Update on Hemostatic Resuscitation

RAHUL J ANAND

MOLLY FLANNAGAN

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◦ 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◦ 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

X

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) 1403-1423Morrison et al. J Trauma. 2011 Mar;70(3):652-63

N Engl J Med 1994; 331:1105-1109 October 27, 1994

• Landmark NEJM article

• Compared immediate versus delayed fluid resuscitation before operative intervention

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

X

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 Low volume product which does not result in hemo-dilution 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

“The Massive Transfusion Protocol (MTP) facilitates the replacement of massive blood loss with appropriate blood products in a timely fashion.”

J Trauma. 2006;60:S91–S96.

Other Authors.

Massive Transfusion Protocols

Standardize replacement of platelets and clotting factors in optimum ration to PRBC

Increase speed and efficiency of transfusion

Arch Surg. 2008; 143(7): 686-91

J Trauma. 2009;66:1616-1624

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 VCUProtocol 1 Keep Ahead Order 4 RBCKeep Ahead Order 4 FFPRelease 8 RBCRelease 6 FFP

Protocol 2Order 1 dose PlateletsOrder 1 dose CryoRelease 8 RBCRelease 8 FFPRelease 1 dose Platelets – (250 – 300cc)Release 1 dose CryoOptional Order Activated Factor VII

Protocol 3Release 4 RBCRelease 4 PlasmaOrder 1 dose PlateletsRelease 1 dose Platelets – (250 – 300cc)

Protocol 4Order 1 dose PlateletsOrder 1 dose CryoRelease 4 RBCRelease 4 FFPRelease 1 dose PlateletsRelease 1 dose Cryo

Protocol 5 Release 4 RBC Release 4 FFPOrder 1 dose PlateletsRelease 1 dose Platelets – (250 – 300cc)

Protocol 6Release 4 RBCRelease 4 FFPOrder 1 dose PlateletsRelease 1 dose Platelets – (250 – 300cc)

Protocol 7Order 1 dose PlateletsOrder 1 dose CryoRelease 4RBCRelease 4 FFPRelease 1 dose PlateletsRelease 1 dose Cryo

Protocol 8 Release 4 RBC Release 4 FFPOrder 1 dose PlateletsRelease 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