Biomedical Engineering Reference
In-Depth Information
Iontophoresis
Iontophoresis, the introduction of various ions into the skin
through the use of electricity, has been increasingly used by der-
matologists to provide pain relief in outpatient procedures. Ion-
tophoresis uses an electric current to overcome some of the
barriers of the skin and assist the penetration through the move-
ment of ions into the skin via sweat glands, hair follicles, and
sebaceous glands. Generally, a constant direct current is used,
although pulsed currents have also been shown to be effective.
Constant direct current is generally limited to 10-15 minutes
and 1 mA/cm
2
secondary to burns that can result from gener-
ated hydrogen and hydroxide ions. Ultimately, iontophoresis can
be used to deliver chemicals to both superficial and deeper layers
of the skin. The advantages of this technique are multifold: (
i
) it
avoids the pain associated with injection and IV modalities;
(
ii
) it prevents the variation in absorption seen with oral medi-
cations; (
iii
) it bypasses first-pass elimination; (
iv
) drugs with
short half-lives can be delivered directly to tissues; and (
v
) rapid
termination can occur. Disadvantages to this technique include
discomfort and erythema at the site of iontophoresis secondary
to pH changes. There is also the potential for skin irritation and
burns; however, these risks can be minimized by thoroughly
cleansing the skin, using well-saturated pads for electrodes, and
ensuring even skin contact (89).
Iontophoresis of lidocaine diluted in distilled water has allowed
for anesthesia to the depth of at least several millimeters. This
mechanism allows for minimal systemic absorption of the drug
and direct delivery of the drug to the tissues. The addition of
epinephrine assists in penetration and increases the duration of
anesthesia. According to the “bottleneck theory,” which states
that there are a threshold number of molecules able to penetrate
the skin via iontophoresis, the duration of current flow and the
amount of applied current predominantly determine drug pen-
etration. Recent research has shown that iontophoresis of 4%
lidocaine with epinephrine (1:50,000) using a mean total current
of 3.4 mA for an average of 8 minutes caused an 80-100% relief
of pain from injections, dermabrasions, superficial laser surgery,
and electrosurgery. Approximately 25% of patients experienced
adverse effects, including erythema, mild tingling, stinging,
burning, and a transient metallic taste. Furthermore, a study
conducted by Greenbaum and Bernstein comparing the efficacy
of iontophoresis of a lidocaine solution for 30 minutes with topi-
cal EMLA applied for 30-60 minutes. Iontophoresis of lidocaine
was found to be more anesthetizing to pinprick. Overall, it seems
that iontophoresis may be very useful in superficial ablative pro-
cedures with lasers, electrosurgery, dermabrasion, scalpel, or scis-
sors. For deeper procedures, this technique can allow for enough
anesthesia to allow for painless infiltration with lidocaine (89).
is effective in reducing or eliminating pain associated with pulsed
dye laser treatments after a 60-minute application period. EMLA
has been shown to be effective on the face and thighs after
25 minutes. Potential side effects that must be considered include
methemoglobinemia (rare), blanching, redness, pruritus, burn-
ing, and purpura. Caution must be exercised when EMLA is
used near the eyes as it may cause chemical eye injuries, includ-
ing but not limited to corneal abrasions and ulcerations.
LMX is another topical anesthetic consisting of 4% or 5%
lidocaine in a liposomal delivery system. After a 60-minute
application period under occlusion, 5% liposomal lidocaine was
shown to be effective in producing anesthesia to laser-induced
pain stimuli. Its efficacy seems to be comparable with EMLA but
superior to Betacaine-LA and tetracaine (see below). Its liposo-
mal delivery system enhances its effects by facilitating penetra-
tion of the anesthetic into the skin and providing sustained
release. A study evaluated the efficacy and onset of action of
EMLA versus LMX using a high-energy pulsed light source.
Results of the study indicated that a maximum anesthetic effect
was achieved 20 minutes after application of LMX, and that a
similar maximum effect was achieved after 1.5 hours of EMLA
under occlusion. Nonetheless, lidocaine toxicity may occur when
LMX is used over large areas for more than 2 hours (90-92).
We use LMX routinely with or without nerve blocks to perform
one- or two-pass erbium:yttrium-aluminum-garnet (Er:YAG)
laser resurfacing of the face (Fig. 16.7). We have found that a
20-minute application of LMX provides adequate anesthesia for
the 20-40 mm ablative effects of the Er:YAG laser at 1-2 J/cm
2
.
Betacaine-LA is another topical anesthetic consisting of
lidocaine, prilocaine, and a vasoconstrictor. Some preliminary
anecdotal reports indicate that this anesthetic may be more
effective than EMLA; however, more controlled research is
necessary. Betacaine-LA is not approved by the FDA. In addi-
tion, Amethocaine 4.0% gel, which contains 4% tetracaine, has
been used extensively in Europe. Studies have indicated that
tetracaine may be significantly effective in reducing pain asso-
ciated with pulsed dye laser treatment. Potential side effects
include local erythema, pruritus, and edema. Tetracaine gel is
a compounded anesthetic containing 4% tetracaine in leci-
thin-gel base. This gel has not yet received FDA approval; how-
ever, it may be beneficial. Another topical anesthetic agent is
Topicaine, consisting of 4% lidocaine in gel microemulsion.
Studies indicate that Topicaine has a very rapid onset of action
with a long duration of effect. Topicaine is FDA approved with
a recommended application time of 30-60 minutes with
occlusion and is gaining popularity in laser hair removal. Side
effects include erythema, blanching, and edema (90).
S-Caine Patch
The S-Caine local anesthetic patch (ZARS, Inc., Salt Lake City,
Utah), which utilizes a disposable, oxygen-activated heating
element to assist in dermal penetration, contains a eutectic 1:1
mixture of lidocaine base and tetracaine base. After it dries,
this peel becomes a flexible membrane that provides inherent
occlusion and is readily removed (Fig. 16.8). Studies have indi-
cated that the S-Caine local patch has been effective in alleviat-
ing pain associated with shave biopsies, venipuncture, and
vascular access procedures.
This peel is currently in FDA Phase III clinical trials, and its
use for laser and surgical procedures is still being investigated.
A randomized, double-blind, placebo-controlled trial with
Topical Anesthesia
In addition to the aforementioned techniques, topical anesthe-
sia continues to be used with laser and surgical techniques.
Recently, the movement toward less aggressive laser resurfac-
ing techniques (such as single-pass CO
2
laser ablation and
nonablative laser remodeling) has increased the demand for
adequate topical anesthetics to replace IV sedation. Generally,
topical anesthetics function by inhibiting sodium channels,
leading to a block of nerve impulse conduction.
As mentioned previously, EMLA cream is a 5% eutectic mix-
ture of lidocaine and prilocaine and remains the most widely
used topical anesthetic. Several studies have indicated that EMLA
