 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 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.)

Adrenergic receptors α- receptors α1α1 α2α2β-receptorsβ1β1β2β2 Introduction(cont.)

Classification of inotropic agents cAMP dependent agents adrenergic agonists dopaminergic agonists: phosphodiesterase III isoenzyme inhibitors: cAMP independent inotropic agents Na+-K+-ATPase inhibitors : 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 β 1-adrenoceptors, increases both heart rate and contractility.  Norepinephrine does not affect β 2- adrenoceptors.  Dose : 2-20µg/min( 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 β 2- adrenoceptor effects.  Dose : 2-20µg/min( 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 vasodilative properties.  As established dobutamine as a first line therapeutic choice in patients with decompensated HF.  Dose : µg/kg/min

 Inodilators  postreceptor” mechanism of action  oral administration.  Milrinone.  Dose : 50 µg/kg over 10 min, then 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) 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.

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)

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.

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 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 surgery Moderately 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

 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.