Pelvic organ prolapse (POP) and stress urinary incontinence (SUI) are common conditions, especially in postmenopausal women with prevalence rates up to 65% for POP and 55% for SUI.1,2 By age 80 years, 11% of women undergo surgery for these conditions.3 Vaginal pessaries are an inexpensive, nonsurgical treatment option for POP and SUI, especially for women with severe medical comorbidities that make the patient a poor surgical candidate.
Nearly all (89%) women who attempt fitting are successfully fitted.4 However, 24 months after successful pessary fitting, approximately half discontinue use.5 One reason for discontinued use is acute pain, which particularly occurs during pessary removal, cleaning, and reinsertion.6 In fact, some research suggests that postmenopausal women with vulvovaginal atrophy experience more pronounced pain and, worse, that nurses and physicians may underestimate patients' pain levels.7,8 The cumulative effect is that, without adequate pain control, some women may discontinue pessary treatment and proceed to surgery with its attendant risks.
Lidocaine–prilocaine cream is well tolerated and has been shown to be effective in reducing pain during minor gynecologic procedures.9,10 It has also been shown to be safe in the geriatric patient population.11 The primary objective of this study was to determine the effect of lidocaine–prilocaine cream on patient self-reported pain as measured by a visual analog scale (VAS) at the time of pessary removal and reinsertion. We hypothesized that use of lidocaine–prilocaine cream would reduce patient pain at both time points. The secondary aim was to assess the ability of physicians at all levels of training to estimate pain during office pessary removal and reinsertion. We hypothesized that physicians would poorly estimate patient pain.
MATERIALS AND METHODS
This was a single-site, randomized, double-blind, placebo-controlled trial conducted in an outpatient urogynecology office at a tertiary referral center in which care is provided by obstetrics and gynecology and urology residents, urogynecology fellows, and urogynecology attending physicians. The study team received Loyola University Chicago Health Sciences Division Institutional Review Board for the Protection of Human Subjects approval, exemption from the U.S. Food and Drug Administration’s investigational new drug regulations (ie, investigational new drug exemption), and registered this trial with clinicaltrials.gov (NCT02380742). Written informed consent was obtained from all participants before allocation to a study group.
Women were eligible to participate in the study if they fulfilled the following inclusion criteria: presenting for routine pessary management for prolapse, SUI, or both with a pessary in place, able to provide written informed consent, and able to complete study activities. Patients were excluded if they were not English-speaking, had a known hypersensitivity or medical contraindication to topical anesthetics, had vaginal erosion present at the time of pessary removal preventing reinsertion of the pessary, or were pregnant or lactating.
Patients were assessed for eligibility when they presented to the office for routine pessary care. Participants were assigned randomly to receive 4 g of lidocaine 25 mg plus prilocaine 25 mg/g cream (ie, EMLA [Eutectic Mixture of Local Anesthetics]) or an equal volume of placebo cream designed to look identical to the lidocaine–prilocaine cream (ie, emollient cream containing purified water, white petrolatum, cetyl alcohol, stearyl alcohol, propylene glycol, glycerin, sodium lauryl sulfate, diazolidinyl urea, lodopropynyl butylcarbamate). Participants were randomized using a double-blind one-to-one permutated block randomization scheme. An independent biostatistician (S.K.) prepared the randomization schedule and loaded the assignments into a secure research electronic database (REDCap). Subsequently, an independent research nurse (M.T.) accessed these assignments to prepare the study drug for each participant. After preparing the study cream in a blinded fashion, the independent research nurse gave it to the principal investigators who applied the cream and collected the pain scores.
Patient age, weight, gravity and parity, months of pessary use, reason for pessary use, type of pessary, size of pessary (diameter in millimeters), use of topical estrogen at least one or more times per week, menopausal status, hysterectomy status, smoking status, sexual activity (one or more times per month was considered sexually active), and pain with intercourse were collected for each participant. Participants were asked to rate their overall satisfaction with their pessary on a 5-point ordinal scale ranging from dissatisfied to very satisfied.
Pain was assessed at three points (baseline, removal, and reinsertion) using a standardized VAS pain score (10-cm-long straight line scaled 0 [no pain] to 10 [severe pain]).12 The scale did not contain any numeric values except the 0 at the beginning and 10 at the end, and a detailed explanation of the VAS was given to each participant before carrying out the study activities. Patients were asked to mark the point that best represented their level of perceived pain intensity at each time point. The distance from 0 to the point marked was measured with a ruler by two separate investigators to ensure agreement on the pain score recorded. To assess the accuracy of electronic VAS measurements in this patient population, participants were also asked to use their index finger to mark their VAS pain level on a second set of electronic VAS scores that were captured at the same time points. This e-VAS measure was captured on an electronic tablet using a similar scale. A research assistant supervised the participant VAS scoring because the physician carrying out the pessary change was blind to the patient scores.
Patients initially marked a VAS pain score at baseline both on paper and on the electronic tablet. They were then placed into the lithotomy position with appropriate draping. The physician (resident, fellow, or attending physician) placed 4 g total equal to 4 mL of either lidocaine–prilocaine cream or placebo cream dispensed from identical-appearing syringes. Two milliliters were placed into the vagina and introduced to the level of the pessary with the physician’s finger, and the other 2 mL were spread on the perineum. After placement of the cream, a timer was set for 5 minutes. After 5 minutes, the physicians removed the pessary per their usual practice. The patient marked a VAS pain score immediately after removal both on the paper and electronic tablet scales. Speculum examination and bimanual pelvic examination were performed per usual practice. The pessary was cleaned and replaced. Participants immediately marked VAS pain scores after reinsertion. Excess study cream was removed from the perineum. The physician performing the examination likewise marked their perception of the patient's pain during pessary removal and reinsertion using a VAS score on paper and the electronic tablet. The patients were then asked if they thought they knew which cream they received. This concluded the study visit.
Power for this trial was based on a priori VAS pain estimates.9 A sample size of 26 per group (n=52) was planned to estimate an absolute mean difference in VAS pain of 2.1 cm at the time of pessary removal (corresponding to a priori estimates of 0.9 cm for the lidocaine–prilocaine group, 3.0 cm for the placebo group, and a common within-group standard deviation of 2.6 cm). Participants' pain scores at removal and reinsertion were compared between the lidocaine–prilocaine and placebo groups using an analysis of covariance controlling for baseline pain. For these models, the assumption of homogenous regression slopes was assessed by allowing an interaction term between the baseline pain score and treatment assignment. A general linear model was also used to compare participants' (lidocaine–prilocaine cream compared with placebo) pain scores at removal and reinsertion after controlling for participants' age.
The paper and electronic VAS scores were assessed for absolute agreement using an intraclass correlation coefficient as described by Rosner,13 and agreement between participants' guesses at their treatment assignment and their actual treatment assignment was estimated using Cohen's κ coefficient. A P value of <.05 was considered statistically significant, and a P value of <.10 was considered as trending toward significance in this low-risk study. All analyses were completed using SAS 9.4.
Figure 1 displays the flow of patients through this study. Between July 2015 and February 2016, 116 patients were assessed for eligibility and 62 were excluded. Fifty-four participants were randomized; one participant assigned to lidocaine–prilocaine cream was withdrawn after receiving the study drug as a result of vaginal erosion preventing the pessary from being reinserted. Therefore, 53 participants were analyzed: 27 in the lidocaine–prilocaine group and 26 in the placebo group. The baseline characteristics were similar between groups except for pessary type with no Gellhorn pessaries in the lidocaine–prilocaine cream group compared with five in the placebo group (Table 1). Participants reported low baseline pain scores using both the paper VAS (mean 0.26, standard deviation±0.61; range 0.00–3.00) and the electronic VAS scale (mean 0.52, standard deviation±0.60; range 0.00–2.90).
After adjusting for baseline pain, participants assigned to the lidocaine–prilocaine cream group had lower pain at pessary removal when compared with those assigned to the placebo group (mean difference=−2.05, 95% confidence interval [CI] −3.69 to −0.41; P=.015). After controlling for both age and baseline pain score, those assigned to lidocaine–prilocaine cream continued to have lower pain when compared with those assigned to placebo (mean difference=−1.81, 95% CI −3.49 to −0.14; P=.035). Regarding reinsertion, participants assigned to the lidocaine–prilocaine cream group had nominally lower pain scores when compared with those assigned to placebo (mean difference controlling for baseline pain=−1.07, 95% CI −2.31 to 0.17), although it did not reach statistical significance (P=.088; Fig. 2). Importantly, patients reported no adverse events or irritations at the time of pessary removal or reinsertion.
We determined the agreement between paper and electronic VAS scores to ensure accuracy of the electronic data capture method, especially in an older patient population. These data capture methods were in superior agreement for both patients and physicians (Table 2). Intraclass correlation coefficient between electronic and paper VAS scores for patients at baseline, removal, and reinsertion were high at 0.835, 0.966, and 0.842, respectively (all P<.001). Similarly, agreement between the electronic and paper VAS scores for the physicians' responses at removal and reinsertion were also high at intraclass correlation coefficient=.984 and intraclass correlation coefficient=.968, respectively (both P<.001).
A secondary aim of the study was to determine the ability of physicians to accurately assess patient pain at the time of pessary removal and reinsertion. A total of 13 unique physicians participated in the study, two attending physicians, three fellow physicians, and eight resident physicians. Using the paper collection form, there was substantial agreement between physicians' subjective assessment of their patients' pain score at pessary removal and patients' objectively reported pain scores (ie, intraclass correlation coefficient=resident: 0.933; fellow: 0.917; attending 0.937; all P<.001). However, at the time of pessary reinsertion, we detected discrepancies between physician training level and patient ratings. As physician training level increased, there was stronger agreement between physician and patient pain scores. That is, among residents, there was no meaningful agreement with patients' pain scores (P=.70). Conversely, despite wide CIs, there was fair agreement between fellows and patients (intraclass correlation coefficient=0.69, 95% CI 0.36–0.86; P=.001) and between attending physicians and patients (intraclass correlation coefficient=0.80, 95% CI 0.28–0.95; P=.01; Table 3).
Twenty-nine of the 53 participants felt they knew their treatment assignment. Fourteen of these participants (48%) correctly identified that they were assigned to lidocaine–prilocaine cream, and five participants (17%) correctly identified that they were assigned to placebo. However, seven participants (24%) incorrectly guessed that they were assigned to lidocaine–prilocaine cream when they were actually assigned to placebo, and three participants (10%) incorrectly guessed that they were assigned to placebo when they were assigned to lidocaine–prilocaine cream. A κ analysis reflected poor agreement between the participants' guesses and actual treatment assignment. After adjusting for agreement by chance alone, participants were only correct approximately 25% of the time and this was not statistically different from 0% agreement (κ=0.25, exact P=.22).
Our study sought to evaluate if a low-risk topical anesthetic cream could improve patients' overall experience with pessaries. Our results support the use of lidocaine–prilocaine cream to reduce pain associated with routine office pessary removal in postmenopausal patients in a urogynecology practice at a tertiary referral center cared for by physicians at all levels of training. Clinicians may wish to include this simple, low-risk intervention to optimize patient comfort and compliance.
Projections of pelvic floor disorders indicate that the number of women with POP will increase from 28.1 million to 43.8 million.14 Because increasing age has been shown to be associated with higher mortality and complication, it is incumbent on us to thoroughly evaluate and maximize nonsurgical management options, specifically in pelvic floor surgery.15 We believe this study highlights one way to maximize pessary use, an important nonsurgical option, by reducing pain at the time of office removal. Although we demonstrated that lidocaine–prilocaine cream leads to less pain with pessary removal than usual care, we have not established that this leads to continuation of pessary use, which is ultimately the goal of any intervention seeking to maximize patient comfort and long-term use.
Lidocaine–prilocaine cream is the best studied topical anesthetic used for minor gynecologic procedures.10 It has been shown to reduce pain when compared with placebo for removal of genital warts, office hysteroscopy, and intrauterine device insertion.16–18 Keskin et al9 had similar findings with the use of lidocaine–prilocaine cream to minimize pain in postmenopausal women during speculum examinations. They found significantly lower pain scores during all phases of speculum examination in the lidocaine–prilocaine group as compared with lubricant gel and control groups. Lidocaine–prilocaine cream and other topical anesthetics have not previously been studied for use in office pessary removal and reinsertion.
We also found that this older patient population can reasonably use electronic technology for data collection as a substitute for paper data collection (ie, an electronic tablet). This study shows that when using the paper VAS pain score as the standard, patients with an average age of 78 years had excellent correlation in their use of an electronic tablet version for the VAS pain score. Bird et al19 also found similar results when testing a new iPad application, the iPad VAS, in a group of 22 older adults ages 65–85 years. As we move forward modernizing our clinical and research practices, it is reassuring that straightforward technologic applications to gather and record patient experiences are a reliable alternative to paper records.
For our secondary aim, physicians' assessments correlated well with patient-reported pain during pessary removal with stronger correlations for experienced physicians in more subtle pain experienced during pessary reinsertion. This indicates as experience increases, an appreciation of more nuanced levels of pain is appreciated.
Strengths of this study are those shared with any randomized, double-blind, placebo-controlled trial: bias was minimized and the causal association between lidocaine–prilocaine and reduced pain at the time of pessary removal was strengthened. Our study design involved only one study visit so no patients were lost to follow-up. We were additionally fortunate to have only one participant with vaginal erosion in our study population, which limited exclusions after randomization to one. An additional strength of this intervention and study is its ease of application in clinical practice. Lidocaine–prilocaine cream can be placed by a medical assistant or registered nurse allowing the care provider to complete care without adding significant time to the visit. Furthermore, the intervention was well tolerated without any adverse events or irritations noted.
One limitation in this study was an intermittent Wi-Fi signal, which was required for electronic data capture. This did not affect the primary outcome of the study but did affect our ability to assess agreement between paper and electronic VAS scores in three of the patients. Another potential limitation may be the possibility that patients underreported their pain in an effort to please their health care provider causing acquiescence bias and underestimation of pain. However, as a result of the effective randomization, this behavior is assumed to be similar in both study arms. In addition, these women were not in significant clinical pain, and the goal was to minimize acute provoked pain at the time of the procedure.
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