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BioGlue

® Surgical Adhesive as a Dural Sealant in Neurosurgery

Clinical Needs and Surgical Technique

Massimo Miscusi, MD, PhD Assistant Professor of Neurosurgery, Sapienza University of Rome, Rome, Italy

1655 Roberts Boulevard, NW • Georgia 30144 • USA • Tel: 770 419 3355 • 800 438 8285 • Fax: 770 590 3753 • www.cryolife.com

- For International Distribution Only -

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1.0 Introduction

Cerebrospinal fluid (CSF) leakage represents a major cause of morbidity in neurosurgery,

exposing patients to infective complications such as meningitis or encephalitis,

intracranial hypotension, or pseudomeningocele with deep or subcutaneous collections of

the same.1 CSF leaks have been associated with approximately a 10% risk of developing

meningitis per year.2 In cranial surgery, skull base approaches carry the largest risk of

CSF leaks.3 Surgery for removal of vestibular schwannoma has been reported to result in

CSF leaks of up to 30%.4 CSF leakage is also a significant clinical concern in spine

surgery, with incidental durotomy being the most frequent causal complication.5 The

reported incidence of CSF leakage in spine surgery is 0.8% to 17%.6,7

Based on aetiology, CSF leakage can be classified as being spontaneous, post-traumatic

or iatrogenic. Spontaneous CSF leakage can be due to hydrocephalus and conditions

resulting in intracranial hypertension, e.g. tumours involving the meninges. Traumatic

CSF leakage can result from both penetrative and non-penetrative head and spine injuries

involving dural lacerations. Iatrogenic CSF leakage is caused by a surgical manoeuvre

and can be a result of directly inflicted damage or an ineffective duroplasty.

Direct damage to the dura is often due to the difficulty of dissecting through fibrotic

tissue, as typified in the aftermath of radiation therapy or a reoperation at a previous

operative site. In such cases, CSF leakage is generally recognised and a repair is

attempted during the surgical procedure.

Ineffective duroplasty can be secondary to sub-optimal surgical technique such as

incomplete suture, ineffective surgical tools, or certain predisposing anatomical factors.

For example, friable dura or the presence of abnormal dural bulging, such as in the

posterior fossa after craniectomy, are factors that increase the risk of ineffective dural

repair. In these cases, the CSF leakage is recognised in the post-operative period as an

external CSF fistula or a subcutaneous collection of CSF.

Duroplasty, when associated with extended craniectomies or laminectomies and atrophy

of subcutaneous tissues, presents with a consistently high risk of CSF leakage, even when

watertight dural closure is achieved intra-operatively. Moreover, CSF leakage is

particularly difficult to treat in posterior fossa surgery or transsphenoidal surgery where

anatomical features make effective duroplasty technically more difficult.

A sealant with the ideal performance properties, whilst not a substitute for optimal

surgical technique, can often help the surgeon overcome the surgical and anatomical risk

factors for CSF leakage and can be an important part of the armamentarium available in

effecting successful duroplasty.

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2.0 Challenging Indications for Effective Duroplasty

Any procedure that requires a dural opening implies a direct challenge to good surgical

repair of the dura. A sealant, where required, in combination with suitable patch

material, can play a vital part in the surgical repair.

The following are indications where dural repair is likely to be more challenging:

• Reoperations both in cranial and spinal surgery

• Extended removal of the dura for the treatment of meningioma

• Traumatic lacerations of the dura adjacent to the cranial base or anterior spine

• Repair of the skull base dura in transsphenoidal surgery

• Posterior fossa craniectomy

In these instances, even when watertight dural closure is apparently achieved by more

traditional means, the risk of post-operative complications of CSF leakage remains

elevated.

In reoperations, the scarring and fibrosis of cranial and spinal dura exposes patients to a

greater risk of iatrogenic injuries and can make duroplasty technically more difficult.

Frequently, the dura loses its physiological elasticity and robustness with deleterious

consequences for effective suturing and resisting the effects of mechanical stresses and

CSF pulses.

The removal of meningiomas from their dural attachments is essential in achieving

complete resection. As dura mater is lost, repair involves the use of patches that are

sutured in place with the native dura. The larger the patch, the more difficult it is to

avoid any CSF leakage due to the increased complexity of effecting watertight repair

over a larger irregular surface area.

Post-traumatic dural lacerations are often technically hard to treat because the dural tear

can be difficult to access, identify, and suture or patch, especially when involving the

base of the skull or anterior aspect of the spinal dura.8

The conventional or extended transsphenoidal route allows access to the intracranial

compartment adjacent to the skull base by opening the bone and dural floor.9 For

example, access to the hypophisis by the transsphenoidal route requires the opening of

the dural sellar floor. At the end of the surgical procedure, especially when the

subarachnoid cisterns have been opened, it is important to achieve perfect reconstruction

of the dural floor to avoid post-operative CSF leakage through the nose and/or throat. In

these circumstances, duroplasty can be technically difficult because of the narrowness of

the surgical corridor and visual field. Moreover, suturing is not possible at the site and

duroplasty is performed only by fat or muscle packing and/or by homologous and

heterologous dural substitute with the help of dural sealants.10

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In surgery where access is via the posterior fossa, the risk of CSF leakage is higher in

craniectomies compared to craniotomies because of the effect of post-operative CSF

pulses. CSF pulses can compromise the integrity of dural sutures if they are not

supported by the presence of bone.11

For this reason, tight and painful bandages are often

applied around the posterior suboccipital region in order to enhance this buttressing

effect.

3.0 Desired Characteristics of the Ideal Sealant for Effective Duroplasty

Good surgical and suturing technique is a prerequisite for effective duroplasty. However,

the challenges described in the previous section allow us to describe the technical

characteristics of a sealant that best complement standard surgical repair. They are as

follows:

• Provides a watertight seal for the surgical suture line

• Reinforces friable dura and adds strength to suture lines providing adequate

robustness to the dura-dura or dura-patch interface to reduce dural bulging due

to CSF pulses

• Helps prevent dural patch migration, if used

• Provides a watertight seal between the native dura and patch material when

suturing is difficult or not possible

• Requires only a thin layer be applied, minimizing potential for compression-

related risk factors

In our experience, BioGlue® Surgical Adhesive (CryoLife,

® Inc., Kennesaw, GA, USA)

possesses all of the above characteristics and has proved useful in the challenging

indications.

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4.0 Surgical Experience with BioGlue

4.1 Repair of Pseudomeningocele

A 53-year-old male was admitted with a recurrent epidermoid tumour in the posterior

fossa (Figure 1). The patient underwent a suboccipital craniectomy and a partial removal

of the tumour 28 years earlier.

Figure 1. MRI Scans Showing Recurrent Epidermoid Tumour.

The patient was reoperated via a suboccipital median approach. On opening, the dura was

found to be extensively scarred and fibrotic. The recurrent tumour, shown in figure 2

immediately below, was then gross-totally removed. At this stage, duroplasty did not

involve the use of BioGlue.

Fibrotic dural edges

Recurrent epidermoid tumour

Figure 2. Appearance of the Recurrent Epidermoid after Dural Opening on Reoperation.

In the early post-operative period, in spite of meticulous banding, he presented with a

large pseudomeningocele at the surgical site and a subcutaneous collection of CSF

(Figure 3).

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Figure 3. Appearance of the Pseudomeningocele in the Early Post-operative Period.

Repair was effected via the same suboccipital approach. The previous sutures had

disintegrated. Duroplasty was re-effected by placement of a xenograft pericardial patch

over the dural breach. The patch was sutured to the dural margin using 2-0 silk. BioGlue

was then applied as a thin layer over the suture line connecting the patch to the dura. The

muscles, subcutaneous tissue, and skin were then sutured as normal. Neither

subcutaneous drainage nor banding was used (Figure 4).

Figure 4. Post Repair Appearance of the Pseuodomeningocele.

There was no recurrence of the pseudomeningocele. The patient went on to develop a

further recurrence of the tumour 3 years later and died after refusing further surgery.

4.2 Repair of Incidental Lumbar Durotomy

A 40-year-old female who underwent L4/L5 discectomy, presented with recurrent

symptoms of L5 radiculopathy approximately 1 year later. A reherniation was diagnosed.

The patient was reoperated via the same interlaminar L4-L5 approach.

In dissecting the scarred dura covering the L5 root to access the herniated fragment, an

incidental durotomy occurred and intra-operative CSF leakage was observed. With

further sharp dissection, the source of the leak was identified as a durotomy

approximately 2-3 mm in length on the posterolateral aspect of the dural sac.

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A small xenograft pericardial patch, approximately 2 cm in length, was adhered to the

dura using a few drops of BioGlue.

After the discectomy, a Valsalva manoeuvre was performed 3 times before closing to

assess the robustness of the repair. The patient was mobilised on the first post-operative

day. This was a departure from our standard protocol that requires patients to be non-

weight bearing for 3 days post surgery in the event of an incidental durotomy of this

nature. There was no sign of any external CSF leakage or subcutaneous collection. The

post-operative MRI scan showed neither a pseudomeningocele nor compression of the

dural sac or nerve root.

4.3 Cranialisation of Frontal Sinus

A 31-year-old woman presented with fever, slight hemiparesis, and continuous seizures

one week after parturition. A MRI scan revealed a left subdural empyema (Figure 5a).

The CT scan showed a fracture of the posterior wall of the frontal sinus at the

supraorbital ridge (Figure 5b). It was hypothesised that spontaneous Valsalva

manoeuvres related to parturition may have provoked a spontaneous fracture of the thin

layer of bone of the frontal sinus walls resulting in laceration of the dura in apposition to

the fracture line (Figure 5b).

Figure 5a. Left Subdural Empyema. Figure 5b. Fracture of the Posterior Wall

of the Frontal Sinus.

The patient was operated on for the evacuation of empyema by a left coronal burr-hole.

After prolonged antibiotic therapy (4 weeks) and the resolution of symptoms, the patient

was reoperated to treat the communication between the frontal sinus and the intracranial

compartment.

After a skin incision along the coronal suture line bilaterally, a frontal left craniotomy

was performed and the left frontal sinus exposed. An intact median bone septum divided

the left and the right frontal sinus. The right frontal sinus was not violated. An evident

fracture of the posterior wall of the left frontal sinus, which appeared very thin, was

demonstrated. On inspection of the dura in contact with the fracture, a small laceration

was identified. The mucosal layer of the frontal sinus was completely removed, and the

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inferior portion of the sinus was closed off by use of a muscle patch to allow its complete

cranialisation. A layer of BioGlue was used to adhere and seal the edges of the muscle

patch and to hold it in place. A xenograft pericardial patch was then applied to the area

of the lacerated dura and was adhered at the periphery using a thin layer of BioGlue

without the use of sutures.

At one month follow-up, the patient had signs of neither infection nor neurological

impairment (Figure 6). A CT scan revealed good results of surgical cranialisation of the

left frontal sinus.

Figure 6. CT Scan Showing Cranialisation of the Left Frontal

Sinus 1-Month Post Surgery.

5.0 Technique Related Considerations for Avoiding CSF Leakage and Infection for

BioGlue Use

All surgery involving the implantation of extraneous materials carry a finite risk of

infection. However, BioGlue has been used safely and effectively for effecting

duroplasty for many years. Kumar et al.1 had a CSF leakage rate of 0.98% (2 patients)

with the use of BioGlue in a 210 patient series. Both of these patients underwent

posterior fossa surgery. Kelly et al.12

demonstrated a reduction in severe CSF leaks

(from 17.9% to 6.7%) and in overall CSF leaks (from 4% to 1.2%) in a comparative

study involving 620 patients who underwent cranial surgery via the transsphenoidal

route.

Presented below are the details of techniques employed at our institution with regards to

obtaining optimal results when using BioGlue to avoid CSF leakage and infection.

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5.1 Skin Preparation and Initial Considerations

Thirty minutes prior to being moved to theatre, 2 g Cefotaxime is administered

intravenously for prophylaxis against potential infections caused by Gram + bacteria,

such as Staphylococcus aureus or Staphylococcus epidermidis (intra-operatively, 2 g / 4

hours; post-operatively, 2 g / 8 hours for 48 hours). Other antibiotics against the same

spectrum of flora may be used as per the Institution’s infection control programme. The

patient’s hair is shaved to a width of just 1.5 cm on either side of the planned incision in

order to minimise any trauma to the skin. The latter is of paramount importance in

preventing infections. The skin is then washed with soap and water.

In theatre, the skin is again washed with soap and water and dried. After positioning of

the patient, the incision site is wiped with Betadine® (Purdue Pharma L.P., Stamford, CT,

USA) three times and dried with sterile swabs. The incision site is then dressed using

transparent sterile antibiotic drapes.

5.2 From Skin Incision to Dural Opening

The skin incision is made with a very thin scalpel. No cautery is used on the skin or sub-

cutaneous tissue to prevent necrosis and reduce the risk of skin infection. Local

anaesthetic mixed with adrenalin (1 part in 1000) is subcutaneously injected along the

incision line to cause vasoconstriction and prevent bleeding. Despite this, diffuse

bleeding from subcutaneous tissue is sometimes a problem and may be overcome by

mechanical means of haemostasis, such as Raney clips.

Muscle detachment or retraction should be performed without resorting to cautery

techniques. Internally, only bipolar cautery techniques (low temperature and fine tips)

are used in order to minimise any necrosis of tissues.

For spine surgery, the use of muscle relaxants can help the surgeon minimise damage to

the large muscles during retraction.

5.3 Dural Opening

Once the craniotomy/craniectomy or laminotomy/laminectomy has been performed, the

dura can then be opened and the flap(s) reflected back. Wet swabs should be placed over

the reflected dura to minimise any dehydration. Wet swabs are also positioned all around

the dural opening to isolate the sections of the surgical field not involved with the

procedure. All major meningeal vessels should be clipped. All other forms of

coagulation should be avoided with regards to the smaller meningeal vessels.

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5.4 Dural Closure

The dura flap(s) are reversed. Clipped edges of the vessels can be used to appose the

dural edges. Bipolar cautery may be sparingly used to effect coagulation at this stage.

The dura is then closed using 2-0 or 3-0 silk interrupted or continuous sutures placed one

cm apart along the length of the incision. Just prior to the last stitch being placed, sterile

water should be injected into the subdural space to remove any air that might otherwise

be trapped and to assess that subdural haemostasis has been achieved.

BioGlue, from a 2 ml syringe, is then applied directly over the previously dried suture

line as a thin layer, not extending more than 1-2 mm beyond the margins of the suture

line itself.

During the surgical procedure, the dura may have retracted or may not be adequate to

achieve closure mandating the use of a patch. The patch needs to be cut to the shape of

the void in the dura or to allow for the absence of dura mater as in the removal of a

meningioma. The edges of the patch should be approximated to the cut edge of the

native dura. Where necessary, a larger patch volume may be warranted to accommodate

cerebral oedema. However, the apposition of the patch and dural edges needs to be

exacting. Silk sutures (2-0 or 3-0) should be used to suspend the native dura below the

edge of the craniotomy to prevent the risk of epidural bleeding. Where a patch is used to

achieve dural closure, a thin layer of BioGlue should be applied over the suture line, as

previously described.

Recently, dural patches not requiring suture have been introduced with some success.

Nevertheless, in our opinion, such patches are not as effective in cases where there is a

high risk of CSF leakage. At our institution, there is currently no experience to

recommend that BioGlue can be used effectively with such patches.

5.4.1 Special Considerations for Incidental Durotomy in Spine Surgery

Incidental durotomies are more likely when the dura is friable and fibrotic, e.g. as in

degenerative disease, re-operation or prior radiation. It is important to delineate any scar

tissue and identify the source of the CSF leak on viable dura. This is best done by

approaching the approximate source of the leak in centripetal fashion and dissecting away

any fibrous material.

Whether or not to use a patch and whether or not to use sutures (4-0 or 5-0 silk) depends

on the location and extent of the durotomy. A durotomy located in a nerve axilla or

anteriorly in the canal could prove difficult to suture. It is perhaps best repaired using a

small patch (approx 0.5 cm x 1 - 2 cm) and being adhered into place using BioGlue.

The quantity of BioGlue to be used can be very critical to the outcome. Only a thin layer

of BioGlue should be applied. For the size of patch described earlier, a few drops of

BioGlue would be adequate. Larger amounts could cause nerve compression simply due

to the pressure exerted by a larger mass in the confined space of the spinal canal.

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5.4.2 Special Considerations on Closure of Air Sinuses and Air Cells

BioGlue is currently indicated for use as a dural sealant, and not as a packing agent to

seal CSF leaks or as an air sinus/cell sealant. Its use for the closure of air sinuses and air

cells requires special consideration, including an understanding of the product’s hydrogel

properties, properties of adjunct materials utilised, and the local anatomy.

Some neurosurgical procedures, e.g. removal of an acoustic neuroma via the middle or

posterior fossa or removal of a pituitary adenoma via the transsphenoidal route, may

expose air cells or air sinuses. The temporal air cells are part of the mastoid region, and

communicate with atmosphere via the middle ear and the Eustachian tube, and are thus

exposed to air and colonised by bacteria. Frontal and sphenoid air sinuses are directly

connected to the rhinopharynx, and are thus similarly exposed to air and open to bacterial

colonisation.

When opened during a neurosurgical procedure, the sinuses or air cells should be

perfectly sealed to avoid CSF leak and contamination of the intracranial compartment by

resident bacteria. BioGlue can be used as part of the modalities to isolate a sinus from

the intracranial compartment or for covering these air cells, but special care is needed.

Filling these cells with non-homologous materials may trap bacteria and cause a focus for

bacterial proliferation and infection. The communication between the sinuses or air cells

and the intracranial compartment should be closed using homologous materials such as

pericranial fascia or fat and not directly sealed with BioGlue. Such materials can be

adhered to the bony margins using a thin layer of BioGlue. BioGlue itself is inherently

bacteriostatic.13

It is worth stressing that BioGlue is a hydrogel. If used to seal the air cells directly,

BioGlue would also desiccate due to exposure to air and compromise the seal. However,

that may not be clinically significant in the longer term as the scar tissue generated would

effectively form a seal.

5.5 Muscle and Skin Closure

After repositioning of the bone flap (craniotomy), or post dural closure in the event of

craniectomy, the cranial muscles should be appositioned and the fascia sutured firmly

using strong resorbable monofilament sutures. In spinal procedures, 2 - 3 stitches may be

required to apposition the paravertebral muscle mass prior to suturing the fascia.

On removal of Raney clips and surgical drapes, some diffuse bleeding may yet be present

from subcutaneous tissue. Once the exposed skin is again prepped with Betadine,

mechanical haemostasis can be achieved by means of subcutaneous sutures rather than

any cautery means to preserve the vascularisation to the injured skin and subcutaneous

tissue.

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Skin should be closed using rapidly resorbing monofilament sutures. Silk sutures should

not be used in order to reduce the risk of skin infection and to avoid suture removal with

recontamination of the surgical wound. Especially for spinal surgery, a continuous

intradermic suture can be used for aesthetic purposes. If a drain has been placed it should

be connected to the suction only after skin closure to avoid skin flora contaminating

tissues deep to the incision.

Once the skin has been closed, the area should be prepped again with Betadine or

hydrogen peroxide prior to application of sterile dressing. Excessive compression or

banding should be avoided to preserve the vascularisation of the skin.

6.0 Conclusion

CSF leakage represents a major cause of morbidity in neurosurgery, exposing patients to

infective complications. Even if watertight dural closure is achieved, the risk of post-

operative leakage remains especially high in some challenging indications.

In such indications, heterologous materials such as sealants and patches are valuable

adjuncts to achieving dural closure and preventing CSF leakage. In theory, due to their

extraneous nature, the use of such materials exposes patients to higher levels of infection

risk even when optimal surgical techniques are used.

To reduce the risks, and realise the benefits of BioGlue, meticulous attention to the

surgical and patient management protocols are a necessity. Used as prescribed, BioGlue

Surgical Adhesive, due to its unique characteristics, can be a very useful aid to effective

duroplasty, especially in some challenging indications.

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References

1 Kumar A, Maartens NF, Kaye AH. Evaluation of the use of BioGlue

in neurosurgical

procedures.

J Clin Neurosci 2003 Nov;10(6):661-4

2 Editorial. BMJ 2001;322:122-123

3 Leonetti JP, Anderson D, Marzo S, Moynihan G. Prevention and management of cerebrospinal

fluid fistula after transtemporal skull base surgery.

Skull Base 2001 May;11(2):87-92

4 Fishman AJ, Marrinan MS, Golfinos JG, Cohen NL, Roland JT Jr. Prevention and management

of cerebrospinal fluid leak following vestibular schwannoma surgery.

Laryngoscope 2004 Mar;114(3):501-5

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Bosacco SJ, Gardner MJ, Guille JT. Evaluation and treatment of dural tears in lumbar spine

surgery: a review.

Clin Orthop Relat Res 2001 Aug;(389):238-47

6 Tafazal SI, Sell PJ. Incidental durotomoy in lumbar spine surgery: incidence and management.

Eur Spine J 2005;14:287-290

7 Awad JN, Moskovich R. Lumbar disc herniations.

Clin Ortho Rel Res 2006;443:183-197

8 Friedman JA, Ebersold MJ, Quast LM. Persistent post-traumatic cerebrospinal fluid leakage.

Neurosurg Focus 2000 Jul 15;9(1):e1

9 Cappabianca P, Cavallo LM, Esposito F, De Divitiis O, Messina A, De Divitiis E. Extended

endoscopic endonasal approach to the midline skull base: the evolving role of transsphenoidal

surgery.

Adv Tech Stand Neurosurg 2008;33:151-99

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Dusick JR, Mattozo CA, Esposito F, Kelly DF. BioGlue for prevention of post-operative

cerebrospinal fluid leaks in transsphenoidal surgery: a case series.

Surg Neurol 2006 Oct;66(4):371-6; discussion 376

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Gnanalingam KK et al. Surgical procedures for posterior fossa tumors in children: Does

craniotomy lead to fewer complications than craniectomy?

J. Neurosurgery 2002 Oct;97(4):821-6

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Esposito F, Duisick JR, Fatemi N, Kelly DF. Graded repair of cranial base defects and

cerebrospinal fluid leaks in transsphenoidal surgery.

Neurosurgery 2007 Apr;60(4 Suppl 2):295-303

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CryoLife, Inc. Data on File

ML0265.001 (10/2008)