Anesthesia

The anesthesia used in permanent makeup is surface anesthesia (external), but infiltration anesthesia (local injection) is sometimes used. For infiltration anesthetics, there are products such as Xylocaine injection, and for eyebrow permanent makeup, there is a topical anesthetic approved by the Ministry of Health, Labor, and Welfare under the trade name Emla Cream. There is no appropriate topical anesthetic approved by the Ministry of Health, Labor, and Welfare for applying eyeliner on the eyelid margin.

First, let's describe the current situation and problems. In the October 2022 issue of Clinical Ophthalmology, a report titled ”A case of keratoconjunctival disorder caused by permanent makeup'' was published.

A 40-year-old woman came to the hospital complaining of pain in both eyes and tearing immediately after eyeliner permanent makeup was applied. Corneal erosion was observed in the eye, and there were no abnormalities in the intermediate translucent body and posterior segment of the eye. Drug-induced keratoconjunctival disorder due to external local anesthetic applied to the skin was diagnosed, and 0.3% tosufloxacin tosilate eye drops (antibacterial) and 0.1% betamethasone sodium phosphate eye drops (an ophthalmic corticosteroid) were started 4 times/day, respectively, and the patient improved without sequelae after 1 week.

The topical anesthetic used for the procedure is an overseas product called MAGIC, and according to its mail-order site, the ingredients are lidocaine 5%, tetracaine 2%, and adrenaline 0.2%. Other than that, there is a possibility that additives such as preservatives or pH adjusters are added, but there is no description other than the main ingredients.

Looking at the case photographs in the article, the corneal conjunctiva in the lower half is cloudy white and stained with fluorescein, indicating that the surface is damaged. Conjunctival hyperemia was not seen, and it looked more like a reaction to irritation than an allergic reaction.

As a consideration, it is written that “Permanent makeup treatments by unqualified people who do not understand the dangers of drugs may cause similar eye disorders in the future.” However, ｔhe exact same results would have been obtained if eyeliner had been applied to the same patient with the same topical anesthetic, even if it had been performed by a qualified person. How could it have been avoided?

The answer, of course, is not to use privately imported topical anesthetics such as MAGIC. So, what could have been used as an alternative anesthesia?

It is safe if performed under infusion anesthesia of the eyelid margin by injection.　However, is it impossible to deal with surface anesthetics?

Basic knowledge of local anesthetics is required here. Let's look at lidocaine as a representative drug. Xylocaine is the trade name of AstraZeneca, and lidocaine is its generic name.

Lidocaine is listed as two substances in the Japanese Pharmacopoeia. Lidocaine and lidocaine injection. The former is insoluble in water (molecular form), and the latter is a hydrochloride salt solubilized in water (ionic form).

Figure 2

Structural formulas of lidocaine (left: molecular form) and lidocaine hydrochloride (right: ionic form).

 The surface of healthy skin (stratum corneum) is weakly acidic with a pH of 4.5 to 6.0, and substances ionized as hydrochloride do not easily permeate. This is because the charged particles electrically repel each other.

 This is easily understood by taking sodium ascorbate (vitamin C) as an example. Recall that sodium ascorbate is also in the ionic form and there is iontophoresis to push it through the skin. With a strong electrode rod, it overcomes the charge on the surface of the stratum corneum and pushes the molecules in.

 On the other hand, when ascorbic acid is esterified with palmitic acid to form a molecule, it becomes electrically neutral and is easily absorbed. Lidocaine in molecular form, not hydrochloride, is much more easily absorbed through the skin.

 Emla cream, which is the only topical anesthetic for the skin approved by the Ministry of Health, Labor, and Welfare in Japan, also contains molecular lidocaine as its main component. Not lidocaine hydrochloride.

 However, there is a reason why this Emla cream is difficult to use on the eyelid margin. This is because the formulation has a pH of 9.2, which is strongly alkaline.

 Lidocaine itself is a weakly alkaline substance and Emla cream is intentionally designed to be strongly alkaline using a pH adjuster. The reason for this is that the more alkaline the ointment base, the more stable the molecular form of lidocaine, It is confirmed by the manufacturer, Sato Pharmaceutical Science Department.

 Another point may be the effect of making the stratum corneum barrier of the skin more permeable. The stratum corneum is strong but weak against alkali. You may have experienced the slippery skin in an alkaline hot spring. This is because the stratum corneum surface melts.

 On the other hand, the conjunctiva of the eye is weak against alkali. This is the reason why Emla cream is difficult to use on the eyelid margin. The package insert for Emla Cream states,“Be careful not to get it in the eyes. (In a rabbit ocular mucosa irritation test, severe and persistent irritation reactions such as conjunctival hyperemia, eyelid swelling, and corneal damage were observed. )”.

 The case of keratoconjunctival damage due to MAGIC reported in Clinical Ophthalmology may have been due to the pH of the formulation rather than allergy.

 There is a product called xylocaine ophthalmic solution (4%). Since it is the same surface anesthetic, has anyone tried to expect the effect by applying this to the eyelid margin? I thought so too.

 I added carboxymethyl cellulose (thickener) to the xylocaine ophthalmic solution to make it into a gel, but it did not work as an anesthetic to the skin at all. That's what it should be because the ionic form of xylocaine hydrochloride is used in xylocaine ophthalmic solution. There are other xylocaine preparations such as injections and xylocaine jelly for urethral and tracheal mucosa, but all of them are hydrochlorides.  Since mucous membranes do not have a stratum corneum, even hydrochloride is sufficiently permeable. And water-soluble agents are more convenient to use because they do not cause turbidity.

 For the above reasons, there is currently no topical anesthetic approved by the Ministry of Health, Labor and Welfare that can be used safely on the skin of the eyelid margin that is near the conjunctiva. Therefore, we must rely on surface anesthetics used overseas, but overseas products do not necessarily list all ingredients and do not provide an interview form that describes the pH of the formulation.

 The most recommended solution is to make topical anesthetic by yourself. Instead of lidocaine hydrochloride, obtain lidocaine and knead it into a suitable ointment base. I've tried several bases, but Plastibase seems to be the best one. Plastibase is frequently used as a base for eye ointments too.

 Figure 3 

A self-made ointment by mixing 10% by weight of lidocaine with Plastibase. Grind it patiently in a mortar. Even if some white particles remain, an anesthetic effect can be obtained. Though the white particles may disappear if lidocaine powder is dissolved in alcohol and then mixed, considering the stimulation to the mucous membrane, it is safe to add nothing.

 Regarding the source of lidocaine, although it is listed in the Japanese Pharmacopoeia, it is not provided as a product by pharmaceutical companies. In fact, this kind of thing is often experienced. Pharmaceutical companies are ultimately profit-making, so they don't do anything that doesn't make a business.

 The easiest way to obtain it is to purchase the reagent. However, most reagent companies limit the purpose of use to research, and if they hear that it is for clinical use in humans, they will refuse to sell it.

 The fact that reagent companies refuse to sell them does not mean that the clinical use of such home-made ointments is illegal. It's just that reagent companies don't want to be held responsible for any adverse events. In theory, it can be said that lidocaine with high reagent-level purity is rather reassuring.

 When purchasing a reagent, you probably won't be asked about the use in detail, but if you are asked, the only way to get the company to understand is to fully explain that it is listed in the Japanese Pharmacopoeia and the responsibility for using the reagent rests with the individual doctor.