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inotropes

inotropes

see also:

introduction

  • inotropes are drugs that increase the force and velocity of myocardial contraction resulting in increased contractility and stroke volume, and therefore cardiac output.
  • vasopressors increase vascular tone, resulting in raised mean arterial pressure (MAP), and systemic vascular resistance.
  • inotropes and vasopressors are used in the Mx of shock such as sepsis / septicaemia
  • the ideal inotrope would be one that increases stroke volume without an increase in myocardial oxygen consumption or arrhythmias but as they usually work by increasing intracellular calcium (an exception is levosimendan), they are usually arrhythmogenic and usually increase myocardial oxygen consumption.
  • most agents have varying effects depending upon their dose given the variation in their activity on the various receptors
  • effects may also occur due to reflex actions, eg. reflex bradycardia with lowered cardiac output may occur with agents that cause hypertension.

choice of agent

  • it would seem dopamine has fallen out of favour in all shock states, but particularly so in septic sock following the SOAP study published in 20061)

septic shock

  • traditionally noradrenaline is 1st line with addition of dobutamine as 2nd line (controversial), and argipressin (vasopressin / ADH) for cas unresponsive to catecholamines.
  • it would seem adrenaline is as effective but tends to be withdrawn more frequently due to metabolic effects, in particular, there appears to be more splanchnic vasoconstriction than with equipotent doses of noradrenaline or dopamine in patients with severe shock.
  • it would seem vasopressin is as effective as noradrenaline

acute decompensated heart failure

  • inotropes may increase mortality

cardiogenic shock

  • unclear as to the best agents, although AHA seems to still recommend dopamine for moderate hypotension and noradrenaline for severe hypotension despite lack of evidence

inotropic agents

adrenaline

  • aka epinephrine is the US
  • an endogenous sympathomimetic agent which stimulates all adrenoceptors including alpha and beta types.
  • infusion results in positive inotropy, positive chronotropy (increased heart rate), and a significant increase in MAP, although beta-2 stimulation of skeletal muscle vascular beds causing vasodilatation may actually cause a fall in MAP.
  • it can potentiate arrhythmias, increases myocardial work and oxygen demand.
  • it's alpha-1 vasocontrictive actions (vasopressor) may result in reduced peripheral, pulmonary, renal and splanchnic perfusion and may contribute to a lactic acidosis.
  • it's significant beta 2 adrenergic agonists actions enhance glycogenolysis and triglyceride breakdown resulting in an hyperglycaemia resistant to insulin and increased lactic acid production.

dopamine

  • a sympathomimetic metabolic precursor of adrenaline and noradrenaline
  • actions are complex and dose-dependent
  • at < 2 mcg/kg/min (so called “renal dose” dopamine) its main action is on dopamine DA1 receptors ⇒ natriuresis and splanchnic vasodilation
  • at 3-10mcg/kg/min its main actions are on beta 1 and beta 2 adrenoceptors
  • at > 10 mcg/kg/min it becomes more like noradrenaline with its main actions on alpha-1 adrenoceptors

dobutamine

  • inotrope with vasodilatation
  • primarily used in refractory heart failure or cardiogenic shock but avoided a sole agent in septic shock due to the risk of hypotension from the vasodilatation.
  • unlike dopamine, it does not selectively cause renal vasodilatation.
  • a synthetic sympathomimetic agent which acts mainly on beta-1 adrenoceptor but with beta-2 agonist actions and some alpha-1 actions as well (the (-) isomer is an agonist at alpha-1 whereas the (+) isomer is an antagonist at alpha-1 with net effect being vasodilation)
  • it is useful in reducing after load in low cardiac output states such as post-MI or post-op cardiac surgery.
  • it can be used in Mx of sepsis / septicaemia in combination with noradrenaline or high dose dopamine to reduce the after load that these agents induce via their alpha-1 actions.
  • C/I in patients with idiopathic hypertrophic subaortic stenosis

noradrenaline

  • an endogenous sympathomimetic agent, its main action is as a alpha-1 agonist with beta-1 agonist actions and little beta-2 agonist actions (thus no skeletal muscle vasodilation nor the glucose metabolism effects as with adrenaline)
  • variable effect on HR and cardiac output:
    • low doses often result in vagal reflex reduction in HR accompanying the rise in MAP, and thus cardiac output may even fall.
  • it's alpha-1 vasocontrictive actions (vasopressor) may result in reduced peripheral, pulmonary, renal and splanchnic perfusion.

isoprenaline

  • a synthetic sympathomimetic agent which acts mainly on beta-1 adrenoceptor but with significant beta-2 agonist actions
  • actions are thus mainly chronotropic and inotropic but its skeletal muscle vasodilation and resultant decrease in MAP limits its use mainly to Mx of severe bradycardia or heart block.

ephedrine

  • a synthetic non-catecholamine agent with direct and indirect actions on alpha and beta adrenoceptors
  • results in longer lasting chronotropic and inotropic actions than adrenaline
  • often used as a bolus in anaesthesia to Mx hypotension, especially if it occurs with bradycardia

metaraminol

  • alpha agonist which can be used as iv bolus peripherally for short term Mx of hypotension
  • also stimulates release of noradrenaline
  • duration of action ~20 min following iv bolus
  • avoid in cardiogenic shock or decompensated mitral regurgitation where increased LV afterload may be harmful.
  • lack of inotropic effect makes it useful in Mx of hypotension with severe aortoc stenosis or hypertrophic cardiomyopathy (HCM or HOCM)
  • marketed as Aramine

PDE3 inhibitors

levosimendan

  • inotropy without negative lusitropy, and potentially less arrhythmogenic as intracellular calcium levels do not increase
  • its vasodilation effects cause dose-related hypotension and headache and precludes loading dose in an haemodynamically unstable patient
  • prolonged duration of action (up to 7 days) due to prolonged half life of its metabolite

resources

  • Senz and Nunnink. EMA Oct 2009 Vol 21, Number 5
1)
Sakr et al. Crit. Care Med 2006; 34:589-97
inotropes.txt · Last modified: 2012/04/12 21:16 (external edit)