Temporal development of unfavourable urodynamic parameters during the first year after spinal cord injury

Objectives: To describe the temporal development of and risk factors for the occurrence of unfavourable urodynamic parameters during the first year after spinal cord injury (SCI). Patients and methods: This population-based longitudinal study used data from 97 adult patients with a single-event traumatic or ischaemic SCI who underwent video-urodynamic investigation (UDI) at a university SCI centre. The first occurrences of unfavourable urodynamic parameters (detrusor overactivity combined with detrusor sphincter dyssynergia [DO-DSD], maximum storage detrusor pressure ≥40 cmH2 O, bladder compliance <20 mL/cmH2 O, vesico-ureteric reflux [VUR] and any unfavourable parameter [composite outcome]) were evaluated using time-to-event analysis. Results: The majority of the population (87/97 [90%]) had at least one unfavourable urodynamic parameter. Most unfavourable urodynamic parameters were initially identified during the 1- or 3-month UDI, including 92% of the DO-DSD (78/85), 82% of the maximum storage pressure ≥40 cmH2 O (31/38), and 100% of the VUR (seven of seven) observations. No low bladder compliance was observed. The risk of DO-DSD was elevated in patients with thoracic SCI compared to those with lumbar SCI (adjusted hazard ratio [aHR] 2.38, 95% confidence interval [CI] 1.16-4.89). Risk of maximum storage detrusor pressure ≥40 cmH2 O was higher in males than females (aHR 8.33, 95% CI 2.51-27.66), in patients with a cervical SCI compared to those with lumbar SCI (aHR 14.89, 95% CI 3.28-67.55), and in patients with AIS Grade B or C compared to AIS Grade D SCI (aHR 6.17, 95% CI 1.78-21.39). No risk factors were identified for the composite outcome of any unfavourable urodynamic parameter. Conclusions: The first UDI should take place within 3 months after SCI as to facilitate early diagnosis of unfavourable urodynamic parameters and timely treatment. Neuro-urological guidelines and individualised management strategies for patients with SCI may be strengthened by considering sex and SCI characteristics in the scheduling of UDIs. Keywords: #Urology; longitudinal studies; spinal cord injuries; survival analysis; urinary bladder, neurogenic; urinary bladder, overactive; urodynamic

Urodynamics Are Essential to Predict the Risk for Upper Urinary Tract Damage after Acute Spinal Cord Injury

We used clinical parameters to develop a prediction model for the occurrence of urodynamic risk factors for upper urinary tract (UUT) damage during the first year after acute spinal cord injury (SCI). A total of 97 patients underwent urodynamic investigation at 1, 3, 6, and 12 months after acute SCI, within the framework of a population-based longitudinal study at a single university SCI center. Candidate predictors included demographic characteristics and neurological and functional statuses 1 month after SCI. Outcomes included urodynamic risk factors for UUT damage: detrusor overactivity combined with detrusor sphincter dyssynergia, maximum storage detrusor pressure (pDetmax) ≥ 40 cmH$_{2}$O, bladder compliance < 20 mL/cmH$_{2}$O, and vesicoureteral reflux. Multivariable logistic regression was used for the prediction model development and internal validation, using the area under the receiver operating curve (aROC) to assess model discrimination. Two models showed fair discrimination for pDetmax ≥ 40 cmH$_{2}$O: (i) upper extremity motor score and sex, aROC 0.79 (95% CI: 0.69-0.89), C-statistic 0.78 (95% CI: 0.69-0.87), and (ii) neurological level, American Spinal Injury Association Impairment Scale grade, and sex, aROC 0.78 (95% CI: 0.68-0.89), C-statistic 0.76 (95% CI: 0.68-0.85). We identified two models that provided fair predictive values for urodynamic risk factors of UUT damage during the first year after SCI. Pending external validation, these models may be useful for clinical trial planning, although less so for individual-level patient management. Therefore, urodynamics remains essential for reliably identifying patients at risk of UUT damage

Urodynamic Investigation: A Valid Tool to Define Normal Lower Urinary Tract Function?

To evaluate whether urodynamic investigation (UDI), the gold standard to assess refractory lower urinary tract symptoms (LUTS), is appropriate to select healthy volunteers with apparent normal lower urinary tract function as control subjects for comparative studies.42 healthy subjects (22 women, mean age 32±10 years; 20 men, mean age 37±12 years) without LUTS were included into this prospective single-centre cohort study. All subjects recorded a 3-day bladder diary, completed validated questionnaires regarding LUTS, and underwent neuro-urological assessment as well as free uroflowmetry. Same session repeat UDI was performed according to "Good Urodynamic Practice" recommended by the International Continence Society, but using an air-charged instead of a water-filled catheter, and evaluated by a blinded investigator.All 3-day bladder diaries, LUTS questionnaires, neuro-urological assessments and free uroflowmetries were within normal limits. Overall (either during the first or second UDI), same session repeat UDI revealed pathological findings in 71% (30/42): Detrusor overactivity was detected in 14% (3/22) and 30% (6/20), post void residual >100mL in 14% (3/22) and 25% (5/20), bladder outlet obstruction in 9% (2/22) and 20% (4/20) and detrusor sphincter dyssynergia in 77% (17/22) and 65% (13/20) of our women and men, respectively. Repeatability of detrusor overactivity (κ = 0.78, 95% CI: 0.54-1.02) and detrusor sphincter dyssynergia (κ = 0.77, 95% CI: 0.55-0.98) showed substantial agreement between both UDIs. All other assessed urodynamic parameters had wide 95% limits of agreement for differences in the parameters indicating poor repeatability.More than 70% of our healthy subjects showed pathological urodynamic findings. Although UDI is the gold standard to assess refractory LUTS, it seems not to be applicable in healthy subjects to define normal lower urinary tract function. Therefore, we do not recommend using UDI to select healthy control subjects

Do We Need Surveillance Urethro-Cystoscopy in Patients with Neurogenic Lower Urinary Tract Dysfunction?

To examine the value of surveillance urethro-cystoscopy in patients with neurogenic lower urinary tract dysfunction (NLUTD) in regard to the conflicting literature as it is generally agreed that patients with NLUTD are at increased risk for bladder cancer.In a cross-sectional study, a consecutive series of 129 patients (50 females, 79 males, mean age 51, range 18-88) suffering from NLUTD for at least 5 years was prospectively investigated using urethro-cystoscopy and bladder washing cytology at a single university spinal cord injury (SCI) center.Due to suspicious urethro-cystoscopy and/or bladder washing cytology findings, 13 (10%) of 129 patients underwent transurethral resection of the bladder lesion and/or random bladder biopsies. Overall, 9 relevant histological findings were found in 5% (7/129) of our patients: bladder melanosis (n = 1), nephrogenic adenoma (n = 3), keratinizing squamous metaplasia (n = 1), intestinal metaplasia (n = 3), and muscle-invasive adenocarcinoma of the bladder (n = 1).Using surveillance urethro-cystoscopy, we found relevant histological findings in 5% of our patients suffering from NLUTD for at least 5 years. Thus, surveillance urethro-cystoscopy might be warranted, although the ideal starting point and frequency remain to be determined in further prospective studies

Antibiotic prophylaxis may not be necessary in patients with asymptomatic bacteriuria undergoing intradetrusor onabotulinumtoxinA injections for neurogenic detrusor overactivity

Many of the patients undergoing intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity (NDO) present with chronic bacteriuria. In these patients, antibiotic prophylaxis has been widely recommended since bacteriuria might impair treatment efficacy and cause urinary tract infections (UTI) but the evidence is limited. The aim of this study was to evaluate if an antibiotic prophylaxis is needed in patients with asymptomatic bacteriuria undergoing intradetrusor onabotulinumtoxinA injections. Between 06/2012 and 12/2014, a consecutive series of 154 patients undergoing a total of 273 treatment cycles were prospectively evaluated. Before treatment urine samples were collected, patients with no clinical signs for UTI underwent onabotulinumtoxinA injections, no antibiotic prophylaxis was given. Asymptomatic bacteriuria was found in 73% (200/273 treatments). Following treatment, UTI occurred in 5% (9/200) and 7% (5/73) of patients with and without bacteriuria, respectively. Intradetrusor onabotulinumtoxinA injections were clinically and urodynamically successful in 70% (192/273). There was no association between bacteriuria and treatment-related adverse events (odds ratio 0.64, 95% CI 0.23-1.81, p = 0.4) nor between bacteriuria and therapy failure (odds ratio 0.78, 95% CI 0.43-1.43, p = 0.4). Thus, we conclude that antibiotic prophylaxis needs to be critically reconsidered in patients undergoing intradetrusor onabotulinumtoxinA injections, especially taking into account the alarming antibiotic resistance worldwide

More Than 15 Years of Experience with Intradetrusor OnabotulinumtoxinA Injections for Treating Refractory Neurogenic Detrusor Overactivity: Lessons to Be Learned

BACKGROUND Intradetrusor onabotulinumtoxinA (BoNT-ONA) injections have become a well-established therapy for refractory neurogenic detrusor overactivity (NDO). However, little is known about long-term outcome and patients' adherence to this treatment. OBJECTIVE To assess long-term outcomes of intradetrusor BoNT-ONA injections and patients' adherence to treatment. DESIGN, SETTING, AND PARTICIPANTS A consecutive series of 52 patients who underwent first intradetrusor BoNT-ONA injections for refractory NDO >10 yr ago were evaluated retrospectively and prospectively at a single university spinal cord injury (SCI) centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary outcome was current neuro-urologic treatment. Secondary outcomes were urodynamic parameters. For data comparison, the paired/unpaired t test, chi-square test, and McNemar test were used. RESULTS AND LIMITATIONS Mean duration since first intradetrusor BoNT-ONA injections was 12±2 yr. Most patients (61% [32 of 52]) suffered from SCI, 15% (8 of 52) from spina bifida, 14% (7 of 52) from multiple sclerosis (MS), and the remaining (10% [5 of 52]) from other neurologic disorders. Almost 60% (31 of 52) of all patients are continuing with intradetrusor BoNT-ONA injections but only 14% (1 of 7) of the patients with MS. Lack of clinical and/or urodynamic response (21% [11 of 52]) and switching to another treatment (antimuscarinics and/or neuromodulation) despite appropriate BoNT-ONA efficacy (19% [10 of 52]) were the reasons for discontinuation. In patients continuing BoNT-ONA treatment, the positive effect was sustained after repeat injections (p<0.05). CONCLUSIONS Although intradetrusor BoNT-ONA injections are a highly effective therapy for refractory NDO, approximately 40% of the patients discontinue treatment over time. All prospective neurologic patients should be given this information, and it needs to be considered in the treatment decision-making process. PATIENT SUMMARY Approximately 60% of the patients treated with intradetrusor onabotulinumtoxinA injections for refractory neurogenic detrusor overactivity continue this therapy long term with good therapeutic effects. STUDY REGISTRATION NUMBER NCT01293110

Urodynamic findings.

<p>Urodynamic findings.</p

Pathological findings during filling cystometry.

<p>Filling cystometry (bladder filling with 30 mL/min) of a 51 years old healthy man: First detrusor overactivity occurs at 125 mL (red-dashed line) with maximum pDet of 54 cmH2O but no detrusor overactivity incontinence, the maximum cystometric capacity is 345 mL. The associated pressure flow study is normal and not shown in the figure.</p

Baseline characteristics.

<p>Baseline characteristics.</p

Pathological findings during pressure flow study.

<p>a) Pressure flow study of a 24 years old healthy woman: The first spike indicates a cough to evaluate correct catheter placement, thereafter permission to void (*) is obtained. The EMG signal during pressure flow study is elevated, the flow is interrupted; consequent spikes in the vesical and detrusor pressure can be seen. Maximum cystometric capacity/voided volume 395 mL, maximum pDet voiding 31 cmH2O at maximum flow rate 25 mL/s, no post void residual. b) The free uroflowmetry in the same subject reveals a normal flow-curve. Maximum flow rate 30 mL/s, voided volume 390 mL, no post void residual. In line with the International Continence Society, we interpret detrusor sphincter dyssynergia in this pressure flow study as a phenomenon provoked by the examination itself, especially also considering the normal flow pattern and the lack of PVR during free uroflowmetry. * = permission to void, EMG = electromyography, pAbd = intraabdominal pressure, pVes = intravesical pressure, pDet = detrusor pressure, Qmax = maximum flow rate, V = volume.</p