Beta-blocker may improve prognosis in patients with septic shock

The use of esmolol (Brevibloc, Baxter), a short-acting beta-blocker, was associated with a better prognosis in patients with septic shock when compared with standard treatment, a preliminary communication published Oct. 23/30 in JAMA reported. Patients who received esmolol had heart rates in the target range, increased stroke volume, maintained a normal mean arterial pressure (MAP), a reduced need for norepinephrine and better 28-day survival.

“We hypothesized that intravenous beta-blockade titrated to achieve heart rate control in septic shock represents an effective approach to enhance myocardial function and improve outcome without increased complications,” wrote the authors, led by Andrea Morelli, MD, of the University of Rome.

Morelli and colleagues conducted a phase 2 study in the intensive care unit of the University of Rome “La Sapienza” Hospital between 2010 and 2012. Patients enrolled in the study were non-pregnant adults who experienced septic shock requiring norepinephrine (Levophed, Sanofi) to maintain a MAP of greater than 65 mmHG despite adequate fluid resuscitation and a heart rate of 95 or higher.

They were all naïve to beta-blocker treatment and also did not have significant cardiac dysfunction or valvular heart disease. The researchers randomly assigned 77 patients to receive a continuous intravenous infusion of esmolol and 77 patients to receive standard care.

The primary endpoint was a heart rate between 80 and 94 over 96 hours. As secondary outcomes, the researchers looked at hemodynamic and organ function measures; norephinephrine doses at one, two, three and four days; and adverse events and mortality within 28 days.

All patients in the esmolol group achieved the target heart rates without an increase in adverse events. The average area under the curve (AUC) for heart rate during the first four days was -28 in the esmolol group compared with -6 in the control group. The average reduction was 18.

Stroke volume was also lower in the experimental group, and patients in the esmolol group didn’t need as much fluid resuscitation. Mortality over the 28 days was 49.4 percent in the esmolol group compared with 80.5 percent in the control group.

The reduction in heart rate and increase in stroke volume decreased the workload of the heart and “[t]ogether with an amelioration in catecholamine-induced toxicity, myocardial performance may be preserved during septic shock thereby facilitating survival,” the authors wrote.

However, additional studies are warranted to confirm their findings, they concluded.

In an accompanying editorial, Michael R. Pinsky, MD, of the University of Pittsburgh, explained that the precise mechanism by which beta-blockers affect septic shock is not yet known.

“[C]linicians may not fully understand the reasons beta-blockers improve outcome, if indeed they do. But first, it will be important to define the patients for whom use of beta-blockers is most indicated and for whom these medications should be avoided,” he wrote.