Historical Vignette
History of Hemostasis in Neurosurgery
Danika Paulo1, Alexa Semonche1, Osamah Choudhry2, Fawaz Al-Mufti3, Charles J. Prestigiacomo4,
Sudipta Roychowdhury5, Anil Nanda1, Gaurav Gupta1
Key words
- Hemostasis
- Historical vignette
- Literature review
- Neurosurgery
Abbreviations and Acronyms
MRI: Magnetic resonance imaging
From the 1Rutgers Robert Wood Johnson Medical School,
Department of Neurosurgery, New Brunswick, New Jersey,
USA; 2New York University, Department of Neurological
Surgery, New York, New York, USA; 3University Hospital,
Department of Neurology, Newark, New Jersey, USA;
4
Rutgers New Jersey Medical School, Department of
Neurosurgery, Newark, New Jersey, USA; and 5Robert Wood
Johnson University Hospital, Department of Radiology, New
Brunswick, New Jersey, USA
To whom correspondence should be addressed:
Gaurav Gupta, M.D.
[E-mail: guptaga@rwjms.rutgers.edu]
Citation: World Neurosurg. (2019) 124:237-250.
https://doi.org/10.1016/j.wneu.2018.12.015
Journal homepage: www.journals.elsevier.com/world-
neurosurgery
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª 2018 Elsevier Inc. All
rights reserved.
INTRODUCTION
Bleeding in the cranial cavity poses chal-
lenges unique to the field of neurosurgery.
Neurosurgeons of the late 19th century used
poorly adapted general surgical instruments,
which were coarse tools from the pre-
antiseptic era.1 Eventually, instruments
capable of intracranial hemostasis were
developed. Understanding this history is
important for future improvement and
innovation. Here we review the evolutionary
steps in neurosurgical hemostasis, which
helped to bring the field through its difficult
infancy. The different methods of obtaining
hemostasis are grouped into 3 categories:
mechanical, chemical, and thermal.
PART I: MECHANICAL METHODS
Controlling Hemorrhage and Shock
Hemorrhage and resultant shock were
common in early neurosurgical operations.
In the late 1800s, special attention was
WORLD NEUROSURGERY 124: 237-250, APRIL 2019
Control of bleeding in the confined area of the skull is imperative for successful
neurosurgery and the prevention of devastating complications such as post-
operative hemorrhage. This paper reviews the historical evolution of methods to
achieve successful hemostasis in neurosurgery from the early 1800s to today.
The major categories of hemostatic agents (mechanical, chemical, and thermal)
are delineated and discussed in chronologic order. The significance of this
article is in its detailed history of the kinds of hemostatic methods that have
evolved with our accumulating medical and surgical knowledge, which may
inform future innovations and improvements.
directed to the position of the patient’s head pressure on the veins, exacerbating venous
and body to decrease bleeding.2 The hemorrhage.7 Harvey Cushing (1869
1939),
German neurosurgeon Fedor Krause the father of modern neurosurgery, devised
(1857
1937)3 and Sir Victor Haden Horsley an inflatable tourniquet in 1904 but
(1857
1916), the founder of modern discarded its use in favor of a simple rubber
British neurosurgery,4 observed that ring with an adjustable buckle.8 In 1914,
bleeding was more profuse in the supine Landon created a metallic tourniquet made
position, which was favored at that time. of flexible steel.9
They recommended elevation of the head George Crile also controlled scalp hem-
in order to decrease cephalic venous orrhage by temporarily clamping the bilat-
pressure, thereby decreasing hemorrhage.2 eral common carotid arteries and closing
The French neurosurgical pioneer Thierry scalp incisions with a running suture on
de Martel (1875
1940) took a step further either side of the incision, leaving an
and advocated the use of a sitting anemic band of tissue. In 1902, he reported
position.5 In 1907, Robert Dawbarn decreased operating time, less operative
reported he dealt with shock by placing blood loss, and no neurologic deficits after
tourniquets around both thighs of his implementing these techniques.10 Charles
patients preoperatively.6 If the blood Frazier (1870
1936), another pioneer of
pressure fell during the operation, he American neurosurgery, later advocated
released the tourniquets to provide an this same method. In contrast, Lothar
autotransfusion.2 Heidenhain (1860
1940) used a tight,
Bleeding from the scalp in the early 20th deep continuous suture on either side of
century was most commonly controlled with an incision, which penetrated all the way
tourniquets. Many surgeons used a simple to the bone, while M. Makkas and
rubber tube or Esmarch bandage (Figure 1), Vorschutz used a back-stitch suture for
both of which were difficult to apply scalp closures.3,11 In 1906, Frederick Kredel
without breaking aseptic technique. George (1903
1961) used fit curved metal plates to
W. Crile (1864
1943), founder of the the contours of the head and compressed
American College of Surgeons, used a them against the scalp using strong silk
rubber dam covering the entire scalp. sutures to arrest bleeding (Figure 2).12
William W. Keen (1837
1932), the first Hobart Hare (1838
1909) concluded in
American neurosurgeon, used a pneumatic 1916 that, of all the tourniquets and
tourniquet or rubber ring. In 1893, M. Allen suturing techniques he tried, Landon’s
Starr (1854
1932) deemed the rubber metallic tourniquet was the most effective
tourniquet a failure, as it could not be hemostatic device.9
applied with sufficient pressure to Frazier and Cushing additionally
compress the arteries; it merely exerted applied manual pressure with gauze pads
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DANIKA PAULO ET AL.
Figure 1. Versatile use of the Esmarch bandage. (From Wikimedia Commons
public domain.)
and hemostatic clamps at the base of the
skin flap and around the margins of a
scalp wound.13,14 Cushing further
controlled scalp bleeding by infiltration
with adrenaline.15 In 1936, the Raney scalp
clip was introduced and remains an
integral part of a neurosurgeon’s tray
today.2 These clips provide safe and
reliable prevention or cessation of scalp
bleeding through application of a
constant closing force. Modern Raney
clips are made of disposable, sterile
plastic and are quick to apply.
Scalp incisions also evolved to minimize
hemorrhage. At first, the cruciate skin inci-
sion was widely used; however, this was
inadequate for visualizing large lesions, and
severe hemorrhage was common. For these
reasons, Horsley advocated a semilunar or
horseshoe skin flap, which avoided the main
scalp arterial trunks; Wilhelm Wagner’s
(1848
1934) horseshoe flap became the
standard during his time.2,16 Francesco
Durante (1844
1934) of Italy used a right-
angled incision with straight limbs. Cush-
ing created a frontal flap by placing 1 arm of
his incision on the forehead.17 Ernest Sachs
(1879
1958) and Walter Dandy (1886
1946)
later adopted a similar incision, hiding it
within the hairline.18,19
Cushing’s Lateral Ventricular Puncture
In most cranial cases, and especially for
posterior-fossa tumors, Cushing used a
ventricular needle to puncture the lateral
ventricle if he saw excessive dural or osseous
“extracranial bleeding.”20 He first reported
this technique in 1909, and it appeared
regularly in records of his pediatric
posterior fossa operations at Johns
Hopkins.20-22 The release of cerebrospinal
fluid (CSF) reduced extracranial bleeding
from the bone and dura and prevented life-
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HISTORICAL VIGNETTE
HISTORY OF HEMOSTASIS IN NEUROSURGERY
forceps” in the Temple of the Oracle at
Delphi.27 These were the earliest known
versions of the hemostats. Ambroise Paré
(1510
1590), a French army surgeon,
contributed the next significant step
toward the modern hemostat. The “bec-
de-corbin,” or crow’s beak, allowed the
surgeon to easily grasp and pinch a
blood vessel shut while it was being
ligated.28 Later, Paré added a spring to
keep the jaws of the instrument open
until the vessel was seized29 (Figure 3).
Karl Ferdinand von Graefe (1787
1840)
modified forceps with a contrivance to
keep them closed and renamed it the
threatening cerebellar herniation on open- “artery forceps.”30 He used this tool in
ing of the dura, which greatly improved the place of artery hooks or tenaculums and
safety of operations in the infratentorial later modified it to carry ligatures.28
space.
Ligatures
Suction
Ligation is among the most ancient of
Before suction, bleeding into the operative
methods of hemostasis; it has been
field portended a disastrous outcome. The
described by various ancient Greek, Roman,
development of suction allowed the surgeon
and Arabian physicians. Hippocrates used
to isolate bleeding points, which could then
“apolinose” flax ligatures, while Galen rec-
be controlled with coagulation or ligation.
ommended Celtic linen and Avicenna used
This allowed hemostasis to become more
twisted hog hairs, which were resistant to
deliberate and precise. Suction was first
rotting.1,31
employed by otolaryngologists in 1914; its
The ligature was lost in the Middle Ages,
first use in neurosurgery was documented in
leaving patients to suffer under iron cau-
1927 by Swedish neurosurgeon Herbert Oli-
tery. It was not rediscovered until 1552,
vecrona (1890
1981).2 Cushing used a hand
when Ambroise Paré ligated the bleeding
bulb-syringe attached to a rubber catheter as
vessels of the leg during an amputation,
a suction apparatus.23 In 1927, Temple Fay
sparing the patient of the torture of the red-
(1895
1963) introduced combined
hot iron.32,33 His adoption of the ligature
irrigation and suction.24 Henry Heyl
(1906
1975) added a hemostatic current to
the tip of the suction instrument.25 Dandy
praised the versatility of suction, writing
that it could be used: “from a torn internal
carotid to a petrosal vein, from aspirating
blood from a blood filled ventricle to
aspirating fluid from the cisternae in
trigeminal and Ménière’s operations and
from cerebral and cerebellar cysts.”26 Early
neurosurgeons struggled with damage to
delicate cerebral structures by inadvertent
suctioning. Frazier designed a narrower
suction tip to prevent this from happening,
which was subsequently named after him.
Gazi Yasargil, a distinguished Turkish
neurosurgeon, developed a variable-
pressure suction machine and a blunted
suction tip to minimize damage to tissue. Figure 2. Diagram of curved metal plates
compressed against scalp. (Used with
Hemostat permission from Krause F. Surgery of Brain
& Spinal Cord. New York, NY: Rebman Co.;
The Greek anatomist and physician Era- 1912.)
sistratus (304
250 BC) described a “leaden
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DANIKA PAULO ET AL.
Figure 3. Portrait of Ambroise Paré and the bec-de-corbin. (Used with
permission from Pare, A. Cinq Livres de Chirugie. Paris: André Wechel; 1572.)
has been called “the greatest improvement
that has ever been made in operative
surgery.”33
As neurosurgery developed into its own
field in the late 1800s, it became apparent
that the ligature was not as useful as it was in
other surgical disciplines. The main appli-
cation of a ligature in neurosurgery was to
ligate the arterial supply to a lesion, as
documented by Horsley in 1886.34 For
tumors, it was routine to use fine silk on
curved needles to encircle the lesion. When
necessary, ligatures made of catgut or silk
could be placed deeply, encircling the
Figure 4. Leaf-cutter ants that served as a natural clip, shown in sketch (A)
and in photograph (B). (Used with permission from Ann Surg. 1911;54:1-19.)
WORLD NEUROSURGERY 124: 237-250, APRIL 2019
HISTORY OF HEMOSTASIS IN NEUROSURGERY
tissue “en-masse.”35 Cushing surrounded
surface lesions with 2 rows of the finest
split silk ligatures and incised between
them.35
Clips
The technique of using clips originated with
South Americans for simple skin wound
closures.36 They pressed the edges of the
wound together and held it over leaf-cutter
ants with powerful jaws.37 As the jaws
closed, they would cut off the ant’s body,
leaving a natural clip (Figure 4). Metal clips
were first devised by the French surgeon
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HISTORICAL VIGNETTE
Gaston Michel,14 and stapling in surgery
was first reported in 1908 by Hültl and
Fischer in Europe.38,37
Cushing introduced his own implant-
able metal clips to neurosurgery.39 The
original Cushing clip was hand-wrought
by wrapping a silver wire tightly around a
metal pencil so that it became ridged
within its longitudinal grooves. A deep
perpendicular groove allowed the user to
cut loops of wire to produce individual
clips, which were then loaded onto a
magazine. Silver was used because of its
association with low rates of infection. In
1911, Cushing published the first account
of his use of Cushing clips in a glioblas-
toma patient.14 After suctioning the
central necrotic portion, Cushing secured
the vessels of the marginal sulci, which
projected into the tumor, by drawing
them into a glass sucker and applying a
silver clip.14
Cushing clips became immensely pop-
ular in neurosurgery and even found use in
general surgical procedures. In some
cases, so many silver clips were placed
that their subsequent movement on skull
films could signal tumor reoccurrence.
With time, their use has been relegated to
larger vessels that could not be coagulated
with electric cautery.
Here we present photographs of the
Cushing clip assembly and apparatus;
previously only sketched drawings from
his original paper have been published
(Figure 5).
Later modifications and improvements
to Cushing clips resulted in the McKenzie
clip.14 As an alternative to silver, some
surgeons used tantalum because of its
greater compatibility with living tissue
and magnetic resonance imaging (MRI)
compatibility.40
Bone Hemostasis Plugging
Bone hemostasis by plugging of bleeding
sites has been described in standard surgery
textbooks as early as 1845.41 Walter Dandy
writes in The Brain that it was a common
practice to hammer sharp bone pegs to
plug the foramen spinosum.42 This
practice was continued until the 1960s.
Krause applied pressure to “bone hooks”
(Figure 6A) to bleeding openings and
twisting the hook back and forth to stop
the bleeding. He also used “ivory pegs”
driven into the bleeding opening and left
in situ, a practice previously described by
239

DANIKA PAULO ET AL.
Figure 5. Photograph of Cushing clips. (Used
with permission; photograph taken by
Gaurav Gupta).
French physicians deMartel and Rochard in
1918.42 Other bone peg materials included
wood26 and cotton wool.43 Krause wrote in
Surgery of the Brain and Spinal Cord that
bleeding from the diploe, the spongy bony
tissue between the external and internal
layers of the skull, could be controlled with
a blow from a Passow chisel (Figure 6B) or
by crushing the lamina externa and interna
with cutting forceps.44
Bone Wax
Horsley is credited with the first known
recorded use of bone wax, which con-
tinues to be used to stop bleeding from
the skull in neurosurgery today.
By the late 19th century, the ancient
technique of trephining was the only
regularly performed cranial surgery. At the
time, bleeding from the skull posed a sig-
nificant obstacle to further developments in
cranial procedures. At first, modeling wax
or candle wax was used to control bleeding
Figure 6. (A) Sketch of Krause bone hooks. (B) Sketch of a Passow chisel. (Used with permission from
Krause F. Surgery of Brain & Spinal Cord. New York, NY: Rebman Co.; 1912.)
240 www.SCIENCEDIRECT.com
HISTORY OF HEMOSTASIS IN NEUROSURGERY
from cranial bones. In 1884, Horsley was
appointed to the University of London,
where he performed extensive experiments
on the localization of brain function and, in
1886, performed the first successful exper-
imental hypophysectomy.45,46
Horsley conducted his own experiments
on bleeding in canine cranial bones and
invited P. W. Squire, a well-known phar-
macist, to assist. Squire invented a formula
using beeswax and almond oil instead of
modeling wax.43 The material was
sterilized by boiling and kept in stoppered
bottles.47 The first successful use of bone
wax in clinical surgery was documented in
The British Medical Journal in 1892 by
Rushton Parker, who used a plug of bone
wax to stop bleeding from the lateral
sinus.48 He credited Horsley for providing
the wax. The bone wax used today is
made of 88% refined beeswax and 12%
isopropyl palmitate, similar to that first
used by Horsley.
However, Horsley’s bone wax could induce
chronic inflammation,49 acted as a
mechanical barrier to bone regeneration,50
and lowered bacterial clearance in
cancellous bone. Associated complications
included foreign body granuloma50-52 and
migration into the sigmoid sinus.49,53,54
These complications prompted research
into alternatives.55-57 In 1950, Geary and
Frantz57 described a resorbable polyethylene
glycol (PEG) composite to deliver the
hemostatic agent, oxidized cellulose. They
demonstrated in a rib fracture model that
their new material was an effective
resorbable hemostatic and, in contrast to
bone wax, only produced a minor
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HISTORICAL VIGNETTE
inflammatory reaction.57 Nevertheless, bone
wax continues to be the most commonly
used bony hemostatic agent.58
Gelatin Sponge
The use of sea sponges, soaked with water
or wine, as a hemostatic was first docu-
mented by the ancient Greeks and
Romans.58,59
In 1945, John Correll and E. C. Wise, 2
chemists at the Research Laboratories of the
Upjohn Company, published a paper
describing a new water-soluble sponge
created by foaming a specially prepared
gelatin solution, which was then air-dried
and sterilized before use.60 The dried
product was light, nonelastic, tough, and
porous and could be cut into any desired
shape. The main advantage was its high
tensile strength, which allowed rough
handling without the risk of disintegration.
Moreover, gelatin is a nonantigenic protein,
despite being made from purified pork
skin, as it is nearly entirely deficient in the
aromatic amino acids, which trigger
anaphylactic and precipitation reactions.31,49
The gelatin sponge could absorb 45 times
its weight in blood and, when wet,
plastered to the irregularities of the
bleeding surface. Thrombin-soaked gelatin
sponge was shown to reduce bleeding from
cancellous bone by up to 75% over control
values.31
On the basis of Correll and Wise’s ex-
periments, Richard Light and Hazel
Prentice did extensive in vivo studies.
From intracranial implantation and histo-
logic examination of tissue in 56 monkeys,
they concluded that the gelatin sponge
was well tolerated by dura and the brain. It
produced a slight cellular reaction com-
parable with that caused by blood clots,
which disappeared by tissue digestion and
phagocytosis within 20
45 days. Light
and Prentice also reported success with
using the gelatin sponge to repair torn
veins, such as the superior sagittal sinus,
without provoking intravascular thrombus
formation compromising the patency of
the vessel. Pilcher reported one of the
largest clinical series on the use of gelatin
sponges in neurosurgery.61
Some surgeons prefer using a gelatin
paste, made by mixing gelatin with normal
saline. In 1 study a 10% reduction in
bleeding time occurred compared with a
gelatin sponge with thrombin.62 Another
advantage is that it does not impede

DANIKA PAULO ET AL.
Table 1. Examples of Styptics and Hemostatics
Styptics
Acids, alum, ferric chloride, ferrous sulphate,
zinc sulphate, lead acetate, silver nitrate, matico, cold,
spider’s web, tannic acid, and all vegetable astringents
proper bone healing. However, use of
commercially available gelatin sponge is
most popular.
In the era of MRI, care must be taken in
interpreting a postoperative MRI because
a mixture of gelatin sponge, blood,
plasma exudates can present as a post-
operative mass of inhomogeneous signal
that can be confused with a pathologic
process like an epidural hematoma or
abscess.63 Other disadvantages of gelatin
sponges include an increased risk of
wound infection and compression of
nearby neural tissue after swelling from
blood absorption.63
PART II: CHEMICAL METHODS OF
HEMOSTASIS
Styptics and Caustic Agents
Styptics were an important method of
hemostasis in the ancient Greek and
medieval periods.64 When applied locally,
they promoted clot formation and
vasoconstriction; however, they also
destroyed neighboring healthy tissue.
Moreover, permanent hemostasis depended
on the resulting eschar, which was often
weak and unreliable.63 Styptics are not used
in modern neurosurgery; for academic
interest, a summary of styptic agents can be
found in Table 1.65
Caustic agents were widely used by the
neurosurgeons of the 17th century. Nicholas
André (born in 1704) of France wrote one of
the earliest descriptions of the surgical
treatment of tic douloureux with use of
caustic stones to prevent rebleeding.63
André’s surgical technique produced less
blood loss and lower risk of rebleeding and
recompression of the trigeminal nerve
compared with traditional use of a scalpel
blade.
Cushing used Zenker solution, a tissue
fixative containing mercuric chloride, po-
tassium bicarbonate, sodium sulfate, and
glacial acetic acid, to destroy residual tu-
mor after resection and seal the meninges
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HISTORY OF HEMOSTASIS IN NEUROSURGERY
Hemostatics
Dilute mineral acids, especially sulfuric; gallic
acid; ergot; digitalis; hamamelis; ipecacuanha;
lead acetate; and oil of turpentine
after craniectomy for pituitary adenomas
and acoustic neuromas.64,66 Horsley used
a weaker (1:10,000) sublimate solution for
irrigation.64
Adrenaline
In 1901, Emil Mayer first documented the
use of adrenaline for hemostasis.4 This
technique has since been widely accepted
by the neurosurgical community at large
and has become a mainstay for initial
skin hemostasis before incision. In 1909,
Braun improved on this by adding
procaine to epinephrine67 and advocated
infiltrating the scalp with this while the
patient is under general anesthesia.
Hydrogen Peroxide
The first published mentions of the use of
hydrogen peroxide in humans are dated in
the late 1980s by Drs. Epstein and
Mawk.68,69 Its primary mechanism of ac-
tion is vasoconstriction; it is also an anti-
septic. Olivecrona popularized its use on
bleeding surfaces of the brain.2
However, hydrogen peroxide is no
longer commonly used because of its
damaging effects on healthy tissue. It
disrupts the blood-brain barrier, which
can result in thrombus formation. Because
it is an uncharged molecule, it has the
ability to cross vessel walls and, on con-
verting to water and oxygen, can lead to
intraluminal bubbles, leading to micro-
embolisms and vessel obstruction.
Hydrogen peroxide can also affect hemo-
dynamic stability intraoperatively (e.g., by
inducing severe bradycardia).
Thrombin and Fibrin
In 1964, British hematologist Robert Mac-
Farlane proposed the classic hypothesis of
the Coagulation Cascade.70 Prothrombin is
converted into active thrombin, which in
turn converts fibrinogen to fibrin; the
final product is a cross-linked fibrin
meshwork that traps erythrocytes and stops
bleeding.
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HISTORICAL VIGNETTE
Thrombin, discovered in the 1830s by
Scottish surgeon Andrew Buchanan
(1792
1882), had to be purified and pro-
duced in mass quantities to be of surgical
use. Some sources credit William H. Howell
(1860
1945) as the first to purify thrombin
in 1910; others credit Schmidt.71,72
Thrombin was then purified in greater po-
tency, notably by Mellanby in 1933 and
Seegers in 1938.73-75 World War II sparked a
huge national program in blood donation,
which provided the resources to produce
large amounts of thrombin and fibrin
foam.76-78 Drs. Karr and Ziff of the Neuro-
logical Institute of New York were the first to
apply it in neurosurgical cases.75,79
Fibrin and fibrinogen were discovered
by Malphighi in 1686 and Fourcroy in the
early 1800s, respectively; fibrinogen was
purified in the late 1800s by Denis80 and
Hammarsten.73 Ernest Grey, Cushing’s
assistant resident in 1915, isolated and
tested sheep’s fibrin on the cerebral
hemispheres of cats.81 He concluded that
fibrin only assisted in the mechanical
formation of the clot; it did not influence
the chemical reactions involved.73 He
noted that clotting could be hastened by
dipping fibrin into a thromboplastic
solution (e.g., Kocher-Fonio-Coagulin),
but this made it cumbersome to use.
Samuel Clark Harvey improved on this by
plasticizing the protein with heat, con-
verting it into a paper-like substance.82
The 20th century brought the discovery
of heparin by William Howell.81 Howell
also demonstrated that hot sponges/
cloths applied to wounds hastened
clotting by accelerating the formation of
thrombin.83
Fibrin Sealants
In 1972, the first successful use of a fibrin
sealant as an adhesive agent for nerve repair
was reported in neurosurgery.84 Fibrin
sealants consist of 2 main components:
fibrinogen and thrombin.63 These
ingredients are loaded into 2 syringes, the
tips of which form a common port; they
are activated when mixed in the presence
of calcium to produce insoluble fibrin.
These bypass the extrinsic and intrinsic
pathways of blood coagulation, replicating
only the final common pathway of
coagulation. In the past, bovine thrombin
was used, but current products use human
thrombin extracted from pooled donor
plasma, although autologous preparations
241

DANIKA PAULO ET AL.
have been described.63 The use of a human
source prevents sensitization to bovine-
derived thrombin.
In contrast, fibrin glues contain fewer
synthetic materials (e.g., cyanoacrylates),
making it biodegradable.85-87 Conse-
quently, it does not result in significant
inflammation, tissue fibrosis, or foreign
body reactions; it is absorbed within days
to 4 weeks.85
Christopher Shaffrey et al.88 at the
University of Virginia reported in 1990 that
fibrin sealant prevented CSF leakage in
90% of patients who received dural closure
operations over a 3-year period. Subsequent
studies have demonstrated its utility in
repair of CSF leaks, sealing vascular
anastomoses, reinforcing aneurysmal
clippings, hemostasis following tumor
resection, and dural closure after
endoscopic operations.85 The risk of
transmitting blood-borne infectious disease
delayed approval by the U.S. Food and Drug
Administration (FDA) until 1998.89
Following that, Tisseel was manufactured
by Baxter Healthcare (Deerfield, Illinois,
USA) and Hemaseel APR was distributed by
Hemacure Corporation (Montreal, Canada).
Disadvantages of using fibrin sealant
include the time required to prepare the
product and the 1
2 minutes required for
the clot to form after application. Fibrin
sealants are therefore most effective for
diffuse capillary oozing or sealing arterial
suture lines when the vessel can be clam-
ped while the clot forms, not in cases of
brisk arterial or unexpected bleeding.90,91
FloSeal
FloSeal Matrix, created by Baxter Health-
care Corporation, consists of a bovine-
derived gelatin matrix and a human-
derived thrombin component that are
mixed just before use.92 A single-barrel
syringe and special applicator tip are
used to apply the mixture to the site of
bleeding. The gelatin granules swell about
20% on contact with blood or bodily fluids
to tamponade the bleeding, while human-
derived thrombin converts fibrinogen into
fibrin monomers, producing a stable clot
that resorbs within 6
8 weeks. FloSeal
stops bleeding at a median time of 2 mi-
nutes (96% success rate within 10 mi-
nutes). Its benefits over other hemostatic
agents are that it works on wet, actively
bleeding tissue and in high-flow bleeds;
conforms to irregular wound surfaces; is
242 www.SCIENCEDIRECT.com
effective on both hard and soft tissue
surfaces; and works in fully heparinized
patients.92-95 It was originally put on the
market in the late 1990s, approved by the
FDA in 1999,96 and the first publications of
its use in surgery were published in
2000.93,97
The first published report of its use in
neurosurgery was in 2002 by Dilantha Elle-
gala et al98 at the University of Virginia. In 19
of 293 patients who had uncontrollable
bleeding during transsphenoidal
procedures, FloSeal stopped the bleeding
immediately, with only 1 case requiring a
second application. Other neurosurgeons
have reported the benefits of FloSeal in
spinal and cranial surgery in decreasing
adhesion and scar formation at the site of
application (for laminectomies),
controlling refractory bleeding, reducing
damage to adjacent healthy tissue, and
shortening operative time.99,100 Its success
has also been documented
supratentorial intracerebral hemorrhage,
intraventricular hemorrhage, bleeding
from venous sinuses, major arteries
including the internal cerebral artery,
tumor beds, and generalized oozing.
However, these reports are anecdotal, as
there are currently no randomized control
trials investigating FloSeal’s efficacy.
Some risks associated with FloSeal
include epidural spinal cord compression (if
accidentally injected into the spinal canal),
perilesional edema (if excess product is not
removed), allergic reaction to bovine
component, and transmission of infectious
disease from the human component.101
Other complications include unintentional
thrombus formation if placed on a
nonactively bleeding vessel or injected
directly into the vessel, anemia, infection,
and hemorrhage.101
Surgiflo
Surgiflo, made by Ethicon (Somerville,
New Jersey, USA), is also a thrombin-
gelatin hemostatic matrix that was
approved by the FDA in 2005 for intra-
operative hemostasis. Unlike FloSeal, the
thrombin in Surgiflo is porcine derived.
Surgiflo develops into a thick matrix that
stays in place during active bleeding,
achieves hemostasis in <2 minutes, and
retains its efficacy and consistency for up
to 8 hours.102
Since its introduction in the early 21st
century, only 16 papers have been published
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HISTORICAL VIGNETTE
HISTORY OF HEMOSTASIS IN NEUROSURGERY
to document the efficacy of Surgiflo in
humans, 6 of which involved the brain or
spine.103-108 One study published in 2012
from Italy found that in comparison with
FloSeal, Surgiflo took approximately 80
seconds less to prepare and biodegraded
about 2 weeks earlier, but these discrep-
ancies did not translate clinically into any
significant difference in hemostatic effi-
ciency.106 Both agents were able to achieve
immediate hemostasis, and neither
resulted in any complications directly
contributable to the hemostatic agent.
Surgiflo has been preferred in
transsphenoidal cases since the long,
malleable applicator tip allows for greater
reach in small spaces. More recently, 2
large multicenter trials set out to compare
the efficacy and cost-effectiveness of Flo-
Seal and Surgiflo in spinal surgery.103,104
While it found no appreciable clinical dif-
ferences between the 2 hemostatic agents,
in FloSeal may be more cost-effective. Another
study, published in 2014, evaluated the ef-
ficacy of Surgiflo in spinal surgery.105 In 67
procedures, Surgiflo was placed into the
spinal epidural space to assist in
hemostasis in cases of refractory bleeding
after application of Surgicel; bleeding
stopped in all cases without any
complications. Research supports that
both FloSeal and Surgicel are safe,
biocompatible, and valuable solutions for
refractory bleeding.
Topical Hemostatic Agents
Muscle Stamps. Leeds physician Charles
Thackrah14 discovered in the early 1800s that
blood collected after flowing over an open
wound coagulated more quickly than if
drawn directly from the blood vessel.109,110
The coagulative action of tissue was
demonstrated more positively by Schmidt,
who mixed blood and tissue in a container
and found immediate coagulation.110 He
proved that tissue has the zymoplastic
capacity to convert prothrombin to
thrombin.73 In neurosurgery,
Cushing72,83,111 and Horsley73 separately
described success with use of freshly cut
muscle grafts to control bleeding from the
dura, dural sinuses, and brain.14 Cushing
used muscle stamps, which were muscles
pounded flat and cut into squares the size
of postage stamps. Dowman111 in 1914
reported his experience with pieces of
fascia for hemostatic effects. Howell
discovered that tissue thromboplastin

DANIKA PAULO ET AL.
explained the procoagulant properties of
tissue.112-114 Consistent with this, Horsley
found that muscle loses its hemostatic
properties after boiling, likely due to the
denaturation of thromboplastin.81 Today,
muscle and fascial grafts are used in
neurosurgery for tight closure and
reconstructive purposes.
Neurosurgical Pledgets and Patties. Until the
late 1900s, unclean cotton collected from
sweepings on the floors of textile mills
was used for surgical dressings. In 1876,
Robert Wood Johnson from New Jersey
heard Joseph Lister, the founder of anti-
septic technique, speak about the “invis-
ible assassins” hiding in unsterile
dressings. Johnson envisioned a new type
of surgical dressing that would be ready-
made, sterile, and sealed in individual
packages. In 1885, R. W. Johnson with his
brothers formed the Johnson & Johnson
Company. By 1890, Johnson & Johnson
was processing cotton and gauze with dry
heat, followed by steam and pressure to
produce a product that was both antiseptic
and sterile. Because of their innovative
cotton products, Johnson & Johnson
became known as “the most trusted name
in surgical dressings.”
Cushing advocated the use of small pled-
gets or “tips” of gauze of various sizes
secured by a black ligature so that even when
bloodstained, they could be easily located.
He also documented the first use of patties,
also called cottonoids or neurosurgical sponges, in
the early 1900s. He found that cotton soaked
with saline was superior to other materials
for washing meningeal surfaces. When
wrung out into flat pads and tagged with a
black suture, these cotton squares were also
the safest and most effective substance for
sponging and temporary packing in deep
cerebral wounds.115 However, these early
patties often frayed and linted, which left
debris that caused inflammation or were
inadvertently left inside the wound.
Cushing’s contemporaries including
Oppeheim, Lanphear, Horsley, and
Kohler2,116 experimented with other
materials, such as iodoform gauze and
even tampons.2,116-118
Today, neurosurgical patties are one of
the most commonly used instruments.
Patties are used intradurally to protect
neural tissue from metal instruments, aid
in dissection, and absorb CSF, blood, or
other fluids. DePuy Synthes optimized
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HISTORY OF HEMOSTASIS IN NEUROSURGERY
their design by using compressed rayon,
which absorbs over 5 times its weight in
<1 second while remaining pliable and
porous.101 The manufacturer also added
blue and green x-ray-detectable indicator
strings and minimized fraying with
precision cutting.101 It has become
standard practice to keep patties wet
before use, as dry patties are more likely
to adhere to neural tissue and cause
damage on removal. Dry patties are also
a potential ignition factor in procedures
using lasers. In 2015, Kinoshita et al119
developed a “nonadherent” neurosurgical
patty design, as well as an objective way
to evaluate the hemostatic efficacy of the
patties.
Oxycel and Surgicel. In 1942, Yackel and
Kenyon62 of Eastman Research laboratories
introduced a novel material: oxidized
cellulose. Oxycel is cellulose oxidized with
nitrous oxide. This oxidation converts
certain hydroxyl groups to carboxyl
groups, thereby solubilizing the material
at physiologic pH. Initially, the
hemostatic action was thought to be
purely mechanical, by providing a matrix
for clot formation. However, experiments
by Frantz, Clarke, and Lattes at Columbia
University in New York demonstrated
specific hemostatic activity from the
reaction between cellulosic acid and
hematin, which produces its characteristic
brown color.115 However, adding
thrombin to enhance Oxycel is ineffective,
as it is destroyed by its acidic pH.
Surgicel is oxidized “regenerated” cel-
lulose (i.e., rayon). Mechanically, Oxycel
and Surgicel are similar. Used alone,
neither would stop oozing from a medium
or large artery or dural sinus bleeding,
which would be better achieved by the
mechanical hemostasis provided by
gelatin sponge.120 Instead, cellulose
products are used adjunctively for control
of capillary, venous, or smaller arterial
bleeding. It rapidly stops bleeding by
acting as a matrix for formation of a clot
that is readily absorbed from the site of
implantation with minimal tissue
reaction. Although the clot is absorbed
anywhere from 2 days to 6 weeks, the
body is incapable of breaking down and
absorbing cellulose, which can result in
chronic inflammation.
The major disadvantage of Oxycel was
that it prevents reepithelialization at the
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HISTORICAL VIGNETTE
injury site. Surgicel is free of this defect
and does not cause any impairment to
healing. The other disadvantages of these
materials include retardation of bone
healing/growth,121 progressive fibrosis and
stenosis of wrapped anastomoses, and
postsurgical compressive neuropathies,
especially in confined areas.122 Although
Surgicel provides a lattice for natural clot
formation, it cannot enhance this process
in coagulopathic patients whose platelet
count or function are compromised.
Microfibrillar Collagen. Microfibrillar
collagen (MFC), also known as Avitene, is a
water-soluble salt form of natural collagen;
its discovery was first reported in 1969 by
Hait.123 The fibers, prepared from purified
bovine dermal collagen, contain
microcrystals 1 micron in length and act by
facilitating platelet aggregation and release
of intraplatelet substances. Because it
enhances platelet functions, it is ineffective
in patients with thrombocytopenia
(<10,000/mL2) and has no effect on the
clotting time, prothrombin time, or partial
thromboplastin time. Because it is a
foreign protein, excess MFC should be
removed as it may exacerbate infection or
abscess formation. In controlling
cancellous bone bleeding, MFC has been
shown to be significantly better than
thrombin powder alone (40%) and
comparable with thrombin-soaked gelatin
sponge (61%), but not as effective as
thrombin-soaked and gelatin paste (75%

85%).124 It also does not interfere with bone
healing and, unlike bone-wax, does not have
an increased risk of developing a foreign
body granuloma.
Intravenous Hemostatic Agents:
Tranexamic Acid and Prothrombin
Complex Concentrate
Tranexamic acid (TXA) is a synthetic lysine
analog that binds plasminogen in place of
fibrin within clots, preventing the activation
of plasmin and impairing fibrinolysis. The
first documented used of TXA was in 1957 by
S. Okamoto, and it is now one of the most
widely used antifibrinolytic agents.125 It is
administered perioperatively for prophylactic
hemostasis before surgery, typically for
trauma.
Several studies have shown significant
reduction in intraoperative and post-
operative blood loss with the use of TXA,
with an accompanying decrease in the
243

DANIKA PAULO ET AL.
Figure 7. (A) Sketch from William T. Bovie’s electrosurgical apparatus patent. (Used with permission
from Bovie WT. Electrosurgical apparatus. Lieber Flarsheim Co, assignee. Patent US18 13902 A.
January 18, 1928.) (B) Sketch of the Bovie apparatus (Used with permission from Surg Obs Gyn.
1928;47:751-784.) (C) Title of Cushing’s seminal article on the Bovie apparatus. (Used with permission
from Surg Gynecol Obstet. 1928;47:751-784.)
need for transfusions and without chang-
ing overall mortality.119,126-129 It does have
potential to cause harm, as there have
been reports of death, ventricular fibrilla-
tion, and generalized seizures, particularly
when high doses are used or if it is applied
intrathecally.130-132 One proposed mecha-
nism for these sequelae is that high doses
of TXA can leach out of the fibrin clots and
impair adhesion of adjacent cells to their
natural extracellular matrix, which is
cytotoxic.133
Although not approved by the FDA for
this use, antifibrinolytics like TXA are
used in cases of intracerebral (ICH) and
subarachnoid hemorrhage (SAH) to
decrease rebleeding rates; however, this
increases stroke risk. A randomized clin-
ical trial to assess the outcome of early
TXA in patients with a SAH and found a
reduction in early rebleeding from 10.8%
to 2.4% and an 80% reduction in
244 www.SCIENCEDIRECT.com
HISTORY OF HEMOSTASIS IN NEUROSURGERY
mortality.134 The ongoing ULTRA trial is a
phase 2/3 investigation into the effect of
TXA on rebleeding rates following
SAH.135 TXA has also been incorporated
into some protocols for controlling
vasospasm after aneurysmal SAH. It is
also useful in the setting of traumatic
ICH; there are studies under way to
assess its efficacy for this use.136,137
Prothrombin complex concentrate (PCC)
is another prophylactic hemostatic. It con-
sists of vitamin K
dependent clotting fac-
tors II, VII, IX, and X and proteins C and S
derived from human blood plasma. Its
primary use is to rapidly reverse the effects
of warfarin and other coumarin anticoagu-
lants before emergency surgery or in severe
intracranial hemorrhage. It is remarkably
effective in neurosurgical emergencies, as
was first noted in the paper published by
Cartmill et al138 in 2000. Their use of PCC in
6 patients on anticoagulants in
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HISTORICAL VIGNETTE
neurosurgical emergencies reduced their
INRs to below 2 in <15 minutes. Another
2007 study reported reduction of the INR
to safe levels (<1.5) in <3 minutes,
comparable with the time to surgery seen
in nonanticoagulated patients.139 More
recently, a 2014 study showed that PCC
reduced INR more quickly than fresh
frozen plasma,140 and additional studies
continue to support the utility of PCC in
neurosurgical emergencies.141
Proteinase inhibitors prevent proteinase
from breaking down a thrombus. Intrave-
nously administered proteinase inhibitors
were used in neurosurgery as early as
1963.142 In the 1970s, a dose of 500,000
kallikrein-inhibiting units was used to
treat coagulopathies discovered intra-
operatively.143 In 1993, Bayer introduced
aprotinin (Triazolyl), a natural proteinase
inhibitor isolated from bovine lung.
Aprotinin found its niche in neurosurgery
for operations involving large cerebral
arteriovenous malformations and highly
vascularized tumors. Studies in the 1990s
and 2000s linked aprotinin to kidney
failure, heart attack, stroke, and increased
risk of death.144,145 Bayer pulled the
product off the market in 2007 at the
request of the FDA. Since then, proteinase
inhibitors have fallen out of favor in
neurosurgical procedures.
PART III: THERMAL METHODS OF
HEMOSTASIS
Irrigation
In the late 1800s, there was a divide be-
tween proponents of hot versus cold water
for irrigation for hemostasis. Both sides
agreed on 2 points: Both temperatures
caused initial vasoconstriction, and cold
irrigation further caused vasospasm. Ad-
vocates of hot irrigation argued that
although warm water could cause vasodi-
latation, which would increase risk of
hemorrhage, applying hot water directly to
a bleeding surface was an effective
hemostatic.
In 1886, Milne Murray conducted exper-
iments with irrigation at 36 F to 123 F on
the uterine vessels in rabbits.4 She showed
that although both cold and hot irrigation
caused initial vasoconstriction, the
vasculature remained fully anemic for
longer under hot water. Further, the cold
irrigation condition showed an intense

DANIKA PAULO ET AL.
Figure 8. Illustration of the coagulating needle and electrocautery machine.
Figure reproduced with permission from the Cushing Center at Yale
University. (Used with permission from J Neurosurg Pediatr.
2004;100:225-231.)
reactionary congestion within 8 minutes,
while the warm irrigation condition just
regained their resting tone. Horsley had
attended Murray’s presentation at the
Edinburgh Obstetrical Society meeting.
He realized: “What we require is a
temperature that stimulates contraction of
small vessels without at the same time
causing heat coagulation of the nervous
system.” He concluded that temperature
to be between 110 F and 115 F.146
Cushing, in his original memoirs from
1911, preferred temperatures between
100 F and 105 F.147 However, not all early
neurosurgeons were fond of irrigation.
Krause remained a strong exponent of dry
asepsis despite the widespread acceptance
of irrigation.148
Simple Cautery and Galvanocautery
Cautery, the practice of destroying tissue
through use of heat, is among the oldest
methods of hemostasis. Descriptions of
this process appear in writings on surgical
techniques dating back to 600 BC in
ancient India. Its use is also described
extensively by Hippocrates, who wrote:
“That what the medicament not quelleth,
the iron doth; and that which the iron
amendth not, the fire extermineth.”14
Around AD 1308, Jehan Ypreman of
Ypres, France described an ingenious,
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HISTORY OF HEMOSTASIS IN NEUROSURGERY
simple method for protecting the flesh
around the artery to be cauterized, which
involves using a sheet of iron perforated
with holes of varying size. These perfora-
tions were positioned over vessels and
allowed the red-hot iron to be applied to
them while minimizing injury to the sur-
rounding flesh.149
During the Middle Ages, cautery came to
replace most other forms of hemostasis. It
was usually performed with specialized
iron instruments, which would be heated
until the metal turned red. This form of
cautery, known as the “fer d’argent,” was a
tortuous affair. Alternatively, scalding hot
oil would be poured into the wound.3
Subsequently, Claude André Paquelin
(1836
1905) invented an ingenious form
Figure 9. Photograph of the Nd:YAG laser
(image source unknown).
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HISTORICAL VIGNETTE
of cautery involving a series of metal
blades or points of different shapes and
sizes that could be fitted to a handle.
These points were hollow inside, filled
with fine platinum wire, and could be
kept heated with benzene vapor. In the
1880s, Paquelin’s cautery was adapted to
neurosurgery.150,151
The next major development was galva-
nocautery, or cautery by an electrically
heated wire. Current is passed through the
wire; the resistance of the wire arrests the
current and converts it to heat. In 1854
Albrecht T. Middeldorpf (1824
1868), a
surgeon in Germany, published the first
account of using electrical current in sur-
gical operations.28 Middeldorpf used a
galvanic current from a zinc-platinum bat-
tery to heat thin platinum wires. With this
tool, it became possible to simultaneously
perform tissue dissection, destruction, and
hemostatic coagulation. His most impor-
tant electrosurgical instruments consisted
of an electrosurgical knife and an electrical
cutting snare for removal of polypoid tu-
mors,151,152 which are the direct ancestors
of modern electrocautery and cautery
snare, respectively.
Jacques-Arsène d’Arsonval (1851
1940)
discovered in 1891 that high-frequency (i.e.,
thousands of oscillations per second) alter-
nating electrical currents did not physio-
logically stimulate muscle, unlike lower
frequency currents, which produced muscle
twitching and pain.153 This set the stage for
advances in medical diathermy and
electrosurgery. In 1907, Pozzi in France
reported that certain malignant growths
could be effectively destroyed using high-
frequency sparks at a distance from the
target.154 He called this “fulguration.”
Additional local dehydration and
coagulation could be achieved by bringing
an even higher frequency of current into
direct contact. In 1911, W. L. Clark
promoted a new electro-scalpel apparatus
that used both a small active electrode and a
larger indifferent electrode, which better
limited cutting to the immediate vicinity of
the active electrode. He proposed the term
“desiccation” to describe its action.7
Professor William T. Bovie, a physicist
at the Huntington Memorial Hospital, is
credited with advancing the field of gal-
vanocautery to modern standards and,
with the help of Harvey Cushing, intro-
ducing it to neurosurgery. The “Bovie
apparatus” developed by Cushing and
245

DANIKA PAULO ET AL.
Bovie was a spark-gap unit that consisted
of 2 small metal conducting pieces sepa-
rated by an air gap, like an automobile
spark plug. When voltage is raised high
enough to jump across the air gap, the air
becomes ionized and functions as a
conductor. Soon after its development, the
Liebel-Flasheim Company of Cincinnati
undertook its commercial production.
Cushing was so encouraged by the success
of this apparatus that he called back many
of his patients with supposedly inoperable
meningiomas and hemangiomas.155 In
1926, Harvey Cushing first used the Bovie
apparatus in a neurosurgical operation
on a patient with a highly vascular brain
tumor whose first surgery, 3 days earlier,
had to be aborted because of failure to
control bleeding.28 However, this hand-
made tool still had its drawbacks. A skil-
led assistant had to operate its elaborate
switchboard, and inhaled anesthetics
could not be used due to fire risk. Soon
thereafter, a more modern version of the
machine was developed to address these
issues (Figure 7A and B).
In 1928, Cushing published a study of a
series of 500 cranial procedures in which
tumor hemostasis was facilitated by the
Bovie apparatus (Figure 7C).156 The terms
“intracapsular tumor enucleation” and
“adequate hemostasis” began to appear
regularly in Cushing’s operative notes in
1927.155 Cushing’s first operative illustration
involving the “coagulating needle” for a
posterior fossa tumor reflects a milestone
in the evolution of techniques in cranial
surgery (Figure 8).
Dusser de Barenne and Zimmerman
studied the effects of electrosurgery on the
brain around 1935.156 They used a carefully
controlled heating element between 122 F
and 176 F (50 C and 80 C) and charted the
depths of destruction of the cerebral
cortex in monkeys after exposure times
from 30 seconds to 5 minutes. They
concluded that a minimum exposure of
30 seconds at a temperature of 122 F
(50 C) or above resulted in death of
nerve cells in the most superficial cortical
layers.156
Spark-gap units like the Bovie wore out
quickly and needed service frequently.
Early in the 1970s, vacuum tubes in the
earlier electrosurgical units were replaced
with printed circuit boards and transistors,
which were more compact, reliable, and
safe than spark-gap devices.156
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HISTORY OF HEMOSTASIS IN NEUROSURGERY
Bipolar Cautery
Bipolar cautery was first used by James
Greenwood of Baylor College of Medicine in
1940.156 In 1953, Edward Malis introduced
the first true bipolar coagulator instrument
at Yale, which was then marketed for
widespread use in 1966.20
The introduction of bipolar coagulation
was an important step allowing neuro-
surgeons to become “microsurgeons.” In
addition to pioneering safer and more
effective microsurgical cautery, the subse-
quent introduction of “nonstick” metal
surfaces has further improved this
important surgical addendum. This new
technique permitted better control of
hemorrhage, was safe to use in patients
with pacemakers and defibrillators, and
enabled soft tissue planing. It also did not
need a grounding pad. Most importantly,
bipolar cautery allowed for fine coagula-
tion of small vessels in areas where uni-
polar coagulation would be hazardous,
such as next to cranial nerves, the brain-
stem, cerebellar arteries, or the fourth
ventricle. Its low impedance output
ensured the voltage would be constant
despite the resistance of the tissue. It was
also safer because the bipolar cut and
coagulated at wattages less than one
quarter that required for monopolar
electrosurgery.
Laser
In 1960, Theodore Maiman, a researcher
from Hughes Research Laboratories in
California, detailed the first operational
laser. He used a ruby medium to produce
a laser pulse of 694 nm wavelength. In
1964, Kumar Patel of Bell Laboratories in
New Jersey described a molecular laser
that uses carbon dioxide as a medium to
produce a continuous-wave laser at 1060
nm. Lasers were first used on the brain in
1965 in experiments by Fine157 and
Earle.158 They used a single high-energy
pulse of ruby laser on the intact crania of
mice, which killed them instantly. Even-
tually, the laser energy was controlled to
create sharply demarcated lesions in neu-
ral tissue. Because of their predictable in-
juries on cranial contents, lasers were used
in models for studying subdural and sub-
arachnoid hemorrhage. In contrast to the
high-powered pulse lasers, it was shown
in 1964 that low-powered lasers have a
selective effect on destroying cancer cells.
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HISTORICAL VIGNETTE
Eventually, the introduction of contin-
uous wave lasers with focused beams
allowed for much more control to improve
cutting accuracy and induce vaporization.
The carbon dioxide laser was found to be
excellent for cutting as it caused little
thermal damage to adjacent tissue. The
argon laser, created in 1967, employed this
technology for coagulation. This laser has
a wavelength of 488
516 nm and can
cover a wider zone of tissue. Because the
laser beams are absorbed by hemoglobin,
this allows for more effective coagulation.
Later in the 1980s, Brown et al.159
demonstrated how the neodymium-
doped yttrium aluminum (Nd: YAG) laser
(1060
1340 nm) had the ability to pene-
trate to a deeper area of tissue for photo-
coagulation and tumor ablation (Figure 9).
The developments of neuronavigation,
MRI thermotherapy, and catheter systems
enabling surgeons target laser light to a
specific location have all contributed to the
development of laser interstitial thermal
therapy (LITT) in 1983. LITT involves tar-
geting laser light interstitially within a
target lesion volume to produce coagulative
necrosis; it has become an increasingly
important option for treatment of epilepsy,
intracranial and spinal tumors, and radia-
tion necrosis.159 Currently, the 2 major
LITT systems are Visualase (Medtronic,
Inc., Dublin, Ireland), which uses a 980
nm laser diode, and NeuroBlate (Monteris
Medical, Inc., Plymouth, Minnesota,
USA), which uses a 1064 nm Nd:YAG
laser. Although 1064 nm wavelength laser
light offers deeper tissue penetration, the
980 nm laser diode system provides faster
tissue heating.160
Aquamantys System
The Aquamantys System (Medtronic)
gained FDA approval for surgical use in
January 2012. This medical device uses
transcollation technology that involves a
combination of pulsatile radiofrequency
delivered by 2 bipolar electrodes and a
conductive liquid such as normal saline.
The system is composed of a generator
and single-use probes, which heat tissue
to a temperature of 100 C while the
conductive liquid evenly conducts energy
into tissue, maintains a clean tip, and
avoids drying out tissues, excessive
smoke, and other electrical risks of over-
heating. This allows for the safe and
effective coagulation of blood vessels,

DANIKA PAULO ET AL.
bone, and other soft tissue, which ulti-
mately reduces blood loss, transfusion
rates, and surgical time. Other electro-
cautery systems char surrounding tissue,
which can lead to more bleeding if the
eschar is peeled away. Other benefits are
the ability to stop epidural bleeding near
critical structures and improve visibility in
the surgical field.
At the time of writing, few studies have
evaluated the safety and efficacy of the
Aquamantys system in neurosurgery. A 2014
study described the use of Aquamantys in 10
patients undergoing resections of brain tu-
mors.161 Effective hemostasis was achieved
in all patients; the group concluded that
the Aquamantys minimizes blood loss and
decreases the length of surgery. Another
study documented its effectiveness in
adolescent idiopathic scoliosis, provided
effective hemostasis in all cases, and
reduced the number of transfusions
needed.162
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Conflict of interest statement: The authors declare that the
article content was composed in the absence of any
commercial or financial relationships that could be construed
as a potential conflict of interest.
Received 1 September 2018; accepted 3 December 2018
Citation: World Neurosurg. (2019) 124:237-250.
https://doi.org/10.1016/j.wneu.2018.12.015
Journal homepage: www.journals.elsevier.com/world-
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