ASSESSMENT
OF URODYNAMIC BLADDER BEHAVIOR ON FILLING WITH SOLUTIONS REPRESENTING
PHYSIOLOGICAL EXTREMES OF URINARY OSMOLARITY
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JOSE C. TRUZZI, HOMERO BRUSCHINI, MIGUEL SROUGI, VALDEMAR ORTIZ
Department of Urology , Paulista School of Medicine, Federal University of Sao Paulo, UNIFESP, Sao Paulo, SP, Brazil
ABSTRACT
Objective:
Verify if there is any difference in sensitive and motor bladder response
in the presence of solutions with different osmolarities, simulating physiological
extremes of urinary osmolarity.
Materials and Methods: Thirty-three patients
(24 men and 9 women) with mean age of 46.4 years (8 to 87 years) took
part in this study. They were all subjected to 2 consecutive urodynamic
examinations. In each exam, the vesical filling was accomplished by using
a hyperosmolar (1000 mOsm/L) or hypo-osmolar (100 mOsm/L) sodium chloride
solution in similar speed. The sequence in which each solution was instilled
was determined by a double blind draw. The urodynamic results obtained
from the infusion of both solutions were compared, regardless the sequence
of administration.
Results: Fifteen patients (45.4%) showed
detrusor hyperactivity, 12 of whom with neurological antecedents. The
mean age of those with detrusor hyperactivity was 45.8 years, against
46.9 for those without hyperactivity. The infusion of the hyperosmolar/hypo-osmolar
solution generated the following results, when comparing patients without
vs. with detrusor hyperactivity: initial sensation of vesical filling
(mL): 167.5 / 159.2 vs. 134.9 / 157.3 (p > 0.05); volume of occurrence
of the first involuntary bladder contraction (mL): 163.9 / 151.9 (p >
0.05); detrusor micturition pressure (cm H2O): 24.0 / 24.4 vs. 13.8 /
27.5 (p > 0.05).
Conclusion: The vesical filling with solutions
simulating extreme urinary osmolarities, accomplished with similar speed
and without previous identification, did not likewise alter the sensitive
and motor urodynamic behavior in the current study.
Key
words: bladder; urodynamics; hypertonic solutions; hypotonic
solutions; overactive bladder
Int Braz J Urol. 2005; 31: 569-78
INTRODUCTION
There
is no consensus in the literature that factors such as pH and urinary
osmolarity can contribute to bladder behavior variations and daily urinary
pattern. Few are the works devoted to the study of vesical responses using
solutions with different physicochemical characteristics and their possible
interactions with the urothelium. It has been demonstrated that solutions
with alkaline pH have greater power of penetration through the cell membrane
of the urothelium’s apical cells (1). Other authors have verified
that acid solutions instilled in the bladder during cystometry, triggered
involuntary vesical contractions in patients without previous vesical
instability (2).
After studying the effects of urinary pH
in bladder sensitivity in asymptomatic voluntary patients, we have concluded
that the more acid the urine more precociously the sensation of vesical
plenitude is manifested (3). There are still evidence of the occurrence
of urinary osmolarity variations and increase of sodium excretion in nocturnal
diuresis in enuretic patients that can potentially relate the sensitive
and motor cystometric behavior to change in bladder contents and osmolarity
(4).
The urothelium is the structure that keeps
an intimate contact with the urine and its participation in bladder sensitive
and motor response up to now is not completely defined. The classic concept
of urothelial impermeability prevailed for decades, but has been questioned
by many studies, such as the one that demonstrated a variation in urine
composition from the renal pelvis to the bladder (5). This interaction
between the urothelium and the urine can be explained by the transport
of sodium that occurs through the apical cells, or yet, by the hypothetical
existence of a countercurrent mechanism, as the ones found in nephrons,
conferring a larger participation of urine in the bladder functioning.
(6). More recently, a synthesis of a substance by the urothelium was demonstrated,
with an inhibitor role of the detrusor activity (7). Such a fact can correspond
to at least one of the physiopathological processes responsible for the
idiopathic detrusor hyperactivity, enuresis, and interstitial cystitis
among other affections of the lower urinary tract.
The aim of this study is to verify if hyper-
or hypo-osmolar solutions, representing the extreme of urinary osmolarity,
promote different responses in urodynamic parameters, when instilled inside
the bladder during the cystometry.
MATERIALS AND METHODS
Sample
Thirty-three patients in an outpatient clinic
follow-up took part in this study, all with indication of an urodynamic
study performed as a subsidiary exam in the diagnostic investigation.
This study was performed in patients with different ages, both sexes,
either with different bladder functional states and the presence or not
of neuropathies (Table-1). By adopting this method, we tried to verify
if some of these conditions could change the cystometric responses when
performed with extreme osmolarity solutions. Were excluded from this study
patients that presented acute infection of the urinary tract, vesical
neoplasia, stenosis of the urethra, in postoperative period of urinary
tract or nervous system diseases in the last 2 months before the exam,
patients in use of drugs that could interfere in the functioning of the
vesico-sphincteric apparatus and presenting psychiatric disturbances.
All patients have received a detailed explanation
of the procedure to be performed and an informed consent was signed. In
the case of patients with less than 18 years old, the authorization for
the performance of the exam was supplied by his/her legal representative.
The study protocol was approved by the university’s medical ethics
commission.
To compare and analyze the results the patients
were classified into 4 groups according to: a) age group, patients aged
more than 40 and less than 40 years of age was defined as divisor, taking
as a base the age median, by statistical approximation, thus constituting
2 similar subgroups, b) sex, male, female, c) presence or absence of detrusor
hyperactivity: the criteria for the inclusion in each group was urodynamic.
The patients that took part in the first group were those that presented
presence of detrusor hyperactivity either in the first or in the second
cystometry performed. The definition adopted for detrusor hyperactivity
was the one established by the International Continence Society in 1988,
i.e., the existence of detrusor contractions registered during the filing
phase, that can be involuntary or provoked and that the patient is not
able to suppress it completely (8). This was the detrusor hyperactivity
definition in use in the beginning of the study. Those that did not fulfill
such requirements took part on the group of patients without detrusor
hyperactivity, d) bearers and non-bearers of neuropathies: were considered
neuropaths the patients that presented any form or neurological disease,
with potential repercussion for the urinary tract, already diagnosed or
being investigated, independently from the primary etiology, time of evolution
of the disease and intensity of the commitment, all the other ones were
classified as non bearers of neuropathies.
Procedures
The osmolarities of the solutions were defined
as 1000 mOsm for hypertonic or hyperosmolar and 100 mOsm for hypotonic
or hypo-osmolar, being those values close to the extremes possible to
be found naturally in human urine (9).
The solutions were manipulated in the nephrology
and the urology labs in our institution by means of a sodium chloride
dissolution P.A. (MerckÒ) in distilled water. In order to reach
the desired osmolarity, the quantity of solute necessary for such was
calculated. Thus, the hyperosmolar solution, with 1000 mOsm, contained
528 mEq/L of sodium chloride that corresponded to the addition of 30.89
grams of the salt in one litter of distilled water. The hyposmolar solution,
with 100 mOsm, contained 52.8 mEq/L of sodium chloride that corresponded
to the addition of 3.089 grams of the salt in one litter of distilled
water.
After the preparation, the solutions were
distributed in the bottles and labeled as “solution A” or
“solution B”. The designation of a certain osmolarity was
always the same. The biochemist responsible for the manipulation of the
solutions denominated solution A, the hyperosmolar, and solution B, the
hypo-osmolar. These denominations were kept secret until the end of the
study.
The urodynamic exams were always performed
by the same urologist. The urodynamic equipment used was Aquarius - LaborieÒ
(Canada), with 3 channels for data obtainment and digital decoding of
traced graphs. The urodynamic studies were only performed after the patient’s
physical exam, anamnesis and verification of subsidiary lab and radiologic
exams.
Cystometry was performed with patients in
the lithotomy position, in the conventional way using a double-channel
urethral catheter 7F (CookÒ), one for the liquid infusion, other
for intravesical pressure registration and rectal balloon for simultaneous
abdominal pressure registration. The solutions used in the cystometry
were at room temperature and the speed of vesical filling was of 50 mL/min.,
controlled by an infusion pump.
Each patient was submitted to 2 sequential
cystometries, each one with a hyper- or hypo-osmolar solution. It was
a double-blind study. The sequence of the solutions to be instilled was
defined by lottery, during each cystometry, in the first patient of this
study. For the following patients the instilling order was alternated
(“quasi randomization”). In this way the sequence for patient
1 as solution A, for patient 2 solution B, in the second cystometry for
patient 2, solution B in the first and solution A in the second and thus
successively up to the last patient. The objective of alternating the
solution sequence was to avoid being tendentious or having interferences
between the 2 successive exams. Once the phase of vesical filling due
to imperious desire to urinate or suprapubic pain referred by the patient
was finished, a flow-pressure micturition study was performed. The patient
assumed either orthostatic or sitting position and presented spontaneous
micturition registered in the flowmeter. The ones that presented detrusor
hyperactivity accompanied by involuntary urine loss before they could
reach and keep a trustable vesical filling for registration (at least
150 mL), were not submitted to the flow-pressure study. The urethral catheter
was kept in position and allowed the measurement of the final residual
urinary volume. After a 5-minute interval to change solutions, the second
cystometry was performed with the other solution.
The urodynamic parameters studied during
the vesical filling were: volume and detrusor pressure at the moment that
the initial sensation of vesical filling and the habitual micturition
desire manifested, functional bladder capacity (maximum volume reached
at the end of filling), pressure at the end of the vesical filling, volume
in which involuntary bladder contractions occurred, the maximum pressure
reached during these events and vesical complacency. In the comparative
study between neuropathy bearers and non-bearers, vesical filling sensation
variables were not assessed due to the error factor in interpreting these
variables on the part of those patients with sphincteric neurogenic affection.
In the phase of vesical voiding or urinary study the following urodynamic
parameters: maximum urinary flow, mean urinary flow, detrusor pressure
at the maximum flow, urinary volume and residual volume. All parameters
studied are in consonance with metric units and definitions established
by the International Continence Society.
Statistical
Analysis
The results obtained for each urodynamic
parameter studied in each group of patients were compared according to
the osmolarity of the solution utilized and with the sequence of the exams
performed (first or second exam). With this measurement, we could establish
whether a difference in the results was due to an osmolar characteristic
of the solution or whether it represented only a tendency result by the
sequence of the 2 urodynamic studies. It was only considered of statistical
significance the difference that occurred independently from the sequence
of the instilled solutions.
In the statistical analysis of the results,
the variables were submitted to logarithmic transformation aiming at stabilizing
the variance (10). For the assessment of the means the multivariate method
of analyzing mean profile, being fixed in 0.05 or 5% the rejection level
of nullity hypothesis.
RESULTS
Basic
Parameters of the Population Studied
The mean ages of the patients that participated
in this study was 46.4 years and the median 47 years. Sixteen patients
presented age inferior to 40 years and 17 patients more than 40 years,
Twenty four patients were male with ages varying from 7 to 87 years (mean
49.2 years) and 9 female, with ages between 14 and 72 years (mean 39.2
yeas). Detrusor hyperactivity was found in 15 patients. The mean age of
patients with detrusor hyperactivity was 45.8 years and of those without
detrusor hyperactivity it was 46.9 years. Twelve bearers of detrusor hyperactivity
were male and 3 were female. Neuropathy was present in 10 patients with
detrusor hyperactivity and in 9 patients without hyperactivity. Only 2
patients did not present involuntary bladder contractions in the first
cystometry and presented during the second. Both were male and the sequence
of the instilling solutions was hypo-osmolar/ hyperosmolar for the first
and hyperosmolar/hypo-osmolar for the second.
Comparison
of the Hyper- and Hypo-osmolar Solutions According to the Parameters Studied
When the urodynamic studies obtained in
the vesical filling and voiding are compared, to the hypo- and hyperosmolar
solutions there was no statistical difference in the results in both age
groups (Table-2).
No difference was found in any of the urodynamic
parameters studied when exams utilizing hyper- and hypo-osmolar solutions
are compared in female and male sexes (Table-3).
There was no significant difference in the
cystometric and flow values in the presence of hyper- and hypo-osmolar
solutions, independently from the presence of detrusor hyperactivity or
from the order in which the solutions were instilled. The volume in which
involuntary bladder contractions occurred and the detrusor pressure reached
during the same did not suffer any interference due to the intravesical
osmolarity change. Aiming at minimizing error factors arising from the
obtainment of only the group mean of the triggering volume of the first
involuntary vesical contraction, we made an individual comparison for
each patient. In 54% of the cases there was a reduction of the volume
in which the involuntary bladder contraction occurred (the reduction varied
from 3 to 40%) when compared hypo- and hyperosmolar solutions. Thirty
eight percent of the patients presented an increase in volume for the
involuntary bladder contractions (increase from 7 to 74%) and in 8% of
the cases there was no variation in volume (Table-4).
Considering the presence or absence of neuropathy,
the results obtained were similar regarding the manifestation of involuntary
bladder contractions as well as in the volume in which they were triggered
and in the maximum detrusor pressure reached, independently from the fact
that the solution is hyper- or hypo-osmolar, of the presence of neuropathy
or not and of the sequence of instilling of solutions. Due to the small
number of patients without neuropathy and with involuntary bladder contractions
(n = 3), these data were not considered in the analysis of this study.
The use of the hyper- and hypo-osmolar solutions did not promote any significant
change in vesical complacency, in the detrusor pressure at the end of
the filling and in the functional bladder capacity in patients with or
without neurological diseases (Table-5).
COMMENTS
The
concept of impermeability of the urothelium, being attributed to it the
simple role of hemato-urinary barrier, has been reassessed the last few
years (6,11,12). Some studies about the urothelium physiology have demonstrated
the existence of an ion transport through its apical cells, which remain
in direct contact with the urine (13). On the other hand, it is not yet
well understood the mechanism involved in the conversion of this transcellular
ion transport into nerve impulses (14). It was recently demonstrated that
there are changes in various physicochemical characteristics of the urine
along its trajectory from the kidney until the bladder (5). One of the
most notorious is the increase in the vesical urinary osmolarity when
compared to the urine obtained directly from the renal pelvis. It is possible
that this osmolar variation have implications in the process that involves
either vesical sensitivity or the triggering of detrusor contraction.
It was experimentally demonstrated in rats that the instilling of hyperosmolar
solutions with acid pH lead to a reduction of the bladder capacity. The
opposite occurred with the administration of alkaline and hypo-osmolar
solutions (15). In this line of research the existence of a parallelism
between the oscillations of the urinary pH in the different phases of
the menstrual cycle in normal women and the standard micturition behavior
presented by them was evidenced. The lesser the urinary pH the more precocious
and with lesser intravesical volumes the micturition desire was manifested
(3). From the report of an inverse relation between urinary osmolarity
and cystometric capacity, it was proposed that the degree of hydration
and the hydro-electrolytic balance are factors that possibly interfere
in the settings of micturition urgency (16).
By developing the present study we have
tried to objectively demonstrate through the performance of an urodynamic
exam, the existence of a direct action of the osmolar urine composition
in the vesical filling sensation and in the contractile mechanism of the
urinary bladder. Observing the answer of one patient to the hypo- and
hyperosmolar solutions and with the same instilling speed, we have minimized
the interference of individual characteristics in the comparison of the
results obtained. Another very important aspect in this work’s method
was the alternate instilling of solutions in each patient, removing thus
the possibility of an error arising from their administration always in
a similar sequence. Therefore, the urodynamic response to the hyperosmolar
solution can be differentiated from the one obtained with the hypo-osmolar
solution, independently from the sequence in which they were instilled.
However, the differences obtained in this
study when compared to the results of instilling hyper- and hypo-osmolar
solutions during vesical filling did not reach statistic significance.
As to the detrusor motricity, it was experimentally
demonstrated in rats, the largest incidence of bladder contractions after
instilling a sodium chloride hypertonic solution, when compared to the
isotonic solution of the same salt (6). In this sense it was already demonstrated
that extracellular hyperosmolarity directly depolarize smooth muscular
cells generating an increase in the detrusor activity whereas hypo-osmolarity
promotes opposite responses (18). In our study, when we compared urodynamic
manifestations in patients with detrusor hyperactivity, we have verified
a lack of difference in urodynamic parameters utilizing both hyper- and
hypo-osmolar solutions. The same lack of statistical difference in motor
vesical behavior was observed in the micturition phase, compared to the
results of the experimental studies described above.
Aiming at establishing if the presence of
neuropathy could act as an interfering factor in detrusor hyperactivity
development, as well as in the other urodynamic variables to both extreme
osmolarity solutions, we have compared the results between patients bearing
a neurological disease and those who did not have such commitment. There
was no significant difference between both groups when exposed to different
solutions, independently from the sequence in which each one was instilled.
We did not obtain different urodynamic responses
when we compared both solutions with osmolarity extremes for all analyzed
variables in the present study. Such fact made us precociously interrupt
the study without the inclusion of new patients when the level of significance
for statistical analysis was reached. We know, from what was exposed,
that the variety of clinical situations of the patients involved in this
study could have acted as a limiting factor in the interpretation of the
results. Thus, little differences in the response during the urodynamic
exam may have not reached statistical significance. On the other hand,
the clinical and even the urodynamic value in those cases are questionable.
It is also possible that the permanence
contact time of each solution with the vesical urothelium, i.e., the necessary
time to reach vesical plenitude, will have been insufficient for the apical
cells to be adapted to the environment they were exposed to and thus,
the receptors responsible for the absorption of sodium. Furthermore it
is correct to suppose that hyperosmolar solutions derive from oliguria
and thus, with longer contact with the urothelium, in normal physiological
conditions. Ferguson emphasized in his revision on the urothelial function
that the mean time to have a change in the distribution of amiloride-sensitive
sodium concentration receptors is of approximately 15 minutes (14). Evidences
published in the last years on a more effective action of urothelium on
vesical sensitive behavior; the alteration in urinary osmolarity along
the excretory system, are strong indications that a more profound research
is necessary in this field of urology.
CONCLUSIONS
Vesical fillings with solutions that simulate extreme urinary osmolarities, performed with similar speed and without previous identification do not alter sensitive or motor urodynamic behavior in patients of the present study. To our knowledge, it is the first double-blind study in the literature where 2 solutions that simulate extreme urinary osmolarities (hyper- and hypo-osmolarities), were tested during an urodynamic study.
CONFLICT OF INTEREST
None declared.
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_____________________
Received: March 3, 2005
Accepted after revision: August 31, 2005
_______________________
Correspondence
address:
Dr. José Carlos Truzzi
Rua Dr. Oscar Monteiro de Barros, 617 / 141
São Paulo, SP, 05641-010, Brazil
Fax: + 55 11 5081-6580
E-mail: jctruzzi@hotmail.com