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!
a) Sympathomimetics: endogenous catecholamines:
Adrenaline (β1 >> β2 and α1 > α2 agonist) via cAMP
|
Dose mcg/kg/min |
α1 | α2 | β1 | β2 | Clinical effect |
| – 0.05 | ++ | ++ |
↑ HR, SV, CO (↓) SVR |
||
| 0.05 – 0.10 | +++ | ↑ HR, SV, CO | |||
| 0.10 – 0.20 | +++ | +++ | +++ |
↑ HR, SV, SVR (↓) CO |
|
| Side effects:Â increasing myocardial oxygen requirement, tachyarrhythmias, worsening diastolic function, tachyphylaxis, hyperglycaemia, lactate increase | |||||
Noradrenaline (α1 > α2 and β1 >> β2 agonist) via cAMP ?
|
Dose mcg/kg/min |
α1 | α2 | β1 | β2 | Clinical effect |
| – 0.10 | +++ | ++ | +++ |
↑ SVR, HR (↓) CO |
|
| 0.10 – 0.20 | ++++ | +++ | +++ |
↑ SVR, HR, SV ↓ CO |
|
| Side effects:Â increasing myocardial oxygen requirement, can cause decrease in CO, tachyphylaxis, hyperglycaemia | |||||
Dopamine (D1 and D2, higher doses: β1 >> β2 and α1 > α2 agonist) via cAMP. Precursor of norepinephrine
|
Dose mcg/kg/min |
α1 | α2 | β1 | β2 | Clinical effect |
| 0.5 – 2 | ↑ increased splanchnic perfusion | ||||
| 2 – 5 | ++ | ↑ HR, SV, CO | |||
| 5 – 10 | ++ | ++ |
↑ HR, SV, SVR (↓) CO |
||
| > 10 | +++ |
↑ SVR ↓ CO |
|||
| Side effects:Â increasing myocardial oxygen requirement, can cause decrease in CO, tachyarrhythmias, tachyphylaxis, hyperglycaemia, immunsuppressive effect, inhibition of thyrotropin releasing hormone | |||||
b) Sympathomimetics: synthetic catecholamines:
Dobutamine (β1 >> β2)via cAMP
|
Dose mcg/kg/min |
α1 | α2 | β1 | β2 | Clinical effect |
| 2.5 – 10 | ++ | ++ |
↑ HR, SV, CO (↓) SVR |
||
| > 10 | +++ | ↑ HR, SV, CO | |||
| Side effects:Â increasing myocardial oxygen requirement, tachyarrhythmias, worsening diastolic function, tachyphylaxis, hyperglycaemia | |||||
Isoprenaline (β)via cAMP
|
Dose mcg/kg/min |
α1 | α2 | β1 | β2 | Clinical effect |
| 0.01 – 1 | +++ | + | ↑ HR, SV, CO | ||
| Side effects:Â increasing myocardial oxygen requirement, tachyarrhythmias, worsening diastolic function, tachyphylaxis, hyperglycaemia | |||||
c) Sympathomimetics: synthetic noncatecholamines:
Phenylephrine (α1 >> α2 agonist) – resuscitation in Fallot spells
|
Dose mcg/kg/min |
α1 | α2 | β1 | β2 | Clinical effect |
| 0.1 – 5 | +++ | ++ | +++ |
↑ SVR ↓ HR (reflex), CO |
|
|
Side effects:Â increasing myocardial oxygen requirement, can cause decrease in CO, tachyphylaxis, hyperglycaemia |
|||||
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:Â arrhythmia, hypotension (ensure appropriate volume load) | |
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:Â arrhythmia, hypotension in the first hours | |
f) Vasoregulatory agents:
Vasopressin (V1 – arterial and V2 – tubular agonist)
|
Dose IU/kg/hr |
V1Â & V2 | Clinical effect |
| 0.01 – 0.06 | +++ | ↑ SVR |
| Side effects:Â increasing myocardial oxygen reqirement, can cause decrease in splanchnic perfusion | ||
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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