Category Archives: Resuscitation

Abstracts, Resuscitation

Best of EAST #1: Ultramassive Transfusion Survival

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All right, let’s kick of this EASTfest with an abstract from one of the Eastern Association for the Surgery of Trauma multicenter studies. This one looked at outcomes after what they term “ultra-massive” resuscitation.

There are a number of definitions for “massive transfusion” which I’ve discussed before. They are basically trauma resuscitations in which the massive transfusion protocol is triggered. The group that designed this study defined ultra-massive resuscitation as one that entails transfusing at least 20 units of packed red cells within 24 hours.

The study focused on factors predicting survival in these patients. They used multivariate logistic regression as well as another regression tool, classification and regression tree analysis (CART). They used these tools to control for age, ISS, mechanism of injury, base deficit, and crystalloid use.

Here are the factoids:

  • A total of 400 patients were studied at 15 trauma centers over an eleven year period
  • Subjects were young (mean 37 years), male (81%), severely injured (mean ISS 34) and in shock
  • Median transfused products were 29u PRBCc, 23u FFP, and 24u platelets
  • Mortality was high with half dying in 24 hours and two thirds not surviving to discharge
  • Transfusion ratios > 1.5:1 for both RBC to plasma and RBC to platelets were strongly association with death
  • CART identified severe head injury, resuscitative thoracotomy, and low platelet count (< 169K / microliter) we association with high mortality
  • The best chance for survival occurred in those without a head injury, no thoracotomy, and higher platelet count

The authors concluded that the failure to meet balanced resuscitation goals was the main concern for mortality, and recommended more attention to meeting ratios.

My comments: I’m not so sure I’ve learned a lot from this abstract. I think we already knew that people with severe TBI or thoracotomy don’t do very well, especially if they need that much blood.

I also worry about the heterogeneity of the population. The variables that were controlled still offer quite a bit of variability in the injuries and condition of these trauma patients. I think this will make it difficult to come to many solid conclusions when looking at something as crude as mortality. 

Here are my questions for the authors and presenter:

  1. Why are there so few patients? An eleven year study with 15 centers participating means that each submitted less than 3 cases per year. Most busy Level I centers have many more than that in a single year. Was there some other kind of data selection or limitation that is not described in the abstract? Do you think there is enough power? See question 3 for more on this.
  2. How did you arrive at an admission platelet count threshold of 169,000/ul? This would seem to be a surrogate for something else going on, and I’m not sure what. But it just seems so arbitrary.
  3. The transfusion ratios are a bit confusing. For ratios less than 1.5:1, there are no error bars. Does this mean that every one of those patients survived? That’s remarkable if so. And the error bars for the groups with a ratio > 1.5:1 are perilously close to the 1 line, and they have quite a range. Is the statistical power really there to convincingly show a difference? This is the most interesting part of the abstract, so please expound upon it.
  4. Explain your use of CART. How did you determine the specific  determine the specific thresholds used in the CART model? Why did you choose to use this tool? For my readers, here is the tree presented in the abstract.
  5. What is the real message of the abstract? We already know that if patients who have a severe head injury or get their chest cracked are probably not going to make it. The transfusion ratio information is somewhat interesting, but there is better quality data out there that defines acceptable ratios. The platelet count information… interesting. What more do you have?

I think there is a lot of potential in this dataset once you overcome the small numbers. I’m very interested in the authors’ presentation!

Reference: Ultra-massive transfusion outcomes in a modern era: an EAST multicenter study. EAST 2021, Paper 1.

 

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Abstracts, Resuscitation

Best Of The AAST #7: TXA And Thromboembolism

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The use of tranexamic acid (TXA) in trauma patients has escalated dramatically since the CRASH-2 trial was published ten years ago. It has become a frequent addition to the massive transfusion protocols used by trauma centers. And we are now even seeing TXA given by prehospital provides when life-threatening bleeding is suspected.

This drug is popular because it is inexpensive (~$100/dose) and is thought to be safe. However, some trauma professionals have been concerned about thrombotic side effects since TXA is a finbrinolysis inhibitor.

The group at the Mayo Clinic performed a retrospective study of seven years of their own data to determine if the concern for thrombotic complications was warranted. They specifically evaluated in-hospital mortality and thrombotic events up to 28 days after injury.  They also scrutinized outcomes in patients who received only the bolus TXA injection, but not the infusion.

Here are the factoids:

  • A total of 848 patients were included in the study, but there was no information as to what the inclusion criteria were
  • Only 212 received TXA; the other 636 were considered the control group, and there were no differences in age, sex or mechanism of injury
  • Thrombotic events occurred in 13% of the TXA patients and only 6% in the control group, which was statistically significant
  • Specific thrombotic events in TXA vs non-TXA patients: DVT was 8.5% vs 3.5% (significant), pulmonary embolism was 3.8% vs 1.9% (NS), MI was 1.9 vs 0.4% (NS), stroke was 2.4% vs 1.1% (NS)
  • Thrombotic events occurred more frequently in patients who received both doses of TXA (23%) vs just the bolus (10%), and this was also significant
  • In-hospital mortality was 21% with TXA vs 10%, which was not significantly different, controlling for confounders

The authors concluded that TXA administration was associated with higher rates of thrombotic events. They went on to state that TXA should not be routinely given for trauma patients in the community setting.

Here are my comments:

This is a bold recommendation from this very small study. The CRASH-2 trial was randomized and placebo controlled, and analyzed their experience with 10,000 subjects in each arm. This retrospective study has only  212 TXA vs 636 control patients. Big difference.

The authors attempt to match the TXA patients with controls. They controlled for age, sex, mechanism, and ISS. But it does not appear that there was any control for injuries known to increase the risk of thrombotic events like spine and pelvic fractures.

And why look at a full 28 day interval for thrombotic events? I would expect most of these events to occur in the first few days. Including an entire month in the study allows thrombotic events from other causes to creep in.

Here are some questions for the presenter and authors:

  • Please comment on how the small numbers in your study may have an impact on the results.
  • What were the selection criteria for your 848 patients? Were they all of your trauma activation patients? If not, is there some selection bias possible?
  • DVT appears to be the driver for your “significant” number of thrombotic events. Yet the other events (MI, stroke, PE) were not significantly different. This seems counter-intuitive, since the DVT numbers themselves numbered only about 20 in each group. Please describe the statistics you used to derive this conclusion.
  • Did you look at the incidence of injuries that are known to increase the risk of thrombotic events in the two groups? If there was an excess of pelvic or spine fractures in the TXA group, this might not be picked up in your analyses and could skew your data.
  • Why did you include thrombotic events for a full 28 days after injury? This allows for later events caused by factors other than the TXA. Show us a redo of your analysis using 5 or 7 day thrombotic events.

These are interesting numbers, but I have to admit that I am skeptical. I’m not clear how community hospital administration of TXA makes it more likely associated with thrombotic events. I will definitely be listening intently to this presentation. And probably asking these questions.

Reference: Risk of thromboembolic events after the use of TXA in trauma patients. AAST 2020, Oral Abstract #15.

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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.

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Resuscitation

Giving TXA Via An Intraosseous Line?

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Seriously injured patients frequently develop coagulopathy, which makes resuscitation (and survival) more challenging. A few years ago, the CRASH-2 study lent support for using tranexamic acid (TXA) in select trauma patients to improve survival. This drug is cheap and has antifibrinolytic properties that may be beneficial if given for life-threatening bleeding within 3 hours of initial injury. It’s typically given as a rapid IV infusion, followed by a slower followup infusion. The US military has adopted its routine use at forward combat hospitals.

But what if you don’t have IV access? This can and does occur with military type injuries. Surgeons at Madigan Army Medical Center in Washington state tried using a common alternative access device, the intraosseous needle, to see if the results were equivalent. This study used an adult swine model with hemorrhage and aortic crossclamping to simulate military injury and resuscitation. Half of the animals then received IV TXA, the other half had it administered via IO. Only the bolus dose was given. Serum TXA levels were monitored, and serial ROTEM determinations were performed to evaluate coagulopathy.

Here are the factoids:

  • The serum TXA peak and taper curves were similar. The IV peak was higher than IO and approached statistical significance (0.053)
  • ROTEM showed that the animals were significantly hyperfibrinolytic after injury, but rapidly corrected after administration of TXA. Results were the same for both IV and IO groups.

Bottom line: This was a very simple and elegant study. The usual animal study issues come into play (small numbers, pigs are not people). But it would be nearly impossible to have such a study approved in humans. Even though the peak TXA concentration via IO is (nearly significantly) lower, this doesn’t appear to matter. The anti-fibrinolytic effect was very similar according to ROTEM analysis.

From a practical standpoint, I’m not recommending that we start giving TXA via IO in civilian practice. We don’t typically see military style injuries, and are usually able to establish some type of IV access within a reasonably short period of time. But for our military colleagues, this could be a very valuable tool!

Reference: No intravenous access, no problem: Intraosseous administration of tranexamic acid is as effective as intravenous in a porcine hemorrhage model. J Trauma 84(2):379-385, 2018.

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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.

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