TOPICS

Reduction in Procedure-associated Pain by Treatment with a Unique Topical Anesthetic Foam Containing 4% Lidocaine

Ellen Frankel, MD,St. Joseph’s Hospital, Providence, Rhode Island

Mark W. Trumbore, PhD, Collegium Pharmaceutical, Cumberland, Rhode Island

Disclosure: Dr. Frankel has received research support from Onset Therapeutics. Dr. Trumbore is employed by Collegium Pharmaceutical.

Abstract
Objective: This study evaluated a unique formulation of lidocaine 4% in an emollient aerosol foam microemulsion system to facilitate rapid delivery of the active ingredient and reduce pain associated with cosmetic dermatologic laser treatment. Design: This was a noncontrolled, open-label, paired, comparison study. Setting: Private practice dermatology clinic. Participants: Ten patients undergoing various cosmetic laser treatments, 18 years of age or older and considered clinically appropriate for study participation. Measurements: Primary endpoints were patient and clinician assessments of procedural pain intensity for the treated and untreated areas. Ratings were recorded on a visual analog scale ranging from “no pain at all” to “the most intense pain imaginable.” Secondary study endpoints included clinician and patient subjective assessments of the lidocaine 4% foam. Results: Mean patient and clinician ratings of pain were significantly lower for areas treated with the lidocaine 4% foam compared with pain ratings for untreated areas. No adverse events were reported. Clinician’s mean ratings for ease of application and overall satisfaction were favorable. Conclusion: The results from this pilot, 10-patient, open-label study suggest that the lidocaine 4% foam may be acceptable to both patients and clinicians for the safe and effective reduction of pain associated with cosmetic dermatologic laser procedures. However, a blinded, placebo-controlled study of a larger population is needed to confirm these preliminary results.

(J Clin Aesthetic Dermatol. 2009;2(4):36–39)

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The number of cosmetic dermatologic procedures (skin injections, chemical peels, laser treatments, and microdermabrasion) performed in the United States continues to expand each year.[1] Patients access these services through a number of venues, including medical spas, laser centers, walk-in clinics, and medical practices offering aesthetic treatments. The American Academy of Dermatology, citing inadequate pain relief as a concern, recognizes this market saturation as a potential risk to patients who may, unknowingly, elect to have these cosmetic procedures performed by unqualified healthcare providers.[2]

As the number of individuals undergoing cosmetic dermatologic procedures increases, demand will also grow for topical anesthetics that are fast acting, nontoxic, and easy to apply and remove, and require no special storage conditions.[3] A variety of over-the-counter (OTC) and prescription topical anesthetics are currently available.[3–11] They vary in relative potency, but all have an appropriate function within the dermatology practice. A commonly prescribed topical anesthetic is a eutectic formulation of lidocaine 2.5% and prilocaine 2.5%.[3,4,6–8] This formulation has several limitations, including a need for occlusion, unpredictable depth and duration of anesthetic effect, vasoconstriction followed by delayed onset of vasodilation after two hours, and undesirable side effects, such as blanching of the skin, pruritus, burning, and purpura.[3,4,6] Dose determination depends on a patient’s age, weight, renal and hepatic function, surface area involvement, treatment duration, and skin barrier function.[3]

Compounded formulations include more potent combinations of lidocaine, benzocaine, prilocaine, and tetracaine.[3,7–11] The efficacy of these formulations, which are not subject to US Food and Drug Administration (FDA) review and approval, remains to be determined and significant concerns remain about their safety.[12–16] In a survey of compounded formulations, 34 percent failed one or more standard quality tests, leading the FDA to caution healthcare practitioners about potential risks associated with the use of these agents.[12,13,16] In addition, the FDA urged patients to question their physician’s selection of topical anesthetic. The FDA describes the ideal topical anesthetic as one that “contains the lowest amount of anesthetic drugs possible that will relieve pain.”[16]

Topical lidocaine in various OTC concentrations provides safe and effective relief for patients undergoing dermatologic procedures.[6–10] A single-center, double-blind, randomized trial comparing lidocaine cream 4% with vehicle for patients receiving botulinum toxin type A treatments reported statistically significant reductions in pain for lidocaine-cream-treated areas.[9] Similarly, a comparison of four topical anesthetics (including the eutectic formulation of lidocaine 2.5% plus prilocaine 2.5% cream, lidocaine 4% cream, tetracaine 4% gel, and a compound ointment consisting of lidocaine, prilocaine, and a vasoconstrictor) demonstrated statistically greater pain relief from a Q-switched Nd:YAG laser at 1064nm compared with a vehicle agent.10 However, side effects from these formulations included blanching, erythema, and local skin irritation, persisting up to two hours postapplication.[10]

Although not indicated for use prior to cosmetic procedures, topical lidocaine 4% has become the gold standard in topical pain control.[12] Not only has topical lidocaine 4% been validated as an effective agent for pain control in cosmetic procedures, but studies have demonstrated that an occluded application of 60g of lidocaine 4% generates no signs of toxicity or systemic effect.[8] While significant progress has been made in the development of safe and effective topical anesthetics, a need remains for agents that offer quick onset of action, adequate duration of analgesic effect, minimal side effects, and an application process that is acceptable to patients. This study assessed the effectiveness and safety of a unique formulation of lidocaine 4% using an emollient aerosol foam microemulsion system (AnestaFoam®, Onset Therapeutics, Cumberland, Rhode Island) to facilitate rapid and efficient delivery of the active ingredient to reduce pain associated with cosmetic dermatologic laser treatment.

Methods
This study evaluated the ability of an OTC lidocaine 4% topical foam—indicated for relief of pain associated with minor cuts, burns, abrasions, sunburn, and insect bites—to reduce pain associated with common cosmetic dermatologic laser procedures. Secondary objectives included assessment of overall satisfaction and the safety of lidocaine 4% foam for the treatment of pain.

The noncontrolled, open-label, paired comparison study enrolled 10 patients. Eligible patients included those who were: 1) undergoing cosmetic laser treatment; 2) 18 years or older; and 3) judged to be clinically appropriate for study participation based on the clinician’s judgment. Patients were excluded from the study if they had comorbid health conditions that might interfere with assessments or participation in the study, including eczema, psoriasis, severe sun damage, or dermatitis. Patients were also excluded if they had damaged, denuded, or broken skin at the designated treatment site or scarring or infection of the treatment area.

Prior to initiating the cosmetic laser procedure, the clinician obtained a brief medical history and patients read and signed a medical release form. The treatment area was divided into two equally proportioned sites. One site was randomly selected for lidocaine 4% foam application. A layer of lidocaine 4% foam was applied and rubbed into the selected area every five minutes for a total of four applications. After the fourth application of lidocaine 4% foam was completed, the clinician waited for five minutes then performed the procedure. The other treatment site received no topical anesthetic.

The primary study endpoints were clinician and patient assessments of procedural pain intensity. Pain ratings for both the treated and untreated areas were recorded on visual analog scales (VAS) ranging from “no pain at all” to “the most intense pain imaginable.” Secondary study endpoints included clinician and patient subjective assessments of the lidocaine 4% foam. The clinician indicated overall satisfaction and ease-of-foam application on a five-point Likert scale ranging from 1 (dissatisfied) to 5 (very satisfied) for each patient. Patients’ subjective assessments of the lidocaine 4% foam included dichotomous ratings of perceived numbing and increased comfort associated with the lidocaine 4% foam during the procedure. Number and type of adverse events were collected by the clinician.

Descriptive statistics were calculated for patient demographics, primary and secondary endpoints, and adverse events. Two-tailed paired comparison student t tests were completed to assess statistical differences in pain intensity between the treated and untreated areas for clinician and patient ratings. The descriptive and inferential analyses were calculated with Microsoft Office Excel 2003.

Results
Ten patients completed the study (Table 1). Seven patients underwent laser hair removal using a 755nm alexandrite laser. Of those, four patients received treatment on their underarms, two on their legs, and one patient received treatment on the neck and jaw. Additionally, two patients endured a 1450nm diode laser session to correct facial acne scarring. Lastly, one patient experienced a facial IPL treatment for telangiectasia and photodamage correction. The mean and median patient ages were 41.4 and 38 years, respectively (range, 37–59). All participants were female Caucasians. Mean clinician VAS ratings of patient pain intensity were 5.67 (range, 2.6–9.5) for the areas treated with lidocaine 4% foam compared with a mean VAS pain rating of 8.61 (range, 6.2–10.4) for untreated areas (P=0.005; Figure 1). Similarly, the mean patient VAS rating of pain intensity was 5.37 (range, 1.9–8.6) for treated areas compared to a mean VAS rating of 8.31 (range, 5.5–11.6) for the untreated areas (P=0.008; Figure 2). Both clinician- and patient-VAS ratings of treated sites demonstrate significantly reduced pain compared to sites receiving no topical anesthesia. No adverse events or side effects were reported by the patients or the clinician.

Secondary endpoints of this study assessed the clinician’s subjective ratings of lidocaine 4% foam. The clinician’s mean ratings for ease of application and overall satisfaction were 4.1 and 3.36, respectively, on five-point scales. Forty percent of patients reported a numbing sensation in areas treated with lidocaine 4% foam, while 70 percent indicated that the treated areas were more comfortable than the nontreated areas during the procedure.

Discussion
In a world crowded with medical spas, laser centers, and medical practices offering aesthetic treatments, patients seeking cosmetic procedures have more options than ever before.[17] Patient retention and referral strategies have become critical programs for successful aesthetic practices. The availability of topical anesthetics during uncomfortable procedures is an effective way to enhance patients’ satisfaction with their overall experience. Dispensing OTC lidocaine 4% foam provides safe, effective, and appropriate anesthetization for minimally invasive, yet uncomfortable laser procedures.

This small, nonrandomized, noncontrolled study was conducted to evaluate the efficacy, safety, and tolerability of lidocaine 4% foam for relief of pain associated with cosmetic laser procedures. Mean patient ratings of pain were significantly lower for areas treated with lidocaine 4% foam compared to untreated areas. Forty percent of patients indicated that lidocaine 4% foam caused a numbing effect, with 70 percent reporting increased comfort levels. These results establish the ability of lidocaine 4% foam to decrease pain and discomfort without provoking excessive anesthetization. Similarly, mean clinician ratings of pain were significantly lower for areas treated with the lidocaine 4% foam compared to untreated areas, indicating patients were noticeably more tranquil during the procedures. The safety profile of the product was very favorable and no adverse events were observed.

Clinician satisfaction with the product was favorable for ease of application and overall product satisfaction. The foam formulation of lidocaine 4% has aesthetic attributes superior to formulations currently on the market, suggesting improved tolerability. The advanced microemulsion foam formulation of lidocaine 4% foam does not require occlusion and is easy for patients to apply without supervision, promoting office workflow and efficiency without compromising patient safety and clinical effectiveness. The lidocaine 4% foam microemulsion formulation was designed to improve the ability of topically applied lidocaine to penetrate the skin without the messiness associated with cream and ointment formulations, while offering the advantage of a rapid, 20-minute interval application to achieve quick, effective, and safe pain relief. Eight of the 10 patients in this study preferred this mode of interval application to single application traditionally used with creams.

The well-established efficacy and safety profile of topical lidocaine 4% makes it a useful tool within the dermatology practice, but there are several disadvantages with previously marketed formulations. The lidocaine 4% foam rubs in and is well absorbed by the skin, obviating the need for an occlusive dressing and messy removal. The lidocaine 4% foam can be stored at room temperature, requiring no special storage arrangements and increasing the feasibility of its use in clinical practice.

The results from this pilot, 10-patient, open-label study suggest that the lidocaine 4% foam may be acceptable to both patients and clinicians for the safe and effective reduction of pain associated with cosmetic dermatologic laser procedures. However, a blinded, placebo-controlled study of a larger population is needed to confirm these preliminary results.

References
1.    Harvard Health Publications. Cosmetic surgery A to Z: a guide to cosmetic procedures and laser skin treatment.  http://www.health.harvard.edu/special_health_reports/Cosmetic_Surgery.htm. Accessed December 12, 2008.
2.    American Academy of Dermatology. Consumer Alert: Questions to ask for safe and successful cosmetic surgery. http://www.newswise.com/articles/view/531866/. Accessed December 12, 2008.
3.    Amin SP, Goldberg DJ. Topical anesthetics for cosmetic and laser dermatology. J Drugs Dermatol. 2005;4(4):455–461.
4.    Kaweski S. Topical anesthetic creams. Plast Reconst Surg. 2008;121(6):1261–1265.
5.    Koay J, Orengo I. Application of local anesthetics in dermatologic surgery. Dermatol Surg. 2002;28(2):143–148.
6.    Alster TS. The lidocaine/tetracaine peel: a novel topical anesthetic for dermatologic procedures in adult patients. Dermatol Surg. 2007;33(9):1073–1081.
7.    Railan D, Alster TS. Use of topical lidocaine for cosmetic dermatologic procedures. J Drugs Dermatol. 2007;6(11): 1104–1108.
8.    Nestor MS. Safety of occluded 4% liposomal lidocaine cream. J Drugs Dermatol. 2006;5(7):618–620.
9.    Carruthers A, Carruthers J. Single-center, double-blind, randomized study to evaluate the efficacy of 4% lidocaine cream versus vehicle cream during botulinum toxic type A treatments. Dermatol Surg. 2005;31(12):1655–1659.
10.    Friedman PM, Fogelman JP, Nouri K, et al. Comparative study of the efficacy of four topical anesthetics. Dermatol Surg. 1999;25(12):950–954.
11.    Guardiano RA, Norwood CW. Direct comparison of EMLA versus lidocaine for pain control in Nd:YAG 1064nm laser hair removal. Dermatol Surg. 2005;31(4):396–398.
12.    Gorgos D. Topical anesthetic safety becomes important focus after recent deaths. Dermatol Nurs. 2005;17(4): 312–313.
13.    FDA Consumer Health Information. Use caution with over-the-counter creams, ointments. http://www.fda.gov/ consumer/updates/otc_creams040108.htm. Accessed October 14, 2008.
14.    Beer K. Numbing alternatives. Skin & Aging. 2008;16(9).
15.    Scheinfeld N. Legal considerations in the application of topical lidocaine. Skin & Aging. 2007;15(9).
16.    US Food and Drug Administration. Life-threatening side effects with the use of skin products containing numbing ingredients for cosmetic procedures. http://www.fda.gov/Cder/drug/advisory/topical_anesthetics.htm. Accessed October 14, 2008.
17.    International Association for Physicians in Aesthetic Medicine (posted on March 4, 2008). “Statistics show clients choosing medical spas over plastic surgeons”. http://www.iapam.com/ArticlesPR/2007 AestheticStatistics.html.

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