Pharmacologic Considerations in the

Cardiac Patient

Wayne E. Ellis, Ph.D., CRNA

04/10/23

Treatment of Ischemia(primary)

• ASA 325 mg immediately

• Thrombolytics (Retevase) – > flow rate than TPA– 2 doses @ 30 min intervals– lyse clots through the activation of

plasminogen

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Primary Treatment

• Antiplatelet agents(abciximab, eptifibatide, tirofiban, integullin)

• GPIIb-IIIa antagonists

• inhibit platelet function by blocking the GPIIb-IIIa receptor, the final pathway of platelet aggregation

• thereby decreasing thrombi development and prevents arterial vessel occlusion

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Percutaneous Coronary Intervention

• Advantages include: higher recanulazation rates

• improved blood flow through the infarct-related vessel

• improved LV function

• lower in-hospital mortality rates

Anesthetic Technique

Goals of Anesthesialoss of consciousness

amnesia

analgesia

suppression of reflexes (endocrine and autonomic)

muscle relaxation

Preoperative Preparation

AnginaMedications to control it

Blood pressure controlledDiastolic < 95 torr

Congestive heart failure treatedDiuretics

Afterload reduction

Bed rest if indicated

Control diabetes

Preoperative Medications

Sedation

Prevent tachycardia

Hypertension

Prepared for hypoxia

Supplemental oxygen

Calcium channel blockers not protective of perioperative ischemia

Antihypertensives continue on day of surgery

Stop Diuretics

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Low Molecular Weight Heparin

• Enoxaparin, Dalteparin

• Anticoagulant activity by binding to antithrombin III, which further binds and inactivates the coagulation factors IIa (thrombin) and Xa

• Advantages include dosed per body wt.

• Given q12 sub q.

• Less trombocytopenia and bleeding

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Opioids

• Advantage relates to the relative lack of myocardial depression – Exception Sufenta, Carfentanil, and high dose fentanyl

• They maintain stable hemodynamics and reduce heart rate

• A primary opioid technique may be of value in the patient with severe myocardial dysfunction

Opioids

AdvantagesExcellent analgesia

Hemodynamic stability

Blunt reflexes

Can use 100% oxygen

Opioids

DisadvantagesMay not block hemodynamic and hormonal

responses in patients with good LV function

Do not ensure amnesia

Chest wall rigidity

Respiratory depression

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Vasoconstrictors

• are useful in the prevention and treatment of ischemia r/t the ability to increase systemic BP

• Phenylephrine improves coronary perfusion pressure, at the expense of increasing afterload and Mv02

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Vasoconstrictors

• At the same time, phenylephrine causes venoconstriction, increasing venous return and left ventricular preload.

• The increase in CPP more than offsets the increase in wall tension

Inhalation Agents

AdvantagesMyocardial oxygen balance altered favorably

by reductions in contractility and afterload

Easily titratable

Can be administered via CPB machine

Rapidly eliminated

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Inhalational Agents

• Disadvantages include myocardial depression

• systemic hypotension with possible tachycardia

• lack of postoperative analgesia

Inhalation Agents

DisadvantagesSignificant hemodynamic variability

May cause tachycardia or alter sinus node function

Possibility of “coronary steal syndrome”

Inhalation Agents

Potential for coronary steal

Alters coronary autoregulation

Alters regional blood flow

Little influence on outcome

Coronary Steal

Arteriolar dilation of normal vessels diverts blood away from stenotic areas

Commonly associated with adenosine, dipyridamole, and SNP

Forane causes steal and new ST-T segment depression

May not be important since Forane reduces SVR, depresses the myocardium yet maintains CO

04/10/23 WE Ellis 20

Antianginal medications

Beta-blockers

Calcium Channel Blockers

Nitrates

Nitropaste morning of surgery

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Nitrates

• Nitroglycerin = venodialator, reduces venous return, decreases wall tension(Mv02) also a coronary arterial dialator.

• Drug of choice for coronary vasospasm• Although primarily is a systemic

venodialator, at high doses causes arterial dilatation and systemic hypotension

Cardioactive drugs

NitroglycerinLower LVEDP

Vasodilator

Poor ventricular function

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Beta Blockers

• Beta blockers reduce myocardial workload(Mv02), and oxygen consumption(V02) by reducing HR,BP, and contractility, and they increase the threshold for ventricular fibrillation.

• Indications for beta blockers include: sinus tachycardia, supraventricular dysrhythmias and hyperdynamic states

Beta Blockers

Negative inotropic effects

Withdrawal following stoppage of beta blockerUnstable angina

Myocardial infarction

04/10/23

Beta Blockers

• Propranolol (non-selective) t1/2 = 4-6 hours

• Metoprolol (B1 selective) t 1/2 = 4-6 hours

• Labatelol (1:7 ratio) t 1/2 = 2-4hours

• Esmolol (Beta1 selective) t1/2 = 9.5 minutes

Esmolol

Control heart rate and blood pressure

Induction

Emergence

Labetalol

Mixed alpha and beta

Control hypertension

Heart rate management

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Ca Channel Blockers

• Evidence for beneficial effects post mi is less compelling

• Nifedipine treatment is associated with a trend towards increased mortality and reinfarction

• Verapamil does not reduce mortality or reinfarction

• Verapamil - useful for slowing the ventricular response in atrial fibrillation/flutter

04/10/23

Ca Channel Blockers

• Cardizem- in pt’s with non-Q wave infarction seems to reduce the reinfarction rate during the 1st 6 months after the infarction, but incidence of late infarction was similar to a placebo.

• Cardizem increases cardiac events in pt’s with LVEF<40% , but decreases their incidence in pt’s with preserved LV function

04/10/23

Ca Channel Blockers

• All Ca blockers depress contractility, reduce coronary and systemic tone, decrease sino-atrial node firing, and impede atrioventricular conduction.

• The negative inatropic effect is greatest with verapamil

• Nifedipine + Cardizem are used in the prevention of coronary vasospasm

Nifedipine

Controlling hypertension

Manage coronary artery spasm

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ACE Inhibitors

• Are effective in reducing ischemic effects after MI

• Treatment should be instituted within the 1st 24 hours of all pt’s with acute mi complicated by symptomatic or asymptomatic left ventricular dysfunction

04/10/23

ACE Inhibitors

• Contraindicated in pt’s with hypotension, bilateral renal artery stenosis, history of a cough or angio-edema with ace inhibitors

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Aspirin

• ASA benefit well established as a secondary prevention

• Antiplatelet therapeutic dose (75-325mg/day)

• other antiplatelet agents such as dipyridamole are not supported in the literature except in pt’s with allergies to ASA who are poor candidates to oral anticoagulants

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Anticoagulants

• Studies of anticoagulant treatment after mi show reduction in death, recurrent MI, and thromboembolitic complications

• However, trials comparing warafin to ASA for secondary prevention show no difference in recurrent infarction or death

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Anticoagulants

• Are indicated for pt’s with ASA intolerance and for those at risk of embolisation from left ventricular or atrial clot(i.e. persistent atrial fib)

04/10/23

Lipid Lowering Agents

• meta analysis of clinical trials show that lipid lowering agents produce a reduction in fatal and non-fatal MI’s and cardiovascular deaths

• Should be given to pt’s with LDL concentration >3.37 mmol/1

Clonidine

Less hypertension

Decreased anesthesia requirements

Anesthetic Management

Regional vs. general

Anesthetic management skills more important than technique

Safest technique is the one the practitioner does best

Regional Anesthesia

Monitor patient more accurately

Control sympathetic responsesFluids

Esmolol

General anesthesia

Avoids sympathectomy

Risks with intubationSympathetic stimulation

Hypoxia

Increased catecholamines

Loss of subjective monitorChest pain

Ischemia

General Anesthesia required

NarcoticsEffective control of catecholamines

Respiratory depression

Prolonged ventilation

Lidocaine

Blunt effects of intubation

1.5 mg/kg 4-6 minutes prior to intubation

Nitrous Oxide

Rarely used due to:increased PVR

depression of myocardial contractility

mild increase in SVR

air expansion

Induction Drugs

Barbiturates

Benzodiazepines

Ketamine

Etomidate

Avoid Ketamine

Hypertension

Tachycardia

Use in trauma

Etomidate

Painful to inject

More CV stability

Barbiturate

Direct depressant

Extended duration of activity

Smaller doses1-2 mg/kg

Add benzodiazepines and narcotic

Benzodiazepines

Quell anxiety

Hemodynamic stability

Extended duration of action

Potential for hypoxia

Lidocaine

Esmolol

Muscle Relaxants

Used to:facilitate intubation

prevent shivering

attenuate skeletal muscle contraction during defibrillation

Muscle Relaxants

Avoid pancuroniumTachycardia

ST segment changes consistent with ischemia

Doxacurium Duration similar to pancuronium

No cardiovascular effects

Avoid Histamine releasing drugs

Curare

Atracurium

Mivacurium <15 mcg/kg

Hypotension

Tachycardia

Nitrous Oxide

Constricts coronary arteries

Aggravates myocardial ischemia

High FiO2 recommendedMaintain saturation at 95-100%

Intraoperative predictors

Choice of anesthetic

Site of surgery

Duration of Anesthesia

Emergency Surgery

Intraoperative predictors

Choice of AnestheticNo difference in infarction rate GETA vs. Regional

No significant hypotension

No significant tachycardia

TURPRegional decreased risk post MI

Reinfarction rateSAB < 1%

GETA 2-8%

Intraoperative predictors

Choice of AnestheticPatient with CHF will benefit from regional

techniqueSympathectomy

Decreased preload

Coronary StealPotent inhalation agents vs. narcotics

Intraoperative predictors

Site of SurgeryThoracic and upper abdominal

2-3 X’s risk of extremity procedures

Duration of Anesthetic> 3 hours > risk of morbidity & mortality

Emergency Surgery2 - 5 X’s greater risk than nonemergent surgery

Postoperative Management

Maintain analgesia

Balance supply and demand

Supplemental oxygen

Continue monitoring into postoperative period

Early transfusion