critical care and emergency medicine pharmacology · pdf file 1 critical care and...

nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1

Critical Care and Emergency Medicine

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

Safe administration of medication in critical care and emergency

settings is paramount to ensure optimal outcomes for patients. The

most experienced medical and nursing clinicians are well aware of the

fragility of critical care patients and the potential for the smallest

mistake to result in serious consequences. Understanding the purpose,

administration, monitoring, and potential consequences of

pharmacological agents available to critical care and emergency

department clinicians is necessary for them to make use of potentially

life-saving treatments.


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 4 hours. Nurses may only claim

credit commensurate with the credit awarded for completion of this

course activity. Pharmacology content is 4 hours.

Statement of Learning Need

Critical care and emergency medicine is a relatively recent

phenomenon in health care, and the role of pharmacists, physicians

and certified nurses trained to work in critical care and emergency

settings have expanded over recent years. As the intensive care units

and emergency departments in hospital increasingly develop to include

computerized equipment and software supporting unit-based services

and highly trained interdisciplinary staff delivering care to patients

diagnosed with critical conditions, so too does the highly important

need of the right medication, dose and route to initially treat, stabilize

and progress patients to a healthier state.


Course Purpose

To provide advanced learning in critical care and emergency

pharmacology for clinicians working in hospital emergency and

intensive care unit settings.

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.

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. ________________ is a process that is sometimes given the abbreviation ADME.

a. Pharmacodynamics b. Biopharmaceutics c. Pharmacokinetics d. Pinocytosis

2. True or False: Studies that assess how drug act in the body

after administration, such as rates of absorption, volume distribution, or rates of elimination, are often generated from clinical research studies on healthy volunteers.

a. True b. False

3. Which of the following processes describes the movement of

a drug from its point of administration to its target location, i.e., the bloodstream?

a. Absorption b. Pinocytosis c. Diffusion d. Transportation

4. Which of the following forms of drug administration generally has the slower rate of absorption?

a. Intravenous administration b. Intramuscular injection c. Subcutaneous injection d. All the above have similar absorption rates

5. ______________ occurs when a cell membrane surrounds

and encloses the particles of the drug.

a. Passive diffusion b. Pinocytosis c. Absorption d. Active transport


Introduction

Medication administration is a common element of medical and nursing

clinical care, and prescribed drugs are typically given to patients in all

areas of medicine. Clinicians working in emergency departments and

critical care units may administer many drugs from different classes.

These medications may sometimes be routine prescription medications

needed for general care of the patient, but often, the drugs are also

given in emergency or life-threatening situations. In the intensive care

unit (ICU) or emergency department (ED), clinicians must be familiar

with the purposes, effects, and appropriate routes of administration of

medications so that they can quickly give them to patients in need.

Overview: Medication Safety

Medication administration involves accounting for the safety of the

patient from the time the dose is prescribed until after it has been

given. Assessing the patient’s clinical status and ensuring the correct

dose and route have been ordered, administering the drug correctly

(and sometimes very rapidly), and observing the patient for the drug’s

effects or for changes in clinical status are all major steps in the

process of giving drugs in the critical care setting. Before discussing

the purposes of common types of critical care medications and their

potential complications, it is important to know how the body responds

to a drug once it has been given as well as what the drug does once it

enters the body to exert its therapeutic effects.

A key element of drug administration is the clinical interventions

necessary during the time surrounding their administration. Often,

drugs given in the critical care environment can have great potential


for complications because of their physiological effects. When

administered rapidly for emergency purposes, many drugs start to

work almost immediately and their effects can impact almost all body

systems. Nitroglycerin, a vasodilator medication often administered for

the management of angina, is an example of a drug that can cause a

rapid drop in the patient’s blood pressure because it relaxes the

smooth muscles of the blood vessels.1 The clinician who administers

nitroglycerin must not only monitor for the effects of the drug on

controlling angina, but also for complications that can develop because

of hypotension, such as dizziness or syncope. In order to understand

drug effects and side effects, the clinician needs to know the

pharmacokinetics and pharmacodynamics.

Pharmacokinetics

When a drug is given for any type of illness or medical condition, it is

regulated in the body through pharmacokinetics, which describes the

processes of absorption, distribution, metabolism, and excretion of a

drug within the body.2 The process is sometimes given the

abbreviation ADME. The term pharmacokinetics is also sometimes

described as what the body does to a drug when it is given. Overall, it

is important to have a basic understanding of pharmacokinetics when

administering drugs in the critical care setting, as changes in the

pharmacokinetics of a drug within the body, whether due to such

factors as a patient’s deteriorating health condition or the presence of

chronic disease, can lead the healthcare provider to make associated

changes in patient care and in the dosage, timing, and even the route

of drug administration.


Each category of pharmacokinetics has a corresponding

pharmacokinetic parameter. Each parameter consists of measurable

factors that can be determined through the calculation of certain

statistical formulas. When a drug is assessed by how it acts in the

body after administration, corresponding pharmacokinetic parameters

can be calculated to determine factors such as the rate of its

absorption, the volume of its distribution, or the rate of its elimination.

This information is often generated from clinical research studies in

which volunteers, who are often healthy, take the drugs for specified

periods and then scientists such as biostatisticians and

pharmacokineticists study the information, apply the formulas, and

determine the results of the drug’s pharmacokinetics based on how it

behaves after being administered to study participants. This allows

those who are manufacturing, dispensing, and administering the drug

to have a better understanding of how it will act in the body and how

differences in factors such as drug concentration or the co-

administration of other drugs or substances will affect

pharmacokinetics.

While this information is extremely valuable, the health clinician

working in the ICU or emergency department and administering

medications to the critically ill patient must keep in mind that since

studies of pharmacokinetics are often done on healthy adults, the

measurements of factors such as volume of distribution or rate of

elimination typically reflect that factor. Among critically ill patients,

however, these parameters may not be the same since illness and

injury often affect how the body processes certain drugs. While the

bedside clinician cannot be expected to understand the exact

pharmacokinetic formulas for parameters and the effects of critical


illness on these items, it makes sense to know how common drugs are

absorbed, distributed, metabolized, and excreted, so that any

alterations in the body systems that perform these functions can be

expected to have a corresponding effect on the pharmacokinetics of

the drug.

Drug Absorption

When a medication is prescribed, it is always given a route through

which it is to be administered. The route of which each drug is given

affects how it will be absorbed into circulation. Absorption is the

process of moving the drug from its initial location after it has been

given (for instance, the stomach or intestinal tract for oral drugs, or

the skeletal muscle tissue for an intramuscular injection) and

transitioning its particles into circulation.

Any drug that is given through an extravascular route, including such

routes as oral tablets or capsules, as an intramuscular or

subcutaneous injection, or via inhalation, must be absorbed into

circulation before it can begin to take effect. This is because drugs that

are not given intravenously are not given directly into the

bloodstream. Alternatively, medications that are given via the

intravenous route are administered directly into the bloodstream and

do not require the additional step of absorption. Therefore, this section

describing the absorption process is mainly focused on extravascular

routes of drug administration that require absorption for the drug to

eventually reach the bloodstream.

The rate and method of absorption depends on several factors,

including the route in which the drug is administered. Drugs that are


given via subcutaneous injection are absorbed through nearby

capillaries that are close to the subcutaneous tissue and the site of

administration. Because there is less vascular access to the

subcutaneous tissue when compared to skeletal muscle tissue used for

an intramuscular injection, the absorption rate of a subcutaneous

injection is slower. Alternatively, medications given orally often first

pass through the stomach, as most drugs are not absorbed in the

stomach cavity, and then enter the small intestine, where they are

eventually absorbed. The rate at which a drug is absorbed also

depends on the type of drug and its overall constitution. Some drugs

are rapidly absorbed based on their chemical compositions, while

others must first be broken down and their chemical makeup

separated before they are able to be absorbed. Other factors, including

the molecular size of the drug particles, as well as the overall solubility

at the site of absorption also affect the rate at which a drug is

absorbed into circulation.

To best facilitate absorption after a drug has been administered, the

drug components must first be broken down from the original form

when it was given. This may mean the dissolution of the substance of

the drug, such as when an oral medication is given in capsule form

that dissolves in the stomach. Some drugs, such as intramuscular or

subcutaneous injections, are prepared within a solution, known as a

vehicle in which the drug is suspended. The vehicle solution is usually

classified as being either aqueous, in which is contains mostly water,

or non-aqueous, which may be oil-based. Injections may also contain

other solvents along with the medication and the solution, particularly

when the drug has low solubility.60,61 After giving an injection, all of


these components must be broken down or dissolved before the drug

can be absorbed.

The term biopharmaceutics refers to the physical and chemical

properties of drugs, as well as their effects in the body.

Biopharmaceutics may be referred to in conjunction with

pharmacokinetics, as the two concepts are interrelated because of how

the drug behaves in the body.5 The intensity of a drug’s effects after it

is absorbed and distributed within the body, the formulation of the

drug, and the solution or vehicle in which the drug is suspended for

administration are just some of the factors involved with how a drug is

absorbed and then used in the body.

Drugs that have very slow rates of absorption are often less desirable

for use when compared to those that can be absorbed rapidly. When a

drug must be administered to combat a critical and potentially life-

threatening situation, drugs that are rapidly absorbed exert their

effects more quickly than those with slower processes of absorption.

Sometimes, a slow rate of absorption cannot be avoided and the

drug’s effects are much more important than the amount of time it

takes for the drug to be absorbed. As an example, drugs that are

administered orally must pass through the intestinal membrane of a

part of the small intestine, often the duodenum, before they can be

absorbed into circulation.

The rate of absorption of oral medications can be affected by various

factors, including the pH of the gastrointestinal system or first-pass

metabolism by the liver, which is a type of filtration process in which

the concentration of the drug is significantly reduced before it ever


reaches systemic circulation.3 Other factors, such as administration of

enteric coated capsules or by giving medications through enteral

feeding tubes can also impact the rate of absorption. Note that some

drugs are specifically given to affect the gastrointestinal system and

are administered enterally for their effects on the stomach and

intestinal tract.

When a drug is administered orally, the majority of absorption takes

place in the small intestine, similar to the absorption of food. Most

medications are not absorbed in the stomach because of the thick

lining of the stomach wall. The rate at which an oral drug is absorbed

is affected by how much time it spends in the stomach before being

transported into the small intestine. Delayed gastric emptying can

ultimately cause a delay in movement of the drug for it to be

absorbed; this is why there are some drugs that must be taken on an

empty stomach, as the presence of food in the stomach can affect

transit time of the drug into the small intestine.

There are four main types of absorption processes. The activity of

absorption is basically a movement of the drug particles across a

membrane into the circulatory system where it can then be

distributed. This movement of particles occurs as passive diffusion,

facilitated passive diffusion, active transport, or pinocytosis.2

• Passive diffusion describes the movement of drug particles across a

membrane from an area of higher concentration to an area of lower

concentration. For example, the fluids that make up the

gastrointestinal tract have a higher concentration than the blood in

circulation. Drugs can be absorbed via passive diffusion using little


to no excess energy and a carrier molecule is not required. Passive

diffusion is the method of absorption by which most drugs are

transferred into systemic circulation.

• Facilitated passive diffusion also does not require energy. It

involves the movement of drug particles across a membrane with

the help of a carrier molecule. It is thought that a carrier molecule

within the membrane combines with a molecule of the drug; this

molecule combination then rapidly crosses the membrane barrier

where the molecule of the drug is then released on the other side.

• Active transport describes the active movement of molecules across

a membrane; the process requires energy to occur. Active transport

utilizes specific molecules, sometimes referred to as carrier

molecules, that can cross the membrane. This process is drug

selective and usually occurs only at specific sites, including within

the small intestine for absorption of oral medications. Because

active transport uses energy, it is able to facilitate the movement of

drug molecules against a concentration gradient, if needed. In this

way, active transport can move drug particles from an area of lower

concentration to one of higher concentration.

• Pinocytosis occurs when a cell membrane surrounds and encloses

the particles of the drug. Once the drug particles are confined, a sac

or cavity is formed that moves toward the center part of the cell

and then is separated. The process requires energy to occur, as it is

an active process, however there are only a few drugs that are

absorbed through pinocytosis.


These methods of absorption by the movement of particles occur not

only with orally administered drugs. As stated, there are various other

techniques of drug administration, and all have different methods of

being absorbed after they are given, but the process of moving

particles across a membrane through diffusion or active transport

remains the same.

Extravascular injections of medications that are given subcutaneously

or intramuscularly involve direct injection of the drug and its

surrounding solution into the tissue, which may include the

subcutaneous fat just under the surface of the skin or deep into the

skeletal muscle tissue. Because these methods administer drugs into

different types of tissue, their methods of absorption also differ. In

general, intramuscular medications are absorbed more quickly than

subcutaneous injections, as muscle tissue contains more blood vessels.

When a drug is given as an intramuscular injection, the substance of

the medication gathers together within the muscle tissue to form a

pocket called a depot. The medication is then absorbed into the

surrounding blood vessels as it is released from the depot, the rate at

which can be affected by various factors, including viscosity of the

medication, the number of blood vessels present along with local blood

supply, and the type of muscle into which the drug was administered.4

Absorption of medications from subcutaneous injections takes longer

because there is less of a blood supply within the subcutaneous tissue

when compared to skeletal muscle tissue. If there is local blood flow

nearby, the drug may be absorbed quickly, particularly if it is not an

overly viscous solution. Drugs that are given in aqueous solutions are

absorbed faster than those that contain oil-based solutions;


medications with high solubility also tend to be absorbed more slowly

than those with low solubility. Some drugs need to exert their effects

quickly and so rapid absorption is preferable to slow; alternatively,

when drugs are meant to work slowly and to exert their effects over a

longer course of time, it is preferable to have longer absorption times.

Other types of medication administration, including intrathecal,

sublingual, rectal, or through inhalation all require the drugs to be

absorbed through a process so that they can enter the circulatory

system. For example, when a drug is administered transdermally as a

patch or ointment applied to the skin, it comes into contact with the

stratum corneum, which is the outermost layer of the epidermis. The

stratum corneum acts as a barrier on the skin surface, therefore, only

a percentage of the drug applied is actually able to breach this initial

barrier and enter the body, passing the skin.61

The size and type of molecules that make up the drug affect the rate

of transdermal absorption. A discussion of the pharmacokinetics of

topical products in the journal Dermatological Nursing conferred that

drugs with small molecules that are better absorbed in fatty tissues

(lipophilic molecules) can be transported well across the stratum

corneum and into its intercellular lipids. When these drugs have

hydrophilic properties, meaning they are better dissolved in water,

they are best able to penetrate the skin to reach the lower layers.61

Underneath the stratum corneum, the skin layers are much more

permeable; penetration of the layers of skin takes place by passive

diffusion. The dermis contains a variety of structures, including hair

follicles and sweat glands, and it also contains blood vessels, into

which the medication is absorbed.


Other factors may influence the rate at which topical preparations are

absorbed into the skin. For example, when an ointment is applied to

the skin and covered by an occlusive dressing, the medication may be

absorbed more quickly than when a layer of the medication is applied

without any cover. The presence of an occlusive dressing on the skin

prevents water loss from the site and supports hydration, causing the

stratum corneum layer to swell and expand slightly, thereby increasing

permeability and the capacity for the drug to enter.61 Other factors

that may affect the rate and amount of drug absorbed transdermally

include the presence of hair at the site, whether any skin conditions or

diseases are present at the affected site, and the variations in skin

permeability seen in different areas of the body.

Regardless of the method of extravascular administration of drugs, in

order for medications to enter systemic circulation, they must all be

released into the fluid or tissues into which they were administered

and then cross the membrane of the circulatory system through one of

the absorptive processes described. Although there are many factors

that can affect the rate of absorption and the amount of the drug that

actually enters circulation, the process of drug absorption is one step

of pharmacokinetics that all drugs, except intravenously administered

drugs, must undergo to exert their effects and to be therapeutically

useful.

Drug Distribution

Once a drug has been absorbed into circulation, the body distributes

the medication to various sites for its own purposes. Bioavailability

refers to exactly how much of a drug enters the circulation and the

rate at which it is absorbed and therefore available to be distributed.


Drugs that are administered extravascularly are generally not

completely absorbed. There are usually traces of the medication that

remain unabsorbed. This reduces bioavailability since there is less of

the drug available for distribution from its original dose. By

comparison, drugs that are administered intravascularly have greater

bioavailability because they do not need to undergo absorption first.

The composition of a drug impacts its rate of absorption and can affect

the bioavailability of the drug within the circulation system. For

example, there are differences between drugs that are administered as

capsules and as tablets, even though they may be the same drug at

the same dose. Their composition as either capsules or tablets can

impact their qualities of absorption because of their formulations. This,

in turn, affects their bioavailability in the bloodstream as well as the

amount to be distributed.

Clinical illness can also affect the rate and bioavailability of a drug

reaching systemic circulation. Changes in the gastrointestinal wall,

such as due to inflammatory bowel disease or gastrointestinal illness,

can affect the lining of the small intestinal tract and its ability to

properly absorb the medication. Other changes related to illness, such

as alterations in circulation or capillary damage can also affect how

drugs are absorbed when they are administered through other routes

as well, including intramuscular or subcutaneous injections.

Drug distribution begins once the medication has entered systemic

circulation. When a drug is administered intravenously, distribution

begins relatively rapidly because the medication is already present in

circulation. When a drug is given through another extravascular route,


it begins to be distributed once absorption has taken place. The

administration of intravenous medications has its benefits and

limitations. It can cause complications associated with infection, tissue

extravasation, phlebitis, or hematoma formation; however, the direct

administration of medication into the bloodstream bypasses the step of

absorption and the bioavailability of the drug is much higher so that it

can be rapidly distributed across the body’s tissues to take effect

quickly. The rate of distribution so that the drug can exert its effects is

a very important element to consider when the drug is given in the

critical care setting, as the outcomes of the drug’s effects often need

to take place very quickly.

Through the circulatory system, the drug is able to be distributed to all

parts of the body that receive blood flow, including all tissues and

organs where the drug exerts its effects. The drug is transported to

sites of action by either binding to elements within the blood that will

carry the drug components, or by traveling as an unbound particle.

How much of the drug is actually distributed depends on plasma

proteins and the amount of tissue binding.62 Typically, when a drug

binds to components in the bloodstream, it is to plasma proteins,

including albumin, alpha-1 acid glycoprotein, and lipoproteins.

However, when a drug is bound nonspecifically to a protein in the

bloodstream, it cannot exert its therapeutic effects. The drug is said to

bind nonspecifically when it binds to a component that is not its

intended receptor. For instance, when a drug is a specific type of

receptor agonist but it binds to protein instead, it is said to be binding

nonspecifically. The unbound part of the medication, though, is free to

cross over into the interstitial space through passive diffusion where it


will reach tissue-binding sites and it will begin to exert its

pharmacological effects.

Just as some factors affect the rate and degree of a drug’s absorptive

processes, there are also some issues that impact the rate of a drug’s

distribution. Different drugs may be distributed at a faster or slower

rate through the bloodstream; the rate of distribution is affected by

factors such as blood flow and the tissue where the drug is being

distributed. When blood flow is slow and perfusion is poor, a drug is

not distributed as rapidly. A drug is distributed more quickly to areas

that receive more blood flow, such as to the lungs or the kidneys.6

Blockages in the circulatory system, including blood clots or

atherosclerotic lesions, can decrease the overall rate of blood flow.

Obstructions that affect the direction of the blood vessels can also slow

the rate of drug distribution if the blood is rerouted around a

physiological barrier to circulation.

The characteristics of a drug can also affect the rate at which it is

distributed. Some drugs are more likely to bind to plasma proteins in

the bloodstream, which affects their rate of distribution. A drug that is

particularly lipophilic may accumulate in areas with high body fat,

which typically has poor perfusion.

There are several sites where the drug can be distributed in addition to

the plasma of the bloodstream, including intracellular fluid and the

interstitial spaces. When a drug is in the bloodstream, it moves from

the plasma into the tissues through the process of diffusion. The

concentration of the drug is initially much higher in the plasma than in

the tissues just after intravenous drug administration or absorption of


an extravascular administration of the drug. Consequently, the drug

moves from an area of higher concentration within the bloodstream to

an area of lower concentration found in the tissues through diffusion.

Once more of the drug has entered the tissues, the process of diffusion

slows when the areas of concentration between the plasma levels and

tissue levels of the drug are more in balance. This point is known as

the post-distribution phase, in which drug concentrations in plasma

and in the tissues are in balance. This is more often true of drugs that

are administered routinely and continuously, such as in the case of an

ongoing prescription drug, where plasma drug levels are constant, as

opposed to an individual administration of a drug. Once a drug reaches

the post-distribution phase, the plasma and tissue concentrations of

the drug are balanced as the drug is eliminated from the body.7

Note that there are some barriers present that affect how well the

drug reaches its target receptor sites; examples include the blood-

brain barrier (BBB) and the placental barrier. The BBB affects how well

a drug is distributed to the brain; it separates the brain from systemic

circulation. In order for a drug to enter the brain, it must be

transported through capillaries of the central nervous system through

the BBB, which is made up of tightly bound cells that act as a semi-

permeable membrane. Some drugs are more readily able to pass

through this barrier than others. For instance, some lipid-soluble drugs

can quickly pass through to enter the brain. Alternatively, some

solutions pass through the BBB much more slowly because the large

size of their molecules make it difficult to move past the barrier’s tight

junction of endothelial cells.


Each drug given has a particular volume of distribution, which

describes how much it will be distributed throughout the body. Most

drugs are not distributed at the same rates or in even concentrations,

and while there are often barriers that affect drug distribution, the

process is a distinct element of pharmacokinetics that moves the drug

from its original site of administration toward exerting its intended

effects.

Drug Metabolism

Once distributed, the drug is metabolized, which describes how the

chemical compound of the drug is converted into an active chemical

substance through the work of enzymes. Most drugs are metabolized

in the liver, but other body areas, including the lungs, plasma, and the

wall of the gastrointestinal tract have the capacity to metabolize drugs

as well.8 The majority of drugs given must be metabolized before they

can be excreted. When metabolism takes place in the liver, the

hepatocytes contain the enzymes needed to complete the metabolic

process.

The metabolism of a drug generally takes place in two stages; in some

cases, a drug will undergo only one of the two phases, but for most,

the metabolic process in the liver involves the drug undergoing Phase

1 followed by Phase 2. During the first phase, the most common

change that takes place is when the drug undergoes oxidation. Within

the liver, certain enzymes are responsible for initiating oxidation; the

most frequent group of enzymes responsible for drug metabolism

within the liver are those of cytochrome P450 (CYP450). Some other

substances that either inhibit or increase their activity can affect these

enzymes. Consequently, a drug that is known to affect CYP450 should


not be administered with a drug that requires the enzyme for

metabolism.

The CYP450 enzymes from this group start the process of oxidation,

which occurs when electrons from the drug are removed. At this point,

the drug becomes a metabolite. Other processes that may occur

during the first phase of drug metabolism and that result in the

breakdown of the drug are reduction, in which there is the removal of

oxygen from the drug; or hydrolysis, in which there is the addition of

water molecules to the drug.

Once the medication has passed through Phase 1, conjugation occurs

in the second phase of metabolism, in which a group of ions binds to

the metabolite. This process occurs within the cytoplasm of the

hepatocyte. Typically, ionized groups that conjugate to the drug

metabolite come from glutathione, acetyl, or methyl groups. The

process of conjugation contributes toward the eventual excretion of

the drug from the body’s system, as the binding of an ionized group

makes the metabolite more water soluble and therefore easier to

excrete.8 The most common reaction that occurs during Phase 2 of

metabolism is glucuronidation, in which enzymes known as UDP-

glucuronosyltransferases catalyze the conjugation reactions that occur

during Phase 2 of metabolism. This process leads to the detoxification

of certain substances and the formation of glucuronides, which are

more water-soluble and facilitate easier excretion of drugs.

While glucuronidation is one of the most common conjugation

reactions of metabolism, there are other forms that can occur as well,

in which a functional group is added to the molecule to facilitate


metabolism. Such examples include acetylation, which is the addition

of an acetyl group, and sulfation, which is the conjugation of a sulfo

group to the molecule.10 As the process of metabolism continues, the

drug’s therapeutic effects are decreased.

Rates of drug metabolism can vary, depending on several factors,

including the age, weight, and hydration status of the patient, the

overall health of the liver or the organ metabolizing the medication,

and the presence of any comorbid conditions that would otherwise

affect the patient’s general state of health.9 When a drug is

metabolized at an abnormal rate, it impacts the therapeutic effects of

the drug on the patient’s body. If a drug is metabolized very rapidly,

the patient may not experience the desired effects of the medication.

Alternatively, if a drug is metabolized too slowly, the patient may be at

risk of toxicity because of buildup of the drug within the body.

The overall outcome of metabolism is to take the parent compound —

which is the initial state of the drug after it has been distributed — and

break it down through metabolism so that it becomes

pharmacologically inactive for eventual excretion. The body must

metabolize drugs for excretion to avoid the buildup of medication

within the system that leads to toxicity and potential organ damage.

Most drugs become pharmacologically inactive through the process of

metabolism, but note that some drugs, when undergoing metabolism,

remain pharmacologically active. This is sometimes called a prodrug;

the initial drug may actually have a weaker effect until it is partially

metabolized, and then its metabolite is more active. An example of a

prodrug is the antihypertensive drug enalapril, a metabolite whose


parent drug is enalaprilat, which does not become pharmacologically

active until it has undergone metabolism.8

Metabolism of a drug is also affected by its half-life, which is the

amount of time that it takes for the concentration of a drug to

decrease by one-half within the body. A drug that has a long half-life

will be present in the body for a longer period and will take longer to

metabolize than a drug with a comparably shorter half-life. This is

important to remember as well, as the rate of a drug’s half-life can

affect its elimination and may lead to a state of toxicity if another dose

of the drug is administered before its half-life has decreased to an

appropriate level. A drug that is distributed through circulation so that

it can undergo metabolism will eventually be eliminated from the

plasma. The removal of a drug from the plasma is known as drug

clearance, which is a factor used in pharmacokinetic formulas to

determine the half-life of a drug and its steady state of concentration.

The half-life therefore describes how long the drug is active in the

body, which may be referred to as the drug’s duration of action. The

half-life of the drug is related to the amount of the drug present in

plasma. It is important to be familiar with the half-life of certain drugs

when giving them to better understand total duration. If plasma

concentrations are measured to determine the amount of drug

present, knowing the half-life of the drug can tell the clinician how

much longer the drug is expected to be at its present concentration in

the plasma before being reduced. Once a drug is administered and it

reaches the bloodstream, the concentration of the drug initially peaks

at the greatest amount that will be present in the plasma before it

begins to decrease. As stated, different drugs have different lengths of


half-lives, so administration of one drug may result in a peak plasma

concentration that lasts longer before the drug is reduced when the

half-life is longer, compared to a shorter period of peak plasma

concentration with a drug that has a short half-life.

To determine whether a drug is exerting its intended effects and the

concentration of the amount of the drug in the body, clinicians often

draw plasma levels. When a drug is being distributed through

circulation, it is often dispensed to more than one site at a time;

consequently, attempting to assess the drug’s concentration within

specific targeted tissues is often not possible. Instead, plasma levels

are typically measured to determine the drug’s concentration in the

body.9 A drug that is administered once or twice will not build up much

of a concentration in the bloodstream and will be cleared from the

plasma after distribution. However, in cases where a drug is

administered routinely, the goal is to develop a steady state within the

bloodstream, or a certain amount of the drug that is constant within

the plasma so that it is therapeutically effective. An example of this is

with the administration of digoxin, which is given for the treatment of

heart failure or chronic atrial fibrillation. Digoxin is administered

routinely, typically on a daily basis. Because of this, its concentration

within the blood plasma is maintained and it can exert its therapeutic

effects. Clinicians can test for digoxin levels in the bloodstream by

assessing plasma values because its chronic administration leads to a

plasma steady state.

The time it takes to reach the steady state of a drug is considered to

be approximately five half-lives of the drug.8 In other words, if the

half-life of a drug is one hour, it would take approximately five hours


for the drug to reach a steady state within the bloodstream. Again,

when a drug’s half-life is longer, it takes longer to reach a steady state

than when a drug has a short half-life. This is also why it is important

to be familiar with a drug’s half-life when administering it to a patient

so as to better understand how long it will take to reach a therapeutic

concentration within the bloodstream.

There may be times when it is preferable to achieve a steady state of a

drug’s concentration quickly, in order to gain the drug’s therapeutic

effectiveness more quickly. A loading dose given at the beginning of a

drug regimen can achieve a steady state in the bloodstream at a faster

pace. This loading dose is then followed by maintenance doses to

sustain a suitable concentration of the drug over time.

Therapeutic drug monitoring of plasma levels is commonly performed

on those drugs that need to achieve a steady state in the bloodstream.

In addition to digoxin, some other examples of drugs that may require

this type of monitoring include lithium, given for treatment of bipolar

disorder, and the anti-seizure medication carbamazepine. In some

cases, peak and trough levels are measured to assess plasma

quantities and the levels of therapeutic effectiveness. For example,

when administering gentamicin as an antibiotic, the patient requires

peak and trough levels, which are performed after dose administration

and just prior to dose administration, respectively. Measuring the peak

involves collecting a blood sample within approximately 30 minutes

after the drug has been given and has had a chance to be distributed.

Alternatively, the trough is measured just prior to giving the drug,

when the concentration of the drug in the body from the last point of

administration would be at its lowest.


There are several considerations to think through when using

therapeutic drug monitoring for patients in the ICU. First, this type of

monitoring is only appropriate for those drugs that require therapeutic

monitoring to check plasma levels, but it does not need to be

performed every day or with each dose. The critical care patient’s

disease state can also affect how the drug is distributed, as well as the

steady state concentration, and so therapeutic drug monitoring may

not be totally accurate in some cases; as a result, it should not be

relied upon as the sole mechanism of determining drug effectiveness.

To sum up, therapeutic drug monitoring in critical care can be a

valuable tool in some cases, but often when there are other indicators

of the patient’s clinical response that are difficult to interpret

otherwise.45 In the case of assessing plasma levels of antibiotics to

determine therapeutic effectiveness, the health clinician should also

consider other signs and symptoms that the patient is responding to

the drugs, including an improved clinical state and resolving signs of

infection.

There are many factors to consider when evaluating a drug’s

distribution and metabolism. The bedside caregiver cannot be

expected to know and remember the rates of metabolism for all of the

drugs being administered, but should understand the basic routes of

metabolism and what can affect its rate of tissue distribution, plasma

concentrations, and conversion to exert its effects so that

accommodations for critical care patients can be made, if needed.

Drug Excretion

Technically, the elimination of a drug from the body begins as soon as

it is administered and it enters the body. When a drug is first being


absorbed, the body is also simultaneously eliminating it, but the rate

of absorption is greater than the rate of elimination, so more of the

drug is absorbed initially.5 Over time, the processes balance out and

eventually, more of the drug is metabolized and excreted when there

is less of the initial drug to be absorbed.

The term clearance describes how a drug is eliminated from the body.

Drug clearance occurs when the drug is brought to the organ of

elimination, often either the liver for metabolism or the kidneys. The

rate of clearance is directly proportional to the amount of drug present

in the plasma, so if there is a large plasma drug concentration, the

rate of drug clearance is increased. When clearance occurs via liver

metabolism, it is known as hepatic clearance. This type of clearance

occurs as a result of liver metabolism of the drug as well as biliary

excretion, which is the transfer of drug metabolites into the bile.64

Hepatic clearance can be affected by such factors as the amount of

hepatic enzymes needed for metabolism, as well as the presence of

any biliary obstructions.

Alternatively, renal clearance describes the elimination of the drug

through the kidneys via the urine. Drugs are excreted by the kidneys

when they enter the renal circulatory system and portions of the drug

are transferred into the urine following glomerular filtration or tubular

secretion within the proximal tubule.64,65 Various factors can also

impact renal excretion of drugs, however, one of the most common

issues with poor renal excretion is because of impaired renal function,

often due to illness or disease, which results in an inability of the

kidneys to properly filter the drug.


As with other elements of pharmacokinetics, drug excretion can be

affected when the patient’s body is unable to adequately eliminate

appropriate amounts of the drug. This increases the risk of a buildup of

the drug within the system and the potential for toxicity. For instance,

a patient with poor kidney function as a result of disease may have

difficulties excreting certain drugs and the health clinician may need to

assess kidney function prior to drug administration or the continuation

of the current dose. There are several formulas that can be used to

estimate kidney function through measurement of creatinine, as

elevated creatinine levels can indicate impaired kidney function.

Historically, the standard of measurement of creatinine levels was the

Cockcroft-Gault equation, which was developed in the 1970s but has

since been replaced by more standardized measurements of

creatinine.

Because many drugs administered within healthcare facilities today are

removed from the body through the work of the liver or the kidneys, it

is important to understand basic tests of liver or kidney function to

determine the effects that critical illness can play on the metabolism

and excretion of drugs. When estimating kidney function, a clinician

should consider the patient’s estimated glomerular filtration rate

(GFR). Besides the change in use of the Cockcroft-Gault formula

(which may still be used in some locations), clinicians have other

formulas that can also determine patient kidney function, including the

Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the

Modification of Diet in Renal Disease (MDRD) formulas that are

standardized and that can accurately determine kidney function.45


While many clinicians, such as those who provide direct patient care,

do not necessarily calculate the GFR of specific patients, nor

implement specific formulas to determine kidney function, they should

still be familiar with the effects of the GFR on a patient’s system to

adequately excrete the drug. Additionally, the health clinicians who are

prescribing orders and making changes in the patient’s plan of care

may be using these formulas to alter the prescription amounts based

on the patient’s condition. Further, it should be noted that many

formulas that estimate kidney function are based on the patient

achieving a steady state of the drug in the plasma, which may or may

not be reflective of a patient in critical care. These are just some of the

factors to take into account when considering how critical care impacts

the pharmacokinetics of various drugs.

Pharmacodynamics

In contrast to pharmacokinetics, the concept of pharmacodynamics

describes a drug’s actions or what a drug does in the body after it is

administered. The action of a drug is determined by its

pharmacodynamic properties; these factors are related to the drug’s

pharmacokinetic factors, and each drug has different properties in how

it behaves once it has been administered. In essence,

pharmacodynamics considers the drug concentration at the site of

action and its therapeutic effects, including any adverse effects that

may occur.

Drugs have sites of action in the body, which are the locations of

where they are expected to exert their effects.5 For example, a beta-

blocker drug’s sites of action are the beta-adrenergic receptors that

they effectively block to prevent the action of some neurotransmitters.


The drug’s action in the body is affected by how it is able to bind with

its specific receptor. There are receptors located throughout the body,

and they have various functions. Nociceptors are those associated with

pain, while thermoreceptors impact body temperature. There are

receptors located in areas such as the heart and the muscles; they are

on the neurons of the central nervous system, and they can be found

inside of cell walls.

Most receptors are made up of amino acids and protein structures. As

such, they can be sensitive to changes in the pH of the surrounding

environment. When this occurs, it could change the receptor’s ability

to bind to different substances. This can then affect a drug’s ability to

bind to certain receptors and therefore, its overall effectiveness. In

general, drugs that interact with receptor sites are classified as being

either agonists or antagonists in their behavior. Receptor agonists

react with the receptor to stimulate it and to cause a change. Often,

there is already a substance in the body that also reacts with the

receptor; the receptor agonist drug therefore acts in a manner similar

to the endogenous substance. When the drug acts on the receptor, it

is said to occupy it, meaning that it takes over the site and prevents

the endogenous substance from affecting the receptor. This occurs for

only as long as the drug compound is in the body. An example of a

receptor agonist is isoproterenol, which works by stimulating beta-

receptors that are normally stimulated by epinephrine.

In contrast, a receptor antagonist blocks the activity of the receptor,

which produces an opposite effect of what agonist activity would be.

As with agonist activity, the receptor antagonist also occupies the

receptor for a period of time while the drug is present and prevents


other substances from interacting with the same receptor. Receptor

antagonists may compete with agonists to be able to occupy certain

receptor sites. The higher the concentration of the drug (receptor

antagonist) within the body then the greater the likelihood the

antagonist will be the substance to occupy the receptor. Receptor

antagonists may also be non-competitive, in that they do not compete

for receptor sites, but they ultimately do not allow the surrounding

agonists to have any effect on the receptor.

A drug is able to exert its effect based on how much of the drug

reaches the receptors. Consequently, when there are issues that

disrupt the pharmacokinetics of the drug, such as its potential for

absorption, there may be less of the drug available at receptor sites to

take action and the drug will not exert as powerful of an effect.

Additionally, some receptor sites have greater density than others and

there are more locations for the drug to act on, meaning the drug is

more likely to exert more of its effects.

Individual patient characteristics will also affect the pharmacodynamics

of a drug. Factors such as a person’s age, overall health or the

presence of chronic illness, and weight or body mass can all impact

drug pharmacodynamics.9 Some people are more sensitive to drug

effects than others. This can occur when there are more drug

receptors available in a location for the drug; as a result, one patient

may have a more pronounced drug effect than the next person with a

slightly lower density of receptors at a similar site.

Each drug also has a specific duration, which is the time that it will

exert its effects in the body. This is perhaps most well known in the


case of insulin, which is typically administered in relation to when and

how long it will be therapeutic compared to a patient’s blood glucose

levels. The duration of insulin, for instance, is how long the drug will

be taking action in the body, which is important to know to be able to

determine the appropriate time for the next dose. The duration of

action of a drug is impacted by how long it is exerting its effects

against its specific receptors. Further, drug tolerance can develop

when a repeated administration of the same drug requires more of the

drug to affect its receptors; the drug, when given normally, does not

exert as strong of an effect at the receptor site and so requires more

to achieve the same results.

The appropriate dose of the drug is decided, in part, by

pharmacodynamics. Because this segment of drug pharmacology is

concerned with drug concentration and its effects in the body, the

appropriate dose of the drug is calculated based on the knowledge of

these two factors, to ensure that the person taking the drug does not

take too much as to cause toxicity, and also to ensure that the person

receives enough to experience the drug’s therapeutic benefits. Proper

dosing is, in fact, achieving a balance that maintains the correct drug

concentration in the body.

While a drug is typically given to exert therapeutic effects and to be

helpful, there are times when unintended effects may also develop as

a result of the drugs actions. Drugs are given because of their

intended actions in the body, meaning, their specificity for certain

receptor sites leads to their therapeutic effects. However, no drug has

absolute specificity; instead, it just acts more on certain receptors

than in other areas.67 As a result, drugs can also cause adverse effects


that can be uncomfortable for the patient and that may require further

monitoring and care. Note that the term side effects are often used

only as a general term for the public when describing adverse drug

reactions.

The different mechanisms that occur when a drug enters the body and

undergoes the process of being absorbed and distributed to its

intended receptor site can cause a number of reactions along the way.

The drug may bind to the appropriate receptor, but it may do so at the

wrong concentration, or it may not produce enough of a reaction.

Almost all drugs cause reactions in the body that are different from,

but that occur in addition to, their intended effects. The severity of

these adverse effects can be mild and imperceptible, or they can be so

significant that they predominate over the desired drug effects.

Adverse effects may also develop when a drug acts as an agonist for a

receptor site that is different from its target site. This phenomenon is

sometimes known as an off-target adverse effect.68 The drug may

have specificity for one type of receptor, but by also acting as an

agonist for other receptors, it can cause different effects. A drug’s

target receptors may be located in more than one area, so the adverse

effects that occur can affect different body systems. A study by Kim, et

al. in the journal Biochemical and Biophysical Research

Communications used a prediction method for identifying unintended

drug effects based on off-target events and found that in most cases,

the drug’s target proteins were located in more than one tissue and

the drug could cause effects impacting multiple tissue areas.68 This

information may be related to why some drugs, while having one


intended effect, can cause adverse effects that seem unrelated to their

original intent.

Another type of adverse event that can occur with drug administration

is an idiosyncratic drug reaction. This describes an adverse effect that

is rare and unpredictable. It generally does not develop with normal

drug administration, but if it does, it is an adverse effect that can be

very serious and even life-threatening for the patient. Whether or not

a drug causes an idiosyncratic reaction is based partly on the drug’s

composition and characteristics, but it is also based on some patient

factors as well, including immune receptors that affect the cell-surface

antigens.69

The random and varied nature of idiosyncratic drug reactions can lead

to some uncertainty with drug administration. Because the health

clinician does not know if or when an idiosyncratic reaction will occur,

the patient could be placed in a state of harm without anyone being

aware of it. Idiosyncratic reactions are difficult to study because they

do not necessarily follow a pattern.69 The clinician who administers any

drugs to patients must then be aware of the possibility of idiosyncratic

reactions at all times, even though they are rare.

Idiosyncratic drug reactions seem to occur in any area of the body,

however, the skin, liver, and the blood cells are areas most often

affected.69 There is often a delay between the time of drug

administration and the onset of symptoms, and the reaction for a

specific drug does not appear to be dose-dependent. An example of an

idiosyncratic drug reaction is the development of drug reaction with

eosinophilia and systemic symptoms (DRESS) syndrome, which is


thought to occur in up to 1 in 10,000 drug exposures. DRESS has

occurred following administration of a variety of drugs; some examples

include phenytoin, minocycline, allopurinol, and sulfasalazine.70

However, the exact cause seems to be associated with a number of

factors, including both immune and non-immunologic elements.

The pharmacodynamics of a drug can also be impacted by patient

factors, and within the critical care setting, the potential for severe

acute or chronic illnesses that affect physiological drug activity is high.

As an example, patients with diabetes often have cardiovascular

complications, and they are often prescribed more medications for

therapeutic management of not only of their diabetes, but for other

consequences as well. An article published in Podiatry Today discussed

the effects of diabetes on both pharmacodynamic and pharmacokinetic

responses and said that while current research related to the effects of

diabetes on pharmacodynamic processes is somewhat limited and still

ongoing, clinical assessments have shown that patients with diabetes

tend to have altered drug responses, particularly following

administration of certain classes of medications, including lipid-

lowering agents and antihypertensives.71 Other chronic diseases or

conditions that have been suggested to affect the pharmacodynamic

processes following drug administration include thyrotoxicosis,

myasthenia gravis, Parkinson’s disease, and malnutrition.72

Undoubtedly, the pharmacodynamic processes that occur within the

body following drug administration are a significant part of how drugs

work, their potential for adverse events, and the overall bodily

response. Just as pharmacokinetic effects are a complex progression of

activity that involve many different formulas and systems, the


pharmacodynamic effects of drugs are also complex and multifaceted.

The clinician who provides direct care and who administers

medications to patients in the emergency department or ICU should

have at least a basic understanding of pharmacodynamics and how

these processes instigate various biochemical and metabolic processes

in the body.

Common Medication Types In Critical Care

When a patient needs intensive care for an illness or severe injury, the

clinician often must know to act quickly, giving drugs to respond to

changes in the patient’s condition or clinical status. The clinician

working in a critical care setting may be faced with administering a

variety of different drugs and it may be challenging to remember the

varied drug classes, common dosages, potential side effects, and

implications for administration. Drugs are often given based on each

patient’s condition and may be used to manage specific symptoms that

affect different organ systems within each person. For example, one

patient in the emergency department may require cardiac medications

to stabilize a potentially life-threatening arrhythmia, while another

may need analgesia to control pain associated with a severe injury.

Often, patients require more than one type of medication.

Prior to administering any drugs, it is important to know some of the

patient’s pertinent medical history, whether any allergies are present,

and the presence of comorbid conditions. Sometimes, this information

is not available and the clinician must quickly respond to the situation

at hand, such as in the case of life-threatening events. Alternatively,

many patients who are managing severe illnesses or who are

overcoming major surgery have well-documented histories and their


caregivers carefully administer medications and monitor clinical

responses over a period of days or weeks of care. In these cases,

patient care plans may be complex and filled with a number of

different drugs and prescribed treatments. Despite the variety of drugs

available for therapy and symptom control, there remain several

classes of medications that are commonly administered in the

emergency department or the ICU, including sedatives, analgesics,

neuromuscular blocking agents, and pressors.

Sedative Medications

Sedative medications are drugs that work by physiologically reducing

excitement, agitation, or anxiety by inducing a state of calm.

Sometimes called tranquilizers, sedatives typically consist of those

drugs classified as barbiturates or benzodiazepines, although some

other drugs may have sedating side effects or may be used as an off-

label method of causing sedation.73 Some of their most common

purposes for administration are for control of anxiety or as an aid for

sleep, however, they are also prescribed as anticonvulsants,

amnesiatics, and as muscle relaxants.

Benzodiazepines work by augmenting the action of the

neurotransmitter gamma-amino butyric acid (GABA), which primarily

has an inhibitory effect on the motor neurons. Benzodiazepines target

GABA receptors, which are some of the most common receptors in the

body. Normally, these receptors respond to GABA, but when

benzodiazepines are given, they act as agonists for these receptors as

well, increasing the effects of GABA and slowing motor activity.73

Benzodiazepines may be considered short-acting or long-acting drugs.

Short-acting preparations are given to exert their effects during a


specific condition and over a brief period of time, whereas long-acting

benzodiazepines may be administered repeatedly and are designed to

build up in concentration within the bloodstream. Although they

primarily are used in controlled situations and are able to achieve

calming effects, the primary adverse effects often seen with

benzodiazepines include poor motor coordination, drowsiness,

confusion, slurred speech, slowed reflexes, and respiratory depression.

Barbiturates are another type of sedative agent that were once more

commonly administered for their calming effects; however, many

barbiturates are no longer used because of safety issues and they

have been replaced with other drugs that are more appropriate.

Barbiturates are made up of barbituric acid and they are typically

classified according to their duration of action. The range of

barbiturate classification spans from ultrashort-acting drugs, which are

most commonly given prior to surgery, to long-acting barbiturates,

which may take up to two hours to produce effects. As with

benzodiazepines, barbiturates act as GABA receptor agonists to slow

motor activity. They are often used for inducing sleep, and many of

the ultrashort-acting preparations are administered during induction of

anesthesia. Long-acting barbiturates are used as sleep aids or for

anxiety, but also to control migraines and as anticonvulsants.74 Due to

their potential for abuse, harmful adverse effects, and significant

withdrawal symptoms, barbiturates used within healthcare are

typically highly controlled and are less often used if other sedatives are

available.

There are other drugs that are administered for their sedating effects

that are not classified as benzodiazepines or barbiturates. Some of


these drugs have been approved for other purposes but they also have

a sedating effect and so are administered in an off-label manner. An

example is the use of some neuroleptic agents, also referred to as

antipsychotics. These drugs, such as haloperidol, produce sedation as

an adverse effect to their intended use for control of psychotic

symptoms. For a patient with no history of mental illness,

antipsychotic medications are often not used as a first choice for

calming, despite their ability to achieve sedation. However, for some

patients in the ICU and ED who are already struggling with delirium

and agitation as a result of psychosis, neuroleptic agents can control

anxiety and can promote sleep.75

Other drugs that are used as induction agents with anesthesia

successfully cause sedation and induce sleep for the patient

undergoing surgery. These drugs are almost always given

intravenously and they not only induce sedation, but can also cause

memory loss of the event. Examples include ketamine and etomidate.

Ketamine is actually a type of anesthetic that produces sedating

effects that include hypnosis, analgesia, and increased sympathetic

activity while maintaining an effective airway and respiratory drive.

Ketamine works as an antagonist to the N-methyl-D-aspartate (NMDA)

receptors to decrease excitability.78 Etomidate is an anesthetic and

hypnotic drug that exerts its effects rapidly after administration; it is

used during induction of general anesthesia, but may also be

administered just prior to certain medical procedures, such as rapid-

sequence intubation. Etomidate supports the action of GABA, leading

to a decrease in overall motor activity, but maintains cardiac and

respiratory functions. It may be administered as an adjuvant to

neuromuscular blocking agents to decrease excitement and anxiety.


Within the emergency department, sedation is often administered

quickly and rapidly, yet its use must be handled in a safe and effective

manner. The American College of Emergency Physicians (ACEP) has

issued recommendations for the specific use of sedatives in the

emergency department in order to provide timely and safe sedation for

patients in need. These guidelines include14 1) the administration of

sedatives only by those who have been appropriately trained and who

have the credentials to be able to care for patients requiring

emergency care, 2) the specific type and amount of sedation should be

individualized to each patient depending on circumstances, 3) each

member of the emergency team who administers sedative medications

should be familiar with their purposes and side effects, 4) patients who

receive sedation should be thoroughly monitored and continually

evaluated before, during, and after their administration, and 5) there

should be appropriate protocols developed for the use of sedation and

the competency of the staff who administer these drugs in each

healthcare facility where they are given.

Sedatives have the potential to cause harmful complications to the

patients for whom they are administered, which means their use in

healthcare must be tightly controlled. Despite their potential

drawbacks, they serve important purposes in the emergency and

critical care environments because they enable clinicians to adequately

assist with calming and reducing patient anxiety. The ICU or

emergency department can be frightening for patients who do not

necessarily understand what is happening. Administration of sedatives

can calm anxiety and fears about the patient’s well-being. Additionally,

patients in critical care often undergo various procedures, which can


cause anxiety and agitation. They often benefit from sedatives to feel

calmer about the procedure or sometimes to sleep through the event.

The majority of sedatives are administered intravenously or orally,

depending on the type of drug and the circumstances during which

they are given. Many patients who take benzodiazepines, for example,

take oral preparations at home. A patient in the hospital who has

difficulty sleeping may be given an oral sedative if he/she can tolerate

taking medication by mouth. Alternatively, sedatives administered

intravenously are typically given to those patients who cannot take

oral drugs or where rapid sedation is needed, such as prior to a

procedure or when a person requires mechanical ventilation. The

distinct purposes of sedatives, as well as their potential problems and

need for monitoring is discussed further below.

Purpose

As stated, sedatives are administered because of their depressant

effects on the central nervous system and their ability to slow down

motor neuron activity. They often leave a person feeling sleepy, calm,

or peaceful. While they are commonly prescribed in the general

population and are usually taken by oral prescription, sedatives are

also commonly administered in critical care. Because of the potentially

unstable nature of these patients, sedative administration requires

thoughtful planning and careful monitoring throughout the entire

process.

While most sedatives are used as sleep aids or for control of anxiety,

their use in critical care may also include management of significant

agitation as well as for patient comfort. Because emergency care may


entail procedures that can be frightening and uncomfortable for the

patient, the administration of a sedative just prior to performing a

procedure can help the individual to relax. As an example, rapid

sequence intubation, which is the process of quickly securing an

airway in a patient who is clinically unstable, requires that the patient

be quickly sedated and calmed prior to intubation in order to better

facilitate the process. Just before starting, the patient may be given an

induction agent as a sedative, which will blunt responses to the

process and which can be used in addition to neuromuscular blocking

agents.

In cases of rapid sequence intubation, the patient is most commonly

given a drug such as etomidate or ketamine, although some

benzodiazepines may be used as well, including midazolam.76 Note

that these drugs are given for sedation prior to the process of rapid

intubation because of their short-acting properties and their

availability. Other drugs, including long-acting benzodiazepines, may

also be given to maintain sedation after the patient has been intubated

and placed on mechanical ventilation.

Sedative medications are also important to control anxiety and

agitation that commonly accompanies a patient’s stay in the ICU. In

addition to the potentially painful procedures that are often necessary

for a critically ill patient, the experience of receiving intensive care can

be frightening and confusing. Many patients in the ICU suffer from

severe agitation and distress, whether due to anxiety and fear or

because of confusion or alterations in levels of consciousness due to

their injuries. Agitation may lead some patients to become aggressive

toward their caregivers and can increase the risk of inadvertent


removal of equipment, such as endotracheal tubes or central venous

catheters. Administration of sedative medications can promote

relaxation and can be calming to reduce some of the agitation and

delirium commonly experienced by patients in the ICU.

The sedatives administered can have varying effects on the patient,

depending on the amount given and the type of drug administered;

when sedatives are given, the amounts and their effects are often

described on a continuum that ranges from very mild effects that are

calming to general anesthesia that induces a complete loss of

consciousness. Mild or minimal sedation, also referred to as anxiolysis,

provides some amount of sedation so that the patient is calmed and

comforted but not so much that it alters his/her level of consciousness.

A patient who receives anxiolysis can still respond to verbal

commands, has normal reflexes, and can breathe spontaneously.14

Moderate sedation may be administered for purposes of keeping a

patient comfortable and subdued, often during the process of

performing a medical procedure. Moderate sedation is sometimes also

referred to as conscious sedation. The patient has not lost

consciousness and is still able to respond to verbal cues. The patient is

still able to breathe independently but has an altered level of

consciousness that is more depressed than an alert state, and may

require some gentle physical stimulation to acquire a response.

Deep sedation induces a greater degree of suppressed levels of

consciousness. When under deep sedation, the patient can be aroused

to respond to verbal or physical stimulation, but it often requires more

aggressive maneuvers to achieve a response. The patient under deep


sedation may or may not maintain a patent airway and, if breathing is

slowed because of the medication, the patient needs respiratory

assistance through endotracheal intubation. Typically, a patient who

undergoes deep sedation has no memory of the events that occurred.

According to an Expert Opinion report by McGrane, et al. in Minerva

Anestesiologica, sedation is prescribed in 42% to 72% of patients

admitted to an ICU, and its use has only been increasing within the

last decade.77 The increases in complexity of procedures performed in

this environment, combined with the technical capabilities of medical

systems have led to many critically ill patients receiving more frequent

administration of sedation. Whether these drugs are given quickly to

control patient responses during critical procedures, or as ongoing

therapy to maintain patient comfort and safety while in the ICU,

sedative use helps health clinicians to achieve overall goals of

providing effective care to those who are critically ill.

Monitoring

While sedative administration is common and their effects serve a

number of purposes, there are still drawbacks to their use.

Inappropriate use of sedatives, whether intentional or not, could cause

serious adverse effects in the patient, some of which can be life-

threatening. Therefore, patient monitoring is an integral part of

sedative administration throughout the timing of each drug dose.

The best, initial step in monitoring patients who receive sedation as

part of critical treatment is for the health facility to have a protocol in

place regarding the process. The actual method of monitoring patients

who have been given sedatives may vary slightly, depending on the

facility’s policies and standards; however, in order for protocols that


guide clinicians monitoring sedated patients to be accurate and

appropriate, they must include guidance on the necessary time

intervals of drug administration, the acceptable depth of sedation, and

the use of further interventions, such as with the administration of

concomitant analgesia. Ideally, the level of sedation should be limited

to the amount necessary to maintain the patient’s comfort, without

causing an unnecessary loss of consciousness.

There are many sedatives that are classified according to schedules,

based on the Controlled Substances Act. Controlled substances are

categorized within one of five schedules, based on their potential for

causing dependency or their risk of being abused. The schedules range

from Schedule I, which consists of powerful, illicit drugs that have no

medical value, such as heroin, to Schedule V drugs, which have limited

quantities of narcotics and have the lowest potential for abuse. While

most sedative medications given within the critical care environment

are administered and controlled by medical clinicians, the use of these

types of drugs should still be closely monitored for signs of increased

tolerance and physical or psychological dependency.

There are no sedative medications that are given by prescription that

are classified as Schedule I. These drugs have no acceptable medical

use and would not be administered in the critical care setting.

Schedule II drugs have a high potential for abuse; sedative

medications that are classified as Schedule II drugs include

secobarbital (Seconal®) and pentobarbital. Examples of sedative

medications that are Schedule III drugs are midazolam (Versed®) and

talbutal (Lotusate®), while sedatives that are in Schedules IV or V


include eszopiclone (Lunesta®), zolpidem (Ambien®), and suvorexant

(Belsomra®).

High concentrations of sedative medications can lead to significant

drowsiness to the point of a loss of consciousness and may slow

respiratory efforts or cause apnea. Other issues associated with

oversedation include insomnia and sleep prevention, hypotension,

constipation, deep vein thrombosis, and increased risk of ventilator-

associated pneumonia, impaired gastrointestinal motility, increased

length of required mechanical ventilation and lengthened weaning

times, amnesia of the hospital event, and muscle wasting.15 Because

of the large number of potential side effects and their significance, the

clinician who administers sedative medications must be familiar with

signs or symptoms that can indicate that the patient has received too

much.

Continual assessment of the patient’s clinical status will help the

clinician to better understand the level of sedation the patient is

experiencing and whether he/she has received the right amount of the

drug. Additionally, clinical assessments can determine if the patient

needs more medication because of discomfort and possibly being

undersedated, so assessing for signs of agitation or vocalization is

warranted. Frequent monitoring also considers whether the patient has

been given too much medication and is experiencing ill effects, as

evidenced by slowed breathing or periods of apnea, changes in levels

of consciousness, and an inability to rouse with stimulation.

Monitoring of sedation can also take place through sedation scales,

which are assessment measures used in a manner similar to


assessment of pain. Many patients are unable to adequately

communicate or explain how they are feeling, particularly if they are

oversedated. An assessment scale to evaluate sedation levels helps

the clinician to closely monitor the patient and can prevent

complications associated with oversedation. One of the more common

tools available for use in critical care is the Richmond Agitation-

Sedation Scale (RASS); this scoring system can be used for any

patient who is at risk of delirium, agitation, or anxiety and who is

receiving sedative medications, but it is particularly useful for those

who have difficulty with communication, such as patients who have

mechanical ventilation.

The RASS requires observation of the patient’s behavior and responses

to stimuli. The responses are scored on a scale that ranges from -5

(unarousable) to +4 (combative, violent, dangerous to staff), with a

score of “0” described as being “alert and calm.”12 The clinician should

first observe the patient to determine alertness; if so, the patient

should receive a score that falls between 0 and +4. If the patient is

not alert, his score will fall between 0 and -5, based on levels of

responsiveness to stimuli, eye opening, or spontaneous movement. A

score of -5 indicates that the patient is unresponsive to any

stimulation. Based on the patient’s RASS score, the caregiver can

titrate sedative medications accordingly to ensure that the patient

needs more or less intervention.

The Riker Sedation-Agitation Scale is another intervention that may be

used to monitor sedation levels and to determine whether a patient is

receiving enough or too much sedative medications for his condition.

The Riker Scale requires patient assessment to evaluate his behavior,


activity, and cognition and then assigns a score based on the outcome.

The scores for the Riker Scale range from 1, in which the patient

cannot be aroused and does not follow any commands, to a score of 7,

in which the patient is considered to have “dangerous agitation” and is

pulling at tubes or catheters, trying to climb out of bed, or is a danger

to staff. An appropriate target score on the Riker Scale is between 3

and 4, in which the patient is calm and cooperative, and follows

commands appropriately.13

Sedatives should not be administered as a method of keeping a patient

constantly subdued and controlled. Historically, sedatives were given

around the clock to patients who required mechanical ventilation in

order to maintain such deep sedation that the individual was relatively

unaware of his condition until he was able to successfully breathe on

his own. Today, sedatives are still commonly administered, but are

often given as adjuvant drugs to promote comfort alongside

analgesics; they should be given as a method of controlling anxiety

and insomnia in the critical care environment, instead of just being

used to keep a ventilated patient restrained and confined. According to

Reade, et al., in the New England Journal of Medicine, sedatives should

only be used when the patient’s pain and delirium have already been

addressed through medication and non-pharmacologic interventions.11

In cases where a patient receives continuous sedative medications

over a longer period, he will eventually need to be weaned from the

drugs in order to achieve a fully conscious and alert state. As an

example, a patient who requires a mechanical ventilator for several

days to assist with respiratory efforts may also receive sedative

medications to reduce anxiety and agitation. When considering


whether the patient can be extubated and removed from the

ventilator, the clinician may need to perform a brief trial of stopping

the sedatives to determine the patient’s neurological state. This period

of rest from the drug is sometimes called sedation cessation or

sedation interruption, and it is done intentionally and on a scheduled

basis to best determine the patient’s response.15 The patient’s

sedation is interrupted for a brief period so the clinician can assess the

person’s neurological status, his ability to communicate, and his

overall levels of agitation. This assessment helps the clinician to

evaluate, along with other factors, whether the patient may be ready

for extubation or if he still requires sedative medications for a longer

period.

The time period for how often to perform sedation interruption varies,

depending on the individual patient’s needs. Some facilities perform

sedation interruption on a daily basis, and there have been some

benefits associated with this practice, including a decreased amount of

time required for the patient to use the ventilator. However, the daily

practice of sedation cessation is not implemented in all locations and

there may also be some complications involved with its routine

performance, including an increased risk of ventilator associated

pneumonia, patient barotrauma, and venous thromboembolic disease.

Healthcare guidelines vary for timing of sedation interruption between

facilities and locations.

As described, the intensity of sedation can vary from mild levels of

intervention that promote comfort and cooperation, to deep sedation

that induces a state of unconsciousness. Deep sedation may be

implemented for some very painful procedures that the patient would


otherwise be unable to tolerate. However, despite the need for deep

sedation in some critical care situations, the majority of patients who

receive emergency or ICU care benefit from mild sedation.

Analgesic Medications

A significant number of patients who require care in the ICU or the

emergency department experience some form of pain, as well as

stress and anxiety. In addition to administration of sedatives to reduce

excitement, analgesic medications are commonly administered to

uphold patient comfort and to keep patients calm. Analgesic

medications are primarily administered to control pain. Uncontrolled

pain can lead to many complications, including an increased length of

stay, severe patient anxiety, and delirium.30 The appropriate use of

analgesics makes a considerable difference in the health and well-

being of the patient in the ICU. The dose, route of administration, and

rate at which the drug is given are all factors that impact the patient’s

levels of comfort and support healing, thereby ultimately affecting

patient outcomes.

There are different classes of analgesic agents available; each of these

drugs may also have more than one route in which it can be

administered, creating a variety of choices when selecting the best

option for pain control. Analgesics may be classified according to the

intensity of pain they are designed to treat; for instance, opioid

analgesics, which can have strong effects, manage moderate or severe

pain, while non-opioid analgesics are typically designed to treat mild

pain, and their effects are not as powerful. The patient in critical care

may experience a range in severity of pain, depending on his current


condition, and often, different strengths of analgesic medications are

available as needed.

Purpose

Pain is an individual experience. What one person considers as very

mild discomfort may be described as intensely painful to another.

Although the experience of pain differs for each person, there are

certain situations that are known to cause pain at certain intensity. For

example, an accident that causes an open leg fracture is understood to

be quite painful for someone experiencing it. Two people with the

same injury may describe their pain at different levels of intensity, but

the experience is somewhat similar in that they feel the same type of

pain; in the case of an open leg fracture, the pain experienced comes

from damage to the soft tissues of the leg.

Analgesics are administered to relieve many different types of pain.

The pain that healthcare providers see and treat in critical care

situations may vary significantly in duration, location, and intensity.

Acute pain describes the feeling of discomfort that has a relatively

short duration (lasting from several hours to days) and that has

developed quickly, often because of the event that caused the pain.

Acute pain often develops as a result of injuries or accidents and is

experienced with soft tissue trauma, inflammation due to an infection,

broken bones, or because of surgery. An individual who seeks care for

treatment of an injury or who is recovering from surgery and who feels

pain is most likely experiencing an acute form.

Chronic pain is described as pain that has been present for longer than

12 weeks.79 In contrast to acute pain, chronic pain is often persistent


and may or may not respond to medication or therapy as treatment. It

may arise initially from an injury or event that caused acute pain, but

may then persist despite efforts at treatment. Untreated chronic pain

can lead to feelings of depression, fatigue, mood changes, and

insomnia. Over time, it may be so debilitating to the affected person

that it impacts his ability to complete normal daily activities. Some

patients who receive care in the hospital already suffer from chronic

pain due to a previous situation; when this occurs, the chronic pain

must also be managed in addition to any acute pain that has

developed as a result of the hospitalization. For example, a patient

who has cancer may have endured chronic pain for months; when

hospitalized for another painful procedure, the patient’s comfort levels

must be addressed by providing pain medication that helps to control

both acute and chronic pain.

In addition to acute and chronic pain, patients may suffer from

different types of pain based on the affected area; these types may

involve neuropathic pain, which can occur following an injury to the

nerves; somatic pain, which often occurs with soft tissue or

musculoskeletal injuries; and visceral pain, which describes pain from

damage to the internal organs. Patients in the ICU may experience any

of these kinds of pain, or more than one type at once. The body

experiences pain through stimulation of nociceptors, which are sensory

receptors located throughout the body, including in the skin, muscles,

joints, and viscera; these receptors are responsible for perceiving

unpleasant stimuli. When stimulated, the nociceptors transmit signals

of pain to the brain via the spinal cord. When the brain perceives the

pain, the reaction can be affected by various factors, including a

person’s genetic composition, personal beliefs about pain, and level of


cognition, among other items. This is why people experience pain

differently and a painful event for one person may be perceived as

excruciating, while the same type of pain causes moderate discomfort

in someone else.

Analgesics are given primarily for the control of pain; there are a

variety of analgesics available on the market and some drugs have

been found to be more beneficial for certain types of pain than others.

For example, non-steroidal anti-inflammatory drugs (NSAIDs) are

beneficial in relieving pain of inflammation, but they also can be

helpful for controlling the pain of muscle cramps.

When tissue damage occurs, the body releases inflammatory

mediators in response. These mediators, including bradykinin,

cytokines, and prostaglandins, can also stimulate nociceptors to send a

signal about pain, which is why inflammation can also be painful for

the affected person. Some drugs are specifically designed to reduce

this pain associated with inflammation, such as inflammatory pain in

the joints because of arthritis. For example, the non-opioid drug

ibuprofen is often used to manage pain and inflammation; it may be

given intravenously, known as Caldolor®. Additionally, some opioids

also affect peripheral nerve receptors and may reduce inflammation,

and these drugs may be more appropriate in cases of severe pain.

Many studies have shown that pain is a very common element

associated with time spent in the ICU and that most patients who

receive intensive care treatment experience pain. Analgesic

medications are therefore significant as part of the overall treatment

plan for many patients receiving emergency and critical care. Ayasrah,


et al., in the International Journal of Health Sciences state that

inadequate pain assessment and treatment is associated with an

increased morbidity and mortality for the patient in the ICU.80 When

time in the critical care environment is extensive and the patient

suffers from poor pain control, he is more likely to experience

complications, necessitating further treatment and resulting in a longer

length of hospital stay. Additionally, patients in the ICU who

experience ongoing, untreated pain are at greater risk of experiencing

distress and discomfort, resulting in post-traumatic stress.11 Routine

assessment of the patient’s pain, from the first contact while providing

emergency care and throughout the patient’s hospital stay is essential

for controlling comfort levels and preventing further complications.

Opioids vs. Non-Opioids

Analgesics are typically classified as being either opioids or non-

opioids, based on whether they contain a natural or synthetic extract

from the opium poppy. Opiates are drugs that are directly derived

from opium extract; opioids are technically the synthetic versions of

opiates in that they produce the same effects and are chemically

similar but not entirely the same. The term “opioid” is now used to

describe both the synthetic and natural versions of these drugs. They

may also be referred to as “narcotics” because of their effects, but

keep in mind that this word also is used to describe illicit drugs that

have no medical value but that produce some of the same effect as

opioids.

Opioids are used to treat moderate to severe pain; they may be given

on a short-term basis in cases of acute pain, but they can also be

prescribed for long-term use for cases in which a patient is


experiencing chronic pain, such as with cancer. Opioids may be

classified as being short-acting or long-acting medications; the

healthcare provider should prescribe and schedule these drugs

accordingly, based on the patient’s condition and whether he requires

immediate pain relief for acute pain, such as within the emergency

department, or whether the patient is suffering from ongoing pain.

Short-acting opioid medications include morphine (Roxanol®),

oxycodone (Oxycontin®), hydromorphone (Dilaudid®), and

hydrocodone (Vicodin®, Norco®). Long-acting opioids include fentanyl

(Duragesic® patch), as well as morphine and oxycodone.28

As with sedatives, opioids are classified according to the Schedule of

Controlled Substances because of their powerful effects and potential

for misuse. In addition to their analgesic effects, opioids can cause

mood changes and alterations in levels of consciousness. Some

patients are at higher risk of physical dependence and abuse of opioids

because of these effects. Additionally, because pain is affected by a

number of factors within each person, including personal response to

painful stimuli and emotional reactions associated with pain, the

effects of opioids can be somewhat sedating and can induce calm in

the patient, which may regulate some of his emotional responses to

the pain.

Opioids work in both the central and peripheral nervous systems by

acting on opioid receptors found in the cell membranes of neurons.

There are four main types of opioid receptors: the mu opioid receptor

(MOP), the kappa opioid peptide receptor (KOP), the delta opioid

receptor (DOP), and the nociceptin orphanin FQ peptide receptor

(NOP), located in various areas of the brain and in the spinal cord. The


different opioids available have affinities for the various opioid receptor

sites; for example, morphine has a high affinity for the MOP, but less

so for KOP or DOP. When an opioid medication is given and it binds to

one of these receptors, it can inhibit the release of some

neurotransmitters as well as by inhibiting the transmission of pain

information released from sensory neurons. This complex process can

occur very quickly following the administration of opioid analgesics,

particularly when the drugs are given intravenously.

Once administered, opioids can exert pain-control effects rather

quickly, depending on the route of administration. It is estimated that

when given intravenously, opioids can peak in their pain control within

10 minutes of administration. When given as an intramuscular

injection, effects typically occur within 30 to 45 minutes, while effects

occur within 60 to 90 minutes after oral administration because of the

extra time that it takes for absorption of the drug into circulation.28

In contrast to opioid analgesics, non-opioid drugs may be given in

cases where the patient is experiencing mild or moderate pain. They

may be administered to control acute pain or may be given on a long-

term basis for chronic pain, depending on patient circumstances.

Additionally, non-opioid analgesics may be the sole drug given for pain

control when it is mild, but they are also beneficial as adjuvant

medications when given with opioids for cases of severe pain. Many

non-opioid analgesics are also effective in relieving inflammation and

swelling. Non-steroidal anti-inflammatory drugs such as ibuprofen or

ketorolac are examples of non-opioid analgesics that control pain and

inflammation. Acetaminophen is another type of non-opioid analgesic


that is commonly administered for mild pain and is particularly useful

in cases of musculoskeletal pain or with minor injuries.

Two types of non-opioid analgesics, salicylates and non-salicylates,

comprise a large number of these drugs. Salicylates come from

salicylic acid, and work to reduce fever and inflammation in addition to

controlling pain. Examples of salicylates include aspirin and

magnesium salicylate (Doan’s® Pills). Salicylates exert their effects by

inhibiting prostaglandins, which decreases the sensation of pain and

alleviates some inflammation. They also have vasodilatory effects, and

some salicylates, particularly aspirin, prevent platelet aggregation, so

they may be prescribed for prevention of blood clots.

Non-salicylates typically have similar abilities as salicylate medications

in that they reduce fever and control mild pain. The most commonly

used non-salicylate medication is acetaminophen, which may be used

among patients who otherwise do not tolerate salicylate medications,

those who have bleeding tendencies, and children. Acetaminophen

also exerts its effects to control pain and fever by reducing synthesis

of prostaglandins, although its exact mechanism of action is still

unclear.29

Non-opioid drugs such as NSAIDs control elements such as pain,

inflammation, and fever by inhibiting cyclooxygenase (COX), which is

an enzyme that promotes the conversion of some substances within

cell walls into prostaglandins that can cause pain, fever, and

inflammation. Note that aspirin, while classified as a salicylate

medication is also considered to be an NSAID. Other examples of

these drugs include celecoxib (Celebrex®), ibuprofen (Advil®,


Motrin®), naproxen (Aleve®, Naprosyn®), and indomethacin

(Indocin®).

Non-opioid analgesics also differ from opioids in that they do not

produce the same side effects of drowsiness or euphoria and they do

not lead to tolerance and addiction. Non-opioid analgesics are not

listed in the Schedule of Controlled Substances and are considered to

be very safe, such that while a healthcare provider may administer

them within the hospital, they can also be purchased without a

prescription.

Analgesics should not be used unless the patient’s comfort level has

been adequately assessed. Monitoring of patient comfort levels is an

ongoing process that involves assessing the patient’s level of pain prior

to giving medication, selecting the most appropriate analgesic for the

patient’s level and intensity of pain, administering the medication

through the correct route and at the correct rate, and continuing to

assess the patient following drug administration to ensure the drug’s

effectiveness.

It may be difficult to adequately assess patient pain, particularly if the

individual has an altered level of consciousness or has difficulty

communicating because of medical equipment. Changes in vital signs,

as evidenced by an increase in heart rate or blood pressure, were once

standard options for assessing pain in the nonverbal patient, but vital

sign changes are no longer considered accurate measures of pain

assessment. Instead, there are several tools that clinicians can

implement to assess pain in the patient who is nonverbal or otherwise


unable to communicate his discomfort. Examples include the

Behavioral Pain Scale and the Critical Care Pain Observation Tool.

Additionally, some critical care patients may have difficulty explaining

the extent and intensity of their pain if they have been given other

drugs to combat their immediate issues. For example, a patient who

has been given sedative medications to control anxiety just prior to

undergoing a procedure may experience changes in his level of

consciousness because of the sedation but he is still experiencing pain.

Still, the healthcare provider in this situation may have a difficult time

determining the extent of his pain and may rationalize that because

the patient is sedated, he is comfortable. This further emphasizes the

critical need for using a pain observation tool if the patient is non-

verbal, even if he has received another type of medication. Continuous

and ongoing assessment of the patient’s behavior and signs or

symptoms of distress is the only way to determine whether further

analgesia is needed.

For patients who can talk and express how they are feeling, use of a

scale, such as a 0 – 10 pain intensity rating, is valuable in assessing

the patient’s level of comfort. The patient may rate his pain on a scale

of 0 to 10, with 0 describing “no pain” and 10 being “the worst pain

imaginable”. This type of intensity rate helps the healthcare provider

to better determine the type of analgesia to use and how much to

give. The patient may be asked again approximately 30 minutes after

receiving the medication to clarify whether the medication is

controlling his pain or if he needs another dose. While the best method

of assessing for pain is through patient self-reporting, there are

obvious times when the patient cannot communicate verbally, such as


with mechanical ventilation or with altered levels of consciousness, and

the caregiver must rely on other cues that signify pain. Utilizing

assessment tools that evaluate patient pain are essential for those

individuals who cannot verbalize or communicate.

A tool designed specifically to assess pain among patients in the

critical care environment is the Critical Care Pain Observation Tool

(CPOT), which can be used quickly and easily and which assesses the

patient’s behaviors that would indicate the presence of pain. The

clinician assesses the indicators of facial expression and whether the

patient appears relaxed, tense, or is grimacing; body movements, in

which the patient may demonstrate agitation and restlessness,

cautious and protective movements, or the absence of movement; and

muscle tension, in which the patient may appear relaxed, tense or

rigid, or may demonstrate a strong resistance to any sort of

movement. Additionally, the CPOT assesses patient vocalization if he is

not intubated, including talking, crying, or sobbing; if the patient is

intubated, the tool assesses for ventilator compliance, and whether he

is tolerating the ventilator, coughing, or fighting ventilation.31

Each patient behavior is given a score from 0 to 2; the highest total

score is 8 points. The closer to a score of 8 that a patient receives

indicates greater pain levels and an increased need for analgesia. To

use the CPOT, the patient should first have a baseline assessment in

which he is observed at rest for one minute. When considering

analgesia use, the patient should then be evaluated during any

procedure that could potentially cause pain, such as with endotracheal

suctioning, turning, or with dressing changes; depending on the

patient’s response, analgesic medications should be administered


according to their prescribed route and time. The caregiver should

then assess the patient both before and at the time of the peak effect

of the analgesic to determine the drug’s overall effectiveness in

relieving the patient’s pain.

The Behavioral Pain Scale (BPS) is another method of assessing for

pain or discomfort among patients who are in the ICU and who cannot

vocalize or communicate how much pain they are experiencing. The

BPS is also a scoring system that considers the patient’s facial

expression and whether it is relaxed, tightened, or grimacing; upper

limb movements, with scoring ranging from being relaxed to slightly

flexed to permanently retracted; and ventilator compliance, which can

include total compliance and relaxation to coughing to fighting the

ventilator and causing asynchrony.32 The BPS is often a simpler

method to use and can be employed quickly and effectively; it is

commonly reserved for intubated patients who have no verbal

communication. Each item on the scale is scored to quantify how much

pain the patient is experiencing so as to guide analgesia use.

Administration of analgesic medications is a common practice in critical

care; based on the numbers of patients in the ICU who experience

some amount of pain during their stay, the probability that a nurse will

need to administer analgesics in this area is quite high. It is therefore

very important to remain familiar with the most common types of pain

medications, as well as their usual routes of administration, common

side effects, and mechanisms of action. By understanding these

principles, the caregiver will be better able to recognize the most

appropriate medication to give in each situation and to maintain the

patient’s comfort.


Paralytic Medications

Paralytic medications are used in the critical care environment to

induce such deep muscle relaxation that the individual is unable to

move. Also known as neuromuscular blocking agents because of their

mechanisms of action, paralytic drugs may be administered during

surgery or short-term procedures to prevent the patient from moving,

they may be given to those who require mechanical ventilation, or

they may be utilized in cases where it is important that the patient

remain still during treatment, such as when an individual has

increased intracranial pressure.

Neuromuscular blocking agents are typically classified as one of two

types: depolarizing agents or non-depolarizing agents. The drugs work

on nicotinic acetylcholine receptors at the post-synaptic junction of

nerve impulses. One of the only depolarizing drugs in current use is

succinylcholine, which works to cause significant muscle relaxation by

acting as an agonist at the nicotinic receptor site. Succinylcholine is

made up of two acetylcholine molecules and when these bind to the

receptor site, they act in the same way, but with a longer duration

than acetylcholine. Acetylcholine is normally metabolized by

acetylcholinesterase however succinylcholine is not. This leads to

depolarization of the membrane, in which there is a shift in the electric

charge within the cell and it temporarily becomes more positive. This

shift causes an initial rapid muscle contraction, but the membrane

potential must be reset before depolarization occurs again. The

muscles then become slack and remain so through the length of the

effects of the drug.17


Succinylcholine is administered as an intravenous infusion and its

effects of neuromuscular blockade are quite rapid. When used,

succinylcholine may be infused for very short periods, such as during a

brief treatment or procedure that only lasts a few minutes. However,

use of depolarizing agents in critical care is becoming less common

because of the risk of certain complications, including malignant

hyperthermia as well as hypokalemia.18 Because it causes complete

muscle paralysis, succinylcholine should always be administered with a

sedative agent that will induce unconsciousness.

In contrast to depolarizing neuromuscular blockade agents, non-

depolarizing agents work in a slightly different manner. Non-

depolarizing agents act as antagonists to the acetylcholine receptor

sites. With administration, they competitively bind to acetylcholine

receptors and prevent depolarization from occurring. Because

acetylcholine is responsible for skeletal muscle contractions, the

patient will develop flaccid paralysis when acetylcholine is blocked

from its receptor sites. In order to stop the effects of non-depolarizing

blockade, either the drug must be metabolized and excreted from the

body without adding a further dose, or a reversal agent may be given

to stop the effects. Typically, this is an anticholinesterase drug such as

neostigmine.

Non-depolarizing agents are further divided into two types:

benzylisoquinolinium compounds and aminosteroid compounds.

Benzylisoquinolinium drugs are made up of short chains of ammonia

molecules that can cause histamine release when they break down in

the bloodstream. Examples of these types of paralytics include

atracurium and cisatracurium.


Aminosteroid compounds consist of one or more ammonia groups

connected to a steroid. They typically do not cause a release of

histamine, which may otherwise cause hypotension and tachycardia.

Some types of aminosteroid compounds include pancuronium and

vecuronium.18

Neuromuscular blockade through the use of paralytics is often

warranted in critical care, particularly in cases where a patient is

undergoing a procedure where excess movement would otherwise be

detrimental. Inducing paralysis must be done for some patients to

uphold their safety and to support their treatment, even if the process

is frightening. In order to maintain patient safety and comfort,

paralytic drugs must always be administered with concomitant

sedatives or anesthesia to avoid awareness or memory of the event.

Purpose

Neuromuscular blocking agents are primarily used when skeletal

muscle paralysis would most benefit the patient. The administration of

these drugs is significant and is not taken lightly; rather, each

situation in which paralytic drugs may be valuable should be

thoroughly assessed for the risks and benefits to the patient, and the

most appropriate type of drug selected based on its duration of action

and overall patient outcomes.

Paralytic drugs are given in many varied situations. During anesthesia

induction for surgery, a patient is often given a paralytic along with a

sedative or induction agent to cause muscle relaxation and sedation.

Paralytics are sometimes administered to patients who have severe

neurologic conditions that cause significant muscle twitching or


spasticity. These drugs are also often administered just prior to

endotracheal intubation to prevent the patient from moving during the

procedure and possibly making the process much more difficult. For

many people, the introduction of a tracheal tube is frightening and

painful and it is a natural response to attempt to block the procedure.

The administration of a neuromuscular blocking agent causes such

muscle relaxation in the patient that the healthcare provider can

complete the intubation much more rapidly when the patient is not

struggling. Additionally, the muscles of the respiratory system and the

vocal cords are relaxed after paralytic administration, making

endotracheal intubation easier with a decreased risk of tissue trauma

with introduction of the tube.

Use of paralytic agents is also commonly associated with mechanical

ventilation of patients, and in these cases, the drugs are administered

over longer periods during the time that ventilation is required. While

this is not its primary purpose, administration of paralytics can be a

practical measure when working with patients who are intubated to

prevent excess movement and possible tube dislodgement. Studies

have shown that of healthcare providers who administer paralytic

agents among patients who require mechanical ventilation, the main

reasons for administration were to combat asynchrony between a

patient’s breathing and ventilator rate, to prevent poor patient

compliance with the ventilator, to reduce patient hypercapnia, and to

inhibit patient hypoxemia.18

Within the ICU, neuromuscular blocking agents have also been

employed for other common reasons, including the control of

intracranial pressure, control of patient agitation and aggression, and


to decrease a patient’s metabolic demand when extremely ill.18 Use of

paralytic agents may facilitate improved oxygenation in some patients,

particularly if the person is otherwise agitated and requires

supplemental oxygen or mechanical ventilation. Induced paralysis,

combined with sedation, reduces the patient’s muscle activity levels

and decreases oxygen consumption.

A study by Price, et al., in the Annals of Intensive Care showed that

use of neuromuscular blocking agents is beneficial among patients

diagnosed with acute respiratory distress syndrome (ARDS). The study

showed that patients with ARDS who received paralytics experienced

improved oxygenation, as evidenced by a decrease in oxygen

requirements and a decrease in lung trauma often associated with

mechanical ventilation. Additionally, the patients showed a statistically

significant decrease in the amount of inflammatory markers present,

including interleukin, which demonstrates that these patients have a

decreased inflammatory response and a potentially improved overall

mortality after a diagnosis of ARDS.18

Research continues about other possible benefits of using paralytics as

part of treatment in the critical care setting. When protocols are in

place that guide and shape their use, paralytics can be safely

administered and may prevent some potentially significant

complications that would otherwise develop because of patient

agitation and distress.

Complications

Use of paralytic agents is not without the potential for complications,

as has been seen across many groups of patients to whom these drugs


are given. Although the neuromuscular blocking effects of these drugs

can better facilitate completion of some procedures, there are

drawbacks to inducing paralysis, some of which may be widespread

and can affect major body systems. Use of paralytics requires

continuous monitoring to observe for complications and to closely

track the patient’s clinical status.

Paralytics cause complete muscle relaxation and paralysis that affects

all muscle groups, including the muscles required for breathing. As a

result, the patient who has been given neuromuscular blocking

medications will be unable to breathe on his own. Most people who are

given paralytic medications require breathing assistance, often through

endotracheal intubation and mechanical ventilation. The inability to

breathe spontaneously and the subsequent need for mechanical

ventilation can lead to a number of respiratory problems, including

barotrauma and ventilator-associated lung injury.

Additionally, because paralytic agents prevent the use of the

respiratory muscles to breathe, the patient also typically lacks the

effective mechanisms of protecting his own airway. Normally, the gag

reflex is present in conscious patients, as well as the routine ability to

swallow. The body normally prevents food and mucus from being

aspirated, but when the muscles are paralyzed, the patient no longer

has this capacity. The gag and swallowing reflexes are not present and

the vocal cords are paralyzed. This can increase the patient’s risk of

aspiration of mucus or stomach contents into the lungs, which can lead

to decreased oxygenation and aspiration pneumonia.


In addition to the possible respiratory complications associated with

neuromuscular blockade, there are some concerns that paralytic

agents increase the risk of patients developing critical illness

polyneuropathy (CIP), a disease state in which a patient is weakened

and suffers from long-term muscle paralysis. The condition is most

often seen following a period where a person spent time in the ICU

and may have received paralytic drugs. CIP causes the muscles to

become flaccid and the patient is often too weak to move, even though

he is no longer receiving paralytics; he may experience paralysis of

certain muscle groups and if intubated, may have difficulties being

weaned off the ventilator due to weakness or paralysis of the

respiratory muscles.19

There have been concerns that prolonged use of neuromuscular

blocking agents contributes to the development of CIP, since the

repeated administration of these drugs and the prolonged, induced

state of muscle paralysis seem to increase the risk of neuromuscular

damage that causes symptoms of CIP. The increased risk seems to be

more commonly associated with aminosteroid drugs instead of

benzylisoquinolinium compounds. Use of paralytics for an extended

period does carry higher risks of complications when compared to the

limited use of these drugs, but research has not shown that use of

neuromuscular blocking agents for less than 48 hours prevents CIP.18

Regardless, clinicians who use paralytic drugs with their patients must

be familiar with the potential for development of CIP and be on guard

to prevent potentially irreversible damage.

As discussed, neuromuscular blocking agents can be beneficial among

patients diagnosed with ARDS, which occurs as fluid build up in the


lungs that significantly compromises breathing and oxygenation in

critically ill patients. Although paralytics have been shown to be

valuable when used as part of ARDS management, there is also some

evidence that they may contribute to pulmonary complications,

particularly during the post-operative period. Many patients receive

paralytic drugs with sedation during surgery so that they will not move

during the procedure. A study by McLean, et al., in the journal

Anesthesiology showed that the use of neuromuscular blocking agents

was associated with an increase in respiratory complications, including

pulmonary edema, respiratory failure, pneumonia, and reintubation.

The study showed that the increase in complications was dose

dependent, in that larger doses of paralytics contribute to greater risks

of complications. However, proper training in the administration of

paralytic drugs and thorough monitoring throughout their use may

diminish some of these risks.20

Other potential complications found to be associated with paralytic

drugs stem from the lack of movement on the patient’s part. When a

person receives a neuromuscular blocking agent, all body systems

must be closely monitored to prevent some of the consequences of

immobility. For example, a patient who is paralyzed cannot turn

himself while in bed and is at risk of skin breakdown, particularly on

areas where there are bony prominences. Lack of movement can lead

to sluggish circulation and an increased risk of deep vein thrombosis.

All patients who are paralyzed need regular eye care and to have the

eyelids closed to prevent drying on the surface of the eye and possible

corneal abrasions.


One of the more disturbing complications that may develop with the

use of paralytic medications is anesthesia awareness, in which a

patient has not been given enough sedative or anesthetic medications

with the neuromuscular blocking agents and is awake and aware of his

surroundings. Due to the neuromuscular weakness and paralysis

involved with these medications, the patient is unable to notify

personnel or even move at all and may remain awake during painful

and frightening procedures. The development of awareness during

such procedures as surgery, while undergoing painful treatments, or

utilizing mechanical ventilation has been described as terrifying by

those who have endured these processes and were unable to move or

speak about what was happening.

While awareness occurs infrequently in most patient care situations, it

is a potential complication that must be considered when administering

paralytics. Situations in which a patient is more likely to experience

awareness include the excessive use of paralytic drugs, a history of

drug addiction in the patient, failure of one or more medical devices

being used for patient care, and inappropriate monitoring techniques.21

Not all patients who experience awareness with paralytics will have the

same feelings. Some people have memories of the time of being

awake or undergoing a procedure but they do not feel pain. There are

some people who also experience an altered level of consciousness in

that they are not fully awake; their encounter is more like that of a

dream in which they are aware of their surroundings but their memory

of the event is inconsistent.

The best methods of guarding against awareness in the patient who

requires paralytic medications is to evaluate the patient’s medical


history, provide the appropriate amount of neuromuscular blockade in

combination with analgesia and sedative medications, and to

continuously monitor the patient throughout the entire time that he

receives these types of medications. The patient’s medical history may

indicate a condition that could increase the risk of awareness with

procedures. A patient with a history of drug abuse may require larger

amounts of medications to elicit a therapeutic effect if he has

developed a tolerance for some kinds of drugs. Patients who take beta

blockers for hypertension are at greater risk of awareness if they

receive low doses of general anesthetic to avoid hypotension.21 As

stated, all patients who receive neuromuscular blocking agents require

concomitant use of medications that induce amnesia, analgesia, and

sedation to avoid development of awareness; appropriate monitoring

techniques for patients receiving paralytic agents are essential in

inducing muscular weakness and paralysis while avoiding other

complications.

Monitoring

Paralytics must always be administered with sedative drugs to calm

the patient and to induce sleep. Paralytics can work without the use of

sedatives and will still cause muscle paralysis. Without the use of

sedatives, the patient would remain awake but would be unable to

move. This is particularly traumatizing for anyone undergoing a

medical procedure and should be avoided as much as possible. The

clinician caring for the patient who receives paralytics must continue to

monitor his level of consciousness to ensure that he is sedated while

paralysis is in effect.


When paralytic drugs are administered continuously, their rate of

administration and depth of paralysis must also be analyzed and

monitored frequently. This can be challenging, particularly when other

drugs are also exerting their effects. However, part of the process of

monitoring paralytic use is to ensure that the patient receives the right

amount of the drug. There is a distinct balance in providing

neuromuscular blockade so that the individual does not receive so

much that the effects are long lasting and there is no ability to move,

versus too little of the drug, in which the patient has purposeful

movements that could be disruptive toward his treatment.

There are various methods of analyzing whether a patient is receiving

the right amount of neuromuscular blocking agents. One method often

employed is known as the ‘train of four’, which is a process in which a

healthcare clinician applies a nerve stimulator to the patient’s skin to

test nerve function. The train of four process can help the clinician to

determine whether the patient is receiving too much of the paralytic

and also if he is not getting enough. To accurately perform the train of

four, the clinician must first have a baseline measurement of the

patient’s nerve function; this involves testing nerve function prior to

administration of any neuromuscular blocking agents. In cases of

emergency when the paralytic drugs are administered quickly, a

baseline measurement may not be available.

Having a baseline measurement helps the provider to better know how

much nerve stimulation to apply when performing the train of four.

The caregiver applies electrodes connected to a nerve stimulator on

the skin near a specific nerve, such as the median or the ulnar nerves.

The machine is set to a low level of impulse delivery and it gives the


electrical stimulus four times in a row. These mild shocks should

stimulate the nearby nerve and cause the muscles to twitch or spasm.

For example, when assessing the ulnar nerve, the electrodes would be

placed on the patient’s forearm. When delivering the four impulses,

one or more of the patient’s fingers may twitch slightly in response to

the stimulation.

The patient is said to have an adequate amount of paralytic

medications on board if his muscles twitch twice out of the four

impulses. If the muscles twitch more than twice out of four impulses,

the patient may need more medication because his muscles do not

appear to be paralyzed. Alternatively, if the patient’s muscles do not

respond to any of the impulses given, he may have been receiving too

much of the paralytic drugs to the point that he is unresponsive.16 The

drugs may be titrated to increase or decrease the dose depending on

the patient’s response to the nerve stimulation, however, each facility

that administers neuromuscular blocking agents should have a

protocol in place for monitoring paralytic use and assessing

responsiveness.

Monitoring use of paralytics through such practices as the train of four

is useful in determining the right balance of what the patient needs for

neuromuscular blockade. When giving these drugs, it is always better

to administer the least amount necessary to induce paralysis, rather

than exceeding the minimum dose and giving too much at once. It

should be noted that not all patients respond to paralytic drugs in the

same way. While monitoring techniques are similar between patients,

each person often requires a different dose and may need more or less

of the drug to achieve adequate paralysis. While there is a range of


acceptable doses and the amounts to give have limits, clinicians

administering paralytics should be aware that patients often require

different amounts and should titrate accordingly. Because of these

differences, it is extremely important to be familiar with the process of

administration, the appropriate methods of monitoring paralysis, and

the effects of monitoring outcomes on medication titration to ensure

the utmost safety for these patients.

Vasopressor Drugs

Vasopressor drugs, commonly referred to as pressors, act on the

circulatory system to improve the overall tone of the blood vessels.

Generally, pressors are administered to increase blood pressure,

particularly in cases where a patient is suffering from hypotension and

poor perfusion and is at risk of developing shock.

Shock occurs when the organs and tissues do not receive as much

blood as they need. All areas of the body have their own metabolic

requirements to continue working properly and they require a certain

amount of blood perfused through the circulatory system. When blood

flow is inadequate, such as because of very low blood pressure,

significant bleeding, abnormal cardiac activity, or an obstruction

somewhere within the circulatory system, the major organs cannot

continue to work in a normal manner and they can develop hypoxia

and eventual ischemia from a lack of blood flow. When this occurs, the

organs shut down from tissue damage and cell death occurs. The cells

of the peripheral tissues, in order to try to maintain metabolic

demands, utilize anaerobic respiration to make energy. This process

creates more carbon dioxide and puts the body into a state of

metabolic acidosis. The progression takes on a cyclical nature in that


increasing acidosis contributes to a worsening of blood pressure and

the affected patient remains hypotensive.22

There are several types of shock that may develop within the critically

ill patient; kinds of shock are typically classified according to their

causes. A patient who needs aggressive treatment for low blood

pressure that causes shock may be suffering from one of three main

types: cardiogenic shock, hypovolemic shock, or septic shock.

Cardiogenic shock develops when the organs do not receive adequate

perfusion because of inadequate cardiac output. The cause of the

decreased cardiac output is usually due to one or more problems with

the heart, including myocardial infarction, cardiac tamponade,

inflammatory myocarditis; valve disorders, including mitral

regurgitation, or cardiac arrhythmia. It may also develop as a result of

ineffective respiratory function that impairs blood flow to the heart,

leading to decreased output and circulation, such as in cases of

pulmonary embolism or drug overdose. An individual who has

developed cardiogenic shock will exhibit significant hypotension,

evidenced by low systolic blood pressure levels and the need for

vasopressor medications to maintain adequate blood pressure;

elevated left-ventricular filling pressures or pulmonary congestion; and

clinical signs of poor organ perfusion, evidenced by pale, clammy skin;

decreased urine output, or altered mental status.81

Cardiogenic shock originally develops due to tissue ischemia from poor

cardiac output, which leads to a cycle of decreased cardiac

contractility, hypotension, and then further tissue ischemia. The

cardiac compromise eventually impacts the entire circulatory system


to the distal capillary beds. Poor perfusion of tissues may lead to

systemic inflammation and capillary vessel leakage. Approximately 80

percent of cases of cardiogenic shock originally stem from myocardial

infarction. The condition can have up to a 50 percent mortality rate.81

The treatment involves improving blood flow by relieving obstructions

in the blood vessels that originally contributed to early ischemia, such

as through percutaneous coronary intervention as treatment of

stenotic coronary vessels.

Typically, a combination of medications and interventions is needed to

control cardiogenic shock and to prevent deterioration of the patient’s

clinical condition. Blood clot development, such as that which causes

pulmonary embolism leading to cardiogenic shock is often treated

through thrombolytic therapy. The patient often requires medications

that improve cardiac contractility and that further cardiac output while

simultaneously increasing blood pressure levels to facilitate perfusion.

Other medical procedures may also be implemented, including

administration of fluids and electrolytes, management of cardiac

arrhythmias, revascularization through surgery, or left-ventricular

support.

Hypovolemic shock describes a state in which there is severely

inadequate tissue perfusion due to a low volume of blood within the

cardiovascular system. The low blood volume is often due to

hemorrhage, and bleeding may be internal or external. Excessive

bleeding is often seen following traumatic injury, but it may also occur

after surgery. Patients who have suffered severe burns are also at risk

of hypovolemia due to loss of plasma volume. Some people who

experience severe vomiting or diarrhea may develop hypovolemia as a


result of shifts in electrolyte levels in circulation. The patient with

hypovolemic shock typically exhibits a very low blood pressure, and

increased heart rate with a thready pulse. Additional signs or

symptoms often include hyperventilation, pallor, and mental status

changes.82

The main goals of treatment of hypovolemic shock are to restore some

of the circulatory volume to be able to provide adequate blood

perfusion to pertinent organs and tissues. This process often involves

fluid resuscitation through rapid administration of crystalloid solutions,

repletion of oxygenated blood volume through administration of blood

products, and the use of medications such as vasopressors to improve

blood pressure. The administration of vasopressor medications is not

indicated until the circulatory volume has been at least partially

restored. In the case of hemorrhagic shock, in which a patient

experiences hypovolemic shock due to blood loss, a research review by

Beloncle, et al., in the Annals of Intensive Care showed that most

experimental data do not indicate the administration of vasopressors

early during treatment and that vasopressors should not be used in

place of fluid resuscitation.83 Further, use of vasopressors too early

during treatment of hemorrhagic shock when the patient has otherwise

not received appropriate fluid resuscitation is associated with an

increased risk of patient mortality.84 Alternatively, once a patient who

is experiencing shock has had cardiovascular volume repletion through

fluid resuscitation, vasopressor medications can be therapeutically

effective in stabilizing blood pressure so that the blood volume that is

available can be better perfused to vital organs.


Septic shock is a specific type of shock that develops following

infection. Sepsis describes a condition in which the organs are

inadequately perfused because of the effects of infection; septic shock

can then develop when perfusion is so limited that the patient

develops organ failure. In the United States, severe sepsis accounts

for 10 percent of all hospital ICU admissions.85 A patient with septic

shock typically exhibits dangerously low blood pressure and often has

an altered mental status. The skin is often cool and clammy and pallor

is present. The rate of progression from severe sepsis to septic shock

may depend on several factors, including the type of causative

infection and the presence of underlying illness in the patient. The

condition can become rapidly fatal if not promptly recognized and

treated.

Initial treatment involves fluid resuscitation, however, one of the

hallmarks of septic shock is that the condition often does not respond

to rapid fluid administration. Vasopressors are often added as part of

treatment when the patient continues to have significant hypotension

despite fluid administration. Vasopressor therapy, including

administration of norepinephrine or epinephrine, can be given

simultaneously with fluids. According to the Surviving Sepsis

Campaign, norepinephrine is the vasopressor of choice to use for

hypotension treatment associated with septic shock, and vasopressin,

given at a low dose concomitantly with norepinephrine can be added to

increase the patient’s mean arterial pressure.86 Additional measures

utilized in the treatment of septic shock may include the administration

of blood products, inotropic therapy to improve cardiac output, and

antimicrobial therapy to control the infection. Many patients with this

type of shock also need mechanical ventilation, insulin administration


for unstable blood glucose levels, and ongoing sedation and analgesia

to maintain comfort.

Vasopressors stimulate adrenergic receptors to improve the tone of

the blood vessels and to cause vasoconstriction, thereby improving

blood pressure and circulation through increased pulmonary vascular

resistance. There are different types of receptors as well as different

kinds of vasopressors. When given, a vasopressor may act as a

receptor agonist or an antagonist to exert its effects. These

baroreceptors are found within the walls of the blood vessels and they

constantly monitor blood pressure and send messages to the brain to

help maintain a normal pressure balance.

The exact hemodynamic responses following administration of pressors

can vary slightly, depending on the drug and its dose, as well as the

patient’s condition. The variations develop because of some of the

differences of the effects on the receptors between the drugs. Some

examples of vasopressors that may be given for management of shock

states among patients in critical care include norepinephrine,

metaraminol bitartrate, and vasopressin. In order to facilitate the best

outcomes among individual patients, selection and use of vasopressors

requires careful monitoring and observation.

Purpose

The main purpose of pressors is to improve the blood circulation of

patients and increase hemodynamic stability. Pressors are most often

given to patients who are hemodynamically unstable in that they have

abnormally low blood pressure and are at risk of shock. Administering

pressors in these situations can cause the blood vessels to constrict


and can help to stabilize blood pressure. When a patient is brought to

the emergency room or is in the ICU and has low blood pressure and

such poor perfusion that he is unable to meet metabolic demands, he

is at risk of a potentially irreversible state of shock and organ damage.

In emergent cases, pressors can be rapidly administered to improve

blood pressure and organ perfusion.

Because pressors are most often given in cases where a patient has

significant hypotension, they may be considered as an early form of

therapeutic treatment to correct hypotension and to prevent tissue

ischemia from a lack of blood flow. However, in cases where patients

are seen with hypotension due to low circulatory volume, such as in

cases of massive blood loss, the individual first requires fluid

resuscitation to correct some of the circulatory volume before

administration of pressors can be considered.

As discussed, vasopressors are often necessary and beneficial, but

guidelines typically recommend that they are initiated once fluid

resuscitation has been started.40 Vasopressors, while powerful in their

effects, could lead to a reduction in blood flow and subsequent

ischemia in other parts of the body. Additionally, when there is

massive fluid loss, such as in the case of hypovolemic shock,

constriction of the blood vessels will not necessarily impact blood

pressure when fluid volume is too low to begin with. Fluid volume

levels must first be corrected enough that vasoconstriction will work in

conjunction with blood flow to correct blood pressure.

Pressors can also be beneficial in protecting blood pressure levels

when extra volumes of fluid are not necessary or would actually be


detrimental to the patient’s care. In some cases where hypotension

occurs that is not necessarily related to volume depletion, rapid

administration of large amounts of fluid is not warranted. In fact, there

are some cases where fluid resuscitation may be injurious to the

patient’s condition when extra volume is not needed, as too much fluid

can promote edema and may damage pulmonary function.40

Pressors improve blood pressure by increasing systemic vascular

resistance (SVR), which describes how much the blood vessels comply

with or constrict against blood flow. This increase then raises arterial

blood pressure. The mean arterial blood pressure (MAP) describes the

relationship between cardiac output and SVR; if the MAP is low, then

the vital organs are not being well perfused, and if the MAP is too high,

it indicates that the heart may be working too hard. In addition to

causing vasoconstriction to improve blood pressure, some pressors

increase cardiac contractility to promote cardiac output. When pressors

stimulate alpha-1 receptors, they improve blood pressure and increase

SVR, and when they stimulate beta-1 receptors, they increase the

heart rate and cardiac contractility.

Some drugs that are considered vasopressin analogs may also be used

for vasoconstriction when given in larger amounts. Vasopressin, also

known as antidiuretic hormone, is a specific hormone normally found

in the hypothalamus. It acts on particular vasopressin (V) receptors to

exert its effects, including V1, V2, and V3 receptors. V1 receptors are

found in smooth muscles of the blood vessels, as well as in the

kidneys, hepatocytes, platelets, and spleen and they control

vasoconstriction. V2 receptors are mainly found in the kidneys and

they exert antidiuretic effects. V3 receptors play a role in temperature


regulation and memory and are primarily located in the pituitary

gland.88

Vasopressin, through its antidiuretic effects, reduces urine output by

helping the kidneys to reabsorb water. During cases of hypovolemia,

vasopressin can help to control further volume loss by exerting

antidiuretic effects; the body often naturally releases antidiuretic

hormone in response to a drop in blood volume anyway, such as with

the case of dehydration or hypotension. Vasopressin acts in the same

manner as anti-diuretic hormone except that it is a synthetic version.

Research regarding the effects and timing of administration of pressors

is ongoing and over time, guidelines as to the type and amount of

pressors to give in cases of shock have evolved. The health clinician

who works with critical care patients who are experiencing any type of

shock and who have severe hypotension should be familiar with the

effects of vasopressors and should stay up to date about changes in

administration guidelines to be able to provide the safest and most

current form of care available.

Summary

The clinician who works in a critical care setting must often be

prepared to act quickly to administer drugs to respond to changes in a

patient’s condition or clinical status. The clinician may be faced with

administering a variety of different drugs and it may be challenging to

remember the varied drug classes, common dosages, potential side

effects, and implications for administration. Drugs are often given

based on each patient’s condition and may be used to manage specific

symptoms that affect different organ systems within each person. For

example, one patient in the emergency department may require


cardiac medications to stabilize a potentially life-threatening

arrhythmia, while another may need analgesia to control pain

associated with a severe injury. Often, patients require more than one

type of medication.

Often, drugs given in the critical care environment can have great

potential for complications because of their physiological effects. When

administered rapidly for emergency purposes, many drugs start to

work almost immediately and their effects can impact almost all body

systems. Assessing the patient’s clinical status and ensuring the

correct dose and route have been ordered, administering the drug

correctly (and sometimes very rapidly), and observing the patient for

the drug’s effects or for changes in clinical status are all major steps in

the process of giving drugs in the critical care setting.

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.



a. Pharmacodynamics b. Biopharmaceutics c. Pharmacokinetics d. Pinocytosis



a. True b. False

3. Which of the following processes describes the movement of

a drug from its point of administration to its target location, i.e., the bloodstream?

a. Absorption b. Pinocytosis c. Diffusion d. Transportation


a. Intravenous administration b. Intramuscular injection c. Subcutaneous injection d. All the above have similar absorption rates



a. Passive diffusion b. Pinocytosis c. Absorption d. Active transport


6. __________________ involves the movement of drug particles across a membrane with the help of a carrier molecule.

a. Passive diffusion b. Pinocytosis c. Facilitated passive diffusion d. Active transport

7. True or False: Drugs that are given in aqueous solutions are

absorbed faster than those that contain oil-based solutions.

a. True b. False

8. When an ointment is applied to the skin and covered by an

occlusive dressing, the medication may ________________ when compared to a layer of medication applied without an occlusive dressing.

a. be absorbed more quickly b. reduce swelling more c. be less hydrating d. decrease permeability

9. The process of drug absorption is one step of

pharmacokinetics that all drugs, except ___________________ drugs, must undergo to exert their effects and to be therapeutically useful.

a. inhalation b. intrathecally administered c. subcutaneously injected d. intravenously administered

10. __________________ refers to exactly how much of a

drug enters the circulation and the rate at which it is absorbed and therefore available to be distributed.

a. Distribution b. Diffusion c. Absorption d. Bioavailability


11. Drugs that are ____________________ have greater bioavailability because they do not need to undergo absorption first.

a. inhaled b. administered intravascularly c. administered extravascularly d. administered topically

12. When a drug is in the bloodstream, it moves from the

plasma into the tissues through the process of

a. absorption. b. pinocytosis. c. diffusion. d. distribution.

13. The point at which a drug’s concentration in plasma and in

the tissues are in balance is known as

a. passive diffusion b. the determinant phase. c. the post-distribution phase. d. the concentration phase.

14. True or False: A drug’s bioavailability in the bloodstream

and its distribution are the same regardless of the drug’s composition or form, i.e., capsules or tablets.

a. True b. False

15. Most drugs are metabolized and converted into an active

chemical substance in the

a. liver. b. lungs. c. plasma. d. gastrointestinal tract.


16. During the first phase or stage of metabolism, known as Phase 1, a drug undergoes

a. absorption. b. conjugation. c. oxidation. d. hydrolysis.

17. The process known as _______________, occurs during

Phase 2 of metabolism; in this phase a group of ions binds to the metabolite within the cytoplasm of the hepatocyte.

a. hydrolysis b. conjugation c. oxidation d. reduction

18. Elimination of a drug from the body begins

a. during excretion. b. during metabolization. c. after absorption. d. as soon as it is administered.

19. One of the most common conjugation reactions of

metabolism is

a. glucuronidation. b. acetylation. c. sulfation. d. methylation.

20. True or False: The process of conjugation contributes

toward the eventual excretion of the drug from the body’s system, as the binding of an ionized group makes the metabolite more water soluble.

a. True b. False


21. A drug referred to as a “prodrug” has which of the following unique properties?

a. It builds up within the system without becoming toxic. b. It metabolizes so it may be excreted from the body. c. It remains pharmacologically active when undergoing

metabolism. d. It can cross the blood-brain barrier.

22. The removal of a drug from the plasma is known as drug

________________, which is a factor used in pharmacokinetic formulas to determine the half-life of a drug and its steady state of concentration.

a. excretion b. elimination c. reduction d. clearance

23. The ____________ of a drug describes how long the drug

is active in the body, which may be referred to as the drug’s duration of action.

a. toxicity b. bioavailability c. half-life d. metabolization

24. A patient is receiving a daily administration of digoxin to

treat a chronic atrial fibrillation. The administration and dose is set based on the drug’s half-life with a goal

a. of total drug clearance. b. of metabolizing the drug more quickly. c. to develop a steady state of the drug in the bloodstream. d. to assure that the initial drug administration is stronger.

25. True or False: As the process of metabolism continues, the

drug’s therapeutic effects are increased.

a. True b. False


26. A nurse is administering gentamicin as an antibiotic for a patient and the nurse wants to measure the trough level of the drug. The nurse should measure the trough level

a. just prior to giving the drug. b. approximately 30 minutes after the drug has been given. c. after administration of the drug. d. at the mid-point of the drug’s half-life.

27. Elevated creatinine levels can indicate

a. that a drug is at its trough level. b. liver dysfunction. c. impaired kidney function. d. that a drug’s concentration is at its highest level.

28. When estimating __________ function, a provider should

consider the patient’s estimated glomerular filtration rate (GFR).

a. spleen b. pancreatic c. liver d. kidney

29. Pharmacodynamics considers a drug’s

a. concentration at the site of action. b. therapeutic effects. c. adverse effects. d. All of the above

30. True or False: For patients in the ICU, therapeutic drug

monitoring must be performed every day or with each dose.

a. True b. False


31. A patient who receives anxiolysis

a. requires a ventilator to assist with breathing. b. can respond to verbal commands. c. has impaired motor skills and reflexes. d. All of the above

32. Isoproterenol works by stimulating beta-receptors that are

normally stimulated by epinephrine, which makes this drug an example of

a. an endogenous substance. b. a receptor agonist. c. a receptor antagonist. d. a metabolite.

33. A patient with a Richmond Agitation-Sedation Scale (RASS)

score of -5 could be described as being

a. combative. b. calm. c. anxious. d. unarousable.

34. An idiosyncratic drug reaction describes an adverse effect

a. that is an off-target event. b. caused by drug tolerance. c. that is rare and unpredictable. d. that is life-threatening.

35. True or False: In contrast to pharmacokinetics, the concept

of pharmacodynamics describes a drug’s actions or what a drug does in the body after it is administered.

a. True b. False

36. In today’s healthcare, sedatives are often administered

a. to keep a ventilated patient restrained and confined. b. to provide round-the-clock sedation for ventilated patients. c. as adjuvant drugs to promote comfort alongside analgesics. d. to keep a patient constantly subdued and controlled.


37. Analgesic medications are primarily administered to control

a. anxiety b. delirium. c. breathing. d. pain.

38. Succinylcholine is a neuromuscular blocking agents,

classified as a depolarizing agent, used for deep muscle relaxation, but it has the following limitation or side effect:

a. It cannot be administered with a sedative agent. b. It cannot be used for short procedures. c. It carries a risk of malignant hyperthermia. d. Its effects as a neuromuscular blockade are slow.

39. One of the more disturbing or frightening complications for

a patient that may develop with the use of paralytic medications is

a. amnesia of the hospital event. b. drug tolerance. c. hypertension. d. anesthesia awareness.

40. True or False: For a patient in intensive care, antipsychotic

medications are often used as a first choice for calming, even though the patient may have no history of mental illness.

a. True b. False


CORRECT ANSWERS:


c. Pharmacokinetics “When a drug is given for any type of illness or medical condition, it is regulated in the body through pharmacokinetics, which describes the processes of absorption, distribution, metabolism, and excretion of a drug within the body. The process is sometimes given the abbreviation ADME. The term pharmacokinetics is also sometimes described as what the body does to a drug when it is given.”



a. True “When a drug is assessed by how it acts in the body after administration, corresponding pharmacokinetic parameters can be calculated to determine factors such as the rate of its absorption, the volume of its distribution, or the rate of its elimination. This information is often generated from clinical research studies in which volunteers, who are often healthy, take the drugs for specified periods and then scientists such as biostatisticians and pharmacokineticists study the information, apply the formulas, and determine the results of the drug’s pharmacokinetics based on how it behaves after being administered to study participants.”


3. Which of the following processes describes the movement of a drug from its point of administration to its target location, i.e., the bloodstream?

a. Absorption “Absorption is the process of moving the drug from its initial location after it has been given (for instance, the stomach or intestinal tract for oral drugs, or the skeletal muscle tissue for an intramuscular injection) and transitioning its particles into circulation.”


c. Subcutaneous injection “… medications that are given via the intravenous route are administered directly into the bloodstream and do not require the additional step of absorption…. Because there is less vascular access to the subcutaneous tissue when compared to skeletal muscle tissue used for an intramuscular injection, the absorption rate of a subcutaneous injection is slower.”



b. Pinocytosis “Drugs can be absorbed via passive diffusion using little to no excess energy and a carrier molecule is not required. Passive diffusion is the method of absorption by which most drugs are transferred into systemic circulation…. Active transport describes the active movement of molecules across a membrane … Pinocytosis occurs when a cell membrane surrounds and encloses the particles of the drug.”


6. __________________ involves the movement of drug particles across a membrane with the help of a carrier molecule.

c. Facilitated passive diffusion “Facilitated passive diffusion also does not require energy. It involves the movement of drug particles across a membrane with the help of a carrier molecule.”

7. True or False: Drugs that are given in aqueous solutions are

absorbed faster than those that contain oil-based solutions.

a. True “Drugs that are given in aqueous solutions are absorbed faster than those that contain oil-based solutions; medications with high solubility also tend to be absorbed more slowly than those with low solubility.”

8. When an ointment is applied to the skin and covered by an

occlusive dressing, the medication may ________________ when compared to a layer of medication applied without an occlusive dressing.

a. be absorbed more quickly “… when an ointment is applied to the skin and covered by an occlusive dressing, the medication may be absorbed more quickly than when a layer of the medication is applied without any cover.”

9. The process of drug absorption is one step of

pharmacokinetics that all drugs, except ________________ drugs, must undergo to exert their effects and to be therapeutically useful.

d. intravenously administered “… the process of drug absorption is one step of pharmacokinetics that all drugs, except intravenously administered drugs, must undergo to exert their effects and to be therapeutically useful.”


10. __________________ refers to exactly how much of a drug enters the circulation and the rate at which it is absorbed and therefore available to be distributed.

d. Bioavailability “Bioavailability refers to exactly how much of a drug enters the circulation and the rate at which it is absorbed and therefore available to be distributed…. Drugs that are administered extravascularly are generally not completely absorbed. There are usually traces of the medication that remain unabsorbed. This reduces bioavailability since there is less of the drug available for distribution from its original dose. By comparison, drugs that are administered intravascularly have greater bioavailability because they do not need to undergo absorption first.”

11. Drugs that are ____________________ have greater

bioavailability because they do not need to undergo absorption first.

b. administered intravascularly “Drugs that are administered extravascularly are generally not completely absorbed. There are usually traces of the medication that remain unabsorbed. This reduces bioavailability since there is less of the drug available for distribution from its original dose. By comparison, drugs that are administered intravascularly have greater bioavailability because they do not need to undergo absorption first.”

12. When a drug is in the bloodstream, it moves from the

plasma into the tissues through the process of

c. diffusion. “When a drug is in the bloodstream, it moves from the plasma into the tissues through the process of diffusion.”


13. The point at which a drug’s concentration in plasma and in the tissues are in balance is known as

c. the post-distribution phase. “Once more of the drug has entered the tissues, the process of diffusion slows when the areas of concentration between the plasma levels and tissue levels of the drug are more in balance. This point is known as the post-distribution phase, in which drug concentrations in plasma and in the tissues are in balance.”

14. True or False: A drug’s bioavailability in the bloodstream

and its distribution are the same regardless of the drug’s composition or form, i.e., capsules or tablets.

b. False “… there are differences between drugs that are administered as capsules and as tablets, even though they may be the same drug at the same dose. Their composition as either capsules or tablets can impact their qualities of absorption because of their formulations. This, in turn, affects their bioavailability in the bloodstream as well as the amount to be distributed.”

15. Most drugs are metabolized and converted into an active

chemical substance in the

a. liver. “Once distributed, the drug is metabolized, which describes how the chemical compound of the drug is converted into an active chemical substance through the work of enzymes. Most drugs are metabolized in the liver, but other body areas, including the lungs, plasma, and the wall of the gastrointestinal tract have the capacity to metabolize drugs as well.”

16. During the first phase or stage of metabolism, known as

Phase 1, a drug undergoes

c. oxidation. “During the first phase, the most common change that takes place is when the drug undergoes oxidation.”


17. The process known as _______________, occurs during Phase 2 of metabolism; in this phase a group of ions binds to the metabolite within the cytoplasm of the hepatocyte.

b. conjugation “Once the medication has passed through Phase 1, conjugation occurs in the second phase of metabolism, in which a group of ions binds to the metabolite. This process occurs within the cytoplasm of the hepatocyte.”

18. Elimination of a drug from the body begins

d. as soon as it is administered. “Technically, the elimination of a drug from the body begins as soon as it is administered and it enters the body. When a drug is first being absorbed, the body is also simultaneously eliminating it, but the rate of absorption is greater than the rate of elimination, so more of the drug is absorbed initially. Over time, the processes balance out and eventually, more of the drug is metabolized and excreted when there is less of the initial drug to be absorbed.”

19. One of the most common conjugation reactions of

metabolism is

a. glucuronidation. “While glucuronidation is one of the most common conjugation reactions of metabolism, there are other forms that can occur as well, in which a functional group is added to the molecule to facilitate metabolism. Such examples include acetylation, which is the addition of an acetyl group, and sulfation, which is the conjugation of a sulfo group to the molecule.”


20. True or False: The process of conjugation contributes toward the eventual excretion of the drug from the body’s system, as the binding of an ionized group makes the metabolite more water soluble.

a. True “The process of conjugation contributes toward the eventual excretion of the drug from the body’s system, as the binding of an ionized group makes the metabolite more water soluble and therefore easier to excrete.”

21. A drug referred to as a “prodrug” has which of the

following unique properties?

c. It remains pharmacologically active when undergoing metabolism. “The overall outcome of metabolism is to take the parent compound —which is the initial state of the drug after it has been distributed — and break it down through metabolism so that it becomes pharmacologically inactive for eventual excretion. The body must metabolize drugs for excretion to avoid the buildup of medication within the system that leads to toxicity and potential organ damage. Most drugs become pharmacologically inactive through the process of metabolism, but note that some drugs, when undergoing metabolism, remain pharmacologically active. This is sometimes called a prodrug; the initial drug may actually have a weaker effect until it is partially metabolized, and then its metabolite is more active. An example of a prodrug is the antihypertensive drug enalapril, a metabolite whose parent drug is enalaprilat, which does not become pharmacologically active until it has undergone metabolism.”


22. The removal of a drug from the plasma is known as drug ________________, which is a factor used in pharmacokinetic formulas to determine the half-life of a drug and its steady state of concentration.

d. clearance “The removal of a drug from the plasma is known as drug clearance, which is a factor used in pharmacokinetic formulas to determine the half-life of a drug and its steady state of concentration.”

23. The ____________ of a drug describes how long the drug

is active in the body, which may be referred to as the drug’s duration of action.

c. half-life “The half-life therefore describes how long the drug is active in the body, which may be referred to as the drug’s duration of action.”

24. A patient is receiving a daily administration of digoxin to

treat a chronic atrial fibrillation. The administration and dose is set based on the drug’s half-life with a goal

c. to develop a steady state of the drug in the bloodstream. “… in cases where a drug is administered routinely, the goal is to develop a steady state within the bloodstream, or a certain amount of the drug that is constant within the plasma so that it is therapeutically effective. An example of this is with the administration of digoxin, which is given for the treatment of heart failure or chronic atrial fibrillation. Digoxin is administered routinely, typically on a daily basis. Because of this, its concentration within the blood plasma is maintained and it can exert its therapeutic effects. Clinicians can test for digoxin levels in the bloodstream by assessing plasma values because its chronic administration leads to a plasma steady state.”


25. True or False: As the process of metabolism continues, the drug’s therapeutic effects are increased.

b. False “As the process of metabolism continues, the drug’s therapeutic effects are decreased.”

26. A nurse is administering gentamicin as an antibiotic for a

patient and the nurse wants to measure the trough level of the drug. The nurse should measure the trough level

a. just prior to giving the drug. “For example, when administering gentamicin as an antibiotic, the patient requires peak and trough levels, which are performed after dose administration and just prior to dose administration, respectively. Measuring the peak involves collecting a blood sample within approximately 30 minutes after the drug has been given and has had a chance to be distributed. Alternatively, the trough is measured just prior to giving the drug, when the concentration of the drug in the body from the last point of administration would be at its lowest.”

27. Elevated creatinine levels can indicate

c. impaired kidney function. “… elevated creatinine levels can indicate impaired kidney function.”

28. When estimating __________ function, a provider should

consider the patient’s estimated glomerular filtration rate (GFR).

d. kidney “When estimating kidney function, a provider should consider the patient’s estimated glomerular filtration rate (GFR).”


29. Pharmacodynamics considers a drug’s

a. concentration at the site of action. b. therapeutic effects. c. adverse effects. d. All of the above [correct answer]

“In essence, pharmacodynamics considers the drug concentration at the site of action and its therapeutic effects, including any adverse effects that may occur.”

30. True or False: For patients in the ICU, therapeutic drug

monitoring must be performed every day or with each dose.

b. False “There are several considerations to think through when using therapeutic drug monitoring for patients in the ICU. First, this type of monitoring is only appropriate for those drugs that require therapeutic monitoring to check plasma levels, but it does not need to be performed every day or with each dose.”

31. A patient who receives anxiolysis

b. can respond to verbal commands. “Mild or minimal sedation, also referred to as anxiolysis, provides some amount of sedation so that the patient is calmed and comforted but not so much that it alters his level of consciousness. A patient who receives anxiolysis can still respond to verbal commands, has normal reflexes, and can breathe spontaneously.”

32. Isoproterenol works by stimulating beta-receptors that are

normally stimulated by epinephrine, which makes this drug an example of

b. a receptor agonist. “An example of a receptor agonist is isoproterenol, which works by stimulating beta-receptors that are normally stimulated by epinephrine.”


33. A patient with a Richmond Agitation-Sedation Scale (RASS) score of -5 could be described as being

d. unarousable. “One of the more common tools available for use in critical care is the Richmond Agitation-Sedation Scale (RASS); this scoring system can be used for any patient who is at risk of delirium, agitation, or anxiety and who is receiving sedative medications, but it is particularly useful for those who have difficulty with communication, such as patients who have mechanical ventilation. The RASS requires observation of the patient’s behavior and responses to stimuli. The responses are scored on a scale that ranges from -5 (unarousable) to +4 (combative, violent, dangerous to staff), with a score of ‘0’ described as being ‘alert and calm.’”

34. An idiosyncratic drug reaction describes an adverse effect

c. that is rare and unpredictable. “Another type of adverse event that can occur with drug administration is an idiosyncratic drug reaction. This describes an adverse effect that is rare and unpredictable.”

35. True or False: In contrast to pharmacokinetics, the concept

of pharmacodynamics describes a drug’s actions or what a drug does in the body after it is administered.

a. True “In contrast to pharmacokinetics, the concept of pharmacodynamics describes a drug’s actions or what a drug does in the body after it is administered.”

36. In today’s healthcare, sedatives are often administered

c. as adjuvant drugs to promote comfort alongside analgesics. “Sedatives should not be administered as a method of keeping a patient constantly subdued and controlled. Historically, sedatives were given around the clock to patients who required mechanical ventilation in order to maintain such deep sedation that the individual was relatively unaware of his condition until


he was able to successfully breathe on his own. Today, sedatives are still commonly administered, but are often given as adjuvant drugs to promote comfort alongside analgesics; they should be given as a method of controlling anxiety and insomnia in the critical care environment, instead of just being used to keep a ventilated patient restrained and confined.”

37. Analgesic medications are primarily administered to

control

d. pain. “Analgesic medications are primarily administered to control pain.”

38. Succinylcholine is a neuromuscular blocking agents,

classified as a depolarizing agent, used for deep muscle relaxation, but it has the following limitation or side effect:

c. It carries a risk of malignant hyperthermia. “Neuromuscular blocking agents are typically classified as one of two types: depolarizing agents or non-depolarizing agents…. One of the only depolarizing drugs in current use is succinylcholine, which works to cause significant muscle relaxation by acting as an agonist at the nicotinic receptor site…. Succinylcholine is administered as an intravenous infusion and its effects of neuromuscular blockade are quite rapid. When used, succinylcholine may be infused for very short periods, such as during a brief treatment or procedure that only lasts a few minutes. However, use of depolarizing agents in critical care is becoming less common because of the risk of certain complications, including malignant hyperthermia as well as hypokalemia. Because it causes complete muscle paralysis, succinylcholine should always be administered with a sedative agent that will induce unconsciousness.”


39. One of the more disturbing or frightening complications for a patient that may develop with the use of paralytic medications is

d. anesthesia awareness. “One of the more disturbing complications that may develop with the use of paralytic medications is anesthesia awareness, in which a patient has not been given enough sedative or anesthetic medications with the neuromuscular blocking agents and is awake and aware of his surroundings.”

40. True or False: For a patient in intensive care, antipsychotic

medications are often used as a first choice for calming, even though the patient may have no history of mental illness.

b. False “For a patient with no history of mental illness, antipsychotic medications are often not used as a first choice for calming, despite their ability to achieve sedation. However, for some patients in the ICU who are already struggling with delirium and agitation as a result of psychosis, neuroleptic agents can control anxiety and can promote sleep.”


References

The References below include published works and in-text citations of published works that are intended as helpful material for your further reading.

1. Physician’s Desk Reference (2017). Retrieved online at http://www.pdr.net/browse-by-drug-name.

2. Le, J. (2016). Overview of pharmacokinetics. Retrieved from http://www.merckmanuals.com/professional/clinical-pharmacology/pharmacokinetics/overview-of-pharmacokinetics

3. Marini, J., Wheeler, A. (2010). Critical care medicine: the essentials. Philadelphia, PA: Lippincott Williams & Wilkins

4. UNC Eshelman School of Pharmacy. (2017). Intramuscular. Retrieved from http://pharmlabs.unc.edu/labs/parenterals/intramuscular.htm

5. Spruill, W., Wade, W., DiPiro, J., Blouin, R., Pruemer, J. (2014). Concepts in clinical pharmacokinetics (6th ed.). Bethesda, MD: ASHP

6. Hedaya, M. (2012). Basic pharmacokinetics (2nd ed.). Boca Raton, FL: Taylor and Francis Group

7. Rosenbaum, S. (Ed.). (2017). Basic pharmacokinetics and pharmacodynamics: an integrated textbook and computer simulations (2nd ed.). Hoboken, NJ: John Wiley & Sons, Inc.

8. Rolfe, V. (2013). Metabolism. http://www.nottingham.ac.uk/nmp/sonet/rlos/bioproc/liverdrug/

9. Edward, K. (2015). Why nurses need to know about pharmacokinetics and pharmacodynamics – informing practice towards better medication competence. Retrieved from http://journalofadvancednursing.blogspot.com/2015/10/why-nurses-need-to-know-about.html

10. Jancova, P., Siller, M. (2012). Phase II drug metabolism, Topics on Drug Metabolism, Dr. James Paxton (Ed.)., InTech, DOI: 10.5772/29996. Retrieved from http://www.intechopen.com/books/topics-on-drug-metabolism/phase-ii-drug-metabolism

11. Reade, M., Finfer, S. (2014). Sedation and delirium in the intensive care unit. The New England Journal of Medicine 370: 444-454. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMra1208705#t=article


12. Nickson, C. (2016). Sedation in ICU. Retrieved from http://lifeinthefastlane.com/ccc/sedation-in-icu/

13. Coviden. (2015). Sedation: tools for assessment. Boulder, CO: Coviden AG

14. American College of Emergency Physicians. (2011). Sedation in the emergency department. Retrieved from https://www.acep.org/Content.aspx?id=75479

15. Jevon, P., Ewens, B. (2012). Monitoring the critically ill patient (3rd ed.). West Sussex, UK: John Wiley & Sons

16. From New to ICU. (2016). How to perform train of four monitoring. Retrieved from http://fromnewtoicu.com/blog/2016/3/11/train-of-four

17. O’Connor, D., Gwinnutt, C. (n.d.). Pharmacology of neuromuscular blocking drugs and anticholinesterases. Retrieved from http://www.anaesthesiauk.com/documents/PharmacologyNMBDsandAnticholinesterasesFinal.pdf

18. Price, D., Kenyon, N., Stollenwerk, N. (2012). A fresh look at paralytics in the critically ill: real promise and real concern. Annals of Intensive Care 2: 43. Retrieved from https://annalsofintensivecare.springeropen.com/articles/10.1186/2110-5820-2-43

19. Zhou, C., Wu, L., Ni, F., Ji, W., Wu, J., Zhang, H. (2014). Critical illness polyneuropathy and myopathy: a systematic review. Neural Regen Res. 9(1): 101-110. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146320/

20. McLean, D., Diaz-Gil, D., Farhan, H., Ladha, K., Kurth, T., Eikermann, M. (2015). Dose-dependent association between intermediate-acting neuromuscular-blocking agents and postoperative respiratory complications. Anesthesiology, Vol 122, 1201-1213. Retrieved from http://anesthesiology.pubs.asahq.org/article.aspx?articleid=2278676

21. Rodrigues Nunes, R., Porto, V., Miranda, V., Quezado de Andrade, N., Carneiro, L. (2012). Risk factor for intraoperative awareness. Revista Brasileira de Anestesiologia 62(3). Retrieved from http://www.scielo.br/pdf/rba/v62n3/en_v62n3a09.pdf

22. Hammerschmidt, M. (2014). Pressors and vasoactives. Retrieved from http://icufaqs.org/

23. Drugs.com. (n.d.). Dopamine side effects. Retrieved from https://www.drugs.com/sfx/dopamine-side-effects.html

24. Algozzine, G., Algozzine, A. Lilly, D. (2010). Critical care intravenous drug handbook (3rd ed.). St. Louis, MO: Elsevier Mosby


25. American Society of Anesthesiologists. (2014). Statement on safe use of propofol. Retrieved from http://www.asahq.org/

26. Davis Drug Guide.com. (n.d.). Morphine. Retrieved from http://www.drugguide.com/ddo/view/Davis-Drug-Guide/51518/all/morphine

27. Drugs.com. (2012). Sublimaze. Retrieved from https://www.drugs.com/pro/sublimaze.html

28. National Safety Council. (2014). Opioid painkillers: how they work and why they can be risky. Itasca, IL: National Safety Council

29. Drahl, C. (2014). How does acetaminophen work? Researchers still aren’t sure. Chemical & Engineering News 92 (29): 31-32. Retrieved from http://cen.acs.org/articles/92/i29/Does-Acetaminophen-Work-Researchers-Still.html

30. ICU Delirium and Cognitive Impairment Study Group. (n.d.). Assess, prevent, and manage pain. Retrieved from http://www.icudelirium.org/pain.html

31. Action, Q.A. (2011). Issues in Pain Therapies and Research. Atlanta, Georgia.

32. ICU Delirium and Cognitive Impairment Study Group. (n.d.). Behavioral Pain Scale (BPS). Retrieved from http://www.icudelirium.org/docs/behavioral-pain-scale.pdf

33. PDR.net. (n.d.). Propofol – drug summary. Retrieved from http://www.pdr.net/drug-summary/diprivan?druglabelid=1719

34. Drugs.com. (n.d.). Isoproterenol. Retrieved from https://www.drugs.com/ppa/isoproterenol.html

35. University of Illinois. (2013). College of Medicine at Chicago. Retrieved from http://chicago.medicine.uic.edu/UserFiles/Servers/Server_442934/Image/1.1/residentguides/final/icuguidebook.pdf.

36. Klabunde, R. (2012). Norepinephrine, epinephrine and acetylcholine – synthesis, release and metabolism. Retrieved from http://cvpharmacology.com/norepinephrine

37. PDR.org. (2017). Levophed. Retrieved online at http://www.pdr.net/drug-summary/Levophed-norepinephrine-bitartrate-868.

38. Hamadah, A., Newman, D., Mulpuru, S. (2014). Acute cardiogenic shock after isoproterenol infusion for induction of atrial tachycardia. The Journal of Innovations in Cardiac Rhythm Management, 5 (2014), 1512-1514.

39. Claris Life Sciences. (2011). Norepinephrine bitartrate injection, USP. Retrieved from http://www.us.clarislifesciences.com/pdf/Norepinephrine/Norepinephrine-Injection-USP-Package-Insert.pdf


40. Bai, X., et al. (2014). Early versus delayed administration of norepinephrine in patients with septic shock. Critical Care 18: 532. Retrieved from https://ccforum.biomedcentral.com/articles/10.1186/s13054-014-0532-y

41. ACLS Algorithms.com. (2016). ACLS and epinephrine. Retrieved from https://acls-algorithms.com/acls-drugs/acls-and-epinephrine/

42. Cyriac, J., James, E. (2014). Switch over from intravenous to oral therapy: a concise overview. J Pharmacol Pharmacother. 5(2): 83-87. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008927/

43. Coe College. (n.d.). Calculating flow rate formulas. Retrieved from http://www.public.coe.edu/departments/Nursing/psychomotorskills/calculatingflowrateformula.htm

44. Stoelting, R., Hines, R., Marschall, K. (2012). Stoelting’s anesthesia and co-existing disease (6th ed.). Philadelphia, PA: Elsevier Saunders

45. Erstad, B. (n.d.). Special caveats of drugs used in critical care medicine, CCM Handbook, McGovern Medical School. Retrieved from https://med.uth.edu/anesthesiology/files/2015/05/Chapter-41-Special-Caveats-of-Drugs-Used-in-Critical-Care-Medicine.pdf

46. Upchurch, J. (2010). Receptors and the autonomic nervous system. Retrieved from https://www.ems1.com/airway-management/articles/893632-Receptors-and-the-autonomic-nervous-system/

47. Ari, A., Fink, J., Dhand, R. (2012). Inhalation therapy in patients receiving mechanical ventilation: an update. Journal of Aerosol Medicine and Pulmonary Drug Delivery 25(6): 319-332.

48. Ari, A. (2012). Aerosol therapy for ventilator-dependent patients: devices, issues, selection & technique. Clinical Foundations. Retrieved from http://www.clinicalfoundations.org/assets/foundations14.pdf

49. MannKind Corporation. (2016). Afrezza. Retrieved from https://www.afrezza.com/

50. Ari, A. and Restrepo, R. (2012). Aerosol Delivery Device Selection for Spontaneously Breathing Patients. AARC Clinical Practice Guidelines. Retrieved online at http://www.rcjournal.com/cpgs/pdf/aerosol_delivery_2012.pdf.

51. Drugs.com. (2015). Albuterol. Retrieved from https://www.drugs.com/pro/albuterol.html


52. Drugs.com. (2016). Ipratropium. Retrieved from https://www.drugs.com/pro/ipratropium.html

53. Hambrecht, R., Berra, K., Calfas, K. (2013). Managing your angina symptoms with nitroglycerin. What about exercise? Circulation 127(22). Retrieved from http://circ.ahajournals.org/content/127/22/e642

54. Elefteriades, J., Tribble, C., Geha, A., Siegel, M., Cohen, L. (2013). House officer’s guide to ICU care: fundamentals of management of the heart and lungs. Minneapolis, MN: Cardiotext Publishing, LLC

55. Ferreira, J., Mochly-Rosen, D. (2012). Nitroglycerin use in myocardial infarction patients: risks and benefits. Circ J. 76(1): 15-21. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527093/

56. Drugs.com. (2016). Nitroglycerin sublingual tablet. Retrieved from https://www.drugs.com/pro/nitroglycerin-sublingual-tablet.html

57. Global RPH. (2016). Vasodilators. Retrieved from http://www.globalrph.com/vasodilators.htm#Nitroglycerin

58. Bersten, A., Soni, N. (Eds.). (2014). Oh’s intensive care manual (7th ed.). Waltham, MA: Butterworth Heinemann

59. Drugs.com. (2016). Labetalol. Retrieved from https://www.drugs.com/pro/labetalol.html

60. Forcon Forensic Consulting. (2004). Pharmacokinetics. Retrieved from http://www.forcon.ca/learning/hitting.html

61. Jones, D. (2016). FASTtrack pharmaceutics dosage form and design (2nd ed.). London, UK: Pharmaceutical Press

62. McAuley, W., Kravitz, L. (2012). Pharmacokinetics of topical products. Dermatological Nursing 11(2): 40-44.

63. Le, J. (2016). Drug distribution to tissues. Retrieved from http://www.merckmanuals.com/professional/clinical-pharmacology/pharmacokinetics/drug-distribution-to-tissues

64. Tantisira, K. and Weiss, S.T. (2017). Overview of Pharmacogenomics. UpToDate. Retrieved online at https://www.uptodate.com/contents/overview-of-pharmacogenomics?source=search_result&search=pharmacokinetics&selectedTitle=1~150.

65. Shargel, L., et al. (2012) Applied Biopharmaceutics and Pharmacokinetics, Sixth Edition. McGraw-Hill.

66. Colwell, C. and Moore, E. (2017). Initial evaluation and management of abdominal gunshot wounds in adults. UpToDate. Retrieved online at https://www.uptodate.com/contents/initial-evaluation-and-management-of-abdominal-gunshot-wounds-in-


adults?source=search_result&search=gunshot%20wound%20treatment&selectedTitle=2~150.

67. Harro, J. (2004). Textbook of biological psychiatry. Appendix A. Wilmington, DE: Wiley-Liss, Inc.

68. Kim, D., et al. (2016). Predicting unintended effects of drugs based on off-target tissue effects. Biochemical and Biophysical Research Communications 469(3): 399-404. Retrieved from http://www.sciencedirect.com/science/article/pii/S0006291X15309645

69. Uetrecht, J., Naisbitt, D. (2013). Idiosyncratic adverse drug reactions: current concepts. Pharmacol Rev 65: 779-808. Retrieved from http://pharmrev.aspetjournals.org/content/pharmrev/65/2/779.full.pdf

70. Khetarpal, S., Fernandez, A. (2014). Dermatological emergencies. Retrieved from http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/dermatology/dermatological-emergencies/

71. Smith, R. (2012). Understanding how diabetes affects patient response to medications. Podiatry Today 25(10). Retrieved from http://www.podiatrytoday.com/understanding-how-diabetes-affects-patient-response-medications

72. Farinde, A. (2016). Overview of pharmacodynamics. Retrieved from http://www.merckmanuals.com/professional/clinical-pharmacology/pharmacodynamics/overview-of-pharmacodynamics

73. Center for Substance Abuse Research. (2013). Benzodiazepines. Retrieved from http://www.cesar.umd.edu/cesar/drugs/benzos.asp

74. Glenbrook South High School. (2010). Barbiturates. Retrieved from http://ic.galegroup.com/ic/scic/ReferenceDetailsPage/DocumentToolsPortletWindow?displayGroupName=Reference&jsid=4b0d8077a90242937c08f7470cd4da34&action=2&catId=&documentId=GALE%7CCV2645000006&u=gotitans&zid=919f2c975b5d714087fb9cb2f2dce0fd

75. Moore, G. and Pfaff, J. (2017). Assessment and emergency management of the acutely agitated or violent adult. UpToDate. Retrieved online at https://www.uptodate.com/contents/assessment-and-emergency-management-of-the-acutely-agitated-or-violent-adult?source=search_result&search=sedation%20and%20antipsychotics&selectedTitle=7~150.


76. Caro, D. (2016). Induction agents for rapid sequence intubation in adults. Retrieved from http://www.uptodate.com/contents/induction-agents-for-rapid-sequence-intubation-in-adults

77. McGrane, S., Pandharipande, P. (2012). Sedation in the intensive care unit. Minerva Anestesiologica 78(3): 369-80. Retrieved from http://www.minervamedica.it/en/getfreepdf/L4zOpYpzi0tFJGArBOMFccDGwygIxB2C514tGhBQaRnU8v0aOMnmCTeoqvxyw%252FuvblX5Polas%252Bo9hd8jRAfOaw%253D%253D/R02Y2012N03A0369.pdf

78. Sleigh, J., Harvey, M., Voss, L., Denny, B. (2014). Ketamine – more mechanisms of action than just NMDA blockade. Trends in Anaesthesia and Critical Care 4(2-3): 76-81. Retrieved from http://www.sciencedirect.com/science/article/pii/S2210844014200062

79. NIH Medline Plus. (2011). Chronic pain: symptoms, diagnosis, & treatment. Medline Plus 6(1): 5-6. Retrieved from https://medlineplus.gov/magazine/issues/spring11/articles/spring11pg5-6.html

80. Ayasrah, S., O’Neill, T., Abdalrahim, M., Sutary, M., Kharabsheh, M. (2014). Pain assessment and management in critically ill intubated patients in Jordan: a prospective study. Int J Health Sci 8(3): 287-298. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257364/

81. Thiele, H., Ohman, E., Desch, S., Eitel, I., de Waha, S. (2015). Management of cardiogenic shock. European Heart Journal 36(20): 1223-1230. Retrieved from https://academic.oup.com/eurheartj/article/36/20/1223/2293258/Management-of-cardiogenic-shock

82. Galeski, D. and Mikkelsen, M. (2017). Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock. UpToDate. https://www.uptodate.com/contents/evaluation-of-and-initial-approach-to-the-adult-patient-with-undifferentiated-hypotension-and-shock?source=search_result&search=hypovolemic%20shock&selectedTitle=1~150.

83. Beloncle, F., Meziani, F., Lerolle, N., Radermacher, P., Asfar, P. (2013). Does vasopressor therapy have an indication in hemorrhagic shock? Ann Intensive Care 3(13). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691630/

84. Orlando Health Surgical Critical Care. (2011). Vasopressor and inotrope usage in shock. Retrieved from


http://www.surgicalcriticalcare.net/Guidelines/Vasopressors%20and%20Inotropes%20in%20Shock.pdf

85. Angus, D., van der Poll, T. (2013). Severe sepsis and septic shock. New England Journal of Medicine, 369: 840-851. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMra1208623#t=article

86. Society of Critical Care Medicine, European Society of Intensive Care Medicine. (2013). Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Retrieved from http://www.survivingsepsis.org/SiteCollectionDocuments/Implement-PocketGuide.pdf

87. Pollard, S., Edwin, S., Alaniz, C. (2015). Vasopressor and inotropic management of patients with septic shock. Pharmacy and Therapeutics 40(7): 438-442. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495871/

88. Mitra, J., Roy, J., Sengupta, S. (2011). Vasopressin: its current role in anesthetic practice. Indian J Crit Care Med. 15(2): 71-77. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145307/

89. Cossu, A., et al. (2014). Vasopressin in hemorrhagic shock: a systematic review and meta-analysis of randomized animal trials. BioMed Research International (2014), Article ID 421291, 9 pages. Retrieved from https://www.hindawi.com/journals/bmri/2014/421291/

90. Kruer, R., Jarrell, A., Latif, A. (2014). Reducing medication errors in critical care: a multimodal approach. Clinical Pharmacology: Advances and Applications 2014: 6 117-126.

91. U.S. Food and Drug Administration. (2016). Regulatory information. Retrieved from http://www.fda.gov/RegulatoryInformation/Guidances/default.htm

92. Drugs.com. (2016, Nov.). Midazolam injection. Retrieved from https://www.drugs.com/pro/midazolam-injection.html

93. U.S. Food and Drug Administration. (n.d.). Ativan (lorazepam) injection. Retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018140s028lbl.pdf

94. Glaucoma Research Foundation. (2016, Aug.). Types of glaucoma. Retrieved from http://www.glaucoma.org/glaucoma/types-of-glaucoma.php

95. Global RPH. (2016). Intravenous dilution guidelines. Retrieved from http://www.globalrph.com/propofol_dilution.htm


96. Loh, N., Nair, P. (2013). Propofol infusion syndrome. Contin Educ Anaesth Crit Care Pain (2013) doi: 10.1093/bjaceaccp/mkt007. Retrieved from http://ceaccp.oxfordjournals.org/content/early/2013/02/20/bjaceaccp.mkt007.full

97. Orlando Health Surgical Critical Care. (2011). Delirium management in the ICU. Retrieved from http://www.surgicalcriticalcare.net/Guidelines/delirium_2011.pdf

98. Drugs.com. (2016, Feb.). Haloperidol. Retrieved from https://www.drugs.com/pro/haloperidol.html

99. Page, V., et al. (2013). Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomized, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine 1(7): 515-523. Retrieved from http://www.sciencedirect.com/science/article/pii/S2213260013701668

100. Mayo Clinic. (2017). Nitroglycerin. Retrieved online at http://www.mayoclinic.org/drugs-supplements/nitroglycerin-oral-route-sublingual-route/description/drg-20072863.

101. Corvallis, Oregon EMS. (n.d.). Droperidol. [Protocol]. Retrieved from http://www.corvallisoregon.gov/ems-protocols/Pharmacology%20Section/Droperidol-Final.pdf

102. Barr, et al. (2013). Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Critical Care Medicine 41(1): 263-306.

103. McKnight, L. (2013). Pain management: non-opioid medications. Pharmacy Times. Retrieved from http://www.pharmacytimes.com/publications/health-system-edition/2013/july2013/pain-management-non-opioid-medications

104. Drugs.com. (2014, Jun.). Dobutamine. Retrieved from https://www.drugs.com/pro/dobutamine.html

105. Drugs.com. (2016, Jul.). Milrinone. Retrieved from https://www.drugs.com/pro/milrinone.html

106. Ventetuolo, C., Klinger, J. (2014). Management of acute right ventricular failure in the intensive care unit. Annals of the American Thoracic Society 11(5): 811-822.

107. U.S. Food and Drug Administration. (2014). Highlights of prescribing information: Revatio. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021845s011,022473s004,0203109s002lbl.pdf

108. Marino, P. (2014). Marino’s the ICU book (4th ed.). Philadelphia, PA: Wolters Kluwer Health


109. Drugs.com. (2016). Ephedrine sulfate injection. Retrieved from https://www.drugs.com/pro/ephedrine-sulphate-injection.html

110. Tiziani, A. (2013). Harvard’s nursing guide to drugs (9th ed.). Chatswood, NSW: Elsevier Australia.

111. Masjedi, M., Zand, F., Kazemi, A., Hoseinipour, A. (2014). Prophylactic effect of ephedrine to reduce hemodynamic changes associated with anesthesia induction with propofol and remifentanil. Journal of Anaesthesiology Clinical Pharmacology 30(2): 217-221. Retrieved from http://www.joacp.org/article.asp?issn=0970-9185;year=2014;volume=30;issue=2;spage=217;epage=221;aulast=Masjedi

112. Ragland, J., Lee, K. (2016). Critical care management and monitoring of intracranial pressure. J Neurocrit Care 9(2): 105-112. Retrieved from https://www.e-sciencecentral.org/articles/?scid=SC000020342

113. Reeder, G. and Prasad, A. (2017). Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy. UpToDate. Retrieved online at https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-stress-takotsubo-cardiomyopathy?source=search_result&search=broken%20heart%20syndrome&selectedTitle=1~63.

The information presented in this course is intended solely for the use of healthcare professionals taking this course, for credit, from NurseCe4Less.com. The information is designed to assist healthcare professionals, including nurses, in addressing issues associated with healthcare. The information provided in this course is general in nature, and is not designed to address any specific situation. This publication in no way absolves facilities of their responsibility for the appropriate orientation of healthcare professionals. Hospitals or other organizations using this publication as a part of their own orientation processes should review the contents of this publication to ensure accuracy and compliance before using this publication. Hospitals and facilities that use this publication agree to defend and indemnify, and shall hold NurseCe4Less.com, including its parent(s), subsidiaries, affiliates, officers/directors, and employees from liability resulting from the use of this publication. The contents of this publication may not be reproduced without written permission from NurseCe4Less.com.