Aims of study:
The demonstration, in the experimental animal, that
after chronic spinalization micturition is controlled by an abnormal spinal
reflex initiated in bladder sensory C-fibers [1] was the rationale for the introduction of
C-fiber desensitization as a novel treatment of patients with detrusor hyperreflexia.
Either intravesical capsaicin[2] or resiniferatoxin[3] were used as desensitizing agents. Recently,
a similar C-fiber mediated spinal micturition reflex was also shown to emerge
in rats [4] and humans [5] with detrusor instability. Desensitization
may, therefore, have a role in the treatment of this bladder dysfunction.
Here we report the results of a preliminary clinical study. Resiniferatoxin
was chosen as the desensitizing agent due to its low pungency[3].
Methods:
Five patients with detrusor instability gave written
informed consent to this study. None had had any form of neurological disease
and all stopped all anticholinergic medication for at least one week. In addition
all patients were screened by hematological and biochemical blood tests, microbiological
urinary investigation and ultrasonographic evaluation of the urinary system.
A fill cystometry performed in a Dantec instrument and a voiding chart of
at least three consecutive days were obtained. Four patients were incontinent
and used pads to collect urine. Treatment consisted of one single instillation
of 100 ml a 50 nM RTX solution in 10% alcohol in saline left inside the bladder
during 30 minutes. All patients were followed at 1 and 3 months after treatment.
Results:
Treatment did not cause pain or any significant discomfort.
Mean urinary frequency decreased from 12±2 to 10±3 (NS) and to 9±2 (p<0.05) times per day at 1 and 3 months,
respectively. Mean daily episodes of urinary incontinence decreased from 5±3 to 0.8±1 (p<0.05) at 1 month and to 0.5±0.6 (p<0.05) at 3 months. First detrusor
contraction occurred at a mean bladder volume of 190±119
ml before treatment and increased to 386±117 ml (p<0.05) at 1 month and to 424±173
ml (p<0.05) at 3 months. At the same time points mean maximal cystometric
capacity also increased from 340±193 ml to 441±139 ml and to 445±170
ml but these changes lack statistical significance. Individual data are shown
in the Table below.
Frequency Incontinence Volume to 1st
contraction Maximal cyst.
|
capacity
|
0
|
1m
|
3m
|
0
|
1m
|
3m
|
0
|
1m
|
3m
|
0
|
1m
|
3m
|
|
F,45
|
14
|
11
|
12
|
7.5
|
2.5
|
1.3
|
70
|
295
|
184
|
184
|
297
|
195
|
|
M,49
|
15
|
9
|
10
|
0
|
0
|
0
|
300
|
420
|
394
|
350
|
422
|
483
|
|
F,29
|
12
|
14
|
7
|
8
|
0
|
0
|
100
|
364
|
563
|
650
|
364
|
563
|
|
M,70
|
11
|
8
|
8
|
3
|
0
|
0
|
150
|
460
|
618
|
170
|
460
|
620
|
|
F,25
|
10
|
8
|
8
|
1.5
|
0.8
|
0.5
|
333
|
492
|
364
|
350
|
664
|
364
|
|
Conclusions: This preliminary study suggests that intravesical
desensitization might be useful in the treatment of patients with idiopathic
detrusor instability and warrants the launching of a larger study.
References:
1-
Urology, 50, Suppl 6A (1997): 36-52. 2- J. Neurol. Neurosurg. Psychiatry,
57 (1994): 169-173. 3-Lancet, 350 (1997):640-64. 4- J. Comp. Neurology,
140 (1988): 864-871. 5- J. Urology 160(1998): 34-38.
Funded in part by Gulbenkian Foundation
