Inotrope use in icu patient fink

Inotropic Therapy

Rationale for Using Inotropic Therapy inthe Critically Ill

REVERSING IMPAIRED MYOCARDIAL CONTRACTILITY

ACHIEVING SUPRANORMAL LEVELS OF OXYGEN DELIVERY

HIGH-RISK SURGICAL PATIENTS

CRITICALLY ILL PATIENTS

inotropic therapy is generallyconsidered includes cardiogenic shock, acute heart failure, or acuteexacerbation of chronic heart failure

use of such therapy in these clinical conditions seems logical on a purelypathophysiologic basis, no demonstration of a beneficial impact onmorbidity and mortality can be found in the literature.

increased mortality rates when given on a long-termbasis to patients with chronic heart failure

the long-term use of inotropes may lead to deterioration of left ventricularfunction through acceleration of myocardial cell apoptosis

deterioration of left ventricularfunction through acceleration of myocardial cell apoptosis

agents have negative inotropic effects, such as b-blockers, is now well establishedwhen1. cardiogenic shock( myocardial infarction or

acute myocarditis bridge to coronary revascularization or recovery

2. Refractory chronic heart failure bridge to transplantation

Inotropic therapy

ACHIEVING SUPRANORMAL LEVELS OF O2 DELIVERY1-High-Risk Surgical Patients

use of supranormal hemodynamic valuesin high-risk patients undergoing surgery as therapeutic endpoints was associated with a reduction in mortalityfrom 33% to 4%.

protocol group, dobutamine and dopamine were given as inotropic drugs—even in the absence of evidence of reduced cardiac contractility—when volume resuscitation (and packedred blood cells if necessary) failed to achieve supranormal values ofmyocardial oxygen delivery (DO2)4 (DO2 > 600 mL/min/m2).

related to the increased DO2 or antiinflammatory effects of catecholamines.

Critically Ill Patients

a pathologic myocardial oxygen consumption/oxygen delivery (VO2/DO2) dependency, presumably due to impaired oxygen extraction capabilities, has been reported invarious categories of acute illnesses such as sepsis and acute respiratory distress syndrome

increased blood lactate, a marker of global tissuehypoxia and to be associated with a poor outcome

manipulation of hemodynamic variablestoward values higher than physiologic values did not demonstrateany benefit

attempt to achieve supranormal hemodynamic targets in thegeneral population of critically ill patients is no longer recommended.in the early phase of septic shock when bloodflow and DO2 are generally low FOR rapidly restore normal global blood flow deleterious consequences of systemic hypoperfusion

EFFECTSINOTROPIC

LUSITROPIC CHRONOTROPIC,

DROMOTROPIC

VASOPRESSORS

Β1 AGONIST/STIMULATION: CHRONITROPIC, INOTROPICΒ2 AGONIST/STIMULATION: VASODILATION, BRONCHODILATIONΑ: VASOCONSTRICTIOND: INCREASES RENAL BLOOD FLOW

Natural as well as synthetic catecholamines enhance the Ca2+ cytosolicamount, which is directly related to the force of contractiona faster decrease in Ca2+ cytosolic concentration aftercontraction and accounting for the lusitropic effect.

Pharmacologic Propertiesof Inotropic Agents

Need to understand how they work to use effectively

Adrenergic precipitation of arrhythmiasDrive the heart too fast resulting in decreased filling time and decreased stroke volumeVasoconstriction of splachnic circulation and coronary arteriesInotropes may make certain patients hypotensive

PHARMACOLOGIC PROPERTIES OF THE INOTROPICAGENTS USED IN CLINICAL PRACTICE

Epinephrine

potent stimulator of α, β1, and β2 receptorscardiac β1 stimulation, epinephrine increases HR and inotropism.

α-mediated venous constriction promoting venous return and cardiacpreload results in increase in cardiac output

Epinephrine also facilitates ventricular relaxation and enhanced coronary blood flow through the increase in myocardial VO2.

Norepinephrine

It is a potent α- and β1-adrenergic agonist,but it has little activity on β2 receptors

α-adrenergic effect tarterial and venous constriction

β1 positive inotropic effect and increase SV

heart rate is unchanged or reduced, and the cardiac output can be unchanged. baroreflex stimulation following vasoconstriction

Coronary blood flow is enhancedsecondary to enhanced cardiac metabolism andbecause of normalization of diastolic blood pressure when low.

Dopamine

-2-5 mcg/kg/min renal flow => D1 receptors

- 5-10 mcg/kg/min => Beta 1 enhances inotropism and increases heart rate increases systolic blood pressure without altering diastolic blood pressure, because stroke volume is enhanced and arterialvascular tone only slightly altered

- 10-20 mcg/kg/min => alpha, vasoconstriction

several types of receptors that are activated at different levels of dopamine concentration

Dobutamine

β1-adrenergic stimulationeffects on adrenergic receptors are complex but

Dobutamine exerts no intrinsic vascular effect, because the vasoconstriction induced by α1 stimulation is counteracted by the β2 vasodilating effect.

Dopexamine

β2 and dopaminergic receptor

induces vasodilation and inotropic effect with substantiallyincreased stroke volume

no effect on α-adrenergic receptors

Isoproterenolβ-adrenergic agonist

β2 vasodilating effect it induces a fall in diastolic and meanblood pressure

β1-adrenergic activation systolic blood pressure is increased

increase in heart rate leads to enhanced cardiac outputincrease in myocardial VO2 is not compensated by coronary blood flow enhancement, so isoproterenol infusion may lead to myocardial ischemia, especially if there is preexisting coronary artery disease

no longer used

Phosphodiesterase Inhibitors

Despite the major role of catecholamines in the management of criticallyill patients with inadequate cardiac output, problems such astachycardia, arrhythmias, increased myocardial VO2, excessive vasoconstriction, or loss of effectiveness with prolonged exposure toβ-agonists may occur

increasing intracellular cAMP concentration

Vasodilation AND left ventricular preload is reduced

inotropic effect and heart rate is increased and increase incardiac output. facilitate ventricular relaxation

Synergic since β-agonists exert their action by increasing theproduction of cAMP, phosphodiesterase inhibition could enhancetheir adrenergic effects.

milrinone and enoximone

Calcium Sensitizers

levosimendan

increase the sensitivity of troponin C for Ca hence the force and duration of the cardiomyocytes’ contraction

increase the activity of the ATPase of the myofibrils,increasing the contractile force

Cardiac Myosin Activators

DECREASE IN β-ADRENERGIC RESPONSE

Hemodynamic Effects of InotropicAgents in Critically Ill Patients

EFFECTS ON CARDIAC OUTPUT

EFFECTS ON ARTERIAL OXYGEN CONTENT

EFFECTS ON TISSUE OXYGEN UTILIZATION

EFFECTS ON CARDIAC OUTPUT

Dobutamine and Dopamine

Epinephrine and Norepinephrine

Dopexamine

Dobutamine and DopamineDobutamine and dopamine are the β-adrenergic agents most widelyused in critically illIn acute heart failure

dobutamine (2.5-10 μg/kg/min) increased CO BY increase in SV in a dose-response dopamine increased SV and CO at 4 μg/kg/min at higher doses. because of an increase in left ventricular afterloadpulmonary artery occlusion pressure decreased with

dobutamine. increased with dopamine.

increase in left ventricular preload only with dopamine.

Dopamine at median or high doses has been one of the first-line catecholamines when arterial pressure remains low despite adequate volume resuscitation as it can exert both an α-mediated increase in arterial tone and a β-mediated increaseHR SV CO INCREASEminimal effects ON SVR

difficulty to predict clinical hemodynamic effects

great heterogeneity in the response to dopamine among septic patients

an increase in cardiac output and a decrease in SVR with dobutamine were reported in septic patients

septic shock WE HAVE DECREASE SVR WE HAVE TO GIVE DOBOTAMINE + VASOPRESSOR AGENT

dobutamine is the decrease in cardiac filling pressures that could allow an additional volume infusion to improve further cardiac output when necessary.

dobutamine can exert a more favorable effect on cardiac contractility than dopamine. recommendation to give dobutamine rather than dopamine

emphasize the unpredictability of the effects ofβ-agonist agents in patients with sepsis.

the absence of positive cardiac response to dobutamine seems a marker of poor outcome in septic shock patients.

Epinephrine and Norepinephrine

these agents have β1-adrenergic properties and thus are ableto increase myocardial contractility, they are used as vasoconstrictiveagents in cases of severe hypotension

the effects of norepinephrine on cardiac output are highly variable among septic patients. By contrast, epinephrine appeared to be a potent inotropic agent in most studies in septic patients

Dopexamineinotropic, afterload-reducing, and renal-vasodilating effects which could be useful for the management of acute exacerbation of congestive heart failureincrease cardiac output in patients with heart failure without altering blood pressure

doses up to 4 μg/kg/min

In cases of human sepsis, dopexamine produced dose-dependent increases in stroke volume and heart rate but dose-dependent decreasein SVR

Under these conditions, dopexamine at dosesranging drom 1 to 4 μg/kg/min could still enhance cardiac outputwithout altering blood pressure.

when an inotropic agent increases cardiac output in critically ill patients, it generally increases DO2 to the same extent

EFFECTS ON ARTERIAL OXYGEN CONTENT

CO D02

EFFECTS ON TISSUE OXYGEN UTILIZATION

reducing oxygen deficit depends on its capacity to provide oxygen in the most hypoxic tissues

concern

redistribution of blood flow is a characteristic pattern of shock states, and, inotropic drugs may also have vasoactive properties that interact with blood flow distribution.

EFFECTS ON TISSUE OXYGEN UTILIZATION

1.Cardiogenic Shock

redistribution of flow is A mechanism to deviate blood flow from nonvital organs towards vital organs

Administration of drugs with vasoactive properties may interfere with vasoregulation of regional blood flow

need to monitor as far as possible perfusion and/or function of critical organs.

Septic Shockmaldistribution of flow

Cause 1.microthrombosis,

2. alteration vascular reactivity

even when systemic oxygen transport is greater than normal.

defective tissueutilization

Result of study

Second, dopamine may have deleterious effects on gut mucosal perfusion29 despite its potential vasodilating action through mesenteric D receptors

Third, epinephrine is the least desirable effects on the splanchnic vasculature

Fourth, dopexamine can exert a favorable effect on splanchnic perfusion

sepsis can modify the impact of endogenous catecholamines and adrenergic drugs on regional blood Flows.

absence of reduction of renal blood flow observed during norepinephrine

to increase MAP toward

normal valuesFirst, dobutamine is likely to exert a beneficial effect on the gut mucosal perfusion

Main Indications for Inotropic Therapy in Patients with Circulatory Failure

• ACUTE HEART FAILURE AND CARDIOGENIC SHOCK

• SEPTIC SHOCK

Indicated

1- improve symptoms and end-organ function in patients with low output syndrome

2-left ventricular systolic dysfunction

3- systolic blood pressure below 90 mm Hg despite adequate filling pressure.

Dopamine is classically recommended as the inotropic agent ofchoice in the presence of SEVERE HYPOTENSION.

dobutamine is considered first-line therapy in the presence of predominant pump failure and volume overload but normal or moderately reduced blood pressure.

dopamine dobutamine low doses has been considered a therapy of interest when dobutamine alone fails to restore an adequate MAP in cardiogenic shock.

dobutamine is associated with an increased risk of death in acute heart failure patients.

Phosphodiesterase inhibitor therapy in chronic heart failure

INDICATION

(1 )patients with advanced heart failure awaiting transplantation

(2 )patients with acute decompensation of chronic heart failure unable to achieve stabilization with standard treatment

(3)patients with long-term b-blocker use, in whom short-term IV milrinone may even be preferred to dobutamine.

SEPTIC SHOCKIn cases of septic shock, dobutamine is generally considered the inotropicdrug of choice when myocardial contractility is severely depressed.

FIRST CHOICE DOBOTAMINE

Detection a vasodilatory effect, its use requires concomitant use of a vasopressor such as norepinephrine.

DOBOTAMINE +Norepinephrine. SEPTIC SHOCK

Epinephrine alternative dobutamine + norepinephrine.

Epinephrine is not recommended as the first-choice drug when treatmentof impaired cardiac contractility is considered

no longer responds to dobutamine administration Levosimendan alternative to dobutamine in case of severe septic myocardial.