Update on Hemostatic
Resuscitation
RAHUL J ANAND
M O L LY F L A N N A G A N
DIVISION OF TRAUMA, CRITICAL CARE, AND
EMERGENCY GENERAL SURGERY
Massive Transfusion
Defined as transfusion of >10 U blood or
Pt blood volume in 24 hrs
Causes
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Trauma
Emergency surgery
AAA repair
GI hemorrhage
CHEST 2009; 136:1654 –1667
Massive transfusion in trauma
Trauma patients with MT have high mortality (19 to 84%)
Mortality Is directly related to number of PRBC units received
CHEST 2009; 136:1654 –1667
Traditional Massive
Transfusion
Crystalloid fluid
PRBC (lacking in clotting factors)
Dilutional coagulopathy
Hypothermia
Acidosis
Liver dysfunction due to shock
Hemostatic Resuscitation
Traditional MT underestimates treatment needed to reverse
coagulopathy
Normalization of body temperature
Hemorrhage control
Transfusion with
◦ FFP
◦ Platelets
◦ Cryoprecipitate
Hemostatic Resuscitation Emerging Consensus
Expedite hemorrhage control
Limit crystalloid resuscitation to prevent dilutional coagulopathy
Transfuse PRBC:FFP:Plts in a 1:1:1 fashion
Frequent lab monitoring
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Lactate
Ionized calcium
Electrolytes
Platelets, Fibrinogen
TEG / ROTEM
So YOU have MASSIVE
BLEEDING – now what?
Secure Access
◦ 2 Large bore IV, or Central line or
◦ Intra-Osseus line
Begin Aggressive Resuscitation
◦ (ATLS suggests 2 L or warmed crystalloid)
STOP the bleeding
Damage Control Resuscitation
FOCUSED SURGERY
PERMISSIVE HYPOTENSION
HEMOSTATIC RESUSCITATION
CHOICE OF
RESUSCITATION
FLUID
Choice of Crystalloid
No real difference between using LR and NS
LR MAY exacerbate hyperkalemia
Hypertonic Saline is no better
TAKE HOME – USE NS (Sparingly)
Kaafarani et al. Scandinavian Journal of Surgery 103:81-88, 2014
Why not Resuscitate with Colloid?
Theoretically may stay intravascular?
SAFE TRIAL
No difference in mortality, ventilator days, renal failure, or LOS
Subgroup analysis – worse mortality in TBI patients
Colloid Take Home Point
Resuscitation is EXPENSIVE
MAY be harmful in patients with TBI, BURN, Trauma
Start with NS – then use PRODUCT if you have to
HYPOTENSIVE
RESUSCITATION
Still Bleeding? – Don’t aim for “NORMAL
BP”
Permissive Hypotension – especially in those with no brain or spinal
cord injury until surgical control of bleeding
Maintain cerebral perfusion – SBP 80’s acceptable until bleeding
stopped
“Hypotensive resuscitation is a safe strategy for use in the trauma
population and results in a significant reduction in blood product
transfusions and overall IV fluid administration … maintaining a target
minimum MAP of 50 mm Hg, rather than 65 mm Hg, significantly
decreases postoperative coagulopathy and lowers the risk of early
postoperative death and coagulopathy.”
Kobayashi et al. Surg Clin N. Am 92 (2012) 1403-1423
Morrison et al. J Trauma. 2011 Mar;70(3):652-63
• Landmark NEJM article
• Compared immediate versus
delayed fluid resuscitation before
operative intervention
N Engl J Med 1994; 331:1105-1109 October 27, 1994
Delayed group compared to traditional resuscitation
Delayed group received no more than 100cc fluid prior to OR
Delayed group had better survival, fever complications, shorter LOS
N Engl J Med 1994; 331:1105-1109 October 27, 1994
Target BP before Hemorrhage
Control
Accept MAP of 50
Decrease dilutional coagulopathy
Avoid hypothetical “pop the clot”
Restrict inflammatory cascade
Kaafarani et al. Scandinavian Journal of Surgery 103:81-88, 2014
1:1:1
1:1 PRBC: FFP Transfusion
Borne out of military
rationale
Walking blood banks with
Fresh Whole Blood
High FFP:RBC ratio (1:1) is
independently associated
with
◦ Improved survival to hospital discharge
◦ Improved overall mortality
J Trauma 2007; 63:805 –813
1:1 Transfusion works for civilians too!
1:1 Platelets: PRBC is also
important
Take home point Re: 1:1:1
Improves 30 day survival
Reduces incidence of pneumonia, pulmonary failure, abdominal
compartment syndrome
LOWER 24 hour transfusion requirement
Johnsson et al. Scand J Trauma, Resus, Emergency Med. 2012
Hemostatic adjuncts
Hemostatic Adjuncts
Factor VIIa
Prothrombin Complex
Tranexamic Acid
Factor VIIa
• CONTROL TRIAL – looked at Use of Factor VIIa in
the management of refractory trauma hemorrhage
• Pro-thrombotic Agent
• TRIAL did not show a significant mortality benefit
• Factor VII also has a variety of thromboembolic
complications – increased significantly over controls
Johnsson et al. Scand J Trauma, Resus, Emergency Med. 2012
Factor VIIa
Alarcon. UPMC Trauma Rounds Winter - 2012
Prothrombin Complex (PCC)
Cocktail of 3 or 4 factors
Can be used to correct INR rapidly in trauma
Less thrombotic complications than Factor VIIa
Annals of Pharmacotherapy, 2011. July / August, Volume 45
Administration of PCC to patients with massive
bleeding
Found to reliably lower INR with a single dose
No thrombotic complication
May warrant a RCT
Smaller studies
Promising results to reverse Coumadin related coagulopathy
Unanswered as to whether should be used with MTP
Matsushima et al. American J Surgery (2015) 209 413-17
Use of PCC for Damage Control
Resuscitation
Low volume product which does not
result in hemo-dilution
Tranexamic Acid
Not a pro-coagulant
Prevents fibrinolyisis
Patients randomized to receive TXA or Placebo 3 hours from injury
TXA found to reduce mortality from bleeding significantly (4.9% vs 5.7%).
The Lancet. Volume 376. July 3, 2010
TXA in the USA
Given more liberally in Europe
“… in most centers, [TXA] is given following individual practitioner
decisions rather … protocol”
Dutton, Anesthesia 2015, 70 (Suppl 1), 108-111
TXA take home point
Tranexamic Acid is an antifibrinolytic
Administration in cases of massive hemorrhage within the first 3 hours
can have an effect on mortality
Massive transfusion
protocols
J Trauma. 2006;60:S91–S96.
“The Massive Transfusion Protocol (MTP)
facilitates the replacement of massive
blood loss with appropriate blood
products in a timely fashion.”
Other Authors.
Massive Transfusion Protocols
Standardize replacement of platelets and clotting factors in optimum
ration to PRBC
Increase speed and efficiency of transfusion
J Trauma. 2009;66:1616-1624
Arch Surg. 2008; 143(7): 686-91
Early activation
Direct notification of the blood bank
Achievement of pre-defined ratios
PI process
All help to improve outcome and survival
MTP here at VCU
“ACTIVATE MTP”
PLACE THE ORDER IN CERNER
Send 2 samples to the blood bank
Transfuse “Emergency Release Uncrossmatched Blood” if you have to
With each release it needs to be ordered again
MTP at VCU
Protocol 1
Keep Ahead Order 4 RBC
Keep Ahead Order 4 FFP
Release 8 RBC
Release 6 FFP
Protocol 5
Release 4 RBC
Release 4 FFP
Order 1 dose Platelets
Release 1 dose Platelets – (250 – 300cc)
Protocol 2
Order 1 dose Platelets
Order 1 dose Cryo
Release 8 RBC
Release 8 FFP
Release 1 dose Platelets – (250 – 300cc)
Release 1 dose Cryo
Optional Order Activated Factor VII
Protocol 6
Release 4 RBC
Release 4 FFP
Order 1 dose Platelets
Release 1 dose Platelets – (250 – 300cc)
Protocol 3
Release 4 RBC
Release 4 Plasma
Order 1 dose Platelets
Release 1 dose Platelets – (250 – 300cc)
Protocol 4
Order 1 dose Platelets
Order 1 dose Cryo
Release 4 RBC
Release 4 FFP
Release 1 dose Platelets
Release 1 dose Cryo
Protocol 7
Order 1 dose Platelets
Order 1 dose Cryo
Release 4RBC
Release 4 FFP
Release 1 dose Platelets
Release 1 dose Cryo
Protocol 8
Release 4 RBC
Release 4 FFP
Order 1 dose Platelets
Release 1 dose Platelets – (250 – 300cc)
Protocol 9 (Alert: MTP: Trauma has been completed. Refer back
to normal Blood Product ordering pathway)
Termination of MTP
Nursing unit will notify TM to slow rate of preparation and delivery of
blood products when bleeding slows to a specified rate.
When the protocol is cancelled, nursing unit will notify TM.
Keep Ahead orders for blood/ blood products can still be utilized for 24
hours from time of entry
LABORATORY
TESTING
Intraoperative Targets
Hemoglobin > 7
INR <2
Platelet Count > 50 K
Fibrinogen > 100
Guide Clot Strength with TEG
Kaafarani et al. Scandinavian Journal of Surgery 103:81-88, 2014
Laboratory Guidance
PT / INR, PTT are warmed to 37C before analysis
This can normalize results and under diagnose coagulopathy
Tests can take 30 minutes to an hour
TEG
Provide clinically relevant information on clot strength
A Quantitative method of giving clot strength over time
Are run at patient temperatures
Takes 5 minutes
Can be used to run “ongoing resuscitation”
Johnsson et al. Scand J Trauma, Resus, Emergency Med. 2012
TEG
Johnsson et al. Scand J Trauma, Resus, Emergency Med. 2012
How about pressors to avoid fluid?
J Crit Care (2010) 25, 173
J Trauma (2011) 71: 565-572
J Trauma (2008) 64: 9-14
Late Resuscitation in ICU
Hemostasis achieved in the OR
“A la carte resuscitation”
Volume Resuscitation Guided in ICU by
◦ Clearance of Lactate
◦ Volume Status Assessment (LTTE)
Generally Tolerate Hgb > 7
In CONCLUSION
Hemostatic Resuscitation
Expedite hemorrhage control
Limit crystalloid resuscitation to prevent dilutional coagulopathy
USE BLOOD EARLY
Transfuse PRBC:FFP:Plts in a 1:1:1 fashion
Factor VII – bad
TXA, PCC may have roles within a MTP
MTP is a good thing
TEG assays