So You Want to Implement MTP… Part 2

Ensuring a well-designed protocol is able to run itself.

You have activated massive transfusion protocol (MTP) for your hemodynamically unstable patient. What do you need to consider? What products comprise MTP? Does your hospital have a system or protocol for MTP?

This is the second of a two-part series on MTP. Part 1 evaluated the products of MTP and when MTP should be activated. This article evaluates implementing MTP, how to perform MTP, adjunctive agents, monitoring patients undergoing MTP and when to terminate MTP.

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Implementation of an MTP

MTP is complex, requiring a set of processes with multiple components.(¹⁾ The first aspect is that resuscitation and MTP is a team game, requiring multiple participants and systems. There should be one massive transfusion protocol (in written form) for your institution. In other words, there should not be separate MTPs for GI bleed, OB, trauma, etc.(¹⁾ This creates confusion and will slow the delivery of the needed blood products. Interestingly, one study published in 2019 found 74% of centers utilize one MTP for all adult bleeding causes, while 58% of adults and 65% of pediatric MTP activations were for non-trauma indications.(²⁾

Implementing an MTP requires discussion of several departments, including the blood bank/hematology, surgery, the ED, anesthesia and others (such as GI and OB/GYN).  This multidisciplinary cooperation is especially important in MTP, which will be used for many sources of hemorrhage. Staff needs to be familiar with the procedures involved, and as with instituting any new protocol, notification of the protocol, education and drills will assist in ensuring a smooth system.

Things we tend to not consider…

How is the MTP activated at your hospital? Should it be something in the EMR? Though centers may use the EMR in isolation, the best way is a phone call to the blood bank.  Person to person communication is better than relying upon an EMR order.

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Once activated, you need a runner between the blood bank and patient. This should be a designated person whose sole job is moving between blood bank and ED/trauma bay. The patient must have an ID band or something affixed to their person to ensure that he/she is the person actually receiving the blood products. Patient blood should be obtained for rapid crossmatch, though universal products will be provided initially, with O Rh negative blood reserved for females < 50 years of age and O Rh positive blood for other patients.

The time of activation and time of product administration should be documented. Lab values, patient hemodynamics and procedures completed are important as well. What about the transport device for blood products? The cheaper the cooler, usually the less insulation ability. There really is nothing wrong with a large picnic cooler; however, keep in mind that platelets and cryoprecipitate should be stored outside the cooler at room temperature.

Who runs the MTP?

The trauma leader often leads the resuscitation, whether emergency physician or trauma surgeon. Once the activation occurs, a well-designed protocol should run itself. However, a trauma resuscitation nurse can often effectively oversee the MTP, ensuring products are delivered and administered appropriately. This decreases the cognitive load on the physician and frees much needed brainpower for the resuscitation, and the nurse can travel with the patient to the OR.

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The Brass Tacks… How do you use a massive transfusion protocol?

Most resuscitations require consideration of multiple components and providing a balanced resuscitation with MTP is no different. Rather than a reactive lab-based system to transfuse products, which follows CBC, coagulation panel or thromboelastography, a better system is the ratio-based MTP. This is proactive, rather than reactive.  Universally compatible blood products (type O Rh-negative and O Rh-positive) RBCs and thawed or liquid packs of FFP (type AB, or low titer A plasma) must be immediately available.(¹⁾

This is an important point: the fastest, most efficient manner in starting the MTP is to have readily available, universal products in the resuscitation bay within a refrigerator (platelets and cryoprecipitate should not be refrigerated). This allows rapid initiation, with a runner then bringing additional products at prespecified intervals. At least 8 units of universal pRBCs and 8 units of AB or low titer anti-B group A FFP should be available upon activation.(¹⁾  Crossmatched products should be administered when able.

There are several strategies for administration of the MTP. One such MTP may use a pack system:

• Pack 1: 4 units FFP, 4 units pRBCs, 1 unit apheresis platelets, 1 10-unit bag of cryoprecipitate. TXA 1g IV should be administered
• Pack 2: 4 units FFP, 4 units pRBCs
• Pack 3: 4 units FFP, 4 units pRBCs, 1 unit apheresis platelets, 1 10-unit bag of cryoprecipitate
• Pack 4: 4 units FFP, 4 units pRBCs
• Pack 5: 4 units FFP, 4 units pRBCs, 1 unit apheresis platelets, 1 10-unit bag of cryoprecipitate

Products should be administered through a blood warmer and rapid transfuser, though platelets and cryoprecipitate should not be transfused through the warmer. The separate “Packs” should be delivered at 15-minute intervals until MTP termination. If the patient is transported, the pack should go with the patient and the runner/blood bank notified in real-time of the patient’s location.

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What other agents are needed in MTP besides the blood products?

Tranexamic acid (TXA) is an integral component of trauma resuscitation and serves as an anti-fibrinolytic.(^1,3,4) It should be provided to patients presenting within three hours of hemorrhagic injury and is administered in 1 g, mixed in 100 ml of normal saline, over 10 minutes. Fibrinogen is a key substrate of clot formation and is rapidly consumed in trauma. Cryoprecipitate functions as a source of fibrinogen and is an important component of MTP.¹ Just 1 unit of cryoprecipitate probably will not cut it; an initial starting dose approaches anywhere from 8-12 units.  Cryoprecipitate should be administered for fibrinogen < 1 g/L.  A low ionized calcium should be repleted with calcium gluconate (or calcium chloride if central access is available), which may improve cardiac contractility, vasomotor tone and coagulation function.

Other products include prothrombin complex concentrate (PCC), which is only recommended for correction of anticoagulant-induced coagulopathy and recombinant VIIa, which is not typically recommended in hemorrhage due to trauma.(¹⁾

Your team has almost completed pack 1, followed by 10 units of cryoprecipitate and 1 g TXA. The runner is present with the next cooler, and you start Pack 2.

On Monitoring…

In the resuscitation, target a temperature > 35 degrees C, pH > 7.2, lactate < 4 mmol/L, base excess < -6, ionized calcium > 1.1 mmol/L, platelets > 50 X 10⁹ /L, PT/PTT < 1.5 X normal, and fibrinogen > 1.0 g/L. These variables represent different components of resuscitation, but all are related. Base deficit and lactate can be regularly monitored and provide valuable information concerning tissue metabolic derangements. A base excess more negative than -6 mmol/L or lactate > 4 mmol/L is associated with shock.^1.5 Lactate clearance of 20% or greater in the first two hours of the resuscitation of bleeding patients is associated with improved mortality.(⁶⁾

A Foley catheter is not only a useful adjunct for diagnosis of a genitourinary tract injury, but measuring urine output is a great way to assess end-organ perfusion in the initial resuscitation.  A patient with 30-50 cc/hour of urine output likely has end organ perfusion.

Monitoring coagulation status is complex and often difficult in MTP, typically requiring more than your standard INR/PT/PTT. Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) can provide real-time evaluation of viscoelastic clot strength and can be invaluable in these situations, especially when determining when MTP can be discontinued.(^7-9)  For more on these measures, visit LifeintheFastLane at https://lifeinthefastlane.com/ccc/thromboelastogram-teg/.

When should the MTP be stopped?

This can be a difficult decision and requires close communication among the trauma leader, resuscitation nurse, runner, blood bank and surgeon. MTP can be discontinued if the following are present: anatomic control of bleeding and physiologic control has occurred (meaning patient hemodynamic status has improved, clotting parameters and CBC normalize or are approaching normal, transfusion pace has slowed substantially).(¹⁾ Anatomic control is not often easy to obtain in the ED and typically requires the surgeon or interventional radiologist declaring control. Until these criteria are met, the MTP should remain active. If the product cooler has been untouched for at least 30 minutes, then it’s safe to consider deactivation. Otherwise, the trauma leader should call the blood bank to discontinue the MTP.  Once the MTP is terminated, the remaining blood products and coolers should be returned to the blood bank/storage facility.

You are now on to Pack 3, and the patient has responded well with improved hemodynamics and a decrease in lactate from 5.4 mmol/L to 4.0 mmol/L. Your surgeon tells you the OR is ready, and you ask the runner and your transfusion nurse to follow the patient and surgical team to the OR, as you and the surgeon anticipate further hemorrhage.

Problems with MTP

There are risks and complications associated with blood product resuscitation, especially in large volumes. Acute/delayed hemolytic transfusion reaction, TRALI, TACO, bacterial/viral infection, graft versus host disease and anaphylaxis are all risks. Other issues include hyperkalemia, dilutional coagulopathy, hypothermia and excessive citrate infusion resulting in hypocalcemia and metabolic alkalosis. However, other logistical issues may prevent MTP.¹ First, MTP requires significant blood product resources, which may not be available at smaller institutions. Type AB plasma is in short supply, and platelets are stored at room temperature and may not be available. Surgical control of bleeding is also vital as a component of DCR.

Is it worth it?

As you can see, MTP requires significant resources. However, in patients experiencing massive hemorrhage, MTP with ratio-based resuscitation can prove life-saving. One study in 2009 evaluated the effect of MTP on mortality in patients requiring massive transfusions.(¹⁰⁾  This before-and-after study found mortality reduced from 45% to 19% after introduction of MTP, despite similar blood product ratios and total amount of blood given. Authors state the improved mortality is likely due to improved system communication and cohesion.(¹⁰⁾

A meta-analysis released in 2018 evaluated 12 retrospective studies, finding no statistically different impact on mortality with MTP versus non-MTP strategies, while the number of total products was similar.(¹¹⁾ Unfortunately, significant heterogeneity limits the conclusions of this meta-analysis. A systematic review evaluating MTP in pediatric patients from four trials also found no improvement in mortality with MTP, but again, heterogeneity limits the findings.(¹²⁾ Granted, we need more data evaluating mortality and morbidity as well as patient populations including head injury and pediatrics, but for now, using a 1:1:1 ratio-based MTP is recommended.

Part 2 Key Points

• MTP is only one component of damage control resuscitation.
• MTP focuses on replacing what is lost with 1:1:1 ratio for plasma to platelets to RBCs.
• Implementation requires a multidisciplinary effort with a written document and protocol.
• Ratio-based, proactive transfusion is recommended in initial stages, rather than a lab-based, reactive approach.
• Important adjuncts include TXA and cryoprecipitate.
• Discontinuation requires anatomic and physiologic hemorrhage control.

References:

1. ACS Trauma Quality Improvement Program. Massive Transfusion in Trauma Guidelines.  https://www.facs.org/~/media/files/quality%20programs/trauma/tqip/massive%20transfusion%20in%20trauma%20guildelines.ashx.  Accessed on 03 February 2019.
2. Thomasson RR,Yazer MH, Gorham JD, et al. International assessment of massive transfusion protocol contents and indications for activation.  2019 Feb 5. doi: 10.1111/trf.15149. [Epub ahead of print]
3. The CRASH-2 Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomized, placebo-controlled trial. Lancet. 2010; 376: 23–32.
4. CRASH-2 collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377(9771):1096-101.
5. Rixen D,Siegel JH. Bench-to-bedside review: oxygen debt and its metabolic correlates as quantifiers of the severity of hemorrhagic and post-traumatic shock. Crit Care. 2005 Oct 5;9(5):441-53.
6. Régnier MA,Raux M, Le Manach Y, et al. Prognostic significance of blood lactate and lactate clearance in trauma patients.  2012 Dec;117(6):1276-88.
7. Whiting D,DiNardo JA. TEG and ROTEM: technology and clinical applications. Am J Hematol. 2014 Feb;89(2):228-32.
8. Pezold M, Moore EE, Wohlauer M, et al. Viscoelastic clot strength predicts coagulation-related mortality within 15 minutes. Surgery. 2011;151(1):48-54.
9. Kashuk JL,Moore EE, Sawyer M, et al. Postinjury coagulopathy management: goal directed resuscitation via POC thrombelastography. Ann Surg. 2010 Apr;251(4):604-14.
10. Riskin DJ,Tsai TC, Riskin L, et al. Massive transfusion protocols: the role of aggressive resuscitation versus product ratio in mortality reduction. J Am Coll Surg. 2009 Aug;209(2):198-205.
11. Sommer N,Schnüriger B, Candinas D, et al. Massive Transfusion Protocols in Non-Trauma Patients: A Systematic Review and Meta-Analysis. J Trauma Acute Care Surg. 2018 Oct 29. doi: 10.1097/TA.0000000000002101. [Epub ahead of print]
12. Sommer N,Schnüriger B, Candinas D, et al. Massive Transfusion Protocols in Non-Trauma Patients: A Systematic Review and Meta-Analysis. J Trauma Acute Care Surg. 2018 Oct 29. doi: 10.1097/TA.0000000000002101. [Epub ahead of print]