Fractional CO2 laser assisted topical articaine anesthesia vs. topical EMLA administration: a randomized controlled study

In laser dermatology, many 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. In for example fractional laser treatment of acne
scars or traumatic scars, where relatively aggressive laser settings are
required, topical anesthesia may be insufficiently effective. On the other hand
infiltration anesthesia is often associated with discomfort and is not
tolerated by patients who are for example needle phobic. This is of particular
importance when larger areas of skin have to be infiltrated. In this case
maximum dosage is also a limiting factor. Earlier research has shown that
topically applied drugs can be effectively delivered to the dermis by
pretreating the skin with an ablative fractional laser at low settings. Hence,
an equal distribution of the drug can be achieved in the tissue. When topically
applied local anesthetics can be delivered to deeper skin layers, this
implicates a relatively simple and painless method of local skin anesthesia.
Relatively large areas of skin can then be anesthesized with low doses of
topical anesthetic. This technique could be used in various cutaneous surgical
and laser procedures.

The objective of this study is to assess the efficacy of skin anesthesia using
fractional laser assisted delivery of articaine hydrochloride 40 mg/ml and
epinephrine 10 µg/ml solution compared to standard anesthesia with topical
eutectic mixture of lidocaine 25 mg/g and prilocaine 25 mg/g cream (EMLA
cream).

Prospective, open label, randomized controlled, within patient trial

In each patient, the lesion will be divided into two comparable regions during
the visit prior to the therapeutic fractional laser treatment. These regions
will then be randomly allocated to either standard anesthesia with EMLA cream
(control region; region I) or ablative fractional laser assisted delivery of
articaine hydrochloride 40 mg/ml en epinephrine 10 µg/ml solution (intervention
region; region II). Patients will be asked to apply EMLA cream at region I
under occlusion two hours prior to the therapeutic laser treatment. Fifteen
minutes before the therapeutic laser treatment, the skin of region II will be
pretreated with the fractional carbon dioxide laser (15% density, 2.5
mJ/microbeam). Directly following fractional laser pretreatment, articaine
hydrochloride 40 mg/ml en epinephrine 10 µg/ml solution will be topically
applied under occlusion at region II for 15 minutes. Subsequently treatment of
both regions will be performed with the same fractional carbon dioxide laser at
the settings used in routine clinical practice. Directly after this therapeutic
laser treatment, patients will be asked to indicate pain on a visual analogue
scale (VAS) from 0-10 (0: no pain; 10: worst imaginable pain) per test region.

Participation in the study requires minimal extra time investment from
patients. 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 or other side effects are usually experienced by
subjects. The dosages of articaine hydrochloride 40 mg/ml and epinephrine 10 µg/
ml solution will be below half of the maximum dosage, so that the occurence of
systemic side effects will be very unlikely. In earlier studies, safe blood
serum concentrations of lidocaine could be maintained following fractional
laser pretreatment of large areas of skin.

When anesthesia by fractional laser assisted delivery of articaine
hydrochloride 40 mg/ml and epinephrine 10 µg/ml solution (intervention) appears
to be less effective than standard anesthesia using EMLA cream (control), the
therapeutic fractional laser treatment may be more painful than it would be in
routine clinical practice. Based on preliminary data, this scenario seems
unlikely. Subjects can withdraw from the study at any moment. For any further
treatment sessions, patients are allowed to choose the most favorable method of
topical anesthesia.

In conclusion, as dosing of the anesthetics is relatively low and fractional
laser pretreatment will not lead to significant side effects, we believe that
the risks are negligible for the subjects participating in this study.