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Study: Epinephrine May Not Be Best Choice for Cardiogenic Shock in MI

— Associated with higher rates of refractory shock than with norepinephrine

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Epinephrine and norepinephrine have a lot in common, but they do not appear to be interchangeable when in comes to treating myocardial shock patients with cardiogenic shock (CS), French researchers cautioned.

In a randomized trial involving 57 patients, the two vasopressor agents produced similar effects on arterial pressure and cardiac index, but epinephrine was associated with a higher incidence of refractory shock, according to Bruno Levy, MD, PhD, of the Universite de Lorraine in Nancy, France, and colleagues.

Refractory shock was seen in 10 of 27 patients (37%) of those in the epinephrine arm, versus two of 30 treated with norepinephrine (7%; P=0.008), the researchers reported in on July 2. As a result, the trial was terminated before the initially projected enrollment of 80 was reached.

"The main result of the present study is that epinephrine use was associated with very transient improvement in cardiac index but with marked safety concerns, including refractory shock," Levy and colleagues wrote. "Compared with norepinephrine, epinephrine administration was also associated with an increase in heart rate, prolonged acidosis, and lactatemia. Other hemodynamic variables did not differ significantly between treatment groups."

The study builds on existing research "by evaluating epinephrine in the most common etiology of CS, and it advances our understanding of the temporal hemodynamic and biochemical changes attributable to epinephrine when used as a first-line agent in CS," as Sean van Diepen, MSc, MD, of the University of Alberta in Edmonton, .

Levy and colleagues said theirs is the first randomized trial comparing the two agents in patients with CS-complicated MI, with patients enrolled in nine French intensive care units from September 2011 to August 2016.

Cardiac index evolution was similar in both the epinephrine and norepinephrine study arms (P=0.43) over 72 hours from baseline. Heart rates rose substantially with epinephrine from during hours 2-24, while staying constant with norepinephrine (P<0.0001).

There were more negative outcomes in epinephrine than norepinephrine. For instance, epinephrine was linked with significant increases in cardiac double product (a surrogate for myocardial oxygen consumption) and lactic acidosis during hours 2-24, whereas they remained unchanged with norephinephine.

Commenting on the study's early termination to Ƶ, van Diepen noted that "refractory cardiogenic shock" was only defined as an outcome to watch when the trial was already well underway. "The interpretation of this endpoint is challenging for several reasons," he said. "The timing of assessment was not provided and it is unclear what components of this composite were driving difference between treatment arms. In addition, there is no clear pathophysiological reason why epinephrine would cause more refractory shock," he emphasized.

Levy and his colleagues also noted that when the study was conducted, "the concept of a cardiac center and heart team was not developed in France. Therefore, in the same hospital, a patient with CS secondary to myocardial infarction might have been treated in a different ICU, leading to a relatively low incidence of this pathology in one specific ICU."

With respect to next steps, the researchers said, "Future studies should compare the myocardial energetic effects of various catecholamines and their impact on clinical outcomes in patients with CS in clinical settings other than AMI."

Disclosures

The study was supported by a grant from INSERM-DHOS.

Levy has received lecture fees from Pulsion, Baxter, Orion, and Lilly; and has received consultant fees from Novartis, Orion, and Baxter.

van Diepen declared he had no relationships relevant to the current work.

Primary Source

Journal of the American College of Cardiology

Levy B, et al "Epinephrine versus norepinephrine for cardiogenic shock after acute myocardial infarction" JACC 2018; DOI: 10.1016/j.jacc.2018.04.051.

Secondary Source

Journal of the American College of Cardiology

van Diepen S "Norepinephrine as a first-line inopressor in cardiogenic shock" JACC 2018; DOI: https://doi.org/10.1016/j.jacc.2018.04.052.