Perioperative care: beta blockers and a little beyond

Perioperative care: beta blockers and a little beyond DeeptiRao

Objectives • Recognize ACC/AHA guidelines for cardiac risk assessment • Understand the controversy surrounding the use of perioperative beta blockers • Understand the complexities and tools used to make decisions regarding perioperative management of antithrombotic therapy

Cardiac evaluation and care algorithm for noncardiac surgery

Major predictors that require intensive management and may lead to delay in or cancellation of the operative procedure--per ACC/AHA guideline summary • Unstable coronary syndromes including unstable or severe angina or recent MI • Decompensated heart failure including NYHA functional class IV or worsening or new-onset HF • Significant arrhythmias including high grade AV block, symptomatic ventricular arrhythmias, supraventricular arrhythmias with ventricular rate > 100 bpm at rest, symptomatic bradycardia, and newly recognized ventricular tachycardia • Severe heart valve disease including severe aortic stenosis or symptomatic mitral stenosis

ACC/AHA guideline summary: Cardiac risk stratification for noncardiac surgical procedures High risk (reported risk of cardiac death or nonfatal myocardial infarction [MI] often) Aortic and other major vascular surgery Peripheral arterial surgery Intermediate risk (reported risk of cardiac death or nonfatal MI generally 1 to 5 percent) Carotid endarterectomy Head and neck surgery Intraperitoneal and intrathoracic surgery Orthopedic surgery Prostate surgery Low risk* (reported risk of cardiac death or nonfatal MI generally less than 1 percent) Ambulatory surgery Endoscopic procedures Superficial procedure Cataract surgery Breast surgery

Estimated energy requirements for various activites • Take care of self • Eat, dress, use toilet • Walk indoors around the house • Walk a block or 2 on level ground • Do light work around the house like dusting or washing the dishes • Climb a flight of stairs or walk up a hill • Walk on level ground at 4 mph • Run a short distance • Do heavy work around the house like scrubbing floors • Participate in moderate activities like golf or dancing • Participate in strenuous activities like swimming or skiing

Revised Goldman cardiac risk index (RCRI) Six independent predictors of major cardiac complications High-risk type of surgery (includes any intraperitoneal, intrathoracic, or suprainguinal vascular procedures) History of ischemic heart disease (history of MI or a positive exercise test, current complaint of chest pain considered to be secondary to myocardial ischemia, use of nitrate therapy, or ECG with pathological Q waves; do not count prior coronary revascularization procedure unless one of the other criteria for ischemic heart disease is present) History of compensated or prior HF History of cerebrovascular disease Diabetes mellitus requiring treatment with insulin Preoperative serum creatinine >2.0 mg/dL (177 mol/L)

Perioperative beta blockers • Perioperative cardiac ischemia • 1-10% of patients older than 50 • Causes • Increased inflammatory mediators • increased sympathetic tone, catecholamine surge • oxygen supply/demand mismatch in heart • Hypercoagulability and decreased fibrinolytic activity • Acute plaque rupture, thrombosis and occlusion How do we prevent this?

Perioperative beta blockers • How do they work? • Decrease cardiac oxygen demand • Antiarrhythmic • Limit sympathetic and neuroendocrine responses to stress • May limit free radical production/inflammation

Perioperative Beta blockers • 1970’s, 1980’s,1990’s • Small trials showing bb reduced risk of periop cardiac events in selected patients with known or suspected cardiac events • Use endorsed by Leapfrog group, AHRQ and National Quality Forum

The effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery—DECREASE • Poldermans, et al 1999 • Randomized 112 “high risk” patients to either standard care or standard care plus bisoprolol • High risk: Risk factors and positive dobutamine echo • Not blinded except to adverse events committee/no placebo • Undergoing major vascular surgery

The effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery—DECREASE • Started bisoprolol at doses of 5mg, increased to 10mg if heart rate >60 bpm 1 week later. • Started bisoprolol average of 37 days prior to surgery (!!!!!!), at least 1 week prior • In hospital • If symptoms or signs of perioperative mi with tachycardia developed, patients received beta-bl (4) • If unable to take bisoprololpostop, heart rate monitored q1hr and given metoprolol iv if hr>80 bpm • Medication withheld if hr<50 bpm or sbp<100 mmhg

The effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery—DECREASE • Followed patients for 30 days postop • 12 lead EKG and ck-mb days 1,3,7 postop

The effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery—DECREASE • For death from cardiac cause: • AAR 13.6% • RRR 80% • NNT 7 • For nonfatal MI: (no events in bisoprolol group) • AAR 17% • NNT 6

The effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery—DECREASE • On the basis of our results, we recommend that high-risk surgical patients receive beta-blockers perioperatively, beginning one to two weeks before surgery. The goal should be to reduce the heart rate to less than 70 beats per minute preoperatively and to less than 80 beats per minute in the immediate postoperative period. Therapy should be continued for at least two weeks postoperatively. • An alternative to this approach would be to omit preoperative noninvasive cardiac testing and prescribe a beta-blocker perioperatively for all patients with clinical risk factors who are undergoing high-risk surgery. • Although our results applied to patients who were undergoing major vascular surgery, we recommend that high-risk patients undergoing other types of noncardiac surgery receive a beta-blocker perioperatively.

The effect of Bisoprolol on Perioperative Mortality and Myocardial Infarction in High-Risk Patients Undergoing Vascular Surgery—DECREASE • So what are some of the problems with the study?

Early Beta-blocker trials • Small in size (63-200) • Used surrogate end points • Study designs were flawed (cohort, unblinded, retrospective)

Perioperative beta-blocker therapy and mortality after major noncardiac surgery • Lindenauer, et al 2005 • Retrospective cohort study • Used data from Premier’s Perspective, database of small to mid sized nonteaching hospitals • Adults undergoing major noncardiac surgery • Compared those who received beta-blockers in first 1-2 days hospitalization vs. not

Perioperative beta-blocker therapy and mortality after major noncardiac surgery • 663,635 eligible patients, 122,338 received beta-blockers

Perioperative beta-blocker therapy and mortality after major noncardiac surgery

Perioperative beta-blocker therapy and mortality after major noncardiac surgery • No significant benefit of perioperative beta-blockade until approx 3 RCRI • What are some problems with this trial?

Recent trials-preop initiation of beta blockade in intermediate risk patients • Metoprolol after Vascular Surgery (MaVS) • No difference in cardiac events • Increase bradycardia and hypotension requiring treatment • Diabetic Post Operative Mortality and Morbidity • Perioperative Beta Blockade (POBBLE)

Effects of extended-release metoprololsuccinate in patients undergoing non-cardiac surgery • Devereaux, et al 2008 • POISE (PeriOperative Ischemic Evaluation) • Small non-cardiac surgery trials suggested that β blockers might reduce the occurrence of major cardiovascular events, although these trials had methodological limitations. • Recent, moderate sized randomised controlled trials of perioperative β blockers did not demonstrate benefit. • To further investigate the effects of perioperative β-blocker therapy, a randomised controlled trial comparing the effect of extended-release metoprololsuccinate with that of placebo on 30-day risk of major cardiovascular events in patients with, or at risk of, atherosclerotic disease who were undergoing non-cardiac surgery.

Effects of extended-release metoprololsuccinate in patients undergoing non-cardiac surgery • 8351 patients with or at risk for atherosclerotic disease • Patients treated with metoprolol extended release • First dose 2-4 hours prior to surgery (100 mg) • Within 6 hours post op (100mg) • 12 hours after surgery (200mg/day) • If could not take po, iv metoprolol given • Continued for 30 days

Effects of extended-release metoprololsuccinate in patients undergoing non-cardiac surgery • Ekg 6-12 hours postop and days 1,2,30 • Ck/mb or troponin 6-12 hours postop and days 1,2,3

Effects of extended-release metoprololsuccinate in patients undergoing non-cardiac surgery • Primary endpoint—cardiovascular death, nonfatal mi, nonfatal cardiac arrest • ARR 1.1% • RRR 16% • NNT 90 • MI • ARR 1.5% • RRR 26% • NNT 66 • CVA • NNH 125 • Death • NNH 200

Effects of extended-release metoprololsuccinate in patients undergoing non-cardiac surgery Our results suggest that for every 1000 patients with a similar risk profile undergoing non-cardiac surgery extended-release metoprolol would prevent: • 15 patients from having a myocardial infarction, • 3 from undergoing cardiac revascularisation, • 7 from developing new clinically significant atrial fibrillation. The results also suggest that extended-release metoprolol would result in: • 8 deaths, • 5 patients having a stroke, • 53 experiencing clinically significant hypotension, and • 42 experiencing clinically significant bradycardia

Effects of extended-release metoprololsuccinate in patients undergoing non-cardiac surgery Our results highlight the risk in assuming a perioperative β-blocker regimen has benefit without substantial harm before the availability of a large randomised controlled trial establishing such findings. Our post-hoc multivariate analyses suggest that clinically significant hypotension, bradycardia, and stroke explain how β blockers increased the risk of death in this trial. Sepsis or infection was the only cause of death that was significantly more common among patients in the metoprolol group than in those in the placebo group.

Effects of extended-release metoprololsuccinate in patients undergoing non-cardiac surgery • What are some of the problems with this trial?

Perioperative Beta blockers • Many of the recent systematic reviews on this topic are “overwhelmed” by the POISE trial, include early trials which are of poor quality, and hampered by the variety of beta blocker chosen and protocol.

So what now?

2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Class 1 recommendations Beta blockers should be continued in patients undergoing surgery who are receiving beta blockers for treatment of conditions with ACCF/AHA Class I guideline indications for the drugs. (Level of Evidence: C)

2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Class IIa Recommendations • Beta blockers titrated to heart rate and blood pressure are probably recommended for patients undergoing vascular surgery who are at high cardiac risk owing to coronary artery disease or the finding of cardiac ischemia on preoperative testing (4,5). (Level of Evidence: B) • Beta blockers titrated to heart rate and blood pressure are reasonable for patients in whom preoperative assessment for vascular surgery identifies high cardiac risk, as defined by the presence of more than 1 clinical risk factor.* (Level of Evidence: C) • Beta blockers titrated to heart rate and blood pressure are reasonable for patients in whom preoperative assessment identifies coronary artery disease or high cardiac risk, as defined by the presence of more than 1 clinical risk factor,* who are undergoing intermediate-risk surgery (6). (Level of Evidence: B)

2009 ACCF/AHA Focused Update on Perioperative Beta Blockade • So only those patients already on beta-blockade or those of high risk who can have their beta-blocker titrated to effect • Why? We are not sure how to use safely. • Patient (low vs high risk) • Type of beta blocker (high beta-1 selectivity) • Dose • Heart rate control without hypotension • Timing of initiation • Anti-inflammatory and plaque stabilizing properties may take days to develop

Surveillance and diagnosis of perioperative mi • Per ACC guidelines: • In patients with high or intermediate clinical risk and undergoing high or intermediate risk surgery • ECG postop, day 1 and day2 • In patients without documented CAD: • Only those with perioperative cardiac dysfunction

Managing the patient on warfarin undergoing an elective surgery---from Jaffer, talk

Is interruption of my patient’s antithrombotic therapy necessary? • Low risk of bleeding for which coumadin can be continued: • Minor dental procedures • Minor dermatologic procedures • Cataract removal • Arthrocentesis • EGD/colonoscopy with or without biopsy

Suggested Patient Risk Stratification for Perioperative Arterial or Venous Thromboembolism

What is the procedural risk of bleeding? • High Bleeding Risk: • CABG or valve replacement surgery • Intracranial or spinal surgery • AAA repair, peripheral artery bypass, and other major vascular surgery • Major orthopedic surgery such as hip or knee replacement • Reconstructive plastic surgery • Major cancer surgery • Prostate and bladder surgery

What is the procedural risk of bleeding? • Perioperative anticoagulation should be undertaken with caution: • Resection of colonic polyps esp sessile polyps>2 cm in diameter • Biopsy of prostate or kidney • Cardiac pacemaker or defibrillator implantation

Perioperative risk of TE • Rate of TE approx 1.6% • Risk of VTE 100 fold greater during the perioperative period relative to the nonoperative period • Surgical milieu induces a hypercoagulable state • However major bleeding is also an issue approx 3% • Full dose bridging leads to 4-6 fold increase in major bleeding…wait couple of days prior to starting full dose and just use prophylactic dose?

Perioperative care: beta blockers and a little beyond