Positive Inotropes Flashcards
Peripheral circulatory failure resulting in underperfusion of tissues
Shock
What does shock result in?
Decrease oxygen delivery to tissues.
Increase in anaerobic metabolism.
What are the 3 types of shock?
Hypovolemic
Septic
Cardiogenic
What does septic shock result in?
Increased CI
Decreased PCWP
Decreased SVR
What does hypovolemic shock result in?
Dec CI
Dec PCWP
Inc SVR
What does cardiogenic shock result in?
Dec CI
Inc PCWP
Inc SVR
Do you have increased or decreased intracellular cAMP with congestive heart failure?
Decreased cAMP
Do you have a downregulation or upregulation of beta receptors with CHF?
Downregulation
In CHF, there is an impaired coupling between what?
Beta receptors and adenyl cyclase
Low cardiac output syndrome occurs when pts are coming off CPB and is a combination of what?
Inadequate oxygen delivery to tissues Hemodilution Mild hypocalcemia Hypomagnesemia Kaliuresis Tissue thermal gradients Variable levels of systemic vascular resistance
What are the risk factors to Low cardiac output syndrome?
DM Increasing age female pre-op decreased LVEF increased duration of CPB
What is the pathophysiology of low cardiac output?
Stunned myocardium (hypocontractile myocardium in response to ischemia and reperfusion) Beta receptor down-regulation has been reported
What is the treatment to low cardiac output syndrome?
Positive inotropes to increase the contractility of normal and stunned myocardium
What is the goal in critically ill patients with low cardiac output syndrome?
Increase levels of O2 delivery (keep SvO2 >70%)
Increase O2 consumption (arterial blood lactate level < 2 mmol/L).
Which positive inotropes are cAMP dependent?
Beta Agonists
Dopaminergic Agonists
Phosphodiesterase Inhibitors
Which positive inotropes are cAMP independent?
Cardiac Glycosides
Calcium
What is the mechanism of action for cAMP dependent positive inotropes?
Beta 1 agonists (promote production) Phosphodiesterase inhibitors (inhibit metabolism)
How do beta1 agonists work for cAMP dependent positive inotropes?
Act thru the G protein to simulate the production of cAMP
Initiate a cascade of reactions that increase intracellular calcium
How do phosphodiesterase inhibitors work for cAMP dependent positive inotropes?
Inhibit phosphodiesterase III allowing cAMP and intracellular Ca to accumulate.
What is the essential ion necessary for contractile function?
Calcium
How do beta receptors work for cAMP dependent positive inotropes?
Catecholamines bind to beta receptors and activate a membrane-bound guanine nucleotide binding protein
This activates adenyl cyclase and generates cAMP.
cAMP increases Ca influx via slow channels and increases Ca sensitivity of Ca-regulatory proteins.
Increase the force of contraction and velocity of relaxation.
What is the mechanism of action for cAMP independent positive inotropes?
Direct-acting inotropes:
Calcium (Increased calcium gradient across the cell) membrane
Digoxin (Inhibits Na-K ATPase)
What are the hemodynamic effects for positive inotropes?
Increased contractility
Increased SV
Often decreased LVEDP and V
What are the hemodynamic effects for “pure” beta1 agonists?
Increased HR
Increased A-V conduction
Decreased SVR and PVR (Beta-2 effect)
Variable effect on Myocardial O2 consumption.
What are the hemodynamic effects for mixed alpha and beta agonists?
Increased vascular resistance (dose and drug related)
Increased Myocardial O2 consumption.
Increased HR
T/F: In the failing circulation, effects of inotropes are less likely to be more pronounced.
False: more likely to be pronounced
What are the indications for positive inotropes?
To increase SV in low flow states in which myocardial contractility is depressed.
Used in combination with other therapies to improve SV and CO by affecting preload, afterload, HR and rhythm.
