Pediau-ic Dermatology Vol. 14 No. 5 397-«X), 1997

Iontophoresis for Anesthesia During PulsedDye Laser Treatment of Port-Wine Stains

Maria Niinez, M.D,,* Enrique S. Miralles, M.D.,* Pablo Boixeda, M.D.,*Francisco Gomez, M.D.,t Bibiana Perez, M.D.,* Victor Abraira, M.D.,t and

Antonio Ledo, M.D.'*

'*Servicio de Dermatohgia and 'rUnidad de Bioestadi'stica, Hospital Ramon v Cajal, Universidad de Alcald,Madrid, Spain

Abstract: Port-wine stains (PWS) are benign, congenital vascuiar mal-formations found in approximately 0,3% of newborns, PWS may be effec-tively treated with the flashlamp pulsed dye laser (FPDL) at 585 nm. How-ever, laser therapy of vascular lesions often produces pain. We performeda prospective double-blind, placebo-controlled evaluation of the ionto-phoresis of lidocaine 5% with epinephrine 1:50,000 and mepivacaine 2%with epinephrine 1:50,000, Thirty-six patients with facial PWS were in-cluded in the study; 13 of them were treated with lidocaine 5% with epi-nephrine, another 13 were treated with mepivacaine 2% with epinephrine,and the other 13 were treated with preservative-free 0.9% NaCI. The painwas graded by the patient on a visual analog scale from 0 to 10, compar-ing the iontophoretically treated area with an adjacent area treated with-out anesthesia. Pain evaluation by patients demonstrated a significantdecrease in the pain of pulsed dye laser impulses using the iontophoresisof lidocaine 5% with epinephrine. No change in the efficacy of pulsed dyelaser treatment of PWS or important side effects were observed in ourpatients, iontophoresis of lidocaine 5% with epinephrine is a safe andeffective method of local anesthesia for pulsed dye laser and it is moreeffective than the iontophoresis of mepivacaine 2% with epinephrine.

Flashlamp pulsed dye laser (FPDL) therapy is ac-cepted as the treatment of choice for port-uinc stains(PWS) ( I ^ ) . Currently available methods of anesthesiahave been employed in FPDL therapy with different re-sults (.5). Recently iontophoresis of lidocaine has beenemployed in anesthesia during FPDL treatment of PWSwith satisfactory results (6). Iontophoresis consists of theintroduction of ions of soluble salts into the tissues, hymeans of an electric cun'ent, for therapeutic purposes (7).It has been u.sed to deliver a large number of medicationsinto the skin, including local anesthetics (8-11).

We performed a double-blind, placebo-controlledprospective evaluation of the iontophoresis of lidocaine5% with epinephrine and mepivacaine 2% \̂ 'ith epineph-rine for the ditninution of pain duritig FPDL treatment ofPWS.

MATERIALS AND METHODS

Patients

Patients with facial PWS larger than 15 cm" and olderthan 6 years coming for FPDL treatment were invited to

.''iddie.ss correspondence to Mari'a Nunc/. M.D.. C/lotge Guillen 2.713, 470(13 Valladdlid. Spain.

397

398 Pediatric Dennatology Vol. 14 Ko. 5 Septemher/October 1997

participate in this study. Thirty-nine patients were en-rolled. There were 26 females and 13 males; tlie averageage v\'as 17.2 years (6 to 36 years). ITiirtecn patients,randomly chosen, were treated with lidoeaine 5% withepinephrine, another 13 were treated with mepivacaine2% with epinephrine, and the remaining 13 were treatedwith preservative-free 0.9% NaCI with epinephrine ascontrols.

lontophoretic Protocol

The lontophoretic delivery system consisted of a eon-stant galvanic generator (Microphor), a medication-delivery eleetrode. and a dispersive eleetrcxJe (Medi-trode) (both supplied by Life-Tech. Inc., Houston. TX).The electrodes used were round with a 4-cm diatneterand they covered an area of 14 cm". Medication-delivervelectrodes containing either lidocaine 5%, mepivacaine2%. or 0.9% NaCI with epinephrine were randomly la-beled 1, 2, or 3. Half of the PWS was marked v\ith asurgical marking pen. In this half area the tnedication-deliver)' electrode was placed. The dispersive electrodewas placed on the ipsilateral forearm in every patient.The constant eleetric current was applied at 3 m.^ for 1.5minutes. Itnmediatcly after finishing the anesthesia pro-cedure, the patients were treated with FPDL. All thepatients received 70 Ia.ser impulses for the treatment ofthe PWS at 7.0 J/cm", 35 of them on the anesthesizedarea and another 35 on the nonanesthesized area.

Evaluation of .-Vnesthe.sia Etflcacy

We employed a Candela llashlamp pulsed dye laser(SPTL-1, Candela Corp.. Wayland, MA) with a wave-length of 585 nm, a pulse duration of 450 JJLS, and a spotsize of 5 mm. Thirty-five laser impulses were applied onthe nonaneslhesizcd area of the PWS and it was ex-plained to the patient that this was the baseline pain (pain= 10), Then the alternate half of the PWS, treated withiontophoresis, was subjected to 35 laser impulses. Thepain w as graded by the patient on a visual analog scale of0 = no pain to 10 = pain sitnilar to the noiianesthesizedarea of the PWS. The side effect.s observed or related bythe patient were recorded. We evaluated the efficacy ofthe FPDL therapy clinically by judging the clearance ofthe PWS from 0% (no clearance) to 100% (maximalclearance).

Statistical Analysis

"Crude" analysis of data was performed primadly withthe Kruskal-Wallis test with Bonferroni's cotTection.Multiple linear regression was cho.sen to assess the rela-

tive effect of tlie anesthesia controlled for possible con-founding variables.

Specification and Coding of BaselinePredictor Variables

In the linear regression, we included five independentvariables in the maximum model: anesthesia, age, se.\,location of PWS, and previous treatments with FPDL.These variables were seleeted by clinical criteria. Theanesthesia was coded 1 for lidocaine, 2 for mepivacaine,and 3 for placebo. The age was cited direetly in years.Sex was coded as 0 for female and 1 for male. Locationof the lesion was coded as 1 for cheek, 2 ibr forehead, 3for chin, 4 for lip, and 5 for neck, if the patient hadreceived previous treatments with the FPDL he vvaseoded as 1, and was coded as 2 if he had not receivedprevious tteatinents. The anesthesia and location vari-ables were transformed into dummy variables accordingto a coding scheme that uses the lidocaine and cheek asthe reference levels, re.spectively. A significant p valueof .05 vvas set up. We used a backward modeling proce-dure with the / ' pattial as the statistic for comparing thesuccessive models. The PREST.'̂ PC package was usedfor statistical analysis.

RKSUI/rS

Thirty-nine patients entered the study and were followedup. In 31 patients the PWS was located on the check, in3 patients on the forehead, in 2 patients on the chin, in 2patients on the lip. and in 1 patient on the neck. Thirty-eight patients had received previous treatments withFPDL. For the patients with previous treattnents withFPDL, 13 patients had never previously received anyanesthesia, 13 patients had received topical anesthesia inat least one session, and in the other 12 patients generalanesthesia was employed on at lea.st one occasion. Therewere tio important .side effects recorded. Patients oftenreported a tingling, burning, or pulling .sensation at themedieation-delivery and dispersive electrode sites. Pro-longed erythema under the negative electrode appearedin four patients and a rnetiillic taste was reported by twopatients. In the "crude" comparisons (Kruskal-Wallis),the iontophoresis of lidocaine 5% with epinephrine andthe mepivacaine 2% with epinephrine were both effec-tive in reducing the pain of FPDL impulses. There was astatistieally significant difference in the diminution ofthe pain betvveen lidocaine with epinephrine and mepiv-acaine with epinephrine (Fig. 1). With the multiple linearregression we obtained a final model with two indepen-dent variables (anesthesia and se.x) with sex as a eon-founding variable. Men reported more pain than wotnenin our study. With the multiple linear regres.sion both the

Ni'ifiez et al: Iontophoresis for Anesthesia 399

Pain mean values

Pain

Figure 1, Pain in visual analog scale(Kruskal-Wallis test), p = .00000.

Lidocaine Mepivacaine Placebo

iontophoresis of lidocaine with epinephrine and mepiv-acaine with epinephrine continued to be effective inreducing the pain of FPDL impulses. There was a .statis-tically significant difference between lidocaine with epi-nephrine and mepivacaine v\ith epinephrine, with the li-dcKaine being more effective in reducing the pain (Tablelj. Men reported 1.13 units more pain than did women inthe visual seale for each anesthesia employed. The sitesteeeiving iontophoresis with epinephrine showed mini-mal degrees of blanching. Preoperative tnarking of theoutline of the PWS vvas not neeessary beeause the PWSretnained visible. There was no significant difference inany patient in the clearance of the area of PWS treatedwith anesthesia compared with the site not reeeiving an-esthe.sia.

DISCUSSION

A wide range in degree of pain is reported by patientstreated with FPDL (4). Topical anesthesia (EMLA, topi-cal lidocaine, ice packs) generalh' did not ptoduee ad-equate analgesia (12-14). Nerve blocks and local infil-tration of PWS wdth anesthetics can be employed, but theprcKedure is painful, and in children their use may behazardous (15). Sedation and general anesthesia are nottotally benign and riskfree (16,17). In iontophoresis theanesthesia is applied under an electrode of the same

T.-\BLE L Re.uilt.',- with the Multiple Linear Regression= 0.2S2: F Model = 25.5!!; p = .()000(l)

Lidocaine (refereiiee)VlepivaeainePlaeehoSex (reference female)

Pain

3.9266.2247.6501.130

charge as the drug, and a dispersive electrode opposite incharge to the drug is placed at a neutral site; both elec-trodes are interconnected by constant electrical current.The advantage.s of this anesthetic method are lack ofdiscomfort for the patient, .sufficient local and minimalsystemic concentration of the anesthetic reached, no vis-ible distortion of tissue, no risk of infection, and safety inchildren (9). The disadvantages are that anesthetics mustbe soluble, the electrodes and an iontophoresis apparatusare needed, the time for anesthesia is longer than withother methods, and it cannot be used on broken skin orhyperkeratotic areas (18). Iontophoresis of lidocaine foranesthesia during FPDL treatment of PWS has also beenused with positive results (6).

Our results show that iontophoresis of lidoeaine 5%with epinephrine and mepivacaine 2% with epinephrineare effective in dimini.shing the pain of FPDL treatmentof PWS, with lidocaine 5% with epinephrine being amore effective anesthetic. In our patients, the degree ofpain was influenced by the sex; men reported a higherdegree of pain than women. Tlie other variables (age,location of PWS, and previous treatments with FPDL)did not influence the degree of pain. Some problem withreliability ma\' exist in our study, because only a fewpatients with PWS in certain locations were included; thesame is tnie for the group of patients who had not re-ceived previous treatments with FPDL. .As this was notthe goal of our study, this problem vvas not considered.

Iontophoresis of lidocaine is capable of increasingskin perfusion in normal skin, but in a recent study,iontophoresis of lidocaine did not increase perfusion ofPWS (5). The addition of an empirically determinedquantity of epineplirine to the local anesthesia enhancedthe therapist's delineation of treatment sites and in-creased the duratton of anesthesia (19). Epinephrine is

400 Pediatric Dermatology Vol. 14 .No. 5 September/October 1997

used at 1/10.000 or 1/100,000 with local anesthetics. Li-docaine plus epinephrine supplied anesthesia for 60 min-utes. We have had no problems with the u.se of epineph-rine. Previous studies found a decrease in skin perfusionin PWS in response to epinephrine, and also with theiontophore.sis of lidocaine with epinephrine. but theyshowed no diminution in the clearance of PWS treatedwith FPDL, as we found in our patients (6,20). We havefound minimal blanching in the area ane.sthesized withiontophoresis; this can be explained because the com-bined va.sodilat()r\' effects of lidocaine and irritative elec-tric current induce increases in tissue perfusion, but theaddition of epinephrine reduced this effect. Side effectsthat appeared were minor and suspension of the proce-dure was not nece.ssary.

In conclu.sion. this study confirms that the iontopho-resis of lidocaine 5% with epinephrine is effective andsafe for local anesthe.sia during FPDL treatment of PWSin adults and in children older than si.\ years of age andIt is more effective than the iontophoresis of mepivacaine2'th with epinephrine. We have demonstrated that thecontrol of pain depends only on the types of anesthesiaand sex, with men reporting more pain than women.Further assessments will be necessary to judge the effi-cacy of this technique in young children and infants.

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