Neuromodulation and urodynamics in lower urinary tract symptoms
Groenendijk, P.M.
Citation
Groenendijk, P. M. (2008, December 9). Neuromodulation and urodynamics in lower urinary tract symptoms. Retrieved from
https://hdl.handle.net/1887/13341
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Chapter 3
3 3
Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence
P.M. Groenendijk, A.A.B. Lycklama à Nyeholt, J.P.F.A. Heesakkers, P.E.V. van Kerrebroeck, R.A. Schmidt, M.M. Hassouna, J.B. Gajewski, F. Cappellano, S.W.
Siegel, M. Fall, H.E. Dijkema, U. Jonas and U. van den Hombergh
BJU International 2008; 101 (3): 325-329
Abstract
Objective: To evaluate the urodynamic data before and 6 months after implantation of sacral neuromodulation (SNM, an established treatment for voiding dysfunction, including refractory urge urinary incontinence, UI) and to assess the correlation between the urodynamic data and clinical efficacy in patients with UI.
Patients and methods: In all, 111 patients with a > 50% reduction in UI symptoms during a per- cutaneous nerve evaluation test qualified for surgical implantation of SNM. Patients were catego- rized in two subgroups, i.e. those with UI with or without confirmed detrusor overactivity (DO) at baseline. At the 6-month follow-up all patients had a second urodynamic investigation, with the stimulator switched on.
Results: At baseline, there was urodynamically confirmed DO in 67 patients, while 44 showed no DO. A review of filling cystometry variables showed a statistically significant improvement in bladder volumes at first sensation of filling (FSF) and at maximum fill volume (MFV) before voi- ding for both UI subgroups, compared with baseline. In 51% of the patients with UI and DO at baseline, the DO resolved during the follow-up. However, those patients were no more clinically successful than those who still had DO (P = 0.73). At the 6-month follow-up, 55 of 84 implanted patients showed clinical benefit, having a ≥50% improvement in primary voiding diary variables.
Patients with UI but no DO had a higher rate of clinical success (73%) than patients with UI and DO (61%), but the difference was not statistically significant.
Conclusion: These urodynamic results show a statistically significant improvement in FSF and MFV in patients with UI with or with no DO after SNM. Although there was a urodynamic and clinical improvement in both groups, patients with UI but no DO are at least as successful as patients with UI and DO. Therefore in patients with UI, DO should not be a prerequisite selection criterion for using SNM.
omodulation for urge urinary incontinence
Introduction
Urge urinary incontinence (UI) is defined as the complaint of involuntary leakage (of urine) ac- companied by or preceded by urgency [1]. It is thought that UI can be caused by overactivity of the detrusor muscle [2], but sensory urgency, urethral instability and psychosomatic factors might also be related [3]. Detrusor overactivity (DO) incontinence is diagnosed during filling cystometry when DO is accompanied by involuntary urine loss [1]. However, conventional filling cystometry is not able to register DO consistently. The reported sensitivity is 77.9% and the specificity 38.7%
[3]. UI with no detectable DO is mostly categorized as sensory UI. Currently, the term ‘overac- tive bladder’ (OAB) is used when defining the symptom complex, disregarding the urodynamic features.
Standard treatments for UI include behavioural modification (pelvic floor muscle exercises), phar- macological therapy (anticholinergics), interventions (biofeedback, external stimulation) and sur- gery (denervation, bladder dilatation, botulinum toxin injections, urinary diversion, augmentation cystoplasty). The introduction of sacral neuromodulation (SNM) for treating UI has provided physicians with an effective and reversible means to address refractory chronic voiding dysfunc- tion [4–8]. However, the debate about urodynamic changes after SNM therapy and the role of urodynamic investigations in identifying patients for SNM therapy is still ongoing. Recently, Groen et al. [9] reported the urodynamic changes after SNM in women with incontinence due to idiopathic DO. We therefore re-analysed our data in women with UI treated with SNM. The purpose of the present study was to characterize the urodynamic outcome of SNM therapy af- ter 6 months of treatment for patients with UI. The prospective, randomized multicentre study (MDT-103) that evaluated clinical efficacy and safety of SNM therapy in the population with UI was published by Schmidt et al. [10]. This report describes the urodynamic findings from the MDT-103 study and their correlation with the efficacy of therapy for UI patients with and without urodynamically confirmed DO.
Patients and methods
In the prospective randomized multicentre study MDT-103, patients from 16 centres worldwide, with UI as a primary complaint, and refractory to conservative treatment, were evaluated for SNM therapy [10]. Only non-neurogenic patients were included in the study. All study candida- tes had baseline screening, including a detailed medical history, urodynamic testing and quality- of-life questionnaires. Urodynamic investigations included uroflowmetry, filling cystometry, and detrusor pressure (Pdet)/flow studies. The primary goal of the urodynamic investigation was to exclude underlying treatable diseases like bladder outlet obstruction (BOO), and to categorize patients into those presenting with or without DO.
After written informed consent was obtained, all patients had a trial period of temporary lead stimulation to quantify the effects of stimulation on UI. This percutaneous nerve evaluation test (PNE) was described previously [11]. Patients who had a > 50% reduction in UI symptoms, as shown in voiding diaries, qualified for surgical implantation of the neuromodulation system
63
(InterStim, Medtronic Inc., Minneapolis, USA). Patients had urodynamic investigations at base- line and 6 months after the implant. The postvoid residual urine volume (PVR) was measured by catheterization or by ultrasonography.
Baseline urodynamics distinguished patients with UI and DO from those with no DO. The compara- bility of results within patients at each site was assured by using the same calibrated equipment.
Implanted patients were asked to undergo urodynamic testing, with the neurostimulator activated, at the 6-month follow-up. At that time, the potential effects of SNM on detrusor function were evaluated, with the clinical efficacy of the treatment. Clinical success was defined as a > 50% impro- vement in the reduction of incontinence episodes per day and/or number of pads used.
The test results between the groups were compared using a two-sample Student’s t-test, with values presented as the mean (SD); the statistical results were adjusted according to the equality of variances and for multiple comparisons of the data.
Results
Fifty-four patients were assessed by uroflowmetry both at baseline and 6 months after the im- plant. The PVR was > 50 mL in eight patients at baseline, vs six at the follow-up. There was a sig- nificant increase only in peak urinary flow rate after SNM (P = 0.049), the other variables (mean flow time, total voided volume and flow time) showing no significant changes.
As determined from the baseline filling cystometry results, the group of 111 randomized patients with UI were divided into two subgroups, those with UI and DO (67, 59 women and eight men), and those with UI and no DO (44). The urodynamic test results are presented for the two groups separately. Six patients of each group left the study before the follow-up assessment and in some the data were missing.
At 6 months, the bladder volume at the first sensation of filling (FSF) and maximum bladder capacity, defined as maximum fill volume (MFV) before the void, indicated larger volumes than at baseline, and were statistically significantly different (Table 1). The mean bladder volume at first involuntary detrusor contraction was larger than at baseline, but not statistically significantly (P = 0.30).
The remaining filling cystometry variables for the patients with UI and DO show favourable 6- month results, as measured by a significantly lower Pdet before voiding and a lower peak Pdet during involuntary detrusor contraction than at baseline (Table 1). Furthermore, there were no negative trends in voiding function in patients with UI and DO at 6 months in the filling cysto- metry data. Urodynamic detrusor behaviour data at the follow-up was available for 51 (76%) of the 67 patients with DO at baseline. Table 2 summarizes the detrusor behaviour before and after SNM, with
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65 Table 1 Water cystometry results at baseline and after 6 months of SNM in patients with UI and DO
Mean (SD)
Urodynamic
variable (n) at baseline at 6 months P*
Bladder volume, mL
At FSF (41) 82.8 (64.7) 167.4 (109.3) < 0.001
% bladder capacity (41) 40.6 (33.3) 54.5 (27.2) 0.03 Pdet, cmH2O (39) 14.2 ± 18.9 11.2 ± 13.9 0.36 Bladder volume, mL
at 1st unstable contraction (22) 104.7 (111.0) 133.7 (125.9) 0.30
% of bladder capacity (21) 54.2 (36.3) 49.7 (34.6) 0.63 Pdet, cmH2O (21) 38.8 (23.7) 28.6 (23.3) 0.06 Bladder volume, mL
at MFV or just before void (45) 254 (138) 328 (148) 0.001 Pdet, cmH2O (43) 27.7 (21.6) 17.7 (16.5) < 0.001 Peak Pdet during cystometry (43) 53.8 (36.4) 33.6 (25.1) < 0.001 Volume at peak Pdet, mL (35) 230 (148) 261 (160) 0.24
*Paired t-test.
the clinical outcome of SNM therapy. Thirty-four patients (51%) with DO at baseline had no DO at the 6-month follow-up, but reported no additional clinical benefit over those who still had DO (P = 0.73).
Based on clinical data, 33 of 54 (61%) patients with UI and DO still present after 6 months showed an improvement of > 50% in the reduction of incontinence episodes at the 6-month follow-up with the sti- mulation on.There was no DO at baseline in 40 women and four men; Table 3 summarizes the 6-month filling cystometry results for these patients, for those who completed both urodynamic investigations.
Comparable with the previous group, there was a statistically significant difference in bladder volume at FSF and at MFV. Of the patients with UI and stable detrusor function at baseline, three of 32 (9%) had DO at 6 months; 22 of 30 (73%) patients with UI but no DO (with available clinical data) had clinical success. Patients with no DO both at baseline and during the follow-up had the best clinical outcome.
Patients with UI and no DO at the follow-up (73%) had a higher rate of clinical success than patients with UI and DO (61%) at the follow-up, but the difference was not statistically significant (P = 0.26).
Paired results for the Pdet/flow study are shown for 66 of the 102 implanted patients followed
up to 6 months (Table 4). Baseline or 6-month results were not available in the remaining patients as they were unable to void during the test with the catheter in place. There were significant dif- ferences in peak flow rate, mean flow rate, total voided volume and Pdet at the start of flow.
Of the urodynamic variables that changed within the study group before and after implantation, and that correlated highly with clinical success, three were identified in a univariate analysis, i.e.
Pdet at MFV, peak Pdet during filling cystometry, and Pdet at the start of flow (Table 5). Urody- namic variables that predicted clinical success, defined as a > 50% improvement, were also analy- sed; the baseline urodynamic variables that were prognostic for a successful clinical outcome were volume at peak Pdet, Pdet at the start of flow, the bladder volume at first detrusor contraction, and the bladder volume at MFV (Table 5).
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Table 2:Detrusor behaviour before and after implant in relation to clinical success Urodynamics, n (%)
at baseline at 6 months Clinical result
DO present, 67 (60) DO +, 25 (49) success, 19 (40); failure, 3 (6) DO –, 26 (51) success, 20 (42); failure, 6 (12) DO absent, 44 (40) DO +, 3 (9) success, 2 (7); failure, 1 (4)
DO –, 29 (91) success, 23 (82); failure, 2 (7)
Table 3: Water cystometry at baseline and 6 months of SNM in patients with UI and no DO at baseline
Mean (SD)
Urodynamic
variable (n) at baseline at 6 months P*
Bladder volume, mL
At FSF (30) 122.2 (78.8) 192.4 (118.4) 0.001
% bladder capacity (30) 42.0 (25.5) 51.1 (25.9) 0.13
Pdet, cmH2O (30) 4.3 (5.8) 4.2 (6.3) 0.91
Bladder volume, mL
at MFV or just before void (32) 313 (117) 365 (115) 0.02 Pdet, cmH2O (32) 7.4 (6.4) 12.1 (15.4) 0.11 Peak Pdet during cystometry (31) 13.7 (14.1) 15.9 (15.6) 0.50 Volume at peak Pdet, mL (30) 266 (138) 339 (135) 0.02
*Paired t-test
67 Table 4: Detrusor pressure/flow results at baseline and 6 months in 102 patients with UI
Mean (SD)
Variable (n) at baseline at 6 months P*
Peak flow rate, mL/s (65) 14.7 (10.0) 17.9 (8.6) 0.02 Mean flow rate, mL/s (64) 6.3 (3.8) 8.3 (5.4) 0.006 Total voided volume, mL (66) 251 (141) 324 (155) < 0.001
Flow time, s (64) 46.0 (28.4) 54.4 (59.3) 0.29
Time to peak flow, s (63) 25.4 (33.5) 27.0 (54.2) 0.84 Pdet at start of flow, cmH2O (54) 27.7 (25.3) 20.6 (15.8) 0.03 Pdet at maximum flow, cmH2O (55) 43.0 (30.6) 41.4 (22.7) 0.69
*Paired t-test.
Table 5: Urodynamic variables correlating with clinical success, and the prognostic urodynamic variables best predicting the clinical outcome
Variable N Pearson correlation P
Pdet at MFV 72 – 0.31 0.007
Peak Pdet during cystometry 73 – 0.25 0.032
Pdet at start of flow 62 – 0.24 0.065*
Best predictors
Volume at peak Pdet 76 – 0.25 0.030
Pdet at start of flow 56 – 0.37 0.004
Bladder volume:
at first detrusor contraction 52 – 0.38 0.005
at MFV 81 – 0.19 0.089*
*Marginally significant.
Discussion
The demand for incontinence treatment will continue to increase as the population age. A better un- derstanding of the pathophysiology, and mode of action of therapeutic options, is needed. SNM has been shown to be effective in restoring normal voiding behaviour in various bladder disorders, like UI.
In principle, the mode of action of SNM is by reinforcing detrusor inhibiting mechanisms, although further exploration is needed to understand in more detail how the micturition reflex is modulated.
Likewise, the role of urodynamics in patient selection for SNM treatment remains to be defined.
The present patients comprised those with refractory UI and implanted with a permanent neuro- stimulator after completing a successful (> 50% clinical improvement) PNE test. At 6 months of follow-up SNM was clinically effective for patients presenting with and with no baseline DO. There was no statistically significant correlation between the likelihood of success and the presence of DO at baseline, although the group with no DO at baseline tended to have a better clinical outcome.
Simple uroflowmetry is not typically used to diagnose or monitor changes in UI over time. Com- pared to the uroflowmetry test before implantation, the 6-month data only showed a significant increase in peak flow rate. There was no increase in total voided volume, although SNM therapy is known to increase bladder volume during urodynamic investigations after implantation. There- fore, uroflowmetry seems to have no role in assessing the results of SNM.
Most studies reporting on the mode of action of SNM and urodynamic changes report the chan- ges during filling cystometry. It is evident that SNM therapy positively influences bladder capacity and sensory variables like the FSF. A clinical improvement is associated with an improvement in urodynamic data; voided volumes almost doubled compared to baseline, and the FSF increased by half [6]. Scheepens et al. [12] reported a correlation between the subjective improvement in patients with OAB and the use of SNM. During SNM therapy, DO reduced on ambulant cysto- metry, that reportedly has a higher specificity and sensitivity than classic filling cystometry. The role of DO detected before SNM is unclear. Recently, Groen et al. [9] reported on the effect of SNM on voiding in women with idiopathic DO with incontinence. In the present study there were fewer patients with DO, but bladder contraction strength, urethral resistance during voiding, and volume-independent urodynamic variables did not change significantly. When focusing on ure- thral behaviour, urethral pressure variations during filling cystometry appeared to be a valuable factor to predict the outcome of SNM therapy. Urethral instability (urethral pressure variations of > 15 cmH2O) disappeared in seven of 13 patients successfully treated with SNM; DO disap- peared in only one of nine patients who had DO before SNM [13].
Bosch et al. [4] found no correlation between symptomatic improvement and urodynamic fin- dings in 18 patients with UI. Shaker and Hassouna [5] questioned the clinical relevance of a diag- nosis of DO during filling cystometry used in patient selection. This discrepancy between clinical results and urodynamic findings is also reported in drug studies for OAB [14]. Elkelini et al. [6]
reported on SNM treatment in 18 patients with UI; a clinical improvement was associated with an improvement in urodynamic data, but in only one of four patients with DO before the implant did the DO resolve. The bladder volume at FSF increased by half while the cystometric bladder capacity increased by 15% [6]. In the present study DO disappeared in 51% of patients with DO
omodulation for urge urinary incontinence
69 at the baseline urodynamic evaluation. In agreement with the findings of Elkelini et al., the blad- der volume at FSF and MFV improved significantly in the present study, in patients with and with no DO. Our data show that patients with UI were able to sense bladder filling at a higher, more appropriate bladder volume at the 6-month follow-up, when SNM was applied.
Clinically, 55 of 84 (65%) patients showed a > 50% improvement in their primary voiding complaint, expressed in the voiding diary as the number of leakage episodes, the number of pads per day or the severity of leakage episodes. Patients with UI but no DO had a higher rate of clinical success than patients with UI and DO. However, of the 23 (49%) patients who still had DO at the follow-up, eight were completely dry, seven had a > 50% improvement and six had < 50% improvement; the 6- month results were not available for the two remaining patients. This clearly indicates that DO before SNM, and whether or not DO is still present at 6 months after the implant, is not a useful factor for either patient selection or assessing the clinical outcome of SNM. Recently, South et al. [15] reached a similar conclusion about the ability of DO to predict the outcome of PNE testing; there was no cor- relation between the presence or absence of DO and the likelihood of response to test stimulation.
Perhaps the regaining of control of the pelvic floor and the external sphincter mechanism is the key to success. This would also explain the association of success and regaining of urethral stability.
While each of the urological tests at baseline provide valuable data for some types of patients pre- senting with voiding dysfunction, they are not regarded as useful in diagnosing UI [16–19]. In the present study, both patients with and with no DO could be selected for implantation. Therefore, in this study, cystometric data were collected to ensure that bladder function was not negatively affected by SNM therapy. However, there was DO in three of 32 patients (9%) that could not be detected at baseline. It is known that DO is not consistently registered by filling cystometry, and therefore can be missed on urodynamic investigation at baseline. In routine urodynamics, DO is an ‘on-the-spot’ finding affected by several factors. It is not consistently registered, as it might be influenced by the patient’s mental state, as well as laboratory techniques, and therefore can be missed on urodynamic investigation at baseline [3].
An increased bladder capacity might lead to a decrease in voiding frequency, as noted from voiding diary data. This benefit of SNM therapy was also apparent in the present study. There was a signi- ficant clinical improvement (defined as > 50% improvement) in patients with and with no DO over baseline for SNM therapy. Patients with no DO seemed to have an additional benefit over patients with DO, although the difference was not statistically significant. Recently, the clinical benefit of SNM therapy in the treatment of refractory UI was re-confirmed [7,8]. The present data show a sta- tistically significant improvement in the urodynamic bladder volume, while the Pdet did not change significantly between baseline and the 6-month follow-up. In patients with baseline DO there was a decrease in Pdet, possibly the result of an enhanced control of pelvic floor muscles and the bladder.
However, in patients with no baseline DO there was no decrease in Pdet during voiding. Therefore, the observed changes in Pdet during voiding are of minor importance in evaluating SNM therapy.
To date, a test stimulation still has the highest predictive value for identifying and selecting pa- tients for SNM therapy. When seeking urodynamic variables that most accurately predicted the outcome of SNM in the present study (Table 5), there were significant changes in bladder volume variables. Combined with the finding that Pdet variables correlated best with clinical success (Ta- ble 5), this might indicate that patients with a low bladder capacity at baseline might benefit most
from SNM, and this could be confirmed by improved Pdet variables. Urodynamic investigations before and 6 months after implantation show that urodynamic volume-dependent variables improve during SNM therapy. Bladder volume and FSF improved significantly, while Pdet during voiding did not change significantly. This results in improved bladder compliance and improved voiding efficiency.
For patients presenting with baseline DO, SNM eliminated DO in 51% of the patients after 6 months. However, the absence of DO did not necessarily accompany the resolution of UI com- plaints. Thus urodynamic investigations only focusing on the presence of DO did not appear to be an accurate tool to measure the efficacy of SNM therapy.
Although there was a urodynamic and clinical improvement in both groups, patients with UI and no baseline DO seem to have an additional benefit over patients with baseline DO. Therefore in patients with UI, urodynamically detected DO should not be a prerequisite in the selection criteria for SNM therapy. The value of classic urodynamics in selecting patients for SNM therapy seems to be limited, at least in selecting them for the operation and to monitor clinical efficacy, but might be valuable for scientific purposes when further exploring the mechanism of action of SNM.
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