Approaching Studies: PARAMEDIC2

Epi

No doubt by now you’ve heard the buzz, that PARAMEDIC 2 is complete and the results are in! If, for some reason you’re sitting there and asking your self, “What are you going on about guys?” then maybe this small write up is for you. Our intention in this write up is not to analyze the data per say, but rather examine the study as whole. We’re going to look at context, themes and take away points in very general terms and ask some questions about the results and methods used. Sounds absolutely riveting, doesn’t it? Well hang on, we promise we’re going to try and make this tolerable – nay, enjoyable? Well buckle up as we take on our first, what we’ll call, casual analysis of this study!

Studies and Paramedics: All That Jargon.

As paramedics in Ontario and Canada, do we truly appreciate research papers on topics that relate to our field? Do we know how to locate them? And when we do find them, do we have the tools to appreciate what makes a “good” study versus a “bad” study? Maybe, maybe not? Every paramedic wants to be clinically sound and provide the best possible evidence based care but due to a plethora of different issues, research appraisal might not have been introduced or taught during their education or career. Anecdotally speaking, paramedics that we encounter are extremely interested in research and eager to absorb it but at times find the approach to be overwhelming and slightly confusing (what’s a P value? CI what?). Again, this is merely our local observation, in our center with a small sample group of paramedics (see what we did there?). Across Canada there are plenty of paramedics who are well versed in the methods of understanding and appreciating research and studies. Our hope with this piece is to firstly provide some resources for those who aren’t really sure where to start their research appraisal journey. Secondly, it’s to examine the above mentioned study. After all, delving into world of critical appraisal can be overwhelming for anyone. Ideally, we want you to take a pragmatic approach to start and just ask questions.

Before we get into the crux of the PARAMEDIC 2  study we’re going to list a few resources to help you along your merry way. First off, we highly recommend taking a look at some work by our friends over at CanadiEM. Specifically this article looking at engaging students in research and critical appraisal. Then there’s the wonderful folks at The Resus Room who have a separate pay for service called The Critical Appraisal Low Down which might be of interest for those of you who want to really dig deep and learn more about research methodology. For those of us who just want to ease into research and study appraisal take a look at this article to get yourself oriented.

Now What: Looking at the PARAMEDIC 2 Study

As we prefaced at the start of this article, we’re not going to break down the statistical analysis of data in this study. There are loads of other, significantly better suited folks out there who have done that much more succinctly and accurately than we ever could. To see those appraisals we would recommend checking out write ups by our colleagues over at: First 10 EM and REBEL EM. We’re simply going to take a causal, generalized look at this study and examine some points of interest.

So now. . . lets get into it: PARAMEDIC 2 (Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest) was recently published in the New England Journal of Medicine. This study was a randomized, double – blind trial involving 8014 patients in the UK that suffered a cardiac arrest. The study was run by paramedic services with the National Health Service (a total of 5 services).

So off the hop, this looks pretty promising. The sample group of patients is large (8,014 patients of which 4015  received epinephrine and 3999 received the saline placebo – a fairly even split). The trial was conducted using randomized and double – blind methods. That means that the patient was randomly assigned to receive either epinephrine or a placebo (in this case normal saline) – this was done by opening a trial pack of unmarked syringes that had a unique number on them to be tracked and the paramedics did not know what was in each. The epinephrine (or placebo) was administered either through IV  or IO at intervals of 3 to 5 minutes. These treatments were continued until a sustained pulse was achieved, resuscitation was discontinued or care was handed over to the hospital staff. So in essence that’s the summary of the study. Yes, there is a lot more info to it than just that but we encourage you all to click on the attached links and read for yourself.

So what did the study conclude? In essence, that the use of epinephrine resulted in a significantly higher 30 day survival rate than use of the placebo. But – and its a big but – there was no significant difference between groups with regards to favourable neurological outcome and those that did survive had significant neurological impairment in the epinephrine group compared to the placebo group.

Alright. . . So Epi is Out?

Oh friends, if it were only that easy. So studies like these are terrific. For the most part this study was very well done. There are a few questions that have caused us to take pause, but nothing that does anything to disservice the authors or their methods. Remember: there is no such thing as a perfect study. Equally, each study type has its own strengths and weaknesses and goals in the end.

Some points we opted to take into consideration:

1.) This study used European Resuscitation Council Guidelines in the pre-hospital arrest – a standardized model.

2.) It did not account for care and treatment after hospital hand over although this care is informed by national guidelines.

3.) The median time between emergency call and ambulance arrival was about 6 minutes in both groups and interestingly the median time between emergency call and time to drug administration in both groups was approximately 21 minutes.

4.) About 37% of the OHCA cases were un witnessed in both groups. About 50% of the cardiac arrests were witnessed arrests in both groups.

5.) Almost 60% of patients in each group received CPR from bystanders.

6.) Other limitations included: no baseline for neurological function in cardiac arrest patients (meaning, if they did survive with cognitive function in tact, was it the same or worse when they were discharged?)

So these are just some of the points from the study that we extrapolated and found particularly interesting. Now lets take a look at the context and themes of this study. The first thing that struck us was the median time between ambulance arrival and drug administration. The median time for both groups was just over 21 minutes. As our friends at REBEL EM pointed out: “This is an important point, as cardiac arrest is believed to have 3 phases: First 5 min = Electrical Phase (Heart Most Amendable to Defib), Next 10 – 15min = Circulatory Phase, and >20min = Metabolic Phase (Acid-Base Derangements).  Epinephrine seems to have its best chances of effect at <20min". An important message to keep in mind when assessing this paper.

Secondly, the care at hospital hand over, while using national guidelines includes variables that can include anything from: understaffing, shift fatigue, perhaps deviation from guidelines, multiple people in differing roles, various crew resource management, equipment, timing, etc… Again, just something to consider when trying to appreciate this study for what it is. There is a deluge of variables there that should also be kept in mind.

With the results reflecting that there was no significant difference between groups in the rate of favourable neurological outcome and in fact, survivors in the epinephrine group had more severe neurological function deficits we need to ask, what are our goals? We often talk about changing the goals of resuscitation not to just obtain return of spontaneous circulation (although that’s the obvious first step we need to achieve) but instead aiming for best neurological outcome. In our practice we focus on as much evidence based medicine as possible to ensure our patient has the best chance of survival with optimal neurological outcome. Whether that means high quality CPR with minimal peri-shock pause, delivering defibrillation early in the arrest, appropriate ventilation and targeting treatment to values with a return of circulation or having bystanders or allied agencies respond for the initial arrest before paramedics arrive, all these things work to promote optimal neurological outcome for our patients.

Where Does That Leave Us?

Undoubtedly questioning everything! In writing this we’re trying to promote understanding in general terms of this study and others. We want to have you, the reader, ask questions about the results and methods. The points above are just our initial observations but at the end of the day, you must think outside the box when reading about a study, its methodology and results. Always ask “why?” followed by “what about…?” when appraising any study. Always keep in mind the myriad of variables that may not have been considered in the study and weigh them against the variables that were taken into account. Keeping in mind, of course, that you simply cannot account for every single variable. And of course: read the whole article. Reach out to colleagues, researchers, professors anyone you can if you cannot find the full article.

So while there are some questions to be answered, PARAMEDIC 2 proves to be an interesting study with results that, in many ways, echo results of previous studies regarding epinephrine use in out of hospital cardiac arrest (OHCA). The authors recognize the limitations to their study towards the end of the paper which is also an important feature of a well formed research paper. So where do we go from here?

Well if you’ve been on the Twitterverse there are resounding calls for studies examing variable dose epinephrine in cardiac arrest or perhaps an epinephrine infusion during the arrest. There has been calls for targeted treatments based on end tidal readings too. The bottom line: there is mounting evidence against the use of epinephrine in OHCA but there is still a lot of work to be done before we put epinephrine to bed completely. PARAMEDIC 2 was a well designed study that did what well designed studies are meant to do: provide some answers but encourage more questions.

– Ivan.

 

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