Clinical Review: Overactive bladder syndrome

Contributed by Miss Jane Boddy, urology specialist registrar and Mr Zaki Almallah, consultant urologist at the Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust.

Urine dipstick: All patients with OAB should be tested for UTI
Urine dipstick: All patients with OAB should be tested for UTI

Section 1 Epidemiology and aetiology
The International Continence Society (ICS) has defined overactive bladder (OAB) syndrome as the presence of urgency with or without urge UI, usually with frequency and nocturia.1

OAB affects both men and women and prevalence rises with age, affecting approximately 16.7 per cent of those aged over 40 years in North America and Europe.2

Urgency and particularly urge incontinence are distressing symptoms that can impact on a patients' physical and psychological well-being.

The majority of patients with OAB present initially to primary care, where they can be diagnosed and managed appropriately without the need for secondary care referral.

Referral may be necessary for certain patients and it is important to understand the indications for this.

Pathophysiology
Normal detrusor contractions are mediated through the release of acetylcholine at the neuromuscular junction.

Once released, acetylcholine binds to postsynaptic muscarinic receptors, in particular the M3 receptor, resulting in detrusor contraction.

Under normal circumstances detrusor contractions only occur during the voiding phase of the micturition cycle.

OAB symptoms are thought to arise when involuntary detrusor contractions occur during the filling phase, a period when the bladder should be at rest.

When this activity is observed during urodynamic investigation it is refered to as detrusor overactivity.

Establishing the exact nature of presenting symptoms is vital in the diagnosis of OAB.

When UI is present, it is important to distinguish between urge and stress incontinence.

Definitions
ICS definitions for urinary incontinence

Stress UI (SUI) is involuntary urine leakage on effort or exertion, or on sneezing or coughing.

Urge UI (UUI) is involuntary urine leakage accompanied or immediately preceded by urgency (a sudden compelling desire to urinate that is difficult to defer).

Mixed UI is involuntary urine leakage associated with both urgency and exertion, effort, sneezing or coughing.

Alternative causes of urgency and frequency

General
- Excessive fluid intake
- Diabetes mellitus/insipidus
- Congestive cardiac failure
- Renal disease
- Neurological disorder
Urological
- UTI bladder tumour/carcinoma in situ
- Bladder stone
- Urethral diverticulum
- Pelvic pain syndrome/interstitial cystitis
Obstetric/gynaecological
- Pregnancy
- Postmenopausal atrophy Pelvic/genital infection
- Pelvic mass (benign/malignant)
- Previous pelvic surgery/radiotherapy
- Prolapse/cystocele

Section 2 Diagnosis
For patients with OAB symptoms with or without urge incontinence who also have stress incontinence, it is important to establish the primary complaint as this requires treatment first.

After clarifying the nature of the presenting symptoms, a number of key areas must be explored to enable identification of any potential predisposing or exacerbating factors, as well to exclude alternative diagnoses.

An obstetric and gynaecological history must be taken, making note of any previous incontinence or pelvic surgery.

History and bladder diary
A history of concurrent neurological or respiratory disease is also important, as are any abnormalities of sexual and bowel function. A drug history will enable detection of drugs known to exacerbate urinary symptoms.

Finally, it is vital to detect 'red flag' symptoms that may indicate more sinister pathology requiring referral. Symptoms include haematuria, pain, recurrent UTI or neurological/locomotor abnormalities.

A useful adjunct to the medical history in the assessment is the bladder diary or frequency-volume chart. Patients are asked to record a number of variables including times of micturition, voided volume and incontinence episodes, for a minimum of three days, encompassing typical variations in usual activities.

A period of three days allows for day-to-day variation while maximising patient compliance. Such diaries enable a number of important parameters to be determined such as fluid intake, functional capacity, frequency, urgency, incontinence episodes and pad usage.

Quality of life questionnaires (for example, International consultation on incontinence quality of life score or Bristol female lower urinary tract symptoms questionnaire) can help assess the impact of symptoms on day-to-day life.

Examination
An examination should be conducted on all patients and include assessment of urinary, gynaecological and neurological systems. Abdominal palpation and vaginal examination will enable identification of a palpable bladder, prolapse or pelvic mass, as well as determine the patient's estrogen status.

It is essential to carry out a urine dipstick for all patients presenting with OAB symptoms. This will exclude UTI. Those with microscopic haematuria or sterile pyuria may need referral.

An MSU sample must be sent for analysis in the event of a positive dipstick. Patients with voiding symptoms, recurrent UTIs, prolapse or a history of previous surgery, where incomplete bladder emptying may exist, should have a post-void residual. This can be done using either a bladder scan or an in-out catheter.

Urodynamics
The use of urodynamics is not required in the routine assessment of OAB or before the start of conservative treatment.

Referral to secondary care for urodynamic investigation is backed for patients with OAB symptoms who fail conservative treatment, have voiding dysfunction or have had previous surgery for stress incontinence or anterior compartment prolapse.

Assessment of OAB in primary care

Initial assessment

  • History and examination +/bladder diary and quality of life questionnaire
  • Urine dipstick +/MSU and post-void residual volume

Aims of initial assessment

  • Categorise as OAB/UUI, SUI or mixed UI
  • Identify predisposing factors/alternative diagnoses
  • Identify 'red flag' symptoms requiring referral:
    - Haematuria
    - Pain
    - Recurrent UTI
    - Neurological/locomotor abnormalities

Section 3 Management
Patients with OAB can usually be assessed, diagnosed and managed in primary care. Most will respond to conservative management, which includes lifestyle modification, bladder training and pharmacological treatment.

One of the important lifestyle modifications recommended is the regulation of fluid intake by avoiding stimulants such as caffeine and alcohol, adjusting the volume of fluid consumed, and avoiding carbonated drinks.

NICE also recommends weight loss in those with a BMI over 30, as it has been shown to reduce the number of urgency episodes.3

Bladder training is a very effective, non-invasive treatment for OAB symptoms and can offer symptomatic cure or improvement. It should be performed for a minimum of six weeks.

Pelvic floor exercises are primarily used in the management of SUI but have been shown to be useful in OAB, to help defer urgency episodes.

Anticholinergic drugs
If frequency remains troublesome despite conservative measures, then an anticholinergic (also known as an antimuscarinic) can be added. Approximately half of patients will benefit from anticholinergics.

These drugs act by inhibiting voluntary and involuntary detrusor contractions and improving both functional capacity and detrusor compliance. This is achieved by the competitive blockade of acetylcholine at the postsynaptic M3 receptor, although they may also act upon afferent receptors in the suburothelial plexus.

Complications are common and include dry mouth (20-30 per cent), constipation (10 per cent), dry eyes, blurred vision due to failure of accommodation (<5 per cent), dizziness, cognitive impairment and difficulty voiding.

Elderly patients are at greater risk of these side-effects and may require a reduced dose. Contraindications to the use of anticholinergics include acute angle glaucoma, myasthenia gravis, significant outflow obstruction, severe ulcerative colitis and GI obstruction.

Anticholinergics vary in their selectivity for the postsynaptic muscarinic receptor, duration of action and mode of administration. The latest generation of anticholinergics is designed to increase efficacy and reduce side-effects by targeting the M3 muscarinic receptor and using extended-release preparations.

NICE recommendeds non-proprietary oxybutynin as first-line treatment and if not tolerated, alternatives such as darifenacin, solifenacin, tolterodine, or different oxybutynin formulations can be tried.3

All patients should be counselled on side-effects prior to treatment and should understand that the drugs aim to ameliorate symptoms. Compliance, however, is poor, and early treatment review is important to enable different formulations to be tried in the event of side-effects.

Other medicationsOther medications that can be of use include intravaginal estrogen in postmenopausal women with vaginal atrophy,4 and synthetic vasopressin (for example, desmopressin)5 or tricyclic antidepressants in those with nocturia. Although desmopressin can reduce nocturia it is important to monitor patients for fluid retention or hyponatraemia.

Its use is contraindicated in those over 65 years of age and those with cardiovascular disease or renal impairment. Likewise, tricyclic antidepressants such as imipramine should be used with caution in the elderly due to cardiac side-effects.

Section 4 Referral for further measures
If conservative measures and anticholinergics fail to control symptoms, then referral is needed for consideration of more invasive treatment options. These include botulinum toxin (BTX) injections, neuromodulation and surgical intervention.

All three aim to increase functional capacity, decrease maximum detrusor pressure and protect the kidneys.

Botulinum toxin injections
BTX is an effective alternative for those who have failed conservative measures. The toxin exists in many forms although only forms A and B are used clinically.

Toxin A is by far the most commonly administered. Toxin A blocks the proteins involved in acetylcholine release at the neuromuscular junction, affecting the micturition reflex.

It is administered intravesically using a cystoscope and can be given under local anaesthetic, as a day case procedure.

Mild flu-like symptoms can occur and may last up to one week. Other complications include haematuria, infection and more rarely, generalised weakness, diplopia, swallowing or breathing difficulties.

Approximately one-fifth of patients will be temporarily unable to void following BTX injections and therefore all patients should be taught how to perform intermittent self-catheterisation prior to the treatment.6

Symptoms are typically relieved for six to 12 months and return as a result of nerve re-sprouting. There is no reduction in efficacy with repeated doses.

Contraindications include myasthenia gravis and Eaton-Lambert syndrome as well as pregnancy, breastfeeding and clotting disorders.

It is important to ensure that patients know BTX remains unlicensed for this indication and that there is a relative lack of long-term follow-up data.

Neuromodulation
An alternative to BTX is neuromodulation. This uses electrical stimulation of afferent bladder nerves to modulate activity in the efferent fibres, and hence suppress reflex involuntary bladder contractions.

There are two main types depending upon the level of afferent stimulation.

Percutaneous tibial nerve stimulation is the minimally invasive option but has had limited success.

Sacral neuromodulation is the invasive option, requiring implantation of an electrical device to stimulate the S3 nerve root. This technique is effective but is only suitable for a select group of patients.

Surgical intervention
If all the above options fail then surgical intervention may be considered.

Options include detrusor myectomy, augmentation cystoplasty and urinary diversion. However, these options are associated with significant morbidity and patients must undergo comprehensive counselling.

Finally, for those patients unfit to undergo surgery a long-term suprapubic catheter could be considered.

OAB is a common complaint that can have a devastating impact on quality of life.

Most patients can be effectively assessed and managed in primary care, using lifestyle modification, bladder training and anticholinergics.

Referral to secondary care should be made for any patient presenting with 'red flag' symptoms or those who fail to improve with conservative measures.

Resources

1. Abrams P, Cardozo L, Fall M et al. The standardisation of terminology of lower urinary tract function: report from the Standard Sub-committee of the Int Continence Society. Neurourol Urodyn 2002; 21: 167-78.

2. Milsom I, Abrams P, Cardozo L et al. How widespread are the symptoms of an overactive bladder and how are they managed? BJU Int 2001; 87: 760-6.

3. NICE. UI: the management of urinary incontinence in women. CG40. October 2006.

4. Cardozo L, Lose G, McClish D, Versi E. A systematic review of the effects of estrogens for symptoms suggestive of overactive bladder. Acta Obstet Gynecol Scand 2004; 83: 892-7.

5. Hashim H, Malmberg L, Graugaard-Jensen C, Abrams P. Desmopressin as a 'designer-drug' in the treatment of OAB syndrome. Neurourol Urodyn 2009; 28: 40-6.

6. Schmid DM, Sauermann P, Werner M et al. Experience with 100 cases treated with botulinum-A toxin injections in the detrusor muscle for idiopathic OAB syndrome refractory to anticholinergics. J Urol 2006; 176: 177-85.

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