Urodynamic and Frequency-Volume Chart Parameters Influencing Anticholinergic Resistance in Patients With Neurogenic Detrusor Overactivity

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Int Neurourol J. 2024;28(3):232-238

Publication date (electronic) : 2024 September 30

doi : https://doi.org/10.5213/inj.2448310.155

Ilker Akarken, Huseyin Tarhan, Hayrettin Sahin

Department of Urology, School of Medicine, Mugla Sitki Kocman University, Mugla, Turkey

Corresponding author: Huseyin Tarhan Department of Urology, School of Medicine, Mugla Sitki Kocman University, Kotekli Mahallesi Marmaris Yolu Bulvari No: 50, Mentese/Mugla 48000, Turkiye Email: drhuseyintarhan@gmail.com

Received 2024 August 2; Accepted 2024 August 26.

Abstract

INTRODUCTION

Neurogenic detrusor overactivity (NDOA) is characterized by involuntary detrusor muscle contractions during the filling phase of a urodynamic study. These contractions may occur spontaneously or be provoked and are commonly associated with neurological conditions. The heterogeneity of NDOA is attributed to the range of underlying neurological disorders, including Parkinson disease, cerebral palsy, multiple sclerosis, spinal cord injury, and meningomyelocele [1]. Patients with NDOA often experience symptoms such as increased urinary frequency, urgency, and urge incontinence, which may or may not accompany urgency. Furthermore, elevated intravesical pressures during bladder filling and/or the presence of vesicoureteral reflux can cause severe renal impairment in individuals with NDOA.

The primary objectives of the treatment of NDOA include the preservation of the upper urinary tract, correction of urinary incontinence (UI), restoration of lower urinary tract function, and improvement of quality of life [2]. Conservative treatment options for NDOA encompass intermittent self-catheterization and pharmacological interventions such as anticholinergic drugs, phosphodiesterase inhibitors, vanilloids, and intravesical therapies with agents like capsaicin or resiniferatoxin [3]. Anticholinergic therapy is the cornerstone of conservative treatment for patients with NDOA. These drugs block muscarinic receptors, thus regulating parasympathetic stimulation and reducing detrusor overactivity (DOA). Consequently, bladder compliance improves, and the symptoms of DOA are alleviated. The anticholinergic medications commonly employed in the management of NDOA include flavoxate, oxybutynin, propantheline, propiverine, tolterodine, trospium, solifenacin, darifenacin, and fesoterodine. These drugs effectively target the pathophysiological mechanisms of NDOA, helping to relieve symptoms [3].

No common terminology has yet been established to assess the response to antimuscarinic therapy in NDOA, and neither the American Urological Association nor the European Association of Urology provide specific criteria for evaluating treatment outcomes in refractory cases of idiopathic DOA and NDOA [4]. Depending on the study, treatment success for episodes of urgency urinary incontinence (UUI) has been defined as a reduction of 50% to 100% from pretreatment levels. Treatment nonresponse has been described as experiencing ≥8 voids in 24 hours with ≥1 urgency episode or as having ≥8 voids in 24 hours with 3 urgency episodes. These criteria are used to assess the effectiveness of treatment and the management of refractory cases in clinical research [5].

objective of our study was to compare the percentage changes in urodynamic findings and frequency-volume chart data from before to after treatment in patients with NDOA who responded to anticholinergics versus those who did not. We aimed to identify specific urodynamic and frequency-volume chart parameters that may influence treatment outcomes. Through this analysis, we hoped to identify factors that could predict the success or failure of anticholinergic treatment in patients with NDOA.

MATERIALS AND METHODS

We retrospectively reviewed the cases of 362 patients who presented with lower urinary tract symptoms and had a history of neurological disease, all of whom required urodynamic evaluation at the urology clinic. After informed consent was obtained, the medical records and urodynamic reports of these patients were evaluated. Patients were excluded from the analysis if they were found to be acontractile on urodynamic testing and had initiated clean intermittent catheterization (CIC); had indwelling catheters, acute urinary tract infections (UTIs), previous urological surgery, or prior treatment; or if their initial urodynamic evaluation was performed at another center. Ultimately, 85 patients with a confirmed diagnosis of NDOA who initiated anticholinergic therapy were included in the study. These patients received an initial urodynamic evaluation and received treatment at our clinic. We retrospectively reviewed the 3-day frequency-volume charts and urodynamic results of all patients.

Prior to the urodynamic study, urine cultures were obtained from all patients to screen for UTIs. Patients diagnosed with UTIs received appropriate antibiotic therapy. Urodynamic evaluations were then performed on those patients who had negative follow-up urine cultures after completing antibiotic treatment.

Urodynamic studies were conducted using the same equipment (Solar Blue; Laborie/Medical Measurement Systems B.V., Enschede, The Netherlands) for all patients. Prior to the urodynamic study, a catheter-based assessment of postvoid residual (PVR) urine volume was performed. For urodynamic testing, an 8F, 2-way air-filled catheter was inserted transurethrally, while an 8F air-filled rectal catheter was placed rectally. The infusion of isotonic fluid commenced at a rate of 20–30 mL/min. Intravesical pressure was measured through the urethral catheter, while intra-abdominal pressure was gauged using the rectal catheter. Detrusor pressure was calculated automatically by subtracting the intra-abdominal pressure from the intravesical pressure.

NDOA was defined as the presence of involuntary detrusor contractions during the filling phase of urodynamic testing. Following the International Continence Society 2020 algorithm for UI in neurological patients, CIC was not initiated in patients with a PVR urine volume of less than 50 mL. All patients diagnosed with NDOA were initiated on a 12-week course of anticholinergic therapy. Those who exhibited a clinical and urodynamic response to therapy were categorized as group R (responders), while those who did not respond were classified as group NR (nonresponders).

During the evaluation of urodynamic findings, specifically the pressure-flow study, we assessed various parameters. These included maximum cystometric capacity (MCC, the highest volume achieved during the urodynamic test), and the volume at the first desire to void (FDV). We also measured the frequency of NDOA, the capacity at the first involuntary detrusor contraction (FIC), the amplitude of NDOA, and bladder compliance, with a value less than 20 mL/cm H2O indicating low compliance. Additionally, we evaluated the maximum detrusor pressure, the maximum flow rate (Qmax), and the detrusor pressure at maximum flow (Pdet-Qmax). During urodynamic testing, the fluid instillation was stopped if the patient did not report a sensation of bladder fullness, if UI occurred, or if the detrusor pressure rose above 60 cm H2O. The volume at which instillation was halted was then documented as both the MCC and the FDV.

Frequency-volume charts, completed by patients before and after 12 weeks of anticholinergic therapy, were analyzed for parameters including daytime and nighttime urination frequency, episodes of urgency, frequency of pad changes, and maximum voided volumes.

In our study, treatment failure was defined as the presence of any of the following on the 24-hour frequency-volume chart: 8 or more voiding episodes, 3 or more episodes of urgency, or a reduction in UUI episodes of less than 50% [5].

The paired samples t-test was utilized to compare pretreatment and posttreatment values within the same group. For comparisons of continuous variables between groups, the independent samples t-test was employed. Logistic regression analysis was conducted to identify factors that could influence treatment outcomes, with the results presented as odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were 2-tailed, and a P-value of less than 0.05 was considered to indicate statistical significance. Statistical analyses were performed using IBM SPSS Statistics ver. 24.0 (IBM Co., Armonk, NY, USA).

RESULTS

Initially, a total of 85 patients were included in the study. However, 12 patients (14.1%) opted out of taking the medications, and 6 patients (7.05%) were lost to follow-up, necessitating their exclusion from the study. This resulted in a final sample size of 67 patients, with their characteristics detailed in Fig. 1. Among the 67 participants, 22 were male and 45 were female, and the mean age was 49.1±16.3 years. Of the patients, 38 (56.7%) were categorized as belonging to group R, while the remaining 29 (43.3%) were considered group NR.

Fig. 1.

Distribution of neurological diseases among the cases.

The urodynamic parameter values and frequency-volume chart measurements before and after treatment for the groups are presented in Table 1.

Table 1.

Pre- and posttreatment measurements of urodynamic parameters and frequency-volume chart data

Upon comparing the changes in urodynamic parameters and frequency-volume chart measurements between group R and group NR, no significant changes were observed in group R for bladder capacity at first involuntary contraction (BIC-FIC, P=0.051), maximum detrusor pressure (P=0.147), Qmax (P=0.496), Pdet-Qmax (P=0.680), PVR urine volume (P=0.093), and urgency episodes per 24 hours (P=0.079). Similarly, in group NR, no significant differences were found in the frequency of NDOA (P=0.456), BIC-FIC (P=0.069), bladder compliance (P=0.272), Qmax (P=0.545), Pdet-Qmax (P=0.752), PVR urine volume (P=0.214), daytime voids (P=0.103), nighttime voids (P=0.326), urgency episodes per 24 hours (P=0.055), and maximum voided volume (P=0.54) (Table 1). When comparing percentage changes between pre- and posttreatment values within groups, no significant differences were observed in BC-FIC (P=0.275), maximum detrusor pressure (P=0.884), Qmax (P=0.748), Pdet-Qmax (P=0.927), PVR urine volume (P=0.064), pad changes (P=0.761), urgency episodes (P=0.165), and voided volume (P=0.676 ) (Table 2).

Table 2.

Comparison of pre- to posttreatment percentage changes in urodynamic parameters and frequency-volume chart measurements between groups

To identify factors influencing treatment failure, changes in urodynamic parameters and frequency-volume chart measurements from pre- to posttreatment were evaluated using univariate analysis. Significant changes were observed in UUI episodes per 24 hours (P=0.001), MCC (mL, P=0.003), frequency of NDOA (P=0.004), and bladder compliance (mL/cm H2O, P=0.003) (Table 3).

Table 3.

Results of univariate and multivariate logistic regression analyses

Upon conducting multivariate analysis on the parameters that demonstrated significance in the univariate analysis, significant findings were observed for the frequency of NDOA (P=0.014) and UUI episodes per 24 hours (P=0.002) (Table 3). These parameters were identified as factors influencing treatment failure.

DISCUSSION

The primary concern for patients with NDOA is UI, resulting from sudden bladder contractions. The goal of treatment in neurogenic bladder dysfunction is to restore continence and to normalize low urinary tract pressures [6]. Approximately 71.5% of these patients use 1 or more anticholinergic drugs over the course of a year [7]. Adherence to treatment within the first year stands at 68% for individuals with NDOA, in contrast to 42% for those with idiopathic DOA. This suggests a higher rate of treatment compliance among patients with NDOA [8].

The response to anticholinergic treatment is characterized by decreases in urinary frequency, urgency episodes, and incontinence episodes, as recorded in a bladder diary. Urodynamic results are assessed using parameters that include MCC, volume at the first detrusor contraction, maximum detrusor pressure, compliance, frequency of detrusor contractions, and residual volume [2]. In our study, we assessed comparable parameters in both the voiding diary and the urodynamic measurements.

Limited research has evaluated the lack of response to NDOA treatment. Many studies have reported on the outcomes of sacral neuromodulation and botulinum toxin application in patients who do not respond to treatment. As previously mentioned, the term “refractory” lacks a consensus definition. A major challenge in assessing treatment success is the heterogeneity of the patient group, which can be attributed to various etiological factors such as multiple sclerosis, Parkinson disease, spinal cord injury, cerebral palsy, and meningomyelocele [1]. Ginsberg et al. [9] found that 76.1% of the patients in their study discontinued treatment due to a lack of response. Nonresponse to treatment has been characterized as experiencing ≥8 voids in 24 hours, ≥1 urgency episode in 24 hours, or both ≥8 voids in 24 hours and 3 urgency episodes [5]. In our study, we defined nonresponse as either ≥8 voids in 24 hours, ≥3 urgency episodes, or less than a 50% reduction in UUI episodes [5].

When comparing the percentage changes in parameters between the 2 groups, we observed significant differences in voids per day (P=0.044) and UUI episodes per 24 hours (P=0.001) but no significant difference in urgency episodes per 24 hours (P=0.165). The change in the number of urgency episodes was not significant in either group R (P=0.079) or group NR (P=0.055).

Most studies have focused on the outcomes of sacral neuromodulation and botulinum toxin treatments in patients with refractory NDOA. Consequently, we encountered a significant limitation, as no comparable study was available that aligned with our study design.

The DIGNITY study, a double-blind prospective randomized study, included 691 patients who were using 1 or more anticholinergics and had 14 or more UI episodes per week [10]. When comparing their baseline values with those of our study, the average number of UI episodes per week in their study was 31.9, the average MCC was 251.85 mL, the Pdet-Qmax was 49.4 cm H2O, the average volume at which involuntary detrusor contractions occurred was 206.85 mL, and the average detrusor compliance was 59.95 mL/cm H2O. In our study, examining the posttreatment parameters of patients who did not respond to anticholinergics, we found that the MCC was 278.07±74.5 mL, the Pdet-Qmax was 38.28±12.6 cm H2O, the BIC-FIC volume was 192.06±6.9 mL, and bladder compliance was 36.48±4.77 mL/cm H2O. In both studies, the patients experienced more than 14 UI episodes per week. The absence of a significant percentage change in UI episodes and DOA frequency during urodynamics may impact the success of treatment.

In a study evaluating the efficacy of propiverine and oxybutynin in patients with NDOA, the initial MCC was 122 mL for the propiverine group and 134 mL for the oxybutynin group, representing a significant difference. The maximum detrusor pressure decreased significantly, changing by -19 cm H2O in the propiverine group and -25.6 cm H2O in the oxybutynin group. Similarly, a significant improvement in detrusor compliance was observed for both groups. In our study, significant changes in MCC and bladder compliance were observed between the 2 groups, but no significant change in maximum detrusor pressure was found. In the frequency-volume chart, a reduction in the 24-hour frequency was noted as 2.9±2.9 for the propiverine group and 2.5±3.3 for the oxybutynin group. We observed a significant percentage change in daily voiding frequency, with a mean difference of 8.48 (P=0.044). Regarding incontinence episodes, the propiverine group experienced a significant reduction of -1.6±2.3, while the oxybutynin group displayed a significant reduction of -1.3±2.0. The maximum voided volume increased by 27±55 mL in the propiverine group and 37±72 mL in the oxybutynin group [11]. Our study also revealed a significant percentage change in UUI episodes of 15.91 and a significant percentage change of 50.58 in maximum voided volume. Through an analysis conducted to identify factors influencing treatment failure, we determined that the change in UUI episodes was a significant factor (P=0.002; 95% CI, 1.022– 1.098).

Amend et al. [6] evaluated the response to high-dose combination anticholinergic therapy in patients who were unresponsive to double-dose monotherapy. Their evaluation revealed no significant improvement in detrusor compliance or reduction in incontinence episodes. However, they did observe significant increases in bladder capacity and reflex volume. In our study, when comparing the percentage changes between anticholinergic responders and nonresponders, we observed significant differences in detrusor compliance, incontinence episodes, and bladder capacity. However, we found no significant disparity in reflex volume (BIC-FC).

Harding et al. [12] conducted a study involving patients with an average age of 50 years who presented with lower urinary tract symptoms. Their findings indicated that low bladder compliance was not a predictor of DOA based on urodynamic studies. Notably, their research did not focus specifically on patients with neurogenic disorders. In our study, we identified the frequency of NDOA and UUI episodes per 24 hours as factors influencing the lack of response to anticholinergic treatment.

The limitations of our study include the absence of a prospective design and a small sample size. Nevertheless, we believe that the insights gained from this sample will lay the groundwork for future prospective studies.

In conclusion, NDOA is a condition with heterogeneous characteristics resulting from a variety of neurological conditions. Our study identified episodes of UUI and the frequency of NDOA in urodynamic measurements as factors influencing the lack of response to anticholinergic therapy, which is a firstline treatment. Our research may serve as a foundation for establishing predictive criteria for the success of anticholinergic treatment through prospective studies involving larger patient populations.

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