Pain Perception During Vulvar Biopsy

Study Overview
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Brief Summary
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The purpose of this study is to compare pain control during vulvar biopsy following either (1) application of EMLA (a eutectic mixture of local anesthetics lidocaine 2.5% and prilocaine 2.5%) cream or (2) injection of 1% lidocaine. We hypothesize that lidocaine will provide better biopsy analgesia, but the benefit will be offset by the pain of lidocaine injection compared to EMLA application, thus there will not be a significant difference in highest pain scores between the two groups.

Detailed Description
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Performing minor procedures in-office is essential to gynecologic practices. In-office procedures allow for evaluation and diagnosis of a variety of conditions while avoiding the expense, anesthesia, and time associated with the operating room. Pain and discomfort are frequently associated with these procedures, and ensuring that the patient has the least amount of discomfort is a priority. Very painful or uncomfortable procedures could potentially discourage a patient from returning to clinic or receiving the follow up that they may need. Psychological, physiologic, and social factors influence a patient's experience of pain. Previous studies, though mostly related to first trimester abortion procedures in the office, indicate that the procedure type, anxiety, depression, and general anticipation of pain predict increased pain during in office gynecologic procedures (1-4). A review by Ireland et al., found that a multimodal approach that includes patient counseling with other techniques is most effective in achieving optimum pain control for procedures (5,6). Vulvar biopsies are associated with significant discomfort, and some form of anesthesia is required. The current standard in our group is to inject local anesthesia prior to vulvar biopsy. However, the injection itself is associated with its own level of pain that is not insignificant, and for many, the anticipation of receiving an injection is anxiety provoking. The use of topical anesthesia in lieu of injection or as pre-injection analgesia is variable. Several previous studies have examined the use of topical anesthetics in the place of or in addition to injected anesthesia. Drouault et al. compared EMLA cream alone to injected lidocaine alone for pain relief in vulvar biopsy and found that pain associated with administration of anesthesia was significantly less for EMLA cream, but better biopsy analgesia was obtained with injected anesthesia. The study considered combined pain scores for both groups for the overall procedure (anesthesia + biopsy), it comments that the combined scores were lower for the EMLA group but failed to reach statistical significance. The study ultimately concluded that EMLA is the less painful procedure to obtain anesthesia and that it can be used as an alternative to injection for biopsies of the genital mucosa (7). This prior study did not compare the highest pain score between groups. Consideration of the highest pain score allows us to assess whether the injection of lidocaine could result in causing more pain than the biopsy itself using EMLA cream alone for anesthesia. Further, the study did not assess the subjects' or the providers' perception of the tolerability and acceptability of performing the procedure using either method. This is an important factor in any in office procedure EMLA cream is the most extensively studied topical anesthetic. It is FDA approved for use as a topical anesthetic on the genital mucous membranes for superficial, minor surgery. EMLA cream requires between 7-10 minutes of absorption time on the genital mucosa for analgesic effect, with variable duration of analgesia following, usually around 15-20 minutes (9). There is a highly variable absorption rate for EMLA cream depending on the characteristics of the epithelium upon which it is applied as well as the duration and surface area of cream applied. On hair-bearing non-mucosal surfaces it can require 60 minutes of application time to obtain analgesic affect (10). The vulvar area is unique in that it contains both mucosal and non-mucosal and hair-bearing surfaces; this could greatly affect the absorption of EMLA and therefore affect analgesia. For this reason, we will exclude from the study patients requiring vulvar biopsy on hair bearing portion of the vulva. Several previous studies have examined the use of topical anesthetics in the place of or in addition to injected anesthesia. Drouault et al. compared EMLA cream to injected lidocaine as described above. The study found that pain associated with administration of anesthesia was significantly less for EMLA cream, but better biopsy analgesia was obtained with injected anesthesia. However, there were some limitations to this study also noted above, that we plan to expand and improve upon with the current study. Zilbert and Lewandoswki studied pre-treatment with EMLA cream prior to anesthesia injection and found that pain was decreased by 50% in patients pretreated compared to placebo prior to lidocaine injection. Van den Berg studied application of EMLA alone versus lidocaine injection alone in punch biopsies and electrocoagulation of genital warts in men. The study found that in the punch biopsy cohort that the total pain scores (application of EMLA + biopsy versus injection of lidocaine + biopsy) were less for the EMLA group than the injected lidocaine group and the difference was statistically significant (11). With its FDA approval for use as a topical anesthetic on the genital mucous membranes for superficial, minor surgery, it can be considered a standard of care to use EMLA for anesthesia prior to biopsy as an alternative to injection of lidocaine (10) As there are no studies that consider the subjects' or the providers' perception of the acceptability or the tolerability of the procedure, this will be novel data for vulvar biopsy. However, acceptability and tolerability have been assessed in other procedural settings, such as in office endoscopic procedures, in which BS-11, a validated 11 point scale, is used to assess pain, anxiety, acceptability, tolerability, and levels of other procedure related symptoms (12-13).

Official Title
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A Comparison of Pain Perception Using Topical EMLA Cream Versus Lidocaine Injection for Vulvar Biopsy: a Randomized Controlled Trial

Conditions
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Any Condition Requiring Vulvar Biopsy

Intervention / Treatment
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* Drug: EMLA
* Drug: Lidocaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females above age 18 presenting to Duke Gynecology Oncology clinic for vulvar biopsy Able to provide informed consent in English and agree to the risks of the study Exclusion Criteria: Not able to provide informed consent Vulvar biopsy on a hair bearing surface

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EMLA<br> | Drug: Lidocaine<br>* Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.<br>|
| Active Comparator: Lidocaine<br> | Drug: EMLA<br>* Patients undergoing a vulvar biopsy will be randomized to receive EMLA cream or a lidocaine injection as their numbing agent prior to the procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Highest Pain Score | The highest pain score recorded (at time of numbing or at time of biopsy) controlled for baseline pain title: Please slide the tab along the line below to indicate pain in the area of your vulva (external genitalia) during numbing OR biopsy min: 0 (no pain) max: 100 (worst pain imaginable) | no more than 5 minutes after numbing or 5 minutes after biopsy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain During Biopsy as Measured by a Pain Scale | self-reported level of pain following the biopsy title: Please slide the tab along the line below to indicate pain in the area of your vulva (external genitalia) during biopsy min: 0 (no pain) max: 100 (worst pain imaginable) | No more than 5 minutes after receiving the biopsy | 
| Baseline Vulvar Pain | self-reported level of vulvar pain immediately prior to the start of the procedure title: Please slide the tab along the line below to indicate pain in the area of your vulva (external genitalia) during biopsy min: 0 (no pain) max: 100 (worst pain imaginable) | no more than 30 minutes prior to procedure | 
| Anxiety Before the Procedure as Measured by an Anxiety Scale | self-reported level of anxiety immediately prior to the start of the procedure title: Slide the tab along the line below to indicate how nervous you feel about the procedure you are about to have min: 0 (not nervous) max: 100 (very nervous) | No more than 30 minutes before the procedure | 
| Generalized Anxiety Disorder 7-item (GAD-7) Score for Baseline Anxiety | Self-reported anxiety score meant to assess a patient's baseline level of anxiety. The score ranges from 0 (minimal anxiety) to 21 (severe anxiety). | no more than 30 minutes before the procedure | 
| Acceptance of the Procedure as Measured by a Satisfaction Scale | self-reported acceptance of the procedure meant to assess a patient's acceptability through a scale title: Please slide the tab along the line below to indicate, overall, how acceptable the procedure performed today was min: 0 (completely acceptable) max: 100 (not at all acceptable) | up to 30 minutes after the procedure | 
| Tolerance of Procedure as Measured by a Satisfaction Scale | self-reported tolerance of the procedure meant to assess a patient's tolerance through a scale Title: Please slide the tab along the line below to indicate, overall, how you would rate the experience of your biopsy procedure today Min: 0 (I could easily handle having this procedure again) Max: 100 (I could never have this procedure done again) | Up to 30 minutes after the procedure | 
| Provider's Opinion of Subject Tolerance as Measured by a Scale | provider-reported measure of how well they believe the patient tolerated the procedure title: Overall, how well did the subject tolerate the procedure today? min: 0 (well tolerated) max: 100 (poorly tolerated) | Up to 30 minutes after the procedure | 
| Provider's Overall Satisfaction With the Procedure as Measured by a Scale | provider-reported measure of how well they believe the procedure went title: Overall, how satisfied are you with the procedure performed today? min: 0 (completely satisfied) max: 100 (not at all satisfied) | Up to 30 minutes after the procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vulvar biopsy