| Reference | 1. Eur J Anaesthesiol Suppl. 1992;5:35-41. <br />
Overview of the effects of intravenous milrinone in acute heart failure following
surgery.<br />
Copp MV(1), Hill AJ, Feneck RO. <br />
Author information: <br />
(1)London Chest Hospital, United Kingdom. <br />
We have reviewed the current data evaluating the effects of intravenous milrinone
in patients following cardiac surgery. Milrinone has been shown to be effective
in the treatment of acute low output syndrome, and a loading bolus infusion of 50
micrograms kg-1 over 10 min causes an increase in cardiac index and a fall in
pulmonary capillary wedge pressure. These effects are easily maintained by a
continuous infusion regimen. Other haemodynamic effects are seen, including
systemic and pulmonary vasodilatation and an increase in heart rate. These
effects are not confined to one patient group, but the increase in cardiac index
does appear to be more pronounced in those patients with poor haemodynamics prior
to treatment. There is a low incidence of adverse events including arrhythmias
and hypotension. Thus milrinone appears to be well tolerated in a broad group of
adult patients recovering from cardiac surgery. <br />
PMID: 1600968 [Indexed for MEDLINE] <br />
2. Eur Heart J. 1989 Aug;10 Suppl C:39-43. <br />
Acute effects of intravenous milrinone in heart failure. <br />
Rettig GF(1), Schieffer HJ. <br />
Author information:
(1)Medizinische Universitätsklinik, Innere Medizin III Homburg/Saar, F.R.G. <br />
Milrinone exerts positive inotropic and dose-dependent vasodilatory effects that
promote haemodynamic improvement after intravenous administration to patients
with heart failure. Bolus doses of 12.5-75 micrograms kg-1 markedly increase
cardiac output and cause a substantial reduction in cardiac filling pressure and
in systemic vascular and pulmonary vascular resistance. There is no evidence of
tolerance to these effects which are maintained during continuous infusion for up
to 48 h. In contrast, there are minimal effects on heart rate or systemic blood
pressure, except at very high doses. At lower filling pressures, milrinone
increases cardiac output more markedly than equally hypotensive doses of pure
vasodilators. This response is accompanied by an increased left ventricular
dP/dtmax and a shift in the left ventricular performance is associated with a
lower myocardial energy requirement. Despite a fall in mean arterial pressure and
transcoronary driving pressure, coronary venous flow is increased and there is a
reduction in the arterio-coronary venous oxygen difference. This reflects a
global improvement in left ventricular diastolic function, characterized by
accelerated early relaxation and greater chamber distensibility. Improved
performance of the right ventricle is due primarily to reduced right ventricular
afterload as milrinone produces minimal inotropic effects on the right ventricle. <br />
PMID: 2680496 [Indexed for MEDLINE] <br />
3. Drugs. 1988 Aug;36(2):158-92. <br />
Milrinone. A preliminary review of its pharmacological properties and therapeutic
use. <br />
Young RA(1), Ward A. <br />
Author information: <br />
(1)University of Arkansas for Medical Sciences, Little Rock. <br />
Milrinone is a bipyridine derivative of amrinone, with approximately 10 to 75
times greater positive inotropic potency, and separate direct vasodilatory
properties. As with amrinone, the relative importance of these properties to
treatment of congestive heart failure still remain controversial. The mode of
action of milrinone appears to be due in part to selective inhibition of a
specific cardiac phosphodiesterase with a subsequent increase in intracellular
cyclic adenosine monophosphate and alteration in intracellular and extracellular
calcium transport. Clinical experience has involved both short and long term
treatment of a limited number of patients with moderate to severe congestive
heart failure refractory to conventional therapy. Milrinone has usually been
administered as intravenous bolus doses (12.5 to 75 micrograms/kg) and/or
continuous intravenous infusion (0.5 microgram/kg/min), or orally (30 to 40
mg/day in divided doses). Milrinone rapidly improves cardiac performance by
enhancing myocardial contractility, and by decreasing systemic vascular
resistance (afterload), left ventricular filling pressure (preload), and
pulmonary arterial pressure. Exercise performance improvement occurs with
enhancement of left ventricular performance but without a significant increase in
myocardial oxygen consumption or significant decrease in mean arterial pressure.
Milrinone has been compared with dobutamine, nitroprusside and captopril in
preliminary short term studies in patients with severe congestive heart failure.
Milrinone significantly increased stroke work index and decreased left
ventricular filling pressure compared to nitroprusside. When compared with
dobutamine, both drugs improved cardiac index (to a similar degree), but
milrinone significantly reduced right atrial pressure, pulmonary capillary wedge
pressure and left ventricular end-diastolic pressure. One small study suggests
that short term effects of intravenous milrinone may be superior to those of oral
captopril, and it appears that the addition of captopril to milrinone therapy may
produce a synergistic haemodynamic effect. Preliminary long term studies suggest
that tolerance to the haemodynamic effects of milrinone does not occur, and that
the drug is well tolerated and without the thrombocytopenic effects, fever and
gastrointestinal complications observed with amrinone. However, it has not been
demonstrated that milrinone improves the prognosis of the disease or the overall
mortality and its propensity to produce arrhythmias has not been fully agreed
upon.(ABSTRACT TRUNCATED AT 400 WORDS) <br />
PMID: 3053125 [Indexed for MEDLINE] <br />
4. Clin Pharm. 1986 Mar;5(3):201-5. <br />
Milrinone, a new agent for the treatment of congestive heart failure. <br />
Hasegawa GR. <br />
The chemistry, pharmacology, pharmacokinetics, dosage, clinical efficacy, and
adverse effects of milrinone are reviewed. Milrinone, which is structurally
similar to amrinone, is an oral agent under investigation for the treatment of
congestive heart failure. The drug produces positive inotropic and vasodilating
effects through unknown mechanisms. Milrinone is well absorbed orally and has a
duration of action of three to six hours. The major route of elimination is
through the kidneys. The usual initial dosage of milrinone is 2.5-5 mg every six
hours; patients whose condition is deteriorating may require 50 mg of the drug
per day. Although most patients report that early in therapy the drug relieves
the symptoms of congestive heart failure, these benefits are not always
sustained. Milrinone does not check the natural progression of disease.
Complaints of side effects are rare, although diarrhea, hyperthyroidism,
aggravation of angina pectoris, worsening of muscle weakness, and increased fluid
retention have been reported. There is evidence to suggest that milrinone may
cause or aggravate arrhythmias, worsen congestive heart failure, and shorten the
length of survival. Experience with milrinone indicates that the drug may be of
limited usefulness in the treatment of congestive heart failure. <br />
PMID: 3514085 [Indexed for MEDLINE]
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