Iontophoresis of lidocaine is a proven method for providing dermal analgesia for cannulation in adults and children [1-3]. It works by accelerating the diffusion of lidocaine across intact skin using a small electric current . Analgesia can usually be achieved within around 10 min [1-3]. Eutectic mixture of local anaesthetic cream (EMLA) is also an effective topical analgesic, but requires around 60 min to be fully effective [6,7]. Although various studies have demonstrated the efficacy of both EMLA and lidocaine iontophoresis against placebo, the two techniques have never been compared in adult patients for venous cannulation using the patients as their own control.
Approval for this study was given by our Hospital's Ethics Committee and all subjects gave informed, written consent. Twenty-eight ASA I-III patients, aged 19-77 yr, undergoing elective ear, nose and throat (ENT) surgery at Queen's Medical Centre were enrolled. Criteria for exclusion included expected difficult venous access, diseased or broken skin on hands and allergy to EMLA, lidocaine or any part of the iontophoresis equipment.
Each patient had EMLA applied followed by sham iontophoresis on one hand and sham cream followed by active iontophoresis on the other. The choice of side for EMLA or iontophoresis was made randomly using a random number table. The allocation of side was made after patient consent to entry into the study.
EMLA cream was applied to the back of one hand over a vein suitable for cannulation. A similar looking placebo cream (Aqueous cream, Adams Healthcare, Leeds, UK) was applied to the other hand and an occlusive dressing (Opsite®; Smith & Nephew, Hull, UK) covered both creams. A length of vein, well within the expected area of anaesthesia, was identified and marked to ensure subsequent cannulation within the anaesthetized area. One hour later, the creams were removed and the skin cleaned with surgical alcohol. A specially designed iontophoresis electrode (TransQ2-GS®; RDG Medical, Croydon, UK), prefilled with 3 mL of lidocaine 4% plus epinephrine 1 in 50 000, was applied to the back of the non-EMLA hand and a dispersive electrode was placed over muscle on the proximal forearm (Fig. 1). An identical system, but without lidocaine, was applied to the other hand. The circuits were attached to an iontophoresis device (Phoressor® II auto; RDG Medical, Croydon, UK) with the hand being the positive electrode. A current of 2 mA was then given for 10 min to the lidocaine hand. The sham electrode had no current applied (Fig. 1).
After completion of iontophoresis the electrodes were removed, any gel remaining on the skin was removed and both elbows covered so that any erythema at the negative electrode was not visible. A second anaesthetist, who was unaware of treatment allocation and did not see any of the iontophoresis, then cannulated a vein under the anaesthetized area using an 18-G cannula. The left-hand vein was always cannulated first. The patient was then asked to score the amount of pain on cannulation for each hand on a 10 point verbal rating scale (no pain to worst pain imaginable), again left hand first. All cannulations took place within 5 min of completion of iontophoresis. In addition, the patient was asked to report any side-effects and the presence of skin changes at the electrode sites were noted. In order to provide some assessment of whether cannulation was more difficult on one side or the other, the time to complete cannulation (skin puncture to cap placed on the cannula) and ease of cannulation was also recorded (easy, moderate and difficult).
Power analysis indicated that 20 patients would be required to detect a difference of 2 points on a 0-10 pain rating score with a power of 0.8 and alpha of 0.05. Pain scores were analysed using U-tests. Time to complete cannulation was analysed using paired t-tests. All analysis was performed using Minitab® 13.3 statistical software (Minitab Inc., State College, Pennsylvania, USA).
Twenty-eight patients were recruited undergoing a variety of ENT procedures - 6 females, 22 males. Eight patients were excluded from analysis. In four patients cannulation was unsuccessful on one side: two, iontophoresis; two, EMLA. One patient requested withdrawal because of intolerable pain and burning at the negative electrode. One patient had surgery performed under local anaesthesia (which violated the experimental protocol), and one patient went for surgery before iontophoresis could be started. The protocol was violated (with insertion of a cannula well beyond the marked area) in one patient.
Pain scores for cannulation on the EMLA side (median 1, range 0-7) were significantly lower than on the iontophoresis side (median 3, range 0-6), P = 0.023. Numbers with no pain (pain score = 0) were eight EMLA and three iontophoresis; minimal pain (≤1), fifteen EMLA and seven iontophoresis; no more than moderate pain (≤3), seventeen EMLA and fourteen iontophoresis; severe or unacceptable pain (≥5), one EMLA and two iontophoresis.
There was no significant difference in time to complete cannulation: EMLA (11.9 s, 4.9 (mean, SD)) vs. iontophoresis (12.4, 3.3), P = 0.7. The anaesthetist reported all cannulations - except the four failures - as easy.
The observed and reported adverse effects are given in Table 1. All erythema and blanching resolved within 1 h. All other adverse effects stopped when iontophoresis ceased.
Using the EMLA and iontophoresis doses in this study we found that EMLA provides better analgesia for peripheral venous cannulation than lidocaine iontophoresis. There may be several reasons why iontophoresis performed less well than EMLA.
The iontophoretic dose may have been too low. The amount of local anaesthetic passing across the skin is related to the total charge, area of the electrode and availability of drug. Using purpose designed iontophoresis, electrodes makes it unlikely that electrode area or drug availability were the limiting factors. Addition of epinephrine to the mixture may theoretically increase the amount of charged lidocaine available for iontophoresis and prolong the duration of action without influencing the depth of penetration of the local anaesthetic . Lidocaine 4% with epinephrine 1 in 50 000 has been successfully used in other studies [8,9]. The concentration of lidocaine in solution does not affect the degree of analgesia . The iontophoretic dose in this study was set at 20 mA min. Previous studies have used larger doses of 30-40 mA min [1-10]. However, in a pilot study in our institution we found that increasing the current to 4 mA resulted in more paraesthesia and some pain, which some patients regarded worse than the pain of cannulation. Even with the dose used in this study, one patient (aged 73 yr) had to be withdrawn because of intolerable burning sensation. Prolonging the duration of iontophoresis would reduce the main advantage of lidocaine iontophoresis, which is a shorter time required to achieve analgesia. Conversely, although the recommended application time for EMLA is 60 min, some authors have suggested that this is too short .
Cannulation may have been more difficult on the iontophoresis side, but there was no evidence for this, either in the time to complete cannulation or the ease of cannulation as reported by the anaesthetist or the failure rate. The blanching or erythema caused by the treatments did not appear to influence ease of cannulation.
Skin puncture may have been outside the anaesthetized area. However, the length of vein that was well within the expected area of anaesthesia was marked on both hands and the one patient in whom this did occur was excluded from analysis. A median pain score of 3 is also lower than would be expected for insertion of an 18-G cannula through unanaesthetized skin .
Blinding may have been inadequate. Every effort was made to blind the subject to the methods used. However, 12 of 20 subjects were aware of paraesthesia at the negative (elbow) active electrode. One subject volunteered that active iontophoresis was occurring through the sham electrode. The information given to the subjects prior to the study clearly stated that the investigators did not know which technique was better so we have no reason to expect systematic bias from the subjects. However this cannot be excluded. We chose not to have an active sham iontophoresis (i.e. electric current, without lidocaine in the gel), as we do not know what effect this would have on the analgesia provided by the EMLA already present.
Previous studies have shown iontophoresis to be effective using a variety of methods [1-3,5,8,13]. However none of these studies has used an 18-G cannula as the stimulus. It may be that a combination of slightly reduced iontophoresis dose and a more painful stimulus was sufficient to reveal a difference in analgesia between the two techniques. Other groups have found iontophoresis to be better than EMLA in children . This may reflect a different patient group, different iontophoretic dose and a smaller stimulus.
This study was not designed to assess the efficacy of iontophoresis per se, which has been done in previous studies. However the pain scores in the iontophoresis group were lower than historical data for insertion of 18-G cannulae through unanaesthetized skin .
EMLA is an effective topical local anaesthetic, which is widely used in the UK. Amethocaine gel (Ametop®; Smith & Nephew, Hull, UK) is reported to work faster for the same or better degree of analgesia [6,7,14,15]. Further work in this area may be better carried out comparing iontophoresis with Ametop®, since Ametop® would further reduce the time advantage of iontophoresis.
In summary, iontophoresis of lidocaine using a 20 mA min dose is less effective than EMLA applied for 60 min prior to cannulation for providing analgesia for peripheral venous cannulation in adults. Although 20 mA min iontophoresis with lidocaine is more quickly effective than EMLA, the superior quality of EMLA analgesia should be borne in mind if these treatments are used electively. A higher iontophoretic dose may have better analgesic effects but this will be at the expense of time or local side-effects.
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