Hypothesis / aims of study
Botulinum toxin A (BoNT-A) improves overactive bladder (OAB) by inhibiting the release of acetylcholine at the neuromuscular junction, thus causing a temporary paralysis. The effects are reversible, hence repeat injections are usually required.
There is paucity of data in the literature regarding the effectiveness, and acceptability of BoNT-A with flexible cystoscopy under local anaesthetic in women with idiopathic OAB.
The objective of this study was to evaluate the effectiveness, safety and acceptability of nurse-delivered intradetrusor botulinum toxin A (BoNT-A) injections for the treatment of refractory female idiopathic OAB within the outpatient setting using a flexible cystoscope under local anaesthetic.
Study design, materials and methods
Prospective cohort study of 41 consecutive women with idiopathic OAB who had not responded to treatment with at least two antimuscarinics and bladder training, and who had urodynamic confirmation of the diagnosis.
At enrolment, participants completed the electronic Patient Assessment Questionnaire (ePAQ) and a 3-day bladder diary.
They received 200 IU of BoNT-A injected into the bladder in 20 injection sites, avoiding the trigone, using a flexible cystoscope (Storz flexible video-urethroscope, 6.5 F; needle Laborie DIS201 inje TAK adjustable tip needle, 4.8F, 23G) under local anaesthesia (11 ml gel of Lidocaine hydrochloride 2% with Chlorhexidine gluconate 0.05% - Instillagel), which was administered into the urethra prior to cystoscopy.
After treatment, each participant completed a pain visual analogue scale (VAS) and a patient satisfaction questionnaire. Two weeks after treatment they had an assessment of voiding with uroflowmetry and post-void residual (PVR) measurement. Follow up was carried out at 6 months. The post-operative evaluation included completion of the ePAQ questionnaire, a 3-day bladder diary and requirement of CISC.
The primary outcome was change in OAB symptoms as determined by the scores in the OAB item on the urinary domain of the ePAQ questionnaire.
The secondary outcomes included rate of voiding dysfunction, determined by the need to self-catheterise at 6 months; tolerability, determined by a pain visual analogue scale (VAS); changes in the 3-day bladder diary and patient satisfaction.
Changes in the primary outcome (scores in the OAB domain of the ePAQ questionnaire) over time were assessed descriptively (means, median, standard deviations etc.) and inferentially using the paired sample t-test or Wilcoxon signed rank test depending on the distribution of the data.
An a priori power analysis indicated that complete records on a minimum of n = 35 women would be needed in order to obtain 80 percent power (beta = 0.20) in a two-sided test using standard levels of nominal significance (alpha = 0.05) assuming a medium effect size (Cohen's d = 0.5). Forty women were planned to be recruited to allow for a 15% drop out rate.
Results
41 women completed the study. The mean age was 53.4 years (SD 10.6, range 33-81). The mean body mass index (BMI) was 31.56 kg/m2 (SD 6.19, range 22-44).
There was a statistically significant reduction in the ePAQ OAB score after treatment [median (IQR), pre 58 (25); post 33 (45) P<0.001].
The rate of voiding dysfunction following treatment, as determined by the need for CISC at 6 months, based on a post-void residual greater than 100 ml, was 24.3% (10/41).
Bladder diary data showed a slight non-significant reduction in urinary frequency [median (IQR), pre 10 (5); post 8 (4)]; as well as an increase in the voided volume (ml) [average (SD), pre 166 (64); post 228 (100) P=0.01] and post-void residual (ml) [average (SD), pre 48 (63); post 116 (130) P=0.02].
The procedure was well tolerated [median (IQR) VAS 4.5 (4)]. Only 7 participants scored the pain at 6 or more.
Participants completed an un-validated patient satisfaction questionnaire at the end of the study. All participants would have the procedure again; and 40/41 (98%) reported that they would recommend the procedure to a friend.
Interpretation of results
This is the first study that reports on the effectiveness and tolerability of a nurse-delivered service of BoNT-A injections for the treatment of female idiopathic OAB in an ambulatory setting using local anaesthetic.
The results show that such a service is effective, well tolerated and acceptable to women.
The effectiveness of BoNT-A in OAB has been previously determined [1]. However many studies have used various types of anaesthetic (within the same study) including none, local anaesthetic, sedation or general anaesthetic; and have used either rigid or flexible cystoscopy accordingly; most included participants with neurogenic bladder, and left the decision as to whether any anaesthetic was required to the treating clinician, based on the degree of bladder sensation for each participant.
Previous studies that have used only flexible cystoscopy under local anaesthetic included either participants with neurogenic bladder exclusively or a mixture of participants with idiopathic and neurogenic bladder.
To our knowledge, the only other study focusing on women with idiopathic OAB, that used local anaesthetic and flexible cystoscopy, was stopped early due to a higher than expected rate of large post-void residual and urinary tract infections [2].
There is no agreement in the literature with regards to the definition of voiding dysfunction. Some studies define it as a PVR of 50 ml, some use 100 ml, and some define it as a PVR greater than 50% of the voided volume. In our unit, we use 100 ml as the cut off for recommending that women do CISC, and this was the criteria used for the study. The rate of voiding dysfunction is in keeping with that reported in the literature.
We chose to use ePAQ for the study, as this is the questionnaire routinely used in clinical practice in our unit. To our knowledge, the minimally important difference (MID) for ePAQ has not been determined, and is therefore unclear as yet whether the statistical significance found in this study translates clinically.