The term inotropic state is most commonly used in reference to various drugs that affect the strength of contraction of heart muscle (myocardial contractility). However, it can also refer to pathological conditions. For example, enlarged heart muscle (ventricular hypertrophy) can increase inotropic state, whereas dead heart muscle (myocardial infarction) can decrease it.

1. INOTROPES AND
VASOPRESSOR
USED IN ICU
PRESENTED BY
PANKAJ SINGH RANA
NURSE PRACTITIONER
1ST YEAR

2. Definitions
 Inotrope
Increases cardiaccontractility
 Vasopressor
Induces vasoconstriction pressure
elevation of meanarterial

3. Use of inotropes & vasopressors
 Tosupport the failing heart
 Tosupport the failing peripheralvasculature
 Tocorrect hypotension during anaesthesia (generalor
regional)

5. Clinical Effects of
Adrenergic Receptors
Alpha1
 Vasoconstriction
 Gut smooth musclerelaxation
 Increased salivasecretion
 Hepaticglycogenolysis
Alpha2
 Inhibit NA & Achrelease
 Stimulate plateletaggregation

6. Beta1
 Chronotropy
 Inotropy
 Gut smooth musclerelaxation
 Lipolysis
Beta2
 Vasodilatation
 Bronchioledilatation
 Visceral smooth musclerelaxation
 Hepaticglycogenolysis
 Muscletremor

7. Dopamine receptors
1. Peripheral DA1 receptors
• mediate renal, coronaryand mesenteric arterial
vasodilatation and a natriuretic response
2. DA2receptors:
• presynaptic receptors found onnerve endings,
• inhibit norepinephrine release from sympathetic nerve
endings,
• inhibit prolactin release and
• may reducevomiting stimulation
• vasoconstriction

8. Drug and Receptor Interactions

9. EPINEPHRINE
Pharmacokinetics
Admin: IV / IM
Elimination: mostly degraded by conjugation withglycuronic and
sulphuric acids and excreted in the urine.
Pharmacodynamics
- stimulates alpha1 and both beta1 and beta2 receptors.
Effects are mediated by stimulation of adenyl cyclase
resulting in an increase incAMP
- beta2 receptors more sensitive to epinephrine than alpha1

11. USES
 Hypotension- usual dose 1-70 mcg/min
 Cardiac arrest- 1-3 mg every 2-3 min during
resuscitation
 Anaphylaxis- 0.3-1mg IM or Subcutaneous.
• Can be given IV in life threatening anaphylaxis ( dilute
1mg in 10ml of NS and give 1mg every 2-3 min.
 Children- 10 mcg/kg for cardiac arrest every 5 min if
necessary, and subcutaneous in severe anaphylaxis or
asthma repeated at 20 min to 4 hours.

12. NOREPINEPHRINE
 alpha and beta1 agonist with no clinically
significant beta2 effects
 used for refractory hypotension
 may result in no change or slight decrease in
cardiac output and oxygen delivery due to
increased afterload

13.  In the non-septic patient produces vasoconstriction in all
vascular beds,
 Including the renal circulation in septic patients increases
BP and SVR, often without altering cardiac output. Often
improves renal blood flow and urine output in these
patients by increasing perfusion pressure without
compromising cardiac output.
 May be useful in cardiogenic shock: increases
coronary perfusion pressure.

14.  norepinephrine has no effect onrenal blood
flow in patients with established acute renal
failure and in hypotensive patients both
epinephrine and norepinephrine may increase
renal blood flow by increasing perfusion
pressure
clinical use
 in doses of 0.01-2 mcg/kg/min reliably and
predictably improves hemodynamic variables
to normal.

15. DOPAMINE
 Immediate precursor of norepinephrine andepinephrine
Pharmacodynamics
Dose dependenteffects:
<5 mg/kg/min predominantly stimulates DA1 and DA2
receptors in renal, mesenteric and coronary bedsvasodilatation
5-10 m g/kg/min: b 2 effects predominate. cardiac contractility
and HR
>10 m g/kg/min: a effects predominate arterial vasoconstriction
and -BP

16. Pharmacokinetics
Marked variability in clearance in the critically
ill. As a result plasma concentrations cannot
be predicted from infusion rates

17. Clinical use
• variable effects due to variable clearance
• increases cardiac output (mainly due to
increased stroke volume) with minimal effect
on SVR in patients with septicshock
• increases pulmonary shuntfraction
• increases urine output without increasing
creatinine clearance in a number of
settings.
• Low dose dopamine does not prevent renal
failure in critically ill patients

18. DOPEXAMINE
• marked intrinsic agonist activity at beta2
receptors
• net effect is reduction in afterload by pronounced
arterial vasodilatation, increased renal perfusion
by selective renal vasodilatation and mild direct
and indirect positive inotropism. Also has
positive chronotropic effect.

19. Dosage
for acute heart failure and haemodynamic support in
patients following cardiac surgery start at 0.5
mcg/kg/min and titrate upwards in increments of 1
mcg/kg/min to a maximum of 6 mcg/kg/min.
Contraindications
- Thrombocytopenia
Caution
- patients with hyperglycaemia and hypokalaemia in
viewof beta-adrenergic activity.

20. DOBUTAMINE
• Possesses the same basic structure as
dopamine but has a bulky ring substitution on
the terminal amino group.
• Synthetic catecholamine

21. Pharmacodynamics
 Strong +ve inotropy due to beta1 agonist effects
 Mild +ve chronotropy
 Overall peripheral effect should be an increase in blood
flow to skeletal muscle (beta2 agonism) and some
reduction in skin blood. These effects are weak
compared to the myocardialeffects.

22. • Net effects are an increase in SV and CO. SVR
may be unchanged or moderately decreased and
arterial pressure may thus rise, fall slightly or
remain unchanged.
• At doses > 15 mcg/kg/min tachycardia and
arrhythmias are more likely.
• Tolerance may be seen after 48-72 hrs,
presumably due to down- regulation of beta
receptors. May necessitate an increase in dose.

23. ISOPROTERENOL
• powerful beta agonist with virtually no alpha
effects
• lowers vascular resistance mainly in skeletal
muscle but also in renaland mesenteric
vascularbeds.
• diastolic BP falls but with usual doses the
increase in cardiac output is usually enough
to maintain or raise mean BP
•positive inotrope andchronotrope
• renal blood flow is decreased in normotensive
subjects but is markedly increased in patients
with cardiogenic or septic shock
•PA pressures areunchanged

24. METHOXAMINE
Pharmacodynamics
 direct and indirect effects.
 alpha agonist and betablocker.
 primary effect is peripheral vasoconstriction resulting in rise
in systolic and diastolic BP.
HR slows due to beta blocking effects and reflex slowing due to
rise in BP.
 no effect on cardiac contractility and so cardiac
output falls.

25. INDICATIONS AND DOSAGE
 hypotensive states due to excessive vasodilatation
eg spinal or epidural block
 5-10 mg IV acts within 2 mins. Effect persists for
about 20 mins. Dose can be titrated against effect in 2
mg boluses

26. Contra-indications
• patients on MAOIs
• history of hypertension
Toxicity
• excessive rise in BP; may precipitate myocardial
ischaemia
• vomiting, headache, desire to micturate, significant
reduction inHR
• treat with IV alpha blocker (eg phentolamine)

27. PHENYLEPHRINE
• similar effects to norepinephrine but probably
even shorter acting
•potent alpha and weak beta agonist
• causes peripheral vasoconstriction and thus a
rise in BP, especially diastolic
• often reflex reduction in heartrate
• only direct effect on heart is to slightly
increase myocardial irritability

28. Phosphodiesterase III
Inhibitors (I)
 Inhibit PDE III isoenzyme increase
intracellular cAMP + cGMP in
myocardial & smooth musclecells
 cAMP phosphorylates cellular protein
kinases
 Myocardium: Ca2+ influx more Ca2+
for contraction & improved Ca2+ reuptake
improved relaxation
 Smooth Muscle: relaxation & 20 vasodilatation

29. Clinical effects
 Increased cardiac contractility without
increasing myocardial oxygen
consumption
 Decreased preload and afterload
 Minimal chronotropic effect

30. Phosphodiesterase III Inhibitors
Clinical uses:
Short term treatment for acute on
chronic severe CCF
Synergistic effect with betaagonists
Role in cardiopulmonary bypass

31. Levosimendan
 Calcium sensitizer
 Action
 Stabilises interaction between Ca2+ & Troponin C by
binding Troponin C in Ca2+ dependentmanner.
 Clinical effects
 Increased cardiac contractility – no increasein
myocardial oxygen demand
 Vasodilatation resulting in decreased preload&
afterload
 Not proarrythmogenic

32. VASOPRESSIN
 Vasopressin, also named antidiuretic
hormone (ADH), arginine vasopressin (AVP)
or argipressin.
MOA
 It increases the amount of solute-free water
reabsorbed back into the circulation from the filtrate
in the kidney tubules of the nephrons.
 AVP constricts arterioles, which increases peripheral
vascular resistance and raises arterial blood pressure

33.  It has a very short half-life, between 16–24 minutes
 It is widely distributed throughout the body and
remains in the extracellular fluid. It is degraded by
the liver and excreted through the kidneys.
 Vasopressin infusions are also used as second line
therapy for septic shock.
 Dose start 0.1 unit/hr to 2.4 unit/hr

34. USES
 Usually given in GI bleeding or esophageal variceal
bleeding
 Also second pressor agent in refractory shock.
 More effective in late vasodilatory shock than
vasopressin alone.
 Complication includes mesenteric ischemia,
hyponatremia, pulmonary vasoconstriction and skin
necrosis.

35. TERLIPRESSIN
 Vasopressin analogue
 Longer acting than vasopressin ( half life- 6hours)
USES
• Shock associated with sepsis and other
inflammation.
• Decrease cardiac output.

36. Treatment with terlipressin
Loading dose- 20 µg/kg followed by
Continuous infusion – 4-20 µg/kg/hr

37. Vasoactive drugs for shock states
Shockstate First-tieragents Second-tieragents
Anaphylacticshock Epinephrine, 1 mL of 1:10,000
solution (100 mg),can be
given as a slow IV push, then
as a 0.02 mg/kg/mininfusion
(5–15 mg/min
Norepinephrine infused at0.1–1
mg/kg/min (0.5–30 mg/min)
Cardiogenic shock,
leftventricular
SBP 70, norepinephrine
infused at 0.1–1 mg/kg/min
(0.5–30 mg/min)
SBP 70–90, dopamine
infused at 15 mg/kg/min
SBP O90, dobutamine
infused at 2–20 mg/kg/min
Amrinone, 0.75 mg/kg loading
dose, then 5–10 mg/kg/min(not
recommended post-MI)
Milrinone, 50 mg/kg loading
dose, then 5–10 mg/kg/min(not
recommended post-MI)
Cardiogenicshock,
pulmonary
embolism
Dobutamine infused at 5
mg/kg/min
Norepinephrine infused at
0.1–1 mg/kg/min
Phenylephrine infused at10–20
mg/kg/min
Hemorrhagicshock Volumeresuscitation Norepinephrine infused at0.1–1
mg/kg/min (0.5–30 mg/min)

38. Neurogenicshock Dopamine infused at5– 15
mg/kg/min
Norpinephrineinfused at
0.1–1 mg/kg/min
Phenylephrine infused at
10–20 mg/kg/min
Septicshock Norepinephrine infused at
0.1–1 mg/kg/min
Dobutamine infused at5
mg/kg/min
Dopamine infused at5–15
mg/kg/min
Epinephrine infused at
0.02 mg/kg/min
Toxic drug overdose
with
shock
Norepinephrine infused
at 0.1–1 mg/kg/min
Phenylephrine infusedat
10–20 mg/kg/min
Glucagon given as a5-mg
IV bolus, then
as a 1–5 mg/hinfusion
Calcium salts:calcium
gluconate, 0.6 mL/kg
bolus,
then a 0.6–1.5mL/kg/h
infusion
Insulin started at0.1
units/kg/h IV and titrated
to a goal of 1unit/kg/h

39. Conclusions
 Inotropes and vasopressor are very essential in
treatment of shock. Smaller combined doses of
inotropes and vasopressors had benefit than a single
agent used at higher doses to avoid dose-related
adverseeffects.
 The use of vasopressin at low to moderate doses
may allow catecholamine sparing.
 In cardiogenic shock complicating AMI, current
guidelines based on expert opinion recommend
dopamine or dobutamine as first-line agents with
moderate hypotension (systolic blood pressure 70 to
100 mm Hg) and norepinephrine as the preferred
therapy for severe hypotension (systolic blood
pressure <70mm Hg) and effective in septic shock.

40. SUMMARY
 Understand appropriate clinical application of vasopressors
and inotropic agents.
 In hyperdynamic septic shock, norepinephrine or
phenylephrine is first-line agent. Vasopressin as second-line
agent to reduce need for other pressors.
 In cardiogenic shock, norepinephrine is preferred initial
agent. After establishing adequate perfusion, Dobutamine
added.
 In anaphylactic shock, 1st line agent is Epinephrine followed
by Vasopressin as second line agent.
 Epinephrine is the 1st line agent in hypotension after CABG.

41.  thankyou