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Alpha-blockers increase the chances of a successful trial without catheter

Three Part Question

In [adult men presenting with urinary retention secondary to benign prostatic hyperplasia] are [alpha-blockers compared with placebo] more likely to lead to a [successful early trial without catheter]?

Clinical Scenario

A previously well 60-year-old gentleman attends your Emergency Department in acute urinary retention (AUR) for the past 10 hours. On closer questioning he reveals a history of preceding lower urinary tract symptoms.

Following the uneventful passage of a urethral catheter, the production of a residual volume <1000ml and the finding of normal renal function, you wonder whether starting a short course of an alpha-blocker prior to discharge from the Emergency Department may increase his chance of an early trial without catheter (TWOC).

Search Strategy

MEDLINE 1950 to September Week 2 2010 using the OVID interface.
[(exp Adrenergic alpha-Antagonists/ OR adrenergic alpha-antagonists.mp OR alpha blocker$.mp OR tamsulosin.mp OR alfuzosin.mp OR exp Doxazosin/ OR doxazosin.mp OR exp Indoramin/ OR indoramin.mp OR exp Prazosin/ OR prazosin.mp OR terazosin.mp) AND (exp Urinary Retention/ OR urinary retention.mp OR Urinary Catheterization/ OR urinary catheterization.mp OR urinary catheterisation.mp OR urethral catheteri$.mp OR bladder catheteri$.mp OR trial without catheter.mp)] LIMIT to humans AND english language AND male AND adult.

Search Outcome

192 papers were found, of which 178 were irrelevant or of insufficient quality. Of the remaining 14, there was 1 Cochrane Review found directly relevant to the three part question, 6 papers included in this review and 7 further papers of interest. These are summarised in the table below.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Tiong et al,
2009,
Singapore
67 men presenting with initial episode of spontaneous AUR secondary to BPH. Patients catheterised then randomised to receive placebo or Alfuzosin for 2 days.Double-blind prospective RCT.Primary outcome – rate of successful TWOC after 2 days.Significantly greater proportion of patients in Alfuzosin group (21/35 or 60%) had successful TWOC compared with placebo group (11/32 or 34%) (p=0.036).Initial data published in 2006 & included in Cochrane review below. Further patients added to initial set to form this published work. Still a small data set, ~30 patients in each arm. This may be too small to detect all predictive factors.
Secondary outcome – intravesical prostatic protrusion (IPP) detected by transabdo-minal USSPatients with grade 3 IPP (>10mm) had a significantly lower chance of successful TWOC (p=0.04) compared to grade 1 (<5mm) and 2 (6-10mm). Remained a significant independent predictor for failed TWOC (p=0.034) on multivariate analysis. This highlights the importance of prostate size as an independent negative predictor of successful TWOC on alpha-blocker.
Zeif & Subramonian (Cochrane review)
2009
UK
696 men in AUR secondary to BPH (5 trials ranging from 44-360 patients) 4 studies used Alfuzosin and 1 used Tamsulosin. 4 used the intervention between 24-72hrs before TWOC and the other for 8 days.Systematic review and meta-analysis of 5 double-blind prospective RCTs comparing alpha-blocker with placebo from UK, USA and Singapore.Primary outcome – successful TWOC.4 studies favoured alpha-blocker & 1 favoured placebo. Overall rates of successful TWOC tended to favour alpha-blocker over placebo. Statistically significant (RR 1.39, 95% CI 1.18 to 1.64) irrespective of alpha-blocker used (Alfuzosin RR 1.31, 95% CI 1.1 to 1.56; Tamsulosin RR 1.86, 95% CI 1.17 to 2.97)(1) Lack of internationally agreed outcome measures for what constitutes successful TWOC: (a) return to satisfactory voiding without need for re-catheterisation within 24hrs (b) ability to void with residual volume of <200ml (c) flow rate >5ml/s with voided volume >100ml & residual volume <200ml (d) successful voiding with residual volume <150ml (2) Only 1 study clearly described method of randomisation & allocation concealment; others stated randomisation but no description of methods or of concealment (3) Different drugs compared for different time periods is also a problem
Prevention of recurrent urinary retention after successful TWOC.1 study showed a favourable outcome for Tamsulosin over placebo that was statistically significant (RR 0.70, 95% CI 0.54 to 0.91). Effect only described for acute phase of study & not long term. Others assessed AUR relapse after successful TWOC but done during 2nd phases of studies where both successful alpha-blocker & placebo participants either re-randomised or continued on alpha-blocker treatment, so these data could not be used for analysis
Need for prostatic surgery.Although assessed in some studies, this outcome measure could not be assessed as both groups pooled together in one group following successful TWOC & either randomised again or continued (or commenced) on alpha-blocker
Persistent lower urinary tract symptoms.In 2nd phase (re-random-isation of successful TWOC patients) 1 study found significant improvement with alpha-blocker compared with placebo at 6/12 (IPSS 8.75 versus 11.45, p=0.012; bother score 1.66 versus 2.27, p=0.004). Due to re-randomisation could not use data as part of pre-defined 2y outcomes
Post-void residual volumes.Although one study reported on this outcome, numbers too small to draw meaningful conclusion (RR 0.82, 95% CI 0.16 to 4.24)
International Prostate Symptom Score (IPSS).1 study described statistically significant improvement with alpha-blocker compared with placebo (IPSS alpha-blocker 8.75 vs placebo 11.45, p=0.012; bother score with alpha-blocker 1.66 vs placebo 2.27, p=0.004)
Alpha-blocker side effects (SEs).SEs described included dizziness, somnolence, fainting, headache, postural hypotension or hypotension, malaise & syncope. 3 studies eligible for assessment. With regard to causing fewer side effects, 2 studies in favour of placebo & 1 favoured alpha- blockers. Overall outcome favoured placebo (RR 1.13, 95% CI 0.69 to 1.85) but not statistically significant.
Drop-out rates.Main reason was need for re-catheterisation. Vaso-dilatation-related SEs caused less drop-outs.
Prieto et al,
2008,
Spain
65 patients with AUR secondary to BPH. 47 evaluable, 46 compliant. 22 had doxazosin (born in even-numbered years), 24 no medication (born in uneven-numbered years) TWOC’d at 1 month.Quasi-RCT.Post-void residual volume measurement and flowmetry as markers of successful TWOC at 6 months, 1 year and 2 years.15/22 (69%) in treatment arm developed AUR within 24 years; 7/22 (31%) successful TWOC. 16/24 (67%) in control group developed AUR within 2 years; 8/24 (33%) successful TWOC. Therefore, no statistical difference between groups in terms of drug efficacy.No blinding – medication or no medication Groups nicely homogenous for age, prostate volume and blood pressure but very small in number, perhaps giving rise to a type I error.
Desgrandchamps et al,
2006,
France
2618 men with AUR enrolled by 658 French urologists.Prospective cross-sectional survey.Successful TWOC.Of 1906 men who had a TWOC, 79% received an alpha-blocker (mainly Alfuzosin) before catheter removal. TWOC was successful in 50.2% and success the rate was significantly higher in men receiving alpha-blocker (53.0% vs 39.6%, p<0.001) before TWOC. In men receiving alpha-blocker, success rate of TWOC also higher (55.2% vs 69.3%) when catheter removed after 1-3 days than for longer duration of catheterisation (45.6% vs 48.6%).Differences in clinical profile (spontaneous & precipitated AUR). BPH found in 52.3% with pAUR compared with 25.9% with sAUR. Those without BPH therefore having smaller prostates are more likely to succeed.
Abeygunasekera et al,
2001,
Sri Lanka
100 consecutive patients with 1st episode of AUR secondary to clinically benign enlarged prostate. All given Prazosin for 1 week then TWOC’d. Successful participants continued drug for 6 months.Prospective cohort study.Successful TWOC.56/94 (60%) initial success. Further 12 of these developed urinary retention during follow up and required surgery. Therefore, 47% successful TWOC at 6 months.Large proportion (71%) of patients had prostates <20g when clinically assessed which is more likely to yield a successful TWOC.
Kim et al,
2001,
USA
33 consecutive men with AUR. All given Tamsulosin for at least 4 days before TWOC. Successful TWOCs continued drug and followed up at 2 weeks, 3 months and regularly after for a median of 6.5 months.Cohort study.Successful TWOC.26/33 (79%). A further 3 had at least 4 days more Tamsulosin and passed a 2nd TWOC to yield 29/33 (88%).Small cohort study (n=33) where all patients given the drug. All 8 with pAUR had successful TWOC compared with 50% with sAUR. Again, these different aetiologies grouped together to draw conclusions.
TURP/ISC during follow up.9 (27%).
Mean symptom score12.9 at 2 weeks, 11.9 at 3 months.
QoL score.2.7 at 2 weeks, 2.8 at 3 months. Correlated strongly with failure of medical therapy.
Post-void residual volume.111ml at 2 weeks, 61.7 at 3 months. Correlated strongly with failure of medical therapy.
Mean peak urinary flow rate.7.7ml/s at 3 months.
Pandit et al,
2008,
India
68 patients (age range 50-91 years, mean 66.1) presenting with spontaneous AUR over a 1-year period. 57 diagnosed as having BPH and most of these had 3-15 days of alpha-blocker (Terazosin, Prazosin or Tamsulosin) prior to TWOC. Retrospective analysis of data from a prospective observational study.Successful TWOC at 1 week.57 patients diagnosed with BPH, of which 45 had TWOC and 12 scheduled instead for earliest possible elective surgery. 31 (68.9%) had successful TWOC. Overall success rate was 70%. Amongst those diagnosed with BPH, mean age, symptom score and prostate volume were recorded, with only symptom score showing a statistically significant difference between the successful and unsuccessful TWOC groups.Observational nature of study is surely its greatest weakness. Single-centre study but they use 3 different alpha-blockers over a wide-range of days prior to TWOC, and Finasteride was advised in addition for those with a larger prostate. Unclear even how many were given alpha-blockers, or how a diagnosis of BPH was achieved, other than presumptively. 2 patients excluded without reasons given. Huge element of bias based on their selective TWOC idea. 12 were not TWOC’d but scheduled for surgery and 15 were designated to be a UTI rather than BPH, so only given antibiotics, but often retrospectively found to have more evidence for the other diagnosis or even both.
Lo et al,
2010,
Hong Kong
248 patients (mean age 71, range 50-93) presenting with 1st episode of AUR secondary to BPH & who could void successfully after initial TWOC following treatment with alpha-blocker over a 4-year period. 19 (7.7%) given Terazosin, 214 (86.3%) given Doxazosin, 15 (6.0%) given Doxazosin gastrointestinal therapeutic system. Most patients (82.3%) received 1 dose prior to TWOC. Prospective cohort study.Primary outcome – failed medical treatment within 5-year follow up period.During this follow up period medical therapy failed for 118 (47.6%) patients, most commonly for recurrent AUR. Percentage of patients with medical failure at 6, 12, 24 & 60 months was 11.6, 14.3, 28.4 & 50.5% respectively.Calculations appear to have been based on the population assuming that the 23 patients who died & 1 lost to follow-up all had successful medical therapy. 436 originally presented with 1st episode of AUR secondary to BPH & therefore 188 failed TWOC initially with alpha-blocker in addition to those who subsequently failed during this follow up period. Different drugs & little detail about when TWOC’d, especially in respect to alpha-blocker doses. Cohort study, so many factors in play, rather that RCT comparing placebo and alpha-blocker, which would have been nicer. Relatively older study population may be a potential reason for failure, because role of age-related detrusor changes may also predispose to failure.
Multivariate analysis to discover significant predictors of medical failure after successful TWOC.Prostate size >50ml & serum PSA level during AUR >10ng/ml. Those with neither risk factor had a 5-year success rate of 63.8% compared with 29.4% for those patients with both risk factors, which was significantly lower (p<0.001).

Comment(s)

Observational studies have suggested successful TWOC rates to be between 23-28% but here we see 48-62% with an alpha-blocker from the studies in the Cochrane review, compared with 26-57% without: a statistically significant improvement. Overall side-effects seen in these studies are low and are a rare cause for study failure. It is uncertain from the data collected whether alpha-blockers reduce the risk of recurrent urinary retention and subsequent need for prostatic surgery, and therefore the cost-effectiveness and recommended duration of alpha-blocker treatment after a successful TWOC remains unknown. A lack of internationally agreed outcome measures for what constitutes a successful TWOC is a significant problem that impedes the likening of the data. Prostate enlargement, reduction of maximum flow rate and moderate or severe symptoms are variables independent of the therapeutic interventions. Micturition recovery after catheter removal seems to be dependent on the circumstances of the episode – since numerous factors are involved. Time also seems to have an impact and the presence of a urethral catheter within the bladder has been found to result in bacterial colonisation of the bladder at a rate of 4%/day, an important factor accounting for a significantly increased morbidity from infection. The National Prostatectomy Audit Steering Group looked at 3966 men undergoing TURP and found those presenting with AUR had a relative risk of perioperative mortality at 30/7 of 26.6, with an increased risk of perioperative complications, including sepsis and bleeding compared with men without a catheter. It is therefore desirable for a patient to undergo a TWOC after an episode of AUR so that they do not need their catheter at the time of surgery. Furthermore, some may not need surgery after an isolated episode of AUR.

Editor Comment

AUR, acute urinary retention; BPH, benign prostatic hyperplasia; FU, follow-up; IPP, intravesical prostatic protrusion; IPSS, international prostate symptom score; ISC, intermittent selfcatheterisation; pAUR, precipitated acute urinary retention; QoL, quality of life; RCT, randomised controlled trial; SE, side-effect; sAUR, spontaneous acute urinary retention; TURP, transurethral resection of prostate; TWOC, trial without catheter; USS, ultrasound scan; UTI, urinary tract infection.

Clinical Bottom Line

The limited available evidence suggests alpha-blockers increase the success rates of early TWOC.

Level of Evidence

Level 1 - Recent well-done systematic review was considered or a study of high quality is available.

References

  1. Tiong HY, Tibung MJ, Macalalag M, et al. Alfuzosin 10mg once daily increases the chances of successful trial without catheter after acute urinary retention secondary to benign prostate hyperplasia. Urologia Internationalis 2009; 83(1): 44-48.
  2. Zeif HJ, Subramonian K. Alpha blockers prior to removal of a catheter for acute urinary retention in adult men. Cochrane Database of Systematic Reviews 2009; 4: CD006744
  3. Prieto L, Romero J, Lo´pez C, et al. Efficacy of doxazosin in the treatment of acute urinary retention due to benign prostate hyperplasia. Urologia Internationalis 2008; 81(1): 66-71.
  4. Desgrandchamps F, De La Taille A, Doublet JD, et al. The management of acute urinary retention in France: a cross-sectional survey in 2618 men with benign prostatic hyperplasia. BJU International 2006; 97(4): 727-733.
  5. Abeygunasekera AM, de Silva S, Gurusingha A, et al. Management of men with a first episode of acute urinary retention due to benign prostatic enlargement. Ceylon Medical Journal 2001; 46(4): 124-125.
  6. Kim HL, Kim JC, Benson DA, et al. Results of treatment with tamsulosin in men with acute urinary retention. Techniques in Urology 2001; 7(4): 256-260.
  7. Pandit RK, Agrawal CS, Chalise PR, et al. Retrospective analysis of management of patients presenting with acute urinary retention due to benign prostatic hyperplasia: A hospital based study. Kathmandu University Medical Journal 2008; 6(4): 448-452.
  8. Lo KL, Chan MC, Wong A, et al. Long-term outcome of patients with a successful trial without catheter after treatment with an alpha-adrenergic receptor blocker for acute urinary retention caused by benign prostatic hyperplasia. International Urology and Nephrology 2010; 42: 7-12.