Norepinephrine seemed to be a safer vasopressor than epinephrine for patients with cardiogenic shock following acute myocardial infarction, according to a small randomized trial conducted in France. Significantly more patients given epinephrine developed refractory cardiogenic shock, causing the study to be stopped early.
“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,” lead author Bruno Levy, MD, PhD, and colleagues wrote in the Journal of the American College of Cardiology. “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.”
Nine French intensive care units participated in the double-blind study, which spanned from September 2011 to August 2016. Fifty-seven patients who underwent successful percutaneous coronary intervention (PCI) were randomized—27 in the epinephrine group and 30 in the norepinephrine group.
The change in cardiac index was similar between the two groups from baseline to 72 hours after drug administration, except for a transient improvement with epinephrine at hour two. However, 10 patients (27 percent) in that group experienced refractory shock, compared to only two patients (7 percent) in the norepinephrine arm.
“To obtain the same effect on global perfusion and tissue oxygenation, epinephrine-treated patients had higher cardiac double product, lactic acidosis, and a differential regulation of growth differential factor 15 pathway (a stress responsive cytokine that increases in response to hypoxia, oxidative stress, inflammation, and cell injury),” the researchers wrote. “Overall, these effects could explain the increased occurrence of refractory CS in epinephrine-treated patients secondary to excessive adrenergic overstimulation.”
The authors acknowledged the small sample size was the primary limitation of their study. They noted different vasoactive therapies may perform differently for various etiologies of cardiogenic shock, such as post-cardiopulmonary bypass or myocarditis.
In a related editorial, Sean van Diepen, MD, MSc, agreed with this latter point, highlighting the lack of quality data on inopressors in the setting of cardiogenic shock.
“No trial of vasoactive therapies in CS has evaluated treatment differences across various hemodynamic phenotypes of CS,” van Diepen wrote. “This perspective should not be misinterpreted as advocacy for any first-line vasoactive agent in CS; rather, it highlights the need to incorporate hemodynamic phenotypes of CS into future trial design and to evaluate the role of routine hemodynamic monitoring and tailoring in a CS population.”