Absorbable fluid adjuvants
With barrier adjuvants, optimal benefit is obtained when the physician can predict potential sites of adhesions. This is not a strict requirement with fluid barriers, which is their chief advantage. Among the agents described below, Sepracoat (Genzyme Corp) is available in the United States, while Intergel (Lifecore Biomedical, Chaska, Minn) was withdrawn from the market in March.
Intergel, a 0.5% ferric hyaluronade formulation, is a sterile nonpyrogenic gel of highly purified sodium hyaluronate, which is ionically cross-linked with ferric ion and adjusted to isotonicity with sodium chloride.11 (Hyaluronic acid is a major component of body tissues and fluids such as peritoneal fluid, where it performs physically supportive and mechanically protective roles.)
Johns and colleagues20 studied Intergel in a randomized, multicenter, third-party– blinded, placebo-controlled study. Of the 265 patients who completed the study, 131 were given 300 mL of Intergel and 134 were given lactated Ringer’s solution (the placebo) at the time of their surgery, through the laparoscopic port. When SLL was performed 6 to 12 weeks after surgery, the mean number and severity of adhesions—overall and at the surgical site—were significantly lower in the Intergel group. Adhesions reformed in 91% of those in the control group, compared with 63% in the Intergel group.
In myomectomy patients, the modified American Fertility Society Score, which uses 24 potential adhesion sites, was reduced by 42% in the Intergel group—a statistically significant improvement.20
One major advantage of Intergel is that it reduces adhesion formation at sites distant from the area of application, secondary to its wide intra-abdominal circulation. However, as mentioned above, sales were voluntarily suspended due to post-market reports of tissue adherence, sterile foreign-body reaction, and late-onset pain that sometimes required surgical intervention. In some patients, persistent residual material was noted at the time of subsequent surgery.
Sepracoat (hyaluronic acid-coat) is a dilute solution of 0.4% hyaluronic acid in phosphate-buffered saline. It is bioresorbable, persists at the application site less than 24 hours, and is completely cleared in less than 5 days.
In a prospective, randomized, blinded, placebo-controlled, multicenter study in 1998, Diamond and colleagues compared Sepracoat with a pure phosphate-buffered saline solution in 227 women undergoing gynecologic procedures via laparotomy.21 The aim of the study was to assess the efficacy and safety of the fluid at sites without direct surgical trauma or adhesiolysis. Both solutions were warmed to room temperature and injected into the abdominal cavity before the procedure began (250 mL after skin incision). The solution was reapplied after irrigation or every 30 minutes (100 mL), and at the end of the procedure (250 mL) before closure. The maximum volume used was 1,000 mL. After application, the fluid was left 1 minute before suctioning. Patients underwent SLL 40 days later, and adhesions were identified at the initial procedure and at SLL.
In the Sepracoat group, there was a reduction in de novo adhesions at nonsurgical sites by a factor of 2.8. The proportion of sites with de novo adhesions also decreased, and 80% of Sepracoat patients had at least 1 ovary that was adhesion-free compared with 58% of placebo-treated patients. These findings occurred in areas of indirect trauma, demonstrating that Sepracoat limited trauma at tissue injury.21
Conclusion
Adhesion prevention is of utmost importance after abdominal myomectomy, especially in patients who desire future fertility. Despite the limited number of prospective, randomized studies, the literature does support the efficacy of various fluid and barrier adjuvants.
Our practice is to use an adjuvant in all abdominal myomectomies. We have long relied on Interceed, which enjoys both ease of application and an excellent safety record. However, as reviewed above, other potentially useful products are available or in development. As ever, the reproductive surgeon should adhere to principles of microsurgery, strive for meticulous hemostasis, and demonstrate respect for tissue integrity.
Dr. DeCherney reports small holdings with Lifecore Biomedical. Drs. Chang and Marin report no affiliations or financial arrangements with any of the manufacturers of products mentioned in this article.