Hemostatic Agents

CONTINUING EDUCATION
Hemostatic Agents: A Guide
to Safe Practice for
Perioperative Nurses
3.0
MARGARET A. CAMP, MSN, BSN, RN
www.aorn.org/CE
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Purpose/Goal
To provide the learner with knowledge specific to the effective
management of bleeding during operative and other invasive
procedures and the use of hemostatic agents to augment the
patient’s natural clotting abilities.
Objectives
1. Discuss why hemostasis is needed during operative and
other invasive procedures.
2. Describe the basic mechanisms that naturally occur to
promote hemostasis.
3. Discuss the clinical indications for the use of hemostatic
agents.
Conflict of Interest Disclosures
Having received money for the development of education
programs and for travel, accommodations, and meeting expenses from Ethicon, Margaret A. Camp, MSN, BSN, RN,
has declared an affiliation that could be perceived as posing
a potential conflict of interest in the publication of this
article.
The behavioral objectives for this program were created
by Rebecca Holm, MSN, RN, CNOR, and Helen Starbuck
Pashley, MA, BSN, CNOR, clinical editors, with consultation
from Susan Bakewell, MS, RN-BC, director, Perioperative
Education. Ms Holm, Ms Starbuck Pashley, and Ms Bakewell
have no declared affiliations that could be perceived as posing
potential conflicts of interest in the publication of this
article.
Sponsorship or Commercial Support
No sponsorship or commercial support was received for this
article.
Disclaimer
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education by the American Nurses Credentialing Center’s
Commission on Accreditation.
AORN recognizes these activities as CE for RNs. This recognition does not imply that AORN or the American Nurses
Credentialing Center approves or endorses products mentioned
in the activity.
http://dx.doi.org/10.1016/j.aorn.2014.01.024
Ó AORN, Inc, 2014
August 2014
Vol 100
No 2 AORN Journal j 131
Hemostatic Agents: A Guide
to Safe Practice for Perioperative
Nurses
3.0
MARGARET A. CAMP, MSN, BSN, RN
www.aorn.org/CE
ABSTRACT
Perioperative hemostasis, the effective management of bleeding during operative
and other invasive procedures, can involve the use of blood, blood products, and
hemostatic agents to augment the patient’s natural clotting abilities. Currently, more
than 50 hemostatic products are available in the marketplace and dozens more are in
development. It is important for perioperative nurses to understand each of the
hemostatic agent categories and their actions, properties, applications, and limitations. This article provides an overview of the normal coagulation process (ie,
clotting cascade) that is activated by the body when there is a bleeding episode; the
management of blood products and the rationale for reducing their use; the financial
implications of hemostatic agent use; and how these agents are used, their clinical
indications, and potential complications from their use. AORN J 100 (August 2014)
132-144. Ó AORN, Inc, 2014. http://dx.doi.org/10.1016/j.aorn.2014.01.024
Key words: clotting cascade, bleeding, hemostasis, hemostatic agents.
S
ince ancient times, people have searched
for ways to effectively control bleeding,
especially when the body’s normal clotting
responses are insufficient to accomplish satisfactory hemostasis (ie, the reduction or stoppage of
blood flow). In early times, bandaging, pressure, or
crude forms of cautery applied to a wound had to
suffice until the idea of using thread to suture
wounds became common; eventually, barbers and
boxers discovered that thrombin could be used to
stop bleeding.1 As early as the 1940s, surgeons
were using thrombin in surgery to stop bleeding.1
The use of thrombin in surgery for hemostasis has
increased exponentially since then. In the past
decade, the emergence of commercially prepared
hemostatic agents has been unsurpassed. In today’s
OR, surgeons have a broad range of products to
help control bleeding. Selecting the right product
for the right procedure and using it correctly has
increasingly become a challenge given the current
depth and breadth of products currently available in
the marketplace.
Effective management of bleeding during operative and other invasive procedures is a critical
factor in achieving optimal patient outcomes. It is
important for the perioperative nurse to understand
the clotting cascade, clinical indications for using
hemostatic agents, the types of hemostatic agents
http://dx.doi.org/10.1016/j.aorn.2014.01.024
132 j AORN Journal August 2014
Vol 100 No 2
Ó AORN, Inc, 2014
HEMOSTATIC AGENTS: A GUIDE TO SAFE PRACTICE
available and their actions, and the potential limitations or complications of these products. In addition, understanding the importance of blood and
blood product management is imperative.
Today, there is increased focus on cost containment because of changes in reimbursement to health
care providers as well as a growing elderly population in the United States with higher acuity levels
and greater use of medical and surgical services.2
These factors are some of the primary drivers that
push providers to look for more efficient and
effective ways to provide surgical care, less costly
alternatives to the traditional surgical procedures,
and ways to use products and supplies more effectively, including blood, blood products, and
other hemostatic agents.
In the United States, operative and other invasive procedures account for the transfusion of more
than 15 million units of packed red blood cells per
year.3 In addition to the knowledgeable use of hemostatic agents, health care providers are encouraged to reduce the use of blood and blood products
because of the evidence that limiting their use improves patient outcomes and reduces the incidence
of surgical site infections, costs, and a patient’s risk
of complications.4 In addition to these concerns and
reasons for reducing blood product usage, there are
also concerns that the supply of blood donors is
declining and the blood supply itself is diminishing
despite a heavy emphasis on blood conservation
measures.3
HEMOSTASIS
During any operative or invasive procedure, surgeons frequently need to achieve some level of
hemostasis. Although the need to control brisk
arterial bleeding is obvious, surgeons also need to
control oozing from small vessels. For example,
Spahn et al5 reported that 50% of trauma-related
deaths are the result of uncontrolled bleeding.
Generally, bleeding from an arterial source can be
controlled by mechanical means, such as direct
pressure with sponges or gauze or the application
of sutures, staples, or clips. Bleeding that is more
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difficult to control occurs when the patient experiences diffuse venous bleeding. This can result in
coagulopathy, which develops because the body is
unable to compensate for the rapid consumption
and dilution of platelets and coagulation factors
during an emergent bleeding episode.6 Therefore, it
is imperative to control bleeding and achieve hemostasis as quickly as possible to avoid the complications of coagulopathy. When a vessel is
damaged either by accident (eg, trauma) or by
intention (eg, surgical incision), basic mechanisms
occur naturally to promote hemostasis: vasoconstriction, the formation of a platelet plug, and
coagulation.7
Vasoconstriction
After vessel injury occurs, vasoconstriction is
the body’s first response to mechanically slow
bleeding. In the vasoconstriction phase, the body
attempts to slow the flow of blood by both local and
systemic mediators. At the local level, thromboxane is released to aid in vessel constriction. The
adrenal glands also release epinephrine, which acts
systemically to increase vasoconstriction and slow
bleeding.8 After vessel constriction, the body responds to quickly form a platelet plug. 7 This
platelet plug is temporary and unstable, and a fibrin
clot needs to form to provide lasting hemostasis.
Platelet Plug Formation
In this phase of hemostasis, circulating thrombin
causes the release of additional platelets that
initiate the formation of a loose platelet plug.
Fibrinogen, a component of the clotting mechanism
or cascade, is responsible for the clumping of
platelets, which adhere to collagen fibers and
release chemicals such as adenosine diphosphate.
The platelets also release other mediators (eg, serotonin, phospholipids, lipoproteins, other proteins)
that are important in the clotting cascade. The
platelet plug acts as a temporary measure to stem
the flow of blood in the injured vessel. Although
the platelet plug is important, its action is to seal
the tear rather than occlude the vessel lumen.3
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Unfortunately, platelet plugs are not effective in
controlling hemorrhage from large vessels, and it is
then that the body’s coagulation mechanisms must
be activated to form a permanent fibrin clot.3
Coagulation
The third phase, coagulation, is a complex bodily
response that involves multiple factors and processes. Coagulation is the transformation of liquid
blood into a gelatin-like substance (ie, a clot).
Approximately a dozen clotting factors normally
exist as inactive proteins in the circulating blood.
An injury to a vessel causes these circulating proteins to be activated. The activation of these clotting factors is sequential in nature; when the first
factor is activated, it automatically causes subsequent factors to be activated in a very specific order.9 This process is known as the clotting cascade
and eventually a clot is formed, which seals the
injured vessel.
CLOTTING CASCADE
The clotting cascade is composed of intrinsic and
extrinsic pathways, and the key mediator of both
pathways is thrombin. Thrombin is derived from an
inactive substance called prothrombin. The clotting
cascade pathways, while triggered by two different
mechanisms, act synchronously. Both of these pathways are complex and merge to create what is
known as the common pathway of hemostasis, the
end product of which is the formation of a fibrin
clot.4 An illustration of the clotting cascade is
available in the article by Overbey et al10 that appears in this issue of AORN Journal.
Intrinsic Pathway
During normal blood flow, inactivated coagulation
proteins circulate in the blood. Under normal circumstances, blood flows briskly and moves these
proteins through the vessels. The lining of the blood
vessels (ie, the endothelium) does not contain
thrombogenic tissue factor or collagen, and it promotes blood flow rather than coagulation.4 The
intrinsic pathway to activate the clotting factors in
134 j AORN Journal
the blood is not initiated from a vessel injury and
can be triggered by blood stasis (eg, deep vein
thrombosis, thromboembolism). When the intrinsic
pathway is activated, it triggers activation of factors
XIIa, XIa, IXa, and Xa in combination with calcium in the blood to initiate coagulation.
Extrinsic Pathway
Damage outside a vessel wall also can activate
a cascade of clotting factors. When the vessel’s
subendothelial connective tissues are exposed to
the escaping blood, they stimulate the activation of
tissue thromboplastin, which causes factor X to be
activated. It is at this point that both the intrinsic
and extrinsic factors converge into the common
pathway. Whenever either pathway is initiated,
the basic response is the exposure of platelets to
collagen, which causes an initial clot to form. It is
important to note that the clotting cascade begins
sooner when the extrinsic pathway is initiated because it bypasses some of the steps required for the
intrinsic pathway process to occur.4
Common Pathway
The common pathway of the coagulation cascade
occurs when the intrinsic and extrinsic pathways of
coagulation meet through activation of factor X.
Activated factor X in combination with platelets,
factor V, and calcium convert prothrombin to
thrombin. The role of thrombin in the coagulation
cascade includes the activation of
n
fibrinogen to form a fibrin clot;
n factor XIII to stabilize the clot;
n platelets to assist in sealing the clot; and
n factors V, VII, and XI, which are needed to
stimulate the production of more thrombin
molecules.
This is essential for fibrin strands to form a mesh
and subsequently form a hemostatic plug.4
There are many factors involved in the clotting
cascade (Table 1). Of these elements, one of the
key factors in achieving hemostasis through both
normal body responses and surgical intervention
HEMOSTATIC AGENTS: A GUIDE TO SAFE PRACTICE
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TABLE 1. Factors Involved in the Clotting Cascade
Fibrinogen
n
n
Prothrombin
n
n
Vitamin K
Calcium
Factor X
Factors XI, XII, XIII
Factor V
Thrombin
Fibrin
Platelets
n
n
n
n
n
n
n
n
n
Intrinsic factors
Extrinsic factors
n
Common factors
n
n
n
Converted to fibrin by fibrinogen
Forms the clot
Converted to thrombin by factor X
Once activated, converts fibrinogen to fibrin
Required to synthesize fibrinogen to fibrin
Promotes platelet aggregation in combination with factors VII, X, XII, and XIII
Combined with other clotting factors converts prothrombin to thrombin
Acts to catalyze other factors in the coagulation process
Another element needed to convert prothrombin to thrombin
Converts fibrinogen to fibrin
Initially forms a loose mesh; in combination with factor XIII facilitates formation of dense fiber mesh
Initially stick to vessel collagen to form a loose plug
Part of the foundation of the fibrin clot along with red blood cells
When an internal vessel injury occurs, factors XIIa, IXa, VIIa, and Xa are activated
When an external vessel injury occurs and the endothelium is disrupted, factors VIIa and X are
activated in combination with calcium and membrane phospholipids
The point where the intrinsic and extrinsic pathways merge or converge through activation of factor X
Subsequently, other elementsdincluding factor V and calcium in combination with plateletsdconvert
prothrombin to thrombin, which causes fibrinogen to form the fibrin clot
(ie, use of commercially prepared hemostatic
agents) is thrombin. Thrombin is the key enzyme in
blood coagulation. It is a sodium-activated protease
and is one of the body’s inherent defense mechanisms. Thrombin was one of the earliest enzymes
identified as a hemostatic agent and was a precursor
to many other vitamin K proteases, such as factors
VIIa, IXa, and Xa, which are critical for the convergence of the intrinsic and extrinsic pathways in
the coagulation cascade.11 Thrombin, whether in its
natural form in the body or as part of a commercially prepared product, has two distinct but opposing functions. It acts to support coagulation
when it converts fibrinogen to a fibrin clot that
holds the platelets in place at the bleed site and
starts the healing process. Conversely, thrombin
acts as an anticoagulant when it activates protein
C.9 For example, when there is no vascular disruption, thrombin improves circulation through its
anticoagulant action.1
TRADITIONAL HEMOSTATIC METHODS
There are three traditional hemostatic methods.
These include mechanical hemostasis via direct
pressure (eg, manual pressure, pressure dressings)
or mechanical products (eg, ligatures [ie, sutures],
staples, clips, clamps), thermal-based energy (eg,
monopolar, bipolar, ultrasonic, laser, argon vessel
sealing), and chemical agents (eg, epinephrine,
vitamin K, protamine, vasopressors).
Mechanical Hemostasis
The most common mechanical approach to control
bleeding is the application of direct pressure to the
bleeding site. Direct pressure is always the first
choice when there is a need to control bleeding; it
is the easiest, simplest, and most cost-effective
method of hemostasis. Direct pressure can be
applied manually or with pressure dressings.
Other mechanical hemostasis methods, such as
sutures, staples, and vascular clips or clamps, also
can be used. Sutures, clips, or ligatures offer a
reasonably easy and cost-effective method to control bleeding; however, the practitioner needs to
understand that the physical configuration of the
product being used may have different reactions in
the patient’s body. Some other considerations when
choosing a product are ease of use (ie, how easy the
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item is to handle) and whether the product will
achieve the desired hemostasis over time. Staples
and clips, which are foreign bodies, increase the
possibility of a foreign body reaction or improper
placement. Another factor to consider is the site of
the bleeding. Although arterial bleeding is more
challenging to control given the volume of blood
involved, arteries are generally easier to control
than diffuse capillary bleeding because of their size
and accessibility. Diffuse capillary bleeding often
involves large, hard-to-reach areas, especially in
minimally invasive procedures. Unfortunately,
mechanical methods are not always practical or
effective, depending on the severity and location of
the bleeding; in addition, although effective for
most bleeding, none of the mechanical methods
may be effective if the patient has a coagulopathy
or has been on anticoagulant medication.12
Thermal-Based Energy
In addition to pressure or other mechanical methods
of hemostasis, surgeons often use thermal energy to
achieve hemostasis. Although the most common
thermal energy application is monopolar electrosurgery, other thermal adjuncts include bipolar
cautery, lasers, vessel sealing devices, ultrasonic
waves, and argon-enhanced coagulation. Generally,
these methods are cost-effective; however, these
approaches may be ineffective on specific bleeding
sites, such as bone, friable tissue, or areas with
diffuse capillary bleeding.3,4 Energy-based hemostasis also carries the potential risk of destroying
healthy tissue and causing burns to adjacent tissue
because of stray currents.3
normal body coagulation mechanisms if they are
not administered correctly.4
TOPICAL HEMOSTATIC AGENTS
When traditional hemostatic methods (eg, mechanical, thermal, chemical) fail to achieve hemostasis, a wide variety of topical hemostatic agents
are available for use. The ideal hemostatic agent
requires ease of use, but it also must be safe, effective, and cost-effective and have US Food and
Drug Administration (FDA) approval. From a
safety perspective, the products need to be free
of infectious diseases and carcinogens, and they
should not have the potential to create immune
reactions in the patient.2
The products must work for the clinical indication for which they are approved, and the surgeon
must use the products according to the clinical
needs of the patient. For instance, using a hemostatic agent as a first response to a bleeding situation may not be ideal if other commonly used
measures (eg, pressure, sutures, thermal energy)
have not been tried. The products must also be easy
to access, prepare, and use. When there is significant bleeding, it is important that the RN circulator
can deliver the sterile product to the field efficiently. For a product to be cost-effective involves
both its acquisition cost and the amount of product
needed to achieve hemostasis. The RN circulator
can help by selecting the correct size of the product needed.
Generally, topical hemostatic agents are assigned
to one of five major groups:
n
Chemical Agents
The use of chemical agents is a third method that
surgeons often use for achieving hemostasis. These
agents include epinephrine, vitamin K, protamine,
and vasopressors. Although they are sometimes
effective, the disadvantages of using these products
are their potential effects on the natural clotting
cascade. Although the role of chemical agents is to
enhance hemostasis, they can negatively affect the
136 j AORN Journal
passive (ie, mechanical) agents (eg, oxidized
regenerated cellulose, beeswax),
n active agents (eg, bovine thrombin, pooled
human thrombin, recombinant thrombin),
n flowables (eg, bovine gelatin particles, human
thrombin, porcine gelatin particles with or without pooled human or recombinant thrombin),
n fibrin sealants (eg, human plasma-derived fibrin
sealants, the patient’s own plasma combined
with bovine collagen and thrombin, the patient’s
HEMOSTATIC AGENTS: A GUIDE TO SAFE PRACTICE
own plasma used to create fibrinogen and
thrombin), and
n adhesives (eg, skin sealants, synthetic tissue
sealants, glutaraldehydes, polyethylene glycol
polymers).
All of the products have unique properties, applications, and safety considerations. For example,
fibrin sealants require the presences of fibrin to be
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effective. Adhesives also provide hemostasis but
have different properties and applications than
other hemostatic agents and do not require a blood
component to be present for activation.3,13 Because
hemostatic agents act in different phases of the
coagulation cascade, it is important for the perioperative nurse, as the patient’s advocate, to be
knowledgeable about the products he or she is
delivering to the surgeon. Table 2 provides a broad
TABLE 2. Commercially Prepared Hemostatic Agents
Category
Passive (ie, mechanical)
Type
Porcine gelatin
Commercial name
n
n
Bovine collagen
n
n
n
n
Oxidized regenerated cellulose
n
n
n
Polysaccharide spheres
Beeswax, paraffin, isopropyl palmate
n
n
n
n
Active
Flowable
Fibrin sealant
Bovine thrombin
Pooled human thrombin
Recombinant thrombin
Bovine gelatin and pooled human thrombin
Bovine gelatin (and/or thrombin)
Pooled human plasma
n
n
n
n
n
n
n
Adhesives
Patient’s own plasma and bovine thrombin
Patient’s own plasma
Polyethylene glycol hydrogels (PEG)
PEG þ trilysine amine
PEG þ human serum albumin
Liquid monomers
n
n
n
n
n
n
n
n
Synthetic tissue sealants
Glutaraldehyde cross-linked with bovine albumin
n
n
GELFOAMÒ
SURGIFOAMÒ powder and sponge
AviteneTM
HelistatÒ
INSTATÒ
UltrafoamTM
SURGICELÒ
SURGICEL FIBRILLARTM
SURGICEL NU-KNITÒ
SURGICEL SNoWTM
AristaTM
VitasureÒ
Bone wax
Thrombin-JMIÒ
EVITHROMÒ
RecothromÒ
FLOSEALÒ
SURGIFLOÒ
EVICELÒ
TISSEELTM
VitagelTM
CryoSealÒ
CoSealTM
DuraSealTM
ProgelÒ
DERMABONDÒ
LiquiBandÒ
SurgiSealÒ
OMNEXTM
BioGlueÒ
GELFOAM and FLOSEAL are registered trademarks and TISSEEL and CoSeal are trademarks of Baxter Corporation, Deerfield, IL. SURGIFOAM, INSTAT,
SURGICEL, SURGICEL NU-KNIT, EVITHROM, SURGIFLO, EVICEL, and DERMABOND are registered trademarks and SURGICEL FIBRILLAR, SURGICEL
SNoW, and OMNEX are trademarks of Ethicon, Johnson & Johnson, Inc, Somerville, NJ. Avitene and Ultrafoam are trademarks of Davol/Bard Company,
Warwick, RI. Helistat is a registered trademark of Integra Life Sciences Corporation, Plainsboro, NJ. Arista is a trademark of Medafor, Minneapolis, MN.
Vitasure is a registered trademark of Orthovita, Malvern, PA. Thrombin-JMI is a registered trademark of Pfizer, New York, NY. Recothrom is a registered
trademark of The Medicines Company, Parsippany, NJ. Vitagel is a trademark of Stryker, Malvern, PA. CryoSeal is a registered trademark of ThermoGenesis
Corporation, Rancho Cordova, CA. DuraSeal is a trademark of Covidien, Boulder, CO. Progel is a registered trademark of NeoMend, Irvine, CA. LiquiBand is
a registered trademark of Cardinal Health, Dublin, OH. SurgiSeal is a registered trademark of Adhezion Biomedical, Wyomissing, PA. BioGlue is a registered
trademark of CryoLife, Kennesaw, GA.
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overview (but is not an all-inclusive list) of many
of the products in these groups. The important
information for the perioperative nurse is which
products fall into which category.
Passive Hemostatic Agents
Passive hemostatic agents also are referred to as
mechanical agents (Table 3). Although they are
relatively inexpensive, easy to prepare, and have no
special storage requirements, most of these products should not be used in confined areas of the
body where swelling would cause problems. They
are effective for areas of minimal bleeding, so they
generally are not effective for diffuse capillary or
brisk arterial bleeding. They require the presence of
blood for activation and do not affect or interrupt
the clotting cascade. Passive hemostatic agents
have been used since the 1940s and were the first
generation of commercially prepared hemostatic agents.14
Active Hemostatic Agents
Active hemostatic agents (Table 4) provide hemostasis within 10 minutes and control bleeding better
than passive agents alone.4 Currently, there are three
available active agents that are based on thrombin
(ie, pooled human thrombin, bovine thrombin, recombinant thrombin). Their function is to provide a
concentrated thrombin that is capable of converting
fibrinogen to a fibrin clot, which provides a framework for platelet aggregation and thrombus formation at the site of the injury.9 The rate of clot
formation is directly proportional to the concentration of thrombin. Although there are products with
TABLE 3. Passive (ie, Mechanical) Hemostatic Agents
Indication
Composition/origin
Minimal
bleeding
Porcine gelatin
Clinical considerations
n
n
n
n
Minimal
bleeding
Bovine collagen
n
n
n
n
n
n
Minimal
bleeding
Oxidized regenerated
cellulose
n
n
n
n
n
n
Minimal
bleeding
Polysaccharide
spheres
Minimal
bleeding
Beeswax, paraffin,
isopropyl palmate
n
n
n
n
n
n
n
Do not inject
Do not use in the presence of infection
Risk of swelling
Risk of granuloma/abscess formation
Do not inject
Do not use in the presence of infection
Risk of swelling
Risk of granuloma/abscess formation
May contribute to adhesion formation
Sticks to the surgeon’s gloves and instruments
Do not inject
Broad indications for use
Bactericidal
Nonhuman/animal source
No preparation needed
Multiple thicknesses
Do not inject
Nonhuman/animal source
No preparation needed
Do not inject
Limited resorption
Inhibits bone regeneration
Increases infection risk
Commercial name
n
n
GELFOAMÒ
SURGIFOAMÒ powders
and sponges
n
AviteneTM sponge and
powder
HelistatÒ
HeliteneÒ
INSTATÒ
UltrafoamTM
SURGICELÒ
SURGICEL FIBRILLARTM
SURGICEL NU-KNITÒ
SURGICEL SNoWTM
n
AristaTM
n
Bone wax
n
n
n
n
n
n
n
n
GELFOAM is a registered trademark of Baxter Corporation, Deerfield, IL. SURGIFOAM, INSTAT, SURGICEL, and SURGICEL NU-KNIT are registered
trademarks and SURGICEL FIBRILLAR and SURGICEL SNoW are trademarks of Ethicon, Johnson & Johnson, Inc, Somerville, NJ. Avitene and Ultrafoam
are trademarks of Davol/Bard Company, Warwick, RI. Helistat is a registered trademark of Integra Life Sciences Corporation, Plainsboro, NJ. Helitene is a
registered trademark of Colla-Tec, Inc, Plainsboro, NJ. Arista is a trademark of Medafor, Minneapolis, MN.
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TABLE 4. Active Hemostatic Agents
Indication
Composition/origin
Localized and
Bovine thrombin
diffuse bleeding
Clinical considerations
n
n
n
n
n
Localized and
Pooled human thrombin
diffuse bleeding
n
n
n
Localized and
Recombinant thrombin
diffuse bleeding
n
n
Commercial name
Broad indications for use
Thrombin-JMIÒ
Should not be used in patients with bovine allergies
Can stimulate antigen formation and interrupt the
clotting cascade
Has potential for infection transmission
Has a “black box” warning
Risk of swelling
EVITHROMÒ
Do not use in patients with allergies to human
blood products
Unknown potential for infection transmission and
interruption of the clotting cascade
RecothromÒ
Commercially manufactured
Clinical studies to date have not demonstrated that
this product produces antigens or affects the
clotting cascade
Thrombin-JMI is a registered trademark of Pfizer, New York, NY. EVITHROM is a registered trademark of Ethicon, Johnson & Johnson, Inc, Somerville, NJ.
Recothrom is a registered trademark of The Medicines Company, Parsippany, NJ.
lower thrombin concentrations that claim to be as
effective as those with higher concentrations (1,000
IU/mL), this should be a consideration in product
selection because higher concentrations yield better
hemostasis (ie, the speed with which thrombin clots
the blood depends on the concentration).3
Safety is a major consideration for thrombin
products, because thrombin acts at the end of the
clotting cascade and its interaction is negatively
affected by coagulopathies, such as clotting factor
deficiencies or platelet malfunction. These agents
are logical choices for patients receiving antiplatelet
or anticoagulant medications. Thrombin also has
several other functions within the body. It can
cause smooth muscle to constrict, activate platelets,
and aggregate platelets at an injury site. It attracts
neutrophils and fibroblasts and induces the formation of new cells for tissue and vascular repair and
remodeling.1
Bovine and recombinant thrombin products are
provided at room temperature but must be reconstituted with saline. Human pooled thrombin comes
fully mixed but frozen and requires thawing before
use; after thawing, it can be stored in a refrigerator
for up to 30 days. The surgeon can apply all of the
active hemostatic products directly to bleeding
surfaces or by using a spray applicator. These
products can be used alone or in combination with
an absorbable gelatin sponge or powder. There are
commercially manufactured kits that do not require
refrigeration and contain a porcine gelatin combined with a lyophilized human pooled thrombin.
The cost of these products is intermediate and
varies by manufacturer.
Perioperative nurses should understand what
happens at the vascular interface when thrombin is
being used and how this determines the efficacy of
the product. The amount of thrombin in the wound
can be affected or inhibited by factors such as hemodilution, absorptive sponges, wound irrigation,
or continuous wiping or blotting. Inhibitors such
as antithrombolytic hormone also can affect the
amount of thrombin in the wound by trapping
thrombin within the clot as the clot forms. The most
effective hemostasis occurs when the thrombin
mixes freely with the blood as soon as it reaches the
surface of the vessel injury.4
It is also important to understand that all thrombins are not created equal. Perioperative nurses need
to understand how the products work and their
AORN Journal j 139
August 2014 Vol 100 No 2
reaction in the body both locally and systemically.
Because thrombin is a component in several of the
other hemostatic agents, this is important for perioperative nurses to understand when providing
hemostatic agents during an operative or other
invasive procedure.
Thrombin is a powerful product that is effective
in controlling both arterial and capillary bleeding. It
is important to discuss what alternative products
might be used that are safer and why. The perioperative nurse must be familiar with the thrombinbased products used, know their origin, and
understand the patient implications. The perioperative nurse has a responsibility to help team
members determine the appropriate product selection based on the patient’s history. Team members
should discuss all pertinent patient information
before the procedure. The nurse should know
whether the patient
n
n
n
n
n
has a history of allergies or reactions to any
hemostatic agents or a history of allergies to
bovine or porcine products,
has a religious or dietary reason for avoiding
hemostatic agents,
uses anticoagulant or antiplatelet medications
(eg, aspirin, other nonsteroidal antiinflammatory medications) or herbal supplements (eg, vitamin E, bilberry, Ginkgo, garlic,
cayenne) that might affect clotting mechanisms,
has a family history of bleeding disorders (eg,
hemophilia, sickle cell anemia), or
is anemic.
It is important for the nurse to assess the patient for
bleeding gums, easy bruising, excessive superficial
bleeds, or severe nosebleeds. The nurse also should
know whether the patient has a history of renal or
hepatic disease because both the kidneys and liver
secrete hormones that affect clotting mechanisms.
If these organs are not functioning correctly, this
can impede the coagulation process.
In addition, the nurse should understand what the
proposed procedure is; the patient’s potential for
bleeding; and the results of the patient’s coagulation
140 j AORN Journal
CAMP
profile, blood type, and cross-match. A signed consent for administration of blood or blood products
or a signed refusal should be verified and, if appropriate and consent for blood has been given, the
nurse should verify that there is autologous blood
product available and determine whether the donation has been verified. He or she should ascertain
whether there are plans for perioperative blood
salvage; if the patient is aware of this; and whether
the patient has any cultural, ethnic, or religious considerations for administration of blood or blood
products. This all should be discussed with the surgical team before the patient is brought to the OR.
Flowable Hemostatic Agents and Flowable
Products
Flowable hemostatic agents (Table 5) have both an
active and a passive component. The action of these
agents is to block blood flow and convert fibrinogen
to fibrin at the bleeding site. The passive component of these agents is a bovine or porcine gelatin
matrix; thrombin may be included as a component
or may be added as an individual item. These agents
produce a pasty substance that can be introduced
directly on a bleeding area, such as the liver or
kidney. These products are commonly used in spine
surgery; the surgeon lays the agent along the gutters
of the spine to reduce bleeding.1
Flowable products are composite hemostatic
agents that use microfibrillar collagen to facilitate
tissue healing and achieve hemostasis. Microfibrillar collagen is derived from bovine or porcine
sources and requires a “wet” field to be effective,
because the presence of blood has mechanical
properties that slow or obstruct the flow of blood
and thrombin to facilitate the conversion of fibrinogen into fibrin. These products conform easily to
the topography of the bleeding area and are easy to
apply. Flowable products require reconstitution,
and their cost is generally higher than that of mechanical or active products. The safety consideration with these products is that their swelling
properties require the surgeon to remove all excess
product after hemostasis is achieved.2
HEMOSTATIC AGENTS: A GUIDE TO SAFE PRACTICE
www.aornjournal.org
TABLE 5. Flowable Hemostatic Agents
Indication
Localized
bleeding
Composition/origin
Bovine gelatin particles and
human thrombin
Clinical considerations
n
n
n
n
n
n
Localized
bleeding
Porcine gelatin particles
with or without thrombin
n
n
n
n
n
n
n
Commercial name
Should not be used in patients with bovine allergies FLOSEALÒ
Risk of swelling
Has potential for infection transmission
Is approved for use in all specialties except
ophthalmology
Cannot be used with blood salvage devices or
cardiopulmonary bypass equipment
Absorbs in 6 to 8 weeks
Can be used in combination with RecothromÒ
SURGIFLOÒ
Should not be used in patients with porcine allergies
Risk of swelling
Has potential for infection transmission when
human thrombin is used
Is approved for use in all specialties except
ophthalmology
Cannot be used with blood salvage devices or
cardiopulmonary bypass equipment
Absorbs in 4 to 6 weeks
FLOSEAL is a registered trademark of Baxter Corporation, Deerfield, IL. Recothrom is a registered trademark of The Medicines Company, Parsippany, NJ.
SURGIFLO is a registered trademark of Ethicon, Johnson &Johnson, Inc, Somerville, NJ.
Fibrin Sealants
Fibrin sealants (Table 6) come in three types: fibrin
sealants, polyethylene glycol (PEG) polymers, and
albumin with glutaraldehyde. These products form
a barrier that is impervious to most liquids. Generally, sealants contain both fibrinogen and thrombin.
When the concentrated fibrinogen and thrombin are
mixed together, they create a fibrin clot that works
by increasing the rate of blood clot formation at the
injury site. The product consistency is a thin liquid
that can be applied as an aerosol spray. Generally,
surgeons use these products in combination with a
flowable agent. These are powerful, unique products
and have separate FDA approval as hemostats, sealants, and adhesives that are indicated for bleeding
control in surgical patients.2
Challenges with these products include reconstitution that may require a trained technician; when
using the patient’s blood to reconstitute the product,
often the concentration of fibrinogen may be low in
the patient’s own blood (eg, fibrinogen concentrations determine the strength of the clot). There is a
learning curve for surgeons who use these products,
and clinical concerns include blood-related reactions
(eg, antibody formation as pooled human thrombin is
a major component).4
One product classified in this category, ArtissTM,
is not a hemostatic agent. The most common clinical application for this product is to use it to adhere
autologous skin grafts to surgically prepared wound
beds in both children and adults with burns. The
cost is similar to that of other sealants. This product
is gas activated and frozen, and it must be thawed.
The product can be used up to 14 days after thawing
at room temperature. This product is not indicated as
an adjunct to other hemostatic agents because it
mimics the last stage of the coagulation cascade.15
TachoSilÒ is an absorbable fibrin sealant patch.
This product controls local, diffuse bleeding but
does not control vigorous bleeding. It can be used as
an adjunct to flowables and in patients with coagulopathies or insufficient fibrinogen as well as for skin
grafts, dural sealing, bone repairs, splenic injuries,
colostomies, and reoperative cardiac surgeries.4
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August 2014 Vol 100 No 2
TABLE 6. Fibrin Sealants
Indication
Composition/origin
Localized and
diffuse bleeding
Human plasmaederived
fibrin sealant
Clinical considerations
n
n
n
n
n
Localized and
diffuse bleeding
Patient’s own plasma
with bovine collagen
and thrombin
n
n
n
Localized and
diffuse bleeding
Patient’s own plasma to
create fibrinogen and
thrombin
n
n
n
n
Contains pooled human plasma
fibrinogen and thrombin
Does not need active blood or bleeding;
has derived fibrinogen for activation
Should not be used with blood salvage
devices or cardiopulmonary bypass
equipment
Has potential for infection transmission
Has risks of air embolus, tissue rupture,
and gas entrapment
Should not be used in patients with
bovine allergies
Has potential for swelling, infection
transmission, foreign body reaction,
and immunologic and coagulation risks
Is approved for use in all specialties
except ophthalmology and
neurosurgery
Requires a trained technician for
processing
Should not be used in patients with
acquired or hereditary hematologic or
coagulation disorders
May not be used for patients on active
anticoagulants or nonsteroidal agents
Clinical studies indicate less effective
clot stability than commercially prepared products
Commercial name
n
TISSEELTM
EVICELÒ
n
VitagelTM
n
CryoSealÒ
n
TISSEEL is a trademark of Baxter Corporation, Deerfield, IL. EVICEL is a registered trademark of Ethicon, Johnson & Johnson, Inc, Somerville, NJ. Vitagel is a
trademark of Stryker, Malvern, PA. CryoSeal is a registered trademark of ThermoGenesis Corporation, Rancho Cordova, CA.
Adhesives
Typically, the commercial products approved as
adhesives (ie, synthetic sealants) are divided into
four classes (Table 7):
n
cyanoacrylates,
synthetic skin sealants and tissue sealants,
n glutaraldehydes, and
n PEG polymers.
n
They vary in strength and surgical applications; however, each product basically glues tissue together. The
adhesive products have a variety of clinical applications and continue to evolve. The products contain
minimal amounts of thrombin but have other components that require careful consideration given
142 j AORN Journal
their chemical interactions and effect on body tissues. For instance, they cannot be used
n
in high tension areas such as joints because they
will not seal as desired or
n on infected or gangrenous tissue, decubiti, or
poorly healing wounds because they contain
formaldehyde.2
CONCLUSION
This article has not covered all products currently
available or all of the potential complications or
untoward events that may occur when using hemostatic agents. Hemostatic agents are powerful
tools in today’s perioperative setting. They allow
Cyanoacrylates
Synthetic skin
sealants
Synthetic tissue
sealants
Glutaraldehydes
Polyethylene glycol
(PEG) polymers
PEG polymers
PEG polymers
n
n
n
n
n
Localized
applications
Localized
applications
Localized
applications
Localized
applications
Localized
applications
Localized
applications
Indication
PEG polymer and a human blood product
PEG polymer and human serum
albumin combine to form a gel
Polyethylene glycol hydrogels that
mix and cross-link at the wound site
Glutaraldehyde linked with bovine
albumin
Monomers form polymers to create
a synthetic tissue sealant
Liquid monomers
Composition/origin
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
n
Do not inject
Used as a replacement for sutures, primarily on facial,
extremity, and torso wounds
Attains the strength of healed tissue after 7 days
Do not inject
Used as an adjunct for vascular reconstruction
Mechanically seals a suture or graft line
Does not replace sutures, staples, or mechanical closure
Do not inject
Commonly used in vascular procedures for sealing
holes around staple lines
Good agent for arterial bleeding
Hypersensitivity is a concern
Is never absorbed and cannot be reapplied to the same
area in the future
Do not inject
Can prevent pericardial adhesions
Good for vascular reconstructions
Noninflammatory
Infection rates are minimal
Should not be used in closed spaces because of product
swelling risk
Do not inject
Aid to prevent cerebrospinal fluid leak
Seal dural incisions
Sprayed on
Contains blue dye for easier identification
Do not inject
Seals air leaks on lung tissues after the tissue has been
sutured or stapled
Clinical considerations
n
n
n
n
n
n
n
n
ProgelÒ
DuraSealTM
CoSealTM
BioGlueÒ
OMNEXTM
DERMABONDÒ
SurgiSealÒ
LiquiBandÒ
Commercial name
DERMABOND is a registered trademark and OMNEX is a trademark of Ethicon, Johnson & Johnson, Inc, Somerville, NJ. SurgiSeal is a registered trademark of Adhezion Biomedical, Wyomissing, PA. LiquiBand is a
registered trademark of Cardinal Health, Dublin, OH. BioGlue is a registered trademark of CryoLife, Kennesaw, GA. CoSeal is a trademark of Baxter Corporation, Deerfield, IL. DuraSeal is a trademark of Covidien,
Boulder, CO. Progel is a registered trademark of NeoMend, Irvine, CA.
n
n
Class
TABLE 7. Adhesives (ie, Synthetic Sealants)
HEMOSTATIC AGENTS: A GUIDE TO SAFE PRACTICE
www.aornjournal.org
AORN Journal j 143
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August 2014 Vol 100 No 2
surgeons to control bleeding during operative and
other invasive procedures and minimize the need
for blood replacement. These products enhance the
view of the surgical field, avoid damage to major
fragile organs, and can shorten procedure times.
They are, however, products that need to be used
appropriately. The perioperative nurse needs to be
knowledgeable about the use of hemostatic agents;
understand what class the agent being requested
falls into; and whether the agent is FDA approved,
clinically cost-effective, and the most appropriate
product for the current situation. This requires
vigilance and knowledge on the part of the perioperative nurse to help ensure that the patient is
receiving care in a safe environment.
5.
6.
7.
8.
9.
10.
11.
12.
Editor’s notes: Artiss is a trademark and TachoSil
is a registered trademark of Baxter Corporation,
Deerfield, IL.
AORN does not endorse any commercial company’s products or services. Although any commercial products that may be referenced in this
material are expected to conform to professional
medical/nursing standards, inclusion of this material does not constitute a guarantee or endorsement
by AORN of the quality or value of such product or
of the claims made by its manufacturer.
References
1. Lew W, Weaver F. Clinical use of topical thrombin as a
surgical hemostat. Biologics. 2008;2(4):593-599.
2. Spotnitz W, Burks S. Hemostats, sealants and adhesives:
components of the surgical toolbox. Transfusion. 2008;
48(7):1502-1516.
3. St Peter E, Kneedler J. Hemostasis [AORN Independent
Study Guide]. Presented at: AORN Congress; March 2-7,
2013; San Diego, CA.
4. Moss R. Management of Surgical Hemostasis: An Independent Study Guide. Denver, CO: AORN, Inc; 2013.
144 j AORN Journal
13.
14.
15.
http://www.aorn.org/search.aspx?searchtext¼Management
%20of%20Surgical%20Hemostasis:%20An%20Indepe
ndent. Accessed February 26, 2014.
Spahn DR, Bouillon B, Cerny V, et al. Management of
bleeding and coagulopathy following major trauma: an
updated European guideline. Crit Care. 2013;17(R76):
1-53.
Bollinger D, Gorlinger K, Tanaka K. Pathophysiology
and treatment of coagulopathy in massive hemorrhage
and hemodilution. Anesthesiology. 2010;113(5):1-26.
Samudrala S. Topical hemostatic agents in surgery: a
surgeon’s perspective. AORN J. 2008;88(3):S2-S11.
Kaur P, Basu S, Kaur G, Kaur R. Transfusion protocol
in trauma. J Emerg Trauma Shock. 2011;4(1):103-108.
Ham SW, Lew WK, Weaver FA. Thrombin use in surgery: an evidence-based review of clinical use. J Blood
Med. 2010;1:135-142.
Overbey DM, Jones EL, Robinson TN. How hemostatic
agents interact with the coagulation cascade. AORN J.
2014;100(2):148-159.
Di Cera E. Thrombin. Mol Aspects Med. 2008;29(4):
203-254.
Spotnitz W, Burks S. Hemostats, sealants, and adhesives
II: update as well as how and when to use the components
of the surgical toolbox. Clin Appl Thromb Hemost. 2010;
16(5):497-514.
Garcia-Roig M, Gorin MA, Castellan M, Ciancio G.
OMNEX Surgical Sealant in the extracorporeal repair
of renal artery aneurysms. Ann Vasc Surg. 2011;25(8):
1141-1148.
Sundaram C, Keenan A. The evolution of hemostatic
agents in surgical practice. Indian J Urol. 2010;26(3):
374-378.
Australian Public Assessment Report for Fibrin Sealant.
Proprietary Product name: Artiss; Sponsor: Baxter Healthcare Pty Ltd. Commonwealth of Australia: Australian
Department of Health and Ageing, Therapeutic Goods
Administration; October 2010:1-53.
Margaret A. Camp, MSN, BSN, RN, is a
perioperative consultant in Aurora, CO. Having
received money for the development of education
programs and for travel, accommodations, and
meeting expenses from Ethicon, Ms Camp has
declared an affiliation that could be perceived
as posing a potential conflict of interest in the
publication of this article.
EXAMINATION
CONTINUING EDUCATION
Hemostatic Agents: A Guide to Safe
Practice for Perioperative Nurses
3.0
www.aorn.org/CE
PURPOSE/GOAL
To provide the learner with knowledge specific to the effective management of
bleeding during operative and other invasive procedures and the use of hemostatic
agents to augment the patient’s natural clotting abilities.
OBJECTIVES
1. Discuss why hemostasis is needed during operative and other invasive procedures.
2. Describe the basic mechanisms that naturally occur to promote hemostasis.
3. Discuss the clinical indications for the use of hemostatic agents.
The Examination and Learner Evaluation are printed here for your convenience. To receive continuing education credit, you must complete the online
Examination and Learner Evaluation at http://www.aorn.org/CE.
QUESTIONS
1.
2.
3.
What percentage of trauma-related deaths are the
result of uncontrolled bleeding?
a. 10%
b. 20%
c. 40%
d. 50%
The inability to control diffuse venous bleeding
can result in a condition known as coagulopathy,
which develops because the body is unable to
compensate for the rapid consumption and dilution of platelets and coagulation factors during an
emergent bleeding episode.
a. true
b. false
The basic mechanisms by which the body
attempts to control bleeding include
1. vasodilation.
2. vasoconstriction.
3. the formation of a platelet plug.
4. coagulation.
Ó AORN, Inc, 2014
a. 1 and 2
c. 2, 3, and 4
b. 1 and 3
d. 1, 2, and 3
4.
Circulating ____________causes the release of
additional platelets that initiate the formation of a
loose platelet plug.
a. prothrombin
b. thrombin
c. fibrinogen
d. lipoproteins
5.
Coagulation is a complex body response
involving multiple factors and processes that
transform liquid blood into a
a. glue-like substance.
b. cement-like substance.
c. gelatin-like substance.
d. fibrin-like substance.
6.
Passive hemostatic agents
1. are relatively inexpensive and easy to
prepare.
2. have no special storage requirements.
August 2014
Vol 100
No 2 AORN Journal j 145
CE EXAMINATION
August 2014 Vol 100 No 2
should not be used in confined areas of the
body under most circumstances.
4. are effective for areas of minimal bleeding.
5. are effective for diffuse capillary or brisk
arterial bleeding.
6. do not require the presence of blood for
activation and function by interrupting the
clotting cascade.
a. 3, 5, and 6
b. 1, 2, 3, and 4
c. 1, 2, 4, 5, and 6 d. 1, 2, 3, 4, 5, and 6
3.
7.
Hemostasis is provided within 10 minutes by
a. injectable hemostatic agents.
b. active hemostatic agents.
c. topical hemostatic agents.
d. mechanical hemostatic agents.
8.
Safety is a major consideration for thrombin
products, because thrombin acts at the end of the
clotting cascade and its interaction is negatively
affected by coagulopathies, such as clotting factor
deficiencies or platelet malfunction.
a. true
b. false
146 j AORN Journal
9.
The amount of ____________ in a wound can be
affected or inhibited by factors such as hemodilution, absorptive sponges, wound irrigation, or
continuous wiping or blotting.
a. prothrombin
b. fibrinogen
c. lipoproteins
d. thrombin
10.
To safely use thrombin-based products, the perioperative nurse must
1. be familiar with the product’s origin and its
patient implications.
2. know of any patient allergies.
3. be aware of any patient dietary restrictions.
4. know whether the patient uses anticoagulant
or antiplatelet medications or herbal supplements that might affect clotting mechanisms.
5. be aware of any family history of bleeding
disorders.
6. know whether the patient has a history of
kidney or liver disease.
a. 1, 2, 4, and 6
b. 1, 3, and 6
c. 3, 4, 5, and 6
d. 1, 2, 3, 4, 5, and 6
LEARNER EVALUATION
CONTINUING EDUCATION PROGRAM
Hemostatic Agents: A Guide to Safe
Practice for Perioperative Nurses
T
his evaluation is used to determine the extent to
which this continuing education program met
your learning needs. The evaluation is printed
here for your convenience. To receive continuing
education credit, you must complete the online
Examination and Learner Evaluation at http://www
.aorn.org/CE. Rate the items as described below.
OBJECTIVES
To what extent were the following objectives of this
continuing education program achieved?
1. Discuss why hemostasis is needed during operative
and other invasive procedures.
Low 1. 2. 3. 4. 5. High
2. Describe the basic mechanisms that naturally occur
to promote hemostasis.
Low 1. 2. 3. 4. 5. High
3. Discuss the clinical indications for the use of
hemostatic agents.
Low 1. 2. 3. 4. 5. High
CONTENT
4. To what extent did this article increase your
knowledge of the subject matter?
Low 1. 2. 3. 4. 5. High
5. To what extent were your individual objectives met?
Low 1. 2. 3. 4. 5. High
6. Will you be able to use the information from this
article in your work setting? 1. Yes 2. No
Ó AORN, Inc, 2014
3.0
www.aorn.org/CE
7. Will you change your practice as a result of reading
this article? (If yes, answer question #7A. If no,
answer question #7B.)
7A. How will you change your practice? (Select all that
apply)
1. I will provide education to my team regarding
why change is needed.
2. I will work with management to change/
implement a policy and procedure.
3. I will plan an informational meeting with
physicians to seek their input and acceptance
of the need for change.
4. I will implement change and evaluate the
effect of the change at regular intervals until
the change is incorporated as best practice.
5. Other: ________________________________
7B. If you will not change your practice as a result of
reading this article, why? (Select all that apply)
1. The content of the article is not relevant to my
practice.
2. I do not have enough time to teach others
about the purpose of the needed change.
3. I do not have management support to make a
change.
4. Other: ________________________________
8. Our accrediting body requires that we verify
the time you needed to complete the 3.0 continuing education contact hour (180-minute)
program: ________________________________
August 2014
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No 2 AORN Journal j 147