vasoactive drugs and shock philip marcus, md mph
TRANSCRIPT
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