Thursday 16 August 2018

Change the guidelines! An RCT of Epinephrine in Out-of-Hospital Cardiac Arrest; the PARAMEDIC2 Trial

Should we still be giving adrenalin in cardiac arrest?

Despite decades of tradition and guidelines, there has never been any good evidence showing adrenalin improves meaningful outcomes.

The PARAMEDIC2 trial was a very well conducted RCT of 8014 patients in the UK with out-of-hospital cardiac arrest. Patients were properly randomised to getting either adrenalin 1mg q3-5 minutes or matching placebo.

Primary outcome in this study was rate of survival at 30 days. But we all know the real outcome of interest is hospital discharge with a favourable neurologic outcome.


The adrenalin group had more patients with ROSC, transport to hospital and ICU resources. Rate of survival at 30 days was marginally better at 3.2% vs. 2.4%. (NNT 112)

Yes, the rates of survival were abysmal.  But remember the patients included in the study did not respond to initial resuscitative efforts (CPR and defibrillation). They were only enrolled when they got down the pathway requiring adrenalin.

But the real outcome of interest; neurologically intact survival?

No difference.

In the end, adrenalin increases resource utilization and increases survival of the neurologically devastated.

Sounds pretty bad to me. Sounds pretty bad to the consumer groups too.

Will this change the guidelines?

Old habits die hard. But there will never be a trial more definitive than this one. It would have been unethical to start this trial if the authorities (in the UK at least) were not prepared to change practice.

But adrenalin may be worse. Ask yourself; does giving a worthless treatment distract the focus from more important resuscitative efforts? This study didn't address this question but I think I know the answer.

Yes, change the guidelines!


Paper critiqued at Emergency Tasmania 2018. Special thanks to Dr Mark Reeves, FANZCA and audience for feedback.

Image result for adrenalin vial

Tuesday 14 August 2018

Fake News: Intraosseous vascular access is associated with lower survival and neurologic recovery among patients with out-of-hospital cardiac arrest

Prior observational studies have challenged the widely held belief that IO access is just as good as IV. This paper further explored the association between IO access and poor outcomes compared to IV.

The authors performed a secondary analysis of a large trial of patients with out-of-hospital cardiac arrest. They were able to identify patients that got IV vs. IO as their means of access.

They excluded patients who had any failed attempts at either route of vascular access or who had both performed.

The primary outcome was favourable neurologic outcome on hospital discharge (mRS <3 i.e. patients could at least walk without assistance).


13,155 were included in the analysis. 5% had IO access and 95% had IV (obviously patients were not randomised to this intervention)

For all outcomes, the IV access was far superior. 7.6% of patients with IV access had favourable neurologic outcome vs. 1.5% with IO.

This is astounding! A huge difference… let’s throw away the IO’s!!!

But there is no way this is true.

No amount of fancy statistics can make up for systematic bias and residual confounding that is present in this cohort study. There is clearly a reason why paramedics went directly to IO rather than IV. The IO group was obviously a “sicker” cohort to start with and had worse outcomes.

Not all cardiac arrest is the same. We know those with witnessed arrest, bystander CPR and shockable rhythms do better. There are also many other factors that influence outcomes.

Capturing all potential confounders in a resuscitation is problematic. When under duress, data is hard to measure accurately. In addition, there are always the unknown confounders that go unmeasured and unadjusted. No statistics can truly fix bad or absent data.

Futhermore, what was the magic medicine they used to account for this five fold increase in favorable outcomes? No drugs have really been shown to work in ALS. 

In the same context of “fake news” sometimes bad evidence is worse that no evidence at all. This study has the very unfortunate possibility to mislead and cause harm. At best, it is hypothesis generating for future prospective study.

For now, reject the fake news and keep drilling your IO’s. 

 Image result for ez-io
Paper critiqued at Emergency Tasmania 2018. Special thanks to Dr Mark Reeves, FANZCA and audience for feedback.