Lidocaine-prilocaine cream (EMLA Cream®) as a topical anaesthetic for the cleansing of leg ulcers. The effect of length of application time

ARTICLE

Mechanical debridement of leg ulcers to remove slough, fibrinous tissue and necrosis is an effective method for attaining an ulcer surface which will enable granulation thus encouraging spontaneous healing or enabling skin grafting [1]. However, the procedure is often very painful, resulting in unsatisfactory cleansing. Topical treatment with a eutectic mixture of local anaesthetics (EMLA) 5% cream has been shown to provide effective anaesthesia for superficial surgery of intact skin, genital mucosa and leg ulcers. The onset time for anaesthesia of intact skin is 60 minutes [2] and of genital mucosa only five minutes [3, 4]. EMLA treatment of leg ulcers for 30 minutes has been shown to significantly decrease pain from surgical cleansing compared to placebo cream [5]. In the present study the analgesic efficacy of EMLA during debridement of leg ulcers was studied after treatment with EMLA for 10, 20 or 60 minutes.

Patients and methods

Study design

The study was designed as a single-blind, three-armed, parallel-group study with stratification for the aetiology of ulcer (arterial, venous and diabetic). A sealed envelope containing information about the randomised treatment allocation of EMLA application for 10, 20 or 60 minutes was opened immediately before treatment. The investigator carrying out the debridement was blinded with respect to knowledge of the application time of EMLA. Before entry into the study each patient was informed about the purpose and procedures of the trial and gave his/her consent to participate. The study was approved by the Ethics Committee at the University of Lund.

Patients

The pain during the cleansing of leg ulcers after treatment with EMLA was assessed in 59 hospitalised patients, 13 men and 46 women, 47 to 94 (median 79) years old. The patients had leg ulcers of venous (n = 39), arterial (n = 19) or diabetic (n = 1) origin. Patients with an ankle/arm index exceeding > 0.5 were assigned to the venous stratum. Seven other patients had diabetes. Six had recently suffered from erysipelas and five of them were still receiving antibiotic treatment. The ulcer area ranged from 2 to 140 cm² and ulceration had persisted for 0.5-60 months. Thirty-seven patients had ongoing medication consisting of analgesics or anti-inflammatory agents prior to the debridement. In addition, one patient with advanced cancer was receiving ongoing morphine treatment.

Anaesthetic and surgical procedure

EMLA 5% sterile cream^® (Astra AB, Södertälje, Sweden) containing 25 mg lidocaine and 25 mg prilocaine per gram was transferred to a 10 ml disposable syringe to facilitate dosing of the amount of cream, 2 g/10 cm² (sufficient to fill the whole ulcer cavity, a maximum of 10 g). The size of the ulcer was calculated by projecting its outline onto transparent film and counting the number of squares (0.25 cm²) on squared paper that were equivalent to the size of the ulcer. After application of cream, the ulcer was covered with plastic film (Glad^®, First Brands, W. Germany). After 10, 20 or 60 minutes of application the cream was wiped away and the cleansing started. The cleansing was carried out by means of tweezers and scissors or a curette and was performed by the same physician in all patients.

Assessments

The presence of necrotic tissue or coatings of fibrinous plaques was recorded prior to the application of EMLA. The pain intensity during the cleansing of the ulcer was rated by the patient on a 100 mm horizontal ungraded VAS with the end-points marked "no pain" (0 mm) and "worst possible pain" (100 mm) [6].

Statistics

The difference in VAS scores between the 10-, 20- and 60-minute groups was tested by a generalised Mantel-Haenszel test, which is directed at the extent to which there is a consistent positive or negative association between the response scores and the treatment level scores in the respective stratum (a stratified test of the rank correlation coefficient) [7]. The ulcer type was used as the stratification variable, and a chi-square approximation to the test statistics was used [7].

A subset analysis was performed in which patients with erysipelas and diabetes were excluded as well as the patient on morphine treatment.

Results

Nineteen patients were treated with EMLA for 10 minutes, 24 for 20 minutes and 16 for 60 minutes (Table I). The size and duration of treated ulcers were similar in all treatment groups, the median areas being 12, 7.5 and 8 cm² respectively and the median ulcer duration 4, 2 and 2 months respectively. In 42 of the patients, a thick layer of necrotic tissue was removed from the ulcer. In these patients, cleansing was carried out using tweezers and scissors, in some cases (n = 24) performed in combination with curettage. In 17 patients, cleansing was performed by curettage only.

The duration of the cleansing procedure varied between 1 and 13 minutes, the median being 3 minutes, with no differences between groups.

Analgesic efficacy

The pain from the cleansing of the leg ulcers decreased with a longer period of EMLA treatment (p = 0.001, Fig. 1). The median VAS pain scores were 41, 20 and 8 mm after 10, 20 and 60 minutes treatment respectively (Fig. 1).

The VAS scores of the patients recently suffering from erysipelas were 27-80 mm (median 42.5) and for the diabetics 2-14 mm (median 4.5). The patient on morphine had a VAS score of 0.

In the subgroup analysis where these patients had been excluded, there was also a significant association between the VAS scores and the application time of EMLA (p = 0.015) with lower VAS scores for longer application times, medians 41, 20 and 9 mm after 10, 20 and 60 minutes respectively.

Adverse reactions

In one patient treated for 60 minutes, moderate maceration of the skin surrounding the ulcer was recorded. There were no spontaneously reported local sensations or other adverse events.

Discussion

In this study the analgesic efficacy of treatment with EMLA was found to increase with the duration of treatment (from 10 to 60 minutes). As patients with erysipelas often experience more pain, and diabetics pain to a lesser degree, a subset analysis was also performed with these patients excluded. Overall, the same results were obtained in this analysis. The pain scores recorded may be compared with those of Holm et al. [5], who reported median VAS pain scores of 18.5 mm after treatment with EMLA for 30 minutes and 84 mm after treatment with placebo cream.

A major improvement in pain relief was obtained in this study between length of application times of 10 and 20 minutes, with a further improvement at 60 minutes. In three other controlled studies [5, 8, 9] a significant analgesic effect after 30 minutes treatment was reported. Because of the generally limited availability of treatment rooms it seems reasonable to recommend an application time of 20-30 minutes. However, since analgesia may increase further with longer treatment, an application time of up to 60 minutes can be used in cases where repeated debridement is necessary and the pain relief after 20-30 minutes has not been sufficient.

Leg ulcer patients have a disease which has a considerable effect on their quality of life [10]. Pain has been reported to be a major concern in these patients [10, 11], and all available methods should therefore be considered in order to reduce both chronic and acute pain. The simple treatment with EMLA cream, described here, which is easy to use in both inpatient and outpatient clinics is a step in that direction. The analgesic efficacy of EMLA for ulcer cleansing was demonstrated in this study, although 65% of the patients were taking analgesics. EMLA has also been shown to decrease post-cleansing pain up to four hours after the procedure [8].

Local anaesthetics of the amide type, which includes lidocaine and prilocaine, are known to be rare sensitisers and the cream does not contain any preservatives. Repeated debridement with EMLA cream up to eight times has been reported, without any signs of sensitisation [8, 12]. As expected, no such events were observed in the present study.

Plasma levels of lidocaine and prilocaine reported following treatment with 5-10 g EMLA cream in a previous study [5] were low, up to 0.8 µg/ml and 0.08 µg/ml respectively, and should be compared to the threshold for initial signs of CNS toxicity, 5-6 µg/ml [13].

The use of sterile preparations in the treatment of leg ulcers was a requirement of the Swedish Medical Products Agency at the time of initiation of this study. The recommendations were later changed and sterile preparations were no longer required [13]. The EMLA sterile cream 5% used in this study has a composition identical to EMLA cream 5%. Furthermore, most leg ulcers are colonised by bacteria. Consequently, there should be no need to use sterile EMLA cream for topical anaesthesia of leg ulcers in the future.

REFERENCES

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