1301Vol. 11 | No. 01 | Jan-Feb 2014 |U R O LO G Y J O U R N A L Percutaneous Nerve Evaluation (PNE) for Treatment of Non-Obstructive Urinary Retention: Urodynamic Changes, Placebo Effects, and Response Rates Farzaneh Sharifiaghdas, Mahboubeh Mirzaei, Babak Ahadi Corresponding Author: Mahboubeh Mirzaee, MD Department of Urology, Urology and Nephrology Research Center, Shaheed Labbafinejad Medical Center, Shaheed Beheshti University of Medical Sciences, Tehran , Iran. Tel: +98 21 22567222 Fax: +98 21 22567282 Email: mirzaeimahboubeh@yahoo. com Received January 2013 Accepted December 2013 Department of Urology, Shaheed Labbafinejad Medical Center, Urology and Nephrol- ogy Research Center, Shaheed Beheshti University of Medical Sciences Tehran, Iran. MISCELLANEOUS Purpose: To evaluate the results of percutaneous nerve evaluation (PNE) implantation in the treatment of non-obstructive urinary retention and report the changes in the urodynamic parameters. Materials and Methods: Patients with non-obstructive urinary retention or incomplete blad- der emptying were included. All patients filled a 7 days voiding diary chart and underwent PNE for one week, and the patient was asked to record the second voiding diary chart and repeat urodynamic study in this period. Then the PNE lead was removed from the S3 fora- men, but the connections remained fixed in place for another 3 days to exclude the placebo effects and the third voiding diary chart was completed by the patient. The patient wasn’t aware of lead removal. Success was defined as, more than 50% improvement in at least one of the urinary tract symptoms. Results: Forty five patients with a mean age of 37.1 years (ranged 9-83 years) were treated with PNE for refractory, non-obstructive urinary retention. Of study subjects 28 complained from complete urinary retention, and 17 had incomplete emptying. Of participants, 28 (62.2%) demonstrated greater than 50% improvement in the urinary symptoms. Urodynamic data, showed a statistically significant increase in maximum flow rate (8 ± 2.2 mL/sec to 16 ± 3.6 mL/sec, P = .06) and voided volume (35 mL to 187 mL, P = .032) in the responders. Any placebo effects in PNE have not been seen. Conclusion: Patients with complete non obstructive urinary retention were good responders to PNE. The placebo effect in sacral nerve stimulation was negligible. Keywords: electric stimulation therapy; humans; urinary incontinence; urination disorders; therapy. 1302 | INTRODUCTION Non obstructive urinary retention is one of the most difficult diseases to manage. These patients not only have some degrees of urinary incontinence but also they suffer from recurrent (urinary tract infection UTI) and decrease of renal function.(1,2,3) Medical treatment and urethral dilation are usually unsuccessful and patients ul- timately have to do intermittent catheterization or to use per- manent catheter.(4) Neuromodulation has been approved by the US Food and Drug Administration (FDA) since 1997 to treat idiopathic overactive bladder (I-OAB) and non-obstruc- tive urinary retention.(5-10) The relative ease of the technique, hopeful results and low complication rate make this therapy a superior alternative to the standard treatment of idiopathic non obstructive urinary retention. Candidates for neuromod- ulation first should undergo a trial known as the percutaneous nerve evaluation (PNE). More than 50% improvement in at least one of the urinary tract symptoms is considered success; this is currently the only proven predictive factor in deter- mining long-term prognosis.(6,7) If the patient is considered a suitable candidate for sacral nerve modulation (SNM), an implantable nerve stimulator (INS) is inserted at the second stage. In this study we assess efficacy and complications of temporary simple lead PNE in non-obstructive urinary reten- tion. MATERIALS AND METHODS Patients with complete or incomplete urinary retention who were refractory to medical treatment (full dose of bethane- chol and baclofen and α-blocker administration) were in- cluded. All of the participants underwent physical examina- tion and filled a 7 days voiding diary chart. Urine analysis and culture, ultrasound imaging, urodynamic study including filling cystometry with electromyography (EMG) patch and cystoscopy was performed to rule out obstruction, infection and malignancy. Residual urine was measured by ultrasound, urodynamic study and cystoscopy. Medical and surgical his- tory were recorded. Exclusion criteria were, morbid obesity (body mass index > 40, for high risk of lead displacement), active urinary tract infection, urinary tract obstruction, and uncorrected coagula- tion disorders. Patients who might need to be evaluated by magnetic resonance imaging in the future or to be treated by radiation therapy or high-frequency diathermy and pregnan- cy were also excluded. PNE lead (conventional PNE-test with thin wire electrodes) was implanted under fluoroscopic guide with local anesthesia in the left or right S3 foramen, on an outpatient basis. The nerve was tested for the appropriate motor responses, plantar flexion of the great toe and anal sphincter contraction (bel- lows reflex) which represented the contraction of the levator muscles. Simultaneous sensory responses at the time of lead placement helped to optimize positioning. The lead was con- nected to an external pulse generator and fixed with adhesive dressings. The patient and his/her caregiver were taught how to replace the battery and regulate voltage. Test period was 1-week, and the patient was being asked to record another 7 days voiding diary chart and urodynamic study was repeated at this period. The PNE lead was removed from the S3 foramen, but the connections and external pulse generator remained fixed in place for another 3 days and the third voiding diary chart was completed by the patient. The patient wasn’t aware of lead removal. More than 50% improvement in at least one of the following parameters was considered positive response: re- duction in the number of catheterization times, increase in the voided volume and the number of voids per day, and de- crease in postvoid residual urine volume. Multichannel urodynamic study was performed in all pa- tients with medium-fill water cystometry (50 mL per minute) and dual-lumen 6 French catheter. The patients were allowed to void in the sitting position and all the events of filling and voiding phases were recorded. The study was approved by the local research Ethics Committee (Urology and Nephrol- ogy Research Center) and the trial was independent of any industry support and involvement. Statistical Analysis Data were analyzed using paired-samples t test with the sta- tistical package for the social science (SPSS Inc, Chicago, Il- linois, USA) version 19.0. A P value of < .05 was considered statistically significant, confidence interval was set at 95%. RESULTS The study results are summarized in Tables 1-4. Of study Miscellaneous 1303Vol. 11 | No. 01 | Jan-Feb 2014 |U R O LO G Y J O U R N A L Percutaneous Nerve Evaluation (PNE) in Non-Obstructive Urinary Retention | Sharifiaghdas et al subjects 31 (68.9%) were female, 28 had complete urinary retention and were dependent on clean intermittent catheteri- zation or permanent catheter, and 17 had incomplete bladder emptying (evaluated by post void residual urine volume). The mean duration of emptying disorders was three years. Twen- ty seven patients had idiopathic urinary retention (60%), and 18 patients (40%) had the past history of spinal cord trauma or tumor, previous pelvic surgery and neurogenic disease. Of the 45 patients, 28 (62.2%) demonstrated greater than 50% improvement in urinary symptoms. Response rate was higher in the complete urinary retention group versus incom- plete emptying (75% vs. 41.1%, P = .023). The details are summarized in Table 1. Patient with idiopathic urinary retention demonstrated bet- ter response rate compared to those with a history of neuro- genic disease (70.3% vs. 50%, P = .167). The patients were divided into four groups according to their age range: 1-18 years, 19-50 years, 51-70 years and > 70 years. The response rate in female and male was 67.7% and 50%, respectively (P = .256). The mean age of men who responded to the test was 30.8 years (41.7 years in non-responders) and 57% of them were neurologic. The patients were categorized into two subgroups groups, re- sponders and non-responders. Comparison between prestimulation and during stimula- tion data on uroflowmetry showed significant increase in the maximum flow rate in responders (from 6.1 mL/sec to 17.6 mL/sec, P < .05). Mean voided volume increase was signifi- cant in responders (from 35 mL to 187 mL, P = .032). Blad- der contractibility index increased in the responders which was statistically significant (from 78.1 to 108.1). Post-void residual urine decreased from 125 mL to 17 mL in voiding di- ary and from 197.3 mL to 40.2 mL in urodynamic study that was not statistically significant. Mean maximum cystometric capacity on standard cystometry increased from 325 mL to 359 mL from the preoperational to post operation time. The post operation pattern of voiding was interrupted flow. The complications were as follow, lead migration in 2 (4.4%), infection in 1 (2.2%), pain at lead site in 2 (4.4%), sensation of electrical shock in 1 (2.2%). According to the permission of ethics committee, the PNE lead was removed from the S3 foramen, but the connections and external pulse generator remained fixed in place for an- other 3 days and the third voiding diary chart was completed by the patient. The patient was not aware of lead removal. None of the responders in the first 7 days observed greater than 50% improvement in the third voiding diary, so it seems that the placebo effect in sacral nerve stimulation is negli- Table 1. Response rate in different study groups with percutaneous nerve evaluation. Variables Patients (no.) Responder (no.) Rate (%) P Total patients 45 28 62.2 Retention Complete 28 21 75.0 .023 Incomplete 17 7 41.1 Gender Male 14 7 50.0 .256 Female 31 21 67.7 Type Secondary 18 9 50 .167 Idiopathic 27 19 70.3 Age range (year) 1-18 7 4 57 .076 19-50 27 20 74 51-70 7 4 57 > 70 5 0 0 1304 | gible .In both responder and non-responder groups voiding dairy chart returned to the base-line. DISCUSSION Neuromodulation was approved by the FDA since 1997 to I-OAB and non-obstructive urinary retention.(5-10) In patients with non-obstructive urinary retention, SNM offers a superior therapeutic alternative to intermittent self-catheterization or indwelling catheters, which significantly influences the quality of life.(11) Long-term results for SNM in patients with chronic urinary retention are better than overactive bladder.(12) In reports, with at least 40 months follow up, success rate was between 55%-86%.(12-16) The best long-term results for SNM have been achieved in patients with non-obstructive urinary re- tention.(13,2) Side effects are low and/or uncommon. Infection, leg discomfort, pain at the lead site are the main complications, the less common adverse events are, bowel dysfunction, tech- nical problems and nerve irritation.(14,17-19) Although the mechanism of action of SNM is not clear, it is told that it affects brain networks, as well as modulation of spi- nal cord reflexes and afferent peripheral nerves. Candidates for neuromodulation must first undergo a screen test. There are two methods for screening, two-stage implantation technique with tined lead test, and the standard one-stage procedure following a positive PNE. The test duration is rather restricted in PNE due to the risk of lead migration, the success rate is between 33%-66% in different reports.(17,20-22) The risk with tined lead is lower, duration of the test is longer (about 4 weeks) and re- sponse rate is higher (about 60%-70%).(22-23) The cost of tined lead and the more difficult process of removal, compared to simple wire, are the drawbacks. Datta and colleagues reported equal results for both techniques in the women with urinary retention (one stage versus two stages) (about 70%).(14) According to the literature, evaluation of the results in the test period is based on more than 50% improvement in subjective and objective measures reported by the voiding diary chart. This is currently the only proven predictive factor in deter- mining long-term prognosis.(7) In this study we evaluated the Table 2. Urodynamic parameters (pre- and postoperative) with percutaneous nerve evaluation. Baseline Postoperative P Group 1* Pdet at maximum flow rate 19 (10-21) 31 (14-39) .107 Bladder contractility index 78.1 (60-115) 108.1 (86-197) .048 Bladder capacity (mL) 325 (226-450) 359 (317-524) .165 Residual urine (mL) 197.3 (110-450) 40.2 (5-145) .059 Maximum flow rate (mL/sec) 6.1 (0-12) 17.6 (15-22) .018 Bladder outlet obstruction index 16.5 (-9-27) -1.1 (-12-23) .096 Time to maximum flow rate (sec) 10.7 (2.6-19.4) 7.7 (2.1-13.9) .185 Voided volume (mL) 35 (0-150) 187 (90-340) .032 Group 2** Pdet at maximum flow rate 18 (12-23) 21 (15-29) .176 Bladder contractibility index 78.4 (61-105) 79.1 (76-98) .436 Bladder capacity (mL) 315 (225-450) 335 (315-470) .175 Residual urine (mL) 179 (120-446) 182 (103-435) .269 Maximum flow rate (mL/sec) 9 (0-12) 9.6 (0-14) .509 Bladder outlet obstruction index 16 (-5-29) 8 (-4-23) .108 Time to maximum flow rate (sec) 10.8 (6-18) 10 (7-30) .285 Voided volume (mL) 37 (0-140) 45 (0-120) .845 Key: Pdet, detrusor pressure. * Patients which responded > 50% to percutaneous nerve evaluation according to voiding diary. ** Patients which didn’t response < 50% to percutaneous nerve evaluation according to voiding diary. The numbers in the pirates are range. Miscellaneous 1305Vol. 11 | No. 01 | Jan-Feb 2014 |U R O LO G Y J O U R N A L pre and posttest urodynamic results, to look for another prob- able objective predictive factor. There are few reports in the literature about urodynamic outcomes after neuromodulation. In 2004, Sgupta and col- leagues reported changes in the urodynamic parameters in 30 women with urinary retention (fowler’s syndrome) who were able to void following neuromodulation. Twenty one underwent a permanent implant and nine had PNE. The re- sults of SNM in this study was attributed to the rise in the detrusor voiding pressure, they concluded that SNM does not relax the external sphincter directly.(24) In our study, 33.3% of patients which responded to PNE were male as detrusor voiding pressure is usually higher in men, although there was an increase in maximum detrusor pressure (from 19 cmH2O to 31 cmH2O), but it was not statistically significant (P = .107). The mechanism of action of SNM is unclear, although it seems both relaxant effect on the sphincter and increase in detrusor pressure are involved. Bannowsky and colleagues performed bilateral PNE in 42 patients (25 retention, 9 hy- persensitive urinary bladder and 8 detrusor hyperactivity). The mean age of participants was 49.2 years (14 male, 28 female). Twenty (47.9%) had positive test results (9 with re- tention, 7 with overactive bladder and 4 with pelvic pain syn- drome). They concluded that tined lead, leads to significantly higher response rate. The criticism over their conclusion is the rather low number of patients in the second group (11 patients).(25) In our study with unilateral PNE in the retention group, re- sponse rate was higher (62.2%). In their study in the group with urinary retention the PNE led to an average increase of the maximum detrusor pressure from 19 cmH2O (± 5 cmH2O) to 32 cmH2O (± 9.7 cmH2O) and a mean reduction of residual urine by 71%; none of them was significant (P = .068). There were 9 patients with retention that had responded to PNE. In their study an average increase in maximum flow rate from 8 ± 2.2 mL/sec to 16 ± 3.6 mL/sec also was not statistically significant (P = .06). However, as they included three dif- ferent groups (retention, overactive bladder and pelvic pain syndrome), the results have not been mentioned each group separately. Our study was focused on the retention group and according to results they were divided into two groups, re- sponders and non-responders. Jonas and colleagues reported the results of 68 patients with non-obstructive urinary retention which responded to PNE, 31 individuals were randomly assigned to a group with de- layed implanted pulse generator implantation after 6 months, in this interval 9% of these patients (only 2 of 22) had more than 50% improvement in their symptoms, compared to the 83% in group with immediate implanted pulse generator implantation.(2) Demographic and clinical characteristics of these two patients were not mentioned in this study. A clini- cal trial in new onset (less than 2 years) idiopathic complete urinary retention with only percutaneous nerve evaluation may be useful. CONCLUSION Table 3. Preoperative urodynamic parameters in responder and non-responder to percutaneous nerve evaluation. Variables Group 1 (Responders) Group 2 (Non responders) P Pdet at maximum flow rate 19 (10-21) 18 (12-23) .543 Bladder contractibility index 78.1 (60-115) 78.4 (61-105) .508 Bladder capacity (mL) 325 (226-450) 315 (225-450) .487 Residual urine (mL) 197.3 (110-450) 179 (120-446) .309 Maximum flow rate (mL/sec) 6.1 (0-12) 9 (0-12) .415 Bladder outlet obstruction index 16.5 (-9-27) 16 (-5-29) .567 Time to maximum flow rate (sec) 10.7 (2.6-19.4) 10.8 (6-18) .576 Voided volume (mL) 35 (0-150) 37 (0-140) .498 Key: Pdet, detrusor pressure. The numbers in the pirates are range. Percutaneous Nerve Evaluation (PNE) in Non-Obstructive Urinary Retention | Sharifiaghdas et al 1306 | In selected patients with non-obstructive urinary retention, SNM offers an effective, minimally invasive treatment op- tion. Patients with complete non-obstructive retention are good responder to PNE. There was not any predictive param- eter of failure of PNE according to urodynamic parameters. None of pre-operative urodynamic parameters could predict the success rate of PNE. Efforts should continue to further optimize patient selection and improvement of the testing technique. The placebo effect in sacral nerve stimulation is negligible. CONFLICT OF INTEREST None declared. Table 4. Findings demonstrating no placebo effect. Responders (n = 28) Pre-stimulation PNE period* Post PNE** Mean Voided volume (mL) 35 187 39 CIC Time per day (mean) 8 1 8 Post void residual urine (mL) 125 17 127 Key: PEN, percutaneous nerve evaluation; CIC, clean intermittent catheterization. *Seven days voiding diary ** The third voiding diary Miscellaneous REFERENCES 1. White WM, Dobmeyer-Dittrich C, Klein FA, Wallace LS. Sacral nerve stimulation for treatment of refractory urinary retention: long-term efficacy and durability. Urology. 2008;71:71-4. 2. Jonas U, Fowler CJ, Chancellor MB. Efficacy of sacral nerve stimula- tion for urinary retention: results 18 months after implantation. 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