Pharmacologic Management of Acute Circulatory Failure: Vasoactive Medications

1
Pharmacologic Management of Acute Circulatory
Failure Vasoactive Medications

• Thank you Suanne Daves, MD

2
What you will hear today

• A short review of Shock
• A look at how the intrinsic sympathetic nervous
  system various drugs that can
  accelerate/enhance the excitation-contraction
  coupling phenomenon in myocytes (improve cardiac
  output).

3
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

4
BP CO x SVR
5
BP CO x SVR
SVR vascular tone
6
A digression to cell biology Cardiac Output and
SVR are all about Calcium
7
all about Calcium
PDE
8
Back to something more familiar Starling
9
The Bodys Neuronal Defense System
10
(No Transcript)
11
(No Transcript)
12
(No Transcript)
13
(No Transcript)
14
(No Transcript)
15
Bohn (2006). Inotropic Agents in Heart Failure.
Heart Failure in Children and Young Adults.
Chang Towbin.
16
PDE
17
When you need to intervene Vasoactive
Medications Goals of treatment

• Provide adequate tissue oxygenation.
• Maintain vital organ function.
• Restore systemic blood pressure.
• Tailor drugs to minimize adverse side effects.

18
(No Transcript)
19
Vasoactive Medications

• Catacholamines
• Vasopressin
• Phosphodiesterase inhibitors
• Calcium sensitizers

20
Catacholamines with inotropic properties

• Epinephrine
• Norepinephrine
• Isoproterenol
• Dopamine
• Dobutamine

21
Bohn (2006). Inotropic Agents in Heart Failure.
Heart Failure in Children and Young Adults.
Chang Towbin.
22
Bohn (2006). Inotropic Agents in Heart Failure.
Heart Failure in Children and Young Adults.
Chang Towbin.
23
Bohn (2006). Inotropic Agents in Heart Failure.
Heart Failure in Children and Young Adults.
Chang Towbin.
24
Bohn (2006). Inotropic Agents in Heart Failure.
Heart Failure in Children and Young Adults.
Chang Towbin.
25
Bohn (2006). Inotropic Agents in Heart Failure.
Heart Failure in Children and Young Adults.
Chang Towbin.
26
Starling again
Improved inotropy CO
27
Catacholamines with pressor properties

• Phenylephrine
• Epinephrine
• Norepinephrine
• Dopamine

28
More Starlingmore preload more CO
Remember too much afterload CO

29
Other Vasoactive Options

• Milrinone
• PDE inhibitor
• Vasopressin
• Vasoconstriction
• Improves sensitivity to catachols
• Levosimendan
• Calcium sensitizing agent

30
Starling again
Reduced afterload improved CO
31
The Downside of Vasoactive Agents
(mostly true for catachols)

• Increased myocardial O2 demand
• Myocardial injury/cell death
• Tolerance/tachyphylaxis
• Arrhythmogenesis
• Peripheral vasoconstriction
• Elevates SVR
• Compromises splanchnic blood flow

32
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.

33

• 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?

34

• Same infant.
• HR 180s (sinus)
• RR 70s
• BP 52/44

35
Key Concepts

• The predominant ß-AR in the heart is the ß1-AR
  (lt75).
• ß2-ARs are largely found in vascular smooth
  muscle.
• ?1-ARs predominate in vascular smooth muscle
  although they are present in the neonatal
  myocardium.

36
Key Concepts

• 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.

37
Key Concepts

• 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.

38
And we continue to look for something better

• A new generation of inotropic agents known as
  calcium-sensitizing 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

Levosimendan
39
(No Transcript)
40
1