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Introduction
Classification of inotropes
Postoperative myocardial dysfunction.
Choice of inotrope
Indications in specific settings
Introduction
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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 (cont.)
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
αreceptors
α1
β-receptors
α2
β1
β2
Classification of inotropic agents
cAMP dependent
agents
cAMP independent
inotropic agents
Other new agents
adrenergic
agonists
Na+-K+-ATPase
inhibitors:
Calcium
Sensitizers
dopaminergic
agonists:
Potassium
channels
inhibitors
vasopressin
phosphodiesterase
III isoenzyme
inhibitors:
Agonists of βadrenergic
receptors
natriuretic brain
peptide
Calcium
Phenylephrine
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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 β2adrenoceptors.
Dose : 2-20µg/min(0.04-0.4 µg/kg/min)
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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 β2adrenoceptor effects.
Dose : 2-20µg/min(0.04-0.4 µg/kg/min)
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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)
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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
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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.
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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.)
Choice of inotropes(cont.)
Enhance the diastolic function
Choice of inotropes(cont.)
Maintain the diastolic coronary perfusion pressure
and 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.)
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Catecholamines are the mainstay of current
inotropic treatment
they can be divided into
more potent (epinephrine, isoproterenol,
noradrenaline) and
milder (dopamine, dopexamine, dobutamine
Levosimendan
PDE inhibitors
Norepinephrine
Dopamine
Dobutamine
Epinephrine
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.
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Indications in specific settings(cont.)
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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
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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)
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Indications in specific settings(cont.)
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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).
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Indications in specific settings(cont.)
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Right ventricular dysfunction:
heart transplantation,
lung transplantation
pulmonary thromboendoarterectomy
left ventricular assist device implantation,
inadequate myocardial protection
Successful management
Right
ventricular
afterload
pulmonary
vasodilators
The contractile
strength
inotropes :
• dobutamine,
•isoproterenol,
• epinephrine,
•PDE inhibitors
maintenance of
the aortic blood
pressure
vasoconstrictors
Conclusion
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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.