Update on topical anesthetics

The pain and distress associated with venous access procedures and needle sticks are common. Several pharmacotherapeutic products are available to pediatric clinicians that may be able to effectively reduce these fears.

Therapy reviews and guidelines from the AAP have been published on the assessment and treatment of pain and anxiety in infants and children. The use of topical anesthetics is encouraged in these guidelines for venous access and minor procedures involving a needle stick.

Unfortunately, evidence exists suggesting that treatment recommendations and strategies for relief or minimization of pain are underutilized. Reasons cited for underuse of topical anesthetics include lack of awareness of product availability, lack of perceived need for their use, costs or the potential for procedure delay.

Topical anesthetic products

The pharmacologic approach most commonly available for the treatment or minimization of pain associated with venous access and needle sticks includes application of topical anesthetics. Several products are available for application to the skin of an infant or child prior to a procedure involving a needle stick. Eutectic mixture of local anesthetics (EMLA) contains lidocaine 2.5% and prilocaine 2.5%, such that this combination has a melting point below room temperature and below each agent’s melting point.

In combination, the mixture exists as liquid oil, and not as a crystal. EMLA has been evaluated in numerous published clinical studies, and its efficacy for venipuncture and intravenous cannulation are well documented. EMLA is labeled for use as a local anesthetic in infants (including neonates and for circumcision) and children on intact skin, on genital mucous membranes for superficial minor surgery and as pretreatment for infiltration anesthesia.

Product labeling for EMLA states that an occlusive dressing should be used with application and application should occur at least 60 minutes prior to the procedure. Maximal analgesia is reached within 120 to 180 minutes after application. For procedures involving genital mucosa, a shorter application time of five to 10 minutes can be used. An advantage of EMLA is its documented efficacy in the neonatal population, including circumcision. EMLA has also been evaluated in at least two studies of routine pediatric immunizations. Studies of measles-mumps-rubella, DTaP-IPV-Hib, and hepatitis B vaccine administration have shown that EMLA reduced pain from needle sticks without affecting antibody response.

LMX4 cream is a topical anesthetic cream containing lidocaine 4% and is available over the counter. LMX4 cream had formally been known as ELA-Max.

Although it is not labeled for use in pediatric venipuncture or intravenous cannulation, several clinical trials have documented its efficacy for this use. LMX4 is labeled for use for minor scrapes/cuts, burns, skin irritations, sunburn and insect bites.

LMX4 has been directly compared with lidocaine-prilocaine cream (30 minute vs. 60 minute application time, respectively) and has demonstrated equivalent efficacy for intravenous cannulation and venipuncture. Few data are available for LMX4 use in children younger than 2. An advantage of LMX4 is its shorter application time. The availability of LMX4 over the counter may be advantageous in some circumstances, although this may cause some third-party insurance carriers not to cover its expense (approximately $56 for a 30 gm tube).

An interesting topical anesthetic product is Synera (Zars Pharma), a topical patch containing a eutectic mixture of lidocaine 70 mg and tetracaine 70 mg. Synera is formulated with an oxygen-activated heating component that is intended to enhance the delivery of lidocaine and prilocaine. Once the patch is opened, the exposure to oxygen activates this heating process. Synera is labeled for use in children ages 3 and older for venipuncture and intravenous cannulation. A Synera patch should be applied 20 to 30 minutes prior to the procedure, and this relatively short application time may be advantageous for some patients.

The latest topical anesthetic product to become available is Zingo (Anesiva). Zingo contains 0.5 mg lidocaine powder in a unique needleless delivery system that incorporates compressed helium to force particles of lidocaine beneath the skin. Zingo is labeled for use in children ages 3 to 18 for venipuncture and intravenous venous access. Zingo possesses the shortest time of onset and duration. Venipuncture or intravenous cannulation can begin one to three minutes after use of Zingo and should be performed within 10 minutes of use.

Other products

Other, more technologically complicated products are available for topical anesthesia of children. Several products make use of iontophoresis, a process using a low-voltage electrical current to force a drug through skin. One system, Numby Stuff (Iomed) (lidocaine/epinephrine), has been used for many years in children and is supported by data from numerous clinical trials. Local analgesia for intravenous procedures, needle sticks, or lumbar punctures is provided within 10 minutes of application. Numby Stuff has been compared with lidocaine/prilocaine cream, with equivalent or superior efficacy. A disadvantage of this product is the potential for unique adverse effects associated with iontophoresis, which may include significant tingling, itching, or burning. Although rare, significant burns have also been reported. A similar product, LidoSite Topical System, includes a patch containing lidocaine 100 mg/epinephrine 0.1% and is delivered by iontophoresis.

Conclusion

Several products are available to clinicians that allow effective topical analgesia and minimization of discomfort from common procedures involving a needle stick. Some evidence exists, however, that these products are underutilized. Less data are available for the use of topical anesthetics to manage pain from routine pediatric immunization schedule administration. Clinical efficacy between these products is generally equivalent, although significant differences exist among them for ease of use, time of onset, availability and cost.

Products such as EMLA and LMX4 are easy to use, but require at least 30 minutes of application. Because of their longer onset, it can be useful to instruct parents or caregivers to apply these creams to their child on probable sites of needle stick at home. LMX4 is available over the counter, but it is relatively expensive. These products should be used with an occlusive dressing, to enhance drug penetration into skin. Occlusive dressings may not be available together with each of these products. Most experience and published trials exist for EMLA, and it has also been evaluated and is labeled for use in neonates. However, EMLA requires the longest application time — at least 60 minutes.

Newer products, such as Synera and Zingo, provide unique application and delivery mechanisms, and allow shorter application times. Less clinical experience exists for these products. Products using iontophoresis are technologically more complicated, but also allow for relatively quick onset of analgesia. However, iontophoresis may result in unique adverse effects some children may find discomforting.

Edward A. Bell, PharmD, BCPS, is Professor of Pharmacy Practice at Drake University College of Pharmacy, Blank Children’s Hospital in Des Moines, Iowa.

For more information:

• Committee on Pediatric Emergency Medicine and Section on Anesthesiology and Pain Medicine, AAP. Relief of pain and anxiety in pediatric patients in emergency medical systems. Pediatrics. 2004;114:1348-56.
• Halperin BA. Use of lidocaine-prilocaine patch to decrease intramuscular injection pain does not adversely affect the antibody response to DTaP-IPV-Hib and hepatitis B vaccines in infants from birth to six months of age. Pediatr Infect Dis J. 2002;21:399-405.
• Halperin SA. Lidocaine-prilocaine patch decreases the pain associated with the subcutaneous administration of MMR vaccine but does not adversely affect the antibody response. J Pediatr. 2000;136:789-94.
• Zempsky WT. Pharmacologic approaches for reducing venous access pain in children. Pediatrics. 2008;122(Supplement 3):S140-S-153.