benzocaine (benzocaine group) or placebo (placebo group) patches. Pain perception (VAS) was recorded immediately after separator placement and after 2, 6, 12, 18, 24, 48 and 72 h., Results: The mean VAS (SD) for the placebo and benzocaine groups were 2.28 (1.08) and 1.63 (0.67), respectively. The pain peaked at 24 h. Significant pain perception differences were observed between groups at 2, 18, 24, 48 and 72 h. Pain perception was not different between genders or jaws investigated (p > 0.05). The Friedman test revealed significant differences in pain perception among various time intervals for benzocaine (χ (2) = 99.84, p = 0.000) and placebo (χ (2) = 102.361, p = 0.000) groups. Significant negative correlations (ρ) were found only between pain perception scores and patient's ages in the placebo group at 18 (-0.438), 24 (-0.526), 48 (-0.565) and 72 h (-0.458)., Conclusion: The recorded mean VAS values were relatively low; however, the benzocaine 20% patches significantly reduced the post-separation orthodontic pain.

The present study concerns the in vitro and in vivo evaluation of benzocaine (BENZO) and lidocaine (LIDO) topical delivery from nanostructured lipid carriers (NLCs). Morphology and dimensional distribution of NLCs have been, respectively, characterized by differential scanning calorimetry (DSC) and photon correlation spectroscopy. The release pattern of BENZO and LIDO from NLCs was evaluated in vitro determining drug percutaneous absorption through excised human skin. Radiant heat tail-flick test was carried out in mice to determine the antinociceptive effect of BENZO and LIDO from NLC. DSC studies revealed that the inner oil phase of NLC plays a significant role in stabilizing the particle architecture and increasing the drug solubility. In vitro evidences show that BENZO and LIDO, when incorporated in viscosized NLC dispersions, exhibited a lower flux with respect to formulations containing the free drugs in the aqueous phase. In vivo study enabled to demonstrate that BENZO and LIDO can be released in a prolonged fashion when incorporated into lipid carriers. The results obtained pointed out NLC capability to act as an effective drug reservoir, thus prolonging the anesthetic effect of BENZO and LIDO., (Copyright © 2010 Wiley-Liss, Inc.)

In a reference-controlled double-blind trial in patients with acute pharyngitis the effects of a newly developed lozenge containing 8 mg of benzocaine (p-aminobenzoic acid ethyl ester, CAS 94-09-7) were compared with those of an identically dosed commercial pastille. 246 patients were randomized to receive either the lozenges (group A, n = 123) or the pastilles (group B, n = 123). Each patient took a total of six doses within 12 h according to the double-dummy principle, with each single dose spaced by 2 h. The primary parameter was the assessment of the responder rate with = 50 % pain relief within 15 min post application. Further parameters included the relative relief of pain in the course of the study and the tolerability of the formulation. After application of the first unit the comparison of groups yielded very similar and statistically not differing results for efficacy in both groups, with responder rates of 25.2 % and 22.0 % in groups A and B, respectively. One adverse drug reaction was observed in group B (burning and tingling feeling on the tongue), which, however, did not lead to discontinuation of study participation. In all other cases tolerability was stated to be "good to very good". The application of the benzocaine lozenges was statistically non-inferior to the use of the pastilles.

A 35% potassium nitrate/20% benzocaine/10% tetracaine/aqueous hydroxyethyl cellulose gel was applied to the teeth and gingiva of 100 patients prior to hygienist-administered maintenance treatments. The application effectively anesthetized the teeth and gingiva so that these maintenance treatments could be performed routinely with genuine patient comfort. As a control in this double-blind study, 100 patients received hydroxyethyl cellulose without the active agents. All patients were volunteers and chosen at random.

Methemoglobinemia, a condition associated with cyanosis and diminished pulse oximetry values, has been reported after use of local anesthetics to facilitate fiberoptic intubation. The majority of reports in the literature detail this development during diagnostic procedures such as endoscopy and bronchoscopy. A case of methemoglobinemia in a multiple-injury patient with an unstable compressive-flexion injury of the cervical spine undergoing fiberoptic intubation is presented. A literature review of this entity is also presented. The patient underwent fiberoptic intubation using topical pharyngeal anesthetics before planned cervical corpectomy, strut grafting and instrumentation. He became acutely cyanotic with abruptly diminished pulse oximetry readings. Subsequent blood gas analysis demonstrated methemoglobinemia. Intravenous methylene blue administration led to an uncomplicated resolution of the condition. Surgeons and anesthesiologists who manage such patients should be aware of methemoglobinemia, a rare but potentially fatal complication related to topical airway anesthetics.

Objective: To estimate whether benzocaine spray applied to the cervix and the endocervical canal before performing office endometrial biopsy improves patient comfort during the procedure., Methods: Eighty-eight women were randomly assigned to receive either 20% benzocaine spray or placebo to the outside of the cervix and into the endocervical canal before an endometrial biopsy was performed. The main outcome measure was pain during the endometrial biopsy, assessed by a visual analog scale. Statistical analysis was performed using Wilcoxon rank-sum test and Student t test., Results: There were no statistically significant differences between the study group and the control group in mean age, race, parity, body mass index, menopausal status, tenaculum use, or history of chronic pelvic pain. No statistically significant differences were found in median pain scores between the 2 treatment groups., Conclusion: Topical benzocaine spray does not appear to offer effective pain control in patients undergoing an endometrial biopsy., Level of Evidence: I.

Background: Methemoglobinemia results from oxidation of ferrous to ferric iron in hemoglobin. In addition to a functional anemia, methhemoglobinemia causes the O2-binding affinity of the remaining O2 sites in the hemoglobin tetramer to increase; essentially shifting the oxyhemoglobin dissociation curve to the left and decreasing O2 delivery. Patients develop profound cyanosis unresponsive to O2 when methemoglobin (MHb) levels exceed 10%. It can be lethal if levels exceed 70%. Benzocaine 20% (Hurricaine) spray, commonly used in endoscopy (EGD) can cause methemoglobinemia. We report our experience., Methods: Two patients out of >1,000 EGDs in 4 yrs developed methemoglobinemia., Results: Patient 1: 34 F, BMI 46, open distal gastric bypass. Patient 2: 26 F, BMI 49, laparoscopic proximal gastric bypass. Both had nausea and vomiting from stomal stenosis requiring EGD for which benzocaine 20% spray was used. Severe cyanosis (despite pulse oximetry readings of 86% and 89%), dyspnea and tachycardia, were seen within 13 and 7 minutes. They were unresponsive to O2, despite being awake and conversant after complete reversal of sedatives. MHb levels were 35.6% and 18.8% (normal <1%). Patients dramatically improved after 1% methylene blue at 1-2 mg/kg IV over 5 minutes. MHb levels dropped to 2.3% and 0.8 % within 150 and 110 minutes. Neither patient had any evidence of pulmonary embolism or DVT or G6PD deficiency., Conclusion: Topical benzocaine 20% (Hurricaine) spray used in EGDs gets absorbed and can cause methemoglobinemia. Sprays should be limited to 1 second. Prompt treatment with 1% methylene blue IV can be life-saving.

Background: Folk remedy use is universal, occurring in all cultures. Folk remedies have been and still are relied on in the black community. In this study, folk remedies refer to herbs, over-the-counter medications, and items traditionally used for cooking that are used to treat a variety of ailments., Objective: To identify folk remedies used to treat fever, colic, and teething among black children in Detroit, Michigan., Methods: Structured interviews were conducted with caregivers of healthy black children <2 years of age who were patients of the general pediatric clinic at Children's Hospital of Michigan. Descriptive analysis of the frequency distribution of the responses was performed., Results: One hundred seven caregivers agreed to participate. All participants were familiar with the use of folk remedies. Most caregivers learned of these remedies from their mothers or grandmothers. Older parents were more likely to use folk remedies, but there was no difference in remedy use among different levels of maternal education., Conclusions: The knowledge and use of folk remedies were active in this black community. Their use seems to be cultural, rather than attributable to decreased access to health care. Physicians should be aware of these remedies, to educate families about remedies that may be harmful. Most remedies used pose no threat to health. In some cases, remedies may be blended with traditional medical treatments to ensure better patient compliance.

Methemoglobinemia is a rare complication that can occur with the use of benzocaine-containing compounds. Two cases of methemoglobinemia are reported, and the pathophysiology and treatment of methemoglobinemia are reviewed. Both patients received topical 20% benzocaine spray before endoscopy. Immediately following the procedure, there was a reduction in O2 saturation assessed by pulse oximetry that was refractory to O2 therapy. Dramatic peripheral and central cyanosis developed. O2 saturation measured by pulse oximetry ranged from 83% to 87% on O2 by nasal prongs and 100% O2 by a nonrebreathing mask. Both patients were mildly confused and one patient complained of a significant headache. The diagnosis of methemoglobinemia was considered and arterial blood gas sampling was performed. In both patients, the arterial blood had a chocolate brown colour. A methemoglobin level of 48% and 18% was noted in patient 1 and patient 2, respectively. Both patients were treated with methylene blue, resulting in a significant improvement with gradual normalization of their O2 saturation within 10 min to 30 min. The use of benzocaine spray may not markedly alter the patient's perception of endoscopy and thus, the routine use of these agents should be questioned. If such agents are used, the physician must be aware of this association to prevent a delay in the diagnosis and management of this rare, but potentially lethal, condition.

Methemoglobinemia (MetHb) remains an uncommon, but potentially fatal disorder. Benzocaine (ethyl aminobenzoate), a topical anesthetic, has been reported to cause acquired MetHb when used during endoscopic or other ambulatory procedures. Reports of severe MetHb following benzocaine-containing preparations in the community, however, are very rare. We discuss this entity by describing an unusual case of severe MetHb in a 5-year-old child, caused by unattended self-use of a benzocaine-containing, pain-relief gel for teething. This case story illustrates the potential lethal risk of over-the-counter topical anesthetics for pediatric use. We review the risks of this potentially deadly disorder and the associated diagnostic challenges. Physicians not familiar with this rare complication may face diagnostic dilemmas, as its presentation is often nonspecific and rapid treatment is essential to prevent life-threatening complications.

Benzocaine is a commonly used topical anesthetic present in many over-the-counter preparations. The development of methemoglobinemia, associated with the use of benzocaine, is potentially fatal. Methemoglobinemia remains unresponsive to the administration of oxygen alone and, in fact, results in greater tissue hypoxemia than the usual monitoring techniques indicate. We report two cases of benzocaine-induced methemoglobinemia occurring 3 months apart at the same institution. A brief discussion regarding methemoglobin is presented.

Unlabelled: Although local anesthetics can, in some situations, alleviate neuropathic pain, currently available preparations are short-acting and nonselective, producing, for example, motor dysfunction. Clinical studies report that a novel suspension preparation of butamben has the advantage of a prolonged duration of action, and it can be used epidurally, without impairment of motor function. In this behavioral study, we investigated the effect of the epidural administration of a 5% butamben suspension on nerve injury-induced allodynia. Behavioral studies were performed using an established animal model of neuropathic pain, which involves a partial ligation of the sciatic nerve. Nociceptive thresholds to mechanical stimulation were determined by the paw withdrawal method. The allodynia to mechanical stimulation induced by partial nerve ligation was significantly attenuated by daily injections, for 5 days, of 10 microL of butamben suspension. The analgesia lasted at least 7 days after the final injection. Daily injections of 10 microL of vehicle, for 5 days, had no significant effect on allodynia. During the period of daily injections, both the butamben and vehicle treated rats had temporary impairment of motor coordination compared with untreated controls. Motor function recovered after the final injection. Neither daily injections of butamben for 2 or 3 days, nor smaller volumes for 5 days (2.5-5 microL), had a long-lasting effect. We conclude that repeated epidural administration of butamben suspension for several days provides long-lasting analgesia in rats with nerve injury-induced allodynia to mechanical stimulation., Implications: In this animal behavioral study, using rats with nerve injury-induced pain, we examined the possible long-term analgesic effects of epidural administration of a suspension of the local anesthetic, butamben. We found that multiple doses for several days were required to provide a prolonged analgesia.

Objective: Phenylpropanolamine (PPA) and benzocaine are non-prescription medications approved for treating obesity. The dose of PPA for weight loss is 75 mg/day. PPA has the same chemical similarity to pseudoephedrine that amphetamine has to methamphetamine. Because benzocaine causes weight loss by altering taste and PPA by central appetite suppression, they may induce additional weight loss when combined. These studies explore the safety and efficacy of low-dose PPA, pseudoephedrine, and PPA with benzocaine in causing weight loss., Research Methods and Procedures: Study 1 compared PPA 12.5 mg tid with 25 mg tid and placebo in a 6-week trial in 108 obese subjects. Study 2 compared pseudoephedrine 120 mg/day and a placebo in a 12-week trial with 72 obese subjects. Study 3 compared 4 groups of 20 obese subjects using PPA 75 mg/day, benzocaine gum 96 mg/day, PPA with benzocaine gum, and a placebo over 12 weeks., Results: Both doses of PPA gave twice the weight loss of placebo, but the difference did not reach statistical significance. Pseudoephedrine was no different than placebo in inducing weight loss. The PPA with benzocaine group had more adverse events than the benzocaine group (p = 0.03), the placebo group (p = 0.03), or the PPA group (p = 0.09) without additional weight loss., Discussion: We conclude that further studies with low-dose PPA for weight loss are indicated, that pseudoephedrine is not effective for weight loss, and that adding benzocaine to phenylpropanolamine increases adverse effects without increasing weight loss.

Chemotherapy-induced oral mucositis can result in inadequate oral intake, local and systemic infection, a prolonged hospital stay, and increased cost of treatment. Treatment of the pain resulting from this condition can greatly lessen these problems. Hydroxypropyl cellulose gel with benzocaine (Zilactin B) has been shown to effectively reduce the pain of mucositis for up to 3 hours.

Background: No established treatment exists for pain relief in symptomatic non-acid oesophagitis. One of the most common topical anaesthetics is benzocaine which has been demonstrated to produce excellent analgesia on oral mucous membranes., Methods: In a prospective, placebo-controlled, balanced, single-blinded study, 26 patients with retrosternal discomfort or odynophagia due to painful non-acid oesophagitis were treated either with oral benzocaine 0.75% solution (n = 14) or with benzocaine-free solvent (placebo, n = 12) at a daily dose of 20-40 mL, for up to 6 consecutive days (median 5.5 days). During the study period patients recorded subjective pain scores for both complaints on visual analogue scales., Results: Benzocaine did not affect pain scores for any of the two symptoms, nor did it alter global subjective or objective assessment of therapy outcome in treated compared to untreated subjects (P > 0.05). There was a non-significant tendency for placebo patients to stop prematurely their study medication more often, because of lack of analgesic efficacy (P = 0.098)., Conclusions: Topical benzocaine cannot be recommended for routine symptomatic pain relief in non-acid oesophagitis. By indirect evidence, it is assumed that pain perception of non-acid oesophagitis is not preferentially mediated by superficially located mucosal nociceptors.

Objective: To determine the efficacy of Auralgan otic solution (combination product of antipyrine, benzocaine, and glycerin) compared with an olive oil placebo in the management of moderate to severe ear pain in children with acute otitis media (AOM)., Design: Children 5 years or older who presented with ear pain and eardrum findings indicative of AOM were randomly assigned to treatment with Auralgan or olive oil drops instilled into the external auditory canal(s) of the affected ear(s). All children were also treated with 15 mg/kg of acetaminophen in a single dose. Ear pain was assessed by means of 2 visual analog seales-a linear scale and a color scale-at study entry and 10, 20, and 30 minutes later (T0, T10, T20, and T30, respectively). Results of the measurements on the 2 scales were evaluated independently and were averaged to determine an ear pain score. A baseline ear pain score of at least 3 points was required for study entry. Four outcome measures regarding ear pain score at T10, T20, and T30 were used: (1) proportion of subjects who showed 50% reduction, (2) proportion of subjects who showed 25% reduction, (3) proportion of subjects who showed a 1 or more point reduction, and (4) mean score over time., Setting: Primary care center and emergency department of a children's hospital., Participants: Fifty-four children aged 5 to 19 years with ear pain and AOM., Results: The Auralgan and placebo groups were comparable regarding age, sex, race, laterality of AOM, and T0 ear pain score. By each of the 4 measures used, the response to treatment consistently favored the Auralgan group, but only at T30 were any differences statistically significant., Conclusion: In children with AOM-associated ear pain who are treated with acetaminophen, topically applied Auralgan appears likely to provide additional relief in varying degree within 30 minutes.

According to Krusen's Handbook of Physical Medicine and Rehabilitation, topical application of ultrasound exerts only an indirect and adjunctive effect as deep-heat treatment. In support of this idea the extensibility of an isolated tendon in a heated water bath is described. The significance of this experiment as a biological phenomenon has never been critically examined. In this article the existence of a segmental reflex is proposed. Such a segmental paradigm is in keeping with the segmental organization and evolution of the locomotor system. It is further suggested that ultrasound and related therapy, if applied segmentally, may have a curative effect.

Objectives: Our purpose was to assess the potential for an external vaginal antiitch cream (20% benzocaine, 3% resorcinol) to significantly increase levels of methemoglobin above normal in healthy women., Study Design: Fifty-five women reporting external vaginal itch were recruited for the study. Each patient was used as her own control with methemoglobin levels being measured before and after use of the cream. Women were instructed to apply a 1-inch strip of cream by fingertip to the external genital area three or four times a day for 7 consecutive days., Results: There were no significant differences in methemoglobin levels before and after use or in levels from a subgroup of women aged > 50 years compared with levels in a younger population., Conclusions: This preparation appears to be safe when used as directed; however, the results cannot be extrapolated to the very young. Nevertheless, lavish or frequent application over wide areas of excoriation might lead to toxic concentrations and methemoglobinemia. Therefore patients with serious vaginal disease should be advised against self-treatment beyond the 7-day limit imposed by the Food and Drug Administration for over-the-counter external analgesic medications.

After analysing of recurrent aphthous stomatitis the clinical and morphological aspects, the authors consider various therapeutic possibilities. They underline the relationship between therapy and clinical aspects of the pathology.

Pharmacological treatment of obesity has been neglected as a viable therapeutic option for many years. Recent long term studies with combinations of obesity drugs gives promise that drugs may play a role in weight maintenance, which classically has been the most difficult aspect of treating obesity. Currently available obesity drugs include centrally acting adrenergic agents and serotonin agonists. Drugs still in development include a lipase inhibitor that produces fat malabsorption, a combined adrenergic-serotonergic reuptake inhibitor, various gut-central nervous system peptides, and a number of beta-3 agonists. Any of these obesity drugs given alone produces modest weight loss, and for most, weight loss continues for as long as medication is given. The most successful drug regimens to date are combinations of phentermine and fenfluramine or of ephedrine, caffeine, and/or aspirin. The former combination produces reduction in body weight and complications of obesity for 2 to almost 4 years in clinical trials to date. More research is needed to document long term efficacy and particularly the long term safety of these and other combinations.

Postoperative reflux gastritis in persons who were operated on for peptic ulcer occurs much more frequently after resection of the stomach (68.6%) than after organ-preserving operations on the stomach (39.4%). The incidence of reflux gastritis after gastric resection depends on the type of gastroenteroanastomosis. It is encountered much less frequently after Roux' operation (9.2%). The pronounced character and frequency of reflux gastritis after organ-preserving operations on the stomach are determined by the type of stomach-draining operations, the localization of the ulcer before the operation, whether in the stomach or the duodenum, the existence of duodenogastric reflux (DGR) before the operation. Measures for the prevention of postoperative reflux gastritis in the management of peptic ulcer are as follows: (a) wide introduction of organ-preserving operations, preferably SPV by itself or in combination with duodenoplasty; (b) formation of Roux' gastroenteroanastomosis when resection of the stomach is indicated. Reflux gastritis must be treated by nonoperative methods, including medicinal, dietetic, and spa therapy. Surgery is indicated in reflux gastritis combined with other diseases of a stomach which had been operated on, for which an operation is necessary, and in occasional cases of erosive reflux gastritis.

Basic modes of action and indications for aluminium and magnesium-containing antacids are reviewed. Antacid properties of Maalox were studied versus those of Almagel in 24 duodenal ulcer patients by the following indices of pH-metry: time of pH response onset, "alkaline time", alkalification area and index. All the features were significantly different when assessed in the body of the stomach. Regular Maalox intake as a main medicine provided good results in the treatment of duodenal ulcer (25 responders), gastric ulcer (14 responders), erosive gastroduodenitis (14 responders), erosive reflux-esophagitis (9 responders). Maalox displayed high symptomatic efficacy, safety, insignificant side effects.

The purpose of this pilot investigation was to determine the usefulness of analgesic onset time as a measure of topical anesthetic efficacy in patients with spontaneous toothache pain. Under blinded conditions, 20 patients with spontaneous toothache pain from an open tooth cavity were randomly assigned to receive either 20% benzocaine or placebo (80% polyethylene glycol). The medication was applied directly to the open cavity in a volume of 3 drops. Patients then depressed a stop watch when they initially experienced pain relief. Patients who did not obtain relief were assigned the maximum onset value of 600 seconds. The average analgesic onset time was 111.8 seconds in the benzocaine group and 289.0 seconds in the placebo group. In the benzocaine group, 90% of the patients reported some pain relief, while a surprisingly high 60% reported some pain relief in the placebo group. The results of this study suggest that in the spontaneous toothache pain model, analgesic onset time is a valuable measure of topical anesthetic efficacy. In addition, polyethylene glycol at a concentration of 80% may not be a totally inactive vehicle.

Purpose: This open-label, multicenter trial evaluated the efficacy of a mucoadherent, anesthetic medication (MGI 209) for relief from painful oral ulcers associated with cytotoxic chemotherapy., Patients and Methods: Twenty-eight eligible cancer patients who had up to five discrete oral ulcers (total area < or = 5 cm2) completed this study. Mean age was 53.5 years (range, 21 to 81). Subjective assessments of oral discomfort before and after an orange juice pain challenge (OJPC), which was measured using a visual analog scale (VAS), and visual estimates of the amount of MGI 209 that remained on treated ulcers were collected at (1) baseline (before MGI 209 treatment); and (2) 30, 60, 120, and 180 minutes posttreatment., Results: Most subjects had low VAS scores (4 or less), which was indicative of oral discomfort, at baseline before and after the OJPC. At 30, 60, 120, and 180 minutes after MGI 209 treatment, most subjects had high VAS scores before and after an OJPC compared with baseline scores, which was indicative of a substantial increase in oral comfort; these differences were statistically significant (P < .0001). Mean percent of MGI 209 estimated to remain on ulcers at the previously mentioned times was 93.7%, 90.3%, 79.6%, and 71.3% of the total amount applied, respectively., Conclusion: Benzocaine hydrochloride in combination with the protective, mucoadherent film-coating relieved discomfort for at least 3 hours even with exposure to an irritating beverage. MGI 209 treatment should allow patients with chemotherapy-induced oral ulcers to drink and eat with significantly diminished pain or no pain.