We evaluated the efficacy of local anesthesia with EMLA cream and lidocaine tape for venipuncture before induction of general anesthesia in the same patients. The study results indicate that EMLA cream is more effective for pain relief during venipuncture than lidocaine tape. The novelty of this study lies in the fact that it compares two local anesthetic methods in the same person. Although some previous randomized-control studies on EMLA cream do exist, their participants were divided into two groups, and each group received only one local anesthetic method . As is well known, there are significant individual differences in pain sensitivity . Hence, it is ideal that the same participant evaluates the effect on venipuncture pain relief with both EMLA cream and lidocaine tape. In addition, in our study, the number of hands anesthetized with EMLA cream that was punctured first was the same to the number of hands anesthetized with the lidocaine tape that were punctured firstly, at 12 hands each. These features of our study design increase the level of accuracy and validity of our results that EMLA cream is more effective for pain relief during venous cannulation than lidocaine tape.
As confirmed by our study, EMLA cream provides more effective pain relief than lidocaine tape. A possible reason for this difference in efficacy is that EMLA cream is a eutectic mixture of local anesthetics that exhibits high skin permeability. However, considering a previous report that EMLA cream is superior to 1% lidocaine infiltration for arterial cannulation , the mechanism of EMLA cream efficacy is not limited to its high permeability. While lidocaine needs to be dissolved in some solvent for its application as an external preparation, EMLA cream does not require a solvent and provides a high concentration of local anesthetics. These two factors, the high permeability and concentrations of local anesthetics, are the mechanisms by which EMLA cream is more effective than lidocaine tape.
In this study, subgroup analysis and the comparison of first and second puncture-pain intensities were performed to clarify the influence of puncture order on pain severity evaluation. The second puncture pain intensity was higher than the first puncture’s pain, although this difference was not statistically significant. Moreover, the VRS in LE group was not statistically significant. These results suggest that the second puncture pain might become more severe than the first puncture pain. According to past reports, there is a positive relationship between anxiety and pain in clinical settings , and anxiolytic drugs can decrease pain caused by medical procedures . In this study, there was some possibility that the participants felt some anxiety caused by first venipuncture pain, resulting in exacerbating the second puncture pain intensity. But, we assessed that this influence on the result of this study could be dismissed because the computer-based randomization was performed to equate the number of firstly punctured local anesthetic site.
In terms of the safety of local anesthetics, local anesthetic toxicity is the most important problem. In our study, serum concentrations of lidocaine and prilocaine were not measured. Oni et al. measured the serum concentration of lidocaine after application of 30 g of 2.5% EMLA cream on facial and neck skin . The average peak serum concentration of lidocaine was 0.44 μg/mL at 90 min after application, despite the removal of the EMLA cream 60 min after its application. Although this concentration was lower than the threshold of lidocaine toxicity, there were significant individual differences. The peak individual concentration of lidocaine in their study was 0.78 μg/mL, which is about twofold that of the average value. There are three major factors responsible for the individual differences in absorption and serum concentrations of local anesthetics. The first is body weight. Previous case reports regarding local anesthetic toxicity in 3-year-old children who received EMLA cream have been published [8, 9]. The application of EMLA in small children, therefore, requires strict attention. The second factor is liver function impairment. Local anesthetics, including lidocaine, are metabolized in the liver (e.g., lidocaine is metabolized into monoethylglycinexylidide by the liver and eliminated by the kidney). Strict attention is also needed during application of EMLA to patients with liver function failure. The last factor is skin disorders. The barrier function of the skin is lost in areas of skin with dermopathy, resulting in excessive absorption of local anesthetics. Juhlin et al. evaluated the plasma concentrations of lidocaine and prilocaine after application of EMLA cream and compared these concentrations between normal and diseased skin patients . In diseased skin patients, the absorption was faster than in normal skin patients, resulting in high plasma concentrations. The peak concentrations of local anesthetics in patients with diseased skin were tens of times higher than those in patients with normal skin. These indicate the need for close attention to be paid when EMLA is applied in patients who have any of the above three factors that can lead to an increase in serum concentrations of local anesthetics, resulting in systemic toxicity of local anesthetics.
Another side effect of topical anesthetics is alteration of skin color, such as pallor and flare. EMLA frequently produces blanching of the skin by causing vasoconstriction . Although this side effect tends to disappear within a few days, it makes venipuncture and venous cannulation difficult . The factors affecting difficult peripheral venous cannulation were investigated by Fields et al. and Piredda et al. [13, 14]. They reported an association between difficulty in peripheral venous cannulation and diabetes, intravenous drug abuse, sickle cell disease, veins with many valves, venous fragility, visibility and palpability, and a history of chemotherapy received via the peripheral cannula. Hence, during venous cannulation in patients with these factors, it might be better to avoid the use of EMLA to facilitate successful cannulation.
This study has two major limitations. The first is that we evaluated pain caused by venous cannulation using only subjective measurements. To evaluate pain objectively, heart rate and blood pressure should be measured before and after venipuncture. But, these parameters were also influenced by emotional factor easily, and the accuracy for evaluating venipuncture pain was very limited. The second limitation is that the serum concentrations of lidocaine and prilocaine were not measured to elucidate the safety of EMLA cream and lidocaine tape. Although none of the patients expressed symptoms of local anesthetic toxicity in this study, the time course of serum concentrations of lidocaine and prilocaine should be measured until 90 min after the application of EMLA to confirm the safety of this drug .