Note: Descriptions are shown in the official language in which they were submitted.
2024~
CATHETER PARTICULARLY USEFUL FOR INDUCING
LABOR AND/OR FOR THE APPLICATION OF A PHARMACEUTICAL
SUBSTANCE TO THE CERVIX OF THE UTERUS
BACKGROUND AND OBJECTS OF THE INVENTION
The present invention relates to a catheter
particularly useful for inducing labor and/or for the
application of a pharmaceutical substance to the cervix
of the uterus.
It has been shown recently that a certain
pharmaceutical substance, namely prostaglandin (PG),
leads to local biochemical and biophysical alterations
in the cervical region that have the effect of reducing
cervical resistance in addition to inducing myometrial
contractions. Endocervical application of this
substance in a gel has been gaining increasing
acceptance for priming the cervix before the induction
of labour or for the induction of labour. A
pre-manuf~actured mixture of 0.5 mg PGE2 and 2.5 mm
triacetin gel ("Prepidil Gel", supplied by Upjohn,
Crawley) is now available, and recent trials exhibited
no gel-specific problems relating to stability,
homogeneity or sterility.
At the present time, the Prepidil Gel is
applied by intra-cervical injection using a syringe
with a simple canula. However, it is extremely
difficult, if not impossible, to administer 3 ml of gel
202~55
in a strictly endocervical fashion without applying
some of the gel retroamniotically, and without having
some flowing back out of the cervical canal to the
vagina.
An object of the present invention is to
provide a catheter particularly useful for this
purpose.
During clinical studies made with the
above-described catheter it was surprisingly discovered
that merely the insertion of the catheter without the
delivery of the pharmaceutical substance also had the
effect in many cases of artificially ripening the
cervix and inducing labor.
Accordingly, another object of the present
invention is to provide a catheter which may be used
for inducing labor by merely inserting the catheter as
described above and without the delivery of the
phamaceutical substance.
Further objects of the present invention are
to provide a method of inducing labor in a female, and
also a method of applying a pharmaceutical substance
directly to the cervical canal of a female.
BRIEF SUMMARY OF THE INVENTION
According to one aspect of the present
invention, there is provided a catheter particularly
useful for application to the cervix of the uterus in
20246~
-- 3
order to induce labour, comprising: a slender,
flexible tube open at one end and closed at the
opposite end; an inflatable distal balloon fixed to the
tube at its closed end and adapted to be received in
the uterus; an inflatable proximal balloon fixed to the
tube at a location spaced a small distance from the
distal balloon in the direction towards the open end of
the tube and adapted to be received in the vagina, with
the connecting portion of the tube between the two
balloons passing through the cervical canal; inlet
means at the open end of the tube connected by conduit
means leading to the two balloons for inflating each
balloon after positioned in the uterus and vagina,
respectively, further inlet means at the open end of
the tube for introducing a pharmaceutical substance;
and an outlet opening in the connecting portion of the
tube between the two balloons delivering the
pharmaceutical substance to the cervical canal.
According to another aspect of the present
invention, there is provided a method of inducing labor
comprising introducing the above-described catheter
into the birth canal of the female with the distal
balloon located in the uterus and the proximal balloon
located in the vagina, and inflating both balloons.
In the preferred embodiment of the invention
described below, the proximal balloon is spaced about
40 mm from the distal balloon; also, the discharge
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-- 4 --
opening has a Longer length, e.g., 5 mm, than a width,
e.g., 2 mm.
Further features and advantages of the
invention will be apparent from the description below.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention is herein described, by way of
example only, with reference to the accompanying
drawings, wherein:
Fig. 1 illustrates one form of catheter
constructed in accordance with the present invention;
and
Fig. 2 is a diagram illustrating the manner
of using the catheter of Fig. 1 for inducing labor
and/or for the application of a pharmaceutical
substance directly to the cervical canal.
DESCRIPTION OF A PREFERRED EMBODIMENT
The catheter illustrated in Fig. 1 comprises
a slender, flexible tube 2 open at one end 2a and
closed at its opposite end 2b by a plug 4 fixed within
that end of the tube. The illustrated catheter further
includes an inflatable distal balloon Bu fixed to the
tube at its closed end 2b, and a second inflatable
balloon By fixed to the tube 2 at a location spaced a
relatively small distance from balloon Bu in the
direction towards the open end 2a of the tube. Balloon
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Bu, hereinafter sometimes referred to as the distal
balloon, is adapted to be received in the uterus of the
female; and balloon Bv, hereinafter sometimes referred
to as the proximal balloon, is adapted to be received
in the cervico-vagina, with the connecting portion 10
of the tube between the two balloons passing through
the cervical canal. This connecting portion 10 of the
tube is formed with an outlet openinq 14, preferably of
an oblong configuration, having a length larger than
its width.
The distal balloon BU to be received in the
uterus is inflatable by a fluid, (e.g., sterilized
saline water), introduced via an inlet 16 adjacent the
open end 2a of the tube 2 under the control of a valve
Vu and fed to the balloon via a conduit 18 integrally
formed with tube 2. Similarly, the proximal balloon Bv
to be received in the cervico-vagina is adapted to be
inflated by a fluid (e.g. sterilized saline water)
introduced via inlet 20 under the control of a valve Vv
and fed to balloon sv via a second conduit 22
integrally formed with the tube. The pharmaceutical
substance to be applied directly to the cervical canal
is introduced via the open end 2a of tube 2, optionally
under the control of a valve Vs, and is fed through the
tube to the outlet opening 14 when located in the
cervical canal.
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-- 6 --
Fig. 1 also illustrates the inclusion of a
palpable demarcation ring 30 located on the proximal
side of the vaginal balloon Bv. This rins enables
correct positioning of the catheter by palpation, even
without cervical visualization. Thus, the catheter may
be inserted into the birth canal of the female while
the female lies supine in bed, thereby avoiding the
discomfort with the lithotomy position and and the
insertion of a vaginal speculum.
The manner of using the catheter illustrated
in the drawings is more particularly illustrated in
Fig. 2.
Thus, while both of the balloons su and BCv
are deflated, the catheter is introduced into the birth
canal of the female patient until the distal balloon su
is located within the uterus. Distal balloon 6 is then
inflated by applying a fluid, e.g., saline water, via
Valve Vu inlet 16 and conduit 18. The catheter is then
manipulated (e.g., withdrawn slightly if necessary) to
locate the deflated proximal balloon Bcy within the
vagina, and that balloon is then inflated by
introducing saline water via its inlet 20 and its
conduit 22. This positions the connecting portion 10
of the tube 2 in the cervical canal at the entrance to
the uterus. The pharmaceutical substance is then
applied via the open end 2a of tube 2, and via the
202465~
-- 7
outlet opening 14 in the connecting portion 10 of the
tube directly to the cervical canal.
The catheter is not to be removed from its
position until the onset of labour or spontaneous
rupture of the membranes.
It will thus be seen that the use of the
illustrated catheter enables the pharmaceutical
substance, such as the above-mentioned pre-manufactured
mixture of 0.5 mg PGE2 and 2.5 ml triacetin gel
("Prepidil Gel"), to be applied in a more precise
manner with no leakage and with substantially no
flowback out of the cervical canal to the vagina.
The illustrated catheter was used for the
induction of labour in women with unripened cervix
~Bishop score 4 or less), and it was found that this
technique was well tolerated by the patients and easy
to perform. It was also surprisingly found that the
insertion, in the manner described above, of the
catheter alone, i.e., without introducing the
above-mentioned pharmaceutical substance, also had
the effect of articifially ripening the cervix and
thereby inducing labor.
As one example, the illustrated catheter may
have a length of 350 mm, an inner diameter of 3.5 mm,
an outer diameter of 5.9 mm, the length of the
connecting portion 10 between the two balloons 6, 8,
202~6~S
-- 8
may be 20 mm, and ~he outlet opening 14 may be 5 mm in
length and 2 mm in width.
CLINICAL STUDIES
Following are the results of clinical studies
made on sixty-nine patients by using the
above-described catheter placed in the cervix for
twelve hours.
MATERIALS AND METHODS
The clinical studies were conducted in three phases as
follows:
Phase 1: A group of 22 women (13 primiparous
and nine multiparous) treated in an open study by
intracervical administration of Prepidil gel through
the illustrated double balloon catheter.
Phase 2: Included 20 women in a double blind
randomized study. Ten of the women were randomized to
a treatment group and received 25 ml of Prepidil gel
(including 0.5 mg PGE2) intrcervically through the
catheter, while the other ten women served as a control
group and were given KY jelly as a placebo, via the
catheter. The medication and the placebo were prepared
under code in identical vials by the hospital
pharmacist.
Phase 3 of the study included the insertion
of the illustrated catheter to 27 women without the
2~2~6~5
g
application of any medication, but with in~lation of
both balloons.
All patients of this study had an
aobstetrical or medical indication for induction of
labor, and an unfavorable cervix (Bishop Score of four
points or less). Excluded from the study were women
with uterine scar, multiple pregnancy, non-vertex
presentations, placental insufficiency, reptured
amniotic membranes, women with a recent failed
induction attempt, those with an indication for a stat
delivery (i.e. fetal distress) and those with a
contraindication for PG administration such as
bronchial asthma). However, women with a
contraindication for PG treatment were included in
Phase C of the study consisting of the use of the
illustrated catheter alone.
Prior to initiation of the procedure every
woman underwent an ultrasonographic examination to
exclude placenta previa and to confirm a vertex
presentation. In addition, a non-stress test,
recording of the patient's temperature and complete
blood count were performed. All women underwent a
pelvic examination by a senior staff member and an
initial Bishop Score was obtained. The catheter was
inserted either with the patient in a lithotomy
position under visualization or by cervical palpation
~24~5
- 1() -
during a pelvic examination with the woman lying
supine.
When both balloons enterred the cervix, the
uterine balloon was inflated through the valve V1,
using 20 ml of sterila saline solution. The catheter
was then pulled out until stopped by the uterine
balloon covering the internal cervical os. At that
point the cervico-vaginal balloon located at the
external os was inflated via valve V2 with 40 ml of
sterile saline solution. The uterine balloon was
further inflated with additional saline to a total
volume of 40 ml ~Fig. 2). The Prepidil gel was
injected through the intracervical instillation valve
V3, followed by 1.5 ml of saline (measured to push the
gel over the catheter's "dead space"). The catheter
was then taped to the inner patient's thigh. The woman
remained in bed rest, wth continuous external
monitoring for two hours, followed by ten hours
of intermittent monitoring.
Twelve hours after the insertion, the
balloons were deflated and the catheter removed. At
removal, or earlier if spontaneous expulsion occured,
the Bishop Score was recorded again. In cases where
the score was five and above, induction of labor was
resumed using artificial rupture of the membranes or
intravenously administered oxytocin. Women with
Bishop Score of less than five points following the
202~6~
~ 11 -
removal of the catheter, were induced only when a
reexamination revealed a more favorable cervix, but no
later than following additional 12 hours. Oxytocin
was administered at a starting dose of 1 mlU/min and
increased periodically to a maximum of 6 mlU/min.
Data concerning timing of procedures and patient's
complaints were recorded on a form prepared for this
purpose. Statistical significance of the difference
between groups was calculated using the Wilkinson
test.
The indication for labor induction in these
patients are summarized in the tables at the end of
this specification. Table I shows that the majority
(35 women) had post term pregnancies and a considerable
number (23 women) were diangosed as having
preeclampsia.
Table II shows the characteristics of the 22
women and the outcome of the induction procudure
in the f irst phase of the study, which included the
insertion of the catheter and the instillation of PGE2
gel to the endocervix. In these women, a mean increase
of 5.4 points was accomplished in the Bishop Score, and
91% of them delivered vaginally. Differences between
the primparous and multiparous women are depicted.
Table III compares the two groups of the
double blind randomized study. The women's age,
pregnancy dates and the mean parity were quite similar
20246~
between the two groups. The mean Bishop Score in time
"0" (1.1 and 1.2) and the change in the Bishop Score
following the removal of the catheter (increasing in
5.7 and 6.0 points) were not statistically different
between the treatment group and the control group,
respectively.
In three of the ten women of the treatment
group and in five of the ten in the control group, the
catheter was spontaneously expelled during the 12 hours
period following its instillation. No significant pain
or discomfort, nor any morbidity, was experienced by
any patient of either group of women.
A mean of 9.5 hours passed from catheter
introduction to the beginning of regular uterine
contractions in both groups. The mean time elapsing
from catheter insertion to delivery, was similar in the
two patients' groups: 22.8 hours in the treatment group
and 21.8 hours in the control group (Table III).
Spontaneous vaginal deliveries occured in a similar
rate in the two second phase groups: nine women of the
treatment group, and nine of the control delivered
vaginally, with one patient of every group undergoing
an instrumental delivery. In addition, one woman of
each study group underwent a cesarean section.
Table IV shows that the newborns in the two
groups were not statistically different in their mean
weights and Apgar Scores.
2 0 ~
- 13 -
Table V details several characteristics of
the 27 women participating in the third phase of the
study, where introduction of a catheter and inflation
of the balloons were not followed by any medication
installed. The mean increase in Bishop Score of that
group was 4.23 points. Eighty five percent of the
patients delivered vaginally in this group patients.
The four patients of that group who underwent a
cesarean section had fetuses weighing 3360 gm to 3600
gm. Two of them had a prolonged second stage and the
other two were diagnosed as having arrest of dilation
with a cervix dilated to 5 cms.
Discussion
Induction of labor in a patient with an
unfavorable cervix is currently attempted by
intravenous administration of oxytocin or by the
vaginal placement of a prostaglandin preparation. Both
induction methods are associated with the initiation of
uterine contractions, sometimes lasting for prologned
periods. However, the most frequent indications for
labor induction at term are preeclampsia and post term
pregnancy, occasionally associated with olygogydramnios
(Table I). Prolonged periods of uterine contractions
in these cases may cause umbilical cord compression,
resulting in fetal distress. Relative placental
insufficiency in these pregnancies may also be
associated with fetal decompensation when prolonged
202~65~
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uterine stimuIation occurs. In addition, long hours of
o~ytocin infusion may lead to water overload, which may
be hazardous in the case of a patient with
preeclampcia.
Therefore, a preferred induction method will
be the one that will lead to cervical ripening without
causing uterine contractions. The technique tested in
this study was initially based on applying PGE2 gel
(Prepidil, Upjohn) directly and solely into the
endocervical canal, by a double balloon catheter
instead of a simple cannula. The two balloons confined
the PGE2 gel (Prepedil, Upjohn) directly and solely
into the endocervical canal, by a double balloon
cathether instead of a simple cannula. The two
balloons confined the PGE2 gel to the cervix itself by
closing the internal and external oses. All women
treated with the catheter and Prepidil had an increase
of three points, or more, in the Bishop Score over 12
hours, with no discomfort or side effects. In a
different article, the use of a cannula to install a
PGE2 gel into the cervix resulted in a failure rate of
24.4% of the women. Those patients required a repeated
instillation of PGE2, 24 hours after the first one, and
in 12.2% a third instillation was given, as no change
was noted in their Bishop Score.
The drawbacks of labor induction by cervical
placement of PGE2 via the double balloon catheter,
202~6~
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which kept the gel in place, close to the cervix, for
long periods. The method had a very high success rate,
was well tolerated by the patients, who reported no PG
side effects. Conceivably, the double balloon catheter
p:revented spillage of the PGE2 gel onto the vagina, and
avoided its absorbtion to the extraamniotic space with
the possible resulting uterine hyperstimulation.
An unexpected result was obtained in the
second phase of the study, involving the performance of
a double blind randomized comparison of PGE2 gel versus
placebo, administered via the double balloon catheter
for ripening of the unripe cervix. The analysis
revealed that there was no significant difference in
the increase of Bishop Score between the two groups.
Induction of labor using a simple (single
balloon) Foley Catheter has been discussed in the
past. Ezimokhai et al (Ezimokhai M. Nwabiweli JN. The
use of Foley's catheter in ripening the unfavorable
cervix prior to induction of labour. Br J Obstet
Gynecol 1980; 87:281-86) reported a failure rate of
20% using a Foley Catheter for instillation of
Prostaglandins for induction of labor. Liberman et al
(Liberman JR, Fiura B, Chaim W, Cohen A. The cervical
balloon method for induction of labour. Acta Obstet
Gynecol Scand 1977; 56:499-503) combined the insertion
of a trancervical Foley Cathether to the intravenous
administration of Oxytocin, and had better results
20246~
than with a Foley Catheter inserted alone. Their
reported mean insertion to labor period with the
combined method was 28.4 hours, as compared to 9.5
hours obtained in the present study. In the present
study, as well as in others, no cases of accidental
rupture of membranes, chorioamnionitis or placental
abruption were caused by the use of a catheter. The
procedure was convenient and well tolerated by most
women.
The findings of the present study indicate
that the ripening of the cervix might have been caused
by the catheter itself. The location of the two
inflated balloons in both sides of the cervix might
have caused mechanical pressure on the cervix, with the
pressure vectors in the direction of the cervix, thus
dilating.
The third part of the study, including the
cervical placement of the catheter and inflation of
both balloons without installing any medication,
supported the finding of the double blind randomized
study by demonstrating a successful ripening effect of
the double balloon catheter itself without significant
uterine contractions or any unwanted side effects. No
significant pain or discomfort was experienced by the
women treated by the catheter. Hencel the major
advantage of the use of the double balloon catheter was
the avoidance of medication; Prostaglandins may
202465~
occasionally cause hypersensitivity and are
contraindicated in patients with medical conditions
such as bronchial asthma. The sole use of the catheter
may also be advantageous in women with a previous
uterine scar, where uterine contractions for prolonged
periods are unadvisable. In addition, patients with
olygohydramnios or with preeclampia may benefit from
ripening of the cervix, without the need for
intravenous administration of oxytocin and fluids.
The above findings suggest that the use of a
double balloon catheter for ripening of an unfavorable
cervix and induction of labor is an effective, safe and
well tolerated novel method of labor induction. Other
findlngs indicate that the same catheter is also
effective for ripening and dilating of the uterine
cervix prior to evacuation during a late-abortion
procedure.
While the invention has been described with
respect to one preferred embodiment, it will be
appreciated that many variations may be made.
202~6~
t -- 18 --
Tabl0 1:
Indications for Labor Induction ;n 69 Women
Indication No. of Percent
womel1of women
Preeclampsla 35 51
post term pr~nancy 23 33
Chronic hypertension ~1 6
Intrauterina ~rowth retardation 3 4
Fetal malformation 1 1.5
Kell blood type incornpatibility 1 1.5
Fetal hydronephrosis 1 1.5
Decre~se in f0tal movements 1 1.5
Total 69 10U
- 2~246~5
- 19 -
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20246~
- 21 _
Table IV:
Characteristics of the Newborn o~ the Women Participatillg
In the Double Blind Randomized Study of Labor Induction
Mean Neonata! Mean Apgar Mean Apgar
weight Score at Score at
in grams minute '1' minute '5'
.
~reatment Group
lCatheter ~ PGE2) 32t9 8.1 9.5
Control Group
~Catheter + Placebo) 3143 8.3 9.7
2~24~55
-- 22 --
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