Challenging Cases in Perioperative Medicine

1. Challenging Cases in Perioperative Medicine Margaret M. Beliveau MD General Internal Medicine Mayo Clinic, Rochester, Mn

2. Disclosures • No relevant industry conflict of interest • I will not be discussing off-label use of drugs • I have 2 teenage drivers, which resulted in all my hair turning grey

4. Objectives • Discuss the management of patients with cardiac stents in the perioperative setting • Discuss the perioperative management of the frail elderly patient with multiple co-morbidities • Discuss issues in hypertension management in the perioperative setting • Discuss the perioperative management of patients with hemophilia

5. Case 1 • A 70 year old man falls while out walking his dog. For the next week, his family notices progressive gait instability. After a second fall, they take him to the emergency room, where he is discovered to have a large right subdural hematoma.

7. Case 1 • He had an ST elevation MI 4 months ago at an outside facility and a drug-eluting stent was placed (paclitaxel). No further information is available. • He also has a history of recurrent DVT and PE has been maintained on warfarin • Bipolar disorder

8. Case 1 • Lexapro 20 mg by mouth daily • Aspirin 325 mg by mouth daily • Warfarin 4 mg by mouth daily • Plavix 75 mg by mouth daily • Atenolol 75 mg daily

9. Case 1 • INR 2.9 on admission • Plan for Burr hole evacuation of subdural hematoma

10. Case 1 • In addition to stopping the warfarin, what do you tell the surgeon with regard to his medications?

11. Case 1 • The patient should undergo the surgical procedure on aspirin and clopidogrel • The aspirin should be stopped, but the clopidogrel should be continued • The aspirin and clopidogrel can be interrupted for the surgical procedure • The clopidogrel can be stopped, but the aspirin should be continued

12. Case 2 • 72 yo man • Nov. 2006- gross hematuria • TURBT, muscle invasive bladder cancer • Cystectomy recommended, but preoperative cardiac evaluation abnormal • Radiation therapy, ended June 2007 • Feb. 2008- recurrent hematuria

13. Case 2 • Chemotherapy given • Ongoing hematuria, now transfusion dependent • Proposed curative cystectomy

14. Case 2 • March 2007- abnormal EKG on preoperative evaluation • Coronary angiogram- CABG recommended, patient refused • 15 bare metal stents placed • July 2007- patient complains of fatigue • Angiogram- restenosis

15. Case 2 • 14 more drug eluting stents placed • 5- LAD, 5- RCA, 4- circumflex • March 2008- adenosine sestamibi positive for ischemia (severe left main disease), small area of infero-septal infarct • Patient remains asymptomatic • Cardiology evaluation: benefits of surgery outweigh risks

16. Case 2 • What do you tell the surgeon with regard to his medications?

17. Case 2 • The patient should undergo the surgical procedure on aspirin and clopidogrel • The aspirin should be stopped, but the clopidogrel should be continued • The aspirin and clopidogrel can be interrupted for the surgical procedure • The clopidogrel can be stopped, but the aspirin should be continued

19. The Story of the Stent • Bare Metal Stent (BMS) first introduced in the US in 1994 • Drug Eluting Stent (DES) became available in 2003 • Over 4 million stents (BMS and DES) placed annually worldwide

20. The Story of the Stent • DES are being deployed in 80%-90% of coronary interventions in the US(the majority of these for “off label” indications) • More than 6 million drug eluting stents have been placed since they became available in 2003

21. The CYPHER (Sirolimus-eluting Coronary Stent) is indicated for: improving coronary luminal diameter in patients with symptomatic ischemic disease due to discrete de novo lesions of length ≤ 30 mm in native coronary arteries with reference vessel diameter of ≥2.5 mm to ≤3.5 mm. The TAXUS (Express Paclitaxel-Eluting Coronary Stent System) is indicated for: improving luminal diameter for the treatment of de novo lesions ≤28 mm in length in native coronary arteries ≥2.5 to ≤3.75 mm in diameter. FDA Indications for Use

22. Off-Label Indications for Drug Eluting Stents • 50%-60% of DES are placed for “off-label” use

23. Iakovou et al JAMA 2005Prospective observational cohort of 2229 consecutive patients who had DES placed 9 month followup Subacute < 30 Days Late > 30 Days Cumulative incidence of stent thrombosis 1.3%

24. Iakovou et alJAMA 2005 • In this study, 29% of the patients who prematurely discontinued dual antiplatelet therapy developed stent thrombosis • Case fatality rate for patients who developed stent thrombosis was 45% • These were all patients who had stent placement, not just patients undergoing non-cardiac surgery

25. What Do You Recommend if a Patient with a Recent Stent Needs Surgery? • Approximately 5% of patients who undergo coronary stenting require noncardiac surgery within 1 year of stenting • Fear of excessive bleeding leads to the generally accepted policy of discontinuing these agents 7-10 days before elective surgery

26. The Perfect Storm Trouble

27. Abrupt discontinuation of clopidogrel Abrupt discontinuation of aspirin • Rebound effect: • Significantly increased inflammatory prothrombotic state • Significantly increased platelet adhesion and aggregation • Excessive thromboxane A2 activity • Surgical intervention with increased prothrombotic and inflammatory state: • increased cytokines, neuroendocrine inflammatory mediator release • increased platelet adhesiveness and persistently high platelet counts • increased release of procoagulant factors • decreased or impaired fibrinolysis Prothrombotic state with incompletely endothelialized stent(s) Stent thrombosis, MI, Death Newsome LT Anesth Analg 2008; 107:570-90

28. Anti-platelet Drugs • Widely used for primary and secondary prevention of cardiovascular disease • Plaque stabilization • Used after placement of intracoronary stents to prevent thrombosis

29. Anti-platelet Drugs • Continuation> increased risk of perioperative bleeding • Interruption>risk of stent thrombosis

30. Anti-platelet Drugs • Aspirin • Thienopyridines (clopidogrel) • GP IIb/IIIa receptor antagonists

31. Anti-platelet Drugs Bleeding risks: • No large prospective randomized trials • Aspirin: risk of bleeding increased by a factor of 1.5, without increased morbidity or mortality • Risk highest in specific procedures: CABG, prostatectomy and intra-cranial neurosurgery Chassot PG BJA 99:316-28, 2007

32. Anti-platelet Drugs • Dual therapy: ASA plus clopidogrel • Moderate increase in surgical blood loss, but not in morbidity, mortality or surgical outcome • Exception: intracranial neurosurgery

33. Risks of maintaining Increased surgical blood loss Increased transfusion rate Withdrawal risks Rebound increased platelet adhesiveness Doubled infarction and death rate in acute coronary syndrome Increased risk of stent thrombosis with high mortality Anti-platelet Drugs

34. Risk of Stent Thrombosis • High risk stents: long, proximal, multiple, overlapping, small vessels, bifurcation • High risk patients: Low EF, diabetes • High risk timing: < 6 weeks after bare metal stent; < 12 months after drug-eluting stent

35. Risk of Stent Thrombosis • If stent not completely endothelialized, risk of acute stent thrombosis increased: • Prothrombotic state induced by surgery

36. Risk of Stent Thrombosis • The most powerful predictor of acute stent thrombosis with BMS is time delay of < 14 days between implantation and interruption of anti-platelet therapy

37. Risk of Stent Thrombosis • Drug-eluting stents: adverse clinical events (MI, death) noted when patients stopped anti-platelet therapy prematurely

38. Discontinue antiplatelet drugs perioperatively Stent thrombosis MI Cardiac death Continue perioperative antiplatelet drugs Surgical bleeding The Perioperative Dilemma

39. The Perioperative Dilemma • Based on currently available data, the risk of withdrawing anti-platelet drugs is greater than continuing them • Withdrawal imposes perioperative cardiac death rate that is increased 5-10 times

40. Chassot PG BJA 99:316-28, 2007

41. Society for Cardiovascular Angiography Clinical Alert, Jan 2007

42. Joint Advisory Recommendations and Noncardiac Surgery • Consider bare metal stent if patient requires PCI and is likely to require invasive or surgical procedure within next 12 months. • Educate patient prior to discharge re: risk of premature antiplatelet discontinuation. • Instruct patient to contact treating cardiologist before antiplatelet discontinuation

43. Joint Advisory Recommendations and Noncardiac Surgery • Healthcare providers who perform surgical or invasive procedures must be made aware of catastrophic risks of premature antiplatelet discontinuation and should contact the treating cardiologist to discuss optimal management strategy

44. Joint Advisory Recommendations and Noncardiac Surgery • Defer elective procedures for which there is bleeding risk until completion of antiplatelet course • 1 month bare metal stent • 12 months drug eluting stent • For patient with drug eluting stents who are to undergo procedures that mandate discontinuation of thienopyridine (e.g., clopidogrel), continue aspirin if at all possible and restart thienopyridine as soon as possible

45. Joint Advisory Recommendations and Noncardiac Surgery • No evidence for “bridging therapy” with antithrombins, warfarin, or glycoprotein IIIB/IIIA agents

46. Proposed Approach for Management of Dual Antiplatelet Therapy with Previous PCI who Require Surgery* Balloon Angioplasty Bare-metal Stent Drug-eluting Stent < 30-45 Days <365 Days < 14 Days > 14 Days >365 Days > 30-45 Days Delay Elective or Non-urgent Surgery Delay Elective or Non-urgent Surgery Proceed to Operating Room with Aspirin Proceed to Operating Room with Aspirin * Based on Expert Opinion, from the ACC/ AHA guidelines, 2007

47. Back to the patients… • Patient 1: Drug-eluting stent, DVT/PE, on warfarin, aspirin and clopidogrel, sub dural hematoma • My recommendations: Stop antiplatelet agents, restart aspirin 5 days after surgery if stable, restart clopidogrel as soon as possible after surgery (10 days-2 weeks per neurosurgeon) • ? Loading dose (300 mg) of clopidogrel

48. Case 1 • The patient should undergo the surgical procedure on aspirin and clopidogrel • The aspirin should be stopped, but the clopidogrel should be continued • The aspirin and clopidogrel can be interrupted for the surgical procedure • The clopidogrel can be stopped, but the aspirin should be continued

49. Back to the patients… • Patient 2: 29 stents, locally invasive bladder cancer • Underwent radical cystoprostatectomy, limited pelvic lymphadenectomy, and ileal conduit formation • Aspirin and clopidogrel held prior to surgery (despite our recommendations) • POD#1:

50. Case 2 • The patient should undergo the surgical procedure on aspirin and clopidogrel • The aspirin should be stopped, but the clopidogrel should be continued • The aspirin and clopidogrel can be interrupted for the surgical procedure • The clopidogrel can be stopped, but the aspirin should be continued