All posts by TheTraumaPro

Best of EAST #6: Does Rh Status Matter In Whole Blood Transfusion?

What goes around comes around. Fifty plus years ago, the only transfusion product available was whole blood. Then the major blood banks discovered that more patients could be treated for specific problems if the blood were fractionated. Packed red cells then became the standard for trauma transfusion and persists to this day.

But there is a move afoot to re-explore the use of whole blood. There are many theoretical advantages, since our trauma patients are bleeding whole blood, not packed cells. Unfortunately, combining a unit of packed red cells, plasma, and platelets does not give you a reconstituted unit of whole blood by a long shot. Check out this diagram:

The challenge is that we are used to only thinking about universal donor red cells (group O Rh-). This is the safest packed cell product to give a patient with an unknown blood type. But unfortunately, it is also one of the hardest to find, present in about 7% of the population.

Packed red cells are nearly plasma free. What we don’t think about with whole blood is the level of antibodies to blood groups that are present in the plasma. Group O blood will have plasma with anti-A and anti-B antibodies. So if we include the plasma with those universal donor red cells, these antibodies may attack the patient’s red cells if he or she is group A, B, or AB and cause a reaction.

Theoretically, this issue can be avoided by using universal donor plasma (group AB+). Since the donor has all of the major group antigens, they will have no antibodies in their plasma. Unfortunately again, this is a rare type and tough to get donors (about 3% of the population).

To avoid potential transfusion reactions, group O whole blood is tested for antibody titers, and only low titer blood is selected for transfusion. Typically Rh- whole blood has been selected to avoid any issues with Rh incompatibility, even though reactions to this antigen are usually mild.

The group at the University of Texas – Houston reviewed their experience using Rh+ low titer group O blood in trauma resuscitations. Their two-year study substituted Rh+ whole blood when Rh- product was not available. They monitored patients for transfusion reactions, renal failure, sepsis, VTE, and ARDS.

Here are the factoids:

  • A total of 637 patients received low titer group O blood during the study period; 448 received Rh+ product and 189 received Rh-
  • Those receiving Rh+ blood were more likely to be male, had lower initial SBP, and a significantly lower GCS (7 vs 12)
  • Overall there were no differences in hemolysis labs, transfusion reaction, complications or mortality
  • The patient groups were then sliced and diced by their own Rh antibody status to see if Rh- patients had an increased likelihood of problems from Rh+ plasma
  • Once again, the Rh- subgroup was significantly different for sex (57% female vs 26% in the Rh+ group), and blunt trauma mechanism (92% vs 70%)
  • And once again no differences were seen in hemolysis, transfusion reaction, complications or mortality

The authors then concluded that Rh+ low titer whole blood is a safe alternative in either Rh+ or Rh- patients.

My comments: Sounds good, right? But wait a minute! This was a non-randomized observational study. It appears that Rh+ whole blood was used when Rh- was unavailable, which was quite a bit of the time. This is clear when you see the demographic differences listed above between the two recipient groups, as well as the subgroups stratified by their own Rh status.

This is the first thing that makes me a bit more skeptical of the recommendation. The other one is something you’ve heard me harp about before… non-inferiority studies. This abstract tries to say that since they did not detect a difference, then the two products are equivalent.

That is only true if there is adequate power in the number of patients studied. If not, you may not be able to show a statistically significant difference. By my own calculations, if the incidence of transfusion reaction in the Rh- group is 1% and the ratio of the patient groups is 0.42, the reported sample size could only show a significant difference if the Rh+ patients had a 5% transfusion reaction rate.

So is it truly non-inferior, or does the study need include a lot more patients? 

Here are my questions for the authors and presenter:

  • What is the impact of the non-randomized patient selection process on your results? The groups and subgroups appear to be very different. Couldn’t this influence your results?
  • Exactly what type of statistical analysis did you use? Your abstract merely lists the software package, not the specific tests applied.
  • Do you believe that your study is sufficiently powered? What assumptions did you use to calculate this?

As we move toward more use of whole blood, the Rh question will be an important one. I look forward to questioning the authors on this one!

Reference: Can Rh+ whole blood be safely used as an alternative to Rh- product? An analysis of efforts to improve the sustainability of a hospital’s low titer group O whole blood program. EAST 2021, Paper 17.

Best of EAST #5: Elderly Falls And Vision Problems

Elderly falls have become a huge problem. There isn’t a night that goes by that we don’t admit at least two or three at our trauma center. There are at least a dozen factors that have been identified that are associated with falls, including:

  • Medications
  • Bone and muscle loss
  • Underlying medical conditions
  • Gait problems
  • Throw rugs and other environmental hazards
  • Visual problems

And many more! But let’s focus on that last one. Vision problems can be due to primary disease, such as glaucoma, or from lack of adequate correction of those problems, such as decreased visual acuity.

The group at West Virginia University is presenting a prevention paper next week. They prospectively studied patients older than 60 years who were admitted to their trauma service over a one year period. They wanted to determine the prevalence of undertreated or undiagnosed eye disease in the population, and to find out if using readily available screening tests could detect this and assist in prevention efforts.

A dilated ophthalmic exam was performed and used as the gold standard. The results were compared to a screening app administered by a trauma provider via an iPad (the eyeTests Easy app). This app can be used to test for visual acuity, macular degeneration, near vision, and astigmatism.

Here are the factoids:

  • A total of 96 patients were enrolled, with an average age of 75 and a predominant mechanism of fall in 79%
  • Significant abnormal vision was undiagnosed in 39% of patients and undertreated in 14%
  • The trauma provider app exam was 94% sensitive and 92% specific
  • Correlation was best on pupil exam (86%), visual fields (58%), and the macular degeneration test (52%)
  • A combination of visual fields and the Amsler grid were associated with significant abnormal vision

The authors concluded that unrecognized visual problems are common, and are present in 53% of their elderly trauma admissions. They also state the the trauma provider exam can identify abnormalities in “most cases” and can identify those who should be screened by an ophthalmologist.

My comments: This is an interesting study that compares a simple, app-based screen with a more sophisticated ophthalmology exam. However, it is not clear what “significant abnormal vision (SAV)” really is. The sensitivity and specificity numbers cited depend on this definition. Is it a positive answer to one of the screening questions? Evidence of macular degeneration? If so, how much? I’m sure that a lot of the elderly (and younger) population have some small irregularities in their vision, but what makes it significant?

The study does show that the app can be used as a screening tool due to the congruence with the “gold standard” ophthalmologic exam. And given that vision is one of the major factors associated with falls risk, it may be a cost-effective tool for reducing it.

Here are my questions for the authors and presenter:

  • What is you exact definition of “significant abnormal vision?” This is critical, because it determines the significance of the rest of your results. If the threshold is set too low, you will detect many anomalies but they may not be clinically significant. This definition needs to be as objective as possible so others can duplicate and take advantage of your work.
  • What do you recommend for workflow to incorporate this tool? Who should do it and when? Should the user focus on particular portions of the app (e.g. Amsler and visual fields, acuity)?
  • Describe your future plans for the longitudinal study mentioned in the abstract.

This is very interesting prevention work. I look forward to the nitty gritty details next week!

Reference: Stop the fall: identifying the 50% of geriatric trauma patients with significant vision loss. EAST 2021, Paper 11.

Best of EAST #4: Futile Trauma Transfers

Level I and II trauma centers are regularly on the receiving end of what may be termed as “futile transfers.” These are patients who have sustained unsalvageable injuries and are initially seen at a lower level center. They are then transferred upstream where they succumb shortly (0-48 hours) after arrival.

As you might imagine, these patients can place a significant burden on resources at the Level I or II center. This is an even more acute situation given the large numbers of COVID patients who also require hospitalization and palliative care services these days.

The group at the University of Kansas sought to put some numbers on this phenomenon. They examined their own experience as one of two Level I trauma centers in the Kansas City metro area. They defined futile care as patients who died or were discharged to hospice care within 48 hours of arrival and who did not undergo operative, endoscopic, or interventional radiology procedures.

Here are the factoids:

  • A total of 1,241 patients were transferred in during the two year study period
  • Of these, 407 had stays of 48 hours or less, and 18 (1.5%) were deemed futile care according to their definition
  • The futile care patients tended to be much older (75 vs 61 years) and were much more severely injured (ISS 21 vs 8)
  • When transport and hospital charges were combined, the average total cost was $56,000
  • Total cost to this hospital was $1.7 million, and this was extrapolated to an annual cost of 27 million for the entire US

The authors concluded that these futile transfers are a small yet costly patient population. They suggested that accurately identifying these patients and providing resources to help referral hospitals figure out how to care for them would be helpful.

My comments: This is a very straightforward descriptive paper that details a problem that every high level trauma center sees on a regular basis. Older patients, typically those with critical head injuries that are beyond treatment, are transferred to the “big house.” The families are frequently told that there are no local resources to provide the care needed, and that the higher level center is their only chance. 

The families then have unrealistic expectations, and are inconvenienced by the travel involved. Wouldn’t it be better to just tell the family that the injury is a really bad one, and provide palliative / hospice care in the local community? Unfortunately, it’s not that simple. Many small hospitals do not have providers who are well-versed in this type of care. Thus, the suggestion to provide resources (people? training?) is a sound one.

This abstract highlights a problem we all face but seldom publicize. Hopefully this one will get us talking. And acting.

Here are my questions for the authors and presenter:

  1. What kind of resources do you think are needed to allow referral hospitals to care for these patients?
  2. How will these hospitals know when care is futile? Will there be an expectation to work with the receiving center to help determine this?

I enjoyed this paper and can’t wait to hear the details!

Reference: Futile trauma transfers: an infrequent but costly component of regionalized trauma care. EAST 2021, paper 9.

Best of EAST #3: Spine MRI Usage After EAST Guidelines

In 2015, EAST published their practice guidelines for spine clearance in the obtunded blunt trauma patient. Click here to view them. They stated that a high-quality CT scan can be used to remove (clear) the cervical collar in these patients. This avoids the use of the expensive and personnel-intensive MRI clearance.

The group at UCSF used the NTDB to review the use of MRI in such patients over an 11 year period. They focused on comatose patients (GCS < 8) with an AIS head > 3 and intubation for more than 72 hours. They used logistic regression to equalize confounders while examining the use of MRI over time, before and after the guidelines were published.

Here are the factoids:

  • More than 75,000 patients from 530 trauma centers were included
  • Patients who were older, Hispanic, uninsured, or involved in a car crash were less likely to undergo spinal MRI
  • Level I centers were more likely to use MRI for clearance than Level II centers
  • Patients evaluated after release of the practice guidelines were 1.7x more likely to undergo MRI for spine clearance (!!)

The authors concluded that spinal MRI use has been increasing since 2007 despite publication of the EAST guideline.

My comments: To me, this indicates one of the following:

  1. Nobody reads the EAST guidelines, or
  2. Trauma programs believe that they alone are able to figure out what is right, and everyone else is wrong

I suspect that it is #2. For some reason, trauma programs insist on doing it their own way despite what decent evidence shows. I think that this represents a defense mechanism to minimize the cognitive dissonance that comes with defying what is published in the literature.

I always encourage programs to borrow/steal what is already out there when crafting their own practice guidelines. Someone else has already done the work, why not take advantage of it? Typically, it’s just an excuse to continue doing things the way they’ve always been done.

This incessant reinventing the wheel becomes tiresome. And for once, I don’t have many questions or suggestions for the authors. Their evidence is pretty well laid out. 

My questions for the author / presenter are:

  1. Do you use MRI for spine clearance in your obtunded blunt trauma patients? And if so, WHY?
  2. Why do you think there are demographic and trauma center level disparities? Is it the teaching environment? Something else?

To everyone else, I say “get over yourself and read the literature!”

Reference: Assessing the e3ffect of the EAST guideline on utilization of spinal MRI in the obtunded adult blunt trauma patient over time. EAST 2021, Paper 7.

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.