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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 emodule 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.
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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.
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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.
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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
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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 lifethreatening cardiovascular conditions. It is critical for nurses to understand
the appropriate use of pressors in order to provide lifesaving treatment to
their patients.
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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
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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
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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
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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
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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.
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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
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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
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
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).
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 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 lowdose 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
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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
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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
Norepinephrine Bitartrate Injection is a concentrated, potent drug
ADMINISTRATION
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).
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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.
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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.
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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.
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
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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.
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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.
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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
WARNING: This is a potent drug: It must be diluted before
ADMINISTRATION
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.
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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.
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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.
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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
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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
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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 multipleuse 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.
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Induction and Maintenance of Mydriasis during Intraocular
Surgery (Adrenalin® 1 mL single-use vial only).
DOSAGE AND
Anaphylaxis (Adrenalin® 1mL Single-Use And 30 Ml Multiple-
ADMINISTRATION
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.
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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 multipledose 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.
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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.
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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).
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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
Phenylephrine hydrochloride produces vasoconstriction that lasts
Pharmacology
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.
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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
Phenylephrine Hydrochloride Injection is intended for the
Usage
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
Headache, reflex bradycardia, excitability, restlessness and rarely
Reactions
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.
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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
Phenylephrine Hydrochloride Injection is generally injected
Administration
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.
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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).
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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.
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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
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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
Vasopressin may be administered intramuscularly or
ADMINISTRATION
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.
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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
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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 shortterm situations. The long-term effects of the agent have not been
reported.43
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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-AMPdependent 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-AMPdependent 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
Intravenous: Acute heart failure
ADMINISTRATION
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.
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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
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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.
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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
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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.
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the nursing knowledge needs met by completing the self-assessment
of Knowledge Questions after reading the article, and providing
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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
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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
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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
6.
d
2. c
7.
b
3. d
8.
a
4. a
9.
c
5. b
10. a
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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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Larabee TM, Liu KY, Campbell JA, Little CM. Vasopressors in cardiac
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Herget-Rosenthal S, Saner F, Chawla LS. Approach to hemodynamic
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A, Gkisioti S, et al. Vasopressin, epinephrine, and corticosteroids for inhospital cardiac arrest. Arch Intern Med. 2009;169:15–24.
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