Vasopressors & Inotropes

Runal ShahMEM

PGY-2

Objectives

• Physiology of vascular receptors• Principles of use of vasoactive agents• Individual drugs• Complications

Adrenergic Receptor Physiology

• Alpha-1• Beta-1• Beta-2• Dopamine

α-1 Adrenergic receptors

• Located in arteriolar walls– Induces significant vasoconstriction

• Present in heart– Slight positive Inotropic effect (increased

intracellular Calcium ).

-β Adrenergic receptors

• β-1 adrenergic receptors are most common in the heart– positive inotropy and chronotropy with minimal

vasoconstriction.• β-2 adrenergic receptors in blood vessels

induce vasodilatation; bronchodilation.

Dopamine receptors

• Present in the renal, splanchnic, coronary, and cerebral vascular beds.

• Stimulation of these receptors leads to vasodilatation.

• Second subtype of dopamine receptors causes vasoconstriction by inducing nor-epinephrine release.

Principles Of Use OfVasopressors and Inotropes

• Hypotension may result from:– Hypovolemia– Pump failure– Pathologic misdistribution of blood flow

• Vasopressors are indicated for:– Decrease of >30 mmHg/20% from baseline SBP or– MAP <60 mmHg– Evidence of end-organ dysfunction due to

hypoperfusion• Hypovolemia must be corrected first

• Use of vasopressors and inotropes is guided by three fundamental concepts:– One drug, many receptors– Dose-response curve– Direct versus reflex actions

Principles Of Use OfVasopressors and Inotropes

Volume resuscitation

• Repletion of adequate intravascular volume, when time permits, is crucial prior to the initiation of vasopressors.– Vasopressors will be ineffective or only partially

effective in the setting of coexisting hypovolemia.

• Fluids may be withheld in patients with significant pulmonary edema due to ARDS or CHF.

Tachyphylaxis

• Responsiveness to these drugs can decrease over time due to tachyphylaxis.

• Doses must be constantly titrated to adjust for this phenomenon and for changes in the patients clinical condition.

Nor-epinephrine

• Acts on both α-1 and β-1 receptors– Potent vasoconstriction as well as a less

pronounced increase in cardiac output

• Paradoxical decrease in HR can occur as a reflex increase in Parasympathetic tone.

• Drug of choice to treat septic shock

Nor-epinephrine

• Norepinephrine is traditionally used as the last measure for cases of hypotension that are refractory to volume infusion and other hemodynamic drugs (e.g., dobutamine, dopamine).

• Norepinephrine is the vasopressor of choice in septic shock and should be added when hypotension is not corrected by appropriate volume infusion.

Epinephrine• Potent β-1 receptor activity and β-2 and α-1

receptor effects.• Result is an increased CO, with decreased SVR and

variable effects on the MAP.• β-1 receptor stimulation may provoke

dysrhythmias.• Greater degree of splanchnic vasoconstriction.

• Most often used in ACLS, treatment of anaphylaxis, as a second line agent in septic shock and for management of hypotension.

Dopamine• At low doses (0.5-5 mcg/kg/min)

– dopamine acts predominately on dopamine-1 receptors in the renal, mesenteric, cerebral, and coronary beds, resulting in selective vasodilatation.

• At moderate doses (5-10 mcg/kg/min)– dopamine also stimulates β-1 receptors and increases

CO, predominately by increasing SV with variable effects on HR.

– Can result in dose-limiting dysrhythmias• At higher doses (>10 mcg/kg/min)

– dopamine stimulates α receptors and produces vasoconstriction with an increased SVR.

Dopamine

• Dopamine is indicated for reversing hemodynamically significant Hypotension caused by – myocardial infarction– Trauma– heart failure– renal failure

• when fluid resuscitation is unsuccessful or not appropriate.

Dobutamine• Dobutamine is a synthetic catecholamine that is

used as a positive inotropic agent, to increase cardiac stroke output in patients with severe, decompensated heart failure.

• Predominant β-1 receptor effect increases inotropy and chronotropy and reduces LV filling pressures.

• Minimal α and β-2 receptor effects result in overall vasodilatation, complemented by reflex vasodilatation to the increased CO.

• Net effect is increased CO, with decreased SVR with or without a small reduction in BP, HR.

Dobutamine• Indicated in short-term positive inotropic support

for the treatment of cardiovascular decompensation secondary to ventricular dysfunction or low-output heart failure.

• It is the preferred agent in septic shock with depressed cardiac output despite adequate left ventricular filling pressures.

• Dobutamine is also usually the preferred agent in the management of cardiogenic shock.

Vasopressin

• Acts like ADH; directly stimulates smooth muscle V1 receptors, resulting in vasoconstriction

• Often used in the setting of DI or esophageal variceal bleeding.

• May be useful in the treatment of refractory septic shock, particularly as a second pressor agent.

Vasopressin

• For the treatment of refractory hypotension, vasopressin is infused at a rate of

• 0.01 to 0.04 unit per minute

Inamrinone and Milrinone

• MoA : Phosphodiesterase inhibitor , increase intracellular c-AMP, Calcium – Increased FoC, Myocardiac contractility, Positive Inotropic and Vasodilator property (Inodilator)

• Indication : for short term use of Decompensated Heart Failure

• S/E : Supraventricular arrhythmias, Hypotension, Headache, Rare : Thrombocytopenia

Inamrinone and MilrinoneInamrinone Milrinone

Onset 2-5 min 5-15min

Action duration 0.5-2 hours 2.5 hours

Dose Bolus : 0.75 mcg/kg IV x 2-3 minMaintenance : 5-10mcg/kg/min IV Infusion

Bolus :50 mcg/kg IV x 10 minMaintenance :0.5-0.75mcg/kg/min IV Infusion

Phenylephrine

• MoA : α effects predominate, minimal β effects, vasoconstriction of vascular beds resulting in increase of SBP, DBP.

• Dose : 100-200 mcg/min IV infusion then tapered according to BP.

• S/E : Severe Bradycardia

Doses and infusions

Agent Dose

Dopamine 5-10 mcg/kg/min

Nor-Adrenaline 0.1-0.5 mcg/kg/min

Adrenaline 0.1-0.5 mcg/kg/min

Vasopressin 0.01-0.04 units/min

ComplicationsHypoperfusion

• Commonly occurs in the setting of inadequate cardiac output or inadequate volume resuscitation.

• Dusky skin changes at the tips of the fingers and toes, renal insufficiency and oliguria, and possible limb ischemia.

• Increase the risk of gastritis, shock liver, intestinal ischemia, or translocation of gut flora with resultant bacteremia.

ComplicationsDysrhythmias

• Stimulation of β-1 receptors.• Increases the risk of sinus tachycardia, atrial

fibrillation, AVnRT, or ventricular tachyarrhythmias.

• Limit the maximal dose and necessitate switching to another agent with less prominent β-1 effects.

ComplicationsLocal effects

• Peripheral extravasation of vasopressors into the surrounding connective tissue can lead to excessive local vasoconstriction with subsequent skin necrosis.

• Vasopressors should be administered via a central line.

• Local treatment with Phentolamine minimize local vasoconstriction.

ComplicationsHyperglycemia

• May occur due to inhibition of insulin secretion.

• Magnitude of hyperglycemia generally is mild.

• More pronounced with Nor-epinephrine and epinephrine than dopamine.

• β >> α (Decreases insulin, Hyperglycemia by Glycogenolysis and Gluconeogenesis)

Vasopressor Use in Septic Shock

• Patients with hyperdynamic septic shock (hypotension, low SVR, and high CI) tend to have warm extremities due to inappropriate hyperperfusion of the skin and soft tissues.– Norepinephrine and Phenylephrine appear more potent

in hyperdynamic sepsis.

• Patients with hypodynamic septic shock (hypotension, low SVR, and low CI) manifest hypoperfusion of the extremities.– Dopamine may be preferable in patients with

hypodynamic sepsis.

Thank You…

Ref:Tintinalli’s Emergency Medicine, 7/e

The ICU book, by Paul Marino, 3/eGoogle