Hi there..more from my journal reading this month!
I would like to believe that epinephrine/adrenaline is not harmful in cardiac arrest or other critical states. I have given so much of it over the years and on occasion believed it has saved lives. Certainly in anaphylaxis I have not doubt it saves lives. For cardiac arrest, cardiogenic shock, septic shock, what of those states?
These American authors demonstrated in a healthy rat model that epinephrine leads to rapid cardiopulmonary deterioration. They suggest it therefore has no basis to be used in cardiac arrest. Many I know would support them. It makes me wonder that the doses we give and the times we give it, might be doing more harm than good. This is a turn around to my previous stance and reflects that one must follow the literature and read the patterns of where science and clinical practice are heading for the care of our critical patients.
Epinephrine Induces Rapid Deterioration in Pulmonary Oxygen Exchange in Intact, Anesthetized Rats
A Flow and Pulmonary Capillary Pressure-dependent Phenomenon
Vijay Krishnamoorthy, M.D. et al.
ABSTRACT
Background: Previous studies indicate epinephrine adversely affects arterial oxygenation when administered in a rat model of local anesthetic overdose. The authors tested whether epinephrine alone exerts similar effects in the intact animal.
Methods: Anesthetized rats received a single intravenous injection of epinephrine (25, 50, or 100 mcg/kg); matched cohorts were pretreated with phentolamine (100 mcg/kg); n 5 for each of the six treatment groups. Arterial pressure and blood gases were measured at baseline, 1 and 10 min after epinephrine administration. Pulmonary capillary pressures during epinephrine infusion with normal and increased flows were measured in an isolated lung preparation.
Results: Epinephrine injection in the intact animal caused hypoxemia, hypercapnia, and acidosis at all doses. Arterial oxygen tension was reduced within 1 min of injection. Hyperlactatemia occurred by 10 min after 50 and 100 mcg/kg. Rate pressure product was decreased by 10 min after 100 mcg/kg epinephrine. Pretreatment with phentolamine attenuated these effects except at 100 mcg/kg epinephrine. In the isolated lung preparation, epinephrine in combination with increased pulmonary flow increased pulmonary capillary pressure and lung water.
Conclusions: Bolus injection of epinephrine in the intact,anesthetized rat impairs pulmonary oxygen exchange within 1 min of treatment. Effects were blunted by -adrenergic receptor blockade. Edema occurred in the isolated lung above a threshold pulmonary capillary pressure when epinephrine treatment was coupled with an increase in pulmonary flow. These results potentially argue against using traditional doses of epinephrine for resuscitation, particularly in the anesthetized patient
Prehospital and Retrieval Medicine - THE PHARM dedicated to the memory of Dr John Hinds 
This isn’t exactly new.
Dr. Mervyn Singer on “Catecholamines should be banned” at Free Emergency Medicine talks.
http://freeemergencytalks.net/2010/04/mervyn-singer-catecholamines-should-be-banned/
Catecholamines are been used to induce heart failure in the lab.
Epinephrine could be called takotsubo in a syringe, but I prefer to call it “a heart attack in a syringe.”
Since most cardiac arrests are apparently caused by heart attack, epinephrine is not a good idea as a routine drug. If we could identify the patients who might benefit – assuming that some patients do benefit, which is not clear – we could avoid using epinephrine on the patients who are harmed by catecholamines.
Resuscitation has an article in press about harm from epinephrine.
Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium.
Glover BM, Brown SP, Morrison L, Davis D, Kudenchuk PJ, Van Ottingham L, Vaillancourt C, Cheskes S, Atkins DL, Dorian P; the Resuscitation Outcomes Consortium Investigators.
Resuscitation. 2012 Jul 31. [Epub ahead of print]
PMID: 22858552 [PubMed – as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22858552
I wrote about it earlier this week.
http://roguemedic.com/2012/09/wide-variability-in-drug-use-in-out-of-hospital-cardiac-arrest-a-report-from-the-resuscitation-outcomes-consortium-part-i/
http://roguemedic.com/2012/09/wide-variability-in-drug-use-in-out-of-hospital-cardiac-arrest-a-report-from-the-resuscitation-outcomes-consortium-part-ii/
We need a good randomized placebo vs. epinephrine study, large enough to be able to identify any populations that might benefit from epinephrine.
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I was timing how long it took you to comment , Tim!
thanks, mate for your info.
now just waiting on Chris Watford to wade in here…
Ben Hoffman, too?
It is an important topic. We use epinephrine in hundreds of thousands of cardiac arrests each year.
We have been using it routinely for half a century.
We still do not have any good evidence that epinephrine improves cardiac arrest outcomes.
Maybe the Resuscitation Outcomes Consortium will arrange this study. The last time I emailed them asking for an epinephrine study, I was told that they were satisfied that the Jacobs trial was all the evidence they need.
They are also unreasonably comfortable with ventilation during cardiac arrest.
I suspect that they have been doing some re-evaluation of their positions.
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*facepalm …. clearly I am too well known 🙂
The number one cause of cardiac arrest is dysrhythmia, the number one cause of dysrhythmia is myocardial infarction so where on earth is the logic in giving adrenaline to patients who we can safely assume have had an infarction just because they pulseless?
If the patient is conscious we wouldn’t give them adrenaline so the biologic plausibility or moreover the pathologic potential does not change just because they fell down and need a zap.
Carry on …..
hey Ben, thanks for comment. If you read the study carefully they used doses of 25, 50 and 100mcg/kg in bolus fashion. Think about the recommended ARC dosing for adrenaline in paediatric cardiac arrest = 10mcg/kg. In an adult 25mcg/kg for an average 70kg person = 1750mcg of adrenaline IV..bolus.
Recommended adult IV adrenaline in arrest is 1mg boluses every 2 CPR cycles for PEA, asystole etc.
This RAT study suggests we are giving too much and too often. By the second dose of adrenaline in current resuscitation guidelines we have already exceeded the 25mcg/kg dosing of this rat study.
Whilst it might be poison to rats, this does not mean necessarily that its poison to humans. At the right dose, like warfarin(another age old rat poison), adrenaline should and does benefit the human body and the treatment of a number of conditions.
Adrenaline has lifesaving therapeutic benefit no arguments there (asthma, anaphylaxis, as an inotrope for people who have severe bradycardia, as a vasopressor in people who have distributive hypovolaemia e.g. septic or neurogenic shock)) however the dosages used are much smaller (most asthma and anaphylaxis guidelines recommend 0.5 mg IM which is 7 mcg/kg and if we use an infusion (1 mg of adrenaline in 1,000 ml of 0.9% NaCl) we are giving 10 mcg/kg/hr)
Should we give smaller amounts of adrenaline to people in cardiac arrest? maybe we should, sounds like a good study hypothesis right there.
thanks Ben. High dose adrenaline has been studied compared with standard dose and not shown to be any better. This rat study shows us maybe why! Lower dose adrenaline sounds plausible and I agree is prob the next step in OHCA drug research.
infusion based adrenaline actually makes a lot of sense..as long as yu got good quality CPR continuously
Dr. Weingardt gave some input on this topic on EMCRIT and his comments made a lot of sense to me. I would agree that OHCA research’s next step is towards lowering the frequency and maximum dosage that we administer for those in arrest, any thoughts on where specifically those parameters should be?
less will be more!
10mcg/kg is the current paediatric dosing and that might be better for adults too…so 700mcg bolus in average adult…no reason why 0.5mg bolus could not be used instead
this rat study suggest 25mcg/kg or greater is harmful in rats…in boluses.
so for 70 kg adult…keeping under less than 1500mg adrenaline total might be one theoretical option.
quite a radical departure from what we currently do though…which is 1mg every 3-5mn of CPR.
Norepinephrine to increase aortic root pressure (like a chemical cross-clamp of the aorta), therefore to directly improve coronary blood flow? It worked for me once (N=1) in an asystolic arrest. The norepi transformed the systole to vfib, which was shocked to a perusable rhythm. How did I get there? I was an ACLS instructor way back in 1995-1996, and norepi was positioned in the algorithm. I have to go looking through the algorithms again for it. Norepi is poorly understood overall in medicine. The next drug I have to look up in this context is methylene blue (a scavenger of nitric oxide that treats vasoplegia, a hypotensive condition that can occur during cardiac surgery or liver transplant that is refractory to normal pressers). Otherwise, methylene blue turns the urine blue (to help urologists find the ureter orifice).
Just a different view…
Thanks Jim !
How was SAM conference ? Should do a podcast on that , ok?
The SAM conference was enlightening–it really helped me “wrap my head” around some larger concepts and ideas that have been brewing in my attitudes, approaches, etc.. To the current and future state of the art. Let’s confer in a week when I have all the videos processed, so I can give you a highlights summary! And Scott Weingart was there with his wife. Yes I videod that too–Scott is going to post it early this week.