PATTERN OF OVERACTIVE BLADDER IN SOUTHEAST NIGERIA

Abstract

Background

Overactive bladder is a distressing condition characterized by the syndrome of uncontrollable urgency, day time frequency, nocturia with or without urgency urinary incontinence.

Aim

To determine the pattern of overactive bladder in two tertiary health institutions in South-East Nigeria.

Study Design

The study is prospective.

Setting

Federal Teaching Hospital, Abakaliki and Niger Foundation Hospital and Diagnostic centre Enugu in southeastern Nigeria.

Method

The study involved 383 patients who were diagnosed with overactive bladder in the two hospitals during the study period. Their demographics, clinical feature, management options and outcome were analyzed.Tolterodine was the anticholinegic used to treat the syndrome while the underlying pathology was treated accordingly.

Result

There were 383 patients out of which 363 (94.8%) patients were males while 20 (5.2%) patients were females with the age range of 37yrs to103yrs with a mean of 63.4yrs. A total of 313 (81.7%) patients had prostatic disease (benign prostatic hyperplasia and cancer of the prostate), while 99 (25.8%) patients had diabetes mellitus. Among the 313(82 %) with prostate disease, two hundred and eighty nine (75.5%) had benign prostatic hyperplasia while twenty four (6.3%) had cancer of the prostate. Urgency, urinary incontinence and fecal incontinence were observed simultaneously in 133 (34.7%) patients during the episode of involuntary painful bladder contraction. In 271 (71%) patients, the overactive bladder was treated with Tolterodine alone and management of the underlying pathology with resolution of symptoms. Few patients benefitted from behavioral therapy.

Conclusion

Overactive bladder in this environment is associated commonly with prostate diseases with urgency of urine, urine and fecal incontinence but responds well to anticholinergic.

Introduction

Overactive bladder (OAB) is a distressing syndrome complex consisting of uncontrollable urgency with or without urgency urinary incontinence associated with day time frequency and nocturia1,2. Using the current international continence society (ICS) definition of OAB, the world wide prevalence is about 11% in men and 13% in women3. In the National Overactive Bladder Evaluation Programme (NOBLE) study, the overall prevalence in the United States was approximately 17% with 16.9% women and 16% men2. Before the current ICS definition of OAB, one European study reported an overall prevalence of OAB in Europe of 16.6%, with 15.6% and 17.4% for men and women respectively2. In the European Prospective Investigation into Cancer and Nutrition (EPIC) study involving five countries, the overall prevalence was 11.8% , with 10.8% and 12.8% for men and women respectively2,4. The overall prevalence in Canada in year 2004 was 18.1% (14.8% men and 21.2% women)5. Overactive bladder affected approximately 100 million people in the western world in 2000 (33 million in the United States and 66million in the European Union)6. In the OAB population, 33% presented with urgency urinary incontinence (OAB wet) while 66% presented without urgency urinary incontinence (OAB dry)7.

The mechanisms contributing to overactive bladder symptoms could be neurogenic or idiopathic in origin8.

The incidence of OAB increases with age; with rapid increase in ageing societies, there is associated tremendous costs. In the United States, the cost of OAB in 2002 was $12.7 billion increasing to $24 billion/year in 2005 6. In five European countries, the estimated cost of OAB in 2000 was €4.2 billion and by 2020 the expected total cost is €5.2 billion2,9. While the impact on social and quality of life of sufferers is enormous, leading to depression, loss of working hours, the actual number of people getting treatment is significantly low due to embarrassment and the patients being ashamed to disclose their symptoms 10.

This prospective study is on 383 patients who presented with Overactive bladder syndrome in two tertiary institutions. The study aimed to find out the various pathological conditions associated with overactive bladder and the response to treatment.

PATIENTS & METHODS

Between January 2010 and January 2014, 383 patients who were seen in two tertiary health institutions, Federal teaching hospital Abakaliki (FETHA) and Niger foundation hospital and diagnostic centre Enugu (NFH), diagnosed with overactive bladder, were studied for various associated pathologies and response to treatment in a prospective fashion. These patients were recruited from the urology clinics and surgical wards of both institutions.

Patients who presented with the symptoms of overactive bladder during the study period were included in the study and the associated pathologies noted.

Exclusion Criteria

1. Patients presenting in urinary retention

2. Those on catheter drainage of the urinary bladder

3. Patients found with cystitis/prostatitis after culture of urine and prostatic secretion

4. Those with mixed or stress urinary incontinence

5. Patients on treatment for glaucoma by the ophthalmologist

6. Those with urinary bladder cancer and stones

7. Those with residual urine volume of ≥200ml of urine ascertained from use of transabdominal ultrasonography

One hundred and thirty one (34.2%) patients were recruited from NFH while two hundred and fifty two (65.8%) patients were recruited from FETHA. Clearance was obtained from the ethical committees of both institutions for the study and consent of the individual patients obtained.

The demographics, clinical features including digital rectal examination, relevant investigations, management and outcome as well as follow-up details were recorded in a proforma.

Patients were questioned on the quantity and nature of fluid intake whether alcohol, caffeine or water. The frequency of intake of such fluid was ascertained from the patients and documented. Drug history particularly diuretics was noted. The International prostatic symptoms score (IPSS) was noted for male patients presenting with lower urinary tract symptoms (LUTS). Complete physical and neurological examinations were carried out for all the patients. Digital rectal examination (DRE) was done.

The laboratory investigations included urinalysis, urine microscopy culture and sensitivity, urine cytology, serum electrolytes urea and creatinine, serum prostate specific antigen were done for the male patients with either benign prostatic hyperplasia (BPH) or cancer of the prostate (CAP).

The prostate volume was determined using transrectal ultrasonography, while residual urine volume was determined for all the patients using transabdominal ultrasonography; prostatic biopsy was done when on digital rectal examination, the prostate was hard or the percentage serum free prostate specific antigen was ≤ 12ng/ml to diagnose prostate cancer. In some patients cystoscopy was done to rule out bladder cancer. Urodynamic studies/cystometry was not done in this study due to the fact that it was not available and also expensive for the populace under study. Co-morbidities like benign prostatic hyperplasia (BPH), cancer of the prostate (CAP), diabetes mellitus (DM), cerebrovascular accidents (CVA) and spinal cord injuries (SCI) were treated simultaneously with OAB.

The patients with bladder outlet obstruction and lower urinary tract symptoms (LUTS) had their respective IPSS documented before commencement and after therapy.

Fluid intake modification was solely used in 9(2.3%) patients.

Either tolterodine 2mg quick release tablet twice daily or 4mg extended release(ER) capsule daily was administered to 374(97.7%) patients for 15 weeks.

Each patient’s response to treatment was evaluated every 3 weeks either by phone calls or by direct discussion and reading patient’s diary if available. In 10(2.6%) patients with spinal cord injury, the dose of tolterodine was doubled to 8mg. The data obtained were analyzed using SPSS one-way anova test, version 17.0 2008.

Results

Out of the 383 patients in this study, there were 363(94.8%) males and 20(5.2%) females with the age range of 37 and 103 years, mean of 63.4 years and a standard deviation of 10 years as shown in figure 1.

Figure 1. AGE DISTRIBUTION OF THE PATIENTS .

Table 1 outlines the modalities of treatment for the OAB and the different pathological conditions implicated in the aetiology of OAB syndrome.

Table 1: MODALITIES OF TREATMENT FOR OVERACTIVE BLADDER AND ASSOCIATED PATHOLOGIES.

Treatment	CVA	DM	CVA+DM	SC Injury	BPH	BPH+DM	CAP±DM	BPH+CVA+DM	CVA+BPH
Tolterodine 2mg BD or 4mg ER dly	11	21	16	11
Tolterodine 2mg BD/4mg dly+ Alfuzosin 10mg dly .					54	7
Tolterodine 2mg BD/4mg dly+ Alfuzosin 10mg dly + Dutasteride 0.5mg dly					62	16		7	15
Tolterodine 2mg BD/4mg dly + Open prostatectomy					87	32
Tolterodine 2mg BD/4mg dly + BIL Orchidectomy + Alfuzosin 10mg dly+Bicalutamide 50mg dly							24
Tolterodine 8mg dly				10
Behavioural therapy					9

Prostatic diseases - both benign prostatic hypertrophy and cancer of the prostate - were present in 313(82%) patients; benign prostatic hypertrophy was present in 289 (75.5%), cancer of the prostate was present in 24(6.3%) patients. Diabetes mellitus and cerebrovascular accidents (CVA) featured in 99(26%) and 49(13%) patients respectively as shown in Table 2.

Table 2. VARIOUS PATHOLOGIES ASSOCIATED WITH OVERACTIVE BLADDER.

Aetiology	No of Patients			(%)
	Total	Male	Female
CVA	11	7	4	3
DM	22	12	10	5.7
BPH	202	202	-	53
CAP	17	17	-	4.5
SC INJURY	21	21	-	5.3
BPH +DM	55	55	-	14.3
CAP + DM	7	7	-	2
CVA + DM	16	10	6	4
CVA + BPH	15	15	-	4
CVA + DM + BPH	7	7	-	2
POST OPEN PROSTATECTOMY	10	10	-	2.6

Urgency urinary incontinence was recorded in 260(68%) patients while urgency urinary incontinence and faecal incontinence were observed simultaneously in 133(35%) patients (Table 3).

Table 3. SYPMTOMS SEEN IN THE PATIENTS.

SYMPTOM	No OF PATIENTS	PERCENTAGE (%)
DAY TIME FREQUENCY	383	100
NOCTURIA	383	100
URGENCY	383	100
URGENCY URINARY INCONTINENCE	260	68
URGENCY URINARY INCONTINENCE + FAECAL INCONTINENCE	133	35
PAINFUL SPASM	311	81.2
BLOOD STAINED URGENCY URINARY INCONTINENCE	121	31.6
SLEEPLESS NIGHT	321	84

In 175(45.8%) male patients, the prostatic volume was between 100-150cm³ (Table 4) while residual urine volume ranging between 51-100ml was observed in 157(41.1%) patients as shown in Table 5.

Table 4. PROSTATE VOLUME IN PATIENTS WITH PROSTATIC DISEASES (CAP + BPH).

PROSTATE VOLUME (cm3)	No OF PATIENTS	PERCENTAGE (%)
50 – 100	104	33.2
100 – 150	175	56
150 – 200	23	7.3
200 – 250	11	3.5
TOTAL	313	100

Table 5. VOLUME OF RESIDUAL URINE.

VOLUME (mls)	No OF PATIENTS	PERCENTAGE (%)
0 – 50	34	8.9
51 – 100	157	41.0
101 – 150	117	30.5
151 – 200	75	19.6
TOTAL	383	100

The overall response showed 280(73.1%) having excellent response, 63(16.5%) having very good response, 23(6%) having good response, while 17(4.4%) had urinary retention in the course of treatment. At the end of treatment for each patient, his/her response was documented and grouped accordingly whether excellent, very good or good. (Table 6 and Table 7)

Table 6. RESULTS OF TREATMENT WITH ANTICHOLINERGIC TOLTERODINE.

AETIOLOGY	EXCELLENT	VERY GOOD	GOOD	URINARY RETENTION
CVA		11
DM	22
CVA + DM		11	5
SC INJURY		11	7	3
BPH	195	14		3
BPH + DM	55
CAP ± DM	8	9		7
BPH + CVA + DM			3	4
CVA + BPH		7	8
Excellent - OAB wet OAB dry, No urgency, No daytime frequency/nocturia
Very Good - OAB wet OAB dry, Urgency eliminated, Daytime frequency nil,, Nocturia ≤ 2
Good - OAB wet OAB dry, Urgency ≤ 2 in 24hrs, Daytime frequency nil, Nocturia ≤ 2

Table 7. SUMMARY OF RESULTS OF TREATMENT.

	EXCELLENT	VERY GOOD	GOOD	URINARY RETENTION	TOTAL
TOTAL NUMBER	280	63	23	17	383
%	73.1	16.5	6.0	4.4	100

Discussion

Despite the increasing prevalence of overactive bladder (OAB) in the society, its aetiopathogenesis is still poorly understood2. Previous terminologies relating to OAB were attributed to involuntary detrusor contractions noted during bladder filling phase of urodynamics. The terminologies then were detrusor instability (idiopathic aetiology) or detrusor hypereflexia (neurogenic aetiology) otherwise coined detrusor overactivity (DO) by the international continence society 11. Abrams and Wein in 1997 came up with the terminology overactive bladder a symptom based definition 11, 12. With this, clinicians do not need to subject a patient with bothersome symptoms to expensive and invasive evaluation before commencing treatment. Furthermore it is not all patients with OAB have DO and not all patients with DO have OAB 2,11. In a retrospective study of 1,076 patients using the new definition of OAB 64% had DO while more than 30% of patients did not have OAB but had DO on cystometry 2. These facts reduce the role of urodynamics as a useful tool for diagnosis of OAB. Furthermore, the international consultation on incontinence recommends that patients with refractory OAB should be investigated with urodynamic testing 13. The keyword in OAB is urgency - an unstoppable desire to micturate. Furthermore, the term urge incontinence has been changed to urgency urinary incontinence to emphasize that the involuntary leakage of urine follows or is preceded by urgency which is pathological and not urge, a normal physiological desire to micturate 1,2.

The pathological conditions that were found in this study to cause or contribute to the symptoms of OAB included bladder outlet obstruction from prostatic disease (benign prostatic hyperplasia and cancer of the prostate) in 313(82%) patients, diabetes mellitus in 99(26%) patients, cerebrovascular accidents (CVA) in 49(13%) and spinal cord injury (SCI) in 21(5.3%) patients, Table 2. Similar findings had been noted in other studies 14, 15. The genesis of symptoms of OAB varied with individuals and may be multifactorial in a single patient 2,14. Thus CVA and bladder outlet obstruction secondary to benign prostatic hyperplasia could coexist in a patient with OAB even when each of them could produce the symptoms. In this series 100 (26.1%) patients had more than one aetiopathogenesis coexisting.

The commonest aetiology of OAB is bladder outlet obstruction and benign prostatic hyperplasia is a major cause of bladder outlet obstruction in males 16. Ten (2.6%) patients who had open prostatectomy elsewhere and presented with OAB symptoms post operatively were included in this study. The surgery took care of the voiding symptoms of the IPSS while the storage symptoms due to the bladder dysfunction/OAB persisted. In another study, similar findings in which 25%-50% percent of detrusor overactivity persists after surgery has been documented 17. In the same vein some patients who used alpha-blockers for medical treatment of LUTS of benign prostatic hyperplasia may have persistence of the storage symptoms synonymous to OAB despite treatment 18. Furthermore, the myogenic theory proposed by Brading asserted that smooth muscle cells become hyperexcitable in association with bladder outlet obstruction (BOO)11. Therefore, increased intravesical voiding pressure overtime from BOO may damage neurons in the bladder wall leading to denervation hypersensitivity. The myocytes are thus hyperexcitable with electrical coupling between the cells. Hence a local contraction can easily spread throughout the entire bladder2,9,11. In this study, 99 (26%) patients had diabetes mellitus (DM) either solely or coexisting with another pathology. In a dedicated diabetic center, 22.5% of patients had OAB and out of these 48% had OAB wet 19. Furthermore in a comparative study of 328 diabetics (males and females) and 333 healthy subjects(males and females) 35.7% of the diabetic group had OAB compared with 4.8% of the healthy subjects a significant statistical difference and questions whether OAB symptoms could represent markers of diabetic neuropathy 20. The facts above heavily implicate diabetes mellitus and bladder outlet obstruction in the aetiopathogenesis of OAB. In the same vein, the neurogenic theory proposed by DeGroat, explains the association of cerebrovascular accident and spinal cord injury with overactive bladder. In these disease conditions, there is either loss of inhibitory control of the urinary bladder from damage to central neural pathways in the brain and spinal cord or unmasking of primitive voiding reflexes both of which can trigger detrusor overactivity2,11

Overactive bladder syndrome is symptom based and thus related to symptoms 21. Urgency, nocturia, and daytime frequency featured in all the patients while OAB wet was present in 260(68%) patients. Out of the 260 patients with OAB wet, 227(59%) had bladder outlet obstruction from prostatic diseases (BPH and CAP). There was late presentation of these patients to the clinics with the result that alterations in the properties of the detrusor myocytes were enormous hence explaining the featuring of many cases of bladder outlet obstruction in the aetiopathogenesis in this study.

Regarding the simultaneous double symptoms of OAB wet and faecal incontinence in 133(35%) patients, Coyne KS et al, noted that faecal incontinence was more common in patients with wet OAB22. Faecal incontinence has been associated with urgency, frequency and urge incontinence with prevalence of combined faecal and urinary incontinence put at 6-9% in a community based study23.

A possible explanation for the simultaneous double incontinence of urine and faeces in these patients is the fact that both the urinary bladder and the rectum have the same embryological origin (cloaca). Both organs are located close to each other in the pelvis, there is a joint peripheral innervations coordinating the functioning of both viscera23.

Furthermore, central processing and perception of afferent activity of both organs converge on the same regions of the brain 23. The total number of female patients in this study was 20(5%). The few patients in this series were referred by gynecologist as women in this part of the world prefer visiting the gynecologist for their medical problems believing that only the gynecologist has the answer to all their medical problems oblivious of the services rendered by urologists. The other reason is that few female patients who are incontinent of urine or faeces spontaneously report their symptoms at visit to the clinics. Due to social stigma, they feel embarrassed, uncomfortable and ashamed to disclose their symptoms as depicted in other studies2,15,26. The clinicians must be proactive in questioning patients to unravel these symptoms.

Treatment options for OAB include behavioural therapy, dietary modification, medical therapy and surgical intervention such as sacral nerve stimulation and augumentation cystoplasty. Also intravesical injection of botulinum toxin type A has been effective in controlling OAB symptoms.

The goals of treatment are: - increase in voided volume with reduction in daytime frequency and nocturia, decrease urgency and reduce urgency urinary incontinence episode2. Nine (2.3%) patients who had BPH and OAB benefitted from behavioural therapy. Advice was given on fluid intake to between 1-1.5 liters in 24 hours to reduce urine production. Also they were advised to refrain from intake of caffeine and alcohol. The urgency, daytime frequency and nocturia were drastically reduced to tolerable levels and the urgency urinary incontinence present in 4 of the patients stopped. Alcohol, caffeine and diuretics have been noted to cause acute urinary incontinence especially in the elderly25. Antimuscarinic drugs are the only treatment with undisputed effectiveness, and for individual patients their value should not be underestimated26.

In the human bladder detrusor muscles, muscarinic receptors present are the M₂ and M₃, with M₂ predominating. However, the M₃ receptors are chiefly responsible for normal micturition contraction26. These two receptors are involved in the pathogenesis of detrusor overactivity, and hence OAB and play a crucial role in the treatment of OAB, since antimuscarinics can abolish or reduce both detrusor overactivity and the symptoms of overactive bladder 26. Tolterodine was the antimuscarinic used in this study. Either the 2mg quick release tablet or the 4mg extended release (ER) capsule was used. It is a competitive inhibitor of the action of acetylcholine on the M₂ and M₃ subtypes of muscarinic receptors of the detrusor. In a bladder that is overactive, tolterodine slows the buildup of pressure during the filling/storage phase, reduces the sensation to urinate increasing bladder capacity. It is not active during the voiding phase because it is a competitive inhibitor. The quantity of acetylcholine released during this phase overwhelms its activity 26. In the subset of patients that had OAB associated with prostatic disease (BPH or CAP), tolterodine was administered simultaneously with alfuzosin (alpha blocker), dutasteride (5 alpha reductase inhibitor), bicalutamide (antiandrogen) in different combinations depending on the associated pathology and the size of the prostate. The reason for this is that these patients have bladder outlet obstruction. The consequent bladder dysfunction from the obstruction is responsible for the storage subset of lower urinary tract symptoms (LUTS) viz daytime frequency, urgency, nocturia and urgency urinary incontinence which is synonymous to OAB syndrome. These storage symptoms in this study were treated with behavioural therapy and tolterodine. The other combination drugs were targeted at the prostate pathology. Combination of tolterodine and alfuzosin, dutastateride and bicalutamide in different combinations in these patients is to optimize relief from both the storage and voiding sub-categories of LUTS and improve the quality of life. Two hundred and ninety nine (78%) patients had reduction in values of both the storage and voiding IPSS values to less than 9 after treatment with improvement in quality of life. Similar combinations of drugs have been used in other studies to treat the voiding and storage symptoms of LUTS15, 18.

In this study, 10(2.6%) patients who had OAB following spinal cord injury had the dose of tolterodine doubled to 8mg daily before decrease in the symptom of OAB. Use of 8mg of tolterodine in spinal cord injured patients with neurogenic OAB has been documented in another study 27.

A one-way classification ANOVA test variation for the extent to which the 383 patients responded to treatment (using their aetiologies as the factor) also suggests that the patients had significant [F (45%) =246-553, P<0.05] different response to treatment based on their aetiologies.

From the statistical analysis above the response to treatment was excellent in 195(51%) patients with bladder outflow obstruction, 21(5.5%) patients of neurogenic OAB and 63(16.4%) of mixed pathology (Table 6). Excellent response in this study means that all the symptoms of OAB syndrome abated.

Tolterodine at the dose used was tolerable to the patients and safe. The adverse effect of dry mouth was noticed in 157(41%) patients. Seventeen (4.4%) patients developed urinary retention. Other studies have reported on the tolerability and safety of tolterodine, in patients suffering from OAB syndrome 18, 26.

Conclusions

Overactive bladder in this environment is associated commonly with prostate diseases with urgency of urine, urine and fecal incontinence but responds well to anticholinergic.

Conflict of interest: None declared