Paradoxical inflammatory reaction to Seprafilm: case report and review of the literature.
Key Words: Seprafilm, paradoxical adhesion, bowel obstruction, peritonitis
It is estimated that postoperative adhesions occur in 67 to 93% of patients undergoing abdominal or pelvic surgery. (1,2) Such adhesions can lead to complications including small bowel obstruction (49 to 74%), infertility (15 to 20%), and chronic pelvic pain (20 to 50%). (3,4) Although the pathophysiology of adhesion formation is not completely understood, numerous surgical adjuncts have been introduced in recent years to decrease the incidence and clinical implication of adhesions. One such method involves the use of a bioabsorbable adhesion barrier composed of sodium hyaluronate and carboxymethylcellulose (Seprafilm, Genzyme Corp, Cambridge, MA). Two randomized, blinded, controlled clinical trials and a prospective study have demonstrated both its safety and efficacy in preventing adhesions in abdominal and pelvic surgeries. (5-7) We report a case of extensive inflammatory reaction in a patient in whom Seprafilm was used during an uncomplicated low anterior resection. An extensive literature search yielded only two other case reports of paradoxical adverse reactions to this adhesion barrier. (8,9)
A 70-year-old female was referred for a low anterior resection for a rectal tumor located 10 cm from the anal verge. Her medical history was significant for hypertension and asthma. Her surgical history included a total abdominal hysterectomy for uterine fibroids in 1975, a bladder lift in 1976, and a right oophorectomy in 2002 for benign disease. At surgery, the scant adhesions from the prior surgeries were lysed and the low anterior resection proceeded uneventfully. A colorectal anastomosis was created and a sheet of Seprafilm was placed between the omentum and the incision during closure. The final pathology showed stage II (T2, N0, M0) adenocarcinoma.
Her postoperative course was marked by a mild tachycardia of 95 to 105 and a low-grade temperature of 100 to 100.5[degrees]F. She reported no abdominal pain, and her white blood cell count was normal. On postoperative day 4, the patient was noted to be very distended and nauseated. A Gastrografin enema did not reveal an anastomotic leak and an abdominal CT scan did not reveal an abscess. A nasogastric tube was placed, and the patient was followed expectantly. Her distention and inability to tolerate oral intake did not improve, although she was not febrile and had a normal white count and differential. Because of her unresolving obstruction, she was returned to the operating room on postoperative day 11.
At laparotomy, she was found to have extensive, dense adhesions involving the abdominal wall, omentum, and multiple loops of small bowel. There were several sites of obstruction with proximal dilation within this mass of adhesed loops. These loops were fused together in several sites, which prevented separation. The adhesions were lysed; however, four enterotomies were created, necessitating an ileocecectomy with a partial omentectomy and ileostomy. The previously created colorectal anastomosis appeared to be intact. However, two loops of ileum were densely adhered to the anastomotic site and so the anastomosis was taken down with the lysis of adhesions. An end-descending colostomy and rectal Hartmann closure was performed. The pathology showed diffuse inflammation with multiple giant cells suggesting a foreign body reaction (Figs. 1 and 2). The patient recovered well and was ultimately transferred to a rehabilitation facility. She was doing well at her 6-week visit.
Postoperative adhesions form after most intraperitoneal procedures. Sixty-seven percent of patients undergoing laparotomy have development of adhesions, according to autopsy studies conducted by Weibel and Majno. (1) After multiple operations, this incidence rises to 93%, as demonstrated in the prospective clinical trial performed by Menzies and Ellis. (2) Such adhesions can cause numerous complications, costing substantial healthcare dollars. According to the National Inpatient Profile, more than 400,000 laparotomies were performed for lysis of adhesions in 1993 in the United States.
The precise cause of adhesion formation is not completely understood, although numerous methods have been used to prevent this complication, including mechanical barriers. Seprafilm is composed of two anionic polysaccharides, sodium hyaluronate and carboxymethylcellulose, which have been chemically modified. This barrier transforms into a gel after being placed in the peritoneum and is reabsorbed in approximately 7 days, after normal tissue repair has taken place and the inflammatory cascade has subsided. It thus prevents adhesions by physically separating raw surfaces temporarily. In two prospective, randomized, blinded, multicenter studies in which Seprafilm was used after pelvic or abdominal surgery, repeat laparotomy or laparoscopy showed a significantly lower rate of adhesion formation and no difference in adverse events in patients who received the membrane and those that did not. (5,6)
Beck et al (7) studied patients undergoing abdominopelvic surgery, the majority of whom had inflammatory bowel disease, and reported an increased incidence of peritonitis (3% Seprafilm versus 1% control). However, the degree to which anastomotic leak contributed to their findings was not clear. An extensive review of the literature for adverse reactions to Seprafilm yielded only two other case studies. Klinger et al (9) published a report on Seprafilm-induced peritoneal inflammation in a patient who had undergone completion proctocolectomy. This patient had a fever and partial small bowel obstruction on postoperative day 4. (10,11) On exploratory laparotomy, an area of intense inflammation corresponding to the site of Seprafilm placement was observed. Histologic examination revealed a foreign body granulomatous reaction. In addition, Remzi et al (8) reported similar observations in three patients who underwent various colorectal surgeries and received Seprafilm.
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The high incidence of postoperative adhesion formation and the morbidity associated with its complications warrant the use of adjuncts such as mechanical barriers. Seprafilm is clinically proven to be safe and effective in preventing adhesion formation. Rarely, however, this substance may cause an intense inflammatory response that resembles peritonitis or may cause a bowel obstruction. Because these findings are uncommon, increased reporting will better clarify the incidence and help identify the cause of such paradoxical reactions.
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2. Menzies D, Ellis H. Intestinal obstruction from adhesions--how big is the problem? Ann R Coll Surg Engl 1990;72:60-63.
3. Hershlag A, Diamond M, DeCherney A. Adhesiolysys. Clin Obstet Gynecol 1991;34:395-401.
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5. Diamond M. Reduction of adhesions after uterine myomectomy by Seprafilm Membrane (HAL-F): a blinded, prospective, randomized, multicenter clinical study. Fertility and Sterility 1996;66:904-910.
6. Becker J, Dayton M, Fazio VW, et al. Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioreabsorbable membrane: a prospective, randomized, double-blinded multicenter study. J Am Coll Surg 1996;183:297-306.
7. Beck DE, Cohen Z, Gleshman JW, et al. A prospective, randomized, multicenter, controlled study of the safety of Seprafilm adhesion barrier in abdominopelvic surgery of the intestine. Dis Colon Rectum 2003;46:1310-1319.
8. Remzi FH, Oncel M, Church JM, et al. An unusual complication after hyaluronate-based bioresorbable membrane (Seprafilm) application. Am Surg 2003;69:356-357.
9. Klingler PJ, Floch NR, Seelig MH, et al. Seprafilm-induced peritoneal inflammation: A previously unknown complication: Report of a case. Dis Colon Rectum 1999;42:1639-1643.
10. Boys F. The prophylaxis of peritoneal adhesions: A review of the literature. Surgery 1942;11:118-168.
11. Harold E. The causes and prevention of intestinal adhesions. Br J Surg 1982;69:241-243.
Of science and the human heart, there is no limit. --U2
Marianne David, BS, Babak Sarani, MD, Farah Moid, MD, Sana Tabbara, MD, and Bruce A. Orkin, MD, FACS
From the Department of Surgery and the Department of Pathology, George Washington University, Washington, DC.
Reprint requests to Bruce Orkin, MD, George Washington University, 2150 Pennsylvania Avenue NW, Washington, DC 20037. E-mail: email@example.com
Accepted March 17, 2005.
RELATED ARTICLE: Key Points
* Seprafilm has been proven to be a safe and effective adhesion barrier after abdominopelvic surgery.
* Rare adverse inflammatory reactions to Seprafilm indicate that certain predisposing factors might exist that contribute to this phenomenon.
* Given the widespread use of adhesion barriers in abdominopelvic surgical procedures, further experimental studies are warranted for investigating the underlying pathophysiological mechanisms for these aberrant inflammatory reactions.