Seminar on Hemodynamic

Drug Infusions
By :- Zemenu R (EMCCR3)
Date:- Jan/17/22 G.C
Outline
• Introduction
• Practical Issue
• General principle
• Vasoactive drug classification
• Specific drugs
• References
Introduction
• Vasopressors - induce vasoconstriction and elevate mean arterial
pressure (MAP).
• Inotropes - increase cardiac contractility.
• Many drugs have both vasopressor and inotropic effects.
• Shock is defined by overt dysfunction of vital organ systems
• The prime objective of circulatory support is to maintain near-optimal
vital organ perfusion.
• Reflected in mental status, urinary output, systemic pH, and lactate
concentration, at acceptable cardiac filling pressures.
• Hypotension may result from
Hypovolemia (eg, exsanguination),
Pump failure (eg, severe medically refractory heart failure or shock
complicating myocardial infarction), or
A pathologic maldistribution of blood flow (eg, septic shock, anaphylaxis)
• Vasopressors are indicated for a decrease of >30 mmHg from baseline systolic
blood pressure, or a mean arterial pressure <60 mmHg when either condition
results in end-organ dysfunction due to hypoperfusion.
Practical Issues
• Volume resuscitation
• Selection and titration
• Route of administration
• Tachyphylaxis
• Hemodynamic effects
• Subcutaneous delivery of medications
• Frequent re-evaluation
General Principles
• The primary goal of vasopressor therapy is to support vital organ
perfusion—not to achieve any specific BP.
• Vasoactive drugs are relatively ineffective in
Volume-depleted patients
Are partially inhibited in the setting of severe acidosis
Glucocorticoid deficiency also blunts the impact of vasomotor agents
May be ineffective when serum concentrations of K + , Mg 2+ , or ionized Ca
2+ are strikingly abnormal.
• Making optimal choices hemodynamic drugs requires

A clear understanding of the operative pathophysiology,

An understanding of adrenergic receptor distribution and action, and
A working knowledge of the pharmacologic alternatives.
• The rational use of vasopressors and inotropes is guided by three
fundamental concepts:
One drug, many receptors
Dose-response curve
Direct versus reflex actions
Classification of Vasoactive drugs and Inotropes
• They are classified by their tendencies to stimulate receptors with
different physiologic actions.
• Alpha effects are vasoconstricting in the peripheral circulation.
• β1 receptor activation is both chronotropic and inotropic.
• β2 effects induce vasodilation and bronchodilation
• Dopaminergic (Δ) receptor activation
Effects on adrenergic receptors
• Adrenergic agents • Nonadrenergic agents
• Adrenaline • Vasopressin
• Noradrenalin • PDE inhibitors
• Dopamine • Calcium sensitizers
• Dobutamine • Angiotensin II
• Phenylephrine
• Ephedrine
• Isoproterenol
Epinephrine (Adrenaline)
• Has potent beta-1 and moderate beta-2 and alpha-1 adrenergic
receptor effects.
• Increases systemic vascular resistance, HR, CO, and BP.
• At low doses it increase CO because of the beta-1 inotropic and
chronotropic effects
• At higher doses the alpha-adrenergic receptor effect predominates
• Pharmacokinetics

• Adverse effects - angina, palpitations, arrhythmias, hypertension,

tachycardia, nausea, vomiting, headache, anxiety, and pulmonary
edema.
• Epinephrine is indicated for
Cardiac arrest
Symptomatic bradycardia unresponsive to atropine
Second line agent in severe sepsis or septic shock.
It is an essential agent for the treatment of anaphylaxis.
 Upper airway obstruction
• Dosage
• Asystole/pulseless arrest, pulseless VT/VF
• 1 milligram IV/IO every 3–5 min until ROSC; 2–2.5 milligrams ET every 3–5 min
until IV/IO access established or ROSC (dilute in 5–10 mL NS or SW)
• Bradycardia
• IV infusion:2–10 micrograms/min; titrate to desired response
• Septic shock
• IV infusion (initial):0.05–2 micrograms/kg/min; titrate every 10-15 min by
increments of 0.02–0.05 microgram/kg/min to desired MAP
• Hypotension after intubation or sedation
• 5–20 micrograms/bolus dose over 20–30s every 2–5 min as needed
• Anaphylaxis
• 0.3–0.5 milligram IM by epinephrine autoinjector or equivalent;
• IV infusion, mix 1 milligram in 500 mL D5W and infuse at 0.5 mL/min and
titrate dose as needed
• Post-extubation stridor or other upper airway obstruction:
• Use the 1:1000 vials up to max. dose 5ml and administer via a nebulizer (if
giving less than 4mg, make up to at least 4ml with 0.9% saline).
• DOSAGE IN PAEDIATRICS:
• Cardiac arrest: 0.1ml/kg of 1:10000 IV 0.1ml/kg of 1:1000 via ETT
• Anaphylaxis: 0.05ml/kg of 1:10000 IV OR 0.01ml/kg of 1:1000 IM
• Severe Croup: Use the 1:1000 vials at a dose of 0.5ml/kg/dose, max.
dose 5ml and administer via a nebulizer (make up to at least 4ml with
0.9% saline).
• IV Infusion: 0.3mg/kg in 50ml D5W at 0.5-10ml/hr (equates to 0.05-
1mcg/kg/min)
Norepinephrine
• Acts on both alpha-1 and beta-1 adrenergic receptors
• Has a peripheral vasoconstrictor (alpha-adrenergic action) and
• Has inotropic stimulator of the heart and dilator of coronary arteries
(beta adrenergic action (β1 > β2)).
• Is indicated for the treatment of acute hypotension and shock.
• It is the initial vasopressor of choice for septic shock refractory to
adequate fluid resuscitation based on the sepsis guidelines.
• Pharmacokinetics

• Adverse effects - bradycardia, arrhythmias, peripheral ischemia,

hypertension, nausea, vomiting, headache, anxiety, and cardiac
arrest.
• Dose
• Post–cardiac arrest care
• Initial: 0.1–0.5 microgram/kg/min; titrate to desired response
• Sepsis/septic shock
• Start 0.02–0.04 microgram/kg/min; typical range, 0.02–1.0 
microgram/kg/min; titrate every 5–10 min by 0.02–0.04 
microgram/kg/min; wean at rate 0.01–0.03 microgram/kg/min
• Dosage in pediatrics:
• IV Infusion: 0.3mg/kg in 50ml D5W at 0.5-10ml/hr (equates to
0.05-1mcg/kg/min)
Ephedrine
• It stimulates both alpha and beta receptors
• Its peripheral actions are due partly to norepinephrine release and
partly to direct effect on receptors.
• Is indicated for drug-induced hypotension (particularly in association
with bradycardia)
• Used commonly in Anaesthesia.
• Administer by direct IV injection of 3-9 mg (1-3ml) and repeat as
required.
• Adverse Reaction
• Hypertension, tachyarrhythmias, palpitations
• Headache, restlessness, anxiety, tension, tremor, weakness, dizziness,
confusion, delirium hallucinations
• Nausea or vomiting
Dopamine
• Is a metabolic precursor of norepinephrine and epinephrine
• Acts on α1-, β1-, and β2-receptors in a dose-dependent fashion.
• At intermediate doses (5 to 10 micrograms/kg/min), dopamine
increases renal blood flow, HR, cardiac contractility, and CO.
• At high doses (>10 micrograms/kg/min), the α-adrenergic effects
dominate, leading to vasoconstriction and increased blood pressure.
• Pharmacokinetics

• Adverse effects - chest pain, hypotension (low doses), hypertension (high doses), ectopic
beats, palpitations, nausea, vomiting, headache, tissue ischemia, and tachycardia.
• Indications
• For reversing hemodynamically significant hypotension
• As an alternative vasopressor agent to norepinephrine
• For symptomatic bradycardia that is unresponsive to atropine.
• Dosage
• Hemodynamic support
• IV infusion:2–20 micrograms/kg/min; titrate by increments of 5–10
micrograms/kg/min to desired response (maximum,50
micrograms/kg/min).
• DOSAGE IN PAEDIATRICS:
• IV:15mg/kg in 50ml of 5% dextrose or normal saline at
0-20mcg/kg/min (0-4ml/hr) 1ml/hr equal 5mcg/kg/min
Phenylephrine
• It is a selective α1-adrenergic agonist that increases systemic vascular
resistance.
• It has no direct effects on heart rate
• Is indicated for the treatment of hypotension and vascular failure in
shock.
• It is used for the reversal of severe hypotension produced by spinal
anesthesia.
• Pharmacokinetics

• Adverse effects - hypertension, low cardiac output, reflex bradycardia,

and arrhythmias(rare) and ischemia's.
• Dosage
• Hypotension/shock
• IV infusion (initial):100–180 micrograms/min or 0.5 microgram/kg/min; titrate
to desired response
• Hypotension after intubation or sedation
• IV bolus:40–100 micrograms/bolus dose over 20–30s every 2–5 min as
needed
• DOSAGE IN PAEDIATRICS:
• IV-2-10 mcg/kg stat (adult 500mcg), then 1-5mcg/kg/min
Vasopressin
• Stimulates V1 receptors in vascular smooth muscle
• Causing direct peripheral vasoconstriction, increases in systemic
vascular resistance
• Also acts on V2 receptors in the kidneys, causing an antidiuretic effect.
• It is primarily used as a second-line agent in refractory vasodilatory
shock.
• It is also used to reduce the dose of the first-line agent.
• Used to promote splanchnic vasoconstriction and reduce the rate of
bleeding in variceal bleeding.
• Pharmacokinetics

• Dosage -≤0.03unit/min with concomitant norepinephrine

• Adverse effects - diaphoresis, nausea, vomiting, headache, urticaria,
arrhythmias, mesenteric and peripheral ischemia, chest pain,
myocardial infarction, bronchoconstriction, and cardiac arrest.
Angiotensin II
• Raises blood pressure by stimulating vasoconstriction and release of
aldosterone.
• It is indicated for septic or other distributive shock when other drugs
such as norepinephrine have failed to increase mean arterial pressure
to target levels.
• Pharmacokinetics

• Adverse effects - thromboembolic events (12.9%), thrombocytopenia

(9.8%), tachycardia (8.6%), fungal infection (6.1%), delirium (5.5%),
and acidosis (5.5%).
• Dosage
• Initial dose 10–20 nanograms/kg/min, titrate in increments of 5–10
nanograms/kg/min every 5min; maximum initial dose, 80
nanograms/kg/min during initial 3 h
• After improvement in blood pressure, down-titrate to 15
nanograms/kg/min every 5–15 min to minimum effective dose;
maximum maintenance dose (after first 3 h), 40 nanograms/kg/min.
Dobutamine
• Is potent inotropic and mild vasodilatory and chronotropic effects.
• It stimulates α- and β-receptors (β1 > β2 > α1)
• Increase contractility and heart rate with neutral effect or possible
decrease in blood pressure.
• Is most frequently used in severe, medically refractory heart failure
and cardiogenic shock
• Should not be routinely used in sepsis because of the risk of
hypotension.
• Pharmacokinetics

• Adverse effects- hypertension, hypotension, tachyarrhythmia,

headache, angina, and hypokalemia.
• Dosage
• Decreased CO
• IV infusion (initial):1–3 micrograms/kg/min; maintenance:2–40
micrograms/kg/min; titrate to desired response
• ACLS (immediately after cardiac arrest)
• IV infusion (initial):5–10 micrograms/kg/min; titrate to desired response.
Milrinone
• Phosphodiesterase (PDE) inhibitors, with inotropic and vasodilatory
actions.
• Result in increased cardiac contractility, peripheral arterial and venous
vasodilation, increased cardiac output, and reduced systemic vascular
resistance.
• Used for the short-term treatment of acute decompensated heart
failure.
• Pharmacokinetics

• Adverse effects - ventricular and supraventricular arrhythmias,

hypotension, angina, and headache.
• Dosage
• Congestive heart failure, acute bridge to definitive treatment
• Loading dose (optional):50 micrograms/kg over 10 min
• Maintenance(continuous IV infusion): 0.375–0.75 microgram/kg/min, titrate
to desired response
References
Tintinalli, J., 2019. Tintinalli's Emergency Medicine: a Comprehensive
Study Guide, 9th Edition. McGraw-Hill Education.
Wellington ICU Drug Manual 2013,2nd ed.
Marino, P., n.d. Marino's The ICU Book. 4th ed.
Marini, J. and Dries, D., 2019. Critical care medicine. 5th ed.
Uptodate.com. 2022. UpToDate.
Thank You !!