Postoperative peritoneal adhesions in adults and their prevention

INTRODUCTION — Postoperative peritoneal adhesions have important consequences to patients, surgeons, and the health system. The adhesions that form in the abdomen following abdominal or pelvic surgery are a normal response to injury of the peritoneal surfaces during surgery, and although adhesions have some beneficial effects, they also cause significant morbidity, including adhesive small bowel obstruction, female infertility, chronic abdominal pain, and increased difficulty with subsequent surgery [1,2]. These issues have refocused attention on our understanding of adhesions, their clinical consequences, and methods of prevention. A number of animal studies and human interventional trials have evaluated a variety of techniques and materials designed to reduce and prevent postsurgical adhesions. Only a handful of agents have been proven safe and effective in humans, and fewer have an evidence base that justifies routine use.

The epidemiology, pathogenesis, approach, and importance of preventing postoperative peritoneal adhesions in adults are reviewed here. The diagnosis and management of small bowel obstruction and infertility are discussed elsewhere. (See "Etiologies, clinical manifestations, and diagnosis of mechanical small bowel obstruction in adults" and "Female infertility: Evaluation".)

INCIDENCE AND BURDEN — Postoperative adhesions cause significant morbidity, including bowel obstruction, female infertility, and chronic abdominal and pelvic pain [3-6].

●Intestinal obstruction – Adhesions are the most common cause of intestinal obstruction in Western countries [7-9]. The incidence varies widely with the nature of the index surgery and the duration of follow-up [7,10-14]. The incidence of small bowel obstruction resulting from postoperative adhesions increases with each subsequent procedure performed in the management of bowel obstruction. In one national study, 5.7 percent of 21,347 readmissions were classified as relating directly to adhesions, and 3.8 percent required operation [12].

●Infertility – Infertility in women can result from pelvic adhesions, which can alter pelvic anatomy and interfere with ovum capture and transport, or from tubal or intrauterine adhesions that hinder sperm transport or embryo implantation. Whereas pelvic peritoneal adhesions and tubal abnormalities are each responsible for approximately 10 percent of cases of female infertility, intrauterine adhesions are a relatively rare cause of infertility. (See "Overview of infertility", section on 'Causes of infertility' and "Intrauterine adhesions: Clinical manifestation and diagnosis".)

●Chronic abdominal pain – The relationship between adhesions and chronic abdominal or pelvic pain is poorly defined. However, there is some evidence indicating that dense adhesions can limit organ mobility, which may cause visceral pain [2,15,16]. (See "Chronic pelvic pain in adult females: Treatment", section on 'When to perform additional surgical procedures aimed to reduce pain'.)

Adhesions, which are found in up to 95 percent of patients who have subsequent surgery, can impose technical difficulties and increase risk for complications, which may include [17-19]:

●Difficult abdominal access related to loss of tissue planes or distorted anatomy

●Inability to perform laparoscopic surgery, continuous ambulatory dialysis, or other intra-abdominal drug delivery

●Inadvertent injury to the small bowel, bladder, or ureters

●Increased duration of surgery and prolonged anesthesia

●Increased blood loss

Nearly 1 percent of all general surgical admissions and 3 percent of all laparotomies relate directly to adhesions [20], which increases the burden of care (economic, manpower, logistics). Furthermore:

●Complications related to or resulting from postoperative adhesions increase the surgical workload and hospital utilization and tax other health care resources, resulting in a significant economic burden; the overall estimated annual costs of managing adhesion-related complications exceed $2 billion in the United States [21].

●Adhesions increase the risk for medical malpractice claims arising from abdominal and pelvic surgery [4,22,23]. Data from the medical defense union in the United Kingdom identified 77 claims related to adhesions over a six-year interval [22]. Allegations included a failure to warn of the risk during the consent process, visceral injuries that occurred during laparoscopy or laparotomy, failure to use specific measures to prevent adhesions, failure to diagnose or delays in diagnosis of complications, and chronic pain and infertility.

PATHOGENESIS — At the molecular level, adhesion formation involves a complex interaction of cytokines, growth factors, cell adhesion molecules, neuropeptides, and numerous other factors secreted by cells in or near the area of trauma [24,25]. The early balance between fibrin deposition and degradation (ie, fibrinolysis) appears to be a critical factor in the pathogenesis of adhesions [26-30]. Peritoneal healing differs from wound healing in that it heals as a surface rather than from edge to edge (like skin). Healing involves a uniform, relatively rapid reepithelialization, regardless of the size of the injury.

Injury to peritoneal surfaces induces a repair response, which consists of an inflammatory reaction involving cellular elements and also tissue and coagulation factors [29,31]. The inflammatory response results in fibrin deposition at the site of injury within three hours after tissue trauma and peaks on postoperative days 4 to 5. Postsurgical peritoneal repair begins with coagulation, which triggers the release of a variety of chemical messengers that mediate a cascade of events. Some of the principal cellular elements involved include leukocytes (polymorphonuclear neutrophils and macrophages) and mesothelial cells. Macrophages, which exhibit increased phagocytic, respiratory burst, and secretory activities, comprise the majority of the local leukocyte population five days after injury. Macrophages also recruit new mesothelial cells onto the surface of the injury, which first aggregate to form small islands across the injured area and then proliferate into sheets of cells that eventually reepithelialize the entire surface, usually by five to seven days after surgical injury.

The progenitor to adhesions is the fibrin gel matrix, which develops in several steps, including the formation and degradation of fibrin polymer and its interaction with fibronectin and a series of amino acids. Protective fibrinolytic enzyme systems in the peritoneal mesothelium, such as the tissue plasminogen activator (tPA) system, can remove the fibrin gel matrix. The pivotal events that determine the path of healing are the opposition of two damaged surfaces and the extent of fibrinolysis. If complete fibrinolysis and resorption of degradation products occurs, reepithelialization will result in a smooth tissue surface, but if that process is disturbed and fibrinolysis does not occur, connective tissue scar and adhesions develop from the ingrowth of fibroblasts, capillaries, and nerves. Surgery diminishes fibrinolytic activity dramatically by increasing levels of plasminogen activator inhibitors and reducing tissue oxygenation [30,31]. Fibrinolysis also can be impaired by thermal injury, desiccation, ischemia, foreign bodies, blood, bacteria, and some drugs; genetic polymorphisms also may play a role in the host's inflammatory and healing response.

CLINICAL PRESENTATIONS AND DIAGNOSIS — Most adhesions are clinically silent. More than 75 percent of patients with symptomatic adhesions have a history of prior surgery, and the remainder have a history of an intra-abdominal or pelvic inflammatory process. When symptoms occur, adhesions may manifest as intestinal obstruction, chronic pain, and, in women, as infertility. The risk factors and clinical features for each of these are described in the linked topics.

●Adhesions are the most common cause of intestinal obstruction in Western countries and should be suspected in any patient with a history of prior abdominal or pelvic surgery who presents with signs and symptoms of obstruction. The presentation can be acute or subacute. (See "Etiologies, clinical manifestations, and diagnosis of mechanical small bowel obstruction in adults", section on 'Etiologies'.)

●Chronic abdominal pain, chronic pelvic pain, and/or dyspareunia [32]. (See "Evaluation of the adult with abdominal pain" and "Chronic pelvic pain in nonpregnant adult females: Causes".)

●Infertility. (See "Overview of infertility" and "Female infertility: Causes" and "Female infertility: Evaluation".)

A diagnosis of adhesions is often based on initial clinical suspicion in a relevant context, which may then be confirmed by direct examination of the abdomen or pelvis via laparoscopy or laparotomy or with indirect methods, such as imaging, which is less accurate and may include ultrasound (demonstrating reduced visceral sliding) or magnetic resonance of the abdomen. Computed tomography (CT) of the abdomen (with oral contrast) and gastrointestinal follow-through studies are less useful in the diagnosis of adhesions but can play a role in the management of patients with suspected small bowel obstruction relating to adhesions. (See "Etiologies, clinical manifestations, and diagnosis of mechanical small bowel obstruction in adults", section on 'Diagnosis'.)

INDICATIONS FOR ADHESIOLYSIS — The indications for surgical lysis of adhesions depend upon the clinical presentation.

●For patients with signs and symptoms of bowel obstruction, abdominal exploration and lysis of adhesions (adhesiolysis) may be needed to manage complications related to obstruction (perforation, ischemia). Adhesiolysis also may be indicated for those with partial obstruction who do not respond to conservative management. (See "Management of small bowel obstruction in adults", section on 'Failure of nonoperative management'.)

●For treatment of infertility and recurrent pregnancy loss, lysis of pelvic adhesions or of intrauterine adhesions may improve fecundity and decrease risk for pregnancy loss. (See "Female infertility: Treatments" and "Intrauterine adhesions: Clinical manifestation and diagnosis".)

●Performing adhesiolysis for pain relief can be effective in certain subsets of patients [2]. Unfortunately, even after lysis, adhesions often reform. (See "Management of small bowel obstruction in adults" and "Female sexual pain: Differential diagnosis".)

MEASURES FOR PREVENTING PERITONEAL ADHESIONS

Fundamentals — Methods for preventing adhesions are directed at the mechanisms of adhesion formation. Preventive measures may (see 'Pathogenesis' above):

●Minimize injury

●Introduce a barrier between injured surfaces

●Prevent coagulation of the serous exudate

●Remove or dissolve the deposited fibrin

●Inhibit the fibroblastic response to the tissue injury

●Involve recombinant tissue plasminogen activator and novel fibrinolytics

●Minimize postoperative infection risk

●Methods for preventing adhesions can be classified broadly as technical measures; physical barriers, which may be solid or liquid; and pharmacologic therapies [3,25]. Given that no specific pharmacologic therapy has been approved for clinical use in the United States, the discussion below focuses on technical measures and physical barriers [33].

●Technical measures limit or prevent the initial peritoneal injury. (See 'Surgical techniques' below.)

●Barrier agents act primarily as a physical separation between the fibrin-coated peritoneal surfaces predisposed to adherence. Barrier agents may be solid or liquid materials. (See 'Physical barriers' below.)

●Normal bowel motility can help keep physical separation of healing surfaces and maintain relative motion between healing surfaces, which in turn prevent or limit adhesion formation. Measures that promote bowel motility in a postoperative patient are discussed elsewhere. (See 'Promotion of bowel motility' below and "Measures to prevent prolonged postoperative ileus".)

●Pharmacologic therapies may be administered locally or systemically and interfere with or modify the peritoneal response to injury. (See 'Ineffective and potentially harmful therapies' below.)

Surgical techniques

Gentle tissue handling — Good surgical technique is the first defense against adhesion formation.

Meticulous hemostasis and gentle, minimal tissue handling are important for limiting the extent of the initial peritoneal injury [16]. Damage to the serosa can be prevented by minimizing trauma, bleeding, and ischemia and by keeping the surgical field moist with frequent irrigation to prevent tissues from drying out.

Traditional laparotomy sponges can be abrasive and should be avoided. Many pelvic surgeons place these sponges in sterile plastic bags, thus preventing the braided cloth from touching the peritoneum when packing is required.

Removing the talc or starch from gloves before entering the peritoneal cavity is a simple, but often neglected, measure that eliminates a source of irritation that predisposes to adhesion formation. The introduction of potentially reactive foreign bodies (eg, excess suture material, lint, talc) should be minimized to reduce the number of nidi for fibrin deposition. Fine, nonreactive suture material should be used wherever possible; silk sutures, which are fibrogenic, should be avoided in the abdomen.

The incidence of adhesions is similar regardless of whether the peritoneum is reapproximated after laparotomy [13,34,35]. Although closing the parietal peritoneum is usually unnecessary, when circumstances require, fine, absorbable suture should be used. Suture materials like polyglactin stimulate little tissue reactivity and are thus preferred over more reactive materials such as chromic catgut sutures or silk.

Laparoscopic surgery — Laparoscopy offers certain advantages over open abdominal surgery with respect to adhesion formation. The abdominal incisions are small, and there is less handling of tissue and exposure to foreign bodies, all of which may help to decrease tissue trauma, compared with laparotomy, and thus reduce the risk for adhesion formation, especially to the abdominal wall [36-38].

Laparoscopic surgery certainly does not guarantee the prevention of adhesions [39]; longer durations of surgery and high insufflation pressures can even increase the risk for adhesion formation [40]. In one study (SCAR), the Scottish National Health Service Medical Record Linkage Database was used to select a cohort of 8849 women who had open gynecologic surgery in 1986, and all readmissions in the subsequent 10 years were reviewed for potential adhesion-related disease [10-12]. The overall rate of readmission directly related to adhesions was 2.9/100 initial operations. When laparoscopic sterilization procedures were excluded, the risk for adhesion-related readmission was comparable for open and laparoscopic gynecologic surgery [11].

Since the publication of the original SCAR study in 1999 [12], the field of laparoscopic surgery has advanced from mostly diagnostic procedures to complex resectional procedures. In an updated study using the same database but in a more contemporary time frame (2009 to 2011), over 50,000 patients underwent open abdominal or pelvic surgery while over 21,000 patients underwent laparoscopic surgery [41]. At five years, compared with open surgery, the laparoscopic approach was associated with a lower incidence of readmissions directly related to adhesions (1.7 versus 4.3 percent; p<0.0001) and a lower incidence of readmissions possibly related to adhesions (16 versus 18 percent; p<0.005). Despite these reduced risks, however, laparoscopic surgery is still associated with adhesion formation resulting in readmissions.

Physical barriers — Physical barriers include solid materials (absorbable sheets, nonabsorbable prosthetic materials) and viscous fluids introduced into the abdomen. All are aimed at keeping damaged peritoneal surfaces separated during the first five to seven days after surgery until after reepithelialization has occurred. Although barriers do appear to limit the extent of adhesion formation, whether they improve clinically important outcomes by reducing the risks for intestinal obstruction, infertility, and chronic abdominal or pelvic pain is less clear [1,42]. (See 'Effectiveness of physical barriers' below.)

The addition of physical barriers is not without risk or cost. The use of the barriers described below prolongs operative time, which increases hospital costs, which is compounded further by the cost of the product itself, for an estimated total of $400 to $700 per procedure. However, when these barriers accomplish what they are designed to do, the benefit of avoiding future surgery outweighs these issues.

Concerns that some barrier agents may predispose to an increase in the incidence of septic complications [43-45] have not been proven, but barriers should not be used to wrap intestinal anastomoses, because the practice may increase the risk for leak [46,47]. In one multicenter trial, 1791 patients having abdominopelvic surgery (the majority for inflammatory bowel disease) were randomly assigned to receive a hyaluronic acid sheet as an adhesion barrier or no treatment [47]. There was no significant difference between the groups in the incidence of abscess (4 versus 3 percent, respectively) or pulmonary embolism (<1 percent in both groups). However, a subpopulation of patients in whom the adhesion barrier was wrapped around a fresh bowel anastomosis more frequently developed anastomotic leak and leak-related events, such as fistula formation, peritonitis, abscess formation, and sepsis.

Adhesion barrier use has also been associated with an increase in intraperitoneal or uterine infections after cesarean section [48]. In one case-control study, adhesion barriers were used in 77 percent of 1498 cesarean section cases, and intraperitoneal or uterine infections occurred in 9.9 and 4.3 percent of those with and without adhesion barriers, respectively [48].

Solid barriers (sheets) — Two absorbable membrane sheets are commercially available. One is a sodium hyaluronate-based carboxymethylcellulose sheet (Seprafilm), and the second is an oxidized regenerated cellulose sheet (Interceed). Both appear safe and effective for preventing adhesions between surfaces to which they are applied but are somewhat difficult to handle and do not prevent adhesion formation at other sites within the abdomen. In addition, there is one nonabsorbable solid barrier (expanded polytetrafluoroethylene) that has been found to prevent adhesions in clinical studies.

Hyaluronic acid sheets — Hyaluronic acid sheets (hyaluronate carboxymethylcellulose) are transparent, absorbable membranes that last for seven days, during which time they prevent the juxtaposition of traumatized tissues.

Hyaluronate carboxymethylcellulose (Seprafilm) is supplied in 5 x 6 inch sheets. The desired shape is cut, and the material is carefully applied with clean instruments over the surgical site. Care should be taken to avoid contacting the viscera and other tissues prior to final placement, and the barrier is best applied with instruments because the membrane can easily stick to gloves and become displaced. The paper backing on the film is then removed carefully, keeping the membrane at the operative site; suturing is unnecessary. The barrier is a brittle film that tends to fracture when bent at sharp angles, making it unsuitable for laparoscopic application.

A meta-analysis of eight randomized trials of patients undergoing intestinal surgery [47,49-55] demonstrated that treatment with hyaluronic acid sheets reduced intra-abdominal adhesions significantly but did not reduce the incidence of postoperative intestinal obstruction (odds ratio [OR] 0.98, 95% CI 0.78-1.23). Hyaluronic acid sheet use also increased septic complications such as abdominal abscess (OR 1.64, 95% CI 1.06-2.54) and anastomotic leak (OR 2.03, 95% CI 1.18-3.50) [43]. Another meta-analysis of nine trials demonstrated a reduction in the incidence of postoperative small bowel obstruction (pooled risk ratio 0.45, 95% CI 0.34-0.60). The benefit was sustained at both two and five years [56].

Oxidized regenerated cellulose — Oxidized regenerated cellulose (ORC) is a commonly employed absorbable adjuvant used for hemostasis. (See "Overview of topical hemostatic agents and tissue adhesives", section on 'Oxidized regenerated cellulose'.)

ORC creates a temporary barrier that prevents adhesions when applied to injured tissue. Initial studies using a version of the product with a loose weave (Surgicel) were inconclusive but suggested some benefit. The knit of the ORC barrier was subsequently modified to create the ORC product used currently (Interceed). The material is effective for reducing postsurgical adhesions because it is absorbed over an interval, which presumably allows sufficient time for fibrin-clot dissolution and reepithelialization of the traumatized peritoneum [57]. A systematic review and meta-analysis identified 11 trials using ORC in gynecologic surgery [38,58-67]. The pooled estimate for three trials comparing ORC with no barrier and judged to have a low risk for bias observed that ORC significantly reduced risk of adhesions (relative risk [RR] 0.51, 95% CI 0.31-0.86) [1].

Interceed is supplied in sheets measuring 1.5 x 2 inches or 3 x 4 inches. The smaller size is appropriate for laparoscopic placement. The barrier is degraded and absorbed within two weeks of application. Application requires several steps:

●The operative site should exhibit normal hemostasis and be free of blood, which reduces the effectiveness of ORC [68].

●Excess fluid should be removed from the peritoneal cavity by gentle aspiration after placing the patient in a reverse Trendelenburg position.

●The Interceed barrier should completely cover the affected area of the operative site and can be moistened gently with sterile irrigant to help maintain its position. Suturing is unnecessary.

Expanded polytetrafluoroethylene — Expanded polytetrafluoroethylene (ePTFE) is a nonabsorbable, flexible prosthetic material used for a variety of surgical reconstructions. The ePTFE is trimmed to overlap the denuded area by 1 cm and sutured into place with nonabsorbable sutures, usually 7-0 or 8-0 nylon or polypropylene.

A small trial of patients having open myomectomy randomly assigned 28 subjects to application of ePTFE suture over the uterine incision or to no barrier [69]. At second-look laparoscopy, more patients receiving ePTFE were adhesion free compared with untreated controls (55 versus 7 percent).

Another small trial involving 32 patients compared ePTFE and ORC in pelvic reconstructive surgery by placing ePTFE on one pelvic sidewall and ORC on the other [70]. Among the 29 patients who had second-look laparoscopy, both ORC and ePTFE decreased adhesions, but ePTFE was judged to be more effective (figure 1). More sidewalls covered with ePTFE had no adhesions (21 versus 7). The ePTFE membrane was removed at laparoscopy in all patients who had a successful second-look procedure.

Liquid barriers (instillates)

Polyethylene glycol — Polyethylene glycol adhesion barrier (Spraygel, Sprayshield) is a synthetic hydrogel that forms within seconds after simultaneous spray of two solutions of polyethylene glycol-based (PEG) liquids onto targeted tissue. Crosslinking between the solutions forms an absorbable, flexible, adherent gel barrier that remains intact for five to seven days before degrading into its components, which are then resorbed and excreted through the kidneys. Spraygel is available in Europe but is not yet approved for use in the United States.

An early trial comparing PEG with placebo in women undergoing myomectomy observed a greater than 60 percent lower adhesion score in treated patients at time of second-look laparoscopy, with no adverse effects [71]. A later systematic review [1] identified seven trials comparing PEG with placebo [71-76]. Whereas the pooled results of four of these trials did not yield a significant difference in the overall incidence of adhesions, adhesion scores were lower in those receiving PEG. A later trial confirmed the safety profile of Spraygel but also failed to demonstrate the barrier was effective for preventing adhesions [77].

Icodextrin solution — A 4% isosmolar solution of icodextrin (Adept) is an alpha-1,4 glucose polymer with prolonged peritoneal residence. It is used as an irrigant during surgery (minimum 100 mL/30 minutes) and is the most promising intraoperative instillate for adhesion prevention. It can be used following laparoscopic adhesiolysis and is the only agent approved in the United States for preventing peritoneal adhesions in gynecologic laparoscopy.

At completion of the procedure, all of the irrigant is removed and 1000 mL of fresh icodextrin 4% is instilled into the peritoneal cavity and left as a fluid reservoir [78]. The solution is slowly absorbed via the lymphatic system, broken down by amylase, and metabolized to glucose (40 g per liter of instillate) over a period of up to four days, thus acting to separate traumatized tissue surfaces during the period of healing when adhesions would normally form. Adept is contraindicated in patients with known or suspected allergy to cornstarch-based polymers (eg, icodextrin, or with maltose or isomaltose intolerance, or with glycogen storage disease). Icodextrin 4% is also contraindicated in the presence of gross abdominal-pelvic infection.

A meta-analysis of four trials comparing icodextrin to no treatment or placebo concluded that icodextrin reduced the incidence of small bowel obstruction (data from a single study, 2 versus 11 percent) but did not reduce adhesion formation or the need for reoperation for adhesive small bowel obstruction (relative risk 0.33, 95% CI 0.03-3.11) [1].

Hyaluronic acid solution, gel, and powder — Hyaluronic acid is an anionic, nonsulfated glycosaminoglycan distributed in connective tissue [79-81].

A systematic review identified four trials comparing hyaluronic acid-containing solutions with placebo [82-85] and found no difference in overall mean adhesions scores but also found that the solutions significantly reduced the proportion of women with adhesions or the extent of adhesions at time of second-look laparoscopy (OR 0.31, 95% CI 0.19-0.51) and the number of women with increased adhesion scores (OR 0.28, 95% CI 0.12-0.66) [80].

A powder form of hyaluronic acid/carboxymethylcellulose (Sepraspray Adhesion Barrier) has been evaluated in the setting of laparoscopic colorectal resections but was found to produce more adverse events [86].

Promotion of bowel motility — As an adjunct to physical separation of healing surfaces, maintenance of relative motion between healing surfaces, mimicking normal peristalsis and mobility, has been proposed to prevent or limit adhesion formation. In humans, impaired postoperative intestinal motility may cause a postoperative ileus, further exacerbated by postoperative pain management with opiates. The small intestine has impaired motility for one to two days postoperatively, whereas the colon has impaired motility for two to three days on average [87]. Several animal studies have demonstrated prevention and treatment of postoperative adhesions with methods utilizing prokinetic agents or anatomically based visceral mobilization and manipulation to promote normal bowel motility and mobility [88-90]. Promoting return to normal bowel motility and early mobility remain areas of future inquiry for human research. Measures that promote postoperative bowel motility and reduce ileus are presented elsewhere. (See "Measures to prevent prolonged postoperative ileus".)

Investigational agents — There are multiple pharmaceutical targets being examined to limit peritoneal adhesion formation with promising preliminary evidence in animal-based studies. These include angiotensin receptor agonists, hypoxia-inducible factor inhibitors, N-acetyl-cysteine, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) [91], neurokinin-1 receptor antagonists, chymase inhibitors, sodium cromoglycate, pirfenidone, and selective small molecule activator protein-1. The theoretical mechanisms for adhesion prevention for most of these targets are reduced inflammation and increased fibrinolysis [33]. However, these studies are often done in animal models with few subjects; thus, more in vivo studies and human trials will need to be conducted prior to utilization [33].

Traditional medicine has also been employed in hope of postoperative adhesion prevention. Punica granatum L flower extract is traditionally used in ancient Persian medicine for its antimicrobial, antioxidant, and anti-inflammatory effects. A study done with 32 rat models taking P. granatum extract orally for eight days demonstrated a decrease in quantity and quality of adhesions [92].

Moving forward, the 2021 Global Expert Consensus Group has worked together to produce a consensus statement to guide future clinical research trials. All are in agreement that more studies need to be conducted to improve antiadhesion therapy and ultimately improve patient outcomes [93].

Ineffective and potentially harmful therapies — A number of other agents have been applied in attempts to prevent postoperative peritoneal adhesions but are considered generally ineffective and possibly harmful.

Since adhesion formation involves an inflammatory reaction, systemic anti-inflammatory agents have been viewed as having potential value in efforts to prevent adhesion formation. A systematic review of randomized trials comparing the use of glucocorticoids or promethazine versus no treatment for adhesion prevention after gynecologic surgery found no evidence for a beneficial effect of treatment [94], but the small number of studies and subjects precluded a confident conclusion. Although there is evidence from animal studies that ketorolac, interleukin 10, and interleukin 4 have efficacy for reducing adhesion formation [95-97], there are no clinical trials of nonsteroidal anti-inflammatory drugs for this purpose involving humans.

Crystalloid solutions should not be expected to prevent adhesion formation, because of their short intraperitoneal time of residence, and this prediction is consistent with clinical observation [98]. The instillation of nonbarrier fluid into the peritoneal cavity at the conclusion of surgery is associated with numerous theoretical and practical concerns [99-104]. Fluid overload may potentially lead to pulmonary edema and may cause abdominal pain and dyspnea. Fluid may potentially leak through laparoscopic incisions, which may cause distress to the patient and require frequent bandage replacement. Extravasation to the vulvar region has been reported in up to 2 percent of patients receiving dextran 70 [104]. Excess intraperitoneal fluid also may reduce opsonization of foreign cells, impair host-cell phagocytosis, and lead to infectious complications. In one animal study, dextran significantly reduced adhesion formation but resulted in peritonitis rather than in abscesses as was observed with instillation of saline [105].

However, it is possible that continuous lavage with crystalloid solutions may be beneficial, although further study is required. In one trial of laparoscopic myomectomy patients, postoperative peritoneal lavage with Lactated Ringer solution for 48 hours reduced adhesion formation assessed by second-look laparoscopy 8 to 10 weeks later [106]. The rates of postoperative complications and small bowel obstruction were not reported.

Other solutions instilled into the peritoneum to reduce adhesion formation have been evaluated and are ineffective. A systematic review found no significant benefit from the use of intraoperative irrigation or infusion of various drugs and liquids, including intraperitoneal steroids (one trial, 61 subjects), dextran (two trials, 210 subjects), or heparin (one trial, 63 subjects) [94]. Antibiotic solutions also are ineffective for preventing adhesions, and, in rats, irrigation of the abdominal cavity with cefazolin and tetracycline resulted in increased formation of peritoneal adhesions [107].

EFFECTIVENESS OF PHYSICAL BARRIERS

Reducing adhesive obstruction — Several of the barrier agents appear to be effective for reducing the incidence and extent of adhesions, but convincing effectiveness for reducing the incidence of adhesive bowel obstruction is available only for hyaluronic acid sheets [1,52,108].

A systematic review and meta-analysis identified nine trials [46,52-55,109-113] comparing hyaluronic acid sheets (Seprafilm) to no barrier [1]. Five studies compared the incidence of reoperations for adhesive small bowel obstruction; three trials were in patients having colorectal surgery, and the other two involved hepatic and gastric surgery. The use of hyaluronic acid sheets significantly reduced the risk for reoperation for adhesive small bowel obstruction, compared with no barrier, in patients having colorectal surgery (relative risk [RR] 0.49, 95% CI 0.28-0.88).

A separate review and meta-analysis [43] identified eight trials comparing Seprafilm to no barrier in 4203 patients [47,49-55]. Although the incidence of severe adhesions (grade 2 or 3) was significantly lower in the group receiving Seprafilm (odds ratio [OR] 0.45, 95% CI 0.22-0.93), the incidence of intestinal obstruction after abdominal surgery was not different.

In a systematic review of trials comparing icodextrin to no adhesion barrier or placebo, icodextrin significantly reduced the incidence of small bowel obstruction by any cause (RR 0.20, 95% CI 0.04-0.88), but the incidence of reoperation for adhesive small bowel obstruction was not different [1].

Improving fertility — The effect of adhesion barriers (oxidized regenerated cellulose [ORC], expanded polytetrafluoroethylene [ePTFE], instillates) on rates of miscarriage or pregnancy in women following gynecologic surgery is unknown. Although many studies have examined surrogate endpoints such as adhesion or fertility scores, most have not studied the effect of adhesion barriers on conception, miscarriage, or live birth rates [58,59,78,80,94,108,114,115]. At present, there is no evidence for higher pregnancy or live birth rates with the use of adhesion barriers.

In one systematic review, no trials were identified reporting data on pregnancy rates for ORC, icodextrin, or polyethylene glycol (PEG) [1]. In another that identified four trials, hyaluronic acid solutions had no significant effect on subsequent pregnancy rates [80].

A review of five trials that compared antiadhesion barrier gels with another barrier gel, placebo, or no adjunctive therapy after hysteroscopic surgery included only one small study that reported pregnancy or live birth (but not miscarriage) rates; although the incidence of new adhesions was reduced, there was no difference in any of the more important clinical outcomes [115]. In a small pilot trial, the use of an antiadhesive gel post-salpingo-ovariolysis did not influence follicular development, as inferred from the results of the day 21 progesterone and folliculogram on days 10 to 12 three months postsurgery [116]. More well-designed and adequately powered randomized studies are needed to assess whether the use of any antiadhesion barriers can improve reproductive outcomes.

Given the absence of evidence that any antiadhesion agent can improve clinical outcomes, surgical adhesiolysis remains an important treatment option. Among infertile women with adnexal adhesions, pregnancy rates were lower in women with untreated adhesions compared with those who had adhesiolysis [117]. Pregnancy rates in treated women were 32 percent after 12 months and 45 percent after 24 months, compared with 11 and 16 percent, respectively, in control subjects. (See "Female infertility: Treatments", section on 'Tubal factor infertility and adhesions'.)

Lessening chronic pain — Laparoscopic adhesiolysis as a therapy for chronic pain is controversial. Adhesiolysis for reducing chronic pain has been studied in two small trials following patients for up to one year with conflicting results [118,119]. In a small multicenter, randomized, double-blind trial with a 12 year follow-up, laparoscopic adhesiolysis was inferior to laparoscopy alone (control group) in chronic pain control and quality of life, and laparoscopy alone conveyed a powerful, long-term placebo effect [120]. A Cochrane review of four trials involving women with chronic pelvic pain showed uncertain benefit of adhesiolysis except for an improvement in the quality of life in terms of emotional wellbeing and social support [121].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bowel obstruction".)

SUMMARY AND RECOMMENDATIONS

●Pathogenesis – The adhesions that form in the abdomen after abdominal or pelvic surgery result from tissue trauma and subsequent healing and are a normal response of the peritoneal surfaces to surgical injury. Adhesion formation involves a complex interaction of many cell-secreted factors in areas of surgical trauma. The balance between fibrin deposition and degradation (ie, fibrinolysis) appears to be the critical factor in adhesion formation. (See 'Incidence and burden' above and 'Pathogenesis' above.)

●Clinical presentations – Although adhesion formation is integral to the healing process, adhesions can cause significant morbidity. Adhesions are the most common cause of bowel obstruction and should be suspected in any patient with a history of prior abdominal or pelvic surgery who presents with signs and symptoms of bowel obstruction. Other clinical consequences of adhesions include infertility and chronic abdominal pain. (See 'Clinical presentations and diagnosis' above.)

●Indications for adhesiolysis – Surgical lysis of adhesions may be indicated under the following clinical circumstances (see 'Indications for adhesiolysis' above):

•For patients who develop signs and symptoms of postoperative bowel obstruction that persists after conservative management

•For treatment of infertility and recurrent pregnancy loss

●Measure for prevention of peritoneal adhesions

•The first-line defense against adhesion formation is meticulous surgical technique. Although laparoscopy generally results in less tissue trauma than laparotomy, the incidence and severity of postoperative adhesions after laparoscopy is not necessarily lower than that after laparotomy. (See 'Surgical techniques' above.)

•For patients at high risk for developing adhesions having laparotomy (eg, gynecologic surgery, repeat laparotomy), we suggest using a solid physical barrier such as Interceed (oxidized regenerated cellulose) for adhesion prevention, rather than a liquid barrier agent or no barrier (Grade 2B). (See 'Physical barriers' above.)

•For patients undergoing laparoscopic lysis of adhesions, we suggest the use of liquid barrier agents such as icodextrin (Grade 2C). (See 'Icodextrin solution' above.)

•We suggest avoiding the use of nonbarrier intra-abdominal fluid solutions, antibiotics, and antithrombotic agents because they are ineffective and potentially harmful (Grade 2B). (See 'Ineffective and potentially harmful therapies' above.)