Pharmacologic Management
of Acute Circulatory Failure:
Vasoactive Medications
Thank you Suanne Daves, MD
What you will hear today
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A short review of Shock
A look at how the intrinsic
sympathetic nervous system &
various drugs that can
accelerate/enhance the excitationcontraction coupling phenomenon in
myocytes (improve cardiac output).
Circulatory Failure / Shock
What is it?
Metabolic demand outstrips supply or
the ability to extract
The anaerobic state leads to
accumulation of lactic acid. Energy
dependent cellular processes cease
Cellular edema, cellular disruption,
cell death….. Organ failure
A digression to cell biology
Cardiac Output and SVR
are all about Calcium
all about Calcium
PDE
Back to something more
familiar: Starling
The Body’s Neuronal Defense System
β1
β2
ά1
β2
ά1
β2
Vasopressin
DA1-2
Vasopressin
Bohn (2006). Inotropic Agents in Heart Failure. Heart Failure in
Children and Young Adults. Chang & Towbin.
PDE
When you need to intervene:
Vasoactive Medications:
Goals of treatment
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Provide adequate tissue
oxygenation.
Maintain vital organ function.
Restore systemic blood pressure.
Tailor drugs to minimize adverse
side effects.
Vasoactive Medications
Catacholamines
Vasopressin
Phosphodiesterase inhibitors
Calcium sensitizers
Catacholamines with
inotropic properties
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Epinephrine
Norepinephrine
Isoproterenol
Dopamine
Dobutamine
Bohn (2006). Inotropic Agents in Heart Failure. Heart Failure in
Children and Young Adults. Chang & Towbin.
Bohn (2006). Inotropic Agents in Heart Failure. Heart Failure in
Children and Young Adults. Chang & Towbin.
Bohn (2006). Inotropic Agents in Heart Failure. Heart Failure in
Children and Young Adults. Chang & Towbin.
Bohn (2006). Inotropic Agents in Heart Failure. Heart Failure in
Children and Young Adults. Chang & Towbin.
Bohn (2006). Inotropic Agents in Heart Failure. Heart Failure in
Children and Young Adults. Chang & Towbin.
Starling again
Improved inotropy
CO
Catacholamines with
pressor properties

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Phenylephrine
Epinephrine
Norepinephrine
Dopamine
More Starling…
more preload = more CO
Remember:
too much
afterload
=
CO
Other Vasoactive Options

Milrinone
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Vasopressin
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PDE inhibitor
Vasoconstriction
Improves sensitivity to catachols
Levosimendan

Calcium sensitizing agent
Starling again
Reduced
afterload
improved CO
The Downside of Vasoactive Agents
(mostly true for catachols)
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Increased myocardial O2 demand
Myocardial injury/cell death
Tolerance/tachyphylaxis
Arrhythmogenesis
Peripheral vasoconstriction
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Elevates SVR
Compromises splanchnic blood flow
Bedside Reality…
A 4-mos-old infant presents to the
ER with irritability, poor po intake,
and tachypnea. The ER doc says
the baby looks “shocky”. They
have started an IV & given
20mL/kg NS.
The infant is awake & quiet.
HR: 170s-180s (sinus)
RR: 70s
BP: 90/68
He is cool peripherally.
His pulses are ‘thready’
pH 7.29/pCO2 38/pO2 82/HCO3
18
Lactate 4.0
Would you begin an
inotrope/pressor?
Which one?
Same infant……….
HR: 180s (sinus)
RR: 70s
BP: 52/44
Key Concepts
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The predominant β-AR in the heart is
the β1-AR (<75%).
β2-ARs are largely found in vascular
smooth muscle.
Ά1-ARs predominate in vascular
smooth muscle although they are
present in the neonatal myocardium.
Key Concepts
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Catacholamines are good in the short
term for hemodynamic support but most
increase myocardial oxygen demand,
increase diastolic pressures, and can lead
to apoptosis
PDE inhibitors, while increasing
intracellular Ca+, are lusiotropic and
inotropic agents that do not increase
myocardial O2 demand and are not
associated with tachyphylaxis.
Key Concepts
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A strategy of combining a PDE inhibitor
with a catecholamine may be the best
approach to support of the myocardium
and circulation.
Most inotropic agents to date have a
common final intracellular pathway of
increased intracellular Ca+, which may
ultimately lead to cell (myocyte) death.
And we continue to look for
something better

A new generation of inotropic agents known as calciumsensitizing agents achieve their positive inotropic effects
without an increase in intracelluar Ca+ or myocardial O2
consumption. Unfortunately they early studies of the
first of these drugs demonstrated less benefit than was
anticipated
1
β1
β2