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

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

Maintenance of adequate oxygen balance is oneof the primary objectives when dealing withpatients undergoing cardiac surgery.

Cardiac output is one of the major components ofoxygen delivery .

Introduction (cont.)

Due to preoperative cardiac lesion and myocardialdysfunction secondary to the events related tocardiac surgery and cardio pulmonary bypass,circulatory support by pharmacological means isfrequently required after surgery.

Introduction (cont.)

Adrenergic receptors

α-receptors

α1 α2

β-receptors

β1 β2

Introduction(cont.)

Classification of inotropic agents

cAMP dependent agents

adrenergic agonists

dopaminergicagonists:

phosphodiesteraseIII isoenzyme

inhibitors:

cAMP independent inotropic agents

Na+-K+-ATPaseinhibitors:

Potassium channels inhibitors

Agonists of β-adrenergic receptors

Calcium

Phenylephrine

Other new agents

Calcium Sensitizers

vasopressin

natriuretic brain peptide

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)

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)

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)

β 1-adrenergic agonist Had positive inotropic and

peripheral vasodilativeproperties.

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

Dose : 2.5-10 µg/kg/min

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.

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

apparatus (especially troponine-T) tointracellular calcium.

Proarrhythmic activity less common. Induce peripheral, pulmonary and coronary

vasodilatation, via ATP-sensitive potassiumchannels

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

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 thesystolic myocardial performance after heart surgery in patientsundergoing cardiopulmonary bypass (CPB)

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 severalstudies.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.

Choice of inotropes(cont.)

Enhance the diastolic function

Choice of inotropes(cont.)

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

Choice of inotropes(cont.)

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.)

Dopamine

Dobutamine

EpinephrineNorepinephrine

PDE inhibitors

Levosimendan

Coronary artery bypass graft surgery:In most cases, no or only mild inotroperequirement.inotropes may be needed in case of preexistingventricular dysfunction or in case of unsuccessfulrevascularization if the intra-aortic balloon pumpalone is not enough.

emergency revascularization of acutemyocardial infarction, dobutamine and PDEinhibitors.

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

Indications in specific settings(cont.)

Chronic heart failure :Combination therapy (i.e. a PDE inhibitoradministered along with a beta-adrenergicinotrope, dobutamine or epinephrine) maytherefore be the treatment of choice in thesepatients

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 andpulmonary vasodilation) and dopamine (to addfurther support whilst maintaining the systemicperfusion 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

Postoperative myocardial dysfunction is amajor concern in the setting of cardiac surgerysince it is extremely frequent and is related to agreater morbidity and mortality.

Inotropic drugs are nowadays an importanttherapeutic tools in the treatment ofperioperative heart failure.

Good selection usually guide our outcome.