1320 | Single Dose Silodosin Prior to Voiding Cystourethrogram: A Pharmacological Ad- junct to Enhance Visualization of Posterior Urethra Deepak Sharanappa Nagathan, Divakar Dalela, Satyanarayan Sankhwar, Apul Goel, Amod Kumar Dwivedi, Rahul Yadav Corresponding Author: Divakar Dalela, MD Department of Urology, Chhatra- pati Shahuji Maharaj Medical University, Erstwhile King George Medical College, Lucknow, UP, India. Tel: +91 522 2256543 Fax: +91 522 2256543 E-mail: drdalela@satyam.net.in Received April 2012 Accepted October 2012 Department of Urology, Chhatra- pati Shahuji Maharaj Medical University, Erstwhile King George Medical College, Lucknow, UP, India. BRIEF COMMUNICATION ABSTRACT Voiding cystourethrogram (VCUG) is needed to ascertain the upper end of urethral stricture. Occasionally, a patient is unable to open the bladder neck with resultant failure of the test. Real- izing the strong and prompt alpha antagonistic action of silodosin, we evaluated single 8 mg dose as a pharmacological adjunct prior to VCUG to overcome this problem. Keywords: voiding cystourethrogram; silodosin; posterior urethra. INTRODUCTION Voiding cystourethrogram (VCUG) is a commonly used technique to image the poste-rior urethra. In contrast to the retrograde urethrogram, opening of the bladder outlet and distension of the posterior urethra are achieved during VCUG. Sometimes pa- tient is unable to void and open the bladder outlet with resultant failure of contrast to reach the upper end of the obliteration. This makes assessment of length of the stricture difficult especial- ly in a case of pelvic fracture urethral distraction defect (PFUDD). Various methods have been used to overcome this problem such as passing a bougie through the suprapubic route, passing ureteric catheter antegradely under cystoscopic guidance into the posterior urethra followed by instillation of contrast and magnetic resonance imaging (MRI). However, these alternative methods are invasive except for MRI. Silodosin is a highly selective α1A-blocker which acts on α1A receptors on bladder outlet and prostate. Silodosin, with rapid onset of action and with its time to peak concentration approxi- Brief Communication 1321Vol. 11 | No. 01 | Jan-Feb 2014 |U R O LO G Y J O U R N A L Silodocin Prior to VCUG | Nagathan et al mately being 2.6 hours,(1) we explored the usefulness of si- lodosin prior to VCUG to improve the opening of bladder outlet and delineate the posterior urethra. MATERIALS AND METHODS All men attending the urology clinic with pelvic fracture urethral distraction defect and stricture urethra with com- plete obliteration of urethral lumen requiring VCUG were included in the study. Children, men who voided per urethra, men with neurogenic bladder/ vesical calculus or having con- traindication to the use of silodosin (severe hepatic or renal impairment) and who refused to give consent were excluded from the study. All men initially underwent VCUG in the conventional manner. Men who failed to open the bladder outlet during conventional VCUG were done repeat VCUG the next day with a single dose of silodosin 8 mg admin- istered three hours prior to repeat VCUG. VCUG was per- formed by filling the bladder with contrast medium (made by 76% sodium diatrizoate with distilled water in the ratio of 1:4) through an indwelling suprapubic catheter. When the patient felt the normal desire to void, voiding command was given and a conventional X-ray film was taken. The X-ray films were reviewed by a senior urologist to note the opening of bladder outlet and visualize the posterior urethra. Baseline demographic characteristics, indication for VCUG, duration of suprapubic catheter and amount of contrast used to fill bladder were noted. The results are presented in means (± SD) and proportions with its 95% confidence intervals. RESULTS Forty men met the inclusion criteria from August 2011 to February 2012. Their demographic data are presented in Ta- ble. The mean age was 41.8 years with an average body mass index of 23.12 kg/m2. The various indications for perform- ing VCUG were PFUDD 20/40 (50%), post traumatic bulbar urethral stricture 7/40 (17.5%), lichen sclerosis 6/40 (15%) and post catheterization stricture 7/40 (17.5%). All men had a suprapubic catheter (SPC) and the mean duration of SPC was 3.5 months. On an average 326.5 mL of contrast was used to fill the bladder to initiate voiding. Of participants 28/40 [70%, 95% confidence interval (CI): 56%-84%] men were found to have bladder outlet opened. A total of 12 men couldn’t initiate voiding at the first VCUG (Figures 1, and 2A). After administration of single dose 8 mg silodosin 3 hours prior to VCUG, opening of bladder outlet was achieved in 10 out of 12 men (83.3%, 95% CI: 55%-104%) thus helping in assess- ing the stricture length (Figure 2B). All men completed the study. None of the men reported any adverse effect following administration of the drug. The most prevalent adverse effects of silodosin are hypotension and ejaculatory disturbances. We looked at postural hypotension by measuring blood pressure at baseline, 0, 5 and 10 minutes after administration of drug. There was no significant drop in the blood pressure after administration of drug and none of the patients complained of ejaculatory disturbances because they were not sexually active during the study period. DISCUSSION It is important to define the length of the stricture before op- erating a case stricture urethra or PFUDD. Various methods such as combined retrograde urethrogram and micturition cystourethrogram,(2) passing of curved metal sound,(2) mag- netic resonance imaging(3) and antegrade urethrogram(4) have been used to overcome this problem. Although combined RGU and VCUG is useful, sometimes bladder outlet does not open because of reduced bladder capacity due to long stand- ing SPC and inability to tolerate the bladder distension suf- ficient enough to open the bladder outlet voluntarily.(5) Pass- Figure 1. Retrograde urethrogram showing complete oblitera- tion at the junction of bulbo-membranous urethra in a man with pelvic fracture urethral distraction defect. 1322 | ing of curved metal sound may be deleterious in some cases with inadvertent injury to the bladder outlet. Antegrade ure- throgram is also useful but is an invasive procedure, requires an expertise and a cystoscope which may not be available at the site of radiology suite to pass the ureteral catheter in posterior urethra. Although MRI is non-invasive, it is costly and urologists are not familiar in interpreting an MRI. Also, at MR imaging it is not easy for the patients to open their bladder outlet continuously by straining and increasing the abdominal pressure. Silodosin is a new α-adrenoreceptor (AR) antagonist and has been approved by the US Food and Drug administration in 2008 for the treatment of lower urinary tract symptoms as- sociated with benign prostatic hyperplasia. Silodosin with its favorable pharmacological profile having rapid onset of ac- tion within 2 hours(6) and higher affinity for α1A adrenergic receptors compared to tamsulosin and alfuzosin(7) is ideal in this circumstance to relax bladder outlet and prostatic urethra to initiate voiding. In the present study 10 out of 12 men who failed to initiate voiding, voided with the use of silodosin thus substantiating the role of a single dose of silodosin prior to VCUG. In two patients SPC was in situ for more than 10 months and contrast back leaked by the side of SPC despite all maneuvers to prevent it. The probable cause for failure to void was the presence of SPC for long term which caused a low compliant and overactive bladder which did not allow the bladder to be filled to its normal capacity. The factors which influence the opening of bladder outlet in- cludes amount of urine in the bladder and an intact nervous system facilitating the micturition process. The micturition process is innervated by parasympathetic nerves (detrusor contractility), sympathetic nerves (bladder outlet relaxation) and somatic nerves (urethral sphincter relaxation). The ben- eficial effects of α1A AR blockers are associated mainly with relaxation prostatic and urethral smooth muscle. However the bladder outlet also consists of bladder neck, prostate, in- traprostaitc urethra and external sphincter. These outlet struc- tures contain α1A AR. (8) Therefore, blocking these receptors reduces resistance and facilitates voiding. During VCUG, few individuals are anxious because of unnatural position and unfamiliar surroundings with resultant increased sympa- thetic drive which may preclude opening of the bladder out- let and failure of the test. Highly selective α1A blockers with short peak onset of action such as silodosin are effective in such circumstances when administered prior to performance Figure 2B. Voiding cystourethrogram shows opening of bladder outlet and delineation of proximal urethra after administration of silodosin. Figure 2A. Voiding cystourethrogram shows failure of bladder outlet to open in same patient. Brief Communication 1323Vol. 11 | No. 01 | Jan-Feb 2014 |U R O LO G Y J O U R N A L REFERENCES 1. Rossi M, Roumeguère T. Silodosin in the treatment of benign pros- tatic hyperplasia. Drug Des Devel Ther. 2010;4:291-7. 2. Goel MC, Kumar M, Kapoor R. Endoscopic management of trau- matic posterior urethral stricture: Early results and follow-up. J Urol. 1997;157:95-7. 3. Sung DJ, Kim YH, Cho SB, et al. Obliterative urethral stricture: MR urethrography versus conventional retrograde urethrography with voiding cystourethrography. Radiology. 2006;240:842-8. 4. Goel A, Gupta A, Dalela D. Antegrade urethrogram: A technique to visualise the proximal bulbous urethral segment in anterior ure- thral stricture. Indian J Urol. 2009;25:415-6. 5. Sandler CM, McCallum RW. Urethral trauma. In: Pollack HM, McClen- nan BL, editors. Clinical urography. 2nd ed. Philadelphia: Saunders; 2000. p. 1819-37. 6. Matsubara Y, Kanazawa T, Kojima Y et al. Pharmacokinetics and dis- position of silodosin (KMD-3213). Yakugaku Zasshi. 2006;126:247- 56. 7. Cantrell MA, Bream-Rouwenhorst HR, Hemerson P, Magera JS Jr. Silodosin for benign prostatic hyperplasia. Ann Pharmacother. 2010;44:302-10. 8. Mattiasson A, Andersson KE, Elbadawi A, Morgan E, Sjögren C. Inter- action between adrenergic and cholinergic nerve terminals in the urinary bladder of rabbits, cats and man. J Urol. 1987:137:1017-9. the test. In the study by Tsumura and colleagues(9) patients with pros- tatic cancer who had prostatic implants as part of brachyther- apy were prophylactically administered silodosin showed significant improvement in the post void residual urine at 6 months vs. tamsulosin. In another study Uchiyama and col- leagues(10) have prospectively studied the effect of silodosin on lower urinary tract symptoms in female and have found silodosin to be effective in improving voiding, storage symp- toms and quality of life. Uroflowmetry parameters improved in most patients along with significant reduction in postvoid residual urine. One of the limitations in the present study was that there was no control group. Also, there are no similar studies to the best of our knowledge to compare our results. Randomized, placebo controlled trial are required to further confirm our findings. CONCLUSION The use of single dose silodosin (8 mg) to effectively open the bladder outlet and visualize the posterior urethra prior to VCUG. CONFLICT OF INTEREST None declared. Table . Demographic data of men undergoing voiding cystourethrogram. Variables Voiding cystourethrogram, n = 40 Age, years (mean) 41.8 (20-70) Etiology, no. (%) Pelvic fracture urethral distraction defect 20 (50.0) Bulbar urethral stricture 20 (50.0) Post traumatic 7 (17.5) Lichen sclerosis 6 (15.0) Post catheterization 7 (17.5) Duration of suprapubic catheterization, months (mean) 4 (1-6) Volume of contrast instilled into bladder to initiate voiding before voiding cystourethrogram, mL 326.5 (150-450) Bladder outlet opened on initiation of voiding 28/40 (70%, 95% CI: 56%-84%) Bladder outlet opened on initiation of voiding with silodosin 10/12 (83.3%, 95% CI: 55%-104%) Silodocin Prior to VCUG | Nagathan et al 1324 | 9. Tsumura H, Satoh T, Ishiyama H, et al. Comparison of prophylac- tic Naftopidil, tamsulosin and silodosin for 125I brachytherapy- induced lower urinary tract symptoms in patients with prostate cancer: randomized control trial. Int J Radiat Oncol Biol Phys. 2011;81:e385-92. 10. Uchiyama T, Yamamoto T, Sakakibara R, Yanagisawa M, Knai K, Mori M. Selective A1A-blocker “silodosin” safety improves female lower urinary tract dysfunctions. Available from: www.icsoffice.org/Ab- stracts/Publish/106/000722.pdf Brief Communication