Diaa M. El-Mowafi - Zagagig University, Egypt

Gynecologic surgery and subsequent bowel obstruction

Diaa M. El-Mowafi
Associate Professor, Obstetrics and Gynaecology
Department of Obstetrics and Gynecology, Benha Faculty of Medicine
Lecturer and Researcher, Wayne State University, Detroit, Michigan, USA
Fellow, Geneva University, Switzerland

Michael P. Diamond
Professor and Director
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology
Wayne State University, Detroit, Michigan, USA

Correspondig Author: Dr. Diaa El-Mowafi 4 Ghazza Street, El-Hossania, El-Mansoura 35111, Egypt. Tel. +2 050 363308 Fax +2 050 332771

Intestinal obstruction is a broad term, which entails cessation of the normal progression of the intestinal contents. Intestinal obstruction can be segregated into complete and incomplete blockage, and be due to mechanical or functional etiologies.

Mechanical obstruction is a term usually applied when there is an actual physical barrier blocking the intestinal lumen, such as bands of adhesion, strangulated hernias, and pressure from pelvic tumors. In contrast, adynamic ileus is used to describe disorders of propulsive motility of the bowel.

Mechanical Intestinal Obstruction

Intestinal obstruction is one of the more common and potentially fatal complications following gynecologic surgery. Forty years ago, mortality rate of 40% to 60% was not uncommon. Currently, the mortality rate has decreased but is still between 10% to 20% for all patients with obstruction of the small intestine.1

Adhesions, usually secondary to previous surgical procedures, are the most common cause of intestinal obstructions in the United States, and are responsible for 49% to 74% of small bowel obstruction in industrial countries.2 Menzies and Ellis3 reported that 93% of 210 patients who had previously undergone abdominal operations had substantial peritoneal adhesions at the time of reoperation. Gynecologic procedures, appendectomies, and other intestinal operations are the three most common type of surgical procedures performed before these occurrences.4,5 Lo et al,6 in 1966, reported a series in which 21% of patients with small bowel obstruction secondary to adhesions have had some form of gynecologic surgery. Melody,7 in 1957, reported that abdominal hysterectomy is the most common operation, which was associated with postoperative intestinal obstruction among 487 gynecological surgeries. In 1983, Ratcliff et al.,15 reviewed 59 cases of admitted women who underwent exploratory laparotomy for relief of small bowel obstruction. They found that 49 patients (83%) had previous abdominal surgery. Of these 49 patients, 38 (78%) had some type of obstetric or gynecologic abdominal procedure, of which 33 of the 49 (67%) had previously undergone a total abdominal hysterectomy.

In 1994, Monk et al.,8 reported that postoperative adhesions occur in 60% to 90% of patients undergoing major gynecologic surgery. The incidence of adhesion-related intestinal obstruction after gynecologic surgery for benign conditions without hysterectomy was approximately 0.3%, increased to 2% to 3% among patients who underwent hysterectomy, and was as high as 5% if a radical hysterectomy was performed.

ADYNAMIC ILEUS

Some degree of adynamic ileus occurs after any intra-abdominal operation as well as in association with nearly all cases of intra-abdominal inflammation. The recovery of motor function of the intestines depends on many factors, including the length of the operation, the extent of handling of the bowel, the degree of chemical and bacterial peritonitis, and the underlying disease. After abdominal operations the patient usually feels hungry and passes flatus within the first three postoperative days. If the patient is not interested in eating, denies flatus and the abdomen is distended and has inaudible intestinal sounds, further diagnostic procedure may be called for. Radiography of adynamic ileus shows distention of both the small and large bowel, with scattered air-fluid levels.

The treatment consists of correction of any electrolyte imbalance, if present, as low serum potassium or sodium as well as hypomagnesemia and severe protein depletion can cause bowel atony. Ambulation, systemic and localized intestinal stimulation by rectal suppositories may be helpful. Otherwise, nasogastric intubation for decompression may be needed.1

PATHOPHYSIOLOGY OF INTESTINAL OBSTRUCTION

Obstruction of the small intestine causes collection of intestinal contents proximal to the obstruction leading to intestinal distention. Swallowed air, that represents over 70% of the air in the gastrointestinal tract, increases this distention. Because the veins and arteries enter the intestinal wall tangentially, the tension on them increases rapidly with distention. The veins, having the lower pressure, show the effect of the increase in tension first. As they are stretched, resistance in them increases, and flow slows down. Fluid rich in protein and salt begins to exude from the capillaries resulting in edema. Intraluminal fluid accumulation increases from both active secretion and decreased absorption. Subsequently, blood cells begin to escape from the capillaries, venous flow finally stops, and as arterial flow continues, blood accumulates in the wall and in the lumen of the bowel. If this process continues unabated gangrene occurs, intestinal integrity is lost and peritonitis quickly follows.1 Importantly, even in the absence of food and liquid ingestion, the volume within the gastrointestinal tract may continue to expand. The total volume of daily secretions into the normal gastrointestinal tract is estimated to be about 10 liters. As much as 7-8 liters of fluid can easily be sequestered in the bowel with intestinal obstruction.

Stagnant bowel contents in a distended loop of ileum show an increase in the number of bacteria. As long as the mucosa is intact and viable, the bacteria are harmless; however, increased intraluminal pressure for a sustained period will produce patchy areas of necrosis that allow some of the intestinal contents to escape into the peritoneal cavity. The main avenue of sepsis from intestinal obstruction is absorption from the peritoneal cavity and not the venous and lymphatic system.9

PATHOPHYSIOLOGY OF ADHESION FORMATION

Following peritoneal injury, the microvasculature beneath the mesothelium becomes disrupted. This is followed by extravasation of serum and cellular elements. Within 3 hours, this proteinaceous fluid coagulates, producing fibrinous bands between abutting surfaces.10 Twelve hours later; polymorphonuclear cells are entangled in fibrin strands, which are subsequently replaced with a macrophage infiltrate. By 48 hours after peritoneal injury, the wound surface is covered with a layer of macrophages.8 In normal peritoneal healing, the fibrinolytic system is triggered to lyse these fibrinous strands within 72 hours of the insult. Within the initial 5 days, re-epithelization of the peritoneal injury occurs. Interestingly, it appears that centripetal growth from the margin of peritoneal wounds contributes little to the healing p; the new mesothelium is derived from the metaplasia of subperitoneal perivascular connective tissue cells that resemble primitive mesenchymal cells.11 Disruption of the existing equilibrium between fibrin deposition and fibrinolysis leads to persistence of the fibrinous strands, which then becomes infiltrated by proliferating fibrobiasts. Subsequently, vascularization and cellular ingrowth occur, and an adhesion is created.10

During mesothelial repair, macrophages and lymphocytes produce growth factors that modulate fibroblast proliferation and collagen synthesis, including platelet-derived growth factor, transforming growth factor-b , fibroblast growth factor, epidermal growth factor, interleukin-l, and tumor necrosis factor-a .12,13 Prostaglandins, particularly prostaglandin E2, are also involved in normal and abnormal mesothelial repair,14,15 most likely through a separate mechanism not related to fibroblast proliferation.16

Adequate blood supply is critical for normal fibrinolysis to occur. Peritoneal injurischemia interferes with fibrinolysis and leads to organization rather than resolution of the fibrin-cellular matrix.8 Ischemia may also induce adhesion formation by stimulating the growth of blood vessels form a non-ischemic to an ischemic site.17 Ischemia may result from excessive handling, crushing, ligating, suturing, cauterizing, or stripping of the peritoneum.

Foreign body reaction causes excessive formation of the fibrin coagulum that stimulates the development of adhesions. Common foreign bodies include sutures as well as cornstarch powder and lint from drapes, caps, gown, masks, and laparotomy pads. It is interesting that foreign bodies in the absence of peritoneal injury are an infrequent cause of adhesion formation.17

The presence of intraperitoneal blood has also been proposed to play a role in adhesion formation, although its actual contribution is not clear. However, free blood in the peritoneal cavity generally does not lead to adhesions, except in the presence of tissue ischemia.19

Infection may result in the development of adhesions by causing the release of proteolytic enzymes, which lead to ischemia and tissue damage, resulting in the formation of adhesions.5

In summary, ischemia seems to play the central role in adhesions formation and factors that compromise blood flow within the area of tissue injury lead to the development of adhesions. Thermal injury,20,21 infection,22 foreign body reaction,22,23 radiation induced endarteritis,24 and impairment of the fibrinolytic activity, all probably act via inducing ischemia to enhance adhesion formation. The thermal effect on adhesion formation called the question about optimal method to achieve hemostasis; is it cautery or sutures as both are incriminated in the etiology of development of adhesions.

DIAGNOSIS OF INTESTINAL OBSTRUCTION

The initial symptom of intestinal obstruction is sudden onset of crampy abdominal pain. This pain is intermittent, with intervals devoid of it which are longer than the periods of pain. The pain is classically periumbilical for a midgut obstruction. Vomiting may accompany the onset of pain with the possibility of recurrence if obstruction persists.

Inspection of the abdomen usually shows distention in persistent obstruction. Loops of intestine with visible peristalsis may be seen beneath the abdominal wall in the very thin patient. High-pitched, tinkling, or metallic intestinal sounds are characteristic of obstruction and occasionally can be heard without a stethoscope. These sounds represent the existence of the air-fluid interface. Motility with violent bursts of peristalsis occurs proximal to the obstruction. The duration of quiet intervals between bursts of peristalsis may suggest the level of obstruction; in high obstruction the time may be 3 to 5 minutes, whereas in low obstruction it may be 10 to 15 minutes.1 Palpation in the early stage of the disease may disclose no tenderness. As distention progresses, it is usual to find tenderness over the point of obstruction.

X-ray study demonstrating distended loop(s) of intestine with air-fluid levels, is suggestive of a mechanical obstruction, whereas grossly dilated loops of small bowel with gas in the colon is typically found is adynamic ileus.7 Computed tomography (CT) was used recently to diagnose postoperative intestinal obstruction due to adhesions.25 The CT findings that suggest strangulated obstruction are serrated beaks, mesenteric edema or vascular engorgement, and moderate to severe bowel wall thickening. In contrast, simple obstruction could be assumed when the beak is smooth, there are no mesenteric changes, and the bowel wall is normal or mildly thickened.

PERITONEAL CLOSURE AND ADHESIVE INTESTINAL OBSTRUCTION

Suturing the parietal peritoneum of the anterior abdominal wall at completion of gynecologic and obstetric surgery was always a tradition. Intuitive logic suggests that it will be of benefit to re-establish normal anatomical relationships and to prevent adhesion formation between the intestines and/or uterus and fascia. However, data supporting this hypothesis is lacking, and in fact it may be incorrect. Importantly, reperitonalization also places pelvic and abdominal contents within the abdominal cavity, and possibly makes fascial closure easier.

The microscopic cellular studies in animals have demonstrated that the broad peritoneal repairative process is different from that of the edge-to-edge skin cicatrization.26 When left undisturbed, peritoneal defects demonstrate mesothelial integrity (reperitonization) by 48 hours and complete indistinguishable healing i.e. without scaring can be achieved by 5 days.27, 28

Adhesions are caused by ischemia, inflammation, and infection rather than by open surfaces. Re-approximation of peritoneal edges or repair of defects via grafts, even with suture material considered to be minimally reactive, results in increased tissue ischemia and foreign-body tissue reaction, and may lead to increased adhesion formation at the site of reperitonization.29

Pietrantini and co-workers30 compared 127 patient in whom the peritoneum was left unsutured after cesarean section with another 121 patients in whom it had been closed with a continuous 000 polyglactin suture. There were no postoperative differences between the two groups regarding the incidence of wound infection, dehiscence, endometritis, ileus, and length of hospital stay. They concluded that peritoneal closure at cesarean delivery provides no postoperative benefits, while unnecessarily lengthening surgical time, anesthesia exposure, and increasing patient costs. Finally, they advocated the elimination of closure of the parietal peritoneum from cesarean technique. However, they did actually evaluate the issue of the frequency of adhesion development as a function of peritoneal closure.

Hull and Yarner31 extended this modality to non-closure of the visceral and parietal peritoneum during lower segment cesarean section. In their randomized study on 113 patients, 59 patient were assigned to closure of both the visceral and parietal peritoneum with absorbable suture. The other 51 patients were left with no peritoneal closure. The incidence of postoperative fever, endometritis, or wound infection was not different between the two groups. The numbers of oral analgesic doses was significantly greater with closure of the peritoneum than without. The frequency with which postoperative lieus was diagnosed in each group was similar. Bowel stimulants were administered more frequently to the closure than to the non-closure patients. The average operating time was shorter for the open group than for the closure one.

Stricker et al32 reviewed 100 cases of female intestinal obstruction where they found that postoperative adhesions was the most common cause being present (59%). Fifty-six percent of those patients had a prior gynecologic surgery, most commonly abdominal hysterectomy. From 11 patients who had records from their previous operation, 9 patients had peritoneal closure; among these patients adhesions were found always to the site of reperitonization. In the 2 patients iwhom the peritoneum was left open, the adhesions causing the obstruction were found away form the site of reperitonization. In their study, Tulandi and others33 confirmed that non-closure of the parietal peritoneum after gynecologic surgery, as compared to closure using chromic cut gut suture did not increase adhesion formation found at second-look laparoscopy (table 1).

 Table 1: Different studies for closure versus non-closure of the peritoneum

MANAGEMENT OF INTESTINAL OBSTRUCTION

CONSERVATIVE MANAGEMENT

Krebs and Goplerud39 reviewed the management of intestinal obstruction associated with gynecological conditions in 368 patients. They found that gastrointestinal intubation successfully relieved 81% of small bowel obstructions caused by postoperative adhesions. This success rate is similar to those reported by other authors.40,41

Carey and Fabri1 recommended three circumstances in which non-operative treatment for intestinal obstruction should be considered. First, patients who had several operative procedures for intestinal obstruction and who are known to have dense intra-abdominal adhesions. Second, patients who develop obstructions in the early postoperative period are also candidates for a trial of nonsurgical treatment. Lastly, intestinal obstruction due to known widespread intra-abdominal cancer may be successfully treated by intestinal tubes as Miller-Abbott or Canter tube. It was claimed that postoperative intestinal obstructions occurring less than 30 days after surgery has a better prognosis than that occurring more than 30 days after surgery.44 It is also reported that partial small bowel obstruction is more likely to respond to tube suctioning than is complete obstruction.40,42 Interestingly, in spite of their high resolution rate with intubation, Krebs and Goplerud39 stated that tube suctioning is rarely successful when the obstruction is caused by neoplasm or strictures associated with radiation.

Meissner43 described in a recent study the technique of intestinal splinting for management of uncomplicated early postoperative small bowel obstruction. He concluded that this splinting rendered a significant reduction of early postoperative complications; the protective efficacy against early reobstruction was clinically apparent but reached borderline significance only. In respect to late intestinal complications, splinting was not superior to simple enterolysis.

Intraluminal stenting of the small bowel has been advocated as a method of reducing the risk of recurrent adhesional obstruction in patients requiring adhesiolysis. This technique was reviewed in 25 patients in a recent study by DeFriend et al44. They reported that intraluminal stenting remains of unproven efficacy. They added that this technique may find a place as an adjunct to adhesiolysis in patients requiring repeated operations for the relief of obstruction due to extensive and dense adhesions; but, in view of the high rate of complications, careful case selection will be necessary.

Non--operative treatment of small bowel obstruction following operations on the ovary, tube or appendecectomy was evaluated by Meagher and Co-workers.45 They clearly stated that a trial of conservative management of small bowel obstruction in such cases may be unsafe or not worthwhile.

We can conclude that patients with small bowel obstruction secondary to adhesions should be operated upon early i.e. within 24 hours but may be treated nonoperatively for 24-48 hours, provided that no signs of strangulation are present or developed. Failure to show improvement during this 48 hours usually requires immediate operative intervention. In general, those patients would have benefited if early operation were done routinely1,46.

OPERATIVE MANAGEMENT

The laparotomy incision should be long enough to allow exploration of the entire abdominal cavity. It is sometimes not advised to use the previous incision to get into the abdomen as this exposes the intestine, that might be attached to the anterior abdominal wall by adhesions, to injury.

The site of obstruction can be located by following the collapsed loop of intestine until the site of distension is identified. The distended bowel is highly susceptible to injury; fine scissors are usually utilized for dissection of the adhesion bands. Retractors, forceps, sponges, and laparotomy pads should be used particularly carefully during this time of the procedure.

Lysis of adhesions with postoperative splinting of the small intestine has usually been the extent of treatment for obstruction by adhesions, although it should be noted that there is little evidence that splinting reduces subsequent bowel obstruction. For obstructions caused by strictures or tumors, treatment usually consists of resection of the obstructed bowel segment and reanastomosis of the healthy ends. Two techniques have been utilized to try to supplement clinical judgement in identifying sufficient blood supply in the segments of bowel to be anastomosed. Intraoperative use of doppler ultrasound along the anti-mesenteric margin of the bowel allows recognition of areas of intact blood supply to support an intestinal anastomosis. Use of intraoperative intravenous fluorescin has been recommended in patients in whom major segments of bowel must be resected; with the aid of a Wood's lamp the fluorescence of the intact blood supply to the bowel can be detected.

While laparoscopic adhesiolysis in acute intestinal obstruction, was reported by Parent and Collegues47, we believe that it potentially carries an extremely high risk of intestinal perforation as well as other structures that may be included in the adhesion bands, and that this approach currently should only be undertaken as part of experimental investigative trials (table 2).

Table 2: Different methods for management of adhesive intestinal obstruction

COLONIC OBSTRUCTION

Postoperative adhesions are not a common cause of large bowel obstruction. Extrinsic compression from ovarian carinoma, inflammatory strictures secondary to radiation therapy, fecal impaction, and intrinsic neoplasm are among the common etiologies of colon obstruction. Treatment of large bowel obstruction is primarily surgical, and decompression of a severely distended colon is achieved by performance of a proximal temporary colostomy, often of the transverse colon. Gastrointestinal intubation for evacuation of swallowed air may still be of value while the patient is being prepared for surgery. Unless there is distention of the small bowel due to an incompetent iliocecal valve, use of a nasogastric tube appears to be appropriate.39

PREVENTION OF ADHESIONS

Postoperative intra-abdominal adhesions develop in over 90% of patients undergoing laparotomy.48 Complete prevention of adhesion in those patients seems to be an unreached goal up till now. Meticulous adherence to the surgical principles for adhesion reduction to the extent possible for the procedure being performed, is fairly well. These principles include minimalization of tissue handling, avoidance of gauze and towels usage for hemostasis as this usually causes minute abrasions to the peritoneum, prevention of tissue desiccation, avoidance of introduction of foreign bodies such as talc into the operative field, the use of non-absorbable or delayed- absorbable sutures rather than the absorbable reactive cut gut, and meticulous hemostasis.

DOES LAPAROSCOPIC SURGERY DECREASE THE INCIDENCE OF POSTOPERATIVE ADHESIONS?

In gynecology, laparoscopic surgery had been extended in the last two decades to involve not only the minor reproductive and gynecologic surgery such as adhesiolysis, but also major one as adnexectomy, hysterectomy and even radical hysterectomy with lymphadenectomy. The advantage of endoscopic surgery is claimed to be reductions in patient's, morbidity, hospital stay, postoperative convalescence period, and costs.

One of the claimed benefits of laparoscopic surgery is a subsequent reduction in postoperative adhesion development. Such a conclusion is supported intuitively by the concepts of lack of use of retractors and packs at laparoscopy, maintenance of a closed abdomen with presumed reduction in peritoneal dryness, less likelihood of introduction of foreign bodies, a reduced likelihood of blind manual dissection of adhesions during abdominal exploration, aless tissue damage as assessed by the length of laparotomy versus laparoscopy incisions.

Luciano and co-workers72 assessed this issue in rabbit horn studies. They demonstrated no intra-abdominal adhesions in those animals with the lesions created laparoscopically, whereas those lesions created at laparotomy were consistently followed by adhesion formation. Furthermore, the investigators then assigned these animals with adhesions to adhesiolysis at laparotomy or laparoscopy and demonstrated greater reduction in adhesion reformation following laparoscopic adhesiolysis. In a study in dogs, Tittel and colleagues45 showed that laparoscopic operations were followed by significantly fewer adhesions; after conventional laparotomy operations extensive adhesions to the abdominal incision and intestinal kinkings due to adhesive bands were found. In a retrospective chart study, Levrant and others74 evaluated 215 women with previous laparotomy, laparoscopy(ies), or no surgery. They concluded that prior laparotomy, whether through a midline vertical or suprapubic transverse incision, significantly increased the frequency of anterior abdominal wall adhesions. Ninety-six percent of adhesions involved omentum and 29% included bowel. No anterior abdominal wall adhesions were found in patients with only previous laparoscopies or without prior abdominal surgery. Furthermore, Nezhat and co-workers75 reported no de novo adhesion formation at the non-operated sites at a second-look laparoscopy done 4-18 months after laser laparoscopy for the treatment of endometriosis associated infertility in 157 patient who underwent laparoscopic adhesiolysis.

On the other hand, Diamond and co-workers76 described in a multicenter study a high (97%) incidence of adhesion formation seen at early (90 days) second-look laparoscopy following laparoscopic adhesiolysis. Moreover, adhesion reformation occurred regardless of the consistency or vascularity of the initial adhesion. This incidence is consistent with that previously reported following adhesiolysis at laparotomy. Therefore, they concluded that adhesion reformation would not be eliminated by utilization of endoscopic surgery per se. Their report also pointed to 12% incidence patients who developed de novo adhesions, (i.e. development of adhesions at sites without adhesion initially).

In summary, we can conclude that until now there is no clear and convincing evidence that laparoscopic adhesiolysis in humans is superior to surgical lysis of adhesions at laparotomy in terms of adhesion reformation and subsequent bowel obstruction.

DOES LASER SURGERY DECREASE THE INCIDENCE OF ADHESION FORMATION?

Sutton77 stated that CO2 laser remains the most precise laser, especially in the ultrapulse mode, for the division of adhesions and the accurate and safe vaporization of deposits of endometriosis. Furthermore, it was claimed that the Nd: YAG laser is more suited to hysteroscopic surgery due to its great depth of penetration, while visible light lasers, (e.g. argon and KTP-532), are more suitable for the management of ectopic pregnancies and ovarian endometriomas as the carbon dioxide beam is absorbed by the water molecule and becomes ineffective in the presence of blood.77 The author concluded that the main advantage of the various lasers is that they allow fertility surgeons to perform operative surgery by the minimally invasive approach of laparoscopy rather than laparotomy.

In separate report, laser ovarian wedge resection was performed in 49 ovaries in 25 infertile patients with deep endometriosis or polycystic ovarian disease resistant to medical treatment. On second-look laparoscopy, McLaughlin78 found that 36-37% of the ovaries had recurring adhesions. The actual pregnancy rate in this study was 60%, the majority of them occurred within the first six months postoperatively. The author concluded that laser ovarian surgery, coupled with second-look laparoscopy, appears efficacious in minimizing adhesion reformation and seems to havelittle adverse on suconception.

In a multicenter prospective study, Diamond and co-workers79 assessed tubal patency and adhesion formation by second-look laparoscopy within 12 weeks after intra-abdominal laser surgery by laparotomy. This surgery included adhesiolysis, neosalpingostomy, fimbrioplasty, vaporization of endometriosis and ovarian wedge resection. Their results were compared with those of another multicenter prospective study that utilized non- laser reconstructive pelvic surgery. Carbon dioxide laser was found to result in a higher tubal patency rate and adhesions were reduced from initial presentation at most sites. However, non-laser reproductive surgery appeared to also have efficacy in the prevention of adhesion formation, with no consistant benefit for laser or non-laser modalities. It was concluded that the CO2 laser does not appear to be a panacea for the treatment of tuboperitoneal causes of infertility.

On the other hand, Dunn 80 examined 11 patients at second-look laparoscopy 12-21 days following laser laparoscopic adhesiolysis without intraoperative adjuvants for adhesion prevention. All patients had adhesion reformation in at least one site of 15 sites had been evaluated for adhesions. Fifty-six percent of available sites had adhesions at second-look laparoscopy, which was not a significant change from the 60% of the sites with adhesions at initial laparoscopy. De novo adhesions formed in seven of the patients at 23% of available sites.

In summary, it is our belief that laser endoscopic surgery can be beneficial in gynecological surgery when used by an experienced surgeon. However, it does not appear that use of a laser per se reduces postoperative adhesions or it's subsequent complications, including intestinal obstruction, when compared to other surgical modalities.

As adhesion formation remains an unavoidable event, so the need for adjuvants for its prevention was called for. A multitude of agents with different mechanism of action have been developed, investigated and tried. Unfortunately, none of them proved its absolute effectiveness in prevention of postsurgical adhesions or getting a universal acceptance from surgeons (table 3).

Table 3: Classes of Adhesion-reduction adjuvants and their proposed mechanism of action

I. Fibrinolytic agents (fibrinolysis, stimulation of plasminogen activators)

• Fibrinolysin

• Streptokinase

• Urokinase

• Hyaluronidase

• Chymotrypsin

• Trypsin

• Pepsin

• Plasminogen activators

II. Anticoagulants (prevention of clot and fibrin formation)

• Heparin

• Citrates

• Oxalates

III. Anti-inflammatory Agents (reduce vascular permeability, reduce histamine release, stabilize lysozomes)

• Corticosteroids

• Nonsteroidal anti-inflammatory agents

• Anti-histamines

• Progesterone

• Calcium channel blockers

• Colchicine

VI. Antibiotics (prevent infection)

• Tetracyclines

• Cephalosporins

V. Mechanical Separation (surface separation, hydroflotation)

• Intra-abdominal instillates:

  • Crystalloid solutions

  • Dextran
  • Mineral oil
  • Silicone
  • Vaseline
  • Carboxymethylcllulose
  • Hyaloronic acid
  • Chelated hyaluronic acid
• Barriers:

  • Endogenous tissues:

    • Omental grafts
    • Peritoneal grafts
    • Bladder strips
    • Fetal membranes

  • Exogenous materials:

    • Fibrin glue
    • Polytetrafluoroethylene
    • Oxidized cellulose
    • Oxidized regenerated cellulose
    • Gelatin
    • Rubber sheets
    • Metal foils
    • Plastic hoods
    • Modified hyaluronic acid & CMC
    • Poloxamer 407
    • Repel

Modified from Diamond MP, DeCherney AH: Pathogenesis of adhesion formation/reformation: Application to reproductive pelvic surgery. Microsurgery 1987: 8 : 103 and Diamond MP, Hershlag A: Adhesion formation/reformation: in Treatment of postsurgical Adhesions, Wiley-Liss, Inc. 1990: 23-33.

The most commonly investigated and used agents are fibrinolytics, anticoagulants, anti-inflammatory agents, antibiotics, and mechanical separating agents.

Fibrinolytic agents act directly by reducing the fibrinous mass and indirectly by stimulating plasminogen activator activity.81 These agents were promising in some animal studies.82.83 and frustrating in others,84 while it was even associated with hemorrhagic complication85 and impairment of wound healing86 in another reports.

Heparin is the most widely investigated anticoagulant for the purpose of prevention of adhesions. Heparin alone was found to be efficacious in two animal studies when added to peritoneal irrigants in high doses, 87,88 while another study did not confirm that89. When added to local mechanical barriers, heparin enhances its antiadhesive effects. This had been reported in experimental studies with amniotic membrane,90 and Interceed (TC7).89 However, these promising results with addition of heparin to Interceed were not confirmed in a clinical trial by Reid and co-workers.91

Anti-inflammatory agents were used to reduce the initial inflammartory response to tissue injury and hence, subsequent adhesion formation. Most of the animal studies showed the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in prevention of adhesions92,93. In spite of that, other studies failed to prove any beneficial effect of intramuscular or intraperitoneal administration of ibuprofen in reduction of preitoneal adhesions in rat and rabbit models.94,95 Unfortunately, no clinical trials with NSAIDs have been published up until now, although, several have been conducted.

The rationale behind the use of antibiotics is prophylaxis against infection, and hence the inflammatory response, that leads to adhesion development. Cephalosporines and tetracyclin98 were among the widely used drugs for this purpose. Unfortunately, there are no well-designed clinical trial supporting this.

Mechanical separation of peritoneal surfaces of the pelvic organs during the most critical wound healing period of 1 to 5 days postoperative, is the practical and most acccepted way nowadays to prevent postoperative adhesions. This separation theoretically may be accomplished by intra-abdominal instillates or barriers, whether endogenous tissue or exogenous materials. Crystalloid solutions, Dextran70, Carboxymethylcellulose, hyaluronic acid and endogenous tissues such as omental grafts, peritoneal grafts, and fetal membranes were among the most commonly used agents for this purpose. Those currently in-use are the newer polymeric barrier films and tissue-protective polymer solutions or gels.

A gel-like, highly viscous, concentrated (1%) sodium hyaluronate solutions has been reported by Shushan et al97 to inhibit postoperative adhesion in a rat uterine horn abrasion model. Another promising new jelly material is a chemically modified bioresorbable hyaluronic acid/carboxymethylceIlulose (HA/CMC) gel (Sepragel, Genzyme Corp., Cambridge, MA). Favorable adhesion prevention had been shown for this gel by Burns et al98 in rat cecal abrasion and rabbit sidewall defect bowel abrasion models.

Interceed is composed of oxidized regenerated cellulose that has been shown to be efficacious in reduction of adhesion after ovarian surgery,99,100,101 tubal surgery,100 and adhesiolysis.102,103 Interceed which is an absorbable barrier, should be applied at the end of the surgical procedure just prior to closure. The most important instructions to maximize efficacy of Interceed are (1) removal of intra-peritoneal irrigants, which usually requires aspiration of all residual fluid remaining in the cul-de-sac with the patient in the reverse Trendelenburg position; (2) inspection to ensure that adequate hemostasis has been achieved as evidenced by Interceed not turning black, and (3) use of sufficiently large piece of Interceed to completely cover the area of interest leaving at least a 5-mm border.104

Gore-Tex is a barrier composed of a polytetrafluorethylene (PTFE) which is nontoxic, nonreactive and antithrombogenic. It is non-absorbable and needs fixation by stitches and hence its surgical removal. The results of a multicenter clinical study confirmed its efficacy in reducing adhesion.105

Seprafilm is a flexible membrane composed of modified hyaluronic acid and carboxymethylcellulose. It adheres well to moist tissue surfaces, and then turns into a gel within 24 hours after placeme. It is absorbed in the body, thereby omiting the need for second operative procedure to remove it. Complete hemostasis is not mandatory for its use. Seprafilm was demonstrated to be efficacious in the reduction of adhesion development in a multicenter recent clinical study conducted by Diamond and co-workers106. In this study, 127 patients underwent myomectomy with at least one posterior uterine incision 1 cm in length. The use of Seprafilm in those patients significantly reduced the incidence of sites adherent to the uterus, as well as the severity, extent, and area of these post- operative adhesions. Additionally, Seprafilm application was not associated with an increase in postoperative complications.

CONCLUSION

Postoperative adhesions are among the commonest causes of intestinal obstruction. The latter is a very serious condition, potentially exposing the patient to bowel perforation, peritonitis, and death within few hours in a considerable percentage of cases. Early diagnosis and treatment of these patients is the key to saving their life. Meticulous adherence to the surgical principles for adhesion reduction, as well as the use of adjuvants created for this purpose can be of great help to decrease the incidence of subsequent postsurgical adhesions, and hopefully bowel obstruction.

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