February 2000
`Volume 35 Number 2
`ISSN 0018-5787
`
`i
`\,
`
`A
`tal pharmacy
`
`(PEER-REVIEWED JOURNAL FOR HOSPITAL AND ORGANIZED HEALTH CARE SYSTEMS PHARMACISTS
`
`‘
`
`_
`.
`
`Editorial
`
`I Medication Error Reporting: Persistence Will Pay Off
`
`1
`
`Ilniv. Iii Minn.
`Bin-Medical
`Library
`
`
`02 ‘17 DU ‘
`
`W
`
`ment Conference Statement on the Safety of
`I Consensus Develop
`livery Systems: Balancing Safety and Cost
`Intravenous Drug De
`
`fear-Reviewed Articles
`
`Lyme Disease: An Overview
`
`.1
`
`il Metered-Dose Inhaler—Spacer Technique in Hospitalized Geriatric
`Patients: Effect of Patient Education by a Pharmacist
`
`
` 'eatures and Columns
`'5 | Managed Care Pharmacist: Ambulatory Payment Classes
`| Policy Making: How the Advisory Committee on Immunization Practices
`Reached Recent Decisions
`
`I Cancer Chemotherapy Update: Carboplatin and Etoposide (CE) Regimen
`
`See table of contents for a complete listing of articles
`
`FACTS AND ®
`COMPARISONS
`the primary source for drug information
`
`(E
`
`EKR Therapeutics, LLC
`
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`

`

`Hospital Pharmacy
`Volume 35, Number 2, pp 150—155
`2000 Facts and Comparisons
`
`SPECIAL REPORT
`
`\ C
`
`onsensus Development Conference
`Statement on the Safety of
`Intravenous Drug Delivery Systems:
`Balancing Safety and Cost
`
`David WBates, MD, * Diane D. Cousins, RPh, Panel Chair ** Elizabeth Flynn, PhD, RPh“
`john WGosbee, MD, A15,” Linda Richason, RN" and Philip 1 Schneider MS, Panel Stdfl“
`
`As cost-containment pressures on health care systems continue, traditional
`practices are searchingfor ways to deliver care less expensively. Intravenous
`drug delivery systems have become a targeted area for cost savings in
`many health care institutions because they are so extensively used. Bench-
`mark systems that have been shown to improve safety, such as unit-dose
`drug distribution and 1V admixture programs, are now being viewed as
`costly alternatives. Likewise, technologies and innovations that have the
`potential to improve efliciency and safety are being critically scrutinized.
`The decision matrixfor selection of1V drug delivery systems needs to care-
`fully balance cost, quality, efiiciency, and safety—relative to the medication
`use process as a whole.
`
`This article presents the final statement of the Consensus Development
`Conference on the Safety of Intravenous Drug Delivery Systems, held on
`September 27-28, 1999, in Phoenix, AZ. The purpose of the conference was
`to provide a balanced assessment of available IV drug delivery systems.
`
`offer guidance for evaluating, apprais—
`ing, and selecting methods for admin—
`istering IV drug therapy. These SYS—
`tems are part of the medication use
`process. As such, they should ensure
`to the fullest extent pOSsible that the
`right drug is given—in the right time,
`by the right route, by the right per—
`son, to the right patient, and at the
`right time.
`IV drug therapy should also be
`monitored for treatment outcomes,
`including monitoring for adverse
`drug events and IV therapy compli-
`cations.
`
`e purpose of the Consen-
`sus Development Confer-
`ence on the Safety of Intra-
`venous Drug Delivery Sys-
`tems was to evaluate the relative safe-
`ty of currently available nonelectron-
`ic IV drug delivery systems.
`An interdisciplinary expert panel
`reviewed six systems, and compared
`them with regard to safety, cost, sim-
`plicity of use, and amount of educa-
`
`tion and training required for safe
`
`and proper use. The evaluation
`focused on IV drug delivery systems
`in acute care hospital settings and did
`not focus on specialized IV systems
`used in intensive care or pediatrics.
`Electronic devices were excluded.
`The recommendations apply to hos-
`pitals of all sizes, although certain sys-
`tems may be most practical given an
`institution’s size, available resources,
`and levels of patient acuity
`The intent of this statement is to
`
`*Chief, Division of Internal Medicine, Harvard/Brigham and Women's Hospital, Boston, MA; "Vice
`President, Practitioner and Product Experience Division, United States Pharmacopeia, Rockville,
`MD; iResearcher, Center for Research on Pharmacy Operations Design, Auburn University,
`Auburn, AL; HDirector, National Patient Safety Registry, National Center for Patient Safety, Veter-
`ans Health Administration,Ann Arbor, MI; #Chief Nursing Officer, Mission Bay Hospital, San Diego,
`CA; itCIinical Professor and Director, Latiolais Leadership Program, College of Pharmacy, The
`Ohio State University, Columbus, OH 45201. E-mail: schneider.5@osu.edu
`The Conference was sponsored in part by an unrestricted grant from Baxter Healthcare Cor-
`poration.
`
`Before addressing the specific
`systems, a number of caveats were
`considered by the panel.Any IV drug
`delivery system will only be as good
`as the safety management systems
`designed around it. Such systems are
`necessarily multidisciplinary, and
`excellent interdisciplinary communi-
`cation will be required for any system
`to be successful. One way to improve
`system performance is to minimize
`the number of steps from prepara-
`tion to administration, Without com-
`
`promising the steps that add to safe-
`ty. It is also safer to give medications
`orally when possible.
`Safe delivery of IV medication
`should include the following:
`° Mechanisms built into the medica-
`
`tion use system that prevent the
`wrong drug or dose from being
`dispensed or administered (eg, a
`double-Check by a pharmacist or
`
`
`150
`Volume 35, February 2000
`
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`

`

`Safety of Intravenous Drug Delivery Systems
`
`Luv
`
`.a»
`». (1,)-
`‘1‘
`, "Valentin
`,w inimwn "m
`
`_—____’__—___———’-
`FIGURE 1. IV push system
`
`bar code labeling)
`
`' Simplification and standardization
`to minimize variability of available
`IV systems and drug concentra-
`tions
`
`' Removal of concentrated solu-
`
`tions from patient care areas
`° Preparation of on-site IV admix-
`tures in the pharmacy whenever
`possible
`' Maximization of nurses’ and phar-
`macists’ time spent
`improving
`patient care; no system should
`replace careful monitoring ()f the
`patient before, during, and after IV
`drug administration.
`' Thorough and proper labeling of
`IV drug doses, including patient—
`specific information
`
`METHODOLOGY
`
`A chairperson was appointed
`and an interprofessional panel of in-
`dependent experts was selected to
`plan the conference. The NIH con-
`sensus
`development
`conference
`methodology was used.‘ A detailed
`review of the literature was per-
`
`formed:’ Speakers were invited to
`present reviews of six IV drug sys-
`tems.
`
`The IV drug delivery systems
`reviewed were IV push (Figure 1),
`volume control chambers (Figure 2),
`augmented IV push (eg, syringe
`
`pumps; Figure 3), point—of-care acti-
`vated systems (Figure 4), pharmacy-
`based IV admixture systems (Figure
`
`5), and manufacturer—prepared prod—
`ucts (Figure 6). A six-person panel
`comprising two physicians, two nurs—
`es, and two pharmacists was asked to
`prepare a consensus statement on
`the safety of IV drug delivery sys-
`tems.
`
`A decision analysis methodology
`was used to rank the systems based
`on four domains: safety, cost, simplici-
`
`ty of use, and education/trainingf
`Systems were numerically scored on
`a scale of 1 to 3,With 1 being a nega-
`tive ranking and 3 being a positive
`ranking.’I‘he scores were then totaled
`to reach a final ranking. In the final
`rankings, safety and cost were given
`higher weights and factored to a 100—
`point scale (safety had a maximum of
`26 points, with cost a maximum of
`28; 18 was the maximum for other
`categories).
`
`RESULTS
`
`The scores and rankings of the
`six IV drug delivery systems are sum-
`marized in Table 1. Three systems—
`manufacturer-prepared, point—of-care
`activated, and pharmacy—based IV
`admixtures~were ranked as being
`
`more safe. Systems ranking lower
`were IV push, augmented IV push,
`
`and volume control chambers.
`
`DISCUSSION
`A detailed review of the litera—
`
`ture summarizing the studies on each
`of these systems was published and
`provided to the panel before the Con-
`ference.-’ The following conclusions
`were reached by the panel based on
`information presented by the speak—
`ers.
`
`Marmfactm‘er—Prepared Products
`(e I, Premixed or Frozen)
`Manufactured products were
`considered by the panel
`to be the
`safest system because of quality
`assurance built into the preparation
`
`process. The final formulations for
`
`
`
`FIGURE 2. Volume control
`chamber
`
`
`
`
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`
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`

`

`Safety of Intravenous Drug Delivery Systems
`
`
`
`FIGURE 3. Augmented IV push
`system
`
`these drug doses are iso—osmotic,
`which may result
`in a lower inci-
`dence of phlebitis.The labeling of the
`product with the name and dose of
`the drug and diluent provides an
`additional safeguard.
`This system lends itself to more
`rapid availability of the dose and does
`not require that doses be calculated
`or manipulated further by the nurse.
`It may also free pharmacists and nurs-
`es to devote more time to other criti-
`cal activities associated with the safe-
`
`ty of IV drug delivery, such as IV to
`PO conversion programs.This system
`is also beneficial to smaller hospitals
`that do not have
`the human
`resources or facilities needed to
`make their own IV doses. Manufac-
`
`may
`products
`turer-prepared
`the
`increase acquisition costs, but
`overall system costs are balanced by
`the reduced preparation costs and
`wastage rates.
`
`Pharmacy-Based
`Intravenous Admixtures
`This system allows for maximum
`flexibility because any dose can be
`prepared, according to patient need.
`Almost all hospitals will use this sys-
`tem for preparation of some IV doses.
`Properly labeled products with
`patient-specific information are pro-
`duced. A pharmacist double-check is
`less likely to be bypassed, resulting in
`an extra safety step built into this sys«
`tem. However, fewer quality checks
`If products are placed directly in
`in product preparation occur with
`patient care areas, a double check by
`FIGURE 4. Point-of—care
`this system compared with manufac-
`a pharmacist
`is more likely to be
`activated system
`turer-prepared products. In addition,
`
`
`152
`Volume 35, February 2000
`
`bypassed, increasing the potential for
`an error unless barcoded products
`that can be scanned at bedside are
`used.Although not all medications or
`doses are available with this system, a
`large percentage is available.
`
`P0int—0f-Care Activated Systems
`These systems have some of the
`advantages of manufacturer-prepared
`products but require an additional
`step to mix the drug and diluent.This
`enables the rapid preparation of less-
`stable drug products at the point of
`care, but introduces a potential for
`error if the drug is not activated or
`the mixing is incomplete. There is
`some evidence that in approximately
`one in two hundred doses, activation
`does not occur. Staff orientation,
`training, and quality assurance are
`needed with this system to ensure
`that complete mixing or activation
`occurs.
`
`These products are suitable for
`
`storage in automated dispensing
`machines.When products are placed
`in patient care areas for direct dis—
`
`pensing, however, double check by a
`pharmacist
`is more likely to be
`bypassed, increasing the potential for
`an error. Although not all doses are
`available with this system, a large pro-
`portion is available.There may be less
`wastage with this system compared
`with pharmacy—based IV admixtures.
`
`there may be delays in getting the
`product to the patient care area in a
`timely manner.
`A full pharmacy—based IV admix-
`ture system may be more practical in
`large hospitals than in small hospi-
`tals. Some data suggest
`that error
`rates for this system are higher than
`with manufacturer—prepared or point-
`of—care activated systems.i
`
`IV Push
`
`Doses that do not require calcu-
`lation can be easily prepared and
`administered at the bedside. Premade
`syringes add an extra measure of safe-
`
`ty.\X/hen the nurse prepares the dose,
`this system allows for the most time-
`
`ly administration of a dose, providing
`that the nurse has time to prepare it.
`However, a system in which nurses
`prepare doses is often missing many
`of the quality checks and safeguards
`of the previous systems, thus calcula-
`tion errors may occur.
`
`
`
`EKR Therapeutics, LLC
`
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`
`Page 4
`
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`

`

` M r10[6’ WM//
`
`
`
`from Bristol-Myers Squibb
`
`{r}? Bristol—Myers Squibb Company
`’ Brisnieton..NI 08543
`
`©1999. Bristol-Myms Squibb Company. Princeton. NJ 05543, U.S.A.
`Ems
`
`EKfifififiafigpeutics, LLC
`
`Exhibit 2011
`
`'1U.S.A‘
`Prime
`a 6%
`
`EKR Therapeutics, LLC Exhibit 2011 Page 5
`
`

`

`Safety of Intravenous Drug Delivery Systems
`
`
`
`FIGURE 5. Pharmacy-based
`intravenous
`admixture system
`
`Pharmacist— or manufacturer-pre-
`pared doses are preferable to nurse-
`prepared doses. Regardless of who
`prepares the dose, however, the rate
`of infusion is less likely to be con-
`trolled. When errors occur,
`the
`adverse effect
`is more immediate,
`therefore there is
`little time to
`respond. Careful selection of those
`
`drugs that can be administered safely
`by IV push is essential. A list of med—
`ications that are approved for
`IV
`push administration should be devel—
`oped and maintained. Extensive train-
`
`ing and competency validation pro—
`grams should be in place for nurses
`who give medications by direct IV
`push.
`
`Augmented IVpus/o
`Augmented IV push systems, like
`syringe pumps, have the advantage of
`better controlling the rate of infusion
`and rely on products prepared in the
`pharmacy, thus providing a double
`
`check and reduced chance of prepa-
`ration error. They have the disadvan-
`
`tages of requiring a major capital
`equipment investment and increas-
`
`ing labor and storage costs compared
`and
`with manufacturer—prepared
`point-of-care systems.
`These systems require increased
`caution and active monitoring for
`infusion therapy complications. They
`also require more training to ensure
`proper use. Careful inventory man-
`agement
`for hardware
`is
`also
`required to ensure that doses can be
`given at the right time.
`
`Volume Control Chambers
`Volume control chambers have
`
`the advantage of providing quick
`access for IV drug delivery and care-
`ful control of fluid volume. They have
`disadvantages in that
`they provide
`poor control over the rate of delivery
`and the opportunity to mix incom-
`patible drugs. Drugs administered
`using this system are in an unlabeled
`container after the drug is placed in
`the chamber, increasing the risk of
`not knowing what is being infused.
`In addition, despite this system
`being similar to the IV push system
`(and having similar safety problems),
`
`training and competency validation
`for nurses are less common with vol-
`ume control chamber systems. These
`systems are more expensive than IV
`pushs, but may be less expensive
`than manufacturer-prepared or point-
`of—care activated systems if therapy
`extends longer than a few days.
`
`CONCLUSION AND PANEL
`RECOMMENDATIONS
`
`Three systems scored higher and
`were viewed by the panel as being
`superior IV drug delivery systems.
`These systems were manufacturer-
`prepared, point-of-care activated, and
`pharmacy-based IV admixture pro-
`grams. Systems ranked lower were IV
`push, volume control chambers, and
`augmented IV push. Most hospitals
`will have to use a combination of sys-
`tems, because all products are not
`available or appropriate as manufac—
`turer-prepared or point-of-care prod-
`ucts.
`
`is recognized that in certain
`It
`circumstances one system may be
`preferable to another. For example, in
`the case of medical emergency and
`for certain drug products, IV push
`may be the preferable system. The
`panel recommends that for general
`
`
`
`FIGURE 6. Manufacturer-prepared products
`
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`

`Safety of Intravenous Drug Delivery Systems
`
`
`Rank
`
`Decision Analysis Scores
`
`System
`
`Point-of-Care
`Activated
`
`Pharmacy-Based
`IV Admixture
`
`IV Push
`
`Augmented
`IV Push
`
`and personnel involved in the process, time performing the tasks, and the learning
`
`Volume
`Manufacturer—
`Control
`Prepared
`Chamber
`
`19
`19
`51
`31
`
`36
`A. Safety’“
`(56 maximum)
`
`12
`B. Cost‘r
`22
`(28 maximum)
`
`C. Sirnplicity*
`18
`( 18 maximum)
`
`D. TrainingM
`(18 maximum)
`E. Total
`(100 maximum)
`
`18
`
`94
`
`85
`
`*Safety is defined in relation to adverse drug events (eg, medication errors
`ees), infection, phlchitis, etc.
`
`and adverse drug reactions), risks (to both patients and employ-
`
`TCost is viewed from the system perspective, and is defined as cost of
`[ion errors and adverse drug events.
`
`:tSimplicity of use is defined as the number of steps
`curve.
`
`"Tralnmg is related to each discipline as necessary and appropriate.
`
`acquisition, labor, education/training, as well as the cost of medica-
`
`use and whenever feasible, the more
`
`highly ranked systems be chosen to
`maximize safety and simplicity, and to
`minimize training requirements.
`When IV push, volume control
`chambers, and augmented IV push
`systems are used, increased vigilance
`may be required to ensure safety.
`Greater costs and staff time may also
`be incurred.
`
`the
`Given the data presented,
`panel found that none of the IV drug
`delivery systems were inherently
`unacceptable. Individual products
`were not evaluated. Organizations
`
`may have incremental costs and safe-
`ty issues when changing systems.
`Bar coding of IV drug doses has
`the potential to improve patient safe-
`ty but standardization of the bar cod—
`ing format is needed to move forward
`
`in this area. Once bar codes are
`included on marketed IV therapy
`products or pharmacy labels, safe
`processes must be designed to
`accommodate this feature. The safety
`
`of point-of—care activated systems
`could be improved by providing
`feedback to confirm activation to the
`end user.
`
`IV drug delivery systems are part
`of a hospital’s unit-dose system, and
`the optimal system Will provide
`doses that do not need to be manipu—
`
`lated at the point of care.
`The panel concluded that further
`work is needed to clarify safety and
`cost issues associated with IV drug
`
`delivery systems. Little work has eval-
`uated the human factors engineering
`
`aspects of these systems, including
`the impact of environmental factors.
`
`Information about medication errors,
`
`adverse drug events, and IV site com-
`plications associated with these sys-
`tems is also insufficient and warrants
`further study.
`
`REFERENCES
`
`1. Guidelines/or the Planning and Man-
`agement of N111 Consensus Conferences
`()nline. Bethesda, Ml): National Institutes of
`Health, Office of the Director, Office of
`Medical Applications of Research; May
`1995, 15. Updated March 1995.
`2. Schneider 1’]. A review of the safety of
`intravenous drug delivery systems. Hos/1
`Pbm‘m. 1999;24:1044—56.
`
`5. Witte KW, ECK TA, Vogel Dl’. Decision
`analysis applied to the purchase of frozen
`premixed intravenous antibiotics. Am J
`1105]) Plzmrnl. 2985;42:855—9.
`4. Flynn EA, Pearson RE, Barker KN. Obser-
`vational study of accuracy in compounding
`i.v. admixtures at five hospitalsAlnj Hos/1
`Pbarm 1997;54:904- 12. I
`
`
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