Abstract
Meshed split-thickness skin grafts (STSGs) secured with 2-octylcyanoacrylate (2-OCA) were compared with meshed STSGs secured by suture and bolster (S&B). The 2 techniques were compared for graft survival, foreign-body giant cell response, inflammatory response, appearance, texture, and application time. Sixteen 2.5 × 2.5 cm meshed STSGs were harvested from the dorsa of 2 pigs for a total of 32 grafts. On each pig 8 grafts were sprayed with 2-OCA, and the other 8 were secured with S&B. Evaluations were performed on postoperative days 14, 24, 48, and 56. Biopsy specimens were obtained on postoperative days 14 and 56. There were no significant differences in percent survival, foreign-body giant cell response, inflammatory response, and appearance between control and study grafts. The average time to apply the 2-OCA onto a graft was 3 seconds, compared with 8 minutes for S&B application. 2-OCA provides a quick and reliable means of securing meshed STSGs and would be especially useful in areas where it is difficult to use S&B, such as total maxillectomy defects.
Meshed split-thickness skin grafts (STSGs) are used frequently by head and neck surgeons. Suturing the graft along with suture and bolster (S&B) placement has been the standard means of securing these grafts; however, this can be time consuming and does not allow for graft monitoring. Additionally, some defects such as the orbit, after orbital exenteration, are not easily amenable to S&B. This study addresses the ability of 2-octylcyanoacrylate (2-OCA) (Nexaband SC; TriPoint Medical LP, Raleigh, NC) to secure a meshed STSG. The 2 methods are compared on the basis of graft survival, foreign-body giant cell response (FBGR), inflammatory response, appearance, texture, and time of application. We hypothesized that 2-OCA would (1) prove as effective as S&B with respect to graft survival, (2) have no significant difference in FBGR, (3) be superior in terms of time required to secure the grafts, and (4) allow for graft monitoring.
METHODS AND MATERIAL
Two 25-kg, female, black-skinned native swine were used. Humane care was provided in accordance with guidelines provided by the NIH and the animal care and use committee at the University of Texas Health Science Center at San Antonio. Thirty minutes before surgery, 300,000 units of benzathine penicillin was administered intramuscularly. Atropine 0.4 mg/kg was administered intramuscularly at the start of the procedure. A mixture of ketamine HCL 100 mg/mL and Rompun (xylazine) 100 mg/mL was injected intramuscularly at a dosage of 1 mL/8 kg. General anesthesia was induced with an inhalational mixture of isoflurane and oxygen administered through an endotracheal tube. Oxygen saturation, heart rate, and respiratory rate were monitored closely, and the isoflurane was adjusted accordingly by the veterinary staff.
Sixteen STSGs were taken from each pig's back and arranged in rows of 8 on either side of the midline (primary surgeon, O.A.T.). A midline strip of skin 4.0 cm wide separated the 2 rows, and within a row, each STSG site was separated from its neighbors by 3.5 cm. Each STSG was 2.5 × 2.5 cm, 0.457 mm thick, and meshed to increase the surface area 3-fold with a Zimmer dermatome and mesher (Warsaw, IN). The dermis from each graft site was then excised with electrocautery down to the premuscular fascia. Subsequently, the meshed STSGs were placed onto the defects. Study and control STSGs were alternated between sides on each row to prevent any bias based on side for all rows of grafts. Five 3–0 chromic sutures (4 corner sutures and 1 center suture) were used to secure each control graft onto its tissue bed. Bolsters were formed with Bacitracin-impregnated fine-meshed gauze and cotton balls and reinforced with 4 2–0 silk sutures from the periphery. The study grafts were secured with the 2-OCA preparation by being sprayed with a single application of 2-OCA provided in the pump-spray container. Subsequently, a thin layer of Bacitracin ointment was applied over the polymerized dressing (Fig 1). Because pigs have a tendency to rub their backs against surfaces, we attempted to protect the grafts against such shearing forces. On the 2-OCA-sprayed grafts, a Telfa pad covered the defect and was stapled to the surrounding skin. The Telfa pad was not firmly adhered to the graft and was placed strictly for graft protection. Two strips of elastic tape were then stapled loosely over the bolster and Telfa pads to further protect against shearing. Lastly, a cotton sheet was draped over the dorsum and secured with a large net dressing.
Mean grades for percent survival, appearance, and texture
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∗ANOVA was calculated with the difference between the mean grades for study and control grafts.
† Statistically significant.
The pigs were given 600 mg of prophylactic oral Primor (sulfadimethoxine and ormetoprim) for 6 days. The same mixture of ketamine HCL 100 mg/mL and Rompun (xylazine) 100 mg/cc was administered intramuscularly at 1 mL/8 kg for each evaluation session. On postoperative day (POD) 7, the Telfa pads were removed from the 2-OCA grafts. The 2-OCA dressing had changed from the initial purple color to a clear color and allowed for easy graft monitoring. On POD 14, bolsters were removed from the control grafts, and the dried layer of 2-OCA had separated from the study grafts and could be removed. Three observers—a veterinarian, a veterinary technician, and the primary author (O.A.T.)—evaluated each graft with regards to percent survival, appearance, and texture on PODs 14, 24, 48, and 56. Percent survival ranged from 0% to 100%. To standardize a grading scale for percent survival, grafts that represented a successful “take” (>95%) and a poor “take” (<50%) were presented to each individual before each grading session. Grafts were graded separately for texture and appearance with the following grading scale: 1, smooth; 2, in-between; and 3, rough. As with percent survival, grafts that represented smooth and rough were presented to each individual before each grading session.
On PODs 14 and 56, one punch biopsy from different sites on each graft was obtained and placed in 10% neutral-buffered formalin solution and, after fixation, each was routinely processed and paraffin embedded. Sections (4 μm thick) were prepared and stained with hematoxylin and eosin, and the presence and severity of FBGR and the inflammatory response were noted. A coauthor (H.S.M.) was blinded as to which technique was used and reviewed all slides. Inflammatory response was evaluated with regard to severity. The scores were based on a scale of 1 to 4: 1, mild response; 2, mild-to-moderate response; 3, moderate response; and 4, severe response. FBGR was evaluated on the basis of focality and severity: 1, no response; 2, mild-focal response; 3, moderate-scattered response; and 4, severe-florid response.
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Intraoperative picture of the alteration of control (S&B) and study (2-OCA) grafts by side for each paired site.
With Dixon and Massey's 2-sampled t test, 1 at least 13 grafts per treatment were necessary to find a 20-unit difference in means for percent survival, with a significance level of P < 0.05 and 0.80 power, for a measure with an SD of 25. Statistical analysis was calculated by use of SAS PROC GLM (Statistical Analysis System Institute, Cary, NC). Paired t test and analysis of variance (ANOVA) were used to determine significance. Paired t test was used to calculate simple comparisons, and ANOVA was used to control for several factors. ANOVA calculations for inflammatory response and FBGR were performed, controlling for pig and graft variability. ANOVA calculations for percent survival, appearance, and texture, were performed, controlling for pig, graft, postoperative time, and rater variability. The degree of interrater agreement was determined by calculation of the Pearson correlation coefficient (r) for percent survival and the κ statistic for appearance and texture. The r values ranged from -1.0 to 1.0, with stronger interrater agreements corresponding to more positive values. The κ statistics ranged from 0 to 1, with higher scores representing agreement above the agreement expected by chance alone.
RESULTS
The mean scores of the study and control grafts for percent survival differed by only 2% and were not statistically significantly different. There was no difference between study and control grafts for appearance. There was a statistical difference (P = 0.03) between the 2 techniques in regards to texture, with the control grafts being smoother (Table 1). The interrater agreement for both control and study grafts, with regards to percent survival, was strong, with r ranging from 0.66 to 0.81. For appearance and texture, interrater agreement was weak, with the highest κ being 0.37 (Table 2). The average time to apply the 2-OCA onto a graft was 3 seconds compared with 8 minutes for S&B application.
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Control (
Pearson r and κ statistic for each pair of observers
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∗Highest r and κ value for each group.
Sections of POD 14 specimens showed that all specimens had intact epithelial surfaces with occasional associated reactive changes consisting of epithelial hyperplasia, tissue redundancy, and hyperkeratosis. The underlying connective tissue consisted of diffuse, immature, fibrocollagenous scar tissue with patchy, mild, subacute-to-chronic superficial, interstitial, and perivascular inflammation (Fig 2A and B). Small foci of FBGR were occasionally observed in and around the deep connective tissue voids. The POD 56 specimens showed similar features but with a decreasing inflammatory component and maturation of the cicatricial tissue (Fig 2C and D).
There was no statistical difference between the mean scores of the study and control grafts for inflammatory response and FBGR (Table 3). All mean scores improved for both study and control grafts with regard to inflammatory response and FBGR between PODs 14 and 56. These improved scores were statistically significant except for the improvement in inflammatory response for the study grafts (Table 4 and Fig 2).
DISCUSSION
Since their discovery in 1949, cyanoacrylates have evoked great interest in use as a “tissue glue,” forming a potentially more convenient means of wound closure than fibrin glue or suturing techniques. 2 Of the different compounds, 2-butylcyanoacrylate (2-BCA) initially was considered the ideal tissue glue for superficial wound closure. Bhaskar et al 3 were successful in applying 2-BCA to the raw surfaces of postgingivectomy wounds in human beings without substantial FBGRs. Ousterhout et al 4 applied 2-BCA to the donor site of a split-thickness skin wound and compared it with fine-meshed gauze. He noted only minimal FBGR in the 2-BCA-treated donor wounds. At the completion of the healing process, there was no cosmetic difference in the sites, and most patients preferred the 2-BCA—treated wounds. With further investigation, however, some unfavorable qualities of the butylcyanoacrylates became apparent. The greatest limitation has been their physical properties. Studies have shown wound-breaking strength of 2-BCA to be equal to that of suture-repaired wounds at 5 to 7 days, but the day 1 breaking strength was only 10% to 15% that of a wound closed with 5–0 monofilament sutures. 5 , 6 Also, after polymerization, the butyl derivatives become brittle and subject to fracture, thus limiting the clinical utility of these adhesives. 7
Unlike the other cyanoacrylates, which have been relatively pure monomers, recent investigations with the longer chain-formulated octylcyanoacrylates containing plasticizers have demonstrated a strong yet flexible 3-dimensional bond. The 3-dimensional breaking strength has been demonstrated to be 3 times that of 2-BCA and closer to that of a 5–0 monofilament nylon, while still retaining the hemostatic, bacteriostatic ease of application and the low-cost benefits of 2-BCA. 7 – 9
Mean grades for all STSGs with regards to inflammatory response and FBGR
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∗ANOVA was calculated with the difference between the mean grades for study and control grafts. No statistical difference was noted.
Mean grades on PODs 14 and 56 for inflammatory response and FBGR
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∗Paired t-test was performed on the difference in mean grades for POD 14 and 56.
† Statistically significant.
Although previous studies have applied cyanoacrylates to the periphery of wounds to secure STSGs, we are not aware of any prior study that has attempted to secure a meshed STSG by spraying a cyanoacrylate onto the graft and allowing it to contact the subcutaneous tissue. 10 , 11 The results of this investigation would support its use in this fashion. Additionally, although neither 2-BCA nor 2-OCA was FDA approved at the time of this study, in August 1998, a 2-OCA received FDA approval for use as a topical skin adhesive and is marketed as Dermabond (Ethicon Inc, Somerville, NJ).
The 2 most important objectives of this study, comparison of experimental and control grafts with regards to survival and FBGR severity, were satisfied with no differences noted. Presenting the observers with examples of good and poor graft “takes” before each grading session produced strong interrater agreement for percent survival. The only statistically significant difference noted in this study was that of a smoother texture noted in the control group. Although we found no significant difference in appearance, a real difference of some magnitude could have been masked by the poor interrater agreement on this variable. However, it is our impression that no real difference was evident and that the study grafts were smooth enough to be acceptable to a facial plastic surgeon planning to use an STSG.
Lastly, S&B clearly took longer than securing the STSG with a single application of 2-OCA. This difference would be further magnified in difficult areas to graft, such as orbital and total maxillectomy defects. Although a cost analysis was not performed in this investigation, studies comparing tissue adhesives versus suture repair of lacerations have shown tissue adhesives to be significantly less expensive. 12 We would similarly anticipate a savings to the patient needing STSG, based on Dermabond currently selling for approximately $25 per applicator, which should be adequate for most otolaryngology applications. To accurately determine the savings for a particular patient, however, a surgeon would need to calculate the savings based on reduction in operating time, suture material, and postoperative management as compared with the cost of the 2-OCA needed.
CONCLUSION
Meshed STSGs secured with 2-OCA showed no difference in graft survival or FBGR compared with S&B. 2-OCA would provide the head and neck surgeon with a quick and reliable means of securing meshed STSGs while allowing direct graft monitoring. It would be especially convenient in difficult to S&B areas such as orbital exenteration and total maxillectomy defects.