Sir James Black Sir James Whyte Black, OM, FRS, FRSE, FRCP (born 14 July 1924) is a Scottish doctor and pharmacologist who invented Propranolol, synthesized Cimetidine and was awarded the Nobel Prize for Medicine in 1988 for these discoveries.
Sympatholytic drugs On the heart: heart rate, contractility, conduction velocity, relaxation rate. Pharmacology of beta blockers
On the vessels: Dominant alpha- adrenoceptor mediated vasoconstrictor influence. Pharmacology of beta blockers (cont.)
Pharmacology of commonly used or novel beta blockers
Therapeutic Indications Pharmacology of beta blockers (cont.)
Contraindications for BB Absolute – Asthma – Sick Sinus Syndrome – Severe peripheral vascular disease – Second or third degree heart block Relative – COPD – Raynaud phenomenon – Bradycardia – Hypoglycemia-prone diabetics in whom the early and warning symptoms of hypoglycemia may be masked.
Non-cardiac surgery is associated with an increase in catecholamines, which results in : an increase in blood pressure, heart rate free fatty acid concentrations. Beta blockers suppress the effects of increased catecholamines and as a result may prevent perioperative cardiovascular events. Beta blockers in non-cardiac surgery
Noncardiac Surgery-Evidence Mangano Study (NEJM 1996;335:1713) – 200 high-risk patients in a RCT DB of atenolol IV peri-op and orally post-op ( 2 days prior and 7 days after) – Long-term follow-up for 2 years – Excluded those who did not survive hospital stay – Reduction in overall and cardiac-related deaths at 6 mo, 1 year and 2 years in the atenolol group.
Noncardiac Surgery-Evidence Poldermans Study (NEJM 1999) – High risk patients with positive dobutamine echocardiograms (n=111) – Randomized to placebo or bisoprolol – Cardiac deaths were reduced from 17% to 3.4% – Nonfatal MI occurred in 17% of placebo group compared to 0% in bisoprolol group
ACC 2006 Guidelines Class I : pre-op BB used for angina or hypertension should be continued. Class I : High cardiac risk patients undergoing vascular surgery should have BB. Class IIa : if preop assessment reveals untreated hypertension, known CAD, or major risk factors for CAD. Class IIb : if preop assessment reveals patients undergoing vascular surgery with low or intermediate cardiac risk. Class III – Contraindication to BB
Care should be taken in applying recommendations on beta-blocker therapy to patients with decompensated heart failure, nonischemic cardiomyopathy, or severe valvular heart disease in the absence of coronary heart disease. Beta blockers in non-cardiac surgery(cont.)
The Best Protocol To Initiate Perioperative Β-blockade? Started a week before surgery Titrated to heart rate-decreasing effect Use shorter acting BB to facilitate adjustment Beta blockers in non-cardiac surgery(cont.)
POISE Perioperative Ischemic Evaluation (POISE) trial, a randomized controlled trial of metoprolol versus placebo in 10,000 patients undergoing noncardiac surgery. Beta blockers in non-cardiac surgery(cont.)
10% of cost of cardiac surgery is for treatment of complications = 1 billion $ in US annually BB reduce post-op atrial fibrillation (AFIB) which is associated with > LOS > cost ($10,000), and > risk of stroke. Withdrawal of BB in the peri-operative period doubles the risk of AF Mainly studied as a post-operative therapy to prevent AF Beta blockers in cardiac surgery
ESC/ACC/AHA Guidelines : Beta blockers as a first-line medication for prevention of AF after CABG in patients without contraindications. In patients undergoing cardiac surgery on pre-existing beta-blocker therapy, this treatment should be continued unless contraindications develop Beta blockers in cardiac surgery(cont.)
NICE Guidelines on AF management post- operativly should be reduced by: Amiodarone Beta-blocker Sotalol or Ratelimiting calcium antagonists Beta blockers in cardiac surgery(cont.)
Sotalol Class II and III antiarrhythmic effects. Lower frequency of postoperative AF. Combination therapy Titrated carefully with regular QT interval monitoring. Caution in renal insufficiency. Beta blockers in cardiac surgery(cont.)
Esmolol Cardioselective beta1 blocker. Ultra-short–acting(10 minutes). Uses: Perioperative control of blood pressure. Control of arrhythmias. Beta blockers in cardiac surgery(cont.)
Esmolol Recently used to induce “minimal myocardial contraction” It gives myocardial protection equivalent to cardioplegia. Scorsin et al(Thor & Cardiovas Sur2003) Esmolol and potassium Continuous normothermic retrograde blood cardioplegia markedly decreased myocardial oxygen consumption with esmolol Beta blockers in cardiac surgery(cont.)
Administrative data may be able to provide some evidence as to baseline rates. Exact criteria for use need to be clarified. Clarification is needed as to the exact timing of therapy and the appropriate patient population