A small study with patients randomised to standard ICU sepsis therapy, or ICU sepsis therapy with beta blockage. We’ve written about the potential for β-blockage in sepsis earlier. This is the first clinical trial. It shows much better survival for the β-blocker group, but there are a few bumps in the road…
The theory is that critical illness like severe sepsis induces a sympathetic storm that overshoots what is needed to keep the body alive. This cathecholamine storm might be harmful for the patient. β-blocking them could countereffect this. We wrote on the theory after a retrospective study here. There is also a good overview article from Shock 2009 here.
The Morelli group did a pilot study first, documenting the effects of beta-blocking in sepsis, and it all looked favourable. They concluded: “This pilot study demonstrated that heart rate control by a titrated esmolol infusion in septic shock patients was associated with maintenance of stroke volume, preserved microvascular blood flow, and a reduction in norepinephrine requirements”. So they did a small randomised trial.
77 patients were randomised to β-blockers or standard treatment. To control the beta-blockade, they used the ultra short-acting β-blocker esmolol on an infusion pump. Clever choice, as they could titrate themselves to the predefined goal of a heart rate between 80-94/min. They mention heart rate might not be the optimal target for the β-blocker group, but it was the easiest and most practical to monitor. Seems fair.
The esmolol group almost halved the mortality of the control group! So this is all good? Hang on: The esmolol group had a mortality of 49%, which seems high. Having nearly halved the mortality from the control group, the control group had a mortality of 80%.
80% mortality in the control group?!? Either these were the sickest sepsis patients the world has ever seen, or the control group treatment must’ve consisted of locking the control group in a room and opening it on day three to see who’s still alive. As a cohort, even a severly sick sepsis cohort, the mortality rate shouldn’t be higher than 40-50% at the most. The latest numbers are showing an overall mortality from severe sepsis of 29%, as we have reported here. So something is not right in this 2012 beta-blocker study. Even with a high incidence of multiresistant bacteria as reported in the Morelli study, it’s hard to explain those mortality rates.
That being said, this study was first and foremost a safety study, and esmolol was shown to give no adverse outcomes. Of course, with the extreme mortality in the control group, adverse outcomes in the esmolol group might be hard to catch. Still, future, larger scale trials are surely in the works, and the results will be very interesting to see.
Impressive mortality reduction by esmolol, but needs additional studies – or a very good explanation on the extremely high overall mortality rates seen in this trial. β-blocker in sepsis was used here without adverse outcomes and is still an interesting concept. But for the time being, nothing more than that.
Review article on β-blockers in sepsis:
beta-Blockers in sepsis: reexamining the evidence, Shock, 2009.