BERKELEY, CA (UroToday.com) - When the neurogenic bladder is refractory to anticholinergics, botulinum toxin type A is used as an alternative.
The neurotoxin type A reduces bladder pressure and increases its capacity and wall compliance. Additionally, it contributes to improving urinary continence and quality of life. This novel therapy is ambulatory and with a low incidence of adverse effects. Due to its transitory nature, it is necessary to repeat the injections in order to sustain the therapeutic effect.
The protocol followed in our study consisted of the following inclusion criteria: patients with neurogenic bladder of any etiology, up to 18 years of age, under clean intermittent catheterization (CIC) programs and oral oxybutynin therapy at maximum doses for weight and tolerance of each patient. Also included were patients refractory to the anticholinergic agent oxybutynin, as evidenced by poorer urodynamic and clinical results over time.
When patients became refractory to oxybutynin, we did not change the therapy scheme to another anticholinergic agent, since most of these patients, although they may at first present detrusor overactivity and respond favorably to anticholinergic therapy, tend to progress towards developing a hypertonic bladder. When this happens, the anticholinergic drugs do not improve bladder compliance much. Thus, we concluded that another anticholinergic drug would not be useful in patients of older age with bladders having high collagen content in their walls.
After the administration of OnabotulinumtoxinA, we continued with the conventional therapy scheme (CIC plus Oxybutynin) because it was not certain that patients would respond favorably to the new scheme (OnabotulinumtoxinA), and because we took into account that the patients’ clinical and urodynamic status had once improved with the conventional scheme, some time ago. We decided to start from this status (the maximum response reached with oxybutynin by each patient) in order to introduce an alternative to that treatment. We believed that weaning patients off oxybutynin would lead to the worsening of the patients’ status. However, we were well aware that the first scheme was far from being the optimal treatment to protect the urinary tract.
In our sample population, all of them were receiving oxybutynin. All of them were refractory to oral oxybutynin and received a maximum dose of 0.3 mg/kg/day or 20 mg/day. We decided on the number of injection sites of OnabotulinumtoxinA (between 45 and 60) considering age, bladder size and the presence of trabeculae and irregularities in the bladder wall. In a very large bladder or bladder with altered surface, it was necessary to administer a considerable number of injections. In addition, quite a great number of patients in our series were adolescents with an average age of 13 years, some of whom were overweight. In this group, the maximum dose used was up to 300 UI. We used 6.6 UI per kilogram of body weight.
For the assessment of urinary incontinence, only 3 patients who had undergone previous accessory procedures at the bladder neck were excluded, but these patients were not excluded from the rest of the evaluation parameters tested.
The patients who showed improved urodynamic results and urinary incontinence scores were reinjected because, in previous studies, it had already been demonstrated that the effect of botulinum toxin in the bladder is transitory, and the maximum duration of this effect is approximately 9 months. We consider that the patients who had responded favorably around the sixth month would continue responding this way with the repeat injections. These were applied between the ninth and twelfth months, when the patient was re-evaluated and a new injection was prepared.
If, after the first or second injection, there was no favorable response, we believed it was pointless to continue injecting botulinum toxin and we decided to offer another type of therapy in order to decrease the bladder pressure, increase the bladder size, or attenuate reflexive contractions. When this point was reached, the patients refractory to OnabotulinumtoxinA were subjected to bladder augmentation. At that moment, those patients were excluded from the protocol, despite knowing that certain patients may have shown a favorable response to the injection/s.
In some cases (4, precisely), patients were refractory to OnabotulinumtoxinA with the first injection, and others proved to be refractory after the second injection. In our study there were two cases with vesicoureteral reflux Grade IV and V who were refractory to onabotulinumtoxinA. During the same injection procedure with botulinum toxin, the vesicoureteral junctions were injected with hyaluronic acid-dextranomere (Urodex or Vurdex), but no favorable response was obtained for reflux. However, after augmentation, cystoplasty was performed without ureterovesical reimplantation, and the reflux disappeared, as well as proteinuria.
After treatment with repeated injections of intradetrusor onabotulinumtoxinA, urinary continence was achieved in up to 77 % of patients and urinary volumes increased. Even though there was considerable improvement in urodynamic variables over the period when all the injections were applied, only compliance improved significantly after the first injection. Overactivity of the detrusor muscle diminished, but it did not disappear completely. The urodynamic studies show improvement with the injections of onabotulinumtoxinA, but the findings are still far from optimal.
The main weaknesses in our study: the older age of patients with neurogenic bladder that was a sequela of myelomeningocele. There are direct relationships between the passing of time and the deterioration of bladder function. With time, the bladder is adding collagen tissue to the wall, and hypertonia plays an important role.
Perhaps in the future, in younger patients when it first become clear that the neurogenic bladder has become refractory to oral anticholinergics, the therapeutic strategy will be to start with a more invasive treatment such as the use of intradetrusor botulinum toxin A first. This schema may serve to reduce the indication for augmentation cystoplasty.
Written by:
Cristian Sager, Carol Burek, Juan Bortagaray, Juan Pablo Corbetta, Santiago Weller, Victor Durán, and Juan Carlos Lopez as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Urology Department, Hospital Nacional de Pediatría “Profesor Dr. Juan P. Garrahan”, Combate de los Pozos No 1881, CPA: C 1245 AAM, Buenos Aires, Argentina
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