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PEDIATRIC ANESTHESIA

Lidocaine Iontophoresis Versus Eutectic Mixture of Local Anesthetics (EMLA^®) for IV Placement in Children

Jeffrey L. Galinkin, MD^*, John B. Rose, MD^*, Kathleen Harris, RN, and Mehernoor F. Watcha, MD^*

*University of Pennsylvania and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania

Address correspondence and reprint requests to Jeffrey L. Galinkin, MD, Department of Anesthesia and Critical Care, Children’s Hospital of Philadelphia, 34th St. and Civic Center Blvd., Philadelphia, PA 19104-4399. Address e-mail to galinkin{at}email.chop.edu

	Abstract

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Pain during venipuncture is a major source of concern to children and their caretakers. Iontophoresis is a novel technique that uses an electrical current to facilitate movement of solute ions (lidocaine) across the stratum corneum barrier to provide dermal analgesia. In this study, we compared dermal analgesia provided by lidocaine iontophoresis and eutectic mixture of local anesthetics (EMLA^®). After informed consent, 26 children, aged 7–16 yr, who required venous cannulation on multiple occasions, were enrolled in this prospective, randomized, crossover study to receive EMLA and iontophoresis on separate occasions. During a third session, each subject received his or her preferred treatment. Pain during venipuncture was assessed by the subject, parent, observer, and technician performing the procedure, by use of a 100-mm visual analog scale. The observer also used the Children’s Hospital of Eastern Ontario Pain Scale to rate the subject’s pain. Ratings of subject satisfaction were also assessed. There were no significant differences between the two groups in the subject-rated visual analog scale or the Children’s Hospital of Eastern Ontario Pain Scale scores. Eleven (50%; 95% confidence interval [CI], 31%–69%) of the 22 subjects who completed both sessions preferred iontophoresis. Five subjects (23%; 95% CI, 10%–44%), including two who did not tolerate treatment with iontophoresis, preferred EMLA, and six (27%; 95% CI, 13%–48%) had no preference for the intervention to provide dermal analgesia. We conclude that lidocaine iontophoresis provides similar pain relief for insertion of IV catheters as EMLA and is a useful noninvasive alternative to establish dermal analgesia for venous cannulation.

IMPLICATIONS: Iontophoresis is a technique that uses an electrical current to facilitate movement of solute ions (lidocaine) across the stratum corneum barrier to provide dermal analgesia. Lidocaine iontophoresis provides similar pain relief for insertion of IV catheters as eutectic mixture of local anesthetics and is a useful noninvasive alternative to establish dermal analgesia for venous cannulation.

	Introduction

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Venipuncture and insertion of an IV catheter are painful, stressful procedures in children and can be a challenge for their health care providers. Pain-free venipuncture can be achieved by the application of a eutectic mixture of the local anesthetics lidocaine and prilocaine (EMLA^®; AstraZeneca PLC, London, UK) (1–5). It has become the treatment of choice when patients desire a needle-free method for topical anesthesia during venipuncture and IV catheter insertion. However, effective analgesia requires the application of EMLA for 60 to 90 min, limiting its usefulness in busy ambulatory health care settings (2,3,6).

Iontophoresis is a novel transdermal drug delivery system that uses an electric current to carry ionized lidocaine through the stratum corneum (7). Drug delivery is proportional to the product of the strength and duration of the current (milliamperes per minute). Lidocaine iontophoresis can provide effective topical anesthesia of the skin and underlying tissues for 42–110 min (8) to permit pain-free venipuncture and placement of IV catheters within 5–15 min (9,10). A commercially available portable iontophoresis system that allows delivery of drug to a depth of 10 mm in 7–10 min by using a current of 4 mA or less (11) has been approved by the Food and Drug Administration of the United States for use in children (Model PM-800; Iomed, Salt Lake City, UT). In this randomized, prospective, crossover study, we compared the efficacy, side-effect profile, and patient preferences for EMLA and lidocaine iontophoresis in children undergoing repeated procedures requiring peripheral IV access.

	Methods

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Twenty-six children were enrolled after approval was obtained from the IRB of the Children’s Hospital of Philadelphia, written informed consent was obtained from the parents or legal guardians, and assent was obtained from the child. All 7- to 16-yr-old children scheduled for procedures requiring peripheral IV catheter placement at the Day Medicine Unit of the Children’s Hospital of Philadelphia on more than two occasions separated by at least 7 days were eligible for enrollment. Children with pacemakers, electrically sensitive hardware, or allergies to tape or local anesthetics; those intellectually incapable of completing the visual analog scale (VAS) and questions on the assessment forms; and those with preexisting neuropathies, sensory or motor deficits of the upper extremities, and skin conditions such as graft-versus-host disease, dermatomyositis, psoriasis, and eczema were excluded.

All subjects were randomized in a Latin square crossover design to receive EMLA and lidocaine iontophoresis during two separate sessions. During the EMLA treatment session, two sites for venipuncture were covered with a thick paste of 2.5 g of EMLA cream, and an occlusive dressing (Tegaderm^®; 3M, St. Paul, MN) for a minimum of 60 min. This was wiped off before placement of the IV catheter. During the lidocaine iontophoresis session, the reservoir of a positively charged delivery electrode was saturated with 1 mL of lidocaine hydrochloride 2% with epinephrine 1:100,000 (Iontocaine^®; Abbott Laboratories, North Chicago, IL). The drug delivery electrode was placed over the site for venipuncture after cleaning the area with a soft cloth and water. A negatively charged grounding electrode was moistened with tap water and placed over the belly of the triceps muscle at least 4 in. from the delivery electrode. Iontophoresis was performed by using a device provided by Iomed (Model PM-800). The initial current was set at 0.0 mA, and the device was programmed to increase the current to 4 mA over 60 s. The iontophoretic treatment was discontinued after a dose of 40 mA/min was delivered.

The iontophoresis equipment, electrodes, EMLA cream, and Tegaderm dressing were removed and the application site cleaned with an isopropyl alcohol wipe before the observer was permitted to enter the room, to ensure that the observer was blinded to the subject’s study group assignment. However, the subject, parents, and technicians caring for subjects enrolled in the study could not be blinded. Vascular access was established by an experienced nurse who was a member of the hospital IV team. The number of attempts and ease of insertion of the IV catheter as assessed by the person performing the procedure were recorded. At each session, subjects and parents were asked to assess the child’s pain intensity and distress during the procedure on a 100-mm VAS. If more than one attempt at venipuncture and IV catheter placement was required, pain scores from the first attempt were used in the analysis. The blinded observer rated the subject’s pain by using the Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) and also recorded the heart rate before, during, and immediately after the intervention. In addition, the subject, parent, observer, and person inserting the IV catheter completed a short questionnaire with the following script:

1. Did you (the subject) feel an effect from the treatment? Please grade this on a scale where 1 = no effect and 5 = strong effect.

2. Did you like the treatment? Please grade this on a scale where 1 = dislike a lot and 5 = like a lot.

The site of venipuncture was examined for signs of erythema, blanching, bruising, and burns. The occurrence of tingling and electric shock during the iontophoresis was recorded. Finally, parents and subjects were asked to state their preference for one of the two treatment regimens, and this was used for IV catheter placement on the third visit.

The primary outcome variable of this study was the VAS pain score as assessed by the subject. A sample size of 20 was calculated on the basis of the following assumptions:

1. The mean and SD for pain scores in the EMLA group would be similar to previously published data in this age group (12).

2. A difference of 5.5 mm in the VAS would be considered clinically important. This difference was chosen because it was one third (33%) of the lower 95% confidence limit of the effect size of EMLA (difference in means of pain scores with EMLA and placebo) (3).

3. The power was 80% at the 0.05 level of significance.

Data analysis was performed on an intention-to-treat basis by using StatView^® for Windows Version 5.0.1 (SAS Institute, Cary, NC). Normally distributed continuous data were analyzed with a paired Student’s t-test. Continuous data not normally distributed were analyzed with Wilcoxon’s ranked sum test. Cohen’s test (13) was used to compare the responses provided by the subject, parent, observer, and technician to the questions regarding the effect and their liking of an intervention. Correlation values of 0.00–0.20 were considered "poor," 0.21–0.40 "fair," 0.41–0.60 "moderate," 0.61–0.80 "good," and 0.81–1.00 "very good" (13). The responses to the second question were used as satisfaction scores with a regimen. Categorical data were analyzed with the ² test with Yates’ continuity correction or Fisher’s exact test, as appropriate. Data are presented as mean ± SD for normally distributed data, as median (interquartile range) for data not normally distributed, numbers, or percentages. A P value of <0.05 was considered statistically significant.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Twenty-six subjects (16 boys and 10 girls) were enrolled in this study, but 4 did not return to complete both arms of the study and were excluded from the data analysis. The IV catheter insertion procedures were performed at least 1 wk apart. The iontophoretic treatment was discontinued before a dose of 40 mA/min was delivered in two subjects, who complained of intolerable tingling, itching, and discomfort from the procedure. These subjects were assigned maximum VAS (100 mm) and CHEOPS (score = 13) scores for this intervention, and both of these subjects preferred EMLA to iontophoresis. Data from the two subjects who could not tolerate iontophoresis were included in the intention-to-treat analysis, which was limited to the 22 subjects who participated in both arms of the study.

There were no significant differences in number of successful IV cannulations on the first attempt, total number of attempts, or the ease of IV catheter insertion when EMLA or iontophoresis was used. There were also no differences in pain scores as assessed by the subject, parent, or observer with the two interventions (Table 1). Similarly, subjects and parents did not assess the distress during the procedure as more with either intervention. Heart rate changes from baseline during catheter insertion did not differ between the two interventions.

No severe adverse events were noted during the study period. However, as described previously, two subjects did not tolerate the electrical stimulation during iontophoresis.

	Discussion

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This study has demonstrated similar pain scores during venous cannulation in children receiving EMLA or iontophoresis for dermal analgesia. This is in keeping with previous studies in adults and children in which iontophoresis compared favorably as a safe noninvasive alternative to subcutaneous lidocaine for venipuncture (14) and as a more rapid-acting and reliable alternative to EMLA in adults (15). Lidocaine iontophoresis can be effectively used in children for dermal analgesia during access for vascular fistulas in renal dialysis patients (16), and it has also been used in emergency room patients for venipuncture (8).

Our study confirms the previous results of Squire et al. (17) that iontophoresis is an effective alternative to EMLA for IV line placement in children. It differs from other studies because we used subjects who required repeated peripheral venous access, so that each subject could serve as his or her own control. However, this patient population is known to have greater anxiety. Factors reported to decrease success rates with EMLA include a short duration of application (<90 minutes), IV cannulation compared with venipuncture, and anxiety in patients (3). Despite the presence of all these factors in our subjects, they did not prefer iontophoresis to EMLA. However, we enrolled older patients in our study, and the results may not apply to infants and toddlers, in whom vascular access is more difficult to establish. These preverbal subjects are also more likely to struggle during the procedure despite adequate dermal analgesia.

Lidocaine iontophoresis takes less time to establish dermal analgesia than EMLA—a major advantage in busy ambulatory surgery centers. It has also been reported to be associated with a deeper penetration of the skin (18) and can ameliorate pain associated with the injection of hyperosmolar solutions and propofol (15,19). However, we and others have noted that some subjects would not tolerate the tingling and burning sensations that are at times associated with the application of iontophoresis (15,16). This occurs more often with higher currents, and allowing the patient to gradually increase the current as tolerated may increase patient acceptance (9). There may also be age-related differences in the ability of a child to accept iontophoresis.

The inability to anesthetize more than one site at the same time with iontophoresis can be a limiting factor (9). Patients’ not completing iontophoresis can lead to a delay in establishing vascular access, and a rescue technique will be required. These delays may result in dissatisfaction of the patient, parent, and other health care workers in the operating room environment. In contrast, EMLA can be applied at two sites simultaneously, allowing for an immediate alternative site for attempting vascular access if the first one fails. However, vasoconstriction with EMLA can make IV cannulation more difficult. This may explain the marked lack of correlation in the EMLA group between the satisfaction scores of the patient and the technician performing the procedure. There are data to suggest that amethocaine gel can establish dermal analgesia faster than EMLA, and it is not associated with vasoconstriction, allowing for easier venous cannulation (20). Unfortunately, this preparation is not available in the United States.

In the current cost-control health care environment, it is not possible to introduce a new technique without comparing the associated costs with the current standard care practice. At present, the manufacturers will provide the Iomed device free of charge if a number of disposable gel electrodes are purchased. In this situation, single-use, disposable gel electrodes will cost the institution US$6.00–US$7.50 per application. In contrast, it will cost the institution US$4.26 for the application of EMLA at one site and US$8.53 at two sites. The higher costs for iontophoresis may be justified in busy day medicine units, where application of EMLA can delay venipuncture (21). However, in the operating room, inhaling nitrous oxide for a few minutes can provide similar pain scores during the insertion of IV catheters to those with the application of EMLA, and at a much lower cost (12,22). Personnel costs, the need for effective evacuation of residual nitrous oxide, and concerns about the potential for serious side effects when nitrous oxide is administered by nonanesthesiologists has limited its use outside the operating room in the United States (21). However, in some European countries it is not uncommon for nonanesthesiologists to administer fixed concentrations of 50% nitrous oxide in 50% oxygen to provide relief from procedure-related pain in children (23).

In conclusion, this study has demonstrated that lidocaine iontophoresis provides pain relief for insertion of IV catheters similar to that of EMLA. Patient acceptance and satisfaction are similar with both techniques. Lidocaine iontophoresis is a useful, noninvasive alternative to EMLA to establish dermal analgesia for venous cannulation, especially when there is limited time available to establish dermal analgesia.

	Acknowledgments

 
The authors gratefully acknowledge the assistance of Paul Gallagher (Department of Biostatistics), Rosetta Chiavacci, RN (Department of Anesthesia and Critical Care), and the nurses from Day Medicine, the Apheresis Center, and the Oncology Clinic at Children’s Hospital of Philadelphia.

	Footnotes

 
Presented in part at the meetings of the Society for Pediatric Anesthesia, Las Vegas, NV, February 20, 1999, and Ft. Meyers, FL, February 26, 2000, and the American Society of Anesthesiology, Dallas, TX, October 11, 1999.

	References

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999