11.7: Treatment

AIMS:

• Protect renal function, prevent infection
• Restore continence
• Restore emptying
• Controlled collection of urine if restoration of function not possible

Planning of treatment is important as the underlying disease and the effect on the lower urinary tract symptoms is almost never stable and neither is the physical condition of the patient. These patients are therefore better cared for in a team situation or with close interaction with the neurologist.

Underlying condition should be stable.

E.g. - The spinal cord injury patient needs to be over the shock phase. The Parkinson patient, on effective treatment. The stroke patient rehabilitated and stable, etc.

Mobility of the patient

The next component of decision making is the mobility of the patient. Both in their ability to get to the toilet as well as good hand function and mobility. Treatment like timed voiding, self intermittent catheterization and catheter care might be impossible for certain patients. In other cases the patient might have access to support like nurses, family or institutions that can help with care of basic body functions, the decision making might differ according to circumstances.

Kidney Function

It is very important for the treating physician to remember the effect of the lower urinary tract symptoms on kidney function before decisions on treatment are made. Unstable bladder with detrusor sphincter dyssynergia (DSD) will lead to impairment of kidney function. If augmentation or diversion procedures are considered, kidney function and upper tract anatomy should be evaluated. Absorption of urea and electrolytes by the intestinal interposition can cause metabolic changes.

Conservative treatment

Conservative treatment entails triggered reflex voiding, bladder expression through crede or valsalva maneuver, timed voiding and fluid restriction. This treatment is normally given for supra-spinal lesions because of balanced bladder function. In the spinal lesions, diffuse neurologic conditions and lower lesions it must only be considered if the bladder is a low-pressure system. The reason is that there may be D-S-D with a risk to kidney function.

Conservative treatment must always form part of the total treatment of the patient, even in cases where more invasive treatment is indicated. It is difficult in the neurologic patient to completely restore normal function, therefore measures like timed voiding, fluid restriction and effort to empty completely need to be emphasized constantly. Pelvic floor exercise are normally not indicated in neurologic conditions but might give some improvement in patients with MS. Electric stimulation or biofeedback have the same limitations.

Catheters

Catheters are used to drain the bladder in patients where retention or incomplete voiding is present. They can also be used in incontinent patients, especially if cognitive function is impaired. Intermittent catheterization can be used if the storage pressures are low, the bladder has a good capacity and there is good hand control. Clean self-intermittent catheterization is still the best way to empty the bladder. It is important to motivate the patient to start doing it. Once they are used to it the result is usually good. The recommended frequency is 4-6 times per day with a bladder capacity of not more than 400ml and a 12-14-size catheter is used. Indwelling catheters are inserted either suprapubically or transurethrally for patients where there is either a high-pressure system or the possibility of selfcatheterization is not available, or in cases where patients lose mobility or cognitive function. There are significantly more risks with indwelling catheters compared to CISC and Silicone catheters should be used. Catheters normally need changing every 3 months but there are some patients that might need more frequent changing. Crystallization and blocking are the biggest problems.

Recommendations On The Use Of Catheters

Self clean intermittent catheterization is superior to any of the other techniques as long as the bladder is not a high-pressure system.

Indwelling catheters are safe and sufficient for short-term management of urinary retention. The use of indwelling catheters routinely for the management of the neurologic bladder is not recommended.

Complications of supra-pubic catheters are similar to those of urethral indwelling catheters. Apart from insertion, that has a higher risk, supra-pubic catheters have the possibility of bowel perforation and urethral catheters cause urethral incompetence over time.

Protective pads and diapers, protective clothing or pads for the incontinent patient is sometimes the only way to protect the patient from skin reactions and a bad odour.

Pharmacotherapy

Pharmacotherapy is mainly used for overactivity of the bladder. There are practical options for improving of bladder emptying. Again, as with the previous treatments, the detrusor function, as well as the urethral function have to be seen as separate entities and a decision on which pharmacotherapeutic agent will work best in each specific instance is important. Only broad guidelines will be given on which treatment modalities will work better for a specific condition.

Drugs Available For Treatment Of Neurologic Lower Urinary Tract Overactivity:

Detrusor muscle relaxing drugs:

• Oxybutynin
• Darifenacin
• Solifenacin
• Tolterodine
• Properverine
• Trosium
• Propantholene
• Flavoxate
• Tri-cyclic anti-depressants

Discussion

Drugs to reduce over activity of the bladder and increase the storage function of the detrusor. The mainstay of treatment in this group are the anticholinenrgic drugs. The newer anticholinergic drugs as in Oxybytinin, Darifenacin, Tolterodene and Solifenacin are all available as a long acting preparations. This gives better long-term effects and less side affects. The side effect profile of the different medications is well known as in central nervous system effects, cardio vascular effects, dry mouth and constipation. There are specific advantages and disadvantages of each of the long acting anticholinergic medications. It is important to decide which ones will work best in a specific case and it is important to make sure the patient complies with the intake of the medication and that the long term effect thereof is measured. With proper care and information the side effect profile is limited. Oxybutynin is also available as an intravesical installation as well as a transdermal absorption application. There is no clear recommendation that any of these drugs is superior in all cases of detrusor over activity.

Drugs work on nerve function

• Valinoïds eg. Capcacin and Resinoferatoxin blocks sensory nerves for afferent sensation to the brain.
• Botulinum toxin

Vaniloids

The study showed that Resinoferatoxin is a much more potent sensory antagonist than Capcacin and is superior in terms of efficacy. In studies it has been shown that the maximum cystometric capacity increased significantly but it did not change detrusor pressure significantly. It is currently recommended that further randomized trials must be done to determine the exact place for this treatment modality. It has been studied in neurogenic bladders and compared to Botox but shown to be less effective.

Botulinum toxin A

Botulinum toxin A is the most potent biologic toxin known to man. It binds the snap 33 docking protein in the nerve terminal. Inhibiting acetylcholine release from the nerve terminal and thus preventing muscle contraction. This can give clinical improvement for six to nine months in neurologic patients by lowering detrusor contraction and increasing bladder capacity. Numerous studies have been done which shows efficacy of the Botulinum toxin, starting within the first six days and has an optimum effect after six weeks. The individual response is fairly specific for a patient. If the effect lasts for six months the first time, the follow up injection will normally also last about that long. The current use in neurologic overactivity is 300 units as an intravesical injection. Two Botulinum type A toxins are available. Botox is most widely used in current studies. Botox is normally given as a 10 unit per m/L in 30 different sites of the bladder. It can be given under general, regional or local anaesthetic. No clear randomized study has been done to evaluate the specific treatment strengths. Botulinum toxin can also be used into the sphincter to reduce the outflow resistance. The dose used in the sphincter is 50 – 100 units. It was clearly shown to reduce the post void residual. The side effect profile is extremely low and systemic complications almost unheard of. Other form of Botulinium A (Dysport) has been studied but not as widely and is also effective with other possible side effects, and different dosage regimens.

Drugs to enhance sphincter function

• Alpha -adrenergic agonists
• Estrogens
• Beta-adronergic agonists
• Tri-cyclic anti-depressants

Several drugs including AlphaAdronergic agonists, Estrogens, Beta-adrenergic agonists, as well as Tricyclic anti-depressants have been used to increase the bladder outlet resistance. There is no clear recommendation whether these can be used for long-term treatment of sphincter deficiency. A noradrenaline serotonin reuptake inhibitor (duloxitene) has been well studied and will increase urethral resistance. The side effect of this is nausea and it is also used in the treatment of depression.

Drugs to facilitate bladder emptying

• Alpha adrenergic blockers – lowers urethral resistance e.g. Tamsulosin, alfuzosin
• Cholinergic - increases detrusor contraction

Discussion

1. Alpha-Adrenergic blockers: Alpha-adreno receptors have been reported to be predominantly present in the bladder base and urethra. Alpha-blockers can therefore be used to lower the resistance of the bladder neck and urethra. They have been proven to lower the detrusor leak point pressure in children.
2. Cholinergic: In general Betanecol chloride seems to be of limited benefit of detrusor areflexia and for elevated residual urine. These drugs should not be used in the presence of detrusor sphincter dyssynergia.

Invasive treatment

Neuromodulation and electrical stimulation

Sacral nerve neuro modulation has been well proven to treat the refractory overactive bladder as well as the imbalance in pelvic floor stimulation. It is essential that there be normal neural connections for this modality to be effective. The efficacy of the sacral neuromodulation also includes afferent stimulation and therefore intact neuropathways are necessary. It does not work in the spinal cord injury or spina bifida patients. The sacral neuromodulation is an electrode placed usually at S3 foramina and left in as a temporary stimulation for 2 to 3 weeks. If there is a more that 50% improvement in their symptoms, a permanent generator is implanted on the lateral aspect of the buttock. This can be set with an external programmer. The placement of the electrode can be done in different positions, periurethrally or next to the pudendal nerve. Sacral root stimulation is currently the most extensively documented.

Electrical Stimulation

Sacral anterior root stimulation. This is not a technique that will normally be done at the urogynaecology clinic but is more for specialized spinal units. It is only performed on spinal patients where a posterior rhizotomy has been done. This is an exciting development but not for discussion at this level.

Augmentation procedures

Detrusor Myectomy: (autoaugmentation)

This will produce a diverticulum in the dome of the bladder if ±20% of detrussor muscle is removed. The urothelium is left intact. It is mostly done as an extraperitoneal procedure. Laparoscopic techniques are also described.

Enterocyctoplasty

It is the best reproducible operation to enlarge bladder capacity and increase storage function of the bladder especially in the small fibrotic bladders. Complications include infection, mucus production and incomplete bladder emptying. Absorption through bowel might lead to metabolic acidosis. Kidney function evaluation is very important before the procedure is considered. Ileum clam cystoplasty is done most often. The urotheluim can be left intact and the bowel muscle used to cover it. This will decrease the mucus production, and absorption.

Bladder replacement

New bladder can be preformed for patients with severely contracted and damaged bladders. Small or large bowel can be used and a good storage pouch will be formed. The pouch is connected to the sphincter. The majority of these patients will have to selfcatheterize.

Procedures to enhance outflow resistance

Bulking agents can be used to increase passive urethral closing pressure. The result of bulking agents is ± 60% in improving the incontinence.

Mid-urethral slings

Mid- urethral slings are classically used for stress urinary incontinence (SUI). They are also very effective in the neurologic patient with SUI. Mid urethral slings can also be used to obstruct the urethra in patients with a hypotonic urethra. It is better to use retropubic midurethral slings for obstructive procedures than trans-obturator routes or mini slings. The patient then has to self catheterized if the outflow is obstructed and the storage function of the bladder is normal.

Artificial sphincter

The artificial sphincter (AMS800) can be used to close the bladder outlet. It is opened using a special valve system and the patient can void spontaneously if she has normal detrusor function. Self-catheterization can also be used with the sphincter if she has voiding dysfunction.

Diversions

Continent urinary diversions: If the normal urinary tract cannot be used for storage and emptying function, a continence pouch can be formed, through which the patient will self-catheterize. The technique is fairly difficult and the complication rate in the long term is relatively high. These include infections, stone formation, mucus production, strictures of the stoma or ureter and metabolic disturbances. Small or large intestine can be used for the pouch and a number of valve mechanism can be formed.

Conduit diversion: an incontinent diversion can be made with ileum and anastomosis of the ureter to a short piece of ileum. The classic Bricker Ileostomy is still used for patients where no restoration of normal urinary tract can be done.

Bladder disconnection

In cases where there is a damaged bladder with a hypoactive or dilated urethra and incontinence, a bladder disconnection should be considered, especially if the patient’s mobility or hand function is not good. The urethra can be closed and a permanent supra pubic catheter placed. The urethral disconnection can be done as a vaginal procedure under local anaesthetic.