introduction classification of inotropes postoperative myocardial dysfunction. choice of inotrope...

INOTROPES IN CARDIOTHORACIC SURGERY

Objectives

Introduction Classification of inotropes Postoperative myocardial dysfunction. Choice of inotrope Indications in specific settings

INTRODUCTION

What is inotrope?

An inotrope is an agent, which increases or decreases the force or energy of muscular contractions .

Positive inotropic agent enhances myocardial contractility so; cardiac output, the amount of blood ejected by the heart with each beat, will also increase.

Introduction

Why inotropes?

Maintenance of adequate oxygen balance is one of the primary objectives when dealing with patients undergoing cardiac surgery.

Cardiac output is one of the major components of oxygen delivery .

Introduction (cont.)

Due to preoperative cardiac lesion and myocardial dysfunction secondary to the events related to cardiac surgery and cardio pulmonary bypass, circulatory support by pharmacological means is frequently required after surgery.

Introduction (cont.)

How do inotropes act?

Adrenergic receptors

α- receptors

α1α2

β-receptors

β1 β2

Introduction(cont.)

CLASSIFICATION OF INOTROPIC AGENTS

Classification of inotropic agentscAMP

dependent agents

adrenergic agonists

dopaminergic agonists :

phosphodiesterase III isoenzyme inhibitors:

cAMP independent

inotropic agentsNa+-K+-ATPase

inhibitors :

Potassium channels inhibitors

Agonists of β- adrenergic receptors

Calcium

Phenylephrine

Other new agents

Calcium Sensitizers

vasopressin

natriuretic brain peptide

Norepinephrine

principal neurotransmitters in the sympathetic nervous system

potent α- adrenoceptor agonist strong vasoconstrictor

norepinephrine stimulates β1-adrenoceptors,

increases both heart rate and contractility.

Norepinephrine does not affect β2-adrenoceptors.

Dose : 2-20µg/min(0.04-0.4 µg/kg/min)

Epinephrine Hormone secreted by the adrenal

medulla Potent α- and β-adrenoceptor agonist. so a powerful vasoconstrictor, a positive

inotrope, and a positive chronotrope. But, diastolic blood pressure may

decrease as a result of vasodilation due to stimulation of β2-adrenoceptor effects.

Dose : 2-20µg/min(0.04-0.4 µg/kg/min)

Dopamine

An endogenous catecholamine Stimulates both adrenergic and

dopaminergic (D1 and D2) receptors. Low-dose infusion (<5 µg/kg/min) Intermediate doses (5-10 µg/kg/min) . Higher doses (>10 µg/kg/min)

Dobutamine

β 1-adrenergic agonist Had positive inotropic and

peripheral vasodilative properties.

As established dobutamine as a first line therapeutic choice in patients with decompensated HF.

Dose : 2.5-10 µg/kg/min

Phosphodiesterase (PDE) inhibitors Inodilators postreceptor” mechanism of

action oral administration . Milrinone. Dose : 50 µg/kg over 10 min ,

then 0.375-0.75 µg/kg/min ,max.: 1.13 mg/kg/min.

Levosimendan It is one of calcium senstizers It act by increasing the sensitivity of

contractile apparatus (especially troponine-T) to intracellular calcium.

Proarrhythmic activity less common. Induce peripheral, pulmonary and coronary

vasodilatation, via ATP-sensitive potassium channels

Dose : is 6 to 12 µg/kg loading dose over 10 minutes followed by 0.05 to 0.2 µg/kg/min as a continuous infusion.

POSTOPERATIVE MYOCARDIAL DYSFUNCTION

Postoperative myocardial dysfunction

Causes: aortic cross-clamping inadequate myocardial protection hypothermia with cardioplegia and topical

iced solutions surgical trauma activation of the complement cascade by CPB reperfusion injury premature or excessive titration of inotropic

agents

Recovery pattern of cardiac function: postoperative changes in the systolic myocardial performance after heart surgery in patients undergoing cardiopulmonary bypass (CPB)

CHOICE OF INOTROPE

Choice of inotrope

Guided The expected need for

inotropes clinical evidence of

depressed myocardial function

Empirical drug choice and titration, with careful hemodynamic monitoring

Table 2. Predictive factors of inotropic support, as highlighted by several studies.Low ejection fraction (< 45%)

History of congestive heart failure

Cardiomegaly

High LVEDP following ventriculogram

MI within 30 days of operation*

Older age (> 70 years)

Longer duration of aortic cross-clamping

Prolonged cardiopulmonary bypass*

Urgent operation

Re-operation*

Female gender*

Diabetes mellitus

LVEDP = left ventricular end-diastolic pressure; MI = myocardial infarction.

* statistical significance for coronary artery bypass surgery only.

Ideal positive inotrope?!!

Enhance contractility without any significant increase in heart rate preload, afterload, and myocardial oxygen consumption.

Choice of inotropes(cont.)

Ideal positive inotrope?!!

Enhance the diastolic function

Choice of inotropes(cont.)

Ideal positive inotrope?!!

Maintain the diastolic coronary perfusion pressure and thus an adequate myocardial blood flow.

Choice of inotropes(cont.)

Ideal positive inotrope?!!

It finally should have rapid titration times and onset of action and a short half-life

Choice of inotropes(cont.)

Catecholamines are the mainstay of current inotropic treatment

they can be divided into more potent (epinephrine, isoproterenol,

noradrenaline) and milder (dopamine, dopexamine,

dobutamine

Choice of inotropes(cont.)

Now , what will you choose?

Dopamine

Dobutamine

Epinephrine

Norepinephrine

PDE inhibitor

s

Levosimendan

Indications in specific settings

Coronary artery bypass graft surgery:In most cases, no or only mild inotrope requirement.inotropes may be needed in case of preexisting ventricular dysfunction or in case of unsuccessful revascularization if the intra-aortic balloon pump alone is not enough.

emergency revascularization of acute myocardial infarction, dobutamine and PDE inhibitors.

off-pump coronary artery bypass graft surgery (dopamine, dobutamine)

Indications in specific settings(cont.)

Chronic heart failure :Combination therapy (i.e. a PDE inhibitor administered along with a beta-adrenergic inotrope, dobutamine or epinephrine) may therefore be the treatment of choice in these patients

Indications in specific settings(cont.)

Diastolic dysfunction :No inotropes at all (or inotropes with a better effect on ventricular relaxation, such as PDE inhibitors, if systolic dysfunction coexists)

Indications in specific settings(cont.)

valvular surgeryModerately severe aortic stenosis,

Inotropic support is rarely needed

Indications in specific settings(cont.)

Chronic aortic insufficiency

Requiring adequate preload and inotropes

Indications in specific settings(cont.)

Mitral stenosis, chronic mitral regurgitation

Treatment with inotropes is warranted.

Indications in specific settings(cont.)

Acute aortic and mitral regurgitation

require aggressive inotropic support even preoperatively

Indications in specific settings(cont.)

Tricuspid regurgitation

Inotropes are beneficial

Indications in specific settings(cont.)

Orthotopic cardiac transplantation:Routine inotropic support includes isoproterenol (to increase the automaticity, inotropism and pulmonary vasodilation) and dopamine (to add further support whilst maintaining the systemic perfusion pressures).

Indications in specific settings(cont.)

Right ventricular dysfunction: heart transplantation, lung transplantation pulmonary thromboendoarterectomy left ventricular assist device implantation, inadequate myocardial protection

Indications in specific settings(cont.)

Successful management

Right ventricular afterload

The contractile strength

maintenance of the aortic

blood pressure

pulmonary vasodilators

inotropes :• dobutamine, • isoproterenol,• epinephrine, • PDE inhibitors

vasoconstrictors

Conclusion

Conclusion

Postoperative myocardial dysfunction is a major concern in the setting of cardiac surgery since it is extremely frequent and is related to a greater morbidity and mortality.

Inotropic drugs are nowadays an important therapeutic tools in the treatment of perioperative heart failure.

Good selection usually guide our outcome.

Any Question?