DRUGS FOR HEMODYNAMIC DISORDER

Widharto ph
Pharmacology & therapy Dept
Faculty of Medicine UGM

PHARMACOTHERAPY OF
SHOCK
KEY CONCEPTS:
1. Continuous hemodynamic monitoring either with an arterial catheter or
with a pulmonary artery (or central venous) catheter with central venous
oxygen saturation measurement
2. Early goal-directed therapy with aggressive fluid resuscitation in the
emergency department within the first 6 hours of presentation
3. Goals of therapy with vasopressors and inotropes
4. Dopamine typically is used as an initial vasopressor agent for hemodynamic
support but is limited by its ability to increase cardiac output (by only 35%)
5. Phenylephrine may be a particularly useful alternative in those who cannot
tolerate tachycardia or tachydysrhythmia with dopamine or norepinephrine
or in patients with known underlying myocardial dysfunction.
6. Epinephrine appears to be effective as a single agent
7. Therapy with vasopressors and inotropes is continued until the myocardial
depression and vascular hyporesponsiveness of shock improve

A pharmacological approach to the

treatment of arrhythmias

The treatment of arrhythmias is

controversial. The following is
intended as a general guide to their
acute treatment.
The for guidance on the use of the
drugs suggested.
Seek expert advice on the long-term
treatment of arrhythmias.

CLINICAL PHARMACOLOGY OF
CATECHOLAMINES
The receptor selectivity of clinically used
vasopressors and inotropes and hemodynamic
effects
Selected Inotropic and Vasopressor Agents
Used in Shock:
Dobutamine
Dopamine
Epinephrine
Norepinephrine
Phenylephrine

DOPAMINE

Dopamine is frequently the initial vasopressor used in septic shock.

Doses of 5 to 10 mcg/kg per minute are initiated to improve MAP.
Most studies in patients with septic shock have shown that at these
doses dopamine increases CI by improving contractility and heart
rate, resulting primarily from its 1 effects.

LOW-DOSE DOPAMINE, In the critical care setting, low doses (1 to 3 mcg/kg

per minute) of dopamine sometimes are used in patients with septic shock
receiving vasopressors with or without oliguria.
The goal of therapy is to prevent or reverse renal vasoconstriction caused by
other pressors, to prevent oliguric renal failure, or to convert it to nonoliguric
renal failure.
Dopamine has been shown to increase renal blood flow and increased urine
output owing to either its dopaminergic effect at low doses, its natriuretic
effects (inhibition of the Na +/K +-adenosine triphosphate of renal tubular
cells), or an increase in CI
In oliguri patients, dopamine may increase fractional excretion of sodium
and increase urine output.

NOREPINEPHRINE
Norepinephrine was first used three decades ago for the
treatment of hypotensive states prior to the development of the
newer synthetic catecholamines dopamine and dobutamine
Recent clinical studies of norepinephrine support the primary
use of norepinephrine to restore blood pressure in septic
shock.32,59 In fact, in a retrospective study of 100 ICU patients
treated with norepinephrine for severe hypotension and
evidence of end-organ hypoperfusion unresponsive to both fluid
resuscitation and dopamine treatment, early norepinephrine
administration was associated with the lowest mortality rate.
Recently, Martin and colleagues,59 in a prospective,
observational cohort study of 97 adult patients with septic
shock, determined that the use of norepinephrine to provide
hemodynamic support was associated with a significant
decrease in hospital mortality

that norepinephrine potentially should be repositioned as the

vasopressor of choice in patients in septic shock because of
its multiple benefits:
(1)It may decrease mortality in septic shock,
(2) it attenuates inappropriate vasodilation and lowglobal
oxygen extraction,
(3) it attenuates myocardial depression at unchanged or
increased cardiac output and increased coronary blood
flow,
(4)it improves renal perfusion pressure and renal filtration,
(5)it improves splanchnic perfusion, and
(6)it is less likely than other vasopressors to cause
tachycardias and tachydysrhythmias.

DOBUTAMINE

Dobutamine is an inotrope with vasodilatory properties (a socalled inodilator), and it is used in the treatment of septic and
cardiogenic shock to increase cardiac index.
Dobutamine has been shown to increase stroke index, left
ventricular strokework index (LVSWI
Most prospective, randomized, controlled studies of goaldirected
therapy with dobutamine were performed for septic shock in
surgical and medically critically ill patients refractory to
concurrently administered vasopressors (dopamine and/or
norepinephrine)
Recent studies have focused on the effects of dobutamine on
gastric mucosal flowand the splanchnic circulation.
Dobutamine should be started with doses ranging 2.5 to 5 mcg/kg
per minute. Although generally a dose response may be seen,
recent evidence suggests that doses in excess of 5 mcg/kg per
minute may provide limited beneficial effects on oxygen transport
values and hemodynamics and may increase adverse cardiac
effects.

PHENYLEPHRINE

very little information is published regarding the clinical efficacy of

phenylephrine.
Its selective -agonism and primarily vascular effects and its rapid onset
and short duration of action. It is generally initiated at dosages of 0.5
mcg/kg per minute and may be titrated quickly to desired effect.
Phenylephrine (0.5 to 9 mcg/kg per minute), when used alone or in
combination with dobutamine or low doses of dopamine, improves blood
pressure and myocardial performance in fluid-resuscitated septic patients
Incremental doses of phenylephrine over 3 hours result in linear doserelated increases in MAP, SVR, heart rate, and stroke index when
administered as a single agent in stable, nonhypotensive but
hyperdynamic, volume-resuscitated surgical ICU patients
At a dosage of 70 mcg/min, phenylephrine improved cardiac index and
MAP by increasing venous return to the heart (increase in CVP and stroke
index) and by acting as a positive inotrope because SVR did not change.
There was a clinically insignificant decrease in heart rate (3 beats per
minute)

There are very few data regarding the effect of phenylephrine on

regional hemodynamics and oxygen-transport variables.
Phenylephrine may be a particularly useful alternative in patients
who cannot tolerate tachycardia or tachydysrhythmias with
dopamine or norepinephrine, in patients with known underlying
myocardial dysfunction, and in patients who are refractory to
dopamine or norepinephrine (owing to -adrenergic receptor
desensitization).

EPINEPHRINE

epinephrine has been reserved as a last-line agent in

hemodynamic support of sepsis
epinephrine is an acceptable choice as a single agent owing to its
combined vasoconstrictor and inotropic effectslactate
concentrations may rise during
the first few hours of epinephrine therapy; however, they
normalize over the ensuing 24 hours in survivors.
There is evidence, however, to suggest that epinephrine, in
contrast to dopamine, may increase the proportion of total cardiac
output delivered to the splanchnic circulation
Epinephrine or norepinephrine was started at a dose of 0.1 mcg/kg
per minute and increased by 0.2 mcg/kg per minute every 5
minutes to reach an MAP of 70 to 80 mm Hg.
the combination of norepinephrine-dobutamine induced a greater
increase in mucosal perfusion than did norepinephrine alone