Fractional CO2 laser assisted delivery of topical anesthetics: a randomized controlled pilot study

In dermatology, many minor surgical and laser procedures are carried out under
local anesthesia of the skin. Anesthesia using topical formulations is time
consuming, as the anesthetic has to be applied at least one hour before
treatment, and is often only partially effective. On the other hand
infiltration anesthesia is often associated with discomfort and is not
tolerated by patients who are for example needle phobic. In the past years,
enhanced and accelerated penetration of various topically applied substances,
including photosensitizers, has been proven by pretreatment of the skin with a
fractional laser, creating a pattern of microscopic ablation craters. This
improvement in drug penetration seems to be regardless of ablation crater
depth. There is limited evidence that transepidermal lidocaine delivery can be
increased by fractional laser pretreatment. These findings might suggest that
local anesthesia of the skin may be achieved by applying an anesthetic drug
topically on a skin surface pretreated with a fractional laser. However, the
exact influence of ablative fractional laser pretreatment on the efficacy of
topically applied anesthetics has never been quantitatively established.
Furthermore, little is known about the role of the formulation of the topical
drug delivered using this method.

The primary objective of this study is to assess the analgesic effect of
fractional carbon dioxide laser assisted delivery of two topical anesthetics
(articaine hydrochloride 40 mg/ml and epinephrine 10 µg/ml solution (AHES) and
eutectic mixture of lidocaine 25 mg/g and prilocaine 25 mg/g cream (EMLA cream)
compared to application of these anesthetics without fractional laser
pretreatment.

The secondary objective is to compare the efficacy of these two different
anesthetics, when applied according to the fractional laser drug delivery
principle.

Prospective, single blinded, randomized, controlled, within subject, pilot
study.

In each subject, four test regions on subject*s back of 1x1 centimeter will be
randomly allocated in a 2x2 design to (1) ablative fractional laser (AFXL)
pretreatment (5% density, 2.5 mJ/microbeam) followed by topical application of
AHES, (2) AFXL pretreatment followed by application of EMLA cream, (3) sham
AFXL followed by application of AHES on the intact skin and (4) sham AFXL
followed by application of EMLA cream on the intact skin. Sham AFXL will be
done by delivering an AFXL pass at 5% density and 2.5 mJ/microbeam right
adjacent to the region of AHES or EMLA application on the intact skin. After
ten minutes incubation time, an AFXL pass will be given as a pain stimulus at
each test region with 5% density and 35 mJ/microbeam. Subjects will be asked to
indicate pain on a visual analogue scale (VAS) from 0-10 (0: no pain; 10: worst
imaginable pain) directly after each pain stimulus.

Subjects participating in the study will be requested to visit the treatment
center once. The time investment will be approximately 20 minutes. Fractional
carbon dioxide laser therapy is a minimally invasive laser procedure with FDA
approval for the device. At the settings used for pretreatment, no pain is
usually experienced by subjects. Without the use of an anesthetic, the pain
stimulus at 35 mJ/microbeam is felt as a firm sting for shorter than one
second. Thereafter, a burning sensation may be felt for approximately one
minute. Local side effects of fractional laser treatment at the settings used
in this study are erythema (always; 1-2 weeks) and swelling (occasionally, 1-4
days).
All together, the burden due to this study is small, side effects are local,
temporary and mild. Systemic side effects are not expected with the doses of
topical anesthetics that will be used in this study. In earlier studies, safe
blood serum concentrations of lidocaine could be maintained following
fractional laser pretreatment of much larger areas of skin. Subjects will
receive a reasonable compensation for the time invested.