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518 Cardio Diabetes Medicine 2017

and cerebral arteries as well as promoting natriure- dysfunction .Lowest effective dose has to be admin-
sis through direct distal tubular effects. The DAD-HF istered with contibuous BP and rhythm monitoring,
study of 60 patients hospitalized for AHF suggested with a more gradual weaning off. Temporary adjust-
that a combination of low-dose frusemide and low- ments to afterload-reducing agents or diuretics may
dose dopamine resulted in comparable urine output assist in weaning. Concomitant use of beta blocker
and dyspnea relief but improved renal function pro- therapy has a competitive antagonism effects on
file and potassium homeostasis compared with high- dobutamine, and higher doses of dobutamine (10 to
dose frusemide. In contrast, the ROSE trial of 241 pa- 20 µg/ kg/min) may be required to obtain the desired
tients with acute heart failure and renal dysfunction hemodynamic effects.
showed that low-dose dopamine did not enhance
decongestion nor improve renal function when add- Adverse effects: Tachycardia, increasing ventricular
ed to diuretic therapy. If low-dose dopamine therapy response to atrial fibrillation, increased atrial and
is initiated, it should be discontinued in the event of ventricular arrhythmias, myocardial ischemia( direct
no response.
toxic effect). It can also cause idiosyncratic adverse
Intermediate-dose dopamine (2 to 10 µg/kg/min) re- effects like eosinophilia and fever. An eosinophilic
sults in enhanced release of norepinephrine which hypersensitivity myocarditis has been reported in 2.4
stimulates the cardiac receptors causing increase in to 23 percent of patients treated with a prolonged
inotropy and mild stimulation of peripheral vasocon- dobutamine infusion. The CASINO (“CAlcium Sensi-
stricting receptors. Dopamine has poor response in tizer or Inotrope or NOne in low output heart fail-
patients with severe systolic dysfunction[2,3]. This ure”) study significantly demonstrated the increased
is because the positive inotropic effect of dopamine mortality with dobutamine compared with placebo,
is largely dependent on myocardial catecholamine consistent with the results of other studies of this
stores, which often are depleted in patients with ad- class of agent.
vanced heart failure, High-dose dopamine (10 to 20 Although initially short term infusion proved clinical
µg/kg/min) by direct agonist effects on alpha1-ad- benefit and was used for chronic home or outpa-
renergic receptors causes vasoconstriction of the tient infusions the FIRST (Flolan International Ran-
peripheral and pulmonary artery. These doses carry domized Survival Trial), dobutamine was associated
a significant risk of precipitating limb and end-organ with worse survival and poorer clinical outcomes and
ischemia and should be used cautiously.
did not improve quality of life during or after the
infusions. However long-term infusions are still used
Dobutamine as a bridge to heart replacement therapy and also
Dobutamine has a direct agonistic effect on β1- and in the palliative care setting.
β2-adrenergic receptors with no vasoconstrictor prop-
erties and less tachycardia and has multiple actions Epinephrine
with variable effect. Beta receptor stimulation results It also has a balanced vasodilator and vasoconstric-
in increased inotropy and chronotropy. At low dos- tor effects. Synthetically manufactured norepineph-
es(1 to 2 µg/kg/min), stimulation of beta2 and alpha rine is uses in the treatment of severe septic and car-
receptors causes vasodilation, reduction in afterload diogenic shock. Typically, norepinephrine is infused
and systemic vascular resistance thereby increases at 0.2 to 1 µg/kg/min.
cardiac output indirectly. At higher doses, (5 to 10 µg/
kg/min) vasoconstriction can occur with decreased Noradrenaline and dopamine: Similar to high-dose
venous capacitance and increased right atrial pres- dopamine, it has a propensity to cause skin necrosis
sure. Tachyphylaxis may occur with infusions lasting and sloughing of tissue and should be given through
longer than 24 to 48 hours, owing in part to receptor a secure intravenous cannula. A comparator study
desensitization. published in 2010 indicated that a subset of patients
with cardiogenic shock derived more survival benefit
Advantages over dopamine: It does not increase sym- from norepinephrine than from dopamine. Although
pathetic norepinephrine signaling or peripheral va- the overall mortality rate was similar between dopa-
soconstriction. Whereas dopamine rises blood pres- mine and norepinephrine the adverse effects with
sure through peripheral vasoconstriction dobutamine the use of dopamine was more than with the use of
does it by solely increasing cardiac output.
norepinephrine
Uses: Generally used in patients with significant Uses: Occasionally some patients in cardiogen-
hypotension and in the setting of significant renal
ic shock may present with vasodilation and hypo-

GCDC 2017