Adhesion prevention agents for gynaecological surgery: an overview of Cochrane reviews

Abstract

Background: Intraperitoneal adhesions are associated with considerable co-morbidity and have large financial and public health repercussions. They have secondary effects that include chronic pelvic pain, dyspareunia, subfertility and bowel obstruction. In women with adhesions, subsequent surgery is more difficult, often takes longer, and is associated with a higher complication rate (Broek 2013). The significant burden of adhesions has led to the development of several anti-adhesion agents, although there is disagreement as to their relative effectiveness.

Objectives: To summarise evidence derived from Cochrane systematic reviews on the clinical safety and effectiveness of solid agents, gel agents, liquid agents and pharmacological agents, used as adjuvants to prevent formation of adhesions after gynaecological pelvic surgery.

Methods: The Cochrane Database of Systematic Reviews was searched using the keyword 'adhesion' up to August 2014. The Cochrane information management system was also searched for any titles or protocols of reviews in progress. Two review authors independently extracted information from the reviews, with disagreements being resolved by a third review author. The quality of the included reviews was described in a narrative manner, and the AMSTAR tool was used to formally assess each review included in this overview. The quality of evidence provided in the original reviews was described using GRADE methods.

Main results: We included two reviews, one with 18 studies comparing solid agents (oxidised regenerated cellulose expanded polytetrafluoroethylene, sodium hyaluronate and carboxymethylcellulose, and fibrin sheets) with control or with each other. The other review included 29 studies which compared liquid agents (4% icodextrin, 32% dextran, crystalloids), gel agents (carboxymethylcellulose and polyethylene oxide, polyethylene glycol gels, hyaluronic acid based gel, 0.5% ferric hyaluronate gel, sodium hyaluronate spray) and pharmacological agents (gonadotrophin-releasing hormone agonist, reteplase plasminogen activator, N,O-carboxymethyl chitosan, steroid agents, intraperitoneal noxytioline, intraperitoneal heparin, systemic promethazine) with control or each other. Both reviews met all of the criteria of the AMSTAR assessment.The reviews included as outcomes both the primary outcomes of this overview (pelvic pain, pregnancy, live birth rate and quality of life (QoL)) and our secondary outcomes (adverse effects, presence or absence of adhesions at second-look laparoscopy (SLL) and adhesion score). However, neither of the reviews identified any primary studies of solid, gel or pharmacological agents that reported any of our primary outcomes. The only studies in either review that reported any of our primary outcomes were studies comparing liquid agents versus control (saline or Hartmann's solution), which reported pelvic pain (two studies), live birth (two studies) and pregnancy (three studies).An external source of funding was stated for 25 of the 47 studies across both reviews; in 24 of these studies the funding was commercial. Solid agents (18 studies)None of our primary outcomes were reported. Adverse events were reported as an outcome by only 9 of the 18 studies. These reported no adverse events. Liquid agents (nine studies)There was no evidence of a difference between liquid agents and control (saline or Hartmann's solution) with respect to pelvic pain (odds ratio (OR) 0.65, 95% confidence interval (CI) 0.37 to 1.14, 1 study, n = 286, moderate quality evidence), pregnancy rate (OR 0.64, 95% CI 0.36 to 1.14, 3 studies, n = 310, moderate quality evidence) or live birth rate (OR 0.67, 95% CI 0.29 to 1.58, 2 studies, n = 208, moderate quality evidence). No studies of liquid agents reported QoL. Adverse events were not reported as an outcome by any of the nine studies. Gel agents (seven studies)None of our primary outcomes were reported. Adverse events were not reported as an outcome by any of the seven studies. Pharmacological agents (seven studies)None of our primary outcomes were reported. Adverse events were reported as an outcome by only one of the seven primary studies. This study reported no evidence of difference in ectopic pregnancy rates between intraperitoneal noxytioline and no treatment (OR 4.91, 95% CI 0.45 to 53.27, 1 study, n = 33, low quality evidence).

Authors' conclusions: There is insufficient evidence to allow us to draw any conclusions about the effectiveness and safety of anti-adhesion agents in gynaecological surgery, due to the lack of data on pelvic pain, fertility outcomes, quality of life or safety. A substantial proportion of research in this field has been funded by private companies that manufacture these agents, and further high powered, independent trials will be needed before definitive conclusions can be made.

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Overview flow diagram.