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Pharmacologic Considerations in the Cardiac Patient. Wayne E. Ellis, Ph.D., CRNA. 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. Primary Treatment.
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Pharmacologic Considerations in the Cardiac Patient Wayne E. Ellis, Ph.D., CRNA
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
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
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 Anesthesia loss of consciousness amnesia analgesia suppression of reflexes (endocrine and autonomic) muscle relaxation
Preoperative Preparation Angina Medications to control it Blood pressure controlled Diastolic < 95 torr Congestive heart failure treated Diuretics 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
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 Low Molecular Weight Heparin
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 Advantages Excellent analgesia Hemodynamic stability Blunt reflexes Can use 100% oxygen
Opioids Disadvantages May not block hemodynamic and hormonal responses in patients with good LV function Do not ensure amnesia Chest wall rigidity Respiratory depression
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
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 Advantages Myocardial oxygen balance altered favorably by reductions in contractility and afterload Easily titratable Can be administered via CPB machine Rapidly eliminated
Inhalational Agents • Disadvantages include myocardial depression • systemic hypotension with possible tachycardia • lack of postoperative analgesia
Inhalation Agents Disadvantages Significant 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
Antianginal medications Beta-blockers Calcium Channel Blockers Nitrates Nitropaste morning of surgery WE Ellis
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 Nitroglycerin Lower LVEDP Vasodilator Poor ventricular function
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 blocker Unstable angina Myocardial infarction
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
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
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
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
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
ACE Inhibitors • Contraindicated in pt’s with hypotension, bilateral renal artery stenosis, history of a cough or angio-edema with ace inhibitors
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
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
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)
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 responses Fluids Esmolol
General anesthesia Avoids sympathectomy Risks with intubation Sympathetic stimulation Hypoxia Increased catecholamines Loss of subjective monitor Chest pain Ischemia
General Anesthesia required Narcotics Effective 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 doses 1-2 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