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Published on 1 September 2004

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Strategies against adhesion formation

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Christelle Nueffer
Pharmacy Intern

Dominique Joly
Hospital Pharmacist

Sylvie Vangreveling
Hospital Pharmacist
Centre Hospitalier de Sainte Catherine
Saverne
France
E:christelle.nueffer@chru-strasbourg.fr

Adhesion formation is a very common complication of abdominopelvic surgery. It causes considerable morbidity, resulting in small bowel obstruction, sterility or abdominopelvic pain, among other problems.

Adhesions are abnormal fibrinous bonds between internal organs or tissues that are usually separate.(1) They are classified as congenital or acquired (inflammatory or postsurgical). The incidence of postsurgical adhesion ranges from 67% to 97%. Although adhesions may occur in different types of operations, 76% of patients diagnosed with adhesions have had an intervention below the transverse mesocolon. Risk factors include ischaemia (such as suture or clamp), foreign bodies (such as glove powder, lint or fibre), inflammation, infection, desiccation (eg, lamp) and presence of blood.

Complications
The main complication of adhesion formation is small bowel obstruction (SBO). Adhesions are the main cause of SBO (74%), which is fatal in 10–15% of cases if the bowel is strangulated.(1,2)

The second complication of adhesion is abdominopelvic pain, with adhesions being present in nearly 40% of patients suffering from pelvic pain.(1,4) Adhesions are also responsible for 15–20% of cases of female sterility. The difficulties on reoperation should also be taken into consideration; in addition, there are economic consequences related to increases in readmissions and reoperations.

Prevention strategies
The only treatment of adhesion is adhesiolysis, which, by generating another adhesion, leads to a preventive strategy development. There are currently two major strategies for the prevention of adhesion: surgical technique improvement and use of adjuvant.

Surgical technique improvement
Surgical technique improvement is developed around three main areas:

  • Reduction of invasiveness. Laparoscopic surgery could be of interest, but studies have not demonstrated the superiority of this technique compared with laparotomy.
  • Reduction of the trauma associated with surgery, by gentle tissue handling, keeping tissues moist, avoiding large abdominal wounds as well as cautery, lasers and retractors, and using micro- and atraumatic instruments.
  • Exclusion of foreign bodies into the body, as there is a link between foreign material (such as starch glove powder, talc, gauze and nonabsorbable suture) and the formation of adhesions.

As the peritoneum has a strong tendency to form adhesions, the modification of surgical techniques is insufficient to stop it.

Use of adjuvant
Adjuvants are traditionally classified in two categories: drugs and barriers.

Drugs
The pathophysiology of adhesion formation is complex and offers many targets for pharmacological intervention. However, when using drug treatments, problems can emerge, as adhesions are ischaemia sites cut off from systemic drug delivery. Thus, antiadhesion agents should prevent the formation of adhesions, not act on the wound healing process. Drugs can target various causes and components of the inflammation and/or the adhesion formation process.

Numerous drugs, such as anti-inflammatory drugs (nonsteroidal anti-inflammatory drugs [NSAIDs] and glucocorticoids), fibrin formation inhibitors (heparin), fibrinolytic agents (streptokinase, urokinase, alteplase and reteplase), antibiotics, phosphatidylcholine and chymase inhibitors, have been used or are still in use for the treatment of the condition. However, none of these drug treatments is completely safe and effective.

Barriers
The use of barriers relies on the fact that adhesion formation requires apposition of two damaged areas. Thus, the interposition of a barrier for a sufficient length of time (5–7 days) could contribute to the prevention of adhesion formation. An ideal barrier should, in addition to being safe and effective, be noninflammatory, nonimmunogenic, persist during the critical remesothelialisation phase, stay in place without suture, remain active in the presence of blood and be completely biodegradable. There are two categories of barriers:

  • Mechanical devices (autologous peritoneal transplants, polytetrafluoroethylene (Gore-Tex, Preclude), oxidised regenerated cellulose (Interceed), hyaluronic acid combined with carboxymethylcellulose (Seprafilm).
  • Macromolecular solutions (crystalloids [sodium chloride, Ringer’s lactate], 32% dextran 70 [Hyskon], hyaluronic acid combined with phosphate-buffered saline [Sepracoat], icodextrin 4% [Adept], auto-crosslinked hyaluronic acid gel [Hyalobarrier], 0.5% ferric hyaluronate gel [Intergel] and sprayable polyethylene glycol [SprayGel]).

In the case of mechanical barriers, the potential sites of adhesion formation must first be established before placement can be determined. In addition, mechanical barriers are expensive and are not convenient for use in laparoscopy.

Antiadhesion solutions
Crystalloids and dextran are ineffective, and their use can be dangerous, with a risk of infection linked to volumes of these agents remaining in the peritoneal cavity for up to 1 week.

As antiadhesion agents are medical devices, information about their compositions and effectiveness is scarce. Four solutions or gels are or have been commercialised. We used the ideal barrier definition to compare them, based on bibliographic data (see Table 1).

[[HPE16_table1_27]]

Intergel has not yet been commercialised, and data on SprayGel are currently insufficient. Only Adept and Hyalobarrier are currently available, with no comparative study having been carried out to date. Both products were tested only in animal studies and in one clinical study, the design of which is questionable. There are some side-effects and contraindications associated with the use of Adept, but not Hyalobarrier. The choice between Adept and Hyalobarrier depends on the type and position of the intervention.

Conclusion
As the effectiveness of antiadhesion solutions will never be proven through conventional randomised controlled studies, due to the size of the representative population sample required (about 10,000),(5) preventive strategies should promote progress of surgical techniques.

References

  1. Liakakos T, Thomakos N, Fine PM, Dervenis C, Young RL. Peritoneal adhesions: etiology, physiopathology, and clinical significance. Dig Surg 2001;18:260-73.
  2. Miller G, Boman J, Shrier I, Gordon PH. Etiology of small bowel obstruction. Am J Surg 2000;180:33-6.
  3. Ellis H, Moran BJ, Thompson JN, Parker MC, Wilson MS, Menzies D, et al. Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study. Lancet 1999;353:1476-80.
  4. Risberg B. Adhesions: preventive strategies. Eur J Surg 1997;577 Suppl:32-9.
  5. Hawthorn RJ. Assessing the value of an adhesion reduction strategy – is there a solution? 10th ESGE Congress; 2001.


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