Objective: To determine if topical 4% amethocaine gel can reduce the pain associated with arterial punctures.
Design: Randomized, placebo-controlled, double-blinded trial with parallel groups.
Setting: Teaching hospital.
Patients: Adults requiring arterial punctures for blood gas estimation as part of routine care.
Interventions: Four percent amethocaine gel applied for 30 min prior to the radial arterial puncture, compared with a placebo gel.
Main outcome measures: Pain scored on a visual analog scale from 0 to 100, and heart rate during the procedure.
Results: The mean pain score for the amethocaine group was 16.0 (SD, 23.3) and for the placebo group was 20.7 (SD, 18.5). The mean heart rates during arterial puncture were 84.1 beats/min (SD, 10.7) for the amethocaine group, and 83.8 beats/min (SD, 12.7) for the placebo group. These differences were not statistically significant.
Conclusion: The topical use of 4% amethocaine gel does not reduce the pain associated with arterial puncture.
Key words: amethocaine; arterial puncture: topical anesthesia
Abbreviation: EMLA = eutectic mixture of local anesthetics
Arterial puncture is a commonly used procedure in clinical practice to obtain arterial blood for monitoring respiratory diseases, It can be associated with significant pain and discomfort. (1,2) Dread of painful injection was admitted by 11 of 100 patients in one report. (3) Acute changes in ventilation during arterial puncture have been shown to produce an error of [greater than or equal to] 10 mm Hg in the estimation of the arterial-alveolar P[O.sub.2] difference in 25% of patients. (4) Studies (1,2) have indicated that use of injectable local anesthetics significantly reduced pain associated with arterial punctures. However, surveys have shown that locally injected anesthetics are often not used, as they can also cause pain, are perceived to be time-consuming, and may make the procedure more difficult. (1)
An eutectic mixture of local anesthetics (EMLA) cream is a mixture of lidocaine and prilocaine that produces topical cutaneous anesthesia. EMLA cream has been used to produce dermal anesthesia before venous cannulation and radial artery cannulation in both children and adults, but application of the cream for 60 min is recommended. (5) A gel containing 4% amethocaine has been shown to provide superior anesthesia at 30 min compared with EMLA cream at 60 min. (6-9) Local AnGel is a gel containing 4% amethocaine that has been developed at the Pharmacy Department of the Royal Children's Hospital in Melbourne, Australia. Other than eye drops, there is no commercial preparation of amethocaine available in Australia, although a preparation called Ametop (Smith & Nephew Healthcare; Hull, UK) is available in some other countries. The safety and effectiveness of local AnGel have been evaluated when used for venous punctures. (8,10) There have been no studies published assessing the effectiveness of topical amethocaine gel for pain relief in arterial punctures. The aim of this study was to investigate the effectiveness of 4% amethocaine gel in reducing the pain associated with radial arterial punctures.
MATERIALS AND METHODS
This is a randomized, placebo-controlled, double-blinded study comparing the single use of 4% amethocaine gel with a placebo gel in parallel groups of subjects.
Patients who required blood gas analysis as a part of their usual clinical care were recruited from the respiratory function laboratory, the respiratory outpatients, the oxygen clinic, and the respiratory ward at the Austin and Repatriation Medical Center, a major teaching hospital in Melbourne, Australia. Inclusion criteria were that they had to speak English, be > 18 years old, and provide informed consent. Patients were excluded if there was a history of allergy to amethocaine or the constituents of the gel, allergy to Opsite dressing (Smith & Nephew; Clayton, Victoria, Australia), a positive Allen test result, an impalpable radial artery, abnormal skin over the radial artery, or a need for urgent blood gas sampling. Women of childbearing potential were also excluded. Randomization was performed by the Austin and Repatriation Hospital Trials pharmacist using a computer program that generated the random numbers, which determined the gel to be used. Randomization was performed for each subject when he or she consented to entry in the study. No subjects were withdrawn after randomization. All subjects who were approached about the study were entered. The Austin and Repatriation Medical Center Human Ethics Committee approved the study.
In the treatment group, a small amount of amethocaine gel (local AnGel, prepared by the pharmacy at the Royal Children's Hospital, Melbourne) was applied over the radial artery, in a patch with a 1-cm diameter. The gel contained 4% amethocaine in a 6% methylcellulose base. An occlusive dressing (Opsite) was placed over the gel for 30 min. The dressing and gel were removed by wiping with an alcohol swab prior to arterial puncture. In the placebo group, a gel identical in appearance was used in the same manner as the gel in the treatment group.
Both the investigators and patients were blinded to the type of gel being used. The code was not broken until the trial was completed. Both the active gel and placebo gel were supplied in single-use tubes. Arterial punctures were performed by respiratory scientists or hospital medical officers experienced with the procedure; 25-gauge needles and standard 5-mL blood gas syringes were used. An oximeter was used to record pulse rate during the procedure. The staff performing the puncture completed an assessment sheet recording: needle size used; numbers of passes through the skin; heart rate immediately before, during, and 5 min after the arterial puncture; success of the procedure; and any side effects of the gel. After the procedure, patients were asked to complete a questionnaire. The primary outcome measure was the amount of pain experienced. This was determined using a visual analog scale (2,5) rating pain experienced during the procedure from 0 to 100 (0 being no pain, 100 being the most severe pain). Secondary outcome measures were heart rate and questions regarding previous and current experience with the procedure. Patients were assessed after 24 h for any delayed side effects.
Assessment of the Visual Analog Scale
A separate group of subjects, who required two arterial punctures by the same person within 7 h of each other, was used to evaluate the inherent variability of the scale. No gel was used in these subjects. They completed the scale immediately after each puncture.
To show a change in pain score of at least 15, 58 subjects were needed for [alpha] = 5% with a power of 80%. Results are expressed as mean (SD). Differences in the visual analog scores and heart rates between the two groups were compared using independent-groups, two-tailed t tests. [chi square] tests were used to assess the responses to the questions with yes/no answers.
Eighty-one subjects were approached about the trial, and all agreed to be entered (Table 1). There were 39 subjects in the placebo group (26 men). There were 42 subjects in the amethocaine group (25 men). The mean ages for the two groups were 64.3 years (SD, 15.2) and 66.4 years (SD, 13.3), respectively. In the placebo group, 31 patients had one pass, 7 patients had two passes, and 1 patient had three passes. In the amethocaine group, 33 subjects had one pass, 8 subjects had two passes, and 1 subject had three passes. These differences were not statistically significant ([chi square]). Also, there were no statistically significant differences between the two groups with respect to the proportions who had previously had arterial punctures, those who had had local anesthetic by subcutaneous injection for an arterial puncture in the past, and those who recalled discomfort associated with previous arterial punctures ([chi square]).
The mean pain score was 20.7 (SD, 18.5) in the placebo group and 16.0 (SD, 23.3) in the amethocaine group (p = 0.32). The mean heart rates before, during, and after the procedure were 85.0 beats/min (SD, 10.3), 83.8 beats/min (SD, 12.7), and 85.2 beats/min (SD, 11.6) in the placebo group, and 84.3 beats/min (SD, 11.2), 84.1 beats/min (SD, 10.7), and 84.4 beats/min (SD, 11.4) in the amethocaine group, respectively. None of these differences were statistically significant. The results are summarized in Table 2.
In the placebo group, 18 of 39 subjects said the gel helped in reducing and 23 of 42 subjects in the amethocaine group said the same. In the placebo group, 27 of 39 subjects preferred to have the gel applied the next time they had an arterial puncture, and 34 of 42 subjects in the amethocaine group said the same. Neither of these differences were statistically different ([chi square]).
Eight of 39 subjects in the placebo group and 9 of 42 subjects in the amethocaine group had more than one pass of the needle through the skin (Table 3). The mean pain scores when there was one pass were 17.4 (SD, 17.3) in the placebo group and 9.6 (SD, 11.2) in the amethocaine group (p = 0.035). The mean pain scores when there was more than one pass were 33.5 (SD, 18.5) in the placebo group and 39.6 (SD, 38.5) in the amethocaine group (p = 0.32). There were no significant differences in heart rates before, during, or after arterial puncture between the placebo and amethocaine groups in each of these two subgroups (independent sample t tests). Also, there were no significant differences in the proportions who thought that the gel helped, or the proportions who would like to have the gel with arterial punctures in the future between the placebo and amethocaine groups in each of these two subgroups ([chi square]).
One subject in the treatment group complained of self-limiting itchiness at the application site. In the placebo group, one subject complained of a tingling feeling at the arterial puncture site after the puncture, one subject complained of a local sensation of swelling, and one subject complained of a transient fainting feeling prior to the arterial puncture.
Assessment of the Visual Analog Scale
Twenty-one different patients had two arterial punctures without any gel. The mean difference in pain score between the two punctures was 1 (SD, 7.8). Thus, 95% of subjects had a repeat pain score within 15.6 of the second puncture without any intervention between the punctures. This reflects the reliability of the visual analog scale. A change in the score of > 15.6 would be needed for a change in pain in response to arterial punctures to be meaningful.
This study has shown that the topical application of 4% amethocaine gel for 30 min was not effective in reducing the pain associated with arterial puncture compared to a placebo gel. It is unlikely that this is a type II error, as considerably more subjects were studied than were needed to demonstrate a meaningful difference in pain scores. A difference of < 15 can be attributed to the variability in the use of the visual analog scale. Giner et al (2) also used the same scale and found a mean difference of 15 between groups who had a mepivacaine injection or a placebo injection before arterial puncture. The difference in pain scores between the groups in our study was 4.7, and so we believe that it is too small to be meaningful. Thus, we are confident in our conclusion.
Even though the other data in our study (the heart rates and answers to the other questions) are not sufficient to address our aim, they do indirectly support our conclusion. There were no differences in the heart rates between the two groups, and there were no differences in the proportions of subjects in each group who said that they experienced pain or discomfort, or who would like the gel used next time.
The degree of pain experienced by our subjects was similar to that experienced by the subjects in the study by Giner et al. (2) We do not feel that there were unusually low levels of pain experienced by our subjects. The distribution of pain scores was similar in both of our groups.
Topical amethocaine has been shown to be effective in reducing the pain associated with venous punctures. (6-10) Its ineffectiveness with arterial punctures is probably due to its effect being confined to pain fibers in the dermis. (6) As veins have few pain fibers in their walls, this is all that is required for venous punctures, but arteries do have pain fibers in their walls. (11) If the gel did not penetrate that deeply to reach the arterial wall, then it would be ineffective with arterial punctures.
When viewing the raw data, it seemed that a benefit may have been present in those subjects only receiving one pass, so a subgroup analysis was performed. However, when doing this analysis, we recognized that its main purpose was to stimulate further research into the effects of amethocaine in more specific situations, rather being able to provide definitive answers. A statistically significant difference was found between the pain scores in the two groups when only one pass was made. As the size of the effect was small, as the study was not designed to specifically assess this, and as the p value associated with this still leaves some doubt about how real the difference was, we do not have confidence in the results of this subgroup analysis. If it was a real difference, an explanation might be that the amethocaine was having a small effect that became apparent when only low levels of pain were present, as when there was only one pass.
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(11) Gabella G. Cardiovascular. In: Williams PL, ed. Gray's anatomy. 38th ed. New York, NY: Churchill Livingstone, 1995
* From the Department of Respiratory Medicine, Austin and Repatriation Medical Centre, Melbourne, Victoria, Australia. Funded by the Department of Respiratory Medicine, Austin and Repatriation Medical Centre, Melbourne, Australia.
Manuscript received August 6, 2001; revision accepted March 19, 2002.
Correspondence to: Christopher J. Worsnop, FRACP, FCCP, Department of Respiratory Medicine, Bowen Centre, Austin Campus, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia; e-mail: email@example.com
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