Here at St.Emlyn’s we are always interested in improving outcomes from serious illness and injury. In many cases the outcome for patients in terms of their quality of life is related to neurological function. Yet we are limited in what we can achieve. Targeted temperature management has failed to deliver its early promise and similarly the initial enthusiasm for sex hormone therapy after brain injury failed to show a significant effect in a larger RCT. What else is out there? Well, laboratory models using erythropoetin (EPO) have shown promise. As we know EPO increases erythropoesis and thus red cell mass (Ed – anyone watching the Tour de France this week?). What you might not know (I didn’t until this week) is that EPO is active on some cells undergoing stress or ischaemia; including the heart and brain. There is biological plausibility and the potential to improve neurological outcomes and so it’s great to see an RCT in the Journal of the American College of Cardiology.
Have a look at the abstract below and then (as we always say), go read the full paper (paywalled sadly).
What kind of study is this?
This is a randomised controlled trial, which is the ideal design for any drug intervention such as this. Interestingly this was not a double blinded study. The researchers were aware of which patients were getting the therapy and it does not look as though there was a placebo arm. I’m not sure why not really, it would presumably have been straightforward to provide placebo syringes but it was not done.
Patients in the EPO group received high doses of the drug over 48 hours post ROSC.
Who was studied?
Patients were included if they had a sustainable return of spontaneous circulation (ROSC) following out of hospital cardiac arrest. Therapy was started as soon as possible and so this could be a therapy relevant to the ED.
The trial was multicentre and based in France. 476 patients were included with 232 randomised to the EPO therapy.
What are the principle outcomes?
The principal outcome measure was neurological function, measured using the CPC scale at 60 days. They also looked at ICU mortality, overall mortality and adverse events.
- CPC 1 – Good cerebral performance (normal life).
- CPC 2 – Moderate cerebral disability (disabled but independent).D
- CPC 3 – Severe cerebral disability (conscious but disabled and dependent).
- CPC 4 – Coma or vegetative state (unconscious).
- CPC 5 – Brain death
What did they find?
For the principal outcome measure of CPC level 1 outcomes at 60 days they found no difference, 32.4% vs 31.2%. Although not a primary outcome, if you split the data at other CPC points there is similarly no difference between the groups.
Mortality at 60 days showed no clinical or statistical difference between the two groups.
There were more adverse events (notably thromboembolism) in the EPO group, which again has biological plausibility.
Can we believe the results?
Yes, I think the design, despite some concerns is unlikely to have hidden a real effect. The concern about increased complications is biologically plausible.
What does this mean for our patients?
It’s another disappointing study for those of us interested in cerebral protection post OOHCA. Here at St.Emlyn’s we think it’s important to report negative trials as well as positive ones. This is a reasonably well designed study that again tells us that there is no magic bullet on the market for neuroprotection, but we must remember that we are not helpless. There are many aspects of care that we can deliver to improve post OOHCA care. The absence of a magic medicine just means that we need to continue to do the basics (and the not so basics) as well as we can. So don’t be disheartened. Keep doing the very best you can for your OOHCA patients.
Have a listen to Scott Wengart’s talk from SMACC Chicago on Intra-arrest care. You might not believe in everything he says, but feel the need to constantly improve, look for small gains and forever doing the best you can.
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