This document discusses various vasoactive drugs used to treat low blood pressure and cardiac issues in critically ill patients. It begins by explaining the immature heart's limited responsiveness to medications and calcium regulation. It then describes different types of effects that agents can have including increasing blood pressure, contractility, heart rate, and relaxation. The remainder of the document delves into specific drugs, outlining their mechanisms, indications, dosages, and side effects. These include catecholamines like epinephrine, norepinephrine, and dopamine, as well as dobutamine, milrinone, vasopressin, nitroprusside, and nesiritide.

1. • VASOPRESSORS AND
INOTROPICS
SAMIR EL ANSARY
ICU PROFESSOR
AIN SHAMS
CAIRO

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

4. Ionized Calcium
• Plays central role in maintaining
myocardial contractility

5. Vascular Smooth Muscle
• Calcium dependent effects
– Agents that increase intracellular cAMP increase
intracellular calcium requirements for contraction,
thus encouraging smooth muscle relaxation and
vasodilation

6. Effects of Agents
• Pressors: increase systemic vascular resistance and
increase blood pressure
• Inotropes: affect myocardial contractility and
enhance stroke volume
• Chronotropic Agents: affect heart rate
• Lusotropic Agents: improve relaxation during
diastole and decrease EDP in the ventricles
• Dromotropic Agents: Affects conduction speed
through AV node; increases heart rate
• Bathmotropic Agents: affect degree of excitability

7. Alpha-Adrenergic Agents
–Alpha1-adrenergic effects:
• Vascular smooth muscle contraction
–Alpha2-adrenergic effects:
• Vascular smooth muscle relaxation

8. Beta-Adrenergic Agents
• Beta1-adrenergic effects:
– Direct cardiac effects
• Inotropy (improved cardiac contractility)
• Chronotropy (increased heart rate)
• Beta2-adrenergic effects:
• Vasodilation
• Bronchodilation

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

11. Epinephrine
• Both an alpha- and beta-adrenergic agent 0.01
mcg/kg/min - 0.3 mcg/kg/min
– Low-dose infusion = β activation
• Increase HR, contractility, decrease SVR
– Higher doses =  activation
• Increased SVR and MAP
• Increased myocardial O2 demand

12. EPINEPHRINE
α1 predominantly
Vasoconstriction
↓ Renal BF
↓ Splanchnic BF
↑ Glucose
β1 predominantly
↑HR
↓ Duration of Systole
↑ Myocardial contract
Periph. arteriolar dil.
↑/ ↓ Renal BF
↑ Renin secretion
↑/ ↓ Splanchnic BF
↑ Glucose
Hypokalemia
Epinephrine
Low Dose
(<0.05-0.1 mcg/kg/min)
High Dose
(> 0.1 μg/kg/min)

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

19. Vasopressin

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.

27. DOBUTAMINE
D- isomer
Stimulates β1 and β2
L- isomer
Stimulates α1
Dobutamine

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

29. Isoproterenol
• Synthetic catecholamine
• Non-specific beta agonist with minimal alpha-
adrenergic effects.
• Causes inotropy, chronotropy, and systemic
and pulmonary vasodilatation.
• Indications: bradycardia, decreased cardiac
output, bronchospasm (bronchodilator).

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

35. PDE Inhibition
Aminophylline
Milrinone
Sildenefil
PDE PDE 3 PDE 5

36. Milrinone
Minimal ↑ HR
↑ CO
Minimal ↑ in
O2 demand ↓ SVR
↓ PVR
Diastolic
Relaxation

37. Other Vasoactive
Agents

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

46. Relative receptor activity of most
commonly used inotropes
α1 α2 β1 β2 DA
Norepinephrine +++ +++ + - -
Epinephrine +++ ++ +++ ++ -
Dopamine ++ + ++ +++ +++
Dobutamine + - +++ + -
Isoproterenol - - ++ ++ -

47. GOOD LUCK
SAMIR EL ANSARY
ICU PROFESSOR
AIN SHAMS
CAIRO