Inotropes and vasopressors

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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: 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: 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: 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: 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: 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: 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: 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: arrhythmia, hypotension in the first hours

f) Vasoregulatory agents:

Vasopressin (V1 – arterial and V2 – tubular agonist)

Dose

IU/kg/hr

V& V2 Clinical effect
0.01 – 0.06 +++ ↑ SVR
Side effects: 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


 All Marc’s PICU cardiology FOAM can be found on PICU Doctor and can be downloaded as a handy app for free on iPhone or AndroidA list of contributors can be seen here.

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