Wound closure is a rapidly growing field. Advances in biotechnology coupled with demands for faster, safer and more efficient treatment and recovery have sparked a renewed interest in surgical glues.

Many approved, established and useful sealants are already on the market, with several more in development. This article will tell you how the five families of tissue adhesives work - fibrin sealant, cyanoacrylate, bovine collagen and thrombin, polyethylene glycol polymer and albumin cross-linked with glutaraldehyde - and offer advice for choosing the right one for your case mix.

Fibrin sealant
Fibrin sealants were the first type of surgical glue available on the U.S. market. The FDA in 1998 approved the first commercially produced glue, Baxter Healthcare's Tisseel VH.

Tisseel VH is approved as a hemostatic agent for use in stopping bleeding associated with cardiac surgery and spleen trauma, and for sealing colon anastomoses at the time of colostomy closure. It's derived from pooled human plasma that has undergone heat pasteurization and antiviral filtration.

The glue is distributed as freeze-dried, refrigerated powders of fibrinogen and thrombin, two human blood proteins that cause clotting. When reconstituted and combined, the mixture polymerizes in 30 seconds to three minutes and biodegrades in most tissues between seven and 14 days.

Risks include a potential danger of viral disease transmission and a possible allergic response to bovine aprotinin, which is used as a stabilizer in the mixture.

Tisseel VH comes with a device that facilitates syringe-based linear application, although additional devices are available to permit spray application for wider areas, endoscopic and laparoscopic uses. Tisseel VH is sold in 1ml, 2ml and 5ml kits. The 1ml kit costs about $100.

In 2003, the FDA approved Ethicon's Crosseal, a second-generation fibrin sealant designed to achieve hemostasis during liver resection procedures.

Crosseal is distributed as two vials of frozen liquid. The first contains pooled human fibrinogen and other clotting proteins; the second, pooled human thrombin and a stabilizer of synthetic tranexamic acid. In addition to heat pasteurization and filtration, the sealant employs solvent detergent cleansing to reduce risks of viral transmission. Once thawed, the liquids can be stored ready for use in a refrigerator for up to 30 days.

In addition to viral disease transmission, Crosseal's risks include the danger of seizures, which can be caused if tranexamic acid comes in contact with the central nervous system.

Crosseal's standard kit is equipped with a needleless transfer system by which the liquids can be transferred to an applicator with a flexible plastic tip capable of linear or spray application. Its kit sizes and costs are similar to those of Tisseel VH.

A third form of fibrin sealant is Orthovita's Vitagel. The product, formerly known as Costasis, is made up of plasma generated from the patient's own blood, bovine thrombin and collagen. The system includes a syringe-based applicator for linear placement of the sealant. In a cost-effective feature, Vitagel lets OR staff prepare the patient's plasma early in the case, then open the thrombin/collagen kit only if a hemostatic agent is required during surgery.

While fibrin sealant has been approved specifically for hemostasis in cardiac, liver, spleen and some colon surgeries, there is a large body of literature suggesting its usefulness in controlling bleeding in other locations or delivering medications as it seals.

Cyanoacrylate
Cyanoacrylates, which are chemically similar to household "super glues," are approved by the FDA for external use only as a means of skin wound closure and as a topical antibacterial barrier.

One formulation, 2-octyl cyanoacrylate, is sold commercially as Ethicon's Dermabond. U.S. Surgical markets another formulation, n-butyl 2-cyanoacrylate, as Indermil.

The two products are recommended as a closure method for low-tension traumatic lacerations and surgical incisions, and may be used in conjunction with, but not in place of, deep dermal stitches. Polymerization occurs in about 30 seconds, and the material is sloughed from the superficial layers of the wound after about seven days. Product risks include foreign body reaction, inflammation, allergic response and carcinogenic potential.

Both are supplied as room-temperature, ready-to-use liquids - Dermabond in a 0.5ml, crushable plastic ampule with a variety of applicator tips, Indermil in a 0.5ml soft plastic "dropper" applicator - and cost $20 to $25 per unit. Ethicon also offers a low-viscosity version of Dermabond.

Bovine collagen and thrombin
As a surgical glue, bovine collagen and thrombin requires active bleeding - and the fibrinogen in blood - for hemostasis to be achieved. Because the glue is relatively solid, however, the blood does not wash it away.

The hemostatic agent, sold as Baxter's FloSeal is supplied in two separate, room-temperature syringes containing bovine collagen in gelatin form and bovine thrombin. When combined into one syringe, the mixture takes the consistency of applesauce and is applied through a blunt tip. The body reabsorbs it in six weeks to eight weeks.

Besides allergic reactions, risks include the potential for coagulopathy based on a patient's production of antibodies to bovine thrombin and/or factor V, which may cross-react with a patient's own clotting factors and result in deficiency.

FloSeal costs $140 for a 4ml kit. Curved applicator tips, 8cm and 10-m in length, are available for spinal and head/neck procedures.

Polyethylene glycol (PEG) polymer
Only one polyethylene glycol (PEG) polymer adhesive is currently on the market. Baxter's CoSeal is approved for use in vascular reconstructions to achieve adjunctive hemostasis by mechanically sealing areas of leakage. Since the material is entirely synthetic, risks are minimal.

The product is stored at room temperature, prepared in minutes on the surgical field and applied with a dual-syringe manual spray applicator. It polymerizes in about a minute into a gel that biodegrades within seven days. CoSeal costs $250 for a 2ml kit.

Albumin cross-linked with glutaraldehyde
CryoLife's BioGlue consists of a glutaraldehyde component that produces cross-linking in the bovine albumin to produce a seal. It has been approved for achieving hemostasis in vascular anastomoses. Its risks include nerve injury, emboli of adhesive and limited growth of pediatric anastomoses.

The formula begins to polymerize 20 seconds or 30 seconds after mixing and reaches its full strength after two minutes. It biodegrades over a period of several months.

BioGlue is supplied in room temperature, dual-syringe kits that come in 2ml, 5ml and 10ml sizes. The two larger sizes can be applied with a resterilizable "gun." The 5ml kit costs about $450.

Choosing the right product
The field of surgical tissue adhesives is similar to that of surgical sutures, in that a variety of materials is required for effective clinical use. Each glue has its own strengths and limitations. Within groups, factors such as cost and local sales support as well as nurse and physician preference may be important in choosing a product.

Surgeons who've been well educated about their use, including extensive hands-on experience, use these agents most effectively. There's a learning curve to the effective use of each of these materials. Practical instruction and clinical support from colleagues in the field are critical to maximize the potential benefits that surgical glues have to offer.