Parameters in fractional laser assisted delivery of topical anesthetics: role of laser type, laser settings, type of anesthetic and occlusion time

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. In the past years,
enhanced and accelerated penetration of various topically applied substances,
including photosensitizers and anesthetics, has been proven by pretreatment of
the skin with an ablative fractional laser (AFXL), creating a pattern of
microscopic ablation channels. In a previous pilot study performed at our
institute, we demonstrated that effective anesthesia could be achieved within
ten minutes after application of a topical anesthetic on skin pretreated with
AFXL at painless settings (METC 2014_139). However, little is still known about
the role of the type of fractional laser used (e.g. CO2 or Er:YAG laser), the
laser settings, the type of anesthetic and the occlusion time on the efficacy
of the anesthesia.

The primary objectives of the present study are to compare the effect of
pretreatment with two different fractional laser modalities (CO2 and Er:YAG
laser) on topical anesthesia and to compare the anesthetic effect of two
different topical anesthetics on fractional laser pretreated skin.

Secondary objectives are to assess the role of the laser settings and occlusion
time.

Prospective, single blinded, randomized, intra subject controlled study.

Subjects will be divided into two groups. In group A, four test regions on each
subject*s back will be randomly allocated to pretreatment with the fractional
CO2 laser at 5% (I) or 15% density (II) or pretreatment with the fractional
Er:YAG laser at 5% (III) or 15% density (IV). After pretreatment, articaine
hydrochloride 40 mg/ml + epinephrine 10 *g/ml solution (AHES) will be applied
on the test regions with 15 minutes occlusion time. In group B, six test
regions will be pretreated with the fractional CO2 laser at 15% density. These
regions will be randomly allocated to application of AHES for 5 (I), 15 (II)
and 25 minutes (III) or application of lidocaine 70 mg/g + tetracaine 70 mg/g
cream (LTC) for 5 (IV), 15 (V) or 25 minutes (VI). After the occlusion time, a
single pulse with the CO2 laser (5% density; 50mJ) will be applied on each test
region as a harmless standardized pain stimulus. In addition, a reference pain
stimulus with the CO2 laser at the same settings will be given on
unanesthetized skin. 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 45 minutes. Fractional
laser therapy is a minimally invasive procedure. At the settings used for
pretreatment, no pain is usually experienced by subjects. Without the use of an
anesthetic, the CO2 laser induced pain stimulus at 50 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.