A guest post by Dr. Andrew Kirkpatrick (@AskEMdoc), an Emergency Medicine resident at the University of Texas Medical School at Houston.
Hypoxia, of course, is lethal to vulnerable cells. Erythropoeitin, in many small trials, has been shown to be neuroprotective after injury. So, given these apparently obvious beneficial and synergistic treatments, the authors of this study set out to answer the question: What happens when a patient with Traumatic Brain Injury (TBI) is given blood and erythropoietin?
This is a randomized control trial with a factorial (2×2) design that tested Erythropoietin (Epo) versus Placebo and Transfusion Threshold of 7.0g/dL versus 10g/dL to determine if either of the above interventions conferred the benefit of improved neurologic recovery in TBI. A total of 200 individuals with TBI were randomized into one of four groups using a block randomization strategy, sorting individuals into groups with and without transfusion thresholds or Epo administration. Both the treatment team and the follow up personnel were blinded to Epo administration, but only follow up personnel could be blinded to transfusion threshold group. Then, to make this study even further convoluted, the Epo dose and frequency was changed mid-stream due to safety concerns, dividing the Epo arm into the Epo1 and Epo 2 groups. They also changed the study from a superiority trial to futility, and unusually selected 0.15 as their one-tailed alpha – a choice severely restricting their ability to reject the null hypothesis.
Determination of primary outcome data was completed utilizing the Glasgow Outcome Scale (GOS) using a variety of strategies, including in person and phone follow up. For all comparisons – both transfusion thresholds and Epo – no statistically significant difference was detected. Given their small sample, they may simply have been unable to produce a difference – as Epo seemed to potentially have some beneficial effect, though transfusion certainly showed no such signal. Risk of death, infection, ARDS, and Cardiovascular complications including VTE were evaluated for as well, and both Epo groups and the 10g/dL transfusion group had significant increased risk of adverse events. And, regarding resource utilization, the transfusion threshold group obviously consumed more blood products.
The study had several limitations including change in Epo protocol with 1/3 of the patients already enrolled, inability to blind clinicians to transfusion threshold, the aforementioned statistical limitations, and generalizability limitations owing to its enrollment at only two trauma centers. Overall the results were unable to demonstrate benefit to either strategy – but were able to demonstrate definite harms. Until further evidence is presented, it is prudent to continue conserving blood products and abstaining from giving ineffective, expensive medication.
“Effect of Erythropoietin and Transfusion Threshold on Neurological Recovery After Traumatic Brain Injury A Randomized Clinical Trial”