Page 91 - 2020 JSOM Winter

makes compliance challenging, the 75th Ranger Regiment and, if applied to our lightest warfighters, roughly matches the
TXA protocol was executed in low-light conditions in less recommendations for high risk cardiothoracic surgery patients,
than 20 minutes on average from time of assessment. Com- but applied in a single flush rather than over 15 minutes. How-
bined, these limited findings suggest that the 2g TXA flush ever, the risk of massive hemorrhage is likely much greater in,
is potentially faster and easier to execute than the slow and for example, an IED blast casualty than for a cardiothoracic
cumbersome 2019 TCCC TXA infusion protocol. surgery patient. Given the empirical evidence that higher levels
of TXA can be more effective than lower doses, the optimal
Although the present case series was too small to determine dosing of TXA in the traumatically injured warfighter remains
the overall safety of this novel approach, present findings an important open area for future research. 7
combined with previous literature suggest the possibility that
the fears associated with the purported adverse effects of Implications
TXA might not be fully congruous with the context of young,
healthy warfighters. The two most commonly feared adverse TXA provides a mortality benefit when administered within
effects associated with TXA administration are hypotension the first 3 hours of traumatic injury. The present case series
4
and seizures. Hypotension, which is hypothesized to be related suggests the possibility that TXA can be administered at a
to rate of administration, is described on the TXA package much faster rate compared to current guidelines. Further, all
insert with recommendations to not exceed 1mL/min (100mg/ six patients were treated with TXA in low-light combat condi-
min). To our knowledge, only one documented case of hy- tions and results were consistent across IV or IO administra-
11
potension associated with TXA administration has been de- tions. While more research is needed, this simplified method
scribed in the literature, and it occurred in a patient who had for accelerated TXA administration rates holds potential for
“an earlier tendency to orthostatic symptoms” during a 1969 improving casualty outcomes and increasing TXA protocol
randomized controlled trial. Seizures related to TXA admin- compliance.
13
istration have been predominantly described in cardiothoracic
surgery patients. A 2015 meta-analysis of 26,079 patients re- Limitations
ceiving TXA during cardiac or thoracic surgery found a cumu-
lative incidence of TXA-associated seizure to be 2.7%, with This retrospective case series was limited by the sample size,
seizure incidence rising with increased TXA dose exposure. which was modest and included only healthy military-aged
12
The current favored mechanism postulates a TXA-induced an- men from a single US military area of operation with injuries
tagonism of gamma-aminobutyric acid type A (GABA ) recep- sustained during a brief observational window. All cases met
A
tors. Notably, the cohort in the 2015 meta-analysis was older the criteria for TXA administration, and while injuries varied
19
than 60 years, with advanced disease processes necessitating in both mechanism and severity, this case series was not com-
cardiothoracic surgery, which does not align well with the prehensive. The results of this case series should therefore be
typical military-aged cohort for which TCCC guidelines were generalized only with appropriate caution.
designed. 2,12 The MATTERs study included warfighters with a
mean age of 24 years old, none of whom experienced a seizure The case series was also limited by the measured variables.
following TXA administration. Future research is required This case series did not account for comorbidities unrelated
10
to determine the side effect profile of a 2g TXA flush in young to the traumatic injury. Further, precise vital signs and injury
healthy warfighters. However, the findings of this case series, severity data were not acquired. Recorded vitals were docu-
in addition to current literature, suggests the potential risks of mented by 75th Ranger medics, who were providing high lev-
a 2g TXA flush could be outweighed by the known mortal- els of care in austere and extremely stressful combat situations.
ity benefit of TXA. In fact, for the 2020 protocol update, the The 75th Ranger medics are instructed to assume a detectable
Committee on TCCC has adopted a TXA dosing and adminis- radial pulse as a minimum estimated systolic blood pressure of
tration protocol similar to the one described in this case series. at least 80mmHg and a carotid pulse as a minimum estimated
(Danielle Davis, senior administrative assistant for Committee systolic blood pressure of 60mmHg, which is less precise than
on TCCC, email communication, July 7, 2020) pressures obtained by sphygmomanometer. The after-action
17
reports (AARs) lacked the necessary data to calculate stan-
The 2g TXA dose is somewhat arbitrary. The 2019 TCCC TXA dardized Injury Severity Scores (ISS). This retrospective case
guidelines mirror the landmark CRASH-2 trial protocol of 1g series investigated occurrences of known TXA adverse effects
infusion over 10 minutes followed by an intravenous infusion during a relatively brief period following drug administration,
of 1g over the following 8 hours. The CRASH-2 authors re- with no evaluation of long-term casualty outcomes.
2,4
lied on cardiac anesthesia literature to develop a fixed dose that
was presumed safe and effective for both larger and smaller Finally, this case series was limited by the retrospective design,
patients. 4,20 Subsequent cardiac anesthesia literature has shown which included no control or comparison cases or groups that
greater efficacy with increased doses of TXA. For example, for used the standard 2019 TCCC TXA protocol versus the modi-
7
patients who have an anticipated high risk of bleeding during fied 75th Ranger Regiment TXA protocols. All retrospectively
cardiac surgery, a recommended bolus dose of 30 mg/kg is evaluated data were obtained from AARs written by the 75th
given over 15 minutes, followed by a 16 mg/kg/h dose until Ranger medics within 48 hours of the time of injury. The stress-
chest closure. This dosage is more than double the TXA pack- ors of the combat environment and the delay in data recording
7
age insert recommendations of 10 mg/kg of body weight IV in could have affected documentation detail and accuracy.
an individual with normal renal function, which is specific to
the US Food and Drug Administration (FDA) approved use of Areas for Future Research
TXA for hemorrhage prevention in hemophilia patients under-
going tooth extraction. The 2g dose investigated in the pres- It is crucial to determine the optimal TXA dose for traumati-
11
ent case series doubles the 2019 TCCC initial dose guidelines cally wounded warfighters and for those wounded collaterally.
2g TXA Flush From the 75th Ranger Regiment | 89