Implementing Beta Blockers and Hemodynamic Dosing Epinephrine for Cardiac Arrest

Epinephrine administration during a cardiac arrest has been a hot topic for quite some time. As I was creating the first cardiac arrest post (linked below), I began to think “why don’t we just administer a better medication?” Spending a stupid amount of time in the middle of the night for several weeks, I believe there might be an answer to how we should resuscitate our cardiac arrest patients. And it doesn’t have to deal with just epinephrine.

And for those who wish to watch the post, feel free to click this video:

In the “Should we abandon pharmacological interventions in our cardiac arrest patients?” post, I talk about the phases of cardiac arrest and how the Beta effects of epinephrine cause our patient’s to deteriorate after achieving ROSC. The whole point of achieving ROSC is to have the patient walk out of the hospital completely neurologically intact. Slamming a rock with enough epinephrine will give it a pulse. Using these strategies will hopefully increase the number of neurologically intact patients.

  1. Early bystander CPR/defibrillation
  2. High performance CPR (minimizing hands off chest time)
  3. No leaning on the chest
  4. About 8 breaths per minute (just enough to see the chest rise to allow venous return)
  5. Hemodynamic dosing of epinephrine
  6. Continuous aggressive management and monitoring of the patient in the ICU (transporting them to a facility capable of this)
  7. Epinephrine on Potassium and Magnesium

We have talked about about the four in the previous post so I won’t hit on them too much here.


As we know, ACLS protocols tell us to utilize giving 1 mg of epinephrine every 3-5 minutes. People have noticed that you can obtain ROSC, but it doesn’t increase the chances of leaving the hospital neurologically intact.

Epinephrine is a nonselective adrenergic agonist that acts on α₁, α₂, β₁, and β₂ receptors. So for those who do not know about adrenergic receptors, let me assist you. Adrenergic receptors are very sensitive to epinephrine (adrenaline) and norepinephrine. These receptors can be utilized by medications to increase BP and cause bronchodilation. Below is a list of the adrenergic receptors and what proteins they have coupled with them.

Alpha 1 receptors cause smooth muscle contraction are are found in our blood vessels and heart. Alpha-2 receptors are located in the brain and periphery. Beta-1 are found in the heart, the kidney, and fat cells. Beta-2 receptors are mostly found in the smooth muscles of the airway. And for this post we won’t hit on Beta-3.

So epinephrine is that cool kid in high school who hangs out with every group no matter who they are. Epinephrine acts on all of these adrenergic receptors. Epinephrine’s alpha effects are great for our patients in cardiac arrest but when we get ROSC, the Beta effects cause an increase in heart rate which will increase the myocardial oxygen requirements. This is not ideal for a patient’s ticked off heart. To get a better understanding of how these receptors work, we will go into the mechanism of action (the next part is pretty nerdy and you don’t have to read it unless you find this super interesting).

Alpha-1 Adrenergic Receptor

Alpha-1 receptors have a Gq protein attached to them. As mentioned before, epinephrine and norepinephrine act on these (epinephrine has a higher affinity than norepinephrine). When the Gq protein is activated, it stimulates phospholipase C. This breaks down into inositol triphosphate (IP3) and diacylglycerol (DAG). These cause an increase of Calcium to leave calcium storage centers. Calcium binds to a protein called calmodulin to make a calcium calmodulin complex. These can phosphorylate different proteins which can allow cations to leak into the cell (among other functions).

Alpha-2 Adrenergic Receptor

Luckily this one is not as complex as Alpha-1. Alpha-2 adrenergic receptor is coupled with a GI protein (inhibitory) that has three parts to it.

  1. Alpha inhibitory
  2. Beta inhibitory
  3. Gamma inhibitory

The alpha inhibitory subunit separates from the beta/gamma subunit. Alpha inhibitory protein binds to adenylyl cyclase (AC) and inhibits it from working. The AC normally converts ATP to cycling AMP (cAMP). cAMP is supposed to activated protein kinase A (PKA). PKA is important because it can phosphorylate other proteins and enzymes. If the alpha inhibitory protein prevents the AC from converting ATP to cAMP, do you think this will happen? Absolutely not.

The Beta and Gamma inhibitory subunit binds onto channel to open them up to allow the positive potassium ion to leave, which makes the cell have a negative charge. This is significant because the alpha-2 receptors are located on the pre-synaptic nerve terminals.

Beta Adrenergic Receptors

The Beta-1,-2, and -3 receptors luckily all do a similar process. When the adrenergic receptor is stimulated by epinephrine or norepinephrine, it will activate a Gs (stimulatory) protein. This protein will lose a GDP and gain a GTP which activates the Gs protein to act on the adenylyl cyclase (AC). This will increase the amount of ATP being converted to cAMP which increases the activation of PKA which will phosphorylate the various proteins and enzymes which can act on other receptors that can cause ions to shift into the cell. So now that we got the receptors all figured out, lets get into how these affect the heart and why epinephrine is good and bad.


So in our heart there are alpha-1 and Beta-1 receptors. Beta-1 is located on the SA node, AV node, bundle of His, and in the actual contractile cells of the myocardium. The B1 receptor when activated increases the action potential which then causes an increase in heart rate, cardiac output, BP, and stroke volume. Increasing the heart rate is not ideal in our sick heart patients as it increases the myocardial oxygen demand. So how would we fix these issues?

Beta Blockers and Hemodynamic Dosing of Epinephrine

Before someone starts yelling that the study suggests we give pure a-2 medications, I understand that is their intention. I am also a realist and know that changes in medicine happen in phases and gradually as more literature arises. There is more support for administering beta blockers along with epinephrine for our cardiac arrest patients than there is for a pure a-2 medication. I would like to see more research into comparing the two, so if there is a study that has come out that I have missed please message us!

What has been mentioned several times in various literatures, is to administer a Beta blocker to cancel out the Beta effects of epinephrine so we only get the positive alpha effects which will increase our CPP; and to only give epinephrine to patients who need it. What do I mean by this? A study was performed on domestic pigs where they administer both Alpha-1 and Beta adrenergic antagonists along with epinephrine. This study found that this cocktail had the same percentage of pigs who obtained ROSC (when compared to other treatments), but it had a higher number of neurologically intact specimens in comparison to other treatments.

We know that overloading our patients with epinephrine is a terrible idea which is why more studies suggest we give a maximum of five doses of epinephrine during an arrest. Now what I love about medicine, is that everyone is completely different in how they react to medications and some people need less or more than others. Dr. Scott Weingart made a podcast (which is located in the references and I HIGHLY recommend listening to it) where he suggests that we give epinephrine as needed (hemodynamic dosing of epinephrine). This will lead to a decrease in the amount that we administer and we would only be administering it to patients who need it at that time. Studies have shown that obtaining a CPP of 15 mmHg or greater gives providers the highest chance of obtaining ROSC. In the study I am referencing, they mention you need a central line and an arterial line to monitor the central venous pressure (CVP) . If you work in the ICU, you might have one of these. If not, Dr. Weingart suggests obtaining an art line and aiming for a diastolic pressure of 35-40mmHg. Now the AHA actually is recommending providers to do this during resuscitation but aim for a diastolic BP of 25-30 mmHg. Dr. Weingart disagrees with these numbers and his reasoning is spot on. In cardiac arrest, we have a have an equalization of arterial pressure and venous pressure. The high pressure will move to the low pressure in the venous system so our central venous pressure (CVP) will be higher in cardiac arrest patients. Another point is in our cardiac arrest patients, if they have coronary lesions, they will need a higher diastolic arterial pressure which is why Scott Weingart recommends hitting a higher number of 35-40 mmHg than what is recommended by the AHA.

Now that is all dandy, but that doesn’t seem to help in the prehospital setting where we don’t have access to art lines and other monitoring devices. So are we just screwed? Nope, we have ETCO2. Whether you drop an ET tube or do a supraglottic airway, we always have ETCO2 on our patients. The number we should look at is an ETCO2 of 20mmHg or higher. You have to say to the providers, “We have to hit an ETCO2 of 20 mmHg. We can do that with better CPR or with epinephrine”.

One last thing on epinephrine which I believe is important to hit on. When you give a ton of epinephrine, it can cause epinephrine toxicity and will cause pressor dependent circulation. This is a fancy term meaning the only reason you have ROSC is due to the crap ton of pressors you slammed into the patient and when those pressors wear off, they will rearrest. Which I feel like we have seen time and time again. So how do we prevent them from doing this? We administer more pressors during ROSC and slowly wean the patient off of them until they can support their own BP. This can usually be accomplished in the ICU as they will have the patient for longer than prehospital and the ED.

Hypomagnesemia and Hypokalemia

For those who do not know, there is several studies that have came out that show that a lot of epinephrine administration during a cardiac arrest can cause hypokalemia and hypomagnesemia. Epinephrine has been seen to decrease serum potassium by stimulating the Beta-2 receptors causing an intracellular shift of potassium. Extreme hypokalemia can cause prominent U waves that can be seen on an ECG. Prominent U waves can prolong the QU interval and increase the likelihood of a R on T to occur and send your patient into Torsades de Pointes which is a big… as the kids say… “oof”.

Oof Size Large | Know Your Meme

Signs of extreme hypokalemia show a down-up morphology on the ECG. In the example below, you can see the T wave is down (black arrow) and the U wave is up (red arrow). This is different from Wellens Syndrome where it is up-down morphology. Here is a post on it if you want to read up on it:

Twelve-lead electrocardiogram taken on admission from a 57-year-old man with severe diarrhea, paralysis of the lower extremities, weakness, inability to walk, and severe hypokalemia (1.31 mmol/L; normal value: 3.5-5.5 mmol/L). Electrocardiography shows bradycardia, a prolonged PR interval, a prolonged QU interval, ST-segment depression, T wave inversion, U waves best seen in the precordial leads (particularly in leads V2-lead 4), and slurring of T waves into U waves (leads II and III), which are consistent with the diagnosis of hypokalemia. Red arrowheads indicate prominent U waves, black arrowheads indicate T wave inversion, and blue arrowheads indicate ST-segment depression.

Do you know what else can can cause Torsades? A prolonged QT interval over 500ms. Which is what hypomagnesemia can cause. So what can we learn from this? Epinephrine causes shifts in our electrolytes, so giving less is better. And because epinephrine acts on the Beta-2 receptor to cause hypokalemia, wouldn’t that mean that the Beta blocker that we administer to the patient would prevent this from happening? Absolutely. So it probably wouldn’t be such a bad idea to do a basic metabolic panel (BMP) on your post arrest patients. And if you see electrolyte issues, then you could one could easily give the required amount to replenish them.


We have gotten better at resuscitating our patients. Maximizing our hands on chest time and early defibrillation is great for our patients. But because of the negative Beta effects of epinephrine such as increased myocardial oxygen demand and the electrolyte shifts, we should look more into administering a Beta blocker in our cardiac arrest patients and reducing the amount of epinephrine given by doing hemodynamic dosing.

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This site is meant to be used for educational use only. We strive to push evidence based medicine with no bias to help you obtain all the important information. You should always follow your protocols that have been set in place. 

Scopeducation Team (Matt)

References (I have school access so you may not be able to access the full articles on some of the references)

Gottlieb, M., Dyer, S., & Peksa, G. D. (n.d.). Beta-blockade for the treatment of cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia: A systematic review and meta-analysis. Retrieved November 29, 2019, from

Heward, S. (2020, July 10). Coronary Perfusion Pressure. Retrieved January 25, 2021, from

Jung, J., Rice, J., & Bord, S. (2018, December). Rethinking the role of epinephrine in cardiac arrest: The PARAMEDIC2 trial. Retrieved January 25, 2021, from

Pellis, T., Weil, M., Tang, W., Sun, S., Xie, J., Song, L., & Checchia, P. (2003, November 17). Evidence Favoring the Use of an α2-Selective Vasopressor Agent for Cardiopulmonary Resuscitation. Retrieved January 25, 2021, from

Ryzen, E., Servis, K., & Rude, R. (n.d.). Effect of intravenous epinephrine on serum magnesium and free intracellular red blood cell magnesium concentrations measured by nuclear magnetic resonance. Retrieved January 25, 2021, from

Scott Weingart, MD FCCM. EMCrit Podcast 130 – Hemodynamic-Directed Dosing of Epinephrine for Cardiac Arrest. EMCrit Blog. Published on August 10, 2014. Accessed on January 23rd 2021. Available at [ ].

Struthers, A., & Reid, J. (1984). Adrenaline causes hypokalaemia in man by beta 2 adrenoceptor stimulation. Retrieved January 25, 2021, from

Sutton, R., French, B., Nishisaki, A., Niles, D., Maltese, M., Boyle, L., . . . Nadkarni, V. (2013, February). American Heart Association cardiopulmonary resuscitation quality targets are associated with improved arterial blood pressure during pediatric cardiac arrest. Retrieved January 25, 2021, from,(IQR%2027%20%E2%80%93%2044).

Veerbhadran, S., Nayagam, A., Ramraj, S., & Raghaven, J. (2016, July 01). Slow Down to Brake: Effects of Tapering Epinephrine on Potassium. Retrieved January 25, 2021, from

Weiss, J., Qu, Z., Shivkumar, K., & Weiss, J. (2017, March 17). Electrophysiology of Hypokalemia and Hyperkalemia. Retrieved January 25, 2021, from

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