.jpg)
Also posted over at Paramedicine 101 (now at EMS Blogs) and at Research Blogging. Go check out the excellent material at these sites.
–
Even though epinephrine (adrenaline) is used automatically in cardiac arrest, and there is evidence that epinephrine helps to produce a pulse (ROSC – Return Of Spontaneous Circulation), there is no evidence that epinephrine improves the only survival statistic that matters – discharge from the hospital with a brain that still works. There were so many deviations from assignment protocol in their 2009 study,[1] that the authors decided to examine the results based on what treatment patients actually received. They refer to epinephrine as adrenaline, which is the same drug. I will use adrenaline for consistency.
Our randomized study was analyzed on an intention-to-treat basis.4 As expected; some patients in the intravenous group had achieved ROSC before adrenaline could be given, while some in the no-intravenous group received adrenaline for different reasons. For example, it was permitted to place the IV line 5 min after ROSC. If re-arrest occurred, adrenaline could be administered if indicated by the CPR guidelines.7 [2]
In the no andrenaline group, 37 of the 433 patients did receive andrenaline.
In the adrenaline group, 85 of the 418 patients did not receive andrenaline.
For 3 patients, the authors were unable to tell whether andrenaline was given and these patients were excluded.
This changes the data to 367 patients in the adrenaline group and 481 patients in the no adrenaline group.
–
Patients in the adrenaline group were more likely to be admitted to hospital and an intensive care unit compared to the no-adrenaline group (OR 2.5 CI 1.9, 3.4 and OR 1.4 CI 1.0, 1.9, respectively). [2]
This is nothing new. Patients receiving andrenaline are more likely to have ROSC. All that really matters is what happens after ROSC.
If the patient loses pulses after ROSC, giving more adrenaline may not produce the desired effect – another ROSC.
–
First look at Table 1. The duration of CPR is much longer with the adrenaline group. Is this because of patients losing pulses?
–
Click on images to make them larger.
–
You can also see how few drugs were given to the no adrenaline group. They were not supposed to receive any drugs, but the use of adrenaline was the only criterion for reassigning patients in this reanalysis of the data. Atropine was given to 2% of the no adrenaline group and amiodarone was given to 2%. Was there overlap of these patients? We can’t tell.
The defibrillations were also significantly different. More patients were shocked in the adrenaline group, but more patients in the adrenaline group were in VF (Ventricular Fibrillation) initially. How many of the patients with PEA (Pulseless Electrical Activity) or Asystole developed VF after adrenaline? More shocks were also used for each patient. Was this due to rearrest?
–
Now looking at Table 2
–
–
Adrenaline starts out 2 1/2 times more likely to produce a pulse (ROSC), but a lot of those patients appear to have lost those pulses before admission to the hospital, since Table 2 shows that 69 of the 175 adrenaline patients admitted with CPR (CardioPulmonary Circulation) in progress. Adrenaline wears off in several minutes and produces a lot of undesirable side effects.
More is not better, especially since the doses of adrenaline being given are already many times larger than would be given to any living human.
Most important is the neurological function. I do not want to be resuscitated with only enough neurological function to spend the rest of my life watching reality TV in a long term care facility, or worse. That is not a successful resuscitation.
Adrenaline = 48% admitted to the hospital, but only 6% alive one year later.
No adrenaline = 27% admitted to the hospital, but 12% alive one year later.
Adrenaline (epinephrine) is not just changing the location of death, but is cutting overall survival in half.
Is getting pulses back a good enough reason to kill half of the patients who could survive?
Of the patients admitted to the hospital, 11% of the adrenaline group were discharged with good brain function.
Of the patients admitted to the hospital, 45% of the no adrenaline group were discharged with good brain function.
–
–
Of the patients admitted to the hospital, 12% of the adrenaline group were alive one year later.
Of the patients admitted to the hospital, 44% of the no adrenaline group were alive one year later.
–
The actual use of adrenaline may be a surrogate marker for patients with bad prognosis, but that has previously only been published from studies without a group randomized to not receiving drugs.21 [2]
There are many limitations of this study, but the authors do not pretend that this is the final answer on adrenaline (epinephrine) in cardiac arrest. They do point out that we are not providing good care by continuing to use adrenaline without studying the outcome that matters – survival with good neurological function.
5% of the no adrenaline group survivors had significant brain damage.
20% of the adrenaline group survivors had significant brain damage.
Maybe the good news is that adrenaline does not produce a lot of survivors.
–
See also –
Cardiac Arrest Management is an EMT-Basic Skill
Cardiac Arrest Management is an EMT-Basic Skill – The BLS Evidence
Cardiac Arrest Management is an EMT-Basic Skill – The Hands Only Evidence
–
Footnotes:
–
[1] Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial.
Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L.
JAMA. 2009 Nov 25;302(20):2222-9.
PMID: 19934423 [PubMed – indexed for MEDLINE]
–
[2] Outcome when adrenaline (epinephrine) was actually given vs. not given – post hoc analysis of a randomized clinical trial.
Olasveengen TM, Wik L, Sunde K, Steen PA.
Resuscitation. 2011 Nov 22. [Epub ahead of print]
PMID: 22115931 [PubMed – as supplied by publisher]
–
Olasveengen TM, Wik L, Sunde K, & Steen PA (2011). Outcome when adrenaline (epinephrine) was actually given vs. not given – post hoc analysis of a randomized clinical trial. Resuscitation PMID: 22115931
Olasveengen, T., Sunde, K., Brunborg, C., Thowsen, J., Steen, P., & Wik, L. (2009). Intravenous Drug Administration During Out-of-Hospital Cardiac Arrest: A Randomized Trial JAMA: The Journal of the American Medical Association, 302 (20), 2222-2229 DOI: 10.1001/jama.2009.1729
.
The post-hoc analysis is pretty damning.
Christopher,
It does not make epinephrine look good, but it is post hoc. I am always suspicious of post hoc papers, because of the tendency to make the data somehow fit the hypothesis, although I do not think that is the case,
Although they did not lose the hospital data on many patients, they don’t have much prehospital data. It is great that they have the recordings of CPR to show that the quality was similar for both groups. Maybe it my lack of understanding of what data they actually have, but I don’t see why they could not determine when there was ROSC, how often rearrest occurred, and why so many patients were admitted with CPR in progress. I would assume that the patients had shockable rhythms or had repeated ROSC, but we do not know.
We need a prospective, placebo controlled, randomized trial that is large enough to show if there are any subgroups that do better with epinephrine, or subgroups that do worse with epinephrine. A study just large enough to show an overall better/worse outcome is not what we need.
I don’t think that epinephrine can be good for every cardiac arrest. That does not mean that there are not some patients who benefit, such as non-MI arrests, but we should not just guess at this – that is how we got into this mess.
.
They have the CODESTAT data, and likely could extrapolate this information.
Amen.
Christopher,
I think they should have been able to get more, or show more, out of the data they have.
They should have been able to use this information, combined with the EMS chart, to determine the order of events. This would have provided some answers to some of the questions we would be expected to have. What was the reason for so many patients being admitted with ongoing CPR? Had they rearrested? Had they been treated with epinephrine initially, or been treated with epinephrine after rearrest? These should not require that the times on the monitors be synchronized with dispatch.
.
I think they admitted with ongoing CPR may have been from the pre-2k5 guidelines (study timeframe 2003-2008).
I’m just now getting Mark Event placed into my routine to enable more accurate record keeping. If only we had transducers in our Luer adapters that recorded flow rates.
Christopher,
This did cross a protocol change, but the authorswere not specific about the data they were able to collect.
–
Or suppose that we did not spend so much time focused on reflexively giving the next drug, getting the IV/IO, or getting the tube, but paid more attention to potentially reversible causes.
I know. It is silly of me to think of medics as capable of thinking. We are just protocol monkeys, but if the patient is not resuscitated by EMS, the patient is not leaving the hospital alive.
.