Ch 34: Sterility What is sterility? Why is sterility so important? The absence of pathogenic bacteria Why is sterility so important? When a product is given parenterally we bypass the body’s normal defenses some areas of the body have a limited ability to fight bacterial infection, (ie, the eye) © 2013-2015

Pyrogenic Contamination Pyrogens are endotoxic products of bacteria You may have a product that is free of bacteria, yet still contains these pyrogenic compounds Pyrogens cause a fever in the host body Our goal is for our product to be both sterile and non-pyrogenic © 2013-2015

Aseptic Technique The process of assuring sterility through our actions Everything we do during sterile product compounding must insure that contamination of the product does not occur The primary contamination factor in the process is the operator © 2013-2015

Basic Tools of the Trade The Syringe Needles and Filters The Medication Bottle The Laminar Flow Hood The IV Bag IV Administration Sets Personal Protective Equipment © 2013-2015

The Syringe Meant to measure, deliver, and administer sterile fluids Parenteral syringes are packaged sterile in a protective wrapping that is also sterile inside Syringes may be packaged with or without a needle attached Available in sizes from 0.5 ml to 50 ml © 2013-2015

The Parts of a Syringe Ring of Piston used to read the volume Collar Tip Barrel Plunger Scale of Measurement Thumb Lip Plunger Piston © 2013-2015

Scales used on a syringe Depends on the intended purpose of the syringe May be marked in milliliters or “units” Be sure you are using the correct type and size of syringe select the scale based on the type of material select the size based on the amount of material © 2013-2015

Reading a Syringe 1 2 3 Always use the plunger ring closest to the tip to read the volume contained in a syringe This syringe contains 4 ml of liquid 4 4ml 5 © 2013-2015

Needles Come in various lengths and diameter The measure of a needle’s diameter is called its “gauge” The more viscous the solution to be drawn into the syringe, the smaller the gauge number on the needle should be © 2013-2015

The Parts of a Needle Bevel Shaft Hub © 2013-2015

The Bevel of a Needle This is what the tip of a needle looks like when magnified approximately 150 times © 2013-2015

Needles Remember, the LARGER the gauge number, the THINNER the needle Therefore, a 29g needle will be much thinner than an 18g needle Length has nothing to do with diameter You can have a 3 inch 22g needle or a 1 inch 18g needle Shorter doesn’t mean larger diameter © 2013-2015

Special Types of Needles There are many special types of needles We will normally only see two types of specialty needles in the pharmacy: Filter needles Safety needles © 2013-2015

The Filter Needle Looks just like a normal needle except in the hub of the needle there is a filter Can catch contaminants either when drawing into the syringe OR when discharging from the syringe, BUT.. The same filter needle should never be used to both withdraw and discharge because the filter action would be nullified © 2013-2015

The Safety Needle Meant to help minimize accidental needle sticks Comes in more than one type: Retractable needle and syringe Once the contents of the syringe are completely discharged, a harder press on the plunger causes the needle to retract into the hub and body of the syringe Mechanical needle guard Sliding mechanism attached to the needle hub that slides down and covers the point of the needle © 2013-2015

Safety Precautions with Needles NEVER try to recap a needle if there is a sharps container that you can use immediately ALWAYS dispose of needles in a biohazard sharps container NEVER put them in a general trash container © 2013-2015

The Multiple Use Vial The most common Plastic or glass with a rubber stopper secured by a metal ring Has preservatives that allow safe use after the stopper has been punctured Once it has been punctured a maximum of a 30 day expiration date should be written on the bottle © 2013-2015

Removing Medication from a Multiple Use Vial Flip off the protective plastic cap from the top of the rubber stopper Swab the rubber stopper with a 70% isopropyl alcohol swab and let dry Since the internal chamber of the vial is sealed, air must be added to the vial to allow the material inside to come out without creating too big of a vacuum © 2013-2015

Problem of “Coring” Whenever a needle pierces a rubber stopper, rubber “cores” from the stopper may be produced You NEVER want a rubber core in the final product! Cores will appear as little rubber specks inside your stock bottle or product always check the stock bottle & finished product against a white background to look for these dark colored specks We must minimize the production of cores © 2013-2015

Preventing Cores Always pierce the stopper with the bevel of the needle facing UP Always apply pressure backward and down as you push the needle through the stopper © 2013-2015

What if our Stock Bottle Already has a Core? The vial should be marked to indicate its presence Use a filter needle to withdraw the contents from the stock bottle, then replace the needle with a regular needle before injecting the solution into the product © 2013-2015

Adding Air to the Vial You never want to add so much air into the vial that you create a positive pressure inside if you did, the pressure would shoot the contents out of the vial, and into the air, as you withdraw the needle Always add slightly less air than the volume you wish to remove this will keep a slight negative pressure in the vial If too much vacuum develops, you can pierce the stopper with a needle by itself allowing the inner and outer pressure to equalize © 2013-2015

Reconstitution in Vials Drugs contained in vials that require reconstitution give us another procedure for equalizing pressure With these drugs a volume of water or other diluent must be added to reconstitute the drug To do this without leaving pressure in the vial, first inject the liquid, then while leaving the needle in the stopper, allow the excess air to return into the syringe and equalize the pressure © 2013-2015

Glass Ampules Made entirely of glass Only for a single use Any excess medication must be discarded The internal chamber is not closed to the outside environment Manufactured so that there is a fracture line around the neck of the ampule © 2013-2015

Before Opening a Glass Ampule Be sure all of the medication is out of the head of the ampule and contained in the main body If it is not, you can move it using one of these methods swirling the ampule in an upright position tapping the head with you finger turning the ampule upside down and then righting it with a swift swinging motion © 2013-2015

Opening a Glass Ampule Swab the neck with 70% isopropyl alcohol Leave the alcohol swab wrapped around the neck Place the head of the ampule between the thumb and first finger of one hand Hold the body of the ampule with the thumb and first finger of the other hand © 2013-2015

Opening a Glass Ampule Quickly “snap” the top off the ampule by applying pressure with both thumbs away from yourself If the ampule does not open easily, rotate it so that a different side of the neck is facing you and try again The ampule should open easily Be careful not to apply so much pressure as to crush the glass between your thumb and finger © 2013-2015

Withdrawing the Contents Since the internal chamber is not sealed, no injection of air is necessary In order to eliminate any risk of glass fragments or paint chips being withdrawn from the container, a filter needle or filter straw must be used © 2013-2015

USP 797 Standards and Requirements Covers Technique Equipment Quality control Requirements depend on the type of compounding done Concepts Clean room= holds compounding area Ante room= supplies, storage, sink © 2013-2015

Requirements to Compound Sterile Products Clean Room Air cleanliness Microbial contamination Preparation Area Laminar Flow Hood Compounding Equipment Sterile Materials All materials used to compound or package sterile products must be sterile themselves © 2013-2015

Sterile Compounding Environment The environment present during sterile compounding has a great influence on the final product. The room where the compounding takes place is called the “Cleanroom” The actual compounding will take place within a specialized piece of equipment known as the “Biological Safety Cabinet” or “Laminar Flow Hood” © 2013-2015

Reducing the Risk of Contamination Cleanroom practices separate room no unnecessary traffic proper attire proper cleaning positive air pressure Biological Safety Cabinet / Laminar Flow Hood creates a protected work environment © 2013-2015

ISO Standards ISO Class refers to the number of particles of a certain size contained in a cubic meter of air ISO Class depends on area Ante Room= ISO Class 8 Clean Room= ISO Class 7 Critical Areas= ISO Class 5 Air quality must be tested every 6 months or whenever equipment is moved in the room © 2013-2015

Laminar Flow Hoods First efforts at maintaining an environment suitable for sterile compounding Provides columns of purified air blown across the work area High Efficiency Particulate Air Filter (HEPA) All sterile product work should be conducted within the hood © 2013-2015

Types of Laminar Flow Hoods Horizontal Flow Hoods first type used airflow blows horizontally across the work surface not appropriate for hazardous chemicals or biological products Vertical Flow Hoods airflow blows vertically down onto the work surface protects the user more than the horizontal flow does Not the best choice for hazardous chemicals or biological products © 2013-2015

Horizontal Flow Hood Workspace HEPA Filter © 2013-2015

Vertical Flow Hood HEPA Filter Workspace © 2013-2015

Biological Safety Cabinets Newer hoods than the horizontal or vertical laminar flow hoods Still functions using columns of air blown through filters Adds filtration of air exhausted either to the room or outside through the exhaust duct There are three classes of BSCs © 2013-2015

Class I BSC Incoming air in a Class I BSC is NOT filtered NEVER use a Class I BSC to prepare a compound where sterility is desired © 2013-2015

Class II BSC There are three categories of Class II BSCs Vary by how much air is recirculated inside the workspace ALL Class II BSCs are suitable for sterile product preparation Still has an opening in front where the operators arms enter the work area © 2013-2015

Class III BSC Totally enclosed and leak proof systems that are exhausted through the building’s external exhaust system No air is returned to the room Access to the work area is only through arm length gloves built into the unit, or double door pass-through boxes on the side Very expensive to purchase and operate © 2013-2015

Isolators Similar in appearance to Class III BSC Exhausted outside the work area Has solid front with arm length gloves and pass-through Isolators recirculate more of the air inside the workspace than do Class III BSCs © 2013-2015

HEPA Filter Thin pleated sheets of boron silicate fibers separated by aluminum Removes 99.997% of all particles 0.3 microns or larger NEVER touch the HEPA filter with anything NEVER spray anything on the filter © 2013-2015

HEPA Filter Health of the filter is tested by air flow rates coming through the filter surface Filter should be inspected every 6 months by a professional service The filter blower should run 24 hours a day if, for some reason, the blower has been shut off, the unit must run for at least 20 minutes before work can commence © 2013-2015

ULPA Filter “Ultra-Low Particle Air Filter” Newer filter design that is closely related to the HEPA filter, yet offer more efficient filtration Designed to remove 99.999% of all particles 0.12 microns or larger BSCs are available with HEPA and ULPA filters © 2013-2015

Personal Protective Equipment - Scrubs - Shoe covers - Hair covers - Face mask - Hand washing facility - Sterile gown - Foaming isopropyl alcohol hand sanitizer - Sterile gloves PPE also protects the patient from you! Personal Protective Equipment © 2013-2015

Proper Hand Washing Correct Equipment Needed Sink the appropriate size, preferably with foot controls for water flow Surgical scrub/brush package Contains antibacterial soap and aseptic lint-free paper towels Correct method to wash hands © 2013-2015

Working in the Hood Remove unnecessary jewelry or personal articles Wash your hands with antibacterial scrub Put on the appropriate protective equipment Assemble the necessary stock bottles, syringes, and other equipment OUTSIDE the hood Wipe the hood down with alcohol and allow to dry © 2013-2015

Working in the Hood Whenever working in the hood or BSC, remember the concept of “First Air” First air is the un-disrupted air flow coming directly from a HEPA or ULPA filtration source It is the “cleanest” air in the workspace Anything that interrupts the flow of clean air causes turbulence in the air flow and introduces the chance of particles in the air ALWAYS work in areas containing First Air © 2013-2015

Working in the Hood Arrange all of the materials inside the hood, to the right or left of the area in which you will work Bring all of the materials in at once – do not keep reaching in and out of the hood Never block airflow to an item with your hands (maintain First Air conditions) Swab all rubber stoppers and IV ports with alcohol swabs Anytime a syringe is uncapped, the point should always be facing the HEPA filter © 2013-2015

Working in the Hood Draw up all ingredients into separate syringes and let the pharmacist check your work Once approved, and with the pharmacist’s consent, you may inject the ingredients into the IV bag Immediately label the IV bag and place a protective cap over the admixture port of the bag © 2013-2015

REMEMBER – NEVER TOUCH, OR SPRAY ANYTHING ON, THE HEPA FILTER Cleaning the Hood At least daily wet all surfaces with bactericidal cleaner, let stand for the appropriate time and wipe clean Several times throughout the workday wipe all the hood surfaces down with 70% isopropyl alcohol REMEMBER – NEVER TOUCH, OR SPRAY ANYTHING ON, THE HEPA FILTER © 2013-2015

Wiping Procedure When wiping down the hood, always follow the proper sequence: use a side to side wiping motion beginning with the area closest to the HEPA filter and proceed towards the open edges all side walls and hanging racks should be wiped similarly if the hood has been used to compound chemotherapy drugs, discard the cleaning towels in a biohazard bag © 2013-2015

Administration of an IV Product The IV Administration Set Can be for manual calibration or for use with an infusion pump © 2013-2015

Infusion Pumps Infusion pumps electronically control the flow of IV fluid through the tubing Each manufacturer uses their own pump design and their own corresponding administration sets © 2013-2015

Filtering Parenteral Solutions Can be contained within the administration set or as a separate entity Filters out particles as small as 0.22 microns Provides final insurance of a product’s sterility (filter traps bacteria) Separate Filter In-Line Filter © 2013-2015

Ch 35: It’s time for MATH! Often times we are expected to calculate a dose of medication that is appropriate for a particular patient You need to be able to calculate a dose for an adult or a pediatric patient for the examination © 2013-2015

Calculating Adult Doses Simple mathematical process Be sure that you read the question CAREFULLY and calculate for the correct units and time periods Is the weight and recommended dose in the same units of weight? Is the question asking for the amount per dose, the daily dose, or the total amount to be dispensed? © 2013-2015

Adult Doses The recommended adult dose of “Drug X” is 40mg/kg/d What does this mean? for every kilogram the patient weighs, they will receive 40mg of the drug per day © 2013-2015

Adult Doses X X 110 kg 40mg 4,400mg x = = 4,400mg 1 1 kg 1 Let’s say the patient weighs 110 kg. Calculate the daily dose Weight x Dose = Answer 110 kg 40mg 4,400mg X x = = 4,400mg 1 1 kg 1 X © 2013-2015

Try Another Recommended dose = 25mg/kg/q8° Patient’s weight = 80kg What is the amount to give for each dose? What is the total amount given in 24 hours? © 2013-2015

Answer X 80 kg 25mg 2,000mg 1 1 kg 1 x = = 2,000mg per dose Weight x Dose = Answer 80 kg 25mg 2,000mg 1 1 kg 1 x = = 2,000mg X per dose Since there are 3 doses in 24 hours, to get the total daily dose you multiply by 3 2,000mg x 3 doses = 6,000 mg per day © 2013-2015

Example What if the units of weight don’t match? Recommended dose = 45mg/kg/q8° Patient's weight = 230 lb What is the correct amount to give per dose? © 2013-2015

Example X X 230 lb 1 kg 230 x = = 104.5 kg 1 2.2 lb 2.2 First use a conversion to calculate the weight in the appropriate units, then calculate the dose Pounds  Kilograms Weight x Conversion = Answer 230 lb 1 kg 230 1 2.2 lb 2.2 x = = 104.5 kg X X © 2013-2015

Example X 104.5 kg 45 mg 4,702.5mg 1 1 kg 1 x = = 4,703mg Now finish the problem as before Weight x Dose = Answer 104.5 kg 45 mg 4,702.5mg 1 1 kg 1 x = = 4,703mg X © 2013-2015

One More Example If you feel adventurous, you can combine all of the conversion factors into one long equation Patient’s weight = 198 lb Recommended Dose = 2 mg/kg/d What is the daily dosage? © 2013-2015

Example 1 2.2 lb 1 kg 2.2 X 198 lb 1 kg 2 mg 396 mg x x = = 180 mg © 2013-2015

CH 36: Calculating Pediatric Dosage Many drugs do not have doses that are recommended for pediatric patients There are several calculations used to convert adult doses to pediatric doses We will cover two of the most frequently used methods © 2013-2015

Young’s Rule Based on the child’s AGE Age in Yrs x adult dose = pediatric dose (Age in Yrs + 12) © 2013-2015

Example Our patient is 4 years old The recommended adult dose = 250mg Calculate the child’s dose using Young’s Rule 4 (4 + 12) x 250 mg = 62.5 mg © 2013-2015

Clark’s Rule Uses the WEIGHT of the child to calculate the dose ALWAYS use pounds to calculate Weight in lb. 150 x adult dose = pediatric dose © 2013-2015

Example Our patient weighs 40 lbs Recommended adult dose = 250mg Calculate the child’s dose using Clark’s Rule 40 lb 150 x 250 mg = 66.7 mg © 2013-2015

Ch 37: Parenteral Calculations Parenteral calculations deal with administration of IV fluids Two main concepts you will learn Flow Rate Dose per Time © 2013-2015

Flow Rate Calculations Flow rate is the speed at which an IV solution is delivered Function of Volume per Time usually reported in milliliters per hour The magical formula volume ÷ time = flow rate Always be sure which time and volume units you are being asked to solve for! Is it ml/min ? Or l/hr? Something else? © 2013-2015

Flow Rate Calculations A patient receives 1 L of IV solution over a 3 hour period. Calculate the flow rate in ml/hr. Note: the volume given is in liters, but the answer asks for milliliters. If the conversion wasn’t so obvious, we would first need to do a conversion of L  ml. volume ÷ time = flow rate 1000 ml ÷ 3 hours = 333 ml/hr © 2013-2015

Another Rate Problem X 0.75 L 1000ml 750ml 1 1 L 1 x = = 750 ml A patient receives 0.75L of IV solution over a 4hour period. Calculate the flow rate in ml/hr. 750 ml ÷ 4 hours = 188 ml/hr Now the conversion is a bit harder, so we do the math 0.75 L 1000ml 750ml 1 1 L 1 x = = 750 ml X © 2013-2015

Solve for Time By manipulating the rate formula, we can solve for time The equation becomes: volume ÷ rate = time © 2013-2015

Solving for Time If an IV is run at 125ml/hr, how long will 1 L last? © 2013-2015

Solving for Time X 1000 ml = 8 hr 125 ml / hr If an IV is run at 125ml/hr, how long will 1 L last? volume ÷ rate = time 1000 ml = 8 hr 125 ml / hr X Milliliters cancel and you are left with the units of hours © 2013-2015

Solving for Volume Play with the formula some more, and now we can solve for volume The equation becomes: rate x time = volume © 2013-2015

Solving for Volume How many ml of IV solution would be required to run an IV for 12 hours at a rate of 60 ml/hr? © 2013-2015

Solving for Volume X 60 ml 12 hr 720 ml 1 hr 1 1 x = = 720 ml How many ml of IV solution would be required to run an IV for 12 hours at a rate of 60 ml/hr? rate x time = volume IT’S REALLY JUST A CONVERSION PROBLEM! X 60 ml 12 hr 720 ml 1 hr 1 1 x = = 720 ml © 2013-2015

Solving for Volume What volume would we need to have on hand if an IV solution is to be run for 100 ml/hr for 8.3 hrs? © 2013-2015

Solving for Volume X 100 ml 8.3 hr 830 ml 1 hr 1 1 x = = 830 ml What volume would we need to have on hand if an IV solution is to be run for 100 ml/hr for 8.3 hrs? 100 ml 8.3 hr 830 ml 1 hr 1 1 x = = 830 ml X © 2013-2015

How is the Fluid Measured? We have spoken of rate in terms of ml per time period How do we measure this milliliter? IV Pumps Automatically measure the volume with matching administration sets Calibrated Administration Sets Can be used without an IV pump Sets will be marked with the calibration 10 gtts / ml 15 gtts / ml 60 gtts / ml © 2013-2015

Fluid Measurement By knowing the calibration (gtt/ml) and the flow rate ordered, we can calculate the necessary rate in drops per minute Don’t get all discombobulated! it is simple conversion calculations! like any conversion problem, arrange your units so they cancel to give the final unit required by the question © 2013-2015

Example A drug order calls for D5W to be administered at a rate of 125ml/hr. Our administration set is calibrated to deliver 10 gtt/ml. How many gtt/min should the nurse use? Ok, thinking caps on….. First we need to convert ml/hr  ml/min Then we multiply times the calibration factor in gtt/ml © 2013-2015

Example X 125 ml 1 hr 10 gtt 1 hr 60 min 1 ml x x = 20.8 gtt/min Convert ml/hr  ml/min x calibration = gtt/min 125 ml 1 hr 10 gtt 1 hr 60 min 1 ml x x = 20.8 gtt/min X Since there is no such thing as a partial drop, we round the answer to 21 gtt/min © 2013-2015

Let’s Try Another An IV is ordered to be run at 80 ml/hr. Our administration set is calibrated at 10 gtt/ml. What rate in gtt/min should be used? © 2013-2015

Let’s Try Another X 80 ml 1 hr 10 gtt 1 hr 60 min 1 ml An IV is ordered to be run at 80 ml/hr. Our administration set is calibrated at 10 gtt/ml. What rate in gtt/min should be used? 80 ml 1 hr 10 gtt 1 hr 60 min 1 ml x x = 13.3 gtt/min X or 13 gtt/min © 2013-2015

Now for One More Twist…. Dose per Unit Time Calculation Don’t Fret! used when a specific dose in weight is needed to be run over a certain time period Don’t Fret! it’s still the same type of calculation you just did, but with one twist you do a proportion calculation first to find out how much volume of fluid contains the desired amount of drug © 2013-2015

Dose per Time 250 mg of a drug is dissolved in 500 ml of NS. The drug order states that 250 mg is to be administered at a rate of 50 mg/hr. Our administration set is calibrated to 15 gtt/ml. Calculate the necessary rate in gtt/min. What are we looking for first? The volume of solution that contains 50 mg © 2013-2015

Dose per Time 500ml x 25,000 = = 100 ml 250mg 50mg 250 250 mg of a drug is dissolved in 500 ml of NS. The drug order states that 250 mg is to be administered at a rate of 50 mg/hr. Our administration set is calibrated to 15 gtt/ml. Calculate the necessary rate in gtt/min. Use a proportion calculation to find the volume SO NOW YOU KNOW THE RATE IN HOURS (100ml/hr) 500ml x 25,000 250mg 50mg 250 = = 100 ml © 2013-2015

Dose per Time X 100 ml 1 hr 15 gtt 1 hr 60 min 1 ml x x = 25 gtt/min Now we just finish as we have been doing 100 ml 1 hr 15 gtt 1 hr 60 min 1 ml x x = 25 gtt/min X © 2013-2015

Class 7 Slides One More Time 10,000 units of Heparin are contained in a bag of 500 ml D5W. The order calls for 1,000 units per hour. Our administration set is calibrated to 15 gtt/ml. What is the resulting flow rate in gtt/min? Give it a try… © 2013-2015 copyright 2013-2015 Mark Greenwald - all rights reserved

The Answer X 500 ml x 500,000 50 ml 1 hr 15 gtt 1 hr 60 min 1 ml First, a proportion to find the volume per hour Then, the usual finale 500 ml x 500,000 10,000u 1,000u 10,000 = = 50 ml 1 hr 60 min 1 ml X 50 ml 1 hr 15 gtt x x = 13 gtt/min © 2013-2015

Questions? © 2013-2015