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Network : Guest Lectures : Chris Smith, MD
Introduction to Botox - Its use for bladder & urethral disorders"
Dr. Christopher Smith, Assistant Professor, Department of Urology, Baylor
College of Medicine, TX USA
Date: October, 2003 - ICN Guest Lecture Series
Smith had hoped to appear in our lecture series but was called up by the
Army Reserves to serve in Germany. He very kindly offered to take our
questions by e-mail, including those submitted by patients in our message
boards. We would like to this opportunity to express our sincere gratitude
for not only his contribution to the ICN but for also working with our
military abroad. We would also like to extend our gratitude to our sponsors
Farr Laboratories (Makers of CystaQ
& ProstaQ) and Algonot
Labs (makers of Algonot,
Cystoprotek and ProstaProtek). Their support of this lecture series
has helped us to continue to provide the best information on IC to patients
and providers throughout the world and at no cost.
GENERAL MECHANISM OF ACTION ---
What is BOTOX and
when was it first discovered??
(Dr. Smith) Botolinum
poisoning was first described in Germany in the late 1700's, usually
the result of sausage poisoning. These patients often experienced paralysis.
In the early 1900's, researchers Dickson and Shevsky discovered that
Botolinum toxin appeared to inhibit nerve function. Finally, in 1949,
Burgen discovered that the toxin works by acting at the nerve synapse.
It blocks acetycholine, a neurotransmitter, thus preventing nerve transmission/function.
In other words, it causes a temporary paralysis.
There are seven
distinct neurotoxins known: A, B, C, D, E, F, and G. Since it's introduction
to clinical use in the 1980's, BTX-A has been used successfully to treat
various conditions, including blepharospasm (eyelid spasm), strabismus,
focal dystonias, muscle spasms and spasticity, hyperhidrosis (excessive
sweating) and achalasia (failure of a sphincter to relax).
In urology, BTX-A
has been used for Detrusor External Sphincter Dysergia (DESD). These
patients have impaired contractions of their sphincter. Its clinical
effects begin within 2 to 3 days and reversible. Research studies have
demonstrated that following urethral injection of Botox, voiding pressures
decreased. We performed a prospective study on 21 patients referred
to our clinic with voiding dysfunction. All patients were evaluated
with videourodynamics. Follow up ranged from 3 to 15 months. Following
urethral injection of botox, voiding pressures decreased an average
of 38%. Sixty seven percent of patients reported an improvement of their
voiding patterns and no complications or side effects were noted.
In the bladder,
data has been accumulating on the clinical application of BTX-A, specifically
for hyperreflexic bladders. One early study by Schurge and colleagues
demonstrated a significant increase in mean maximum bladder capacity
(296ml to 480ml) and a significant decrease in detrusor voiding pressure.
A follow up study, long-term study by the same investigational team
studied 87 patients with detrusor hyperreflexia reported clinical responses
that lasted from 4 to 14 months and observed no adverse effects.
What other Urological/pelvic
floor conditions has BOTOX-A been used for?
(Dr. Smith) BTX-A
injections have extended beyond the realm of neurogenic bladders to
patients with non-neurogenic voiding and storage disorders. Radziszewski
and associates reported favorably on the effects of intravesical BTX-A
injections in a pilot study of patients with either idiopathic bladder
overactivity or functional outlet obstruction. Following intravesical
or sphincteric BTX-A injections patients demonstrated resolution of
incontinence and improved voiding efficiency.
Ziemann and colleagues
presented their experience using BTX-A with severe urgency-frequency
syndrome that was not responsive to other therapies. Four of seven patients
responded to treatment with decreases in frequency and increased bladder
Does BOTOX remain
in the specific organ or place injected or does it have the potential
(Dr. Smith) There
was some old evidence using radiolabeled botulinum toxin that identified
it in the central spinal cord but most investigators think this was
a breakdown product and not actually functional botox. For the most
part, most current evidence is that botox works peripherally. Because
it is focally injected, systemic side effects are minimal.
Several IC patients
have now participated in research studies for Botox. How could it be helping
an interstitial cystitis or pelvic floor dysfunction patient??
(Dr. Smith) We are
currently investigating Botox for refractory cases of IC on a case by
case basis. I do not personally know of any ongoing IC trials. We would
like to design a trial in the near future based on some early clinical
results. However, I must caution that the word is still out on whether
Botox will be an effective treatment option for patients with IC
Based upon your
research experience, is BOTOX in the bladder completely reversible? How
long does it take to reverse?
(Dr. Smith) Yes,
typically effects will begin to wear off within 4-6 months although
I have had patients with overactive bladders last as long as 9 months
from one injection
excited about this as a new therapeutic tool??? Is it gaining popularity?
(Dr. Smith) I think
urologists want to get more excited about botox as a tool particularly
for neurogenic and overactive bladders but the real problem is a reimbursement
issue/lack of FDA approval. The word is still out on whether Botox will
be an effective treatment option for IC
What is the short
term versus long term therapeutic value of a therapy like BOTOX?
Botox is relatively
easy to administer, requiring 30 minutes of IV sedation or general anesthesia,
it takes effect within 5-7 days, and if it works it will last 4-6 months.
What is known about
long-term effects of BOTOX used in the bladder? How do the long term studies
look, if any??
(Dr. Smith) There
are no clinical studies looking at long-term effects of botox (>5yrs)
but some recent literature as well as personal experience suggest that
patients tolerate multiple (up to 5) repeated injections with at least
equal and maybe prolonged results with each injection.
--- CONSIDERING TREATMENT ---
Who qualifies for
BOTOX? What do you look for in a patient??
(Dr. Smith) I use
Botox as a later treatment option for patients with neurogenic or overactive
bladders who have failed oral and, sometimes, intravesical therapies
and are at the point where the next step would be invasive surgery (interstim
vs bladder augmentation, etc)
What are the side
effects if any?
(Dr. Smith) I have
not personally identified any systemic side effects using Botox therapy.
However, there are a few case reports where higher dose botulinum toxin
or different formulations of botox led to generalized upper extremity
weakness in a few spinal cord injured patients. There have also been
a few case reports of stress urinary incontinence in patients after
urethral injections although myself and Mike Chancellor have not seen
any cases in over 50+ urethral injections
What's the regular
course of treatment with BOTOX???
(Dr. Smith) Patients
are treated as an outpatient under IV sedation or general anesthesia.
In rare cases, a motivated patient can also be treated in the clinic
with local anesthesia
How long does it
take to feel the full effects of the treatment?
(Dr. Smith) In our
experience, 5-7 days after bladder injection, 2-3 days after sphincter
Can it be used
with other traditional bladder treatments like Elmiron or DMSO?
(Dr. Smith) As I
stated earlier, Botox would be a last resort in a motivated IC patient
who is willing to investigate this as a potential treatment option.
In other words, these patients would have failed Elmiron/DMSO, and other
treatments and all to the point where more invasive options are the
only ones available (e.g. Interstim, cystectomy, etc).
a BOTOX treatment with immediate pain relief? Would it potentially help
reduce the symptoms for patients experiencing IC flares??
(Dr. Smith) I don't
know-typically, patients who are treated with Botox are in significant
pain at the time of treatment.
How can a patient
find a doctor experienced with BOTOX? How should they look??
(Dr. Smith) Right
now, I only know of a few doctors experimenting with botox for IC (myself,
Michal Chancellor in Pittsburgh and Ray Rackley in Cleveland)-there
may be more, I just don't know.
What type of training
should a doctor receive to qualify??
(Dr. Smith) The
actual procedure for injection is fairly simple and does not require
Should a patient
participate in a research study first??
(Dr. Smith) The
real problem is funding-I would like to fund a pilot study of Botox
in IC to see if there is some value in pursuing this as a treatment
option. Currently, no one wants to fund (e.g. pay for drug which costs
--- DURING TREATMENT ---
How are the treatments
performed?? Is it usually done with a hydrodistention, under anesthesia??
(Dr. Smith) Usually
under anesthesia with hydrodistension
How many actual
shots are given during a treatment? One patient reported 25 separate BOTOX
injections into her bladder muscle during a treatment. That seems extreme.
(Dr. Smith) 20-30
injections. We need to spread toxin around the bladder, particularly
the trigone and base of the bladder
Which type of anesthesia
(general or spinal) is usually preferred?
(Dr. Smith) Whichever
the patient is more comfortable with, we even use IV sedation.
POST TREATMENT ---
What does the patient
feel after a treatment???
(Dr. Smith) Like
after a hydrodistension
Is retention a
problem after treatment??? Is it normal to send a patient home with a
catheter for a few days?? Will patients run the risk of needing to cath
(Dr. Smith) In patients
where a higher dose (200 versus 100 units) is used I sometimes have
noticed problems with elevated residuals or even retention in rare cases.
We try to avoid this by only injecting bladder base and trigone and
using lower doses (100 units). I always instruct patients about potential
for need to catheterize after surgery although, like toxin effect, this
would be reversible as well.
W. Post op care???
What usually helps the patients feel comfortable??
(Dr. Smith) Pyridium,
MISC. AUDIENCE QUESTIONS ---
BOTOX work as an intravesical instillation like DMSO or must it always
(Dr. Smith) As of
now, it needs to be injected. Ideally, it would make treatment much
more practical if it could be delivered by liquid instillation
told me that BOTOX need only be given about 4 times to have the effects
last just about forever on the particular spots it was used. Is this true
of the bladder too?
(Dr. Smith) There
is some anecdotal evidence that some patients see longer effects with
multiple treatments but no hard evidence and no evidence in literature
that injection effects become permanent.
I read that after
several treatments you need the injections less frequently, is this true?
(Dr. Smith) If it
is, I would understand that the toxin will be less likely to disappear
from the bladder... am I right?
As I stated before, some anecdotal evidence by clinicians but no hard
evidence in literature that I know of
Can BOTOX hurt
(Dr. Smith) No evidence
that I know of from bladder or urethral injections
is that BOTOX can weaken or damage muscles. Is that true??
(Dr. Smith) Botox
essentially weakens or can even paralyze muscles by impairing the nerves
these muscles. However, the effects are reversible, and muscles eventually
regain their normal/abnormal function.
Dr. Smith's Contact
A search of the National
Library of Medicine (PubMed) web site will produce the latest research
studies on the use of botox in the bladder.
Christopher Smith, MD,
Baylor College of Medicine,
6560 Fannin Street, Suite 2100,
Houston, TX 77030
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