Review Article

Blood-loss Management in Spine

Surgery

Abstract
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Jesse E. Bible, MD, MHS Substantial blood loss during spine surgery can result in increased
Muhammad Mirza, MD patient morbidity and mortality. Proper preoperative planning and
communication with the patient, anesthesia team, and operating room
Mark A. Knaub, MD
staff can lessen perioperative blood loss. Advances in intraoperative
antifibrinolytic agents and modified anesthesia techniques have
shown promising results in safely reducing blood loss. The surgeon’s
attention to intraoperative hemostasis and the concurrent use of local
hemostatic agents also can lessen intraoperative bleeding.
Conversely, the use of intraoperative blood salvage has come into
question, both for its potential inability to reduce the need for
allogeneic transfusions as well as its cost-effectiveness. Allogeneic
blood transfusion is associated with elevated risks, including surgical
site infection. Thus, desirable transfusion thresholds should remain
restrictive.

S ubstantial blood loss can occur

during spine surgery, especially
during revision procedures or surgery
independent of the preoperative
hematocrit
comorbidities.5
level and patient

to manage deformity. Limiting blood The management of blood loss

From the Department of Orthopaedics
and Rehabilitation, Penn State Health
Milton S. Hershey Medical Center,
Hershey, PA.
None of the following authors or any
immediate family member has
received anything of value from or has
stock or stock options held in a
commercial company or institution
related directly or indirectly to the
subject of this article: Dr. Bible,
Dr. Mirza, and Dr. Knaub.
J Am Acad Orthop Surg 2018;26:
35-44
DOI: 10.5435/JAAOS-D-16-00184
Copyright 2018 by the American
Academy of Orthopaedic Surgeons.
loss is of critical importance when
attempting to reduce potential asso-
ciated morbidity and mortality.
Blood loss can result in changes in
physiologic fluid shifts, coagulop-
athy, antibiotic dilution, and the need
for transfusions.1 Red blood cell
transfusion has been shown to sup-
press human T cell proliferation.2
Therefore, it is not surprising that
perioperative allogeneic blood
transfusion has been associated with
postoperative surgical site and uri-
nary tract infections following lum-
bar spine surgery.3,4
The economics of blood loss also
must be considered. Addressing
blood loss during surgery increases
operating room time, and the cost of
transfusion is not insignificant.
Transfusion of a single unit has been
associated with increased lengths of
stay after elective spine surgery,
should begin long before the patient
enters the operating room. It requires
a coordinated effort on the part of the
surgeon, the patient, and the patient’s
other physicians, as well as the
anesthesia team. Surgeons also must
be aware of the additive effect of
continued blood loss after the patient
leaves the operating room and its
effect on patient outcomes and the
cost of care.
Preoperative
Considerations
Medications Taken at Home
Many patients take over-the-counter
and prescription medications and
herbal supplements. Several common
drugs and supplements increase the
risk of bleeding. The clinician should
carefully review the medications

January 15, 2018, Vol 26, No 2 35

Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Blood-loss Management in Spine Surgery
taken by all patients who are sched-
uled for surgery and should dis-
continue those that can promote
bleeding to avoid excessive intra-
operative blood loss.
NSAIDs, Including Aspirin
NSAIDs include aspirin and non-
aspirin inhibitors. The potential
effects of NSAIDs on bleeding varies,
and a schedule for discontinuation by
agent prior to surgery is shown in
Table 1. Nonselective, nonaspirin
NSAIDs such as ibuprofen, naproxen,
ketorolac, and indomethacin revers-
ibly inhibit both cyclooxygenase
(COX) enzymes (COX-1 and COX-2)
and thus indirectly decrease throm-
boxane A2 production, which nor-
mally promotes platelet aggregation.
Selective NSAIDs (eg, celecoxib) target
COX-2 and, as a result, have a lesser
effect on platelet function.
The time at which nonaspirin
NSAIDs should be discontinued before
surgery is not well defined. Some
authors recommend discontinuing
NSAIDs based on drug-specific half-
lives; however, these half-lives corre-
late poorly with actual COX enzyme
inhibition and its effect on platelet
aggregation.6 With most NSAIDs,
such as naproxen and indomethacin,
platelet function normalizes within 3
days of discontinuation.7 When ibu-
profen is stopped, platelet function
returns to normal within 24 hours of
the last dose.8
Aspirin irreversibly inhibits COX-1
and COX-2. The use of aspirin in the
perioperative period may increase
intraoperative blood loss and hem-
orrhagic complications. The large
randomized PeriOperative ISchemic
Evaluation-2 trial of 10,000 non-
cardiac surgery patients found that
perioperative aspirin use significantly
increased the risk of major bleeding
(P = 0.04).9 In a meta-analysis of
49,590 patients, an increased rate of
intraoperative bleeding complica-
tions by a factor of 1.5 was noted
36
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
when low-dose aspirin was contin-
ued.10 The authors of that study also
reported, however, that aspirin ces-
sation was the preceding event in
10% of patients in whom acute
coronary syndrome, stroke, and
peripheral artery occlusion devel-
oped following noncardiac surgery.
The literature on aspirin use in the
setting of spine surgery is limited. A
retrospective single-surgeon com-
parison involving 168 lumbar fusions
did not find a difference in intra-
operative blood loss between patients
never taking aspirin and those stop-
ping aspirin 3 to 7 days before sur-
gery.11 Similarly, Kang et al12 did
not find a difference in surgical
blood loss between lumbar fusion
patients never taking aspirin and
those stopping low-dose aspirin 7
days before surgery.
Spine surgeons can choose to err on
the side of caution by having all
patients stop aspirin 7 days before
surgery out of concern for excessive
intraoperative blood loss as well as the
possibility of epidural hematoma,
especially at the spinal cord level. In
some patients, however, such as those
at risk for aspirin withdrawal syn-
drome (ie, patients experiencing myo-
cardial infarction within the prior 6
weeks or undergoing placement of a
drug-eluting stent within the prior 12
months), stopping aspirin can have
other negative consequences. The
recent literature has demonstrated
risks associated with aspirin with-
drawal in patients with cardiac stents,
as well as potential benefits of its con-
tinuation.13 An observational study of
200 patients with cardiac stents found
no difference in blood loss, transfu-
sions, complications, or 30-day read-
mission rates between patients
remaining on aspirin and patients
stopping aspirin use 5 days before
spine surgery.14 No spinal epidural
hematomas or stent thrombi were
noted in either group, but this fact
could be explained by the rare
occurrence of these events and the
Journal of the American Academy of Orthopaedic Surgeons
overall small sample size. Stent
thrombosis occurs an average of 10
days but as few as 4 days after aspirin
withdrawal. In addition, aspirin
withdrawal may be associated with a
large proportion of all late stent
thrombosis events resulting in acute
coronary syndrome.15
Platelet Inhibitors Other Than
Aspirin
Platelet receptor blockers commonly
are used following cerebrovascular
events, recent acute coronary syn-
dromes, or recent coronary or vas-
cular stent placement. A schedule for
discontinuation by platelet inhibitor
(excluding aspirin) prior to surgery is
shown in Table 1. The obvious con-
cern with premature and/or tempo-
rary cessation of platelet inhibitors is
stent thrombosis, which is a rare but
potentially catastrophic event. Pre-
mature discontinuation of anti-
platelet therapy, including aspirin,
has emerged as one of the most
powerful independent predictors of
stent thrombosis. Elective spine sur-
gery should be postponed until
the minimum period of required
antiplatelet therapy has been com-
pleted, based on the stent type. This
period is commonly 6 weeks for bare
metal stents and 6 to 12 months for
drug-eluting stents. If such a delay is
not possible, then the spine surgeon,
the cardiologist, and the patient must
have a detailed discussion regarding
the risks, benefits, and alternatives.
Currently, the American College of
Cardiology and the American Col-
lege of Chest Physicians suggest
continuing antiplatelet therapy peri-
operatively if surgery is required
during this early period of stent life.
If clopidogrel is discontinued
because of surgical bleeding risk, it
should be stopped 7 days before
elective surgery to allow the recovery
of normal platelet function.16 Clo-
pidogrel is commonly resumed
within 12 to 24 hours after surgery.
 Jesse E. Bible, MD, MHS, et al

Table 1
Drugs and Their Potential Effects on Intraoperative Bleeding
Minimum
Cessation
Time to
Eliminate
Approximate Potential
Plasma Half- Bleeding
Drug Class Drug Life (h) Effect on Bleeding Effect (d)a

NSAIDsb Diclofenac 1–2 Inhibits COX enzymes, inhibiting 1

platelet aggregation (reversibly)
Ibuprofen 2 Inhibits COX enzymes, inhibiting 1
platelet aggregation (reversibly)
Indomethacin 4–10 Inhibits COX enzymes, inhibiting 3
platelet aggregation (reversibly)
Ketorolac 5–7 Inhibits COX enzymes, inhibiting 3
platelet aggregation (reversibly)
Etodolac 6–7 Inhibits COX enzymes, inhibiting 3
platelet aggregation (reversibly)
Sulindac 8–16 Inhibits COX enzymes, inhibiting 3
platelet aggregation (reversibly)
Naproxen 12–17 Inhibits COX enzymes, inhibiting 3
platelet aggregation (reversibly)
Piroxicam 50 Inhibits COX enzymes, inhibiting 7
platelet aggregation (reversibly)
Selective COX-2 inhibitor: 11 Inhibits COX-2 enzymes, 1
celecoxib inhibiting platelet aggregation
(reversibly)
Aspirin 6 Inhibits COX enzymes, inhibiting 7
platelet aggregation
(irreversibly)
Platelet inhibitors Clopidogrel 1 Irreversibly blocks platelet ADP 7
(excluding aspirin)c receptor
Prasugrel 2–15 Irreversibly blocks platelet ADP 7
receptor
Ticagrelor 7–9 Reversibly modifies platelet ADP 5
receptor
Ticlopidine 20–50 Irreversibly blocks platelet ADP 14
receptor
Long-term anticoagulant Warfarin 20–60 Inhibits vitamin K–dependent 5d
agentsd clotting factor synthesis
Enoxaparin (LMWH) 3–5 Binds antithrombin, irreversibly 1d
inactivating thrombin
Unfractionated heparin 0.5–2 Binds antithrombin, irreversibly 4–5 h
inactivating thrombin
Dabigatran 7–14 Reversibly inhibits 3d
thrombin
Rivaroxaban 5–13 Reversibly inhibits thrombin 3d
Apixaban 9–14 Reversibly inhibits thrombin 3d
Edoxaban 10–14 Reversibly inhibits thrombin 3d

ADP = adenosine diphosphonate, COX = cyclooxygenase, LMWH = low-molecular-weight heparin

a
Can be substantially longer in patients with impaired renal and/or hepatic function
b
The range of minimum cessation times to eliminate potential bleeding effect is 1 to 7 days.
c
The range of minimum cessation times to eliminate potential bleeding effect is 5 to 14 days.
d
The range of minimum cessation times to eliminate potential bleeding effect is ,1 to 3 days.

January 15, 2018, Vol 26, No 2 37

Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Blood-loss Management in Spine Surgery
However, as with preoperative ces-
sation, the period for restarting
platelet inhibitors and the potential
need for a loading dose should be
individualized to each patient. Fac-
tors that must be considered include
the type and magnitude of spine
surgery, the potential risks of
thrombosis and late epidural hema-
toma, and the possibility of a
bleeding diathesis or hypercoagula-
ble state.
Long-term Anticoagulation
Transient interruption of anticoagu-
lant therapy for a procedure increases
the risk of thromboembolism. Given
the high risk of bleeding and its asso-
ciated complications, however, little
question exists that interruption is
warranted before spine surgery. The
duration of preoperative and post-
operative interruption and the need
for bridge therapy should be based on
the estimated thromboembolic risk,
the bleeding risk, and the specific
anticoagulant being discontinued.
Patients at high thromboembolic risk
include those with atrial fibrillation,
prosthetic heart valves, and recent
venous or arterial thromboembolism
(ie, within the preceding 3 months).17
Ideally, this decision should be made
after consulting with the patient’s
cardiologist, vascular surgeon, and/or
primary care provider. Warfarin
should be discontinued 5 days before
elective surgery and, when possible,
the prothrombin time and interna-
tional normalized ratio (INR) should
be checked the day before surgery
(Table 1). The goal INR is #1.4
before proceeding with surgery. It is
estimated that if warfarin is stopped 5
days before surgery and restarted
immediately afterward, patients
would have a subtherapeutic INR for
approximately 8 to 10 days.18
Therefore, in patients at high risk for
thromboembolism, preoperative and
postoperative bridging agents may be
appropriate.
38
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Low-molecular-weight heparin or
unfractionated heparin can be used
when bridge therapy is required.
Based on the subcutaneous half-life
of 3 to 5 hours, low-molecular-
weight heparin should be dis-
continued 24 hours preoperatively.
Likewise, unfractionated heparin has
a half-life of 45 minutes; therefore,
an intravenous infusion should be
stopped 4 to 5 hours before surgery,
and the last subcutaneous dose
should be given the evening before
surgery. Restarting therapeutic-dose
low-molecular-weight or un-
fractionated heparin should be de-
layed for at least 48 to 72 hours
following spine surgery because of
concerns for excessive postoperative
bleeding and potential epidural
hematoma.
Newer direct oral anticoagulants,
such as dabigatran, rivaroxaban,
apixaban, and edoxaban, have shorter
half-lives and can be discontinued
approximately 2 to 3 days before sur-
gery. Because of the mechanism of
action of these medications, routine
prothrombin time, partial thrombo-
plastin time, and INR coagulation
tests have not been validated for
monitoring their anticoagulant effect.
Therefore, they cannot be used to
determine whether the anticoagulation
effect has resolved after their discon-
tinuation. In general, it is thought that
bridge therapy is not required with
these agents because of their rapid
offset and onset. In patients at very
high risk for thromboembolism, how-
ever, bridge therapy can be considered.
The surgeon should consult with the
patient’s other healthcare providers
regarding the use of these medications
in the perioperative period.
Supplements
It is estimated that up to 25% of
patients undergoing surgery use
vitamin, herbal, or other types of
supplements.19 Garlic, ginkgo, gin-
seng, fish oil, flax seed oil, and saw
Journal of the American Academy of Orthopaedic Surgeons
palmetto decrease platelet aggrega-
tion. Chamomile inhibits clotting.
Vitamin E and vitamin K alter
coagulation. Green tea, which con-
tains vitamin K, also alters coagula-
tion. Supplements potentially can
affect perioperative bleeding and
should be stopped at least 14 days
before surgery.
Preoperative Estimation of
Blood Loss
Based on the magnitude and expected
duration of surgery as well as the
surgeon’s experience level, a pre-
operative estimation of intra-
operative blood loss should be
possible. Expected blood loss should
facilitate planning by the surgeon,
the operating room team, and the
anesthesia team. An accurate esti-
mation of blood loss should result in
increased cost-effectiveness with re-
gard to use of preoperative blood
typing and screening or cross-
matching, intraoperative cell sal-
vage (ICS), and antifibrinolytic
agents. Patient factors associated
with increased blood loss include a
high body mass index, advanced age,
and bleeding diatheses.20,21 Surgical
factors that have been correlated
with increased intraoperative blood
loss include the number of spinal
levels (laminectomies and/or fusion),
the use of instrumentation, revision
procedures, iliac crest bone graft
harvest, and interbody fusions. Fur-
thermore, surgery to manage trauma
or tumors has the potential for ele-
vated blood loss.
Even given all of these variables,
some surgeons still use the estimation
of 200 mL of blood loss per lumbar
level fused. Although this amount can
overestimate actual intraoperative
blood loss, more often, it likely
underestimates the amount. More
predictive models for estimated
blood loss have been published,20,21
but nothing can substitute for the
main surgeon’s careful assessment,

considering her or his own experi-
ence and the planned surgical
technique.
Autologous Blood Donation
The transfusion of allogeneic packed
red blood cells (PRBCs) carries risk,
and preoperative autologous PRBC
donation has been pursued as a
potential alternative. Routine autol-
ogous PRBC donation is potentially
flawed because it can create iatro-
genic anemia, resulting in an
increased chance of postoperative
transfusion. It also may lead to a
perception that the donated blood
should be used, thereby lowering the
transfusion threshold and resulting in
unnecessary transfusion of autolo-
gous PRBCs. Although this type of
transfusion is less risky than alloge-
neic transfusion, it still carries some
risk of medical error. Conversely, the
donated blood frequently goes
unused, which is a waste of money
and resources. The clinician might
expect autologous donation to be
cost-effective in patients treated for
adult spinal deformity, given the
potential for substantial perioper-
ative blood loss. However, nearly one
third of patients from the Interna-
tional Spine Study Group who pre-
donated blood before adult
deformity surgery did not receive
their donated blood.22 Furthermore,
autologous donation did not protect
against allogeneic exposure because
one fourth of patients who donated
blood still received allogeneic blood.
Intraoperative
Considerations
Intraoperative Cell Salvage
When used in cardiovascular surgery,
ICS and autologous transfusion have
been found to be a safe and effective
tactic for potentially reducing the
need for allogeneic blood use.20,23
Little question exists that ICS can
January 15, 2018, Vol 26, No 2
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
provide utility in spine procedures
with the potential for considerable
blood loss, such as those for adult
deformity or extensive lumbar revi-
sion cases. Another indication for
ICS is in patients whose religious
beliefs preclude the use of allogeneic
blood products. Patients with large
numbers of antibodies also may
benefit from ICS because the supply
of allogeneic blood products can be
drastically limited. The cost-
effectiveness of routine use of ICS
is less clear, however.20,23
In a study by Kelly et al,20 the
routine use of ICS was not found to
be cost-effective during lumbar
fusions of three levels or fewer. The
authors found that in patients in
whom blood loss $500 mL
occurred, the use of ICS became cost-
effective, a finding that is consist
with the prior literature. It is
important to determine which
patients will have estimated blood
loss .500 mL so that the set-up and
use of this specialized equipment is
not wasted, as well as the time of
dedicated personnel. As discussed
previously, the primary surgeon
must perform a thorough assessment
of expected blood loss based on his
or her experience and technique as
well as consideration of patient
factors.
When using ICS in spine surgery,
the recovery rate of RBCs is
approximately 38% to 40%.23 This
rate is markedly lower than that
found in cardiovascular surgery.23
Methods to improve efficiency
include using an open-tip suction
wand with pressures ,100 mm Hg,
using fewer sponges, rinsing sponges
to collect RBCs, and avoiding blood
pooling and clotting. Other precau-
tions include limiting antibiotic
irrigation, water, povidone-iodine,
and solution warmer than 42°C
within the circuit. Collagen-based
products should not be used with
ICS. Gelatin sponges, oxidized cel-
lulose, and thrombin are safe to use
Jesse E. Bible, MD, MHS, et al
with ICS but should not be aspirated
directly into the circuit.
ICS is contraindicated in patients
undergoing spine surgery for malig-
nancy and infections. The general
risks of ICS include transient hemo-
globinuria and pulmonary compli-
cations from reperfusion of debris. In
addition, as with any RBC trans-
fusion, ICS transfusion can deplete
coagulation factors and result in
coagulopathy. It is generally recom-
mended that, for every 1,000 mL re-
turned, 1 unit of fresh plasma be
given.
Anesthetic Techniques
Hypotensive Anesthesia
The safety and efficacy of controlled
hypotension techniques have been
evaluated mainly in pediatric scolio-
sis surgery. Surgeons have proposed
the use of controlled hypotension in
adult spine trauma and degenerative
spine cases and in adult deformity
procedures. Hypotension is induced
using intravenous vasodilating
agents to maintain a target systolic
blood pressure ranging from 50 to
80 mm Hg. Early studies focusing on
pediatric scoliosis showed substantial
reductions of up to 55% in blood loss
using these techniques without
adverse sequelae.24
It is believed that controlled hypo-
tension reduces local blood flow, re-
sulting in decreased extravasation
from the surgical wound. Although
this technique can help reduce
bleeding from soft-tissues, it theoret-
ically should not substantially affect
the epidural venous plexus pressure
and intraosseous pressure, because
both are independent of arterial
blood pressure.
Although controlled hypotension
is reported to be safe, the major
concern of end-organ perfusion
remains. Two areas of great concern
to spine surgeons of end-organ per-
fusion are the spinal cord and the
optic nerve.
39
Blood-loss Management in Spine Surgery
Core Temperature Control
Hypothermia-induced hemorrhagic
diathesis occurs through the impair-
ment of platelet function and altered
coagulation enzyme activity. Peri-
operative hypothermia occurs
through a combination of several
factors, including a low operating
room temperature, administration of
room-temperature fluids, alterna-
tions in thermoregulation from gen-
eral anesthesia, and evaporation
from surgical wounds. Hypothermia
is more common during the first hour
of anesthesia.25 Even small decreases
in body temperature can have large
effects in physiologic hemostasis.
Mild hypothermia (a reduction of
,1°C) can increase blood loss as
much as 16%, with a related 22%
increased risk for transfusion.26
Simple methods to help minimize
perioperative hypothermia include
elevating the ambient temperature of
the operating room—especially dur-
ing the patient’s first hour in the
room—and minimizing skin expo-
sure. The latter method involves not
only the exposure of the surface-area
of the skin but also the duration of
the time exposed; both can be
extended easily and extensively with
the placement of an arterial line,
Foley catheter, and/or neuro-
monitoring. Efforts should be made
to minimize any so-called unneces-
sary preoperative skin exposure until
the drapes are applied. Forced-air
warming blankets can be applied
before draping to assist with the
active prevention of intraoperative
hypothermia. Depending on the
planned area of surgical exposure,
upper and lower body warming
blankets can be used. When the
patient is positioned on an open
spine frame, a blanket can be placed
underneath the patient.
Antifibrinolytic Agents
Aprotinin, tranexamic acid (TXA),
and ɛ-aminocaproic acid (EACA) are
40
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
lysine analogs that inhibit the binding
of fibrin to plasmin or plasminogen.
Aprotinin, a naturally occurring
inhibitor, initially was found to
reduce perioperative bleeding but was
removed from the market because of
a suggested increased risk of renal
and cardiac complications. Both of
the synthetic analogs, TXA and
EACA, are being used more fre-
quently in orthopaedic surgery and
are considered relatively safe,
although some concerns remain
regarding possible thrombotic events,
generalized seizures, and renal failure.
TXA is 6 to 10 times more potent
than EACA in its ability to bind to
plasminogen and plasmin. A com-
mon TXA dosing regimen includes a
10 mg/kg loading dose followed by a
1 mg/kg/h infusion, whereas EACA is
loaded at 100 mg/kg, with a 10 mg/
kg/h continuous infusion.27
TXA has well-established efficacy
in reducing blood loss in joint ar-
throplasty. A randomized controlled
trial of patients with adolescent idio-
pathic scoliosis found that, compared
with saline controls, TXA signifi-
cantly reduced surgical blood loss
(P = 0.015) but did not significantly
reduce transfusion rates.28 TXA was
more effective at reducing post-
operative drainage and total blood
loss than EACA was.
The authors of a randomized con-
trolled trial of patients undergoing
adult spinal deformity surgery found
slightly differing results in patients
undergoing posterior fusion of five
levels or more.27 EACA significantly
reduced perioperative bleeding
compared with placebo (P = 0.007).
TXA also reduced bleeding com-
pared with placebo, but the differ-
ence did not reach statistical
significance. EACA demonstrated
significant reductions in post-
operative transfusion rates and the
amount of blood transfused com-
pared with TXA (P = 0.042).
A 2015 meta-analysis reviewed 11
randomized controlled trials in
Journal of the American Academy of Orthopaedic Surgeons
which TXA was used in spine sur-
gery in 644 patients.29 The authors
determined that TXA use reduced
intraoperative, postoperative, and
total blood loss by a mean of 219
mL, 119 mL, and 202 mL, respec-
tively. They also noted a reduction
in transfusion with TXA use. Con-
cerns exist regarding the potential
thrombogenic nature of TXA, but
the findings of this study did not
bear them out; one myocardial
infarction occurred in the TXA
group, and one deep vein throm-
bosis occurred in the placebo
group.
In vitro data have shown that anti-
fibrinolytic agents reduce osteoblast
bone mineralization.30 In the setting
of spine fusion surgery, this factor
potentially could lead to higher rates
of failed fusion. In vivo data from a
recent spine fusion study in mice
showed that EACA significantly
enhanced the fusion bone mass (P ,
0.001), whereas TXA did not have a
major effect on fusion compared
with saline controls.30
Rotational
Thromboelastometry
Rotational thromboelastometry is
a rapid method of testing the defi-
ciency in coagulation pathways,
platelet adhesion/aggregation, clot
strength, and fibrinolysis in whole
blood during surgery. With the
specific information provided by
this test, the surgeon and anesthesia
team have a better understanding of
the exact deficiencies in the blood
clotting pathways, which enables
more specific treatment. This tech-
nique theoretically can result in
reduced intraoperative and post-
operative bleeding and may limit
the use of PRBCs when other blood
products, such as fresh-frozen
plasma, cryoprecipitate, and plate-
lets, are indicated. Naik et al 31 re-
ported a reduction in the amount
of blood products needed in major

spine surgery when rotational
thromboelastometry was used with
or without TXA. They also re-
ported reduced costs with use of
rotational thromboelastometry.
Patient Positioning
Surgical positioning is important
in minimizing blood loss intra-
operatively. The reverse Trendel-
enburg position decreases central
venous pressure and potentially can
help reduce intraoperative blood loss.
Prone positioning can cause increased
intra-abdominal pressure and com-
pression on the vena cava, causing
venous congestion into the valveless
veins of the Batson epidural plexus.
Dedicated spine frames are designed
to allow the abdomen to hang free and
reduce intra-abdominal pressure.
Proper use of these frames, along with
appropriate positioning of the pads,
may help limit intraoperative bleed-
ing. Park32 noted a significant
reduction in intra-abdominal pres-
sure (P , 0.05) and blood loss (P ,
0.05) with wide pad supports com-
pared with narrow pad supports on
the Wilson frame.
Surgical Techniques
Dissection
The dermis overlying the neck and
back can be well-perfused, which
potentially may result in considerable
blood loss if ignored. This dermal
oozing can be minimized with local
skin infiltration of 1:500,000 epi-
nephrine before incision or localized
low-energy electrocautery after inci-
sion. Meticulous hemostasis should
be maintained with each level of
deeper dissection through the fat and
fascia levels. Subperiosteal dissection
should be continued over the bony
anatomy to minimize bleeding from
the paraspinal musculature.
Monopolar electrocautery remains
the mainstay for hemostatic dissec-
tion. Typically, bipolar electro-
January 15, 2018, Vol 26, No 2
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
cautery has been used near neural
tissue (ie, epidural space) to limit the
zone of thermal injury or collateral
damage. Bipolar electrocautery also
can be helpful in cauterizing large
surface areas of ooze, however, by
leaving the tips 5 to 8 mm apart and
running them parallel to bleeding
muscle or fat.
Saline-irrigated radiofrequency
bipolar hemostatic sealers combine
radiofrequency energy with saline
irrigation to cause contraction of
vascular collagen at tissue tempera-
tures ,100°C. This device is unlike
unipolar electrocautery, in which
temperatures exceed 300°C. In addi-
tion, saline irrigation helps conduct
energy, with resulting hemostasis
over a broad area of cut surfaces.
Most higher-quality studies evalu-
ating hemostatic sealers have been
focused on joint arthroplasty. A
prospective study of 100 pediatric
patients with spine deformities who
were randomized to treatment with
or without a bipolar sealer found a
substantial reduction in intra-
operative blood loss (407 mL versus
696 mL, respectively) and in alloge-
neic transfusion rate with use of the
bipolar sealer.33 In a smaller retro-
spective case control study of 74
patients, Frank et al34 found similar
results, but also noted that the
average incremental equipment cost
was $493 per surgical case when the
bipolar sealer was used.
To limit unwanted low-pressure
bleeding, previously exposed areas
currently not being worked on should
be packed with patties and/or sponges.
Sponges can be soaked lightly in diluted
thrombin or epinephrine for a more
lasting effect after removal. Likewise,
specialized hemostatic sponges con-
taining the inorganic minerals also can
be used for this purpose.
Local Agents
Continuous bleeding from bony
sources can contribute to substantial
Jesse E. Bible, MD, MHS, et al
intraoperative and postoperative
blood loss. A very thin layer of bone
wax can be applied to mechanically
seal bleeding bony surfaces. This wax
should not be applied to bony sur-
faces expected to be part of future
arthrodesis, however, because bone
wax hinders osteogenesis.35 Fur-
thermore, only the smallest amount
of wax should be used because it
remains at the site indefinitely, pro-
motes chronic inflammatory reac-
tions, and creates a nidus for
potential infection.
Other topical hemostatic alterna-
tives also can promote a local
inflammatory reaction; however,
such a reaction is limited because of
the absorbable nature of the alterna-
tive agents. In addition to controlling
bony bleeding, these absorbable
agents are especially useful in con-
trolling epidural venous bleeding.
These absorbable agents can be cate-
gorized as passive or active (Table 2).
Passive agents promote platelet
aggregation, leading to clot forma-
tion. They include gelatin-, cellulose-,
and collagen-based products. Active
agents induce the formation of a
fibrin clot at the end of the coagula-
tion cascade and include thrombin
and hemostatic matrices containing
thrombin.
Postoperative
Considerations
Drains
Postoperative hematoma may
increase the risk for surgical site
infection or symptomatic epidural
hematoma; postoperative drains are
used in an attempt to minimize the
risk of postoperative hematoma. A
commonly cited disadvantage of
drain use is the potential for increased
postoperative blood loss. Supporters
of this potential downside theorize
that the drain draws blood away
from the acute surgical site, thereby
reducing the intra-wound pressure
41
Blood-loss Management in Spine Surgery

Table 2
Absorbable Topical Hemostatic Agents for Minimizing Intraoperative Bleeding
Type of Mechanism of
Agent Agent Product Action Advantages Disadvantages

Passive Bone wax Generic bone wax Physically occludes Highly effective on Remains indefinitely,
bleeding bone bone surfaces promotes chronic
channels inflammatory
reaction, serves as
nidus for infection,
hinders local
osteogenesis
Gelatin-based Gelfoam (Pfizer), Gelfilm Serves as a Liquefies in ,1 wk, Has potential to swell
sponge (Pfizer), Surgifoam mechanical matrix dissolves in 4–6 to twice its original
(Ethicon) to facilitate clotting wk, has neutral pH, size, leading to
has minimal effect neural
on osteogenesis compression
Oxidized cellulose Surgicel (Ethicon) Swells into gelatinous Dissolves in 2–6 wk, Has swelling
mass as it absorbs has local potential as it
blood (always apply antimicrobial effect absorbs blood,
dry), mechanical due to low pH leading to neural
matrix facilitates compression; low
clotting, reduces pH inactivates
surrounding pH thrombin and
contributing to inhibits
coagulative osteogenesis
necrosis
Microcrystalline Avitene (Davol), Platelets adhere to Absorbs in ,8 wk, Can bind to neural
collagen Instat (Johnson & its fibrils, platelet has minimal tissues, temporarily
Johnson), Helistat activate through swelling potential inhibits
(Integra so-called release osteogenesis
LifeSciences) reaction
Active Thrombin THROMBIN-JMI (King Promotes Fast-acting Immunogenic
Pharmaceuticals), conversion of reaction with
Evithrom (Omrix fibrinogen to fibrin bovine thrombin
Biopharmaceuticals),
rhThrombin
(ZymoGenetics)
Hemostatic matrix Floseal (Baxter), Surgiflo Gelatin granules Fast-acting Requires some local
(gelatin plus (Ethicon) swell, providing bleeding for
thrombin) tamponade effect fibrinogen source
Thrombin converts Tamponade effect Can swell up to 20%
fibrinogen to fibrin helps local arterial 10 min after
bleeding, absorbs application
in 4–6 wk
Fibrin sealant Tisseal (Baxter), Evicel Thrombin converts Provides end None
(thrombin plus (Ethicon) fibrinogen to fibrin, products for clot
fibrinogen) fibrinogen forms formation, is
clot effective in
heparinized
patients

and preventing the tamponade effect
of the hematoma against further
bleeding.
In support of this theory of increased
postoperative blood loss, in a retro-
spective review of 500 patients who
underwent spinal fusion to manage
adolescent idiopathic scoliosis, Diab
et al36 found that patients in whom
postoperative drains were used
received significantly more post-
operative transfusions compared with
patients in whom postoperative drains
were not used (43% versus 22%,
respectively; P , 0.001). This finding
also has been observed in the joint
arthroplasty literature regarding post-
operative drain use.37 When the data
reported by Diab et al36 were com-
bined with those from two other spine
surgery studies in a recent meta-

42 Journal of the American Academy of Orthopaedic Surgeons

Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.

analysis, however, the authors of the
meta-analysis failed to find a statisti-
cally significant difference between
postoperative blood loss with and
without a postoperative drain (P =
0.07).38
Ketorolac
Ketorolac is a potent NSAID that has
established analgesic efficacy for the
relief of moderate to severe pain after
surgery. Some spine surgeons avoid its
use in patients who undergo spine
fusion because of concerns regarding
its potential inhibitory effect on the
actual fusion process. Other surgeons
limit ketorolac use because of concerns
regarding postoperative bleeding,
given that it is a reversible COX
inhibitor. Much of the concern within
the medical community regarding
bleeding arose after the publication in
1996 of the findings of a postmarket-
ing surveillance cohort study of par-
enteral ketorolac use in medical and
surgical patients.39 The authors of that
study reported an increased odds ratio
of 1.02 for surgical site bleeding
(including dressing spotting) for ke-
torolac (39.6%) compared with that
for opiates (38.6%). They also noted a
dose-response relationship for surgical
site bleeding at higher doses of .105
mg/d. Based on these findings, a black
box warning was issued regarding the
bleeding effects of ketorolac.40
A meta-analysis of 27 randomized
controlled trials found no significant
increase in postoperative bleeding
with ketorolac use compared with
controls (2.5% versus 2.1%, respec-
tively; P = 0.72).41 Postoperative
bleeding was defined as bleeding
necessitating postoperative trans-
fusion, readmission, or reoperation.
Allogeneic Blood
Transfusion
The focus on allogeneic transfusion
risk has shifted from disease trans-
mission to immunomodulatory effects,
potentially leading to an increased risk
January 15, 2018, Vol 26, No 2
Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
for nosocomial infection.2-4 This
information, along with the knowl-
edge that more restrictive transfusion
thresholds are acceptable, has led to a
paradigm shift toward more restrictive
transfusion thresholds.
The decision to transfuse should be
based on the patient’s hemoglobin
(Hb) level and symptoms of anemia,
including chest pain, congestive heart
failure, and tachycardia that is not
responsive to fluid or postural hypo-
tension.42 The Transfusion Require-
ments in Critical Care clinical trial
showed no difference in overall
mortality between a most restrictive
transfusion threshold (Hb 7 g/dL)
and a more liberal threshold (Hb 10
g/dL).43 Subsequent studies have
shown no mortality and no difference
in morbidity with the more restrictive
transfusion protocols. Although the
definition of restrictive transfusion
protocols varies within the literature,
Hb 7 g/dL is the typically agreed on
restrictive threshold. However, it is
important to remember that for
patients with previous cardiovascular
disease, careful clinical evaluation
and a more personalized transfusion
threshold may be warranted.
Summary
Proper preoperative planning and
communication among the patient,
the anesthesia team, and the operating
room staff are essential in minimizing
blood loss in spine surgery. Intra-
operative antifibrinolytic agents and
modified anesthesia techniques have
shown promising results in safely
reducing blood loss. The surgeon’s
attention to intraoperative hemosta-
sis through dissection techniques and
the use of local hemostatic agents also
can lessen intraoperative bleeding.
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