Anil R. Shah, MD1; Aaron N. Pearlman, MD1; Kevin M. O’Grady, BS, BA2; Tappan K. Bhattacharyya, MSc, PhD, DSc2; Dean M. Toriumi, MD2
1.Division of Facial Plastic and Reconstructive Surgery
Department of Otolaryngology—Head and Neck Surgery
NYU School of Medicine
New York, New York 10016
2. Division of Facial Plastic and Reconstructive Surgery Department of Otolaryngology—Head and Neck Surgery University of Illinois at Chicago
1855 West Taylor Street
Chicago, Illinois 60612
To Be Presented:
Combined Otolaryngology Spring Meeting
American Rhinologic Society
April 27, 2007
San Diego, CA
Corresponding Author: Anil R. Shah, MD
Department of Otolaryngology, Head and Neck Surgery
NYU School of Medicine
530 1st Avenue, SKI 7U New York, NY 10016
Key Words: CSF leaks, dural tear, dura mater, AlloDerm, acellular dermal matrix, skin artificial, fibrin tissue adhesive, post-operative complications, intra-operative complications, duraplasty
Disclosure: This study was in part funded by LifeCell Corp. (The Woodlands, Tx), the manufacturers of Alloderm.
Background: The management of cerebrospinal fluid (CSF) leaks can be challenging. Acellular dermal grafts derived from human cadavers can be used as a replacement material when autogenous materials are unavailable. Fibrin tissue adhesive (FTA) is a wound support product that has been used for hemostatic and tissue fixation purposes. The combined use of acellular dermis in conjunction with fibrin tissue adhesive for dural repair remains a subject of study.
Objective: To evaluate wound healing and tissue compatibility characteristics of acellular dermal substitute material when used both with and without fibrin tissue adhesive, for repair of a dural tear in a chinchilla model.
Methods: 49 chinchillas were included in this randomized case-control study. The squamous portion of the temporal bone was removed to expose the tegmen. A 2 x 2 mm dural defect was removed to create an iatrogenic CSF leak. Animals were then randomly assigned to one of three treatment groups; Group 1: acellular dermis alone, Group 2: acellular dermis with FTA, Group 3: fibrinogen, acellular dermis and FTA. Surgical sites were examined grossly at 1 and 2 week intervals. Temporal bones were examined histologically.
Grossly, groups 2 and 3 had significantly less visible CSF leak and brain herniation noted at both 1 and 2 week intervals when compared to group 1. Histologic results confirmed the gross results demonstrating the best seal in group 2 and 3.
Acellular dermis combined with FTA provided superior support compared to acellular
dermis alone in repair of induced dural defects.
The dura mater is a structure necessary for protection and sterility of the central nervous system1. It may be disrupted due to a variety of processes including trauma, tumor removal and other surgical procedures. These tears can lead to cerebrospinal fluid (CSF) leakage, pneumocephalus, and meningitis2. Repair of the resultant tears often necessitates the use of a replacement tissue.
The repair of a dural tear is challenging due to several factors including dural shrinkage and damage to existing dura. Suture techniques may compromise existing dura due to trauma from tissue handling and needle penetration. Donor site morbidity must also be considered when harvesting autogenous tissues for dural repair. Furthermore, CSF leaks have a high rate of recurrence after standard repair3.
The search for the ideal dural substitute began more than one hundred years ago. The first attempted duraplasty was in 1892 by Beach, who successfully used gold foil to treat a cerebral cicatrix in a young girl2. Since that time, many materials have been used ranging from metals, plastics, xenoplastic membranes, alloplastic and homologous tissues. Complications associated with each include meningocerebral adhesions, Creutzfeldt-Jakob disease, aseptic lymphatic meningitis, and donor site morbidity. Autologous tissue has been safely used in the past with a high rate of efficacy. However, it is associated with separate incisions, donor site morbidities, and limited by the amount of tissue available.
Alloderm (LifeCell Corp, The Woodlands, TX) is an acellular dermal matrix produced from human cadaver skin. It is commonly used throughout the body for a wide range of resurfacing procedures, nasal septal repair, and full-thickness burns. Acellular dermis is available in a variety of sheets and sizes and must undergo rehydration prior to use. It is advantageous to autogenous material in that it is non-immunogenic material, lacks donor site harvest morbidity, and is readily available. Prior case series have demonstrated acellular dermis to be safe and effective in human dural replacement4.
Fibrin tissue adhesive (FTA) is a wound support product composed of fibrinogen and thrombin from human serum that has been used extensively for hemostatic and tissue fixation purposes. Eliminating the potential tearing of suture placement and providing support to tissue grafts, FTA is a completely resorbable alternative to prior fixation techniques.
The combined use of acellular dermis and FTA is a technique that deserves formal investigation. This combination of products removes the morbidity of suturing fascia together and eliminates creating holes in tenuous. Also, when donor tissue is scarce, acellular dermis may be a suitable alternative. Finally, FTA would potentially provide a watertight seal immediately, which may directly impact rates of infection and ultimately, recovery.
We hypothesize that the combined use of acellular dermis and FTA will create a superior reconstruction of dural defects compared to acellular dermis alone.
This study was approved by the University of Illinois Institutional Review Board and Animal Care Committee. 49 chinchillas were used in total and separated randomly into three experimental groups.
Initially, the chinchillas underwent mastoidectomy as follows: Anesthesia was achieved using ketamine (15mg/kg) and pentobarbital (25mg/kg). A right postauricular incision was made with a 15 blade and the soft tissues were elevated. The temporal bone was drilled to a circular defect with a 4 mm cutting burr. The underlying dura was then easily identified and a 2mm x 2mm defect was created using a Rosen needle. Care was made not to traumatize the underlying brain or surrounding tissues.
Once the standardized dural defect was created, it was repaired according to group assignment. Group 1: the dural defect was repaired with acellular dermis alone tucked under the bony defect and served as the control for this study. Group 2: the dural defect was repaired with by placing acellular dermis between the bony defect and dura followed by an outer layer of FTA. Group 3: the dural defect was repaired with an underlying layer of fibrinogen, then acellular dermis, followed by FTA placed on the outer surface. In all groups, the overlying soft tissue was closed with 3-0 nylon sutures. The animals were given daily doses of cefazolin postoperatively.
Under anesthesia, the repair site was examined for evidence of CSF leak, graft displacement, infection, and brain herniation. This was carried out under anesthesia at week one or week two. After gross examination, the animals were sacrificed and the temporal bones were examined histologically. Animals were chosen randomly for sacrifice at week one versus week two.
The temporal bones were embedded in paraffin, sectioned with a microtome, and stained with hematoxylin/eosin. The sections were examined for differences between groups in inflammatory cells and any microscopic differences.
A total of 49 chinchillas were used in this study; Group 1: 19, Group 2: 15, Group 3:
15. No animals developed complications unrelated to the experimental protocol and all animals lived to the study endpoints. No significant differences were seen between weeks one and two for any experimental group.
Group 1 (acellular dermis alone): 18 (95%) had CSF leaks, 18 (95%) had brain herniation, 6 (32%) had graft displacement, and 2 (11%) had gross infection.
Group 2 (acellular dermis and FTA): Only 1 (7%) animal had evidence of a CSF leak, and none had herniation, graft displacement, or infection present.
Group 3 (acellular dermis, fibrinogen and FTA): 15 animals. None of the animals had
CSF leak, graft displacement, or brain herniation at weeks 1 or 2.
There was no statistical difference between group II and group III. However, there was a statistically significant difference (CI > 95%) when comparing the proportion of CSF leak in the animals treated with acellular dermis alone (Group 1) versus those treated with acellular dermis and FTA (Group 2 and 3).
The histologic results agreed with the gross observations. There was no inflammatory reaction to either the acellular dermis or FTA noted. Acellular dermis and FTA were both well tolerated by host tissue. It was noted on the histologic samples that the combination of FTA and acellular dermis had a superior seal than acellular dermis alone as the gap between the periphery of the bone and the graft was lessened. No incidence of adhesion formation was noted in the treatment groups. The acellular dermis was present in its original form and had not been replaced by fibroblasts or neovascularization in all treatment groups at week 2. (figures 1-3)
Acellular dermis has been successfully used as a dural replacement for CSF leaks. The combination of acellular dermis and FTA offers several benefits to the surgeon. Firstly, it avoids the harvesting of additional tissue. Also, it avoids dural trauma from suturing. Additionally, there is a limitless supply of dural replacement. And finally, the fibrin tissue adhesive provides an early effective seal against CSF leak. This is important in providing a water tight seal as early as possible to reduce potential infection and speed patient recovery.
Previous studies have demonstrated the safety of acellular dermis as a dural replacement. Chaplin et al demonstrated in a mini pig model that acellular dermis was effective as dural replacement and was tolerated histologically. The xenoderm grafts were repopulated by fibroblasts with neovascularization at one month and remodeled to resemble the connective tissue of dura by 3 months5. Warren et al also demonstrated acellular dermis as an effective means for repair of the dura. In 200 patients, they demonstrated excellent results in repair of defects with easy handling and lack of adhesion formation noted between acellular dermis and brain3. However, in these studies a running suture technique was used to secure the dermal graft in place.
FTA has been applied successfully to the use of autogenous tissue grafts for the repair of dural defects6-9. Siedentrop et al studied the use of fibrin sealant in combination with a muscle graft to close induced CSF leaks using a chinchilla model. They demonstrated that at 3 weeks post-repair, the tegmen defect had been closed by bone, connective tissue or both. Furthermore, the meninges had regrown and the underlying brain appeared normal. There was no evidence of CSF leak, infection, or inflammation9.
The use of FTA as a method for securing acellular dermis in dural repair is a technique that has likely been used clinically, but has not been reported formally. Acellular dermis requires stabilization to prevent graft displacement and support to prevent brain herniation. We found that using FTA in combination with acellular dermis provided superior support over acellular dermis alone in repair of dural defects. There was no apparent benefit to first applying fibrinogen to the defect, followed by the graft and FTA (group 3) Our results were similar to that of Siedentrop at week 2, though the acellular dermis remained in it original state without vascular in-growth.
This study confirms that FTA in combination with acellular dermis provides a superior seal in the repair of dural defects compared with acellular dermis alone in a chinchilla model. FTA is a viable alternative to traditional techniques to secure dural grafts and should remain in the armamentarium of the skull base surgeon.
The combination of acellular dermis with fibrin tissue adhesive is superior to that of acellular dermis alone in the repair of induced dural defects in the chinchilla model. The use of these materials is both safe and effective.
- Beach HHA. Compound comminuted fracture of the skull: epilepsy for five years, operation, recovery. Boston Med Surg J. 1890; 122:313-15.
- Beach HHA. Gold foil in cerebral surgery. Boston Med Surg J. 1897; 136:281-82.
- Warren, WL, Medary MB, Dureza CD, Bellotte BJ, et al. Dural repair using acellular human dermis: experience with 200 cases: technique assessment. Neurosurgery. 2000; 46 (6):1391-96.
- Constantino PD, Wolpoe ME, Govindaraj S, Chaplin JM, et al. Human dural replacement with acellular dermis: clinical results and a review of the literature. Head & Neck. 2000; 22(8):765-71.
- Chaplin JM, Constantino PD, Wolpoe ME, et al. Use of an acellular dermal allograft for dural replacement: an experimental study. Neurosurgery. 1999; 45(2):320-33.
- Yoshimoto T, Sawamura Y, Houkin K, Abe H. Effectiveness of fibrin glue for preventing postoperative extradural fluid leakage. Neurol Med Chir (Tokyo). 1997; 37(12):886-90.
- Menovsky T, de Vries J, van den Bergh Weerman M, et al. Stability of fibrin sealant in cerebrospinal fluid: an in vitro study. Neurosurgery. 2002; 51(6):1453-5.
- Patel MR, Caruso PA, Yousuf N, Rachlin J. CT-guided percutaneous fibrin glue therapy of cerebrospinal fluid leaks in the spine after surgery. Am J Roentgenol. 2000; 175(2): 443-6.
- Siedentop KH, O’Grady K, Park JJ, Bhattacharya T, Sanchez B. Fibrin sealant for treatment of cerebrospinal fluid leaks. Am J Otol. 1999; 20(6):777-80.
- Citardi MJ, Cox AJ, Bucholz RD. Acellular dermal graft for sellar reconstruction after transphenoidal hypophysectomy. Am J Rhinol. 2000; 14(1):69-73.
Figure 1: Group 1 (acellular dermis only) at week one. Note the large gap between the acellular dermis (AD) and the temporal bone (T). (B) Brain.
Figure 2: Group 2 (FTA and acellular dermis) at week two. Acellular dermis (AD) well positioned deep to the temporal bone (T) and dura mater (DM). No adhesions are present between AD and the brain (B).
Figure 3: Group 3 (Fibrinogen, FTA, acellular dermis) at week two. Acellular dermis (AD) present in original form without fibroblast invasion or neovascularization. (T) temporal bone, (DM) dura mater, (B) brain.