6.2: Botulinum Toxin
- Page ID
- 15599
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Botulinum Toxin, which is produced by the bacterium, Clostridium Perfringens, is the most potent toxin known to man. It is a Gram positive, anaerobic
Chapter bacteria which is commonly found in the soil and 1g of the toxin can kill 1 million people. It blocks the release of acetylcholine at the neuromuscular junction in the detrusor muscle. Amongst those who have contributed to the science of Botulinum Toxin, credit must be given to Schantz who purified the toxin and enabled its mass production. Its first clinical use was in 1980 when it was used to treat strabismus. There are 7 subtypes, A, B, C, D, E, F , G, however only Toxins A and B are available commercially. The Botulnum A Toxin preparation, Botox® (Allergan Inc.) is probably the most well known, but there is an alternative called Dysport® (Ipsen Pharma). Botulinum Toxin B is marketed by Solstice.
Botox® has been more extensively evaluated in the literature than Dysport®, but there are now a number of studies that now confirm its efficacy. Botox® is three times more potent than Dysport and most reports use 300u for Neurogenic DO and 200u for Idiopathic DO. Exact dosages for Dysport are less clear and ranges from 500u to 1000u are administered.
The toxin is usually administered using either a flexible or rigid cystoscope using a flexible 26 gauge needle that is threaded through the working channel of the scope. The toxin is diluted into 20 ml of normal saline and injected in 1ml aliquots under local or general anaesthesia. Most practitioners avoid injecting the bladder trigone because of the theoretical risk of reflux. Recent work has, however, shown that trigonal injections are not associated with reflux and have equivalent efficacy to the extratrigonal administration. When a flexible cystoscope is used, the Botox can be given using local anaesthetic gel but sedation or general anaesthesia is usually necessary when using a rigid scope.
Schurch et al were the first to use intradetrusor Botox injections for the treatment of severe detrusor overactivity in spinal cord injured patients. Profound improvements were demonstrated, with 17 of 19 patients achieving continence. A large amount of data has emerged since then suggesting excellent efficacy in Neurogenic DO. Schurch et al reported again in 2005 on 59 NDO patients. This was double blind placebo controlled parallel group study. They gave patients either placebo, Botox 200u or Botox 300u. Up to six months follow-up, they reported a 50 % reduction in incontinence episodes with 49% of the cohort reporting being dry. The urodynamic findings compared to placebo were remarkable with highly significant increases in maximum cystometric capacity at two, six and 24 weeks compared to placebo.
Following the success in NDO a number of studies began looking at the treatment of Idiopathic DO. The problem with IDO is the risk of voiding dysfunction – since unlike in NDO, most of these patients have normal voiding function. Popat et al published the first data on IDO using Botox, achieving continence rates of 57%. The incidence of de novo voiding dysfunction was 19%. In a further randomized controlled trial, Sahai et al report profound improvements in multiple outcomes following the injection of Botox when compared to placebo.
The main adverse event following Botulinum injections is temporary urinary retention, with a reported incidence of between 19% to 35%. Women who develop this complication are required to perform clean intermittent self catheterization or have a suprapubic catheter inserted.
The Botulinum Toxin effect on the detrusor lasts for approximately six to nine months and it usually requires repeat administration following this. As the urgency and urge incontinence return, normal voiding is also regained in those women who developed urinary retention.
An important factor to take into consideration is the cost of the Botulinum Toxin product. Botox is sold in vials of 100u and a single course of 300u would have a cost in excess of R6000. Dysport has only recently been launched in South Africa and would have a comparable price tag. One would need to add to this the costs of administration, including surgeons fees, theatre time and disposables.