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J&D Educational Services
Parenteral Preparation
The Texas Tech University – HSC- School of Pharmacy is accredited by The Accreditation
Council For Pharmaceutical Education (ACPE) as a provider of continuing
Pharmaceutical Education.
Course Administered By:
J&D Educational Services, Inc
PO Box 130909
The Woodlands, Texas 77393-0909
Voice: 1-866-747-5545
Fax: 1-281-298-8335
www.jdeducation.com
Parenteral Drug Therapy
And I.V. Admixture
A Knowledge Based Course
By
Jeff Blackburn, C.Ph.T., MBA – Healthcare Administration
ACPE No. 0096-9999-12-006-H01-T
Release Date: 02/14/2012
Expiration Date: 02/14/2015
Total number of pharmacy continuing education hours: 8 hours (0.8 CEU’s)
Course Cost:
$25.00 (to be paid at time of testing)
Average time to Complete:
Approximately eight hours including testing
Course Value:
Eight Contact Hours
Reading:
51 Pages
Final Exam:
50 Questions
Completion Requirements:
Answer 70% of questions correctly. Eval.
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STATEMENT OF NEED
The compounding of sterile preparations is an integral part of any health-system setting.
While the majority of perenteral products are prepared using commercially available
medications and diluents solutions, pharmacy departments still prerform intravenous
manufacturing. The reasons for this vary greatly, but can include:
1. Special patient populations such as pediatrics, geriatrics, or the terminally ill (pain
management). For these patients, the appropriate strengths for certain drugs may
not be available.
2. Some patients might be allergic to the diluents and preservatives in commercially
available products.
3. Some drugs are unstable and require preparation to be dispensed every few days.
4. A combination therapy that a prescriber desires, but that is not currently
commercially available.
OBJECTIVES
At the completion of this activity, the participant will be able to::
1. List the three factors that must be eliminated in the preparation and manufacture
of parenteral preparations.
2. List the volume limitations of the intramuscular, subcutaneous, and intradermal
routes of administration.
3. State the antimicrobial agent that must be avoided in parenterals being
administered to neonates.
4. Describe the production facility requirements for a parenteral preparation area.
5. Describe the importance of tonicity, osmoticity, osmolality as it relates to the
compounding of sterile products.
6. Given a list of drugs, match the delivery system with the most appropriate method
of administration for that agent.
7. List the important factors in determining drug compatibility.
8. List the fluids that are commonly administered with blood products.
9. Match the type of filter with the most appropriate application described.
10. Given an order for a parenteral nutrition solution, calculate the non-protein
calories and grams of nitrogen for the solution prescribed.
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INTRODUCTION
An intravenous infusion (IV) is the installation of a large amount of fluid and/or
electrolytes, or nutrient substances into a vein. It is given to patients who require extra
fluid or to those who cannot take fluids or nutrient substances orally. An IV is also a port
for administration of medication. A physician is responsible for ordering the type of
solution, the amount to be given, and the rate at which it is to be infused.
When drugs need to be injected, any one of several routes can be used to administer the
drug. The most common injectable routes of administration are intravenous (in the vein),
intramuscular (in the muscle), and subcutaneous (in the skin).
The compounding of sterile preparations is an integral part of any health-system setting.
While the majority of parenteral products are prepared using commercially available
medications and diluents solutions, pharmacy departments still perform intravenous
manufacturing. The reasons for this vary greatly, but can include:
• Special patient populations such as pediatrics, geriatrics, or the terminally ill (pain
management). For these patients, the appropriate strengths for certain drugs may
not be available
.
• Some patients might be allergic to the diluents and preservatives in commercially
available products.
• Some drugs are unstable and require preparation to be dispensed every few days.
• A combination therapy that a prescriber desires, but that is not currently
commercially available.
Intravenous Administration
Intravenous administration of drugs has advantages over other routes of administration
because it provides the fastest route to the bloodstream. There are no barriers like skin or
muscle to absorb the drug first, which allow the most rapid onset of action. If someone
cannot take medication by mouth because he is unconscious or vomiting, then
intravenous administration is the best route. Since the inner lining of a vein is relatively
insensitive to pain, drugs that can be irritating if given by another route can be given
intravenously as a slow rate without causing pain. Drugs that can be diluted to reduce
irritation can be given only intravenously because the tissue and skin around the other
routes of administration cannot accommodate large volumes.
There are two types of intravenous administration. The first is an intravenous injection in
which the prepared medication is drawn up into a syringe and administered immediately.
The amount of medication is usually a small volume pushed through an IV line that is
already in place on the patient.
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The second type of administration is an IV infusion. Infusions are given to overcome
dehydration, to build up depleted blood volumes, and to serve as an aid for the
administration of medications. An infusion allows a larger volume to be given at a
constant rate, depending on the drug to be administered. Infusions can be administered
continuously or intermittently. Continuous infusions are used to administer larger
volumes of solutions over several hours at a slow, constant rate. Intermittent infusions are
used to administer a relatively small volume over a shorter time at specific intervals.
Parenteral (Greek word – para enteron – beside the intestine) is the route of
administration of drugs by injection under, or through, one or more layers of the skin or
mucous membranes. Since the life of the patient is affected by such injections,
developments in the process technology have established a means for improving the
quality of the product.
The process necessary for parenteral preparations must include the following Good
Manufacturing Practices that accomplish the procedures below:
1. Exclusion and elimination of particulate matter.
2. Exclusion and elimination of pyrogens.
3. Exclusion and elimination of bacterial growth and contamination.
There may come a time in hospital practice where one is asked to manufacture a product
for injection that is not available commercially. The knowledge of what is required in the
process technology will help make the decision whether such a product can or cannot be
safely prepared by the hospital pharmacist.
Fluid and Electrolyte Overview
All bodily functions rely on the proper distribution of fluids and electrolytes between the
intracellular and extracellular compartments. The balance of fluid and electrolytes is
controlled by renal, hormonal, and metabolic functions.
Fluids
Water is the largest single component of the human body. Sixty percent of an adult’s
body weight consists of water. This fluid is distributed with 45 percent being
intracellular and 15 percent being extracellular.
Electrolytes
Electrolytes are minerals in your body that have an electric charge. They are in your
blood, urine and body fluids. Maintaining the right balance of electrolytes helps your
body’s blood chemistry, muscle action and other processes. Sodium, calcium, potassium,
chlorine, phosphate and magnesium are all electrolytes.
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Levels of electrolytes in the body can become too low or too high. That can happen
when the amount of water in the body changes. Causes include some medicines,
vomiting, diarrhea, sweating or kidney problems. Problems most often occur with levels
of sodium, potassium or calcium.
Routes of Administration
There are a number of routes currently used to administer parenteral medication. The
main routes include the following:
•
Intradermal (I.D.)
•
Subcutaneous (S.C.)
•
Intramuscular (I.M.)
•
Intravenous (I.V.)
The Intradermal route is primarily used for diagnostic tests as well as some vaccines.
Standard amount injected ranges from 0.01 to 0.1 ml. Recommended needle size is 26g,
3/8" in length. The drug is injected into the outer layer of the skin. Very little systemic
absorption occurs, making this route ideal for producing a local effect as in allergy
testing. (A tuberculin syringe is generally used with 26g or 27g needle, 1/2" – 5/8" in
length.)
The Subcutaneous route allows for more rapid delivery of a drug compared to the oral
route, and slower, sustained drug administration than intramuscular administration.
Standard amount injected ranges from 0.5 to 2 ml. Recommended needle size is 25-27g,
1/2" to 1" in length. Minimal tissue trauma occurs with this route, and absorption occurs
mainly through the capillaries. Heparin and insulin are usually administered
subcutaneously. Some drugs may also be given by subcutaneous infusion. This procedure
is usually used for patient administration of home medication. An infusion pump is
required for subcutaneous infusions, to assure proper administration. Insulin may be
administered by continuous subcutaneous infusion, as well as deferoxamine mesylate
(desferal).
The Intramuscular route deposits medication within the muscle tissue, allowing for
absorption by a network of blood vessels. The rate of absorption is slower than the
intravenous route, but faster than the subcutaneous route. Depending upon the muscle site
used, volumes injected range from 0.5 to 5 ml. Needle sizes vary from 25g to 20g, 5/8” to
1” in length. Some injectable antibiotics (i.e., cephalosporins) suggest mixing the drug
with lidocaine before intramuscular injection in an attempt to reduce the pain upon
administration to the patient. Intramuscular injections can elevate serum levels of
creatine phosphokinase (CPK). Because of this, intramuscular injections are usually
avoided in cardiac patients, to avoid possible errors in suspecting myocardial damage.
The "z" Track method of intramuscular injection is reserved for drugs that may leak back
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into subcutaneous tissue after injection. Iron preparations irritate and discolor
subcutaneous tissue, and are therefore given by "z" track intramuscular injection into the
upper quadrant of the buttocks.
The Intravenous route of injection produces rapid effects. The larger the vein, the more
diluted the drug will become as it travels into the bloodstream, which will minimize
irritation. The recommended size of needle is 25g, 5/8" in length for slow injections, 19g23g, 1"-1.5" in length for larger, longer injections of volumes, such as 0.5 to 50 ml.
Larger volumes of drugs are administered by intravenous infusion, rather than injection.
A general rule of thumb for administering intravenous injection is that most drugs are
administered slowly, over 1-2 minutes or longer.
Other Routes of Administration:
•
Intra-arterial – injection into an artery for localizing the effect of a drug. It is
mainly used for diagnostic purposes. Some chemotherapeutic agents may be
administered (i.e., methotrexate) by this route.
•
Intracardiac – Injection into the heart chamber
•
Intra-articular – Injection into a joint.
•
Hypodermoclysis – Injection of a large volume of solution into the subcutaneous
tissue.
•
Intraspinal – Injection into the spinal column.
•
Intrasynovial – Injection into a joint fluid area.
•
Intrathecal - Injection into the spinal fluid.
.
Only solutions may be given intravenously. Suspensions, emulsions, or solutions may be
given intramuscularly, intradermally, or subcutaneously. An example of an emulsion that
can be given intravenously is Fat Emulsion. The oil used for the solvent in Fat Emulsion
(soybean and/or safflower oil) is emulsified in water for injection using egg yolk
phospholipids as the emulsifying agent and glycerin as the stabilizer. Intrathecal
injections cannot contain any preservatives. A fatal toxic syndrome is associated with
administration of solutions containing benzyl alcohol as a preservative to infants. Large
quantities of preservatives administered to patients via injections have been associated
with various toxicities due to sodium bisulfite or paraben accumulation.
Categories of Injections
Injections may be classified into five general formulations:
1. Solutions ready for injection.
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2. Dry, soluble products ready to be combined with a solvent prior to use.
3. Suspensions.
4. Dry, insoluble products ready to be combined with a solvent prior to use.
5. Emulsions.
The type of injection formulation determines the route of administration. The desired
route also places restrictions on the type of formulation required. Suspensions cannot be
administered intravenously, because the soluble particles could block blood vessels.
Likewise, solutions to be given intrathecally must be free of all impurities and
preservatives due to the sensitivity of the nerve tissue to irritant and toxic substances.
Aqueous solutions given intravenously provide immediate physiological action.
Modification of the injection formulation can slow the onset or prolong the action of the
drug. Dry solids that contain no buffers or added substances are labeled as the sterile
drug. If the dried sterile form contains added substances, then the drug is labeled
“for injection".
PARENTERAL PREPARATIONS
Vehicles
The preparation of a parenteral product encompasses four general areas:
1. Components and Containers
2. Facilities and Procedures
3. Control of Quality
4. Packaging and Labeling
The components of a sterile pharmaceutical must be of the highest quality necessary for
that specific formulation. Component requirements will vary for different formulations.
The components utilized may include vehicles, solutes, containers, and closures.
The delivery of the active ingredient to body tissues for absorption is accomplished by
the vehicle. The vehicle component of a sterile product normally has no therapeutic
activity and is non-toxic. Vehicles that are composed of drugs presented in aqueous
solutions are normally rapidly and completely absorbed. Water- immiscible liquids
decrease absorption, and suspensions are affected by viscosity of the vehicle, wetting
capacity of the solid particles, (dispersion and redispersion of particles to prevent caking
and settling of the particles – flocculation and deflocculation); solubility equilibrium and
distribution coefficient between the vehicle and aqueous body system.
Water for Injection
The most important vehicle for parenteral products is water. Water used for parenteral
preparations must be prepared by either distillation or reverse osmosis, and contain no
added substances. Sterile water for injection and irrigation must meet United States
Pharmacopeia (USP) requirements. Sterile water for injection (SWFI) and water for
injection (WFI) are not the same vehicle. Water for injection USP is high-purity water
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intended for use as a vehicle for injectable preparations as per USP standards. Water for
injection may not contain added substances. SWFI may contain a bacteriostatic agent
when in containers of 30 ml capacity or less. The restrictions that prevent inclusion of
bacteriostatic agents in volumes greater than 30 ml is designed to prevent administration
of a large quantity of bacteriostatic agents that may induce toxic effects. Certain aqueous
vehicles are requested for parenterals, due to their isotonic properties. These vehicles
minimize the pain felt upon injection. Sodium chloride injection, Ringers injection,
Dextrose injection, Dextrose and Sodium Chloride injection, and Lactated Ringers
injection are all aqueous vehicles used for administration of parenterals.
Water-Miscible vehicles are used as a portion of the vehicle in the formulation of some
parenterals because of their "solvent" capacity. Ethyl alcohol, and polyethylene glycol are
examples of such water-miscible vehicles. Ethyl alcohol is used in the preparation of
cardiac glycoside solutions. Glycols are used in barbiturates, alkaloids and some
antibiotic solutions.
Nonaqueous vehicles are fixed oils of vegetable origin that will be metabolized upon
administration. The USP specifies limits on nonaqueous vehicles; in particular, the fact
that these oils may not interfere with the therapeutic efficacy of the drug. Ethyl oleate,
isopropyl myristate, benzyl benzoate, castor oil, and sesame seed oil are examples of
nonaqueous vehicles.
Solutes
Medicinal components used in sterile products must be of the best chemical grade
available. If the parenteral grade of a compound is available, this form should be used for
sterile preparations. A few parts per million of ionic contaminants in the chemical used
can cause stability problems in a preparation. The level of microbial and pyrogenic
contamination, solubility characteristics, and gross particulate matter must be ascertained
before use of the solute. Both the proper salt and crystalline form of the solute must be
selected for use in the sterile preparation. When possible, the anhydrous form of the
chemical should be used to avoid microbial and pyrogen entrapment in the water moiety
of the chemical.
Antimicrobial Agents
Substances added to parenteral products to prevent growth of microorganisms must be
added to preparations contained in multiple-dose containers. The compounds most
frequently used include the following:
1. Phenylmercuric nitrate and thimerosal
2. Benzethonium chloride and benzalkonium chloride
3. Phenol and cresol
4. Chlorobutanol
Limits on the concentration and amount added to the product are governed by the USP.
There is no universal agent satisfactory for all preparations. A change in the
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concentration of the drug can also limit the effectiveness of the preservative utilized.
Antimicrobial agents must be compatible with all components of the formulation, which
includes the container. Inactivation or binding of the antimicrobial agent due to leaching
by the rubber closure on the container must be considered. Reports of toxicity to
preservatives have been reported. Toxic symptoms in patients have occurred due to the
absorption of sodium bisulfite in peritoneal dialysis solutions, and due to the phenol used
as a preservative in glucagon. The fatal toxic syndrome that resulted in the death of two
premature infants due to the use of benzyl alcohol has made all medical professionals
painfully aware of the potential toxicity of preservatives in sterile products.
Pyrogens
Pyrogens are metabolic products of living microorganisms, or the dead microorganisms
themselves, which induce a specific pyrogenic response upon injection. These bacterial
endotoxins occur whenever microorganisms are allowed to grow. They may be present as
unexpected contaminants in a finished sterile product as a result of inadvertent
contamination during processing. Besides fever, other symptoms include chills, pains in
the back and legs and malaise. Pyrogens are rarely fatal. They produce significant
discomfort for the patient, however. The elimination of pyrogens cannot occur by
filtration, nor the usual autoclaving cycle. Pyrogens can be destroyed by heating at a
temperature of 250o Fahrenheit for 45 minutes. Heating with strong alkali or oxidizing
solutions will also destroy pyrogens. Sources of pyrogen contamination include the water
used as the solvent, the containers with which the solution has come into contact during
preparation, packaging, storage, or administration; or the chemicals used in the
preparation of the solution. Pyrogens can be eliminated from metal and glass containers
by dry heat. Repeated rinsing with pyrogen-free water for injection, can also help to
remove pyrogens. The Limulus lysate test can be utilized to test parenteral preparations
for the presence of pyrogens. When this reagent comes into contact with pyrogens, the
lysate causes gelation of the solution being tested within 60 minutes of initial exposure.
Freedom from pyrogens is a required characteristic of all sterile preparations. The use of
good manufacturing practices, as well as the increased use of disposable equipment, has
helped minimize the occurrence of pyrogens in parenteral products.
Containers
Containers are an integral part of a sterile product formulation. No container is totally
inert, or insoluble, or without some effect on the liquid contained therein. This is
particularly true for aqueous solutions in containers. The selection of the container for a
sterile product formulation must therefore be based on the composition of the container,
solution, and the treatment to which it will be subjected. Plastic containers
(thermoplastic polymers) are flexible, light, and not breakable. Permeation of vapors and
other molecules through the wall of the plastic container, leaching of constituents from
the plastic into the product, and sorption of drug molecules (adsorption/absorption) may
however, occur with the use of the plastic containers. Glass is employed as the container
of choice for most injections. The USP has classified glass into three categories:
Type 1 – borosilicate glass (suitable for most products)
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Type 2 – soda lime treated glass (suitable for buffered solutions)
Type 3 – soda lime glass (suitable for anhydrous liquids or dry substances only)
Application of a silicone coat to the glass can minimize product adherence to the glass
walls. Light sensitive products are protected by placing them in amber glass containers.
Single dose container size is limited to 1000 ml by the USP and 30 ml is the maximum
size for a multi-dose container. Rubber closures are used to seal vials and are held in
place by aluminum bands designed to permit the introduction of needles into a vial and
provide resealing on withdrawal. Rubber closures are used as plungers on syringes, seals
on irrigation bottles, medication ports on plastic IV fluids and flexible irrigation solution
containers. Typical rubber composition includes latex (natural rubber), and/or a synthetic
polymer, vulcanizing agents, accelerators, activators, fillers, and antioxidants. These
components are then shaped and molded to provide a product with sufficient elasticity to
fit well and reseal immediately. Because of this array of components, compatibility must
be determined with the rubber contacts to determine if the reaction is detrimental.
Facility Requirements
For several decades, pharmacy organizations have tried to improve standards of practice
regarding sterile products by publishing guidelines for all aspects of preparation.
However, the suggestions were not accepted across the board and many practice sites
regarded the guidelines as too tedious and costly. The lack of consistency among sterile
compounders was brought to national attention when several well-publicized adverse
events occurred involving compounded sterile products, including patient death.
The United States Pharmacopeia (USP) is a private organization that publishes a
reference book of drug product standards. Since 1938, the United States Food and Drug
Administration (FDA) has regarded the USP-NF as their official source for drug
standards. In an attempt to standardize the compounding of sterile pharmaceuticals, USP
addressed the topic in a recent revision and USP Chapter <797> has been in effect since
January 1, 2004. The practice guidelines are more than a suggestion of better standards.
The requirements in Chapter <797> are enforceable by state boards of pharmacy, federal
agencies and accreditation organizations (e.g., JCAHO, ACHC, etc.). Most importantly,
Chapter <797> applies to any practice site where sterile pharmaceuticals are
compounded, not only pharmacies. Sterile products are classified into three risk levels
which require more aggressive requirements as the risks associated with the
contamination of the sterile product increase. (Low Risk, Medium Risk and High Risk)
Low Risk
Products must meet these requirements:
A. Prepared in ISO Class 5 environment using only sterile ingredients.
B. Simple manipulations involving ampules, vials and syringes with fewer than three
additives
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.
After preparation, the following beyond use dating applies to low risk products if sterility
testing is not completed:
A. Controlled room temperature – 48 hours
B. Refrigerated (2°-8°) – 14 days
C. C. Frozen (*-20°) – 45 days
Medium Risk
Medium risk products are compounded under the same conditions as low risk products
but meet one or more of the following conditions:
A. Combining multiple sterile products into a product for multiple patients or one
patient multiple times. (e.g., batch preparations)
B. Complex aseptic manipulations over an extended period of time.
C. Products containing more than three additives or requiring complicated aseptic
manipulations (e.g., TPN)
D. Preparation administered over several days that does not contain a bacteriostatic
agent.
After preparation, the following beyond use dating applies to medium risk products if
sterility testing is not completed:
A. Controlled room Temperature – 30 hours
B. Refrigerated (2°-8°) – 7 days
C. Frozen (*-20°) – 45 days
High Risk
High risk products exhibit characteristics A or B:
A. Products compounded from non-sterile ingredients or compounded with
nonsterile components, containers, or equipment.
B. Products prepared by combining multiple ingredients, sterile or non-sterile, by
using an open-system transfer or open reservoir before terminal sterilization or
subdivision into multiple units to be dispensed.
After preparation, the following beyond use dating applies to high risk products if
sterility testing is not completed:
A. Controlled room temperature – 24 hours
B. Refrigerated (2°-8°) – 3 days
C. C. Frozen (*-20°) – 45 days
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One major area addressed by USP Chapter <797> is the environment required for
compounding sterile pharmaceuticals. The aseptic preparation area should be clean, of
sufficient size, well lighted, and separated from other pharmacy operations to minimize
potential contamination. Floors should be non-porous, washable, and disinfected daily.
An example of a recommended floor plan would contain the following areas:
1. STOCKROOM – for bulk storage of drugs and IV fluids.
2. ANTEROOM – an area adjacent to the buffer zone where supplies are unboxed
for use. Hand-washing and gowning also occur in this area.
3. BUFFER ZONE OR CLEAN ROOM – a controlled area providing an ISO
Class 8 or better air quality. Access to this area is limited to necessary personnel
to minimize particles and contaminants.
4. ASEPTIC PREPARATION AREA – the "fill area" where products are prepared
using a device that maintains an ISO Class 5 environment (horizontal laminar
flow hood, vertical laminar flow hood, appropriate Class II biological safety hood
or barrier isolator). Adequate sinks and counter space should be available in the
anteroom. Stainless steel shelving is recommended for all areas. The aseptic
preparation area should be a positive pressure area with sealed walls, floor and
ceiling. All surfaces should be smooth, easy to clean and not shed particles into
the environment. All three risk levels should have an anteroom, buffer zone and
ISO class 5 workspace, however there are different recommendations for floor
plans based upon the risk level. For example, a low risk sterile products room is
not required to have a barrier or wall dividing the anteroom from the buffer zone.
An area for preparation of high risk products should have a definite barrier or wall
between the two areas. Monitoring of the environment varies based on risk level
of the sterile products and quantity of products prepared each week.
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CHARACTERISTICS OF STERILE PRODUCTS
Terminology
Knowledge of the common terms associated with parenteral preparations is required of
the practitioner.
Sterile Products – Products free of all living microorganisms, pyrogens, and particulate
matter.
ISO class 5 Hood – Certified vertical or horizontal environment that contains no more
than 100 particles per cubic foot that are 0.5 micron (micrometer) or larger in size, also
known as a Laminar Flow Hood. This area is approved for sterile product preparation.
HEPA Filter – High efficiency particulate air filter which removes 99.97% of particles
that are 0.3 micrometer or larger. This is the functional part of an ISO class 5 hood.
Aseptic Technique – The ability to manipulate sterile preparations devices, and other
components that excludes the introduction of microorganisms.
Class II Type A Biological Safety Cabinet – The type of hood required for
chemotherapy preparation is a vertical flow hood, with a front air "barrier" to protect the
operator. Room air is pulled into the front grille and then filtered by the HEPA filter. The
air then passes vertically downward through the work zone, and again through the front
intake and rear exhaust grilles. It then passes through the HEPA filter and is re-circulated.
COMMON IV SOLUTION TERMINOLOGY
D5LR Dextrose 5% in Ringers Lactate
D5W Dextrose 5% in Water
NS Normal Saline, 0.9% Sodium Chloride
1/2NS 0.45% Sodium Chloride
D5 1/4 NS Dextrose 5% in 0.22% or (0.225%) Sodium Chloride
D5 1/3 NS Dextrose 5% in 0.33% (or 0.3%) Sodium Chloride
Methods of Sterilization
Sterilization is the complete destruction or elimination of microorganisms as confirmed
by appropriate test results. Chemical sterilization methods include gas sterilization
(ethylene oxide gas), and surface disinfection (phenolics, use of 70% ethanol). Physical
sterilization processes are divided into thermal and non-thermal. Thermal methods
include dry heat (oven) and moist heat (autoclave). Non-thermal methods utilize
ultraviolet light (UV), ionizing radiation, or filtration. The selection of the sterilization
process is determined by limitations of each method as well as its effectiveness and final
effect on the material being sterilized. Autoclaving is the most reliable thermal method,
and should be utilized whenever possible. Dry heat sterilization is effective for stainless
steel pots, and glassware. Thermolabile solutions are effectively sterilized with filtration.
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Ethylene oxide gas is preferred for stainless steel-teflon syringe systems, plastic tubes
and devices. Chemical methods are least effective sterilization methods, and are therefore
restricted to use as surface cleaners. Steam sterilization "autoclaving" is dependent upon
cycle time. Equipment and objects must be double-wrapped with lint- free poly-paper.
Penetration of the steam and lag time determines sterilization of the object. Maintenance
of sterility is contingent on dry wraps after the process and a static air state within.
Sterility Testing
All mechanically sterilized items must be packaged in an indicator-type material or have
indicator tape firmly affixed to the object. Upon meeting sterilizing conditions, this tape
changes color, indicating sterilization conditions have been obtained. Biological
indicators containing resistant bacterial spores are also placed throughout the load. For
control purposes, all items sterilized must be properly double wrapped in lint free polypaper cloth with an outer muslin wrap, and have the initials of the operator, date and load
number for that day. The environment where sterile products are prepared is also
monitored and tested to assure standards are maintained. Laminar flow hood HEPA
filters should be tested and certified twice a year as well as whenever moved, or damage
is suspected.8 Microbiological quality of the air in the environment should be tested
routinely. Two types of air sampling may be accomplished. Passive air sampling is
accomplished by use of "settling plates." Petri dishes containing growth media are
exposed to the environment. Two plates should be exposed continually during the
process; one close to the compounding area, and the other in a "worst case" area. Colony
counts of three or more indicate that corrective actions are required. Active air sampling
is a quantitative method used to measure microbial growth in the air. Specialized
equipment is required for this test. Microbial monitoring of the surfaces where aseptic
processing occurs should also be conducted. Colony counts should be zero in critical
areas.
Process validation of personnel in the sterile products area must also be conducted. The
risk level of products made by the pharmacy will determine the frequency and procedure
necessary. Quality assurance for low and medium risk products require annual media-fill
testing, but the procedure for medium risk is more complicated, requires more
manipulations and more complex procedures to complete the process. High- risk products
require semi-annual media- fill testing. The process includes starting the testing with
non-sterile ingredients. Test products for all risk levels are incubated and monitored for
14 days for microbial growth.
High-risk products that meet certain conditions must be tested for sterility prior to
administration. The use of the "QT Micro" and "QT Tester" by QI Medical provides a
method to test the operator’s technique and sterility of the final product. The testing
containers are incubated for 7-14 days to determine if aseptic technique was utilized.
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Tonicity, Osmoticity, Osmolality, Osmolarity
IV fluids may be classified as isotonic, hypertonic, or hypotonic depending on the effect
they exert on the intra- and extracellular fluid compartments.
Isotonic solutions are used to expand extracellular fluid (ECF) volume. A solution is
isotonic if there is no net gain or loss of water across the permeable membrane. Isotonic
solutions contain the same concentration of solute-to- fluid as that of the body fluid, and
therefore exert the same osmotic pressure (iso-osmotic) as the ECF in a normal steady
state. Normal saline, Lactated Ringers solution, and dextrose 5% in water all function as
isotonic solutions.
Hypertonic solutions exert osmotic pressures greater than that of the extracellular fluid.
Hypertonic solutions are used to shift ECF into the blood plasma.12 Rapid administration
of hypertonic solutions can cause dehydration and circulatory overload. Dextrose 5% in
0.9 sodium chloride, dextrose 5% in lactated Ringers, 3% sodium chloride, and 5%
sodium chloride are examples of hypertonic fluids.
Hypotonic solutions such as 0.45% sodium chloride and 0.3% sodium chloride are used
to aid the kidneys in the excretion of solutes by providing free water, sodium, and
chloride. Excessive use of these hypotonic fluids can lead to hypotension, cellular edema,
and cell damage.
Osmotic pressure is a factor that determines the physiologic acceptability of a solution
for use in the body. Osmoticity has a direct therapeutic action, such as the use of mannitol
to increase the osmotic pressure of tubular urine which then induces diuresis. The use of
saline laxatives also employs the use of osmotic pressure variances to clear out the colon.
Osmolality refers to a weight- to-weight relationship between the solute and the solvent.
An osmolal concentration of one means the solutions contains 1 osmol of solute per
kilogram of water. Osmolality is not affected by temperature.
Osmolarity refers to a weight-to-volume relationship between the solute and the solvent.
An osmolarity of one is a solution that has a concentration of 1 osmol of solute per liter
of solution. A 1 osmolal solution of a solute is more concentrated than a 1 osmol
solution. The USP requires that solutions which provide intravenous replenishment of
fluid, nutrients, electrolytes as well as osmotic diuretics state the osmolar concentration in
milliosmols/L (mOsm/L) except where volumes are less than 100 ml. Dextrose 5% in
lactated Ringers has a stated osmolar concentration of 524 mOsm/L, whereas the
osmolarity of 0.9% sodium chloride is 291.4 mOsm/L.
When formulating parenterals, the solution should have its tonicity adjusted if possible to
make the solution isotonic. Hypertonic and hypotonic solutions are usually administered
in small volume, slowly, and into large veins for further rapid dilution and distribution.
Issue irritation, pain on injection, electrolyte shifts are all attributed to the injection of
solutions with tonicity variances from the normal serum. Osmoticity is a major factor in
the determination of either peripheral or central administration of a solution. Nutritional
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solutions with hyperosmotic concentrations of nutrients must be administered centrally to
avoid hemolysis and other vascular complications. Peripheral infusions should not have
an osmolarity exceeding 700-800 mOsm/L. Osmolarity of blood is 285 mOsm/L.
General Preparation Guidelines
The American Society of Hospital Pharmacists, IV solution manufacturers, and colleges
of pharmacies all have published books, videos, and literature concerning the preparation
steps required in the compounding of sterile products. The reader is referred to the ASHP
Guidelines on Quality Assurance for Pharmacy-Prepared Sterile Products published in
the American Journal of Health System Pharmacy for an intense review of the specifics
required.
Sterile products should be prepared in an ISO Class 5 horizontal or vertical laminar flow
hood (LFH). This hood should operate for a minimum of thirty minutes before product
preparation can begin. Personnel should wash hands with a suitable germicidal agent for
an appropriate length of time before beginning product preparation. The use of gloves,
masks, scrubs is suggested per risk level guidelines and required by USP Chapter <797>.
All aseptic manipulations should be performed at least 6 inches within the horizontal
hood, or three inches above the surface of a vertical hood. The hands and objects should
be positioned as to not block the air flow between the HEPA filter and the objects. Great
care should be taken to avoid touch contamination.
All container closures should be disinfected by swabbing or spraying with alcohol. The
LFH should be cleaned initially, and as required throughout the day, working from the
back (area closet to the HEPA filter) to the front (open end) with a germicidal solution
(isopropyl alcohol), before preparations begin. The sterile product order should be
reviewed for completeness, compatibility, and fluid therapy considerations before
preparation is begun. All components are gathered that are required for the preparation of
the product again before actual preparation is begun. The smallest syringe and needle that
will accommodate the volume needed are utilized to prepare the product. After the
product is prepared, it should be checked for clarity and presence of particulate matter.
The label should be double-checked with the components utilized before attachment to
the container.
The label should contain the following information:
[Patient Name and Room Number] [Date of Preparation]
[Solution Name and Volume] [Additive Name and Volume]
[Beyond Use Date] [Administration Rate]
[Storage Instructions] [Ancillary Precaution Labels]
[Total Volume]
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The physician may order infusion to be administered at rates that must be calculated by
the pharmacist for safe and accurate administration by the nurse. Some common
questions are reviewed.
A. Microgram/Kilogram/Minute
Patient – 176 Pounds
Drug – Dopamine 800mg in 500ml D5W
Dose – 5 mcg/kg/min, calculate dose in ml/hr
Procedure
:
1 Convert weight from pounds to kilograms 176 ÷ by 2.2 = 80 kg
2. Calculate the milligram per ml concentration of the drug involved. 800 mg ÷ 500
ml = 1.6 mg/ml
3. Multiply the milligram concentration by 1000 to obtain the microgram
concentration per ml. 1.6 x 1000 = 1600 mcg/m
4. Determine dose required. 5 mcg x 80 kg = 400 mcg/min required 1600mcg/1ml
= 400 mcg/x ml 1600x = 400 x = 400 ÷ 1600 x = 0.25 ml per minute
5. Change mls per minute to mls per hour.0.25ml x 60 min = 15ml /hr
B. Units of Drug Per Hour Heparin 20,000 units in 500 ml D5W Dose = 1000 units
per hour Calculate dose in ml/hr
Procedure
:
1. Calculate units per ml. 20,000 units ÷ 500 = 40 units per ml
2
Calculate dose from concentration given. 40 units/ml = 1000 units/x 40x = 1000
x = 25 ml/hr
C. Compound a Sodium Chloride Concentration as Ordered
Physician Order – Prepare 1/4 NS 1000 ml
1. Determine sodium chloride content of NS. (There are 154 mEq of sodium
chloride in a 1000 ml solution.)
2. Determine amount of sodium chloride needed for ¼ NS 1000 ml.154 ÷ 4 = 38.5
mEq sodium chloride
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3. Determine volume of sodium chloride needed to add to solution by calculating
volume from concentration available in pharmacy. Sodium chloride
concentration = 4 mEq/ml Volume required: 38.5 mEq/x ml 4 = mEq/1ml
38.5 = 4 x 9.6ml = x
INTRAVENOUS FLUIDS
Classification of Intravenous Fluids
Large volume injections intended to be administered by intravenous infusion are
commonly call IV fluids. IV fluids are also referred to as IV solutions, even though the
USP refers to IV solutions as injections, as they are intended to be administered by
infusion or injection
.
IV fluids are classified into three broad categories:
1. Hydrating solutions
2. Replacement solutions
3. Special solutions
Hydrating fluids are utilized in patients to correct volume deficits, and provide venous
access. These are dextrose or dextrose-saline combination fluids. Another purpose of
these fluids is to determine adequacy of renal function and to promote renal function
when volume deficit exists. Hydrating solutions of dextrose contain very little caloric
content, (D5W – 1000 ml = 170 calories) and are not to be utilized to maintain patients
who are unable to eat. Replacement solutions are used to meet daily maintenance needs
plus correct deficits of water and electrolytes in patients. Examples of replacement fluids
include Lactated Ringers injection, Normosol® and Plasmalyte® solutions. These
solutions are usually used in surgical patients and contain sodium, potassium, calcium
chloride in substantial amounts. Some solutions also contain magnesium, lactate, acetate
and gluconate. Because of their electrolyte content, replacement solutions are ideal fluids
to replace losses of water and electrolytes due to vomiting, gastrointestinal (GI) suction,
fistulas, diarrhea, and abnormal sweating. Special solutions include hypertonic fluids
(3% sodium chloride), parenteral nutrition fluids, and other special therapy fluids.
IV Fluid Terminology
Intravenous solutions are given to maintain or replace fluids in the body. These solutions
are also employed as delivery vehicles to administer prescribed medications
intravenously. A medication added to an intravenous fluid is called an additive, and the
completed preparation is called an intravenous admixture.
A large volume parenteral (LVP) is a preparation containing between 250 ml and 3000
ml of a sterile solution. A small volume parenteral (SVP) is a preparation containing a
small volume of solution, up to and including 150 ml. SVPs are used to administer
intermittent medications such as antibiotics. SVPs are also known as secondary
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medications, as they are administered by co-infusing the SVP into the primary solution
(also known as the LVP). Piggyback administration is the method of intravenous
infusion by which two solutions from two containers flow into a patient’s vein through a
common injection site.
Delivery System
A number of systems are used for delivery of secondary medications by IV infusion.
These include the following:
1. Minibags/Minibottles
2. Volumetric Chambers
3. Syringes
4. Controlled-Release Infusion Systems
Minibags/Minibottles
Addition of a drug to prefilled containers of IV fluids, also known as piggyback
solutions, partial- fills, minibags, minibottles, is one of the most common delivery
systems used in hospitals today. The solutions available include normal saline and
dextrose 5% in water. Sizes include 25ml, 50 ml, and 100 ml. The Abbott Add-Vantage®
system provides a method for locking certain medication vials to the mini-bag for
dilution when administration is being accomplished. Frozen systems provide pre- mixed
small volume parenteral antibiotics ready to be administered upon thawing. Premixed
piggybacks of certain drugs (i.e., Zantac®, Tagamet®) are also available from
manufacturers already mixed in iso-osmotic mini-containers for administration.
Volumetric Chambers
Volumetric chambers are clear, graduated cylinders that are built into an IV set. These
chambers are known as Solusets® or Buretrols®, and offer a means to deliver a specific
volume of fluid to a patient, as well as a specific medication when added to the chamber.
These chambers were widely used before the advent of the minibags. Incompatibilities,
drug identity, bacterial contamination, and expense are problems that have forced the
majority of use of these sets to be limited to volume-restricted patients.
Syringes
Dilution of a drug in a small volume of fluid (1-50 ml) for administration over a short
period of time can be accomplished using a syringe. Syringe pumps can be used to
accomplish this drug delivery; usually for 30-60 minute administration. The syringe
pump delivery system allows a small amount of fluid to be used to deliver drugs, which is
of particular value in pediatric patients as well as critical care patients that are fluid
restricted.
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Controlled-Release Infusion System
The IVAC Corporation marketed the CRIS system in 1986. This system employed the
use of an adaptor which allowed drugs to be administered directly from a vial, via
attachment of the vial to the adaptor on the IV set. This system requires standard size
vials. Further, a greater amount of drug is administered at the beginning of the infusion
than at the end, and the device is relatively expensive. The drug solution in the vial must
be more dense (have a higher specific gravity) than the primary IV solution for the drug
to be completely delivered, which limits the use of the system. This system is rarely used
anymore in the U.S. The MICROS system (Membrane Intravenous Controlled-release
optimal system) uses the principle of electrodiffusion for drug delivery. This device
contains a permeable membrane coated with biocompatible chemicals that generate
electropotential energy when in contact with ionically charged drugs. Neutrally charged
drugs will not be completely delivered utilizing this system. The MICROS system does
offer membrane filtration in conjunction with multiple drug delivery and minimal volume
which may be a useful delivery system in the pediatric population. This system is no
longer available.
Packaging System
Intravenous solutions are available in glass and plastic containers. Polyvinyl chloride,
flexible, non-vented containers are available from Baxter (Viaflex®), Hospira (Lifecare®)
and Ethylene/propylene copolymer flexible containers from McGaw (Excel®). Glass
containers must be administered using a “vented” administration set, otherwise, the
solution will not be able to flow. Glass containers contain a vacuum inside. Air intake is
essential for the solution to flow correctly. Plastic containers are flexible and collapse as
fluids flow out, and they do not contain a vacuum. Plastic containers therefore do not
require a vented set. Plastic containers have an injection portal for the addition of drugs.
The use of a 20 gauge needle and minimum number of punctures is recommended for
these injection sites. Multiple injection ports are available from various manufacturers to
prevent multiple punctures which would be required in admixing some parenterals.
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TYPES OF IV ADMIXTURE
Continuous Infusions
Administration of a drug by continuous infusion prevents fluctuating blood level peaks
and troughs. Drugs with narrow therapeutic ranges (i.e., heparin, lidocaine, and
aminophylline) should be administered by continuous infusion. Regulation of the rate of
infusion can be titrated to clinical response. Higher steady state levels can be attained by
faster administration rates, however, this will not shorten the time to reach steady state by
the drug. The rate of the infusion is influenced by the condition of the patient, body
surface area of the patient, age, type of fluid being administered, fluid composition, and
the patient’s tolerance to the infusion. Patient’s weight and desired therapeutic effect are
the two dominant driving factors for rate of infusion. The cardiac and renal status of the
patient affects the desired rate of administration. Rapidly infusing fluids can overwork an
impaired heart and renal damage may cause fluid retention Pulmonary edema and
cardiovascular disturbances can occur depending on the age of the patient.
If the fluid is being utilized to administer a drug, the effects of administering that drug
too fast must be considered. Potassium is a common additive to IV solutions. Potassium
is very irritating to the veins, and exerts deleterious effects on the heart if administered
rapidly. Potassium is generally administered at a rate of 10-20 mEq/hr and no more than
80 mEq of potassium should be added to a liter of fluid. In urgent cases, as much as 40
mEq/hr of potassium may be administered.16 Dilution of potassium is required before
administration to the patient. Minimum dilution for administration in potassium
deficiency is 20 mEq/50 ml solution, given over 1 hour. Cardiac monitoring and serum
potassium level monitoring are required for administration of potassium using these
methods.
As a general rule of thumb, administration of 2-3 liters of fluid a day is acceptable for the
average patient. More fluid may be required in certain disease states. In pediatric patients,
the usual volume of fluid administered is the range 100-500 ml, depending on the age and
disease state of the patient.
Flow rate calculation is an important part of fluid administration. To calculate flow rate,
the drop delivery of the administration set must be known. This varies per manufacturer,
from 10-60 drops/ml. The volume of fluid to be administered, as well as total infusion
time must also be known.
Example: Administer 1000 ml of D5W over 8 hours
Volume = 1000 ml
Time of Infusion = 1000 ml/8 = 125 ml/hr
Administration Set = 10 drops/ml (macrodrip set)
Drops/ml of set/60 minutes x total hourly volume = drops/minute 10 drops/ml ÷ 60
minutes x 125ml/hr = 20 drops/minute
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Note that for all 10 drop/ml sets, one can divide the total hourly volume by 6 to get
drops/minute. If the set administers 15 drops/ml, then divide hourly volume by 4, since
15 drops/ml divided by 60 = 1/4. For a 60 drops/ml set (microdrip) divide the hourly
volume by 1, since 60 drop/ml divided by 60 minutes = 1.
The infusion should be checked frequently to maintain the required flow rate. Height of
the solution bottle, clot in the needle, position of the needle, change in temperature or
composition of the fluid, and trauma to the vein are all factors that affect infusion
administration. The use of an infusion control device versus frequent (hourly) checks is
usually utilized to maintain required flow rates.
Intermittent Infusions
Antibiotics are generally administered by intermittent infusion over 30-60 minutes.
Intermittent infusions allow for peak concentrations in the serum to be reached.
Intermittent infusions are drugs diluted in volumes of usually 50-100 ml. This dilution
helps to reduce vein irritation, and intermittent therapy aids in drug stability. Advantages
of this type of infusion are that intermittent infusions help to avoid incompatibilities, and
a larger dose of drug can be administered using this method versus direct push.
Intermittent administration places a higher concentration of drug in the serum, and this
higher concentration gradient allows for diffusion to occur into the affected tissues
yielding peak drug levels to effectively eliminate the infection. Intermittent therapy is
not recommended for drugs of narrow therapeutic range, as high levels may lead to toxic
effects.
A common dilution "rule of thumb" to use when administering antibiotics is to dilute
1g/50ml, 2g/100ml, etc. Certain antibiotics require further dilution due to vein irritation.
Examples of these include the following:
1. Ciprofloxacin – 400 mg/200 ml
2. Doxycycline – 200 mg/100 ml
3. Vancomycin – 1000 mg/250 ml, 500 mg/100 ml – 250 ml of solution
4. Erythromycin – 100 ml-250 ml due to vein irritation
The clinician is advised to check the hospital’s policies and procedures for minimum
dilution of all drugs, as well as the package insert to determine volume and type of
solution required for safe administration of the drug.
Irrigations
Irrigations are solutions used to wash a body cavity or a wound. Common solutions
utilized for this purpose are sterile water for irrigation, sodium chloride for irrigation,
acetic acid solution, glycine and Neosporin® GU irrigant. Irrigations are sterile solutions
that are subject to the same strict manufacturing controls as injections, however, they
may be packaged in containers designed to empty rapidly, and usually contain over 1000
ml of fluid.
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Surgeons commonly use several liters of irrigation solutions during procedures to
maintain tissue integrity, remove blood and provide a clear field of view. There are
various types of irrigation solutions that can be used. Glycine (1.5%) can be used to
eliminate the risk of intravascular hemolysis. Sorbitol (3%) is a non-hemolytic urologic
irrigant. Neosporin® GU irrigant can be added to 1000 ml of normal saline and used as an
irrigant. These irrigation solutions require a special cysto-administration set so that they
can be connected to a catheter for delivery.
BASIC PRINCIPLES OF IV COMPATIBILITY
Drug Product Stability Factors
Drug stability and compatibility are critically important in the provision of safe and
effective drug therapy to hospitalized patients. Hospital pharmacists and technicians are
subjected daily to multiple questions regarding the impact of administering drugs
utilizing various delivery systems to critically ill patients. With the technology available
today, multiple drugs may be administered simultaneously to a patient. Determining the
compatibility of such regimens is of great importance.
Drug product decomposition is the result of a chemical or physical reaction. This results
in a reduction in potency, shelf- life, expiration time, utilization time, and loss of active
drug available for delivery to the patient. Hydrolysis and oxidative reactions may
produce therapeutically inactive agents, as well as possible toxic substances.
Incompatibility refers to the physicochemical reactions that produce a change in the drug
due to concentration-dependent precipitation and acid-base reactions. The administration
of drugs in various delivery systems is therefore dependent upon balancing the
concentration of the drug(s) being delivered as well as the maintenance of the pH of the
environment in which the drug is administered.
Drugs are classified as "Incompatible" when the resulting combination results in a
subtherapeutic quantity of the drug being available for delivery, and/or because toxic
decomposition products result. A minimum of 90% of the drug must remain intact and
be available for delivery. Parenteral products with short stability and tight storage
requirements are required to have more than 100% of the labeled potency (100% +/10%) due to their chemical instability. A product may lose less than 5% of its potency but
still be termed incompatible if the combination generates toxic decompositions products.
Types of Incompatibilities
It is estimated that over 30% of the commonly utilized drugs are incompatible or unstable
when added or combined with usual fluids and agents. Incompatibilities may be
therapeutic, physical, or chemical in nature. Therapeutic incompatibilities are drug
interactions that occur when two or more drugs with antagonistic or synergistic
pharmacologic properties are combined. Physical incompatibilities are also termed
"visual" incompatibilities because the drug-drug or drug vehicle combination results in a
change in the solution’s appearance, color, clarity, or formation of a precipitate, turbidity,
or evolution of a gas. Physical incompatibilities may be the result of solubility changes,
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container interactions, and changes in pH. The basic chemistry equation that states the
following: "Acid + Base = Salt and Water" should be remembered to avoid physical
and chemical incompatibilities.
Chemical incompatibilities are the result of hydrolysis, oxidation, photolysis, reduction,
or complexation, and generally can be identified by analytical methods. Solvolysis is the
decomposition of a drug due to solvent reaction. Photolysis is the degradation of a drug
due to light. Oxidation is a prime cause of product instability. Drugs containing an ester
or an amide linkage are prone to hydrolysis (i.e., cocaine, tetracaine). All
incompatibilities actually have a chemical basis, however this classification scheme helps
depict the types of problems encountered when combining drugs and fluids for delivery
to the patient. If the addition of a particular drug or fluid to another drug or fluid has not
been documented, the use of these applied principles of physical chemistry will help
depict the compatibility and stability of these drugs. INCOMPATIBILITIES ARE
BOTH PHYSICAL AND CHEMICAL IN NATURE. CHANGES IN A
SOLUTION’S APPEARANCE OR FORMATION OF A PRECIPITATE MAY
OCCUR.
Acid-Base Environment of the Drug
The factor that is most responsible for incompatibilities is pH. The acid-base
environment of the drug (pH) is critically important to the solubility and stability of the
drug. The portion of the drug in its ionized form and the solubility of the un- ionized form
is controlled by pH. A drug may be formulated at a high pH sufficient enough to make it
soluble. If the pH is lowered, the drug’s solubility may be exceeded, resulting in the
precipitation of the drug (i.e., Phenytoin sodium in D5W). Amines (such as dobutamine,
dopamine, epinephrine, and morphine) are basic and are generally soluble in basic media.
The degradation of ampicillin in solution is caused by pH changes. The reaction rate
constant of ampicillin is lower at a pH of between 5-7, versus a pH of 3.0 or greater than
9. Ampicillin sodium contains the penicillin beta- lactam structure that hydrolyzes under
acidic or basic conditions. Ampicillin sodium forms a slightly basic solution in water, and
a change in pH toward acidity can cause precipitation. The pH range of D5W (dextrose
5% in water) varies from 3.5-6.5, depending on the free sugar acids present (formed
during the sterilization process) and the storage of D5W. Ampicillin in normal saline will
lose less than 10% of its potency in 8 hours, however, the same amount of activity will be
lost in 4 hours if ampicillin is dissolved in D5W. The low pH range of D5W (pH 3.5 6.5) induces faster degradation of the drug than would occur at the higher pH range of
normal saline. In general, solutions of high pH are incompatible with solutions of low
pH, due to the poor solubility of the free acids and bases that are formed.
Solubility
Water is the most common solvent utilized in parenteral products. Poorly water-soluble
drugs may be dissolved in non-toxic, non- irritating, pharmacologically inactive
substances such as ethanol, propylene glycol, glycerin, and/or mixtures of polyethylene
glycol. A drug is maintained in solution as long as its concentration is below is saturated
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solubility. Diazepam injections consist of 40% propylene glycol, 10% ethanol, 1.5 %
benzyl alcohol, benzoic acid and sodium benzoate and water. If diazepam is diluted 1:10
with water, D5W, or NS, a precipitate forms. This is because this dilution exceeds its
saturated solubility by 10- fold. Precipitation can also occur as a result of the formation
of sparingly soluble salts. If calcium chloride or gluconate is mixed with sodium
bicarbonate, an insoluble calcium carbonate salt is formed and a precipitate occurs.
Solubility of a weak acid or weak base drug depends on pH. The total solubility of a drug
or drug combination may be calculated at any pH by knowing the solubility of the acid
and salt form as well as the dissociation constant of the acid. A particular drug-drug
combination compatibility is dependent upon the solubility of its combined product
which is in turn dependent upon the drug concentration, dilution, ordering of mixing, and
solution type.
Concentration
Drug stability and compatibility vary depending upon drug concentration of the final
product in a selected vehicle. Trimethoprim/sulfamethoxazole (Septra®, Bactrim®) is an
example of a medication whose stability varies upon drug-to-vehicle dilution. Dilutions
of 5 ml per 75 ml of dextrose 5% in water (D5W) should be used within 2 hours, whereas
5 ml per 125 ml of D5W should be used within 6 hours. Concentration dependency is
very important in syringe delivery systems and ambulatory pump infusion therapy.
Precipitation of a drug will not occur as long as the drug concentration doesnot exceed its
saturation solubility.
An example of a common effect of solubility and concentration is placing sugar in a glass
of iced tea. The iced tea will hold a certain concentration of sugar. When solubility of the
iced tea is exceeded by the concentration of sugar in the tea, then the sugar precipitates
out.
Other Factors
Other factors can influence the compatibility of drugs. The buffer capacity of the
solution, the order in which the drugs are mixed, expose to light, temperature, amount of
time in which the drugs are in contact, and complexation of the drugs are all factors
which influence drug compatibility and stability.
Buffers are agents which resist pH changes. Drug solubility is related to pH changes,
therefore buffers are used to stabilize solutions against chemical degradation due to
changes in pH. The buffer capacity of total parenteral nutrition solutions (TPNs) is
determined by amino acid composition and concentration, as well as pH of the solution
and presence of other additives. Most intravenous solutions have a negligible buffer
capacity, and the pH of the solution is determined by the additives. The buffer capacity
of TPN solutions allows calcium and phosphate to be mixed together in the same solution
in certain concentrations. However such a combination is not possible in other
intravenous solutions.
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The order of mixing drugs also affects the final pH of the solution, influencing the
solubility and stability of the drug combination. Some drugs are sensitive to light.
Different wavelengths of the light affect the degradation process in varying degrees.4 The
number of chemical reactions also increases as time elapses from the point of mixing to
the point of administration. Drugs may bind together (complexation) when mixed.
However, an example that results in enhanced solubility is the complexation of caffeine
and sodium benzoate.
Temperature determines the rate of chemical reactions which can lead to product
degradation. Reactions catalyzed by enzymes are temperature dependent. Overall drug
stability is related to its solubility, which can increase or decrease with high or lower
temperatures. Lowering the temperature may decrease drug solubility which may induce
instability and precipitate formation. Likewise, increasing temperature may increase
solubility and enhance the solubility of the drug. Drugs exist in solution at specific
temperature ranges. To avoid reactions due to temperature changes, drugs are required to
be stored at specific temperature ranges.
Solution Compatibility
The use of intravenous fluids as vehicles for drug administration has provided a method
of reducing the irritation potential of the drug, as well as providing a convenient system
for continuous drug therapy. The use of intravenous fluids for restoration of electrolyte
balance is common practice. The addition of sodium chloride, potassium chloride, and
calcium gluconate individually to commonly utilized intravenous solutions does not
present any compatibility problems. Utilizing the acetate salt form of sodium and
potassium also does not present a problem when these are added individually to
intravenous fluids. Combinations of electrolytes are routinely added to total parenteral
nutrition solutions. The type of salt utilized is important to keep imbalances from
occurring. The use of chloride salt of calcium is not recommended due to the propensity
of divalentcations to dissociate and induce solubility problems.
Solution compatibility must be checked utilizing the manufacturer’s product information,
as well as various other standard reference sources, before adding the drug to the
solution. Reading the label on the drug package may help indicate the solubility
characteristics of the chemical. The presence of solvents such as polyethylene glycol,
and/or ethyl alcohol can indicate reduced solubility of the drug. Erythromycin is
compatible with dextrose and normal saline. However, normal saline cannot be
used to constitute erythromycin vials, as this solution, as well as any solution that
contains inorganic ions, will cause a precipitate to form. Only preservative- free sterile
water for injection should be utilized to constitute an erythromycin vial. Once the drug is
in the solution, it can then be added to normal saline without precipitation. Erythromycin
Add-Vantage® containers may be constituted with normal saline in this piggyback
delivery system without precipitation problems.
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PREDICTING COMPATIBILITY IS LIKE LOOKING INTO A
CRYSTAL BALL
Additive Compatibility
Determining the compatibility of an additional drug combined in solution with another
drug can be somewhat like looking into a crystal ball. Incompatibility is both a physical
and chemical reaction, and determining if a chemical reaction has occurred in not an easy
task. Physical (visual) changes and stability of the components with less than 10%
decomposition occurring are the criteria utilized by most citations in predicting
compatibility. Professional judgment is required in utilizing the information provided to
determine the compatibility of the drugs involved. Conflicting information is often found
regarding various drug-drug combinations. Because of this, the clinician should crosscheck references, i.e., check drug A with drug B, then check drug B monograph
concerning combination with drug A. Use of more than one reference is also advocated.
The effects of pH, concentration, time, temperature, buffer capacity, and dilution should
be considered in the final determination of compatibility.
If the compatibility of a particular drug combination has not been documented,
consideration of what types of reactions that the drug combination might undergo can
help predict compatibility. Knowledge of the structure of the drug (i.e., is it an amide,
lactam, phenol, catechol, etc.) will determine what reactions may occur.
Oxidation is a primary cause of product instability. The rate of oxidation is proportional
to concentration, time, and temperature. Antioxidants such as sodium sulfite or sodium
metabisulfite may be employed in these systems. Phenol drugs, most steroids, and most
tricyclic compounds are susceptible to oxidation.
Hydrolysis is also influenced by pH and temperature. A general rule of thumb is for every
ten degrees rise in storage temperature, the rate of the reaction doubles or triples.
Hydrolysis increases the decomposition of the drug and decreases the amount of active
ingredient. Esters and amides are examples of drugs that undergo degradation through
hydrolysis.
Photodegradation of a drug (i.e., chlorpromazine) limits the stability of the drug. The
intensity, wavelength, size, shape, color, and composition of the container are also
variables which influence the velocity of the photolysis reaction. Furosemide,
nitroprusside, and tetracyclines are examples of drugs which undergo photolytic
degradation.
The aqueous solubility of a weak acid or a weak base is dependent on pH. The solubility
of a weak acid in a solution at a given pH is the sum of the concentrations of the acid and
salts forms. For a drug that is a weak base, the high pH allows the free form of the drug
to exist, and the solution can contain no more than the saturation solubility of this form.
The total solubility of a drug is therefore dependent upon the drug pKa and solution pH.
Drug pKa is the method utilized to express the negative log of the acidity constant, or of
the basicity constant, pKb.
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USE DRUG pKa, SOLUTION pH, and SOLUBILITY TO HELP
CALCULATE COMPATIBILITY
Drug pKa attempts to relate the relationship between structure and the acid or base
strength of the drug. The effect of the biological pH on the relative ionization of acid and
basic drugs can be expressed using the Henderson-Hasselbach equation:
pKa - pH + log acid/base
Formulation changes and altered storage conditions can greatly affect drug stability.
Consideration of the structure of the drug, its solubility, potential stability, and its
probability for admixture problems, are essential for preventing intravenous compatibility
problems.
Drug in Syringe Compatibility
Small volume delivery systems present multiple challenges for the clinician. Not only
must physical and chemical interactions be considered, but also the influence of tubing
composition, length, diameter, injection site, and the amount of drug delivered per
specified period of time should be well-thought out. Certain drugs absorb to glass, plastic,
and require filtration devices for administration. Drug solution osmolality and pH, and
drug solution density are all factors in determining final syringe volumes, administration
times, and stability/compatibility.
Manufacturers publish recommended concentrations for syringe delivery systems that
result in lower osmolalities and help avoid infusion phlebitis. The main factor in
determining syringe compatibility is the concentration of the drugs to be combined. The
clinician can avoid concentration-dependent incompatibilities between drugs by
decreasing the amount of time the drugs are combined, use of larger volumes of solution,
and attention to the order of mixing.
All of these can assist the clinician in determining the compatibility of the mixture. Most
literature citations limit syringe combinations to a thirty minute time frame when
predicting compatibility. Interaction with the syringe plastic, stability questions, as well
as other concerns make this time limit a good "rule of thumb".
Y-Site Compatibility
Administration of drugs via a y-injection site of an administration set being used to infuse
a primary solution is a method utilized frequently in hospitals. The small concentration
(1:1 ratio) of the mixture can avoid certain compatibility problems that would occur if the
drugs were admixed or otherwise combined with the drugs in solution. The clinician
should consult the various compatibility references for information concerning y-site
compatibility of drugs.
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Total Parenteral Nutrition Compatibility
A great deal of work has been accomplished in the area of total parenteral nutrition
compatibility. For years, the placement of non-electrolyte, non-vitamins is this complex
solution was inconceivable. Utilizing a TPN solution as a vehicle for administration of
other drugs has recently gained acceptance. The drug concentration to be added, pH and
type of additive, volume and duration of mixing are all considerations in determining
TPN compatibility. The routine admixture of an H-2 antagonist has become standard in
most hospitals to help decrease costs as well as the need for multiple admixtures for a
single patient. The concentration of amino acids, pH of the solution, buffer capacity, and
dextrose concentration are important factors to consider when additives are requested.
The higher the concentration of amino acids and dextrose, the better the environment for
addition of high concentrations of calcium and phosphate.
Inline Filter Compatibility
Inline filters are used in many facilities of administration sets to prevent particulate
matter contamination as well as reduce other complications resulting from intravenous
therapy. The National Coordinating Committee on Large Volume Parenterals stated in
1980 that drugs administered in concentrations of less than 5 mg/24 hours or in
concentrations of less than 5 mcg/ml, should not be administered through inline filters
unless documentation exists that the drug will not be absorbed or adsorbed through the
filter. Many chemotherapy agent manufacturers now advocate the use of a filter for drug
administration. The composition of the filter membrane (cellulose ester vs. nylon) is
important in determining possible additive loss. The volume of solution to be
administered is also of critical importance in determining drug loss. The volume of a
solution to be administered is also of critical importance in determining drug loss via the
administration equipment. The clinician should review the literature before administering
drugs through inline filtration devices.
Basic Precautions
There are some basic precautions that can help reduce the risk of an incompatibility
occurring.
1. Use Freshly Prepared Solutions
Ideally, all solutions should be discarded after 24 hours. Solutions may not have been
stored properly or storage temperatures maintained as required, which can produce
incompatibilities even before any other agents are added.
2. Keep the Number of Drugs Utilized to a Minimum
As the number of drugs utilized increases, the chance for incompatibilities to occur also
increases.
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3. Thoroughly Mix Each Additive
Thoroughly mixing the drug with the vehicle as each are added can help prevent
complexation and other problems from occurring.
4. The Order of Mixing Additives Affects the Compatibility
Diluting drugs before admixing, as well as adding problem additives last (i.e., calcium in
a TPN solution) can help prevent incompatibilities from occurring.
5. Be Aware of Compatibility Problems in Advance of Mixing
Pharmacists and nurses should keep a reference file of quick answer charts to avoid
compatibility problems.
Predicting Incompatibilities
When attempting to predict compatibility, the principles of admixture compatibility
discussed throughout this module should be applied. The philosophy of "When In Doubt,
Call It Out" may be applied if prediction is impossible. Alternative solutions include the
following:
1. Utilize another route or site of administration if possible. (i.e., IV push, IM, via TPN,
through another site)
2. Physically separate problem drugs from each other by staggering the administration
interval. (i.e., two drugs prescribed at q6h – give one on a 6-12-6-12 time schedule, and
the other on a 4-10-4-10 time schedule)
3. Use heparin lock for administration, central line, or other peripheral site.
4. Thoroughly flush the line between drugs so contact is avoided.
5. Administer the drugs as close to the catheter as possible, and utilize dilution and Y-site
administration techniques.
Below are two sample problems for attempting to use some of the principles that have
been discussed for predicting compatibilities.
Sample Problem #1: The patient is on a continuous infusion of aminophylline, 4mg/1ml
concentration. The doctor has also written an order for Cefazolin 1g IVPB q8h. Can
these two drug be administered together?
Aminophylline: pH 8.6-9.0, alkaline solution, would be incompatible with acids as
precipitation would occur
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Cefazolin Sodium: pH 4.5 - 6.0, below 4.5 precipitation occurs, above 8.5
hydrolysis occurs
Answer #1: Incompatible, a separate line would be needed for aminophylline ideally, and
a heparin lock site should be used for administration of the antibiotic. It would be
incorrect to stop the continuous infusion to administer the antibiotic, as maintaining a
therapeutic level of theophylline is critical.
Sample Problem #2: The patient is in the intensive care unit and is to receive Dopamine,
Dobutamine and heparin continuous infusions. Can all three be administered together?
Dopamine HCL: pH 2.5 - 4.5
Dobutamine HCL: pH 2.5 - 5.5
Heparin Sodium: pH 3.8 0 7.6
Answer #2: Dopamine and Dobutamine are catechols, and as such, are subject to
oxidation which often causes discoloration. When combined with heparin in
concentrations of 50,000 units/1 or less, they are compatible. There have been conflicting
reports regarding such combinations, however, most references now report such a
combination as compatible
When determining compatibility of multiple drugs, the structure of the drug (i.e.,
catechol, amide, carboxylate, etc.) can help to predict solubility, type of reactions that
may occur at various pH ranges, and compatibility of the additives. Utilizing this informa
tion with published information should aid in determining the compatibility of various
drug classes and combinations.
BLOOD COMPONENTS
Objectives of Transfusion Therapy
Blood has long been regarded as a life-saving fluid. Although blood transfusions have
saved lives, there have been many instances of detrimental consequences after receiving
this fluid. Acute hemolytic reactions, transmission of infectious disease (i.e., hepatitis,
AIDS), and febrile reactions have all been complications of transfusion therapy.
The objectives of transfusion therapy are as follows:
1. Provide adequate blood volume and prevent hemorrhagic shock;
2. Increase oxygen-carrying capacity of the blood; and
3. Replace platelets and/or clotting factors to maintain homeostasis.
Blood preparations that may be transfused include whole blood, packed red cells,
platelets, granulocytes, plasma, and plasma components (fibrinogen, albumin, and plasma
substitutes). Patient identification, inspection of blood product, proper administration
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technique, and close observation are all important rules that must be followed for safe
transfusion therapy.
Compatibility with Intravenous Fluids
The pH (usually 4.0-5.5) and tonicity of intravenous fluids (hypo/hypertonic) make
almost all IV fluids incompatible with the administration of blood. Hemolysis of the
blood cells would occur if dextrose 5% in water were administered with blood. Lactated
Ringers solution contains calcium, and would cause clotting of blood in the infusion set if
administered with citrated solutions of blood. Normal saline (0.9% sodium chloride
injection) is the only intravenous fluid that is compatible with blood, as this solution is
isotonic, and although pH of this solution is acidic, (pH 4.0) infusion of saline with blood
components will not harm the blood product. No other preparation-antibiotics, inotropic
agents, etc., should ever be administered with blood. When these preparations are
administered, there is a dilution of the product before harm can occur to the blood.
However, if administration of these products would occur simultaneously with blood,
hemolysis would occur with these non-diluted products being infused with a blood
product. Normosol® R (pH 7.4) is a product made by Abbott Laboratories that is isotonic
and has a neutral pH, thus it is approved for use with the administration of blood. This
product should not be utilized, however, unless hospital policy permits use of this
specialty solution.
Use of Blood Filters
Blood must always be administered through a blood filter specifically designed for the
particular component’s administration. Straight and Y-type blood sets are available for
administration of blood. Normal saline is utilized in the Y-site set to aid in transfusion
procedures. Mesh and microaggregate filters are available for administration of blood
products. Mesh filters range in size from 70-170 micrometers in size. Microaggregate
filters are preferred to the nylon screen mesh filters due to the latter’s inability to trap
microemboli, reduced flow, and clogging problems.
Microaggregate blood filters vary in size from 20-40 micrometers. Correct priming and
flushing of the filter is important to prevent administration problems. These procedures
may differ depending on manufacturer. Therefore the clinician should be advised to
consult the package for instructions before use. In general, blood filter sets should not be
used for more than 4 hours. High efficiency leukocyte removal filters for red blood cells
and platelets are available for use in the administration of these products. The clinician is
advised that these filters are not interchangeable. The proper blood filter and
administration set is required for safe administration of all blood component therapy to
the patient.
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IV FILTRATION
Literature Review
Contamination of the intravenous system can occur virtually at any point, from the time
of manufacture until the infusion is terminated. In an effort to improve the quality of
patient care in the administration of intravenous fluids, the United State Pharmacopeia
and the Food and Drug Administration (FDA) established standards of practice
associated with the manufacture and use of parenterals. The newly expressed limits for
particulate inclusions in large-volume infusions were defined as 50 particles per ml that
are equal to or greater than 25 microns. The limit for small volume parenterals was
defined as 1000 particles per container equal to or greater than 25 microns. These
intrinsic contamination limits were the results of the identification of particles within
solutions from the rubber stopper, glass fibers, mica flasks and metal shavings. The
compendia also convened a coordinating committee to investigate and evaluate current
manufacturing and hospital procedures involving intravenous solutions.
Published reports of infections and fatalities involving the use of commercial and hospital
manufactured parenteral products are abundant. In 1953, Michaels and Rubner
documented the first recognized case of sepsis due to intravenous fluid contamination. In
1960, Drews reported finding microscopic particles in the anterior chamber of the eye of
cataract surgery patients. Traced to the saline used for irrigation during the procedure,
the particles were thought to be only a nuisance. In 1964, Garran and Gunner reported
gross particulate contamination of commercially prepared intravenous fluids. In 1971,
these same investigators identified foreign particles lodged in the lungs of an infant who
died after receiving 2500 ml of intravenous fluids.6 The FDA convened a symposium on
"The Safety of Large Volume Parenterals" in 1966. At this symposium, Dr. Albert Jonas
presented a paper entitled, "Potentially Hazardous Effects of Introducing Particulate
Matter into the Vascular System of Man and Animals." In this report, Dr. Jonas cited an
instance in which a particle produced partial occlusion of the central retinal artery which
could have resulted in blindness. In a series of papers published by Turco and Davis,
infusion products were found to contain 2,200 particles greater than 5 microns in size. In
1973, the particle counts had been reduced to 76-488 particles greater than 5 microns in
size per liter of solution.
Between 1966 and 1970, there were two fatalities and eight cases of gram- negative
bacteremia in which resultant endotoxic shock and fungemia from the administration of
contaminated intravenous solutions occurred. In 1970-71, nine deaths and over 400 cases
of gram-negative septicemia resulted from one manufacture’s contaminated intravenous
solutions. Injectable drugs and intravenous solutions should be sterile and as particle-free
as possible. Whenever a drug must be mixed, reconstituted, transferred, or otherwise
exposed to the environment, contamination is almost unavoidable. These incidences of
contamination and the consequences they produce emphasize the need for improved
manufacturing and quality control of intravenous solutions. The lack of knowledge of
these adverse events as well as their clinical significance can adversely affect patients
receiving intravenous therapy, in particular neonates, geriatrics, debilitated and immunecompromised patients.
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Sources of Contamination
Both biological and non-biological contaminants may be found in intravenous solutions.
Contamination of the manufacturing area may occur due to airborne contaminants, the
original solutions and its ingredients, equipment used, and the personnel involved in the
manufacturing, distributing, manipulating or administering of these products. Intrinsic
contamination that arises during the manufacturing process can be reduced by the use of
filtration. Blackhouse, et al, examined the intrinsic particulate contamination of thirtynine commonly used small volume parenterals and found a wide variation in total particle
counts between various drugs, batches of drugs, and in both powdered drugs and drugs
already in solution1. Drugs in solution were found to contain ten times less the particles
than those formulated as powders. If these same powdered drugs were administered to an
intensive care patient, it was calculated that the patient would receive particulate
contaminants far in excess of the FDA limits (>1,000/container).
Various manipulations involved in the administration of drugs and infusions can generate
particulate contamination. Each time a glass ampule is opened, glass particulate
contamination occurs. Sabin, et al, found that metal-etched ampules generated more glass
contamination than amber ampules and these particles were then taken up through
syringe needles with the medication. Administration sets can contribute to plastic
particulate contamination. Mehrkens, et al, found that an average intensive care patient
could receive over 2 million particles of particulate contamination within a 24-hour
period.
Fate of Injected Particles
The host’s response to infused particles (contaminated) varies with size, shape, chemical
nature, and location where the particles become occluded or lodged. Major pathological
consequences encountered include the following:
1. Direct blockage of blood vessels by foreign matter
2. Clot formation and emboli due to erythrocyte adherence to particles
3. Inflammatory reactions with subsequent local granulomas secondary to particles
embedded in tissue
4. Antigenic reactions with allergenic responses
The pulmonary vascular bed acts as a filter for infused particles. Particles introduced into
the venous system travel to the right atrium of the heart, through the tricuspid valve, and
into the right ventricle. They are then pumped into the pulmonary artery, and on through
the pulmonary vasculature, whereupon, particles are eventually trapped in the extensive
capillary system of the lungs. These capillaries range from 7-12 microns in diameter.
Five microns is the suggested "allowable size" for a particle in the pulmonary capillary
bed, as larger particles are likely to become lodged in this area. Arteriolar occlusion
inhibits oxygenation and other metabolic activities. Particles may gain access to the
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systemic circulation via large arteriovenous shunts. A serious occlusion could then occur
in a small arteriole of the brain, kidney, or eye.
Schroeder, et al, and Kanke, et al, identified the fate of injected particles as a function of
their size. The following conclusions were noted:
1. The majority of particles 8 microns or larger are filtered out by the lungs and
lodge there indefinitely.
2. Particles of 3 microns in size are filtered by the lung, cleared by phagocytosis, and
ultimately migrate to the liver or spleen where they remain indefinitely.
3. A steady rise in the leukocyte count is thought to be induced by an inflammatory
response secondary to pulmonary microembolization of injected particles.
4. 4. Large numbers of particulate matter may be tolerated before a physiological
effect may be seen.
5. Injected particulate matter may produce EKG changes.
Questions still remain regarding the role of particulates in disease production. The illeffects produced by these contaminants can be either systemic or local. Systemic effects
are the result of the removal of particulates, primarily by the lungs. Local effects involve
pain, erythema, induration and palpable venous cord at the infusion site. These effects are
classified as infusion phlebitis which has been attributed to the composition of the
infusion set and catheter, specific drugs, pH of infused solutions, concentration and rate
of infused intravenous fluids, method of skin preparation prior to venipuncture, and
bacterial migration around the intravenous site.
Twenty-seven to forty-seven percent of all patients who receive intravenous fluids for as
long as 72 hours develop infusion phlebitis. In 1973, Ryan, et al, reported a reduced
incidence of infusion phlebitis from a level of 50% to less than 10% through the use of a
0.45 micron filter. Many studies since then have shown decreasing incidences in excess
of 50% with the use of inline filtration in the presence of infusion phlebitis. The presence
of an inline 0.2 micron filter was found to increase cannula-site life in neonates from 4959 hours in 1989.
Filter Characteristics
In 1975, Rapp, et al, indicated that the ideal filter for IV therapy should possess the
following qualities:
1. It should be totally retentive of bacterial and particulate contamination.
2. It should not allow air passage to the patient.
3. It should not interfere with the flow rates of the solution.
4. It should be easy to use.
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There are two categories of filtration media. These are classified as depth and screen
filters.
Depth Filters derive their name from the fact that filtrations occurs within the "depths"
of the filter matrix. Depth filters consists of fibrous materials bonded together to form a
flow channel maze. Contaminants are removed by entrapment or absorbed by the filter
fabric. The pore structure of depth filters is neither regular nor defined. Retention
efficiency is not stated in absolute terms which make these filters inappropriate for
terminal filtration. Nominal ratings are applied to depth filters, which state the particle
size above which a certain percentage of all particles will be retained. An example of
such a "pre- filter" would be a coffee filter or a 5 micron conical filter.
Screen Filters retain particles on their surface by physically "screening" them from a
liquid like a sieve. Retention is a surface rather than a depth phenomenon. Screen filter
structures consist of a polymeric matrix with pores of precise predetermined parameters.
Filter needles are examples of screen filters and are used to filter out large particulate
matter (filter is 5 micron in size). Screen filters are limited in their use by their small
surface area, as can be exhibited when trying to administer 50 ml of mannitol to a patient
via a filter needle. In this instance, the use of a depth filter would allow a larger surface
area for the drug to be filtered, and decrease resistance, allowing such a solution to be
administered more quickly, thus more safely.
Membrane Filters, which are a type of screen filter, are biologically inert, thin,
microporous sheets manufactured from cellulose, nylon, polyolefin, or polysulfone
materials. A sponge-like interlocking pore structure gives this type of filter a uniform,
rigid matrix whose retention ability is not affected by pressure build up or surges. The
current “fourth generation” filters combine all of the best features of the depth filter,
screen filter, as well as air elimination, air venting, rigid housing, and positive charge for
best results.
Filter Size as a Function of Protection Desired
Filters used in hospital practice range in size from 0.22 micron to 0.5 micron. The choice
in the size of filter selected is determined by the amount and the degree of protection
desired. Types of protection afforded by membrane filters include the following:
microbial, particulate, air embolism and phlebitis. The filter size selected also
determines the amount of potential interference with the following parameters: flow rate
and throughput. Throughput is the volume of fluid which will pass through the filtration
system before it clogs. Porosity (the ratio of pore volume to total filter volume) increases
with the pore size of the filter.
Example: A 0.22 micron filter is 75% porous, whereas a 0.8 micron filter is 82%
porous. The 0.22 micron filter is the only size filter that effectively eliminates the
passage of all fungi and bacteria to the patient. The 0.22 micron filter is known as a
sterilizing filter, whereas the 0.45 micron filter blocks most, but not all bacteria and fungi
passage. The Pall 0.22 micron filter and the Braun Supro 0.22 micron filter are the only
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filters that have been shown to prevent pass-through of endotoxin from the pyrogens
retained on the filter matrix. If IV filters are to be used in administration systems for
longer than 24 hours, their endotoxin retention properties become clinically significant
issues. Air passes freely through 5 and 10 micron filters. Even when these filters are wet,
no protection against air embolism is afforded. When a 0.22 micron filter is wet, 55 psi
of pressure is required to break the filter and allow air to pass through. The use of 0.22
micron filters to provide protection against air embolism should be a consideration in
patients having central venous lines. Filter clogging is not as prevalent with the new
"third generation" filters, as an air- venting, air-eliminating mechanism is utilized to help
prevent clogging. If a filter is clogged, it could be due to an accumulation of debris, or
possibly air entrapment.
Drug binding to the surface areas of the filter appears to be limited to small quantities of
drugs and also to only a limited selection of drugs. Millipore corporation provides
guidelines for the small volume filtration of drugs. The National Coordinating
Committee on Large Volume Parenterals recommendations suggest that drugs in
concentrations of less than 5 mcg/ml or in quantities of less than 5 mg/24hours should not
be infused through inline filters until studies have confirmed the binding associated with
these drugs. The composition of the filter membrane has a significant effect on drug
binding, as does the volume of solution, specific gravity of the drug and solution, and
type of drug to be filtered. Cellulose ester membrane filters have been found to decrease
the amount of certain drugs delivered, whereas nylon membrane types do not.
In 1979, the National Coordinating Committee on Large Volume Parenterals (NCCLVP)
published their recommendations for the use of IV filtration. In 1985, the National
Intravenous Therapy Association (NITA) published their guidelines on the use of
filtration. Both organizations endorse and advocate the use of a 0.22 micron aireliminating final filter in IV therapy administration. Each organization stated that use of a
final 0.22 micron filter in hyperalimentation (excluding lipid-containing solutions),
immune compromised patients, and in patients receiving infusions containing multiple
additives, and where additives being received are known to be high in particulates, is
advocated. An example of such would be an antibiotic supplied in powder form, ready for
dilution. Both organizations summarized their recommendations by stating that whenever
the benefits outweigh the risks, the use of a filter should be considered. The use of a 1.2
micron filter on all total parenteral nutrition solutions containing lipid is now advocated
to prevent the administration of particulate contaminants which may not be visible due to
the lipid component in the TPN solution.
The cost effectiveness of IV filters has been discussed in many articles throughout the
past few years. The major complication of intravenous therapy in a hospital is infusion
phlebitis. This complication leads to IV restarts, increased procedures to treat the
phlebitis, and patient discomfort. If the cost of a restart, equipment and nursing time
involved, is compared to the cost of the filter, one will find that the cost of the filter is far
less than the cost and discomfort to the patient for the restart. The use of a filter can
replace additional extension sets placed on the patient per hospital policy. Different
tubing and port requirements can usually be accommodated by the manufacturer. The
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pharmacist’s job in this task is to assure that the use of the filter does not adversely affect
the amount of drug administered to the patient. Consideration of community standard of
practice in regards to filter use, as well as a review of the administration techniques,
phlebitis rate, and restart rate in a hospital for intravenous therapy can demonstrate
justification for incorporation of such equipment into daily procedures.
FLOW CONTROL DEVICES
Rational for Use of Flow Control Devices
Conventional gravity-fed infusion systems do not maintain accurate flow rates.
Inaccurate flow rate can lead to delayed or toxic patient responses, increased phlebitis
and thrombophlebitis. Infiltration, pulmonary edema with consequent impairment of
renal and cardiac function, fluid overload, shock, and metabolic problems are
complications that may be induced by inaccurate flow rates. The IV administration set is
affected by many variables which alter the accuracy of the system. Drip chamber
variations, viscosity of the solution being administered, plastic cold flow, clamp slippage,
tubing variations, patient movement and blood pressure changes are some of the factors
that can affect the accurate administration of a fluid. These factors led to the development
of mechanical infusion devices to control the administration of fluids.
Infusion Controllers
Infusion controllers work by gravity, and function by counting drops electronically. The
control on the system is regulated automatically rather than manually. Controllers
increase the accuracy of the flow rate of the solution being administered, and have the
ability to help detect infiltration of air, empty containers, and excessive or deficient flow
rates. Controllers can achieve a drop rate accuracy of +/- 2% of the programmed settings.
Most controllers are able to use standard administration sets, which help to control
operating costs. Controllers count drops, and increase or decrease flow rate according to
this observation of the drop rate. Accurate drop rates do not mean accurate volumes
delivered, as variances in drop size due to flow rate and solution viscosity can affect
volume of solution actually administered.
Controllers are less complex, and are therefore easier to use and less costly. The
inaccuracy in volume cannot be ignored, however, and the use of controllers should be
limited to non-critical care drugs. Some controller/pump combination devices are now
available. However, volumetric accuracy and occlusion pressure limits are still
considered problematic.
Infusion Pumps
Infusion pumps are devices that utilize piston-cylinder, or peristaltic propulsion to deliver
a given volume or fluid. The delivery of fluid by pumps is measured in milliliters versus
drops and operation is independent of gravity flow. In cassette-less pumps, a series of
finger-like projections compress the tubing against a back plate, moving the fluid like a
wave within the tubing. These cassette-less pumps may be called linear peristaltic pumps.
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Other pumps available on the market force fluid through a pumping chamber, providing a
high pressure, measured in psi (pressure per square inch) to force fluid through the
tubing. The pressure exerted by a “gravity only” IV solution is 2 psi. Central lines require
a pressure of 10 psi to pump fluid into the cavity. Pumps generally exert 8-12 psi while
pushing fluid through the tubing. If an infiltration occurs, the additional pressure at the
site should alarm the pump, and discontinue the infusion. Some peristaltic pumps have
been found to exert a pressure of 30-40 psi while pumping. It is imperative that health
care practitioners understand the mechanics of the infusion pump, and assure that all
safety mechanisms are available to prevent the pump from continuing to infuse, if an
infiltration or extravasation should occur.
The fill volume of the delivery set required by each device should also be reviewed by
the clinician. If drugs are administered by syringe using a pump, the volume required to
reach the patient from the syringe on the cassette must be noted so that the drug being
delivered will actually reach the patient as required. The use of microbore tubing can
greatly decrease the volume required to prime pump tubing. However, microbore tubing
also increases the pressure required to pump specific solutions, as well as impeding fast
delivery of large volumes to a patient in a trauma situation.
Infusion devices have enhanced drug delivery to the patient by providing the practitioner
with a method to accurately administer various volumes (0.1 ml to 1000 ml) over specific
time frames. The safety alarms included in these devices have also provided a method to
alert practitioners so various hazards are avoided.20 The ability of some of these devices
to deliver multiple drug regimens safely and accurately has greatly enhanced drug
delivery, in particular, in the intensive care setting.
TOTAL PARENTERAL NUTRITION (TPN)
Basics of Total Parenteral Nutrition
Total parenteral nutrition (TPN), hyperalimentation (HA, or hyper-A) are terms used to
describe the nutritional support supplied to the patient via the parenteral route. Total
parenteral nutrition provides the patient’s total energy and nutrient requirements and is
administered through a central line. Peripheral vein nutrition (PVN) provides a limited
amount of calories and protein by administration of a less-concentrated solution of amino
acids and dextrose via a peripheral vein.
TPN is used when patients are unable to use their GI tract for a period exceeding 3
weeks. PVN is utilized for short-term nutrition. TPN solutions are exceedingly
hypertonic, with an osmolarity that ranges from 6-8 times that of normal (1800-2400
mOsm/L). Because of this, central venous administration is required so the solution is
rapidly diluted by high blood volume flow rates. PVN solutions are more dilute solutions,
with osmo larity ranges from 900-1100 mOsm/L. Co-administration of lipid emulsions
with these diluted dextrose formulations (final concentration of dextrose 7.5-10%) can
help decrease phlebitis as well as increase caloric intake in these patients.
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Nutritional support is required in patients in the following conditions:
1. Inadequate GI function
2. Disease state or treatment prevents adequate oral nutrition
3. Patient requirements exceed that which is available from enteral formulas
Before parenteral nutrition is begun, a nutritional assessment of the patient should be
completed. Anthropometric measurements (height, weight, arm- muscle circumference,
triceps skin-fold), visceral protein status (albumin, serum transferrin), basal energy
expenditure estimation (BEE-Harris-Benedict equation), and an anergy panel (PPDintermediate strength, mumps, candida) will help determine the patient’s current
nutritional status, nitrogen balance, and caloric needs.
When assessing visceral protein status, serum albumin levels below 3 grams/deciliter
indicate depleted protein reserves. Serum transferrin can be used to predict the proteincalorie status of a patient. A rise in the level of this iron-transport protein indicates an
improvement in the nutritional status of the patient.
The basal energy expenditure calculation estimates the non-protein requirements of the
patient. An estimation of 25 calories per kilogram per 24 hours is a useful formula to
predict calorie requirements.
Protein requirements are usually met through administration at a rate of 1 gr/kg/24 hrs.28
Some disease states require 1.5 grams of protein/kg/24hrs.28 Hepatic disease patients can
handle no more than 20 grams/24hrs, and are gradually titrated up as their clinical status
allows. Renal failure requires strict limitations of protein, depending on renal status.
Pediatric patients require a special mixture of amino acid, due to their increased growth
requirement.
Components of Total Parenteral Nutrition
The main components of a total parenteral nutrition solution are dextrose and amino
acids. Electrolytes, vitamins, and trace elements are also added in sufficient amount to
satisfy daily requirements. In the absence of adequate calories for energy, the body
begins breaking down protein to be used as an energy source. This breaking down of the
body’s own protein sources to satisfy daily energy requirements leads to a negative
nitrogen balance and a catabolic state in the patient. The provision of exogenous calories
to a patient can promote nitrogen sparing. The average patient requires 150-200 calories
per gram of nitrogen to maintain a positive nitrogen balance. The major source of nonprotein calories in TPN is dextrose. The caloric yield of a carbohydrate is 4
calories/gram. Dextrose as found in IV solutions, is a monohydrous carbohydrate
("watereddown carbohydrate"), and yields 3.4 calories/gram. Dextrose is the main
contributor to the osmolarity of the TPN solution. Usual concentrations are used to make
TPN’s range from 30-70% dextrose (final concentration of dextrose is 15-35%).
The use of dextrose as the total "fuel" for the patient can result in hyperglycemia,
glucosuria, and respiratory problems due to production of increased amounts of carbon
dioxide with the metabolism of glucose.
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Parenteral Preparation
Crystalline amino-acids are used as the protein source in TPN. Various solutions of
amino-acids are available. The majority of the solutions contain a mixture of essential
and non-essential amino-acids. Various concentrations are available, ranging from 3.515%. The typical patient on TPN receives approximately 18 grams of nitrogen daily in
the form of amino acids. Neonates have greater protein requirements (2.5-3g/kg/day) to
promote nitrogen balance. Protein requirements slowly decrease with age. Special
formulations of amino-acids are utilized in the pediatric population because of special
nutrient, as well as electrolyte requirements. There are two special amino-acid formulas
available that meet the need of the pediatric patients. These formulas, TrophAmine 6%
(Kendall McGaw) and Aminosyn-PF 7% (Abbott) contain less methionine,
phenylalanine, and glycine than products developed for adults. Hepatamine 8% (B.
Braun) is rich in branched-chain amino-acids and is used in the treatment of hepatic
encephalopathy. Nephramine 5.4% (B. Braun), Aminosyn-RF 5.2% (Abbott), RenAmin
6.5% (Baxter), and Aminess 5.2% (Kabi) are special renal crystalline amino-acid
formulas.
Nephramine, Aminosyn-RF, and Aminess contain only essential amino-acids, while
RenAmin contains both essential and non-essential amino- acids. Kidney damage
necessitates use of high concentrations of dextrose, special amino-acid formulations, and
decreased volumes of nutritional solutions to be used in these patients. Histidine and/or
arginine are also found in these renal amino-acid formulations.
Lipid emulsion is administered 3 times weekly to prevent fatty acid deficiency in longterm TPN patients. Lipid may also be used as a calorie source. Lipid emulsions are
available in 10% and 20% concentrations, and are derived from soybean oil, safflower
oil, or a combination of both. The 10% lipid emulsion yields 1.1 calories/ml, the 20%
provides 2 calories/ml. To minimize the possibility of fat overload or fat embolism, no
more than 3 grams/kg/day should be administered to adults. Fat emulsions may be used
as a calorie source comprising of 30% or more of the non-protein calories of a solution.
The patient’s fat tolerance should be monitored by reviewing serum triglyceride levels
and liver function studies. Fat overload symptoms include headache, irritability, low
grade fever, abdominal pain, nausea, hepatomegaly, coagulopathy, and splenomegaly.
The drug of choice to clear lipids from a patient’s plasma is intravenous heparin.
An "all- in-one TPN” or “3- in-1 TPN” is a solution that contains a 24- hour complete
nutritional formula of dextrose amino-acids and lipid, all mixed together with
electrolytes, trace elements, and vitamins in a single large volume flexible plastic IV bag.
When mixing the 3- in-1 solution, the dextrose and amino-acids should be admixed first.
The lipid should be added last to prevent lipid emulsion from creaming or cracking due to
the pH variances of these 3 entities. The 3- in-1 total nutrient admixture is a cost
effective method of providing TPN to the stabilized patient, at home or in the hospital.
Calculating Calories
Calories in a TPN solution should be provided from a non-protein source. Fifty percent
dextrose provides 50 grams of dextrose per 100 ml solution, for a total of 250 grams of
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Parenteral Preparation
dextrose in 500 ml of solution. Dextrose provides 3.4 calories/gram of dextrose x 250
grams, yielding 850 calories.
Fats provide 9 calories per gram of substrate. Lipids used in TPN solutions however, are
lipid emulsions, with glycerol added to the emulsion for osmolarity. This lipid emulsion
provides 1.1 calories per ml of 10% emulsion, and would yield 550 calories per 500 ml of
a 10% solution. Proteins provide the nitrogen source necessary for protein synthesis.
Using the standard 8.5% amino-acid 500 ml solution, this would mean 8.5 grams of
amino-acid per 100 ml, 42.5 grams of protein equivalent amino-acid in 500 ml. To
calculate the grams of nitrogen, the total grams of protein is divided by 6.25. Dividing
42.5 grams of protein by 6.25 determines that 6.8 grams of nitrogen are available from
500 ml of an 8.5% amino acid solution.
Calorie-to-nitrogen ratios are frequently discussed in nutritional support therapy. This
ratio is determined by dividing the total non-protein calories available by the grams of
nitrogen provided. A TPN solution containing 8.5% amino-acids, 500 ml and Dextrose
50%, 500 ml would yield 850 non-protein calories per 6.8 grams of nitrogen, which
equals 125 non-protein calories/gram of nitrogen. This 125:1 ratio is a suitable ratio, and
higher ratios of 150-200 npc/gram of nitrogen may be used in higher stressed, septic, or
trauma patients. The metabolic effects of TPN must be monitored to prevent
complications from developing in the patient.
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J&D Educational Services
Parenteral Preparation
Final Exam
1. The injectable route of administration that is injected into the skin is:
a.
b.
c.
d.
Intravenous
Intramuscular
Subcutaneous
None of the above
2. The injectable route of administration that is injected into the muscle is:
a. Intravenous
b. Intramuscular
c. Subcutaneous
d. None of the above
3. The injectable route of administration that is injected into the vein is:
a.
b.
c.
d.
Intravenous
Intramuscular
Subcutaneous
None of the above
4. Intravenous administration of drugs has advantages over other routes of
administration because it provides the fastest route to the bloodstream.
a. True
b. False
5. The process necessary for parenteral preparations must include the following
Good Manufacturing Practices:
a.
b.
c.
d.
Exclusion and elimination of particulate matter
Exclusion and elimination of pyrogens
Exclusion and elimination of bacterial growth and contamination
All of the above
6. ___ percent of an adult’s body weight consists of water.
a.
b.
c.
d.
90
25
45
60
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Parenteral Preparation
Final Exam
7. Which of the following is NOT an electrolyte?
a.
b.
c.
d.
Calcium
Potassium
Kava
Chlorine
8. The __________ route is primarily used for diagnostic tests as well as some
vaccines.
a.
b.
c.
d.
Intramuscular
Intradermal
Intravenous
Subcutaneous
9. Some drugs may also be given by subcutaneous infusion.
a. True
b. False
10. __________ route of administration is an injection into the heart chamber.
a.
b.
c.
d.
Intra-arterial
Intracardiac
Intraspinal
Intrathecal
11. Solutions, suspensions, and emulsions may all be given intravenously.
a. True
b. False
12. Intrathecal injections cannot contain any preservatives.
a. True
b. False
13. Which of the following is NOT a general area of preparation of a parenteral
product?
a.
b.
c.
d.
Components and Containers
Facilities and Procedures
Patient Counseling
Packaging and Labeling
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J&D Educational Services
Parenteral Preparation
Final Exam
14. The most important vehicle for parenteral products is __________.
a. Water
b. Potassium
c. Magnesium
d. Chlorine
15. ________________ are examples of water-miscible vehicles.
a.
b.
c.
d.
Ethyl alcohol
Polyethylene glycol
Both a and b
None of the above
16. Concerning antimicrobial agents, there is no universal agent satisfactory for all
preparations.
a. True
b. False
17. __________ are metabolic products of living microorganisms, or the dead
microorganisms themselves, which induce a specific pyrogenic response upon
injection.
a.
b.
c.
d.
Containers
Pyrogens
Solutes
Antimicrobial agents
18. Plastic is employed as the container of choice for most injections.
a. True
b. False
19. According to the USP, which category of glass is most suitable for buffered
solutions?
a. Type 1 – borosilicate glass
b. Type 2 – soda lime treated glass
c. Type 3 – soda lime glass
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J&D Educational Services
Parenteral Preparation
Final Exam
20. According to the USP, which category of glass is most suitable for anhydrous
liquids or dry substances only?
a. Type 1 – borosilicate glass
b. Type 2 – soda lime treated glass
c. Type 3 – soda lime glass
21. For a medium risk product, the following beyond use dating applies:
a.
b.
c.
d.
Controlled room temperature – 48 hours
Controlled room temperature – 40 hours
Controlled room temperature – 30 hours
Controlled room temperature – 24 hours
22. All three risk levels should have an anteroom, buffer zone and ISO class 5 work
space; however there are different recommendations for floor plans based upon
the risk level.
a. True
b. False
23. The ability to manipulate sterile preparations, devices, and other components that
excludes the introduction of microorganisms is called:
a.
b.
c.
d.
Sterile products
ISO class 5 Hood
HEPA Filter
Aseptic Technique
24. Products free from all living microorganisms, pyrogens, and particulate matter are
called:
a.
b.
c.
d.
Sterile products
ISO class 5 Hood
HEPA Filter
Aseptic Technique
25. _________________ is the complete destruction or elimination of
microorganisms as confirmed by appropriate test results.
a.
b.
c.
d.
Tonicity
Osmoticity
Sterilization
Osmolality
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J&D Educational Services
Parenteral Preparation
Final Exam
26. __________ solutions such as 0.45% sodium and 0.3% sodium chloride are used
to aid the kidneys in the excretion of solutes by providing free water, sodium, and
chloride.
a.
b.
c.
d.
Isotonic
Hypertonic
Hypotonic
None of the above
27. ___________ solutions are used to expand extracellular fluid (ECF) volume.
a.
b.
c.
d.
Isotonic
Hypertonic
Hypotonic
None of the above
28. _________ solutions exert osomotic pressures greater than that of the
extracellular fluid.
a.
b.
c.
d.
Isotonic
Hypertonic
Hypotonic
None of the above
29. ___________ refers to a weight-to-weight relationship between the solute and the
solvent
.
a. Osmotic pressure
b. Osmolality
c. Osmolarity
30. ___________ is a factor that determines the physiologic acceptability of a
solution for use in the body.
a. Osmotic pressure
b. Osmolality
c. Osmolarity
31. ___________ refers to a weight-to-volume relationship between the solute and the
solvent.
a. Osmotic pressure
b. Osmolality
c. Osmolarity
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J&D Educational Services
Parenteral Preparation
Final Exam
32. Sterile products should be prepared in an ISO Class 5 horizontal or vertical
laminar flow hood (LFH). This hood should operate for a minimum of ___
minutes before product preparation can begin.
a. 5 minutes
b. 10 minutes
c. 15 minutes
d. 30 minutes
33. ______________ solutions include hypertonic fluids, parenteral nutrition fluids,
and other special therapy fluids.
a. Hydrating solutions
b. Replacement solutions
c. Special solutions
34. ____________ solutions are used to meet daily maintenance needs plus correct
deficits of water and electrolytes in patients.
a. Hydrating solutions
b. Replacement solutions
c. Special solutions
35. _____________ fluids are utilized in patients to correct volume deficits, and
provide venous access
a. Hydrating solutions
b. Replacement solutions
c. Special solutions
36. Drugs with narrow therapeutic ranges should be administered by continuous
infusion.
a. True
b. False
37. Antibiotics are generally administered by _________ infusion.
a. Continuous
b. Intermittent
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J&D Educational Services
Parenteral Preparation
Final Exam
38. Drug product decomposition is the result of a _____________.
a.
b.
c.
d.
Chemical reaction
Physical reaction
Either A or B
None of the above
39. The factor that is most responsible for incompatibilities is pH.
a. True
b. False
40. ________ are agents which resist pH changes.
a.
b.
c.
d.
Buffers
Solutes
Micro antibacterial agents
All of the above
41. The order of mixing drugs has no affect on the final pH solution.
a. True
b. False
42. Concerning drug in syringe compatibility, a good rule of thumb cited in most
literature limit syringe combinations to a _____ time frame when predicting
compatibility.
a.
b.
c.
d.
10 minute
30 minute
60 minute
120 minute
43. The pH (usually 4.0-5.5) and tonicity of intravenous fluids (hypo/hypertonic)
make almost all IV fluids compatible with the administration of blood.
a. True
b. False
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J&D Educational Services
Parenteral Preparation
Final Exam
44. ________ filters retain particles on their surface by physically “screening” them
from a liquid like a sieve.
a. Depth
b. Screen
c. Membrane
45. _________ filters, which are a type of screen filter, are biologically inert, thin,
microporous sheets manufactured from cellulose, nylon, polyolefin, or
polysulfone materials.
a. Depth
b. Screen
c. Membrane
46. __________ filters derive their names from the fact that filtrations occurs withing
the “depths” of the filter matrix..
a. Depth
b. Screen
c. Membrane
47. ___________ __________ are devices that utilize piston-cylinder, or peristaltic
propulsion to deliver a given volume or fluid.
a. Infusion Controllers
b. Infusion Pumps
48. ___________ ___________ work by gravity, and function by counting drops
electronically.
a. Infusion Controllers
b. Infusion Pumps
49. The main components of a total parenteral nutrition solution are:
a.
b.
c.
d.
e.
Dextrose and amino acids
Electrolytes
Vitamins
Trace elements
All of the above
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J&D Educational Services
Parenteral Preparation
Final Exam
50. The 3 in 1 total nutrient admixture is a cost effective method of providing TPN to
the stabilized patient, at home or in the hospital.
a. True
b. False
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