| Abstract|| |
Acute urinary retention (AUR) is one of the most important long-term complications of benign prostatic hyperplasia (BPH). Nitric oxide (NO) as a transmitter can relax smooth muscles of the bladder neck and external sphincter. Several studies have reported that sublingual isosorbide dinitrate (ISDN), as a NO donor, can lead to significant decrease in resting pressure of the external sphincter, and its rapid onset of action may be useful in the treatment of AUR. This study was designed to asses the effect of ISDN on AUR in patients with BPH. In this clinical trial, 60 men with BPH-induced AUR were randomly selected via a simple sampling method. Participants were randomly divided into case and control groups. Patients in the case group received 200 mg of sublingual ISDN and participants in the control group received placebo. After 20 min, participants were asked to void spontaneously and the urine was collected in scale containers. Following this, urethral catheterization was done on all the participants and the residual urine was measured. Data were analyzed using SPSS version 15. There was no significant difference in the mean age of the two groups (P-value = 0.28). The mean voided urine volume in the case group was 201 mL and, in the control group, it was 18 mL (P = 0.004). About 30% in the case group and 3.3% in the control group could void spontaneously after receiving ISDN or placebo (P = 0.006). In the case group, there was a significant correlation between voided urine volume and total urine volume in the bladder (P = 0.03) and in the size of the prostate (P = 0.001). Our study shows that ISDN can be effective in the treatment of BPH-induced AUR with decrease in bladder outlet resistance. ISDN is more effective in younger men and in those with smaller prostates.
|How to cite this article:|
Tadayyon F, Izadpanahi M, Aali S, Mazdak H, Khorrami MH. The effect of sublingual isosorbide dinitrate on acute urinary retention due to benign prostatic hyperplasia. Saudi J Kidney Dis Transpl 2012;23:782-5
|How to cite this URL:|
Tadayyon F, Izadpanahi M, Aali S, Mazdak H, Khorrami MH. The effect of sublingual isosorbide dinitrate on acute urinary retention due to benign prostatic hyperplasia. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2013 May 23];23:782-5. Available from: http://www.sjkdt.org/text.asp?2012/23/4/782/98160
| Introduction|| |
Benign prostatic hyperplasia (BPH) is an important health problem that has involved millions of men all over the world.  Histological prevalence of BPH rapidly increases from the fourth decade of life, and reaches to 100% by the eighth decade of life.  The clinical signs and symptoms of BPH include bladder outflow obstruction, poor bladder emptying, urinary retention, urinary tract infection, hematuria and renal failure.  Acute urinary retention (AUR), which is defined as an acute inability to void, is an urologic emergency and remains one of the most important long-term complications of BPH. ,,, The relative risk of AUR increases with age, symptom severity of BPH, prostate larger than 30 mL, flow rate less than 12 mL/s and high levels of prostatic specific antigen (PSA). ,
Smooth muscle is a major cellular part of BPH, and includes about 40% of hyperplastic prostate.  Studies have shown that adrenergic agonists (like norepinephrine) have a role in human prostate constriction and alfa blockers can improve symptoms of BPH.  The first-line treatment for AUR is catheterization, concomitant use of alfa blockers with catheterization, increases the chance of normal voiding and trial without further need for a catheter. ,
Nitric oxide (NO) as a transmitter can relax smooth muscles of the bladder neck and external sphincter via cyclic GMP (cGMP). , Several studies have reported that administration of sublingual isosorbide dinitrate (ISDN), as a NO donor, can lead to significant decrease in resting pressure of external sphincter and relaxation of smooth muscles of the bladder neck, and its rapid absorption and rapid onset of effect (4-5 min) may be useful in the treatment of AUR. ,,,,,,
Catheterization, which is the standard treatment for AUR, is an invasive method and has serious complications like urethral stenosis and infection.  Because there is no accepted medical treatment for AUR, and because sublingual ISDN is not expensive, easily available and has fewer complications compared with catheterization, we designed this study to assess the effect of ISDN on AUR in patients with BPH.
| Patients and Methods|| |
This study was a clinical trial on patients with BPH and AUR who were referred to urological emergency wards in the teaching hospitals in Isfahan, Iran. The Ethics Committee of the Isfahan University of Medical Sciences approved this study. A total of 60 men with BPH-induced AUR were randomly selected via a simple sampling method. Inclusion criteria were: patients with AUR due to BPH and acceptance for receiving sublingual ISDN. Exclusion criteria were: patient's non-acceptance, AUR due to urethral stenosis, AUR with neurologic disorders like neuropathy or spinal cord injury, G6PD deficiency, history of drug hypersensitivity, systolic blood pressure (SBP) less than 90 mmHg and AUR not related to BPH.
Written informed consents were obtained from all the participants. After obtaining proper history and conducting physical examination, 60 patients who satisfied the inclusion criteria were randomly divided into two groups: case group and control group, with 30 subjects in each group. Patients in the case group received 200 mg of sublingual ISDN and those in the control group received sublingual placebo. After 20 min, participants were asked to void spontaneously and their urine was collected in scaled containers. Following this, urethral catheterization was performed on the participants and the residual urine was measured and noted. All the above procedures were performed by a urology assistant who was aware of the objective of the study. Demographic data, history and physical examination findings and measured urine volumes were recorded in specific questionnaires.
Data were analyzed using SPSS version 15. "t " test was used for comparison of mean of urine output between two groups and Pearson correlation coefficient was used for assessment of correlation between volume of urine voided after ISDN and total urine volume in bladder.
| Results|| |
In this clinical trial, 60 men with BPH-induced AUR were randomly divided into case and control groups, with 30 participants in each group. [Table 1] shows the mean and standard deviation of variables in the two groups. The mean voided urine volumes were 201 mL and 18 mL in the case and control groups, respectively (P = 0.004).
|Table 1: Characteristics of patients in the isosorbide dinitrate and placebo groups.|
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No significant difference was observed in the SBP between the two groups before and after administration of ISDN (P = 0.07). The mean reduction of SBP with ISDN was 18 mmHg and, with placebo, it was 10.5 mmHg. The mean reduction of diastolic blood pressure (DBP) with ISDN was 6 mmHg and, with placebo, it was 3.5 mmHg. Nine participants (30%) in the case group and one (3.3%) in the control group could void spontaneously 20 min after administration of the medication; the difference was statistically significant (P = 0.006). Data analysis in the case group showed significant inverse correlation between total urine volume in the bladder and the volume of urine voided (P = 0.03). This suggests that more urine in the bladder leads to less voided volume after administration of ISDN. According to Pearson correlation coefficient, there was significant inverse correlation between voided urine volume and age (P = 0.007) and between size of prostate and voided urine volume (P = 0.001) in the case group. There was no significant correlation between urine output and SBP and DBP, duration of BPH and history of AUR.
| Discussion|| |
Bladder catheterization is the standard method for treatment of AUR. Because no medical treatment has been approved for AUR and BPH is the most common cause of AUR in men, finding a useful non-invasive treatment for AUR is necessary and valuable. ,,, On the other hand, as AUR is an urologic emergency,  short-acting medication with immediate effect on relaxation of bladder outlet is necessary. NO can relax smooth muscles via increasing cGMP. Many studies have shown that change in the NO-cGMP path can cause BPH and lower urinary tract symptoms (LUTS) like AUR. ,,
Studies have reported that local or systemic administration of NO donors like ISDN can reduce the infra-vesical resistance and improve the BPH-induced AUR. ISDN via increase in NO and cGMP can relax smooth muscles. ISDN has a rapid onset of action with few side-effects, and is not costly. ,, Evidences have shown that long-term use of NO may prevent or reduce progress of BPH. 
Klotz et al, in their study in 1999, showed that oral NO donors can improve peak flow rate, International Prostatic Symptom Score and post-void residual volume in patients with cardiac diseases.  Montner et al showed that ISDN can decrease pressure in the bladder neck area in healthy young men (mean age = 25.5 years) and can rapidly decrease bladder outlet resistance.  Reitz et al concluded that NO donors like ISDN as a potential pharmacologic choice can decrease bladder outlet obstruction in patients with spinal cord injury.  In another study, Reitz et al showed that sublingual ISDN in healthy men can decrease resting pressure in the external sphincter of the bladder. 
Our study showed that sublingual ISDN, compared with placebo, can significantly improve BPH-induced AUR (P <0.05). Our results are in concordance with the results of other studies; ,,, however, our study is the first study that assessed the effect of ISDN in patients with BPH-induced AUR.
The most common side-effect of ISDN is headache  and, in our study, only four participants developed headache that rapidly subsided with oral acetaminophen.
The results of the current study show that the efficacy of ISDN in BPH-induced AUR is inversely correlated with age and prostatic size. This finding could be due to lesser size of prostate in younger men and higher amount of fibromuscular tissue in smaller prostates. Thus, ISDN can be a useful treatment modality in younger men with BPH-induced or postoperative AUR. This result is similar to that of Montener et al,  and Reitz et al,  although in their studies the mean age of the study patients was less than our study and the participants did not have BPH-induced AUR. ,
We conclude that ISDN can be effective in the treatment of BPH-induced AUR with decrease in bladder outlet resistance. ISDN is more effective in younger men and smaller prostates. Further studies are necessary to assess the efficacy of ISDN as a pharmacological treatment for BPH-induced AUR.
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Assistant Professor, Department of Urology, Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan