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

  • 1,106 views
Uploaded on

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.

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
    Be the first to like this
No Downloads

Views

Total Views
1,106
On Slideshare
0
From Embeds
0
Number of Embeds
4

Actions

Shares
Downloads
19
Comments
0
Likes
0

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

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