I heard crying as I turned the corner to the emergency department. The emptiness of the department in the early morning hours made the wails more noticeable. In a room, I saw an 8-month-old infant with a bloody shirt and a deep laceration on her chin. Earlier, her estranged father had kicked the family's kitchen door and shattered the glass paneling as he attempted to enter the home. An aunt, startled by the intrusion, had dropped the infant onto a piece of glass lying on the kitchen floor.
Gauze saturated with lidocaine 2%, epinephrine 1:1,000, and tetracaine 2% (LET) was quickly placed on the infant's chin. Her wails subsided. I inspected her laceration for foreign bodies and proceeded to irrigate the wound. It was surprising how little she cried during the procedure. Perhaps she was exhausted from all of her crying earlier that morning, or perhaps the pacifier was finally making a difference. Most likely, the topical analgesia had begun to work.
However, the silence did not last long. In an attempt to give adequate analgesia, I needed to inject the wound with buffered lidocaine. Even with two nurses restraining her trunk, extremities, and head, it was difficult to work on a moving chin. With each cry or quiver, her chin moved and I needed to move the needle accordingly. It was a challenge to suture a moving target.
This experience heightened my respect for topical anesthetics. They are especially useful for children, who usually have needle phobia and often refuse to swallow medications. Moreover, it is impossible to explain the long-term benefit of a painful procedure to an 8 month old.
We can, however, minimize the negative impact by making procedures as comfortable as possible. For example, LET is a low-cost topical combination of local anesthetic and vasoconstrictor that reduces the burning sensation from subsequent lidocaine injection. Applying LET to lacerations is itself relatively painless and requires only a few seconds. With better topical pain control, there is less need for restraint or sedation.
Topical therapy has a wide range of applications. Focused local treatments for skin diseases may minimize systemic side effects, such as growth retardation and adrenal suppression induced by corticosteroids. Mupirocin, an antibiotic ointment, is an effective treatment for local impetigo and eradication of the methicillin-resistant Staphylococcus aureus carrier state. Topical treatment of skin infections also spares patients from other adverse side effects of oral and intravenous antibiotics, such as diarrhea and subsequent diaper dermatitis.
However, one major disadvantage of topical anesthetics is their relatively slow rate of onset of action. LET's onset of action begins 20 to 30 minutes after application, compared with 45 to 90 seconds after injection of lidocaine. Eutectic lidocaine-prilocaine cream (EMLA) works best after 1 hour. The reason is that EMLA diffuses slowly across the stratum corneum. Moreover, LET is effective only on open wounds; it does not otherwise penetrate the stratum corneum.
The topical route does not significantly decrease the risk of systemic side effects in all cases. For example, the combination of tetracaine 0.5%, epinephrine 1:2,000, and cocaine 11.8% (TCA gel) has been used since 1980. Systemic absorption of the cocaine has been associated with hyperexcitability, euphoria, hypertension, tachycardia, and possibly seizures. This toxicity has resulted in several deaths. Newer combinations that do not contain cocaine, such as LET and EMLA, are safer alternatives. Likewise, topically applied corticosteroids can have adverse systemic effects. Even hydrocortisone, a topical corticosteroid of the lowest potency, has been reported to cause adrenal suppression in rare, extreme situations.1 Thus, topical therapy often has effects that are beyond "skin-deep."
Advanced pharmacokinetics guides drug formulation with vehicles that optimize topical delivery. For example, corticosteroid ointments are more potent than creams. The addition of propylene glycol increases the bioavailability of corticosteroids across the stratum corneum. With increased diffusion, there is greater potential for toxicity. Systemic side effects from topical agents will likely become a bigger issue in the future as the potency of percutaneous medications increases. It is also important to remember that children, with their increased ratio of surface area to weight and immature hepatic and renal function, are at greater risk of toxic side effects than are adults. Premature neonates especially have increased absorption via their thinner epidermis.
Transcutaneous delivery of medication is especially useful in pediatrics and may someday change the way that we treat many childhood ailments. However, we must also be aware of the potential adverse effects of these medicines.
A topical medication helped ease the pain of my patient with the injured chin. With her laceration numbed and her tears dried, my job became much easier. She fell asleep after the third buried suture was placed. When she woke up, her grandmother changed her into a yellow outfit with a bonnet. She then waved good-bye as she smiled, above her bacitracin-coated suture line.
1. Hendrikse JC, Moolenaar AJ. Adrenal suppression with topical hydrocortisone butyrate. Dermatologica. 1973;147:191-197.