Topical Hemostatic Agents in Neurosurgery 2011

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Moderator : Dr P.S.

Chandra
Dr Deepak Gupta
Hemostasis in neurosurgery
 One of the most important aspects of surgery.
 Control of bleeding without ligature unlike in
abdominal and other surgeries ligatures and packs
rarely useful.
 Many hours lost in bleeding control
Topical hemostats
 Agents that help in controlling bleeding.
 Ideal topical hemostat:
Ø safety,
Ø efficacy,
Ø usability,
Ø cost, and
Ø Approvability
Sources of bleeding
 Scalp/muscles
 Bone
 Dura and sinuses
 Brain: capillary/venous/arterial
Muscle
 1st used by Sir Harvey Cushing
 Mechanism : mechanical plus as a source of tissue
thromboplastin.
Cotton Balls and Cotton Patties
 Mainly mechanical by applying gentle pressure.
Gelatin sponge ( Gelfoam )
 Introduced in the 1940s for neurosurgical procedures.
 Derived from purified pork skin gelatin.
 Mechanical barriers to bleeding by forming a matrix.
 Absorbs approximately 45 times its weight in blood and can
expand to approximately 200% of its initial volume.
 Not to be used in combination with blood salvage
equipments as their fibres can pass through the 40 mm
filters of salvage systems.
 Can be used dry or saline soaked, better when excess saline
is removed as compare to supersaturated.
Microfibrillar collagen (Avitene)
 Collagen which is derived from bovine skin binds tightly to
blood surfaces.
 Causes minimal swelling especially when compared to
Gelfoam .
 serving as a matrix for clot formation and enhancing
platelet aggregation, degranulation, and release of
clotting factors which then combine with plasma factors
to produce fibrin clot
 May reduce the number of free platelets in normal
individuals .
 Loses effectiveness in thrombocytopenia(<10,000).
 It is absorbed in 3 months and needs to be applied dry.
Oxidised regenerated cellulose (Surgicel)
 Introduced in 1940s.
 Surgicel (Ethicon) is an oxidized cellulose polymer
(the functional unit is poly anhydroglucuronic acid)
formed by dissolving pure α-cellulose (plant derived)
in an alkaline solution.
 It is then regenerated into continuous fiber, knitted
into gauze, and oxidized.
 Applied dry, absorbs within 4 to 8 weeks.
 Forms a brownish or black gelatinous mass in contact
with blood.
 Acts as a physical matrix to which platelets can adhere
which, in turn, aids in clot formation
 Additional pressure of the mass also contributes to the
haemostatic process.
 They create an acidic environment and are bactericidal.
 Cellulosic acid facilitates hemostasis by denaturing blood
proteins.
 Needs to be applied dry.
 They can be best removed by gentle irrigation with saline.
 Oxycel (Becton Dickinson) is another oxidized
cellulose polymer product that is similar.
 Surgicel is composed of solid fibers with irregular
contours on cross-section, whereas Oxycel is
composed of hollow “twisted tubule” fibers.
SURGICEL Fibrillar
 Oxidized regenerated cellulose(1969)
 Layers can be peeled off in desired amounts.
 conforms to irregular surfaces, even hard-to-reach
areas
 surgical visualisation is improved by ability to
cauterise directly through it
 fully absorbed within 14 days
 Oxidised regenerated cellulose as a cause of
paraplegia after thoracotomy: case report and
review of the literature.Spinal Cord. 2005
Jul;43(7):445-7.
 Rapid closure technique in decompressive craniectomy. Güresir
E, Vatter H, Schuss P, Oszvald A, Raabe A, Seifert V, Beck J. J
Neurosurg. 2011 Apr;114(4):954-60. Epub 2010 Jan 29. Total of
314 patients. The surgical time is significantly shorter
without increased complication rates or additional
complications. Cranioplasty after a RCDC procedure
was also feasible, fast, safe and not impaired by the
RCDC technique.
Active
Thrombin
 Thrombin is marketed as bovine (Thrombin-JMI, King
Pharmaceuticals, Bristol, TN), human pooled plasma
(Evithrom, J&J), and recombinant (Recothrom,
Zymogenetics, Seattle, WA).
 Thrombin directly activates fibrinogen and converts it into
fibrin monomers.
 Can be used directly or combined with gelatin sponge
 Bovine thrombin is antigenic.
 If injected into large vessels can lead to thrombosis and
complications.
 The three commercially available thrombins are functionally
equivalent in terms of efficacy with 95 percent or greater of
patients achieving hemostasis within 10 minutes of application
and approximately two-thirds of patients achieving hemostasis
within 3 minutes. Chapman WC, Singla N, Genyk Y, McNeil JW,
Renkens KL Jr, Reynolds TC, Murphy A, Weaver FA. A phase 3,
randomized, double-blind comparative study of the efficacy and
safety of topical recombinant human thrombin and bovine
thrombin in surgical hemostasis. J Am Coll Surg 2007;205: 256-65
 The human antibodies to bovine FII and FV have been
linked to coagulopathy and potentially fatal
complications.
(Sarfati MR , Dilorenzo DJ, Kraiss LW, Galt SW. Severe coagulopathy following
Intraoperative use of topical thrombin. Ann Vasc Surg 2004;18:349-51.)
Complications
 Nidus of infection
 Inflammatory reaction (esp. avitene)
 Antigenicity (animal products)
 Mass effect (esp. gelatin)
 Gossipiboma
Bone wax
 Pioneered by Sir Victor Horsley(1892).Horsley’s wax:
bees wax, 7 parts; almond oil, 1 part; salicylic acid, 1
part.
 Modern wax: 88% refined beeswax and 12% isopropyl
palmitate (softening agent).
 Effective in controlling bleeding from bone
 Once smeared across the bleeding edge, immediate
hemostasis occurs.
Complications
 Bone wax inhibits osteogenesis.
 Increases infection rates (the number of bacteria
needed to produce osteomyelitis is reduced by a factor
of 10,000).
 Remains as a foreign body for many years.
Ostene
 Sterile mixture of water-soluble alkylene oxide
copolymers.
 Inert artificial material feels and works like wax.
 Does not increase infection rates, does not interfere
with bone healing, and is non-inflammatory.
Flowables
 Human plasma thrombin with bovine gelatin matrix.
(Floseal, Baxter, Fremont, CA)
 Create a granular hemostat that employs both active
and mechanical components to achieve hemostasis.
 It is applied as a paste to which it is recommended that
gentle pressure be applied with a moist saline sponge
for 2 minutes to achieve hemostasis.
 Hemostatic matrix sealant in neurosurgery: a clinical and
imaging study. Roberto Gazzeri & Marcelo Galarza &
Massimiliano Neroni & Alex Alfieri & Marco Giordano. Acta
Neurochir (2011) 153:148–155. Effective hemostasis, defined as cessation of
bleeding, was achieved no later than 3 min after topical agent application in all
patients except in 11 cases out of 214 cases it was used.
 The role of FloSeal in reducing epidural fibrosis in a rat
laminectomy model.. Dogulu F, Durdag E, Cemil B, Kurt
G, Ozgun G Neurol Neurochir Pol. 2009 Jul-Aug;43(4):346-51.
Application of FloSeal at a laminectomy site may be useful
to decrease adhesion at the interface between the dura
mater and epidural fibrosis.
 A study in cardiac, vascular, and spinal or orthopedic
patients designed to show equivalence between bovine
thrombin gelatin matrix and bovine thrombin with
porcine gelatin sponge demonstrated statistically significant (p <
0.001) superiority of the flowable matrix product for percent of
patients with hemostasis at 10 minutes, 96 percent (149/156)
versus 77 percent (118/153). Package Insert. Floseal, Baxter.
2005.
Fibrin sealent
 Human plasma derived fibrin sealent
 Fibrin glue(Tisseel/evicel)
 Commercially available/autologous.
 2 components:
 a)fibrinogen, factor13, fibronectin, aprotinin,
plasminogen, cryoprecipitate
 b)thrombin and calcium
 After mixing, fibrinogen is converted to fibrin
 Aprotinin inhibits premature fibrin degradation
 Supply a source of fibrinogen to the site of injury and
do not need active bleeding or blood-derived
fibrinogen to polymerize.
Use
 For hemostasis and tissue sealing
 To reinforce dural closure and prevent CSF leak.
 In anastomosis of nerves and nerve grafts
(Micro neural anastomosis with fibrin glue : an experimental study. Suri A,
Mehta VS, Sarkar C .Neurology India.2002)
 Fixation of bone fragments to repair skull defects.
Hydrogen peroxide
 3% solution is used in neurosurgery
 Use is very controversial
 Mechanism : mechanical obstruction of the
microvasculature, mechanical removal of tissue debris,
and vasoconstriction. Exact mechanism is not known.
 Primarily used to achieve hemostasis after complete
tumor removal of the surrounding arachnoidal
surface of the brain.
 Recent evidence suggest significant tissue damage in
surrounding functional brain.
 INTRATUMORAL HYDROGEN PEROXIDE INJECTION
DURING MENINGIOMA RESECTION. Roger Lichtenbaum,
M.D. Neurosurgery 59[ONS Suppl 4.]:ONS-470–ONS-473, 2006.
 Hydrogen peroxide–induced stroke: elucidation of the mechanism
in vivo. Melike Mut, M.D., Ph.D J Neurosurg 110:94–100, 2009
 Comparative safety and efficacy of topical hemostatic agents in a
rat neurosurgical model Neurosurgery. 2008 Oct;63(4 Suppl
2):369-72.
 Avitene, FloSeal, and Surgicel performed better (defined as
complete hemostasis within 1 minute) than control (no
treatment). Residual material was not present at any time
with Arista, markedly contrasting with the presence of
residual material in 100% of lesions in the Avitene, FloSeal,
and Surgicel groups on Day 14. Avitene and FloSeal also
demonstrated a propensity for causing granuloma
formation, whereas Arista and Surgicel showed no such
evidence
 The use of local agents: Surgicel and Surgifoam.
Eur Spine J (2004) 13 (Suppl. 1) : S97–S10.
 The use of absorbable porcine gelatine and regenerated, oxidised
cellulose as haemostats in intraspinal surgery must be
considered safe and beneficial. However, the appropriate use of
haemostats requires a certain understanding of their advantages,
limitations and the nature of complications associated with their
application
Conclusion
 Proper surgical principle remains the key.
 Judicious use of hemosatic agents is advised.

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