VASOPRESSORS: THERAPY AND PHARMACOLOGY · VASOPRESSORS: THERAPY AND PHARMACOLOGY ... therapeutic option for the treatment and management of cardiovascular ... Arterial blood gases

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VASOPRESSORS:

THERAPY AND

PHARMACOLOGY

Jassin M. Jouria, MD

Dr. Jassin M. Jouria is a medical doctor, professor of academic medicine, and medical

author. He graduated from Ross University School of Medicine and has completed his clinical

clerkship training in various teaching hospitals throughout New York, including King’s

County Hospital Center and Brookdale Medical Center, among others. Dr. Jouria has passed

all USMLE medical board exams, and has served as a test prep tutor and instructor for

Kaplan. He has developed several medical courses and curricula for a variety of educational

institutions. Dr. Jouria has also served on multiple levels in the academic field including

faculty member and Department Chair. Dr. Jouria continues to serves as a Subject Matter

Expert for several continuing education organizations covering multiple basic medical

sciences. He has also developed several continuing medical education courses covering

various topics in clinical medicine. Recently, Dr. Jouria has been contracted by the

University of Miami/Jackson Memorial Hospital’s Department of Surgery to develop an e-

module training series for trauma patient management. Dr. Jouria is currently authoring an

academic textbook on Human Anatomy & Physiology.

Abstract

Blood vessels can be constricted using a medical intervention known as

vasoconstrictors, or pressors. This strategy is typically used to staunch

hemorrhaging and stop acute blood loss. Low blood pressure associated with

shock is typically treated with pressors in order to avoid loss of

consciousness and oxygen deprivation to the heart, brain, and other vital

organs. It is critical for nurses to understand the appropriate use of pressors

in order to provide lifesaving treatment to their patients.


Continuing Nursing Education Course Planners

William A. Cook, PhD, Director, Douglas Lawrence, MA, Webmaster,

Susan DePasquale, MSN, FPMHNP-BC, Lead Nurse Planner

Policy Statement

This activity has been planned and implemented in accordance with the

policies of NurseCe4Less.com and the continuing nursing education

requirements of the American Nurses Credentialing Center's Commission on

Accreditation for registered nurses. It is the policy of NurseCe4Less.com to

ensure objectivity, transparency, and best practice in clinical education for

all continuing nursing education (CNE) activities.

Continuing Education Credit Designation

This educational activity is credited for 2 hours. Nurses may only claim credit

commensurate with the credit awarded for completion of this course activity.

Pharmacology content is 2 hours.

Statement of Learning Need

Vasopressor administration is an important skill for nurses to learn in a

variety of clinical settings and for different patient conditions involving low

blood pressure and decreased cardiac output.

Course Purpose

To provide nursing professionals with basic knowledge of vasopressor

treatment, including different types of vasopressor medication.


Target Audience

Advanced Practice Registered Nurses and Registered Nurses

(Interdisciplinary Health Team Members, including Vocational Nurses and

Medical Assistants may obtain a Certificate of Completion)

Course Author & Planning Team Conflict of Interest Disclosures

Jassin M. Jouria, MD, William S. Cook, PhD, Douglas Lawrence, MA,

Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures

Acknowledgement of Commercial Support

There is no commercial support for this course.

Activity Review Information

Reviewed by Susan DePasquale, MSN, FPMHNP-BC

Release Date: 1/1/2016 Termination Date: 4/25/2018

Please take time to complete a self-assessment of knowledge, on

page 4, sample questions before reading the article.

Opportunity to complete a self-assessment of knowledge learned

will be provided at the end of the course.


1. Vasopressors are commonly used in conjunction with:

a. Barbiturates

b. Inotropes

c. Steroids

d. Blood thinners

2. Pressors are used to treat a number of conditions, but their

primary function is to treat:

a. High blood pressure

b. Stroke

c. Shock

d. Hypoglycemia

3. The primary mechanism of pressors is to target receptors in the:

a. Brain

b. Central nervous system

c. Heart

d. Peripheral blood vessels

4. _______________________ works by increasing mean arterial

pressure and cardiac output through an increase in stroke volume.

a. Dobutamine

b. Dopamine

c. Ephedrine

d. Vasopressin

5. Which of the following drugs is used to maintain blood pressure

during instances of hypovolemia?

a. Vasopressin

b. Phenylephrine

c. Dobutamine

d. Ephedrine


Introduction

Patients who experience low blood volume or decreased cardiac output

require treatment that will initiate an increase in blood pressure and cardiac

output, with the goal of increased perfusion. This is necessary in patients

who are experiencing cardiovascular syndromes, as well as those who are at

risk of developing these syndromes during procedures such as cesarean

sections. Blood vessels can be constricted using a medical intervention

known as vasopressors, or pressors. This strategy is typically used to

staunch hemorrhaging and stop acute blood loss. Low blood pressure

associated with shock is typically treated with pressors in order to avoid loss

of consciousness and oxygen deprivation to the heart, brain, and other vital

organs.

Vasopressors, often used in conjunction with inotropes, are an important

therapeutic option for the treatment and management of cardiovascular

syndromes. Pressors increase vascular tone and elevate arterial pressure.

These agents are reserved for use in critically ill patients who are

experiencing significant hemodynamic impairment. They are typically used

when fluid administration does not produce adequate results in the

restoration of normal arterial pressure and organ perfusion. Pressors can

also be used in instances when a patient is undergoing surgical procedures

that may impact arterial pressure and organ perfusion. In these instances,

the agents will be used in conjunction with anesthetics.

Pressors are typically administered over a short period of time, with the goal

of providing immediate, but typically not complete, recovery from life-

threatening cardiovascular conditions. It is critical for nurses to understand

the appropriate use of pressors in order to provide lifesaving treatment to

their patients.


Purpose Of Vasopressor Medication

Vasopressors, which are also called pressors, are medications that are used

to initiate an increase in blood pressure and cardiac output, with the goal of

increased perfusion.1 There are a number of different pressors that can be

used, and each performs a specific function. The primary mechanism of

pressors is to target receptors in the peripheral blood vessels, thereby

causing them to squeeze tighter and push blood from the extremities to the

core.2 When this occurs, the peripheral blood maintains the function of the

heart, thereby allowing additional blood to circulate through the core organs.

In addition to this primary function, some pressors will also target the heart

by increasing the heart rate and initiating increased cardiac output.3 By

increasing blood pressure and maintaining adequate perfusion, pressors

provide a means for nutrient and oxygen delivery to the vital organs.

Pressor types are selected based on the needs of the patient and the specific

condition being treated. In most instances, pressors are titratable and will be

dosed on a continuum based upon the intended, and actual, clinical effect.

Use of Vasopressors

Vasopressors, often in conjunction with inotropic agents, are used primarily

to treat and manage various types of shock. The combination of

vasopressors and inotropic agents provides a multi-faceted approach to the

management of shock. The vasopressors increase vascular tone and elevate

arterial pressure, while inotropic agents increase myocardial contractility and

cardiac index.4 The combination of the two agents provides a comprehensive

treatment approach.

These agents are reserved for use in critically ill patients who are

experiencing significant hemodynamic impairment. They are typically used


when fluid administration does not produce adequate results in the

restoration of normal arterial pressure and organ perfusion.5 Pressors can

also be used in instances when a patient is undergoing surgical procedures

that may impact arterial pressure and organ perfusion. In these instances,

the agents will be used in conjunction with anesthetics.6

While vasopressors can be used in other medical circumstances, the primary

use is in instances of shock. There are a number of different types of shock,

and the specific type of pressor used will depend on the type of shock and

the patient’s specific needs. Vasopressors are commonly used to treat

vasodilatory shock caused by sepsis or other factors, but they are also used

sporadically in other forms of shock as well.7 In cardiogenic shock, pressors

may be used to maintain adequate coronary perfusion pressure. In instances

of hypovolemic shock and obstructive shock, pressors can help temporize

and maintain perfusion pressure while waiting for primary therapy to take

effect.8

Shock

Shock occurs as the result of a variety of pathophysiological mechanisms.

There are a number of different types of shock, and each one is caused by a

specific condition. The main forms of shock that are treated with pressors

include cardiogenic shock, hypovolemic and hemorrhagic shock, and septic

shock. While there are other forms of shock, they are not commonly treated

with vasopressors.

The primary cause of shock is decreased blood flow. However, the type of

shock is defined by the mechanism in which the blood flow is affected. The

most common mechanisms of shock include heart complications, changes in


blood vessels, or reduction in blood volume. Some medications can also

impact blood flow, thereby causing shock.9

Cardiogenic Shock

Cardiogenic shock is primarily caused by left ventricular failure, which often

occurs as the result of ST elevation myocardial infarction (STEMI) after

cardiac arrest.10 It is characterized by decreased cardiac output and

evidence of tissue hypoxia in the presence of adequate intravascular

volume.11 It has a mortality rate of 70 – 90% when left untreated.9 It is an

emergency that will require immediate treatment to prevent irreversible

damage to the vital organs. Rapid diagnosis and subsequent initiation of

pressors to maintain blood pressure and cardiac output is essential. Patients

will require admission to the intensive care setting (if not already admitted)

to obtain immediate treatment. The primary focus will be on the restoration

of coronary blood flow, with additional treatment occurring once the patient

has been stabilized.8

Cardiogenic shock can often be diagnosed through basic observation. Most

patients will show the following:10

Hypotension

Absence of hypovolemia

Clinical signs of poor tissue perfusion (i.e., oliguria, cyanosis, cool

extremities, altered mentation)

Findings on physical examination include the following:

o Skin is usually ashen or cyanotic and cool; extremities are

mottled

o Peripheral pulses are rapid and faint and may be irregular if

arrhythmias are present


o Jugular venous distention and crackles in the lungs are usually

(but not always) present; peripheral edema also may be present

o Heart sounds are usually distant, and third and fourth heart

sounds may be present

o The pulse pressure may be low, and patients are usually

tachycardic

o Patients show signs of hypoperfusion, such as altered mental

status and decreased urine output

o Ultimately, patients develop systemic hypotension (i.e., systolic

blood pressure below 90 mm Hg or a decrease in mean blood

pressure by 30 mm Hg)

However, final diagnosis will be confirmed using the following laboratory

studies:12

Biochemical profile

Complete blood count (CBC)

Cardiac enzymes (i.e., creatine kinase and CK-MB, troponins,

myoglobin, LDH)

Arterial blood gases (ABGs)

Lactate

Brain natriuretic peptide

Imaging studies

Echocardiography

Chest radiographs

Ultrasonography

Coronary angiography

Electrocardiography


Vasopressors are used in the early stages of treatment to ensure adequate

cardiac output. The following table provides the dosage amounts of each

type of pressor:13

Dopamine

Dopamine is a precursor of norepinephrine and epinephrine and

has varying effects according to the doses infused. A dose of less

than 5 mcg/kg/min causes vasodilation of renal, mesenteric, and

coronary beds. At a dose of 5-10 mcg/kg/min, beta1-adrenergic

effects induce an increase in cardiac contractility and heart rate.

At doses of approximately 10 mcg/kg/min, alpha-adrenergic

effects lead to arterial vasoconstriction and an elevation in blood

pressure. The blood pressure increases primarily as a result of

the inotropic effect. The undesirable effects are tachycardia and

increased pulmonary shunting, as well as the potential for

decreased splanchnic perfusion and increased pulmonary arterial

wedge pressure.

Norepinephrine

Norepinephrine is a potent alpha-adrenergic agonist with minimal

beta-adrenergic agonist effects. Norepinephrine can increase

blood pressure successfully in patients who remain hypotensive

following dopamine.

The dose of norepinephrine may vary from 0.2-1.5 mcg/kg/min,

and large doses, as high as 3.3 mcg/kg/min, have been used

because of the alpha-receptor down-regulation in persons with

sepsis.

Epinephrine Epinephrine can increase the mean arterial pressure (MAP) by

increasing the cardiac index and stroke volume, as well as

systemic vascular resistance (SVR) and heart rate. Epinephrine

decreases the splanchnic blood flow and may increase oxygen

delivery and consumption.


Administration of this agent is associated with an increase in

systemic and regional lactate concentrations. The use of

epinephrine is recommended only in patients who are

unresponsive to traditional agents. The undesirable effects are an

increase in lactate concentration, a potential to produce

myocardial ischemia, the development of arrhythmias, and a

reduction in splanchnic flow.

Hypovolemic and Hemorrhagic Shock

Hemorrhagic shock occurs as a result of severe blood loss. This loss of blood

impacts the circulating blood volume and affects lower organ perfusion

pressure, which impairs delivery of oxygen to the tissues.14 When patients

experience a massive hemorrhage, they can develop hypovolemia or

isovolemic anemia. These conditions can further exacerbate damage.15

Therefore, early detection and treatment is necessary to prevent long-term,

significant damage. Hemorrhagic shock is often the result of gastrointestinal

bleeding and trauma. However, in some instances, patients may experience

hemorrhagic shock from other factors such as ruptured abdominal aortic

aneurysms, postpartum bleeding, ruptured ovarian cyst or ectopic

pregnancy, or other conditions that can cause sudden severe blood loss.16 In

many instances, the blood loss will only occur internally and may not be

detectable until damage has occurred.16

The use of vasopressors is sometimes considered for hemorrhagic shock, but

there is little clinical evidence that they are effective. In fact, pressors are

rarely used in the United States, as fluid loading is typically the treatment of

choice.17 However, there is ongoing research as to the use and effectiveness

of pressors in the treatment of hemorrhagic shock, and there may be


implications for the future use of the agents in the management of

hemorrhagic shock.18

Septic Shock

Septic shock occurs as the result of an infection. It is a systemic

inflammatory response that leads to a state of acute circulatory failure,

which is characterized by persistent arterial hypotension.7 Septic shock can

occur as the result of infection in any area of the body. Therefore, it is

necessary to identify infections early so that they can be monitored.11 The

following signs and symptoms can be indicative of the development of

sepsis.19

Head and neck infections:

Severe headache, neck stiffness, altered mental status, earache, sore

throat, sinus pain or tenderness, cervical or submandibular

lymphadenopathy

Chest and pulmonary infections:

Cough (especially if productive), pleuritic chest pain, dyspnea, dullness

on percussion, bronchial breath sounds, localized rales, any evidence

of consolidation

Cardiac infections:

Any new murmur, especially in patients with a history of injection or

intravenous (IV) drug use

Abdominal and gastrointestinal (GI) infections:

Diarrhea, abdominal pain, abdominal distention, guarding or rebound

tenderness, rectal tenderness or swelling


Pelvic and genitourinary (GU) infections:

Pelvic or flank pain, adnexal tenderness or masses, vaginal or urethral

discharge, dysuria, frequency, urgency

Bone and soft-tissue infections:

Localized limb pain or tenderness, focal erythema, edema, swollen

joint, crepitus in necrotizing infections, joint effusions

Skin infections:

Petechiae, purpura, erythema, ulceration, bullous formation,

fluctuance

It is important to note that some patients, especially those with severe

sepsis, may not show typical signs of septic shock. Vasopressors are used to

treat septic shock that does not respond to fluid resuscitation. The following

guidelines provide information for treating septic shock with pressors:20

Vasopressors should be promptly begun in patients in persistent septic shock despite

fluid resuscitation; vasopressors can be begun and continued simultaneously with fluid

resuscitation, especially in patients with severe hypotension.

Vasopressors should be begun initially to target a mean arterial pressure (MAP) of 65

mm Hg (Grade 1C).

Norepinephrine (Levophed) should be provided as the first-line vasopressor (Grade 1B).

Epinephrine is considered the next-line agent for septic shock after norepinephrine in

the Surviving Sepsis Guidelines. When norepinephrine is insufficient to maintain MAP 65

mm Hg, epinephrine should be added to or substituted for norepinephrine (Grade 2B).

Vasopressin at 0.03 units/minute is appropriate to use with norepinephrine, either to

improve perfusion (increase MAP) or to reduce the required dose of norepinephrine

(ungraded recommendation).


Vasopressin is not recommended for use as a single vasopressor for septic shock

(ungraded recommendation).

Vasopressin doses higher than 0.03 – 0.04 units/min are recommended to be reserved

only for dire situations of septic shock refractory to standard doses of multiple

vasopressors (ungraded recommendation).

Dopamine is suggested to not be used as an alternative to norepinephrine in septic

shock, except in highly selected patients such as those with inappropriately low heart

rates (absolute or relative bradycardia) who are at low risk for tachyarrhythmias (Grade

2C). Dopamine is recommended not used in low doses in a so-called renal-protective

strategy (Grade 1A).

Phenylephrine is recommended to not be used for septic shock, except when: 1) septic

shock persists despite the use of 2 or more inotrope/vasopressor agents along with low-

dose vasopressin; 2) cardiac output is known to be high, or 3) norepinephrine is

considered to have already caused serious arrhythmias (Grade 1C).

An arterial catheter for hemodynamic monitoring should be placed as soon as practical,

if resources are available, for all patients requiring vasopressors (ungraded

recommendation).

Dobutamine should be tried for patients in septic shock who have low cardiac output

with high filling pressures while on vasopressors, or who have persistent evidence of

hypoperfusion after attaining an adequate mean arterial pressure and intravascular

volume (with or without vasopressors) (Grade 1C).

A dobutamine infusion up to 20 mcg/kg/min can be added to any vasopressor(s) in use.

Dobutamine is also an appropriate first-line agent in patients with severe sepsis and low

cardiac output, with a preserved mean arterial pressure (i.e., who are not in septic

shock) (Grade 1C).

Dobutamine is recommended not to be used to deliberately raise cardiac output to

higher than normal levels in an attempt to improve perfusion

Surgical Anesthesia Hypotension

Hypotension is a common occurrence that affects approximately fifty percent

of patients who receive spinal anesthesia.21 It is caused by the blockage of


the sympathetic nerves and can cause significant complications in patients

who have a cardiac history. These patients are at risk of developing

myocardial ischemia, even with minor drops in blood pressure.22 Some

patients may also develop cases of bradycardia with asystole that can lead

to cardiac arrest, although this is typically the result of myriad complications

and not limited to autonomic dysfunction.21

Patients should undergo a thorough examination and assessment prior to

surgery to identify any risk factors that may contribute to the development

of hypotension. In some situations, these patients may receive vasopressors

in conjunction with anesthesia to prevent complications.23 In patients who

develop hypotension during surgery, treatment will begin with fluid

replacement, typically in the form of crystalloids followed by colloids. If fluid

replacement is not effective, pressors will be added as a secondary

treatment.24

Common Vasopressors

There are six primary types of vasopressors that can be used in patients,

and the specific type used will depend on the patient’s needs and the specific

condition.

Norepinephrine

Norepinephrine is used to increase mean arterial pressure through

vasoconstriction, while only causing a minor increase in cardiac output and

stroke volume. It is a powerful pressor, especially when titrated.25 The

dosage amounts will vary across a broad spectrum depending on a variety of

factors.26 It is especially useful in patients who are experiencing septic

shock, as it does not cause deterioration of the cardiac index or organ


function.27 Due to the lack of significant side effects and mortality,

norepinephrine is often used as a first-line vasopressor in the treatment of

shock.13

The following table provides a basic overview of the drug facts regarding

norepinephrine:28

INDICATIONS For blood pressure control in certain acute hypotensive states

(i.e., pheochromocytomectomy, sympathectomy, poliomyelitis,

spinal anesthesia, myocardial infarction, septicemia, blood

transfusion, and drug reactions). As an adjunct in the treatment of

cardiac arrest and profound hypotension.

DOSAGE AND

ADMINISTRATION

Norepinephrine Bitartrate Injection is a concentrated, potent drug

which must be diluted in dextrose containing solutions prior to

infusion. An infusion of LEVOPHED should be given into a large

vein (see PRECAUTIONS).

Blood volume depletion should always be corrected as fully as

possible before any vasopressor is administered. When, as an

emergency measure, intraaortic pressures must be maintained to

prevent cerebral or coronary artery ischemia, LEVOPHED

(norepinephrine bitartrate) can be administered before and

concurrently with blood volume replacement.

Diluent: LEVOPHED (norepinephrine bitartrate) should be diluted

in 5 percent dextrose injection or 5 percent dextrose and sodium

chloride injections. These dextrose containing fluids are protection

against significant loss of potency due to oxidation.

Administration in saline solution alone is not recommended. Whole

blood or plasma, if indicated to increase blood volume, should be

administered separately (for example, by use of a Y-tube and

individual containers if given simultaneously).


Average Dosage: Add the content of the vial (4 mg/4 mL) of

LEVOPHED (norepinephrine bitartrate) to 1,000 mL of a 5 percent

dextrose containing solution. Each mL of this dilution contains 4

mcg of the base of LEVOPHED (norepinephrine bitartrate). Give

this solution by intravenous infusion. Insert a plastic intravenous

catheter through a suitable bore needle well advanced centrally

into the vein and securely fixed with adhesive tape, avoiding, if

possible, a catheter tie-in technique as this promotes stasis. An IV

drip chamber or other suitable metering device is essential to

permit an accurate estimation of the rate of flow in drops per

minute.

After observing the response to an initial dose of 2 mL to 3 mL

(from 8 mcg to 12 mcg of base) per minute, adjust the rate of flow

to establish and maintain a low normal blood pressure (usually 80

mm Hg to 100 mm Hg systolic) sufficient to maintain the

circulation to vital organs. In previously hypertensive patients, it is

recommended that the blood pressure should be raised no higher

than 40 mm Hg below the preexisting systolic pressure. The

average maintenance dose ranges from 0.5 mL to 1 mL per

minute (from 2 mcg to 4 mcg of base).

High Dosage: Great individual variation occurs in the dose

required to attain and maintain an adequate blood pressure. In all

cases, dosage of LEVOPHED (norepinephrine bitartrate) should be

titrated according to the response of the patient. Occasionally

much larger or even enormous daily doses (as high as 68 mg base

or 17 vials) may be necessary if the patient remains hypotensive,

but occult blood volume depletion should always be suspected and

corrected when present.

Central venous pressure monitoring is usually helpful in detecting

and treating this situation.


Fluid Intake: The degree of dilution depends on clinical fluid

volume requirements. If large volumes of fluid (dextrose) are

needed at a flow rate that would involve an excessive dose of the

pressor agent per unit of time, a solution more dilute than 4 mcg

per mL should be used. On the other hand, when large volumes of

fluid are clinically undesirable, a concentration greater than 4 mcg

per mL may be necessary.

Duration of Therapy: The infusion should be continued until

adequate blood pressure and tissue perfusion are maintained

without therapy. Infusions of LEVOPHED (norepinephrine

bitartrate) should be reduced gradually, avoiding abrupt

withdrawal. In some of the reported cases of vascular collapse due

to acute myocardial infarction, treatment was required for up to

six days.

Adjunctive Treatment in Cardiac Arrest: Infusions of LEVOPHED

(norepinephrine bitartrate) are usually administered intravenously

during cardiac resuscitation to restore and maintain an adequate

blood pressure after an effective heartbeat and ventilation have

been established by other means. [LEVOPHED's (norepinephrine

bitartrate’s) powerful beta-adrenergic stimulating action is also

thought to increase the strength and effectiveness of systolic

contractions once they occur].

Average Dosage: To maintain systemic blood pressure during the

management of cardiac arrest, LEVOPHED (norepinephrine

bitartrate) is used in the same manner as described under

Restoration of Blood Pressure in Acute Hypotensive States.

Parenteral drug products should be inspected visually for

particulate matter and discoloration prior to use, whenever

solution and container permit. Do not use the solution if its color is

pinkish or darker than slightly yellow or if it contains a precipitate.

Avoid contact with iron salts, alkalis, or oxidizing agents.


Dopamine

Dopamine was one of the first pressors, and is considered a natural

precursor to norepinephrine and epinephrine. However, unlike

norepinephrine, its effects are dose-specific.29 Dopamine works by increasing

mean arterial pressure and cardiac output through an increase in stroke

volume. Dopamine does not tend to cause an increase in heart rate.30 In

recent studies, low doses of dopamine have been found to increase renal

blood flow, thereby reducing the risk of renal failure in critically ill patients.25

The following table provides an overview of dopamine drug facts:31

HOW SUPPLIED

LEVOPHED (norepinephrine bitartrate) injection, USP, contains the

equivalent of 1 mg base of LEVOPHED (norepinephrine bitartrate)

per 1 mL (4 mg/4 mL).

Supplied as: 5 mL vials (4 mL fill, 4 mg/4 mL) in boxes of 10 (NDC

No. 0409-3375-04)

SIDE EFFECTS

Body As A Whole: Ischemic injury due to potent vasoconstrictor

action and tissue hypoxia.

Cardiovascular System: Bradycardia, probably as a reflex result of

a rise in blood pressure, arrhythmias.

Nervous System: Anxiety, transient headache.

Respiratory System: Respiratory difficulty.

Skin and Appendages: Extravasation necrosis at injection site.


INDICATIONS

DOPAMINE (dopamine hydrochloride) is indicated for the

correction of hemodynamic imbalances present in the shock

syndrome due to myocardial infarctions, trauma, endotoxic

septicemia, open heart surgery, renal failure, and chronic cardiac

decompensation as in congestive failure. Where appropriate,

restoration of blood volume with a suitable plasma expander or

whole blood should be instituted or completed prior to

administration of DOPAMINE (dopamine hydrochloride). Patients

most likely to respond adequately to DOPAMINE (dopamine

hydrochloride) are those in whom physiological parameters, such

as urine flow, myocardial function, and blood pressure, have not

undergone profound deterioration.

Multiclinic trials indicate that the shorter the time interval between

onset of signs and symptoms and initiation of therapy with volume

correction and DOPAMINE (dopamine hydrochloride), the better

the prognosis.

Poor Perfusion of Vital Organs: Urine flow appears to be one of the

better diagnostic signs by which adequacy of vital organ perfusion

can be monitored. Nevertheless, the physician should also observe

the patient for signs of reversal of confusion of comatose

condition.

Loss of pallor, increase in toe temperature, and/or adequacy of

nail bed capillary filling may also be used as indices of adequate

dosage.

Clinical studies have shown that when DOPAMINE (dopamine

hydrochloride) is administered before urine flow has diminished to

levels approximating 0.3 mL/minute, prognosis is more favorable.

Nevertheless, in a number of oliguric or anuric patients,

administration of DOPAMINE (dopamine hydrochloride) has

resulted in an increase in urine flow, which in some cases reached

normal levels.


DOPAMINE (dopamine hydrochloride) may also increase urine flow

in patients whose output is within normal limits and thus may be

of value in reducing the degree of preexisting fluid accumulation.

It should be noted that at doses above those optimal for the

individual patient urine flow might decrease, necessitating

reduction of dosage. Concurrent administration of DOPAMINE

(dopamine hydrochloride) and diuretic agents may produce an

additive or potentiating effect.

Low Cardiac Output: Increased cardiac output is related to the

direct inotropic effect of DOPAMINE (dopamine hydrochloride) on

the myocardium. Increased cardiac output at low or moderate

doses appears to be related to a favorable prognosis.

Increase in cardiac output has been associated with either static

or decreased systemic vascular resistance (SVR).

Static or decreased SVR associated with low or moderate

increments in cardiac output is believed to be a reflection of

differential effects on specific vascular beds with increased

resistance in peripheral beds (i.e., femoral) and concomitant

decreases in mesenteric and renal vascular beds. Redistribution of

blood flow parallels these changes so that an increase in cardiac

output is accompanied by an increase in mesenteric and renal

blood flow. In many instances the renal fraction of the total

cardiac output has been found to increase.

The increase in cardiac output produced by DOPAMINE (dopamine

hydrochloride) is not associated with substantial decreases in

systemic vascular resistance as may occur with isoproterenol.

Hypotension: Hypotension due to inadequate cardiac output can

be managed by administration of low to moderate doses of

DOPAMINE (dopamine hydrochloride), which have little effect on

SVR.


At high therapeutic doses, the alpha adrenergic activity of

DOPAMINE (dopamine hydrochloride) becomes more prominent

and thus may correct hypotension due to diminished SVR.

As in the case of other circulatory decompensation states,

prognosis is better in patients whose blood pressure and urine

flow have not undergone profound deterioration. Therefore, it is

suggested that the physician administer DOPAMINE (dopamine

hydrochloride) as soon as a definite trend toward decreased

systolic and diastolic pressure becomes evident.

DOSAGE AND

ADMINISTRATION

WARNING: This is a potent drug: It must be diluted before

administration to patient.

Suggested Dilution: Transfer contents of one or more ampules or

vials by aseptic technique to either 250 mL or 500 mL of one of

the following sterile intravenous solutions:

1.Sodium Chloride Injection, USP

2. Dextrose (5%) Injection, USP

3. Dextrose (5%) and Sodium Chloride (0.9%) Injection, USP

4. 5% Dextrose in 0.45% Sodium Chloride Solution

5. Dextrose (5%) in Lactated Ringer's Solution

6. Sodium Lactate (1/6 Molar) Injection, USP

7. Lactated Ringer's Injection, USP

DOPAMINE (dopamine hydrochloride) has been found to be stable

for a minimum of 24 hours after dilution in the sterile intravenous

solutions listed above.

As with all intravenous admixtures, dilution should be made just

prior to administration.

Do NOT add DOPAMINE (dopamine hydrochloride) Injection to

Sodium Bicarbonate or other alkaline intravenous solutions, since

the drug is inactivated in alkaline solution.


Mixing of dopamine (dopamine hydrochloride) with alteplase in the

same container should be avoided as visible particulate matter has

been observed.

It is recommended that dopamine (dopamine hydrochloride) not

be added to amphotericin B solutions because amphotericin B is

physically unstable in dopamine (dopamine hydrochloride) -

containing solutions.

Rate of Administration: DOPAMINE (dopamine hydrochloride),

after dilution, is administered intravenously through a suitable

intravenous catheter or needle. An IV drip chamber or other

suitable metering device is essential for controlling the rate of flow

in drops/minute. Each patient must be individually titrated to the

desired hemodynamic and/or renal response with DOPAMINE

(dopamine hydrochloride). In titrating to the desired increase in

systolic blood pressure, the optimum dosage rate for renal

response may be exceeded, thus necessitating a reduction in rate

after the hemodynamic condition is stabilized.

Administration rates greater than 50 mcg/kg/minute have safely

been used in advanced circulatory decompensation states. If

unnecessary fluid expansion is of concern, adjustment of drug

concentration may be preferred over increasing the flow rate of a

less concentrated dilution.

Suggested Regimen

1. When appropriate, increase blood volume with whole blood or

plasma until central venous pressure is 10 to 15 cm H2O or

pulmonary wedge pressure is 14-18 mm Hg.

2. Begin administration of diluted solution at doses of 2-5

mcg/kg/minute DOPAMINE (dopamine hydrochloride) in

patients who are likely to respond to modest increments of

heart force and renal perfusion.


In more seriously ill patients, begin administration of diluted

solution at doses of 5 mcg/kg/minute DOPAMINE (dopamine

hydrochloride) and increase gradually, using 5 to 10

mcg/kg/minute increments, up to 20 to 50 mcg/kg/minute as

needed.

If doses of DOPAMINE (dopamine hydrochloride) in excess of 50

mcg/kg/minute are required, it is suggested that urine output be

checked frequently. Should the urine flow begin to decrease in the

absence of hypotension, reduction of DOPAMINE (dopamine

hydrochloride) dosage should be considered.

Multiclinic trials have shown that more than 50% of the patients

were satisfactorily maintained on doses of DOPAMINE (dopamine

hydrochloride) less than 20 mcg/kg/minute. In patients who do

not respond to these doses with adequate arterial pressures or

urine flow, additional increments of DOPAMINE (dopamine

hydrochloride) may be employed in an effort to produce an

appropriate arterial pressure and central perfusion.

3. Treatment of all patients requires constant evaluation of

therapy in terms of the blood volume, augmentation of

myocardial contractility, and distribution of peripheral

perfusion.

Dosage of DOPAMINE (dopamine hydrochloride) should be

adjusted according to the patient's response, with particular

attention to diminution of established urine flow rate,

increasing tachycardia or development of new dysrhythmias

as indices for decreasing or temporarily suspending the

dosage.

4. As with all potent intravenously administered drugs, care

should be taken to control the rate of administration so as to

avoid inadvertent administration of a bolus of drug.


Parenteral drug products should be inspected visually for

particulate matter and discoloration prior to administration,

whenever solution and container permit.

HOW SUPPLIED

Dopamine (dopamine hydrochloride) HCl Injection, USP is

available as follows:

Dopamine HCl

mg per volume fill

200 mg/5 mL Vial

(40 mg/mL)

(color-coded WHITE)

400 mg/5 mL Vial

(80 mg/mL)

(color-coded GREEN)

800 mg/5 mL Vial

(160 mg/mL)

(color-coded YELLOW)

SIDE EFFECTS The following adverse reactions have been observed, but there are

not enough data to support an estimate of their frequency.

Cardiovascular System

ventricular arrhythmia (at very high doses)

ectopic beats

tachycardia

anginal pain

palpitation

cardiac conduction abnormalities

widened QRS complex

bradycardia

hypotension

hypertension

vasoconstriction


Respiratory System

dyspnea

Gastrointestinal System

nausea

vomiting

Metabolic/Nutritional System

azotemia

Central Nervous System

headache

anxiety

Dermatological System

piloerection

Other

Gangrene of the extremities has occurred when moderate

to high doses were administered for prolonged periods or

in patients with occlusive vascular disease receiving low

doses of dopamine (dopamine hydrochloride) HCl.

A few cases of peripheral cyanosis have been reported.

Epinephrine

Epinephrine, also commonly called “adrenaline”, is an injectable adrenaline

that is used primarily to treat anaphylaxis due to allergic reactions caused by

multiple agents.32 The drug is synthesized, stored and released from the

chromaffin cells of the adrenal medulla and is used to increase arterial

pressure. It works by increasing both the cardiac index and peripheral


vascular tone.33 Epinephrine also increases delivery of oxygen, but it is not

consistent in its results.

While epinephrine produces significant results in the treatment of

anaphylaxis, it does have the potential to decrease regional blood flow. This

is especially common in the splanchnic circulation.34

Epinephrine is quite effective in increasing blood pressure in patients who do

not respond to other agents. However, because epinephrine often effects

gastric blood flow while increasing lactate concentrations, it is typically used

as a second-line agent for patients who are unresponsive to traditional

agents.35 The following table provides an overview of the drug facts for

epinephrine:36

INDICATIONS Adrenalin® is available as a single-use 1 mL vial and a multiple-

use 30 mL vial. The 1 mL vial is for use intramuscular,

subcutaneous, and intraocular use. The 30 mL vial is for

intramuscular and subcutaneous use only, and is NOT FOR

OPHTHALMIC USE. Anaphylaxis (Adrenalin® 1 mL Single-Use

And 30 mL Multiple-Dose Vials)

Emergency treatment of allergic reactions (Type I), including

anaphylaxis, which may result from allergic reactions to insect

stings, biting insects, foods, drugs, sera, diagnostic testing

substances and other allergens, as well as idiopathic anaphylaxis

or exercise-induced anaphylaxis. The signs and symptoms

associated with anaphylaxis include flushing, apprehension,

syncope, tachycardia, thready or unobtainable pulse associated

with hypotension, convulsions, vomiting, diarrhea and abdominal

cramps, involuntary voiding, airway swelling, laryngospasm,

bronchospasm, pruritus, urticaria or angioedema, swelling of the

eyelids, lips, and tongue.


Induction and Maintenance of Mydriasis during Intraocular

Surgery (Adrenalin® 1 mL single-use vial only).

DOSAGE AND

ADMINISTRATION

Anaphylaxis (Adrenalin® 1mL Single-Use And 30 Ml Multiple-

Dose Vials)

Inject Adrenalin® intramuscularly or subcutaneously into the

anterolateral aspect of the thigh. The injection may be repeated

every 5 to 10 minutes as necessary.

For intramuscular administration, use a needle long enough (at

least 1/2 inch to 5/8 inch) to ensure the injection is administered

into the muscle.

Monitor the patient clinically for the severity of the allergic

reaction and potential cardiac effects of the drug, with repeat

doses titrated to effect. Do not administer repeated injections at

the same site, as the resulting vasoconstriction may cause tissue

necrosis. Inspect visually for particulate matter and discoloration

prior to administration. Do not use if the solution is colored or

cloudy, or if it contains particulate matter.

Adults and Children 30 kg (66 lbs) or more: 0.3 to 0.5 mg (0.3

mL to 0.5 mL) of undiluted Adrenalin® administered

intramuscularly or subcutaneously in the anterolateral aspect of

the thigh, up to a maximum of 0.5 mg (0.5 mL) per injection,

repeated every 5 to 10 minutes as necessary. Monitor clinically

for reaction severity and cardiac effects.

Children less than 30 kg (66 lbs): 0.01 mg/kg (0.01 mL/kg) of

undiluted Adrenalin® administered intramuscularly or

subcutaneously in the anterolateral aspect of the thigh, up to a

maximum of 0.3 mg (0.3 mL), repeated every 5 to 10 minutes

as necessary. Monitor clinically for reaction severity and cardiac

effects.


Induction And Maintenance Of Mydriasis During Intraocular

Surgery (Adrenalin® 1 mL Single-Use Vial Only): Adrenalin®

must be diluted prior to intraocular use. Dilute 1 mL of

Adrenalin® 1 mg/mL (1:1000) in 100 to 1000 mL of an

ophthalmic irrigation fluid to create an epinephrine concentration

of 1:100,000 to 1:1,000,000 (10 mcg/mL to 1 mcg/mL).

Use the irrigating solution as needed for the surgical procedure.

After dilution in an ophthalmic irrigating fluid, Adrenalin® may

also be injected intracamerally as a bolus dose of 0.1 mL at a

dilution of 1:100,000 to 1:400,000 (10 mcg/mL to 2.5 mcg/mL).

Inspect visually for particulate matter and discoloration prior to

administration.

Do not use if the solution is colored or cloudy, or if it contains

particulate matter. Note: The Adrenalin® 30 mL multiple-dose

vial is not for ophthalmic use. USE ONLY THE ADRENALIN 1 ML

SINGLE-USE VIAL FOR OPHTHALMIC USE.

HOW SUPPLIED Adrenalin® 1 mg/mL (1:1000) epinephrine injection, 1 mL

solution in a single-use clear glass vial and 30 mL solution in a

multiple-dose amber glass vial.

Adrenalin® 1 mL Single-Use Vials

Each carton contains 25 single-use vials containing 1 mL

Adrenalin® (epinephrine injection, USP) solution 1 mg/mL

(1:1000) in a 3 mL clear glass vial.

Adrenalin® 30 mL Multi-Dose Vials

Each carton contains either 1 multiple-dose vial or 10 multiple-

dose vials containing 30 mL Adrenalin® (epinephrine injection,

USP) solution 1 mg/mL (1:1000) in a 36 mL amber glass vial.

Vial and contents must be discarded 30 days after initial use.


Store between 20°C to 25°C (68°F to 77°F). (See USP Controlled

Room Temperature). Epinephrine is light sensitive. Protect from

light and freezing. Inspect visually for particulate matter and

discoloration prior to administration. Do not use the solution if it

is colored or cloudy, or if it contains particulate matter.

SIDE EFFECTS Common adverse reactions to systemically administered

epinephrine include anxiety, apprehensiveness, restlessness,

tremor, weakness, dizziness, sweating, palpitations, pallor,

nausea and vomiting, headache, and respiratory difficulties.

These symptoms occur in some persons receiving therapeutic

doses of epinephrine, but are more likely to occur in patients

with heart disease, hypertension, or hyperthyroidism [see

WARNINGS AND PRECAUTIONS].

Due to the lack of randomized, controlled clinical trials of

epinephrine for the treatment of anaphylaxis, the true incidence

of adverse reactions associated with the systemic use of

epinephrine is difficult to determine. Adverse reactions reported

in observational trials, case reports, and studies are listed below

by body system:

Cardiovascular: angina, arrhythmias, hypertension, pallor,

palpitations, tachyarrhythmia, tachycardia, vasoconstriction, and

ventricular ectopy.

Angina may occur in patients with coronary artery disease

Arrhythmias, including fatal ventricular fibrillation, have

occurred, particularly in patients with underlying organic heart

disease or patients receiving drugs that sensitize the heart to

arrhythmias. Rapid rises in blood pressure associated with

epinephrine use have produced cerebral hemorrhage, particularly

in elderly patients with cardiovascular disease.


Respiratory: respiratory difficulties.

Neurological: dizziness, disorientation, excitability, headache,

impaired memory, lightheadedness, nervousness, panic,

psychomotor agitation, sleepiness, tingling, tremor, and

weakness.

Psychiatric: anxiety, apprehensiveness, and restlessness.

Gastrointestinal: nausea, vomiting.

Other: Patients with Parkinson's disease may experience

psychomotor agitation or a temporary worsening of symptoms

Diabetic patients may experience transient increases in blood

sugar

Accidental injection into the digits, hands or feet may result in

loss of blood flow to the affected area [see WARNINGS AND

PRECAUTIONS]. Adverse events experienced as a result of an

injection into these areas include increased heart rate, local

reactions including injection site pallor, coldness, hypoesthesia,

and tissue loss, or injury at the injection site resulting in

bruising, bleeding, discoloration, erythema, and skeletal injury.

Skin: sweating.

Adverse Reactions Associated With Intraocular Use (For

Mydriasis)

Epinephrine containing sodium bisulfite has been associated with

corneal endothelial damage when used in the eye at undiluted

concentrations (1 mg/mL).


Phenylephrine

Phenylephrine is used to increase blood pressure through vasoconstriction.

It is fast acting, with a short duration, which makes it an ideal choice as a

pressor.24 However, its ability to reduce cardiac output has been questioned.

Due to the lack of adequate information regarding its ability to reduce

cardiac output, phenylephrine is primarily used to treat fluid-resuscitated

patients with septic shock.23 However, even in these instances, it is used as

a second-line agent.

In some instances, phenylephrine is useful in the treatment and

management of spinal shock and vasoplegia following cardiac bypass. It is

used in these instances when tachyarrhythmias limit available treatment

options with other pressors.37

The following table provides an overview of the drug facts regarding

phenylephrine:38

Clinical

Pharmacology

Phenylephrine hydrochloride produces vasoconstriction that lasts

longer than that of epinephrine and ephedrine. Responses are more

sustained than those to epinephrine, lasting 20 minutes after

intravenous and as long as 50 minutes after subcutaneous

injection.

Its action on the heart contrasts sharply with that of epinephrine

and ephedrine, in that it slows the heart rate and increases the

stroke output, producing no disturbance in the rhythm of the pulse.

Phenylephrine is a powerful postsynaptic alpha-receptor stimulant

with little effect on the beta receptors of the heart. In therapeutic

doses, it produces little if any stimulation of either the spinal cord

or cerebrum. A singular advantage of this drug is the fact that

repeated injections produce comparable effects.


The predominant actions of phenylephrine are on the cardiovascular

system. Parenteral administration causes a rise in systolic and

diastolic pressures in man and other species. Accompanying the

pressor response to phenylephrine is a marked reflex bradycardia

that can be blocked by atropine; after atropine, large doses of the

drug increase the heart rate only slightly. In man, cardiac output is

slightly decreased and peripheral resistance is considerably

increased.

Circulation time is slightly prolonged, and venous pressure is

slightly increased; venous constriction is not marked. Most vascular

beds are constricted; renal splanchnic, cutaneous and limb blood

flows are reduced but coronary blood flow is increased. Pulmonary

vessels are constricted, and pulmonary arterial pressure is raised.

The drug is a powerful vasoconstrictor with properties very similar

to those of norepinephrine but almost completely lacking the

chronotropic and inotropic actions on the heart. Cardiac

irregularities are seen only very rarely even with large doses.

Indications and

Usage

Phenylephrine Hydrochloride Injection is intended for the

maintenance of an adequate level of blood pressure during spinal

and inhalation anesthesia and for the treatment of vascular failure

in shock, shock-like states and drug induced hypotension or

hypersensitivity. It is also employed to overcome paroxysmal

supraventricular tachycardia, to prolong spinal anesthesia and as a

vasoconstrictor in regional analgesia.

Adverse

Reactions

Headache, reflex bradycardia, excitability, restlessness and rarely

arrhythmias.

Overdosage: Overdosage may induce ventricular extrasystole and

short paroxysms of ventricular tachycardia, a sensation of fullness

in the head and tingling of the extremities.


Should an excessive elevation of blood pressure occur it might be

immediately relieved by an a-adrenergic blocking agent (i.e.,

phentolamine). The oral LD50 in the rat is 350 mg/kg, in the mouse

120 mg/kg.

Dosage and

Administration

Phenylephrine Hydrochloride Injection is generally injected

subcutaneously, intramuscularly, slowly intravenously or in dilute

solution as a continuous intravenous infusion.

In patients with paroxysmal supraventricular tachycardia and, if

indicated, in case of emergency, Phenylephrine Hydrochloride

Injection is administered directly intravenously.

The dose should be adjusted according to the pressor response.

DOSAGE CALCULATIONS

Dose Required Use Phenylephrine Hydrochloride Injection 1%

10 mg 1 mL

5 mg 0.5 mL

1 mg 0.1 mL

For convenience in intermittent intravenous administration, dilute 1

mL Phenylephrine Hydrochloride Injection 1% with 9 mL Sterile

Water for Injection, USP, to yield 0.1% Phenylephrine

Hydrochloride Injection.

Dose Required Use Diluted Phenylephrine Hydrochloride

injection (0.1%)

0.1 mg 0.1 mL

0.2 mg 0.2 mL

0.5 mg 0.5 mL

Mild or Moderate Hypotension:

SUBCUTANEOUSLY OR INTRAMUSCULARLY: Usual dose, from 2 mg

to 5 mg. Range, from 1 mg to 10 mg. Initial dose should not

exceed 5 mg.


INTRAVENOUSLY: Usual dose, 0.2 mg. Range, from 0.1 mg to 0.5

mg. Initial dose should not exceed 0.5 mg.

Injections should not be repeated more often than every 10 to 15

minutes. A 5 mg intramuscular dose should raise blood pressure for

one to two hours. A 0.5 mg intravenous dose should elevate the

blood pressure for about 15 minutes.

Severe Hypotension and Shock - Including Drug-Related

Hypotension: Blood volume depletion should always be corrected as

fully as possible before any vasopressor is administered. When, as

an emergency measure, intraaortic pressures must be maintained

to prevent cerebral or coronary artery ischemia, phenylephrine can

be administered before and concurrently with blood volume

replacement.

Hypotension and occasionally severe shock may result from

overdosage or idiosyncrasy following the administration of certain

drugs, especially adrenergic and ganglionic blocking agents,

rauwolfia and veratrum alkaloids and phenothiazines tranquilizers.

Patients who receive a phenothiazine derivative as preoperative

medication are especially susceptible to these reactions. As an

adjunct in the management of such episodes, Phenylephrine

Hydrochloride Injection is a suitable agent for restoring blood

pressure.

Higher initial and maintenance doses of phenylephrine are required

in patients with persistent or untreated severe hypotension or

shock. Hypotension produced by powerful peripheral adrenergic

blocking agents, chlorpromazine or pheochromocytomectomy may

also require more intensive therapy.

Continuous Infusion: Add 10 mg of the drug (1 mL of 1 percent

solution) to 500 mL of Dextrose Injection, USP or Sodium Chloride

Injection, USP (providing a 1:50,000 solution).


To raise the blood pressure rapidly, start the infusion at about 100

mcg to 180 mcg per minute (based on 20 drops per mL this would

be 100 to 180 drops per minute).

When the blood pressure is stabilized (at a low normal level for the

individual), a maintenance rate of 40 mcg to 60 mcg per minute

usually suffices (based on 20 drops per mL this would be 40 to 60

drops per minute). If the drop size of the infusion system varies

from the 20 drops per mL the dose must be adjusted accordingly. If

a prompt initial pressor response is not obtained, additional

increments of phenylephrine (10 mg or more) are added to the

infusion bottle.

The rate of flow is then adjusted until the desired blood pressure

level is obtained. (In some cases, a more potent vasopressor, such

as norepinephrine bitartrate, may be required). Hypertension

should be avoided. The blood pressure should be checked

frequently. Headache and/or bradycardia may indicate

hypertension. Arrhythmias are rare.

Spinal Anesthesia-Hypotension: Routine parenteral use of

phenylephrine has been recommended for the prophylaxis and

treatment of hypotension during spinal anesthesia. It is best

administered subcutaneously or intramuscularly three or four

minutes before injection of the spinal anesthetic.

The total requirement for high anesthetic levels is usually 3 mg,

and for lower levels, 2 mg. For hypotensive emergencies during

spinal anesthesia, phenylephrine may be injected intravenously,

using an initial dose of 0.2 mg. Any subsequent dose should not

exceed the previous dose by more than 0.1 mg to 0.2 mg and no

more than 0.5 mg should be administered in a single dose. To

combat hypotension during spinal anesthesia in children, a dose of

0.5 mg to 1 mg per 25 pounds body weight, administered

subcutaneously or intramuscularly, is recommended.


Prolongation of Spinal Anesthesia: The addition of 2 mg to 5 mg of

phenylephrine hydrochloride to the anesthetic solution increases the

duration of motor block by as much as approximately 50 percent

without any increase in the incidence of complications such as

nausea, vomiting or blood pressure disturbances.

Vasoconstrictor for Regional Analgesia: Concentrations about ten

times those employed when epinephrine is used as a

vasoconstrictor are recommended. The optimum strength is

1:20,000 (made by adding 1 mg of phenylephrine hydrochloride to

every 20 mL of local anesthetic solution). Some pressor responses

can be expected when 2 mg or more are injected.

Paroxysmal Supraventricular Tachycardia: Rapid intravenous

injection (within 20 to 30 seconds) is recommended. The initial

dose should not exceed 0.5 mg, and subsequent doses, which are

determined by the initial blood pressure response, should not

exceed the preceding dose by more than 0.1 mg to 0.2 mg and

should never exceed 1 mg. Parenteral drug products should be

inspected visually for particulate matter and discoloration prior to

administration, whenever solution and container permit.

How Supplied Phenylephrine Hydrochloride Injection, USP 1% (10 mg/mL) is

supplied as follows: 1 mL Single Dose vial packaged in 25s

5 mL vial*packaged in 25s.

Vasopressin

Vasopressin is primarily used to maintain blood pressure during instances of

hypovolemia. It also restores impaired hemodynamic mechanisms while

inhibiting pathological vascular responses during shock.35 In its natural


state, it is a peptide hormone that is synthesized in the hypothalamus. It is

released by the pituitary gland in response to decreased blood volume.

Low doses of vasopressin are typically administered to pressor-refractory

patients as a means of raising blood pressure.34 In most instances,

vasopressin is used as a replacement therapy to counter relative deficiency

rather than as a direct vasopressor.39 The following table provides an

overview of the drug facts for vasopressin indication, doses and uses:40

INDICATIONS Vasopressin is indicated for prevention and treatment of

postoperative abdominal distention, in abdominal roentgenography

to dispel interfering gas shadows, and in diabetes insipidus.

DOSAGE AND

ADMINISTRATION

Vasopressin may be administered intramuscularly or

subcutaneously. Ten units of vasopressin (0.5mL) will usually elicit

full physiologic response in adult patients: 5units will be adequate

in many cases. Vasopressin should be given intramuscularly at

three-or four-hour intervals as needed. The dosage should be

proportionately reduced for children. (For an additional discussion

of dosage, consult the sections below.)

When determining the dose of vasopressin for a given case, the

following should be kept in mind.

It is particularly desirable to give a dose not much larger than is

just sufficient to elicit the desired physiologic response. Excessive

doses may cause undesirable side effects - blanching of the skin,

abdominal cramps, nausea, which, though not serious, may be

alarming to the patient. Spontaneous recovery from such side

effects occurs in a few minutes. It has been found that one or two

glasses of water given at the time vasopressin is administered

reduce such symptoms.


Abdominal Distention: In the average postoperative adult patient,

give 5 units (0.25 mL) initially, increase to 10 units (0.5mL) at

subsequent injections if necessary. It is recommended that

vasopressin be given intramuscularly and that injections be

repeated at three-or four-hour intervals as required. Dosage to be

reduced proportionately for children.

Vasopressin used in this manner will frequently prevent or relieve

postoperative distension. These recommendations apply also to

distention complicating pneumonia or other acute toxemias.

Abdominal Roentgenography: For the average case, two injections

of 10 units each (0.5 mL) are suggested. These should be given two

hours and one-half hour, respectively, before films are exposed.

Many roentgenologists advise giving an enema prior to the first

dose of vasopressin.

Diabetes Insipidus: Vasopressin may be given by injection or

administered intranasally on cotton pledgets, by nasal spray, or by

dropper. The dose by injection is 5 to 10 units (0.25 to 0.5mL)

repeated two or three times daily as needed. When vasopressin is

administered intranasally by spray or on pledgets, the dosage and

interval between treatments must be determined for each patient.

Parenteral drug products should be inspected visually for particulate

matter and discoloration prior to use, whenever solution and

container permit.

HOW SUPPLIED Vasopressin Injection, USP 20units/mL is supplied as follows:

For intramuscular or subcutaneous use:

10 units per 0.5 mL multiple dose vial

20 units per 1mL multiple dose vial

200 units per 10 mL multiple dose vial


SIDE EFFECTS Local or systemic allergic reactions may occur in hypersensitive

individuals. The following side effects have been reported following

the administration of vasopressin.

Body as a Whole: anaphylaxia (cardiac arrest and/or shock) has

been observed shortly after injection of vasopressin.

Cardiovascular: cardiac arrest, circumoral pallor, arrhythmias,

decreased cardiac output, angina, myocardial ischemia, peripheral

vasoconstriction and gangrene.

Gastrointestinal: abdominal cramps, nausea, vomiting, and passage

of gas.

Nervous System: tremor, vertigo, "pounding" in head.

Respiratory: bronchial constriction.

Skin and Appendages: sweating, urticaris, and cutaneous gangrene.

Dobutamine

Dobutamine is primarily used as an agent to treat acute heart failure,

especially when it is caused by cardiac surgery, septic shock, or cardiogenic

shock.41 It acts by stimulating the beta-adrenoceptors of the heart, which

results in an increase in contractility and cardiac output.42

For patients with cardiac conditions, dobutamine is used primarily for short-

term situations. The long-term effects of the agent have not been

reported.43


The following table provides a basic overview of dobutamine:44

INDICATIONS Dobutamine is indicated when parenteral therapy is necessary for

inotropic support in the short-term treatment of adults with cardiac

decompensation due to depressed contractility resulting either from

organic heart disease or from cardiac surgical procedures.

Experience with intravenous dobutamine in controlled trials does not

extend beyond 48 hours of repeated boluses and/or continuous

infusions.

Whether given orally, continuously intravenously, or intermittently

intravenously, neither dobutamine nor any other cyclic-AMP-

dependent inotrope has been shown in controlled trials to be safe or

effective in the long-term treatment of congestive heart failure. In

controlled trials of chronic oral therapy with various such agents,

symptoms were not consistently alleviated, and the cyclic-AMP-

dependent inotropes were consistently associated with increased

risk of hospitalization and death. Patients with NYHA Class IV

symptoms appeared to be at particular risk.

DOSAGE AND

ADMINISTRATION

Intravenous: Acute heart failure

Adult: 2.5-10 mcg/kg, up to 0.5-40 mcg/kg according to patient's

heart rate, cardiac output, BP and urine output.

Intravenous: Cardiac stress test

Adult: 5 mcg/kg/min for 8 min using a 1 mg/ml solution, dose is

then increased at 5 mcg/kg/min until 20 mcg/kg/min, with each

dose being infused for 8 min before the next increase. Monitor ECG

and stop infusion if arrhythmias, marked ST segment depression or

other adverse effects occur.

HOW SUPPLIED Dobutamine Injection USP, 20 mL single dose vial contains

dobutamine hydrochloride, equivalent to 250 mg dobutamine per 20

mL; ten vials per carton.

SIDE EFFECTS Increased heart rate and BP, ectopic beats, palpitation. Nausea,

headache, chest pain, palpitation, dyspnea, paraesthesia, leg

cramps. Tissue necrosis at site of extravasation. Potentially Fatal:

Cardiac arrhythmias, allergy (rare), MI and hypotension.


Primary Routes Of Vasopressor Delivery

There are three primary routes of delivery for vasopressors:

Orally

Injected or Intravenously

Topically

However, while there are three different delivery mechanisms, the most

common delivery method is through injection or intravenously.45 Due to the

need to deliver the pressor quickly, this route is the most efficient and most

effective.46

Vasopressors in the Operating Room

Vasopressors are often used in the operating room (OR) to help prevent

surgical hypotension. In most instances, the pressor will be administered by

the anesthesiologist in conjunction with anesthesia.6 The primary function of

vasopressors in surgery are maintaining patient stability. Typically,

vasopressors are administered in conjunction with inotropes, which are

agents that are used to influence muscle contractions.47 The two agents

work together to provide a therapeutic approach to controlling

cardiovascular syndromes in the operating room.

Vasopressors in the Intensive Care Unit

Vasopressor use is common in the intensive care unit (ICU), as many

patients experience some form of shock while receiving treatment.

Therefore, ICU staff persons are specially trained to administer pressors and

monitor patient response.48 Due to the severe trauma and significant health

concerns of patients in the intensive care unit, pressors must be

administered sparingly and monitored closely. ICU staff is expected to


adhere to specific guidelines when treating patient with pressors.49 The

following is a list of the most important precautions and guidelines for the

use of pressors in the ICU:45

Hypovolemic and septic shock patients should always be given volume

resuscitation prior to vasopressors or inotropes. If preload is inadequate,

vasopressors will cause further reductions in cardiac output, and inotropes will

worsen tachyarrhythmias and induce ischemia.

The PDIs and sympathomimetic amines with [beta] effects that increase CI

should be used with caution in patients with severe aortic or pulmonary valve

stenosis until the stenosis or obstruction is surgically relieved. If valvular

pathology remains, severe myocardial ischemia may occur. These agents may

also aggravate outflow tract obstruction in idiopathic hypertrophic subaortic

stenosis. This may result in a decrease in CI as a higher quantity of blood is

trapped in the ventricle.

Sympathomimetic amines and PDIs can cause arrhythmias, and all of these

agents can cause myocardial ischemia. Therefore, cardiac monitoring is

imperative in the clinical use of these pharmacologic agents. Electrolytes

(especially potassium and magnesium) should be monitored and replaced, if

needed, to reduce the likelihood of arrhythmias. Halogenated anesthetics may

sensitize the myocardium to arrhythmias from sympathomimetic amines.

Monoamine oxidase inhibitors such as the antidepressants phenelzine and

tranylcypromine, the anti-Parkinson agent selegiline, and the antimicrobial agent

linezolid increase the pressor response to sympathomimetic amines. It is

recommended to avoid these combinations if possible. If sympathomimetic

amines are needed in patients on MAO inhibitors, start at one tenth the usual

dose.


Alternatives To Vasopressor Treatment

In many instances, vasopressors will not be the first treatment utilized. In

fact, it is common to begin treatment with fluids rather than pressors.50

Pressors are typically used when fluid pushing is not successful.51 These fluid

expanders are referred to as plasma volume expanders, as they restore

intravascular volume by increasing oncotic pressure.52 There are two

primary types of plasma volume expanders:

Crystalloid Fluids

Crystalloid fluids are balanced salt solutions that cross capillary walls and

produce early, significant expansion.53 However, their effects are short-term.

Commonly used crystalloids include:

Normal saline

Hartman’s solution

Ringer’s solution54

Colloid Fluids

Colloid fluids are large molecular fluids that are easily retained in the

intravascular space.55 They are considered to be a better option than

crystalloids to expand circulatory volume due to their long-term duration.56

Commonly used colloids include:57

Gelatins

Hetastarch

Albumin

Plasma protein fraction

Dextran


Summary

Patients who experience low blood volume or decreased cardiac output

require treatment that will initiate an increase in blood pressure and cardiac

output, with the goal of increased perfusion. This is necessary in patients

who are experiencing cardiovascular syndromes, as well as those who are at

risk of developing these syndromes during procedures such as cesarean

sections. Blood vessels can be constricted using a medical intervention

known as vasopressors, or pressors. This strategy is typically used to

staunch hemorrhaging and stop acute blood loss.

Low blood pressure associated with shock is typically treated with pressors

in order to avoid loss of consciousness and oxygen deprivation to the heart,

brain, and other vital organs. Pressors are typically administered over a

short period of time, with the goal of providing immediate, but typically not

complete, recovery from life-threatening cardiovascular conditions. It is

critical for nurses to understand the appropriate use of pressors in order to

provide lifesaving treatment to their patients.

Please take time to help NurseCe4Less.com course planners evaluate

the nursing knowledge needs met by completing the self-assessment of Knowledge Questions after reading the article, and providing

feedback in the online course evaluation.

Completing the study questions is optional and is NOT a course requirement.


1. Vasopressors are commonly used in conjunction with:

a. Barbiturates

b. Inotropes

c. Steroids

d. Blood thinners

2. Pressors are used to treat a number of conditions, but their

primary function is to treat:

a. High blood pressure

b. Stroke

c. Shock

d. Hypoglycemia

3. The primary mechanism of pressors is to target receptors in the:

a. Brain

b. Central nervous system

c. Heart

d. Peripheral blood vessels

4. ___________________ is an injectable adrenaline that is used

primarily to treat anaphylaxis due to allergic reactions caused by

multiple agents.

a. Epinephrine

b. Dobutamine

c. Dopamine

d. Vasopressin


5. Cardiogenic shock is primarily caused by _____________________,

which often occurs as the result of STEMI after cardiac arrest.

a. Right ventricular failure

b. Left ventricular failure

c. Aneurysm

d. Stroke

6. Which of the following drugs is used as an agent to treat acute

heart failure, especially when it is caused by cardiac surgery, septic

shock, or cardiogenic shock?

a. Ephedrine

b. Phenylephrine

c. Dopamine

d. Dobutamine

7. _______________________ works by increasing mean arterial

pressure and cardiac output through an increase in stroke volume.

a. Dobutamine

b. Dopamine

c. Ephedrine

d. Vasopressin

8. Which of the following drugs is used to maintain blood pressure

during instances of hypovolemia?

a. Vasopressin

b. Phenylephrine

c. Dobutamine

d. Ephedrine


9. ____________________ shock is characterized by decreased

cardiac output and evidence of tissue hypoxia in the presence of

adequate intravascular volume.

a. Hypovolemic

b. Septic

c. Cardiogenic

d. Hemorrhagic

10. ______________________ are balanced salt solutions that

cross capillary walls and produce early, significant expansion

a. Crystalloid fluids

b. Colloid Fluids

c. Gelatins

d. Plasma protein fractions

Correct Answers:

1. b

2. c

3. d

4. a

5. b

6. d

7. b

8. a

9. c

10. a


References Section

The reference section of in-text citations include published works intended as

helpful material for further reading. Unpublished works and personal

communications are not included in this section, although may appear within

the study text.

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2. Ferguson-Myrthil N. Vasopressor use in adult patients. Cardiol Rev.

20(3):153–8.

3. Larabee TM, Liu KY, Campbell JA, Little CM. Vasopressors in cardiac

arrest: a systematic review. Resuscitation. 2012 Aug;83(8):932–9.

4. Ellender TJ, Skinner JC. The use of vasopressors and inotropes in the

emergency medical treatment of shock. Emerg Med Clin North Am.

2008 Aug;26(3):759–86, ix.

5. Herget-Rosenthal S, Saner F, Chawla LS. Approach to hemodynamic

shock and vasopressors. Clin J Am Soc Nephrol. 2008 Mar 1;3(2):546–

53.

6. Original research Vasopressor choice for hypotension in elective

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ephedrine-or-phenylephrine-,19,14657,0,1.html

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21. Ngan Kee WD, Khaw KS. Obstetric Anesthesia - Hypotension and

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2009;111:753–65.

24. Ngan Kee WD, Khaw KS, Ng FF, Lee BB. Prophylactic phenylephrine

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25. De Backer Daniel. Shock: Dopamine vs Norepinephrine. Lancet.

2010;362:779–89.

26. Golembiewski JA. Vasopressors used in the critical care setting. Journal

of Perianesthesia Nursing. 2003. p. 414–6.

27. Martin JB, Wheeler AP. Approach to the Patient with Sepsis. Clinics in

Chest Medicine. 2009. p. 1–16.

28. Levophed (Norepinephrine Bitartrate) Drug Information: Indications,

Dosage and How Supplied - Prescribing Information at RxList


http://www.rxlist.com/levophed-drug/indications-dosage.htm

29. Iversen SD, Iversen LL. Dopamine: 50 years in perspective. Trends in

Neurosciences. 2007. p. 188–93.


30. Ungless MA. Dopamine: The salient issue. Trends in Neurosciences.

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31. Dopamine (Dopamine Hydrochloride) Drug Information: Indications,

Dosage and How Supplied - Prescribing Information at RxList


http://www.rxlist.com/dopamine-drug/indications-dosage.htm

32. Simons KJ, Simons FER. Epinephrine and its use in anaphylaxis:

current issues. Curr Opin Allergy Clin Immunol. 2010;10:354–61.

33. Callaway CW. Epinephrine for cardiac arrest. Curr Opin Cardiol.

2013;28:36–42.

34. Mentzelopoulos SD, Zakynthinos SG, Tzoufi M, Katsios N, Papastylianou

A, Gkisioti S, et al. Vasopressin, epinephrine, and corticosteroids for in-

hospital cardiac arrest. Arch Intern Med. 2009;169:15–24.

35. Gueugniaud P-Y, David J-S, Chanzy E, Hubert H, Dubien P-Y,

Mauriaucourt P, et al. Vasopressin and epinephrine vs. epinephrine

alone in cardiopulmonary resuscitation. N Engl J Med. 2008;359:21–30.

36. Adrenalin (Epinephrine) Drug Information: Side Effects and Drug

Interactions - Prescribing Information at RxList [Internet]. [cited 2014

Mar 20]. Available from: http://www.rxlist.com/adrenalin-drug/side-

effects-interactions.htm

37. Doherty A, Ohashi Y, Downey K, Carvalho JC. Phenylephrine Infusion

Versus Bolus Regimens During Cesarean Delivery Under Spinal

Anesthesia. Anesthesia & Analgesia. 2012. p. 1.

38. PHENYLEPHRINE HYDROCHLORIDE INJECTION [BAXTER HEALTHCARE

CORPORATION] [Internet]. [cited 2014 Mar 22]. Available from:

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e74f-46c5-b93d-34d07cffe1fd

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T, et al. Employing vasopressin as an adjunct vasopressor in


uncontrolled traumatic hemorrhagic shock. Three cases and a brief

analysis of the literature. Anaesthesist. 2005 Mar;54(3):220–4.

40. Pitressin (Vasopressin) Drug Information: Description, User Reviews,

Drug Side Effects, Interactions - Prescribing Information at RxList


http://www.rxlist.com/pitressin-drug.htm

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with septic shock are independent of its systemic effects* [Internet].

[cited 2014 Mar 22]. Available from:

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of_dobutamine_on_microcirculatory.18.aspx

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Feasibility of using a real-time 3-dimensional technique for contrast

dobutamine stress echocardiography. J Am Soc Echocardiogr. Elsevier;

2006 May 1;19(5):540–5.

43. Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock

SJ, et al. Levosimendan vs dobutamine for patients with acute

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American Medical Association; 2007 May 2;297(17):1883–91.

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Reviews, Drug Side Effects, Interactions - Prescribing Information at

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48. Mello PMVC, Sharma VK, Dellinger RP. Shock overview. Semin Respir

Crit Care Med. 2004;25:619–28.

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50. Lee J, Kothari R, Ladapo J, Scott D, Celi L. What matters during a

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51. Hammond TN, Holm JL. Limited fluid volume resuscitation. Compend

Contin Educ Vet. 2009;31:309–21.

52. Pinsky MR, Brophy P, Padilla J, Paganini E, Pannu N. Fluid and volume

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53. Vincent J-L. FLUID RESUSCITATION: COLLOIDS VS CRYSTALLOIDS.

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ABJ. Crystalloid or colloid fluid loading and pulmonary permeability,

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