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β -b locker’s in Anesthesia

β -b locker’s in Anesthesia. Donald M. Voltz, M.D. Assistant Professor of Anesthesiology Case Western Reserve University/University Hospitals of Cleveland. Goals. To provide everyone with enough information to begin comfortably using beta-blockers in the perioperative period. Objectives.

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β -b locker’s in Anesthesia

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  1. β-blocker’s in Anesthesia Donald M. Voltz, M.D. Assistant Professor of Anesthesiology Case Western Reserve University/University Hospitals of Cleveland

  2. Goals • To provide everyone with enough information to begin comfortably using beta-blockers in the perioperative period.

  3. Objectives • Physiology of Adrenergic Receptors • β -adrenergic antagonists • Clinical Application of β-blockers • Cardiac Protection • Hemodynamic Control • Decreasing Anesthetic Requirements • Guidelines for Beta-blocker Usage in the OR

  4. β -adrenergic Receptor Physiology

  5. β-blocker Receptor Types • β 1 Receptors • Predominant receptor on cardiac myocytes • β 2 Receptors • Involved in contraction and relaxation of heart failure • Peripheral vasodilitation and bronchial dilatation • β 3 Receptors • Negative inotropy via NO-dependant pathway • May play a role in deterioration of cardiac function in heart failure

  6. β – Receptor Biologic Responses • Chronotropy • Dromotropy • Inotropy • Cellular Growth • Cellular Death (apoptosis)

  7. β-Receptor Intracellular Signaling

  8. β -Receptor Down-Regulation • Phosphorylation (down regulation) • Translocation (sequestration) • Degredation

  9. β -Receptor Down-Regulation • Down-regulation begins within a few hours after an elevation of catecholamines • Initial phase is the uncoupling of receptor and signal transduction • Late phase results in degradation of receptors • Down-regulation has been reported to persist for 1 week after laparotomy, thoracotomy, and cardiac bypass

  10. β -Receptor Down-Regulation

  11. Cell Death – Necrosis and Apoptosis • Catecholamines are toxic to cardiac cells • Tachycardia with Isoproterenol significantly increased apototic death than ventricular pacing • Cardiac cell death is reduced in patients with subarachnoid bleeding when treated with atenolol

  12. β -adrenergic Antagonist Medications

  13. β -adrenergic Antagonists

  14. β1/ β2 selectivity

  15. Ancillary Properties of β-blockers • Membrane-Stabilizing Activity • Intrinsic Sympathomimetic Activity • Lipid Solubility • Antioxidant Activity • Anti-adhesive Activity • α1-Antagonistic Activity

  16. Clinical Actions of β -blockers • Lowering heart rate • Decreasing blood pressure • Decreasing atherosclerotic plaque stiffness • Decreased platelet activation • Anti-arrhythmic effects • Cardiac protection – not HR dependant • Decrease in anesthetic and analgesic requirements • Improvement of immune response

  17. Cardiac Effects of β-blockade

  18. Clinical Evidence for β –blocker Use

  19. Clinical Applications for β -blockade • Cardiac Protection • Hemodynamic Control • Immune Modulation • Modulation of Coagulation • Decreased Anesthetic Requirements

  20. Myocardial Protection • Well studied in vascular patient’s who are at high risk for perioperative cardiac events • Evolving evidence supports there use as a standard of care in at risk patients • Likely to find increasing role in the future

  21. Effect of Atenolol on Mortality and Cardiovascular Morbidity after Noncardiac Surgery Dennis T. Mangano, Ph.D., M.D., Elizabeth L. Layug, M.D., Arthur Wallace, Ph.D., M.D., Ida Tateo, M.S., for The Multicenter Study of Perioperative Ischemia Research Group

  22. Mangano, et al. 1996 • Randomized trial of atenolol vs. saline (n=99, n=101) • Patient followed for 2 years • Mortality decreased in atenolol group • 0% vs 8% at 6 months • 3% vs 14% at 1 year • 10% vs 21% at 2 years

  23. Wallace, et al. 1998 • 200 pts randomized to atenolol or saline • EKG, Holter monitor, and CPK w/ MB were followed 24 hr prior and 7 days after surgery • Atenolol 0,5, or 10 mg or placebo prior to induction and every 12 hours until po than qd for 1 week

  24. Wallace, et al. 1998 • Decreased perioperative myocardial ischemia • 17/99 esmolol vs 34/101 placebo (days 0-2) • 24/99 esmolol vs 39/101 placebo (days 0-7)

  25. Polderman, et al. 1999 • 846 pts with one or more cardiac risk factors; 173 positive dobutamine stress tests • Bisoprolol in 59; Placebo in 53 • Nonfatal MI • 0% bisoprolol • 17% placebo group • Cardiac Death • 3.4% bisoprolol group • 17% placebo group

  26. What Patients are at Risk

  27. B-blockers & At Risk Patients • Presence of CAD • History of Myocardial Infarction • Typical Angina or Atypical Angina with + Stress Test • At Risk for CAD (2 or more of the following) • Age >65 years • Hypertension • Active Smoker • Serum Cholesterol > 240 mg/dl • Diabetes Mellitus

  28. B-blockers and Cardioprotection • How well are we doing with at risk patients? • Not Very Well!

  29. Prophylactic beta-blockade to prevent myocardial infarction perioperatively in high-risk patients who undergoing general surgical procedures.Taylor RC, Pagliarello G.Can J Surg. 2003 Jun;46(3):216-22 • 236 pts for laparotomy • 143 pts at risk for CAD • 60.8% did not receive B-blockers pre-op • 33% pts had B-blockers discontinued

  30. The Effect of Heart Rate Control on Myocardial Ischemia Among High-Risk Patients After Vascular Surgery Khether E. Raby, MD, FACC*, Sorin J. Brull, MD, Farris Timimi, MD, Shamsuddin Akhtar, MD, Stanley Rosenbaum, MD, Cameron Naimi, BS, and Anthony D. Whittemore, MD Anesth Analg. 1999 Mar;88(3):477-82

  31. The Effect of Heart Rate Control on Myocardial Ischemia Among High-Risk Patients After Vascular Surgery • Vascular Pts at High Risk for CAD underwent 24 hrs Holter Monitoring • 26 of 150 pts had significant ischemia as measured by ST-depression – PreOp • Randomized to Esmolol gtt (n=15) or Placebo (n=11) • Titrated to HR 20% below ischemic threshold • Holter Monitoring for 48 hrs PostOp

  32. The Effect of Heart Rate Control on Myocardial Ischemia Among High-Risk Patients After Vascular Surgery • Ischemia Present Post-Op • 73% in Placebo Group (8 of 11) • 33% in Esmolol Group (5 of 15) • Number of Hours HR < Ischemic Threshold • 9 of 15 pts in Esmolol group <20% and all without ischemia • 4 of 11 pts in Placebo group <20%. 3 of 4 without ischemia

  33. Anti-Arrhythmic Effects • High risk pts with CAD under-going noncardiac surgery have PVC’s or ventricular tachyarrythmias (50% incidence) • Cardiac surgery pts are at high risk of developing atrial fibrillation • Blunting sympathetic tone decreases incidence of both atrial and ventricular tachyarrythmias • β-blockers counteract epinephrine-induced hypokalemia

  34. Balanced Anesthesia andBeta-blockers

  35. B-blockers and Anesthetic Reduction

  36. Michael Zaugg, M.D.; Thomas Tagliente, M.D., Ph.D.; Eliana Lucchinetti, M.S.; Ellis Jacobs, Ph.D.; Marina Krol, Ph.D.; Carol Bodian, Dr.P.H.; David L. Reich, M.D.; Jeffrey H. Silverstein, M.D. ANESTHESIOLOGY 1999;91:1674-1686

  37. Beneficial Effects from B-Adrenergic Blockade in Elderly Patients Undergoing Noncardiac Surgery • N=63 patients for noncardiac surgery • Monitored – Neuropeptide Y, epinephrine, norepinephrine, cortisol, and ACTH • Randomly assigned • Group 1: no atenolol • Group 2: Pre- and Post-operative atenolol • Group 3: Intraoperative Atenolol

  38. Beneficial Effects from B-Adrenergic Blockade in Elderly Patients Undergoing Noncardiac Surgery

  39. Beneficial Effects from β-Adrenergic Blockade in Elderly Patients Undergoing Noncardiac Surgery • Beta-blockade did not change neuroendocrine stress response • Lower Narcotic Requirement • Groups II and III – 27.7% less fentanyl • Lower Anesthetic Requirements • Group III – 37.5% less isoflurane (BIS same in all groups) • Lower PACU Morphine requirements • Shorter PACU times

  40. Beta-blockers and Bariatric Surgery • Randomized Study of Morbidly Obese Patients Undergoing Gastric Bypass • Metoprolol vs. Placebo • Evaluate • Intraoperative Volatile Requirements • PACU Pain Requirement • PCA Usage

  41. Atenolol May Not Modify Anesthetic Depth Indicators in Elderly Patients – A Second Look at the Data Zaugg, et. al. Can J Anesth 2003; 50: 638-42

  42. Atenolol May Not Modify Anesthetic Depth Indicators in Elderly Patients – A Second Look at the Data • Does atenolol result in light anesthesia with the reduction of volatile agents? • Are our abilities to adequately judge anesthetic depth impaired with atenolol?

  43. Atenolol May Not Modify Anesthetic Depth Indicators in Elderly Patients – A Second Look at the Data • 45 patients from the prior study we used (post hoc) • Collected HR, MAP, SBP, and BIS output • Subgroups were analyzed • Group I n=12 • Group II n=16 • Group III n=17

  44. Atenolol May Not Modify Anesthetic Depth Indicators in Elderly Patients – A Second Look at the Data • Group III received 39.5% less isoflurane than Group I • Group II and III received 21% less fentanyl than Group I • All Groups had similar intraoperative BIS levels (53-54) • Atenolol reduces anesthetic requirements but not modify depth of anesthesia indicators

  45. β-Blockers and Memory • Lipophilic β-blockers can cross the blood-brain barrier • Propranolol has been shown to blunt storage of emotionally charged events • Some thoughts that perioperative β-blockade may be useful to blunt recall

  46. Esmolol Promotes Electroencephalographic Burst Suppression During Propofol/Alfentanil Anesthesia Jay W. Johansen Anesth Analg 2001; 93:1526-31

  47. Esmolol Promotes Electroencephalographic Burst Suppression During Propofol/Alfentanil Anesthesia • N=20 patients • Alfentanil Groups (50 or 150 ng/ml) • Saline vs Esmolol infusion • Monitored BIS output and Suppression Ratio

  48. Esmolol Promotes Electroencephalographic Burst Suppression During Propofol/Alfentanil Anesthesia • BIS Output • Esmolol – 40% reduction (37→22) • Saline – no change • Suppression Ratio • Esmolol – 13.4 fold increase (5 → 67) • Saline – no change

  49. Efficacy of esmolol versus alfentanil as a supplement to propofol-nitrous oxide anesthesia Smith, J. Van Hemelrijck, and P. White Anesth Analg 2003;97:1633-1638

  50. Efficacy of esmolol versus alfentanil as a supplement to propofol-nitrous oxide anesthesia • N=97 patients for arthroscopy • Compared esmolol to alfentanil

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