Inotropes and vasopressors

Definition:

Inotropes: sympathomimetic agent which act on the sympathetic (or adrenergic) nervous system (β-receptors) resulting in positive inotropic (increase in contractility), chronotropic (increase in heart rate), dromotropic (increase in conduction of impulse) and lusitropic effect (improved diastolic relaxation)

Vasopressors: sympathomimetic agent which act on the sympathetic (or noradrenergic) nervous system (α-receptors) resulting in vasoconstrictor effect

The ideal vasoactive support agent: effect on cardiac output/effect on SVR/effect on myocardial oxygen consumption/no tachyphylaxis does not exist!

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a) Sympathomimetics: endogenous catecholamines:

Adrenaline (β1 >> β2 and α1 > α2 agonist) via cAMP

Noradrenaline (α1 > α2 and β1 >> β2 agonist) via cAMP ?

Dopamine (D1 and D2, higher doses: β1 >> β2 and α1 > α2 agonist) via cAMP. Precursor of norepinephrine

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b) Sympathomimetics: synthetic catecholamines:

Dobutamine (β1 >> β2)via cAMP

Isoprenaline (β)via cAMP

Dose mcg/kg/min	α1	α2	β1	β2	Clinical effect
0.01 – 1			+++	+	↑ HR, SV, CO
Side effects: increasing myocardial oxygen requirement, tachyarrhythmias, worsening diastolic function, tachyphylaxis, hyperglycaemia

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c) Sympathomimetics: synthetic noncatecholamines:

Phenylephrine (α1 >> α2 agonist) – resuscitation in Fallot spells

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d) Phosphodiestarase inhibitors:

Milrinone via cAMP

Dose mcg/kg/min	Clinical effect
Load: 50mcg/kg
0.2 – 1	↑ CO (positive inotropic and lusitropic effect) ↓ PVR, (SVR)
Side effects: arrhythmia, hypotension (ensure appropriate volume load)

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e) Myofilament calcium sensitisers:

Levosimendan via increasing sensitivity to calcium

Dose mcg/kg/min	Clinical effect
Load: 1.25mcg/kg over 10min
Infusion: 0.2	↑ CO (positive inotropic and lusitropic effect)
Side effects: arrhythmia, hypotension in the first hours

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f) Vasoregulatory agents:

Vasopressin (V1 – arterial and V2 – tubular agonist)

Dose IU/kg/hr	V1 & V2	Clinical effect
0.01 – 0.06	+++	↑ SVR
Side effects: increasing myocardial oxygen reqirement, can cause decrease in splanchnic perfusion

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References:

[1] Am Heart J 2002 Jan; 143(1) : 15-21: Hoffman TM et al: Prophylactic intravenous use of milrinone after cardiac operation in pediatrics (PRIMACORP) study.

[2] Lancet 2002, 306: 196-202: Follath F et al: Efficacy and Safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study); a randomised double-blind trial.

[3] Curr Opin Crit Care. 2010 Oct;16(5):432-41: Parissis et al: Inotropes in cardiac patients: update 2011

[4] Curr Opin Anaesthesiol. 2009 Aug;22(4):496-501: Salmenperä et al: Levosimendan in perioperative and critical care patients.

[5] Pediatr Cardiol. 2004 Nov-Dec;25(6):623-46: Barnes et al: The pediatric cardiology pharmacopoeia: 2004 update

[6] Pediatr Crit Care Med. 2006 Sep;7(5):445-8: Namachivayam P et al: Early experience with Levosimendan in children with ventricular dysfunction.

[7] N Engl J Med. 2008 Feb 28;358(9):877-87: Russel et al: Vasopressin versus norepinephrine infusion in patients with septic shock

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