Download Inotropes and fluids

Inotropes and fluids
Dr Cath Spoors
Consultant, Anaesthesia and Burns Intensive Care
Broomfield Hospital, Chelmsford
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Fluids and fluid challenges
Why use drugs to affect the CVS?
Definitions
Receptors
Drugs
Practice points, pearls and pitfalls
Fluids
• Primarily affect preload
• Optimising preload will have a positive
inotropic effect
• Blood also affects oxygen carrying capacity
• Blood products will affect coagulation
• Hypovolaemia may be absolute or relative
Preload
Spotting hypovolaemia
Spotting hypovolaemia
Spotting hypovolaemia
Fluid overload
Fluid challenge
Fluid challenge
• Step change in intravascular volume / venous return
• Choose your parameter
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CVP
SVV
FTc
SV
• 250ml is reasonable (consider less if prone to cardiac
failure/overload). Consider a straight-leg raise
• Record pre-challenge, immediately after, then after 10-15
min
• The aim is a sustained improvement
• Transient usually indicates room for further fluid
• No improvement – either patient is “full” or the
hypovolaemia is very severe.
• Consider other pathologies (e.g. tamponade, PE)
Inotropes
Why use drugs to affect the CVS?
• Improve the flow
– The amount of blood delivered
• Improve pressure
– To allow delivery of oxygen and substrates
• Improve distribution
– To defend vital organs
Why use drugs to affect the CVS?
• Improve the flow
– The amount of blood delivered
• Improve pressure
– To allow delivery of oxygen and substrates
• Improve distribution
– To defend vital organs
Optimise the circulation without over-stressing it
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Inotrope
Chronotrope
Lusitrope
Vasopressor
Agonist
Antagonist
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Inotrope – increases force of contraction
Chronotrope
Lusitrope
Vasopressor
Agonist
Antagonist
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Inotrope – increases force of contraction
Chronotrope – increases heart rate
Lusitrope
Vasopressor
Agonist
Antagonist
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Inotrope – increases force of contraction
Chronotrope – increases heart rate
Lusitrope – increases rate of cardiac relaxation
Vasopressor
Agonist
Antagonist
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Inotrope – increases force of contraction
Chronotrope – increases heart rate
Lusitrope – increases rate of cardiac relaxation
Vasopressor – constricts blood vessels
Agonist
Antagonist
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Inotrope – increases force of contraction
Chronotrope – increases heart rate
Lusitrope – increases rate of cardiac relaxation
Vasopressor – constricts blood vessels
Agonist – activates a receptor
Anatgonist
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Inotrope – increases force of contraction
Chronotrope – increases heart rate
Lusitrope – increases rate of cardiac relaxation
Vasopressor – constricts blood vessels
Agonist – activates a receptor
Antagonist – opposes a receptor
“Squeeze harder!”
- Inotrope
“Send the air to
the bag!”
- Vasopressor
“Pump faster!”
- Chronotrope
“Let go in
between!”
- Lusitrope
Receptor
Site
Effect
α1 adrenergic
Vascular smooth muscle
Liver
Vasoconstriction
Glycogenolysis; potassium release
α2 adrenergic
CNS: pre-synaptic
Inhibit noradrenaline release:
negative feedback loop causing
sedation, vasodilatation, muscle
relaxation
β1 adrenergic
Myocardium
Increased heart rate and contractility
β2 adrenergic
Vascular smooth muscle
Vasodilatation (peripheral and renal
circulation)
Dopaminergic
D1 – renal, coronary,
mesenteric
D2 – nerve endings
Vasodilatation
Effects are dose-dependent
V1 (vascular)
Vascular smooth muscle
Cardiac myocytes
Platelets
Efferent glomerular
arterioles
Vasoconstriction - coronary and
cerebral sparing
Other sites of drug action
• Direct intracellular (phosphodiesterase
inhibitors, levosimendan, calcium)
• Guanylate cyclase (methylene blue – blocks
nitric oxide-induced vasodilatation)
• Inhibition of inflammation (steroids)
Decisions, decisions...
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Noradrenaline
Adrenaline
Dopamine
Dobutamine
Dopexamine
Milrinone
Enoximone
Levosimendan
Metaraminol
Vasopressin
Terlipressin
Methylene blue
Corticosteroid
Calcium
Noradrenaline
• Endogenous catecholamine
• Secreted as a hormone from the adrenal medulla
• Released from sympathetic nerve endings -spills over into
circulation during mass sympathetic stimulation
• Acts on α1 adrenergic and β1 adrenergic receptors
• Vasoconstriction – increased SVRI and re-distribution of
blood flow to heart, brain, and skeletal muscle
• Inotropy; theoretically chronotropy but offset by reflex
bradycardia due to α1 effect
• Increased mean arterial pressure (MAP)
• Increased myocardial oxygen demand
• May distribute blood flow away from skin, splanchnic
circulation, and renal circulation – e.g. if used before
correction of hypovolaemia
Metaraminol
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Predominantly acts at α1 receptors
Vasoconstrictor action
Reflex bradycardia can be marked
Can be given in small IV boluses
Often used in anaesthesia to counteract
vasodilatation (e.g. from spinal or epidural)
• Can be used as a bridge to a noradrenaline
infusion
Adrenaline
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Endogenous catecholamine
Main hormone secreted from adrenal medulla
Sympathetic neurotransmitter
Acts non-selectively on all adrenergic receptors
Chronotropic and inotropic
Vasoconstriction – re-distribution of blood flow to
heart, brain, and skeletal muscle
Used during CPR
Bronchodilator (used in status asthmaticus)
Drug of choice in anaphylaxis
Increases myocardial oxygen demand
May cause lactic acidosis
May cause hyperglycaemia
Dopamine
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Endogenous catecholamine
Precursor of noradrenaline and adrenaline
Acts at dopaminergic, β1 and α1 receptors
Actions are dose-dependent: low doses (0.53mcg/kg/min) cause coronary, renal, mesenteric, and
cerebral vasodilatation via D1 and D2 receptors;
intermediate doses (3-10mcg/kg/min cause β1mediated inotropy, chronotropy, and some increase in
SVR; and high doses (>10mcg/kg/min) cause α1 effects
i.e. vasoconstriction
• “Renal” dose controversial
• Inhibits peristalsis – may cause ileus
Dobutamine
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Synthetic catecholamine
Strong β-agonist (β1 and β2) – “inodilator”
Potent inotrope
β2 effects cause vasodilatation but α1 effect
predominate at higher doses
• Significant increase in oxygen consumption
(dobutamine stress test)
• Can cause ventricular arrhythmias
• Tolerance can be an issue
Comparative receptor actions of
catecholamines
Dopexamine
• Synthetic catecholamine
• β2 agonist. Also active at D1 and D2 receptors;
and inhibits neuronal catecholamine uptake
• Vasodilation which can be profound
• Mild positive inotropy/chronotropy
• Reduces afterload via generalised
vasodilatation but can cause hypotension
Phosphodiesterase inhibitors
• Milrinone/enoximone
• Increase calcium availability within the myocyte and
therefore the force of contraction
• Also enhance calcium return to sarcoplasmic reticulum,
enhancing cardiac relaxation (lusitropy)
• Cause vasodilatation due to effects in vascular smooth
muscle
• Heart rate minimally affected
• Do not significantly increase myocardial oxygen
consumption
• Useful in acute right ventricular failure due to dilatory
effects on pulmonary arteries (reduces right ventricular
afterload)
• Can cause significant hypotension in hypovolaemic patients
• Vasopressors may be required in addition
Levosimendan
• Calcium sensitiser – enhances the molecular
mechanics of muscle contraction
• Binds to cardiac troponin C
• Positive inotropy without increasing
myocardial oxygen consumption
• Vasodilatory in pulmonary circulation –
offloads the right ventricle
• Does not increase intracellular calcium – less
arrhythmogenic than PDEIs
Vasopressin
• Acts on peripheral vasopressin receptors
• Effects are preserved during hypoxia and severe
acidosis
• Greatest effects in gut, muscle, and skin
• May be dilatory to pulmonary, coronary, and cerebral
circulation (but high doses may cause cardiac
ischaemia)
• Increases free water resorption in kidney (can cause
hyponatraemia)
• Increases cortisol secretion by stimulating ACTH
release from pituitary
Methylene Blue
• Inhibits guanylyl cyclase, preventing nitric
oxide-induced vasodilatation
• May improve outcomes in vasoplegic
syndrome after cardiopulmonary bypass
• Effects in other pathologies not well-studied –
use is empirical generally
• Interferes with sats probe!
Weaning inotropes
• The inotropes will wean when the patient gets
better – not the other way around
• Wean the most harmful ones first (adrenaline)
• Wean when MAP exceeds target by around
5mmHg
• There is no shame in not being able to wean
• Weaning inotropes seems more difficult at night
• Keep assessing fluid balance: inotropes are NOT a
contraindication to diuretics if the patient is fluid
overloaded
• Don’t use pain or distress as inotropes!