Best Practice in Shock

Management : Vasoactive drug

Akekarin Poompichet, M.D.
Division of Critical Care Medicine
Department of Internal Medicine
Siriraj Hospital

Hemodynamic Formula
MAP CVP

=
=
=
=

CVP
MAP

V = IR
CO x SVR
P = QR
SV x HR x SVR
(EDV ESV) x HR x SVR
EDV x (EDV ESV) x HR x SVR
EDV
= EDV x (EDV ESV) x HR x SVR
EDV
= EDV x EF x HR x SVR

Preload

Rhythm

Contractility

Afterload

Four Phases in Shock Treatment

Salvage

Optain minimal acceptable

MAP
Perform live saving measure

Optimization

Provide adequate O2
delivery
Optimize CO, SvO2, lactate
Provide organ support
Minimize complications
Wean from vasoactive
agents
Achieve negative fluid
balance

Stabilization

De-escalation

O2 delivery = ((1.34 x Hb x O2sat) + (0.0031 x PaO2)) x CO

Adrenergic receptor
Alpha-1
receptor
Vasoconstri
ction
Mydriasis
Increase
internal
sphincter
tone of
bladder

Alpha-2
receptor
Inhibition
of NE
release
Inhibition
of Ach
release
Inhibition
of insulin
release

Beta-1
receptor
Tachycardia
Increase
cardiac
contractility
Increase
lipolysis
Increase
renin
release

Beta-2
receptor
Vasodilatat
ion
Bronchodil
atation
Increase
glycogenol
ysis
Increase
glucagon
release
Relax
uterine
smooth m.

Hemodynamic Effects of Vasopressors

Cardiac output, venous return

Net effects : CVP, C.O.

Cardiac function curve

Venoconstriction

Venous function curve

-2

0
Pra, CVP

Vasoconstriction

Adrenergic drugs

Dobutamine
Dopamine
(moderate
dose)

Alpha

Beta-1

Beta-2

++
+++

+
+++

Dopamine (high
dose)
Epinephrine

++

+++

+++

+++

++++

+++

Norepinephrine
Phenylephrine

+++
+++

+
-

Marinos. The ICU Book, 4th edition, 2014

Alpha adrenergic receptor

Bertram G.Katzung, Basic and Clinical Pharmacology

12th edition, 2012.

Beta adrenergic receptor

Beta-agonist

Milrinone

Marinos. The ICU Book, 4th edition, 2014

Dopamine
Low dose (< 5 (3) g/kg/min) : activates
dopamine-specific receptors
Increase in natriuresis and urine output
Renal effects are minimal or absent in
patients with AKI

No benefit in AKI prevention

Dopamine
Moderate infusion rates (5 (3) 10
g/kg/min) : stimulates -Receptors in the
heart and peripheral circulation
Increase in myocardial contractility and
heart rate

Circulation 1978; 57:378384

Dopamine
High infusion rates (>10 g/kg/min) : dosedependent activation of alpha-receptors in
the systemic and pulmonary circulations
vasoconstriction
Clinical use
Cardiogenic shock : mechanical assist devices are
preferred for cardiogenic shock
Septic shock : norepinephrine is preferred for septic
shock
Dosage : Dopamine 200 (250) mg in NSS 100 (125) mL
Started at a rate of 35 g/kg/min (without a loading dose)
Increments of 35 g/kg/min to achieve the desired effect
Should be delivered into central veins

Dobutamine
Alpha

Beta-1

Beta-2

++

Dobutamine
Positive inotropic effect
Positive chronotropic effect

Peripheral vasodilatation
Increase in cardiac work and myocardial O2 consumption

Clinical use
Decompensated heart failure due to systolic dysfunction
Myocardial depression associated with septic shock
Dosage : Dobutamine 200 mg (250 mg) in NSS 100 (125) mL
Started at an infusion rate of 35 g/kg/min, increments of 3
5 g/kg/min

Norepinephrine
Norepinephrine

Alpha

Beta-1

Beta-2

+++

Vasoconstriction

Positive inotropic effect

Positive chronotropic effect

In patients with septic shock, renal blood flow is increased by

norepinephrine

Clinical use : Distributive shock, (cardiogenic shock, obstructive

shock)
Dosage : Concentration 4 mg in 5% DW 250 mL
Started at a rate 0.02 g/kg/min, titrated upward or downward
to maintain MAP at least 65 mmHg

Epinephrine
Epinephrine

Alpha

Beta-1

Beta-2

+++

++++

+++

Vasoconstriction

Vasodilatation
Bronchodilatation

Positive inotropic effect

Positive chronotropic effect
Several metabolic effects : lipolysis, glycolysis, and increased lactate
production and hyperglycemia
Clinical use : cardiac arrest, anaphylactic shock, refractory shock
Dosage : Epinephrine 10 (11) mg in NSS 100 (110 ) mL
Start at 0.05 ug/kg/min (0.5 mg/hr)

Hemedynamic effects of adrenergic drugs

Stroke volume index (SVI) = stroke volume/ BSA

Crit Care Med 2003; 31:16591667

Phenyleprine
Phenylephrine

Alpha

Beta-1

Beta-2

+++

Vasoconstriction
Bradycardia, decrease in stroke volume (usually in patients with
cardiac dysfunction), hypoperfusion of the kidneys and bowel
Clinical use : Hypotension from spinal anesthesia, limit usage in
critical care setting
Dosage : initial IV dose is 0.2 mg, which increments of 0.1 mg
to a maximum dose of 0.5 mg, rate 0.10.2 mg/min

Vasopressin
Binding to V1A receptors on vascular smooth muscle
Remains unclear benefits : relative vasopressin
deficiency, hypersensitivity, or both

Clinical use : refractory vasodilatory shock, CPR (ACLS

cardiac arrest algorithm)

Dosage
0.0 1 to 0.05 units/min as an adjunctive agent in the
treatment of vasodilatory septic shock
40 units in CPR

Milrinone
Combine inotropic and vasodilating properties
(inodilator)
Phosphodiesterase inhibitor, Decreasing the metabolism
of cyclic AMP
May also be useful when -adrenergic receptors are
down-regulated or in patients recently treated with betablockers

More likely to produce hypotension (compare with

dobutamine)
Dosage
50 ug/kg over 10 min., 0.375-0.75 ug/kg/min , not exceed
1.13 mg/kg/day

Calcium
Indication
Hypocalcemia
Hyperkalemia --- Bradyarrythmia
Beta blocker/ calcium channel blocker overdose
Refractory hypotension
Dosage :
10% calcium gluconate 10-30 mL slowly push
10% calcium chloride 5-10 mL slowly push

Vasopressor Calculation/ Adjustment

Ud/min (mL/hr)

= 6 x BW(kg) x dose (ug/kg/min)

100 x conc.

Ud/min (mL/hr)

= 6 x dose (ug/min)
100 x conc.

Concentration

= mg/ mL

Vasopressor adjustment : q 5-10 minutes

Dopamine or norepinephrine as first-line vasopressor therapy

Dopamine
NE
When BP could not be maintained with a dose of 20 g/kg/min
for dopamine or a dose of 0.19 g/kg/min for NE, open-label
NE, E, or vasopressin could be added

Primary outcome was the rate of death at 28 days after

randomization
Secondary end points included the number of days without
need for organ support and the occurrence of adverse events

Cardiogenic Shock (LV dysfunction)

MAP CVP = preload x contractility x HR x afterload

Cardiogenic Shock (LV dysfunction)

SBP < 90 mmHg

Dopamine
If not response : NE

If BP stable
: Dobutamine
: Milrinone
(0.375-0.75 ug/kg/min

SBP < 70 mmHg

NE

Refractory shock
: Epinephrine
: Mechanical devices IABP, LVAD, ECMO,
transplantation

Cardiogenic Shock : Bradyarrythmia

MAP CVP = preload x contractility x HR x afterload

HR < 50/min
Symptom : shock, chest pain, syncope, alteration of
consciousness, HF

Atropine

If not response
: TCP
: Dopamine 2-10 ug/min
: Epinephrine 2-10 ug/min
Consider early use of TCP, epinephrine

Septic Shock
MAP CVP = preload x contractility x HR x afterload

Within 3 hrs

Within 6 hrs

1) Measure lactate level

2) Obtain H/C prior to
administration of antibiotics
3) Administer broad spectrum
antibiotics
4) Administer 30 mL/kg
crystalloid for hypotension or
lactate 4 mmol/L

5) Vasopressors (for
hypotension that does not
respond to initial fluid
resuscitation) to maintain
MAP 65 mmHg
6) In the event of persistent
arterial hypotension despite
volume resuscitation (septic
shock) or initial lactate 4
mmol/L):Meausure
- CVP
- ScvO2
7) Remeasure lactate if initial
lactate was elevated

Stepwise Vasoactive Drug Use in Septic Shock

For macrocircirculation
Norepinephrine

Alternative 1st line : Dopamine

Epinephrine

Phenylephrine

Vasopressin

For microcirculation

Dobutamine

Time to Start Vasopressor in Septic

Shock
Rational of Vasopressor use :
Vasopressor therapy is required to sustain life and maintain
perfusion in the face of life-threatening hypotension, even when
hypovolemia has not yet been resolved

Sepsis Campaign Guideline, 2012

MAP CVP = preload x contractility x HR x afterload

Obstructive shock (RV failure)

Identify precipitating factor

Correct hypoxemia
Avoid PEEP/ hypercapnia/ acidosis

Reverse hypotension
Rapid assessment of volume status :
CVP, PCWP, echo
Fluid challenge test : if CVP < 5 mmHg
Early vasopressor use : NE, Dopamine
Pulmonary vasodilator
Inhaled epopostrenol/ NO
If not hypotension : IV epopostrenol
or oral sidenafil

Contractility
Dobutamine
Milrinone

Neurogenic Shock
MAP CVP = preload x contractility x HR x afterload

SBP < 90 mmHg : Dopamine

SBP < 70 mmHg : NE

Adrenal Crisis
MAP CVP = preload x contractility x HR x afterload

Norepinephrine
Hydrocortisone

Anaphylactic shock
MAP CVP = preload x contractility x HR x afterload

Intramuscular
epinephrine
(1:1000) 0.3-0.5
mL
Epinephrine IV drip
if no response
Antihistamine
Hydrocortisone
Others : Beta 2agonist, oxygen