Objectives. Children view needle sticks as the worst source of pain and fear in the hospital setting. In an effort to minimize the pain of needle sticks, the use of eutectic mixture of lidocaine and prilocaine (EMLA) has become standard practice in many children’s hospitals. Unfortunately, EMLA requires at least 60 minutes to be fully effective and reportedly may cause vasoconstriction, leading to difficult vein cannulation. A newly available local anesthetic (ELA-Max) may require less time and cause less vasoconstriction. The purpose of this randomized crossover study was to investigate the anesthetic equivalence of EMLA and ELA-Max.
Methods. Thirty well children (14 girls and 16 boys) who were between the ages of 7 and 13 years volunteered to have EMLA applied to the dorsal aspect of 1 hand for 60 minutes and ELA-Max applied to the other hand for 30 minutes. Right and left hands were randomized to treatment type and order of intravenous (IV) insertion. Clinical Research Center nurses, blind to the anesthetic randomization, attempted to insert a 22-gauge Teflon IV catheter into a vein in each hand. The children rated pain during IV insertion on the Oucher scale, and the nurse rated the difficulty of the insertion.
Results. There was no significant difference in pain ratings for hands that were treated with EMLA (mean: 20.5) or with ELA-Max (mean: 24), and there was no difference for the difficulty of vein cannulation. Children’s preprocedure state anxiety was positively associated with pain ratings.
Conclusions. ELA-Max, applied for 30 minutes before IV cannulation, has an anesthetic effectiveness similar to EMLA applied for 60 minutes. Some children rated IV insertion pain fairly high for both hands (eg, 60 on a 0- to 100-point scale) despite anesthetic treatment. Preprocedural anxiety may affect the perception and/or rating of pain. There were no differences between hands that were treated with EMLA or with ELA-Max for success of IV insertion.
Venipuncture for laboratory tests and intravenous (IV) insertion are common medical procedures, and many children with chronic illnesses have these procedures done repeatedly during the course of their treatment. Needle insertion is the most frightening and bothersome medical procedure for children.1 Studies have shown that children’s previous distress during medical procedures is a predictor of future distress.2–4 Some children develop needle phobia that is extremely difficult to treat.
Topical anesthetic creams have been developed to minimize the discomfort of venipuncture and many children’s hospitals have adopted the use of eutectic mixture of lidocaine and prilocaine (EMLA) as part of their pain management standard of practice. Numerous studies have shown that EMLA decreases pain sensation for children during needle sticks.4–7 The anesthetic is more effective for simple venipuncture than for IV cannulation.5
Despite the effectiveness of EMLA, some practitioners choose not to use it. Time is 1 issue. The medication must be left on the skin for at least 60 minutes to be effective. Also, EMLA may constrict the vein, making IV cannulation more difficult.8 A recently marketed 4% lidocaine cream known as ELA-Max may act more quickly and may produce less vasoconstriction. The manufacturer suggests that ELA- Max provides dermal anesthesia after 30 minutes. ELA-Max is a nonprescription lidocaine cream. The lidocaine molecules are encapsulated in a lipid layer, which reportedly enhances absorption into the dermal layers. No published studies have evaluated the efficacy of ELA-Max cream during venipuncture in children.
The purpose of this study was to assess the equivalence of 2 commercially available local anesthetics: EMLA and ELA-Max. The research hypotheses were that there is no significant difference for pain sensation with IV insertion between hands that are treated with EMLA or with ELA-Max and that there is no significant difference for ease of IV insertion.
EMLA cream (AstraZeneca Pharmaceutical LP, Wilmington, DE) is an emulsion in which the oil phase is a eutectic mixture of lidocaine and prilocaine in a ratio of 1:1 by weight. The eutectic mixture has a melting point below room temperature; therefore, both anesthetics exist as a liquid oil rather than as crystals. Each gram of EMLA cream contains 25 mg of lidocaine, 25 mg of prilocaine, emulsifiers, thickening agents, sodium hydroxide to adjust the product to a pH approximating 9, and purified water. EMLA cream is commercially available by prescription only.
ELA-Max (Ferndale Laboratories, Inc, Ferndale, MI) is a topical anesthetic cream that contains only lidocaine as an anesthetic agent. Each gram of ELA-Max contains 40 mg of lidocaine, lecithin, propylene glycol, carbomer 940, benzyl alcohol, vitamin E acetate, cholesterol, triethanolamine, polysorbate 80, and purified water. ELA-Max is commercially available as an over-the-counter medication. Ferndale Laboratories provided ELA-Max samples for this study.
This study was approved by the institutional review board and was conducted in the Clinical Research Center (CRC) at the University of Iowa Hospitals and Clinics. Local advertisements invited children between the ages of 7 and 13 years to volunteer for this study. This age group was chosen for 2 reasons. At 7 years, children are more likely to understand the assent process, and they are more reliable when reporting sensations such as pain. With the onset of puberty, around 13 years, children develop larger veins that are easier to cannulate. All of the children who volunteered for this study were in age-appropriate school grades, had normal sensation on the dorsal aspect of the hands, and had no history of allergy or reaction to lidocaine ointments or injections. Parents signed written consent, and the children gave verbal and written assent for study procedures.
Children were randomized to have EMLA placed on the dorsum of the right or left hand. Either an investigator or 1 of the CRC nurses marked a vein on the hand, applied 2.5 g of EMLA on the mark, and placed a semiocclusive dressing over the ointment. The application time was recorded. Thirty minutes later, 2.5 g of ELA- Max was applied to the opposite hand in the same manner. When the EMLA had been in place for 60 minutes, it was removed and the hand was wiped clean. The ELA-Max was removed in the same manner after it had been in place for 30 minutes.
While the children were waiting for the anesthetics to take effect, they were asked to rate their current level of anxiety on a 10-point vertical thermometer-like scale. They were also asked about previous experiences with needle sticks and their usual coping styles. Most of the waiting time was spent watching television or reading.
Within 10 minutes after the anesthetics were removed, a CRC nurse, who was blind to the type of anesthetic on each hand, inserted a 22-gauge Teflon IV catheter into the vein on 1 hand. The order of right and left hands for IV insertion was randomized. During the IV placement, the children were recumbent, blocked from watching the needle stick, and asked to concentrate on the sensations in the hand. When the nurse either cannulated the vein or felt that it was not possible to cannulate without extensive maneuvering, the child was asked to rate his or her pain on the Oucher scale. The needle was then removed, an adhesive bandage was placed, and the nurses rated the difficulty of the IV placement. The procedure was repeated on the opposite hand. The children received $40 for their participation in the study.
The Oucher is used to assess pain intensity in children as young as 3 years and includes 2 separate scales.9 One is a series of 6 photographs showing a child in varying degrees of discomfort and is used by children who are unable to count by number. Children who are able to count to 100 by ones or tens and can identify the larger of 2 numbers use the vertical numeric scale (0–100) that is printed next to the faces. All of the children in this study were able to use the numeric scale. The Oucher has been tested for validity and reliability9 and is widely used for clinical and research purposes. The correlation between the Oucher and the Visual Analog Scale for pain has been reported to be 0.89 (P < .01). Discriminant validity was established by investigating the relationships between the Oucher and 2 fear report measures. The associations between the numerical Oucher scale and the Hospital Fears Rating Scale and Scare Scale were very low, with Gamma coefficients of −0.003 and 0.075, respectively.10
In this study, anxiety was measured because anxious feelings have been shown to influence pain perception. The validity of comprehensive state anxiety scales for children, such as the State-Trait Anxiety Inventory for Children, have recently been questioned.11 Visual analog scales have been recommended as a simple way to assess state anxiety.12 Therefore, children’s self-report of state anxiety was measured with a thermometer-like scale. The thermometer scale is a vertical measure divided by 10 evenly spaced marks. The instructions to the children are, “Pretend that all of your worried or anxious feelings are in the bulb or bottom part of the thermometer. If you have a little bit of anxiety or worry, the feelings might come up in the thermometer just a little bit. If you have a lot of worry or anxiety, the feelings might go up, even all the way to the top. Put a line on the thermometer showing where your anxiety or worry level is right now.”
Ease of IV insertion was rated by the CRC nurse using 5 categories of difficulty: vein easy to find, vein a little difficult to find, vein difficult to find, vein very difficult to find and cannulate, and unable to cannulate vein. The CRC nurses are expert in IV cannulation and perform venipuncture for children in research studies as part of their routine practice.
A power analysis for testing the pain prevention equivalency of the 2 anesthetics was based on data obtained in our previous study.4 With α set at 0.05, a sample of 30 subjects gave a power of 0.9 to detect a 10-point difference on the 0- to 100-point pain scale. Data were entered into an SPSS database (SPSS, Inc, Chicago, IL), double-checked, and analyzed with nonparametric statistics for paired data.
Fourteen girls and 16 boys volunteered to be in this study. None of the children withdrew before completing the study. The children ranged in age from 7.4 to 12.9 years (mean: 10.8 years). All of the children were English speaking, white, and in the school grade appropriate for their age. Most of the children had no experience with painful medical procedures or needle sticks other than routine immunizations and dental examinations. Four of the children had a history of stitches for accidental cuts, 2 had had minor surgery, 1 had had a tooth pulled, and 1 had had allergy shots. Only a few children identified specific coping strategies, such as holding a parent’s hand or thinking of happy things, for dealing with potentially painful medical procedures. Seventeen of the children said that they preferred not to watch the needle stick, 8 preferred to watch, and 5 stated that they had no preference. The children’s self-reported anxiety scores before the IV sticks ranged from 0 to 9 on the 10-point thermometer scale. The median anxiety score was 1, with a mean of 2.4 (±2.3).
Pain scores on the Oucher scale ranged from 0 to 70 (mean: 20.5 ± 22.7) for the hand that was treated with EMLA and from 0 to 60 (mean: 24 ± 17.6) for the hand that was treated with ELA-Max (Table 1). The Wilcoxon signed ranks test for paired data showed no significant difference (z = −1.01; P=.31). Paired differences (individual subjects’ ELA-Max hand score minus the EMLA hand score) are displayed in Fig 1. The Mann-Whitney U test did not show a significant association between order of IV stick and pain ratings or between gender and pain ratings. There was a positive association (r=0.399; P = .029) between anxiety ratings and average pain scores.
The CRC nurses rated ease of IV stick on a 5-point scale. For the 60 IV sticks (2 per subject), 21 were rated “easy,” 14 were “a little difficult but needle went right in,” 2 were rated “difficult to find vein,” and 23 were rated “unable to cannulate vein.” The scores were collapsed into 2 categories to determine differences. Category 1 included all successful cannulations, no matter how difficult, and category 2 comprised unsuccessful cannulations (Table 2). For 14 of the children, IV insertion was successful in both hands; for 7 children, the nurse was unable to cannulate either hand. Cannulation was successful for the EMLA-treated hand and unsuccessful for the ELA-Max-treated hand in 3 children, and the opposite occurred in 6 children. The McNemar cross-tabulation test showed no significant difference for success in vein cannulation (P=.508).
EMLA and ELA-Max seem to be equally effective local anesthetics for IV insertion. A positive aspect of ELA-Max is that it is effective after just 30 minutes. For this study of children, the ELA-Max manufacturer (Ferndale Laboratory) recommended that we use a semiocclusive dressing over the anesthetic cream, to ensure that the cream stays in place. It is not known whether the dressing was a factor in the effectiveness of the product. Clinically, however, a dressing is a very practical part of applying local analgesia, because children may have difficulty staying inactive enough to keep the cream in place.
A strength of this study is that the subjects were relatively naïve to medical procedures and voluntarily had needles placed. The children were able to lie still and concentrate on the sensations felt during needle sticks. Had this study been done with children who needed IV placement for medical treatment, there may have been some question about the validity of the pain scores. Children’s pain perception can be influenced by previous experiences, anxiety, and coping mechanisms. Children who have had numerous needle sticks may be sensitized to needle pain and thus report more pain.
The strength of the study design is also a limitation. The children who volunteered for this study certainly were not bothered by the thought of needles, and they may have had higher-than-average pain thresholds. However, the range of pain scores (0–70) indicates individual variation in either pain sensitivity or effectiveness of local anesthetics. Only 10 subjects reported pain at 10 or less for both of the needle sticks. Another 10 children reported pain at 30 or more for both needle sticks. It seems that for some children, these 2 local anesthetics just do not work very well. Our conclusion is that EMLA and ELA- Max are equally effective and equally ineffective for needle insertion pain. However, it should be noted that all of the children in this study were white. The effectiveness of these medications for people with different skin tones should be investigated.
This study found no significant difference between EMLA and ELA-Max for success of IV cannulation. Successful vein cannulation occurred with 60% of the hands that were treated with EMLA and 67% of the hands that were treated with ELA-Max. These numbers are somewhat lower than reported elsewhere. Squire et al13 reported successful IV cannulation in 84% of veins that were treated with EMLA. A possible explanation is that the CRC nurses, knowing that the IV was not needed for clinical reasons and would be removed immediately, were not very aggressive in maneuvering the needle. They were asked to make a “reasonable” effort to cannulate the vein.
An advantage of the ELA-Max product is that it contains only lidocaine and therefore does not carry with it the risk of triggering methemoglobinemia. This may be of particular importance when treating neonatal patients. Although the package insert for ELA-Max does not address use in infants, our Division of Neonatology decided that its use should match that of EMLA. The EMLA dosage limit for infants from 37 weeks’ gestational age to 3 months is 1 g per day, to cover no more than 10 cm2.
Another difference between the 2 products is that a semiocclusive dressing is not necessary for ELA- Max, according to the manufacturer. In practice, it would be easy to contain the cream on the skin by simply putting a cotton ball over the cream and then wrapping the site with a clear plastic wrap.
At the time that this study was done, the cost of the 2 products was approximately the same. Our hospital decided to stock both products until there is a clear preference for one. We were hesitant to eliminate EMLA for 2 reasons. First, the new product does not seem to be better than EMLA in reducing pain, and second, neither EMLA nor ELA-Max eliminates all pain for all children. When new products are introduced, it is normal to focus on negative feedback from users rather than on research-based evidence.
The prevention of pain during medical procedures is important. Children should have the opportunity, when possible, to have a local anesthetic applied before venipuncture and IV insertion. ELA-Max applied for 30 minutes is as effective as EMLA applied for 60 minutes in preventing pain. However, neither anesthetic tested in this study was completely effective for all children. Children should be told that local anesthetics can help but may not take away all of the pain.
This study was supported by a grant from the Children’s Hospital of Iowa Children’s Miracle Network Research Fund and grant MO1 RR00059 from the General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health.
We thank Dixie Ecklund, Kathy Eyres, Gail Herzog, Mary Lou Linder, Donna Rasley, Bridget Zimmerman, and the Clinical Research Center staff for assistance.
- Frank NC, Blount RL, Smith AJ, Manimala MR, Martin JK. Parent and staff behavior, previous child medical experience, and maternal anxiety as they relate to child procedural distress and coping. J Pediatr Psychol.1995;20 :277– 289
- ↵Kleiber C, Craft-Rosenberg M, Harper D. Parents as distraction coaches during i.v. insertion: a randomized study. J Pain Symptom Manage.2001;22 :854– 864
- Robieux I, Kumar R, Radhakrishnan S, Koren G. Assessing pain and analgesia with a lidocaine-prilocaine emulsion in infants and toddlers during venipuncture. J Pediatr.1992;118 :971– 973
- Copyright © 2002 by the American Academy of Pediatrics