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Topical anaesthetics: What's new?
  1. Kelly D Young
  1. Correspondence to Dr Kelly D Young, Department of Emergency Medicine, David Geffen School of Medicine at UCLA, Harbor-UCLA Medical Center, 1000 W. Carson Street, Box 21, Building D-9, Torrance, CA 90275, USA; kyoung{at}emedharbor.edu

Abstract

Topical anaesthetics, often used by anaesthetists, dentists and dermatologists, have increasingly been recognised for their utility in paediatrics. With topical anaesthetics, the ‘ouchless’ paediatric practice becomes an achievable goal. The primary drawback to their use is the length of time for anaesthetic effect, but planning ahead and making use of newer formulations and adjuncts can overcome this barrier. This update will review topical anaesthetic formulations available, adjuncts to reduce the time to anaesthesia, adverse effects, common indications and products on the horizon.

  • Anaesthetics
  • Pain
  • Accident & Emergency
  • Analgesia
  • Clinical Procedures

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Topical anaesthetics for intact skin

Several products are available for use on intact skin (table 1). The pain of any skin-breaking procedure such as venipuncture, intravenous catheter placement, intramuscular injection, vaccination, arterial puncture or local anaesthetic infiltration prior to lumbar puncture or abscess incision and drainage can be reduced with these topical anaesthetics.1

Table 1

Topical anaesthetics

Eutectic mixture of local anaesthetics (EMLA) should be applied under an occlusive dressing; plastic wrap secured with tape is a low-cost option. A strip squeezed out of the tube that is 1.5 inches×0.2 inches (38 mm×5 mm) is 1 g. On intact non-mucosal skin, depth of anaesthesia reaches 3 mm after 60 min and 5 mm after 120 min. Although EMLA produces vasoconstriction and blanching, it does not decrease vein catheterisation success.2 The prilocaine component of EMLA increases the risk of the rare adverse effect methemoglobinemia. EMLA is not approved for neonates <37 weeks' gestation. There is some evidence that EMLA placed on skin abscesses in preparation for incision and drainage is associated with an increased incidence of spontaneous drainage.3

LMX4, formerly Elamax (4% liposomal lidocaine), and LMX5 (5% liposomal lidocaine) are available without prescription in the USA, in contrast to EMLA, and LMX4 is also available widely globally. The liposomal vehicle improves skin penetration, reducing the time to efficacy to 30 min. LMX4 produces a similar depth of anaesthesia to EMLA in a shorter time, does not require an occlusive dressing (although one is often used to avoid messiness) and does not carry as high a risk of methemoglobinemia. One gram of cream is equal to a 5 cm ribbon squeezed out from a 5 g tube, or a 3.5 cm ribbon from a 30 g tube.

Ametop or Amethocaine (4% tetracaine gel) is more lipophilic than lidocaine or prilocaine, such that anaesthesia at a similar depth to EMLA is achieved after 30 min under an occlusive dressing. As an ester rather than an amide, amethocaine is metabolised by tissue esterases such that systemic levels are very low. Amethocaine is available in the UK, Canada, Australia and New Zealand. Unlike EMLA, amethocaine is vasodilating, which has been postulated to result in improved vein cannulation success. This vasodilation may result in erythema, itching, oedema and rarely, blistering. Some studies have found amethocaine to be more efficacious than EMLA, while others have found them to be equal.4 ,5

Synera (USA) or Rapydan (some parts of Europe) is an adhesive patch containing 70 mg lidocaine, 70 mg tetracaine and an oxygen-activated heating element; the heat improves skin penetration.6 The patch's active medication covers an area of 10 cm2. Anaesthesia is obtained in 20 min, at an average depth of 6.8 mm. Pliaglis, formerly S-caine peel, a thick cream of 7% lidocaine/7% tetracaine that hardens into a flexible film that can be peeled off prior to the skin-breaking procedure, is marketed in the USA, Canada, Europe and Argentina. However, it is approved for adults only.

Topicaine (4% lidocaine gel) is available without prescription in the USA. However, without lipophilicity or a vehicle or heating element to improve skin penetration, efficacy for skin-breaking procedures is less than other available topical anaesthetics.

Vapocoolant ethyl chloride is sprayed onto the skin immediately before the skin-breaking procedure and provides variable anaesthesia. Advantages include immediacy of effect, but disadvantages include possible decreased efficacy compared with EMLA, and intolerance of the cold sensation in some children.

Non-Food and Drug Administration (FDA)-approved topical anaesthetics of varying composition are also compounded by independent pharmacies in the USA, and primarily marketed to adults for laser dermatologic procedures. However, many of these products have been associated with significant adverse effects.7

Needle-free options for infiltrating local anaesthetics are also available to achieve superficial dermal anaesthesia (table 2). J-tip, the most widely used, is a single-use system that includes a small gas cartridge that uses pressurised gas to propel medication subcutaneously. It comes in 0.25 and 0.5 mL sizes. Zingo similarly used pressurised gas to inject 0.5 mg powdered lidocaine intradermally. Zingo is not currently being marketed, but Powder pharmaceuticals states that it plans to reintroduce it. Powdermed and Powderject use similar technology for vaccination. Dermoject is a reusable needle-free jet injection system; the system must be sterilised between uses. Use of these, combined with newer local anaesthetics that pose a lower risk of adverse effects, may provide a more rapid-onset method of anaesthesia for minor needle procedures without slowing patient flow.8 All of these injection systems, however, create a loud sound on injection that may startle children.

Table 2

Methods to speed skin permeation of local anaesthetic

Finally, Lidoderm is a slow-release 5% patch approved for the treatment of postherpetic neuralgia pain in the USA, and Versatis comes as a 5% lidocaine plaster or patch in the UK and parts of Europe and Central America. Neither are approved for use in children, and even a used patch still contains a large amount of residual lidocaine, such that a small child who chews or ingests a patch can experience significant toxicity.

Learning points

  • EMLA, Ametop and LMX4 provide anaesthesia for venipuncture and intravenous catheter placement.

  • Alternatively, J-tip needle-free injection system can be used to inject lidocaine subcutaneously.

  • Vapocoolant sprays are another more rapid onset option, but may be less efficacious.

Adjuvants to reduce time to anaesthetic effect

Several delivery methods have been investigated to reduce the time for skin penetration of local anaesthetics (table 2). Methods focus on improving lipophilicity, and breaking down the stratum corneum barrier.9 ,10

Iontophoresis uses a low-level electric current and lidocaine's natural polarity to enhance transdermal delivery. Depth of anaesthesia is 10 mm within 10 min of application. However, the electric current can be unpleasant for some children. Several commercial machines (NeedleBuster, NumbyStuff, LidoSite) were available in the past. Although they are no longer being actively marketed, some centres may still have and use these machines.

Lasers can be used to microablate the top layer of the stratum corneum, shortening the transit time for drug delivery into the skin. A previous product, Epiture Easy Touch, is no longer being marketed. A new product P.L.E.A.S.E. (Precise Laser EpidermAL SystEm) is available in Europe.

Ultrasound (sonophoresis or phonophoresis) uses the acoustic cavitation caused by ultrasonic sound waves to disrupt the lipid bilayers of the stratum corneum and enhance drug delivery. Sontra Medical, which previously made SonoPrep, merged with Echo Therapeutics, which is now developing the Prelude SkinPrep System.

Heat has been shown to shorten time to efficacy for EMLA, as well as to counteract the vasoconstrictive properties of EMLA. Time to anaesthesia with the self-heating patch Synera (USA) or Rapydan (parts of Europe) is shortened to as brief as 10 min.

Finally, use of standing protocols enables effective use of the time spent waiting for topical anaesthetic efficacy. Patients can have topical anaesthetics applied at home if an upcoming indication is known (eg, planned blood draw, immunisation) or at triage/check-in when the need is recognised (eg, laceration), and during the wait time for onset of anaesthesia other aspects of their medical visit (registration, vital signs, history and physical examination) can take place.

Topical anaesthetics for laceration repair

Topical anaesthetics may be sufficient for repair of smaller, superficial lacerations in highly vascular and thin-skinned body areas such as the face (table 1). If additional anaesthesia is needed, topical anaesthetics can lessen the pain of local anaesthetic skin infiltration. Topical anaesthetics also lessen the discomfort of tissue adhesive application11 and stapling of small scalp wounds (local anaesthetic infiltration is recommended for more than a few staples).

TAC (tetracaine 0.5%, adrenaline or epinephrine 0.05% and cocaine 11.8%) is the oldest topical anaesthetic used on open wounds. Similar to subsequently developed LET or LAT (lidocaine 4%, adrenaline or epinephrine 0.1% and tetracaine 0.5%), onset of anaesthesia is within 20–30 min, often heralded by blanching of the skin edges due to the epinephrine component. Popularity of TAC has fallen due to cocaine-related toxicity.

LET or LAT, compounded by the pharmacy as an aqueous solution or in a methylcellulose gel form, is equally efficacious without the complications use of cocaine brings. A cotton ball (not gauze) soaked with aqueous solution or 1–3 mL of gel is placed into the open wound, and often held in place by caretakers, who should wear gloves to avoid exposing themselves to anaesthetic. There is a theoretical concern regarding use of vasoconstricting epinephrine on end-arteriole areas (fingers, toes, nose, ears, penis), although many view this as a myth that has been debunked.12

Although EMLA was developed and approved for use on intact skin and mucosa, its use on lacerations has been studied, comparing favourably to TAC, but with lower anaesthetic efficacy compared with LET.13

A novel 4% lidocaine anaesthetic putty, which flows over a wound then creates an easily removable firm covering, has been developed and may be marketed in the future.14

Topical anaesthetics for disease entities and procedures

Topical anaesthetics can be a useful adjunct in the management of several disease entities and when performing certain procedures (table 3). While topical anaesthetics provide analgesia, they will be less helpful when anxiety is the primary contributor to the child's distress and should be combined with non-pharmacological cognitive behavioural techniques, distraction and anxiolysis as needed. Also, in some children, the distress of topical anaesthetic application may outweigh the benefits.

Table 3

Procedure and disease-specific applications for topical anaesthetics

Benzocaine intraoral spray is commonly used to facilitate intraoral procedures, benzocaine gels and liquids are sold over the counter for treatment of teething and stomatitis pain, and over-the-counter benzocaine topical sprays are sold to treat sunburn pain. Benzocaine-based prescription otic solution (Antipyrine and Benzocaine drops, brand name Auralgan) may decrease the pain of otitis media. The FDA released a warning regarding the risks of methemoglobinemia with benzocaine products in 2011, however.

Viscous lidocaine has been used to facilitate urethral catheterisation, and ear and nasal foreign body removal, and nebulised lidocaine for nasogastric tube placement. Uro-jet is a commercial device specifically made for injecting viscous lidocaine into the urethral meatus. Viscous lidocaine is also commonly mixed with liquid antacid and diphenhydramine to create a ‘magic mouthwash’ to treat the pain of stomatitis. This use has not been studied much, the evidence that is available does not support improved oral intake and there are concerns that children will swallow the ‘mouthwash’ and experience toxicity.15

Learning points

  • LET solution or gel is useful for laceration repair.

  • Viscous lidocaine may be used before urethral catheterisation.

  • Nebulised lidocaine may be used before nasogastric tube placement.

Adverse effects of topical anaesthetics

The primary adverse effects of consequence from systemic absorption of topical anaesthetic are cardiac and central nervous system (CNS). CNS symptoms include dizziness, headache, metallic taste, blurred vision and seizures. Seizures are treated as usual with benzodiazepines and other anticonvulsants. Cardiac symptoms include bradycardia, hypotension, dysrhythmias and even cardiac arrest. Standard paediatric resuscitation algorithms should be followed with the exception of avoidance of lidocaine and other class I antidysrhythmics. For severe refractory cardiac dysrhythmias, intralipid 20% 1.5 mL/kg over 1 min, then 0.25 mL/kg/min infusion, has been effective (http://lipidrescue.squarespace.com/).

Methemoglobinemia is another potentially serious adverse effect, seen primarily with EMLA (due to the prilocaine component) and benzocaine. Risk is very low overall (0.035% in a study of adults undergoing procedures16), but is slightly increased in young infants and when the patient receives other methemoglobin-forming drugs such as acetaminophen, sulfonamides, nitrous oxide, phenytoin and phenobarbital.1 Methemoglobinemia presents with cyanosis, low-pulse oximetry readings, altered mental status, dizziness, shortness of breath, and left untreated, may progress to coma. The antidote is methylene blue, which is converted in the body to leukomethylene, which acts as an electron donor to promote the conversion of the iron moiety of haemoglobin from the abnormal ferric (Fe3+) back to the normal ferrous (Fe2+) state.

Minor adverse effects are common and include local skin irritation, erythema, blanching if epinephrine is a component, oedema with amethocaine and vasoconstriction (EMLA) or vasodilation (amethocaine).

Conclusion

Topical anaesthetics are useful for a variety of skin-breaking procedures and also for the treatment of pain associated with several disease entities. A significant barrier to use is the time delay for effect; several methods to reduce this time are being explored. Serious adverse effects are uncommon, but when they do occur, primarily involve methemoglobinemia, cardiac and CNS symptoms.

Test your knowledge

  1. Which of the following will likely take the longest to produce skin anaesthesia?

    1. EMLA

    2. Amethocaine

    3. LMX

    4. Synera/Rapydan

    5. J-tip+lidocaine

  2. Which of the following is the best choice for laceration repair of a simple facial laceration on the cheek?

    1. EMLA

    2. Amethocaine

    3. TAC

    4. LET/LAT

    5. J-tip+lidocaine

  3. Which of the following is not a potential adverse effect of topical anaesthetic toxicity?

    1. Cardiac toxicity

    2. Seizures

    3. Apnoea

    4. Methemoglobinemia

    5. All of the above are potential adverse effects

  4. Which of the following is a recommended option for treatment of severe topical local anaesthetic cardiac toxicity?

    1. Procainamide

    2. Beta-blocker

    3. Disopyramide

    4. Intralipid

    5. Methylene blue

Answers to the quiz are on page 110.

Answers to the questions on page 109

  • 1 (A); 2 (D); 3 (C); 4 (D).

References

Footnotes

  • Competing interests None.

  • Provenance and peer review Commissioned; externally peer reviewed.