Rockford Cardiology ConferenceMarianne Pop, Pharm.D., BCPS2/24/2018

Describe the pathophysiology of cardiogenic shock

Identify inotropes and vasopressors used in the management of cardiogenic shock

Recognize adjunct agents used in the management of cardiogenic shock

Differentiate between the inotropes and vasopressors used in the management of cardiogenic shock

Speaker has nothing to disclose.

Cardiomyopathy Acute exacerbation of heart failure Myocardial infarction Cardiac arrest Myocarditis

Arrhythmias Atrial and ventricular Bradyarrhythmias

Mechanical Severe aortic or mitral valve insufficiency Acute valvular defects

BP = CO x SVRCO= HR x SV

↓ Systolic blood pressure ↓ Cardiac index

↑ Left ventricular diastolic pressure

Inadequate tissue oxygenation

Tachycardia to overcompensate for poor stroke volume and cardiac output

Multiple organ dysfunction

Irreversible cell destruction

Pump FailureDecreased

Tissue Perfusion

Shock Response

Receptor Location Action Effect

α1 Systemic Vasculature Vasoconstriction ↑ SVR

β1 Myocardium↑HR

↑contractility ↑CO

D KidneySplanchnic Vasculature

Renal & Mesenteric Vasodilation

↑UOP

V1 Systemic Vasculature Vasoconstriction ↑ SVR

BP = CO x SVRCO= HR x SV

α = SVR β = CO

Isoproterenol

Dobutamine

Dopamine

Epinephrine

Phenylephrine

Norepinephrine

Milrinone

PDE inhibitor =

CO + SVR

Distributive shock

Hypovolemic shock

Code situation

Cardiogenic shock

Cardiomyopathy

Vasopressin

V 1 = SVR

Inotropes: increase cardiac contractility

Vasopressors: induce vasoconstriction and elevate mean arterial pressure (MAP)

Indications: patients with decreased perfusion resulting in end-organ dysfunction due to

Decrease >30 mmHg from baseline or SBP < 90 mmHg

MAP <65 for > 30 minutes

Pharmacology: Primarily a β1 agonist with minimal α activity contractility > HR

Dose: 2.5 – 20 mcg/kg/min titration provider specific

Pearls: Max of 40 mcg/kg/min per manufacturer not guidelines Can lead to tachycardia Primarily used in decompensated HF to CO Vasodilation can cause hypotension myocardial oxygen demand High risk for arrhythmias (especially at higher doses)

Pharmacology: Phosphodiesterase enzyme inhibitor

▪ contractility = CO, vasodilation = SVR

Dose: 0.2-0.5 mcg/kg/min titration provider specific Using a loading dose increases risk for hypotension

Pearls: Primarily used in decompensated HF patients

Long half-life (~2.5 hrs) = prolonged vasodilation

High risk for arrhythmias

Pharmacology: Pure β agonist; contractility and HR = CO

Dose: 2 – 10 mcg/min titration provider specific Onset: immediate, duration: 10 – 15 minutes

Pearls: May cause hypotension (β2 activity)

Increases HR in patients refractory to atropine

Useful in bradyarrhythmias, AV block, and torsades

Pharmacology: Potent α agonist with some β1 effects Vasoconstriction (SVR & MAP) + modest increase in

HR (CO)

Dose: 0.5-30 mcg/min titrate 1 mcg/min every 15 minutes or 0.05 to 0.4 mcg/kg/minute

Pearls: Only causes a modest increase in HR Lower arrhythmia risk

Pharmacology: Equal α and β activity, β1 > β2

SVR (vasoconstriction), contractility and HR = CO

Dose: 1-10 mcg/min titrate 1 mcg/min every 15 minutes or 0.01 to 0.5 mcg/kg/minute

Pearls: 1st line therapy for anaphylactic shock, cardiac arrest

May decrease splanchnic blood flow

Increase serum lactate

Can lead to tachycardia before BP rises

Pharmacologic effects are dose dependent: Low dose (1-5 mcg/kg/min): renal blood flow, UOP Moderate dose (5-10 mcg/kg/min): HR, CO High dose (>10 mcg/kg/min): BP, vasoconstriction

Dose: 2-20 mcg/kg/min titrate 1-2 mcg/kg/min every 30 minutes

Pearls: Can lead to tachycardia and arrhythmias myocardial oxygen demand

Pharmacology: V1 = Vasoconstricts vascular smooth muscle = SVR

V2 = Reabsorbs H2O from renal collecting duct = UOP

Dose: 0.02 – 0.04 units/minute titration provider specific

Pearls: myocardial & peripheral ischemia at higher doses

Effects preserved during hypoxic or acidotic conditions

Increases vascular sensitivity to norepinephrine

Typically added for shock refractory to fluids/pressors

•Norepinephrine•Dobutamine

Cardiogenic

Shock

Vasopressor/Inotrope

α1 β1 β2 D V1/V2

Norepinephrine ++++ ++ + Ø Ø

Epinephrine +++ +++ ++ Ø Ø

Dopamine ++ +++ + ++++ Ø

Vasopressin Ø Ø Ø Ø +++

Dobutamine + +++ + Ø Ø

Milrinone Ø +++ Ø Ø Ø

Isoproterenol Ø ++++ +++ Ø Ø

Agent Class Dose Action Benefits Contraindications

Nitroglycerin (Tridil) IV

Nitrate 10-20 mcg/minute, titrate (10-20mcg/minute every 5-15 minutes) up to 200 mcg/minute

Vasodilator that relaxes smooth muscle

Dilation of both venous and arterial blood vessels

Hypotension; compensatory tachycardia

Nitroprusside(Nitropress) IV

Nitrate 5-10 mcg/minute; titrate (every 5 minutes) to achieve desired hemodynamic effect; usual dosage range: 5-300 mcg/minute

Dilates veins and arteries

Dilation of both venous and arterial blood vessels

Acute heart failure associated with reduced peripheral vascular resistance

Nesiritide(Natrecor) IV

Natriuretic peptide

2 mcg/kg (bolus optional); continuous infusion at 0.01 mcg/kg/minute

Dilates veins and arteries

Reduces pulmonary capillary wedge pressureand improves dyspnea

Hypotension

Agent Class Dose Action Benefits Contraindications

Furosemide(Lasix)IV/PO

Loop diuretic

Patient dependent40 mg

Inhibits reabsorption of sodiumand chloride

↑ water, sodium, chloride, magnesium,and calcium excretion to decrease edema

Severe electrolyte depletion

Bumetanide (Bumex)IV/PO

Loop diuretic

Patient dependent1 mg

Inhibits the sodium-potassium ATPasepump; blocks reabsorption of chloride

Induces diuresis in renal insufficiency; treatmentfor edema associated with heart failure

Anuria, severe electrolyte depletion

Torsemide(Demadex)IV/PO

Loop diuretic

Patient dependent10 mg

Inhibits the sodium, potassium, chloridecarrier system in the loop of Henle

↑ urinary excretion of sodium chloride and water without significantly altering the GFR

Known hypersensitivity to sulfonylureas;caution with hepatic disease

Metolazone(Zaroxolyn)PO

Loop diuretic

2.5-20 mg Inhibits the sodium, potassium, chloridecarrier system in the loop of Henle

↑ diuretic effect when given concurrentlyWITH Furosemide

Anuria, known hypersensitivity

Ethacrynic acid (Edecrin) IV/PO

Loop diuretic

50-200 mg/day

Inhibits reabsorption of filteredsodium

Known sulfa allergy; renal insufficiency

Severe electrolyte depletion

Spironolactone (Aldactone)PO

Potassiumsparing diuretic

12.5-50 mg/day

Competes with aldosterone receptor sitesto increase sodium and water excretion

Potassium sparing Renal failure

Agent Class Dose Action Benefits Contraindications

Ticagrelor(Brilinta)PO

Cyclopentyltriazolo-pyrimidine

180 mg load for PCI Reversibly inhibits the P2Y12platelet receptor

Short half-life and reversible antiplatelet effect

Risk of bleeding; history of intracranialhemorrhage; liver impairment

Prasugrel(Effient)PO

Thienopyridine 60 mg load for PCI Reversibly inhibits the ADP P2Y12platelet receptor to block platelet activation

Faster onset of action, higher levels of plateletinhibition, lower incidence of resistance

↓ liver function, history of pathological bleeding

Clopidogrel(Plavix)PO

Thienopyridine 600 mg load for PCI Reversibly inhibits the ADP P2Y12platelet receptor to block platelet activation

Platelet inhibition Hold 7 d before surgery to decrease risk of bleeding;genetic resistance; ineffective in some patients

Cangrelor(Kengreal)IV

Non-thienopyridine 30 mcg/kg IV bolus prior to percutaneous coronary intervention (PCI), then 4 mcg/kg/min IV infusion for at least 2 hours or for the duration of PCI

Reversibly inhibits the ADP P2Y12platelet receptor to block platelet activation and aggregation

IV formulation Bleeding

Agent Class Dose Action Benefits Contraindications

Aspirin Antiplatelet 325 mg for PCI Inhibits platelet cyclooxygenase and conversion of arachidonicacid to prostaglandins andthromboxane A2

↓ myocardial infarction and cardiac mortalityin first month

Bleeding

Abciximab(ReoPro)

Antiplatelet 0.25 mg/kg bolus administered 10-60 minutes before PCI, infusion of 0.125 mcg/kg/minute (max: 10 mcg/minute) for 12 hours

Inhibits GP IIb/IIIareceptorsresponsible for platelet aggregation

Adjunct to percutaneous transluminal coronaryangioplasty for the prevention of abruptclosure of arteries in high-risk patients

Bleeding, thrombocytopenia

Eptifibatide(Integrilin)

Antiplatelet 180 mcg/kg bolus (max: 22.6 mg) immediately before PCI, continuous infusion of 2 mcg/kg/minute (max: 15 mg/hour). A second 180 mcg/kg bolus (max: 22.6 mg) 10 minutes after the first bolus

Reversibly binds to GP IIb/IIIato inhibit platelet aggregation

Prevents platelets from binding with fibrinogen

Kidney dysfunction

Tirofiban(Aggrastat)

Antiplatelet Bolus 25 mcg/kg administered over 5 minutes PCI; Maintenance infusion: 0.15 mcg/kg/minute

Reversibly binds to GP IIb/IIIato inhibit platelet aggregation

Prevents platelets from binding with fibrinogen

Reduce dose in kidney dysfunction

Some patients may require fluids

Delicate balance of medications needed to maintain adequate perfusion

Monitor effects of medications Hypoxia and acidosis may blunt the effects of vasopressors and

inotropes

Epinephrine and dopamine most likely to cause tachycardia

Milrinone and dobutamine most arrhythmogenic

Monitor intake and output

Rockford Cardiology ConferenceMarianne Pop, Pharm.D., BCPS2/24/2018

Cardiogenic Shock. National Heart Lung and Blood Institute, U.S. Department of Health and Human Services, www.nhlbi.nih.gov/health-topics/cardiogenic-shock Accessed 21 February 2018.

Management of Cardiogenic Shock: AHA Scientific Statement.” American College of Cardiology, www.acc.org/latest-in-cardiology/ten-points-to-remember/2017/10/06/11/36/contemporary-management-of-cardiogenic-shock Accessed 21 February 2018.

Reynolds, Harmony R., and Judith S. Hochman. “Cardiogenic Shock.” Circulation, American Heart Association, Inc., 5 Feb. 2008, circ.ahajournals.org/content/117/5/686 Accessed 21 February 2018.

Warise L. Understanding cardiogenic shock: a nursing approach to improve outcomes. Dimens Crit Care Nurs. 2015 Mar-Apr;34(2):67-78.

Warise, L. Understanding Cardiogenic Shock. Dimens Crit Care Nurs. 2014;34(2):67-78.