Tag Archives: transfusion

Best Of AAST 2021: Are We Getting Better At Balanced Resuscitation?

The way we resuscitate major trauma patients has been changing over the past decade. Even the 10th edition of the ATLS course has recognized that so-called balanced resuscitation is important. This concept limits the use of crystalloid and relies more heavily on blood component administration in ratios that more closely approximate whole blood.  Balanced resuscitation typically translates as the use of less than two liters of crystalloid, and blood product transfusion ratios of 1:1 to 2:1 (PRBC to plasma).

We have also recognized the critical importance of rapid control of major hemorrhage, which is best accomplished in an operating room.  The group at the University of Arizona massaged the TQIP database to see if these changes are having a significant impact on our patients.

They looked at five years worth of data, specifically reviewing information on adult patients with both transfusion and laparotomy occurring within four hours of arrival. The authors performed regression analyses to identify trends over the study period.

Here are the factoids:

  • Nearly 10,000 patients met study criteria with a mean age of 44 and ISS 34
  • Patients were in shock, with mean SBP 78 and median number of transfusions of 9 PRBC and 6 plasma
  • Time to laparotomy decreased from 1.87 hours to 1.37 hours over the five year period
  • 24-hour mortality decreased from 23% to 19% during the study
  • Blood product ratio decreased from 1.93:1 to 1.73:1
  • The authors state that the blood product ratio was independently associated with 24 hour mortality (odds ratio of 1.09) and in-hospital mortality (1.10) (??)

The authors conclude that resuscitation is becoming more balanced and time to surgery shorter, with a significant improvement in mortality.

Bottom line: Well, this is an interested study of associations. It uses a large database, which of course limits some of the information available. There are obvious trends toward faster time to OR (by 30 minutes) and a 4% improvement in survival. But the transfusion ratio really looks to be about the same. 

Let’s do the math, assuming that an average of 10 units of PRBC were given. A ratio of 1.93 would mean that 5.2 units of plasma were give (1425 cc, assuming 275 cc per unit). The ratio of 1.73 noted in 2017 would then be 5.8 units, or 1590 cc. This is an increase in FFP transfusion of 165 cc.

The authors stated that the improvement in transfusion ratios was statistically associated with the improvement in survival. I think this is one of those situations where there is a big difference between statistical significance and clinical significance. Do you really think that giving just 165 additional ccs of plasma could have that much overall effect on survival?

My suspicion is that there is a true association between the more rapid time to OR (and presumably surgical control) and survival. It’s just that the numbers were not clean enough to meet statistical rigor.

This is an interesting abstract, and shows that we are slowly getting better at controlling bleeding. But I think the most important takeaway is that we are not as good at balanced resuscitation as we think we are. We seem to be hovering at the 2:1 ratio, and only very slowly moving toward 1:1.

Questions for the authors / presenter:

  • Were you able to see a correlation between time to OR and survival?
  • Please comment on the association between transfusion ratios and survival, especially given the very small change over time.
  • Please clarify the in-hospital mortality and 24-hour mortality variables. In-hospital mortality suddenly pops up at the end of the results, but was never mentioned before.

Reference: AFTER 9,000 LAPAROTOMIES FOR BLUNT TRAUMA, RESUSCITATION IS BECOMING MORE BALANCED AND TIME TO INTERVENTION SHORTER: HOW LOW CAN WE GO? AAST 2021, Oral abstract #3.

Rapid Infusers: How Fast Can They Go?

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:

How Quickly Does Hemoglobin Drop After Acute Bleeding?

We all know that hemoglobin / hematocrit drop after blood loss. We can see it decreasing over the days after acute bleeding or a major operative procedure (think orthopedics). And we’ve been told that the hemoglobin value doesn’t drop immediately after acute blood loss.

But is it true? Or is it just dogma?

A reader sent me a request for some hard references to support this. When I read it, I knew I just had to dig into it. This is one of those topics that gets preached as dogma, and I’ve bought into it as well.

Now, I have personally observed both situations. Long ago, I had a patient with a spleen injury who was being monitored in the ICU with frequent vital signs and serial blood draws (but I don’t do that one anymore). He was doing well, then became acutely hypotensive. As he was being whisked off to the OR, his most recent hemoglobin came back at 10, which was little changed from his initial 11.5 and certainly no independent reason to worry.

But hypotension is a hard fail for nonoperative solid organ management. In the OR, anesthesia drew another Hgb at the end of the case, and the value came back 6.

Similarly, we’ve all taken care of patients who have had their pelvis fixed and watched their Hgb levels drop for days. Is this anecdotal or is it real? The doctor / nursing / EMS textbooks usually devote about one sentence to it, but there are no supporting references.

I was only able to locate a few older papers on this. The first looked at the effect of removing two units of red cells acutely. Unfortunately, the authors muddied the waters a little. They were only interested in the effect of the lost red cell mass on cardiac function, so they gave the plasma back. This kind of defeats the purpose, but it was possible to see what happened to Hgb levels over time.

Here were there findings over time for a group of 8 healthy men:

Time Hbg level
Before phlebotomy 14.4
1 week after 11.7
4 weeks after 12.6
8 weeks after 13.6
16 weeks after 13.9

So the nadir Hgb value occurred some time during the first week after the draw and took quite some time to build back up from bone marrow activity.

That’s the longer term picture for hemoglobin decrease and return to normal. What about more acutely? For this, I found a paper from a group in Beijing who was trying to measure the impact of Hgb loss from a 400cc blood donation on EEG patterns. Interesting.

But they did do pre- and post-donation hemoglobin values. They found that the average Hgb decreased from 14.0 to 13.5 g/dl during the study, which appeared to be brief. Unfortunately, this was the best I could find and it was not that helpful.

Bottom line: Your patient has lost whole blood. So, in theory, there should be no Hgb concentration difference at all. But our bodies are smart. The kidneys immediately sense the acute hypovolemia and begin retaining water. The causes ongoing hemodilution within seconds to minutes. Additionally, fluid in the interstitial space begins to move into the vascular space to replace the volume lost. And over a longer period of time, if no additional fluid is given the intracellular water will move out to the interstitium and into the vascular space.

But these things take time. There is an accelerating curve of hemodilution that takes place over hours. The slope of that curve depends on how much blood is lost. A typical 500cc blood transfusion will cause a 0.5 gm/dl drop over several minutes to an hour. We don’t have great data on the exact time to nadir, but my clinical observations support a hyperbolic curve that reaches the lowest Hgb level after about 3 days.

Unlike this curve, it levels off and slowly starts to rise after day 3-4 due to bone marrow activity.

The steepness of the curve depends on the magnitude of the blood loss. After a one unit donation, you may see a 0.5 gm/dl drop acutely, and a nadir of 1 gm/dl. In the case of the acutely bleeding patient with the spleen injury, the initial drop was 1.5 gm/dl. But two hours later it had dropped by over 5 gm/dl. 

Unfortunately, the supporting papers are weak because apparently no one was interesting in proving or disproving this. They were more interested in cardiac function or brain waves. But it does happen. 

Here’s the takeaway rule:

In a patient with acute bleeding, the initial hemoglobin drop is just the tip of the iceberg. Assume that this is only a third (or less) of how low it is going to go. If it has fallen outside of the “normal” range, call for blood. You’ll need it!

References:

  1. Effect on cardiovascular function and iron metabolism of the acute removal of 2 units of red cells. Transfusion 34(7):573-577, 1994.
  2. The Impact of a Regular Blood Donation on the Hematology
    and EEG of Healthy Young Male Blood Donors. Brain Topography 25:116-123, 2012.

 

Best of EAST #2: Blood Transfusion And Nosocomial Infection

This abstract falls into the “interesting, but how can we use this bit of information” category. We’ve known that transfusing packed red cells raises nosocomial infection rates for at least 15 years. The group led by MetroHealth in Cleveland combined forces with the Vanderbilt trauma group to re-look at their data from the PAMPer trial with respect to trauma patients.

The PAMPer trial (Prehospital Air Medical Plasma) examined the effect of tranfusion of two units of plasma in the air ambulance on mortality, transfusion need, and complications. Half of the patients got plasma plus standard care, and the other half standard care alone.

This abstract uses PAMPer trial data to examine the impact of giving any amount of blood on nosocomial infection in these patients. These infections included pneumonia, bloodstream infection, C Diff colitis, empyema, and complex intra-abdominal infection.

The group retrospectively analyzed the prospectively collected PAMPer data and used logistic regression models to test for an association.

Here are the factoids:

  • A total of 399 patients with the usual trauma demographics were included (younger male, moderately injured, blunt mechanism)
  • Ten percent of patients died, and 23% developed nosocomial infections
  • Pneumonia was by far the most common complication (n=67) with all others in the low teens or below
  • Although only two thirds of patients received plasma, 80% were given PRBCs and 27% received platelets
  • Patients who received any amount of packed cells had a 2.3x increase in nosocomial infections, and the number given increased the rate of nosocomial infection (1.06x)

The authors concluded that patients in the PAMPer trial who received at least one unit of blood “incurred a two-fold increased risk of nosocomial infection” and that this risk was dose dependent.

My analysis: The biggest obstacle for me to buy into this work is the enrolled patient group. Studies in which you borrow someone else’s data are always a bit problematic. You have no control over the variables, as they’ve been determined by someone else.

In this case, the dataset could only be controlled for age, sex, and ISS. But what about all the other stuff that might have an impact on infections? Things like pulmonary injury, the 20% of patients who had penetrating injury, and severe TBI patients with their propensity to develop VAP.

The odds ratios of the associations were a bit on the low side. Sure, the overall nosocomial infection odds ratio was 2.37 but the confidence interval was 1.14 to 4.94. This is very wide and it means that the odds could have been anywhere from 1.14x to almost 5x. This suggests that the study group may not have been large enough to give us a clear picture. And the odds ratio for number of PRBC units vs infection was only 1.06 with a tighter confidence interval. So even if it is present, this association is very, very weak. I like to see ridiculously large odds ratios when reviewing observational studies like this where the input data is constrained.

My final comment on this study deals with its utility. These are trauma patients. They are bleeding. We’ve known that transfusions may increase the nosocomial infection rate in critically ill patients for at least 15 years. But we will still have to give the patients blood. So what are we to do?

Here are some questions for the authors and presenter:

  • Please comment on the limitations you faced using the PAMPer dataset. Were you satisfied with the range of variables available? Which additional ones would you have liked to work with?
  • Do you feel that the 399 patients provided enough statistical power for analysis? The confidence intervals are large and very close to the OR=1 line.
  • What should we do with your conclusions? Can we translate this into clinical practice?

One final note: the patients did not “incur increased risk.” Rather, there was an association with increased risk of infection. We really don’t know if it was from the blood or something else that was not recorded in the PAMPer dataset.

Reference: Dose-dependent association between blood transfusion and nosocomial infections in trauma patients: a secondary analysis of patients from the PAMPer trial. EAST 2021, Paper 3.

Can We Use Type A Plasma For Emergency Transfusion?

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.