Anesthesia for patients with coronary artery disease

undergoing non-cardiac surgery

Gamal Fouad S Zaki, MDProfessor of

AnesthesiologyAin Shams University

gamalzaki@gmail.com

In Non-Cardiac Surgery:• Stress associated with surgery

is extreme & persistent• 4-5% of patients with or at risk

of heart disease suffer cardiac complications perioperatively

• Perioperative MI carries a 15-25% hospital mortality Shah 1990, Badner 1998, Kumar 2001

• Cardiac arrest has a hospital mortality of 65% and is an independent predictor of death during the following 5 yrs

Epidemiology

• Incidence of CAD on the rise• Aging population: age group >65 years:

– will increase by 25% in next 30 years (USA)– Largest number of surgical procedures

• Number of non-cardiac surgical procedures in older persons will increase

• Prevalence of CAD increases with age• More likely to get patient with CAD in OR

Historical Background

1952

1977

1986

1982+

1985-6

1990

1995+

1996

Late90s

Perioperative MI identified as a problem

Goldman Cardiac Risk Index

Detsky: Modified Cardiac Risk Index

Specialized tests for risk stratification

Intraoperative risk factors identified

Postop Ischemia main outcome predictor

β-Blockers fight ischemia

ACC/AHA Guidelines

From Risk Stratification to Risk Modification

Myocardial Oxygen Balance

Supply Demand

• Coronary blood flow

CPP=AoDP-LVEDP

• Arterial O2 Content

• Inotropic state

• Systolic wall tension

• Heart Rate

Slow, empty, well perfused

Supply ischemia: hemodynamically silent

Myocardial Oxygen Imbalance

Supply

Demand

• Tachycardia / hypotension• Increase LVEDP

• Coronary stenosis

• Coronary A (graft) spasm

• Plaque erosion/rupture/triggers

• Tachycardia

• Increase Contractility

• Hypertension

Pathology of Atheroma

Foam Cells

T-Lymphocytes

Triggers of Plaque Rupture:

• Smoking

• Hypercholesterolemia

• Inflammatory Response

• Shear Stress

Pathophysiology of Perioperative MI• Unknown:

– Myocardial O2 supply/demand imbalance (perioperative stress)

– Rupture of Atheromatous plaques:Dawood MM, Gutpa DK, et al. Pathology of

fatal perioperative myocardial infarction: implications regarding pathophysiology and prevention. Int J Cardiol 1996;57:37-44.

• Triggers of plaque rupture: hemodynamic sheer stress, coronary spasm, plaque ischemia and inflammatory process

• Perioperative factors: systemic inflammatory response, sympathetic hyperactivity, and hypercoagulability (platelet hyperaggregability)

Preoperative assessment

Goals:• Identify high risk patients who may benefit

from pharmacologic optimization and/or revascularization

• Plan for intraoperative management• Plan for postoperative management• Produce a risk assessment useful for

patient and surgeon

Preoperative Preparation

Components:• History / Examination• Non-Invasive Testing• Preoperative Optimization:

– Control medical conditions: HTN, BA– Employ pharmacologic protection– Minimal role for preoperative revascularization

CABG, Angioplasty

Lee Revised Cardiac Risk Index

• High risk surgical procedure• History of ischemic heart disease• History of congestive heart failure• History of TIA or stroke• Preoperative insulin therapy• Preoperative serum creatinine >2.0 mg/dL

• Update 2002• Based on “Clinical Predictors” functional capacity,

underlying medical conditions, surgicalrisk• Intervention rarely necessary to reduce surgical

risk unless indicated w/o surgery• Preoperative Evaluation: not “Clearance”• Produce risk profile useful for making treatment

decisions by: patient, surgeon, anesthesiologist• Testing: only when likely to influence treatment• Modified Cardiac Risk Index: Detsky

History: Exercise Tolerance

Reilly et al. Self-reported exercise tolerance and the risk of serious perioperative complications. Arch Intern Med. 1999;159:2185-92

• 600 non-cardiac surgery pts• Questioned about number of blocks they could

walk, or flights of stairs they could climb• Poor exercise tolerance: < 4 blocks or 2 flights,

(< 6 METs: metabolic equivalents)more periop complications (20.4% vs. 10.4%), more myocardial ischemia, cardiovascular and neurologic complications

• If assessment not possible (knee): further testing

Cardiac stress testing

• Why does inducible ischaemia on stress testing not predict perioperative events satisfactorily?

• Stress testing predicts intermediate and long term prognosis of CAD patients.

(Lee, Boucher. N Engl J Med 2001;344:1840)

• The culprit is extrapolating this to short term perioperative (96 hrs) outcome

• Difference may be in the etio-pathology: plaque rupture vs. supply/demand imbalance

Dobutamine Stress Echocardiography

• Commonly chosen, good predictive value• New or worsened RWMA: positive• Represent areas at risk of ischemia• Dynamic assessment of LV function• Patients with RWMA in 1-4 segments

benefit from beta blockers

>5 segments do not benefit, need intervention. Boersma et al. JAMA 2001

• Low predictive value of positive non-invasive tests, preop revascularization not beneficial

• Trigger a cascade of riskier interventions• Increased cost, delayed surgery• β-blockers and may be statins shown to

reduce perioperative ischemia• Need to shift emphasis from risk stratification

to risk modification: drugs

Grayburn et al. Cardiac events in patients undergoing noncardiac surgery: shifting the paradigm from noninvasive risk stratification to therapy. Ann Intern Med 2003;138:506

“The paradigm is shifting from predicting which patient is at high risk for having a perioperative cardiac event to minimizing the likelihood of such an event with specific perioperative pharmacologic therapy”

Preoperative Revascularization

• prior CABG confers protection against perioperative cardiac events Paul SD, Eagle KA. Med Clin N Amer 1995

• Not recommended for all high risk patients for non-cardiac surgery. Combined risks of CABG followed by non-cardiac surgery is greater than surgery alone.

• Angioplasty: not recommended before non-cardiac surgery, angioplasty within one month of non-cardiac surgery associated with increased complications and death. Kaluza et al. Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am Coll Cardiol 2000;35:1288-94

• ACC/AHA Guidelines recommended waiting a minimum of 2-4 weeks after Angioplasty

Pharmacologic Optimization

• β-adrenergic blockers• α2-adrenergic agonists• Nitroglycerine: IV, Transdermal??• Calcium channel blockers• Antiplatelet drugs• Statins (HMG-CoA Reductase Inhibitors) • ACE Inhibitors• LMWH

• Design: RCT; 200 Veterans for non-cardiac surgery

• Inclusion: Known CAD or 2 or more CAD risk factors.

• Exclusion: CHF, 3rd degree AVB, Bronchospam, HR<55 or SBP<100

• Intervention:– Perioperative: Atenolol 5mg given IV on call to OR.

Repeated 5 minutes later.– Postoperative: Same regimen repeated immediately

post-op. Starting on POD#1 Atenolol 50-100mg PO qd (or placebo) was given.

• Outcome:– Primary: All cause of mortality at D/C and at 2 years.– Secondary: Survival free from MI, unstable angina,

CHF, need for revascularization.• Results:

– 6 in-hospital deaths, including 3 from PMI (2 in placebo group and 1 in atenolol) NS

– 30 deaths during 2 years follow-up including 21 deaths in placebo and 9 in atenolol.

Overall Survival in 2 Years after Noncardiac Surgery among 192 Patients in Atenolol and Placebo Groups Who Survived to Hospital Discharge.

Event-free Survival in 2 Years after Noncardiac Surgery in 192 patients in Atenolol and Placebo Groups who Survived to Hospital Discharge

• Design: RCT 112 patients• Inclusion: abdominal aortic or infrainguinal arterial reconstruction

with:• Age>70, angina, prior MI, CHF, ventricular arrhythmias, diabetes,

class III symptoms AND• Dobutamine echo → stress induced wall motion abnormalities AND• Not on a beta blocker already, no extensive resting wall motion

abnormalities, no evident LM or 3VD.Intervention:

Bisoprolol 5mg qd (or placebo) started at least 1 week prior to surgery; increased to 10mg if HR>60, continued postoperatively Stopped for HR<50 or SBP<100.Endpoints:Death from cardiac causes or nonfatal MI

Results• Mortality: 9 (17%) cardiac deaths in placebo arm vs 2

(3.4%) in bisoprolol arm p=.002 ARR 13.5%; NNT=7.• Nonfatal MI: 9 (17%) nonfatal MIs in placebo group and

0 in bisoprolol group ARR 17%; NNT=6• Combined endpoint 34% in placebo arm suffered cardiac

death or nonfatal MI vs 3.4% in the bisoprolol group ARR 31%; NNT=3

Advantages over Mangano’s study:

Patient homogeneity. Higher risk patientsExclusion of prior beta blocker use. Use of oral β-blocker

Kaplan-Meier estimates of cumulative percentage of patients who died of cardiac causes or had a non-fatal MI during perioperative period.

Retrospective study of 800,000 major noncardiac surgery pts, of whom 18% received BB in the first 2 hospital days.Perioperative BB associated with a reduced risk of in-hospital death among high-risk (RCRI), but not low-risk, patients. Patient safety may be enhanced by increasing the use of beta-blockers in high-risk patients.

Intraoperative Management Monitoring: • ECG• Non-Invasive BP• Temperature• Invasive Blood Pressure: Arterial line• CVP• TEE• PA Catheter ?

Intraoperative Management Monitoring: ECG• V5 most sensitive London et al. Anesthesiol 1988

• V4 most sensitive Landesberg et al. Anesthesiol 2002

• Two or 3 precordial leads will detect >90% of ischemia from 12 leads

• OR monitors: only one precordial lead• Automated ST-segment analysis of at least 2

leads considered standard.

Intraoperative Myocardial Ischemia: Localization by continuous 12-lead electrocardiography. London M et al. Anesthesiology 1988

Landesberg et al. Anesthesiol 2002Histogram showing the incidence in which prolonged ischemia was first noted by each lead at the onset of ischemia in all 38 longest ischemic events and in the 12 ischemic events that progressed to MI

Landesberg et al. Anesthesiol 2002 Histogram showing the incidence of all leads demonstrating greater than 1 mm relative ST deviation during peak ischemia and the lead with maximal ST deviation in the 12 patients with myocardial infarction.

Automated ST-segment Analysis

I-point J-point J+60mS

Intraoperative Management Monitoring: TEE

Regional function is evaluated in terms of:

Wall Motion (endocardial excursion)

& / or

Wall Thickening

Intraoperative Management: Regional or General Anesthesia• Long lasting debate• No scientific evidence supporting either• More important: sound physiologic goals:

Hemodynamic stability, normothermia, avoidance of anemia

• Although 50% of ECG ischemia is hemodynamically silent, there is association between Tachycardia and both intraoperative and postoperative ischemia

Intraoperative Management: Regional or General Anesthesia• Opioid based gives hemodynamic stability

but may require postoperative ventilation• Often GA + epidural block• Volatile Agents: possess Cardioprotective

properties, “Anesthetic Preconditioning”: reduce infarct size, attenuate endothelial dysfunction: open mitochondrial ATP sensitive K channel: mito KATP

• Only Epidural Anesthesia/Analgesia with local anesthetics+opioids capable of attenuating neuroendocrine stress response

Cardiac Troponin I in the SEVO and Propofol Groups

SEVO Propofol

Volatile agents and opioids induce preconditioning

Anesthetic Postconditioning

Myocardial EdemaInfarct Size

LAD Ligation in Anesthetized dogs

Intraoperative Management: Regional or General AnesthesiaRodgers A. Reduction of postoperative mortality and

morbidity with epidural or spinal anaesthesia: results from overview of randomised trials.BMJ 2000; 321(7275): 1493

• Meta-analysis of 141 trials, 9559 patients• Mortality reduced by 1/3 with neuraxial

blockade 103/4871 vs. 144/4688 patients• Decreased odds of DVT(44%), PE (55%),

transfusion (50%), pneumonia (39%), and respiratory depression (59%) (all p<0.001)

Intraoperative Management: Regional or General Anesthesia

Rigg JR. Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial. Lancet 2002; 359(9314): 1276-82

• Prospective trial, with1 of 9 comorbid states, 915 patients, major abdominal surgery

• Randomized: Epidural + General A with postop epidural analgesia (72 hrs) vs. General A

• 30 day Mortality: 23/447 Epidural vs. 19/441 control• No difference in mortality and major morbidity• Significant reduction in Respiratory failure & Pain

Scores with Epidural

Intraoperative Management: Regional or General Anesthesia

Singh N et al. The effects of the type of anesthesia on outcomes of lower extremity infrainguinal bypass.

J Vasc Surg 44: 964-970, November 2006• Prospectively collected database of National

Surgical Quality Improvement Program (NSQIP)• The NSQIP database identified 14,788 patients

(GETA, 9757 pts; SA, 2848 pts; EA, 2183 pts) underwent infrainguinal arterial bypass

• 99% Males, Mean Age: 65.8 yrs

Intraoperative Management: Regional or General Anesthesia

Singh N et al. The effects of the type of anesthesia on outcomes of lower extremity infrainguinal bypass. J Vasc Surg 44: 964-970, November 2006

• Type of anesthesia affected graft failure• Compared to SA and EA, GETA associated with:

– More graft failure at 30 days– More cardiac events (MI, C Arrest), – More postoperative pneumonia

• No difference between SA and EA regarding graft failure and cardiac events

• GETA is not the best strategy

Intraoperative Management: Regional or General Anesthesia

My Preference: BOTH• Epidural Catheter inserted after fluid preloading,

test dose, then 8 ml of your favorite LA, wait for sure signs of onset of block, then induce:

• General Anesthesia: Fentanyl 2μg/kg, wait for at least 3min, Thiopentone 2-4 mg/kg, your favorite non-depolarizer, ETT, Isoflurane 0.6-1.2%, or Sevo 1-2%, normocarbia. Maintain Epidural block (LA + Opioid), Little or no IV fentanyl

• Postop: Ropivacaine 0.2% + Fentanyl 2μg/ml

SEVO

Postoperative Management:

• First 3 postoperative days: Period of greatest risk of cardiac complications

• Hypercoagulability, Increased adrenergic stress• Management focused on factors increasing risk of

cardiac complications:– Tachycardia– Anemia– Hypothermia, shivering– Hypertension– Hypoxemia– Inadequate analgesia

Postoperative Management:

• Most postoperative ischemia is silent:• Most MIs preceded by prolonged ST

depression• Early detection and aggressive management

MAY prevent progression to MI• Detective strategy:(Silent)

– ST-segment Monitoring: automated, continuous– 12 Lead ECG q. 8 hrs in day1, then daily for day

2, 3– Serial Enzymes: Cardiac Troponins (TnT, TnI)

Postoperative Management:

• Cardiac Troponins (TnT, TnI)• More specific than CK-MB• More prognostic value, Suggest treatment strategy

• Unstable Angina: some have small rise TnT<0.1 ng/ml, increased M&M, respond to LMWH, Gp IIb-IIIa blockers

Time to rise Peak rise Normalized

CK-MB 3-5 hrs 10-18 hrs 2-3 days Gold standard Not Prognostic low specificity

TnT 3.8 hrs 18 hrs, 3ds 5-14 days High sensetivity & specificity, Prognostic

TnI 3-12 hrs 24 hrs 5-10 days not affected by CRF, slow rise

Postoperative Management:Cardiac complications

Treatment based on extrapolation from non-operative setting, AHA/ACC guidelines:

• Transmural Q-wave MI• Non Q-wave MI (NQWMI)• Unstable Angina

Postoperative Management:Transmural Q-wave MI

• Goal: quickly reopen occluded vessel• Aspirin: early• Thrombolytics contraindicated post surgery??• If Lytics CI: consider Cath/Stent• β-Blockers: aggressive block• NTG: only for ongoing ischemia• ACE Inhibitors: improve LV remodelling• Heparin: when lytics CI• Magnesium: good, Statins: evolving evidence• LMWH, Gp IIb/IIIa blockers: no evidence

Postoperative Management:Non Q-wave MI (NQWMI)

• Majority of perioperative MI• Higher Morbidity, equal Mortality to QWMI• Cardiac status closer to Unstable Angina• Diagnosis: Cardiac Enzymes• β-Blockers & Aspirin for all NQWMI• NTG: only for ongoing ischemia• Heparin: 48 hours, improves outcome• LMWH: used instead, caution, no reversal• Gp IIb/IIIa blockers ?? Used in non-operative

Postoperative Management:Unstable Angina

• Goal: prevent progression to MI, death• β-Blockers & Aspirin: dec MI, Mortality• NTG: only for ongoing ischemia, nitrate tolerance

develops in 24-48 hrs continuous administration• Heparin: 48 hours, improves outcome• Angio / stent??• Troponin Positive Unstable Angina

(Minor Myocardial Injury):

LMWH & Gp IIb/IIIa blockers: Abciximab, Agrastat

Epilogue:

• CAD patients are high risk patients• Optimum strategy is multimodal:

– Improved preoperative assessment– Sympatholytic pharmacologic optimization– Intraoperative management based on

physiologic goals & scientific evidence– Postoperative Monitoring: “detective”

• Postoperative MI, U Angina: inc M & M:β-Blockers & Aspirin, selective use of invasive

procedures

Detectives

• Postconditioning:

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Devereaux, P.J. et al. CMAJ 2005;173:627-634

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