Tag Archives: blood

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.

Equipment

Rapid Infusers: How Fast Can They Go?

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The rapid infusion pump is a mainstay of high volume trauma resuscitation. According to the manufacturers, these devices can now deliver fluids at up to 1000 ml/minute. Or can they?

Here is a chart from the manufacturer of the Belmont rapid infuser. This shows the (theoretical) flow rates achievable for each of their two devices (max flow rate of 750 ml/min and 1000 ml/min models). The charts show the maximum flow rates for crystalloid or blood for various sizes of IV catheters that are 2″ long.

Notice two things:

  • The flow rate decreases exponentially as the size of the IV catheter decreases
  • The difference in flow rate between blood and crystalloid diminishes as the catheter size increases

These observations can be explained by something I’m sure you haven’t thought about since high school physics: Pouiseulle’s Equation. Of course you remember, right?

The equation states that the flow of a fluid (F) is proportional to the fourth power of the radius of the catheter and the pressure gradient across the two ends of it (delta P), and inversely proportional to the viscosity of the fluid (greek letter eta) and the length of the catheter (L).

What does this mean in practical terms?

  • The pressure gradient is fixed at about 300 mm Hg (the pressure bag or pump) so you can essentially ignore this factor
  • The viscosity (measured in centipoise) is based on the fluid begin given. Crystalloid (water) has a viscosity of 1. Whole blood has a viscosity of about 2.7, and packed cells are about 10. This means that our typical infusion of PRBC flows 10 times more slowly than saline.
  • The length and diameter of the IV catheter are controlled by the trauma professional who inserts it, and it has a massive impact on flow. This is particularly true for the diameter (gauge), which varies directly as the fourth power.

So let’s put all these numbers together. Let’s assume that we are using balanced resuscitation and are infusing lots of blood, not crystalloid. The choice of IV catheter is the most important factor for a successful volume resuscitation! Here’s a table I constructed that lists the approximate relative flow rates for several catheter types. I use a 9 Fr introducer as the gold standard and have defined the flow rate for that device as 1.

IV Catheter Internal Radius Length Relative flow
9 Fr Introducer 1.5 mm 10 cm 1
14 Ga IV 0.8 mm 5 cm 1/6 x
Triple lumen cath 0.3 mm 20 cm 1/1265 x

Bottom line: High-speed volume resuscitation forces us to squeeze a thick (and hopefully warm) liquid through a small straw into our patient’s vein. The smaller and longer the straw, the harder it is to do that. I think that people underestimate how much of an impact the choice of catheter makes.

Always use the largest and shortest possible access for rapid infusion. Ideally, this should be a large, straight introducer. Some have a side port (e.g. Cordis) at a right angle to the catheter, but this introduces some extra resistance and will slow the infusion rate. A large bore (14 Ga) short (2 inch) IV catheter is good, but will only flow at one sixth the rate of an introducer.

And never use anything with more than one lumen! The typical triple lumen catheter has three lines that are either 20 or 21 Ga. They are tiny and very long. Looking at the table above, you will be lucky to infuse a few cc’s per minute through one of these, compared to hundreds of cc’s via a straight introducer.

References:

Abstracts

Best Of EAST #5: Keeping Blood From Going Bad

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What goes around comes around. Whole blood was the only transfusion product available until about 60 years ago, when the whole blood banking system switched to fractionating blood products. Now we are discovering the benefits of whole blood again. The military has been using fresh whole blood for some time. As civilians, we’ve had less access to whole blood. But once obtained, it must be used within 21 days. This is half the storage time for the usual bag of packed red cells, and may result in some waste of this valuable product.

The group at the University of Cincinnati wondered if fractionating and preserving an expiring bag of whole blood might extend the life of those red cells. They obtained 21- day old (expiring) whole blood and separated the red cells, preserving them using the usual technique. They then analyzed the cells weekly until expiration at 42 days for viability, storage damage and coagulation status.

Here are the factoids:

  • The number of units tested was not listed in the abstract
  • Damage from storage of the extracted red cells appeared to be consistent with normal damage expected from packed red blood cells
  • When mixed with plasma with a 1:1 ratio, clotting time, clot formation time, and maximum clot formation did not change as the salvaged cells aged

The authors concluded that the salvaged cells aged just like packed RBCs. They suggested that this may provide a method for extending the life of whole blood and allowing transfusion into patient in hemorrhagic shock.

My comment: This is an intriguing paper and suggests a way of extending the life and use of valuable whole blood. It appears to have been well done and analyzes standard markers of red cell dysfunction. However, the authors did not provide the number of units they tested. This is critical, since they are trying to show that the values tested are statistically the same (no difference between packed RBCs and those salvaged from whole blood). Some of their comparison numbers appear very different, but are not statistically significant. I worry that the number of units tested might be too small to show a difference.

Here is my question for the authors and presenter:

  1. Exactly how many units of whole blood did you use in this study? And did you do a power analysis to ensure that you don’t have a Type II error (false negative) with the “not significant” results?

This is a great idea and stands to save money and stretch our supply of blood!

Reference: Save it – don’t waste it! Maximizing utilization of erythrocytes from previously stored whole blood. EAST Annual Assembly abstract #6, 2020.

Resuscitation

Use Of Whole Blood For Massive Transfusion

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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.
Resuscitation

Why Do We Use Fractionated Blood Components?

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Tomorrow, I’ll be writing about the use of the newest and greatest blood product: whole blood. Wait, isn’t that what we started out a hundred years ago? How is it that we are even debating the use of blood component therapy vs whole blood? Most living trauma professionals only remember a time when blood components have been infused based on which specific ones were needed.

Prior to about 1900, blood transfusion was a very iffy thing. Transfusions from animals did not go well at all. And even from human to human, it seemed to work well at times but failed massively at others. In 1900, Landsteiner published a paper outlining the role of blood groups (types) which explained the reasons for these successes and failures. With the advent of blood storage solutions that prevented clotting, whole blood transfusion became the standard treatment for hemorrhage in World War I.

When the US entered World War II, it switched to freeze-dried plasma because of the ease of transport. However, it quickly became clear that plasma-only resuscitation resulted in much poorer outcomes. This led to the return to whole blood resuscitation. At the end of WWII, 2000 units of whole blood were being transfused per day.

In 1965, fractionation of whole blood into individual components was introduced. This allowed for guided therapy for specific conditions unrelated to trauma. It became very popular, even though there were essentially no studies of efficacy or hemostatic potential for patients suffering hemorrhage. The use of whole blood quickly faded away in both civilian and military hospitals.

The use of fresh whole blood returned for logistical reasons in the conflicts in Iraq and Afghanistan. A number of military studies were carried out that suggested improved outcomes when using whole blood in place of blood that has been reconstituted from components. That leads us to where we are today, rediscovering the advantages of whole blood.

And that’s what I’ll review tomorrow!