This is the new hotness in critical care discussions – the co-administration of intravenous esmolol to critically ill folks on high-dose vasopressor support in the ICU. It's a fascinating thought – considering the alpha- and beta-stimulation of norepinephrine necessary to maintain central perfusion, co-administration of a sympatholytic seems self-defeating, in a sense.
However, this may not be the case. There are multiple dose-dependent effects of catecholamines on different tissues, as well as concern the tachycardia resulting from sympathomimetic myocardial stimulation in sepsis results in adverse outcomes. Based on prior observational evidence, these authors performed a randomized, open-label trial of esmolol co-administration in a cohort of critically ill patients on vasopressor support.
They randomized 154 patients with HR >95 and septic shock to esmolol, titrated to a HR between 80 and 94 bpm, vs. usual care. The hemodynamic variables showed, despite the use of esmolol, norepinephrine dosage was not significantly increased in order to maintain MAP. Improvements in stroke volume compensated for a lower heart rate, resulting in non-significantly lower cardiac index. However, what has everyone fascinated – the control group had 90% in-hospital mortality, compared with 67% for the esmolol group. I don't think anyone disagrees this is statistically significant and clinically important.
There were differences in baseline variables between groups. The etiology of sepsis was substantially tilted towards peritonitis in the esmolol group, with obviously different causative organisms. Lactic acid, base excess levels, and SAPS II scores favored the esmolol group. The lead author and one co-author also have financial conflicts of interest with Baxter, the makers of esmolol (Brevibloc). Financial conflicts, open-label, and the size of the study all make me wary of reproducibility and the magnitude of the effect size.
So, there are problems warranting additional and independent confirmation. That said, the mortality benefit observed in this study is large enough I wouldn't contest anyone who wanted to go ahead and start trying this in their highest-predicted mortality subset. However, I'd also consent patients/families to this therapy as experimental and prospectively collect data for at least retrospective pre-/post- comparisons.
"Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in Patients With Septic Shock A Randomized Clinical Trial"