Vasopressors and inotropes

Dopamine

• Endogenous catecholamine and metabolic precursor of noradrenaline and adrenaline
• Acts on dopaminergic, alpha-1, beta-1 and beta-2 receptors
• At intermediate doses (5-15mcg/kg/min) increases renal blood flow, HR, cardiac contractility and cardiac output
• At high doses (>15mcg/kg/min), alpha adrenergic effects predominate leading to vasoconstriction and inreased blood pressure
• Low dose ‘renal-protective’ dopamine dosing is no longer recommended due to lack of evidence supporting its use

Dopamine

• Pharmacokinetics
  • Renal, hepatic and plasma metabolism
    • 75% to inactive metabolites by MAO
    • 25% to noradrenaline
  • Excreted in urine as metabolites
  • Half-life 2min
  • Onset <5 min and duration <10 min
• Indications
  • Hypotension due to CCF, MI, trauma and renal failure
  • No longer recommended as first-line in sepsis
  • Second-line for symptomatic bradycardia unresponsive to atropine
• Gradually wean off when discontinued to avoid hypotension
• Adverse effects
  • Chest pain, palpitations, hypertension, ectopic beats, nausea, vomiting, headache, gangrene and tachycardia
  • Extravasation can cause tissue necrosis and is treatable with phentolamine
  • CI in phaeo, tachyarrhythmias and VF

Adrenaline

• Hepatically metabolised by MAOi and COMT
• Urine excretion as inactive metabolites
• Half-life 2min
• Onset 1-2 min; duration 2-10 min
• Recommended as addition to or substitution for noradrenaline in severe septic shock when additional agent required
• Adverse effects include angina, palpitations, arrhythmias, HTN, nausea, vomiting, headache, anxiety and pulmonary oedema
• Extravasation may cause necrosis and can be treated by phentolamine
• Anaphylaxis 0.3mg IM q5min as required
• 0.1mg IV (1:10 000) over 5 min; 1-20mcg/min infusion

Noradrenaline

• Alpha-1, beta-1 > beta-2
• Leads to inotropic stimulation of heart and coronary artery dilation
• Metabolised by MAO and COMT
• Renally excreted as inactive metabolites
• Half-life 3 min
• Onset 1-2 min, duration 5-10min

Phenylephrine

• Selective alpha-1 adrenergic agonist
• Lacks beta-activity
• Can cause reflex bradycardia and reduced CO as a result
• Hepatic metabolism via oxidative deamination (50%), sulfation (8%) and some glucuronidation to inactive metabolites
• Excreted as inactive metabolites in urine
• Half-life alpha 5min, terminal 2-3 hours
• Immediate onset and 15-20 min duration
• Used for treatment of hypotension and shock but not recommended for cardiogenic or septic shock
• 50-150mcg/min infusion starting dose with 40-60mcg/min maintenance rate
• Can give 100-500mcg boluses q10-15min
• Adverse effects
  • HTN, decreased CO, reflex bradycardia, arrhythmias
  • Renal, mesenteric, myocardial ischaemia
  • Peripheral ischaemia
  • Use with caution in bradycardia, hyperthyroidism, heart block and CAD

Vasopressin

• Endogenous noradrenergic vasopressor
• Stimulates V1 receptors in smooth muscle causing direct peripheral vasoconstriction and improves cerebral/cardiac perfusion
• No inotropic or chronotropic effects on the heart
• Can cause reflex bradycardia and reduced CO
• Also acts on V2 receptors to produce antidiuretic effect
• Hepatically and renally metabolised with mostly renal excretion
• Half-life 10-20 min
• Immediate onset and 10min duration
• Can add to noradrenaline at rate up to 0.03U/min to raise MAP or reduced NA dosing but should not be used as single agent for septic shock
• Doses higher than 0.04U/min should only be used for salvage therapy
• Adverse effects
  • Diaphoresis, nausea, vomiting, headache, urticaria, gangrene, arrhythmia, mesenteric ischaemia, MI, bronchoconstriction, venous thrombosis and cardiac arrest

Dobutamine

• Synthetic dopamine analogue with potent inotropic, mild vasodilatory and mild chronotropic effects
• Competitive agonist at alpha and beta-receptors (beta-1>2>alpha)
• Mainly increases contractility and HR with neutral effect on BP
• Metabolised in tissues and liver to inactive metabolites that are then excreted in urine
• Half-life 2 minutes and peak effect 10-20min
• Indicated for cardiogenic shock, septic shock (especially if evidence of myocardial dysfunction or low CO)
• Continuous infusion 2mcg/kg/min up to 40mcg/kg/min (max 20 in septic shock)
• Adverse effects:
• Hypertension, hypotension, tachycardia, arrhythmias, myocardial ischaemia, angina, hypokalaemia
• Use in AF can lead to RVR
• Use post-MI may lead to increased O2 demand
• Ineffective in presence of aortic stenosis and should be avoided
• Concomitant use of MAOi ay lead to prolonged HTN
• Prolonged use has been associated with increased mortality

Milrinone

• Inotrope with vasodilatory properties
• Phosphodiesterase III inhibitor leading to inhibited breakdown of cAMP
• Leads to increased cardiac contractility and peripheral arterial and venous dilatation
• For short-term treatment of cardiogenic shock
• 50mcg/kg IV loading dose over 10 minutes then 0.25-0.75mcg/kg/min infusion
• Loading dose often omitted in hypotensive patients
• 2.5 hour half-life (prolonged in renal failure)
• Mostly renally excreted as unchanged drug
• Adverse effects – Ventricular and supraventricular arrhythmias, hypotension, angina, headache, thrombocytopaenia, LFT derangement
• Not recommended for septic shock
• Long-term use is associated with increased mortality

Last Updated on October 28, 2020 by Andrew Crofton