The Effect of a Eutectic Mixture of Local Anesthetic Cream on Wrist Pain during Transradial Coronary Procedures
- Volume 19 - Issue 1 - January, 2007
- Posted on: 8/1/08
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There has been growing interest in transradial coronary procedures due to the rare incidence of complications at this puncture site, elimination of the need to limit the patient’s activity and the possibility of early patient discharge.1,2 Furthermore, use of the radial artery as a vascular access route is expected to expand due to the miniaturization and improvement of the devices, improvement of the techniques and increasing experience by operators with transradial coronary procedures. However, unlike the femoral approach, patients who undergo transradial coronary procedures complain primarily of wrist pain at the puncture site.
A eutectic mixture of local anesthetic (EMLA) cream, composed of lidocaine 2.5% and prilocaine 2.5%, is known to be an effective topical anesthetic agent. It is used for a variety of painful cutaneous procedures on intact skin, including phlebotomy, intravenous catheterization, arterial cannulation and lumbar puncture.3–5 Despite the usefulness of EMLA cream, it is not widely used in standard clinical practice because the optimal preprocedure application time frame is unknown, and differing results are reported in terms of efficacy depending on the procedure for which it is used.
We hypothesized that applying EMLA cream would effectively reduce wrist pain without adverse drug reactions during transradial coronary procedures and evaluated the optimal time range for preprocedure application of EMLA cream.
Patients and Methods
Patients. From October 2003 to March 2004, 400 consecutive patients scheduled for elective coronary angiography or percutaneous coronary intervention via the radial artery were included. Patients were excluded if they presented with a negative Allen’s test on both wrists, chronic renal failure requiring current dialysis, chronic renal failure that would require dialysis in the future and any known allergy to contrast medium or local anesthetics. Written, informed consent was obtained from the patient or family member(s) before the procedure.
Methods. The study period was divided into two phases. The Phase I study was the initial trial of 147 patients from October to December 2003 to evaluate the efficacy and safety of EMLA cream during transradial coronary procedures. The Phase II study was designed to evaluate the optimal time range for EMLA cream application before the start of a procedure for adequate reduction of wrist pain in 400 cases from October 2003 to March 2004.
The sequences of EMLA or placebo application, right or left hand application and the sequences of radial artery puncture were randomized by a simple randomization table. The subjects and the physician performing the radial artery cannulation were blinded as to which wrist was treated with placebo and which received the EMLA cream. The EMLA or placebo cream was applied on the wrist from 2 to 4 hours before the procedure in the Phase I study. In the Phase II study, patients were randomized to 5 time groups according to the preprocedure application time range.
The experiment investigators provided blinded tubes containing either EMLA cream or placebo, which was an odorless white cream that resembled the EMLA cream. All EMLA and placebo creams were applied to both wrists 2 cm above the styloid process of the radius and then covered with a transparent 5-cm dressing (Figure 1). The amount of EMLA or placebo cream used was 2.5 g, the standard adult dose.
The patient was not premedicated, and local anesthesia with 0.6 mL of lidocaine using a 24-gauge needle was performed at the time of the procedure. Radial artery puncture was tried using 20 G-catheter needle (Sindonbang Company, S. Korea), and a 5, 6 or 7 Fr arterial sheath (Terumo Company, Japan) was inserted depending on the type of procedure.
Each patient was asked to identify the pain score that best described the pain he/she experienced on the cream application site immediately after radial cannulation. The pain was evaluated when it was felt at the time of the initial puncture and at arterial sheath insertion. The pain score was assessed by the visual analogue scale (VAS) and a 4-category verbal rating scale (VRS-4).6 On the VAS, the patients indicated their pain intensity by making a mark on a 10-cm long line that included descriptors labeled at each end of the line of pain intensity (e.g., from “no pain” to “pain as bad as it could be”). The patient was instructed to regard the VAS as a continuum and to make a mark at the point along the line corresponding to his/her current level of pain. The score was determined by measuring the distance from the left end of the line to the patient’s mark. Scoring of VRS-4 consists of a finite list of intensity descriptors: 1 point = “no pain”; 2 points = “a little pain”; 3 points = “painful, but tolerable”; 4 points = “most pain possible”.
In the event the patient underwent a repeat coronary procedure (n = 42), we also asked about the patient’s perception of the change in his/her pain from the previous study by percentage change of pain perception. We evaluated the safety profiles, local reactions (erythema, contact dermatitis) and systemic reactions (central nervous system side effect of local anesthetics, urticaria, angioedema and bronchospasm), as noted on the EMLA label.
The primary endpoint was the patient’s pain experienced during radial cannulation and sheath insertion as assessed by VAS and VRS-4. The secondary endpoint was the optimal time frame for EMLA cream application prior to the procedure for relief of pain without the occurrence of adverse drug reactions.
Statistics. In this study, the minimum clinically significant difference in VAS scores used was 13 mm, as determined by Todd et al.6 Using the difference of 13 mm and a standard deviation of 27 mm, as determined by our preliminary data in this study, we calculated the sample size to be 70 subjects in each group to achieve a power of at least 80% at the 5% significance level for the primary endpoint.Continuous variables are expressed as mean and standard deviations. A two-tailed Student’s t-test and ANOVA (post hoc analysis: Scheffe) were used to determine the differences between clinically significant changes in pain among the groups. A Likert score analysis for VRS-4 scoring was performed and expressed mean and standard deviations. A p-value < 0.05 was considered statistically significant. Statistical analysis was performed using the SPSS 12.0 statistical program (SPSS, Inc., Chicago, Illinois).
Four hundred consecutive patients were enrolled in this study. Five patients were excluded from the analysis because of incomplete study data.
Phase I study of efficacy and safety of EMLA cream. The clinical characteristics of 147 cases in the control and EMLA groups are listed in Table 1. There were no differences in age, gender, procedure time or clinical diagnosis between the two groups. Wrist pain during lidocaine infiltration and sheath introduction was reduced significantly in the EMLA group compared to the placebo group as assessed by VAS (control: 49 ± 24, EMLA: 19 ± 22; p = 0.001) and VRS-4 (control: 2.3 ± 0.5, EMLA: 1.5 ± 0.6; p = 0.001). There was a significant negative correlation between VAS and the time frame of drug application (r = -0.476; p = 0.001). The application of EMLA cream markedly reduced wrist pain as expressed by the percentage of change compared to the previous procedure (control: 135 ± 45, EMLA: 60 ± 41%; p = 0.01) in cases of repeat transradial coronary procedures (n = 42) for follow-up angiography. Multivariate regression for age, sex, EMLA application and puncture site as independent variables and the VAS score as the dependent variable demonstrated that EMLA application (beta: -0.517; p < 0.001) was the only significant independent variable.
Phase II study to determine the optimal duration of EMLA efficacy. The baseline clinical characteristics of 395 cases in the control and EMLA groups according to the preprocedure application time frame are listed in Table 2. There were no statistical differences in age, sex, procedure site or clinical diagnosis among the groups.
There was a reduction in both VAS (control: 49 ± 29, EMLA 0–1 hour: 39 ± 27) and VRS-4 (control: 2.4 ± 0.6, EMLA 0–1 hour: 2.0 ± 0.6) at the time point of EMLA 0–1 hour compared to the control group, but this was not statistically significant. However, there was a significant difference in the pain score between the control and EMLA 1–2 hours groups as determined by VAS (control: 49 ± 29, EMLA 1–2 hours: 32 ± 24) and VRS-4 (control: 2.4 ± 0.5, EMLA 1–2 hours: 1.9 ± 0.6). There was a significant difference in the VAS between the EMLA 1–2 hours and EMLA > 4 hours groups (EMLA 1–2 hours: 32 ± 24, EMLA > 4 hours: 14 ± 18), but there was no statistical difference in the VRS-4 (EMLA 1–2 hours: 1.9 ± 0.6, EMLA > 4 hours: 1.5 ± 0.5).
There were no major adverse drug reactions. Minor local erythema occurred in 12 cases (3.5%), and was particularly frequent in the EMLA 3–4 hours (6.6%) and EMLA > 4 hours (11.9%) groups.