Effect of Urethral Analgesia on Voiding
Condition: Urethral Analgesia
Study type: Interventional

Summary: 
      The purpose of this study is to evaluate how urethral analgesia impacts voiding efficiency in
      healthy women. The investigator hypothesizes that anesthetizing the urethral with lidocaine
      gel will decrease voiding efficiency as measured by standard bladder testing (urodynamic
      testing).
    

Detailed description: 
      1. Purpose of the Study The purpose of this study is to determine whether urethral sensory
           feedback has a role in the micturition (bladder emptying) reflex in female controls
           during routine office Urodynamic Studies (UDS). UDS are current clinical tests of
           urethral and bladder function and consist of several individual studies including
           filling cystometry, pressure-flow studies, and urethral pressure profilometry (UPP).
           Filling cystometry focuses primarily on sensation and activity of the bladder during the
           filling (or storage) phase of the micturition (voiding) cycle. Pressure-flow studies
           (which include voiding cystometry) are used to assess the motor activity of the bladder
           muscle during bladder emptying. UPP assesses urethral sphincter motor function and has
           traditionally been used to evaluate stress urinary incontinence. Perineal patch
           electromyography (EMG) is often added to UDS to assess for pelvic floor muscle
           recruitment during voiding, which may suggest voiding dysfunction.

        2. Background & Significance The storage and elimination of urine is regulated by neural
           circuits in the brain and spinal cord to coordinate function between the urinary bladder
           and the urethra. During the micturition (bladder emptying) reflex, the elimination of
           urine is facilitated by bladder wall contraction and urethral wall and pelvic floor
           muscle relaxation. Urine that subsequently flows through the urethra also activates
           sensory nerves to amplify bladder contractions and maintain efficient bladder emptying.
           Incomplete voiding and urinary retention occurs when these mechanisms are disrupted or
           poorly coordinated.

           Incomplete bladder emptying due to detrusor underactivity is an understudied health
           concern for women in the United States. The overall incidence detrusor underactivity in
           women has not yet been reported in the literature. One study by Wu et al. (2005)
           determined that 7.8% of patients in an outpatient rehabilitation facility had symptoms
           of incomplete bladder emptying; whereas, 21% of people without symptoms had elevated
           post void residuals when universally screened. Their population consisted of 350
           patients, of which two-thirds were women. Lower urinary tract symptoms, including
           urinary urgency, frequency and incomplete bladder emptying, have been shown to decrease
           quality of life, increase healthcare utilization, decrease workplace productivity, and
           impact intimate relationships.

           The current clinical management options for women with retention are intermittent or
           indwelling catheterization, urethral dilation, or reconstructive surgery. These
           treatments, however, often fail to completely resolve lower urinary tract symptoms and
           the patients may develop chronic retention complications such as overflow incontinence,
           hydroureter, hydronephrosis, infection, or renal failure. In order to improve
           therapeutic outcomes, there is still a need to clarify the specific mechanisms that
           underlie detrusor underactivity in women. Our proposed studies will be contributing to
           the growing body of literature implicating urethral sensory feedback as a candidate to
           recover efficient bladder emptying.

        3. Hypothesis and Justification Overall Hypothesis: Urethral afferent nerve fiber
           activation augments bladder contractions for efficient voiding and urethral anesthesia
           will disrupt sensory feedback and impair bladder emptying.

           Specific Aim 1: To assess voiding efficiency (voided volume/{voided volume + residual
           volume}) in women controls with and without urethral anesthesia Hypothesis 1a: Voiding
           efficiency will be lower when the urethra is anesthetized during micturition
           pressure-flow studies Hypothesis 1b: Detrusor contraction at maximum flow rate
           (Pdet@Qmax) and duration of detrusor contraction will be reduced when the urethra is
           anesthetized during micturition pressure-flow studies Hypothesis 1c: Voiding while
           anesthetized will lead to increased valsalva-voiding (increased intra-abdominal
           pressure, Pabd) and an intermittent urinary stream during micturition pressure-flow
           studies

           Specific Aim 2: To assess whether urethral anesthesia gel improves discomfort during the
           UDS Hypothesis: Visual Analog Scale (VAS) scores for pain will be lower during the UDS
           when the urethra has been anesthetized

           Studies supporting Specific Aims:

           i. Micturition with Urethral Anesthesia Distension and fluid flow in the urethra has
           been previously demonstrated to evoke sensory nerve discharge. Nerve firing originating
           from the urethra is then able to initiate contractions in the filling bladder and
           increase the amplitude and duration of ongoing bladder contractions. This
           pudendal-bladder reflex has been shown to be necessary for efficient bladder emptying
           because disruption to urethral sensory feedback by transection of the sensory branch of
           the pudendal nerve or intraurethral anesthesia reduces voiding efficiency in the rat.
           Urethral anesthesia in humans has also been demonstrated to increase post void residual
           and alter symptoms experienced during the voiding phase.

           This investigator's approach is novel as this study will characterize voiding in healthy
           women who will be randomized to placebo versus urethral analgesia. Investigators will do
           this by performing UDS, which will include all clinical tests for bladder function, with
           or without urethral anesthesia (2% lidocaine hydrochloride jelly or plain aqueous gel).

           ii. Pain Perception During Catheterization Urethral catheterization elicits mild to
           moderate pain in women. The use of lubricant anesthetic on the catheter is one available
           option to manage tissue trauma and pain perception. Several studies have reported that
           2% lidocaine gel reduces procedural pain during female urethral catheterization. Others
           however, have found that lubricant anesthetic and catheter size, does not effect the
           perception of pain in urethral catheterization in women. These discrepant reports
           suggest a consensus has not been reached on the efficacy of lubricant anesthetic and
           pain perception in women.

        4. Subject Recruitment: Subjects will be recruited from Duke Hospital and Duke University
           Campus via newspaper advertisements and paper fliers.

        5. Design and Procedures To account for screen failures, it is anticipated that a total of
           40 female controls will be screened to achieve n=20 for completed UDS. Subjects will
           perform a baseline voiding test (uroflow), then will be randomized to undergoing
           urodynamic studies with or without urethral analgesia. Participants will be randomized
           to their arm of the study using a random number generator (MatLab). Study staff and the
           subjects will be blinded to the treatment regimen; thus, this study design is a
           randomized double-blind placebo-controlled trial. Inclusion and exclusion criteria are
           listed in a separate section.

      Study Visit Questionnaires and Tests After their phone screen, (3.i), participants will be
      scheduled for the study visit. All study procedures will take place at the Duke Urogynecology
      Office at Patterson Place. Participants will undergo informed consent on arrival to their
      study visit. Subjects will provide a urine specimen for a point of care urinalysis and
      pregnancy test. Pre-procedure vital signs, including height and weight will be obtained.
      Subjects will fill out the following questionnaires: Lower Urinary Tract Symptoms Tool,
      Sociodemographics and Functional Comorbidity Index and complete a Medication List.

      If subjects have a negative urinalysis and pregnancy test they will be randomized. If either
      of their point of care tests is positive (per exclusion criteria), they will be excluded from
      the study and referred to their primary care physician.

      Prior to performing UDS, the subject's bladder will be scanned transabdominally with a
      standard clinic bladder scanner. This will ensure adequate urine is within the bladder to
      start the first test.

      The participant will then be placed in the dorsal lithotomy position and a pelvic exam will
      be performed to confirm no pelvic organ prolapse past the hymen during valsalva. Uroflow
      testing will then begin. Subjects will then undergo a 2-hour wait and be given water to
      re-fill their bladder. After two hours, Urodynamic testing will be performed.

      Order of Studies Performed During Urodynamic Testing: Complex Uroflowmetry, Complex
      Cystometry, Urethral Pressure Profilometry, Micturition Pressure-flow Study

      The Visual Analog Scale (VAS) will be administered to assess discomfort at the following
      times; after uroflow but before PVR (baseline), immediately after the urethral catheter is
      placed, after 100mL of fluid has been instilled, and at full bladder capacity (MCC).

      After the completion of the UDS procedures, subjects will have completed their study visit.
    

Intervention name(s): lidocaine gel; Plain aqueous gel
Intervention type(s): Drug; Other
Other intervention name(s): Urojet 2% gel; KY gel
Intervention MeSH terms: Lidocaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: voiding efficiency; detrusor underactivity; urodynamics