Management of Acute Urinary Retention

Introduction

Acute urinary retention (AUR) represents the most common urological emergency characterized by intense suprapubic discomfort and a sudden and painful inability to urinate despite having a full urinary bladder.^1-2-3      In practice, the condition is more common in men than women, by 13:1, and most frequently occurs in elderly men with underlying obstruction attributable to benign prostatic hyperplasia (BPH); often precipitated by factors inhibiting bladder contractility or increasing bladder outlet resistance.⁴

Risk factors

A number of factors predispose to the development of AUR, of which male gender, increasing age and severity of lower urinary tract symptoms (LUTS), depressed peak urinary flow rates, high postvoid residual (PVR) urine, and progressive enlargement of the prostate are particularly significant.^5-7   Importantly, the risk of AUR development correlates positively with the International Prostate Symptom Score (IPSS); and men with BPH have a 10- year risk of AUR development between 4% and 73%.

Causes of AUR

AUR is most often secondary to obstruction, but may also be related to trauma, neurologic disease, medication, infection, and occasionally psychologic issues.⁸  Causes can therefore be classified dependent on the underlying etiology as obstructive, infectious and inflammatory, pharmacologic, neurologic, or others (Table 1).  ^1,2,4,9,10         Often more than one mechanism may exist in a single patient  ¹¹  , and this is particularly relevant in the older patient, wherein several underlying factors interact to precipitate an episode of AUR.

Regardless, BPH is identified as the single most frequent cause of AUR in practice (Figure 1).⁸   It results in bladder neck obstruction through two mechanisms: prostate enlargement, and constriction of the prostatic urethra from excessive alpha-adrenergic tone in the stromal portion of the prostate gland.²   In individual cases, risk of AUR in BPH can be predicted based on prostate volume, serum prostate-specific antigen (PSA) level, and symptom severity.  ⁴

Diagnosis of AUR

Based on the severity, patients with AUR can present with complete lack of voiding, incomplete bladder emptying, or overflow incontinence. As such, although the onset of AUR episode will be sudden in almost all cases; urinary symptoms, such as difficulty starting urine, weak stream, feeling of bladder fullness, and possible urinary tract infection (UTI) and pain with urination, may be noticed prior to AUR. Diagnosis in most cases will therefore be supported by history and physical examination (Figure 2), selected diagnostic testing such as bladder ultrasound (Table 2), amount of urine returned with catheterization, and post-void residual volume.^1,2

In cases of BPH-induced AUR, there is a typical history of multiple LUTS, including frequency, urgency, nocturia, straining to void, weak urinary stream, sensation of incomplete bladder emptying, and stopping and starting of urinary stream.²   In such cases, a detailed medication history should be obtained, with special attention to factors that are known to cause urinary retention, even if considering an age dependent predisposition.

As well, abdominal and rectal/pelvic examination and investigations should be performed so as to convert the probable diagnosis based on history into a more definite one.^4,  12   Amongst imaging modalities, bladder ultrasonography is a preferred initial test because it is noninvasive and more comfortable for the patient, and because complications (such as UTI) can be avoided.

Management of AUR

The first and foremost intervention in AUR is to relieve the retention and achieve prompt and complete decompression by inserting a urinary catheter into the bladder.¹  Such quick, complete emptying of the obstructed bladder is safe, simple and effective, and is the recommended optimal method for decompressing the obstructed urinary bladder.¹³   Standard transurethral catheters – Foley’s catheter  ¹⁴   – are readily available and can usually be inserted with ease. However, if urethral catheterization is unsuccessful or contraindicated, the patient should immediately be referred to a physician trained in advanced catheterization techniques, such as placement of suprapubic catheter, which in fact is superior to urethral catheterization for short-term management.  ²

Treatment approaches

Less invasive approaches are in vogue to treating patients who present with the symptoms, sign, and condition of urinary retention.¹⁵   Catheterization provides immediate relief of an acute event; however, many men will ultimately have failure of a trial without a catheter (TWOC). As well, the catheter is uncomfortable, restricts activities, and is a potential source of infection if left in place for long-term. Hence, if possible, the use of chronic urethral indwelling catheters should be discouraged in order to avoid complications, whilst making efforts to prevent AUR, particularly in men at high risk for the condition.  ⁴   Such a potential morbidity associated with prolonged catheterization has consequently led to an increasing use of a TWOC after 1-3 days.  ¹⁶   It involves catheter removal after 1-3 days, allowing 23-40% of patients to void successfully, so that definite surgery, if needed, can be performed at a later stage.  ¹⁷   This is consistent with the American Urological Association (AUA) guidelines, which state that surgical intervention should only be considered after at least one attempted trial of voiding after catheter removal.

Further definite treatment following catheterization should be effectively tailored, dependent on the etiology of AUR (Figure 3).¹   A complete description of treatments for all possible etiologies would be beyond the scope, and this review focuses only the most common cause of AUR, i.e., BPH. Urology consultation may be needed for invasive diagnostic testing or management of refractory cases; particularly, cases of neurogenic bladder should be referred for urodynamic testing to guide ongoing management.²

Medications

Alpha-blockers

While the optimal amount of time to leave a catheter in place in patients with BPH is unknown; in addition, chances of urinary retention are considerably high if the bladder is simply drained. In this context, it has been shown that men with BPH have a higher chance of a successful voiding TWOC at 2-3 days if they are treated with alpha-adrenergic blockers (such as tamsulosin) for 3 days starting at the time of catheter insertion.²   Alpha-blockers relax prostatic smooth muscle cells, decreasing the resistance to urinary flow, and thus improve urinary urodynamic parameters of obstruction, providing quick symptomatic relief.¹⁸   Such a successful outcome – successful TWOC – is independent of the duration of catheterization, while affected by several intrinsic factors (Box 1).^19,20       Hence, most consultants follow the approach and initiate alpha-blockers with urethral catheterization or immediately following it.²¹

Alpha-blocker treatment is also generally safe and well-tolerated. While use of anticholinergic therapy has historically been contraindicated in patients with LUTS associated with BPH, because of concerns for developing and precipitating AUR;^4,  22   in contrast, alpha-blockers have low side effects that are comparable to placebo and consistent with known pharmacology.²³   Anticholinergic drugs may precipitate urinary retention by inhibiting detrusor contractility, and therefore warrant caution in elderly men with underlying BPH, who might be frequently receiving other drugs for comorbid conditions; most medications administered for depression, allergies, Parkinson disease, and overactive bladder (OAB) have anticholinergic properties.  ^4,  24   Male patients on anticholinergic treatment who are reporting increased hesitancy or showing signs of increasing postvoid residual urine or clinical evidence of retention should therefore be warned to stop the anticholinergic element of the combination therapy immediately. Conversely, alpha-adrenergic receptor-blocking agents decrease resistance along the bladder neck, prostate and urethra by relaxing the smooth muscle, and allowing passage of urine. Hence, they reduce bladder outlet obstruction by decreasing the alpha-adrenergic tone of the smooth muscle within the prostate, and lessen the symptoms related to urinary storage.

Advantage of tamsulosin in AUR

Alpha-antagonists are perhaps the most effective agents used to treat moderate-to-severe and bothersome symptoms associated with bladder outlet obstruction secondary to BPH.²⁵    Chances of men with AUR from BPH returning to normal voiding are particularly high if alpha-blockers are started at the time of catheter insertion.^1,2   In this context, an advantage of tamsulosin over doxazosin and terazosin is that a therapeutic dose can be administered at the onset of AUR, thereby reducing the time for attempting catheter removal.²⁶   Multiple clinical evidences support this application of tamsulosin in AUR related to BPH. Lucas and colleagues²⁷   evaluated the efficacy of tamsulosin compared to placebo for treating catheterized patients with AUR caused by BPH, and demonstrated that men catheterized for AUR could void more successfully after catheter removal if treated with tamsulosin, and were less likely to require re-catheterization. Similarly, a recently reported Mexican study by Maldonado-Ávila M et al²⁸   showed that tamsulosin had a tendency to be more effective than alfuzosin in a successful catheter removal. In this study, TWOC was successful in 43.2% patients in the tamsulosin group, 35.2% in the alfuzosin group, and 26.3% in the placebo group (Figure 4).

5-alpha reductase inhibitors (5-ARIs)

5-ARIs constitute another useful class of drugs in patients with BPH. In contrast to alpha-blockers, which target the dynamic component of bladder outflow obstruction; 5-ARIs reduce the static component and improve LUTS by decreasing prostate volumes in the presence of BPH.¹⁸   5-ARIs achieve this by blocking conversion of testosterone to dihydrotestosterone (DHT), which is the main hormone responsible for pathological enlargement of prostate. Hence, they interfere with the natural course of disease and provide long term benefits in terms of decreased incidence of AUR and surgery. A reduced relative risk of AUR (57%) and surgical intervention (48%) was shown with dutasteride treatment compared with placebo at 2 years (both p < 0.001 vs. placebo); the reduction was maintained to 4 years during the open-label phases of the studies.^29,30      Within class, the non-selective inhibitor of 5-alpha reductase – dutasteride – achieves more complete suppression as compared to selective inhibitor of type-1 isoenzyme – finasteride – demonstrating a theoretical superiority. This also translates into better symptomatic improvement and less incidence of AUR and surgery than finasteride.¹⁸  

It thus follows that if the cause of AUR is BPH; consider starting an alpha-adrenergic blocker and/or 5-ARI. Herein, while alpha-blockers facilitate catheter removal following episodes of AUR; 5-ARIs target the underlying disease process and significantly reduce the risk of AUR in men with enlarged prostates, and are therefore most useful in long-term.⁴   These complementary effects provide a sound rationale for combination therapy with alpha-blockers/5ARIs to provide greater and more durable benefits.

Flavoxate

The presence of phosphodiesterase enzymes in the prostate and the detrusor muscle of the bladder suggest that phosphodiesterase inhibitors like flavoxate may be appropriate therapy for BPH related LUTS. Flavoxate hydrochloride is a flavone derivative with smooth muscle relaxing activity, which is used for disorders caused by smooth muscle spasms. The drug may be used in patients with hyperactive bladder who do not achieve symptom relief and quality of life improvement with conservative management; as it was found to increase bladder capacity significantly, without increasing the post-void residual (PVR) urine in such patients.³¹

Importantly, the drug is free from the concerns associated with use of anticholinergics(note: anticholinergic drugs have been considered hazardous in BPH because of concerns that they may predispose to AUR³²  ), and can be used to alleviate the symptoms of LUTS. A Cochrane meta-analysis that demonstrated that adverse effects were generally worse in the anticholinergic groups than flavoxate adds to the favorable tolerability profile seen with flavoxate.³³   These beneficial effects hence make it appropriate for use in more vulnerable elderly population, with no risk of side effects or AUR.

Flavoxate can be used either alone or in combination with an alpha-1 adrenoreceptor blocker to alleviate LUTS. Supplemental administration of flavoxate – in favor of an antispasmodic and relaxant effect on the prostatic and bladder neck tissues³⁴   – with an alpha1-adrenoceptor blocker may be considered in patients with BPH, particularly in absence of significant PVR volumes, for a more effective improvement of quality of life.³⁵   The combination would result in significant benefits in quality of life scores, patient satisfaction, urinary frequency, storage symptoms and IPSS scores.  ³⁶   An Indian study by Dash A³⁷   also appears validating this fact. It demonstrated that taking a combination of tamsulosin with flavoxate significantly improved IPSS, irritating symptoms and quality of life, with good safety.³⁷

Preventing a second episode of AUR

There exists a high probability of experiencing a second episode of AUR immediately following a TWOC, the likelihood of which ranges from 38% to 56%, depending on the PVR urine volume, size of the prostate, and time interval between catheter insertion and the TWOC. As mentioned above, use of an alpha-blocker before catheter removal is advocated in such cases³⁸  , given an increased likelihood of a successful TWOC with tamsulosin.⁴

Furthermore, long term treatment with 5-ARI, or a combination therapy with 5-ARI and alpha-adrenergic blocker, may be required to maximize the prevention of subsequent episodes of AUR.²   Such a use of combination therapy is reasonable approach, particularly in men with large prostates, and should be the treatment of choice for those at high risk of disease progression.^4,18   Overall, the combination therapy has an advantage in maintaining patients in less severe symptom states.³⁹   In this context, data from the CombAT trial provides further evidence to support the use of long-term combination therapy (tamsulosin plus dutasteride) in men with moderate-to-severe LUTS because of BPH and prostatic enlargement.⁴⁰   The trial showed that combination therapy with tamsulosin and dutasteride significantly reduced the relative risk of AUR or BPH-related surgery compared with either monotherapy at 4 years. Combination therapy significantly reduced the risk of BPH clinical progression, supporting the long term use of combined therapy with dutasteride plus tamsulosin in men with moderate-to-severe BPH symptoms and a slightly enlarged prostate.^40,42       Safety and tolerability of dutasteride plus tamsulosin was consistent with previous experience of this combination and with the monotherapies.

Incidentally, tamsulosin with dutasteride combination is available in a unique single tablet containing tamsulosin with ADS (Advanced Delivery System) advantage (Box 2). Tamsulosin with ADS technology is a new improved formulation/delivery system of tamsulosin, which ensures continuous and consistent drug release throughout the entire length of the gastrointestinal tract, including the colon where water is poorly available. It results in a more constant exposure to tamsulosin over 24 hours with a smaller peak-to-trough fluctuation than the conventional formulations, and also reduces/eliminates the dependency on food.

Additional preventive measures to circumvent AUR include using the IPSS scale at each office encounter and avoiding constipation; anticholinergic medications can cause constipation as a side effect, which should be avoided. Furthermore, knowledge of the baseline serum PSA and/or prostate volume is also helpful to aid physicians in predicting the risk of BPH-related outcomes and choosing therapy for BPH. Often, patients having a subsequent episode of AUR, or who require surgery, have higher PVR urine following their successful TWOC, and thus may be differentiated as candidates for close follow-up and early intervention.⁵⁰

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