1 BioGlue Surgical Adhesive as a Dural Sealant in

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
- For International Distribution Only -
1655 Roberts Boulevard, NW • Georgia 30144 • USA • Tel: 770 419 3355 • 800 438 8285 • Fax: 770 590 3753 • www.cryolife.com
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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:
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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:
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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 compressionrelated 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 nonweight 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 subcutaneous 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 postoperative 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
5
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
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surgery.
Adv Tech Stand Neurosurg 2008;33:151-99
10
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
11
Gnanalingam KK et al. Surgical procedures for posterior fossa tumors in children: Does
craniotomy lead to fewer complications than craniectomy?
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12
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
13
CryoLife, Inc. Data on File
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ML0265.001 (10/2008)