Category Archives: Resuscitation

Massive Transfusion: What’s The Right Ratio?

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.

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AAST 2019 #1: Survival Benefit Of Pelvic REBOA

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is one of the new, shiny toys in the trauma professional’s toy chest. Research papers on the topic are increasing exponentially, but human data was not even published until 2014! This is still a new device and we are trying to learn more about it.

The AAST set up an Aortic Occlusion for Resuscitation in Trauma and Acute Care (acronym is AORTA, ugh!) to help accumulate data for this not-often used technique. Hopefully, compiling comprehensive use and outcome data will speed our appreciation of the usefulness of this device.

A multi-institutional trauma group massaged the AORTA registry to examine the potential benefits of using the technique in patients with pelvic fractures leading to severe blood loss. They specifically looked for patients with the balloon inflated in Zone 3 to decrease bleeding from below the aortic bifurcation. Here’s a diagram of the zones:

The authors identified a total of 109 patients pelvic fractures with bleeding from below the bifurcation.

Here are the factoids:

  • The presenting patients arriving without CPR all had similar base deficit, lactate, and systolic BP. This shows us that the two groups are the same, but only for these three parameters. GCS was lower in the open aortic occlusion group. This could certainly contribute to a higher overall mortality in this group.
  • Overall mortality was significantly lower in the REBOA group that included those arriving with CPR in progress (35% vs 80% for open occlusion)
  • And when CPR patients were excluded, the mortality was significantly lower (33% vs 69%)
  • One in ten patients undergoing REBOA suffered vascular access complications (vascular repair required, limb ischemia, distal embolization, or amputation)
  • Complications among survivors were not different between the groups, nor were hospital or ICU lengths of stay or blood usage

The authors state that their data shows a “clear survival advantage” in those patients who undergo REBOA. Furthermore, this was accomplished without increasing systemic complications. They finally conclude that REBOA should be “strongly considered” for patients in shock due to pelvic trauma.

Not quite so fast here. There are several more factors in play than meet the eye.

First, a study that massages a REBOA database was generally constructed to see if REBOA is beneficial, especially in this time of rapid investigation. And it was performed by institutions who are using it regularly. This could introduce a significant degree of confirmation bias, since we all try to see what we already believe to be true (“REBOA is good”).

The authors are basing this “clear survival advantage” on overall mortality where only a few confounding factors have been controlled for. The GCS wild-card here is a perfect example. It could have considerably contributed to mortality in the open group, making it look bad. Who determined whether REBOA or open technique would be used, and why? This can have a major impact. What other factors might be present that are not even recorded in the database?

It is also stated that this increased survival was accomplished without increasing systemic complications. Perhaps, but that may be true of only the ones examined, or those recorded in the registry. Many may be missing. And what about the 10% incidence of limb issues in the REBOA group? This is a major problem and should not be glossed over. Although the patients that required a vascular repair were reported to do well, the others with ischemia or limb loss obviously did not.

Bottom line: Reading abstracts is like reading scientific papers, only more difficult because information is missing due to length limitations. Look at the title. Look at the conclusions. But don’t believe anything until you can understand every one of the results listed. And be sure to think about all the things that have to be left unsaid because of the size of the abstract! 

Having said all that, I still have to be careful that this doesn’t trigger my own confirmation bias. My take is that REBOA is still an investigational device. We need further comprehensive data to make sure that survival and safety are properly balanced.

Here are some questions for the presenter and authors:

  • The abstract describes the number of cases identified as 109; 84 REBOA and 25 open occlusions of the aorta. This seems to include patients undergoing CPR upon arrival, and these are excluded from some of the statistics. However, I can’t get the mortality percentages to match for the group that supposedly includes CPR patients. For example, the overall REBOA (includes CPR) mortality percentage is 35.17%. Multiplying this by 84 gives 29.5 patients. But multiplying the 33.33% mortality (CPR-excluded group) by 84 yields 28 patients. So are the 109 patients listed in the abstract the CPR-excluded group or not?
  • The open aortic occlusion group had a lower GCS. Did you look at how this might have contributed to the higher observed mortality? Although numbers are already low, is there any way to match for this to clarify the picture?
  • Do you have any information yet on longer term outcomes in the two groups? This will become very important as we come to balance raw survival with quality of life and complications.

Great abstract! I’m looking forward to the presentation, and hopefully more answers!

Reference: SURVIVAL BENEFIT FOR PELVIC TRAUMA PATIENTS UNDERGOING RESUSCITATIVE ENDOVASCULAR BALLOON OCCLUSION OF THE AORTA: RESULTS OF AAST, AORTIC OCCLUSION FOR RESUSCITATION IN TRAUMA AND ACUTE CARE SURGERY (AORTA) REGISTRY. AAST 2019 Oral Abstract #3.

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Little-Known Whole Blood Transfusion Program: Part 2

In my last post, I described a long-standing whole blood transfusion program that was implemented by Royal Caribbean Cruise Lines (RCCL)about 10 years ago. Today, I’ll dig into the specifics of their protocol and review their results.

Here is an image of the protocol. You can click it to download a full-size pdf copy.

Here are the key points in the protocol:

  • It is only implemented if it will take more than 4 hours to get the patient ashore for more advanced care
  • If the patient is hemodynamically stable, permissive hypotension to MAP 75 is encouraged and TXA infusion / Vitamin K administration are considered when appropriate. The patient disembarks at the next port of call with advanced hospital capabilities.
  • If hemodynamically unstable, two large bore IVs are maintained, TXA and Vitamin K are given when appropriate, and whole blood collection and administration are initiated. Helicopter / coast guard transport is deemed acceptable to closest advanced hospital.

And here are the guidelines for donor selection:

  • The donor hierarchy is:
    • sexual partner of the patient
    • male passenger with blood donor card
    • male passenger without blood donor card
    • female passenger with blood donor card (beware of TRALI)
    • medical staff members
    • crew
  • Only one unit is taken from each donor, and they must not be anemic

Here are the factoids describing RCCL’s seven year experience with the program:

  • 73 patients received transfusions, including 67 passengers and 6 crew
  • Mean hemoglobin on presentation was 6
  • A total of 1-6 units were given
  • Six patients ultimately died; no details were given
  • There were no ABO seroconversions, and only two adverse reactions occurred, both allergic
  • The majority of the medical staff felt that this was a valuable program

Bottom line: This is the first whole blood transfusion program I have seen outside of hospitals and the military. Royal Caribbean has incorporated lessons learned from both in developing their protocol. It includes all the principles of balanced resuscitation, including limiting crystalloids, permissive hyportension, and 1:1:1 transfusion ratios. There are many other opportunities to implement similar protocols in areas where medical capabilities are austere, and this protocol should be used as a model to develop them.

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A Little-Known Whole Blood Transfusion Program

I’m just getting back from a speaking engagement at the 30th Annual (!) Parkview Trauma Symposium in Fort Wayne, Indiana. I love traveling around the country and speaking, because I have the opportunity to hear other fascinating speakers and pick up new tidbits for personal use and to share. This was one of my favorite symposia and the speakers were fantastic.

My colleague, Scott Thomas, is the Trauma Medical Director at Memorial Hospital of South Bend in Illinois and gave an excellent talk on goal directed, whole blood transfusion. The use of whole blood is growing in the US, as I’ve written about previously. However, I was totally unaware of the systematic use of this product in a unique industry: cruising.

Royal Caribbean Cruise Lines (RCCL) implemented a whole blood transfusion program in 2008 on a subset of its more than 40 cruise ships. The guests on cruise ships tend to be an older population, similar to what many trauma centers in the US encounter. Similarly, many have medical comorbidities that require them to take anticoagulants or antiplatelet agents, and they may develop bleeding conditions while on board.

A good deal of cruise time is spent at sea and away from ports that have major medical facilities. Helicopter transport from the ship is not readily available due to distance from shore, so patients who experience serious illness must be cared for in the onboard medical facilities until within striking range of a faster coast guard ship. It is not practical to store blood on board, so bleeding patients presented a real problem in the past.

In response to this, RCCL implemented a program that was very forward thinking for its time. It emphasized:

  • Transfusion based on hemodynamics, not a hemoglobin reading
  • Anticoagulant reversal, if possible
  • Use of TXA
  • Limited use of crystalloid
  • Permissive hypotension
  • Use of fresh, whole blood

Wow! And this was 10 years ago. In my next post, I’ll start working through the protocols and logistics that RCCL uses for this program in the (relatively) austere medical / trauma environment aboard a cruise ship.

Related post:

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Use Of Whole Blood For Massive Transfusion

We’ve been using fractionated blood components in medicine, and trauma specifically, for over 50 years. So why doesn’t component therapy work so well for trauma? Refer to the following diagram. Although when mixed together the final unit of reconstituted blood looks like whole blood, it’s not. Everything about it is inferior.

Then why can’t we just switch back to whole blood? That’s what our trauma patients are losing, right? Unfortunately, it’s a little more complicated than that. The military has been able to use fresh warm whole blood donated by soldiers which has been stored for just a few hours. That is just not practical for civilian use. We need bankable blood for use when the need arises.

This ultimately means that we need to preserve the blood, and this requires a combination of preservatives to prevent clotting and keep the cellular components fresh, and refrigeration to avoid bacterial growth. This is not as simple as it sounds. Adding such a preservative to whole blood dilutes it by about 12%. And there are concerns that cooling it may have effects on platelet function. Recent data suggests that platelet function in cooled whole blood is preserved, but platelet longevity is decreased.

There are other issues with the use of whole blood as well. It contains a full complement of white blood cells, and this may be related to reports of venous thrombosis, respiratory distress, and even graft vs host disease. Unfortunately, removing the white cells (leukoreduction) also tends to remove the platelets, and there is little literature detailing the safety of this practice.

Another problem is the plasma component in whole blood. Universal donor (type O) whole blood may contain significant amounts of anti-A and anti-B antibodies. For these reasons, most blood banks limit the number of whole blood units transfused to a handful. A recent paper from OHSU in Portland details a massive transfusion in which 38 units were given to one patient. There was no transfusion reaction, but platelet counts dipped precipitously. All centers currently using whole blood utilize only low-titer anti-A and anti-B units.

So does whole blood work as expected in the civilian arena? The data is still incomplete, but the total transfusion volume appears to be decreased in patients without severe brain injury. With the increased interest and use of whole blood, it is imperative that more safety and efficacy studies are forthcoming.

Here are some tips on getting started with your own whole blood program:

  • Develop a relationship with a supplier of whole blood. Hammer out the details of the exact product (product age, leukoreduction, titer levels, returnability if not used).
  • Obtain approval from your hospital’s Transfusion Committee!
  • Work with your blood bank to develop processes to ensure proper availability and accountability. What is the maximum number of units that can be used in a patient? When should units be returned to the general pool to ensure they are not wasted?
  • Decide where whole blood will be available. Obviously, the blood bank will house the majority of the product. But should you have it in an ED refrigerator? On air or ground EMS units? These situations demand several extra layers of oversight and add greatly to complexity.
  • Educate, educate, educate! Make sure everyone involved, in all departments, are familiar with your new MTP!

References:

  1. Whole blood for resuscitation in adult civilian trauma in 2017: a narrative review. Anesth Analg 127(1):157-162, 2018.
  2. Massive transfusion of low-titer cold-stored O-positive whole blood in a civilian trauma setting. Transfusion, Epub Dec 27, 2018.
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