Definition
Urinary urgency, usually accompanied by increased daytime frequency and/or nocturia, with or without urinary incontinence, in the absence of UTI or other detectable disease
Urgency – complaint of sudden, compelling desire to pass urine which is difficult to defer
Urgency urinary incontinence – involuntary loss of urine associated with urgency
Frequency – complaint of voiding occurring more frequently than deemed normal by the individual (or caregiver)
Epidemiology
- Up to 10 – 16 % incidence in both men and women.
- 6 % associated with urinary incontinence.
- Prevalence increases with age, but OAB is not a normal part of ageing.
- Significant impact on QoL as well as financial and economic impact.
Pathophysiology / hypotheses
No clearly definable cause or direct pathophysiological mechanism can be identified.
Appears to be an imbalance in inhibitory and excitatory neural pathways to the bladder, or increased or unregulated afferent signalling
- Urothelium based hypothesis
- Hypothesised that urothelium actively responds to local mechanical, osmotic, inflammatory and chemical stimuli by triggering afferent nerves
- May be that in OAB intrinsic aberrations in homeostatic processes at level of urothelium trigger excess afferent stimulation
- Myogenic based hypothesis
- Localised detrusor contractions (‘micromotions’) may be excessively interpreted by afferent signals triggering sensation of urgency
- Micromotions in OAB may also become coordinated and trigger possibly urodynamic DO
- Visceral afferent cross-talk
- Afferent signals from other pelvic organs may be misinterpreted by brain as coming from bladder and triggering sensation of urgency
- Abnormal central handling of afferents
- Even in non-pathological state constant afferent signals sent to brain during filling (guarding reflex) – dysregulated modulation of these signals (normally subconscious) may be perceived as urgency
- Other theories under investigation
- Possible microbiome changes
Differential diagnoses (to exclude)
- Neurogenic bladder
- Bladder cancer
- Bladder stones
- Foreign body
- Ureteric stone
- Bladder pain syndrome
- Pelvic organ prolapse
- Bladder outlet obstruction
- UTI
- Diabetes insipidus
- Medical causes of nocturia
- Fluid overload
- Pelvic floor dysfunction
- Genitourinary syndrome of menopause
- Excessive fluid or caffeine
- TB
Work up
Don’t forget bladder diary and questionnaires
History:
- Characterise symptoms
- UUI/SUI/obstructive/mixed
- Pads/day, most bothersome symptoms
- Duration of symptoms, precipitants
- Red flag symptoms
- Haematuria, recurrent UTIs
- Medical history
- Competing co-morbidities, preclusions to GA, anti-cholinergic contra-indications
- Medications
- Lasix, anticoagulants, anticholinergic burden
- Previous surgery
- Any pelvic or abdominal surgery, particularly gynaecological
- Social history
- Level of bother
- Fluid intake, caffeine, triggering foods, smoking, alcohol intake
Exam:
- General – habitus, frailty, scars, pads, full bladder
- Pelvic – atrophy, prolapse, prostate
- Demonstrable stress incontinence
Investigations
- Bladder diary, questionnaires (ICIQ), flow rate and post-void residual
- Urine microscopy and culture
- Urine cytology if appropriate
- Bloods if not previously done – renal and liver function +/- PSA
- Ultrasound KUB
- ?Urodynamics
- If considering advanced therapies, or diagnostic dilemma
- ?Cystoscopy
- If concerns regarding alternate diagnosis – TCC, bladder stone, Hunner lesions, foreign body
Urodynamics
Urodynamics are essential to diagnose detrusor overactivity, but the absence of urodynamic DO does not preclude the diagnosis of OAB.
Not necessary in index cases or before trials of non pharmacological or simple medical therapies.
Can be considered or should be done:
- Prior to second line or more invasive treatments i.e. botox or SNS
- “will affect the decision to pursue or avoid an invasive, irreversible or potentially morbid treatment”
- Neuropaths
- Doubt about the diagnosis (rule out or quantify obstruction)
- High post void residual volumes
- Prior incontinence surgery (looking for obstruction)
The primary aim of urodynamics is to reproduce the patient’s symptoms and identify or exclude any factors which may change treatment (should be question oriented).
Two main urodynamic findings associated with OAB are detrusor overactivity and early or exaggerated filling sensation.
- Phasic DO – increasing contractions as volume increases, may or may not lead to incontinence
- Terminal DO – single involuntary detrusor contraction occurring at cystometric capacity, causing incontinence and often complete emptying
Non-phasic increases in pDet should be regarded as changes in compliance.
Approx 60 – 70 % men and 40 – 50 % women with OAB (OAB-dry) will show DO on UDS. Over 90 % of men with OAB-wet will have DO.
Other notes on UDS for OAB:
- If increased bladder sensation but no DO, can try and replicate normal triggers i.e., running water
- Consider filling rate, higher filling rate can induce DO but then may affect voiding, or could even mask DO
- Critical to assess for obstructed voiding and residual volumes
- Higher PVRs predict need for catheterisation after botox
- OAB symptoms are probably unlikely to improve without treatment of concomitant BOO – but – treatment of BOO does not necessarily improve OAB symptoms
- Terminal DO at reduced capacity predicts persistence of OAB symptoms after outlet treatment
- Fill either sitting or standing – OAB symptoms usually occur when in these positions
- Urodynamic report should clearly state whether usual symptoms were reproduced
Management
Quality of life condition – treatments determined by patient’s level of bother.
Potential risks and benefits should be weighed up and discussed (including financial, logistical, and any other considerations).
- Conservative
- Medical (anticholinergics, beta agonists, oestrogens)
- Advanced (botox, SNS, PTNS)
- Last-line (augment, diversion, catheters)
Goals of assessment and treatment:
- Exclude alternate or sinister diagnoses
- Improve quality of life and manage symptoms
- Reduce or get rid of incontinence
- Minimise side effects or harms
- Usually aiming for ‘control’ rather than ‘cure’
Conservative strategies
- Review and optimise medications and other co-morbidities (Lasix, diabetes)
- Limit caffeine and other bladder irritants (alcohol, soft drink, citrus, chocolate, spicy foods)
- Fluid restriction
- Weight loss
- Stop smoking
- Bladder re-training – delayed voiding with increasing delay
- Pelvic floor physiotherapist and pelvic floor muscle training
- Cognitive strategies – scheduled voiding
Medications
Bladder has more M2 receptors than M3, but M3 seems most important for detrusor contraction.
Predominantly B3 receptors of the 3 beta subtypes.
Oxybutynin
- Dose 2.5 – 5 mg up to TDS
- Blocks M1, M2 and M3 muscarinic cholinergic receptors, preventing parasympathetic stimulation and smooth muscle (detrusor) contraction.
- Tertiary amine which crosses blood-brain barrier.
- Contra-indications – acute open angle glaucoma, urinary retention, myasthenia gravis, impaired gastric emptying
- Cautions – elderly, cognitively impaired, multiple anticholinergic medications
- Side effects – dry mouth 80 %, constipation, dry eyes, blurred vision, urinary retention, confusion and cognitive changes, dizziness
- < 30 % compliance
- Efficacy – improvement in UUI episodes, NNT 9 for cure
Oxytrol (oxybutynin patch)
- Dose 3.9 mg / 24 hrs, changed twice a week
- Avoids first pass metabolism and reduces primary metabolite N-desethyloxybutynin which is implicated in dry mouth
- 10 % withdrawal due to skin effects – itch and erythema – occurs in > 20 %
Solifenacin
- Dose 5 – 10 mg daily
- Tertiary amine anti-cholinergic which is more selective for M3 receptors
- Metabolised by liver/CYP450
- Multiple RCTs comparing to tolterodine and placebo – reduces frequency, UUI
- Less adverse effects than oxybutynin but dry mouth and constipation still happen.
- Beneficial effects recorded at one week and got better over the first month.
Tolterodine
- IR dose 1 – 2 mg BD, or ER 2 – 4 mg OD (“Detrusitol”)
- No selectivity for receptors, but low lipophilicity and its metabolites imply limited penetration to CNS
Darifenacin
- Daily dose 7.5 – 15 mg (“Enablex”)
- Uroselective for M3 receptors.
- Seems to have relatively low rates of dry mouth and constipation.
Notes on anti-cholinergics
- Adherence is poor – side effects, cost, expectations of success all implicated
- No anti-cholinergic is clearly better than another from available evidence
- Extended release medications seem better tolerated and are preferred
- If poor response, can dose escalate, try a different anti-cholinergic, or combine with a beta3-agonist
- Patients must be monitored for side effects and efficacy
- Always check for glaucoma, delayed gastric emptying, myasthenia gravis, other anti-cholinergic medications
- Be careful of elderly and frail
Anti-cholinergics and cognitive function and old frail patients
- Elderly frail patients probably have less therapeutic efficacy and more risk of adverse effects
- There is lack of data as most trials exclude these patients
- Most data from trials only follow patients for 3 months and long term treatment effects unclear
- Cognitive deficits are commonly reported by the elderly on anti-cholinergic medications
- Longitudinal cohort studies have suggested deterioration in cognitive function and brain atrophy in patients using anticholinergics
- Difficult to truly assess given lack of long term follow up data and confounding factors in population (co-morbidities, polypharmacy, objective measures of baseline cognition)
- Always assess cognitive function and anti-cholinergic burden prior to starting these medications in elderly
Medications – non anti-cholinergic options
Mirabegron
- Daily dose 25 – 50 mg.
- Beta-3 receptor adrenergic agonist – activation of adenylyl cyclase -> cAMP -> smooth muscle relation.
- Metabolised in liver via multiple pathways.
- Multiple trials showing improvements in UUI and frequency.
- Dry mouth and constipation are equal to placebo.
- Contra-indicated in severe uncontrolled hypertension. Use caution with hepatic failure or renal impairment (start lower dose). Caution if prolonged QT interval.
- Small increases in HR and BP seen in trials, dose dependent. May cause headache.
Essentially as efficacious as anti-cholinergics, with adverse effects minimised.
Can be combined with anti-cholinergic safely and may improve efficacy.
No long term data on cognitive function available.
Oestrogen
- Topical oestrogen can be used to treat GSM – and subsequent OAB symptoms associated.
- Safe, and should be offered to all post-menopausal women with evidence of vaginal atrophy.