Authors: Nicolas Hermieu, Camille Chesnel, Maëlys Teng, Evanguelos Xylinas, Idir Ouzaid, Jean‐François Hermieu, Gérard Amarenco, Claire Hentzen
Categories: Urodynamics, bladder detrusor muscle, bladder outlet obstruction, pathophysiology, urinary bladder, urodynamics, Clinical Article
Source: Neurourology and Urodynamics
Doi: 10.1002/nau.25113
Bladder outlet obstruction alters detrusor contractility, reducing the bladder**'**s ability to respond to large filling with a risk of urinary retention.
The objective was to assess the effect of bladder filling volume on detrusor contractility in men with bladder outlet obstruction.
A prospective multicenter study in two pelviperineology departments. Male patients eligible for urodynamics (IPSS score > 7) were included from January to July 2022. In case of absence of bladder outlet obstruction on pressure‐flow studies, they were secondarily excluded. The primary endpoint was the maximum isometric detrusor pressure during a stop‐test, corresponding to detrusor contractility, measured at 3 filling volumes (50%, 75%, and 100% of cystometric capacity).
Fifty‐two patients performed urodynamics, of whom 12 were excluded because of lack of obstruction or inability to perform the stop‐test. Detrusor contractility was significantly higher for a 75% bladder filling than 50% and for a 75% filling than 100%, with a mean difference of 19.5; confidence interval (CI) 95% [14.3; 24.8] and 12.2; CI 95% [6.9; 17.5] cmH2O respectively (p < 0,01).
In case of bladder outlet obstruction in men, detrusor contractility depends on bladder filling volume, with reduced contractility when the bladder was underfilled or overfilled. This phenomenon could help to explain the mechanisms of urinary retention in men with bladder outlet obstruction.
Keywords: bladder detrusor muscle, bladder outlet obstruction, pathophysiology, urinary bladder, urodynamics
Affecting more than 20% of the population, lower urinary tract disorders are frequent. Among these, voiding dysfunction and urinary retention still raise pathophysiological, etiopathogenic and therapeutic questions. These voiding disorders can be related to a bladder outlet obstruction, most frequently benign prostatic hyperplasia in men, and/or an impaired detrusor contractility. Bladder outlet obstruction may itself lead to a progressive detrusor contractility alteration, decreasing the ability of the detrusor to respond to high bladder filling with thus a risk of urinary retention. ^1^ A better understanding of the factors related to detrusor contractility is therefore essential for the diagnostic and therapeutic management of voiding disorders.
The detrusor contraction efficiency depends on many factors, including the smooth muscle fibers degree of elongation, and therefore on the bladder filling volume. This influence of bladder filling volume on detrusor contractility in healthy subjects was confirmed non‐invasively by Van Mastrigt and Huang Foen Chung in 2006 on 1020 volunteers. ^2^ In addition to the filling volume, detrusor contractility could be influenced by other factors such as detrusor structural changes, bladder wall vascular alterations, bladder outlet obstruction severity, sensory afferent alterations, and time from the onset of the symptoms.
The relationship between detrusor contractility and bladder filling volume, found in healthy subjects, is not yet known in case of lower urinary tract disorders. The primary objective of this study was to evaluate the impact of bladder filling volume on detrusor contractility in case of bladder outlet obstruction in men. The secondary objectives were first to evaluate the impact of the desire to void on detrusor contractility, second to investigate the factors that can impact detrusor contractility in men with bladder outlet obstruction, and third, to verify the correlation between detrusor contractility measured by the stop‐test technique and the other pressure‐flow studies parameters.
This study was a prospective, multicenter, observational, standard care clinical study. The protocol received a favorable opinion from the French ethic committee Sud‐Est VI on March 05, 2021 (n°21.01.15.56020). The participants received oral and written information. Their nonopposition was notified in their medical file before final inclusion.
Participation was offered to patients followed for urinary voiding symptoms, benign prostatic hyperplasia, or preoperatively for prostatic hyperplasia surgery in two French pelvi‐perineology centers.
Patients were recruited from January 31, 2022, to July 13, 2022. Inclusion criteria adult male, indication for urodynamics, benign prostatic hyperplasia, IPSS (International prostate symptom score) > 7 that is, moderate to severe urinary symptoms. ^3^ The noninclusion criteria were neurological pathologies modifying detrusor contractility specially lower motor neuron lesions and underactive bladder. After urodynamics, patients were excluded if (1) there was no bladder outlet obstruction on the pressure‐flow study, (2) micturition was obtained by involuntary detrusor contraction or abdominal straining, (3) micturition was impossible, and (4) anticholinergic treatments had not been stopped 48 h before urodynamics.
Epidemiologic data were collected (age, body mass index, history of urologic disorders, IPSS, and USP [Urinary Symptom Profile] ^4^ scores, treatments).
Each patient performed urodynamics including flowmetry, cystometry, pressure‐flow study, and urethral profilometry. Urodynamics was performed in a semi‐sitting position, at a filling rate of 50 ml/min, through an 8 French 2‐way perfused urethral catheter. The pressure‐flow study confirmed the presence of bladder outlet obstruction using the International Continence Society nomogram and excluded non‐obstructed or equivocal patients. ^5^ , ^6^
Detrusor contractility was measured by the stop‐test technique, consisting in measuring the bladder pressure during a voluntary restraint effort just after the initiation of micturition. ^7^ This pressure corresponds to the maximum isometric detrusor pressure, representative of the detrusor contractile power. The stop‐test was repeated at three filling volumes, corresponding to 50%, 75%, and 100% of the bladder capacity measured during the initial cystometry. The bladder was filled to 50% of its capacity, the patient then initiated micturition and the first stop‐test was performed. The filling was completed to 75% of capacity, including the volume emitted during the first stop test, and the second stop‐test was performed. Finally, the filling was completed to 100% of capacity, including the volume emitted during the second stop test, and the last stop‐test was performed. The isometric detrusor pressure measurement at each stop‐test was collected.
The primary outcome was the value of the maximum isometric detrusor pressure at the stop test, measured at three normalized filling volumes for each patient (50%, 75%, and 100% of their cystometric capacity).
Secondary outcomes maximum isometric detrusor pressure regardless of bladder filling volume, and the difference in isometric detrusor pressure between filling to 50% and 75% of capacity according to modification of desire to void.
Demographic data were described by the number of patients analyzed and associated percentages, or by means and their standard deviations.
For the primary objective, the measures of detrusor contractility at each stop test were compared in pairs by a random‐effect linear regression contractility at 50% filling versus contractility at 75% and contractility at 75% versus contractility at 100%. Because of the risk of alpha risk inflation, the significance level was set at 2.5%. The number of participants required was calculated at 40.
For the secondary objectives, different cofactors were included in the random‐effect linear regression model to assess their effect on contractility regardless of filling volume. The postvoid residual (PVR) was also included in the regression model to assess the influence of contractility on PVR. To assess the correlation between the stop‐test measure of contractility and the pressure‐flow study parameters (bladder contractility index [BCI], bladder outlet obstruction index [BOOI], detrusor pressure at maximum flow [PdetQmax]), a Spearman's correlation test was performed. Finally, the impact of the desire to void on contractility was assessed by a second random‐effect linear regression model. For secondary objectives, the alpha risk was set at 5%.
The statistical software R freeware (version 3.6.3; The R Foundation) was used for the statistical analyses.
Of the 52 patients who performed urodynamics in this study, 40 patients were included in the analysis. Twelve patients were six without bladder outlet obstruction on the pressure‐flow study, five who failed to urinate during the test, and one who could not tolerate the test conditions. Details of the inclusions are summarized in Figure 1. Table 1 lists the clinical and urodynamic characteristics of the study population.
Figure 1 Flow chart
Maximum isometric detrusor pressure was significantly higher for 75% bladder filling than for 50%, with a mean difference of 19.5 cmH2O, CI 95% [14.3−24.8]; (p < 0.01), and significantly higher for 75% bladder filling than for 100%, with a mean difference of 12.2 cmH2O, CI 95% [6.9−17.5]; (p < 0.01).
Figure 2 represents the evolution of contractility measured by stop‐test function of filling volume.
Figure 2 Expressing detrusor contractility as a function of bladder filling volume. On the abscissa, the bladder filling volume expressed as a percentage of the bladder capacity measured during cystometry. On the ordinate, the maximum detrusor isometric pressure during the stop test, corresponding to detrusor contractility and expressed in cmH
2O.
Among the 40 patients studied, 19 had an appearance of desire to void between the stop‐tests performed at 50% and 75% of bladder filling. The mean increase in maximum isometric detrusor pressure between the stop‐tests at these two volumes was 14.8 (±14.7) cmH2O in the absence of desire to void and 24.8 (±22.5) cmH2O when a bladder filling sensation appeared, that is, a significant difference of 10.1 cmH2O, CI 95% [3.38−16.8]; (p < 0.01).
The mean time from the onset of urological disorders was 4.2 (±3) years. The longer the urological disorders were present, the more the contractility was impaired, with a statistically significant decrease in contractility of 3.1 cmH2O, CI 95% [0.92−5.3]; (p < 0.01) per year of evolution.
The other parameters (age, severity of lower urinary tract symptoms assessed by symptom scores, prostate volume) did not show a significant effect on detrusor contractility (Table 2).
The study of the correlation between contractility regardless of filling volume measured by the stop‐test technique and the pressure‐flow study showed a moderate correlation between the maximum isometric detrusor pressure and the following BCI (rho = 0.43; [p < 0.01]), BOOI (rho = 0.44; [p < 0.01]) and PdetQmax (rho = 0.46; [p < 0.01]).
The mean PVR was 118 (±123) ml. The more the detrusor contractility was impaired, the more the PVR increased, with a statistically significant increase in PVR of 17.2 ml, CI 95% [8.8 to 310.6]; (p = 0.04) per cmH2O of decreasing contractility.
In this prospective study in men with bladder outlet obstruction, detrusor contractility was dependent on bladder filling volume. Indeed, a volume corresponding to 75% of the bladder capacity was associated with a significant increase in contractility compared to a filling volume corresponding to 50% and 100% of its capacity. The change in the desire to void between the stop‐test at 50% and 75% of capacity resulted in a greater difference in contractility. Over the other possible associated factors, only the time from the onset of the urinary disorder was found to affect bladder contractility.
Van Mastrigt and Huang Foen Chung in 2006 found the same relationship between contractility and bladder filling volume in healthy subjects, with an optimal volume of 264 (±122) ml leading to maximum contractility. This optimal volume is close to the average volume at 75% filling in our study measured at 296 (±115) ml and corresponding to the highest contractility. To explain the decrease in contractility beyond 264 ml, they assumed the existence of detrusor fatigue related to the repetition of measurements, up to 10 per patient. As only three measures were performed in our study, this hypothesis is probably not sufficient to explain the results. To explain the decrease in contractility at low volume, the authors assumed that in case of low urine flow, contractility was underestimated. This artifact, related to the noninvasive measurement technique used (condom catheter), disappeared when contractility was measured by stop‐test because it is independent of the flow rate. ^2^ , ^8^ Other studies did not find the same results. In Groen et al study in 2000, contractility measured from PdetQmax decreased with repeated measurements regardless of the bladder filling, due to urodynamics habituation and improved pelvic relaxation with repeated measures. ^9^ In Sjöberg and Nyman study in 1981, contractility did not depend on bladder filling but was measured at fixed volumes of 200 and 400 ml and maximum capacity. ^10^ Normalized volumes as a percentage of capacity were used in our study to avoid this artifact because a fixed volume did not correspond to the same degree of filling for all participants.
The hypothesis of a relationship between contractility and bladder filling has a physiological basis. Smooth muscle cell studies have shown that the isometric tension developed by the contraction of a muscle measured at an incremental degree of elongation increase to a maximum value and then decrease with higher degrees of elongation. This phenomenon, reported by Minekus and Van Mastrigt in 2001 on porcine bladder and Seydewitz et al in 2017 by three‐dimensional modeling, applied to any muscle including the to contract properly, a muscle needs to be sufficiently, but not excessively stretched. ^11^ , ^12^ Structural and physiological analysis of the bladder wall also shows a reorganization of collagen fibers with bladder filling, which could also have a role in the decreased contractility associated with large filling volumes. Thus, the relationship between bladder filling volume and detrusor contractility is actually probably more of a relationship between filling volume and the bladder as a whole.
The study of the relationship between filling volume and contractility finally requires analysis of the concept of desire to void, which is closely related to volume. The onset of desire seemed to be associated with a larger contractility increase between a bladder filled to 50% and 75% than in the absence of change in desire. Smith et al found that underactive detrusor was associated with an alteration of filling perception rather than patients with undercontractile detrusor had a delayed perception of desire, but at equivalent desire, contractility was similar to patients without detrusor underactivity. ^13^ The absence of desire, leads to a lack of afferences to the cerebral centers of micturition, which can impact the importance of the effector signals delivered, as demonstrated in particular in rats using electrodes implanted on the bladder afferent nerves. ^14^ This could underline the role of the desire to void in detrusor contractility efficiency.
In this study, detrusor contractility appeared to degrade over time with bladder outlet obstruction, and PVR increased with contractility impairment. These results are consistent with those of Chen et al. who showed a decrease in BCI and an increase in PVR over time ^15^ and Guo et al. who demonstrated that more than 75% of patients with urinary retention had impaired contractility, ^1^ supporting the hypothesis of a progressive degradation of contractility related to bladder outlet obstruction.
In contrast, age did not appear to impact contractility. The influence of age on contractility is still controversial today. Studies by Beltrame et al. in 2015 in humans and Hardy et al. in 2019 in mice did not show a relationship between age and contractility, ^16^ , ^17^ whereas a 2010 review of the literature concluded that contractility progressively decreased with age. ^18^ Prostatic volume was also not correlated with contractility. The correlation between prostatic volume and urodynamic obstruction is still unclear with conflicting results between studies. ^19^ , ^20^ , ^21^ Sullivan and Yalla study in 1996 showed a significant increase in detrusor isometric pressure with the degree of urodynamic obstruction, ^22^ so contractility seemed to depend more on urodynamic obstruction than on anatomical obstacle.
In daily practice, the measurement of contractility by stop‐test tends to be replaced by nomograms applied to pressure‐flow study data, such as the International Continence Society nomogram and the BCI, which are easier to perform. ^5^ , ^23^ We found a moderate correlation between contractility measured by stop‐test and BCI and BOOI, consistent with previous findings. ^22^ , ^24^
This study is the first to specifically focus on the influence of bladder filling volume on detrusor contractility in patients with bladder outlet obstruction, particularly at risk of urinary retention. The prospective evaluation systematized by a single evaluator, the homogeneity of the study population, and the use of a validated tool to assess contractility allow to limit reproducibility biases between evaluators and to generalize the results in the population of patients with bladder outlet obstruction such as prostatic hyperplasia. Finally, the filling volumes were adjusted on the cystometric capacity, probably more relevant than fixed volumes that do not correspond to the same degree of filling for all participants.
This study has several limitations. The different thresholds of bladder capacity were chosen arbitrarily to perform the stop‐tests (50%, 75%, and 100% of capacity). Thus, it was not possible to estimate contractility regardless of the bladder filling volume or to determine the optimal volume leading to the maximum contractility. Urodynamics and even more pressure‐flow studies do not reproduce the physiological conditions of filling and micturition and can therefore impact the ability to empty the bladder. However, as the subject was his own witness, this bias had little influence on the analysis. The stop‐test technique to measure detrusor contractility was performed at the very beginning of the void. Indeed, as the study was about the influence of the filling volume, the bladder volume at the time of the stop‐tests had to be perfectly controlled. Most studies performed the stop‐test in the middle of micturition, which may complicate the comparison of results. ^7^ Finally, the order of filling volumes was not randomized and the stop‐tests were always performed in the same order. It has been suggested that the repetition of the measurements could lead to detrusor fatigue and therefore a decrease in the observed contractility, ^2^ but the initial increase observed at 75% does not support this hypothesis and because of the relatively small number of measurements, the impact on the results is probably small.
This study opens several perspectives. First, the demonstration of the impact of bladder filling volume on contractility allows a better understanding of the phenomena of urinary retention in male patients with a bladder outlet obstruction. It also demonstrates the variability of the data obtained according to the conditions of the examination. Thus, the conditions to assess bladder contractility can impact the results, depending on the choice of the technique (nomogram vs. stop‐test), or the mode of realization (filling volume to optimize the pressure‐flow study, with normal desire to void vs. maximum capacity), and it would be interesting to define the optimal conditions. Finally, in clinical practice and real‐life management, this study suggests the possibility to recommend micturition at normal desire, without waiting for a strong desire in these patients with chronic bladder outlet obstruction, however further studies are required to confirm these results.
In case of bladder outlet obstruction in men, detrusor contractility depends on bladder filling volume, with reduced detrusor contractility when bladder is underfilled or overfilled. Moreover, contractility seems to progressively deteriorate with the evolution of lower urinary tract disorder, decreasing the detrusor capacity to respond to a high filling volume. This phenomenon could participate in the mechanisms of urinary retention in male patients with bladder outlet obstruction.
Project development, data collection, and manuscript writing: Nicolas Hermieu, Jean‐François Hermieu, Gérard Amarenco, and Claire Hentzen. Project development and data collection: Camille Chesnel, Evanguelos Xylinas, Maëlys Teng, and Idir Ouzaid.
The authors declare no conflict of interest.
Approval from the French ethic committee Sud‐Est VI on March 05, 2021 (n°21.01.15.56020). The non‐opposition of the patients was collected and notified in their medical file.
This work was supported by grants from the SIFUD‐PP, the Association Française d'Urologie and Lilial ‐ GREEN GRC01 Sorbonne University.
Hermieu N, Chesnel C, Teng M, et al. Effect of bladder filling volume on detrusor contractility in men with bladder outlet obstruction. Neurourol Urodyn. 2023;42:445‐452. 10.1002/nau.25113
The data that support the findings of this study are available from the corresponding author upon reasonable request.
The data that support the findings of this study are available from the corresponding author upon reasonable request.