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`;:i;g;}1§i€u;xlw.%rfimflw,yaxflnmlfiwmm
`
`Actavis - IPR2017-01104, Ex. 1027, p. 1 of 15
`
`Actavis - IPR2017-01104, Ex. 1027 p. 1 of 15
`
`

`

`Entered according to Act of Congress, in the year 1885 by Joseph P Remington,
`in the Office of the Librarian of Congress, at Washington DC
`
`Copyright 1889, 1894, 1905, 1907, 1917, by Joseph P Remington
`
`Copyright 1926, 1936, by Joseph P Remington Estate
`
`Copyright 1948, 1951, by The Philadelphia College of Pharmacy and Science
`
`Copyright © 1956, 1960, 1965, 1970, 1975, 1980, 1985, 1990, by The Philadelphia College of
`Pharmacy and Science
`
`All Rights Reserved
`
`Library of Congress Catalog Card No. 60-53334
`
`ISBN 0-912734-04-3
`
`~:_\'-~'! ~-~_~,t~ ~ '_
`\:;0--:/f i~#-'l -b_ -_,_
`The use of structuralifo"flmUl:;~]r!~"us~and the USP Dictionary of Drug Names is by
`permission of The USP Convention. The Convention is not responsible for any inaccuracy
`contained herein.) { fl (
`
`; ~ ( '~
`
`NOTICE-This tex,t isen.ofA~t,er;<f;,ed to]epr,~~!ff"[jt, nor shall it be interpreted to be, the equivalent
`of or a subsiit'itte Yhl-t:h~ bfticf'fiH.!ftiterl States Pharmacopeia ( USP) and/or the National
`Formulary (NF). In the event of any difference or discrepancy between the current official
`USP or NF standards of strength, quality, purity, packaging and labeling for drugs and
`representations of them herein, the context and effect of the official compendia shall
`prevail.
`
`Printed in the United States of America by the Mack Printing Company, Ea.~ton, Pennsylvania
`
`Actavis - IPR2017-01104, Ex. 1027 p. 2 of 15
`
`

`

`Table of Contents
`
`Port 1
`
`Orientation
`
`1 Scope .....•.....•....•...•.......•. • · · ·. ·
`2 Evolution of Pharmacy •.•..•••••...•.••.....
`3 Ethics .•••.......•••••.....••••••.......•..
`4 The Practice of Community Pharmacy ••.....••.
`5 Opportunities for Pharmacists in the Pharmaceuti-
`cal Industry ..•.........•..........•..••...
`6 Pharmacists in Government .••......•.•......
`7 Drug Information .•..•••.....•.•..........••
`8 Research •......••..••......•.••..........
`
`Port 2
`
`Pharmaceutics
`
`9 Metrology and Calculation ....•••..••........
`10 Statistics ••......•.•••••......•••••........
`11 Computer Science .......•..••........•.....
`12 Calculus ••...•..........•.........•...•...
`13 Molecular Structure, Properties and States of
`Matter .•••.....••••••...•..•.•.•......•.•
`14 Complex Formation ••••.........••......•.•
`15 Thermodynamics ........•..••......••......
`16 Solutions and Phase Equilibria ...........•....
`17
`Ionic Solutions and Electrolytic Equilibria ••......
`18 Reaction Kinetics .•••••••....••.•..•......•.
`19 Disperse Systems .•.•••.......••••.•.....•.•
`20 Rheology ....•••..•.......••.......•..•...
`
`Port~
`
`Pharmaceutical Chemistry
`
`Inorganic Pharmaceutical Chemistry ••......••.
`21
`22 Organic Pharmaceutical Chemistry ...•........
`23 Natural Products •..•.....•••......••.•••...
`24 Drug Nomenclature-United States Adopted
`Names •.•..••..••••••.....•••..•........•
`25 Structure-Activity Relationship and Drug
`Design ...••..••......•••.••......•••.....
`
`Port4
`
`Testing and Analysis
`
`26 Analysis of Medicinals • • . . • . . • . • • . • . . . . . . • • .
`27 Biological Testing
`• . . . . . . • . • • • . . . . . • . • • • . . . .
`28 Clinical Analysis • . . . . . . . • • . . • . . . . . . . . . • . . . .
`29 Chromatography . . . . . . . . • • . . • . . . . . . • . . . . . . .
`30
`Instrumental Methods of Analysis . . . . . . . . . . • . .
`31 Dissolution . • . • . . • • • • • • . . . • • . • • . . . • . . . . . . • •
`
`3
`8
`20
`28
`
`33
`38
`49
`60
`
`69
`104
`138
`145
`
`158
`182
`197
`207
`228
`247
`257
`310
`
`329
`356
`380
`
`412
`
`422
`
`435
`484
`495
`529
`555
`589
`
`Port 5
`
`Radioisotopes in Pharmacy and Medicine
`
`32 Fundamentals of Radioisotopes • . . • . . . • . . . . . . •
`33 Medical Applications of Radioisotopes
`. . . . . . • • •
`
`605
`624
`
`Port 6
`
`Pharmaceutical and Medicinal Agents
`
`34 Diseases: Manifestations and Patho-
`physiology . . . . . • • • • • • . . . . . . . . • • . . • . . . . . • . .
`35 Drug. Absorption, Action and Disposition . . . . . • . •
`36 Basic Pharmacokinetics • • . . . . . . • • • • . • . . . . . . . •
`37 Clinical Pharmacokinetics . . . . . . . . . . . • . . . . . • . .
`38 Topical Drugs . . • . . . . . . . . • . • . . . . . . . . . • . . . . . .
`39 Gastrointestinal Drugs . . . • . . . . . . . . . . . . . . . • . . .
`.. 40 Blood, Fluids, Electrolytes and Hematologic
`Drugs • • • • . . . . . . . • . • • • . . . . . • • • . . . . . . . . . . . •
`41 Cardiovascular Drugs
`. . . . . . . . . . . . • . • . . . . . . • .
`42 Respiratory Drugs
`. . . . . . • . • . . . . . . . . . . . • . . . . .
`43 Sympathomimetic Drugs . . . • . . . . . . . . . . . . . . . . .
`
`655
`697
`725
`7 46
`757
`774
`
`800
`831
`860
`870
`
`889
`
`44 Cholinomimetic Drugs • • . . . . . . . . . • . . • • • . . . . . .
`45 Adrenergic and Adrenergic Neuron Blocking
`898
`. . . . . . . • • . . . . . . . . . •. . . . . . . . . . . . . . . . .
`Drugs
`907
`46 Antimuscarinic and Antispasmodic Drugs • . . • . . .
`·47 Skeletal Muscle Relaxants ...•... , • • • . • . . . . . .
`916
`929
`48 Diuretic Drugs
`. . . . . . • • • . . . . . . . . . . • . • . . . . . . .
`943
`49 Uterine and Antimigraine Drugs
`. • . . . . . . . . . • . .
`948
`50 Hormones . . . . • . . . • . . . . . . . . • • . . . . . . . . . . . . . .
`1002
`51 Vitamins and Other Nutrients • • • • • . • • • . . . . . . . .
`1035
`52 Enzymes
`. . . . . . • . . • . • . . . . . . . . . . . . • • • . . . . . .
`1039
`53 General Anesthetics • . • . . . . . . . . . • . . . • . . . . . . .
`54 Local Anesthetics . . • . . . . . . . • . . • . . . . . . . . . . . . .
`1048
`1057
`55 Sedatives and Hypnotics . . . . • . • . • . . . . . . . . . . . .
`1072
`56 Antiepileptics
`. . . • • . . . . . . . . . • . . . . . . . . . . • . . .
`1082
`57 Psychopharmacologic Agents
`. . . . • • • . • • . . . . . .
`1097
`58 Analgesics and Antipyretics . . . . . . . • . . . . . . . . . .
`1123
`59 Histamine and Antihistamines • . • . . . . . . . • . . . . .
`60 Central Nervous System Stimulants . . . . . . • . • • • •
`1132
`1138
`61 Antineoplastic and Immunosuppressive Drugs . . .
`1163
`62 Antimicrobial Drugs . . . .. .. . . . .. . .. . .. • .. . .. .
`1242
`63 Parositicides . • . . . . . . • . . • • . . . . . . . . • . . • . . . . . .
`1249
`64 Pesticides . . . . . . • . . . . . . . . . . . . . . . . . . . . . . . . . .
`1272
`65 Diagnostic Drugs . • • . . . . . . • • . . . . . . . . . . . . . . . .
`66 Pharmaceutical Necessities
`. . . • • . . . . . . . . . . • • • 1286
`67 Adverse Drug Reactions • . . . . . . . . . • • . • . . . . . . .
`1330
`68 Pharmacogenetics ..••.•••...•.•••••••.......• 1344
`69 Pharmacological Aspects of Drug Abuse . . • . . . . .
`1349
`70
`Introduction of New Drugs
`. . . . . . • . . . . . . . . . . . .
`1365
`
`Port7
`
`Biological Products
`
`71 Principles of Immunology ..•...•..........•..
`72
`Immunizing Agents and Diagnostic Skin
`Antigens ........••..•.....••..............
`73 Allergenic Extracts ..••••.•......••••••......
`74 Biotechnology and Drugs .••.......•.••...•..
`
`1379
`
`1389
`1405
`1416
`
`Porte
`
`Phormoceuticol Preparations and Their
`Manufacture
`
`75 Preformulotlon ........•.•....•.••••••. , ....
`76 Bioavailabllity and Bioequivalency Testing .••..
`77 Separation ..•.••.........••..•......••....
`78 Sterilization .•...••.....•••••..............
`79 Tonicity, Osmoticity, Osmolality and Osmolarity .
`80 Plastic Packaging Materials .•.•.....••.......
`81 Stability of Pharmaceutical Products .......•...
`82 Quality Assurance and Control .............••
`83 Solutions, Emulsions, Suspensions and
`Extractives .••.....••.•••.•....•.••.•......
`84 Parenteral Preparations .•......•.•••.•......
`85
`Intravenous Admixtures ...•.................
`86 Ophthalmic Preparations ...•••........•.....
`87 Medicated Applications ....•..•........•....
`88 Powders •.•••.....•.•.••........•.........
`89 Oral Solid Dosage Forms •••......•..•••......
`90 Coating of Pharmaceutical Dosage Forms ...... .
`91 Sustained-Release Drug Delivery Systems ..... .
`92 Aerosols •..••.......•...•.......••.•......
`
`1435
`1451
`1459
`1470
`1481
`1499
`1504
`1513
`
`1519
`1545
`1570
`1581
`1596
`1615
`1633
`1666
`1676
`1694
`
`Port 9
`
`Pharmaceutical Practice
`
`93 Ambulatory Patient Core
`94
`Institutional Patient Care
`95 Long-Term Care Facilities ..•.................
`96 The Pharmacist and Public Health ............•
`
`1715
`1737
`1758
`1773
`
`XV
`
`Actavis - IPR2017-01104, Ex. 1027 p. 3 of 15
`
`

`

`97 The Patient: Behavioral Determinants ....•....•
`98 Patient Communication ..••....•..•.•..••..•
`99 Drug Education ...••.•..•.•......•..••.....
`100 Patient Compliance
`' •••..•.•..••.•.••.•....•
`101 The Prescription .•.••.••..........•..•......
`102 Drug lnte.roctions •.•••..•••.......•..•.•••• '.
`103 Clinical Drug Literature ...••.......•.••.•••••
`104 Health Accessories •..••••.••.•••.•••.••... •'
`105 Surgical Supplies ...•.••••••.•.••...••••....
`
`1788
`1796
`1803
`1813
`1828
`1842
`1859
`1864
`1895
`
`.Poison Control ...••..............••.....•..
`106
`107 Lows Governing Pharmacy ................. .
`108 Community Pharmacy Economics and
`Management .........••.........•.....•..
`109 Dental Services .••• ·· .....•.....•..........•
`
`1905
`1914
`
`1940
`1957
`
`Index
`
`Alphabetic Index .......•••.....•....... , ••
`
`1967
`
`xvi
`
`Actavis - IPR2017-01104, Ex. 1027 p. 4 of 15
`
`

`

`CHAPTER 85
`
`Intravenous Admixtures
`
`Salvatore J Turco, PharmD
`Professor of Pharmacy
`Temple University School of Pharmacy
`Philadelphia. PA 19140
`
`It has been estimated that 40% of all drugs administered in
`hospitals are given in the form of injections and their use is
`increasing. Part of this increase in parentera),therapy is due
`to the wider use of intravenous fluids (IV fluids). In the last
`decade the use of IV fluids has doubled, increasing from 150
`million units to 300 million units annually: Not only do IV
`fluids continue to serve as the means for fluid replacement,
`electrolyte-balance restoration and supplementary nutri(cid:173)
`tion, but they also are playing major roles as vehicles for
`administration of other drug substances and in total paren(cid:173)
`teral imtrition (TPN). TPN fluids are finding greater use as
`the means of administering other drugs because of conve(cid:173)
`nience, the means of reducing the irritation potential of the
`drugs and the desirability for continuous and intermittent
`drug therapy. The techniques for providing TPN parenter(cid:173)
`ally have improved steadily in the last decade, and such use
`is increasing markedly. The use of IV fluids for these pur(cid:173)
`poses requires the compounding of specific intravenous ad(cid:173)
`mixtures (parenteral prescriptions) to meet the clinical
`needs of a given patient. However, the combination of drug
`substances in an IV fluid can promote parenteral incompati(cid:173)
`bilities and give rise to conditions not favorable for drug
`stability. A new area of specialization has been created for
`hospital pharmacists who can develop the expertise to pre(cid:173)
`pare these solutions-recognizing their compatibility and
`stability problems and the potential for contamination(cid:173)
`and participate in the administration of the solutions. The
`complex compounding of an order for TPN requires know(cid:173)
`ledgeable personnel capable of making accurate calcula(cid:173)
`tions, compounding and having aseptic technique. The par(cid:173)
`enteral prescription is becoming increasingly important in
`hospitals. Centralized admixture programs are now found
`in 70% of the nation's hospitals having 300 beds or more.
`Equipment available for administering IV fluids has become
`more sophisticated, and has made possible increased accura(cid:173)
`cy of dosage and led to the development of new com.:epl~ and
`methods of nutrition and drug therapl.
`
`Intravenous Fluids
`
`Large-volume injections intended to be administered by
`intravenous infusion commonly are called IV fluids and are
`included in the group of sterile products referred to as large(cid:173)
`volume parenterals. These consist of single-dose injections
`having a volume of 100 mL or more and containing no added
`substances. Intravenous fluids are packaged in containers
`having a capacity of 100 to 1000 mL. Minitype infusion
`containers of 250-mL capacity are available with 50- and
`100-mL partial fills for solution of drugs when used in the
`"piggyb&ck" technique (ie, the administration of a second
`solution through a Y-tube or gum-rubber connection in the
`administration set of the first intravenous fluid, thus avoid(cid:173)
`ing the need for another injection site). In addition to the
`IV fluids, this group also includes irrigation solutions and
`solutions for dialysis.
`Intravenous fluids are sterile solutions of simple chemi-
`
`cals such as sugars, amino acids or electrolytes-materials
`which easily cah be carried by the circulatory system and
`assimilated. Prepared with Water for Injection USP, the
`solutions are pyrogen-free. Because of the large volumes
`administered intravenously, the absence of particulate mat(cid:173)
`ter assumes a significant role in view of possible biological
`hazards resulting from insoluble particles. Absence. of par(cid:173)
`ticulate matter or clarity of IV fluids is as important at the
`time of administration following their manipulation in the
`hospital as it is at the time of manufacture of the injection.
`Limits for particulate ,matter occurring in IV fluids, or
`iarge-volume injections used for single-dose infusion, are
`defined in the USP. This represents the first regulatory
`attempt to define limits for particulate matter in paren(cid:173)
`terals. Limits also apply to multiple-dose injections, small(cid:173)
`volume injections or injections prepared by reconstitution
`from sterile solids. The USP defines particulate matter as
`extraneous, mobile, undissolved substances, other than gas
`bubbles, unintentionally present in parenteral solutions.
`The total numbers of particles having effective linear di(cid:173)
`mensions equal to or larger than 10 JLm and larger than 25 JLm
`are counted. The IV fluid meets the requirement of the test
`if it contains not more than 50 particles per mL which are
`equal to or larger than 10 11m, and not more than 5 particles
`per mL which are equal to or larger than 25 JLm in linear
`dimension.
`Intravenous fluids commonly are used for a number of
`clinical conditions. These include
`Correction of disturbances in electrolyte balance.
`Correction of disturbances in body fluids (fluid replacement).
`The means of providing basic nutrition.
`The basis for the practice of providing TPN.
`Use as vehicles for other drug substances.
`
`In both of the latter two cases it has become common prac(cid:173)
`tice to add other drugs to certain IV fluids to meet the
`clinical needs of the patient. Using IV fluids as vehicles
`. offers the advantages of convenience, the means of reducing
`the irritation potential of the drug and a method for continu(cid:173)
`ous drug therapy. However, the practice requires that care(cid:173)
`ful consideration be given to the stability and compatibility
`of additives present in the IV fluids serving as the vehicles.
`This approach also demands strict adherence to aseptic
`techniques in adding the drugs, as well as in the administra(cid:173)
`tion of the IV fluids. These procedures are discussed later
`in the chapter. The IV fluids commonly used for parenter(cid:173)
`als are shown in Table I.
`Many disease states result in electrolyte depletion and
`loss. Proper electrolyte concentration and balance in plas(cid:173)
`ma and tissues are critical for proper body function. Elec(cid:173)
`trolyte restoration and balance are achieved most rapidly
`through administration of IV fluids. Required electrolytes
`include sodium and chloride ions, which in normal saline
`more closely approximate the composition of the extracellu(cid:173)
`lar fluid than solutions of any other single salt; potassium,
`the principal intracellular cation of most body tissues and an
`essential for the functioning of the nervous and muscular
`
`1570
`
`Actavis - IPR2017-01104, Ex. 1027 p. 5 of 15
`
`

`

`Table 1-Fiuids Used Commonly for IV Use
`
`INTRAVENOUS ADMIXTURES
`
`1571
`
`Injection
`
`Concentration(%)
`
`Alcohol
`withD5fWa
`with D5/W in NSSb
`Amino Acid (Synthetic)
`Aminosyn II (Abbott)
`FreAmine III (McGaw)
`Travasol (Baxter)
`Ammonium Chloride
`Dextran40
`inNSS
`in D5/W
`
`Dextran 70
`inNSS
`inD5/W
`Dextrose (Glucose, D5/W)
`Dextrose and Sodium
`Chloride
`
`Invert Sugar
`(Fructose and Dextrose)
`Lactated Ringer's
`(Hartmann's)
`NaCl
`KCl
`CaCb
`Lactate
`Mannitol
`also in combination with
`dextrose or sodium
`chloride
`Multiple electrolyte
`solutions
`varying combinations of
`electrolytes, dextrose,
`fructose, invert sugar
`Ringer's
`NaCl
`KCl
`CaCl2
`Sodium Bicarbonate
`Sodium Chloride
`
`Sodium Lactate
`
`Sterile Water for Injection
`
`"5% Dextrose in water.
`b Normal Saline Solution.
`
`5
`5
`
`3.5; 7
`8.5
`3.5; 5.5; 8.5
`2.14
`
`. 10
`10
`
`6
`6
`2.5-50
`Varying concn of dextrose
`from 5-20 with varying
`concn of sodium chlo(cid:173)
`ride from 0.22-0.9
`5, 10
`
`0.6
`0.03
`0.02
`0.3
`5
`10
`15
`20
`
`0.86
`0.03
`0.033
`5
`0.45; 0.9;
`3;5
`l/6M
`
`pH
`
`4.5
`
`5;25
`6.6
`6.0
`4.5-6.0
`
`5
`4
`
`5
`4
`3.5-6.5
`3.5-6.5
`
`4.0
`
`6.0-7.5
`
`Therapeutic Use
`
`Sedative, analgesic, calories
`Sedative, analgesic, calories
`Fluid and nutrient replenisher
`
`Metabolic alkaloids
`Priming fluid for extracor(cid:173)
`poreal circulation
`Priming fluid for extracor-
`por~al circulation
`
`Plasma volume expander
`Plasma volume expander
`Fluid and nutrient replenisher·
`Fluid, nutrient and electrolyte
`replenisher
`
`Fluid and nutrient replenisher
`
`Systemic alkalizer; fluid. and
`electrolyte replenisher
`
`5.0-7.0
`
`Osmotic diuresis
`
`5.5
`
`5.0-7.5
`
`8
`4.5-7.0
`
`6.3-7.3
`
`5.5
`
`Fluid and electrolyte
`replacement
`·
`
`·
`
`Fluid and electrolyte
`replenisher
`
`Metabolic acidosis
`Fluid and electrolyte
`replenisher
`Fluid and electrolyte
`J,"eplenisher
`·
`Diluent
`
`systems as well as the heart; magnesium, as a nutritional
`supplement especially in TPN solutions and phosphate ion,
`important in a variety of biochemical reactions. In addition
`to the number of standard electrolyte fluids shown in Table
`I, a large number of combinations of electrolytes in varying
`concentrations are available commercially. Some of these
`electrolyte fluids also contain dextrose.
`Dextrose Injection 5% (D5/W) is the most frequently used
`IV fluid, eithe"-" for nutrition or fluid replacement. It is
`isotonic and administered intravenously into a peripheral
`yein; 1 g of dextrose provides 3.4 cal and 1 L of D5/W
`supplies 170 cal. The body utilizes dextrose at a rate of 0.5 g
`per kg of body weight per hr. More rapid administration
`can result in glycosuria. Therefore, 1 L of D5/W requires
`1% hours for assimilation. The pH range of D5/W can vary
`from 3.5 to 6.5. The wide range permitted is due to the free
`sugar acids present and formed during the sterilization and
`storage of the injection. To avoid incompatibilities when
`other drug substances are added to Dextrose Injection, the
`possible low pH should be considered in using it as a vehicle.
`
`More concentrated solutions of dextrose are available and
`provide increased calorie intake with less fluid volume. Be(cid:173)
`ing hypertonic, the more concentrated solutions may be irri(cid:173)
`tating to peripheral veins. Highly concentrated solutions
`are administered in a larger central vein. Other IV fluids
`used for intravenous admixtures and providing calories in(cid:173)
`clude solutions containing invert sugar. There is some evi(cid:173)
`dence that fructose, unlike dextrose, may be used in diabetic
`patients; the 10% injection is hypertonic and proVides 375 cal
`per L. Invert sugar consists of equal parts of dextrose and
`fructose; it is claimed that the presence of fructose promotes
`more rapid utilization of dextrose.
`Intravenous fluids containing crystalline amino acids can
`provide biologically usable amino acids for protein synthesis
`(Chapter 51). Protein contributes to tissue growth, wound
`repair and resistance to infection. The protein requirement
`for the normal adult is 1 g per kg per day; children and
`patients under stress require greater amounts. Attempts
`are made to maintain a positive nitrogen balance, .indicating
`that the protein administered is being utilized properly and
`
`Actavis - IPR2017-01104, Ex. 1027 p. 6 of 15
`
`

`

`1572
`
`CHAPTER 85
`
`not broken down and eliminated through the urine as creati(cid:173)
`nine and urea, which are normal waste products. In a posi(cid:173)
`tive nitrogen balance patients are taking in more nitrogen
`than they are eliminating. In a negative nitrogen balance
`there is more nitrogen being eliminated through the urine
`regularly than is being administered intravenously. This
`means that tissues are continuing to be torn down and repair
`is not necessarily taking place. Amino Acid Injection can
`afford the total body requirements for proteins by the proce(cid:173)
`dure known as TPN (discussed below) or be used for supple(cid:173)
`mental nutrition by peripheral administration. In addition
`to the amino acids, these nutritional injections also may
`contain dextrose, electrolytes, vitamins and insulin. Fat
`emulsion (Intralipid, Kabi Vitrum AB; Liposyn II, Abbott
`and Travamulsion; Travenol) sometimes is used concur(cid:173)
`rently but usually administered at another site.
`
`Packaging Systems
`
`Containers for intravenous fluids must be designed to
`maintain solution sterility, clarity (freedom from particulate
`matter) and nonpyrogenicity from the time of preparation,
`through storage and during clinical administration. Con(cid:173)
`tainer closures must be designed to facilitate insertion of
`administration sets through which the injections are admin(cid:173)
`istered, at a regulated flow-rate, into suitable veins.
`IV
`fluids are available in glass and plastic containers; the latter
`may be made from either a flexible or semirigid plastic mate(cid:173)
`rial. IV fluids are supplied in 1000-mL, 500-mL and 250-
`mL sizes in addition to 250-mL capacity containers pack(cid:173)
`aged with 50 or 100 mL of D5/W or Sodium Chloride Injec(cid:173)
`IV fluids in glass containers are
`tion for piggyback use.
`packaged under vacuum, which must be dissipated prior to
`use. For fluid to leave the IV glass container and flow
`through the administration set, some mechanism is neces(cid:173)
`sary to permit air to enter the"Container. Current flexible
`plastic systems do not require air introduction in order to
`function. Atmospheric pressure pressing on the container
`forces the fluid to flow.
`All glass and plastic containers are single-dose and should
`be discarded after opening even if not used. Intravenous
`fluids are packaged with approximately 3% excess fill to
`allow for removal of air from the administration set and
`permit the labeled volume to be delivered from the contain(cid:173)
`er. The containers are graduated at 20-mL increments on
`scales that permit the volume in container to be determined
`either from an upright or inverted position. Glass contain(cid:173)
`ers have aluminum and plastic bands for hanging, while
`plastic containers have eyelet openings or plastic straps for
`attachment to IV poles.
`
`Table II-IV Fluid Systems
`
`Source
`
`Container
`
`Characteristics
`
`Baxter
`
`Baxter ( Viaflex)
`
`McGaw
`
`McGaw (Accumed)
`
`Abbott
`
`Abbott (Lifecare)
`
`Glass
`
`Plastic
`
`Glass
`
`Plastic
`
`Glass
`
`Plastic
`
`a Part of administration set.
`
`Vacuum
`Air tube
`Polyvinyl chloride
`Flexible
`Nonvented
`Vacuum
`Air tube
`Polyolefin
`Semirigid
`Vacuum
`Air filter"
`Polyvinyl chloride
`Flexible
`Nonvented
`
`Fluids for IV use are available from three sources; all
`provide both glass and plastic containers. The glass-con(cid:173)
`tainer systems of Baxter and McGaw are similar. The char(cid:173)
`acteristics of current packaging systems are summarized in
`Table II.
`
`Administration Sets
`
`Administration sets used to deliver fluids intravenously
`are sterile, pyrogen-free and disposable. Although these
`sets are supplied by different manufacturers, each for its
`own system, they have certain basic components. These
`include a plastic spike to pierce the rubber closure or plastic
`seal on the IV container, a drip (sight) chamber to trap air
`and permit adjustment of flow rate and a length (150 to 450
`em) of polyvinyl chloride tubing terminating in a gum~rub­
`ber injection port. At the tip of the port is a rigid needle or
`catheter adapter. An adjustable clamp (screw or roller
`type) on the tubing pinches the tubing to regulate flow.
`Since the gum-rubber port is self-sealing, additional medica(cid:173)
`tion can be added to the IV system at these ports of entry.
`Glass containers that have no air tubes require air-inlet
`filters designed as part of the administration set (Abbott).
`See Figs 85-1 to 85-5.
`
`Administration Procedures
`
`In the administration of IV fluids, the primary IV contain(cid:173)
`er provides for fluid replacement, electrolyte replenishment,
`
`~Needle
`adapter
`
`Injection
`site
`
`Fig 85-1. Parts of basic administration sets.
`
`G Target area
`
`(for IV spike)
`
`Solid rubber
`Stopper
`(cannot be penetrated
`by needle)
`
`500 ml
`
`1000 mL
`
`250 ml capacity
`(Piggyback)
`Fig 85-2. Abbott IV glass container. The air venting is provided
`through the air filter located in the spike of the administration set.
`See Fig 85-1.
`
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`
`

`

`INTRAVENOUS ADMIXTURES
`
`1573
`
`Additive
`Injection
`Port (Not a hole)
`
`Vent
`Hole
`
`Administration~.
`
`"·t>
`Spike Hole~
`
`Safety
`Seal
`
`Puncture Proof
`Seal (Aluminum)
`
`A
`
`Latex
`Diaphragm
`
`B
`
`Additive
`port
`
`Spike
`
`IOOOrnL
`
`500mL
`
`250mLCapaclty
`(Piggyback)
`Fig 85-3. Baxter and McGaw glass containers. The plastic air tube
`allows the air to enter the bottle as the fluid is infused into the patient.
`The spike of the administration set is not vented. See Fig 85-1.
`
`'::::-
`
`c
`
`drug therapy or nutrition; the fluid can be infused over a 4-
`to 8-hr period. In some cases an IV fluid is infused slowly
`for the purpose of keeping the vein open (KVO). This will
`allow additional drugs to be administered when required.
`The primary IV fluid also can serve as a vehicle for other
`drugs to be administered, thus becoming an intravenous
`admixture (IV drip) and results in continuous blood levels of
`added drugs once the steady state has been reached.
`In preparing an IV fluid for administration, the following
`procedure is used.
`
`Additive
`port
`(A) Abbott (Lifecare) polyvinyl chloride flexible container;
`Fig 85-4.
`(B) Baxter ( Viaf/ex) polyvinyl chloride flexible container; McGaw
`·(Accumed) polyolefin semirigid container, front and side views.
`These containers take nonvented administration sets. See Fig 85-1.
`
`Air filter..-(cid:173)
`(bocterial
`retentive)
`
`Vented
`Set
`
`Non-Vented
`Set
`
`Non-Vented
`Set
`
`Fig 85-5. Setting up a primary IV fluid for administration.
`
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`
`

`

`1574
`
`CHAPTER 85
`
`1. The spike adapter of the administration set is inserted into the
`stopper or seal of the IV container. See Fig. 85-5.
`2. The IV fluid is hung on a stand at bedside and air is purged from
`the administration set by opening the clamp until fluid comes out of
`needle. The tubing is then clamped off. See Fig 85-5.
`3. The venipuncture is made by member of the IV team, floor nurse
`or physician.
`4. The infusion rate is adjusted by slowly opening and closing the
`clamp untilthe desired drop rate, viewed in the drip chamber, is ob(cid:173)
`tained. The usual running time is 4 to 8 hr (usually 125 mL are delivered
`in 1 hr). Drugs such as heparin, insulin, lidocaine or dopamine may be
`present in the IV drip. When potent drugs are present, the flow rates
`will vary depend on the clinical condition of the patient. Sets are
`calculated to deliver 10, 15, 20, 50 or 60 drops per mL depending on the
`manufacturer. See Fig 85-5.
`Intermittent administration of an antibiotic and other
`drugs can be achieved by any of three methods:
`(1) direct
`intravenous injection (IV bolus or push), (2) addition of the
`drug to a predetermined volume of fluid in a volume-control
`device or (3) use of a second container (mini bottle, mini bag)
`with an already hanging IV fluid (piggybacking).
`Direct Intravenous Injection-Small volumes (1 to 50
`mL) of drugs are injected into the vein over a short period of
`time (1 to 5 min). The injection also Cll.n be made through a
`resealable gum-rubber injection site of an already hanging
`IV fluid. This method is suitable for a limited number of
`drugs but too hazardous for most drugs.
`Volume-Control Method-Volume-control sets provide
`a means for intermittent infusion of drug solutions in precise
`quantities, at controlled rates of flow. These units consist of
`calibrated, plastic, fluid chambers placed in a direct line
`under an established primary IV container or more often
`attached to an independent fluid supply. In either case, the
`drug to be administered is first reconstituted if it is a sterile
`solid and injected into the gum-rubber injection port of the
`volume-control unit. It is then further diluted to 50 to 150
`mL with the primary fluid or the separate fluid reservoir.
`Administration of the total €!.rug-containing solution re(cid:173)
`quires 30 to 60 min and produces a peak concentration in the
`blood followed by a valley if the dosage is discontinued. The
`following volume-control sets are available commercially:
`Soluset, Abbott; Buretrol, Baxter and Metriset, McGaw.
`The procedure for setting up an intermittent IV infusion
`with a volume-control set is as follows:
`
`1. Using aseptic technique, the spike of the volume-control set is
`inserted into the primary IV fluid or a separate t1uid container. See Fig
`85-6.
`2. Air is purged from tubing of the volume-control set by opening the
`clamps until fluid comes through.
`3. The clamp is opened above the calibrated chamber and it is filled
`with .25 to 50 mL fluid from the primary IV container or separate fluid
`container.
`4. The clamp is closed above the chamber.
`5. The medication is injected through the gum-rubber port of the
`volume-control unit.
`6. The clamp above the chamber is opened to complete the dilution
`to the desired volume (50 to 150 mL), then closed.
`7. Flow commences when the clamp below the volume-control unit is
`opened.
`
`<
`
`Piggyback Method-The piggyback method (Figs 85-7
`and 85-8) refers to the intermittent IV drip of a second
`solution, the reconstituted drug, through the venipuncture
`site of an established primary IV system. With this setup
`
`-Slide
`---clamp
`
`50 or IOOmL
`LVP fluid
`
`Filter or/
`valve
`
`~Clamp
`
`the intermittent administration of a
`Fig 85-7. Piggyback method:
`second solution through the venipuncture site of an established
`primary IV system.
`
`Fig 85-6. Volume-control set.
`
`Fig 85-8. Piggyback administration setup.
`
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`
`

`

`the drug can be thought of as entering the vein on "top" of
`the primary IV fluid, hence the designation "piggyback."
`The piggyback technique not only eliminates the need for
`another venipuncture, but also achieves drug dilution and
`peak blood levels within a relatively short time span, usually
`30 to 60 min. Drug dilution helps to reduce irritation, and
`early high serum levels are an important consideration in
`serious infection requiring aggressive drug therapy. These
`advantages have popularized the piggyback method of IV
`therapy, especially for the intermittent administration of
`antibiotics. In using the piggyback technique, the secon(cid:173)
`dary unit is purged of air and its needle inserted into a Y(cid:173)
`injection site of the primary set or into the injection site at
`the end of the primary set. The piggyback infusion is then
`started. Once it is completed, the primary fluid infusion
`will be restarted. See Fig 85-8.
`Primary IV administration sets are available that have a
`built-in check valve for use in piggyback administration.
`When the piggyback is connected to one of these sets and
`started, the check valve automatically closes off the primary
`infusion. When the piggyback runs out, the check valve
`automatically opens, thereby restarting the primary infu(cid:173)
`sion. The check valve works because of'pressure differ(cid:173)
`ences. To achieve this difference, the primary container is
`hung lower than the secondary bottle by means of an exten(cid:173)
`sion hanger. See Fig 85-9.
`Manufacturers have introdu