Myburgh, John — Beta blockers and De-stressing the Septic Patient
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Myburgh, John — Beta blockers and De-stressing the Septic Patient

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John Myburgh on the emerging evidence for the use of beta-blockade in sepsis. Direction for future research.

John Myburgh on the emerging evidence for the use of beta-blockade in sepsis. Direction for future research.

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Myburgh, John — Beta blockers and De-stressing the Septic Patient Myburgh, John — Beta blockers and De-stressing the Septic Patient Presentation Transcript

  • 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
  • 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 Noradrenaline Adrenaline Cortisol
  • Cardiac failure Spectrum of pathology Compensated Decompensated Acute Chronic
  • Spectrum of treatment Compensated Decompensated Neurohormonal modulation Acute Chronic Pharmacological augmentation Cardiac failure
  • Spectrum of treatment Compensated Decompensated Acute Chronic ACE inhibitors AT-II inhibitors βBlockade Catecholamines Diuretics 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 2005-2007 PCI 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: 2003-2008 1061/ 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, RCT Catecholamine-dependent sepsis 65-70 vs 80-85mmHg x 5 days
  • MAP targets Asfar:NEJM 2014 p=0.57 p=0.74 Multicentre, pragmatic, POC, RCT Catecholamine-dependent sepsis 65-70 vs 80-85mmHg x 5 days
  • Lactate targets James: Lancet 1999 Myburgh: ICM 2008
  • Heart rate target
  • Phase II, single centre, open-label prospective RCT Β-blocker naïve 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
  • 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 Kennedy 1917-1963 “Too often we enjoy the comfort of opinion without the discomfort of thought”