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

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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