Esmolol for septic shock: more than just heart rate control?

Excessive adrenergic stimulation may be associated with several adverse events and contribute to increase mortality in critically ill septic patients. Few clinical data exist on the effects of adrenergic blockade in this setting. The objective of this study was to investigate the effect of a short acting b-blocker (esmolol) in septic shock patients. In a single-center, controlled, open-label, phase 2 trial (from November 2010 to July 2012), Morelli et al. randomized patients with a need of norepinephrine to maintain a mean arterial pressure above 65 mmHg to receive either esmolol or standard of care. Patients were included if, after 24 hours of initial resuscitation, hypovolemia was excluded (wedge pressure ≥12 mmHg or central venous pressure ≥8 mmHg) and heart rate was above 95 bpm. Patients were excluded if they were younger than 18 years, had previous b-blockers therapy, cardiac index was ≤2.2 L/min/m² with wedge pressure >18 mmHg, were diagnosed with significant cardiac valvular diseases or were pregnant. The primary outcome was the reduction in heart rate between 80 and 94 bpm over a 96-hr period. Secondary outcomes included norepinephrine requirement, hemodynamic changes, organ function, adverse events and 28-day mortality. A total of 154 patients, 77 for each group, were enrolled. Esmolol was more effective than standard treatment to reduce heart rate within target limits; also, b-blocker therapy was associated with an increased stroke volume and left ventricular work index when compared to the control group. These favorable hemodynamic effects were associated with a better control of lactate levels, a higher reduction in norepinephrine and fluids requirement. Mortality was 49.4% in the esmolol group and 80.5% in the control group (P<0.01). This is the first study showing an improvement in cardiac function and 28-day mortality in septic patients adding b-blockers to standard therapy. We discussed several statistical and methodological limitations that may influence the generability of these results.