Acute Urinary Retention: a review of the aetiology and management

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1 (2004) 7, & 2004 Nature Publishing Group All rights reserved /04 $25.00 Review Acute Urinary Retention: a review of the aetiology and management K Thomas 1 *, K Chow 1 & RS Kirby 1 1 Urology Department, St George s Hospital, London, UK Acute retention of urine (AUR) is a common urological emergency characterised by a sudden inability to pass urine associated with lower abdominal pain. In recent years, the natural history and incidence of AUR has become better understood, however, further research into methods to prevent it and evaluation of the impact an episode of AUR has on the patient is required. This review provides an overview of the current management of AUR in men and the impact of the condition on patients quality of life. (2004) 7, doi: /sj.pcan Keywords: acute urinary retention; catheterisation; quality of life; benign prostatic hyperplasia Introduction Acute retention of urine (AUR) is a common urological condition that often presents as an emergency with a sudden inability to pass urine associated with lower abdominal pain. 1,2 The reported incidence varies between studies from a 4 to 73% 10-year risk of AUR. 3,4 One of the most common causes of acute urinary retention is benign prostatic hyperplasia (BPH), which with an ageing population is likely to increase. It may be anticipated, therefore, that the incidence of AUR will also rise, unless preventative measures are taken for the treatment of BPH. 5 The immediate management of this condition varies between institutions, but usually involves placement of a urinary catheter either, supra-pubic or urethral, medical therapy and either immediate admission to hospital or discharge home with outpatient follow-up. 6,7 In recent years, the natural history and incidence of AUR has become better understood, however, further research into methods to prevent it and evaluation of the impact an episode of AUR has on the patient is required. This review provides an overview of the current management of AUR in men and the impact of the condition on patients quality of life. Search methods A Medline search using databases from 1966 to 2003 was conducted using the words acute AND retention AND *Correspondence: K Thomas, Urology Department, Ashford Hospital, Middlesex, UK. specialkthomas@hotmail.com Received 28 August 2001; revised 9 October 2003; accepted 20 October 2003 urin* in the title, limited to English language. From this search 465 records were identified. Further information was gathered from related references within the articles identified and by hand searching recent abstracts at urological scientific meetings. Of the 465 records identified, 121 were case reports of unusual cases of AUR. Aetiology The precise aetiological factors responsible for the development of AUR are still unproven but the main mechanisms postulated are (Table 1): (1) increased resistance to flow of urine via mechanical or dynamic means 8 (2) interruption of sensory innervation or motor supply to detrusor muscle 9 (3) overdistension of the bladder. 1,2,10 Increased resistance to the flow of urine can occur secondary to a mechanical obstruction such as stricture or prostatic enlargement, or less commonly an increase in either the smooth or striated muscle tone. Interruption of the sensory or motor nerve supply to the detrusor muscle is caused by a variety of pathologies, for example, spinal cord lesion (traumatic or neurological), diabetic neuropathy, cerebrovascular accident. Overdistension of the bladder is seen after a general anaesthetic or a large fluid challenge (often with alcohol). Postoperative AUR occurs during a prolonged procedure with the patient uncatheterised and in men who have had mild symptoms of BPH preoperatively. It is also exacerbated by the use of opiates, concomitant anticholinergic administration and the generalised increase in alpha-adrenergic activity that exists after surgery. 11

2 Table 2 Potential neuromodulators in the bladder 33 Table 1 Pathogenesis of AUR Pathogenesis Increased resistance to flow Interruption of sensory or motor innervation to detrusor Example Prostatic hyperplasia Urethral stricture Detrusor sphincter dysynergia Spinal cord lesion Cerebrovascular lesion Diabetes mellitus Acetylcholine (ACh) Noradrenaline (NAd) Vasoactive polypeptide (VIP) Neuropeptide Y (NYP) Substance P (SP) Enkephaline Somatostatin Nitric oxide (NO) Overdistension Postoperative Opiate analgesia Large volume alcohol consumption Table 3 Risk factors for AUR Risk factor Parameter Relative risk Confidence interval A scientific explanation for the clinically observed aetiologies has been explored, with the following processes thought to be involved; 1. prostatic infarction neurotransmitter modulation. 15,16 3. stromal epithelial tissue ratio. 17,18 Prostatic infarction has been discussed as a potential cause for AUR by several authors Spiro et al evaluated the potential role of prostatic infarction as a cause of AUR by examining open prostatectomy specimens of 200 patients. The first 100 patients had large prostates and AUR, while the second group of 100 patients had elective surgery for BPH. In all, 85% of the AUR group had histological evidence prostatic infarction compared with 3% of the elective group. It has also been proposed that the elevated prostate-specific antigen (PSA) found in patients with AUR is secondary to prostatic infarction. 14 Experimental work in animals has suggested that there may be multiple neuromodulators affecting the nerves that supply the bladder and urethra (Table 2). 15,16 Reversible and irreversible changes are seen when AUR is induced experimentally in animals. In particular, changes in the nonadrenergic, noncholinergic neurotransmitters have been reported in rats. It has been shown that if the episode of AUR is not relieved, cell death in ganglia in the bladder wall can occur within 24 h and is well established by 48 h. A retrospective study in a small number of patients (10) found that the ratio of stromal to epithelial tissue was decreased in patients with AUR compared with agematched controls. 17 This finding was confirmed by another group, who conducted a prospective study of the TURP specimens of 70 patients (35 with AUR and 35 with symptomatic BPH). The AUR group had a significantly higher epithelial component 71%, compared with the BPH group 60% (Po0.01). 18 The cause for this observation is uncertain, but it may explain why finasteride, which acts on the epithelial component, is effective in the prevention of AUR. Identification of risk factors The exact aetiology of AUR is still unclear, however, there are studies that have identified risk factors for AUR in men and calculated the overall risk at 5 7/1000 year (Table 3). Age a 470 y Symptoms a IPSS Prostate volume a 430 ml Flow rate a o12 ml/s Risk factor Parameter Area under the curve PSA b Transition zone index c a Jacobsen et al. 19 b Roehrborn et al. 22 c Kurita et al. 25 The most comprehensive of these is the Olmstead County trial, which identified a cohort of men in the general population aged between 40 and 79 y. 19 Those with previous history of prostatectomy, prostate cancer or any other condition except benign prostatic hyperplasia were excluded from the study. The 2115 men recruited underwent an interview, completed a questionnaire and had their flow rate measured. Of these, 537 (25%) were randomly selected for a clinical examination, PSA measurement and trans-rectal ultrasound (TRUS) of the prostate. The men were followed up for a median average of 50 months. The risk of AUR was shown to be increased with age, from 1.6% risk at 5 y for men aged y to 10% for men aged between y. The symptom correlation was also found as men with moderate to severe symptoms had three times the risk of AUR compared with those with none to mild symptoms. In younger men, symptoms of double voiding and stopping and starting appeared most significant. A single peak flow rate measure of o12 ml/s correlated with a four times risk of AUR and a prostate volume 430 ml was associated with a threefold increase in risk. Potential limitations of this study were the retrospective collection of follow-up data, the ethnic and socio-economic status of the population studied, who were mostly white, middle class men. Also, the age range of the men was below that of most patients admitted with acute retention in the UK and elsewhere. 20 These factors mean that caution should be taken in extrapolating the findings to hospital practice elsewhere in the world. The risk factors discussed have also been identified in other studies. In a population-based study of 6100 male health professionals aged between 45 and 82 y, it was found that older age (470 y), moderate or severe lower urinary tract symptoms and the use of medications with

3 34 adrenergic or anticholinergic side effects significantly increased the risk of AUR. 21 The placebo arms of trials of pharmaceutical treatments for BPH provide useful epidemiological data and have demonstrated that PSA, prostate volume and symptom severity significantly affect the risk of AUR With increased use of TRUS, the transition zone index (TZI ¼ transition zone volume/total prostate volume) has recently been suggested as a predictor for acute retention. 25 Treatment Catheterisation The initial management of AUR of urine is prompt relief of retention and pain by catheterisation of the bladder. This can be achieved via the urethral or supra-pubic route, each of which has its merits. Depending on the cause of the episode of AUR, local policy, the patient s physical condition and social circumstances they may be discharged with the catheter or admitted into hospital. Urethral catheterisation is performed more commonly than supra-pubic because of concern regarding the potential complications of inserting a supra-pubic catheter and that the personnel (ie accident and emergency staff, family practitioners) who first see patients with AUR are generally more familiar with this method. 26,27 A prospective study of 86 patients with AUR catheterised described a significantly lower incidence of urinary tract infection (18 vs 40%) and stricture formation (0 vs 16.7%) with supra-pubic vs urethral catheters. 28 It was also commented that trial without catheter was easier as it merely required clamping and unclamping of the supra-pubic catheter. The relatively high stricture rate may be explained in part by the now outdated use of latex catheters by this group; however, the incidence is still likely to be higher than when the supra-pubic route is used. The lower infection rate with supra-pubic catheterisation was also reported by a group, who randomised patients to urethral vs suprapubic catheterisation. 29 Also, it was noted that patients found the supra-pubic catheter was more comfortable and easier to manage. Despite these findings the majority of patients with AUR are still managed with a urethral catheter, probably due to the continuing perception of supra-pubic catheterisation as a potentially hazardous procedure. 30 A novel suggestion recently by one group is that patients with AUR can be managed by clean intermittent self-catheterisation (CISC). 31 The authors found that the CISC group had a higher rate of spontaneous voiding (56 vs 25%) and lower infection rate (32 vs 75%) compared with the indwelling catheter group. They concluded that patients found CISC acceptable and manageable and experienced fewer complications than those with an indwelling catheter do. An area of debate is the timing of the removal of a catheter (trial without catheter or TWOC). While some have found no difference in success rates at 24 and 48 h, 32 others have suggested a benefit to waiting longer, particularly in men with large residual volumes 41l. 33 It has recently been suggested that prostate size g, residual volume 41 l and age 475 y may reduce the chance of successfully voiding after a TWOC. 34 It has also been suggested that the use of an alpha blocker may improve the success rate of a TWOC. 35 Pharmacotherapy There has been an increasing trend towards the use of drugs in both the prevention and treatment of AUR due to prostatic obstruction. The two main classes of drugs used are alpha blockers and 5 alpha-reductase inhibitors. Alpha blockers act by relaxing the smooth muscle in the bladder neck and prostate thereby decreasing the resistance to urinary flow. The potential role of alpha blockers in the treatment and prevention of AUR was first described 25 y ago. 36 Since then different types of alpha blockers have been produced and reported to have differing side effect profiles. 37 The impact of some of these in the prevention of AUR has been compared against placebo. A double-blind study of 2084 patients randomised to terazosin or placebo, reported no difference in the incidence of AUR in each group during the 1 y follow-up period. 38 In contrast, a study of 81 patients with AUR randomised to receive either alfuzosin or placebo for 48 h prior to trial without catheter after 24 h showed that those patients on alfuzosin had a significantly increased chance of passing a trial without catheter, 55 vs 28% (P ¼ 0.03). This effect was sustained over 18 months of follow-up. 39 Finasteride was until recently the only 5 alphareductase inhibitor available, although now a newer agent, dutasteride, is available. 40,41 They act by selective inhibition of 5 alpha-reductase responsible for the conversion of testosterone to dihydrotestosterone. 42 In a large double-blind randomised placebo-controlled trial, 3040 men with moderate to severe lower urinary tract symptoms and enlarged prostates were recruited. 43 Over a 4 y period, they were treated daily with either 5 mg finasteride or placebo. AUR developed in 99 (7%) men in the placebo group vs 42 (3%) in the finasteride group. This represents over a 50% risk reduction for developing AUR. However, because of the relatively rarity of AUR, 15 men would have to be treated for 4 y to avoid one episode of AUR. Similar reductions in the risk of events such as heart attack or stroke occur with statins and antihypertensive medication. 44 A pooled analyses of three randomised trials comprising 4222 men with moderately symptomatic BPH treated with either finasteride or placebo for 2 y reported 81 episodes of AUR (24/2113 finasteride group, 57/2109 placebo group). 42 The hazard ratio for the occurrence of AUR was consistent among the studies with a 57% decrease in the hazard rate for patients treated with finasteride compared with placebo (Po0.001). Combination therapy Prevention of the progression of BPH and in particular AUR has been studied using the combination of an alpha-blocker and a 5 alpha-reductase inhibitor by several investigators Two four-arm randomised placebo-controlled trials compared placebo with an alpha-blocker, finasteride and combination therapy. Lepor et al used terazosin, whereas

4 the Kirby group used doxazosin with similar results. Both groups found that the alpha-blocker was an effective treatment for BPH and that over the study period of 1 y, finasteride or combination therapy was no more effective than an alpha-blocker alone. The medical therapy of prostatic symptoms (MTOPS) study, a 5-y multicentre clinical trial evaluated whether the treatment with doxazosin and finasteride was more effective than using either drug alone in preventing the clinical progression of BPH. 47 One of the endpoints for establishing the progression of BPH was AUR. The combination therapy and finasteride significantly reduced the long-term risk of AUR (crude rate per 100 patient years; placebo 0.6, doxazosin 0.4, finasteride 0.2, combination therapy 0.1). It was also noted that men in the placebo group with higher baseline serum PSA, prostate volumes and ages and lower flow rate were significantly more likely to progress. Surgical intervention At present, TURP still remains the gold standard surgical treatment for patients with AUR. It reduces the risk of developing AUR by a factor of eight. 48 It is not without risk, however, and if patients who have had an episode of AUR have a TURP they are at a higher risk of per-operative complications. 49 The National Prostatectomy Audit found that men undergoing a TURP within 30 days of an episode of AUR had an excess risk of death (relative risk 26.6, CI ). 20 With greater insight into the potential morbidity and occasional mortality associated with this procedure, alternatives have been sought in the form of pharmacotherapy and minimally invasive techniques. Most of these new technologies are still based on the endoscopic removal or ablation of prostatic tissue; Electrovaporisation, laser resection (holmium, Nd-YAG, ELAP, interstitial), interstitial radiofrequency (TUNA) and microwave thermotherapy (TUMT) Temporary or permanent urethral stents are available to keep the prostatic urethra open, but only provide modest improvements in symptoms with a high incidence of complications such as migration, infection, encrustation, obstruction secondary to prostatic ingrowth and calculus formation. 51 These problems have limited their current use to elderly infirm patients unfit for surgery. 53,54 Some patients may still be unable to void after a TURP. 55 Urodynamic evaluation has not been shown to predict this in patients under the age of 80 y as detrusor failure may recover postoperatively. 33 Therefore, urodynamics are not recommended for routine preoperative evaluation in this age group. The presence of residual volume ml, lack of detrusor instability, detrusor pressure at maximum fill of o9 cm water and maximal detrusor pressure o28 cm water were all found to predict treatment failure. Quality of life As AUR usually involves an emergency admission to hospital and insertion of a catheter, it is perhaps not surprising that some patients may find the event traumatic. There have been a few studies, that have looked at the impact of an episode of AUR on the patient, but this has remained a relatively neglected aspect of the management of this condition. A recent retrospective study of the management of patients with AUR in one surgeon s practice over a 23 y period showed that 90% of patients were discharged home with a catheter to await surgery. 56 While at home 72% of patients experienced some complication, 69% found the catheter uncomfortable and 65% found it inconvenient particularly with respect to finding adequate toilet facilities. Another group prospectively evaluated the impact of discharging patients with AUR home with a catheter by means of a self-completion questionnaire. 57 A total of 101 patients were seen with AUR and discharged home immediately with a catheter. In all, 93% of the questionnaires were completed. Unlike the previous group, the majority of patients (87%) did not find that the catheter limited their activities in anyway, although all of them had experienced at least one complication. The questionnaire used was not a validated measure, however, it did show that despite having complications from the catheter most of the patients still found having a catheter at home acceptable. This study challenges the perception of most clinicians that patients do not like having a catheter. Further work is required using validated questionnaires, a longer follow-up period and a broader evaluation of all aspects of quality of life to define the impact of AUR and having a catheter at home on patients. Future research There are various aspects of the management of AUR that should be targeted in the future: (1) catheters (2) minimally invasive therapy (3) medical therapy (4) quality of life Catheters are crucial in the management of AUR. The ideal catheter material would be inert, malleable, biocompatible and be resistant to colonisation with bacteria. In the future, newer technology in catheter design should make some of these properties possible and, therefore, reduce some of the complications associated with having a catheter. Evolution of minimally invasive techniques will make daycase treatment of BPH feasible, which should reduce the time patients spend at home with a catheter following an episode of AUR. As discussed previously, the use of combination therapy for the treatment of BPH offers the opportunity to prevent the progression of BPH and, therefore, episodes of AUR. Newer agents are under development and may prove to be even more effective than the current formulations. An episode of AUR can have an adverse effect on a patient s quality of life, which is further exacerbated by delay in treatment and, prolonged period of catheterisation. Awareness of the impact of AUR on a patient and streamlining of the treatment of AUR so that prompt effective care is delivered would reduce the impact it has on the patients, quality of life. 35

5 36 Discussion Although AUR is an age-old condition, it remains a modern day management problem. As demonstrated by Modi et al, treatment of patients with AUR may be considered to be regressing rather than progressing. 56 New pharmacological agents will emerge over then next few years as will variations on TURP using modern methods of tissue ablation. However, as clinicians we must not lose sight of the impact of these treatments on our patients. When introducing new therapies in the future the effect of these on the patients quality of life in addition to their clinical effectiveness must be evaluated if we are to improve our management of this common and disturbing condition. References 1 Emberton M, Anson K. in men: an age old problem. BMJ 1999; 318: Choong S, Emberton M.. Br J Urol 2000; 85: Ball A, Feneley R, Abrahams P. The natural history of untreated prostatism. Br J Urol 1981; 53: Birkhoff J, Wiederhorn A, Hamilton M, Zinsser H. 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