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.
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