April 5, 2022
Esmolol to Treat the Hemodynamic Effects of Septic Shock: A Randomized Controlled Trial.
Esmolol has been proposed to treat tachycardia associated with vasodilatory/hyperdynamic septic shock patients to counteract the effect of beta stimulation. Controlling the heart rate may improve cardiac output by allowing more time in diastole. However, there is a concern that the use of beta-blockade may worsen cardiovascular decompensation related to its negative inotropic and hypotensive effects.
This phase II trial evaluated the epinephrine-equivalent dose (for the vasopressor vasopressin, the dose of vasopressin was multiplied by 2.5 to create a norepinephrine equivalent dose; for the vasopressor phenylephrine, the dose of phenylephrine was divided by 10 in order to create a norepinephrine equivalent dose.). The trial revealed that the NED after 6 hours of initiation of the study drug was higher in esmolol group compared to the placebo group, but it was not statistically different. The study also showed that time to shock-reversal was not different between the two groups, inflammatory markers were not different between the groups except for a lower C-reactive protein in the esmolol group, and there was decreased oxygen consumption in a subset of the esmolol patients.
Esmolol has been previously studied in a phase II trial back in 2013 and was published in JAMA. The study revealed that among 154 patients, esmolol resulted in more control in the heart rate, improved stroke volume index, higher left ventricular work index, lower lactatemia, lower fluid requirement, and lower norepinephrine dose. 28-day mortality was 49.4% in the esmolol group vs 80.5% in the control group (adjusted hazard ratio, 0.39; 95% CI, 0.26 to 0.59; P < .001).
I do not see that the current study adds much to what we already know from the JAMA study other than that we need to investigate if there is a patient-centered outcome in using esmolol in a large, well-designed randomized trial.