EACH year more than 10 million wounds are CLINICAL INVESTIGATIONS. LET versus EMLA for Pretreating Lacerations: A Randomized Trial

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1 ACADEMIC EMERGENCY MEDICINE March 2001, Volume 8, Number CLINICAL INVESTIGATIONS LET versus EMLA for Pretreating Lacerations: A Randomized Trial ADAM J. SINGER, MD, MARY JO STARK, RN Abstract. Objective: To compare the anesthetic efficacy of EMLA cream (eutectic mixture of local anesthetics) with that of LET solution (lidocaine, epinephrine, tetracaine) for pretreating lacerations prior to lidocaine injection. Methods: This was a randomized, double-blind clinical trial in a convenience sample of 60 patients aged 1 to 59 years with traumatic lacerations. Eligible wounds were uncomplicated, clean lacerations 6 hours old. Finger and toe lacerations were excluded. At the time of initial presentation to triage, patients were randomized to LET or EMLA. A nurse applied the topical anesthetic into the laceration with a 5-mL syringe. A physician assessed the laceration edges for the presence of blanching and adequacy of anesthesia to a 27-gauge needlestick. Supplemental lidocaine was then infiltrated through the wound edges and the pain of infiltration was recorded by the patient (or guardian) on a 100-mm visual analog scale marked most pain at the high end. A sample of 44 patients had 90% power to detect a 20-mm difference in injection pain (two-tailed = 0.05). Results: Sixty patients were randomized to LET (29) or EMLA (31). Median age was 8.5 years; 23% were female. Most lacerations were facial and closed with sutures. There was no difference in baseline characteristics between groups. More wounds treated with LET were anesthetic to a needlestick than wounds treated with EMLA (73% vs 40%, p = 0.01); however, there was no between-group difference in the median pain of lidocaine infiltration (LET 12 mm vs EMLA 13 mm, p = 0.89). Conclusions: Pretreatment of simple lacerations with LET or EMLA at the time of patient presentation results in similar amounts of pain of subsequent local infiltration of lidocaine. Key words: lacerations; local anesthesia; LET; EMLA. ACADEMIC EMERGENCY MEDICINE 2001; 8: EACH year more than 10 million wounds are cared for in emergency departments (EDs) throughout the United States. 1 Many of these are traumatic lacerations requiring primary closure. Since wound preparation and closure are often painful, some form of local anesthesia is usually required. While infiltration of a local anesthetic is the most effective and commonly used method of anesthesia, it too is painful. 2 As a result, several methods have been proposed for reducing the pain associated with local anesthetic injection, including buffering and warming of the anesthetic solution, using a small needle, injecting into the subcutaneous plane, slowing the rate of injection, and injecting through the wound edges. 3 A recent study has demonstrated that pretreatment of lacerations From the Department of Emergency Medicine, State University of New York at Stony Brook, Stony Brook, NY (AJS, MJS). Received October 2, 2000; revision received November 3, 2000; accepted November 13, Presented at the SAEM annual meeting, San Francisco, CA, May Address for correspondence and reprints: Adam J. Singer, MD, Department of Emergency Medicine, University Medical Center, L4-515, Stony Brook, NY Fax: ; asinger@epo.som.sunysb.edu with a topical lidocaine epinephrine tetracaine gel (LET) significantly reduces the pain of lidocaine injection when compared with a placebo. 4 By having nurses apply LET at the time of the patient s initial presentation to the triage desk, these investigators were able to overcome one of the major disadvantages of topical anesthetics, i.e., their delayed onset of anesthesia. Since most patients were not seen by a physician for at least minutes, there was usually adequate time for onset of anesthesia. 4 While many topical anesthetic combinations have been evaluated [such as a eutectic mixture of lidocaine and prilocaine (EMLA), LET and a combination of tetracaine adrenaline cocaine (TAC)], a recent study suggested that EMLA cream may be the most effective topical anesthetic for repair of lacerations. 5 However, EMLA cream is more expensive than most other topical anesthetics, may be associated with methemoglobinemia on rare occasions, and is currently approved for use on normal intact skin only. The objective of the current study was to compare the amounts of pain of lidocaine injection and adequacies of anesthesia of traumatic lacerations pretreated with LET or

2 224 LET VS EMLA Singer, Stark LET VS EMLA FOR PRETREATING LACERATIONS TABLE 1. Inclusion and Exclusion Criteria Inclusion criteria Patient at least 1 year old Uncomplicated lacerations less than 6 hours old thought to require closure Exclusion criteria Patient age less than 1 year Multiple trauma Peripheral vascular disease Diabetes mellitus Bleeding diathesis Pregnancy Personal or family history of keloids or hypertrophic scars Allergy to any study medication Medications predisposing to methemoglobinemia Bites Puncture wounds Crush injuries Presence of devitalized tissue Infected or heavily contaminated lacerations Lacerations more than 6 hours old The presence of a rash Lacerations on the digits, nose, ears, penis EMLA at the time of initial patient presentation to the triage desk. We hypothesized that there would be no between-group difference in these outcomes. METHODS Study Design. A randomized, double-blind, controlled trial design was used to compare the amounts of pain of lidocaine injection and the proportions of adequately anesthetized wounds after topical application of LET or EMLA at the time of triage in healthy patients with simple lacerations. This project was approved by the institutional review board. Study Setting and Population. The trial was conducted in the ED of the State University of New York at Stony Brook, a tertiary care center with an annual census of 65,000. A convenience sample of patients with lacerations that the triage nurse thought would require some form of wound closure was enrolled. Specific inclusion and exclusion criteria are shown in Table 1. Study Protocol. Patient lacerations are routinely evaluated by the triage nurse. At the time of initial presentation to triage, patients meeting all eligibility requirements were randomized to treatment with either topical application of LET gel (lidocaine 2%, epinephrine 1:1,000, tetracaine 2%) or EMLA cream (eutectic mixture of lidocaine 2.5% and prilocaine 2.5%, Astra USA, Inc., Westborough, MA). After obtaining written informed consent from the patients or their guardians, the next in a series of opaque consecutively numbered 5-mL syringes containing the study solution was used. The syringes had similar appearances. The syringes were prepared by hospital pharmacy personnel not connected to the ED or enrollment process, and assignments were generated by a computerized random number program. There were equal proportions of syringes containing LET and EMLA. After enrollment of the first 44 patients (the study target number), data analysis demonstrated that the proportions of facial lacerations and children differed between the two study groups. As a result, an additional 16 patients were enrolled stratified by age and wound location in order to ensure similar baseline characteristics. Throughout the entire study, double-blinding of study assignment was maintained. The topical anesthetics were injected into the laceration with a syringe (without needle) and the wound was covered with sterile dry gauze that was secured with adhesive tape. The wound was injected with up to 5 ml of study gel or cream or a smaller amount as allowed by wound size. Nurses were instructed to inject enough topical anesthetic to completely fill and cover the wound; however, no attempt to standardize the amount of anesthetic used was made. The doses of LET and EMLA were chosen to keep the total dose of lidocaine below the toxic range assuming that all of the lidocaine was absorbed (5 mg/kg). Care was taken to avoid unintentional spillage into the eyes, nose, or mouth by covering them with dry gauze. Application of the study medication required less than 1 minute. After topical application of the study medication, patients or their guardians (for patients less than age 8) assessed the pain of application on a 100-mm visual analog scale (VAS) marked most pain at the high end. A wound registry data sheet was prospectively completed for all patients in the study using a closed-question format. 6 Information recorded included patient demographics (age, sex, race); medical history and medications; wound characteristics (etiology of wound, time of injury, wound location, length, shape and margin, degree of contamination, and presence of foreign bodies); wound preparation (type of anesthetic, method of irrigation or scrub and solution used, and wound debridement); and wound closure techniques. All lacerations were then assessed by an attending emergency physician or an experienced physician assistant who determined the presence of blanching of the wound edges. The practitioners were asked to guess which study medication was applied to the wounds. The practitioners also determined whether the wound edges were anesthetized to a stick with a 27-gauge needle. Wounds were then slowly injected with lidocaine 1% using

3 ACADEMIC EMERGENCY MEDICINE March 2001, Volume 8, Number a 30-gauge needle at the discretion of the practitioner through the lacerated wound edges. Immediately after injection the patient or his or her guardian (for patients under age 8) assessed the pain of infiltration on the 100-mm VAS. Administration of the VAS was performed by a trained research assistant 7 who was also blinded to study medication assignment. Wounds were then managed following standard principles of care 3 at the discretion of the emergency practitioner. All patients were either seen in the ED or contacted by phone within one week to determine the presence of wound infection. Wounds were considered to be infected if they required antibiotics for treatment by any health care provider. 6 Outcomes. The primary outcomes were the pain of lidocaine infiltration assessed by the patients or their guardians on a previously validated 100-mm VAS measured to the nearest millimeter 8 and the proportion of lacerations that were adequately anesthetized to a 27-gauge needlestick. Secondary outcomes were the pain of topical application of the study medication on a similar VAS and the presence of wound infection. Infection was assessed with respect to erythema, edema, pain, and temperature using a four-point scale for each. The overall clinical impression of infection has been shown to be reliable with high interobserver concordance. 6 For patients who did not return to the ED for follow-up within one week, infection was considered present if patients had been prescribed an antibiotic by a physician for a wound infection. Data Analysis. Data were entered into Access 97 (Microsoft, Inc., Redmond, WA) and imported into SPSS 8.0 for Windows (SPSS, Inc., Chicago, IL) for statistical analysis. Continuous variables are presented as medians with interquartile ranges (IQRs). Categorical data are presented as percent frequency of occurrence. For both pretreatment characteristics and outcomes, continuous variables were compared using a Mann-Whitney U test for nonparametric data. The 2 test was used to compare categorical variables. Analysis of variance was used to control for potential confounding variables (such as age, wound location, and buffering of anesthetic). For all tests, statistical significance was set at a level of Sample size calculations were based on prior estimates of the pain associated with anesthetic injection. 2 The sample size necessary to detect a 20- mm between-group difference in pain with a power of 0.90 and of 0.05 using a two-tailed t-test was Figure 1. Study profile.

4 226 LET VS EMLA Singer, Stark LET VS EMLA FOR PRETREATING LACERATIONS Figure 2. Box plot of pain of lidocaine injection by treatment. The hatched boxes represent the interquartile range, while the bold line is the median. The whiskers denote the range. 22 in each group. 9 A difference of less than mm on a visual analog pain scale is not believed to be of any clinical significance. 10,11 RESULTS During a four-month study period, a convenience sample of 65 patients were screened for enrollment in the study and five patients were excluded (Fig. 1). The median age of the 60 enrolled patients was 8.5 years (range, 1 to 59 years), and 23% were female. Roughly three fourths of the wounds were located on the face and 42 of the 60 occurred in children under age 18. The median wound length was 2 cm (range, 0.5 to 10 cm). The patients in the two groups were similar for age, gender, wound length, and wound location (Table 1). Nearly all wounds were closed with sutures (39), tissue ad- TABLE 2. Patient and Wound Characteristics LET (n = 29) EMLA (n = 31) p-value Children less than age 18, no. (%) 22 (76%) 20 (65%) 0.41 Females no. (%) 7 (24%) 7 (23%) 0.56 Facial lacerations no. (%) 22 (76%) 22 (71%) 0.84 Median length (IQR*), cm 2 ( ) 2 (1 3.0) 0.62 Median duration of application (IQR), minutes 34 (26 45) 40 (34 50) 0.21 Blanching of edges no. (%) 15 (58%) 16 (53%) 0.74 Practitioner correctly guessed solution no. (%) 13 (50%) 13 (43%) 0.62 Buffered lidocaine no. (%) 5 (20%) 6 (21%) 1.00 Median volume of injected lidocaine (IQR), ml 2 ( ) 2 ( ) 0.58 Type of closure no. (%) 0.23 Suture Staples Tissue adhesive 15 (52%) 6 (21%) 4 (14%) 24 (77%) 3 (10%) 2 (6%) *IQR = interquartile range.

5 ACADEMIC EMERGENCY MEDICINE March 2001, Volume 8, Number TABLE 3. Outcomes LET (n = 29) EMLA (n = 31) p-value Median pain of application (IQR*), mm 5 (0 13) 0 (0 1) Completely anesthetized wounds no. (%) 19 (73%) 12 (40%) 0.01 Supplemental lidocaine injection in closed wounds no. (%) 23 (79%) 28 (97%) 0.29 Median pain of injection for entire group (IQR), mm 12 (4 36) 13 (6 32) 0.89 Median pain of injection for ages 8 or older (IQR), mm 16 (10 34) 13 (8 32) 0.36 Median pain of injection for ages less than 8 (IQR), mm 7 (1 29) 14 (5 32) 0.46 ED follow-up no. (%) 15 (52%) 14 (45%) 0.80 Wound infections no. (%) 0 (0%) 0 (0%) 1.00 *IQR = interquartile range. hesive (9), or staples (6). Methods of wound closure were similar between groups (Table 1). The median duration of topical anesthetic application was 40 minutes (range, 15 to 135 minutes). The median topical anesthetic application times were similar between groups (Table 1). Of the 54 wounds that were closed, 51 received supplemental injection of lidocaine. The proportions of patients whose wounds were closed who received supplemental injection of lidocaine were similar in the two groups (92% for LET vs 97% for EMLA, p = 0.47). Wounds treated with LET were more frequently anesthetic to a stick with a 27-gauge needle than wounds treated with EMLA (73% vs 40%, respectively, p = 0.01). However, there was no difference in the median pain of supplemental lidocaine injection between the two groups (Fig. 2 and Table 2). There was also no between-group difference in pain of injection when only pain assessments performed by the patients themselves (i.e., age >7) were included (LET 16 mm vs EMLA 13 mm, p = 0.36). There was also no difference in the primary outcomes after controlling for age, buffering, and/or wound location. The median pain of topical anesthetic application was 5 mm lower in the group of patients assigned to EMLA (Table 3). Of all patients, 29 returned to the ED for followup and 31 were contacted by phone. All patients contacted by phone had been seen by their private physicians. There was no between-group difference in the proportion of patients who returned to the ED for follow-up (Table 3). There was no wound infection in either group. DISCUSSION Since their application is relatively painless and without risk of an unintentional needlestick, a variety of topical anesthetics have been used alone or in conjunction with supplemental lidocaine injection for laceration repair. A combination of tetracaine, adrenaline, and cocaine (TAC) has been most extensively studied and shown to be an effective topical anesthetic prior to laceration repair, especially in children and for facial and scalp lacerations. 12 However, cocaine is a controlled substance that requires special documentation and storage procedures. Furthermore, improper use of TAC has on rare occasions resulted in seizures 13 and death, 14 all of which have led to its recent loss of favor. Various combinations of lidocaine (1% to 4%), adrenaline (1:1,000 to 1:2,000), and tetracaine (0.5% to 2%) have compared favorably with TAC, without the risks and administrative hassles associated with cocaine. 15 LET is also at least ten times less costly than TAC 15 and easy to prepare from its constituents, leading to its increasing popularity for use prior to laceration repair. EMLA cream is a eutectic mixture of local anesthetics (prilocaine and lidocaine) suspended in an oil-in-water suspension. Since the melting point of this mixture is less than either of its components, EMLA is a liquid at room temperature allowing a high concentration of anesthetics (80%) within the emulsion droplets of the cream even though it contains only a 5% total concentration of local anesthetics. This high concentration of the local anesthetics within the high-water-content medium results in enhanced transdermal penetration of the active agents. 16 EMLA cream has been shown to produce reliable topical anesthesia for a variety of painful cutaneous procedures such as venipuncture, 17 lumbar puncture, 18 vaccination, 19 and circumcision. 20 While EMLA is not approved for use over nonintact skin, Zempsky and Karasic recently compared the anesthetic efficacy of EMLA with that of TAC for suturing 32 uncomplicated extremity lacerations. They found that the EMLA-

6 228 LET VS EMLA Singer, Stark LET VS EMLA FOR PRETREATING LACERATIONS treated wounds were more often repaired without the need for supplemental anesthesia than were the wounds treated with TAC (85% vs 45%, p = 0.03). 5 They concluded that EMLA was superior to TAC for anesthesia of simple extremity lacerations. One of the major disadvantages of EMLA cream is its relatively slow rate of absorption and onset of anesthesia. Most studies suggest that approximately one hour is required prior to anesthetic onset after application of EMLA to intact skin. This slow rate of absorption may be enhanced by stripping the stratum corneum (the major barrier to transdermal drug delivery) with adhesive tape 21 ; however, tape stripping is impractical for open wounds. While it seems reasonable that the absorption of EMLA would be more rapid when applied to an open wound, this has not been well established. Indeed, the study by Zempsky and Karasic suggests that the onset of topical anesthesia is almost one hour even after application to open wounds. 5 Other topical anesthetics may have a more rapid onset of action than EMLA; however, all require at least minutes before wound repair can proceed, leading to considerable delays in patients lengths of stay in the ED. This delay between topical application and wound repair can be obviated by having a nurse apply the anesthetic as soon as the patient presents to the triage desk. Indeed, a recent study comparing the amounts of pain of lidocaine injection after pretreatment of lacerations with either LET or placebo at the time of patient triage demonstrated the feasibility and effectiveness of such an approach. 4 Since, to the best of our knowledge, EMLA cream has never been directly compared with LET, our study was designed to compare the efficacies of these two topical anesthetics after being applied as soon as the patients presented to the triage desk. In the current study, the proportion of wounds anesthetic to a needlestick was greater for patients assigned to the LET group. It is possible that had more time elapsed between anesthetic application and wound evaluation, more EMLA-treated wounds would have been anesthetic. However, this would have required the practitioner to wait an additional half hour (on average), prolonging the patient s stay in the ED, which would have defeated one of the purposes of the study. In addition, the amounts of pain of subsequent lidocaine injection (which is more clinically relevant than the mere presence of anesthesia to needlestick) were similar whether lacerations were pretreated with topical LET or EMLA cream. Also, the proportions of wounds requiring supplemental lidocaine after pretreatment with either topical anesthetic were not significantly different. While there was a statistically significant difference noted between the groups in the pain of topical anesthetic application in favor of EMLA, this difference of 5 mm does not appear clinically significant. Indeed, a study by Todd et al. suggests that any difference of less than 13 mm on a pain VAS is of no clinical significance. 10 Since LET is considerably less expensive than EMLA ($1 2 vs $8 16, respectively) and EMLA is not recommended for use in open wounds, we believe that LET is the more appropriate topical anesthetic for pretreating lacerations prior to their repair. Furthermore, topical application of EMLA cream may be associated with rare occurrences of methemoglobinemia. 22 Another potential advantage of pretreating wounds with LET as soon as the patient presents at triage is the reduction in the patient s overall ED length of stay. While we did not measure length of stay in this study, it is intuitive that having lacerations ready for injection when the emergency practitioner first evaluates them would indeed save time. The alternative would be for the emergency practitioner to apply a topical anesthetic and wait for an additional minutes before its onset, or proceed with lidocaine injection and wound closure without the benefit of topical anesthesia. Prior to having nurses routinely apply LET at the time of initial triage, they should be carefully instructed on the appropriate indications and contraindications for its use. For example, use of epinephrine containing solutions should be avoided in the digits. In the current study, the median duration of EMLA application was only 40 minutes, 15 minutes less than the average time required for it to cause effective anesthesia in a prior study of extremity lacerations. 5 This may have biased the results against EMLA cream. However, the objective of the current study was to achieve adequate anesthesia of the lacerated wound edges that would allow relatively painless injection of supplemental lidocaine. It was not our intention to achieve anesthesia of the skin surrounding the wound edges that would allow painless wound closure without any additional anesthetic. The time required for the lacerated wound edges to become adequately anesthetized is probably shorter than the time required for the skin surrounding the wound to become anesthetized. We routinely inject supplemental lidocaine into wounds that have been pretreated with a topical anesthetic, and see little advantage of proceeding to wound closure without this supplemental injection. It is usually impossible to predict which patients will require further anesthetic during the later stages of wound closure, and most will. Indeed, injection of lidocaine adds very little time to the length of procedure yet ensures painless completion of wound closure. Fur-

7 ACADEMIC EMERGENCY MEDICINE March 2001, Volume 8, Number thermore, our purpose was also to allow the physician to inject wounds with lidocaine as soon as patients were examined and not need to wait up to an hour after the topical anesthetic was applied. We do not believe that our results contradict those of Zempsky and Karasic. 5 Due to our small sample size, separate subgroup analysis for facial or extremity wounds as well as for wounds that were repaired without supplemental lidocaine was not possible. Thus, direct comparisons between these two studies is not possible. LIMITATIONS AND FUTURE QUESTIONS Our study has several other limitations that merit discussion. First, while laceration preparation followed basic principles of wound care, 3 it was not standardized. Thus, we did not control for a variety of potential confounding variables that may have affected the pain of infiltration (such as speed and location of injection or buffering of the injected lidocaine). We attempted to control for practitioner experience by limiting the study to our immediate care area where most wounds are closed by an attending emergency physician or a physician assistant with more than 15 years of experience. We also instructed practitioners to inject the lidocaine slowly with a 30-gauge needle. While buffering of lidocaine and the volume injected were not standardized, no difference was noted between groups in either of these two parameters. Second, in the current study the consistencies of the LET gel and EMLA cream were different. It is possible that use of different types of topical anesthetic consistencies (such as solutions, gels, and creams) may have altered the results. However, we chose to compare the two currently available topical anesthetic formulations in our ED. Third, we did not wait the recommended one hour after applying EMLA to wounds prior to injecting them. We also did not cover EMLA-treated wounds with an occlusive dressing as recommended for intact skin. This may have biased the results against EMLA. However, one of the goals of applying a topical anesthetic at the time of patient presentation was to allow immediate infiltration of wounds when the patient was first seen by an emergency practitioner, and this was usually around half an hour. Waiting for an additional half hour in cases of EMLA-treated wounds would have defeated our objective of allowing practitioners to inject all wounds when first seen. Dry gauze was used to cover lacerations in order to adsorb oozing blood. Fourth, most wounds were located on the face. This may limit the generalizability of our results to non-facial wounds and explain the differences between our results and those of Zempsky and Karasic. 5 Fifth, our data included pain assessments performed both by patients and their guardians (for children less than 8). This method has been reported previously. 4 A recent study by Kelly limited to children between 8 and 15 years old suggests that parents pain scores may not be highly correlated with their childs ratings. 23 However, even when our data analysis was limited to pain ratings performed by patients at least 8 years old, we could not detect a significant between-group difference in the pain of injection. Post hoc analysis indicated that the power of our sample size to detect a 20-mm difference between groups in the pain of injection was 75% and 56% for the older and younger age groups, respectively. Furthermore, in order to be truly representative of patients sustaining lacerations, we thought that our study should include all age groups. Only half of the patients returned to the ED for follow-up. Thus, in half of the patients the determination of wound infection (a secondary outcome) was based on whether the patients had received an antibiotic from a physician to treat infection. While patients specificity at diagnosing wound infections is quite high, they lack sensitivity. 24 We therefore relied on the patients physicians to determine the presence of infection. However, some patients may not have identified infection and thus were never seen by their physicians. As a result, our study may have underestimated the incidence of infection in either of the study groups. Since the proportions of patients returning to the ED for follow-up were similar regardless of treatment assignment, this would have applied equally to both groups. Additionally, the study sample size was too small to detect any differences in infection rate between the groups. Finally, this was a convenience sample and not a consecutive series, thus we cannot exclude a selection bias. However, this would have applied equally to both study groups, since the study was both randomized and blinded. Future studies should include more extremity lacerations and other anesthetic formulations that may allow closure of wounds without the need for and additional infiltration of lidocaine. CONCLUSIONS Our study suggests that pretreatment of uncomplicated lacerations at the time of patient presentation to the triage desk with LET or EMLA cream results in a similar reduction in the pain of subsequent injection of lidocaine. Since it is less expensive and not contraindicated in open wounds, we believe that LET is the preferred topical anesthetic. Early application of LET at triage also has the potential to reduce the patient s ED length of stay, and should be considered in all eligible lacerations.

8 230 LET VS EMLA Singer, Stark LET VS EMLA FOR PRETREATING LACERATIONS The authors thank Dr. Henry C. Thode Jr. for his assistance with the statistical analysis. References 1. McCaig LF, Stussman BJ. National Hospital Ambulatory Medical Care Survey: 1996 Emergency Department Summary. Advanced data from Vital Health Statistics; no Hyattsville, MD: National Center for Health Statistics, 1997 (DHSS publication no. (PHS) ). 2. Singer AJ, Richman B. Comparison of patient and practitioner assessment of pain from commonly performed emergency department procedures. Ann Emerg Med. 1999; 33: Singer AJ, Hollander JE, Quinn JV. Evaluation and management of traumatic lacerations. N Engl J Med. 1997; 337: Singer AJ, Stark MJ. Pretreatment of lacerations with lidocaine, epinephrine, and tetracaine at triage: a randomized double-blind trial. Acad Emerg Med. 2000; 7: Zempsky WT, Karasic RB. EMLA versus TAC for topical anesthesia of extremity wounds in children. Ann Emerg Med. 1997; 30: Hollander JE, Singer AJ, Valentine S, Henry MC. Wound registry: development and validation. Ann Emerg Med. 1995; 25: Hollander JE, Valentine SM, Brogan GX. Academic associate program: integrating clinical emergency medicine research with undergraduate education. Acad Emerg Med. 1997; 4: Huskisson EC. Visual analogue scales. In Melzack R (ed). Pain Measurement and Assessment. New York: Raven Press, 1983, pp Cohen J. Statistical Power Analysis for the Behavioral Sciences. Hillsdale, NJ: Lawrence Erlbaum Associates, Todd KH, Funk KG, Funk JP, et al Clinical significance of reported changes in pain severity. Ann Emerg Med. 1996; 27: Singer AJ, Kowalska A, Thode HC. Determination of the significance of pain severity and the minimal clinically significant difference on a pain scale [abstract]. Acad Emerg Med. 1999; 6: Hegenbarth MA, Altieri MF, Church F, et al. Comparison of topical tetracaine, adrenaline, and cocaine anesthesia with lidocaine infiltration for repair of lacerations in children. Ann Emerg Med. 1990; 19: Daya MR, Burton BS, Schleiss MR, et al. Recurrent seizures following mucosal application of TAC. Ann Emerg Med. 1988; 17: Dailey RH. Fatality secondary to misuse of TAC solution. Ann Emerg Med. 1988; 17: Ernst AA, Marvez-Valls E, Nick TG, Weiss SJ. LAT (lidocaine adrenaline tetracaine) versus TAC (tetracaine adrenaline cocaine) for topical anesthesia in face and scalp lacerations. Am J Emerg Med. 1995; 13: Steward DJ. Eutectic mixture of local anesthetics (EMLA): what is it? What does it do? J Pediatr. 1993; 122:S21 S Robieux I, Kumar R, Radhakrishnan S, Koren G. Assessing pain and analgesia with a lidocaine prilocaine emulsion in infants and toddlers during venipuncture. J Pediatr. 1991; 118: Halperin DL, Koren G, Attias D, et al. Topical skin anesthesia for venous, subcutaneous drug reservoir and lumbar puncture in children. Pediatrics. 1989; 84: Taddio A, Nulman I, Goldbach M, Ipp M, Koren G. Use of lidocaine-prilocaine cream for vaccination pain in infants. J Pediatr. 1994; 124: Taddio A, Stevens B, Craig K, et al. Efficacy and safety of lidocaine prilocaine cream for pain during circumcision. N Engl J Med. 1997; 336: Singer AJ, Shallat J, Vallentine S, Doyle L, Thode HC. Cutaneous tape stripping to enhance topical drug absorption. A randomized controlled trial. Acad Emerg Med. 1998; 5: Jakobson B, Nillson A. Methemoglobinemia associated with a prilocaine lidocaine cream and trimethoprim sulfamethoxazole: a case report. Acta Anaesthesiol Scand. 1985; 29: Kelly A. Lack of correlation between parent and child visual analogue scale pain score: a challenge for pediatric pain and analgesia research [abstract]. Acad Emerg Med. 2000; 7: Seaman M, Lammers R. Inability of patients to self-diagnose wound infections. J Emerg Med. 1991; 9:215 9.