Renal bed during laparoscopic partial nephrectomy for a 2-cm exophytic tumor. The arterial bleeding seen here was controlled with bipolar electrocoagulation, and the venous bleeding was controlled with fibrin sealant. (Photograph courtesy of Chandru Sundaram, MD)

Tissue sealants have been used for several years in a number of surgical specialties, including urology. Of the various types of tissue sealants, fibrin sealants are the most widely used.

Although commercial fibrin sealants have been used extensively in Europe and other countries since the 1970s, they were not approved by the FDA until 1998. Fibrin glue is now being used in a variety of surgical situations as a hemostatic agent or as a tissue adhesive. An advantage of fibrin glue is that it is biodegradable and therefore does not result in significant inflammatory tissue fibrosis or foreign body reaction. Furthermore, fibrin glue may promote angiogenesis, local tissue growth, and repair.

This article discusses the mechanism of tissue sealants, how they are prepared and applied, their applications in urology, and potential complications.

How fibrin sealant works Fibrin sealant acts by following the final pathway of the coagulation cascade. Fibrinogen is converted into fibrin, causing linking of the fibrin monomer that results in an insoluble complex. This process can also be effective in patients who are coagulopathic.

The commercially available fibrin sealants in the United States include Tisseel (Baxter Healthcare Corp., Glendale, CA) and Hemaseel (Haemacure Corp., Montreal). Sealants typically consist of two components: a sealer protein solution and a thrombin solution. The sealer protein solution contains vapor-heated, freeze-dried human sealer protein concentrate and a fibrinolysis inhibitor solution. The thrombin solution contains human thrombin that is vapor-heated and freeze-dried in a calcium chloride solution. The sealer protein concentrate contains fibrinogen made from pooled human plasma, and the fibrinolysis inhibitor is of bovine origin containing aprotinin.

The two components are reconstituted to form the sealer protein solution. This solution, when combined with the thrombin solution at the surgical site, forms the fibrin sealant that sets into an elastic coagulum. The fibrin sealant is manufactured with a two-step vapor-heating process to help with virus removal or inactivation.

Preparing the sealant For the purposes of this article, I will discuss the preparation and use of Tisseel. Preparation of the product's two component solutions can take up to 20 minutes and therefore must be prepared when the need is anticipated. The sealer protein concentrate is reconstituted with fibrinolysis inhibitor solution using a combined heating and stirring device called Fibrinotherm (Baxter). The sealer protein concentrate should be fully dissolved within 20 minutes.

Reconstitution of the sealer protein concentrate can also be achieved using a water-bath or an incubator. The thrombin solution is reconstituted in a calcium chloride solution. During reconstitution of both solutions, it is important that iodine and preparations containing iodine not be used since contact with solutions containing alcohol, iodine, or heavy metal ions can denature the Tisseel products.

The sealer protein solution and the thrombin solution are applied using a Duploject system (Baxter), which consists of a clip for two identical disposable syringes with a common plunger, allowing equal volumes of the two components to be injected through a joining piece before being mixed in the application needle/catheter.

The sealant can also be applied with the Tissomat spray device (Baxter), a control unit that delivers a homogenous layer of Tisseel fibrin sealant under pressurized gas. The fibrin glue can also be applied via a variety of catheters and applicators. In addition, it can be used laparoscopically via a 35-cm long catheter or endoscopically via a 180-cm length flexible catheter.

It is important that the surfaces to be sealed are held in the desired position for 3 to 5 minutes to ensure that the sealant adheres to the tissue. The fibrin sealant reaches its ultimate strength after about 2 hours, although 70% of the strength is attained in about 10 minutes. The application of the sealant must be completed within 4 hours of reconstitution.

Urology applications Fibrin glue is FDA approved for hemostasis during cardiac surgery and splenic injuries, and for colonic sealing. It has also been widely used for several indications in urology, primarily for hemostasis and/or as a tissue adhesive (J Urol 2002; 167:1218-25). Fibrin sealant is ineffective with active arterial bleeding but is ideally suited to diffuse bleeding during surgery.

Fibrin glue has been effective in limiting bleeding during renal trauma and for renal-sparing surgery. Several groups have used fibrin sealant during treatment of renal trauma and for renal-sparing surgery.

Urlesberger and associates used fibrin sealant for partial nephrectomy and renal trauma (Eur Urol 1979; 5:260-1). The fibrin sealant was applied to the cut surface of the parenchyma and covered with a collagen patch. The collecting system was closed with sutures.

Recently, fibrin sealant has been used for laparoscopic renal-sparing surgery. However, it is usually used in addition to other hemostatic techniques including bipolar coagulation, argon beam coagulator, and ultrasonic scalpel (J Urol 1998; 159:1152-5).

Fibrin sealant for laparoscopic partial nephrectomy can be used for venous bleeding from the kidney on the cut surface of the kidney (see above) and is not effective by itself for gross arterial bleeding. Fibrin sealant and Gelfoam (Pharmacia, Peapack, NJ) have been used in porcine studies to seal the collecting system. Fibrin glue can also be used in conjunction with a collagen hemostatic sponge (Helistat, Integra Life Sciences Corp., Plainsboro, NJ).

Fibrin has also been used to assist with the anastomosis for a laparoscopic pyeloplasty. Janetschek and associates have used the product in conjunction with sutures during fengerplasty for the treatment of ureteropelvic junction obstruction (Urol Clin North Am 2000; 27:695–704).

Fengerplasty (Heinke-Mikulicz repair) involves longitudinal incision of the ureteropelvic junction. The longitudinal incision is then sutured transversely along the principles of Heineke-Mikulicz pyloroplasty.

Eden and associates have used fibrin glue for laparoscopic dismembered pyeloplasty (Br J Urol 1997; 80:382-9). In these patients, however, fibrin must be used in conjunction with sutures because of the fibrinolytic activity of urokinase in the urine.

Fibrin glue can similarly be used in conjunction with sutures for ureteral anastomosis. The number of sutures applied can be minimized in the presence of fibrin glue, and this may be especially useful during the laparoscopic approach.

Fibrin sealant has been used to assist vasal anastomosis during vasovasostomy. However, sutureless vasovasostomy with fibrin glue has not been successful.

Other urologic applications for fibrin glue include endoscopic treatment of vesicovaginal fistula, vesicoperineal fistula, and fistulas between the ileal conduit and the skin and colovesical fistula. Fibrin glue in these situations can be used when surgery is contraindicated or in high-risk patients. It can also be used during the time the patient is awaiting an elective surgical repair.