ANESTHESIA FOR NON CARDIAC SURGERY IN PATIENTS WITH

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

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

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

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

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

Scoring system for LST Risk score for prediction of LST Renal failure Bifurcation lesion Diabetes Brachytherapy Each 20% fall in EF Low 0 6 points 4 points 2. 5 points 0. 25 points Medium 6 High 9 Very High 13 19

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

Discontinuation of Aspirin and Clopidogrel Loss of antiplatelet effect Rebound increase in COX 1 and TXB 2 Increased thrombin and decreased fibrinolysis Surgery ⁺ Prothrombotic state Loss of antiinflammatory protection by clopidogrel Stent thrombosis & MI

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

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.

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

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

Drug eluting stents Mc. Fadden 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.

Avoid preoperative coronary Choose BMS if revascularization, unless 6 Surgery needed from thereweeks tostrong and exists a 12 months proven indication Bleeding diathesis Patient unable or unwilling to receiveballoon Consider long term clopidogrel angioplasty if surgery is BMS – 6 within 6 needed DES if Choose weeks. –Avoid stents surgery ismonths DES 12 needed after 12 months Continue antiplatelet therapy during surgery Surgeons anesthesiologists cardiologists

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?

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.

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

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

Delay surgery 6 weeks BMS 12 months DES

Major adverse cardiac events 10 (%) Bare metal stents Drug eluting stents 8 6 4 2 0 0 2 4 6 8 10 12 14 Time from stent until surgery (months) 16 18

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

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

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

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

Option 1 : Continue therapy Dental extractions Cataract surgery Dermatologic surgery

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

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

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.

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

Other drugs Reversible P 2 Y 12 receptor antagonists are undergoing clinical trials Cangrelor is a parenteral, reversible direct P 2 Y 12 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 AZD 6140 is an oral, reversible direct P 2 Y 12 receptor antagonist with a half life of 12 hrs.

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

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)

Anesthetic drugs metabolized by CYP 3 A 4 like midazolam can irreversibly inhibit this enzyme which metabolizes clopidogrel into its active form, modulating its antiplatelet effect

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

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

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

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

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

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

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

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

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

Thank you