Hypothesis / aims of study
Among adverse effects of intradetrusor onabotulinumtoxinA (BTX-A) injections is an increased risk of elevated post-void residual (PVR), which may require postoperative clean intermittent catheterization (CIC).
Predicting possible factors associated with CIC could improve treatment decision-making and counseling of women undergoing BTX-A treatment. In this study, we aimed to evaluate the CIC rate in a clinically representative cohort of women undergoing their first BTX-A treatment and to investigate factors predictive of initiating CIC.
Study design, materials and methods
This was a retrospective cohort of Danish women, who had their first BTX-A treatment due to overactive bladder (OAB) syndrome between January 2015 and October 2022. We included women both with and without urgency urinary incontinence (UUI), who had pretreatment urodynamic studies (UDS).To identify predictive factors of CIC, the following data were reviewed in the electronic medical record: Demographics, medical and gynecological history, UDS, pretreatment bladder diary, uroflowmetry, objective examinations, information on BTX-A treatments, and information on PVR reporting. Botox® Allergan 100 International Units were injected in the detrusor at 10-20 sites. Statistical analyses included univariate and multivariate logistic regression analyses, examining the odds of CIC. Wilcoxon rank sum test, Pearson’s Chi-squared test, and Fisher’s Exact test were used to compare the differences between variables in the outcome groups.
Results
We included 397 women who had pretreatment UDS in the analysis. Overall median age at first BTX-A treatment was 68 (Q1-Q3: 54-76) years. The CIC rate was 8.6% (n=34) following the first BTX-A treatment. Baseline demographics and characteristics did not differ significantly between the CIC group and the non-CIC group. Median time interval between the first BTX-A treatment and PVR diagnosis was 13.5 days (Q1-Q3: 6.8-21.3). In the CIC group, 16 (47.1%) had a PVR exceeding 300 mL, 10 (29.4%) had a PVR between 200 and 299 mL, and 7 (20.6%) had a PVR<200 mL. One woman had no PVR documented in the medical record. CIC duration was eight weeks or more for 16 (47.1%) of the women, 5 (14.7%) performed CIC for four to eight weeks, and 7 (20.6%) for less than four weeks. CIC duration was not documented in the medical records for six women (17.6%).
Women with a urogynecological history of UUI had a 70% reduced risk of undergoing CIC (OR 0.30, 95% CI: 0.09-0.97). Previous urogynecological surgeries, including anterior colporrhaphy and midurethral sling (MUS) increased the likelihood of CIC (anterior colporrhaphy: OR 3.86, 95% CI: 1.65-8.99; MUS: OR 2.75, 95% CI: 1.20-6.29).
In pretreatment UDS, the CIC group had significantly higher median maximum cystometric capacity (MCC), compared to the non-CIC group (350 mL (Q1-Q3: 253-441.5) vs 290 mL (Q1-Q3: 174-400), p=0.017). PVR was not associated with a significant risk of CIC, neither when calculated as a continuous variable (OR 1.00, 95% CI: 1.00-1.00) or as a categorical variable higher than 100 mL (OR 1.53, 95% CI:0.75-3.13).
In a multivariate logistic regression analysis, previous anterior colporrhaphy (OR 3.71, 95% CI:1.52-9.06), and 10 mL increment in MCC (OR 1.03, 95% CI: 1.00-1.06) were identified as predictive factors of CIC, while UUI was a protective factor against CIC (OR 0.23, 95% CI:0.07-0.79). The association between MUS and CIC became statistically insignificant in the multivariate analysis, although there was a trend indicating an increased risk of CIC. In the pretreatment bladder diaries, a bladder capacity of 500 mL or more increased the risk of CIC more than two times (OR 2.46, 95% CI: 1.06-5.70). Reported leakages in the bladder diary were associated with a 64% reduction in the risk of CIC (OR 0.36, 95% CI: 0.17-0.77).
Interpretation of results
CIC rates of up to 48% following the first BTX-A treatment have been reported in the literature, compared to 8.6% in our study. In our clinic, we do not routinely schedule post-operative follow-ups for all women unless the healthcare provider assesses a potential risk. Furthermore, our criteria for initiating CIC were based on larger posttreatment PVRs, as our clinical guideline defines PVR requiring CIC as PVR>200 mL with clinical symptoms or PVR> 350 ml without symptoms. Our criteria for initiating CIC are more conservative than many previous studies, which could explain a lower CIC rate in our cohort. We found a significant association between previous anterior colporrhaphy and an increased risk of CIC, which was confirmed in a multivariate analysis. Urinary retention is a well-known, transient postoperative adverse effect following anterior colporrhaphy, but was not previously identified as a risk factor for CIC in women undergoing BTX-A treatment. Similarly, we found a two-fold increased risk of CIC in women who had undergone MUS in the univariate analysis, which is supported by studies that found an association between a history of previous anti-incontinence procedures for stress urinary incontinence and urinary retention following BTX-A treatment. These findings provide new and valuable information that can improve counseling on BTX-A treatment, as anterior colporrhaphy and MUS are commonly performed urogynecological procedures. From pretreatment UDS, we confirm an association between MCC and an increased risk of CIC, as reported in the literature. We could not confirm an association between PVR and CIC. An increased pretreatment PVR is a well-known risk factor for posttreatment PVR requiring CIC. The absence of a significant association between pretreatment PVR and posttreatment CIC in our study is likely to be explained by low pretreatment PVR measurements. All included women had a pretreatment PVR lower than 100 mL, emphasizing that we do a careful assessment before referring our patients to BTX-A treatment.
Bladder diary variables revealed that bladder capacity >500 mL and lack of leakages were associated with an increased risk of CIC, which was in alignment with findings from the UDS.