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Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your ORs For The Future

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Page 1: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Staying Ahead of Cardiac IschemiaStaying Ahead of Cardiac Ischemia

Glynne Stanley MB.ChB., FRCAGlynne Stanley MB.ChB., FRCA

Boston University School of MedicineBoston University School of MedicineBoston University School of MedicineBoston University School of Medicine

2nd Annual Ellison Pierce Symposium Positioning Your ORs For The Future2nd Annual Ellison Pierce Symposium Positioning Your ORs For The Future

Page 2: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

• Summarize the scope of the problem

• Discuss perioperative myocardial infarction

• Discuss the literature on pharmacological intervention

• Try to Address the Beta-blocker dilemma!

• Summarize the scope of the problem

• Discuss perioperative myocardial infarction

• Discuss the literature on pharmacological intervention

• Try to Address the Beta-blocker dilemma!

ObjectivesObjectives

Page 3: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Scope of the ProblemScope of the Problem

Non-cardiac cases /year 30 million

At risk 6 million

MI’s 50,000

Deaths 20,000

Surgical cardiac deaths 50%

PMI incidence 5.6%

Cost / year 20 billion

Non-cardiac cases /year 30 million

At risk 6 million

MI’s 50,000

Deaths 20,000

Surgical cardiac deaths 50%

PMI incidence 5.6%

Cost / year 20 billion

Page 4: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

• AHRQ• AHA• ACS• ASA• AORN

• AHRQ• AHA• ACS• ASA• AORN

• CDC• CMS• VA• IHI• JCAHO

• CDC• CMS• VA• IHI• JCAHO

Goal: reduce surgical complications and mortality 25% by 2010.Goal: reduce surgical complications and mortality 25% by 2010.

Page 5: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your
Page 6: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your
Page 7: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Who is at risk?Who is at risk?

• Lee’s Revised Cardiac Risk Index

– High risk surgical procedure

• Intraperitoneal, intrathoracic, vascular

– History of IHD

• History of MI, +ve ETT, angina, Q waves

– History of CHF

– History of cerebrovascular disease

– Insulin therapy

– Creatinine > 2.0mg/dl

• Lee’s Revised Cardiac Risk Index

– High risk surgical procedure

• Intraperitoneal, intrathoracic, vascular

– History of IHD

• History of MI, +ve ETT, angina, Q waves

– History of CHF

– History of cerebrovascular disease

– Insulin therapy

– Creatinine > 2.0mg/dl

Page 8: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Who is at risk?Who is at risk?

• High risk surgery* no CAD 0.9%• High risk surgery* w/ CAD 2.7%• Vascular patient with CAD 8.5%

*thoracic, abdominal, head and neck

• High risk surgery* no CAD 0.9%• High risk surgery* w/ CAD 2.7%• Vascular patient with CAD 8.5%

*thoracic, abdominal, head and neck

Page 9: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Who is at risk?Who is at risk?

Risk of Major Cardiac EventRisk of Major Cardiac Event

POINTS CLASS RISK

0 I 0.4%

1 II 0.9%

2 III 6.6%

3 or more IV 11%

Page 10: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

• Some studies have suggested up to a 28 fold risk in next 6 months of another event

• 20% two year survival!

• This is a BIG DEAL!

• Some studies have suggested up to a 28 fold risk in next 6 months of another event

• 20% two year survival!

• This is a BIG DEAL!

BUT…if a patient survives a PMI…

BUT…if a patient survives a PMI…

Page 11: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

medlib.med.utah.edu/.../ MYOCARD/MI010.html

Mechanisms of MI Mechanisms of MI

Page 12: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Mechanisms of MI: Plaques Mechanisms of MI: Plaques

Low-lipid, Low-lipid, fibrous-capped plaquesfibrous-capped plaques

CollateralizationCollateralization

TachycardiaTachycardia

Non-Q wave MINon-Q wave MI

Stable(quiescent)Stable(quiescent)

Unstable(vulnerable)

Unstable(vulnerable)

Inflamed, lipid-laden Inflamed, lipid-laden thin-capped plaquesthin-capped plaques

May appear benignMay appear benignAngiographicallyAngiographically

Rupture / OcclusionRupture / Occlusion

Q wave MI Q wave MI

Page 13: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

• Other factors

– Sympathetic nervous system

– Hypercoagulable state and thrombosis

– Endothelial ischemia triggering spasm

– Perioperative milieu

– (Hypoxia and hypotension!)

• Other factors

– Sympathetic nervous system

– Hypercoagulable state and thrombosis

– Endothelial ischemia triggering spasm

– Perioperative milieu

– (Hypoxia and hypotension!)

Mechanisms of MI Mechanisms of MI

Page 14: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Are PMI’s Different?Are PMI’s Different?

• Baseline ECG abnormalities

• Presence of diabetes, CHF and angina

• 50% SILENT!

• Frequently Non-Q wave

• Occur day of or day after surgery

• Long-term mortality is higher

• Concept of the troponin leak

• Baseline ECG abnormalities

• Presence of diabetes, CHF and angina

• 50% SILENT!

• Frequently Non-Q wave

• Occur day of or day after surgery

• Long-term mortality is higher

• Concept of the troponin leak

Page 15: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Landesberg et al. Continuous ECG monitoring and ST trend analysis and troponin-I

• Ischemia duration strongly associated with peak cTn-I level

• Ischemia preceded in all cases by heart rate increase

• Majority of ischemic events including those culminating in PMI started within 2 hours of the end of surgery

Landesberg et al. Continuous ECG monitoring and ST trend analysis and troponin-I

• Ischemia duration strongly associated with peak cTn-I level

• Ischemia preceded in all cases by heart rate increase

• Majority of ischemic events including those culminating in PMI started within 2 hours of the end of surgery

Are PMI’s Different?Are PMI’s Different?

Page 16: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Plaque rupture in 46% - 55% of patients*

• Time to death patterns:

- Non-plaque rupture deaths within first 3 days

- Plaque rupture deaths were evenly distributed up to 17 days post-op

Plaque rupture in 46% - 55% of patients*

• Time to death patterns:

- Non-plaque rupture deaths within first 3 days

- Plaque rupture deaths were evenly distributed up to 17 days post-op

*Cohen and Aretz, 1999 Dawood et al, 1996

Post-Mortem StudiesPost-Mortem Studies

Page 17: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Are PMI’s Different?Are PMI’s Different?

• Similar mechanism as seen in non-surgical patients:

- Lower grade coronary stenosis

- Unstable/vulnerable plaques

- Acute thrombosis with luminal occlusion

- Poor collateralization

• Similar mechanism as seen in non-surgical patients:

- Lower grade coronary stenosis

- Unstable/vulnerable plaques

- Acute thrombosis with luminal occlusion

- Poor collateralization

Page 18: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

But… many patients may have an infarction that is, at least in part, related to prolonged ischemia

But… many patients may have an infarction that is, at least in part, related to prolonged ischemia

Page 19: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Furthermore, the story may be even more sinister since troponin levels are only points on a continuum of myocardial damage.

Furthermore, the story may be even more sinister since troponin levels are only points on a continuum of myocardial damage.

Page 20: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Kim et al, studied 229 patients undergoing aortic, infra-inguinal vascular or amputation surgery

– Troponins measured immediately post op and days 1, 2 and 3

– 98 patients had Troponin cTn-I >0.35ng/ml (lower limit of detection)

– Likelihood of death in the first 6 months increased dramatically as the troponin levels rise

Kim et al, studied 229 patients undergoing aortic, infra-inguinal vascular or amputation surgery

– Troponins measured immediately post op and days 1, 2 and 3

– 98 patients had Troponin cTn-I >0.35ng/ml (lower limit of detection)

– Likelihood of death in the first 6 months increased dramatically as the troponin levels rise

Page 21: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Troponin level

(ng/ml)< 0.35 0.4 – 1.5 1.6 – 3.0 > 3.0

Odds ratio

for death (95% confidence interval)

1.0 1.3 4.3 4.9

Odd ratio of death in first 6 months of vascular surgery compared With perioperative troponin levels. (Kim et al, Circulation, 2002)

Odd ratio of death in first 6 months of vascular surgery compared With perioperative troponin levels. (Kim et al, Circulation, 2002)

Page 22: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Landesberg et al. 447 patients for major vascular surgery

Landesberg et al. 447 patients for major vascular surgery

• Troponins measured postoperatively

– A 1–5 year follow-up

– Odds ratio for death increased steadily with post-operative troponin levels.

• Data for non-vascular surgery is needed to look at a broader risk population

• Troponins measured postoperatively

– A 1–5 year follow-up

– Odds ratio for death increased steadily with post-operative troponin levels.

• Data for non-vascular surgery is needed to look at a broader risk population

Page 23: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Early & Delayed Myocardial Infarction After Abdominal Aortic Surgery.

(Le Manach et al, Anesthesiology, 2005)

Early & Delayed Myocardial Infarction After Abdominal Aortic Surgery.

(Le Manach et al, Anesthesiology, 2005)

• Intense troponin analysis 1,136 consecutive patients for AAA

• 163 patients (14%) had one abnormal cTnI

– 106 (10%) always < 1.5ng/ml (MD group)

– 57 had cTnI > 1.5ng/ml and were considered to have had a PMI

• 21 patients (2%) were early (EPMI) (mean 37hrs)

• 34 patients (3%) were delayed (DPMI) (mean 74hrs)

• Intense troponin analysis 1,136 consecutive patients for AAA

• 163 patients (14%) had one abnormal cTnI

– 106 (10%) always < 1.5ng/ml (MD group)

– 57 had cTnI > 1.5ng/ml and were considered to have had a PMI

• 21 patients (2%) were early (EPMI) (mean 37hrs)

• 34 patients (3%) were delayed (DPMI) (mean 74hrs)

Page 24: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

• Key points: Two distinct patterns of cTnI

– EPMI rise in cTnI NOT preceded by period of MD (subinfarction)

– DPMI preceded by > 24 hrs of increased cTnI ie subinfarction MD

– If cTnI not risen by 48 hrs has a negative predictive value of 99.6%

• Key points: Two distinct patterns of cTnI

– EPMI rise in cTnI NOT preceded by period of MD (subinfarction)

– DPMI preceded by > 24 hrs of increased cTnI ie subinfarction MD

– If cTnI not risen by 48 hrs has a negative predictive value of 99.6%

Early & Delayed Myocardial Infarction After Abdominal Aortic Surgery. (Le Manach et al, Anesthesiology, 2005)

Early & Delayed Myocardial Infarction After Abdominal Aortic Surgery. (Le Manach et al, Anesthesiology, 2005)

Page 25: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

• EPMI probably represents acute plaque deterioration and acute coronary occlusion

• DPMI probably represents prolonged ischemia of postulated by Landesburg (similar to unstable angina Class IIIA)

• Monitoring for low-level troponins in the early post-operative period may give a “Golden Period” of opportunity for optimization of care and reduction in MD and PMI

• EPMI probably represents acute plaque deterioration and acute coronary occlusion

• DPMI probably represents prolonged ischemia of postulated by Landesburg (similar to unstable angina Class IIIA)

• Monitoring for low-level troponins in the early post-operative period may give a “Golden Period” of opportunity for optimization of care and reduction in MD and PMI

Early & Delayed Myocardial Infarction After Abdominal Aortic Surgery. (Le Manach et al, Anesthesiology, 2005)

Early & Delayed Myocardial Infarction After Abdominal Aortic Surgery. (Le Manach et al, Anesthesiology, 2005)

Page 26: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Part II

What has been done so far to affect outcome?

Part II

What has been done so far to affect outcome?

Page 27: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

The Use of Beta-blockers in CAD

The Use of Beta-blockers in CAD

• Beta-blockers after AMI reduces mortality by 24%

• Only 50%-60% utilization of beta-blocker

• Highest risk patients have the best response

• Beta-blockers after AMI reduces mortality by 24%

• Only 50%-60% utilization of beta-blocker

• Highest risk patients have the best response

Page 28: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Reduced Hemodynamic Stress

??? Platelet Action

??? Metabolic

Increased Diastole

Improved myocardial blood flow

Decreased Ventricular Arrhythmias

Reduced VF threshold

Spectrum of potential

benefits of beta-blockade

Spectrum of potential

benefits of beta-blockade

Plaque stabilization

Antiarrhythmicaction

Improved oxygensupply/demand

Page 29: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Perioperative Beta-blockers Perioperative Beta-blockers

• Randomized, double-blind, placebo controlled trial of 200 patients

• Intravenous atenolol 30 mins pre-op and post-op for up to 7 days

• 2 year mortality for atenolol group 10% vs. 21% in control (p=0.019)

• Combined cardiac outcomes similar reduction

• Randomized, double-blind, placebo controlled trial of 200 patients

• Intravenous atenolol 30 mins pre-op and post-op for up to 7 days

• 2 year mortality for atenolol group 10% vs. 21% in control (p=0.019)

• Combined cardiac outcomes similar reduction

Mangano and Wallace. NEJM, 1996

Page 30: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Beta-blockersBeta-blockers

• Atenolol shown to reduce incidence of Holter monitored perioperative ischemia

• Ischemia reductions associated with reduced risk of death at 2 year point.

• Atenolol shown to reduce incidence of Holter monitored perioperative ischemia

• Ischemia reductions associated with reduced risk of death at 2 year point.

Wallace, Anesthesiology, 1998

Page 31: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Beta-blockers in Major Vascular Surgery

Beta-blockers in Major Vascular Surgery

Positive dobutamine echocardiography– Bisoprolol started an average of 37 days

before surgery

– Death from cardiac causes or non-fatal PMI 34% in untreated group and 3.4% in the bisoprolol group

– In-hospital mortality significantly reduced

Positive dobutamine echocardiography– Bisoprolol started an average of 37 days

before surgery

– Death from cardiac causes or non-fatal PMI 34% in untreated group and 3.4% in the bisoprolol group

– In-hospital mortality significantly reduced

Poldermans, NEJM, 1999

Page 32: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Beta-blockersBeta-blockers

• May reflect the higher risk patient population, already pre-selected by non-invasive testing

• The authors suggest that it may be acceptable in many cases for the prophylactic use of a beta blocker to replace non-invasive testing

• May reflect the higher risk patient population, already pre-selected by non-invasive testing

• The authors suggest that it may be acceptable in many cases for the prophylactic use of a beta blocker to replace non-invasive testing

Page 33: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Beta-blockersBeta-blockers

• 1351 patients for vascular surgery

• 1097 had DSE

• Categorized by risk factors and NWMAs

• Allows rationalization of testing

• High risk subset not helped

• 1351 patients for vascular surgery

• 1097 had DSE

• Categorized by risk factors and NWMAs

• Allows rationalization of testing

• High risk subset not helped

Poldermans, JAMA, 2001

Page 34: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Car

dia

c C

omp

lica

tion

s. %

0

5

10

1.2

0

4/327 0/480

5

10

3.0

0.9

16/528 2/2150

5

10

5.8

2.0

6/103 1/500

5

3333

2.8

6/18 1/360

5

3333

36

5/15 4/11

Determine Risk Score

Assign 1 Point for Each of the Following Characteristics: Age 70 years, Current Angina, Prior Myocardial Infarction, Congestive Heart Failure,

Prior Cerebrovascular Event, Diabetes Mellitus and Renal failure

0 < Score < 3 (55%)Score – 0 (28%) Score 3 (17%)

Dobutamine Stress Echocardiography (DSE)

No New Wall-Motion Abnormalities (11%)

New Wall-Motion Abnormalities in 1-4 segments (4%)

New Wall-Motion Abnormalities in 5 segments (2%)

Non β Blocker use

β Blocker use

Page 35: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

BUT NOT EVERYONE IS CONVINCED !

A number of negative studies and commentaries have

emerged

BUT NOT EVERYONE IS CONVINCED !

A number of negative studies and commentaries have

emerged

Page 36: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Beta-Blockers Adverse EffectsBeta-Blockers Adverse Effects

• Withdrawal phenomena

• Bradycardia 28%

• Hypotension and pulmonary edema

• High conduction abnormalities

• Withdrawal phenomena

• Bradycardia 28%

• Hypotension and pulmonary edema

• High conduction abnormalities

Page 37: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Are the recommendations to use perioperative beta-blocker therapy in

patients undergoing noncardiac surgery based on reliable evidence?(Devereaux PJ et al, CMAJ 2004)

Are the recommendations to use perioperative beta-blocker therapy in

patients undergoing noncardiac surgery based on reliable evidence?(Devereaux PJ et al, CMAJ 2004)

• Very critical of original Atenolol trial

• Very skeptical about Poldermann’s data

• Very cautious about recommended beta-blockers to intermediate-risk and low-risk groups

• Very critical of original Atenolol trial

• Very skeptical about Poldermann’s data

• Very cautious about recommended beta-blockers to intermediate-risk and low-risk groups

Page 38: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Metoprolol After Vascular Surgery. (Yang H, et al Can J Anesth 2004;51)

Metoprolol After Vascular Surgery. (Yang H, et al Can J Anesth 2004;51)

• ~500 patients randomly assigned to metoprolol or placebo in patients undergoing vascular surgery

• No significant benefit: 1 major event averted for every 50 patients treated and this result was not significant (p=0.4)

• Rate was not controlled

• ~500 patients randomly assigned to metoprolol or placebo in patients undergoing vascular surgery

• No significant benefit: 1 major event averted for every 50 patients treated and this result was not significant (p=0.4)

• Rate was not controlled

Page 39: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Randomized, Blinded Trail on Perioperative Metoprolol Versus Placebo for Diabetic Patients

Undergoing Noncardiac Surgery.(Juul AB Et Al. AHA Scientific Sessions 2004)

Randomized, Blinded Trail on Perioperative Metoprolol Versus Placebo for Diabetic Patients

Undergoing Noncardiac Surgery.(Juul AB Et Al. AHA Scientific Sessions 2004)

• 921 patients with diabetes randomly assigned to metoprolol or placebo

• Similar rates of death or cardiovascular complications at 18-month follow-up

• But…– surgeries relatively low risk

– Co-morbidities of population other than DM low

– Inconsistent and relatively low metoprolol dosing

– Wide confidence interval

• 921 patients with diabetes randomly assigned to metoprolol or placebo

• Similar rates of death or cardiovascular complications at 18-month follow-up

• But…– surgeries relatively low risk

– Co-morbidities of population other than DM low

– Inconsistent and relatively low metoprolol dosing

– Wide confidence interval

Page 40: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Effect of chronic beta-blockade on perioperative outcome in patients undergoing noncardiac

surgery: an analysis of observational and case control studies.

(Giles JW et al. Anaesthesia, 2004)

Effect of chronic beta-blockade on perioperative outcome in patients undergoing noncardiac

surgery: an analysis of observational and case control studies.

(Giles JW et al. Anaesthesia, 2004)

• 18 studies of chronic beta-blocker use and non-coronary surgery

• No studies demonstrated protective effect

• Beta-receptor up-regulation

• Ischemia demonstrated at lower HR

• Perils of beta-blocker withdrawal clear

• 18 studies of chronic beta-blocker use and non-coronary surgery

• No studies demonstrated protective effect

• Beta-receptor up-regulation

• Ischemia demonstrated at lower HR

• Perils of beta-blocker withdrawal clear

Page 41: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Chronic beta-blocker useChronic beta-blocker use

• Herlitz et al. Cardiology 1995

– 3504 patients presenting with acute MI

– No difference in mortality at 1 month between those on chronic beta-blockers and those who were not

• ?? Up-regulation of beta-receptors

• Obvious perioperative parallels

• Herlitz et al. Cardiology 1995

– 3504 patients presenting with acute MI

– No difference in mortality at 1 month between those on chronic beta-blockers and those who were not

• ?? Up-regulation of beta-receptors

• Obvious perioperative parallels

Page 42: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Perioperative beta-blockade (POBBLE) for patients undergoing infrarenal vascular surgery; results of

a randomized double-blind controlled trial. (Brady AR et al. J Vasc Surg. 2005 Apr;41.)

Perioperative beta-blockade (POBBLE) for patients undergoing infrarenal vascular surgery; results of

a randomized double-blind controlled trial. (Brady AR et al. J Vasc Surg. 2005 Apr;41.)

• No effect seen…..

• But with only 103 patients they had less than a 1 in 3 chance of seeing a 50% effect which is an optimistic expectation

• Study is really not contributory

• No effect seen…..

• But with only 103 patients they had less than a 1 in 3 chance of seeing a 50% effect which is an optimistic expectation

• Study is really not contributory

Page 43: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Perioperative Beta-Blocker Therapy and Mortality after Major Non Cardiac Surgery

(Lindenauer et al, NEJM July 2005)

Perioperative Beta-Blocker Therapy and Mortality after Major Non Cardiac Surgery

(Lindenauer et al, NEJM July 2005)

• Massive observational study

• Matched 119,632 patients to controls

• Looked at Beta-blocker use by including patients who “first” received the drug during the 1st or 2nd day of hospital stay

• Classified patients according to the Revised Cardiac Risk Index (RCRI)

• Massive observational study

• Matched 119,632 patients to controls

• Looked at Beta-blocker use by including patients who “first” received the drug during the 1st or 2nd day of hospital stay

• Classified patients according to the Revised Cardiac Risk Index (RCRI)

Page 44: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

• If RCRI was 3 or greater the risk reduction was up to 43% (in keeping with the main studies in the area)

• If RCRI was 2 then there no clear benefit

• However, in groups with RCRI of 0 and 1, there was no benefit from beta-blockers and even possible harm.

• If RCRI was 3 or greater the risk reduction was up to 43% (in keeping with the main studies in the area)

• If RCRI was 2 then there no clear benefit

• However, in groups with RCRI of 0 and 1, there was no benefit from beta-blockers and even possible harm.

Perioperative Beta-Blocker Therapy and Mortality after Major Non Cardiac Surgery

(Lindenauer et al, NEJM July 2005)

Perioperative Beta-Blocker Therapy and Mortality after Major Non Cardiac Surgery

(Lindenauer et al, NEJM July 2005)

Page 45: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

• Data is large but still retrospective and very hard to control (although rigorous analysis was used)

• Beta-blocker use in the first 2 days may have been in response to problems in patients with low RCRIs

• No knowledge of heart rate control

• NO KNOWLEDGE OF BETA BLOCKER WITHDRAWAL

• Data is large but still retrospective and very hard to control (although rigorous analysis was used)

• Beta-blocker use in the first 2 days may have been in response to problems in patients with low RCRIs

• No knowledge of heart rate control

• NO KNOWLEDGE OF BETA BLOCKER WITHDRAWAL

Perioperative Beta-Blocker Therapy and Mortality after Major Non Cardiac Surgery

(Lindenauer et al, NEJM July 2005)

Perioperative Beta-Blocker Therapy and Mortality after Major Non Cardiac Surgery

(Lindenauer et al, NEJM July 2005)

Page 46: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

PeriOperative ISchemic Evaluation (POISE) randomized controlled trial, comparing

metoprolol and placebo started a few hours preoperatively and continuing for 30 days in non

cardiac surgery.

PeriOperative ISchemic Evaluation (POISE) randomized controlled trial, comparing

metoprolol and placebo started a few hours preoperatively and continuing for 30 days in non

cardiac surgery.

• 10,000 patients

• All risk groups

• Again probably not large enough to show a difference in those with 1 or NO risk factors

• 10,000 patients

• All risk groups

• Again probably not large enough to show a difference in those with 1 or NO risk factors

Page 47: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

So what are we left with??So what are we left with??

• The lower risk groups are a dilemma

• Risk reduction, if any, is much less

• BUT…They comprise a large number of patients

• So in absolute terms many patients may still benefit

• Common sense approach may be all we end up with!!

• The lower risk groups are a dilemma

• Risk reduction, if any, is much less

• BUT…They comprise a large number of patients

• So in absolute terms many patients may still benefit

• Common sense approach may be all we end up with!!

Page 48: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Alpha-2 AgonistsAlpha-2 Agonists

• Mivazerol

• Dexmedetomidine

• Clonidine

• Mivazerol

• Dexmedetomidine

• Clonidine

Page 49: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Survival for clonidine-treated versus placebo-treated patients. Survival curves for 2 yr after surgery for 290 patients treated with clonidine (n = 125) and placebo (n = 65).

Clonidine reduced the incidence of death (P = 0.01 by log-rank test and P = 0.01 by Wilcoxon test).  

Wallace: Anesthesiology, Volume 101(2).August 2004.284-293

Page 50: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your
Page 51: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

StatinsStatins

• Mortality in statin group 8% vs 25%*

• Cardiac events in placebo group 26% vs. 8%**

*Poldermans et al, Circ., 2003

**Durazzo et al, J Vasc Surg, 2003

• Mortality in statin group 8% vs 25%*

• Cardiac events in placebo group 26% vs. 8%**

*Poldermans et al, Circ., 2003

**Durazzo et al, J Vasc Surg, 2003

Page 52: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

StatinsStatins

• Possible mechanisms of protection

– Attenuate plaque inflammation

– Induce plaque stability

– Antithrombogenic

– Antiproliferative

– Inhibition of plaque leukocyte adhesion

• Possible mechanisms of protection

– Attenuate plaque inflammation

– Induce plaque stability

– Antithrombogenic

– Antiproliferative

– Inhibition of plaque leukocyte adhesion

Page 53: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

DECREASE – IV TRIALDECREASE – IV TRIAL

• ONGOING STUDY

• 6000 patients

• Non-cardiac/vascular and not minor surgery

• Fluvastatin and bisoprolol

• Four groups of patients

• Results expected Spring 2008

• ONGOING STUDY

• 6000 patients

• Non-cardiac/vascular and not minor surgery

• Fluvastatin and bisoprolol

• Four groups of patients

• Results expected Spring 2008

Page 54: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

CABG / PTCA Prior to SurgeryCABG / PTCA Prior to Surgery

• Risk of CABG- Neurocognitive defects 95% - Stroke 3.0%- Death 3.2%

• Risk of death from non-cardiac surgery after CABG is 1.5%

• CARP Trial

– No benefit from prophylactic CABG

• Risk of CABG- Neurocognitive defects 95% - Stroke 3.0%- Death 3.2%

• Risk of death from non-cardiac surgery after CABG is 1.5%

• CARP Trial

– No benefit from prophylactic CABG

Page 55: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Does Pre-op PTCA or PTI Help?Does Pre-op PTCA or PTI Help?

• Stent < 6 weeks before non-cardiac surgery

• MI 18%

• Bleeding 28%

• Death in 20%

• When stent placed 1 day before surgery:

- mortality 100%!

• Stent < 6 weeks before non-cardiac surgery

• MI 18%

• Bleeding 28%

• Death in 20%

• When stent placed 1 day before surgery:

- mortality 100%!

Grzegorz, et al. FACC 2000

Page 56: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Part III Part III

Page 57: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Current Recommendations ???Current Recommendations ???

APSF, Summer 2002:

The evidence for perioperative beta-blocker therapy justifies…

“immediate and widespread implementation”

APSF, Summer 2002:

The evidence for perioperative beta-blocker therapy justifies…

“immediate and widespread implementation”

Page 58: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Current Practice ???Current Practice ???

• 95% aware of the literature

• 93% believe it

• 57% administer prophylactic beta blockers

• 9% admitted to a formal protocol

• 95% aware of the literature

• 93% believe it

• 57% administer prophylactic beta blockers

• 9% admitted to a formal protocol

Van DenKerkhof et al, Anesth.Analg 2003

Page 59: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Current RecommendationsCurrent Recommendations

• Poldermans & Boersma. NEJM July, 2005

• “….pending the availability of data (from ongoing trials) we believe it is appropriate to continue beta-blocker therapy in patients at low or intermediate risk…further information is needed before perioperative use of beta-blockers should be considered routinely in other patients at low or intermediate risk.”

• Poldermans & Boersma. NEJM July, 2005

• “….pending the availability of data (from ongoing trials) we believe it is appropriate to continue beta-blocker therapy in patients at low or intermediate risk…further information is needed before perioperative use of beta-blockers should be considered routinely in other patients at low or intermediate risk.”

Page 60: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Cardiac Risk Reduction Therapy

Copyright 2003 Art Wallace, MD PhD

Cardiac Risk Reduction Therapy

Copyright 2003 Art Wallace, MD PhD

Page 61: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your
Page 62: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

Refer to Cardiology

Aortic StenosisCongestive Heart FailureUnstable AnginaNew Onset AnginaChange in Anginal PatternAngina without Medical TherapyPTCA or Stent

Proceed with Surgery

Coronary Artery Disease

Patient Scheduled for Surgery With

Peripheral Vascular Disease

Two Risk Factors:Age > 65HypertensionDiabetesCholesterol > 240 mg/dlSmoking

If patient has a specific contraindication (asthma not COPD) to beta blockers:Clonidine 0.2 mg PO tablet night before surgeryClonidine TTS#2 Patch (0.2 mg/24 hours) night before surgeryClonidine 0.2 mg PO table morning of surgery.Hold for systolic blood pressure less than 120.

If Unable to take beta blockers

Beta Blockers:Atenolol 25 mg po qd to start, if heart rate greater than 60 and systolic blood pressure greater than 120 mmHg. Titrate dose to effect.Atenolol or Metoprolol IV on day of surgery.Atenolol or Metoprolol IV post op until taking PO then.Atenolol 100 mg PO qd for at least a week post op (hold for heart rate less than 55 or systolic blood pressure less than 100 mmHg)If known CAD or PVD continue beta blocker indefinitely.

Page 63: Staying Ahead of Cardiac Ischemia Glynne Stanley MB.ChB., FRCA Boston University School of Medicine 2 nd Annual Ellison Pierce Symposium Positioning Your

SummarySummary

Long Term ImplicationsLong Term Implications

Spectrum of

Injury

Spectrum of

Injury

Aggressive Therapy

Aggressive Therapy

EducationEducation

PreventionPrevention