1. Progress in Vascular Anesthesiology Donald M. Voltz, M.D. Assistant Professor of Anesthesiology Case Western Reserve University/University Hospitals of Cleveland

2. Overview Beta-blockers Fluid Therapy Regional Anesthesia

3. Beta-blockers in Vascular Patients Are We Using Too Few?

4. Вeta-Blockers Cardioprotection Hemodynamic Control Anesthetic Modification

5. B-blockers and Cardioprotection Well studied in vascular patient population Evolving evidence supports there use as a standard of care in at risk patients Likely to find increasing role in the future

6. B-blockers Evidence for Use

7. 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 Next Next Volume 335:1713-1721December 5, 1996 Number 23

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

9. 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

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

11. 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 0% bisoprolol 17% placebo group 17% placebo group Cardiac Death 3.4% bisoprolol group 3.4% bisoprolol group 17% placebo group 17% placebo group

12. What Patients are at Risk

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

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

15. 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

16. 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

17. 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 Titrated to HR 20% below ischemic threshold Holter Monitoring for 48 hrs PostOp

18. The Effect of Heart Rate Control on Myocardial Ischemia Among High-Risk Patients After Vascular Surgery Ischemia Present PostOp 73% in Placebo Group (8 of 11) 73% in Placebo Group (8 of 11) 33% in Esmolol Group (5 of 15) 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 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 4 of 11 pts in Placebo group <20%. 3 of 4 without ischemia

19. B-blockers - Types EsmololMetoprololLabetelolAtenolol

20. Esmolol Ultra-short acting Quick onset (peak effect by 5 min) Loading dose 0.5 mg/kg Beta 1 selective IV route only Expensive

21. Metoprolol Can be given IV or PO Long acting (q6h dosing) Beta 1 selective Large doses may decrease the selectivity

22. Labetelol Can be given PO and IV Selective alpha 1 and nonselective beta 1,2 Alpha:Beta blocking properties 3:1 oral and 7:1 IV. (not clinically seen)

23. Atenolol Beta 1 selective Can be given IV or PO

24. B-blocker Adverse Reactions Bradycardia – is it symptomatic??? Bronchospasm in COPD/Asthma patients – no evidence to suggest problem in these patients with selective agents Heart Failure – use carefully in patients with low EF, however, has been shown to improve function with ACEI in end-stage CHF

25. Summary for At Risk Patients Preemptive Bradycardia Think about heart rate as separate from blood pressure Be aggressive with heart rate control Incorporate into preoperative and postoperative care. Involve Primary Care Physician Involve Primary Care Physician Involve Vascular Surgeon and Nursing Involve Vascular Surgeon and Nursing

26. Balanced Anesthesia and Beta-blockers

27. B-blockers and Anesthetic Reduction

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

29. 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

30. Esmolol Promotes Electroencephalographic Burst Suppression During Propofol/Alfentanil Anesthesia BIS Output Esmolol – 40% reduction (3722) Esmolol – 40% reduction (3722) Saline – no change Saline – no change Suppression Ratio Esmolol – 13.4 fold increase (5 67) Esmolol – 13.4 fold increase (5 67) Saline – no change Saline – no change

31. 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

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

33. Efficacy of esmolol versus alfentanil as a supplement to propofol-nitrous oxide anesthesia Esmolol decreased time to eye opening (7.2 vs 9.8 min) Esmolol reported more pain in PACU Esmolol required more opiods in PACU

34. Esmolol Potentiates Reduction in Minimal Alveolar Isoflurane Concentration Jay W. Johansen, et al. Anesth Analg 1998; 87:671-6

35. Esmolol Potentiates Reduction in Minimal Alveolar Isoflurane Concentration N=100; divided into 5 groups Isoflurane alone Isoflurane alone Isoflurane with large dose esmolol (250 mcg/kg/min) Isoflurane with large dose esmolol (250 mcg/kg/min) Isoflurane with Alfentanil Isoflurane with Alfentanil Isoflurane, Alfentanil, small dose esmolol (50 mcg/kg/min) Isoflurane, Alfentanil, small dose esmolol (50 mcg/kg/min) Isoflurane, Alfentanil, large dose esmolol (250 mcg/kg/min) Isoflurane, Alfentanil, large dose esmolol (250 mcg/kg/min)

36. Esmolol Potentiates Reduction in Minimal Alveolar Isoflurane Concentration MAC levels after steady state Isoflurane – 1.28% Isoflurane – 1.28% Iso + large dose Esmolol – 1.23% Iso + large dose Esmolol – 1.23% Iso + Alfentanil – 0.96%* Iso + Alfentanil – 0.96%* Iso + Alfentanil + small dose Esmolol – 0.96% Iso + Alfentanil + small dose Esmolol – 0.96% Iso + Alfentanil _ large dose Esmolol – 0.74%** Iso + Alfentanil _ large dose Esmolol – 0.74%**

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

38. N=63 patients for noncardiac surgery Monitored – Neuropeptide Y, epinephrine, norepinephrine, cortisol, and ACTH Randomly assigned Group 1: no atenolol Group 1: no atenolol Group 2: Pre- and Post-operative atenolol Group 2: Pre- and Post-operative atenolol Group 3: Intraoperative Atenolol Group 3: Intraoperative Atenolol

39. Beneficial Effects from B-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 Groups II and III – 27.7% less fentanyl Lower Anesthetic Requirements Group III – 37.5% less isoflurane (BIS same in all groups) 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 Intraoperative Volatile Requirements PACU Pain Requirement PACU Pain Requirement PCA Usage PCA Usage

41. Fluid Therapy for Vascular Patients Are We Using Way Too Much?

42. AAA Change in Anesthetic Care Retrospective study of AAA and anesthesia Patients for elective infra-renal AAA in 1991 and 2001 End-Points Time to extubation Time to extubation Intraoperative Fluid Administration Intraoperative Fluid Administration Time to return of Bowel Function Time to return of Bowel Function

43. AAA and Crystaloid Use

44. AAA Length of Stay

45. AAA and Bowel Function

46. Fluid Therapy in Vascular Patients Ensure adequate end-organ perfusion Treat hypotension of reperfusion with a combination of fluid and vasopressors Replace blood loss with blood, not crystaloid Question replacing insensible losses and NPO deficits by formulas.

47. Vascular Surgery and Regional Anesthesia

48. Benefits of Regional Anesthesia Cardiac Protection Preservation of Pulmonary Function Lower graft thrombosis Decrease postoperative hypercoagulable state Faster return of bowel function Superior postoperative analgesia Better immune function

49. Regional Anesthesia and Cardiac Protection Thoracic epidural a must, no benefit from lumbar catheter High level to block cardiac accelerator fibers Maintain an infusion or PCEA post- operatively for maximal benefits Low risk of bleeding if placed 1 hour prior to systemic heparinization

50. Regional Anesthesia and Cardiac Protection Still not clear Some studies show no difference The role of beta-blockers to control sympathetic response confounding No clear evidence regional is superior

51. Regional Anesthesia and Cardiac Protection Problems with regional anesthesia studies and cardiac protection Groups not normalized to heart rate? Groups not normalized to heart rate? Is the benefit only from cardiac accelerator fibers being blocked? Is the benefit only from cardiac accelerator fibers being blocked? Are there other benefits of beta-blockers not being used because of a high epidural level? Are there other benefits of beta-blockers not being used because of a high epidural level?

52. Is Reduced Cardiac Performance the Only Mechanism for Myocardial Infarction Size Reduction During beta-Adrenergic Blockade? Stangeland, L. Grong, K. Vik-Mo, H. Anderson, K. Levken, J. Cardiovasc Res 1986;20: 322-30

53. Stangeland, et al. Anaesthetized cats to elucidate if decreased heart rate was the mechanism for cardiac protection. Treated groups with either timolol or alinidine (clonidine derivative that decreases HR independently of Beta- receptors) Induced regional ischemia (LAD occlusion for 6 hours)

54. Stangeland, et al. Alinidine Group: Decreased Necrotic Area to 77% of control Decreased Necrotic Area to 77% of control Timolol Group: Decreased Necrotic Area to 65% of control Decreased Necrotic Area to 65% of control This data suggested another mechanism for beta-blocker cardioprotection other than heart rate control This data suggested another mechanism for beta-blocker cardioprotection other than heart rate control

55. Regional Anesthesia and Pulmonary Function FRC is decreased due to Diaphragmatic dysfunction of upper abdominal or thoracic incisions Diaphragmatic dysfunction of upper abdominal or thoracic incisions Decreased chest wall compliance Decreased chest wall compliance Incisional Pain Limitations Incisional Pain Limitations

56. Regional Anesthesia and Pulmonary Function Advantages for thoracic and upper abdominal surgery Unclear benefits in lower abdominal and peripheral surgery No Change in hospital LOS Time and Post-Op labor intensive Time to place Time to place Requires pain service to follow Requires pain service to follow

57. Regional Anesthesia and Pulmonary Function Currently are not using thoracic epidurals for AAA surgery Pain control in ICU and on Floor is adequate Surgeons and Anesthesiologists are in agreement to post-operative pain control

58. Regional Anesthesia and Pulmonary Function No increased incidence in pneumonia No delay in extubation for elective aortic or lower extremity surgery

59. Regional Anesthesia and Graft Thrombosis Improvement in lower extremity blood flow Decrease sympathetic activation and stimulation of coagulation system Systemic absorption of local anesthetics block thromboxane A2, platelet aggregation and reduce blood viscosity Large meta-analysis done in orthopedics looking at DVT. Abdominal surgery patients had a less significant effect Minimization of blood loss.

60. Regional Anesthesia and LOS No increase in LOS at our institution Unclear in literature if LOS is improved with regional anesthesia

61. Double-masked Randomized Trial Comparing Alternate Combinations of Intraoperative Anesthesia and Postoperative Analgesia in Abdominal Aortic Surgery Norris, E.J. et al. Anesthesiology 2001;95:1054-67

62. Norris et al. N=168 pts for elective aortic surgery Randomized to either epidural with light GA vs. GA alone Pts either with PCA or PCEA for 72h postoperatively

63. Norris et al. Postoperative outcomes were similar in groups MI, reoperation, renal failure, pneumonia MI, reoperation, renal failure, pneumonia LOS and direct medical costs LOS and direct medical costs VAS Pain Scores VAS Pain Scores Epidural groups with shorter Time to extubation (19 vs. 13 hours) Time to extubation (19 vs. 13 hours) ICU discharge (46 vs. 43 hours) ICU discharge (46 vs. 43 hours) Return of Bowel Function (111 vs. 102 hours) Return of Bowel Function (111 vs. 102 hours)

64. Regional Anesthesia and Bowel Function Thought to relate to narcotic use as well as sympathetic reflex arcs Thought is decreased sympathetic slowing while maintaining parasympathetic peristalis Problems with randomized studies are higher amounts of narcotics. Lower narcotic usage has impacted post- operative ileus in out institution

65. Regional Anesthesia and Vascular Surgery - Summary Not presently known if regional superior to beta-blockade for cardioprotection Regional may be beneficial in severely reduced pulmonary function patients Pain control is similar with IVPCA vs PCEA Unclear if additional factors are significant in vascular patients

66. THE END Vascular Anesthesia at University Hospitals of Cleveland