Although every child and adult will have a painful minor procedure, such as a venipuncture, at some time, little attention is paid to the relief of this pain. For many people, especially children, the pain is not minor to them. About 10% of adults in the US have "needle phobia," an intense fear of needles that triggers immediate anxiety and a vasovagal response that can lead to shock (American Psychiatric Association, 2000). The fear usually begins in childhood, and "needle phobic" individuals may avoid seeking medical care (Morrison and others, 1998). As nurses, we have an obligation to minimize every kind of pain, and the use of topical anesthetics has greatly enhanced our ability to decrease or prevent pain from procedures, such as skin punctures.
Two Topical Local Anesthetic Options
Currently, two safe and effective topical local anesthetics are available: EMLA (eutectic mixture of local anesthetics; AstraZeneca) and ELA-Max (Ferndale Laboratories). This article focuses on the comparison of these two products and the implications for use in children.
EMLA is a prescription topical anesthetic emulsion cream that is applied to the skin and covered with an occlusive dressing for at least 60 minutes (depending on the required depth of penetration). Each gram of EMLA contains 25 mg of lidocaine and 25 mg of prilocaine. As a eutectic mixture, no lipophilic solvent is required which ensures the rapid release of local anesthetics from the emulsion and the highest concentration possible in the aqueous phase. These characteristics allow the drug to penetrate the dermal layers of the skin. The major factor affecting absorption of EMLA into the dermal layers is skin hydration.
ELA-Max is a new over-the-counter (OTC) topical anesthetic that is advertised by the manufacturer, Ferndale Labs, to produce dermal anesthesia in 15 to 30 minutes without occlusion. It is available in both a 4% or 5% lidocaine concentration. The 4% ELA-Max is recommended for dermal use and contains 40 mg of lidocaine per gram. The lidocaine molecules are encapsulated in a lipid layer (liposomes) to enhance absorption into the dermal layers.
Pediatric Research
Two pediatric studies have compared the efficacy of ELA-Max to EMLA before IV cannulation. Kleiber and others (2002) recruited 30 healthy, white children (mean age 10.8 years; range 7.4 to 12.9 years; 14 females) to receive an IV in both hands (22-gauge Teflon catheter). EMLA (for 60 minutes) and ELA-Max (for 30 minutes) were randomly applied to each hand before the procedure. Both local anesthetics were covered with an occlusive dressing. During the waiting period, the children rated their current anxiety on a thermometer-like visual analogue scale (VAS) divided into 10 evenly spaced marks (0 = no anxiety; 10 = a lot of anxiety). After IV cannulation was completed, the children rated the pain of the procedure using the numeric scale (0-100) of the Oucher pain rating scale (Beyer and others, 1992). The nurses performing the procedure, who were considered expert in IV cannulation, rated the ease or difficulty of IV insertion using five categories.
There was no significant difference in the children's mean pain scores between the EMLA (range 0-70; mean 20.5 22.7) and ELA-Max (range 0-60; mean 24 17.6). Cannulation was successful in 60% of those who received EMLA and 67% of those who received ELA-Max. For the 60 IV attempts (2 per hand), 23 (38%) attempts were unsuccessful. The authors offered a possible explanation for the high failure rate. Since the IVs were only for a research, not a clinical purpose, the nurses may not have been very aggressive in trying to find a vein.
There was a significant and positive association (r=.399, p=0.029) between the children's anxiety ratings and average pain scores. In other words, as the pain rating increased, the anxiety rating also increased and vice-versa. There were no significant associations between using the right or left hand for IV and pain ratings or between gender and pain ratings.
The authors concluded that a 30-minute occlusive application of ELA-Max was as effective as a 60-minute occlusive application of EMLA in reducing pain of IV cannulation in the hands of older children. They cited advantages of ELA-Max: it does not require a prescription; does not contain prilocaine, which can rarely cause methemoglobinemia; and may not require occlusion (as stated by the manufacturer, although occlusion was used in this study).
The authors noted that the absence of prilocaine in ELA-Max is important when treating neonates. Rarely, prilocaine can cause methemoglobinemia (the physiological range of methemoglobin is usually 1-2%), a condition in which some of the blood's hemoglobin oxidizes to the ferric form, which is incapable of binding molecular oxygen for transfer to cells. The signs of methemoglobinemia include cyanosis and hypoxemia; the blood has a chocolate hue. It is reversible when treated promptly with IV methylene blue. Elevated concentrations of methemoglobin up to 5-6% are considered to be of no clinical significance. Treatment of symptomatic methemoglobinemia is usually not needed unless methemoglobin concentrations are above 25-30%. (Hjelt 1995; Law 1996).
Although the ELA-Max package insert (revised 06/01) states that a single application of a thick layer of cream in a child weighing more than 10 kg should not be applied over an area larger than 100 cm2, the study hospital's Division of Neonatology decided to apply the same criteria as for EMLA. In this case, the dosage of EMLA for infants from 37 weeks of gestational age to three months of age or a weight of less than 5 kg is 1 gram per day to cover an area no more than 10 cm2. The study's hospital pharmacy chose to stock both products until there was a preference for one. At the time of this writing, the cost of the two topical anesthetics in a 5-gram tube is about the same.
In another study, Eichenfield and others (2002) randomly assigned 117 children mean age of nine years (range 5 to 16 years) to receive one of four topical local anesthetic treatments: ELA-Max without occlusion vs EMLA with occlusion for 30 minutes and ELA-Max vs EMLA both with occlusion for 60 minutes before phlebotomy. The children rated the pain of the venipuncture on a 0 to 100 VAS. There were no significant differences in mean pain ratings for any of the groups. The authors concluded that ELA-Max unoccluded for 30 minutes was as effective as EMLA occluded for 60 minutes (mean pain rating of 10.9 and 8.2, respectively). However, ELA-Max unoccluded for 30 minutes was also as effective as EMLA occluded for 30 minutes (mean pain rating 10.9 and 10.8, respectively).
The importance of the Eichenfield study vs. the Kleiber study is that the topical anesthetics were compared for the same application times. Since Eichenfield found no difference between ELA-Max and EMLA at 30 minutes, Kleiber can only conclude that ELA-Max at 30 minutes is as effective as EMLA at 60 minutes. Her findings cannot be construed to mean that ELA-Max is superior to EMLA because ELA-Max works faster.
Adult Research
Studies (supported by Ferndale Labs) have compared the effectiveness of EMLA to a 5% liposomal lidocaine or to ELA-Max for different types of pain in adults. In one study 13 healthy volunteers rated the pain of gentle pinpricks on the volar surface of the arm after EMLA and 5% liposomal lidocaine was applied for 30 minutes without occlusion. Another 6 healthy volunteers underwent the same procedure but with occlusion. The outcome measure was number of painless pricks out of 10 pricks on each site at 0, 15, 30, 60, and 90 minutes following removal of the cream. There were no significant differences between EMLA and the 5% liposomal lidocaine at any time period with or without occlusion (Bucalo, Mirikitani, and Moy, 1998).
Another study compared ratings of pain (0 to 10) produced by pulses from the Epilight high energy pulsed light source, a device typically used for hair removal. Ten subjects rated the pain without an anesthetic, then 1.5 hours after application of EMLA with occlusion, and at 5-minute intervals after application of ELA-Max without occlusion for up to 30 minutes. Six of 10 subjects reported some anesthetic effect after a 5-minute application of ELA-Max. Seven of 10 subjects reported maximal pain control after a 20-minute application of ELA-Max, which was similar to the pain control of EMLA after 1.5-hour application. Although the findings are favorable for ELA-Max's anesthetic efficacy at 20 minutes for the Epilight "at a standard setting," there was no comparable data for EMLA at 20 minutes (Altman and Gildenberg, 1999).
Finally, Koppel, Coleman, and Coleman (2000) compared the efficacy of EMLA vs. ELA-Max using a 35% trichloroacetic acid (TCA) on the face for a medium depth chemical peel in 10 female volunteers. First, 70% glycolic acid was applied to the face for 2 minutes and then removed with water. After the face was dried, test areas were covered with EMLA, ELA-Max, and a placebo cream all without occlusion for 30 minutes then removed. Next TCA was applied and patients rated the pain on a scale of 0 to 10 upon application, when a frost appeared, and after petrolatum was applied as a cover to the peeled areas. The subjects rated their pain as significantly less in the areas treated with the anesthetic creams than the placebo at each time interval, but there were no significant differences between mean pain ratings for EMLA and ELA-Max.
Some conclusions can be drawn from the available research. ELA-Max and EMLA with or without occlusion have similar efficacy at 5, 15, 30, and/or 60 minutes in children (N=147) for venipuncture pain and in adults for pain from gentle pinpricks (N=19) and from TCH application (N=10).
Safety Of Topical Local Anesthetics
Minimal safety information is available on the use of ELA-Max in children. In the Eichenfield study, serum lidocaine concentrations were determined in 10 patients after a 60-minute ELA-Max application. The mean age of the patients was 7.9 years (range three to 15 years). Nine patients had levels 0.2 ug/mL, with one result of 0.3 ug/mL, indicating no clinically significant systemic absorption of lidocaine. Serum concentrations considered toxic must exceed 5 ug/mL.
Conversely, numerous studies have been published on the safety of EMLA in premature and full-term neonates and children of all ages. Seven cases of methemoglobinemia have been published. In most instances, EMLA had been used in large doses and for extended applications or together with other methemoglobin-inducing agents (see references for case reports).
For practical and safety reasons, both ELA-Max and EMLA should be applied under occlusion in children to prevent accidental ingestion or application to the eyes. Since ELA-Max is OTC and the 5-gm tube does not have a child-resistant closure, the drug must be stored safely. A 5-gm tube contains 200mg of lidocaine, a dose that can be toxic to a small child. The recommended maximum dose of intradermal lidocaine is 4 to 5 mg/kg. The manufacturer of ELA-Max also warns that the cream should not be left on the skin for more than two hours.
Since nurses are often involved in performing painful procedures, such as IV cannulation, they should be aware of topical anesthetics that can safely and effectively reduce or eliminate the pain of many minor invasive procedures. With the research information currently available for ELA-Max, nurses should apply the cream using the same guidelines for EMLA. With the availability of a convenient OTC product, it is essential to give family members correct information for the dose and timing of ELA-Max. Currently, EMLA is being repackaged in the United States with a child-resistant closure, but as with all drugs, these two products must be stored safely out of children's reach.
April 17, 2003