The document profiles Dr. Laxmi Shrikhande, an Indian gynecologist who has received several awards and honors for her contributions to women's health. It then discusses adhesion prevention options, noting that good surgical technique is fundamental to reducing adhesion formation and that barrier agents such as oxidized regenerated cellulose and fluids can also help decrease postoperative adhesion rates when used appropriately. Pharmacological agents have generally not proven effective for adhesion prevention.
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Dr. Laxmi Shrikhande on Adhesion Prevention Options
1. Dr. Laxmi Shrikhande MD; FICOG; FICMCH;FICMU
Director-Shrikhande Fertility Centre, Nagpur
Senior Vice President FOGSI 2012
Associate member RCOG, London
Member of European Society of Human Reproduction
Received Bharat excellence Award for contribution to women’s health
Chairperson HIV Committee FOGSI 2009-12
Received best FOGSI committee award
National Editor-The Journal of OB / GY of India
Vice Chairperson Elect Indian College of OB/GY
Publications-Thirteen National & seven International
Editor-FOGSI Focus on HIV in women
Editor-FOGSI Focus on SUI- Myths & Facts
Presented Papers at FIGO,SAFOG,AOFOG, IFFS
3. What are adhesions
• Adhesions are defined as abnormal attachments
between tissues and organs.
• Intra-abdominal adhesions may be classified as
congenital or acquired.
• Congenital adhesions are a consequence of
embryological anomaly in the development of the
peritoneal cavity.
4. Acquired adhesions
• Acquired adhesions result from the inflammatory
response of the peritoneum that arises after intra-
abdominal inflammatory processes (e.g. acute
appendicitis, pelvic inflammatory disease, exposure
to intestinal contents and previous use of
intrauterine contraceptive devices), radiation and
surgical trauma.
• It has been reported that the majority of acquired
adhesions (about 90%) are post-surgical.
6. Factors
• Factors associated with the formation of post-
surgical adhesions include
– tissue trauma,
– infection,
– ischaemia,
– reaction to foreign bodies (sutures, powder from gloves,
gauze particles etc.),
– haemorrhage,
– tissue overheating or desiccation and
– exposure to irrigation fluids.
7. Incidence
• The incidence of intra-abdominal adhesions ranges
from 67% to 93% after general surgical abdominal
operations and from 60% to 90% after gynecological
procedures.
• adhesion formation is considered as one of the most
common post-operative complications .
8. Symptoms
• Post-surgically, many adhesions may be asymptomatic or
can lead to a broad spectrum of clinical problems, including
• intestinal obstruction,
• chronic pelvic or abdominal pain and
• female infertility,
• requiring re-admission and
• often additional surgery, while at the same time
• they can complicate future surgical procedures.
9. Prevention
• The major strategies for adhesion prevention in
gynecological surgery aim at the optimization of
surgical technique and use of adhesion-prevention
agents.
• Laparoscopic surgery in gynecology represents the
most innovative surgical approach, compared with
laparotomy since it has been shown from a large
number of clinical, and also experimental studies,
that it is associated with less development of de novo
adhesions.
10. Prevention
• Without any doubt, the most important factor is the
operating surgeon, whose attention to proper
surgical technique will serve as a mainstay for
prevention of adhesion formation.
11. Good surgical technique is fundamental to any
adhesion reduction strategy:
• Carefully handle tissue with field enhancement
(magnification) techniques.
• Focus on planned surgery and, if any secondary
pathology is identified, question the risk: benefit ratio
of surgical treatment before proceeding.
• Perform diligent haemostasis and ensure adequate
use of cautery.
• Reduce cautery time and frequency and aspirate
aerosolised tissue following cautery.
12. Good surgical technique is fundamental to any
adhesion reduction strategy:
• Excise tissue rather than coagulate to reduce
fulguration, e.g. in endometriosis.
• Reduce duration of surgery.
• Reduce pressure and duration of pneumoperitoneum
in laparoscopic surgery.
• Reduce risk of infection.
• Reduce drying of tissues.
• Use frequent irrigation and aspiration in laparoscopic
and laparotomic surgery.
13. Good surgical technique is fundamental to any
adhesion reduction strategy:
• Limit use of sutures and choose fine non-reactive sutures.
• Avoid foreign bodies when possible.
• Avoid non-peritonised implants and meshes.
• Minimize use of dry towels or sponges in laparotomy.
• Use starch- and latex-free gloves in laparotomy.
• Avoid mechanical uterine curettage. Medical management of
spontaneous or induced abortion may be recommended
rather than surgical management. In case of uterine curettage
- use aspiration technique.
• Reduce the use of electrosurgical energy in hysteroscopic
surgery (rather use “cold” mechanical instruments).
14. How to choose Adhesion prevention agents
• Surgeons should consider the use of adhesion
reduction agents as part of the adhesion reduction
strategy.
16. Non pharmacological agents
• Modern non-pharmacological agents are available as films,
gels, powder or fluids, and have shown to be safe and
effective to reduce the risk of post-operative adhesions ,
although, the new substances lack long-term evidence
•Ahmad G, O’Flynn H, Hindocha A, Watson A (2015) Barrier agents for adhesion prevention after gynaecological surgery.
Cochrane Database of Systematic Reviews.
•Gao X, Deng X, Wei X, Shi H, Wang F, et al. (2013) Novel thermosensitive hydrogel for preventing formation of abdominal
adhesions. Interantional Journal Nanomedicine of abdominal adhesions. Int J Nanomedicine 8: 2453-2463.
•Qin F, Ma Y, Li X, Wang X, Wei Y, et al. (2015) Efficacy and mechanism of tanshinone IIA liquid nanoparticles in
preventing experimental postoperative peritoneal adhesions in vivo and in vitro. Int J Nanomedicine 10: 3699-3717.
17. Non pharmacological agents
• The selection will depend on the
– type of surgery,
– extension of the surface to be covered,
– presence of diffuse bleeding,
– expected use of post-operative drainage and
– costs.
• For example, some substances should not be applied on
bleeding surfaces, on sutured bowel or in the uterine cavity,
and films should not be overlapped.
18. Non pharmacological agents
• In addition, surgeons should follow the mode of use specified
by the producer, and keep in mind that most of agents are
not recommended in presence of infection, malignancy, bowel
leakage or for intravascular use.
• On the other hand, non-pharmacological agents , which have
proved to be ineffective or to impair with the normal
postsurgical re-epithelialization process, like colloids,
crystalloids or steroids should not be used.
De Wilde RL, Brölmann H, Koninckx PR, Lundorff P, Lower AM, et al. (2012) The Anti-Adhesions in Gynecology
European field guideline. Gynecol Surg 9: 365-368.
20. Pharmacological agents
• A wide variety of pharmacological agents have been
used in attempts to prevent or attenuate the
formation of post-surgical adhesions, but none of
them has been found to be effective.
• The use of drugs for adhesion prevention has some
obstacles that affect their efficacy.
• Ischaemia and inadequate blood supply are important
factors in adhesion formation and these also
decrease systemic drug delivery inhibiting their
effectiveness.
21. Pharmacological agents
• Peritoneum has an extremely rapid absorption
mechanism, that limits the half life and efficacy of
many intra-peritoneally administered agents.
• Anti-adhesion agents must not affect normal wound
healing, which has steps in common with adhesion
formation (fibrinous exudate, fibrin deposition,
fibroblast activity and proliferation).
Trew, G: Postoperative adhesions and their prevention. Rev. Gynaecol. Perinat.Pract. 2006;6: 47–56.
22. Non-steroidal anti-inflammatory drugs
• Non-steroidal anti-inflammatory drugs (NSAID)
affect adhesion formation by several mechanisms.
• They act by modifying arachidonic acid metabolism
and altering cyclooxygenase activities.
• This results in decreased vascular permeability,
platelet aggregation, and coagulation and enhanced
macrophage function.
• A number of locally and systemically administered
NSAID have been used in experimental trials.
23. Non-steroidal anti-inflammatory drugs
• No relevant clinical trials assessing the effectiveness
of NSAID in adhesion prevention have been
published to date in patients undergoing
gynaecological surgery.
• Their clinical efficacy is questionable probably
because of inadequate concentrations at the sites of
surgical trauma or by rapid absorption from the
peritoneal membrane.
Risberg, B. Adhesions: preventive strategies. Eur. J. Surg. Suppl. 1997;32: 39.
24. Antibiotics
• Antibiotics are commonly used for prophylaxis
against post-operative infections and hence may
retard the inflammatory response that leads to
adhesion formation.
• Peritoneal irrigation with antibiotic solutions does
not reduce adhesion formation, while it has been
shown that in some cases it may promote them.
Rappaport, W.D., Holcomb, M., Valente, J., Chvapil, M. Antibiotic irrigation and the
formation of intraabdominal adhesions. Am. J. Surg. 1989;158: 435–437.
25. Fluid barriers
• Fluids constitute an ideal barrier agent because their action is
not limited to the site of application.
• Their function is provided by hydrofloration of intra-
peritoneal structures in the liquid that is infused into the
peritoneal cavity at the end of the surgical procedure.
• Hydrofloration provides a temporary separation between raw
peritoneal surfaces allowing independent healing without the
formation of adhesions.
• Possibly, fluid circulation in the peritoneal cavity contributes
• to the prevention of adhesion formation by diluting fibrinous
exudates released from traumatized surfaces
26. Fluid barriers
• Fluid barriers may prevent adhesion formation both at the
traumatized area and elsewhere in the pelvis.
• The instillation of fluids in the peritoneal cavity may be
associated with some undesirable side effects, such as leakage
from the incision, labial oedema, feeling of fluid moving
around, abdominal discomfort, abdominal distension and
complications such as pulmonary and peripheral oedema.
• Large volumes of intra-peritoneal fluids may decrease the
peritoneum ability to confront bacterial infections.
Sutton, C., Minelli, L., Garcıa, E., et al.Use of icodextrin 4% solution in the reduction of
adhesion formation after gynaecological surgery. Gynecol. Surg. 2005;2: 287–296.
28. Anti-adhesive barriers
• The failure of pharmacological regimens to prevent adhesion
formation has led to the revival of the barrier technique.
• With the barrier technique, traumatized peritoneal surfaces
are kept separated, during mesothelial regeneration, thus
precluding adherence of adjacent organs and tissues and
reducing the development of adhesions.
• The separation can be achieved by the use of solid (films or
gels) or fluid barriers.
Trew, G: Postoperative adhesions and their prevention. Rev. Gynaecol. Perinat.Pract.
2006;6: 47–56.
29. Anti-adhesive barriers
• Anti-adhesive barriers are currently the most useful adjuvant
for prevention of post-operative adhesion formation.
• Numerous substances have been used as mechanical barriers
to separate tissue surfaces.
• Most of these materials are of historical interest only and had
no effect or even aggravated adhesion formation.
Arora, M., Jaroudi, K.A., Hamilton, C.J., Dayel, F. Controlled comparison of intercede and amniotic membrane graft in the
prevention of postoperative adhesions in the rabbit uterine horn model. Eur. J. Obstet. Gynecol. Reprod. Biol. 1994;55: 179–182.
Seifer, D.B., Diamond, M.P., DeCherney, A.H. An appraisal of barrier agents in the reduction of adhesion formation following
surgery. J. Gynecol. Surg. 1990; 6: 3–10.
30. Surgical adhesion barriers
• Surgical barriers may help to decrease postoperative
adhesion formation but cannot compensate for poor
surgical technique.
31. Interceed
• Oxidized regenerated cellulose (Interceed) is an absorbable
adhesion barrier that requires no suturing. It is degraded into
monosaccharides and absorbed within 2 weeks after
application.
• The product has been shown to reduce adhesion formation in
randomized controlled clinical trials , all of which have
demonstrated benefit for reducing the incidence and extent
of new and recurrent adhesions by 50%–60% after both
laparoscopic and open abdominal surgical procedures.
Li TC, Cooke ID. The value of an absorbable adhesion barrier, Interceed, in the prevention of adhesion
reformation following microsurgical adhesiolysis. Br J Obstet Gynaecol 1994;101:335–9.
32. Interceed
• However, there is scant evidence that the reduction
in adhesions resulting from use of oxidized
regenerated cellulose improves fertility.
Sawada T, Nishizawa H, Nishio E, Kadowaki M. Postoperative adhesion prevention with an
oxidized regenerated cellulose adhesion barrier in infertile women. J Reprod Med 2000;45:387–9.
33. Interceed
• Complete hemostasis must be achieved, as the product is
rendered ineffective when saturated with blood.
• A study in humans (in contrast to the results from animal
studies) found that adding heparin to oxidized regenerated
cellulose provided no additional benefit .
• Oxidized regenerated cellulose (in the form of Interceed) has
been approved by the FDA for use in the United States for
reducing adhesions.
Reid RL, Hahn PM, Spence JE, Tulandi T, Yuzpe AA, Wiseman DM. A randomized clinical trial of
oxidized regenerated cellulose adhesion barrier (Interceed, TC7) alone or in combination with heparin.
Fertil Steril 1997; 67:23–9.
34. Fibrin glue
• Fibrin glue (Tissucol; Baxter International, Deerfield, IL, USA)
is a biological product.
• Fibrin glue is made by mixing human fibrinogen with bovine
thrombin, calcium and factor XIII.
• Obviously, the use of human blood products raises a
theoretical risk for transmission of infectious diseases.
• According to the pathogenesis of adhesions, application of
fibrin glue at the traumatized peritoneal surfaces should
increase adhesion formation.
Evrard, V.A., De Bellis, A., Boeckx, W., Brosens, I.A. Peritoneal healing after fibrin
glue application: a comparative study in a rat model. Hum. Reprod. 1996;11: 1877–
1880.
35. Fibrin glue
• Possibly, fibrin glue application confines fibrin deposition and
averts the development of attachments between opposing
tissue surfaces.
• In animal studies, the use of fibrin glue has been shown to
decrease adhesion formation and reformation but clinical data
are limited. Fibrin glue has not been approved by the FDA for
use in USA.
• So far, no relevant data from trials in humans have been
published.
The Practice Committee of the ASRM. Control and prevention of peritoneal adhesions
in gynecologic surgery. Fertil. Steril. 2006;86: S1–S5.
Hellebrekers, B.W., Trimbos-Kemper, G.C., van Blitterswijk, C.A., Bakkum, E.A.,Trimbos, J.B. Effects of
five different barrier materials on postsurgical adhesion formation in the rat.
Hum. Reprod. 2000;15: 1358–1363.
36. The ideal adhesion barrier
The ideal adhesion barrier should meet the following criteria:
(1) achieves effective tissue separation;
(2) has a long half-life within the peritoneal cavity so that it can
remain active during the critical 7-day peritoneal healing
period;
(3) is absorbed or metabolized without initiating a marked
proinflammatory tissue response;
(4) remains active and effective in the presence of blood;
(5) does not compromise wound healing; and
(6) does not promote bacterial growth.
37. Take Home Message
• There is no evidence that anti-inflammatory agents reduce
postoperative adhesions.
• There is insufficient evidence to recommend peritoneal
instillates such as icodextrin to reduce adhesions.
• The FDA-approved surgical barriers Seprafilm, Interceed, and
the Gore-Tex Surgical Membrane have been demonstrated
effective for reducing postoperative adhesions.
• However, there is no substantial evidence that their use
improves fertility, decreases pain, or reduces the incidence of
postoperative bowel obstruction.
38. Take Home Message
• Good surgical technique was advocated as the main
way to prevent postoperative adhesions.
• This included strict adherence to the basic surgical
principles of minimizing tissue trauma with
meticulous hemostasis, minimization of ischemia and
desiccation, and prevention of infection and foreign
body retention.
A wide variety of pharmacological agents (Table 2) have been used in attempts to prevent or
attenuate the formation of post-surgical adhesions, but none of them has been found to be
effective. The use of drugs for adhesion prevention has some obstacles that affect their efficacy.
Ischaemia and inadequate blood supply are important factors in adhesion formation
and these also decrease systemic drug delivery inhibiting their effectiveness. Peritoneum has an extremely rapid absorption mechanism, that limits the half life and efficacy of many
intra-peritoneally administered agents. Anti-adhesion agents must not affect normal wound
healing, which has steps in common with adhesion formation (fibrinous exudate, fibrin deposition,
fibroblast activity and proliferation) [19,25]. The clinical effectiveness of these agents
has been evaluated in a systematic review and meta-analysis that analysed data from relevant
randomized controlled trials (RCT) published up to 2005 [26].
A wide variety of pharmacological agents (Table 2) have been used in attempts to prevent or
attenuate the formation of post-surgical adhesions, but none of them has been found to be
effective. The use of drugs for adhesion prevention has some obstacles that affect their efficacy.
Ischaemia and inadequate blood supply are important factors in adhesion formation
and these also decrease systemic drug delivery inhibiting their effectiveness. Peritoneum has an extremely rapid absorption mechanism, that limits the half life and efficacy of many
intra-peritoneally administered agents. Anti-adhesion agents must not affect normal wound
healing, which has steps in common with adhesion formation (fibrinous exudate, fibrin deposition,
fibroblast activity and proliferation) [19,25]. The clinical effectiveness of these agents
has been evaluated in a systematic review and meta-analysis that analysed data from relevant
randomized controlled trials (RCT) published up to 2005 [26].
Non-steroidal anti-inflammatory drugs (NSAID) affect adhesion formation by several mechanisms.
They act by modifying arachidonic acid metabolism and altering cyclooxygenase activities.
This results in decreased vascular permeability, platelet aggregation, and
coagulation and enhanced macrophage function. A number of locally and systemically administered
NSAID have been used in experimental trials.
No relevant clinical trials assessing the effectiveness of NSAID in adhesion prevention have
been published to date in patients undergoing gynaecological surgery. Their clinical efficacy
is questionable probably because of inadequate concentrations at the sites of surgical trauma
or by rapid absorption from the peritoneal membrane [3,19,27].
Non-steroidal anti-inflammatory drugs (NSAID) affect adhesion formation by several mechanisms.
They act by modifying arachidonic acid metabolism and altering cyclooxygenase activities.
This results in decreased vascular permeability, platelet aggregation, and
coagulation and enhanced macrophage function. A number of locally and systemically administered
NSAID have been used in experimental trials.
No relevant clinical trials assessing the effectiveness of NSAID in adhesion prevention have
been published to date in patients undergoing gynaecological surgery. Their clinical efficacy
is questionable probably because of inadequate concentrations at the sites of surgical trauma
or by rapid absorption from the peritoneal membrane [3,19,27].
Antibiotics are commonly used for prophylaxis against post-operative infections and hence
the inflammatory response that leads to adhesion formation. Peritoneal irrigation with antibiotic
solutions does not reduce adhesion formation, while it has been shown that in some
cases it may promote them [45].
22. Fluid barriers
Fluids constitute an ideal barrier agent because their action is not limited to the site of application.
Their function is provided by hydrofloration of intra-peritoneal structures in the liquid
that is infused into the peritoneal cavity at the end of the surgical procedure. Hydrofloration
provides a temporary separation between raw peritoneal surfaces allowing independent healing
without the formation of adhesions. Possibly, fluid circulation in the peritoneal cavity contributes
to the prevention of adhesion formation by diluting fibrinous exudates released from
traumatized surfaces. Fluid barriers may prevent adhesion formation both at the traumatized
area and elsewhere in the pelvis. The instillation of fluids in the peritoneal cavity may be associated
with some undesirable side effects, such as leakage from the incision, labial oedema, feeling
of fluid moving around, abdominal discomfort, abdominal distension and complications
such as pulmonary and peripheral oedema. Large volumes of intra-peritoneal fluids may decrease
the peritoneum ability to confront bacterial infections [3,17,76].
22. Fluid barriers
Fluids constitute an ideal barrier agent because their action is not limited to the site of application.
Their function is provided by hydrofloration of intra-peritoneal structures in the liquid
that is infused into the peritoneal cavity at the end of the surgical procedure. Hydrofloration
provides a temporary separation between raw peritoneal surfaces allowing independent healing
without the formation of adhesions. Possibly, fluid circulation in the peritoneal cavity contributes
to the prevention of adhesion formation by diluting fibrinous exudates released from
traumatized surfaces. Fluid barriers may prevent adhesion formation both at the traumatized
area and elsewhere in the pelvis. The instillation of fluids in the peritoneal cavity may be associated
with some undesirable side effects, such as leakage from the incision, labial oedema, feeling
of fluid moving around, abdominal discomfort, abdominal distension and complications
such as pulmonary and peripheral oedema. Large volumes of intra-peritoneal fluids may decrease
the peritoneum ability to confront bacterial infections [3,17,76].
The failure of pharmacological regimens to prevent adhesion formation has led to the revival
of the barrier technique. With the barrier technique, traumatized peritoneal surfaces are
kept separated, during mesothelial regeneration, thus precluding adherence of adjacent organs
and tissues and reducing the development of adhesions. The separation can be achieved
by the use of solid (films or gels) or fluid barriers [19,25]. Anti-adhesive barriers are
currently the most useful adjuvant for prevention of post-operative adhesion formation. Numerous
substances (Table 3) have been used as mechanical barriers to separate tissue surfaces.
Most of these materials are of historical interest only and had no effect or even
aggravated adhesion formation [48,49]. An anti-adhesive agent should be effective, safe, economical
and easy to use in both open and laparoscopic surgery [50]. The clinical effectiveness
of several of these agents has been evaluated in two recent Cochrane reviews [26,51].
The failure of pharmacological regimens to prevent adhesion formation has led to the revival
of the barrier technique. With the barrier technique, traumatized peritoneal surfaces are
kept separated, during mesothelial regeneration, thus precluding adherence of adjacent organs
and tissues and reducing the development of adhesions. The separation can be achieved
by the use of solid (films or gels) or fluid barriers [19,25]. Anti-adhesive barriers are
currently the most useful adjuvant for prevention of post-operative adhesion formation. Numerous
substances (Table 3) have been used as mechanical barriers to separate tissue surfaces.
Most of these materials are of historical interest only and had no effect or even
aggravated adhesion formation [48,49]. An anti-adhesive agent should be effective, safe, economical
and easy to use in both open and laparoscopic surgery [50]. The clinical effectiveness
of several of these agents has been evaluated in two recent Cochrane reviews [26,51].
Fibrin glue (Tissucol; Baxter International, Deerfield, IL, USA) is a biological product. Fibrin
glue is made by mixing human fibrinogen with bovine thrombin, calcium and factor XIII [92]. Obviously, the use of human blood products raises a theoretical risk for transmission of
infectious diseases. According to the pathogenesis of adhesions, application of fibrin glue at
the traumatized peritoneal surfaces should increase adhesion formation. Possibly, fibrin
glue application confines fibrin deposition and averts the development of attachments between
opposing tissue surfaces. In animal studies, the use of fibrin glue has been shown to
decrease adhesion formation and reformation but clinical data are limited. Fibrin glue has
not been approved by the FDA for use in USA [22,47]. So far, no relevant data from trials in
humans have been published.
Fibrin glue (Tissucol; Baxter International, Deerfield, IL, USA) is a biological product. Fibrin
glue is made by mixing human fibrinogen with bovine thrombin, calcium and factor XIII [92]. Obviously, the use of human blood products raises a theoretical risk for transmission of
infectious diseases. According to the pathogenesis of adhesions, application of fibrin glue at
the traumatized peritoneal surfaces should increase adhesion formation. Possibly, fibrin
glue application confines fibrin deposition and averts the development of attachments between
opposing tissue surfaces. In animal studies, the use of fibrin glue has been shown to
decrease adhesion formation and reformation but clinical data are limited. Fibrin glue has
not been approved by the FDA for use in USA [22,47]. So far, no relevant data from trials in
humans have been published.