Contemporary
Adhesion Prevention
by Gere diZerega, MD
Click here to
see Dr. Sinervo's update on adhesions.
Many people have re-examined what we know about peritoneal repair.
Several studies have shown conclusively that microsurgical techniques
alone cannot prevent adhesion formation. In six studies from 1982 to
1987, from 55 to 100% of patients had pelvic adhesions at second-look
surgery.
In addition to causing pain, adhesions are expensive. Costs include
subsequent surgeries to free adhesions, doctor visits, pain medication
and millions of dollars in lost work time.
A fairly recent approach to adhesion formation has been the use of a
physical barrier, such as Interceed. In order to understand this
approach, it is first necessary to understand how the peritoneum heals.
In 1919, it was shown that peritoneum heals differently from skin. If
you scrape your knee, healing occurs from the outside edges. Gradually,
the raw spot in the center becomes smaller as the skin regenerates. In
the peritoneum, islands of regenerated peritoneum occur over the entire
surface at once. This means that large peritoneal wounds heal as quickly
as small ones.
How long does it take? Most investigators agree that regeneration is
complete within three to eight days.
Inflammation
Inflammation is an integral part of post-surgical repair. A major
challenge in identifying drugs and physical barriers is the requirement
that they do not further inflame an already inflamed area.
How Adhesions Are
Formed
Typically, adhesions begin with a fibrin matrix that occurs during
coagulation. Over the next few days (in the rat model) a variety of
cellular elements become encased in fibrin matrix, which are gradually
replaced by vascular granulation tissue containing macrophages,
fibroblasts and giant cells. By four days post-injury, most of the
fibrin is gone and more fibroblasts and collagen are present. Through
days five through ten, fibroblasts align within the adhesion. At two
weeks, the relatively few cells present are predominantly fibroblasts.
At one to two months, the collagen fibrils organize into discrete
bundles.
Eventually, the adhesion matures into a fibrous band, often holding
small calcifications. Extensive adhesions often contain blood vessels.
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| These are
adhesions of the ovary.
Click the slide to see the image
in full color and larger. |
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Historical Approaches to
Adhesion Prevention
Most studies that looked at using corticosteroid drugs to help prevent
adhesions reported little success. The pharmacologic properties of
corticosteriods (they are anti-inflammatories) suggests they would be
helpful in adhesion prevention. Why is this not the case? One
possibility is that peritoneal surgery simply overwhelms the therapeutic
benefits of the dose. If a higher dose is used, the effects on other
organs (immunosuppression and delayed wound healing) outweighs any
positive benefit.
NSAIDs
Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs that
ease the post-surgical inflammatory response. Some studies have shown a
marked reduction in adhesion formation in animal models when the drug
was given peri-operatively. Another study showed that two doses of
Ibuprofen post-operatively did not help, but a five-dose barrage did.
When the NSAIDs were administered intraperitoneally, adhesions reduction
resulted.
Areas devascularized by surgery are hypoxic, thus permitting fibrin
persistence and adhesion formation. Devascularized sites are prime
adhesion candidates. However, these sites are not readily available to
drugs given systemically. Perhaps another method of drug delivery would
help.
Dextran
Dextran is a water-soluble glucose polymer originally used as a plasma
expander. The weight most often considered in adhesion studies is a 32%
solution of dextran 70 suspended in glucose. Hyskon is the best known
brand name. Hyskon is slowly absorbed in five to seven days. Hyskon
draws fluid equal to 2-1/2 to 3 times the original volume into the
pelvis.
Animal studies were split. Some found that using Hyskon reduced the
number and severity of adhesions. Other studies did not show positive
results.
In people, Hyskon studies were also mixed. Some found that patients
treated with Hyskon had fewer and less severe adhesions than patients
treated with saline (Ringer's lactate). Other studies found no
differences between treatments.
Hyskon carries with it side effects that include temporary weight gain,
vulvar edema, leg edema, pleural effusion, and coagulopathy. Rarely, a
patient may be allergic to it.
Barrier Agents
Barrier agents include mechanical barriers and viscous solutions. Many
different mechanical barriers have been tried, but they are generally
inadequate because they interfere with the blood supply or produce
foreign body reaction. However, there are some exceptions.
Ideally, a barrier agent for adhesion prevention should be non-reactive,
maintain itself during the critical stages of peritoneum regeneration,
and then be absorbed by the body. Oxidized regenerated cellulose (Surgicel
and Interceed) appear to satisfy these criteria. In addition, they do
not support bacterial growth.
The first surgical studies were done with Surgicel. A few days after
placement with sutures, Surgicel changes to a gelatinous mass and is
absorbed. Some animal studies were very promising, but others were not.
Surgicel was altered by its manufacturer with some positive studies then
resulting.
Interceed
Interceed is a newer product of the same type. It was designed to last
longer in the pelvis than Surgicel. In addition, it didn't require
sutures, if the pelvis were kept very dry. Animal studies yielded mixed
results.
Early clinical studies were very positive, and Interceed was approved by
the FDA in 1989 as the first product specifically indicated for
reduction of postsurgical adhesions. Many studies since then have shown
that the proper use of Interceed is useful in reducing formation of
adhesions after surgery.
Gore-Tex
Gore-Tex has also been tested for adhesion prevention. Unlike Interceed
and Surgicel, Gore-Tex is not absorbed by the body and must be anchored
in place. It is used in heart surgery. However, its use in gynecological
procedures is far from certain. A comparison study of Interceed and
Gore-Tex showed that both reduced adhesions, although Interceed
performed better.
Peritoneal Closure
Studies have shown that it is not necessary to suture the peritoneum to
help it heal after surgery. Indeed, two studies showed that using
stitches made the adhesions worse. Therefore, it is better to leave the
peritoneum unsutured after surgery. It will heal satisfactorily on its
own.
Crystalloid Solution
The most common method used to try to prevent adhesion formation after
surgery is to use a crystalloid solution. The best known are Ringer's
and plain saline. However, several studies have shown that these
solutions do not help prevent adhesion formation. The most common amount
of solution used is 200mL. This is absorbed by the body in about six
hours. Peritoneal repair takes many more hours. Adding more solution
isn't the answer, either. Five thousand mL of solution takes about five
days to absorb. However, such a large amount may reduce the body's
ability to fight infection.
Laparoscopy
Although many clinicians assume that laparoscopic surgery will reduce
post-operative adhesion formation, the data is not compelling. However,
de novo adhesion formation was substantially reduced by
laparoscopic surgery.
Further Developments
Much progress has been made. Use of barrier methods, however, is limited
to surgical situations where the area in question can be completely
covered. In addition, Gore-Tex needs to be anchored, and Interceed
requires hemostasis and removal of excess peritoneal fluid.
The development of new aids to prevent postsurgical adhesion formation
is encumbered by the way the peritoneum heals, access to the peritoneal
cavity, limitations of animal models, and the complexities of
interperitoneal circulation and transperitoneal transport.
Important Questions
Remain:
Why do some patients form adhesions after trauma while others do not?
What are the differences between adhesion reformation and de novo
adhesions?
What are the different potential for adhesion formation due to general
surgery, endometriosis, cancer, infection and ovulation?
A direct cause-and-effect relationship between adhesions prevention and
outcome measures is difficult to establish. Screening of potential tools
is time consuming and expensive. For a company to invest in this
therapeutic area only to find a disparity between preclinical animal
results and clinical trials is disappointing and costly. Soon,
regulatory agencies must set guidelines of "effectiveness" and delineate
clinical settings for definitive evaluation of usefulness.
To date, no treatment has proven uniformly effective in preventing
postoperative adhesions formation. Surgical techniques that preserve
good blood flow as well as the use of mechanical barriers, provide
clinical benefits to the patient today.
Dr. Albee Responds
Dr. diZerega's article is thorough and
objective. His expertise in this area is evidenced by his huge list of
publications. I am very impressed by his work. And, as he makes clear,
pelvic adhesions can cause terrible problems.
I'll spend the rest of this space explaining
what I do here at the Center for Endometriosis Care to minimize adhesion
formation.
In my opinion, the single most important thing I
do to lessen the chance for adhesion formation is our thorough,
painstakingly meticulous approach to the surgery. That approach includes
the following items:
-
I aim for complete
hemostasis. This means I accept absolutely no bleeding or oozing
from any surface area.
-
I handle all tissues with
atraumatic instruments so there is no crushing of tissues.
-
Because all abnormal tissue
is excised instead of laser ablated, fulguration or cautery, I
minimize the amount of devitalized tissue left behind. This
greatly reduces adhesion formation.
-
Bleeding vessels that
cannot be controlled with the laser are bipolar cauterized
intermittently to minimize heat accumulation.
-
If an ovarian capsule that
has been opened to remove endometriosis does not naturally fall
into an opposed position, I suture it closed to lessen the
exposed raw surface.
-
I do float the pelvic
tissues with saline at the end of the procedure.
-
When I think it will be
advantageous, I use Interceed on the uterus or ovary.
I acknowledge Dr. diZerega's report that a
published study that proves laser dissection creates fewer adhesions has
not yet been seen. However, it has been my experience that laser
dissection can cause less tissue trauma and less heat-related injury, if
it is used according to the principles outlined above. Any technique is
only as good or bad as the surgeon using it, which helps explain the
wide disparity of results at the hands of different surgeons who use
similar techniques.
At the Center for Endometriosis Care, the
majority of our problems with adhesions have come from our stage III and
IV patients. We routinely remove all adhesions we see when we operate on
a patient. Because endometriosis can hide beneath adhesions, it is vital
to completely excise the scar tissue to be certain no endometriosis is
left behind.
Occasionally, I will perform a second surgery on a patient I have
operated on before. Should those cases reveal adhesions, it is usually a
straightforward process to cut through them with the laser and remove
the source of pain. If all the endometriosis was removed at the first
surgery, the resulting adhesions were formed post-operatively. Without
deep dissection or endometriosis to cause re-formation, I feel the
chance for de novo adhesions is minimal. This lets us safely cut
through them, restoring the anatomy to normal and relieving any ongoing
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