Myburgh, John — Beta blockers and De-stressing the Septic Patient
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Beta-blockers: destressing the septic patient UNSW John Myburgh MBBCh PhD FCICM FAICD The George Institute for Global Health St George Clinical School, University of New South Wales
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John Myburgh on the emerging evidence for the use of beta-blockade in sepsis. Direction for future research.
Transcript of Myburgh, John — Beta blockers and De-stressing the Septic Patient
Beta-blockers:destressing the septic patient
UNSW
John MyburghMBBCh PhD FCICM FAICD
The George Institute for Global Health St George Clinical School, University of New South Wales
Arthur Guyton 1919-2003
Cardiac function
Right atrial pressure (mmHg)
0
10
Venous return
l/min
Cardiac function
Mean systemic pressure
Guyton: 1953
Cardiac failure
Right atrial pressure (mmHg)
0
10
Cardiac failure
Normal
Normal
l/min
Guyton: 1953
Cardiac failure
Right atrial pressure (mmHg)
0
10
Cardiac failure
Francis : Am Heart J 1982
l/min
Venoconstriction
Cardiac failure
Right atrial pressure (mmHg)
0
10
Catecholamines Catecholamines
l/min
Francis : Am Heart J 1982
Septic shock
Right atrial pressure (mmHg)
0
10 Normal
Normal
Jacobsohn: Can J Anes 1997
l/min
Septic shock
Right atrial pressure (mmHg)
0
10 Vasoplegia
l/min
Vasoplegia
Jacobsohn: Can J Anes 1997
Septic shock
Right atrial pressure (mmHg)
0
10
Cardiac depression
l/min
Jacobsohn: Can J Anes 1997
Septic shock
Right atrial pressure (mmHg)
0
10
l/min
Fluid / catecholamines
Catecholamines
Jacobsohn: Can J Anes 1997
Hein: Cell Tissue Research 2006
Neurohormonal vasoregulation
Neurohormonal vasoregulation
Sadowska : J Physiol Pharm 2006
VP
NoradrenalineAdrenaline
Cortisol
Cardiac failure
Spectrum of pathology
Compensated Decompensated
Acute
Chronic
Spectrum of treatment
Compensated Decompensated
Neurohormonal modulation
Acute
Chronic
Pharmacologicalaugmentation
Cardiac failure
Spectrum of treatment
Compensated Decompensated
Acute
Chronic
ACE inhibitorsAT-II inhibitors
Blockade
CatecholaminesDiuretics
Cardiac failure
Cardiac failure and β-blockade
Abraham: Arch Int Med 2001
Carvedilol: NYHA II-III
Bisoprolol: NYHA III-IV
β-blockade and outcomes in CHF
Shibata: Eur J Heart Failure 2001
Mortality and hospital admission
Pooled effect: 0.68, P<0.00001
ACS / PCI and β-blockade
ACS / PCI and β-blockade
Whole cohort: (n=3 692) Low LVEF: (n=450)
Bao: Cardiovasc Interv Ther 2013
Database registry 2005-2007PCI within 24h STEMI
Β-blockade at hospital dischage
Angus: NEJM 2013
β-blockade and sepsis
Ackland: Crit Care Med 2010
Hepatic
Myocardial
48h pre-LPS
6h post-LPS
Previous β-blockade and sepsis
Macchia: Crit Care Med 2012
Database linkage: 2003-20081061/ 8404 patients with sepsis
28-day mortality:β-blocker: 188/1061 (17.7%)No β-blocker: 1857/ 8404 (22.1%)
OR 0.78 (0.66 to 0.93)
Rivers: NEJM 2001
MAP targets
MAP targets
Myburgh: ICM 2008
MAP targets
Asfar:NEJM 2014
Multicentre, pragmatic, POC, RCTCatecholamine-dependent sepsis65-70 vs 80-85mmHg x 5 days
MAP targets
Asfar:NEJM 2014
p=0.57 p=0.74
Multicentre, pragmatic, POC, RCTCatecholamine-dependent sepsis65-70 vs 80-85mmHg x 5 days
Lactate targets
James: Lancet 1999 Myburgh: ICM 2008
Heart rate target
Phase II, single centre, open-label prospective RCTΒ-blocker naïveCatecholamine 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
Conclusions
Neurohormonal regulation is a complex biological process.
Neurohormonal modulation is a complex therapeutic intervention
β-blockade is a small component of modulatory therapy
Conclusions
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 studies
Conclusions
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 Kennedy1917-1963
“Too often we enjoy the comfort of opinion without the discomfort of thought”
