ONABOTULINUM TOXIN-A FOR OVERACTIVE BLADDER

The propose of this study is to evaluate the effect of Botulinum A intradetrusor injection on patients with overactive bladder refractory to oral anticholinergics and safety of the drug. Patients with overactive bladder (excluding patients with neurological or pathological causes) were enrolled in this study, those patients did not benefit of oral medications with anticholinergic effect, and they were assessed for history of their problem and kept a urinary diary for three days before the start of the procedure. They were also examined, and ultrasound for post voiding residue with urinary flow rate was kept in records. Injection of 200 IU of onabotulinom toxin-A in the detrusor muscle. The drug effect was studied one month after injection on patient’s symptoms, including day and night frequency, urgency and urge incontinence by keeping a three days’ urinary diary postoperatively. The maximum flow rate and the post voiding volume were also measured. Postoperative complications in the form of haematurea, urinary tract infection and retention of urine were recorded. There was a significant decrease in the number of voiding during both day and night from 10.7±1.68 SD, 2.09±0.93 SD to 4.407±1.394 SD, 1.257±0.752 SD respectively which is statistically significant difference (t (135) =6.377, P≤0.001), (t (135) =0.837, p≤0.001), this was associated with a reduction in the number of episodes of incontinence from 1.37±0.975 SD to 0.6815±0.676 SD. The postvoiding volume was increased remarkably. Complications includes urinary tract infection and retention of lower tract local effects only. In conclusion, the use of onabotulinom toxin-A in the treatment of refractory overactive bladder is effective in reducing patients’ symptoms and discomfort as well as being a safe option for treatment. Introduction veractive bladder (OAB) is a group of symptoms including frequency, nocturea, urgency and urge incontinence that exists in a patient after excluding pathological and neurological causes. The patient might pass urine more than eight times during day time and more than one time during night with strong desire to pass urine with or without involuntary passage of urine. These symptoms can affect the quality of life of those patients to a degree that can have a financial impact by changing the productivity of those patients. The treatment of overactive bladder can be in the form of behavioral therapy as first line treatment and the second line treatment will be in the form of oral drugs either antimuscrinic or β 3-adrenoceptor agonist, and the third line is in the form of intradetrusor injection of Botox, peripheral tibial nerve stimulation or sacral neuromodulation. Patients with overactive bladder usually are treated by the first two lines of treatment if there condition persist and it is unresponsive then they are shifted to the third line of treatment. One way is by the injection of the detrusor muscle with onabotulinum toxinA. Botox is a neurotoxin protein produced by the bacterium Clostridium botulinum a gram positive anaerobic bacterium, there are several indications for Botox in addition to overactive bladder it may be used for focal hyperhidrosis, blepharospasm, strabismus, chronic migraine as well as the wildly spread cosmetic use. Botox is broken into 7 O


Introduction
veractive bladder (OAB) is a group of symptoms including frequency, nocturea, urgency and urge incontinence that exists in a patient after excluding pathological and neurological causes.The patient might pass urine more than eight times during day time and more than one time during night with strong desire to pass urine with or without involuntary passage of urine.These symptoms can affect the quality of life of those patients to a degree that can have a financial impact by changing the productivity of those patients 1,2 .The treatment of overactive bladder can be in the form of behavioral therapy as first line treatment and the second line treatment will be in the form of oral drugs either antimuscrinic or β 3-adrenoceptor agonist, and the third line is in the form of intradetrusor injection of Botox, peripheral tibial nerve stimulation or sacral neuromodulation.Patients with overactive bladder usually are treated by the first two lines of treatment if there condition persist and it is unresponsive then they are shifted to the third line of treatment.One way is by the injection of the detrusor muscle with onabotulinum toxin-A.Botox is a neurotoxin protein produced by the bacterium Clostridium botulinum a gram positive anaerobic bacterium 3,4 , there are several indications for Botox in addition to overactive bladder it may be used for focal hyperhidrosis, blepharospasm, strabismus, chronic migraine as well as the wildly spread cosmetic use.Botox is broken into 7 O Bas J Surg, December, 22, 2016 neurotoxins (labeled as subtypes A,B,C,D,E,F and G) they are different serologically and antigenically but similar structurally There are two main commercial types: botulinum toxin type A and botulinum toxin type B. The subtype for overactive bladder is onabotulinum toxin-A, it act by attaching to the presynaptic nerve terminals at specific high affinity sites thus preventing the release of acetylcholine and blocking the neurotransmission as a result the muscle involved will be paralyzed .This was the principle by which Botox was used in overactive bladder to control the involuntary detrusor muscle contraction and it's undesirable urinary symptoms.

Materials and methods
From march 2016 a total of 135 patients with overactive bladder(after excluding other pathological and neurological causes for their symptoms) were treated with intradetrusor injection of onabutulinom toxin-A in Basrah General Hospital, this was done by the same surgeon using G21F cystoscope and the procedure was carried out under general anesthesia using a flexible endoscopic needle (Figure 1) in a way that the injection site forms a wheel by inserting the needle end to about 0.5 cm in the bladder wall (Figure 2).The dose used was 200 IU for all patients and it was injected in 20 different sites avoiding injecting the trigon and the ureteric orifices (Figure III).

Results
In this study 135 patients were enrolled, excluding all patients with pathological and neurological causes for their symptoms, they were 83 females and 52 males (Table I).The age range was 21-65 with a mean age of 41.8 years ± 12.6 SD (Table II).

Discussion
The use of onabotulinum toxin A have revolutionized the treatment of overactive bladder in the last decade 5 .There was a lot of controversy regarding the recommended dose a dose range from 100 I.U. up to 300 I.U. was used for patients with variable bladder dysfunction with variable results, we have used a mid-point dosage of 200 I.U., we can see from our results that there was a better response to the 200 I.U.dose than the 100 I.U.as seen in a study by Victor W. in 2013 6 were the incontinence episode was reduced from 2.65 to 0.87 comparing to our study the reduction was from 1.37 to 0.68 episodes of incontinence .The mean number of day voiding was reduced from 10.7 to 4.407 per day in our study comparing to 11.7 reduced to 11.2 using the 100 I.U.dose conducted by Victor W, Nitti et al in 2016 7 the increased dose was associated with a better reduction in day time voiding frequency .Kessler et al reported that the mean post voiding volume after injecting 300I.U. was increased from 10 ml to 140 ml while in our study using the 200I.U. the mean volume increased from 33.4 to only 98.53 which is an important factor in minimizing the incidence of retention and the need for clean intermittent catheterization 8 .Linda Brubaker reported an incidence of post injection urinary tract infection of 44% which was higher than that reported by our study it was 17.55% which is almost half the incidence in their study 9 , the incidence of culture positive urinary tract infection was 9.7% reported by Greer T. in 2016 10 , these results are close to what was found in this study indicating that local complications in the form of urinary tract infection are tolerable.The data collected reported 5.4% patients had retention requiring clean self-intermittent catheterization which is very close to the reported 4% incidence of retention found by a study done by Nitti VW et al in 2013, the same result was found in similar studies 11 .This was solved by self-catheterization for six weeks.The maximum flow rate was found to decrease from 15.03ml/sec at baseline to 10.296 ml/sec after the injection which seems to be related to the increase in the post voiding volume which is related to the decrease bladder detrusor activity, this was in contrast to what was reported in 2016 by Yuh-Chen Kuo and Hann-Chorng Kuo 12 in their study they had an increase in maximum flow rate form 15.51ml/sec at base line to 17.69 ml/sec., this difference could be attributed to the difference in timing of measuring the maximum flow rate of urine which is done after three months in their study and by that time probably the effect of the drug will start to fade away in comparison to the one month post injection time of measurement of the flow rate in this study during which the effect is at its maximum.

Conclusion
This study can verify that using Botulinum Toxin A is effective in relieving the symptoms of overactive bladder with a dose dependent relationship, and low incidence rate of serious complications making it a safe procedure that can be tolerated by patients and strongly recommend it for refractory cases of overactive bladder.