β-blockade and sepsis
Ackland: Crit Care Med 2010
Previous β-blockade and sepsis
Macchia: Crit Care Med 2012
Database linkage: 2003-2008
1061/ 8404 patients with sepsis
β-blocker: 188/1061 (17.7%)
No β-blocker: 1857/ 8404 (22.1%)
OR 0.78 (0.66 to 0.93)
Phase II, single centre, open-label prospective RCT
Catecholamine dependent sepsis : MAP>65, CI > 2.2 l/m/m2
Esmolol 25mg/hr + 50 mg/h to HR 80-94
Morelli: JAMA 2013
The quest for meaningful outcomes
NICE-SUGAR: NEJM 2009 DECRA: NEJM 2011
Neurohormonal regulation is a complex biological process.
Neurohormonal modulation is a complex therapeutic intervention
β-blockade is a small component of modulatory therapy
The efficacy of β-blockade in chronic heart failure has been
determined in large RCTs.
The efficacy of β-blockade after ACS remains uncertain
The biological effects of β-blockade in inflammatory states are
complex, but tantalising based on animal and observational
Caution is required with neuroendocrine intervention in
critically ill patients.
A pragmatic RCT to test the effects of β-blockade on patient-
centred outcomes in sepsis is required.
John F Kennedy
“Too often we enjoy the
comfort of opinion
without the discomfort of