A Cross-sectional Survey on the Use of Tranexamic Acid in the Pre-hospital Setting
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C ONTR IBUTIO N
A Cross-sectional Survey on the Use of Tranexamic Acid
in the Pre-hospital Setting
MEAGAN KOZHIMALA, MD-ScM’21; NICHOLAS ASSELIN, DO, MS; MARK R. ZONFRILLO, MD, MSCE
A BST RA C T of epistaxis compared to acute packing.7 There have been
S T UD Y OBJECTIVE : Tranexamic Acid (TXA), an anti- several published studies and case reports regarding the
fibrinolytic, has been used in military trauma cases and use of TXA in emergency medicine for various indications,
civilian Emergency Departments for several years. This including gastrointestinal hemorrhage,8 traumatic hemor-
rhage,9 and hemoptysis.10 However, its use in EMS is more
study aims to evaluate protocols for the administration
recent and there is limited knowledge on the use of protocols
of TXA across Emergency Medical Services (EMS) regions
for pre-hospital administration of TXA and how they might
in the United States.
differ across the United States (US). This study aimed to
M E THOD S: An anonymous survey was distributed by evaluate the prevalence of specific protocols in the EMS set-
the National Association of Emergency Medical Techni- ting across US regions and identify the inclusion/exclusion
cians (NAEMT) to its members. criteria utilized.
RE SULTS: A total of 264 eligible responses were received.
Respondents included paramedics (62.5%), emergency
METHOD S
medical technicians (EMTs) (9%), critical care paramed- This cross-sectional survey study was determined to be
ics (11%), and other health care professionals (19%). The exempt from review by our institutional review board.
majority of protocols included criteria for blood pres- Participation was voluntary and anonymous. Consent was
sure (67%), heart rate (53%), and age (66%). Notable implied by clicking on a link. The survey targeted paramed-
variations included TXA dilution and indications for ics and emergency medical technicians (EMTs). Participants
traumatic brain injury. also included nurses, physicians, and other health care pro-
C ONCLUSION: TXA has been widely implemented in fessionals involved in transport of patients to a hospital. Par-
EMS protocols since the CRASH (Clinical Randomiza- ticipants were excluded if they did not provide civilian care
tion of an Antifibrinolytic in Significant Hemorrhage) in the pre-hospital setting in the U.S. The 23-item survey
trials. However, there remains significant variations in was designed with Qualtrics (Qualtrics, LLC; Provo, Utah).
indications and dose concentrations. It included multiple choice and free text questions and
incorporated skip logic. The survey was reviewed by content
K E YWORD S: TXA, Tranexamic Acid, Pre-hospital,
and methods experts, as well as by the National Associa-
EMS protocol tion of Emergency Medical Technicians (NAEMT) technical
board. To ensure clarity of survey items, the questionnaire
was piloted with survey design experts and paramedics prior
INTRO D U C T I O N to wider distribution to the NAEMT website. The complete
Tranexamic Acid (TXA), an anti-fibrinolytic, was originally survey instrument is available upon request.
used in the military to control hemorrhage in trauma vic- Questions focused on the presence of prehospital TXA
tims.1 The Clinical Randomization of an Antifibrinolytic in protocols and the inclusion/exclusion criteria utilized.
Significant Hemorrhage (CRASH) trials indicated that early Specific survey items were based upon the published liter-
use of TXA for trauma patients with or at risk of hemorrhage ature from the CRASH-2 trials2 as well as the protocol by
was correlated with a significant reduction in mortality.2 Strosberg and colleagues.11 Participants were also asked to
Since the 1960s, TXA has been part of civilian care in obstet- indicate in which region of the U.S. they practice. The five
rics and gynecology,3 otolaryngology,4 and emergency medi- NAEMT regions consist of the following states:
cine. More recently, it has been used by Emergency Medical East region: CT, DE, ME, MD, MA, NH, NJ, NY, PA, PR, RI, VT, VA, DC, WV
Services (EMS) prior to the patient’s hospital arrival.5 Sev- South region: AL, AR, FL, GA, KY, LA, MS, NM, NC, OK, SC, TN, TX
eral published research studies over the years show bene- Great Lakes region: IL, IN, MI, MN, OH, WI
fits and complications of TXA. The use of TXA was shown
Western Plains region: CO, IA, KS, MO, MT, NE, ND, SD, UT, WY
to decrease mortality in uterine hemorrhage.6 One ran-
domized controlled study showed that topical use of TXA West region: AK, AZ, CA, HI, ID, NV, OR, WA
significantly decreased bleeding time and recurrence rates Responses were collected in December 2019.
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RESU LT S protocol from another system or source (8%, n=15), regional
Demographics and Existence of Protocols EMS Agency (10%, n=17), internal committee (9%, n=18),
Of the 268 responses received, 264 were included for this and an external committee (4%, n=7).
study. Four were excluded for the following reasons: did not
provide care in a pre-hospital setting (n=2), part of military Comparison of Existing Protocols
care (n=1), and located outside of the U.S. (n=1). Of the 264 Inclusion Criteria: In all 5 regions, the majority of responses
responses, 62.5% (n=180) of respondents were paramedics, indicated their institutions’ protocols had requirements
8.7% (n=25) were EMTs, 10% (n=29) were critical care para- for evidence of age-appropriate shock determined by vital
medics and 19% (n=54) identified as another health care pro- signs. A majority (54%, n = 61) of participants indicated a
fessional, including flight nurses, transport physicians, EMS minimum age criterion for administering TXA. Minimum
physicians, and respiratory therapists. The respondents’ age criteria ranged from 2-18 years old with a mode of 16
demographics are shown in Table 1. years old. Minimum heart rate criteria were included in
53% (n=60) of the respondents’ institutions’ protocols, most
Table 1. Demographics of survey participants commonly >110 bpm (55%, n=33) and >120 bpm (23%,
n=14). Other minimum heart rates included 115 bpm (n=3),
Role # %
100 bpm (n=4), and 130 bpm (n=2). A systolic blood pres-
Paramedic 180 62.5 sure (SBP) requirement was indicated in 60% (n=70) of par-
Critical care paramedic 29 10.1 ticipants’ protocols, nearly all with the threshold of SBP<
Emergency medical technician (EMT) 25 8.7 90mm Hg (94%, n=66). Time criteria was indicated by 74%
(n=85) and a requirement of injury or bleeding occurrence
Flight paramedic 12 4.2
within 3 hours of TXA administration was selected by 93%
Advanced EMT (or other intermediate) 7 2.4 (n=79). Other responses had the following time windows:
Flight nurse 6 2.0 1 hour (n=2), 2 hours (n=2), and 8 hours (n=1).
Critical care transport nurse 4 1.4 Exclusion Criteria: An allergy or hypersensitivity to TXA was
Emergency medical services physician 5 1.7 indicated by 45% (n=77) as an exclusion criterion and dissem-
Other physician 3 1.0 inated intravascular coagulation was part of the exclusion
Respiratory therapist 1 0.4
criteria for 20% (n=34). In addition, 23% (n=39) of partici-
pants stated their protocol had exclusion criteria that were
Emergency medical responder 1 0.4
not included as survey options which included: traumatic
“Other” 15 5.2 brain injury (TBI), drowning, prior thromboembolic disease,
* There were 288 roles selected by 264 respondents dialysis, renal failure, cardiac arrest, and pregnancy (specif-
ically > 24 weeks gestation). Approximately 11% (n=18) of
Three-quarters (n=198) of survey participants stated that participants stated their protocols had no exclusion criteria.
TXA administration was within the scope of practice for
EMS and used at their institution. Of survey participants Medication Administration
who use TXA in their setting, a majority (62%), stated its Intravenous (IV) delivery of TXA was indicated in 56%
use is controlled by a protocol or standing order, followed by (n=109) of responses, with 41% (n=79) also allowing intraos-
provider judgement (20%), and medical director (13%). Few seous (IO) delivery. Alternative delivery such as transder-
participants (5%) selected “Other,” which included the use mal, topical, and intranasal was reported by 3% (n= 6).
of an online medical control system or physician authoriza- All participants who indicated their institution had a TXA
tion. Of the 198 respondents who stated that TXA admin- protocol (100%, n=165) stated that their protocol had dose
istration was within the scope of practice for EMS, not all requirements, with 16% (n=18) of participants stating, “1000
completed the subsequent questions which is reflected in mg in 250 cc NS” and 29% (n=32) had “1 g mixed in 50 cc”.
the following analyses. However, the majority of the respondents, (46%, n=51), stated
a different concentration from the options offered. Of those 51
Development of Insitutional Protocols respondents, 90% (n=46) stated their protocol had a concen-
Participants shared how their existing protocol for TXA tration of 1 gm in 100 cc of NS. One participant had “Trauma
was developed and 37% (n=72) indicated development arrest 1 gm IVP” and one indicated weight-based dosing.
by a medical director. Several (31%, n=50) indicated a A majority (83%, n=137) of participants with TXA pro-
multi-disciplinary approach to development, involving tocols at their institutions stated that their system did not
medical directors, EMS services, trauma committee, and have other options for treating acute blood loss, such as
State Departments of Health. An individual breakdown of administration of blood products. And 17% (n=28) stated
the various means of creating a protocol were reported as they did have other options, including packed red blood
follows: State Departments of Health or other state agency cells, plasma, fresh frozen plasma, and QuickClot® (kaolin
(14%, n=28), EMS services (13%, n=26), adopting an existing impregnated gauze).
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Actual Use of Protocol in Possible Administration of TXA When asked to describe the settings where they delivered
The survey also assessed how many times participants care, most participants stated Urban (32.59%, n=132) or
assessed a patient for use of TXA over the past year, most Rural (33.83%, n= 137); 26.17% (n=106) were suburban, and
commonly more than 4 times within the year (31%, n=34) about 7% (n=28) were “Austere/Very Rural.” Of those par-
and zero instances in the past year (28%, n=36). The remain- ticipants, the distribution of those that indicated the exis-
ing frequencies for TXA assessment were as follows: 1 time tence of a protocol at their institution was as follows: 86%
(14%, n=15), 2 times (15%, n=16), 3 times (5%, n=5), and 4 (n=24) for austere settings, 73% (n=101) for rural, 64% (n=68)
times (4%, n=4). The regional distribution of frequencies for for suburban, and 61% (n=81) for urban.
TXA administration across regions is shown in Table 2. In all 5 regions, the majority of responses indicated that
For those situations where patients were assessed regard- TXA administration was regulated by a protocol or standing
ing the administration of TXA, a majority (42%, n=86) were order. The exact breakdown by region is seen in Figure 1.
related to trauma. Other instances comprised of the fol- Of participants that did administer TXA to patients in the
lowing: gastrointestinal hemorrhage (10%, n= 21), signs of pre-hospital setting, a majority (36%, n=44) indicated that
shock (9%, n=18), obstetrics/gynecological hemorrhage (7%, they administered TXA within 16–30 minutes from onset
n=15), epistaxis (5%, n=11), wounds (5%, n=11), TBI (4%, of injury or bleed. The rest of the time frames from onset of
n=9). TBI was indicated as a reason for assessment for TXA
administration in all regions, except the East region. Figure 1. Regional distribution of how TXA administration is authorized
Table 2. Regional distribution of frequencies for TXA administration in
2019 in the pre-hospital setting
Frequency East South Great Western West TOTAL
Lakes Plains
(n=30) (n=37) (n=19) (n=11) (n=11) (n=180)
0 times 40% 24% 24% 41% 36% 31%
1 time 10% 14% 25% 25% 0% 14%
2 times 13% 21% 14% 4% 18% 15%
3 times 0% 5% 5% 8% 10% 5% Table 4. Average time for administration of TXA from onset of injury
4 times 0% 5% 4% 0% 18% 4% across regions
> 4 times 37% 31% 28% 22% 18% 31% Average East South Great Western West TOTAL
Time Lakes Plains
Regional Distributions (n=27) (n=38) (n=20) (n=6) (n=8) (n=121)
The regional distribution of responses were: East (36%, < 5 min 0% 0% 0% 0% 0% 0%
n=62), South, (31%, n=52), Great Lakes (17%, n=29), Western 5–15 min 15% 8% 10% 9% 22% 12%
Plains (8%, n=14), and West (8%, n=13). This distribution 16–30 min 48% 50% 30% 18% 22% 36%
compared to the regional distribution of NAEMT members
31–60 min 11% 24% 35% 27% 44% 27%
can be seen in Table 3. The region with the highest percent-
age of respondents who reported TXA administration pro- > 60 min 0% 3% 5% 0% 0% 3%
tocols were from the South region (38%, n=37), followed by Other 11% 0% 10% 9% 0% 5%
the East region (24.7%, n=24), Great Lakes (16.5%, n=16), Unsure 15% 15% 10% 37% 12% 17%
Western Plains (9.3%, n=9), and West (11.3%, n=11). The
ascending order of regional distribution of overall survey Table 5. Average transport time across regions
participants did not exactly match that of NAEMT mem- Average East South Great Western West TOTAL
bers. However, the ascending order of survey participants Time Lakes Plains
who stated they had a TXA protocol did align with that of (n=30) (n=38) (n=20) (n=11) (n=11) (n=110)
NAEMT members’ regional distributions. < 15 min 20% 13% 20% 17% 18% 17%
15–30 min 47% 61% 40% 41% 45% 51%
Table 3. Geographic distribution of survey participants and NAEMT
members based on EMS regions 31–45 min 30% 18% 25% 17% 36% 25%
46–60 min 3% 3% 15% 17% 0% 6%
Region East South Great Western West
Lakes Plains > 60 min 0% 3% 0% 0% 0% 0%
Survey (n=164) 36% 31% 17% 8% 8% Other 0% 0% 0% 0% 1% 1%
NAEMT (n=101,805) 24% 38% 13% 10% 15% Unsure 0% 2% 0% 8% 0% 0%
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injury or bleed were as follows: 5–15 min (36%, n=44), 31–60 administration times and average transport times, none of
minutes (27%, n=33), >61 minutes (3%, n=4). Across all 5 these times surpassed the recommended 3-hour window for
regions, TXA administration was predominantly 16–30 min- administering TXA.
utes from onset of injury. Only the South and Great Lakes This study is limited by its small sample size and is
regions indicated TXA administration >1 hour from injury subject to selection bias. The survey was directed towards
onset. The regional distribution for time of TXA administra- members of a national EMS organization, limiting the gen-
tion from injury onset is presented in Table 4. eralizability of results. However, the representation of par-
Average transport times varied across regions (Table 5). ticipants across regions offers a reasonable sample of the
However, all 5 regions had a majority (49%, n=63) of its par- current state of protocols for TXA administration in EMS.
ticipants indicate an average transport time of 15–30 min- Compared to the regional distribution of NAEMT members,
utes. An average transport time of over an hour was only where majority were from the South region, participants
indicated by the South region. The West region did not have showed a majority of responses from the East region. One
any average transport time greater than 45 minutes. possibility is bias of recognition due to participants knowing
our institution is located in the East region. However, the
participants that had a TXA protocol at their institution did
DISC U S S I O N align with the regional distribution of NAEMT members,
The results offer a novel, national perspective on EMS TXA possibly showing a link to protocols and the influence of the
protocols. The creation of protocols varied among partici- organization. Additionally, information that was provided
pants and many indicated several means of development. A might not be accurate if participants answered questions
majority of responses indicated that protocols shared sim- based on memory of protocol criteria, subjecting this study
ilarities for inclusion criteria for heart rate, age, and blood to recall bias and subjective survey language could have
pressure. Additionally, these criteria values matched those been misinterpreted.
that were introduced by Strosberg et al11 and aligned with
the findings of the CRASH-2 trials.2 The CRASH-2 trial
demonstrated that TXA administration after 3 hours of C ONC LU SION
injury was correlated with increased mortality. The major- Protocols are an important part of TXA administration in the
ity of protocols described in this survey study indicated an pre-hospital setting. In our survey, the majority of reported
inclusion criteria of < 3 hours from onset of bleed for TXA protocols had several similarities, including inclusion crite-
to be administered, although there were outliers. Similarly, ria for blood pressure, heart rate, and age. While many of
most participants who received TXA were administered a these criteria aligned with original TXA protocols, there was
concentration of 1 gm/100cc over ten minutes. This con- variability in the relative inclusion of TBI and the admixture
centration is different from the original protocol included in concentration for TXA. The persistence of these variations
Strosberg et al, which recommended a 1g/50 cc dose.11 This along with those in inclusion and exclusion criteria suggest
could be explained by the known adverse effect of hypoten- a joint scientific statement from national organizations that
sion with rapid infusion of TXA at >100mg/min.12 oversee EMS care may be beneficial in encouraging evi-
The survey responses identified variability in inclusion dence-based protocols. In 2019, the National Highway Traf-
and exclusion criteria. Some institutions included TBI as an fic Safety Administration created broad guidelines for EMS
indication for TXA use while others stated it was a clear care in the National EMS Scope of Practice model;16 how-
contraindication. The 2018 TICH-2 trial13 (tranexamic acid ever, this guidance does not include any medications. Based
for hyperacute primary intracerebral hemorrhage) results on the variation in protocols observed in our survey, it may
showed no significant difference in functional status of be beneficial to consider the addition of specific medications
patients receiving TXA vs placebo. However, the more to this model, including TXA, to optimize a standard of care
recent CRASH-3 trial results showed that TXA administra- for patients in the pre-hospital setting.
tion within 3 hours for mild-moderate head injury resulted
in significant mortality reduction and improved functional
status without increased adverse effects.14 In contrast, there
was no significant difference in mortality for severe head References
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