Using topical anesthetics for common procedures in children

March 2003

The fear of needles is one of the most anxiety-producing events children encounter in the setting of a physician’s office or hospital. A variety of nonpharmacologic methods have been employed to reduce this anxiety. Pharmacologic means can also be used, primarily by the application of topical anesthetics.

Numerous topical anesthetic products are available, both by prescription and over the counter (OTC). Many of these products, however, are indicated to reduce discomfort associated with such problems as minor burns or abrasions (eg, benzocaine, dibucaine and tetracaine). Other agents (eg, lidocaine, dyclonine and cocaine) are used for local anesthesia on or around mucous membranes. Iontophoresis, a method of topical drug administration using an electrical current, has also been suggested as a viable means of inducing local anesthesia. Published studies have found iontophoresis to be an effective method.

Perhaps the most commonly used local anesthetics are products applied to intact skin prior to the use of needles for intravenous cannulation or venipuncture, or prior to the use of various dermatologic procedures. Two products in particular — EMLA (AstraZeneca) and ELA-Max (Fernadale) — are available for these uses and will be discussed in this month’s column.

EMLA Cream and ELA-Max Cream are the local anesthetic products pediatric clinicians are probably most familiar with. EMLA (acronym for Eutectic Mixture of Local Anesthetics) is a eutectic mixture containing 2.5% lidocaine and 2.5% prilocaine, and is available by prescription. A eutectic mixture melts at a lower temperature than any of its ingredients. The eutectic mixture in EMLA has a melting point below room temperature, and therefore, lidocaine and prilocaine exist as liquid oil. EMLA is also available as an anesthetic disc for application over a 10 cm² area. EMLA cream may be applied according to the infant’s or child’s age and weight (table 1). It is recommended that EMLA be applied at least 60 minutes prior to its anticipated use. An occlusive dressing (available as Tegaderm (3M) dressings with the 5-gm tube, but not the 30-gm tube) should be applied over the cream. Ordinary plastic wrap (eg, as available in most kitchens) may also be used. EMLA currently is undergoing “restricted availability” and may be only available in hospital settings. The manufacturer is redesigning the product applicator to be more child-resistant. It is anticipated that widespread availability should occur by mid-year.

ELA-Max (available OTC) contains only lidocaine (4%) as the anesthetic agent, in a lipid-encapsulated layer. Although it has been used as a local anesthetic prior to venipuncture or IV cannulation, its approved indications only include pain relief from minor skin disorders (eg, abrasions, burns). Studies indicate that ELA-Max may be applied 30 minutes prior to its anticipated use. Package labeling for ELA-Max does not state that an occlusive dressing should be used, although such a dressing may be helpful in keeping the cream in place. Only one of the available ELA-Max product lines contains Tegaderm dressings. ELA-Max is also available as a 5% cream (prescription, ELA-Max5 Anorectal Cream) indicated for pain and discomfort relief from anorectal disorders.

EMLA has been studied and shown effective for inducing local anesthesia for a variety of dermatologic uses. Several studies have been published that have directly compared EMLA and ELA-Max.

Kleiber compared EMLA to ELA-Max in 30 children (7 to 13 years of age) in a randomized, single-blind manner, for use prior to IV catheter insertion. EMLA was applied to one hand of the child for 60 minutes and ELA-Max to the other hand for 30 minutes. Occlusive dressings were used for both products. The Oucher scale was used to assess pain. The products were equally effective in inducing local anesthesia and ease of vein cannulation. Mean Oucher ratings were 20.5–24/100; some children reported relatively high ratings (60/100) despite use of EMLA or ELA-Max. Anxiety was also measured and found to correlate with pain ratings.

Eichenfield compared EMLA to ELA-Max for venipuncture in a double-blind, randomized, crossover trial of 117 children (5 to 17 years of age). Study patients received both products applied for 30 minutes and 60 minutes on two separate occasions. ELA-Max was evaluated both with and without an occlusive dressing. A visual analog scale (VAS) was used to assess pain. Observed behavioral distress scores were also evaluated. Overall, no differences in efficacy (VAS and distress scores) were found between EMLA and ELA-Max. Interestingly, a 30-minute application time of EMLA (with occlusion) was found equally effective as a 30-minute application time of ELA-Max (without occlusion). Similarly, equal efficacy was noted between EMLA (with occlusion) and ELA-Max (with occlusion) applied for 60 minutes. Mean VAS scores were approximately 8 to 12/100 (range 0 to 100).

EMLA has also recently been evaluated for its effects upon pain associated with routine immunization administration. Because it has been shown that lidocaine and prilocaine may have antibacterial and antiviral effects, the use of EMLA prior to immunization may potentially alter immunization efficacy. Two recent studies evaluated the anesthetic effect and the immune response to several antigens after EMLA application. EMLA was applied as a patch (1 gm) 60 to 180 minutes prior to immunization to 109 6-month old infants and to 56 0-2 month old infants in a randomized, double-blind, placebo-controlled study by B. Halperin. Infants were then routinely immunized with hepatitis B (Recombivax) and DTaP-IVP-Hib (Pentacel). Antibody titers were measured at 0-2, 6 and 7 months. There was no difference in the antibody response between the treatment and placebo groups as measured by geometric mean antibody titers, seroconversion rates, or postimmunization antibody titers. Interestingly, a statistically significant difference in pain score was seen only in the 6-month group, which may be due to small sample sizes. In a similar study S. Halperin measured antibody responses to MMR immunization in 165 12-month infants in a randomized, double-blind, placebo-controlled manner. EMLA was applied as a 1 gm patch 60 to 180 minutes prior to immunization. There was no difference in the antibody response between the groups. Pain scores among the patients receiving EMLA were lower than infants receiving placebo (P<.05).

Lander compared EMLA to placebo to evaluate potential predictors of success of EMLA use. Children aged 5 to 18 years (n=258) were evaluated in a double-blind, randomized manner. EMLA was applied for 90 minutes prior to venipuncture or IV cannulation. Pain and anxiety were assessed. EMLA was more successful for venipuncture (84% of attempts) than IV cannulation (51% of attempts). A longer duration of application and lower anxiety ratings was found to correlate with successful anesthesia. Mean application times for the group assessed as having a “poor” outcome (based upon VAS pain ratings) were 95.6 minutes (lowest 65.8 minutes), and 106.8 minutes (lowest 76.3 minutes) for those having a “good” outcome. The study found that >90 minutes of application is necessary for effective anesthesia.

Application time

The most practical difference between EMLA and ELA-Max, which is most often discussed in literature, is application time. As discussed above, EMLA is labeled for an application time of 60 minutes or more, while ELA-Max has been evaluated primarily using 30-minute application times. A shorter application time may have some benefit, particularly in relatively acute situations when local anesthesia is needed as soon as possible. Evaluation of the studies described above, as well as other published studies, indicates that it is not clear that shorter application durations of ELA-Max are always equally effective as longer application durations of EMLA. In Eichenfield’s study no difference in efficacy was found between EMLA and ELA-Max when the application duration was 30 minutes. Another study compared EMLA and ELA-Max in 60 minute and 90-minute application durations in a relatively small number of volunteer adults, and found no difference in efficacy for either application duration. Other study authors have recommended application durations >60 minutes for EMLA.

Another difference between EMLA and ELA-Max is the use of an occlusive dressing. Package labeling for EMLA includes the recommendation that an occlusive dressing be applied, while ELA-Max may be used without an occlusive dressing. A benefit of using an occlusive dressing was not apparent in Eichenfield’s study. From a practical standpoint, however, an occlusive dressing may be more likely to keep the applied cream in place, while also preventing the infant or child from rubbing it off. Clinicians should note that not all of the EMLA or ELA-Max products are packed with Tegaderm dressings. Common plastic wrapping may also be used.

Adverse events with EMLA and ELA-Max are generally mild and may include blanching or erythema. Such events in comparative studies have occurred with similar frequencies. The concern of systemic absorption and potential toxicities are apparent for many topically applied drugs. Package labeling for EMLA indicates that 60 gm applied to a >400 cm² area for 24 hours in adults results in systemic lidocaine levels that are only 5% of the known toxic blood level.

Another potential adverse effect of EMLA is methemoglobinemia. Metabolites of prilocaine have been implicated in oxidizing hemoglobin to methemoglobin. Most case reports have occurred in young infants (<3 months), for it is believed that young infants are immature in the necessary quantity of erythrocyte methemoglobin reductase. Methemoglobinemia has also been reported in older children, although application of excessive amounts of EMLA cream has been responsible. Various medications may also result in or contribute to methemoglobinemia (eg, sulfonamides, phenobarbital, phenytoin). A study of EMLA application (normal dose) to 30 children (1 to 6 years of age) found methemoglobin levels to peak at 0.85%. Symptoms of methemoglobinemia generally do not appear until methemoglobin levels reach 10% to 20%. It is also important to note that lidocaine CNS toxicity may occur with excessive dosing, as this has been reported.

EMLA and ELA-Max have been shown in clinical studies to be equally effective in inducing local anesthesia in children, allowing for easier venipuncture and IV cannulation. A potential benefit of ELA-Max may be a shorter application time, although this is not entirely clear. The most effective (and practical) application time requires further study. Anxiety has been shown to relate to local anesthetic efficacy. Methods to reduce anxiety as well as application of local anesthetics are likely to be beneficial. Both EMLA and ELA-Max are relatively safe products. However, significant toxicity is possible, and caregivers should be counseled on appropriate use.

For more information:

• Kleiber C. Topical anesthetics for intravenous insertion in children: a randomized equivalency study. Pediatrics. 2002;110:758-761.
• Eichenfield LF. 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. Pediatrics. 2002;109:1093-1099.
• Lander J. Determinants of success and failure of EMLA. Pain. 1996;64:89-97.
• Frayling IM. Methemoglobinemia in children with prilocaine-lignocaine cream. British Medical Journal. 1990;301:153-154.
• Rincon E. CNS toxicity after topical application of EMLA cream on a toddler with molluscum contagiosum. Pediatr Emerg Care. 2000;16:252-254.
• Halperin BA. Use of lidocaine-prilocaine patch to decrease intramuscular injection pain does not adversely affect the antibody response to diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b conjugate and hepatitis B vaccines in infants from birth to six months of age. Pediatrics. 2002;21:399-405.