Written by Thomas Davis
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Among patients with cardiogenic shock secondary to acute myocardial infarction (AMI), epinephrine led to a significantly increased rate of refractory shock compared to norepinephrine.*
Why does this matter?
Acute coronary syndrome is the most common cause of cardiogenic shock. Recent AHA guidelines on cardiogenic shock identified norepinephrine as the likely preferred vasopressor based on the landmark SOAP II trial. This study compared norepinephrine to dopamine and found a mortality benefit among the cardiogenic shock subgroup treated with norepinephrine. However, the AHA guidelines expressed some reservations about the study’s vague definition of cardiogenic shock and the heterogenous subtypes of cardiogenic shock. This study addresses these concerns with a very focused RCT.
It’s been a rough month for epi
This was a double-blind RCT in 9 French ICUs that randomly assigned 57 patients to either epinephrine or norephinephrine for cardiogenic shock following percutaneous coronary intervention for AMI. The study was terminated early due to increased refractory shock among patients receiving epinephrine compared to those receiving norepinephrine (37% vs 7%, respectively, p = 0.008). Epinephrine was associated with a trend towards increased death on day 7 (p = 0.08). All patients had a pulmonary artery catheter. Many of these hemodynamic measures were no different between the two groups (e.g. cardiac index, mean arterial pressure, etc.) However, epinephrine significantly increased tachycardia and affected several metabolic measures, such as increased lactate, metabolic acidosis, and cardiac double product—a surrogate marker myocardial oxygen consumption.
Source
Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction. J Am Coll Cardiol. 2018 Jul 10;72(2):173-182. doi: 10.1016/j.jacc.2018.04.051.
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Reviewed by Clay Smith
*Editor’s note: Thanks to Scott Weingart for catching a potential flaw in our conclusion. The main driver of “refractory shock” was increased lactate. However, lactate increases when patients are given epinephrine, and that may or may not indicate worsening tissue perfusion. Take a look at the comments below this post, this article on EMCrit, and this oldie but goodie from the lead author, Dr. Levy. However, there were some other issues with patients on an epi drip compared to norepi that were concerning. These are outlined in the comments…
~ Clay Smith
This should not even remotely be the conclusions drawn from this study
Hey Scott. Thanks for bringing this up. That is a great point that an elevated lactate is not at all unexpected for patients on an epi drip. They defined refractory shock as: "major cardiac dysfunction assessed according to echocardiography, elevated lactate level, and acute deterioration of organ function (e.g., oliguria, liver failure) despite the use of >1 mg/kg/min of epinephrine/norepinephrine or dobutamine >10 mg/kg/min and/or intra-aortic balloon support and sustained hypotension (SAP <90 mm Hg or MAP <65 mm Hg) despite adequate intravascular volume." When I went back and combed through the supplementary material, it looks like elevated lactate was the primary driver of "refractory shock" leading to early stopping of the study. So, epi may have been a confounder. I missed this in the original article, as it was only clear in the supplementary appendix. It seems there are some other concerns though with epi: increased HR, slower lactate clearance, lower pH, trend toward increased 7-day mortality, statistically significant increased of death/ECMO in the epi group at 7 days and nearly significant trend at 28 days. I really appreciate this real-time feedback and have added an addendum to the original post.
you will definitely get increased HR, that is a feature not a bug. The lower pH is from the lactate, and the lactate is from aerobic glycolysis so non-important.
i am no supporter of epi first. i use norepi, but we can’t really draw conclusions about this from this study.
don’t trust a study group that puts lactate in their endpoints for an epi study.
great work on resending an email to readers!! great stuff.
s