BJA Advance Access published online on February 20, 2008
British Journal of Anaesthesia, doi:10.1093/bja/aen003
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Topical anaesthesia and intravenous cannulation success in paediatric patients: a randomized double-blind trial
Department of Emergency Medicine, St George Hospital, Kogarah NSW 2217, Australia
* Corresponding author. E-mail: glenn.arendts{at}sesiahs.health.nsw.gov.au
Accepted for publication January 2, 2008.
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Abstract |
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Background: It is not known whether the choice of topical anaesthetic influences the likelihood of successful i.v. cannulation in the paediatric population. The null hypothesis of this study was that no difference exists in the initial success rate of cannulation between two commonly used topical anaesthetics.
Methods: A randomized double-blind trial conducted on patients between the age of 12 months and 12 yr presenting to a tertiary hospital emergency department. Patients requiring cannulation were randomized to either 4% amethocaine gel (AnGEL) or 5% lidocaine and prilocaine in a 1:1 emulsion (EMLA). The primary endpoint was success of initial attempt at i.v. cannulation.
Results: One hundred and seventy-seven patients were analysed of 203 enrolled. The success rate of AnGEL (73/97, 75%) and EMLA (59/80, 74%) did not significantly differ (
21 0.05, P=0.82).
Conclusions: No difference exists in the cannulation success rates between the two anaesthetics. The choice of topical anaesthetic in paediatric cannulation should be based on other factors such as cost, time to anaesthesia, efficacy of the agent, and adverse effect profile.
Keywords: anaesthetics local, EMLA; anaesthetics local, tetracaine; veins, cannulation
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Introduction |
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Cannulation of paediatric patients is commonplace and can be distressing to children and their families. In the Emergency Department (ED), it is standard practice for children requiring cannulation to receive topical anaesthesia before the procedure. Two commonly used agents are EMLA® (eutectic mixture of local anaesthetics; 5% lidocaine and prilocaine in a 1:1 aqueous emulsion) and AnGEL® (4% amethocaine gel). Several studies have demonstrated that EMLA cream decreases the pain associated with venipuncture and venous cannulation.1–3 Amethocaine has also been shown to be an effective topical anaesthetic, in varying studies equal4–12 or superior13–15 to EMLA in efficacy.
Lidocaine/prilocaine and amethocaine differ in their vasoactive effects. There is a biphasic vasoactive response to the application of EMLA, with initial vasoconstriction.16 Topical amethocaine in various forms has intrinsic vasodilatory effects and the resulting erythema is a recognized side-effect of application.10 15 It has been suggested that the vasoconstriction that follows application of EMLA may hinder cannulation and that an anaesthetic with vasodilatory properties would be advantageous,14 but no studies have addressed whether the choice of local anaesthetic influences cannulation success rate in children. If this were found to be the case, there would be implications for practice; the use of an agent that facilitates cannulation would have both clinical and resource benefits.
Our study was designed to determine whether there was any difference in cannulation success on first attempt using the two different topical anaesthetics.
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Methods |
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The study conformed to the principles of ethical research adopted by the World Medical Association (http://osr.od.nih.gov/guidelines/helsinki.html, accessed May 2006). Approval for the study was sought and obtained from the South Eastern Sydney Area Health Service (Southern Sector) Ethics Committee (http://sesiweb/STG/pages/divisions/execdir/Ethics/ethics.asp, accessed January 2006).
The study involved two topical anaesthetics: EMLA and AnGEL. EMLA is registered for use in the paediatric population in Australia by the Therapeutic Goods Administration (TGA) (http://www.tga.gov.au, accessed June 2007). AnGEL is not registered by the TGA but is available for use under the exempted goods provisions on contract between individual hospitals and the manufacturer. Topical amethocaine is approved by the FDA in the USA.
The study setting was the ED of a tertiary referral hospital and trauma centre in the southern suburbs of Sydney, Australia. The ED sees approximately 10 000 paediatric patients among an annual census of 51 000. The study was conducted over a 6 month period from May 2006.
Patients aged between 12 months and 12 yr of age who required cannulation as part of their clinical care were eligible for the study. Exclusion criteria were known allergy to either agent or inability for cannulation to be delayed for 1 h due to an emergent clinical condition. Eligible patients were enrolled with the informed consent of parent or guardian. Once enrolled, patients were randomized by the selection of a sealed trial package. Within this package were a data collection sheet and two sealed envelopes that contained the randomization sequence predetermined by computer generation. The first envelope was labelled ‘Instructions for Nurse’ and instructed the nurse to place EMLA on the right dorsal hand and antecubital fossa, and AnGEL on the left dorsal hand and antecubital fossa, or vice versa. Both anaesthetics were applied under occlusive dressings. The patient was blinded to which anaesthetic was on which side. One hour later, the nurse removed the dressings and topical anaesthetics and took no further part in the cannulation. After the anaesthetics were removed, the cannulating staff member, blinded to the contents of the first envelope, opened the second envelope labelled ‘Instructions for Cannulator’ that randomized them to cannulate either the left or the right upper limb as their first attempt. This staff member could choose either the hand or antecubital fossa on the side to which they had been randomized, and the diameter of the cannula. Successful cannulation was defined as being able to freely instil 5 ml of normal saline through the secured cannula. If the first attempt was unsuccessful, the cannulator was no longer restrained by the study and could choose any site for subsequent cannulation attempts.
After cannulation, the staff member completed the data collection sheet containing clinical information on the patient and details of the cannulation. The sheet was placed in a sealed box and data were entered by one of the investigators into a password protected Microsoft Excel® database. Statistical analysis was undertaken using a software package (SPSS, v11, Chicago, IL, USA). Categorical variables were analysed using Pearson’s 2 test, and continuous variables using the Student’s t-test.
Before the commencement of the trial, an audit of consecutive cannulations performed on all children in the ED, with either EMLA or no anaesthetic, revealed an initial attempt success rate of 60%. On the basis of a clinically meaningful improvement to 80%, it was determined that 81 patients would be required in each arm of the study to have 80% power of detecting a statistically significant difference at a threshold of 5%. In anticipation of a non-completion rate of 20%, it was planned to enrol 200 patients.
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Results |
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Figure 1 summarizes the study. Of the 203 randomized patients, 26 were not cannulated. In 25 cases, this was due to an improvement in their clinical condition; one patient (an 8-yr-old female) was withdrawn from the study when her parent requested cannulation on the side opposite to which she had been randomized. Analysis of the remaining 177 patients was on an intention to treat basis, including patients where there was a protocol violation (age range outside the 12 month to 12 yr criteria, cannulation not performed on the side to which patient randomized).
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Table 1 shows the baseline characteristics did not vary between the two groups. A considerable number of data sheets did not note whether the hand or antecubital fossa was the site chosen by the cannulator for their initial attempt, but where this was recorded there was no difference found between the AnGEL and the EMLA groups.
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The initial cannulation success rates with AnGEL (73/97, 75%) and EMLA (59/80, 74%) did not differ significantly (
21 0.05, P=0.82). Of the 45 cases where the first attempt was unsuccessful, cannulation was successful on the second attempt in 36 (80%), the third attempt in 6 (13%), the fourth attempt in one (2%), and was not attempted in another two cases.
There was a significant increase (21 4.07, P=0.03) in reported adverse effects with AnGEL (n=13, 13%) compared with EMLA (n=3, 4%). One patient with AnGEL developed blistering; otherwise the reported events were minor and included erythema, wheal, and pruritis.
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Discussion |
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We found the choice of AnGEL or EMLA had no influence on the likelihood of successful cannulation at first attempt, despite the well-documented difference in vasoactive properties of the two agents.
EMLA is known to cause vasoconstriction, although it may also result in vasodilation with long application times of up to 180 min.15 16 The 60 min application time used in our study should not have been associated with vasodilation caused by longer application times for EMLA, and is unlikely to explain the results.
Unlike EMLA, AnGEL has known vasodilatory properties.7 17 Our results, however, suggest this does not improve success rates for cannulation. We hypothesize three explanations for these results. First, that the magnitude of vasoactive changes with either agent is insufficient to change the likelihood of cannulation success. Secondly, that the vasodilation benefit of AnGEL is counterbalanced by increased oedema or other dermal changes that impede cannulation. For the purpose of blinding, we chose a 60 min application time for AnGEL, a shorter time may offer equivalent anaesthesia and a more advantageous balance between vasodilation and oedema. Finally, it is possible that physiological influences on vein size are more important than any pharmacological effects of topical anaesthetics. The patients in our study by definition were ill enough to require presentation to an ED and cannulation. Hence, the peripheral vasoconstriction associated with their clinical conditions such as fever, dehydration, or pain may have a greater influence on vein diameter and cannulation success than the choice of anaesthetic. In a population undergoing, for example, elective general anaesthesia these physiological influences may not be present.
There are a small number of studies that have looked indirectly at ease of cannulation with topical anaesthesia, but none that have had this as the primary endpoint. A Cochrane review examining efficacy of amethocaine gel and EMLA for pain relief during cannulation in children aged 3 months to 15 yr found amethocaine to be superior.14 This effect persisted regardless of application times, and whether pain was assessed by the children or by observers. The review also postulates that the vasodilation caused by amethocaine may facilitate cannulation. In the studies analysed, few data were available concerning the number of attempts before achieving successful cannulation. One study included in the meta-analysis did examine ease of cannula insertion. This was assessed via a rating scale completed by the cannulator, rather than a concrete endpoint as our study did. This study found no difference in difficulty of cannulation.11 A study comparing EMLA and topical amethocaine for cannulation in adults found that amethocaine provided superior analgesia, and also made cannulation easier (as graded subjectively by cannulator).15 This study enrolled only 32 subjects, and used large-gauge (16 G) cannulae. Another study evaluating EMLA vs tetracaine for analgesia for paediatric cannulation also found amethocaine (tetracaine) to be superior, but this study found no difference with regard to ease of cannulation.13
Comparative costing analyses of dermal anaesthetic agents identify significant financial difference between the two agents. As of September 2007, AnGEL is $A22.81 per 30 g and $A5.40 per 5 g; EMLA is $A43.39 per 30 g and $A9.05 per 5 g (personal communication; ORION Laboratories, Sydney, Australia).
Our study has one notable limitation, the difference between the cannulation success rate in our pilot audit (60%) and the success rate in the study proper (75%). As not all eligible patients requiring cannulation were enrolled into the study, it is possible that this discrepancy indicates selection bias. We did not specify the diameter of cannula used for cannulation and left this to the discretion of the cannulator as would be usual clinical practice, but it is possible that not standardizing cannula diameter resulted in unintended confounding bias. Although all attempts were made to achieve blinding of the cannulator, the difference in dermal effects of the two agents may have resulted in some cannulators accurately guessing to which arm of the study they had been randomized. Our study did not compare pain scales or satisfaction ratings for the two agents because we felt this had been adequately addressed in research published elsewhere, but if we had measured these it may have added to this body of research.
In conclusion, our study did not demonstrate any difference in the rate of successful cannulation in children with either anaesthetic. The choice of topical anaesthetic for use in the paediatric emergency population can be based on other research suggesting possible benefits of amethocaine gel, including better anaesthesia and lower overall costs, balanced against the increased number of minor adverse events with this agent.
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Funding |
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No pharmaceutical company or other funding was sought or provided for this research.
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References |
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