VasopressorsRasha Sarhan, MSC, B.Sc.Pharm, Pharm D Candidate

Shock

Shock

ObjectivesDefine shock.

Define and interpret various hemodynamic parameters [mean arterial pressure (MAP), preload, afterload, Cardiac output (CO)].

List types, causes, and symptoms of shock.

Describe the pharmacology, doses and use of vasopressors.

Explain practical issues with using vasopressors.

Apply knowledge to a patient with a shock syndrome

Shock

A state of cellular and tissue hypoxia due to

reduced oxygen delivery and/or increased

oxygen consumption or inadequate oxygen

utilization.

SBP < 90 mmHg or reduction of > 40 mmHg

with perfusion abnormalities* despite

adequate fluid resuscitation.

* End organ hypoperfusion (lactic acidosis, oliguria,

mental status deterioration).

Preload (PCWP)

Represents the amount

of blood available to the

left ventricle for pumping

and is influenced by

venous return to the left

atrium.

Normal = 12 - 18 mmHg

Dry < 12 mmHg

Wet > 18 mmHg

Afterload (SVR)

Represents the ventricular wall

tension required for expulsion

of ventricular blood volume

into the aorta during

contraction.

Normal = 1000 - 1600 dynes-sec/m2

Arterial dilation < 800 dynes-sec/m2

Arterial constriction > 1800 dynes-sec/m2

Definitions

MAP = 1/3 SBP + 2/3 DBP

MAP = CO X SVR

CO = HR X SV

The stroke volume is

determined by:

Preload

Afterload

Myocardial contractility

SVR is

determined by:

Vessel length

Blood viscosity

Vessel tone

Shock Symptoms

Hypotension

Tachycardia

Abnormal mental status

Cool clammy cyanotic skin

Metabolic acidosis

oliguria

Shock

Classification & Etiology

• Hypovolemic: (hemorrhagic, Non-hemorrhagic).

• Cardiogenic: (MI, cardiomyopathy, arrhythmia).

• Distributive: (septic, non-septic).

• Obstructive:

• Pulmonary Vascular: [Pulmonary embolus, severe pulmonary

hypertension (PAH)].

• Mechanical: (Tension pneumothorax, pericardial tamponade,

constrictive pericarditis, restrictive cardiomyopathy).

Hypovolemic Hemorrhagic Trauma, GI bleed (e.g., varices, peptic

ulcer)

Non-

hemorrhagic

Gastrointestinal losses, skin losses; renal

losses, hypoaldosteronism, third space

losses.

Cardiogenic Cardiomyopathy MI, HF exacerbation, cardiac arrest,

hypotension, cardiopulmonary bypass,

advanced septic shock, myocarditis.

Arrhythmia fibrillation, flutter, reentrant tachycardia,

complete heart block.

Mechanical Severe aortic or mitral valve insufficiency.

Distributive Septic Infection ( Gram +ve , Gram –ve, viral,

fungal, parasite, mycobacterium)

Inflammatory shock –SIRS; neurogenic

shock, anaphylactic shock, drugs and toxins,

endocrine shock.

Non-Septic

Obstructive Pulmonary

vascular

Pulmonary embolism (PE), Pulmonary artery

hypertension (PAH).

Mechanical Tension pneumothorax (trauma, iatrogenic,

ventilator-induced), pericardial tamponade,

constrictive pericarditis, restrictive

Hypovolemic Shock

Goal is to increase preload (PCWP) by

replacing fluid loss with blood, crystalloid,

or colloid.

Cardiogenic Shock

Goal is to increase cardiac output

(CO) with inotropic pharmacotherapy

(dobutamine) and reduce afterload

(SVR) with vasodilators.

Septic Shock

Goal is to increase preload (PCWP) with

fluid replacement (crystalloid, then

colloid), then increase afterload (SVR)

with vasopressor (e.g. dopamine,

norepinephrine, phenylephrine,

vasopressin).

Neurogenic Shock

Goal is to increase afterload (SVR)

with vasopressor (e.g. phenylephrine,

norepinephrine).

Combined ShockPatients with pancreatitis or sepsis have distributive shock but may have hypovolemic and cardiogenic component.

Patients with cardiomyopathy may present with cardiogenic shock and hypovolemic shock.

Patients with severe traumatic injury may have hemorrhagic and distributive shock

Patients with spinal cord injury can have distributive and cardiogenic shock.

Vasopressors Goals of Therapy

PCWP = 8 to 12 mm Hg ( up to 15 mm Hg in

specific patients).

MAP ≥ 65 mm Hg.

Mixed venous Oxygen saturation (SvO2) ≥ 65%.

Central venous Oxygen saturation (ScvO2) ≥

70%.

Lactate Clearance ≥ 20%.

Receptors

α 1 β 1 β 2 Dop V1 V2

CO − − − −

Preload

(PCWP)

− − − − − −

Afterload

(SVR)

−

Urine

output

− −

Dopamine (Dop)

• Receptors: D1, D2, β1, α1*

• Use:

• At (3 to 10 mcg / Kg/ min), increases CO in cardiogenic shock.

• At (10 to 20 mcg / Kg/ min), increases afterload (SVR) and urine output in septic shock.

• Dose: 1 to 20 mcg / kg/ min.

• Monitoring: Blood pressure (BP); Heart rate (HR); urine output, renal function, serum glucose, CO, PCWP, and SVR.

Dobutamine (Dob)

• Receptors: β1, β2, α1

• Use: Increase CO and decrease

afterload in cardiogenic shock.

• Dose: 1 to 20 mcg / kg/ min.

• Monitoring: BP, ECG, renal function,

urine output, CO, PCWP, and SVR.

Norepinephrine (Nepi)

• Receptors: α1, β1, β2

• Use: Increase afterload (SVR) in septic and neurogenic shock.

• Dose: 8 to 20 mcg / min.

• Monitoring: BP, HR, CO, urine output, infusion site for extravasation or necrosis.

Epinephrine (Epi)

• Receptors: α1, β1, β2

• Use: Increase afterload (SVR) in

neurogenic shock or as an add on in

septic shock.

• Dose: 1 to 10 mcg / min.

• Monitoring: BP, HR, continuous cardiac

monitoring, serum lactate, site of

infusion for blanching/extravasation.

Phenylephrine (Phen)

• Receptors: α1

• Use: Increase afterload (SVR) in

neurogenic shock, or as salvage - add on

- to other vasopressors.

• Dose: 100 to 180 mcg / min.

• Monitoring: BP, HR, CO, local skin

blanching, extravasation.

Vasopressin (Vas)

• Depleted in septic shock

• Receptors:

1. Vascular V1 receptors: Cause vasoconstriction.

2. Renal V1 and V2 receptors: Increases GFR and net increase urine output.

3. Pituitary gland V3: Increase serum cortisol.

• Dose: 0.02 to 0.04 units / min.

• Monitoring: Fluid input, urine output, HR, BP, skin blanching.

Vasopressors Pharmacology

Dop Dob Nepi Epi Phen Vas

α1✚ ✚✚ ✚✚✚ ✚✚✚ ✚✚✚ 0

β1✚ ✚✚✚ ✚✚ ✚✚ 0 0

β20 ✚✚✚ ✚⁄✚✚ ✚✚ 0 0

D1,D2✚✚ 0 0 0 0 0

V1, V20 0 0 0 0 ✚

Dose1 to 20

mcg/kg/min

1 to 20

mcg/kg/min

8 to 20

mcg/mi

n

1 to 10

mcg/min

100 to 180

mcg/min

0.02 to 0.04

units/min

Vasopressor IV Infusion Chart

Medication Indication BolusInitialIVinfusion

Titration

Usualdose

Maximumdose/duration

Diluent/Line

DobutamineDecreasedcardiac

outputNoBolus

0.5to1mcg/Kg/min

By2.5

mcg/kg/minAccordingto

response~

every5min

2to20

mcg/

kg/min

҂Upto40

mcg/Kg/

min

NS/D5W/LR

DoNotaddSod

Bicarbonate

PeripheralDobutamine

PostcardiacArrestACLS

5to10

mcg/Kg/min

0.5to1

mcg/Kg/min

2to20mcg/

kg/min

DopamineCardiogenic/septicShock,CHF/renal

failureNoBolus 2to5mcg/kg/min

5to10mcg/kg/minincrements

¥Upto20-50

mcg/kg

/min

NS/D5W

DoNotaddSod

Bicarbonate

CentralLine

Epinephrine3

Hypotension/SepticShockorasanaddontoother

vasopressors

NoBolus₠0.1to0.5

mcg/Kg/min

0.05to0.2

mcg/kg/minute

every10-15mintotarget

MAP

1to10

mcg/min

€Upto10

mcg/min

NS/D5W

CentralLine

Epinephrine

Asystole/pulselessarrest

ACLS

1mgIVorI.O.

Give1mgevery3to5minuntilreturnof

spontaneouscirculation.

Upto0.2

mg/Kg(totaldose)

InBBand

CCBoverdose

NS/D5W/

LR

Central

Line*2.5mgendotracheal Dilutein5to10mlNSorsterilewater

Epinephrine Anaphylaxiso mgIV

over5min

5to15mcg/min

Norepinephrine4Levophed®

Hypotension/Shock

NoBolus 8to12mcg/min

Titrateto

desiredresponseby

2mcg/min

1to

4mcg

/min

Upto20mcg/min

NS/D5W

Central

Line

SummaryTypes of Shocks: hypovolemic, Cardiogenic, Septic, neurogenic.

Hypovolemic Shock: goal is to increase preload with fluids1st.

Cardiogenic Shock: goal is to increase cardiac output (CI) with dopamine (1-10μg /Kg/min), or dobutamine.

Septic Shock: goal is to increase preload with fluids1st , then increase afterload with, dopamine, norepinephrine, phenylephrine, or vasopressin.

Neurogenic Shock: goal is to increase afterload with norepinephrine, phenylephrine.

SummaryNepi is the initial vasopressor, 8 to 20 μg / min.

Dop alternative to Nepi in patients with low CO or HR. Dop

receptor effect is dose dependent, 1 to 20 μg / kg / min.

Dob used in patients with cardiogenic shock 1 to 20 μg / kg /

min.

Epi used as an add on to increase MAP, 1 to 10 μg / min.

Vasopressin used as an add on to Nepi to increase MAP,

0.03 Unit / min.

Phen used in neurogenic shock or as an add on to increase

MAP, 100-180 μg / min.