TXA use in Trauma: An Update

 TXA is a weak inhibitor of fibrinolysis, displacing plasminogen from fibrin and reducing
plasmin activity
 It acts to tip the balance of all those complex molecular interactions Dr. Coats described
away from clot breakdown, but not so far as to create a theoretically hypercoagulable
state
 Significance was defined as a bleed causing a drop in systolic blood pressure below 90
mmHg, heart rate greater than 110 bpm or a bleed risk great enough that the clinician
thought blood transfusion would likely be required.
o In practice, this latter part of the inclusion criteria was treated as synonymous
with the question of whether to type and cross-screen a patient’s blood
 CRASH-2 Trial, 2010: TXA treatment protocol resulted in a significant reduction in both
all-cause mortality and risk of death due to bleeding by 1.5% and 0.8% respectively (p
value 0.0035 and 0.0077) if administered within the first three hours of injury.
Importantly, there was no evidence of increased thrombotic events
 CRASH-2 trial excluded patients with primary traumatic brain injury, a large subset of
emergency department populations, based on data from a 2003 study connecting TXA
use with increased cerebral edema in subarachnoid hemorrhage
o CRASH-3 trial is currently ongoing, which will attempt to guide usage in this
specific patient subset
 In addition, the mortality benefit is entirely lost if TXA is given later than three hours
after injury
o It should be noted that there is a paucity of data describing the effect of TXA in
the presence of recombinant factor VIIa and therefore it is not recommended for
concomitant use at this time
 TXA is an inexpensive intervention at roughly 100 USD per gram
 MATTERs trial: study found a reduction in 48-hour mortality from 18.9% in the control
group to 11.3% in the TXA group, a 7.6% reduction in mortality
 Annals of Emergency Medicine published a policy paper recommending the use of TXA
per CRASH-2 protocol in trauma patients at risk of significant hemorrhage without
isolated traumatic brain injury:
o TXA TRAUMATIC HEMORRHAGE DOSAGE
 1 g IV bolus in 100 mL NS within first 3 hours of incident
 1 g IV in 500 mL NS over the following 8 hours
 Contraindications: Primary head trauma, factor VIIa administration
Consider Tranexamic Acid for Traumatic Hemorrhage
 Hemorrhage is responsible for 30% of in-hospital trauma deaths worldwide every year
 TXA is an analog of the amino acid lysine that blocks the lysine binding site on
plasminogen, preventing its conversion to plasmin, which in turn degrades fibrin
o Preventing fibrin breakdown, TXA acts as a hemostatic agent (promotes
coagulation) and should therefore decrease blood loss in any bleeding condition
 CRASH-2, Clinical Randomization of an Antifibrinolytic in Significant Haemorrhage, trial
o Inclusion criteria: hemodynamic instability (SBP<90, HR>110) and “suspected
hemorrhage.”
o Reduction in the risk of death of 1.5% in those that received TXA, without an
increase in vaso-occlusive events (ie, PE, DVT, AMI).
o No difference in the amount of blood products given between the groups
o Mortality benefit of TXA was only observed within the first three hours after a
traumatic injury; after three hours, TXA actually increased mortality
 MATTERs Study, Military Application of Tranexamic acid in Trauma Emergency
Resuscitation, assessed the application of TXA to a sicker population
o Unadjusted absolute reduction in mortality in the TXA group of 6.5%
 Subgroup of patients that underwent a massive transfusion (>10 units
pRBC’s within 24 hrs), there was a decrease in mortality of 13.5% in the
TXA group
 Patients who received TXA had a significant decrease in
hypocoagulability (INR > 1.5; aPTT > 1.5x normal)
 Of note: rates of venous thromboembolism and pulmonary embolus,
though rare and non-fatal, were increased in the TXA group.
 Authors suggested this was due to the higher injury severity
rather than TXA but we cannot know for sure
How and When to Use TXA for Trauma Patients
Indications:
 Adults with acute traumatic injury leading to significant hemorrhage and requiring blood
transfusion.
 May be beneficial in trauma patients with significant hemorrhage and evidence of
hyperfibrinolysis on rotational electrothromboelastometry (ROTEM).
 Should only be given less than 3 hours from the time of injury.
 Dosing: 1 gram IV bolus over 10 minutes, followed by 1 gram continuous IV infusion
over 8 hours.
 Cost: About $60 per 10 mL (1 gram)
RESUSCITATION OF The Pregnant Trauma Patient – Pearls & Pitfalls

 Best fetal resuscitation is good maternal resuscitation. Optimizing maternal
hemodynamics and oxygenation, will ensure the best fetal outcomes
 The FAST is less sensitive for free fluid in the pregnant patient than in non-pregnant
patients. Sensitivity decreases with increasing gestational age, likely due to altered
fluid flow within the abdomen.
o FAST was most sensitive in the 1st trimester and least in the 3 rd
 Authors theorize this may be due in part to compression of the paracolic
gutters and altered intra-abdominal fluid flow in late pregnancy.
 Expect a difficult airway, optimize pre-oxygenation and positioning, and expect
significant edema and mucosal friability.
o The same factors that predict a difficult airway in the non-pregnant population
(Mallampati score, body habitus, short neck, and large incisors) are also
predictive of a difficult airway in pregnancy. However there are other changes in
pregnancy that can increase the difficulty of intubation:
 Airway edema associated with the progesterone-mediated increase in
total-body water as well as increased mucosal friability and as a result a
higher likelihood of bleeding during manipulation.
o Risk of aspiration is also increased due to decrease in lower esophageal sphincter
tone and increased intra-abdominal pressure from the gravid uterus.
 Decrease the risk of aspiration, positive pressure ventilation should be
avoided if possible. If bagging is required lower volumes and slower
inhalation times are recommended.
o Oxygen consumption increases throughout pregnancy by 30-60%, however there
is a decrease in total lung volume due to upward displacement of the
diaphragm. Desaturate much more quickly
 Minute ventilation is increased, primarily through an increase in tidal
volume (rather than an increase in RR)
 Estimation of minute ventilation based solely on respiratory rate will
underestimate ventilatory needs due to increased tidal volume
 In late pregnancy, consider placing a chest tube higher than you would in a non-
pregnant patient.
o Cephalad displacement of the diaphragm up to 4 cm
o Insertion of a chest tube in the 3rd or 4th intercostal space instead of the 5th
 The patient should be positioned to reduce compression of the great vessels by the
gravid uterus.
o The weight of the gravid uterus falls posteriorly in the supine patient, and may
compress the IVC and aorta causing reduced venous return and resultant
hypotension
o Placing the patient in 15 – 30 degrees of left lateral tilt may improve cardiac
output by 30-50%
 Attempt to obtain supra-diaphragmatic intravenous or intraosseous access for volume
resuscitation and medication administration.
o The gravid uterus causes compression of the IVC and may reduce venous return
from the lower extremities, limiting the utility of volume or resuscitation or
medication administration by infra-diaphragmatic access.
 CT imaging should be performed as clinically indicated; diagnostic studies, including CT
of the abdomen and pelvis, will not expose the fetus to an unsafe amount of radiation.
Contrast agents should be used if indicated.
o Doses of less than 50 mGy are not associated with increased rates of fetal
anomaly or loss
 A fetal dose of 50 mGy increases the risk of childhood cancer from 1:2000
to 1:1000, and increases the lifelong risk of cancer by 2%
o A CT of the head, C-spine, chest, abdomen, and pelvis exposes the fetus to 25.2
mGy.
 Perimortem cesarean section should be performed by emergency providers in cases of
maternal cardiac arrest and a pregnancy sufficiently advanced to cause aortocaval
compression. Ideally this would be initiated within 4 minutes of arrest; however even
after substantial delay may be beneficial to both mother and fetus.
o AHA guidelines recommend prompt perimortem C-section to alleviate aortocaval
compression and allow extra-uterine fetal resuscitation
o Older guidelines recommended waiting 4-5 minutes after arrest before
beginning perimortem cesarean section
o The 2010 AHA guidelines do NOT recommend a mandatory trial of medical
therapy prior to initiating cesarean section, and suggest that in some cases
including clearly non-survivable maternal injury, it may be beneficial to the fetus
to begin the procedure as soon as maternal arrest occurs.
o Even in the case of a nonviable fetus, perimortem cesarean section may improve
maternal hemodynamics by alleviating aortocaval compression. AHA guidelines
suggest that it should be considered for pregnancies thought to be 20 weeks or
greater, which can be estimated by finding the uterine fundus at or above the
level of the umbilicus
o For viable fetuses, outcomes are best when delivery occurs within 5 minutes of
maternal arrest, however there have been fetal survivors delivered after delay as
great as 30 minutes
o Lack of a complete surgical tray should not prevent initiation of perimortem
cesarean section. Knife and scissors are the only instruments needed. Due to the
low cardiac output associate with maternal arrest minimal bleeding should be
expected unless ROSC occurs. Consideration should be given to concomitant
thoracotomy if indicated
The PROPPR trial with John Holcomb
 Our current definitions of massive transfusion are outdated. Better may be the Critical
Administration Threshold–if you give 3 units of blood in any 1 hour period, it is a
massive transfusion. But…
 Dr. Holcomb doesn't wait for the 3 unit threshold. At his shop, they try to make the 1st
unit transfused plasma or platelets and start matched transfusion from that point
forward.
 In the PROPPR trial, only about 2/3 of the patients received TXA, but CRASH2 indications
would have had all of them receive it. Dr. Holcomb uses TEG to decide, and wants to see
more RCTS (they are being done) to better clarify the role of TXA. For more on that
though, see my podcasts with Tim Fabian and Karim Brohi. Vicoelastic tests may be
insensitive to fibrinolysis based on these discussions.
 The Kaplan-Meier curves for a 3 hour endpoint showed a statistically significant
mortality difference between the two groups, but this was not one of the allowed
primary outcomes.
One Platelet, One Plasma and One RBC – PROPPR Trial
 SGEM bottom line: a 1:1:1 transfusion strategy is a reasonable approach to adult
patients who require a massive transfusion and seems to achieve more hemostasis and
less death from exsanguination at 24 hours without increased complications.
 Clinical Application: For adult patients who require massive transfusions a 1:1:1: is not
superior to a 1:1:2 strategy. The PROPPR data suggests giving platelets earlier and in
higher ratios
REBOA
The Shock Trauma Center (STC) Approach to REBOA:
Gain Access to the Common Femoral Artery with Femoral A-line Kit
 Just like normal, except make sure you are hitting common femoral and not superficial
femoral artery. The point of entry should be 2cm below inguinal ligament (estimate
ligament by anterior superior iliac to pubic tubercle). This may be much higher than you
are used to.
 Use either 18 arterial line set or Cook 5f Central Venous Cath (G02070)
Float the Wire
 STC uses Boston Scientific Amplatz superstiff wires (0.035in/260 cm/straight floppy tip)
 Measure externally from the catheter to the level of the 2nd rib–mark this level on the
wire (At STC, they use Avery 5422 stickers)
 Advance the wire floppy-end first to the marked depth
 Confirm location with either radiograph or fluoro before proceeding
 Mark the proximal end of the wire with a pen on the sterile drape
Place the Sheath
 At STC, they use a Check-Flo Performer Introducer (12 fr, 30cm)
 Remove the femoral artery catheter
 Measure the introducer externally from groin to just below the umbilicus (make sure
you are measuring the catheter, not the dilator). Mark with a sticker
 In some cases, you need to dilate the vessel to accept the introducer; in most cases the
internal dilator is sufficient
 Place the introducer to the previously marked level
 Critical Move: Removal of the dilator can screw everything up. The operator should lock
the sideport of the dilator between their fingers and grip tight and with the other hand,
hold the wire proximally. Allow assistant to pin and pull the dilator. If they mess up, you
are still controlling the sheath and the wire. If some of the wire gets pulled, have your
assistant reinsert without you letting go of sheath or wire.
Place the Coda Catheter/Balloon
 Grab a CODA balloon catheter (32 mm-balloon)
 Measure externally; Zone 1 is measured to the xiphoid, Zone 3 is measured to just above
the umbilicus. Measure at the proximal portion of the balloon
  Remove all air from the balloon using saline syringe
 Insert the CODA catheter
 The wire stays stationary throughout
Inflate the Balloon
 Use a 30 ml syringe, ideally filled with 20 ml of NS and 10 ml of omnipaque (lohexol);
use just saline if contrast not available
 Inflate until resistance goes to moderate (would love to know what luminal pressure this
corresponds to). In general, this corresponds to 12-22 mls depending on the size of the
aorta–but this must be individualized to the patient. The actual infaltion is far harder
than you may think. For me, it is the maximal force I can apply with 1 hand.
Secure Everything for Transport
 Here's how they do it at STC
  Mark the levels of everything so you can verify there has been no migration

Get an Xray when time allows

Balloon in Zone-3
Balloon in Zone-1

Go to Definitive Management
 The introducer sheath will need to be removed under direct observation after cutdown,
with arterial repair (at least until smaller catheters are developed)