Information provided here is intended as a lay overview
only and not as any sort of endorsement. Any product
described here must be used by a medical doctor
in accordance with the Instructions for Use and
taking a Patient's individual circumstances into
Products Approved by FDA for Adhesion Prevention,
Reduction in Pelvice and/or Abdominal Cavities
* INTERCEED (TC7),
made by Johnson
Placed over the site of surgical injury, this knitted
fabric dissolves within 30 days or so. The idea is
that the sheet keeps organs apart that would otherwise
stick (adhere) together. Once healing is complete,
the sheet dissolves leaving the two organs properly
Since 1989, it has been approved only for open (non-keyhole)
gynecologic surgery with a good record of safety and
in this paper authored by
Dr. Wiseman in 1999.
Althought it is not approved in the USA for use in
laparoscopice (key-hole) surgery, INTERCEED is often
used "off-label". Only small clinical studies to evaluate
INTERCEED in laparoscopy have been performed with mixed
results, possibly because almost perfect control of
bleeding (required for INTERCEED's action) may not
have been achieved, or INTERCEED was dislodged from
its site of placement.
Early studies suggested that a small
amount of Heparin added to the INTERCEED may
not only enhance its action, but also overcome
the detrimental effect that bleeding has on the beneficial
action of INTERCEED. Unfortunately, this work was
never pursued, neither
was a modified form of INTERCEED, which also functioned
better than the original INTERCEED, both in the absence
and presence of bleeding.
* Seprafilm, made by Genzyme (previously called HAL-F)
This film looks like a thin, slightly brittle clear
"fruit roll-up" that gels soon after contact with moist
body tissues. It workes and is used in much the same
way as INTERCEED, except that it is also approved for
General Surgery. Like INTERCEED, it is not approved
in the USA for laparoscopic use, aothought with considerable
technical difficulty, it can be applied in laparoscopic
surgery "off-label". Approved in 1996, it has now had
a long history of safety and effectiveness similar
to that of INTERCEED and a number of studies have preorted
its use in a variety of procedures as well as the reduction
of obstruction in some cases. It should not be wrapped
around the bowel that has been cut open.
Some surgeons have made a gel by cutting small pieces
of Seprafilm and mixing them with saline. A study conducted
by Genzyme with a standard preparation called "SepraSpray" has yielded what appear to be unimpressive results.
* Adept, marketed by Baxter
Adept is a solution containing a carbohydrate polymer.
A large volume (about 3 liters) is instilled into the
abdominal cavity after surgery causing them to float,
keeping them apart and preventing them from sticking
to each other. Because of the the composition of the
product, liquid stays in the abdominal cavity for several
more days that plain saline (salt) solutions commonly
used by surgeons. Although, it has the advantage that
it is easy to apply and it can be used laparoscopically,
clinical data suggest that its effectiveness is at
best marginally better than salt solutions, also
when used in large volume.
recent study in gynecological surgery concluded
that there was no evidence of clinical effect, although
undergoing bowel adhesiolysis, the recurrence
did appear lower in patients treated with ADEPT.
It should be noted that small (eg 300ml) volumes
of saline used to float tissues apart do
not appear to
reduce adhesions, thus the data from the Adept study
does suggest that large volumes of physiological saline
solutions may have some benefit in reducing adhesions.
Products not approved for
Adhesions prevention, but often used "off-label"
*Note that some of these products may be approved
in countries other than the USA for adhesion prevention.
* Evicel - made by Johnson & Johnson
Evicel is a type of "Fibrin Glue", a two component
product made from naturally occurring molecules extracted
from human blood. It is mainly used to control bleeding
during surgery. A number of studies in animals and
humans have suggested that fibrin glues of various
types can reduce adhesions. One
study using a similar,
but not identical experimental version of Evicel did
suggest that indeed this type of fibrin glue may reduce
adhesions in humans.
Evicel has the advantage that is can easily be applied
laparoscopically, it can be spayed over a large area,
is a naturally occurring material and can control mild
Other types of fibrin glue, such as Tisseel and Tissucol,
made by Baxter has
also been used by some surgeons to reduce adhesions.
Note - there are a number of important differences
between different types of fibrin glue that could determine
how effective each type is.
* Coseal, made by Baxter
Coseal is a two-component, synthetic product used
to seal leakage after surgery on blood vessels. It
has been sprayed or applied over areas of surgical
injury to reduce adhesions both in animal models and
human trial with 71 patients undergoing myomectomy.
Coseal is marketed
in Europe not only as a sealant, but also to prevent
or reduce post surgical adhesions. Coseal
is the same as what was formerly known as Adhibit.
* Surgiwrap, made by MAST BioSurgery
SurgiWrap (and its cousins OrthoWrap and CardioWrap)
is a clear thin sheet of a dissolvable polymer similar
to the kind used in dissolvable sutures. Full clinical
studies of the kind conducted for INTERCEED or Seprafilm
that it prevents or reduces adhesions have not been
published and the product is approved in the
USA to “reinforce soft tissues where weakness exists”.
Based primarily on animal
studies and due to technicalities in the regulation
of medical devices in the USA, the
literature for the USA states that
the product “Maintains
a physical barrier between opposing soft tissues” and “Retains
tensile strength for 6-8 weeks ensuring tissue separation
during the critical wound healing period” and implies
that the product reduces or minimizes “Soft Tissue
Attachments”. The company’s
literature for Surgiwrap intended for marketing outside
the USA clearly claims that that SurgiWrap “prevents
adhesion formation”. Naturally this difference
has come to the attention of American surgeons who have
traveled abroad and combined with a number of reports
of adverse events such as the presence of a tissue
reaction and the emergence of fragments of the sheet through the
vagina which in
one case was reported to have “lacerated
her partner”, the product does not seem to enjoy
* PRECLUDE Peritoneal Membrane made by WL Gore
This product is being discontinued after December
2011. It never had the same kind of formal approval
in the USA that INTERCEED, Seprafilm or ADEPT did of
adhesion prevention, but after enjoying a fairly long
period of use to reconstruct tissues, for example in
hernia repair, the claim was added sometime in the
early 1990s “for use in peritoneal reconstruction
where minimal adhesions to a prosthetic material are
desired”. PRECLUDE is a thin sheet of porous
ePTFE (Teflon). Although
some studies showed in the 1990s that Preclude (previously
known as GoreTex surgical
Membrane) reduced adhesions, many surgeons were reluctant
to use it since it did not degrade and required a subsequent
operation to remove it.
Versions of the product to minimize adhesions in cardiac and
cranial (dural) surgery.
Drugs for Adhesion Prevention
There are no drugs currently approved for the prevention
or removal of adhesions. Research in this area, most
of it in animals, has focused mainly on drugs that
can be applied directly into the abdominal cavity
at the time of surgery. Most of the drugs tested
have been directed either at the clotting process
(preventing or reversing the deposition of fibrin
- the natural glue that causes the initial attachment
or adhesion of tissues) or the inflammatory process
(which results in the formation of scar).
clinical data did suggest that heparin, when
applied to INTERCEED may not only enhance its action
but also overcome the detrimental
effect that bleeding has on the beneficial action of
INTERCEED. This was never pursued formally. Data from
the pivotal general
surgical trial for Seprafilm in patients
with ulcerative colitis undergoing bowel surgery
did suggest that patients receiving long term corticosteroids
prior to surgery had lower rates of adhesion formation
than those that did not. The effect was best seen in
patients also receiving Seprafilm.
Studies, never published but widely known to have
been performed in the 1980s and 1990s using Non-Steroidal
Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen
and tolmetin applied as solutions to the peritoneal
cavity failed to result in the use of these drugs clinically.
tPA (Tissue Plasminogen Activiator) is a drug causes
the dissolution of fibrin. Several small pilot studies
had been performed but never pursued and a
recent study failed to show a difference between
treatment and control groups.
Newer generations of these classes of drugs have been
tested in animals, bit so far without any formal clinical
trials. Other classes of drugs tested include anti-oxidants,
anti-angiogenic drugs, anti-fibrotic drugs, hormonal
drugs, cytokine inhibitors, anti-inflammatory cytokines
and COX-2 inhibitors.
Hernia and Tissue Reconstruction Meshes
A number of products exist for the reinforcement of
soft tissues after major dissections, including hernias.
Adhesions to these meshes is a common problem and
the designers of some products have attempted to
reduce this problem. These products may feature claims
akin to those of the Preclude products and include
(not exhaustively): Sepramesh
PROCEED (Johnson & Johnson).
These and other surgical meshes may be used not only
in hernia repair but also for Pelvic Organ Prolapse
and Stress Urinary Incontinence. Regarding these kinds
of products in general, FDA has issued a
Public Health Notification on October 20 2008. There
was also an
update on July 13, 2011 regarding complications
associated with some of these meshes that when used for
hernia repair complications include “adverse
reactions to the mesh, adhesions (when the loops of
the intestines adhere to each other or the mesh), and
injuries to nearby organs, nerves or blood vessels
. Other complications of hernia repair can occur with
or without the mesh, including infection, chronic pain
and hernia recurrence.”
When used for Pelvic Organ Prolapse and Stress Urinary
Incontinence the “most frequent complications
included erosion through the vagina, infection, pain,
urinary problems and recurrence of the prolapse and/or
incontinence. In some cases, erosion of the mesh and
scarring of the vagina led to discomfort and pain,
including pain during sexual intercourse. Some patients
needed additional surgery to remove the mesh that had
eroded into the vagina. Other complications included
injuries to nearby organs such as the bowel and bladder,
or blood vessels.”
Since serious complications may occur with the use
of Surgical Meshes it is important that you discuss
with your doctor the risks and benefits of meshes as
well as the type of mesh you may be given and its likelihood
of producing an adverse reaction.
Other Products of Interest
* INSUFLOW, made by Lexion Medical
This novel device warms and humidifies the gases used
to inflate the abdominal cavity during laparoscopic
surgery. Because these cold, dry gases (carbon dioxide)
are pumped at pressure they create a “wind-chill
effect” which damages the surface layer (peritoneum)
of organs in the abdominal cavity, a finding made in
a study by Dr. Wiseman
Although the company does not claim it,
it is well accepted that damage to the peritoneal layer
contributes to the formation of adhesions. In addition
use of the
device helps to reduce hypothermia, postoperative
pain and recovery time after surgery.
Products Marketed Outside of the USA
* SprayGel and SprayShield, made by Covidien
SprayShield is a synthetic two component product
that forms a gel when applied to an organ. It
is a modified
version of SprayGel which demonstrated clinical
effectiveness in reducing adhesions in small studies
involving gynecologicand general surgery
Although all the details are unclear,
it seems that SprayGel was discontinued because of
problems relating to possible adverse reasons and the
ability of the gel to form properly in the carbon dioxide
environment that is used in laparoscopic surgery. SprayGel
was, and SprayShield is marketed in Europe and we understand
that a recent clinical trial in the USA was discontinued
because the product failed to demonstrate efficacy
or because of problems with patient recruitment.
There is very little know about the safety
and effectiveness of SprayShield, but Covidien has
undertaken to provide more information which we will
post. Covidien has decided for business reasons not
to seek FDA approval, and has told us that marketing
support in Europe is a low priority for them. For a
more detailed update of the status of SprayShield please
see our review here.
* Hyalobarrier and Hyalobarrier Endo, made by Fidia
Advanced Biopolymers, now Anika Therapeutics
Hyalobarrier, sometimes referred to as ACP Gel, is
made from hyaluronic acid, a naturally occurring
lubricant in the body.
clinical trials have demonstrated effectiveness
of in gynecologic surgery
* INTERCOAT, also known as Oxiplex AP made by Johnson & Johnson,
licensed from Fziomed
This gel made is applied
directly to raw surgical surfaces. Efficacy in gynecologic
study was demonstrated
* Prevadh, made by Sofradim-Covidien in France
collagen film and fleece composite that in animals
was able to reduce adhesions even in the presence
of bleeding and appeared safe in an uncontrolled
clinical study of 78 patients.
for reducing adhesions in procedures outside of the
or pelvic cavities.
(This is not an exhaustive list, and it also includes
products that have no formal claim of adhesion prevention)
||Nasal / Sinus
|Preclude Dura Substitute
|Oxiplex (also Medishield)
||Spinal, tendon & nerve Surgery
Products where data
exists for prevention of clinical outcomes related
Note that products may or may not have regulatory
approval to market their products based on these studies.
Only a selection of positive studies are shown below.
Prevention of IntraUterine Adhesions
Tsapanos et al., 2002
SprayGel Abbott et al., 2004
ACP Gel Guida et al., 2004
ACP Gel Acunzo et al., 2003
Intercoat Sardo et al., 2011
Prevention of adhesions after C Section
Seprafilm Fushiki H; Ikoma T; Kobayashi H, and Yoshimoto
H. Efficacy of Seprafilm as an Adhesion Barrier in
Cesarean Sections. Obstetric and Gynecological Treatment
[Japanese]. 2005; 91(5):557-561.
et al., Peritoneal adhesion prevention at cesarean
section: an analysis of the effectiveness of an absorbable
adhesion barrier. J Reprod Med. 2011 Mar-Apr;56:103-9.
(shows effect of INTERCEED)
Reduction of pain after adhesion-related surgery
Seprafilm Khaitan et al., 2003
Reduction of bowel obstruction
Mohri et al., 2005
et al., 2006
Products where data exists for improvement of fertility
after adhesion-related surgery (not necessarily with
INTERCEED Sawada et al.,2000
* Sepracoat (also HAL-C), made by Genzyme was a hyaluronic
acid based liquid that was used to coat tissue surfaces
during surgery. It demonstrated clinical efficacy against
de novo adhesions caused by tissue handling.
Its approval in the USA was rejected, and the product
sold for a short time in Europe before poor sales led
to its voluntary discontinuation sometime around 2000.
* INTERGEL, made by LifeCore, marketed by Johnson & Johnson
was a gel of hyaluronic acid cross-linked with iron.
With demonstration of clinical efficacy in the US
and Europe .long
it received FDA approval in 2002 after an unusual and
controversial route but was withdrawn about one year
later after reports
of tissue reactions, increased rates of infection, late onset pain and some deaths.
Research conducted by the IAS suggested
that these effects may
have been more prevalent in patients who carried gene
mutations for Haemochromatosis, a disorder of
iron regulation, or women who had had prior hysterectomies,
possibly because of an increased tendency to accumulate
iron. Additional article.
L was a gel containing Dextran Sulphate
made by Gliatech for use in spinal surgery. It was approved
by FDA in 1997. A version for tendon and nerve surgery
was available in Europe and after a successful preclinical
study conducted by Dr. Wiseman, a clinical trial, also
designed by Dr. Wiseman had began to show promising results
in pelvic surgery. Rapid sales of the ADCON L product
began to be marred by a series of issues relating to
problems in manufacturing, the company’s failure
to report adverse events, and their alleged manipulation
of data in a clinical trial. The company essentially
placed in a “regulatory” limbo by FDA until
it could, to FDA’s satisfaction put its house in
order. A new management did indeed do this, but the effect
of the FDA action forced the company to declare bankruptcy
in 2002 when the product was sold to Wright Medical Technologies.
Although not available in the USA, the product continues
to be sold elsewhere as ADCON Gel indicated for spine,
tendon and nerve surgery by BiosCompass, Inc
* Hyskon, made by Pharmacia, was
a syrupy liquid used to expand the uterus during hysteroscpic
In the mid 1980s its was used off-label in the USA
to prevent adhesions by pouring it into the abdominal
cavity in the aim that it would lubricate raw tissue
surfaces and prevent them from sticking. Some
studies provided somewhat positive data,
the reverse and concerns of adverse reactions as well the emergence
of other barriers led to its demise.
Information about adverse reactions reported to FDA
can be obtained through:
MAUDE - Manufacturer and User Facility Device Experience
If you think you have suffered an adverse reaction
to any medical product, you should certainly contact
your doctor and if necessary call the Emergency Services
or go to the nearest Emergency Room. You are also free
to report the event to the FDA by contacting the FDA's
MedWatch Adverse Event Reporting program either online,
by mail or FAX.
Online : MedWatch
Online Voluntary Reporting Form (3500)
Mail : use postage-paid FDA form 3500 available
at: MedWatch Forms
5600 Fishers Lane,
Interested in participating in a clinical trial?
Go to ClincalTrials.gov
to search for clinical trials relating to adhesions,
or any other therapeutic area.
Centerwatch is another site where you can find information
trials on adhesions.