INTRODUCTION
The pathophysiology of increased postvoid residual (PVR) volume is not well understood because the interactions between the bladder outlet resistance and the strength of the detrusor contractions are complex [1]. In men, the detrusor contraction strength (DCS) indexes predict better an increased PVR volume when compared to bladder outlet obstruction (BOO) indexes, and the relative bladder outlet resistance (defined as the ration between a BOO index and a DCS index) have an even higher predictive capacity [2]. However, due to the anatomic differences between men and women, their voiding dynamics differ significantly, and the diagnostic criteria developed for men are inappropriate for use in women [3].
It is necessary to keep in mind some additional considerations such as when women void with abdominal straining, defined by a raise in abdominal pressure during voiding over the premicturition baseline. It has been reported that voluntary abdominal straining increases the free maximum flow rate (Qmax) by an average of 30% in healthy women [4]. This increase in urinary flow rate is not due to greater DCS, but rather to the energy supplied by the abdominal muscles, and its effect is difficult to integrate into any urodynamic model of voiding function [5]. This is why important previous studies that evaluate the voiding phase in women have been concerned with this aspect, either asking patients to urinate without abdominal strain [6] or excluding those patients with increased abdominal pressure during voiding [7]. Moreover, it has been proposed that women with stress urinary incontinence (SUI) have lower urethral resistance [8], which would explain why they urinate at higher urinary flows and lower detrusor pressures than asymptomatic women [9]. On the other hand, younger women or those who are premenopausal generate higher detrusor pressures during voiding [10, 11].
Few investigations have compared the urodynamic [12] characteristics of women with and without increased PVR volume. However, we are not aware of studies addressing the association among PVR volume, BOO and DCS parameters in women, which could behave differently compared to men.
The aims of this study were: (1) to compare voiding parameters in women with and without increased PVR volume, (2) to correlate these parameters with PVR volume and PVR percentage and (3) to describe their ability to predict increased PVR volume. As this is a study focused on the pathophysiology of increased PVR volume, we did not consider any other clinical information. To our knowledge, this is the first study to address this matter.
MATERIALS AND METHODS
This is a retrospective cross-sectional study of urodynamics data prospectively acquired from consecutive symptomatic women in a university reference center between January 2015 and December 2019. These patients were screened and those with diseases affecting the spinal cord (traumatic spinal cord injuries, multiple sclerosis, transverse myelitis, spina bifida) were excluded. The information was entered into an electronic database when the clinical evaluation and urodynamics were conducted in accordance with the definitions and recommendations of the International Continence Society (ICS) and the International Urogynecological Association (IUGA) [13–15]. All patients provided written informed consent at the time of the urodynamic study, and the project was approved by the institutional Scientific Ethics Committee to guarantee the confidentiality of the data.
First, a noninvasive uroflowmetry was performed in private and the PVR volume was measured by catheterization (it was repeated in patients presenting a free or intubated Qmax ≤12 mL/sec or voided volume<150 mL). Then, a filling cystometry was performed interactively. A double lumen 6F urethra-vesical catheter was used for bladder filling and intravesical pressure measurement, and a rectal 8F punctured balloon catheter was used to measure abdominal pressure. External pressure transducers were placed at the level of the upper edge of the pubic symphysis and the system was zeroed to atmospheric pressure. Room temperature 0.9% saline solution was infused at a rate of 70 mL/min. Pressure transmission was evaluated with coughs at the beginning and end of each testing, every 1 minute throughout the study, and before and after each major event, to correct artifacts immediately; this was the only method used to provoke detrusor overactivity. The stress test was conducted in a standardized and stepped manner, with the use of progressively increasing cough intensity, following successive stages in case urodynamic SUI was not demonstrated: (1) with 300 mL infused in the sitting position, (2) with 300 mL infused in standing position, and (3) at maximum cystometric capacity in standing position (with the corresponding height change of the transducers). In patients with a maximum cystometric capacity less than 300 mL, it was generally evaluated in the sitting and standing position. An attempt was made to obtain 3 abdominal leak point pressure values with cough, with the lowest value being considered. The pressure-flow study was carried out in private. Finally, PVR was measured through the urethro-vesical catheter immediately after voiding.
Of the 858 women that were screened during this period, 32 were excluded for having diseases affecting the spinal cord and 339 due to abdominal straining during voiding (defined as an elevation of abdominal pressure ≥10 cm H2O above premicturition baseline at time Qmax) [7, 10], leaving 487 patients for the analysis (59%). In this group we identified 70 women with increased PVR volume (≥50 mL) both in the free uroflowmetry and pressure-flow study. This cutoff value could be regarded as important, according to a dedicated working group of the ICS Urodynamics Committee [16]. Fifteen patients were excluded due to discrepancy of Qmax between free uroflowmetry and pressure-flow study (Qmax of more than 10 mL/sec higher in the free uroflowmetry than in the pressure-flow study, arbitrarily), leaving 55 women for the analysis (cases). A number was assigned to these patients after sorting them alphabetically and they were matched with the same number of patients without increased PVR volume, controlling by age, presence of urodynamic SUI and premicturition bladder volume (as the potential power of the detrusor increases with higher bladder volumes, such that with the same detrusor pressure a greater urinary flow is possible) [17], without considering any of their voiding parameters (controls). Controls were selected first by presence or absence of urodynamic SUI, then by age±3 years and finally by the closer premicturition bladder volume (Fig. 1). None of these patients were taking medications that were active on the lower urinary tract at the time of the urodynamic study.
The following urodynamic parameters were considered: presence of urodynamic SUI, detrusor overactivity and bladder compliance, premicturition bladder volume, voided volume, PVR volume, PVR percentage ([PVR volume/premicturition bladder volume]×100), opening detrusor pressure, Qmax, detrusor pressure at maximum flow (PdetQmax), and maximum detrusor pressure. The following simple voiding indexes were calculated: 2 BOO indexes (female BOO index, female-BOOI: PdetQmax – 2.2 Qmax; urethral resistance, UR: PdetQmax/Qmax2) [18, 19], one DCS index (projected isovolumetric pressure 1, PIP1: PdetQmax+Qmax) [6, 20], and 2 “relative BOO” indexes (female-BOOI/PIP1 and UR/PIP1).
Student t-test or Wilcoxon rank-sum test (quantitative variables) were used to compare voiding parameters in women with and without increased PVR volume. For the evaluation of the qualitative variables, the chi-square test or Fisher exact test was applied. Linear regression analysis was applied to correlate simple voiding indices with PVR volume and PVR percentage. The area under the curve (AUC) of the receiver operating characteristic (ROC) analysis was calculated to describe diagnostic accuracy of these indexes for increased PVR volume. The AUC were compared using the test of equality of ROC curves with Bonferroni adjustment of P-values. Statistical analysis was processed with Stata 18 (StataCorp LLC, College Station, TX, USA) and statistical significance was defined as 2-sided P-value <0.05.
RESULTS
One-hundred ten women aged 65.9±13.7 (range, 20–87) years were analyzed. Only 4 patients had neurological diseases potentially affecting the lower urinary tract: 4 previous cerebrovascular accidents (2 in each group, at least 6 years before). Table 1 shows the comparison of the urodynamic characteristics between women with and without increased PVR volume. Bladder compliance was significantly lower in patients with increased PVR volume, but only 1 woman had a compliance less than 12.5 mL/cm H2O (from the increased PVR volume group). All voiding parameters were significantly different between women with and without increased PVR volume, except for PIP1. Thirty-eight women had PVR volume ≥100 mL, 20 women had PVR volume ≥150 mL, and only 8 women had PVR volume ≥200 mL.
The correlations between simple voiding indexes and PVR volume and PVR percentage using linear regression analysis are shown in Table 2. The best correlation was found using female-BOOI, however, this being small. PIP1 did not correlate with PVR volume or PVR percentage, and “relative BOO” indexes did not improve the correlations.
DISCUSSION
Justification of the Parameters Used
This study evaluated female voiding using simple parameters. Both female-BOOI and PIP1 are well accepted indexes for the evaluation of female voiding function, but not UR [20]. Solomon et al. [18] plotted PdetQmax values against the corresponding Qmax values and used cluster analysis to determine the one-axis equation that best divided radiographically obstructed and unobstructed patients according to the video-urodynamic criteria of Nitti et al. [21]. They subsequently used this approach to determine a flow-pressure relationship above which BOO is likely to exist, proposing the female-BOOI. UR tests have the main objective of quantifying the loss of pressure (=energy) caused by resistance to the bladder outlet, but they have the problem of considering the bladder outlet as a rigid tube [19]. Although it stopped being used some time ago [22], we thought it was appropriate to include it due to the ease of its calculation. PIP1 corresponds to a projected isovolumetric pressure using bladder output relation curves simplified by straight lines with a fixed slope of 1 cm H2O/mL per second (instead of 5 cm H2O/mL per second of the Schäfer nomogram in men), described by Tan et al. [6]. Although this method was described in elderly women with urgency incontinence, to our knowledge it is the only parameter that has been successfully compared to the detrusor isovolumetric pressures measured by “stop test” in women, providing a more reliable estimate of it [6]. Moreover, PIP1 has comparable and consistent results with the parameter k of the Valentini-Besson-Nelson mathematical model (VBN model) [23]. We would have also liked to report the values of the power factor “Watts factor,” however the information on the change in bladder volume during urination was not available, which prevented us from calculating the detrusor shortening velocity [24]. Nevertheless, the calculation of “Watts factor” still contains approximations and assumptions, and in the author’s own words, it “may not necessarily be any more useful than simpler estimates of contraction strength” [24].
Comparison With Previous Studies
Very few studies have compared urodynamic parameters in women with and without increased PVR volume. Comparison with the current study is difficult, not only because of the different definition of increased PVR volume, but also because of the important methodological differences. When comparing urodynamic parameters in women ≥65 years of age with overactive bladder, without controlling for factors that modify the voiding pattern and bladder power, Park et al. [12] only found greater PdetQmax, greater bladder capacity and greater frequency of interrupted voiding pattern in those with increased PVR volume, defined as ≥100 mL. This differs from what was found in our study, in which all voiding parameters were significantly different between women with and without increased PVR volume, except for PIP1. Unfortunately, we did not record the presence of interrupted urinary flow, which prevented us from making comparisons.
As we have stated above, in men, the DCS indexes better predict an increased PVR volume than the BOO indexes, and the “relative bladder outlet resistance” has even greater predictive capacity [2], These differs from the results of this study carried out in women, where the BOO indexes (female-BOOI and UR) correlated with PVR volume and PVR percentage and presented a good ability to predict increased PVR volume, unlike the DCS index (PIP1), and where “relative bladder outlet obstruction” indexes did not improve the correlations. The low bladder outlet resistance of the female lower urinary tract could modify the relationship between BOO, DCS, and PVR volume. These relations are very difficult to study due to the high frequency of abdominal straining in female voiding [10, 11, 25], and because its effect is difficult to integrate into any urodynamic model of voiding function [5]. However, it should be noted that few patients in our study group had very high PVR volumes (only 8 of them had a PVR volume ≥200 mL). Our patients may have been at an early stage of the functional changes that occur in the bladder due to BOO, with increased detrusor pressures previous to the phase of decompensation (detrusor underactivity) [26]. We may speculate that women with the worst DCS (and possibly higher PVR volumes) may have voided with abdominal straining, being excluded from the study, limiting the analysis of results.
We are not aware of previous studies evaluating the association of PVR volume with parameters of BOO and DCS in women, nor assessing the predictive value of increased PVR volume for these parameters. As such, our results contribute to a better understanding of the pathophysiology of increased PVR volume in women.
Strengths and Limitations
This study has the following strengths: (1) Patients were evaluated in a standardized way, urodynamics data were prospectively acquired, and definitions and recommendations of ICS and IUGA were followed. (2) Women voiding with abdominal straining were excluded. (3) Factors that influence the voiding pattern and bladder power, such as age, presence of SUI, and premicturition bladder volume were controlled. This study has the following limitations: (1) Retrospective. (2) Relatively small sample size and few patients with very high PVR volumes (which may be explained by the fact that patients with voiding dysfunction are expected to void with abdominal straining). (3) Low number of patients with reduced DCS (defined as PIP1 less than 30) [6].
In conclusion, this matched case-control study of women who voided without abdominal straining, in which variables that affect voiding dynamics and bladder power were controlled, shows that the BOO indexes (female-BOOI and UR) correlated with PVR volume and PVR percentage and presented a good ability to predict increased PVR volume, unlike the DCS index (PIP1). These results contribute to a better understanding of the pathophysiology of increased PVR volume in women, and will need to be confirmed in larger studies.
