2. Myocardial Contraction
• Contractility increases over 1st months of life
along with:
– Sympathetic nerve fibers within myocardium
– Total concentration of endogenous
norepinephrine
• There is a greater dependence of CO on HR
than contractility during this time
3. Immature Heart
• Limited responsiveness to medications
– noncontractile content
– availability of releasable NE
– Less mature sympathetic system
– Underdeveloped intracellular calcium regulatory
mechanisms
– functional reserve capacity
9. Dopaminergic Agents
• Dopaminergic Agents
– Several types of receptors located throughout
body (D1-D5)
– Certain (esp. D1-like & D2-like) dopaminergic
receptors increase renal and mesenteric blood
flow
10. Catecholamines
• Sympathomimetic amines that contain O-
dihydrobenzene
• Dopamine, epinephrine and norepinephrine are
endogenous
• Dobutamine and isoproterenol are synthetic
• Sustained use or antecedent CHF can lead to down-
regulation of β-receptors and decrease efficacy
13. Epinephrine
• Indications for its use as a continuous infusion are:
– low cardiac output state
• beta effects will improve cardiac function
• alpha effects may increase afterload and
decrease cardiac output
– septic shock
• useful for both inotropy and vasoconstriction
14. Epinephrine
• Adverse effects include:
– Anxiety, tremors,palpitations
– Tachycardia and tachyarrhythmias
– Increased myocardial oxygen requirements and
potential to cause ischemia
– Decreased splanchnic and hepatic circulation
(elevation of AST and ALT)
– Anti-Insulin effects: lactic acidosis,
hyperglycemia
15. Norepinephrine
• An epinephrine precursor that acts primarily on
receptors
• Used primarily for alpha agonist effect - increases
SVR without significantly increasing C.O.
• Used in cases of low SVR and hypotension such as
profound “warm shock” with a normal or high C.O.
state- usually in combination with dopamine or
epinephrine
• Infusion rates titrated between 0.05 to 0.3
mcg/kg/min
16. Norepinephrine
• Differs from epinephrine in that the
vasoconstriction outweighs any increase in
cardiac output.
– i.e. norepinephrine usually increases blood
pressure and SVR, often without increasing
cardiac output.
17. Norepinephrine
• Adverse Effects:
– Similar to those of Epinephrine
– Can compromise perfusion in extremities and may
need to be combined with a vasodilator e.g.
Dobutamine or Nipride
– More profound effect on splanchnic circulation
and myocardial oxygen consumption
18. Vasopressin
• A peptide hormone released by the posterior
pituitary in response to rising plasma tonicity
or falling blood pressure
• Antidiuretic and vasopressor properties
• Deficiency of this hormone results in diabetes
insipidus
20. Vasopressin
• Administration
– intravenous, intramuscular, or intranasal routes
– IV is route for vasopressor activity
– The half-life of circulating ADH is approximately 20
minutes, with renal and hepatic catabolism via
reduction of the disulfide bond and peptide
cleavage
21. Vasopressin
• Administration
– interacts with two types of receptors
• V1 receptors are found on vascular smooth
muscle cells and mediate vasoconstriction
• V2 receptors are found on renal tubule cells
and mediate antidiuresis through increased
water permeability and water resorption in
the collecting tubules
• Use in refractory septic shock with low SVRI in
pediatrics?
22. Dopamine
• Intermediate product in the enzymatic
pathway leading to the production of
norepinephrine; thus, it indirectly acts by
releasing norepinephrine.
• Directly has , and dopaminergic actions
which are dose-dependent.
• Indications are based on the adrenergic
actions desired.
23. Dopamine
• renal perfusion 2-5 mcg/kg/min (dopaminergic
effects) by sensitivity of vascular smooth muscle to
intracellular calcium
• C.O. in Cardiogenic or Distributive Shock 5-
10mcg/kg/min ( adrenergic effects)
• Post-resuscitation stabilization in patients with
hypotension (with fluid therapy) 10-20 mcg/kg/min
( adrenergic effects) peripheral vasoconstriction,
SVR, PVR, HR.
24. Dose Dependent effect of Dopamine
<5 mcg 5 - 10 mcg > 10 mcg
↑Contractility
Minimal change in
HR and SVR
↑ Renal BF
↑ Splanchnic BF
Modest ↑ CO
↑ Renal BF
↓Proximal Tub. Na
Absorbtion
↑ Splanchnic BF
↑ HR,
Vasoconstriction
↑/ ↓ Renal BF
↓/↑ Splanchnic BF
25. Dobutamine
• Synthetic catecholamine with 1 inotropic effect
(increases stroke volume) and 2 peripheral
vasodilation (decreases afterload)
• Positive chronotropic effect 1 (increases HR)
• Some lusotropic effect
• Overall, improves Cardiac Output by above beta-
agonist acitivity
26. Dobutamine
• Major metabolite is 3-O-methyldobutamine, a
potent inhibitor of alpha-adrenoceptors.
– Therefore, vasodilation is possible secondary to
this metabolite.
• Usual starting infusion rate is 5 mcg/kg/min,
with the dose being titrated to effect up to 20
mcg/kg/min.
28. Dobutamine
• Used in low C.O. states and CHF e.g.
myocarditis, cardiomyopathy, myocardial
infarction
• If BP adequate, can be combined with
afterload reducer (Nipride or ACE inhibitor)
• In combination with Epi/Norepi in profound
shock states to improve Cardiac Output and
provide some peripheral vasodilatation
30. Isoproterenol
• Occasionally used to maintain heart rate
following heart transplantation.
• Dose starts at 0.01 mcg/kg/min and is
increased to 2.0 mcg/kg/min for desired
effect.
• Avoid in patients with subaortic stenosis,
and hypertrophic cardiomyopathy or TOF
lesions because increases the outflow
gradient
31. Milrinone/Amrinone
• Belong to class of agents “Bipyridines”
• Non-receptor mediated activity based on
selective inhibition of Phosphodiesterase Type
III enzyme resulting in cAMP accumulation in
myocardium
• cAMP increases force of contraction and rate
and extent of relaxation of myocardium
• Inotropic, vasodilator and lusotropic effect
32. Milrinone/Amrinone
• Advantage over catecholamines:
–Independent action from -receptor
activation, particularly when these
receptors are downregulated
(CHF and chronic catecholamine use)
33. Milrinone
• Increases CO by improving contractility,
decreased SVR, PVR, lusotropic effect;
decreased preload due to vasodilatation
• Unique in beneficial effects on RV function
• Protein binding: 70%
• Half-life is 1-4 hours
34. Milrinone
• Elimination: primarily renally excreted
• Load with 50 mcg/kg over 30 mins
followed by 0.25 to 0.75 mcg/kg/min
• No increase in myocardial O2
requirement
38. BNP
{ Brain natriuretic peptide }
• Secreted by ventricles in response to ↑
wall stress and volume overload
39. NESRITIDE
{Recombinant Human BNP}
• Venous and arteriolar dilator, acts on
Guanylate cyclase
• It reduces RA pressure, PCWP and cardiac
index
• Dose: Infusion 0.01- 0.03 mcg/kg/min
• Hypotension
40. Nesiritide
• Nesiritide (recombinant human BNP) is a vasodilator
with other theoretical effects including:
– natriuresis, neurohormonal inhibition, and reverse
remodeling
– In the setting of Heart Failure, it has been shown
to reduce pulmonary capillary wedge pressure
and improve shortness of breath relative to
placebo
– Linked to possible renal failure and increased
mortality in some patient populations
41. Vasodilators
• Classified by site of action
• Venodilators: reduce preload - Nitroglycerin
• Arteriolar dilators: reduce afterload Minoxidil and
Hydralazine
• Combined: act on both arterial and venous beds and
reduce both pre- and afterload Sodium Nitroprusside
(Nipride)
42. Nitroprusside
• Vasodilator that acts directly on arterial and
venous vascular smooth muscle.
• Indicated in hypertension and low cardiac
output states with increased SVR.
• Also used in post-operative cardiac surgery to
decrease afterload on an injured heart.
• Action is immediate; half-life is short;
titratable action.
43. Nitroprusside
• Toxicity is with cyanide, one of the metabolites of the
breakdown of nipride.
• Severe, unexplained metabolic acidosis might
suggest cyanide toxicity.
• Dose starts at 0.5 mcg/kg/min and titrate to 5
mcg/kg/min to desired effect. May go higher (up to
10 mcg/kg/min) for short periods of time.
44. Nitroglycerine
• Direct vasodilator as well, but the major
effect is as a venodilator with lesser effect
on arterioles.
• Not as effective as nitroprusside in lowering
blood pressure.
• Another potential benefit is relaxation of
the coronary arteries, thus improving
myocardial regional blood flow and
myocardial oxygen demand.
45. Nitroglycerine
• Used to improve myocardial perfusion
following cardiac surgery
• Dose ranges from 0.5 to 8 mcg/kg/min.
Typical dose is 2 mcg/kg/min for 24 to 48
hours post-operatively
• Methemoglobinemia is potential side effect