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ANDRIANTO
KAMALIA HALID
INOTROPIC AND VASOPRESSOR IN
HEART FAILURE
DEPARTEMENT CARDIOLOGY AND VASCULAR MEDICINE
MEDICAL FACULTY OF AIRLANGGA UNIVERSITY- Dr. SUTOMO TEACHING HOSPITAL
SURABAYA
A 70-y.o man with an ischemic cardiomyopathy anda left ventricular ejection fraction of 18 % brought to
the emergency room. He was somnolent. BP is lower
than usual at 72/55 mmHg, HR 70 bpm. There were
ronkhi in bilateral lungs and extremities were cool
with trace edema, and he was oliguric with baseline
creatinin 1.8.
CASE
What is patients hemodinamicprofile
Should we start an inotrope
HEMODINAMIC PROFILE
CASE
SHOULD WE START AN INOTROPE ?
CASE
Cardiogenic shock with organ dysfunction is aClass I indication for temporary
inotropic/vasopressor therapy to support
perfusion while revascularization or other
definitive therapies are administered.YES
Intravenous inotropic/vasopressor drugsmight be reasonable for this patient.
GOAL OF THERAPY IN HEART FAILURE
Rapid relief of symptoms (typically
dyspneu) by resolution of congestion.
Maintenance or restoration of
adequate end-organ perfusion & func.
INOTROPES & VASOPRESSOR
Physiological Principles
MAP = CO x SVR
CO = HR x SV
Preload Contractility Afterload
INOTROPE
VASOPRESSOR
HEART FAILURE
CATECHOLAMINES via cAMP
PDE INHIBITORS via cAMP
Ca2+ SENSITIZIERS
VASOCONSTRICTION
VASODILATION
AIM : NORMAL BP (MAP)
1
2
1
POSITIVE INOTROPIC EFFECT
Opie LH, et al. Drugs for Heart.7th Edition. 2009
INOTROPIC AGENTS USED IN HEART FAILURE CONDITIONS
Inotropes with vasoplegic properties
Inotropes with vasopressor activities
Agents with primary vasopressor activities
Others Inotrope
DOBUTAMINE
INOTROPES WITH VASOPLEGIC PROPERTIES
Syntetic catecholamine with a strong affinity forboth 1 and 2 receptors (3:1) ratio.
CV efect is to increase CO by increasing
myocardial contractility with relatively little
increase HR.
Initiated at an infusion rate of 2g/kg/min
(without a loading dose) titrated upward by 1-2g/kg/min every 15-30 min.
Biolo A, et al. Cardiac Intensive Care, Second Edition. 2010
Macas A, et al. Acta Medica Lituanica. 2012
MILRINONE
INOTROPES WITH VASOPLEGIC PROPERTIES
Phosphodieaterase inhibitors (PDIs) increase level of
cAMP increased myocardial contraction
Hemodynamic effects are increases CO as well as decrease
in PCWP and pulmonary & arterial vascular resistance.
Administrated as a 25 50 g/kg (iv) bolus over 10 min. constant infusion at 0.25 0.75 g/kg/min.
Biolo A, et al. Cardiac Intensive Care, Second Edition.2010
Rubin S, et al. Heart Failure: Pharmacologic Management, First Edition. 2006
Calcium sensitizer agent which increases myocardial contractility byincreasing myofilament senstivity to calcium.
Levosimendan increase CO and reduces PCWP and SVR in patients withsevere HF.
The effects are dose-dependent at infusion rates ranging from 0.05 0.6g/kg/min to increase stroke volume and cardiac index.
LEVOSIMENDAN
INOTROPES WITH VASOPLEGIC PROPERTIES
Rubin S, et al. Heart Failure: Pharmacologic Management, First Edition. 2006
Macas A, et al. Acta Medica Lituanica. 2012
DOPAMINE
INOTROPES WITH VASOPRESSOR ACTIVITIES
An endogenous catecholamine and immediate precursor of norepinephrine and
epinephrine.
Pharmacological effects of dopamine are highly dose dependent.
At low dose (< 3 g/kg/min) Promotes diuresis
Intermediate (2-5 g/kg/min) HR & contractility
Higher doses (5-15 g/kg/min)Arterial & Venous
Constriction
Biolo A, et al. Cardiac Intensive Care, Second Edition. 2010
Macas A, et al. Acta Medica Lituanica. 2012
EPINEPHRINE
INOTROPES WITH VASOPRESSOR ACTIVITIES
Endogenous catecholamine with high affinity for 1,
2 and 1 adrenoreceptors
Epinephrine plays little role in the acute
management of HF, except when complicated by
severe hypotension.
Continuous infusions may be started at a low dose (0.5 1 g/min) andtitrated upward to 10 g/min, as needed.
Biolo A, et a. Cardiac Intensive Care, Second Edition. 2010
Christopher B, et al. Circulation. 2008
NOREPINEPHRINE
AGENTS WITH PRIMARY VASOPRESSOR ACTIVITIES
An endogenous catecholamine with potent 1 and mild 1adrenergic activity.
The main CV effect is dose-dependent arterial and venousvasoconstriction.
NE may be used to provide temporary circulatorysupport in the setting of hemodinamically
significant hypotension.
NE is titrated to improve BP at doses of 2 10g/min/I,V
Biolo A, et al. Cardiac Intensive Care, Second Edition. 2010
Macas A, et al. Acta Medica Lituanica. 2012
Digoxin has tradionally been considered to be a positive inotropic agents(via inhibition of Na+ - K+ - ATPase and secondary activation of the Na+ -Ca2+ membrane exchange pump).
Besides its weak positive inotropic effect, it slows the ventricular rate,especially in atrial fibrillation, which allows better ventricular filling in CHFwith atrial fibrillation.
CHF : 8-12 mcg/kg in divided doses (q4-8h) over 12 to 24 hours. Normally,give 50% of the total digitalizing dose in the initial dose, then give 25% ofthe total dose in each of the two subsequent doses at 8 to 12 hr intervals.
Lower maintenance doses of digoxin (0.125 0.25 mg/day) orally to avoidthe toxic effects
DIGOXIN
OTHER INOTROPIC
Opie LH, et al . Drugs for the Heart, 7th Edition. 2009
Campbell TJ, et al. MJA. 2003
How to choose inotropicagents ?
ACUTE HEART FAILURE
INDICATIONS FOR INOTROPIC BASED CLINICAL CONDITION OF HEART FAILURE
AHF WITH HIPOPERFUSION
Demonstrate impaired CO, fail
to improve in end-organ
perfusion
Dobutamine & Milrinone are the most
commonly used therapy
Levosimendan may be an alternative to
dobutamine.
Rubin S, et al. Heart Failure: Pharmacologic Management, First Edition. 2006
CARDIOGENIC SHOCK
INDICATIONS FOR INOTROPIC BASED CLINICAL CONDITION OF HEART FAILURE
Peripheral
constriction
Anuria or
oliguria
Low Systolic
BP
Dopamine initiated at moderatedoses (5 g/kg/min) in
hypotensive HF patients.
Addition of Dobutamine mayneed to considered in LV filling
pressure.
If the patients remain
hypotensive Norepinephrine may
be needed.Opie LH, et al. Drugs for Heart.7th Edition. 2009
Rubin S, et al. Heart Failure: Pharmacologic Management, First Edition. 2006
ESC GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF ACUTE AND
CHRONIC HEART FAILURE
RECOMMENDATIONS CLASS LEVEL
Patient with hypotension, hypoperfusion or shock
An i.v. infusion of an inotrope (e.g. dobutamine) should be considered in patients with
hypotension (SBP
ESC GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF ACUTE AND
CHRONIC HEART FAILURE
RECOMMENDATIONS CLASS LEVEL
Patient with AF and a rapid ventricular rate
I.V administration of a cardiac glycoside should be
considered for rapid control of the ventricular rate.
I C
McMurray JV et al. ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012. Eurheartj. 2012
DIGOXIN
Administration of inotropes and vasopressors in HF aims to improve myocardialcontractility and to increase systemic vascular resistence.
Inotropes with vasoplegic properties (dobutamine, milrinone and levosimendan)required in the management of HF patients with hypoperfusion.
Inotropes with vasopressor activities (dopamine and or norepinephrin) widelyused in cardiogenic shock conditions .
Digoxin therapy in patients with chronic HF was improved symptoms anddecrease the frequency of hospitalization.
Side effects and toxicity monitoring should be performed in patients whoreceived inotropic therapy.
SUMMARY
Emergency Management
Administer Fluids Blood transfusions Cause-specific interventionsConsider vasopressors
Arrhythmia
Bradycardia Tachycardia
Systolic BP
Greater than 100 mm Hg
Systolic BP
70 to 100 mm Hg
NO signs/symptoms
of shock
Systolic BP
70 to 100 mm Hg
Signs/symptoms
of shock
Systolic BP
less than 70 mm Hg
Signs/symptoms of shock
Dobutamine
2 to 20
mcg/kg per
minute IV
Low Output -
Cardiogenic Shock
Nitroglycerin
10 to 20 mcg/min IV
Dopamine
5 to 15
mcg/kg per
minute IV
Norepinephrine
0.5 to 30 mcg/min IV
Hypovolemia
Administer
Furosemide IV 0.5 to 1.0 mg/kg Morphine IV 2 to 4 mg Oxygen/intubation as needed Nitroglycerin SL, then 10 to 20 mcg/min IV if SBP greater than 100 mm Hg
Dopamine 5 to 15 mcg/kg per minute IV if SBP 70 to 100 mm Hg and signs/symptoms of shock present
Dobutamine 2 to 20 mcg/kg per minute IV if SBP 70 to 100 mm Hg and no signs/symptoms of shock
Fir
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ine
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Sec
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ine
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Th
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n
See Section 7.7in the ACC/AHA Guidelines for
Patients With ST-Elevation Myocardial Infarction
Check Blood Pressure
Clinical signs: Shock, hypoperfusion, congestive heart failure, acute pulmonary edema
Most likely major underlying disturbance?
Further diagnostic/therapeutic considerations (should be considered in nonhypovolemic shock)Diagnostic Therapeutic
Pulmonary artery catheter Intra-aortic balloon pump Echocardiography Reperfusion/revascularization Angiography for MI/ischemia Additional diagnostic studies
Acute Pulmonary Edema
Check Blood Pressure
Systolic BP
Greater than 100 mm Hg
and not less than 30 mm Hg
below baseline
ACE Inhibitors
Short-acting agent such as
captopril (1 to 6.25 mg)
Circulation 2000;102(suppl I):I-172-I-216.
INOTROPIC COMPARISON