Update on Perioperative Medicine Hugo Quinny Cheng, MD Division of Hospital Medicine University of California, San Francisco

Update on Perioperative Medicine Who needs a preoperative cardiac stress test? What are the benefits and risks of -blockers? Can statins prevent postoperative MI? When can patients with stents go to the OR? How should chronic anticoagulation be managed? Should arthroscopy patients get DVT prophylaxis? Is preoperative smoking cessation beneficial?

Preoperative Stress Testing A 65 y.o. man with a history of coronary artery disease and long-standing diabetes will undergo radical prostatectomy. He had a myocardial infarction in 2003, but now has no cardiac symptoms. Meds: lovastatin, atenolol, glyburide, benazepril, ASA Exam: BP=115 / 70 HR=60; normal heart & lung exam ECG: NSR, LVH, otherwise normal

65 y. o. man s/f radical prostatectomy 65 y.o. man s/f radical prostatectomy. History of remote MI and long-standing diabetes. He is currently asymptomatic. Stress test prior to surgery No stress test is needed Make him carry a copy of Harrison’s up a flight of stairs

“New Standard” Cardiac Risk Index Predictors: Higher risk operation* Ischemic heart disease Congestive heart failure Diabetes requiring insulin Creatinine > 2 mg/dL Stroke or TIA Predictors Complications** 0 0.5% 1 1.3% 2 4% 3 or more 9% * Defined as intraperitoneal, intrathoracic, or suprainguinal vascular surgery ** Defined as MI, pulmonary edema, cardiac arrest, complete heart block Lee, et al. Circulation, 1999

Control HR & go to OR (IIa) 2007 ACC/AHA Guideline Good Functional Capacity? Go to OR yes ≥ 3 predictors 1 or 2 predictors no predictors* no or ? Go to OR Control HR & go to OR (IIa) Vascular surgery? Consider stress test if results will change management (IIa) no yes or (IIb) * CAD, CHF, DM, CKD, CVA/TIA

770 vascular patients with 1 or 2 of following: Age > 70, MI, angina, CHF, DM, stroke / TIA, Cr > 1.8 No stress test (n = 384) Stress test (n = 386) 34 with extensive ischemia (9%); 12 had PCI or CABG 352 with no or limited ischemia 1.8% 30-day CV Death or MI 2.3% 1.1% 15% Poldermans et al. JACC, 2006

Extensive Ischemia Predicts High Risk 101 patients undergoing vascular surgery, all with ≥ 3 risk predictors and stress test showing extensive ischemia Poldermans, et al. JACC, 2007

Reducing Risk with Medical Management A 75 y.o. woman will undergo hemicolectomy next week. She has a history of diabetes and a remote stroke, but no current cardiovascular symptoms. Start a -blocker Start a statin Start both -blocker & statin No new medications needed

Cardiac Mortality & Nonfatal MI (%) - 111 patients undergoing vascular surgery - All had ischemic potential on dobutamine echo - Randomized to beta-blocker or standard care 40 Cardiac Mortality & Nonfatal MI (%) 7 14 21 28 10 20 30 Days after Surgery Bisoprolol Standard Care Poldermans, et al. NEJM, 1999

POISE: PeriOperative Ischemia Evaluation 8351 patients with s/f major noncardiac surgery CAD, CHF, CVA/TIA, CKD, DM, or high-risk surgery Not already taking -blocker Metoprolol XL (immediately preop until 30 days postop) Placebo Patients followed for 30 days after surgery: 1° Endpoint: cardiac mortality & nonfatal arrest or MI Poise Study Group. Lancet, 2008

Poise Study Group. Lancet, 2008 POISE: Results Metoprolol XL: Reduced cardiac events (mostly nonfatal MI) but Increased risk of stroke & total mortality Poise Study Group. Lancet, 2008

POISE: Treatment Protocol 2-4 h OR 0-6 h 12 h 1st dose Metoprolol 100 mg XL* 2nd dose Metoprolol 100 mg XL* 3rd & daily dose Metoprolol 200 mg XL*^ * Study drug held for SBP < 100 or HR < 50 ^ Daily dose reduced to 100 mg if persistent bradycardia or hypotension

Poldermans et al. Presented at ESC, 2008 DECREASE III 497 statin naive patients s/f vascular surgery Fluvastatin XL 80 mg/day Started > 1 month preop Continued > 1 mo postop Placebo Patients followed for 30 days after surgery: Clinical Endpoint: cardiac death or nonfatal MI Poldermans et al. Presented at ESC, 2008

Poldermans et al. Presented at ESC, 2008 DECREASE III: Results Fluvastatin XL: Reduced the composite outcome of cardiac death & nonfatal MI No difference in rates of LFT or CPK elevation Poldermans et al. Presented at ESC, 2008

DECREASE-IV 1066 patients with estimated 1-6% risk of postoperatived cardiac complications Randomized to: Bisoprolol Fluvastatin XL Bisoprolol + Fluvastatin Double placebo Drugs started average 34 days prior to surgery Primary endpoint: 30-day CV death or nonfatal MI

DECREASE-IV Results Bisoprolol-treated patients had fewer complications Trend towards benefit with statins No safety issues * P < .002 * * Dunkelgrun et al. Ann Surg, 2009

Perioperative -blockers in 2009 Strong indications: Already using -blocker to treat angina, HTN, arrhythmia Patients with ischemic potential having vascular surgery Possible indications: Patients with ischemic potential having high-risk nonvascular surgery (e.g., > 5 hours or > 500 cc blood loss) Multiple risk predictors* in vascular or other high-risk surgery (*Coronary disease, renal insufficiency, diabetes) Titrate dose up gradually (rarely start immediately preop)

Statins: 2007 ACC/AHA Guideline Definite indications (class I): Continue statin if already taking prior to surgery Probable indications (class IIa): All vascular surgery patients Possible indications (class IIb): At least one risk predictor* in any intermediate risk surgery *Coronary disease, renal insufficiency, diabetes, CVA/TIA

Delaying Surgery After Coronary Stent A woman falls and suffers a cervical spine fracture. One month ago, she received a sirulimus-eluting stent for stable angina. The neurosurgeon won’t operate unless aspirin and clopidogrel are held for her surgery. Non-operative management in a halo for next 2 months is offered as an alternative. What do you recommend to the patient & surgeon?

Patient with recently placed drug-eluting stent has a c-spine fracture Patient with recently placed drug-eluting stent has a c-spine fracture. Surgeon won’t operate unless aspirin & clopidogrel are held perioperatively. Hold ASA & clopidogrel Hold ASA & clopidogrel but bridge with heparin Keep her in a halo for next 2 months

Does Heparin Bridge Prevent Stent-related Complications? Prospective study of 103 patients with coronary stent placed within 12 months having noncardiac surgery Antiplatelet drugs continued or held < 3 days All patients received heparin drip or enoxaparin 14% of patient stented within 35 days of surgery suffered cardiac death or MI, or needed re-do PCI Conclusion: High rate of cardiac complications even when bridging anticoagulants used Vicenzi et al. Br J Anaesth, 2006

ACC/AHA Guidelines for PCI Avoid PCI unless patient has independent indications Avoid PCI if patient may have upcoming surgery that requires stopping dual antiplatelet therapy Delay elective surgery in patients with recent PCI Balloon angioplasty: 2 - 4 weeks Bare metal stent: 4 weeks Drug eluting stent: 12 months If clopidogrel must be stopped, try to continue ASA No evidence for bridging with other agents

Managing Perioperative Anticoagulation Two patients who take coumadin underwent THA. One has atrial fibrillation due to HTN. The other has a mechanical AVR. Neither has a history of stroke or any other comorbidity. Heparin bridge for AVR only Heparin bridge for AF only Heparin bridge for both Heparin bridge for neither

Two patients who take coumadin underwent THA. One has AF due to HTN Two patients who take coumadin underwent THA. One has AF due to HTN. The other has a mechanical AVR. Neither has a history of stroke any other comorbidity. Heparin bridge for AVR only Heparin bridge for AF only Heparin bridge for both Heparin bridge for neither

Thromboembolic Risks with Non-rheumatic Atrial Fibrillation CHADS-2 Score: 1 point for CHF, HTN, Age > 75, DM 2 points for Stroke/TIA Score 0 - 2: < 5% annual stroke risk Score 3 - 4: 5-10% Score 5 - 6: > 10% Annual Stroke Risk Albers et al. Chest, 2001

Thromboembolic Risks with Mechanical Valves Annual Incidence Cannegieter, et al. Circulation, 1994

Effect of Mechanical Valve Location & Design on Thromboembolic Risk Aortic RR = 1.0 Mitral RR = 1.8 Valve Design: Caged Ball RR = 1.0 Tilting Disk RR = 0.7 Bi-leaflet RR = 0.6 Cannegieter, et al. Circulation, 1994

Perioperative Anticoagulation: 2008 ACCP Guidelines Atrial Fibrillation Mechanical Valve Recommend CHADS2 = 5-6, recent CVA, or rheumatic AF Any MVR; older (caged-ball or tilting disc) AVR; recent CVA Full dose heparin bridge CHADS2 = 3-4 Bileaflet AVR plus one additional stroke risk factor Full or low dose heparin CHADS2 = 0-2 Bileaflet AVR without AF or other stroke risk factor Low dose or no heparin Full dose = therapeutic dose of heparin IV or LMWH SC Low dose = DVT prophylaxis dose of heparin SC or LMWH SC

DVT Prophylaxis Which DVTs matter? Symptomatic versus asymptomatic Proximal versus distal 2008 American College of Chest Physicians: Weights DVT risk greater than bleeding risk Treats asymptomatic DVT as important

RCT of LMWH in Knee Arthroscopy Background: 2008 ACCP guidelines recommend LMWH if additional risk factors for DVT are present. Study Design: ~1300 patients randomized to compression hose or LMWH x 7 days after knee arthroscopy. All patients underwent screening ultrasound. Results: Combined incidence of death or any clot reduced in patients receiving LMWH (0.9% vs 3.2%). Almost all clots were either asymptomatic or distal. Non-significant trend for increased bleeding. Conclusions: LMWH superior to compression hose after knee arthroscopy (NNT = 43). Impact on symptomatic DVT small. Camporese et al. Ann Intern Med, 2008.

Preoperative Smoking Cessation A middle-aged man will undergo repair of a ventral hernia in 1 month. He currently smokes one pack of cigarettes per day. How do you counsel him? Quit smoking now to prevent postoperative complications. It’s always good to quit, but it’s too late to affect your risk of complications. Don’t stop smoking! You will actually increase your surgical risk by quitting!

Effect of Smoking Cessation Time since quitting p < .001 Complication Rate (%) Warner, Anesthesiology 1984

Preoperative Smoking Cessation Counseling RCTs of Preoperative Smoking Cessation Counseling: 120 patients undergoing arthroplasty in 6-8 weeks 117 patients undergoing various operations in 4 weeks 60 patients undergoing colorectal resection in 2-3 weeks Intervention: Smoking cessation counseling at weekly meetings (or by telephone) & offer free nicotine replacement products Outcomes: Postop complications, especically wound related (e.g., dehiscence, infection, hematoma)

Smoking Cessation 6-8 Weeks Before TKA or THA Moller et al. Lancet, 2002

Smoking Cessation 4 Weeks Before Surgery Lindstrom et al. Ann Surg, 2008.

Smoking Cessation 2-3 Weeks Before Colorectal Surgery Sorensen, et al. Colorectal Dis, 2003

Take Home Points Reserve stress testing for higher risk patients -- Limited ischemia ok, but extensive ischemia = high risk Start -blocker cautiously & only in high risk patients Delay surgery in patients with recent stent placement Individualize thrombotic risk assessment when managing perioperative anticoagulation Consider LMWH for knee arthroplasty patients Smoking cessation for ≥ 4 weeks may be beneficial