Chapter 16: Aseptic Technique, Sterile Compounding, and IV Admixture Programs

Learning OutcomesDescribe basics of intravenous drug therapy Describe key elements of working in laminar airflow workbenches List types of contamination in a laminar flow hood & describe how to minimize their risks Perform basic manipulations needed to prepare a sterile product by using aseptic technique Describe the risks of handling cytotoxic & hazardous drugs

Learning OutcomesList steps in drug preparation & handling that are unique to cytotoxic & hazardous drugsList typical ingredients of total parenteral nutrition solutionsDescribe manual & automated means of preparing total parenteral nutrition solutionsDescribe benefits of having a formal intravenous admixture programDescribe how USP 797 has impacted preparation of sterile products

Key TermsAseptic techniqueBiological safety cabinetCoring Free flow protectionHEPA filter Laminar airflow workbench (LAFW)Large volume parenteral (LVP)Total parenteral nutrition (TPN)Small volume parenteral (SVP)

Parenteral Drug AdministrationParenteral not through digestive tract Intravenous (IV)Intramuscular (IM)Intrathecal (IT)Epidural IntraarticularIntraarterial IntraocularIntraperitonealSubcutaneous (SQ, SC, SubQ)

Risks of Intravenous TherapyInfectionAir embolusBleedingAllergic reactionIncompatibilitiesExtravasationParticulate MatterPyrogens Phlebitis

Types of IV AdministrationInfusionsContinuousIntermittent

IV ContainersLarge Volume Parenterals (LVPs)Small Volume Parenterals or Piggyback SystemsAdd-VantageVial Spike SystemsFlexible Plastic BagsGlass Containers

Basic Continuous IV TherapyLarge volume parenteral (LVP) hung on an IV pole 36 inches above patients bedflow maintained by gravitySterile tubing attached to LVPprimary IV setCatheter in patients vein

LVPUsually a simple solution of dilute dextrosesodium chlorideor combination of bothAdditivesswab rubber stopper with alcohol & let dryinject drug into fluidremove bottle vacuum

Non-coring Technique

Administration SystemsContinuous Infusionsmore effective & less toxic than when given intermittentlybasic fluid & electrolyte therapyblood productsdrugs that require tight administration control Intermittent Injectionsperiodic administration increases efficacy reduces toxicity

Pre-Mixed AdmixturesManufactured LVPs with additivesstable in solution for longer periods of timeavailable in many of sizes (250 mL, 500 mL, 1000 mL) Exampleslidocainepotassiumnitroglycerindopamineaminophylline

RTU AdvantagesReduce handling by pharmacyReduce potential for contaminationEmergency situations-stocked in patient care areaStandard concentrations of IV medicationsdecrease potential medication errors in compounding & administration

Pharmacy Prepared AdmixturesVolumes (100 mL, 250 mL, 500 mL, or 1000 mL)Containers (glass, plastic, bag, bottle or syringe)Syringe Systemssyringe pumpsvolume control chambersgravity feed intravenous push systems

Syringe Systems Pharmacy fills syringes with drugs & labelsstability in syringes related to drug concentrationSyringe Pumpsadjusted to administer volume over given period of timepumps are operated by battery or compressed springmay administer single dose or pre-programmed intervalsdoses must be sent from pharmacy in standard syringe sizes & concentrations

Electronic Infusion DevicesElectronic infusion devicesincrease precision & accuracyin fluid restricted patientswhen drug must be administered at precise rateSmart pumps alert user to problems infusion settings outside recommended rangeupdates may be sent to pumpspump log data may be sent to information system

Volume Control ChambersBuretrol or VolutrolSyringes used to administer drugs through volumetric chamberdrug injected through port on top of chambersolution added from primary LVPminimal amounts of fluid can be given per dosebeneficial in fluid-restricted or pediatric patientsimportant that medication is followed by IV flush

Gravity FeedSyringes can use gravity to administer drugsvented set allows air to enter syringeinexpensive & requires no other special equipmentIntravenous Pushinjected directly into IV tubingprimary IV set is usually clamped offDrug delivered directly to patientRapid onset of effects of drug

Patient Controlled AnalgesiaVery effective in managing painPatient administers dose as soon as pain feltReduces nursing timePump programmedBasal rateBolus when patient pushes buttonExample: max 1 mg of morphine every 15 minutesIf patient pushes button in 10 minutes, drug not released but attempt recorded so that pump tracks if pain not controlled

Unique Infusion DevicesImplanted pumpdrug reservoir for continuous low-dose chemotherapy administrationElastomeric infusion device (EID)acts as its own pumppressure of container forces drug through tubing

Administration SetsPrimary IV Setattached to the LVPcan be one of several varietiesDrip chamber-estimate administration rate by counting drops as they fall through chamberDrip chambermacrodrip or minidrip based on size of droptubing is labeled according to number of drops it produces from 1 milliliter of solution

Drip SetsMacro-drip sets deliver 10-20 drops per 1 mLMinidrip sets deliver sixty drops per 1 mL Rate controlled by roller clamp or electronic infusion deviceDrugs injected through portseither Y-sites or flashballs

Venous Access DevicesPeripheral insertion most common Peripheral catheters-limitations on what can be infused & at what rateCentral cathetermore complicatedriskier to insert & maintainfewer restrictions concentration of drugrate of administrationtime venous access can remain in place

Peripheral CathetersPlastic-flexible & most comfortable for patient Steel needle with short end of tubingscalp vein or butterfly may be left in the patients vein if flushedCentral catheterstemporary or permanentaccess vein with high blood flow

Catheter ExamplesPermanent cathetersHickmanBroviacPort-a-cath Peripheral catheter peripherally inserted central catheter (PICC)PICC inserted peripherallyflexible catheter threaded through venous system & its tip ends near hearthigh volume of blood flow

IV Miscellaneous InformationHeparin Lockmaintain catheter access to veinresealable rubber diaphragmprovide port for intermittent use concentration of heparin used in heparin locks is usually 10 units/mL or 100 units/mLNeedleless Systemsreduce risks of needle sticksrequired in some states & some healthcare systems

IV Misc. Information ContinuedFinal Filterslocated in the tubingused to remove particles in IV solutionused with drugs that have a risk of particulate matter or crystals in final solutionexamples of drugs requiring filtersphenytoinmannitol

Aseptic PreparationAdmixture preparation program includes:1. Development & maintenance of good aseptic technique in personnel who prepare & administer sterile products2. Development & maintenance of sterile compounding area, complete with sterilized equipment & supplies3. Development & maintenance of skills needed to properly use laminar airflow workbench (LAFW) or laminar airflow hood

Aseptic Technique Manipulating sterile products without compromising their sterilityproper use of LAFWstrict aseptic technique Conscientious work habits

Sterile Compounding AreaCompounded sterile products (CSPs) must be free of living microorganismspyrogensvisible particles Reduce number of particles in airno cardboard in clean roomClean work surfaces & floors dailyClean walls, ceilings, & shelving monthly

Sterile Compounding AreaSegregate compounding areaminimize traffic in sterile compounding area remove trash d frequently & regularlyFilter incoming airUltraviolet irradiationAir-lock entry portalsSticky mats

Sterile Compounding AreaUse anteroom for non-aseptic activities order processinggowninghandling of stockISO Class 5 environmentno more than 100 particles per cubic foot that are 0.5 micron or larger in sizeLAFWs are used to achieve an ISO Class 5 environment

Laminar Airflow WorkbenchesPrinciple of LAFWstwice-filtered laminar layers of aseptic air continuously sweep work area inside hoodprevents entry of contaminated room air2 common types of LAFWs horizontal flowvertical flow

IV HoodsVertical Hoods used for preparing hazardous medicationsDesigned to protect preparer from exposure to hazardous medications

Horizontal Hoods most common for sterile preparation of IV solutions

Horizontal LAFWAir moves from back to front Electrical blower draws room air through a prefilterRemoves gross contaminants Should be cleaned or replaced on regular basisPrefiltered air moves through final filterEntire back portion of hoods work area is HEPAhigh efficiency particulate airRemoves 99.97% of particles that are 0.3 micron or larger

Vertical LAFWAir emerges from the top and passes downwardExposure to airborne drug particulates minimizedUsed for preparation of antineoplasticsReferred to as biological safety cabinets (BSCs)Space between the HEPA filter and the sterile objectcritical area.Must prevent downstream contaminationZone of turbulence

LAFW PrinciplesPosition away from excess traffic, doors, air vents, etc.Must run for 15 -3o minutes if turned off & back onAll interior working surfaces should be cleaned70% isopropyl alcohol/other disinfecting agentclean, lint-free cloth

Cleaning LAFWsClean sides of hoods using up & down directionstart at HEPAwork toward outer edge of hoodOrder of cleaningwalls 1stfloor of hood 2nd

Cleaning LAFWsFrequencybeginning of each shiftbefore each batchnot longer than 30 minutes following previous surface disinfection when ongoing compounding activities are occurringafter spillswhen surface contamination is known or suspected

Cleaning LAFWsIf materials not soluble in alcohol, initially use waterfollow with alcoholDo not use spray bottles of alcohol in hoodLet alcohol air dryClean Plexiglas sides -warm, soapy waterAlcohol will dry out Plexiglasclouds & cracks

Additional LAFW InstructionsNothing should come in contact with HEPA filterNothing in hood that is not essential IV preparationno paper, pens, labels, or traysNo jewelry on hands or wristsTalk & cough away from LAFWNo smoking, eating, drinking in aseptic area Manipulations at least six inches within hood

Additional LAFW InstructionsMust test LAFWs at least every 6 monthsAlso test if hood moved, or if filter damage suspectedSpecific tests airflow velocityHEPA filter integrityStrict aseptic technique must be used

Aseptic EnvironmentPersonal Attire -CoverShoes, head & facial hair, use face masks/eye shieldscover scrub suits when leaving pharmacyHandwashingtouch is most common source of contaminationscrub hands, nails, wrists, forearms to elbows for at least 30 seconds with a brush, warm water, & appropriate bactericidal soap Glovingonly sterile until they touch something unsterile

Equipment & SuppliesSyringes

SyringesVolume of solution- 1/2 to 2/3 of syringe capacityMeasuring-line up final edge to calibration mark on barrel Open syringe package in hood to maintain sterilityPeel wrapper & discard out of hood Leave syringe tip protector in place until time to attach needleTo attach needle to Luer-lock-type syringe turn is usually sufficient to secure needle to syringe

NeedlesNote componentsOften color-coded=gauge Vented needlesFilter needlesDead space

VialsRubber stopper Powders or liquids70% isopropyl alcohol Avoid coringNormalize pressureReconstitutionSDV or MDV Preservative considerations

AmpulesMove fluid to body of ampuleSwab neck with alcohol padBreak at neck Tilt ampule, needle bevel downUse filter needle

Prefilled SyringesManufactured ready-to-inject syringesCommonly given IM, IV, or subcutaneously Convenient for administrationemergency situations Most likely to be kept in patient care areas

Preparation of IV AdmixturesPharmacist inputs order into computer systemAssemble all materials & visually inspectClean hood-only needed products in hoodDisinfect all injection surfacesWithdraw & measure drug fluidRemove air bubbles from syringeDiscard syringes & uncapped needlesRecapping needles is generally unsafe practiceuse one-handed scoop method if recap needed

Closures & SealsLuer Tips for syringes when final product being dispensed is not intended for injectionoraltopicalIV port seals Tamperproof caps

Automated Compounding Sterile product preparation is technically complexVerification challengingAutomation can eliminate preparation errorsEnclosed IV preparation environments & roboticsused in high volume situations or may prepare patient specific doses

Labeling of IV PreparationsPatient name, identification #, room #Bottle or bag sequence numberName & amount of drug(s) added Name & volume of admixture solution Final total volume of admixturePrescribed flow rate (in milliliters per hour) Date & time of scheduled administrationDate & time of preparation Expiration date Initials of person who prepared/checked IV admixture Auxiliary labeling Bar coding

Beyond Use Date (Exp Date)Label & final sterile product- validated by registered pharmacistLabel with beyond use date (BUD)stabilitysterilityPolicies & proceduressubstantiated by referencespublished literaturereasonable professional judgment

Cytotoxic & Hazardous DrugsHazardous agentsspecial procedures for labeling, storage, transportspecial clothingBiological Safety Cabinets (BSCs)special handling of spills & waste Additional information is available from ASHPTechnical Assistance Bulletin on Handling of Cytotoxic and Hazardous Drugs

Protective ApparelDisposable coveralls 0r or solid front gownLow-permeability, lint-free fabricLong sleeves & tight-fitting elastic or knit cuffsWash hands before putting on the gloves & after removing themOne or two pairs of gloves may be requiredTuck one pair under cuffs of gown & place second pair over cuffs

First AidEyewash fountain in work area with hazardous drugs Appropriate first aid equipmentFollow established first aid proceduresObtain medical attention without delay & document injury

Biological Safety Cabinet (BSC)Type of vertical LAFWDesigned to protect workers BSCs must meet standards set by National Sanitation Foundation (NSF Standard 49)Do not use horizontal LAFWs to prepare hazardous drugs

BSCFront air barrier-protects handler from contact with hazardous drug dusts & aerosolsTypes of Class II BSCsType A Type B BSCs must be operated continuously, 24/7Inspected & certified every 6 monthsClean work surface, back, side walls with water or cleaner recommended by cabinet manufacturer

BSCDisinfect work surface with 70% isopropyl alcoholDo not to use excessive amounts of alcoholTreat cleaning supplies as hazardous wasteDecontaminate on weekly basis/immediately after spill Refer to facilitys procedure on hood maintenance for specific cleaning procedures & schedules

Preparing Hazardous DrugsSame as regular drugs EXCEPTattach & prime IV sets before adding hazardous drugmaintain slight negative pressure inside vial or use chemotherapy dispensing pinuse syringes & IV sets with locking fittingsuse oversize syringe for reconstitutionapply warnings on IV bag (Hazardous)place IV in sealable bag to contain any leakage

Waste Disposal & Spill CleanupSpills-use spill kitcleanup should follow established procedures kits contain protective gear,eye protectionrespiratorutility & latex glovesdisposable gown or coverallsshoe coversscoop, plastic container for glass fragments, absorbent spill pads, gauze & disposable toweling, absorbent powder, & sealable, thick plastic waste disposal bags

Total Parenteral NutritionTPNs aka hyperalimentationContaincarbohydratesproteinfatswaterelectrolytesvitaminstrace elements

TPN TherapyMeets nutritional needs for patientswho cant eatwho will not eatwho should not eat who cannot eat enough to sustain their needs due to increased nutritional requirements from their medical condition

Components of TPNsBase componentsdextrose (carbohydrates) amino acids (protein)may also include fat & waterAdditives electrolytesvitaminstrace elements (micronutrients)drugs such as heparin, insulin, H2 antagonists

ComponentsDextrose -usually a 50% or 70%final dextrose concentration ~25% if via central veinmaximum of 1012.5% for peripheral administrationProtein usually 8.5%, 10%, or 15% special formulations for pediatric patients, kidney disease, liver disease, high stress situation (ICU pts)Fats (or lipids)-10% or 20% fat emulsionsemulsions separately through peripheral IV lineor may be added to TPN solution: 3-in-1 solution

Components WaterElectrolytes to meet daily metabolic needssodium, potassium, chloride, acetate, phosphate, magnesium, calciumadministered as a specific salt of productcan cause precipitation: wrong sequence or concentrations of electrolytes are added to bagVitamins- MVI for multiple-vitamin infusionVitamin K (phytonadione)Trace elements for proper enzymatic reactions

Example of TPN OrderDextrose 250 gAmino acids 42.5 gSodium chloride 60 mEqPotassium chloride 40 mEqPotassium phosphate 20 mEqCalcium gluconate 1 gMagnesium sulfate 1 gTrace elements 2 mLMVI 10 mLTotal volume 1000 mLInfuse at 100 mL per hour. Also give: Vitamin K 10 mg intramuscularly (IM) every week, 10% fat emulsion 500 mL intravenously three times per week.

TPN Form Preprinted order forms Reduce error May be required in some hospitalsEach facility designs components of preprinted forms

Preparation of TPN SolutionsAutomated compounder 2 primary versions of TPN compounders1st-provides a separate compounder for base solutions and electrolytes 2nd -uses one compounder to infuse all compounded ingredients Gravity fill preparation

AdministrationCentral line immediate dilution of administered solution by bloodallows use of very concentrated solutionPeripheral parenteral nutrition (PPN)same components as TPNnot as concentratedmay not meet all the patients nutritional needs

Pediatric IV Drug AdministrationDoses individualizedcalculated based on patients body weightIntermittent doses via syringe through volume control chamber or by using syringepumpmaximize accuracy Minimize amount of fluid Calculations should be checked & double-checked

Epidural AdministrationSpecial catheter into epidural space of spineDrug injected at nerve ending-dose greatly reducedAll solutions must be free of preservativesEpidural patient controlled analgesia Continuous infusionsBolus injections

Admixture ProgramsPolicies & ProceduresSpaceTrainingEquipmentStandard & Non-Standard PreparationsLabelingHandling

Quality Assurance ProgramASHPs Technical Assistance Bulletin on Quality Assurance for Pharmacy-Prepared Sterile Productspreparationexpiration dating labelingfacilitiesequipment personnel education trainingevaluation end-product testing

USP Chapter 797Refer to USP Chapter 797, Pharmaceutical CompoundingSterile Preparations recommendations & regulations regarding IV admixture programsdifferent levels of risk for productsfourth class, immediate-use CSPstrainingpolicies & proceduresgarb, aseptic technique, process validation, end-product evaluation

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