Tag Archives: MTP

Resuscitation

Best Of EAST #2: Pay Attention To Platelet Ratios In Your MTP!

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More MTP stuff! Every trauma center has a massive transfusion protocol, and current literature encourages them to try to achieve an “optimal” transfusion ratio. The literature has converged on a red cell to plasma ratio of somewhere between 1:1 and 2:1. Less has been written about platelet ratios, and trauma centers often don’t pay as much attention to this ratio when reviewing MTPs.

But is it important? The trauma group at the Massachusetts General Hospital examined the impact of platelet ratios on mortality in patients undergoing MTP. This was another TQIP data analysis, performed over a nine year period.

The authors defined massive transfusion as ten or more units of PRBC in the first 24 hours, or any number of units of red cells, plasma, or platelets given within the first four hours. They also defined “balanced” as a ratio of RBC to FFP and RBC to platelets <2. Multivariate regression analysis was performed to gauge the impact of ratios and achievement of a balanced resuscitation on 24-hour mortality.

Here are the factoids:

  • A total of 7,520 patients in the dataset underwent MTP
  • Nearly 83% achieved RBC to FFP balance, but only 6% had RBC to platelet balance (!)
  • Patients with both balanced FFP and platelets had the lowest mortality at 24 hours
  • Mortality increased by 2x with unbalanced plasma, a little more than 2x with unbalanced platelets, and 3x if both were out of balance (see figure)

The authors concluded that the platelet component of the MTP was frequently out of balance, and that it is associated with mortality to a greater degree than with unbalanced plasma.

Bottom line: This paper confirms my observations that trauma centers pay a lot more attention to the red cell to plasma ratio and don’t get as excited when the platelets are out of line. Part of this is probably due to confusion over how to count platelet packs. Typically they are delivered in packs called “pheresis” or “apheresis.” Each is the equivalent of about 6 units of platelets (check with your blood bank for more exact numbers). This means that a ratio of 6 RBC to 5 plasma to 1 platelets would be considered balanced. But a ratio of 28:28:2 would not.

According to this abstract, the use of sufficient platelets is important. This makes sense. However, the exact mechanism cannot be determined from this type of study. It could be a direct effect of not having enough platelets to form good clot. Or it could be something completely outside the clotting mechanism, just an association with something in the care processes that occurs as these patients undergo resuscitation. 

The why doesn’t matter so much, though. This abstract presents compelling data that suggests that we really need to pay attention to the platelet ratios given during the MTP. They should be analyzed just as closely as plasma ratios during PI review, and changes to the MTP process implemented to normalize this important ratio.

Here are my questions for the authors and presenter:

  • There is a statement in the methods section that is not clear. “only patients with steady RBC/PLT and RBC/FFP ratios between 4-and 24-hr were analyzed.” What is your definition of “steady?”
  • Did you see any mortality patterns in the data you analyzed that might suggest why lower platelet volumes were more deadly?

This was a nicely done abstract, and I look forward to the live presentation and the finished manuscript!

Reference: DON’T FORGET THE PLATELETS: BALANCED TRANSFUSION AND THE INDEPENDENT IMPACT OF RBC/PLT RATIO ON MORTALITY IN MASSIVELY TRANSFUSED TRAUMA PATIENTS. EAST 25th ASA, Oral abstract #1.

Resuscitation

Best Of EAST #1: When Is MTP Blood Use Too Much?

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The 35th Annual Scientific Assembly of the Eastern Association for the Surgery of Trauma (EAST) begins in only a month! I will be there, sitting in the front row listening to all the great presentations. As usual, I have selected some of the abstracts that I find most interesting and will be sharing my thoughts on them with you over the coming weeks.

Let’s start out with a paper about the massive transfusion protocol (MTP). Blood has always been a scarce resource. And now, thanks to COVID, it is becoming even more so. Every trauma professional reading this has likely been involved in a trauma resuscitation that has used dozens of units of blood and other products. Unfortunately, most of the patients who require this much do not survive.

How does one balance the rapid use of many, many units of blood products with the (un)likelihood of survival and the impact of having less blood for other patients in your hospital or future incoming trauma patients? In other words, when does the use of additional blood become futile? Until now, there have been no real answers to these questions.

The trauma group at George Washington University did a deep dive into the TQIP database seeking some guidance on this topic. They reviewed five years of data, targeting patients who received at least one unit of blood within four hours of arrival. Four-hour and 24-hour mortality was analyzed to determine the point at which additional blood products did not improve survival.

The authors looked at the data two ways. They analyzed the results for all comers, as well as for patients who received balanced resuscitation. Balanced was defined as a red cell to plasma ratio in the range of 1:1 to 2:1. Results were controlled as best as possible for age, sex, race, highest AIS in each body region, comorbidities, advanced directives, and the type of surgery performed to control bleeding.

Here are the factoids:

  • Nearly 100,000 patient records were analyzed, and about 30,000 patients were found to have balanced resuscitation
  • In the all-comers group, mortality plateaued after 41 units at 4 hours and 53 units at 24 hours
  • In the balanced resuscitation patients, mortality plateaued at 40 units (4 hours) and 41 units (24 hours)

The authors concluded that this data should be used as markers for resuscitative timeouts to assess the plan of care.

My comments: This paper is very focused and provides some apparently straightforward results. However, it required some sophisticated statistical analysis to sift through the many variables that need to be controlled to obtain meaningful results. From reading the abstract, it appears that they did a good job of this.

I believe the lower number of units needed by 24 hours in the balanced resuscitation group demonstrates the benefit of getting the MTP ratios right. Non-balanced resuscitation is less efficient / effective and requires the use of more products to hit the mortality plateau.

This paper supports my opinion that a resuscitation timeout is a useful tool in helping us protect our valuable blood product resources and ensuring availability for as many patients in need as possible. What would this look like? Here are my thoughts:

  • Assign one person to monitor the MTP process in real-time. This obviously cannot be the surgeon or a member of the anesthesia team. Or even the operating room crew, as everyone will be very busy. The best practice I’ve seen is to have a dedicated trauma nurse or APP in the ED/OR recording the process on a specialized form and directing which units to give to keep the resuscitation balanced.
  • Call a timeout when the magic threshold is reached. This paper suggests that 40 is a good number.
  • Require that another trauma surgeon come into the room and review the patient condition, operative findings, and progress thus far. The two surgeons should then come to a consensus regarding utility vs futility of further surgery. Based on that decision, the operative procedure either continues or stops.
  • If the operation is to continue, then more timeouts should occur after a defined number of additional products are given.

Here are my questions for the authors / presenter:

  • The statistical analysis required is fairly advanced. Please explain in simple language why the specific regression analysis with bootstrapping was selected.
  • How do you envision applying the thresholds discovered in your paper?

This is an exciting paper and provides important information about the MTP process. I’m looking forward to hearing it in person!

Reference: CRESTING MORTALITY: DEFINING A PLATEAU IN ONGOING MASSIVE TRANSFUSION, EAST 25th ASA, oral abstract #14.

Complications

Can We Use Type A Plasma For Emergency Transfusion?

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Trauma patients tend to try to bleed to death. And trauma professionals try to stop that bleeding. They also frequently have to replace the blood products that were lost, which includes red blood cells, plasma, platelets, and more.

From a red blood cell standpoint, we have a long history of using group O- packed red cells as the so-called universal donor product. The problem is that only about 5% of the world population has this blood type, so it can be scarce.

To address this, many centers have moved toward using O+ blood for select patients. This blood type is much more prevalent (about 50% worldwide). The only difference is the positive Rh factor which has little impact on males, or females who are not in their child-bearing years. If an allergic reaction occurs, it is typically mild.

But what about plasma? This is interesting stuff. When selecting red cells, we want them to have no ABO group antigens on them so they don’t provoke a reaction. But plasma is just the opposite. We don’t want any ABO group antibodies in it. And the only plasma without antibodies comes from people who have all of them (A and B) on their red cells. This means people with type AB+ blood. Unfortunately, this is the other rare blood type, so there’s not a lot to go around. Worldwide, about 5% of people are AB+ and less than 1% are AB-.

So why couldn’t we do something like we did with packed red cells and substitute a more common blood type that evokes little immune response? The American Association of Blood Banks (AABB) has authorized both AB and A plasma for use in emergency situations. Unfortunately, the safety profile for using group A has not been very well studied, particularly in trauma patients needing massive transfusion.

The authors of the PROPPR study re-analyzed the data from it to try to answer this question. As you may recall, PROPPR was published in 2015 and compared safety and effectiveness of transfusion ratios at 1:1:1 to 1:1:2 (plasma : platelets : red cells).

The study group selected patients from the dataset who received at least one unit of emergency release plasma (ERP), defined as product given before the patient’s ABO type had been determined. Nicely enough, 12 sites transfused group AB ERP and 9 sites gave group A. One site gave both A and AB.

The authors looked at in-hospital mortality at 30 days, and a host of complications. Here are the factoids:

  • A total of 584 of the 680 patients in the PROPPR study received emergency release plasma
  • The median number of units given was 4, and there was no difference between A and AB groups
  • There were statistically significant baseline differences between the groups, including blood type, SBP, percent in shock (SBP<90), blunt mechanism, positive FAST that were probably not very clinically significant
  • The number of transfusions of all products were significantly  higher in the A plasma group
  • Complications were significantly higher in the A plasma group, specifically from SIRS, pulmonary problems, and venous thromboembolism (VTE)
  • There were no acute hemolytic transfusion reactions and three febrile reactions

The authors concluded that, statistically, the use of group A plasma was not inferior to the use of group AB. The authors stated that cautious use of group A is an acceptable option, especially if group AB is not readily available.

Bottom line: Here we go again. Always be careful when reading a study that suggests non-inferiority of one thing compared to another. There are a lot of potential issues here:

  • The PROPPR trial data was not designed to answer questions about plasma usage, so the data is being highjacked a bit
  • Participating centers did not have a standardized way to determine the group that received ERP, so some data anomalies will be present
  • The A and AB study groups were different in many ways at baseline, particularly with respect to how much product they received
  • The primary outcome, 30-day mortality, was underpowered and could never show a significant difference

So with significant baseline differences in study groups and a potentially underpowered study, don’t read non-inferiority as meaning that use of group A plasma is okay. We still just don’t know. What this study really shows is that you can “get away with” using low titer group A plasma if you run out of AB. But it shouldn’t be your go to product yet. To figure out the real safety profile, we need to do a real “PROPPR” study. Get it?

Reference: Group A emergency-release plasma in trauma patients requiring massive transfusion, J Trauma 89(6):1961-1067, 2020.

Abstracts, Resuscitation

Best of AAST #1: What Has The MTP Bought Us?

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Let’s kick off my reviews of AAST 2020 abstracts with a paper on the results of recent advances in hemorrhage control. Over the past 10+ years we have seen the following new (and old) tools move into more widespread use:

  • Massive transfusion protocol (MTP) with a goal of 1:1 ratios of red cells to plasma
  • Availability of liquid plasma for more rapid use in the MTP
  • Addition of tranexamic acid (TXA) to resuscitation
  • Resurgence of tourniquet use by prehospital providers
  • Adoption of REBOA and TEG
  • Transfusion with whole blood

The authors analyzed their experience after serially introducing these tools to their resuscitation strategies, and studied their impact on overall mortality.

They retrospectively reviewed the experience over a 12 year period at their large Level I trauma center. Here are the factoids:

  • The reviewed a total of 824 MTP events. To put this into perspective from a volume standpoint, this is a little over one MTP activation per week.
  • Patients were primarily young (median age 31), male (81%), with a penetrating mechanism (68%). Median ISS was 25
  • Prehospital times were significantly longer at the end of the study, but the authors state that there was no correlation with an increase in in-hospital mortality
  • During the entire study, overall mortality ranged from 38% to 57%, and logistic regression did not identify an effect from any of the interventions

The authors concluded that their mortality rates have not improved despite all of the advancements we have added over the past decade. They suggest that future efforts should attempt to move targeted hemorrhage control backwards in time, out of the ED and toward to injury scene.

Here are my comments: This is an interesting and simple-appearing study. Overall, the authors didn’t really show that any of our “modern” resuscitation interventions did much for their patients at all.  There was a suggestion that tourniquet implementation and use of whole blood tended toward improving things.

But don’t be fooled by simplicity. There are many, many factors that enter into whether an individual patient lives or dies. When you fail to see a significant result in a study, first look at the methods and tools used for measurement. Are they powerful enough to discern changes? Do they cover enough of the factors that promote survival, not just our resuscitative advances? Or is the tool looking at the wrong things?

One big difference at this center is the sheer volume of penetrating trauma. This could have a major impact on survival, and may be very different from the experience of most centers that have predominantly blunt injury mechanisms.

And some questions for the authors:

  • What exactly is your definition of mortality? Made it out of the ED? Lived twenty four hours? Thirty days? This makes a big difference in how you look at the results.
  • Since you have only about one MTP event per week, do you think your numbers are large enough to actually detect a mortality difference? 
  • Did you consider looking at your unexpected survivors to see if there were any common threads in their care that might have made the difference? Maybe some of our resuscitative advances do make a difference, but only in specific subsets of patients.
  • Can you speculate about the reasons for longer prehospital times, and the impact on mortality?
  • How would you recommend pushing hemorrhage control back toward the scene? New tools for prehospital providers? More advanced providers in the rigs? This is an intriguing concept and it would be interesting to hear your thoughts.

This is a thought provoking paper that questions our assumptions about our time-honored resuscitation tools. I look forward to hearing it live next month!

Reference: After 800 MTP events, mortality due to hemorrhagic shock remains higha nd unchanged despite several hemorrhage control advancements; is it time to move the pendulum? AAST 2020 Oral Abstract #1.

Resuscitation

Massive Transfusion: What’s The Right Ratio?

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In my last post, I analyzed a survey that studied the massive transfusion protocol (MTP) practices of academic Level I trauma centers in the US. What centers do is one thing. But what does the literature actually support? A group from Monash University in Melbourne, Australia and the National Health Service in the UK teamed up to review the literature available through 2016 regarding optimal dose, timing, and ratio of products given during MTP.

One would think that this was easy. However, the search for high quality ran into the usual roadblock: the fact that there is not very much of it. The authors scanned MEDLINE for randomized, controlled studies on this topic, and found very few of them. Out of 131 articles that were eligible, only 16 were found to be suitable for inclusion, and 10 of them were still in progress. And only three specifically dealt with the ratio question. Even they  were difficult to compare in a strict apples to apples fashion.

Here are the factoids that could be gleaned from them:

  • There was no difference in 24-hour or 30-day mortality between a ratio of 1:1:1 (FFP:platelets:RBC) vs 1:1:2
  • However, a significantly higher number of patients  achieved hemostasis in the 1:1:1 group (86% vs 78%)
  • There was no difference in morbidity or transfusion reactions in the two groups
  • One study compared 1:1 component therapy with whole blood transfusion and found no difference in short-term or long-term mortality or morbidity

Bottom line: As usual, the quality of available data is poor if one limits the field to randomized, controlled studies. Ratios of 1:1:1 and 1:1:2 appear to be equally effective given the limited information available. A number of papers not included in this review (because of their less rigorous design) do seem to indicate that higher ratios of RBC (1:3-4) appear to be detrimental. And as time passes, more and hopefully better studies will be published.

What does this all mean for your MTP? Basically, we still don’t know the best ratio. However, it is recommended that your final ratios of FFP:RBC end up somewhere between 1:1 and 1:2. The only way to ensure this is to set up your MTP coolers so the the ratio of product they contain is better than 1:2. This means more plasma than 1 unit per 2 units of red cells. 

If you set it at the outside limit of 1:2, then that is the best ratio you can ever get assuming everything goes perfectly. However, if you have to thaw frozen plasma, use too much emergency release PRBC before activating MTP, or someone cherry-picks the coolers to transfuse what they think the patient needs, the ratios will quickly exceed this boundary.

So be sure to load your coolers with ratios that are closer to 1:1 to ensure that your final ratios once MTP is complete are what you want them to be. And monitor the final numbers of every one of your MTP activations through your trauma performance improvement program so you know what your patients are really receiving.

Reference: Optimal Dose, Timing and Ratio of Blood Products in Massive
Transfusion: Results from a Systematic Review. Transfusion Med Reviews 32:6-15, 2018.