1. ANESTHESIA FOR NON CARDIAC SURGERY IN PATIENTS WITH CORONARY STENTS
Dr. Mahesh Vakamudi
Professor and Head
Department of Anesthesiology, Critical Care and Pain Medicine
(ISO 9001:2008 CERTIFIED)
Sri Ramachandra University
Chennai

2. Magnitude of the problem
2 million patients undergo PCI annually
90% of these patients receive one or more intracoronary stents
5% of these patients will undergo non cardiac surgery in the first year after stenting

3. > NUMBER Percutaneous coronary interventions
Coronary artery bypass surgeries
Increase procedural success
Stents commonly placed
Decrease restenosis

4. Why this lecture?
In patients who have coronary stents, perioperative coronary stent thrombosis is a catastrophic complication
Non cardiac surgery, especially if surgery is performed immediately after stenting and particularly if dual antiplatelet therapy is discontinued – increases this risk
Maintain balance between risk of bleeding and stent thrombosis is our dilemma.
What do we do? That’s what this lecture is about

5. Which patients are prone for stent thrombosis?
Patients with a suboptimal angiographic result
Those with high risk lesions
Small vessels
Bifurcation lesions
Those with diabetes and renal failure
Those whose dual antiplatelet therapy has been stopped

6. Risk score for prediction of LST
Scoring system for LST
Risk score for prediction of LST
Renal failure
6 points
Bifurcation lesion
Diabetes
4 points
Brachytherapy
2.5 points
Each 20% fall in EF
0.25 points
Low
Medium
High
Very High 6 9 13 19

7. Why thrombosis? STENT THROMBOSIS Early surgery
Stents not endothelialized
Prothrombotic state due to surgery
Stopping antiplatelets
Early surgery
STENT THROMBOSIS

8. ⁺ & Discontinuation of Aspirin and Clopidogrel
Loss of anti-inflammatory protection by clopidogrel
Rebound increase in COX 1 and TXB2
Loss of antiplatelet effect
Increased thrombin and decreased fibrinolysis
Stent thrombosis ⁺
&
Surgery
Prothrombotic state MI

9. Coronary angioplasty without stents
Abrupt vessel collapse due to acute recoil and vasospasm
Stent placement injures vessel wall and causes scar tissue growth inside the stent
Stent restenosis
Bare metal stents
Prevent neointimal hyperplasia
Delay endothelialization
Drug eluting stents
but
Antiproliferative and immunosuppressive properties
Late stent thrombosis
Platform + Carrier
(Stent + Drug)

10. None out of 15 patients who underwent surgery after 15 days died
Incidence of deaths
Bare metal stents
8 out of 25 patients who underwent surgery within 2 weeks died – 7 of MI, 1 of bleeding
None out of 15 patients who underwent surgery after 15 days died
Kaluza GL, Joseph J, Lee JR, Raizner ME, Raizner AE.
Catastrophic outcomes of noncardiac surgery soon after coronary stenting.
J Am Coll Cardiol 2000;35:1288 –94.

11. Bare metal stents
The risk of death, MI, or stent thrombosis was elevated for 6 weeks, not for just 2 weeks
Of 27 patients who underwent non cardiac surgery within 3 weeks of BMS, 86% of those who stopped antiplatelets died
Sharma AK, Ajani AE, Hamwi SM, et al. Major noncardiac surgery
following coronary stenting: when is it safe to operate? Catheter
Cardiovasc Interv 2004;63:141–5.
Wilson SH, Fasseas P, Orford JL, et al. Clinical outcome of patients undergoing noncardiac surgery in the two months following coronary stenting. J Am Coll Cardiol 2003;42:234–40.

12. DES First generation DES elute Second generation DES elute Sirolimus
Paclitaxel
Second generation DES elute
Zotarolimus
Everolimus

13. Drug eluting stents
McFadden et al. (19) reported DES thrombosis in 3 patients undergoing surgery late (343 to 442 days) after implantation.
Nasser et al. (20) reported sirolimus-eluting stent (SES) thrombosis in 2 patients after surgery performed 4 and 21 months after SES implantation.

14. Avoid preoperative coronary stenting
Avoid preoperative coronary revascularization, unless there exists a strong and proven indication
Choose BMS if
Surgery needed from 6 weeks to 12 months
Bleeding diathesis
Patient unable or unwilling to receive long term clopidogrel
Stent selection (BMS vs DES)
Consider balloon angioplasty if surgery is needed within 6 weeks. Avoid stents
Delay surgery
Choose DES if surgery is needed after 12 months
BMS – 6 weeks
DES – 12 months
Optimize antiplatelet therapy
Continue antiplatelet therapy during surgery
Surgeons
anesthesiologists cardiologists
Education and collaboration

15. Avoiding revascularization
CARP trial
510 stable patients with CAD undergoing major vascular surgery
Randomized to revascularization (by CABG or PCI) or no revascularization
Similar incidence of postoperative MI and 27 month survival in both the groups
So, first ask the question: Is revascularization necessary?

16. Revascularization without stents (Balloon only)
Patients with acute coronary syndrome and those with profound ischemia on non invasive testing do need revascularization
Can be done without stents: Percutaneous balloon angioplasty
In this study, when surgery was done 11 days after PCI, only 1 patient died and 1 had an AMI
Gottlieb A, Banoub M, Sprung J, Levy PJ, Beven M, Mascha EJ.
Perioperative cardiovascular morbidity in patients with coronary artery
disease undergoing vascular surgery after percutaneous transluminal
coronary angioplasty. J Cardiothorac Vasc Anesth 1998;12:501– 6.

17. When surgery after Balloon angioplasty?
2002 ACC AHA guidelines
Delaying noncardiac surgery for 6 to 8 weeks was discouraged because restenosis could have occurred
Performing noncardiac surgery too early after the PCI also may be risky because acute or subacute closure after balloon angioplasty usually occurs within hours to days after the procedure.
Delay surgery for 1 week after balloon angioplasty

18. If stenting can’t be avoided
Complex lesion or inability to achieve optimal result with balloon angioplasty
Choose the right stent
Surgery needed with 12 months: Choose BMS
Surgery can be delayed for > 12 mth: DES
BMS endothelialize more rapidly than DES
Sirolimus eluting stent preferable as it requires 3 mths of antiplatelet therapy than a paclitaxel eluting stent that requires 6 mths of clopidogrel

19. Delay surgery
6 weeks BMS
12 months DES

20. Time from stent until surgery (months)
Major adverse cardiac events (%)
Bare metal stents 10
Drug eluting stents 8 6 4 2 2 4 6 8 10 12 14 16 18
Time from stent until surgery (months)

21. RISK OF PERIOPERATIVE STENT THROMBOSIS WITH DES
Stents implanted in left main coronary artery
Stents implanted in bifurcations
Greater total stent length (multiple/overlapping stents)
Heightened platelet activity (surgery, DM, malignancy)
In stent restenosis
Left ventricular dysfunction
Localized hypersensitivity vasculitis
Penetration by stent into necrotic core
Plaque disruption into non stented segment
Renal failure
Diabetes mellitus
Resistance to antiplatelets
Inappropriate discontinuation of antiplatelet medications

22. What are the steps to prevent stent thrombosis in these patients coming for non cardiac surgery?

23. Periop antiplatelet therapy
Continue dual antiplatelet thearpy during and after surgery
Discontinue clopidogrel but “bridge” the patient to surgery with Glycoprotein IIb/IIIa inhibitor or an antithrombin, and restart clopidogrel as soon as possible after surgery
Discontinue clopidogrel before surgery and restart it as soon as possible after surgery

24. Impact of aspirin on bleeding
Most studies in cardiac and vascular surgery
Safe in doses of 75 – 150 mg
Increases bleeding by a factor of 1.5, no effect on morbidity and mortality
Avoid in TURP and intracranial surgery (as bleeding in these situations can be life threatening)
Continue aspirin monotherapy in elective non cardiac surgery

25. Option 1 : Continue therapy
Dental extractions
Cataract surgery
Dermatologic surgery

26. Option 2: Bridging therapy
Bridge using short acting antiplatelet or an anticoagulant
Platelet inhibitors are the more logical choice as stent thrombosis is a platelet mediated phenomenon
Cessation of heparin in a patient not on antiplatelets can cause rebound effect and stent thrombosis

27. Bridging therapy
A shortacting GP IIb/IIIa inhibitor (tirofiban or eptifibatide) or thrombin inhibitor, or both, is substituted for clopidogrel during the perioperative period
Role
Prevent platelet aggregation
Displace fibrinogen from GP IIb/IIIa receptors
Block signaling processes

28. Bridging therapy
Tirofiban and eptifibatide are administered parenterally
Have half-lives 2 h
Eliminated by renal clearance.
Infusion rate is reduced by half in patients with reduced renal function
Platelet function returns to 60%–90% of normal after the infusion is stopped for 6–8 h.

29. When bridging therapy? Surgeries with high risk of bleeding
Intracranial
Spinal
Retinal

30. Other drugs
Reversible P2Y12 receptor antagonists are undergoing clinical trials
Cangrelor is a parenteral, reversible direct P2Y12 inhibitor
Half-life of 5–9 min allows 100% recovery of platelet function 1 h after the infusion is discontinued
4 mcg/kg/min infusion achieves complete platelet inhibition when measured at 4 min
AZD6140 is an oral, reversible direct P2Y12 receptor antagonist with a half life of 12 hrs.

31. Problems with bridging therapy
Expensive
Logistically difficult
Exposes patients to risks associated with a prolonged hospitalization
Some claim that it confers no protection against intraoperative stent thrombosis

32. Option 3: Stop antiplatelets
Neurosurgery
Restart clopidogrel after surgery
600 mg loading dose – Maximal inhibition of platelet aggregation in 2 – 4 hours (takes 6 hrs with 300 mg)
Reduces the incidence of hyporesponsiveness to platelets (which are activated due to surgery)

33. Anesthetic drugs metabolized by CYP3A4 like midazolam can irreversibly inhibit this enzyme which metabolizes clopidogrel into its active form, modulating its antiplatelet effect

34. Steps: Preoperative evaluation
Determine the type of stent: BES, SES, PES
When were stents implanted?
Determine location of stent in coronary circulation
How complicated was the revascularization?
Is there a previous history of stent thrombosis?
What antiplatelet regimen is being followed?
Determine co-morbidities?
What is the recommended duration of antiplatelet therapy for this patient?
Co-ordinate with cardiologist

35. Steps
Perform procedure in centers where there is 24 hr interventional cardiology coverage for emergency PCI

36. Intraop management Tight hemodynamic control Use of beta blockers
Good HR control
Good BP control
Decrease sympathetic outflow and therefore decrease platelet activation

37. Regional anesthesia in patients on antiplatelets
Advantages
Attenuation of hypercoagulable state
Systemically absorbed LA have antiplatelet effect
Follow ASRA guidelines
For patients receiving bridging therapy with eptifibatide or tirofiban, 8 h must elapse before a neuraxial blockade can be performed

38. Management of stent thrombosis
ST segment elevation acute myocardial infarction
Reperfusion
Thrombolytic therapy less effective than primary PCI
Platelet mediated phenomenon
Risk of bleeding
All that is required during PCI is aspirin and one dose of heparin or bivalirudin

39. Role of platelet transfusion
Transfused platelets are not inhibited by serum therapeutic levels of antiplatelets
The thrombogenic surface of stents may attract and activate donor platelets to an even greater extent than endogenous platelets
Platelet transfusions to be avoided except in instances of life threatening bleeding

40. Algorithm for patients with DES for NCS
Emergency
Semi emergency
Elective
Assess risk of bleeding
DES > 1 yr
DES < 1 yr
Low
Intermediate
High
STOP
Length of DAPT
Stop Anti PLT
Continue DAPT
> 1 yr
< 1 yr
Assess risk of thrombosis
Stop clopidogrel
Continue LD aspirin
Low
High
Proceed with surgery
Hosp Admn
? IV Anti PLT

41. Education
In a survey of anesthesiologists, 63% were not aware of recommendations about the appropriate length of time between stent placement and a subsequent surgical procedure, and one-third recommended no delay or a delay of only 1 to 2 weeks, which is insufficient for BMS, and even more so for DES
Patterson L, Hunter D, Mann A. Appropriate waiting time for
noncardiac surgery following coronary stent insertion: views of Canadian
anesthesiologists. Can J Anaesth 2005;52:440 –1

42. Take home points Many patients come for non cardiac surgery after PCI
Stent thrombosis is a catastrophe
Remember the stepwise approach to the issue

43. Thank you Avoid preoperative coronary stenting
Stent selection (BMS vs DES)
Thank you
Delay surgery
Optimize antiplatelet therapy
Education and collaboration