ARTICLE
The introduction of CO2 lasers for the treatment of HPV-related
anogenital lesions was a major step foreword in the therapeutic approach
to the disease, the benefits of this technique resulting from minimal
tissue aggression and the absence of scarring, compared with conventional
therapy. Moreover, this approach is consistent with the rationale of genital
mucosa management since large surface areas are frequently involved due
to the multicentric and plurifocal aspects of papillomavirus-related lesions
of the anogenital tract. General or spinal anaesthesia are the most frequently
used techniques for laser treatment of large surface areas of genital
warts or multicentric intraepithelial neoplasia. The injection of local
anaesthetics is a painful procedure sometimes causing bleeding which hinders
penetration of the laser beam, thus reducing treatment efficacy. A topical
local anaesthetic was therefore the solution enabling a simple ambulatory
approach to the anaesthesia of such lesions. The cream formulation of
lidocaine/prilocaine (EMLA) has proven effective in providing superficial
anaesthesia of the skin and mucous membranes.
Material and methods
One hundred and twenty patients (95 men and 25 women) between the ages
of 18 and 45 years were enrolled in the study. All were programmed to
receive laser treatment for condyloma acuminata or intraepithelial neoplasia
of the cervix, vagina, vulva, perineum and anus for the women and of the
penis and anterior urethra for the men. Exclusion criteria for this study
included pregnancy and patients presenting chronic or inflammatory affections.
All female patients were assessed with a Pap smear, colposcopy and biopsy.
Those presenting several sites affected by HPV-related lesions underwent
complete anogenital colposcopy. Lesions were then categorised according
to site. The overall lesion surface area was evaluated by adding together
the surface areas of each site. Three groups were identified. Small lesion
areas (LA < 1 cm2), average lesion areas (1 cm2
< LA < 5 cm2) and large lesion areas (LA > 5 cm2).
On the cervix, lesions were classed into 4 categories according to their
topography within the transformation zone. The first category corresponded
to lesion areas less than or equal to a quarter of the transformation
zone. The second category included lesions covering a surface area between
a quarter and a half of the transformation zone. The third category was
for lesions with a surface covering between half and three quarters of
the total area of the transformation zone and the fourth category comprised
lesions extending over the entire transformation zone. The application
time of EMLA on each site was randomised into 3 sub-groups. Application
time in the first sub-group was between 1 and 4 min. In the second sub-group,
it was between 5 and 15 min and for the third sub-group, it was between
15 and 30 min. EMLA cream was applied to the surface of the different
areas of the cervix. It was applied in a thicker layer on the vulva and
the perineum. The cream was inserted into the urethra and the anal canal
using an applicator. The dose of cream used was practically identical
on each lesion area; a thin or average layer was applied over each of
the lesions following identification by colposcopy. When pain was of moderate
or strong intensity, a further layer of cream was applied or supplementary
anaesthesia was achieved using a local intra-lesional anaesthesia which
is easier to use in these conditions. Each patient assessed his/her pain
using a 100 mm rating scale. The score indicated by the visual analogue
scale was arbitrarily classed into four groups: VAS scores of 0, 1 to
30, 31 to 60 and 61 to 100. A VAS score of 0 indicated absence of pain.
VAS 1 to 30 was for mild pain. VAS 31 to 60 was indicative of moderate
pain and a VAS score of 61 to 100 corresponded to intense pain. Local,
intra-lesional rescue anaesthesia was administered to all patients indicating
VAS scores of 61 to 100 and also to a certain number of those with a VAS
score of 31 to 60.
The aim of this study was to assess the anaesthetic effect of EMLA cream
in the treatment of single or multicentric HPV-related anogenital lesions,
according to the following criteria.
- The localisation of the lesions within the anogenital tract including
the urethra in men and the anal canal in women.
- The surface area of the lesions.
- The application time.
Results
One hundred and twenty patients, 95 women and 25 men, were enrolled
in this study. The average age of patients was 28 years. Most of the lesions
were condyloma acuminata with the exception of those situated on the cervix
where intraepithelial neoplastic lesions were treated. In all, 50 women
presented cervical lesions, 23 had vulvar lesions, 12 had lesions of the
perineum and the anus and 10, intra-anal-canal lesions (Table
I). Of the male patients, 10 presented with intra-urethral lesions
and 15 with lesions of the penis. The extra-cervical lesions were all
condyloma acuminata. Multicentric lesions associated with those treated
by EMLA cream were not assessed by this anaesthetic procedure during treatment.
Thus, the results reported in the document refer only to the isolated
sites treated by this anaesthetic procedure.
Table II presents the
pain score on the visual analogue scale according to the localisation
of the lesions. It can be observed that, regardless of the localisation
and the duration of application, 41% of the 120 patients received complete
anaesthesia. Of the 23 patients presenting vulvar lesions, 14 (61%) received
complete anaesthesia compared with the patients presenting with lesions
of the perineum and the anus (5 out of 12: 41%). However, this difference
was not statistically significant (p = 0.4). Only 20% (10 out of 50) of
the patients with cervical lesions had complete anaesthesia. Lesions of
the penis were completely anaesthetised in over half the cases (7 out
of 15: 55%). One outstanding feature was the particularly effective anaesthesia
obtained in the intra-anal mucosa (7 out of 10: 70% of cases) and intra-urethral
mucosa (6 out of 10: 60% of cases). The absence of pain was significantly
more noteworthy within the anal canal compared with the uterine cervix
(p = 0.003). Irrespective of the surface area of the lesions or the application
time, anaesthesia was complete (VAS 0) or satisfactory (VAS 1 to 30) in
70% of the cases (85 out of 120).
Table III shows
the anaesthetic efficacy according to the surface area of the lesions.
Regardless of the site or application time, small lesion areas (LA <
1 cm2) obtained complete anaesthesia in 87% of cases (33 out
of 38) and this result was statistically significant compared with lesion
surface areas of 1-5 cm2 (p < 0.001) or greater than 5 cm2
(p < 0.00001). Satisfactory anaesthesia was obtained on moderate-sized
lesion areas with a VAS score of 1 to 30 in 36% of the 14 patients treated.
Finally, the majority (84%) of the lesion areas larger than 5 cm2
obtained average or very insufficient anaesthesia compared with that reported
for smaller surface areas. In all, of the 70 patients presenting extra-cervical
HPV lesions, 39 (55%) had complete anaesthesia irrespective of the lesion
surface area but this was more noteworthy on a small surface area. Likewise,
for cervical lesions, the surface area was an essential feature determining
the pain score (Table IV).
Of the 50 patients presenting with cervical lesions, only 10 (20%) received
complete anaesthesia with EMLA cream. Nevertheless, the most satisfactory
results were observed in patients presenting a small lesion area (<
1/4 of the surface of the transformation zone). As a result, 90% of the
10 patients presenting with a small surface area intraepithelial neoplasia
received complete anaesthesia during laser treatment and 75% of the 20
patients presenting with intraepithelial neoplasia covering one quarter
to half of the surface of the transformation zone received satisfactory
anaesthesia (VAS score 0 and 30). Finally, when the lesions covered more
than half the surface of the transformation zone, the anaesthetic effect
was reported as average or nil in most cases.
The effect of EMLA cream is significantly greater on lesions covering
less than half the transformation zone (p < 10- 5). When
this was the case, 84% of patients rated the anaesthetic effect between
0 and 30 compared with only 25% of those with lesions covering more than
half the transformation zone.
Application time of EMLA cream is the third criterion for anaesthetic
efficacy. Regardless of the site or the lesion surface area, the duration
of drug application is the principal factor in providing effective anaesthesia.
Of the 49 patients who received complete anaesthesia, 25 (51%) had an
application time of 1 to 4 min and 16 (33%) an application time of 5 to
15 min. Adequate anaesthesia was obtained by 80% of the 36 patients of
this group (VAS score 1 to 30). Of the 17 patients who did not achieve
any anaesthetic effect, 11 (65%) had a drug application time of 1 to 4
min (Table V). Nevertheless,
the correlation between the application time of EMLA cream and a total
absence of pain or reduced pain is not significant, p = 0.5 in both cases.
Discussion
This study shows that local anaesthesia with EMLA cream may be an interesting,
effective and low-cost alternative to general or intra-lesional anaesthesia
in patients undergoing treatment for condyloma acuminata or intraepithelial
neoplasia. The extent of anaesthetic efficacy depends primarily on application
time. Between 3 and 5 min application of EMLA cream provides adequate
anaesthesia for treatment to be administered without discomfort for the
patient or disturbance for the surgeon. EMLA cream provides a weaker anaesthetic
effect over extensive lesion areas than small lesion areas, irrespective
of the localisation in extra- or intra-cervical sites. It would appear
important to highlight one particularly interesting aspect regarding the
effective anaesthesia obtained within the intra-anal and urethral mucosa;
this enabled outpatient treatment of the majority of these individuals
who would otherwise have required a general anaesthetic. Finally, anaesthesia
of extra-cervical sites is more effective than that of the uterine cervix.
With regard to drug application time, most studies concur in recommending
that a period of 4 to 20 min of EMLA cream enables aggressive treatment
of condyloma lesions without pain or with an acceptable degree of pain
[1]. Other authors have shown that a 5 min application of the cream is
adequate to provide anaesthesia of vulvar lesions [2, 3]. Yet further
studies have demonstrated that the anaesthetic efficacy may diminish with
an application time beyond 15 to 20 min [3]. The rapid onset of the anaesthetic
effect and its efficacy, particularly within the mucous membranes are
also consistent with reports by other authors [3-5]. EMLA cream 5% would
also appear to be more effective in providing local anaesthesia and particularly
effective in providing local, intra-lesional anaesthesia [4, 6, 7]. Moreover,
anaesthesia of the skin has also been demonstrated and shown to be favourably
comparable to that produced by lidocaine emulsion alone [8-10]. In all
cases, and even in the patients for whom anaesthesia was not complete,
local intra-lesional anaesthesia with xylocaine could be administered
without discomfort to patients thus enabling treatment to be completed
effectively [6, 7]. These observations have also been reported by other
authors [1, 3]. Consequently, we would recommend anaesthesia with EMLA
cream as a first line treatment for condyloma acuminata. Anaesthesia with
EMLA cream, prior to any directed biopsy on the anogenital region may
also be considered a realistic proposal.
CONCLUSION
In conclusion, EMLA cream may be proposed to provide adequate anaesthesia
of HPV-related genital lesions; satisfactory results can expected for
small surface area cervical lesions, for moderate surface area lesions
of the vulva, perineum and anus and finally, for intra-urethral and intra-anal
mucous membrane lesions of moderate surface areas, with a mean drug application
time of 4 to 5 min. This approach enables aggressive treatment of these
lesions in outpatient conditions ensuring non-negligible comfort for both
the patient and the practitioner. The cost-benefit aspect of this approach
is the second advantage which should be highlighted since it avoids both
hospitalisation and general or locoregional anaesthetics for a certain
number of patients. Finally, application of EMLA cream as an anaesthetic
prior to directed biopsies in the anogenital region would appear to be
a useful practice which would benefit from further study.
Article accepted on 2/10/00
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