Vasoactive Drugs and Shock

Philip Marcus, MD MPH

Shock

• Acute, generalized, inadequate perfusion of critical organs

• Serious pathophysiologic consequences if continued

• Disturbed metabolic function at organ and cellular levels

• Disorder of cellular O2 utilization– Usually low-flow state– Maldistribution

Shock

• Clinical Manifestations– Hypotension– Oliguria– Acidosis– CNS dysfunction

Physiologic Measurements• Pulmonary Capillary Wedge Pressure

– Index of LV preload

• Cardiac Output• Systemic Vascular Resistance

– Index of LV afterload

• Mixed Venous O2 saturation (SvO2)

• O2 delivery = CO x caO2

• O2 consumption = CO x (caO2 – cvO2)

Causes of Shock

• Cardiogenic

• Obstructive

• Oligemic

• Distributive

Cardiogenic Shock

• Arrhythmias• Cardiac mechanical factors

– Regurgitant lesions– Obstructive lesions

• LV outflow• LV inflow

• Cardiomyopathies– Impaired LV contractility– Impaired LV compliance

Obstructive Shock

• Cardiac tamponade

• Constrictive pericarditis

• Pulmonary embolism

Oligemic Shock

• Hemorrhagic intravascular depletion

• Nonhemorrhagic intravascular depletion– Vomiting– Diarrhea– Dehydration– Peritonitis– Pancreatitis– ascites

Distributive Shock

• Abnormal vascular volume distribution– Results from decreased regional vascular resistance

• Etiologic factors– Sepsis, endotoxemia– Metabolic factors

• Respiratory failure, renal failure, drug OD

– Endocrinologic factors• Ketoacidosis, hyperosmolar state, hypothyroid

– Neurologic factors– Anaphylaxis

Low Preload Shock

• Reduced PCWP

• Reduced CO

• Elevated SVR

• Reduced svO2

• Treatment = Volume infusion

Hemorrhage, solute loss

Cardiac Dysfunction Shock

• Elevated PCWP• Reduced CO• Elevated SVR• Reduced svO2

• Treatment– Inotropic agents– Vasodilators– Volume

Systolic Failure: Ischemia, infarction

Diastolic Failure: Tamponade

Valve Dysfunction

Low Afterload Shock

• Reduced or Normal PCWP• Elevated CO• Reduced SVR• Elevated svO2

• Treatment– Volume infusion– Vasoconstrictors– ? Inotropic agents

Sepsis, Anaphylaxis, Adrenal crisis, Toxic shock

Combined Disorders

• Normal PCWP

• Reduced CO

• Elevated SVR

• Reduced svO2

• Treatment– Volume infusion, then– Inotropic agents

Low preload & Cardiac Dysfunction

Indications for Vasopressors

• Decrease of > 30 mmHg from baseline systolic BPOR

• Mean arterial pressure (MAP) < 60 mmHg

when either condition results in end-organ dysfunction due to hypoperfusion. Hypovolemia must be corrected prior to institution of vasopressor therapy.

Fundamental Concepts

• One drug, many receptors– A given drug often has multiple effects

because of actions upon more than one receptor

• Dose-response curve– Many agents have dose-response curves– Primary adrenergic receptor subtype activated

by the drug is dose-dependent

• Direct vs. reflex actions

Isoproterenol

activity• Positive Inotropic activity• Positive Chronotropic

activity

• Increased MVO2

• Increases CO, Decreases SVR

• Increases systolic BP, decreases diastolic BP

• Used in cardiac standstill and for profound bradyarrhythmias

Use in hypotension limited to situations in which hypotension

results from bradycardia; High affinity for β-2 receptors results in

vasodilatation and a decrease in MAP

Epinephrine

activity• Positive inotropic activity• Positive chronotropic activity• Constricts arterioles in skin, mucosa and

splanchnic circulation• Increases systolic BP, decreases diastolic BP• Decreases SVR via dilatation of skeletal muscle

vasculature– Enhances blood flow

• Used primarily in cardiac standstill and hypotension following cardiac surgery

α receptor induced vasoconstriction offset by β-

2 receptor vasodilatation

NorepinephrineLevarterenol

• Peripheral vasoconstrictor– Arterial and venous– α adrenergic activity

• Inotropic action– β-1 action

• Reflex bradycardia may occur– Secondary to potent pressor activity

NorepinephrineLevarterenol

• Used in acute hypotensive states– Following sympathectomy– Following removal of pheochromocytoma– Spinal anesthesia– Septic shock

• Extravasation– Necrosis and sloughing– Antidote…phentolamine

Phenylephrine

• Pure α-agonist

• Elevates SVR

• Causes reflex bradycardia

• Equal effectiveness as norepinephrine– No chronotropic effects– No inotropic effects

• Danger of extravasation

Dopamine

• Endogenous catecholamine

• Acts directly on α and β1 receptors

• Acts also on Dopamine receptors

• Dose-dependent effects– Low-dose = dopaminergic effects– Medium-dose = β effects– Medium to high-dose = α and β effects– High-dose = α effects

Dopamine

• Dopaminergic effects– Vasodilatation of renal, mesenteric, coronary,

splanchnic and cerebral vasculature– Natriuretic effects

• Increases RBF and GFR• Induces redistribution of intrarenal blood flow to

juxtamedullary nephrons• Direct tubular action• Increases urinary cAMP

Dopamine

• β1 actions– Inotropic effects

• Increases CO• Less chronotropic effects than isoproterenol• Releases NE…further increases CO

• α effects– Increases SVR– Increases MAP– Can reduce urine output– Dopaminergic receptors antagonized

Dopamine

• Rapid onset of action– 2 – 4 minutes

• Rapid metabolism– t1/2 < 10 minutes

– First-order kinetics– MAO + COMT

Dopamine

• Indications– Low cardiac output– Compromised renal function

• Assure adequate filling pressures– Fluid administration

• Use in conjunction with nitroprusside to inhibit vasoconstriction

• Extravasation– Necrosis and sloughing

• Nausea and vomiting often occur

Dobutamine

• Direct-acting catecholamine

• Chemically related to dopamine

• Principally stimulates β1 receptors within myocardium– INOTROPIC– Minimal chronotropic effects– No α or β2 effects– No dopaminergic effects

Dobutamine

Dobutamine

• Increases contractility– Increases CO without tachycardia– No arrhythmogenic or vasodilatory effects– No vasoconstriction

• Rapid onset of action– 1 – 2 minutes

• Rapid metabolism– t ½ ~ 2-3 minutes– COMT

Dobutamine

• Useful in low cardiac output states– Acute and chronic heart failure without

hypotension

• Used in acute MI and following cardiac surgery

• IHSS contraindication

• Usual dose = 5-20 mcg/kg/min

Dopexamine

• Synthetic catecholamine• Used in Europe• Systemic and pulmonary vasodilator effects• Lesser agonist activity at Dopamine receptors

(1/3 potency of dopamine)• Positive inotropic effect• Increases cerebral, renal and splanchnic blood

flow• Augments CO in chronic LV dysfunction

following CABG and acute MI with LV dysfunction