1. Vasoactive Drugs and Shock
Philip Marcus, MD MPH

2. 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

3. Shock Clinical Manifestations Hypotension Oliguria Acidosis
CNS dysfunction

4. 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)

5. Causes of Shock
Cardiogenic
Obstructive
Oligemic
Distributive

6. Cardiogenic Shock Arrhythmias Cardiac mechanical factors
Regurgitant lesions
Obstructive lesions
LV outflow
LV inflow
Cardiomyopathies
Impaired LV contractility
Impaired LV compliance

7. Obstructive Shock Cardiac tamponade Constrictive pericarditis
Pulmonary embolism

8. Oligemic Shock Hemorrhagic intravascular depletion
Nonhemorrhagic intravascular depletion
Vomiting
Diarrhea
Dehydration
Peritonitis
Pancreatitis
ascites

9. 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

10. Hemorrhage, solute loss
Low Preload Shock
Reduced PCWP
Reduced CO
Elevated SVR
Reduced svO2
Treatment = Volume infusion
Hemorrhage, solute loss

11. 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

12. Sepsis, Anaphylaxis, Adrenal crisis, Toxic shock
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

13. Low preload & Cardiac Dysfunction
Combined Disorders
Normal PCWP
Reduced CO
Elevated SVR
Reduced svO2
Treatment
Volume infusion, then
Inotropic agents
Low preload & Cardiac Dysfunction

14. Indications for Vasopressors
Decrease of > 30 mmHg from baseline systolic BP OR
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.

15. Fundamental Concepts One drug, many receptors Dose-response curve
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

16. Isoproterenol b1 + b2 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

17. Epinephrine a1, b1 + b2 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

18. Norepinephrine Levarterenol
Peripheral vasoconstrictor
Arterial and venous
α adrenergic activity
Inotropic action
β-1 action
Reflex bradycardia may occur
Secondary to potent pressor activity

19. Norepinephrine Levarterenol
Used in acute hypotensive states
Following sympathectomy
Following removal of pheochromocytoma
Spinal anesthesia
Septic shock
Extravasation
Necrosis and sloughing
Antidote…phentolamine

21. Phenylephrine Pure α-agonist Elevates SVR Causes reflex bradycardia
Equal effectiveness as norepinephrine
No chronotropic effects
No inotropic effects
Danger of extravasation

22. 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

23. 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

24. Dopamine β1 actions α effects Inotropic effects Increases SVR
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

26. Dopamine Rapid onset of action Rapid metabolism 2 – 4 minutes
t1/2 < 10 minutes
First-order kinetics
MAO + COMT

27. Dopamine Indications Assure adequate filling pressures
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

28. 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

29. Dobutamine

30. Dobutamine Increases contractility Rapid onset of action
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

31. 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

32. 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