E NARRATIVE REVIEW ARTICLE

Initiation and Termination of Massive Transfusion

Protocols: Current Strategies and Future Prospects
John C. Foster, MD,* Joshua W. Sappenfield, MD,† Robert S. Smith, MD,‡ and Sean P. Kiley, MD†

The advent of massive transfusion protocols (MTP) has had a significant positive impact on
hemorrhaging trauma patient morbidity and mortality. Nevertheless, societal MTP guidelines
and individual MTPs at academic institutions continue to circulate opposing recommendations
on topics critical to MTPs. This narrative review discusses up-to-date information on 2 such
topics, the initiation and termination of an MTP. The discussion for each begins with a review of
the recommendations and supporting literature presented by MTP guidelines from 3 prominent
societies, the American Society of Anesthesiologists, the American College of Surgeons, and
the task force for Advanced Bleeding Care in Trauma. This is followed by an in-depth analysis
of the main components within those recommendations. Societal recommendations on MTP
initiation in hemorrhaging trauma patients emphasize the use of retrospectively validated mas-
sive transfusion (MT) prediction score, specifically, the Assessment of Blood Consumption and
Trauma-Associated Severe Hemorrhage scores. Validation studies have shown that both scor-
ing systems perform similarly. Both scores reliably identify patients that will not require an MT,
while simultaneously overpredicting MT requirements. However, each scoring system has its
unique advantages and disadvantages, and this review discusses how specific aspects of each
scoring system can affect widespread applicability and statistical performance. In addition, we
discuss the often overlooked topic of initiating MT in nontrauma patients and the specific tools
physicians have to guide the MT initiation decision in this unique setting. Despite the serious
complications that can arise with transfusion of large volumes of blood products, there is con-
siderably less research pertinent to the topic of MTP termination. Societal recommendations on
MTP termination emphasize applying clinical reasoning to identify patients who have bleeding
source control and are adequately resuscitated. This review, however, focuses primarily on the
recommendations presented by the Advanced Bleeding Care in Trauma’s MTP guidelines that
call for prompt termination of the algorithm-guided model of resuscitation and rapidly transition-
ing into a resuscitation model guided by laboratory test results. We also discuss the evidence
in support of laboratory result–guided resuscitation and how recent literature on viscoelastic
hemostatic assays, although limited, highlights the potential to achieve additional benefits from
this method of resuscitation.  (Anesth Analg 2017;125:2045–55)

C
oncerns regarding improper administration of mas-
sive transfusions (MTs) led to the development and
implementation of massive transfusion protocols
(MTPs) in the mid to late 2000s.1–6 These protocols were
designed to establish a method for the timely and coordi-
nated delivery of blood products throughout the hospital
and to develop evidence-based guidelines for the delivery
of blood products and adjunctive therapies.1,7–9 In support of
their overall efficacy, data have since shown that, compared
with MT events in hospitals without an MTP, MTP-guided
resuscitation is associated with significant improvement in
overall patient survival, as well as reductions in blood prod-
uct utilization, blood product waste, and incidence of com-
plications associated with blood product transfusions.10–13
From the *University of Florida College of Medicine, Gainesville, Florida;
†Department of Anesthesiology, University of Florida College of Medicine,
Gainesville, Florida; and ‡Division of Acute Care Surgery, Department of
Surgery, University of Florida College of Medicine, Gainesville, Florida.
Accepted for publication July 17, 2017.
Funding: None.
The authors declare no conflicts of interest.
Reprints will not be available from the authors.
Address correspondence to Joshua W. Sappenfield, MD, Department of An-
esthesiology, University of Florida College of Medicine, 1600 SW Archer Rd,
PO Box 100254, Gainesville, FL 32610. Address e-mail to jsappenfield@anest.
ufl.edu.
Copyright © 2017 International Anesthesia Research Society
DOI: 10.1213/ANE.0000000000002436
As of 2017, MTPs have been widely adopted by aca-
demic institutions within the United States.14 Despite this,
a comparison of interhospital MTPs revealed that they vary
extensively with regard to the criteria for initiation, the role
of point-of-care-testing (POCT), the end points for termina-
tion, and the indications for therapeutic adjuncts to blood
products such as crystalloid fluids, calcium, tranexamic
acid, and prothrombin complex concentrates.14,15 This lack
of MTP uniformity is concerning, especially given the litera-
ture demonstrating the benefits provided by evidence-based
MTPs and the consequences of inappropriate MTP utiliza-
tion.9–13,16–19 It also raises some questions, including whether
there is sufficient evidence to permit the development of a
standardized MTP, and whether geographic differences in
trauma patient demographics would affect the efficacy of a
standardized MTP at individual trauma centers.
With these questions in mind, the goal of this article is
to provide a narrative review on 2 contended topics that
are invaluable to MTP guidelines: the decision to initiate an
MTP and the decision to terminate 1. Through an analysis of
the evidence-based methods available for guiding the deci-
sion to initiate and terminate an MTP, this article aims to
discuss the following: the comparative strengths and weak-
nesses of validated approaches to guiding MTP initiation
and termination, the potential for integrating these methods
into a standardized MTP, and any additional research topics
that would fill gaps in the existing literature.

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 EE NARRATIVE REVIEW ARTICLE

METHODS Societal Guidelines

Recommendations on the initiation and termination of
MTPs and their supporting references were sourced from
respective MTP guidelines published by the American
Society of Anesthesiologists (ASA), the American College
of Surgeons (ACS), and the European Society for Advanced
Bleeding Care in Trauma (ABC-Trauma).20–22 Additional
evidence not referenced in these papers was obtained
through literature searches in PubMed from December 2006
to January 2017 using the keyword “massive transfusion
protocol” and MeSH terms “shock, hemorrhagic/blood,”
“shock, hemorrhagic/diagnosis,” “wounds, stab/mortal-
ity,” and “wounds, gunshot/mortality.” Search results
were limited to randomized control trials (RCTs), non-RCT
studies, and systematic reviews with human subjects and
in the English language. Whole articles were screened for
their relevance to the subject of initiation and termination
of MTPs, and then incorporated into the narrative review if
they were determined to contain new and relevant informa-
tion regarding this topic.
INITIATION OF MASSIVE TRANSFUSION
PROTOCOLS
Patient survival during massive hemorrhage is critically
dependent on rapid identification and control of the bleeding
source(s). This is evident from 1 institution’s observations
of a significant reduction in overall and hemorrhage-related
mortality after the simultaneous application of several hem-
orrhage control interventions, termed the “bleeding control
bundle.”23 An additional component of the bleeding control
bundle that assists in hemostasis and delaying death from
exsanguination is the early initiation of an MTP.23–25 This
statement is supported by observations that patient mortal-
ity after massive hemorrhage significantly improves with
decreased time between patient presentation and MTP acti-
vation, and with decreased delays between MTP activation
and the initiation of an MTP.13,17,26–28 Evidence-based guide-
lines for the prompt identification and early resuscitation of
patients requiring an MT is therefore a crucial topic within
MTPs.
Despite evidence of mortality benefits with early MTP ini-
tiation, the enduring question remains how a physician can
quickly and accurately determine whether a hemorrhaging
patient requires an MT.29 Within the trauma literature, there
are numerous publications outlining the various imaging
modalities, MT prediction tools, estimated blood loss guide-
lines, laboratory markers of tissue perfusion, and compo-
nents of the patient’s history and examination that are meant
to supplement clinical reasoning and aid in the decision to
initiate an MTP.29–48 Conveniently, the MT literature has
been compiled and analyzed by several prominent medi-
cal societies, including the ASA, ACS, and ABC-Trauma, for
the purpose of providing physicians with evidence-based
recommendations regarding MT and MTPs.20–22 These up-
to-date MTP guidelines have all been completed or updated
within the past 5 years and, because of their recognition and
reach, have significant potential to influence the practice of
anesthesiologists, surgeons, and emergency medicine phy-
sicians involved in the initial evaluation and management
of trauma patients.14,49 Given the significant influence of the
ACS, ASA, and ABC-Trauma societies and their in-depth
analysis of the MT literature, it is prudent to use their guide-
lines as an initial tool to identify evidence-based modalities
for guiding the decision to initiate and terminate an MTP
after traumatic injury.
The recommendations from the ASA, ACS, and ABC-
Trauma on MTP initiation after traumatic injury are pre-
sented in Table 1.20–22 Each guideline similarly recommends
a systematic approach to MTP initiation that combines the
clinical assessment of tissue perfusion and estimated blood
loss with a validated MT prediction score.20–22 Utilizing clin-
ical reasoning when guiding MTP initiation is essential, as
was established by studies demonstrating clinical reason-
ing to be 65.6% sensitive and 63.8% specific for predicting
MT requirements.39 The positive predictive value (PPV)
and negative predictive value (NPV) of clinical reasoning
were 34.9% and 86.2%, respectively.39 While these values
would suggest that clinical reasoning alone is insufficient to
independently guide the initiation of an MTP, it remains a

Table 1.  Societal Recommendations for Initiation of Massive Transfusion Protocols

American Society of Anesthesiologists
  Identify patients requiring a massive transfusion with the following:
   Positive Assessment of Blood Consumption Score
  Consider the following risk factors when evaluating massive transfusion requirements:
   Positive Larson Score
   Blood transfused in the emergency department or trauma bay
American College of Surgeons
  Criteria to trigger a massive transfusion should include 1 or more of the following:
   Positive Assessment of Blood Consumption Score
   Immediate surgery or angioembolization necessary for bleeding source control
   Blood transfused in the emergency department or trauma bay
   Persistent hemodynamic instability after initial fluid resuscitation
Task Force for Advanced Bleeding Care in Trauma
  The decision to initiate a massive transfusion should consider the following elements:
   Trauma-Associated Severe Hemorrhage Score
   Estimated blood loss
   Mechanism and severity of injury
   Advanced Trauma Life Support guidelines on hemorrhage classification
   Advanced Trauma Life Support guidelines on response to initial fluid resuscitation
The recommendations made by the American Society of Anesthesiologists, American College of Surgeons, and Task Force for Advanced Bleeding Care in Trauma
societies within their massive transfusion protocol guidelines pertaining to the topic of massive transfusion protocol initiation.

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 Initiation and Termination of Massive Transfusion Protocols

valuable decision-making tool, especially when laboratory scoring system can be immediately calculated and inter-
values or imaging are still pending or altogether unavail- preted once all variables are obtained. In addition, the 97%
able. The MT prediction score components of MTP recom- NPV indicates that a negative ABC score is highly success-
mendations will be discussed individually subsequently. ful in correctly identifying patients who will not require an
MT, which is arguably the most important feature of an MT
MT Prediction Scores for Guiding MTP Initiation prediction score. However, as this scoring system is used as
The US-based societies, the ASA and ACS, both recom- an early predictive tool for identifying patients at risk for
mend the Assessment of Blood Consumption (ABC) score requiring an MT, the 55% PPV is concerning. It indicates
(Table 2) as a simple, 4-variable scoring system for rapidly a tendency for a positive ABC score to overtriage patients
predicting MT risk in trauma patients and aiding in the into receiving an unnecessary MT. If used independently,
decision to initiate an MTP.20,21 The initial validation of this would lead to an increased likelihood of blood prod-
the ABC score was conducted using trauma patient data uct wastage and complications associated with blood prod-
sets recorded at the Vanderbilt University Medical Center uct transfusions. An additional limiting feature of the ABC
between 2005 and 2006.30 The ABC score correctly pre- score is that it is not sensitive for other sources of major
dicted the retrospective need for MT in 84% of cases, with bleeding, including severe injuries to extremities, retroperi-
a sensitivity of 75% and specificity of 86%.30 Revalidation toneal vasculature, and pelvic vasculature.16,30
of the ABC score was conducted using trauma patient In place of the ABC score, the ABC-Trauma guide-
data sets recorded at 3 large level 1 trauma centers in the lines recommend utilizing the Trauma-Associated Severe
United States (Parkland Memorial, Johns Hopkins, and Hemorrhage (TASH) score (Table  2) for predicting MT
Vanderbilt University Medical Center) between 2006 and risk in trauma patients and aiding in the decision to initi-
2007.16 The revalidation data concluded that the ABC score ate an MTP.22 In comparison to the simplistic ABC score,
was 75-90% sensitive and 67%-88% specific with regard the TASH score is a 7-variable, 28-point, weighted scoring
to its ability to retrospectively predict MT requirements system that was developed through multivariate analysis
within 24 hours of trauma.16 The PPV and NPV were 55% of trauma patient data sets recorded between 1993 and 2003
and 97%, respectively.16 in the multicenter Trauma Registry of the German Trauma
The major advantages of the ABC score are that the Society (TR-DGU).48 Retrospective validation of the score
4-scoring variables and cutoff values are easy to recall, that within the same registry demonstrated that the TASH score
all variables can be rapidly obtained in the prehospital set- was able to correctly classify 88.8% of patients with regard
ting and at initial presentation, and that the unweighted to their MT requirements.48 The retrospective revalidation
of the TASH score was conducted using patient data sets
Table 2.  The Trauma-Associated Severe recorded from 2004 to 2007 in the TR-DGU database.31 This
Hemorrhage Score and Assessment of Blood study concluded that the TASH score was 31% sensitive and
Consumption Score 98% specific for correctly predicting MT requirements after
Trauma-Associated Severe Hemorrhage Score trauma.31 Although the PPV and NPV were not provided,
Variable Value Points using the provided values for sensitivity, specificity, and the
Systolic blood pressure (mm Hg) <120 1 2004–2007 TR-DGU MT incidence of 8.4%, we were able to
Systolic blood pressure (mm Hg) <100 4 calculate a PPV of 58.7% and NPV of 93.9%.31
Heart rate (beats/min) >120 2 The validation and revalidation data on the TASH score
Focused assessment with sonography Positive 3
for trauma examination
suggests that it is very similar to the ABC score in that a
Hemoglobin (g/dL) <12 2 negative score accurately identifies patients who will not
Hemoglobin (g/dL) <11 3 require an MT, but that a positive score will often incorrectly
Hemoglobin (g/dL) <10 4 predict MT requirements in patients who do not require an
Hemoglobin (g/dL) <9 6 MT. Despite the similarities, there is 1 notable feature of the
Hemoglobin (g/dL) <8 8
TASH score that favors its potential for widespread imple-
Base excess (mMol/L) Less than −2 1
Base excess (mMol/L) Less than −6 3 mentation within a standardized MTP. This feature is the
Base excess (mMol/L) Less than −10 4 ability for users to modify several score parameters, includ-
Sex Male 1 ing the values and points for each TASH score variable, the
Unstable or open fracture Femur 3 positive cutoff threshold on the 0- to 28-point scale, and the
Unstable or open fracture Pelvis 6 TASH score algorithm for predicting individual patient MT
Score range TASH: 0–28
risk, thereby altering the statistical performance of the scor-
Positive score cutoff TASH: ≥16
Assessment of Blood Consumption Score ing system.31 This feature could be of significant value as
Variable Value Points it presents physicians with the ability to internally validate
Systolic blood pressure (mm Hg) ≤90 1 and fine-tune the TASH score and MT prediction algorithm
Heart rate (beats/min) ≥120 1 within each institution—as was done by the authors in the
Focused assessment with sonography Positive 1
revalidation study—and thereby fit the scoring system to
for trauma examination
Mechanism of injury Penetrating 1
better predict MT requirements specific to the local trauma
Score range ABC: 0–4 patient population.
Positive score threshold ABC: ≥2 There are, however, several concerns with the TASH
Abbreviations: ABC, Assessment of Blood Consumption; TASH, Trauma- score that may limit its widespread applicability, espe-
Associated Severe Hemorrhage. cially in the time-sensitive setting of a massive hemorrhage.

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 EE NARRATIVE REVIEW ARTICLE

Unlike the ABC score, the TASH score requires 2 laboratory

results, hemoglobin and base excess, to result before com-

Table 3.  Data on Patient Demographics From the Trauma Registries Utilized During Validation, Revalidation, and Comparison Studies of the TASH
ABC Score Revalidation

3 US Level 1 Trauma
pleting the score calculation. If these values are obtained by
POCT, the complete TASH score has been shown to require

2006–2007
Centers
on average 7:56 minutes to calculate.50 In comparison, the

30–38
70–86
41–82
18–59

19–24

13–15
Study

Abbreviations: ABC score, Assessment of Blood Consumption score; TASH score, Trauma-Associated Severe Hemorrhage Score; TR-DGU, Trauma Registry of the Deutsche Gesellschaft für Unfallchirurgie.
…

…
…
ABC score’s variables can be calculated in 5:02 minutes; it
should be noted that this does not consider use of prehospi-
tal data for ABC score calculation which would reduce this
time by several minutes.50 While the specific laboratory vari-
ables necessary for the TASH are relatively quick to acquire
with use of POCT, they still present an additional obstacle
that delays the decision to initiate an MTP, particularly at

ABC Score Validation

US Level 1 Trauma
hospitals with limited staff and resources. The calculation of

2005–2006
the TASH score, with its weighted scoring system, multiple

Center
Study
variables, and array of possible results, is also much more

47

70
83
17

11
18
13
…

…
…
complicated than the ABC score. This complexity could
present a barrier that reduces physician compliance with
the scoring system and increases the potential for errors
in scoring and interpretation, altogether leading to further
delays in the initiation of an MTP.

Prince of Wales Hospital

Australian Royal Prince

Alfred Trauma Registry
Score Validation Study
Directly Comparing the MT Prediction Scores

2006–2009
During the initial development of the ABC score at the

44

76
94
6

27
14
14
5
…

…
Vanderbilt University Medical Center, the authors also cal-
culated the TASH score for each patient to directly compare
the 2 scoring systems. The area under the receiver operating
characteristic (AUROC) of the TASH and ABC scores were
0.842 and 0.859, respectively, with a difference that was
Six Scoring System
Comparison Study
European TR-DGU
found to be statistically insignificant.30 These results showed

2002–2010
that the TASH score’s ability to retrospectively predict MT
requirements for trauma patients in the urban United States
46

73
95
5
24
22

6
…

…
…
was very similar to that of the ABC score. However, in 2012,
a European study retrospectively calculated 6 unique MT
scoring methods, including both the ABC and TASH scores,
using trauma patient data sets from the TR-DGU database.32
TASH Revalidation Study

The TASH score had an AUROC of 0.889, which was sig-

European TR-DGU

nificantly greater than the ABC score’s surprisingly low

2004–2007

AUROC of 0.763.32 Mitra et al51 also directly compared the

43

73
95
5
26

11
14
8
…

TASH and ABC scores using trauma patient data sets from
the Australian Royal Prince Alfred trauma registry. Mitra et
al51 found the TASH score to have an AUROC of 0.90, again
significantly greater than the ABC score’s AUROC of 0.78.
The ABC score’s reduced statistical performance measures
TASH Validation Study

when calculated with data from outside the urban United

European TR-DGU
1993–2003

States raises concerns regarding its widespread applicabil-

ity within a standardized MTP.
39

74
95
5
26

10
19
14
…

An explanation for the significant reduction in the ABC

score’s ability to retrospectively predict MT, and the TASH’s
consistent ability to predict MT, when tested across dissimi-
lar trauma databases may lie in the differences between
Penetrating injury mechanism (%)

trauma demographics. Data on patient demographics from

Injury Severity Score (median)

the United States, European, and Australian trauma regis-

Glasgow Coma Score (mean)

Massive transfusion rate (%)

Injury Severity Score (mean)
Blunt injury mechanism (%)

tries utilized during the validation of the ABC and/or TASH

In-hospital mortality (%)
Patient Demographics

scores are shown in Table 3.16,30–32,48 There are several dispar-

and ABC Scores

ities between the trauma registries that are evident from this
Age in y (median)

table, including differences in the Injury Severity Scores,

Age in y (mean)

Male sex (%)

mean patient age, prevalence of MT, and relative percentage

of penetrating mechanisms of injury. Of these epidemiologi-
cal variables, the relative percentage of penetrating injury is
the only 1 that is not only predictive of MT risk but also an

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 Initiation and Termination of Massive Transfusion Protocols
important MT prediction score variable (Figure) and whose
value may affect a scoring system’s AUROC (AUROC is
independent of disease prevalence, which in this scenario is
the prevalence of MT).30,48,52 As the prevalence of penetrat-
ing injury has the potential to directly affect the statistical
performance of the ABC score, understanding the epidemi-
ological differences in injury patterns between the United
States and other countries is imperative.
Epidemiological data from the TR-DGU report the per-
centage of traumatic injuries with a penetrating mechanism
as ranging from 4.8% to 5.3%.29,30,46 Of the penetrating inju-
ries encountered in an urban European setting, approxi-
mately 80% are stab wounds (overall incidence of 4.7%) and
20% are gunshot wounds (overall incidence of 1.1%).53 The
Royal Prince Alfred Hospital in Australia presents simi-
lar statistics, with 5.7% of all traumatic injuries having a
penetrating mechanism and with <1% attributable to gun-
shot and stab wounds.54 These numbers differ from those
observed in the urban Unites States, where the percentage of
traumatic injuries with penetrating mechanism ranges from
18% to 59%.27,48 In addition, the urban United States encoun-
ters a higher percentage of gunshot and stab wounds, with
1 urban trauma center observing that 5.8% of all traumatic
injuries encountered were from gunshot wounds and 6.3%
from stab wounds.55–57
These observations are noteworthy as the mechanism
of injury has a significant effect on patient morbidity and
mortality. Epidemiological studies have observed that, in
comparison to blunt mechanisms of injury, patients with
penetrating trauma are significantly more likely to die at the
scene of injury, to die within the first 6 hours after trauma,
and to require emergency intervention for hemorrhage con-
trol.56,58 Moreover, gunshot wounds have case-fatality rates
that are higher than any other mechanism of injury.55–57 This
epidemiological data highlight the substantial risk for mas-
sive endothelial damage that occurs with penetrating mecha-
nisms of injury, especially gunshot wounds, thereby placing
patients at increased risk for hypovolemia, decreased tissue
perfusion, and the lethal combination of the hypothermia,
metabolic acidosis, and coagulopathy.59 In addition, these
data likely explain the observation made during the ABC
validation study of an association between penetrating
Figure. Contribution of each variable to the TASH
and ABC scores. Histogram with each variables
used to calculate the ABC and TASH scores.
The bars represent the percentage contribu-
tion of each variable’s score toward each scor-
ing system’s total score. ABC score indicates
Assessment of Blood Consumption score; FAST
Examination, Focused assessment with sonogra-
phy for trauma Examination; SBP, systolic blood
pressure; TASH score, Trauma-Associated Severe
Hemorrhage Score.
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Copyright © 2017 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
mechanisms of injury and MT risk in the United States, and
why the ABC score’s ability to identify patients requiring
a MT would be diminished when applied to patient data
from European and Australian trauma registries.
With variations in trauma patient demographics as a
likely explanation for the ABC score’s relatively poor perfor-
mance when applied to trauma registries outside the urban
United States, one would also expect that the ABC score’s
performance in the rural United States, where the preva-
lence of both penetrating trauma and gunshot wounds is
reduced relative to urban areas, to also decline.60 This con-
cern was addressed in a small retrospective study that com-
pared the ABC and TASH scores for their ability to predict
MT requirements in a rural United States trauma setting.
The authors observed that the ABC score’s performance,
with an AUROC of 0.81, was similar to that observed in
its validation and revalidation studies.47 The results of this
study would suggest that the effects rural trauma demo-
graphics have on the statistical performance of the ABC
score is minimal, and would support the application of the
ABC score in the rural setting. However, as trauma demo-
graphics are variable across the United States, trauma cen-
ters that observe patient characteristics differing from those
presented in this rural ABC validation study should con-
sider revalidation or coapplication of both the TASH and
ABC scores to reduce the likelihood of false-negative MT
predictions.
Initiating MT in the Nontrauma Patient
Although the field of acute care surgery is the foundation
for research on MT and MTPs, massive hemorrhage after
traumatic injury is not the only reason for initiating an
MTP.61 The percentage of overall MTP activations that occur
in nontrauma patients is extremely variable and hospital
specific, ranging from 8% to as high as 50%.62–64 Despite the
high prevalence of MTs that occur in nontrauma patients,
literature discussing the role of MTPs outside of trauma is
limited and MTP guidelines often overlook MTP initiation
in nontrauma patients.20–22,64,65 In addition, although the use
of MTPs to guide resuscitation in massively hemorrhaging
nontrauma patients is associated with significantly decreased
time to delivery of blood products and a significant increase
 EE NARRATIVE REVIEW ARTICLE
in the percentage of transfusions delivering balanced ratios
of blood products, MTPs have not been shown to improve
patient outcome in this setting.66,67 One possible explanation
for the lack of observed mortality benefit may relate to the
abundance of MTP “overactivations” that occurs outside
of trauma.62,63 These overactivations, which are defined as
MTP activations in which patients do not receive sufficient
blood products to meet the classic definition of an MT, indi-
cate that hemorrhage outside of trauma is characterized by
considerably fewer cases of truly massive hemorrhage for
which MT has been proven to be beneficial.17
Due to the high percentage of MTPs occurring in non-
trauma patients, the high prevalence of MTP overactiva-
tions in the nontrauma setting, and the lack of objective
data to suggest mortality benefits, precise guidelines
for guiding MTP initiation in nontrauma patients are
imperative. Unfortunately, the decision to initiate an
MTP in the hemorrhaging nontrauma patient does not
benefit from the ability to apply validated scoring sys-
tems, such as those utilized in trauma. However, the suc-
cess of risk prediction scores for guiding intervention
in patients with gastrointestinal bleeding, most notably
the Glasgow-Blatchford score, would suggest that new
MT prediction scores specific to nontrauma hemor-
rhage could be developed.68 In addition, the Glasgow-
Blatchford score shares multiple variables with both the
TASH and ABC scores, implying that development of
an MT prediction score for use in nontrauma patients
would likely benefit from using the existing MT predic-
tion scores as templates.30,48,68
In cases where blood loss can be measured or estimated,
the decision to initiate an MTP in all hemorrhaging patients
could be supported by whether or not the patients meet cri-
teria for “massive hemorrhage.”1,5,6,8,69–72 However, due to
the lack of validated criteria for defining massive hemor-
rhage and concerns regarding the inaccuracy of blood loss
estimates, new literature has proposed utilizing the “inten-
sity of resuscitation” as a surrogate marker for hemorrhage
severity.69,73,74 The authors who proposed the idea of resusci-
tation intensity observed that trauma patients who received
4 or more units of any fluid, including crystalloid or various
blood products, within 30 minutes of arrival had significant
increases in 6- and 24-hour mortality rates.74
Interestingly, newer definitions of MT that define it as
a threshold transfusion rate of at least 3–4 units of packed
red blood cells (RBCs) per hour also mirror the idea of
resuscitation intensity.75,76 In addition, the transfusion
rates of 3–4 RBCs per hour are notable as they are the
transfusion rates at which patient mortality begins to
increase, again paralleling the observations of resuscita-
tion intensity.75,76 Therefore, through prospective moni-
toring of “resuscitation intensity” using evidence-based
blood and crystalloid threshold transfusion rates as sur-
rogates for massive hemorrhage, physicians have meth-
ods for identifying hemorrhaging nontrauma patients
at significant risk for higher mortality rates that would
potentially benefit from a formal MTP initiation. In the
absence of MT prediction scores, resuscitation intensity
offers a valuable objective method for aiding in the deci-
sion to initiate an MTP in the nontrauma setting.
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Hemostatic Resuscitation in the Prehospital
Setting
Given the negative effect that time delays before MT initia-
tion have on patient outcomes and the high hemorrhage-
related mortality rates that occur within the first hour after
trauma, the prolonged transport times reported in both
rural and urban settings are alarming.13,17,26,27,56,77–81 These
prolonged prehospital transport times are likely responsible
for increased patient mortality, and in the setting of massive
hemorrhage this effect is likely even greater.82–84 In addition
to existing protocols that successfully reduce prehospital
transport time and transfer delays, implementing guide-
lines for hemostatic resuscitation of hemorrhaging trauma
patients in the prehospital setting has significant potential
to improve patient survival.
Several hospital systems around the world have
researched the use of blood products during prehospital
transport.85 Although the current level of evidence is low
and the results are variable, prehospital transfusion of
plasma is associated with improved neurological outcomes,
reduced blood product requirements, and improved early
mortality.86–91 Whole blood has also shown mortality benefit
in the prehospital setting. Whole blood transfusions have
been used during military special operations with great
success, and programs in the United States have success-
fully implemented methods for acquisition, banking, and
transfusion of whole blood.92 In the military trauma setting,
whole blood was shown to decrease mortality, reduce trans-
fusion volumes, and better correct coagulation parameters
compared to individual components of whole blood.93–96
Despite these accomplishments, at this time the greatest
benefit whole blood is limited to resuscitation in the pre-
hospital setting where whole blood provides several critical
components necessary to support hemostasis in a compact
package.97–99
TERMINATION OF MASSIVE TRANSFUSION
PROTOCOLS
Prolonged resuscitation with large volumes of blood prod-
ucts puts patients at risk for developing numerous physi-
ologic disturbances and severe complications.18 However,
while physicians must be cautious to avoid prolonged and
unnecessary MTs, the decision to terminate an MTP should
not be premature. Failure to adequately resuscitate the
patient can lead to protracted tissue ischemia, increased
bleeding risk, and increased patient mortality.100 These
opposing issues detail the importance of evidence-based
guidelines for the termination of MTPs.
Societal Guidelines
The MTP guidelines presented by the ASA, ACS, and ABC-
Trauma regarding MTP termination are presented in Table 4.
These societies similarly recommend guiding MTP termina-
tion with clinical judgment and the fulfillment of 3 broad cri-
teria. These include bleeding source control or a decelerating
rate of blood loss, stable or improving hemodynamic vital
signs, and decreasing or absent vasopressor requirements.20–22
As MT is designed to provide hemostatic resuscitation during
periods of massive hemorrhage, evidence of slowing blood
loss and adequate resuscitation is judicious, evidence-based
ANESTHESIA & ANALGESIA
 Initiation and Termination of Massive Transfusion Protocols

Table 4.  The Societal Recommendations for Termination of Massive Transfusion Protocols

American Society of Anesthesiologists
  The following criteria should be met before termination of a massive transfusion:
   Bleeding source control
   Stable hemodynamic vital signs
American College of Surgeons
  The following criteria should be met before termination of a massive transfusion:
   Bleeding source control
   Stable hemodynamic vital signs
   Decreasing vasopressor dependence
Task Force for Advanced Bleeding Care in Trauma
  The decision to terminate an algorithm-guided model of resuscitation and transition to a laboratory
result–guided model of resuscitation should occur when laboratory data first results
  The following are recommended resuscitation targets:
   Hemoglobin concentration between 7 and 9 g/dL
   Prothrombin time and partial thromboplastin time <1.5× normal values
   PLT >50 × 109/L (PLT >100 × 109/L in patient with traumatic brain injury or active bleeding)
   Fibrinogen >1.5–2 g/L
   No recommendations regarding viscoelastic hemostatic assay parameters
The recommendations made by the American Society of Anesthesiologists, American College of Surgeons, and Task Force for Advanced Bleeding Care in Trauma
societies within their massive transfusion protocol guidelines pertaining to the topic of massive transfusion protocol termination.
Abbreviation: PLT, platelets.

criteria for guiding the termination of an MTP.100 The ABC-
Trauma guidelines, however, are unique in their recommen-
dation for prompt termination of the algorithm-guided model
of resuscitation that delivers fixed ratios of blood products
and rapidly transitioning into a resuscitation model guided
by laboratory test results, even when patients do not meet the
previously stated MTP termination criteria.22
Laboratory Testing for Guiding MTP Termination
The information presented in this article has thus far illus-
trated the importance of MTPs during the resuscitation of
hemorrhaging trauma patients in whom survival is depen-
dent on rapidly restoring circulating blood volume while
simultaneously correcting anticipated trauma-associated
coagulopathies. However, in patients requiring prolonged
resuscitation with blood products due to persistent hemor-
rhage, the algorithm-guided method of resuscitation used
during an MT would theoretically benefit from supplemen-
tation with a model that utilizes laboratory results to guide
further resuscitation. A laboratory result–guided method
would allow for accurate correction of specific abnormalities
of hemostasis and oxygen-carrying capacity, while simulta-
neously reducing unnecessary blood product transfusions.
This approach to resuscitation is supported by MT litera-
ture demonstrating that when laboratory result–guided
resuscitation is used in conjunction with algorithm-guided
resuscitation, patients require fewer blood products, patient
morbidity is reduced, and there is an improvement of objec-
tive hemostatic markers.101–104 Furthermore, increasing
uncertainty regarding the efficacy and safety of an extended
algorithm-guided MT with fixed ratios of plasma to RBCs
and platelets to RBCs has fostered the notion of transition-
ing to a laboratory result–guided resuscitation at the earliest
opportunity.73,105–110 This model of laboratory result–guided
resuscitation has been successfully used at select hospitals in
Denmark, where it is termed the “Copenhagen Concept.”111
It is also being intermittently applied in select hospitals in
the United States when the results of laboratory tests can be
obtained in a clinically relevant timeframe.111
The majority of the ABC-Trauma’s recommendations
regarding laboratory result–guided resuscitation specifi-
cally pertain to the use of conventional coagulation assays
(CCAs). However, increasing focus is now being directed
toward viscoelastic hemostatic assays (VHAs) as a method
to guided resuscitation in hemorrhaging trauma patients.
Given that a critical aspect of MT is supporting hemosta-
sis, VHAs have significant potential as they can further
elucidate trauma-associated coagulopathy by identifying
disruptions at specific intervals in the cell-based model
of hemostasis, including impaired thrombin generation,
impaired clot strength, and aberrant fibrinolysis.112 This
information is also capable of being presented rapidly and
in real time, with early rapid thromboelastography values
available within 5 minutes and all data within 15 minutes
of running the test; in comparison, CCA results can take up
to 48 minutes to return.113,114 Fast turnaround times are criti-
cal during MT as they not only allow for rapid identifica-
tion and treatment of coagulopathies but they also lessen
the physiological changes that may occur between drawing
the laboratory test and treating the abnormal result. The
benefits of VHAs over CCAs were shown in a RCT that
compared CCA- and VHA-guided resuscitation of trauma
patients after MTP activation.115 The authors observed that
mortality was significantly lower and fewer patients died
due to hemorrhage in the VHA group.115 Additionally,
VHA-guided resuscitation was associated with decreased
transfusion of platelets and plasma during the first 2 hours
of resuscitation.115 These results would suggest that VHA-
guided resuscitation is superior to CCA-guided resuscita-
tion in hemorrhaging trauma patients.
Despite the potential for VHAs to guide laboratory result-
based resuscitation in trauma patients, as well as historical
data on the success of VHA-guided resuscitation during
cardiac surgery and liver transplantation, research evaluat-
ing the morbidity and mortality outcomes of VHA-guided
resuscitation after trauma has yielded limited results.67,116–120
A 2014 systematic review evaluated 55 observational stud-
ies on the use of VHAs to diagnose coagulopathy and guide

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 EE NARRATIVE REVIEW ARTICLE
blood product transfusions after trauma.116 The findings
were overall inconclusive, and only 1 of these observational
studies directly compared the results of VHA-guided resus-
citation to the traditional algorithm-guided resuscitation in
hemorrhaging trauma patients. The results from this study
showed no overall difference in volume of blood product
transfused, ventilator days, intensive care unit days, or
overall patient mortality between the 2 treatment groups.121
The authors did, however, observe that VHA-guided resus-
citation significantly improved mortality in a cohort of pen-
etrating trauma patients that received more than 10 units of
RBCs (54.1% mortality for MTP versus 33.3% mortality for
VHA).121 What is most evident from this systematic review
is the lack of RCT data directly comparing MT with algo-
rithm- and VHA-guided resuscitation. Nevertheless, the
available data would suggest that VHA-guided resuscita-
tion after trauma may have a beneficial role in supplement-
ing the algorithm-guided approach to resuscitation within
the early rounds of an MT, especially in patients who con-
tinue to massively hemorrhage and are thus persistently at
high risk for tissue hypoperfusion and trauma-associated
coagulopathy.59
Finally, when considering laboratory result–guided
resuscitation during massive hemorrhage, it should be
noted that 1 of the primary benefits of an MTP that may be
lost is the rapid delivery of a balanced ratio of blood prod-
ucts to the patient’s bedside.3,13,67 Therefore, if the decision
to transition from an algorithm-guided approach to a labo-
ratory result–guided resuscitation protocol is made, phy-
sicians should continue the official MTP to benefit from a
continuous and timely delivery of blood products.
CONCLUSIONS
The advent of MTPs in the past 10 years has had a signifi-
cant positive impact on hemorrhaging trauma patient mor-
bidity and mortality. However, despite years of ongoing
research, academic institutions and societal guidelines on
MTPs are still unable to reach agreements on the best meth-
ods for guiding the initiation and termination of MTPs. The
lack of consensus regarding these critical MTP components
warrants an analysis and comparison of the current MTP
initiation and termination guidelines as well as the relevant
literature.
The ABC and TASH scores are validated MT prediction
scores recommended by several MTP guidelines for aiding
in the decision to initiate an MTP in hemorrhaging trauma
patients. Both scoring systems reliably identify patients
who do not require an MTP after trauma while demonstrat-
ing a tendency to incorrectly overpredict MT requirements.
The ABC score’s uniquely simplistic scoring system, easy-
to-remember variables, and rapid calculation have made it
a prominent component of MTPs in the United States. Still,
the effect that local trauma demographics, specifically, the
prevalence of penetrating trauma, may have on the statis-
tical performance of the ABC score highlights an area for
additional research.
The decision to initiate an MTP outside of the trauma
setting does not benefit from the ability to apply validated
MT prediction scores. However, risk prediction scores
for guiding the decision to intervene in cases of gastro-
intestinal hemorrhage are supportive, and they evaluate
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Copyright © 2017 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
variables similar to those found in MT prediction scores.
This highlights the potential for developing effective MT
prediction scores for use in hemorrhaging nontrauma
patients and for using current trauma MT prediction
scores as templates. Also of considerable value in the set-
ting of massive hemorrhage in nontrauma patients is the
concept of resuscitation intensity, which is considered a
surrogate marker for hemorrhage severity. This concept
allows physicians to identify hemorrhaging patients with
an elevated mortality risk through their RBC and fluid
transfusion rates, and thereby identify high-risk patients
who may benefit from an MTP initiation. Further research
to determine the ability of resuscitation intensity to guide
MTP initiation in the setting of nontrauma hemorrhage is
required.
Last, despite the serious complications that can arise with
transfusion of large volumes of blood product, the topic of
MTP termination has considerably less relevant research
compared to MTP initiation. Current societal recommenda-
tions regarding MTP termination emphasize clinical rea-
soning to identify patients with bleeding source control and
adequate resuscitation. The ABC-Trauma’s guidelines pres-
ent an additional recommendation for prompt termination
of the algorithm-guided model of resuscitation and rapidly
transitioning into a resuscitation model guided by labora-
tory test results. Literature has shown that CCA-guided
resuscitation during massive hemorrhage leads to fewer
blood product transfusions and improved patient mortal-
ity. Furthermore, the encouraging literature on VHAs and
their ability to surpass CCAs with regard to identifying and
treating coagulopathies emphasizes the potential of these
tests to further enhance the benefits obtained through utili-
zation of laboratory result–guided resuscitations during the
termination of MTPs. RCTs directly comparing algorithm-
guided and laboratory result–guided resuscitation methods
are needed before further recommendations can be made
regarding the functional role for this approach to guide
MTP termination. E
DISCLOSURES
Name: John C. Foster, MD.
Contribution: This author helped with the conception of the work,
drafting of the manuscript, critical revision of the manuscript, and
approval of the final manuscript.
Name: Joshua W. Sappenfield, MD.
Contribution: This author helped with the conception of the work,
drafting of the manuscript, critical revision of the manuscript, and
approval of the final manuscript.
Name: Robert S. Smith, MD.
Contribution: This author helped with the conception of the work,
drafting of the manuscript, critical revision of the manuscript, and
approval of the final manuscript.
Name: Sean P. Kiley, MD.
Contribution: This author helped with the conception of the work,
drafting of the manuscript, critical revision of the manuscript, and
approval of the final manuscript.
This manuscript was handled by: Marisa B. Marques, MD.
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