Catecholamine Death Match

I will pre-frame this blog with saying that my thoughts in this post are not ones in which you should in anyway take as suggested medical advice. I have had a particular interest in coronary perfusion during cardiac arrest for the past few years now. A study in 1990 by Paradis et al, concluded that unless a patient is able to achieve a coronary perfusion pressure (CPP) greater than 15mmHg, there was no chance of ROSC. Recent literature clarifies that this threshold is actually quite a bit higher, and CPP should be redefined as a "total dose, rather than a threshold." While I am not advocating ROSC as soul end-point, it is one of the steps in the path of survival. 

Epinephrine was shown to increase coronary perfusion pressure by 30% for approximately three minutes in a study by Sun S, et al. This study is where we get our current recommendation to administer one milligram of epinephrine every three to five minutes. There are a few important points we need to keep in mind regarding epinephrine in cardiac arrest.

1. We do not give epinephrine for anything other than its alpha affects in the diastolic period.

2. Beta stimuli during cardiac arrest can potentiate arrhythmias while increasing myocardial oxygen demand (Mv02).

3. Epinephrine use is associated with no increase in survival.

It has been suggested in the past that vasopressin may be used to replace either the first or second epinephrine in cardiac arrest. Besides showing no benefit over epinephrine, vasopressin is associated with significant coronary artery constriction and has been removed from the ACLS guidelines in 2015. 

We know that moments following cardiac arrest our vessels begin to equalize in pressure. This pressure is known as the mean systemic filling pressure (MSFP). In order to have enough pressure on the systemic side of the aortic valve during diastole, we need to shuttle blood right to left with chest compressions. To expedite and potentiate this process we need to give an agent that will primarily effect alpha mediated receptors, while not stimulating an aggressive beta two adrenergic response. This sounds a lot like a tachycardic & hypotensive septic patient in which we remove dopamine and begin levophed. The reason we switch to an agent such as levophed is to not exacerbate the primal compensation to hypotension (tachycardia), but assist in increasing mean arterial pressure (MAP). There is however a reduced attention to the dangers of beta stimulation of a patient that is in cardiac arrest. I believe that the increased stimulation of sarcoplasmic reticulum calcium dump of epinephrine  within myocytes during cardiac arrest can increase the threshold needed to successfully defibrillate out of lethal arrhythmia's. This may be the reason we see an increased attention to refractory ventricular fibrillation, double sequential defibrillation, and intra-arrest beta blockers (Esmolol). 

So Why Hasn't Levophed Been Studied In Cardiac Arrest?

This question has plagued me for awhile now. I am not able to find exactly why we would think its a good idea to trial a drug like vasopressin in cardiac arrest, however not study an agent such as norepinephrine? I did some research on the effects of norepinephrine on coronary perfusion.

A paper published in Circulation by Peter M Yurchak, MD.  showed improvement in MAP with no decrease in flow. While this does report an increase in resistance, it was overcome by an increase in diastolic pressure. This seems like the ideal agent in the setting of cardiac arrest.

What Would Be The Dose?

I can not for sure say what the dose needed to improve vasoplegia and increase coronary perfusion pressure would be. However I do not believe we have determined the correct dose of epinephrine either. I believe blanket dosing is bad medicine and see a future of customized primarily alpha response titrated to either MAP or ETC02.

In dog studies a dose of 1mcg/kg was compared with 0.1 mcg/kg given as a bolus. The effects showed an initial increase in coronary perfusion pressure and increase in flow, followed by an increase in coronary resistance. Once again this increase in resistance was overcome by an increase in diastolic pressure. This prevented an interruption in blood flow.

In my opinion norepinephrine appears to be a superior agent to epinephrine in cardiac arrest. 

I usually would keep these notes to myself until I feel the content is ready to be put out on FOAMfrat. However, I feel that this blog does not serve as a compass to guide your practice. It is merely a shared journal with other clincians. I have hundreds of notes on my phone with concepts such as the ones expressed in this blog. Some will remain thoughts and others may begin a dialogue that leads to a change in practice. 

-Tyler Christifulli

Reference Links

http://circ.ahajournals.org/content/circulationaha/30/2/180.full.pdf

http://circres.ahajournals.org/content/circresaha/34/6/812.full.pdf

https://www.ncbi.nlm.nih.gov/pubmed/20693888

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922866/