PEDIATRICS Vol. 109 No. 6 June 2002, pp. 1093-1099
A Clinical Study to Evaluate the Efficacy of ELA-Max (4% Liposomal Lidocaine) as Compared With Eutectic Mixture of Local Anesthetics Cream for Pain Reduction of Venipuncture in Children
From the Division of Pediatric and Adolescent Dermatology, Children’s Hospital, San Diego, and Departments of Pediatrics and Medicine, University of California, San Diego School of Medicine, San Diego, California
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Objective. A double-randomized, blinded crossover trial was performed to assess the efficacy of ELA-Max (4% liposomal lidocaine) as compared with eutectic mixture of local anesthetics (EMLA) for pain relief during pediatric venipuncture procedures. Safety was assessed by evaluation for topical or systemic effects and measurement of serum lidocaine concentrations.
Methods. A total of 120 children who were scheduled for repeat venipuncture for non–study-related reasons at 2 sites participated in the study. Patients were doubly randomized to treatment regimen (study medication application time of either 30 or 60 minutes) and to the order of application of the topical anesthetics for each venipuncture. The primary outcome measures were the child’s rating of pain immediately after the venipuncture procedures using a 100-mm visual analog scale (VAS) tool and the parent’s and blinded research observer’s Observed Behavioral Distress scores.
Results. Both ELA-Max and EMLA seemed to alleviate venipuncture pain. There was no clinically or statistically significant difference in the patient VAS scores within the 30-minute or 60-minute treatment groups, and there was no clinical or statistical difference in VAS scores between the 30-minute ELA-Max treatment without occlusion and the 60-minute EMLA treatment with occlusion. There were no clinically or statistically significant differences between treatment with ELA-Max and EMLA in parental or blinded researcher Observed Behavioral Distress scores, the most frequent response at any observation time being "no distress."
Conclusion. This study demonstrates that a 30-minute application of ELA-Max without occlusion is as safe and as effective for ameliorating pain associated with venipuncture as a 60-minute application of the prescription product EMLA requiring occlusion.
Key Words: topical anesthesia • liposomal lidocaine • pain • eutectic mixture of local anesthetics
Abbreviations: EMLA, eutectic mixture of local anesthetics • VAS, visual analog scale • OBD, Observed Behavioral Distress • SD, standard deviation
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Venipunctures are common procedures in pediatric care and may be a source of pain, discomfort, and distress for children, parents, and health professionals. Eutectic mixture of local anesthetics (EMLA) cream, a topical anesthetic that contains a mixture of 2.5% lidocaine and 2.5% prilocaine, was approved by the Food and Drug Administration for use as a topical anesthetic in 1992. Many published reports document its adult and pediatric analgesic effectiveness in a variety of procedures, such as venipuncture,1–3 intravenous catheterization,4 various urology procedures,5 circumcision,6 lumbar punctures,7 laser treatments,8 skin graft harvesting,9 ulcer debridement,10 and various skin surgeries.11 Standard recommendations state that EMLA should be applied for a minimum of 60 minutes with occlusion, although it has been reported that longer application times may be necessary for some procedures.12–14 Because of long application times, use of EMLA may not be practical or optimal in all settings.
ELA-Max, in both 4% and 5% liposomal lidocaine preparations, has been shown to be an effective topical skin anesthetic.15–18 Liposomes have been used to enhance the action of various topical medications, including anesthetics, by facilitating the rate and extent of drug absorption and protecting the drug from being rapidly metabolized. Liposome-encapsulated lidocaine medications remain in the epidermis after topical application, affording fast, lasting anesthetic relief.19,20 ELA-Max is recommended for use with a 30-minute application time without occlusion.
This study was designed to evaluate the anesthetic effects and safety of ELA-Max as compared with EMLA cream for venipuncture procedures in children using various application times and techniques.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Participants
A total of 120 children, 5 to 17 years of age (20 children in San Diego, CA; 100 children in West Palm Beach, FL), who were scheduled for at least 2 venipunctures for non–study-related reasons at 2 sites, participated in the study. Each child demonstrated appropriate understanding of the visual analog scale (VAS) before initiating study procedures. Patients who participated in the study were not taking any analgesic or anxiolytic medications and had no previous experience with or known allergies to either of the study medications (ELA-Max or EMLA). In addition, patients with concurrent skin disease of such severity that it would interfere with therapeutic evaluation were excluded from the study. Parents or guardians who accompanied the child had to be available to observe both venipunctures and had to be willing to complete the Observed Behavioral Distress (OBD) scoring tool. Informed consent was obtained.
Design
Subject demographic information, including gender, race, birth date, height, and weight, was collected. The study used a crossover design of 2 sets of patients. Children were randomized into 1 of 2 regimens: the 30-minute regimen, in which each patient received 30-minute applications of both ELA-Max and EMLA and in random order, or the 60-minute regimen, in which each received a 60-minute application of both products in random order on different venipuncture days. Randomizations were generated and maintained by Ferndale Laboratories, Inc. Regimen 1 consisted of 2 treatments: 1) ELA-Max, approximately 2.5 g, applied without occlusion for a 30-minute application time before venipuncture and 2) EMLA cream, approximately 2.5 g, applied with occlusion (using Tegaderm) for a 30-minute application time before venipuncture. Regimen 2 also consisted of 2 treatments: 1) ELA-Max, approximately 2.5 g, applied with occlusion (using Tegaderm) for a 60-minute application time before venipuncture, and 2) EMLA cream, approximately 2.5 g, applied with occlusion (using Tegaderm) for a 60-minute application time before venipuncture.
EMLA was used under occlusion in both regimens, as it is used standardly. ELA-Max was tested both with and without occlusion. Except for study personnel who dispensed and applied the topical anesthetic (noted as unblinded), all personnel present at time of venipuncture (the patient, the parent, the phlebotomist, and the research observer) were blinded to which test article was used. For the 30-minute regimen, blinding was maintained by having a third party place and remove the topical agents with and without occlusion, with the observed behavioral test scorer brought into the venipuncture room after removal of the topical creams. To prevent any prolonged patient waiting in the event of a failed venipuncture, 2 venipuncture sites were prepared for treatment during the first visit. The venipuncture site used successfully for the first study venipuncture was noted.
On the second visit, the same site that had been used successfully for the treatment 1 venipuncture was prepared and used for the second venipuncture, except for 1 patient in whom different venipuncture sites were used for each venipuncture. After the appropriate application time, the anesthetic cream was removed. Staff observed and recorded skin erythema, pallor, skin discomfort, or pruritus. The venipuncture was then performed and observed. Any adverse events were documented. After completion of the venipuncture, the child completed the VAS to assess procedural pain. Both the parent and a blinded research observer completed the OBD tool, which ranked observed patient distress at placement of the tourniquet (anticipatory), at the needle insertion (insertion), and at the placement of the adhesive bandage (recovery). The phlebotomist rated the difficulty of the venipuncture. The second venipuncture procedure was performed at least 24 hours after the first. Procedures were repeated as outlined above. Children and parents were also queried concerning any intercurrent adverse events related to the previous venipuncture. In 10 randomly chosen regimen 2 ELA-Max–treated patients at 1 of the sites, a 2-mL blood sample was collected at the time of venipuncture for serum lidocaine determinations.
Measures
The primary outcome measures were the child’s rating of pain immediately after venipuncture procedures and the parent’s and blinded research observer’s OBD scores. Children used a standardized 100-mm VAS tool, which uses a horizontal scale that ranges from "no pain at all" (happy face on the extreme left side of the scale) to "the worst pain imaginable" (sad face on the extreme right of the scale21). The parent and research observer rated behavioral distress on a 6-point numerical scale (0 = not distressed to 5 = extremely distressed) during 3 parts of the procedure: 1) anticipation, from treatment room entry until the tourniquet was placed; 2) needle insertion; 3) recovery, at time of placement of adhesive bandage on venipuncture site.
Blinded staff also rated the difficulty of the venipuncture procedure as easy (blood was drawn with 1 insertion), difficult (blood was drawn with 1 insertion but included probing for vein), or very difficult (blood was drawn but needed more than 1 needle insertion).
Statistical Methods
SAS version 6.12 statistical software (SAS Institute, Cary, NC) was used, and statistical significance was defined as P 
.05. Demographic and background characteristics for all patients were summarized by application time and initial treatment combinations. Continuous variables—age, height, and weight—were compared between treatments within application times using either the 2-sample t test or Wilcoxon’s 2-sample test. Discrete variables—gender, race, and history of any allergies—were compared between treatments within application times using 
2 tests.
The patients’ self-ratings of pain by VAS were initially analyzed within each application time using a 2-period, 2-treatment crossover model with terms for center (San Diego or West Palm Beach), treatment sequence (ELA-Max followed by EMLA or EMLA followed by ELA-Max), their interaction, patient within sequence within center, period (application 1 or 2), period by center interaction, treatment (ELA-Max or EMLA), and treatment by center interaction. Preliminary assessments of the center, carryover, and carryover by center interaction terms were made by testing these terms using patient within sequence within center as the error term. None of these effects was statistically significant (P > .185 in all cases), indicating consistency of outcomes at the 2 centers and no evidence of carryover effect.
A reduced model, removing all terms involving center, was run on the combined data. This analysis indicated no statistically significant differences between treatments, treatment sequences, or periods (P > .137). Other analyses included comparisons of VAS pain scores, actual time that product was in contact with the skin, and actual elapsed time between removal of test product from skin and venipuncture initially using a 2-way analysis of variance model with terms for center, treatment, and the center by treatment interaction. When the interaction was found to be not statistically significant, a reduced analysis of variance model, including only the center and treatment main effect terms, was used. Because each measure had a small number of outcomes considerably different in magnitude from the majority, the analyses were conducted on ranked data. Discrete efficacy variables were analyzed between treatments for each application time using the Cochran-Mantel-Haenszel test, which tested for treatment differences after adjusting for center effect. Safety data were tabulated by way of counts and percentages.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Statistical testing revealed that there were no significant investigator influences in any category, and therefore data from both sites were combined for analysis. Additional statistical testing showed that there was no carryover effect from the use of one study medication before the other, and the average time between venipunctures was 13.6 ± 9.7 days. A total of 120 patients entered the trial, which could generate up to 240 observations. A total of 117 patients were evaluable. Three patients were excluded from analysis because of incomplete data or serious protocol violation.
Demographics
The demographics of the intent-to-treat group are listed in Table 1 and are reported by treatment regimen (application time 30 or 60 minutes), 60 patients in each regimen. Approximately 87% of the patients in all groups were Hispanic, but there were no statistically significant differences in age, height, weight, gender, or race between those patients randomized to either regimen or treatment.
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Study Variables
Application Times
This study was performed under normal use conditions, and the actual application time for patients in each regimen and treatment category varied nominally from the assigned application time of 30 and 60 minutes. For regimen 1, the mean application time was 30.08 minutes (59 observations) for ELA-Max and 30.47 minutes (59 observations) for EMLA. For regimen 2, the mean application time was 60.00 minutes (58 observations) for ELA-Max and 60.09 minutes (58 observations) for EMLA. These variances were not clinically significant for either the 30-minute or 60-minute application.
Time Between Treatment Removal and Venipuncture
There were no statistically significant differences in the time interval between the removal of either product and the venipuncture procedure. In regimen 1, the mean time interval was 12.90 minutes (standard deviation [SD] = 10.82) in the ELA-Max treatment group versus 13.4 minutes (SD = 10.72) in the EMLA treatment group. In regimen 2, the time interval between treatment removal and venipuncture was 12.83 minutes (SD = 10.95) with ELA-Max and 16.88 minutes (SD = 14.60) with EMLA.
Difficulty of Venipuncture
The venipuncture difficulty did not differ significantly between the treatment groups (Table 2). Overall, regimen 1 and regimen 2 treatment groups had ratings of " easy" in 79.9% of the observations, attesting to the comparability of the treatment groups.
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Efficacy Measures
All efficacy results reported are based on evaluable patients who completed the study. This evaluable group consisted of 59 patients in regimen 1, who each received a 30-minute application of both products in random order, resulting in a total of 118 observations. Fifty-eight patients in regimen 2 each received a 60-minute application of both topical products in random order, resulting in 116 observations. Three patients from the intent-to-treat group were excluded from evaluation; 2 of these were because of discontinuation from the study before treatment by patient request, and 1 patient was considered not evaluable as a result of a protocol deviation (documentation stated that the drug was applied for 5 minutes rather than the required 60 minutes).
VAS Scores
Mean VAS scores were low in all treatment groups; 81.2% of all VAS scores were 10 mm or less on a 100-mm scale, and there was no clinically or statistically significant difference in the VAS scores within the 30-minute or 60-minute treatment groups (Table 3). Comparison of the treatment regimens as recommended in product package inserts was performed, specifically, application of ELA-Max for 30 minutes without occlusion and application of EMLA for 60 minutes with occlusion. VAS scores in these treatment groups did not show statistically significant differences.
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Although there was no significant difference in the VAS scores within treatments, there was a trend for more patients to have lower VAS scores when treated with ELA-Max than when treated with EMLA in the 30-minute treatment group, but this number did not reach significance (Fig 1). This trend was not observed in the 60-minute treatment group (Fig 2).
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OBD Scores
There were no statistically significant differences between treatment with ELA-Max and EMLA in parental or blinded researcher OBD scores at any observation time (anticipatory, insertion, recovery) for regimens 1 and 2. The most frequent response for the parental OBD scores for regimen 1 (30-minute application time) was the observation of "no distress" at anticipation (ELA-Max: 72.9%; EMLA: 72.9%; P = .956), at insertion (ELA-Max: 67.8%; EMLA: 74.6%; P = .385), and at recovery (ELA-Max: 91.5%; EMLA: 91.5%; P = .930). Similar data were seen for blinded researcher OBD scores for regimen 1 (30-minute application time). The most frequent response was "no distress" at anticipation (ELA-Max: 78.0%, EMLA: 81.4%; P = .675), at insertion (ELA-Max: 72.9%; EMLA: 72.9%; P = .907), and at recovery (ELA-Max: 91.5%; EMLA: 89.8%; P = .773).
Likewise, examination of the parental OBD scores for regimen 2 (60-minute application time) found that the most frequent response was the observation of "no distress" at anticipation (ELA-Max: 84.2%; EMLA: 78.9%; P = .466), at insertion (ELA-Max: 77.2%; EMLA: 75.9%; P = .964), and at recovery (ELA-Max: 91.2%; EMLA: 91.2%; P = .971). The blinded researcher OBD scores for regimen 2 (60-minute application time) showed that the most frequent response was the observation of "no distress" at anticipation (ELA-Max: 81.0%; EMLA: 84.5%; P = .436), at insertion (ELA-Max: 74.1%; EMLA: 86.2%; P = .059), and at recovery (ELA-Max: 89.7%; EMLA: 96.6%; P = .084).
Comparison of OBD Scores
Parental and research observer OBD scores at the time of needle insertion were compared for treatment regimens listed in the package insert, ELA-Max applied for 30 minutes without occlusion and EMLA applied for 60 minutes with occlusion. There were no statistically significant differences in parental or research observer scores for the OBD tool at anticipatory, insertion, or recovery periods. The parents and research observers were in agreement from 72.9% to 87.9% of the time at anticipation, from 69.5% to 84.2% of the time at insertion (Table 4), and from 87.7% to 91.5% of the time at recovery.
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Safety Measures
Skin Reactions After Treatment Applications
In the overwhelming majority (>84%) of treatments, no skin reactions of any type were observed at the treatment site (Table 5). There were no statistically significant differences in skin reactions at the treatment site to either study medication at the 30-minute or 60-minute application times. However, more than twice the incidence of "pallor" was observed in patients who were treated with EMLA for 60 minutes with occlusion (n = 9) than in patients who were treated with ELA-Max for 30 minutes without occlusion (n = 4).
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Lidocaine Concentrations
Serum lidocaine concentrations were determined in 10 patients after 60-minute ELA-Max application. The mean age of the patients was 7.9 years, with a range of 3 to 15 years. Nine patients had levels <0.2 µg/mL, with 1 result of 0.3 µg/mL, indicating no clinically significant systemic absorption of lidocaine from ELA-Max when applied for 60 minutes with occlusion (twice the duration recommend for efficacy according to package inserts). Serum concentrations considered toxic must exceed 5 µg/mL, displaying an adequate margin of safety.22 These results corroborate those found by Axelrod et al,23 who assessed serum lidocaine concentrations with ELA-Max use in adult volunteers.
Adverse Events
There were no serious adverse events. Sixty-four events that affect 45 patients were recorded over the course of the study. Only 3 events, all mild in nature, were graded by the medical staff as "probably" related to treatment. Two patients had adverse events at the site of medication application after EMLA use for 30 minutes with occlusion; 1 patient reported tingling and numbness, and 1 patient was observed to have significant pruritus. One patient who was treated with ELA-Max for 60 minutes with occlusion was noted to have mild itching and redness at the application site, which resolved spontaneously.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Unfortunately, painful clinical procedures and interventions are commonplace in pediatric practice. Children may be particularly susceptible to long-lasting untoward psychological effects from a minor, brief, painful event such as venipuncture.24 Multiple studies have documented the perception of pain in infants and children and that painful stimuli elicit significant hormonal and metabolic responses that are suppressed with anesthesia.25,26 In this study, children who underwent routine repeat venipuncture treated with either ELA-Max 4% or EMLA for either 30 or 60 minutes with and without occlusion reported low levels of pain.
EMLA cream has widespread use and acceptance in pediatric practice, although it has limitations to its successful use. Because EMLA achieves poor penetration through intact skin, occlusive dressings are used. Perhaps more clinically significant are standard use recommendations that EMLA be applied under occlusion for a minimum of 60 minutes before a planned procedure, with longer application times often advised.8,27–29
For the 30-minute treatment group, there was a trend for subjects to report lower VAS scores when treated with ELA-Max as compared with EMLA. This difference did not reach significance but was noticeable despite that there were more difficult and very difficult venipunctures for ELA-Max treatments than with the EMLA. There was no clinically or statistically significant difference in the patient VAS scores within the 60-minute treatment group or between the 30-minute ELA-Max treatment without occlusion and the 60-minute EMLA treatment with occlusion. Similarly, blinded parents and researcher observers found no differences between the ELA-Max and EMLA treatments with the most frequent OBD score at any observation time being "no distress" in all treatment groups. This study displays comparable venipuncture pain relief effects and safety of ELA-Max and EMLA under the conditions studied.
A topical anesthesia with a faster onset than EMLA may have significant advantages in clinical practice over those that require longer application times. For example, "prenumbing" the skin with topical anesthesia before injection of local anesthesia becomes easier to perform within a 30-minute application time. In some pediatric cases, it may be practical to have the patient wait in the clinician’s office while the ELA-Max is applied before procedures.
This study did not demonstrate any statistically significant advantage from occlusion of ELA-Max. However, active children may benefit from the addition of an occlusive dressing merely from a practical standpoint; the dressing may hold the anesthetic cream in place. The influence of occlusion on the time course of ELA-Max–induced cutaneous anesthesia should be investigated further.
Methemoglobinemia has been reported in infants and children who have been treated with EMLA cream. The complication is believed to result from deficient methemoglobin reductase in the setting of a methemoglobin stress.30–32 This risk of methemoglobinemia from EMLA was thought to be limited to the first 3 months of life, correlating with low levels of activity of the enzyme nicotinamide adenine dinucleotide cytochrome b5 reductase, which increases to normal with age. However, recent reports have documented methemoglobinemia from EMLA use in older children.33,34 Prilocaine and its metabolites, 4 hydroxy-2-methylaniline and 2 methylaniline (o-toluidine), have been implicated as the methemoglobin stressors in EMLA cream. ELA-Max, however, does not contain prilocaine and therefore would not be expected to increase the risk of methemoglobinemia in infants younger than 3 months.
No serious adverse events were detected in this study. Two patients had adverse events at the site of medication application after EMLA was applied for 30 minutes with occlusion. One of these patients reported tingling and numbness, and 1 patient complained of pruritus at the application site. One patient who was treated with ELA-Max for 60 minutes, with occlusion, experienced mild itching and redness.
Although this study suggests that ELA-Max may offer advantages over commonly used topical anesthetics, the study did not compare the product’s efficacy at prolonged application times. Studies have demonstrated that EMLA works best with longer application times (90–120 minutes),35 although prolonged application times may be impractical in a clinical situation.
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CONCLUSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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This study demonstrates that ELA-Max, a 4% liposomal lidocaine preparation, seems to be an effective and safe product to ameliorate pain associated with pediatric venipuncture and offers new options to standardly used topical anesthetic preparations before cutaneous procedures in children. ELA-Max seems to offer satisfactory anesthesia at 30- and 60-minute application times and may offer considerable advantages over EMLA cream. Additional studies evaluating ELA-Max’s utility before other painful cutaneous procedures in children (skin biopsies, cutaneous excisional surgery, intralesional injections, etc) are required, and studies are currently under way.
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ACKNOWLEDGMENTS |
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This research was supported by Ferndale Laboratories, Inc (Ferndale, MI) and the Pediatric Dermatology Division, Children’s Hospital (San Diego, CA).
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FOOTNOTES |
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Received for publication Aug 15, 2001; Accepted .
Reprint requests to (L.F.E.) 8010 Frost St, Ste 602, San Diego, CA 92123. E-mail: leichenfield{at}ucsd.edu
This study was initiated by the principal investigator, who, along with the other authors, has no financial or commercial relationships with Ferndale Laboratories.
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics
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S. Leahy, R. M. Kennedy, J. Hesselgrave, K. Gurwitch, M. Barkey, and T. F. Millar On the Front Lines: Lessons Learned in Implementing Multidisciplinary Peripheral Venous Access Pain-Management Programs in Pediatric Hospitals Pediatrics, November 1, 2008; 122(Supplement_3): S161 - S170. [Abstract] [Full Text] [PDF]
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 J. Pershad, S. C. Steinberg, and T. M. Waters Cost-effectiveness Analysis of Anesthetic Agents During Peripheral Intravenous Cannulation in the Pediatric Emergency Department Arch Pediatr Adolesc Med, October 1, 2008; 162(10): 952 - 961. [Abstract] [Full Text] [PDF]
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W. T. Zempsky, J. Bean-Lijewski, R. E. Kauffman, J. L. Koh, S. V. Malviya, J. B. Rose, P. T. Richards, and D. J. Gennevois Needle-Free Powder Lidocaine Delivery System Provides Rapid Effective Analgesia for Venipuncture or Cannulation Pain in Children: Randomized, Double-Blind Comparison of Venipuncture and Venous Cannulation Pain After Fast-Onset Needle-Free Powder Lidocaine or Placebo Treatment Trial Pediatrics, May 1, 2008; 121(5): 979 - 987. [Abstract] [Full Text] [PDF]
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 R. Cregin, A. S Rappaport, G. Montagnino, G. Sabogal, H. Moreau, and J. J. Abularrage Improving pain management for pediatric patients undergoing nonurgent painful procedures Am. J. Health Syst. Pharm., April 15, 2008; 65(8): 723 - 727. [Abstract] [Full Text] [PDF]
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M. Franz-Montan, A. L. R. Silva, K. Cogo, C. d. C. Bergamaschi, M. C. Volpato, J. Ranali, E. de Paula, and F. C. Groppo Liposome-Encapsulated Ropivacaine for Topical Anesthesia of Human Oral Mucosa Anesth. Analg., June 1, 2007; 104(6): 1528 - 1531. [Abstract] [Full Text] [PDF]
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N. L. Schechter, W. T. Zempsky, L. L. Cohen, P. J. McGrath, C. M. McMurtry, and N. S. Bright Pain Reduction During Pediatric Immunizations: Evidence-Based Review and Recommendations Pediatrics, May 1, 2007; 119(5): e1184 - e1198. [Abstract] [Full Text] [PDF]
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American Academy of Pediatrics, American Academy of Pediatric Dentistry, C. J. Cote, S. Wilson, and the Work Group on Sedation Guidelines for Monitoring and Management of Pediatric Patients During and After Sedation for Diagnostic and Therapeutic Procedures: An Update Pediatrics, December 1, 2006; 118(6): 2587 - 2602. [Abstract] [Full Text] [PDF]
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 C V Bellieni, D M Cordelli, M Raffaelli, B Ricci, G Morgese, and G Buonocore Analgesic effect of watching TV during venipuncture Arch. Dis. Child., December 1, 2006; 91(12): 1015 - 1017. [Abstract] [Full Text] [PDF]
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P. J. Sharek, R. Powers, A. Koehn, and K. J.S. Anand Evaluation and Development of Potentially Better Practices to Improve Pain Management of Neonates Pediatrics, November 1, 2006; 118(Supplement_2): S78 - S86. [Abstract] [Full Text] [PDF]
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 C. V. Fernandez and G. Frager Reducing procedural pain Can. Med. Assoc. J., January 17, 2006; 174(2): 206 - 206. [Full Text] [PDF]
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A. Taddio, H. K. Soin, S. Schuh, G. Koren, and D. Scolnik Liposomal lidocaine to improve procedural success rates and reduce procedural pain among children: a randomized controlled trial Can. Med. Assoc. J., June 21, 2005; 172(13): 1691 - 1695. [Abstract] [Full Text] [PDF]
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M. Migdal, E. Chudzynska-Pomianowska, E. Vause, E. Henry, and J. Lazar Rapid, Needle-Free Delivery of Lidocaine for Reducing the Pain of Venipuncture Among Pediatric Subjects Pediatrics, April 1, 2005; 115(4): e393 - e398. [Abstract] [Full Text] [PDF]
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 O Quaba, J S Huntley, H Bahia, and D W McKeown A users guide for reducing the pain of local anaesthetic administration Emerg. Med. J., March 1, 2005; 22(3): 188 - 189. [Abstract] [Full Text] [PDF]
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W. T. Zempsky, J. P. Cravero, and Committee on Pediatric Emergency Medicine, and Sec Relief of Pain and Anxiety in Pediatric Patients in Emergency Medical Systems Pediatrics, November 1, 2004; 114(5): 1348 - 1356. [Abstract] [Full Text] [PDF]
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 C. S. Houck Taking `ouch' out of doctor visits easier than ever AAP News, August 1, 2004; 25(2): 66 - 66. [Full Text] [PDF]
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 L. Hefler, C. Grimm, S. Leodolter, and C. Tempfer To Butterfly or To Needle: The Pilot Phase Ann Intern Med, June 1, 2004; 140(11): 935 - 936. [Full Text] [PDF]
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 R. D Goldman ELA-max: A New Topical Lidocaine Formulation Ann. Pharmacother., May 1, 2004; 38(5): 892 - 894. [Abstract] [Full Text] [PDF]
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J. Luhmann, S. Hurt, M. Shootman, and R. Kennedy A Comparison of Buffered Lidocaine Versus ELA-Max Before Peripheral Intravenous Catheter Insertions in Children Pediatrics, March 1, 2004; 113(3): e217 - 220. [Abstract] [Full Text] [PDF]
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