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.

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

  1. 1. 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
  2. 2. Arthur Guyton 1919-2003
  3. 3. Cardiac function Right atrial pressure (mmHg) 0 10 Venous return l/min Cardiac function Mean systemic pressure Guyton: 1953
  4. 4. Cardiac failure Right atrial pressure (mmHg) 0 10 Cardiac failure Normal Normal l/min Guyton: 1953
  5. 5. Cardiac failure Right atrial pressure (mmHg) 0 10 Cardiac failure Francis : Am Heart J 1982 l/min Venoconstriction
  6. 6. Cardiac failure Right atrial pressure (mmHg) 0 10 Catecholamines Catecholamines l/min Francis : Am Heart J 1982
  7. 7. Septic shock Right atrial pressure (mmHg) 0 10 Normal Normal Jacobsohn: Can J Anes 1997 l/min
  8. 8. Septic shock Right atrial pressure (mmHg) 0 10 Vasoplegia l/min Vasoplegia Jacobsohn: Can J Anes 1997
  9. 9. Septic shock Right atrial pressure (mmHg) 0 10 Cardiac depression l/min Jacobsohn: Can J Anes 1997
  10. 10. Septic shock Right atrial pressure (mmHg) 0 10 l/min Fluid / catecholamines Catecholamines Jacobsohn: Can J Anes 1997
  11. 11. Hein: Cell Tissue Research 2006 Neurohormonal vasoregulation
  12. 12. Neurohormonal vasoregulation Sadowska : J Physiol Pharm 2006 VP Noradrenaline Adrenaline Cortisol
  13. 13. Cardiac failure Spectrum of pathology Compensated Decompensated Acute Chronic
  14. 14. Spectrum of treatment Compensated Decompensated Neurohormonal modulation Acute Chronic Pharmacological augmentation Cardiac failure
  15. 15. Spectrum of treatment Compensated Decompensated Acute Chronic ACE inhibitors AT-II inhibitors βBlockade Catecholamines Diuretics Cardiac failure
  16. 16. Cardiac failure and β-blockade Abraham: Arch Int Med 2001 Carvedilol: NYHA II-III Bisoprolol: NYHA III-IV
  17. 17. β-blockade and outcomes in CHF Shibata: Eur J Heart Failure 2001 Mortality and hospital admission Pooled effect: 0.68, P<0.00001
  18. 18. ACS / PCI and β-blockade
  19. 19. 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
  20. 20. Angus: NEJM 2013
  21. 21. β-blockade and sepsis Ackland: Crit Care Med 2010 Hepatic Myocardial 48h pre-LPS 6h post-LPS
  22. 22. 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)
  23. 23. Rivers: NEJM 2001 MAP targets
  24. 24. MAP targets Myburgh: ICM 2008
  25. 25. MAP targets Asfar:NEJM 2014 Multicentre, pragmatic, POC, RCT Catecholamine-dependent sepsis 65-70 vs 80-85mmHg x 5 days
  26. 26. 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
  27. 27. Lactate targets James: Lancet 1999 Myburgh: ICM 2008
  28. 28. Heart rate target
  29. 29. 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
  30. 30. The quest for meaningful outcomes NICE-SUGAR: NEJM 2009 DECRA: NEJM 2011
  31. 31. Conclusions Neurohormonal regulation is a complex biological process. Neurohormonal modulation is a complex therapeutic intervention β-blockade is a small component of modulatory therapy
  32. 32. 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
  33. 33. 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.
  34. 34. John F Kennedy 1917-1963 “Too often we enjoy the comfort of opinion without the discomfort of thought”

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