THE USE OF VASOPRESSOR

AND INOTROPES IN THE

EMERGENCY DEPARTEMENT
FOR THE TREATMENT OF
SHOCK

ELYA ENDRIANI, dr, SpAn

KSM ANESTESIOLOGI DAN TERAPI INTENSIF
RSUD PROVINSI NTB
SHOCK??
Condition in which perfussion to the tissues is not matched
with the demand for O2.

Delivery O2 (DO2) doesn’t meet O2 consumtion (VO2)

DO2 = CO x CaO2
CaO2 = (1,34xHbxSaO2)+(0,003x PaO2)
CO = SV x HR
 THE HEART

Pump Function of the

heart  Influence the
Cardiac Output

CO = Stroke Volume x HR
DETERMINANTS OF CARDIAC OUTPUT
(CO)
Contractility

Preload Stroke Afterload

Volume
Heart Rate

Cardiac Output
ASSESMENT OF THE MAJOR FEATURES OF
SHOCK
1. PHYYSICAL EXAMINATION ( confused, delayed
capillary refill time, oligouri, cool peripheral
extremitas)
2. HEMODINAMIC VARIABLE( MAP, pulse pressure)
3. GLOBAL METABOLIC PARAMETERS (lactat, arterial
base excess, mixed venous oxygen saturations)
CON’T
Increasing DO2 is the main goal in Tx shock

Hydraulic (IV fluid)

Pharmacologic (inotropic, vasopressor )

Hematologic (transfusion )

Mechanical techniques
SHOCK CATEGORIZED
Systemic
Stroke Cardiac
Shock Type Heart Rate Vascular
Volume Output
Resistance
Cardiogenic Increased Decreased Decreased Increased

Hypovolemic Increased No change No change Increased

or decreased or decreased
Distributive Increased Increased (no Increased Decreased
(Spinala) (normal or changea)
decreaseda)

a Denotes physiologic variation in spinal shock caused by a predominant

decrease in sympathetic input.
In some cases, more than one type of shock maybe present
GLOSSARY OF TERMS

Inotropes Agents that improve myocardial contractility and

enhance stroke volume
Pressors Agents that increase systemic vascular resistance
and increase blood pressure
Chronotropic Increase heart rate
Lusotropic improve relaxation during diastole and decrease
EDP in the ventricles
CARDIOVASCULAR MEDICATIONS

Main actions of most of the following cardiovascular

medications will be determined by the adrenergic effects
of the medications.
Can either be:
Alpha-adrenergic
Beta-adrenergic
Dopaminergic
ALPHA-ADRENERGIC MEDICATIONS

Alpha1-
adrenergic • Vascular smooth muscle contraction
effects
Alpha2- • Vascular smooth muscle relaxation--
this is a very mild effect only at low
adrenergic doses of an alpha-adrenergic agent
effects like epinephrine
BETA-ADRENERGIC MEDICATIONS
Can be divided into:

Beta1-adrenergic effects: Beta2-adrenergic effects:

Direct cardiac effects • Vasodilation

• Bronchodilation

Inotropy (improved
cardiac contractility)

Chronotropy (increased
heart rate)
EPINEPHRINE
Both an alpha- and beta-adrenergic agent

Therefore, indications for its use as a continuous infusion are:

low cardiac output beta effects will improve cardiac function

state
alpha effects may increase afterload
and decrease cardiac output

septic shock useful for both inotropy and

vasoconstriction
EPINEPHRINE
•Actions are dose dependent (mcg/kg/min):
–0.02-0.08 = mostly beta1 and beta2 stimulation.
• increased cardiac output
• mild vasodilation

–0.1-2.0 = mix of beta1 and alpha1

• increase cardiac output
• increase SVR = vasoconstriction

–> 2.0 = mostly alpha1

• increase SVR, and may decrease CO by increasing afterload
NOREPINEPHRINE
Major endogenous neurotransmitter
Liberated by postganglionic adrenergic nerves
Employed primarily for its alpha agonist effect - increases SVR (and
B.P.) 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
Infusion rates titrated between 0.05 to 1 mcg/kg/min
NOREPINEPHRINE
In general, norepinephrine differs from epinephrine in that
at doses used in clinical practice, the vasoconstriction
outweighs any increase in cardiac output.

i.e. norepinephrine usually increases blood pressure and SVR, often

without increasing cardiac output.
 DOPAMINE

Intermediate product in the enzymatic pathway leading to the

production of norepinephrine; thus, it indirectly acts by
releasing norepinephrine.
Directly has alpha, beta and dopaminergic actions which are
dose-dependent.

Indications are based on the adrenergic actions desired.

DOPAMINE
Improve renal perfusion 0.5- 3 mcg/kg/min
Improve C.O. in mild to moderate Cardiogenic or Distributive
Shock 5-10mcg/kg/min
Post-resuscitation stabilization in patients with hypotension (in
conjuction with fluid therapy) 10-20mcg/kg/min
DOBUTAMINE
Synthetic catecholamine with inotropic effect (increases
stroke volume) and peripheral vasodilation (decreases
afterload)
Positive chronotropic effect (increases HR)
Some lusotropic effect
Overall, improves Cardiac Output by above beta-
agonist acitivity
 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.
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
MILRINONE/AMRINONE

Belong to new 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
AMRINONE
First generation agent - limited use now
Long half-life (4.4 hours) with potential for prolonged
hypotension after loading dose
Associated with thrombocytopenia
Dosage: Load with 0.75 mg/kg with infusion rate of 5-10
mcg/kg/min
Milrinone is preferred drug from this group
MILRINONE
 Increases CO by improving contractility, decreased SVR,
PVR (?), lusotropic effect; decreased preload due to
vasodilatation
 Unique in beneficial effects on RV function
 Half-life is 1-2 hours
 Load with 50 mcg/kg over 30 mins followed by 0.3 to
0.75 mcg/kg/min
 No increase in myocardial O2 requirement
 INOTROPIC

Dobutamin Milrinone
Inotropik Inotropik
Vasodilator vasodilator

Adrenalin
Nor-adrenalin
Dopamin Inotropik
Inotropik Vasokonstriktor
vasokonstriktor
 CONTROL OF ARTERIOLAR
SMOOTH MUSCLE

Vasopressin
Site of action of vasopressin 
On Vasopressin receptor
V1  located on arterial smooth muscle
V2  are found in renal tubules

Kee VR, hemodynamic Pharmacology of Intravenous

vasopressor. Crit Care Nurse 2003, 23:79-82
Figure 19.14
Apply vasopressors (for hypotension that
does not respond to initial fluid
resuscitation) to maintain a mean arterial
pressure (MAP)≥65 mm Hg
Vasopressin 0,03 unit/ minute can be
added to NE  with intent to ↑ MAP
or decreasing NE dosage
 VASOPRESSOR

Vasopressin
•Reduce of0.03 units/minute requirements
Norepinephrine can be added to
norepinephrine (NE) with intent of either raising
72% within 72 h 2011
MAP or decreasing NE dosage (UG).
•Significant increase in liver enzymes and total
Low dose vasopressin
bilirubin is not
conc and recommended
a significant as
decrease
the single initial vasopressor for treatment of
in platelet count occurred
sepsis-induced hypotension
•Arginine vasopressin was effective in
Vasopressin doses > than 0.03-0.04 units/minute
reversing systemic hypotension
should be reserved for salvage therapy (failure to
(Anesth Analg 2011;93:7–13)
achieve adequate MAP with other vasopressor
agents) (UG)
 VASOPRESSIN AND THE CVS
CHERYL L HOLMES ET AL . CRIT CARE 2004 ; 8: 15 - 23

Vasopressin is emerging as a rational therapy for

vasodilatory shock state
Restores vascular tone in vasoplegic caused by
catecholamine resistant
In intact animal model  coronary vasodilator 
through control of endothelial tone
In CPR  vasopressin leads to superior resuscitation
outcome compared with adrenalin  ROSC 
caused by improvement of coronary circulation
VASOPRESSIN AND THE CVS
CHERYL L HOLMES ET AL . CRIT CARE 2004 ; 8: 15 - 23

High dose  Decreased the slope of the left

ventricular end diastolic pressure volume
relation  indicating a depression of left
ventricular performance
ButAtbyLow dose of vasopressin
maintaining  positive
constant coronary flow 
inotropic
myocardial DO2andiscoronary vasodilator
maintained
At high dose coronary vasocontrictor
But in case of coronary vasoconstriction
and negative inotropicity
(disrupted of endothelial system )  DO2 ↓
 DRUG OPTION Special
Drug Receptor Affinity Dose Adverse Events
Conciderations
Vasopressor
Tachycardia
Norepinephrine 0.05 – 1
α1 > β1 Peripheral/GI
(Levophed®) mcg/kg/min
ischemia
β1 > α1 Tachycardia
Epinephrine 0.05 – 0.5
Low doses = β Peripheral/GI
(Adrenalin®) mcg/kg/min
High doses = α ischemia
Renal protective doses
DA = <5 mcg/kg/min
Dopamine 5 – 20 Tachycardia of < 5 mcg/kg/min
β1 = 5-10 mcg/kg/min
(Inotropin®) mcg/kg/min Arrhythmias should not be used
α1 = 10-20 mcg/kg/min

Phenylephrine α1 0.5 – 5 Tachyphylaxis

Reflex bradycardia
(Neosynephrine®) mcg/kg/min
Don NOT titrate
[doses >0.04
Vasopressin V1 Cardiac/ mesenteric
0.04 units/min units/min can result in
(Pitressin®) ischemia Skin lesion
cardiac ischemia]

Inotropes
Dobutamine 5 – 20 Arrhythmias
 CON’T
Receptor activity
Vasoactive agent α1 α2 β1 β2 Dopamine Other Clinical effect
Epinephrine ++++ +++(+) +++ 0(+) 0 ↑ in SVR predominates,
vasodilator in low dose
↑ CO by ↑ inotrope and ↑
HR
Ephedrine ++ 0 ++(+) ++ 0 ↑ in SVR predominates
Mild ↑ CO by ↑ inotropes
Norepinephrine ++++ +++ +++ 0(+) 0 ↑↑ in SVR predominates
because of alpha effects
↓ CO s/t ↑in SVR offset by
inotrope
↑ HR at higer doses may
limit clinical effectiveness
Phenylepherine +++ 0 0 0 0 ↑↑ in SVR predominates
CO neural at low doses s/t
↑ venous return offsets the
↑ SVR effect on CO
At high doses, ↑ in SVR
predominates with ↓ CO
0, no effect; +, minimal receptor stimulation; ++, mild; +++, moderate; ++++, strong; -, debate activity; (), variable effects; ↑, increase; ↓, decrease.
Abbreviations: CO, cardiac output; HR, heart rate; PDE, phosphodiesterase; SVR, systemic vascular resistance
Vasoactive agent α1 α2 β1 β2 Dopamine Other Clinical effect
Dopamine
0.5-2 μg/kg/min 0 (+) + + ++ Dopamine Dose 1-↑ by ↑
inotrope
3-10 μg/kg/min + (+) ++ + ++ Dose 2-↑ SVR and
↑ CO by ↑
inotrope and ↑ HR
10-20 μg/kg/min +(+++) (+) ++(++) +(+) ++ Dose 3-↑ in SVR
predominates
↑ HR at higer
doses may limit
clinical
effectiveness
Dobutamine 0(+) 0(+) ++++ +++ 0 ↑↓ SVR
↑ CO by ↑
inotrope
Minimal stimulation
to HR
Isoproterenol 0 0 ++++ ++++ 0 ↓ SVR
↑ CO by ↑
inotrope and ↑ HR
↓ SVR often limits
utility in shock
Vasopressin 0 0 0 0 0 VI receptor ↑↑ in SVR
predominates
Amrinone/milrinone 0 0 0 0 0 PDE inhibition ↓ SVR
↑ CO by
phoshodiesterase
inhibition
0, no effect; +, minimal receptor stimulation; ++, mild; +++, moderate; ++++, strong; -, debate activity; (), variable effects; ↑, increase; ↓, decrease.
Abbreviations: CO, cardiac output; HR, heart rate; PDE, phosphodiesterase; SVR, systemic vascular resistance
Vasoactive agent α1 α2 β1 β2 Dopamine Other Clinical effect
Dopamine
0.5-2 μg/kg/min 0 (+) + + ++ Dopamine Dose 1-↑ by ↑
inotrope
3-10 μg/kg/min + (+) ++ + ++ Dose 2-↑ SVR and
↑ CO by ↑
inotrope and ↑ HR
10-20 μg/kg/min +(+++) (+) ++(++) +(+) ++ Dose 3-↑ in SVR
predominates
↑ HR at higer
doses may limit
clinical
effectiveness
Dobutamine 0(+) 0(+) ++++ +++ 0 ↑↓ SVR
↑ CO by ↑
inotrope
Minimal stimulation
to HR
Isoproterenol 0 0 ++++ ++++ 0 ↓ SVR
↑ CO by ↑
inotrope and ↑ HR
↓ SVR often limits
utility in shock
Vasopressin 0 0 0 0 0 VI receptor ↑↑ in SVR
predominates
Amrinone/milrinone 0 0 0 0 0 PDE inhibition ↓ SVR
↑ CO by
phoshodiesterase
inhibition
0, no effect; +, minimal receptor stimulation; ++, mild; +++, moderate; ++++, strong; -, debate activity; (), variable effects; ↑, increase; ↓, decrease.
Abbreviations: CO, cardiac output; HR, heart rate; PDE, phosphodiesterase; SVR, systemic vascular resistance
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