Category Archives: Complications

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.

 

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Routine Duplex Screening For Venous Thromboembolism

Venous thromboembolism (VTE) is a potential problem for all hospitalized patients, and traumatic injury is yet an additional risk factor for its occurrence. Most trauma centers have some kind of risk assessment tool to help the tailor their chemoprophylaxis regimen to patients most at risk. But far fewer have adopted the use of screening ultrasounds to monitor for new onset VTE that would dictate conversion to therapeutic treatment.

Unfortunately, in the US, the Centers for Medicare and Medicaid Services (CMS) has deemed VTE as a “never” event and penalizes hospitals when they report it. One of the unintentional consequences of this (or is it?) is that hospitals may then pressure trauma programs to avoid surveillance in order to “make the numbers look better.” Remember Law X from Samuel Shem’s House of God?

X. If you don’t take a temperature, you can’t find a fever.

Similarly, if you don’t do a duplex screen, you probably won’t detect VTE. Now granted. some patients develop classic symptoms like edema, pain, and tenderness. But not that many.

But is this wise? My contention has been that if the patient doesn’t develop symptoms that catch your attention, yet they develop VTE that you don’t know about, they are at risk for more serious complications like pulmonary embolism (PE). And you are blithely unaware.

The trauma group at Intermountain Medical Center in Salt Lake City performed an elegant study to determine the impact of screening for VTE in their trauma patients. They performed a prospective, randomized trial on trauma patients admitted over a 30-month period. Patients were included if they were judged to be at moderate to high risk based on their risk assessment profile (RAP) score. Patients were excluded if they were children, had VTE or PE within 6 months prior to hospitalization, or had some type of hypercoagulable state.

Patients were sequentially randomized to no duplex screening vs screening on days 1, 3, 7, and then weekly thereafter. The primary outcome measure was PE during the hospital stay. Secondary outcomes consisted of a number of factors relating to development of DVT.

Here are the factoids:

  • Nearly two thousand patients were enrolled, with about 995 patients in each group and no differences in demographics
  • The ultrasound group had significantly more below-knee (124 vs 8) and above knee (19 vs 8) DVT identified (no surprise there)
  • The ultrasound group had significantly fewer pulmonary emboli than the no ultrasound group (1 vs 9) (lots of surprise here!)
  • Mortality was similar during the hospital stay and for 90 days after

Bottom line: If you look for it, you will find it! This is the definition of surveillance bias. But in in this study, looking for clots in the legs may also decrease the number of patients who develop symptomatic pulmonary embolism. How could this be?

There are a few possibilities. The majority of DVT found in the surveillance group were located distally. Although there is some uncertainty as to how likely these are to embolize, it is probably very low. So let’s ignore them for now and assume that only the proximal clots might embolize.

This leaves an extra 11 DVT found in the surveillance group over and above the no-ultrasound group. Despite that, the surveillance group had only one PE vs 9 in the no-ultrasound group!

Another explanation was that the ultrasound guided changes in management, shifting to management to therapeutic drug dosing. The authors did not find a significant difference between the use of therapeutic vs prophylactic dosing between the groups. But there was a difference. Although the overall study was well-powered, there really weren’t enough numbers to show whether there was a true difference in therapeutic dosing. Fourteen patients in the ultrasound group got therapeutic anticoagulation compared to only 4 in the no-surveillance group. I think this is the actual reason.

Overall, this is a well-designed and well-executed study that shows why taking the Ron Popeil approach to DVT prophylaxis (“set it and forget it”) doesn’t work. Patients do occasionally develop proximal DVT on standard chemoprophylaxis (and frequently develop distal DVT), but it doesn’t always result in obvious signs and symptoms. This study shows that if you don’t look for it, you may not know until they suddenly develop chest pain, air hunger, and worse! So consider carefully if your practice guideline doesn’t yet include surveillance.

Reference: Trauma Patients at Risk for Venous Thromboembolism who Undergo Routine Duplex Ultrasound Screening Experience Fewer Pulmonary Emboli: A Prospective Randomized Trial. J Trauma, publish ahead of print, Publish Ahead of Print. DOI: 10.1097/TA.0000000000003104, February 4, 2021.

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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.

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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.

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Syncope Workup in Trauma Patients – Updated With CPG

Syncope accounts for 1-2% of all ED visits, and is a factor in some patients with blunt trauma, especially the elderly. If syncope is suspected, a “syncope workup” is frequently ordered. Just what this consists of is poorly defined. Even less understood is how useful the syncope workup really is.

Researchers at Yale retrospectively looked at their experience doing syncope workups in trauma patients. They were interested in seeing what was typically ordered, if it was clinically useful, and if it impacted length of stay.

A total of 14% of trauma patients had syncope as a possible contributor to their injury. The investigators found that the following tests were typically ordered in these patients:

  • Carotid ultrasound (96%)
  • 2D Echo (96%)
  • Cardiac enzymes (81%)
  • Cardiology consult (23%)
  • Neurology consult (11%)
  • EEG (7%)
  • MRI (6%)

Most of this testing was normal. About 3% of cardiac enzymes were abnormal, as were 5% of carotid imaging and 4% of echocardiograms.

Important! Of the patients who underwent an intervention after workup, 69% could have been identified based on history, physical exam, or EKG and did not depend on any of the other diagnostic tests.

Is it possible to determine a subset of this population that may show a higher yield for this screening? Surgeons at Temple University in Philadelphia found that there was little utility in using carotid duplex studies. They did note that patients with a history of heart disease were more likely to have an abnormal EKG, and that an abnormal EKG predicted an abnormal echo. Overall, only patients with a history of significant cardiac comorbidity, older age, and higher ISS had findings requiring intervention.

Bottom line: Don’t just reflexively order a syncope workup when there is a question of this problem. Think about it first, because the majority of these studies are nonproductive. They are not needed routinely in trauma patients with “syncope” as a contributing factor.  Obtain a good cardiac history, and if indicated, order an EKG and go from there. See the practice guideline proposed by the Temple group below. And be sure to include the patients primary doctor in the loop!

References:

  1. Routine or protocol evaluation of trauma patients with suspected syncope is unnecessary. J Trauma 70(2):428-432, 2011.
  2. Syncope workup: Greater yield in select trauma population. Intl J Surg, accepted for publication June 27, 2017.

 

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