CDR and TPN

Question 1

When may workers be exposed to cytotoxic drugs and related waste?

Answer 1

Workers may be exposed during drug preparation, drug administration, patient care activities, spill management, waste disposal, when handling patient body substances and when handling cytotoxic contaminated laundry

Question 2

How can exposure to cytotoxic drugs occur?

Answer 2

• Inhalation
• Ingestion
• Dermal absorption
• Mucosal absorption
• Percutaneous injury

Question 3

What are the effects of exposure to cytotoxic drugs?

Answer 3

• Contact dermatitis, local toxic or allergic reaction—may be as a result of direct contact with skin or mucous membranes
• Cytogenic abnormalities and mutagenic activity related to biological uptake by exposed workers
• Alterations to normal blood cell counts
• Excretion of the drugs or metabolites in the urine of exposed workers
• Abdominal pain, hair loss, nasal sores and vomiting
• Liver damage
• Fertility changes
• Foetal loss and malformations of the offspring of exposed pregnant women

Question 4

What is the training required for staff preparing cytotoxics?

*

Answer 4

• Procedures required on receipt of a request for a cytotoxic agent „
• How to fill out a worksheet and assemble the required materials for cytotoxic reconstitution. „
• Changing procedures required prior to working in a clean room environment „
• General working of laminar airflow cabinets and isolators „
• Cleaning and disposal procedures prior to and following aseptic procedures
• Storage and transportation of cytotoxics „
• Background information on commonly used cytotoxics „
• Local policies and procedures adopted by the hospital trust or health authority

Question 5

What is the procedure for using a cytotoxic drug suite?

Answer 5

• Before entering the anteroom, remove all jewellery (e.g. bracelets, earrings, rings and watches) „
• Enter anteroom, put on overshoes, mask, protective eyewear and hood or head cover, ensuring that hair is enclosed „
• Wash hands and forearms in sink in anteroom with antimicrobial soap solution, scrub for two minutes „
• Rinse hands with water and dry hands with a sterile non-linting wipe or under a hand drier „
• Put on sterile coverall, two pairs of sterile powder-free latex gloves or one pair of purpose manufactured gloves, and enter preparation area „
• While in clean room, change gloves as necessary when torn, punctured, contaminated, as per manufacturers instructions or as determined by a risk assessment „
• At the completion of a work session in the CDSC, remove both pairs of gloves prior to exiting the clean room „
• Remove other PPE in anteroom

Question 6

What type of cytotoxic drug safety cabinet is used? How does it offer environmental protection and personnel protection?

Answer 6

Class II biological safety cabinet –> protects operator, product and environment.

Environmental protection from volatile cytotoxic compounds

• activated charcoal exhaust filter
• post-use overrun switch for purging –> runs for 5-10 minutes to ensure cytotoxic drugs will leave the chamber

Personnel protection

• Downstream HEPA filter, the product will receive first air
• Disposal mechanism for contaminated filter

Question 7

Can isolators be used for cytotoxic drug reconstitution? What does it protect?

> Isolators are used in hospital pharmacy departments as an alternative to clean rooms for the small scale aseptic processing of sterile products

Answer 7

Yes it can be used for cytotoxic drug reconstitution

• protect operator
• protect product

Question 8

What are 0.2 micron hydrophobic filter venting needles used for?

Answer 8

For IV bag, the contaminated air of the cytotoxic drug can escape, the hydrophobic filter stops it before the air can leave the bag

Question 9

Provide TWO examples of a needle-free closed system delivery device used for cytotoxic drugs.

Answer 9

Question 10

What are the sources of cytotoxic spills? What may spills involve?

Answer 10

• cytotoxic drugs in all forms (e.g. liquid, tablets or creams) „
• drugs spilt or leaking during preparation, storage and transport of packaged drugs „
• cytotoxic drugs spilt during administration „
• transport of patients with cytotoxic drug therapy in situ „
• body substances contaminated with cytotoxic drugs „
• cytotoxic contaminated laundry „
• cytotoxic waste in all forms.

Question 11

How to deal with spillage?

Answer 11

• Spills of cytotoxic drugs and related waste must be dealt with immediately as they present a high risk of exposure to workers
• Spills may occur in all areas where cytotoxic drugs and related waste are handled, stored, transported and disposed.
• People in the immediate vicinity of a cytotoxic spill should be alerted immediately that a spill has occurred and requested to stay clear.
• Ancillary workers should assist only in containment of a spill while alerting trained worke

Question 12

Explain the process of what to do if a spill occurs outside the cytotoxic drug safety cabinet in a FRED facility (Flow-Regulated Environmental Design)?

ps if the spill is inside the CDSC, then can clean it.

Answer 12

• Press the button ‘supply fan stop button for spill solution’ –> it will reduce pressure in the room containing CDSC
• Anteroom will have higher pressure –> flow into the room containing CDSC

Question 13

What is the strategy for cytotoxic waste management? What are the key elements?

Answer 13

• Cytotoxic contaminated waste is a hazard, and workers must be protected from the risk of exposure at all steps in the waste management process, from generation to destruction
• A waste management strategy should include the key elements of identification, segregation and containment of waste, transport, storage and disposal of waste, and personal protective equipment
• The strategy should define safe systems of work, such as standard operating procedures and spill management, and include training and information for all workers handling and transporting contaminated waste

Question 14

What are the examples of cytotoxic waste?

Answer 14

• Cytotoxic pharmaceuticals past their recommended shelf life, unused or remaining drugs in all forms, contaminated stock, and cytotoxic drugs returned from patients „
• Contaminated waste from preparation processes „
• Sharps and syringes, ampoules and vials „
• Intravenous infusion sets and containers „
• Empty cytotoxic drug bottles „
• Cotton wool from bottles containing cytotoxic drug
• Used HEPA filters and other disposable contaminated equipment
• Contaminated PPE (e.g. gloves, disposable gowns, shoe covers, RPE)
• Swabs, cloths, mats and other materials used to clean cytotoxic contaminated equipment or to contain spills
• Contaminated body substance receptacles (e.g. disposable vomit bags)
• Dressings, bandages, nappies, incontinence aids and ostomy bags
• Heavily soiled and contaminated bedding that is unable to be cleaned

Question 15

What is cytotoxic contaminated laundry defined as? What are some examples?

Answer 15

• Cytotoxic contaminated laundry is defined as linen or clothing which has been contaminated with cytotoxic drugs or contaminated body substances, including urine, faeces, vomitus, bile, and fluids drained from body cavities
• Contaminated laundry may include bed linen, towels, curtains, gowns, coveralls, washable PPE, and any other washable item
• Only linen that is obviously wet with perspiration be treated as cytotoxic contaminated laundry. Otherwise the linen can be treated as general laundry

Question 16

SA questions CDR

A) Provide practical advice on how to prevent or minimise occupational exposure to cytotoxic drugs during reconstitution

B) Discuss how the cytotoxic waste should be managed

Question 17

When may TPN be required? What is added to a sterile infusion bag? How is it administered to the patient?

Answer 17

For patients requiring long-term nutrition, total parenteral nutrition (TPN) may be required

• The components of a TPN formulation are added to a sterile infusion bag and administered to the patient via a catheter, via a peripheral vein or a central vein

Question 18

What are the indications for TPN? Provide FIVE answers

Answer 18

• Gastrointestinal diseases „
• Major trauma „
• Major abdominal surgery „
• Malignancy of the small bowel „
• Radiation enteritis

Question 19

What are the components of a TPN formulation? Provide SIX answers.

Answer 19

• Water „
• Protein source (AA)„
• Energy source – carbohydrate and possibly fat (dextrose, glucose) „
• Electrolytes „
• Trace elements „
• Vitamins and minerals

Question 20

Where is the site of infusion for TPNs?

Answer 20

​TPNs are administered into a large vein in the neck, the chest, the groin, or the abdomen, generally through a peripherally inserted central catheter (PICC)

Question 21

What is it known as when one or more sterile products are added to an IV fluid for administration? How to maintain the characteristics of sterile products, namely, sterility and freedom from particulate matter and pyrogens?

Answer 21

IV admixture

Maintain characteristics of sterile products –> imperative that they be manipulated in a suitable environment by use of aseptic techniques

Question 22

What is the SOP of IV admixtures?

Answer 22

• Review request „
• Plan procedure carefully „
• Assemble (collect) all materials into a basket (1 per admixture)
• Label – prepare final label for completed product „
• Preparation – AT with attention to mixing „
• Inspect „
• Label „
• Check „
• Log book entry

Question 23

How is the compounding of TPN formulations achieved?

Answer 23

• Review request by Pharmacist
• Aseptic conditions (ISO 5 environment) using a laminar airflow cabinet within a clean facilities.
• Rechecking the calculations by pharmacist before compounding.
• Additive sequence in compounding
• Inspection of final product

> protect product, don’t need to protect operator, therefore LAF cabinet is sufficient

Question 24

What factors affect the physicochemical compatibility and stability of TPN admixtures?

Answer 24

Infusion container, administration sets, filters, and concentrations of “reactive” but essential additives

Stability important: aqeuous and oily component –> fat is one of the ingredients –> end up as an emulsion (not stable)

Question 25

What are infusion containers made from?

Answer 25

Polyvinyl chloride (PVC) bags constructed with the plasticiser, di(2-ethylhexyl) phthalate (DEHP), have largely been replaced with bags made with ethylene vinyl acetate (EVA) or other less reactive materials

• DEHP, a carcinogen in laboratory animals, has been found to leach from the PVC containers under certain “lipophilic” conditions (eg, infusion of lipid emulsions and blood products) and has also been associated with facilitating the losses of certain vitamins and the destabilization of lipid emulsions

Question 26

What are the THREE types of TPN bags? What do they consist of?

Answer 26

1. dual-chamber bags that allow certain unstable TPN admixture components (eg, lipid emulsions) to be mixed just before use
2. multichamber bags, to be mixed but that are designed to minimize the compounding tasks by use of standardized nutrient compositions
3. multilayered bags designed to protect labile components from certain degradation processes (eg, oxidation) that occur in the plastic bags

Question 27

Why may formation of rigid, crystalline co-precipiates occur in TPN?

Answer 27

1. Poor compounding techniques
2. Inadequate knowledge of admixture components (select right type of electrolytes if reaction occurs)
3. Assignment of excessively long beyond-use date

Question 28

What are the THREE different acid dissociation constants for phosphate (calcium phosphate)?

Answer 28

Trivalent anion

1. pKa1 2.12 (the monobasic or “M” form) –> 2g/100mL
2. pKa2 7.21 (the dibasic or “D” form); and –> 0.02g/100mL
3. pKa3 12.67 (the tribasic “T” form) –> 0.002g/100mL –> least soluble

• producing monobasic calcium phosphate, dibasic calcium phosphate, and tribasic calcium phosphate salts (in decreasing aqueous solubility)

Question 29

Which form of calcium phosphate may result in precipitation and death for patients?

Answer 29

The dibasic form was shown in postmortem examinations to be the culprit

• Although tribasic calcium phosphate is even less soluble than the dibasic form, it requires a final pH of 11 or higher to be present in significant quantities, a condition that clearly falls outside the range of any TPN admixtures used in the clinical setting. dibasic calcium phosphate (CaHPO4)

Question 30

Does the danger of calcium phosphate precipitiation decrease or increase with decreasing pH?

Answer 30

• Decrease, as pH drops(more acidic), the danger of calcium phosphate precipitation REDUCES

Question 31

How should the order of compounding occur for calcium and phosphate for TPN?

Answer 31

Generally, phosphate should be added first, and calcium should be added near the end of the compounding sequence to take advantage of the maximum volume of the parenteral nutrition formulation

Question 32

Why can the coalescence of IV Lipid Emulsions (IVLEs) be dangerous? Why does instability occur? Where can IVLEs get trapped in the body?

Answer 32

• All IVLEs are thermodynamically unstable and therefore have short shelf lives
• Instability of IVLEs is manifested by the growth of submicron droplets (ie, 450 nm or 0.45 Pm) into large fat globules (5 Pm), a process known as coalescence
• The major concern for unstable IVLEs is the trapping of large-size globules in the capillaries of the lung

Question 33

What temperatures may have potentially significant consequences with respect to coprecipitation reactions and inappropriate beyond-use dates?

Answer 33

The inappropriate assignment of beyond-use dates for TPN, especially at room temperatures, may have potentially significant consequences with respect to coprecipitation reactions

Question 34

For inappropriate beyond-use dates;

A) What happens when vitamins are added for periods exceeding 24 hours such as asorbic acid

B) What happens when Vitamin A permeates the infusion container

Answer 34

A)

• Can degrade to its terminal degradation product oxalic acid, which then can react with free calcium ions, forming the insoluble product calcium oxalate

B)

• Causing clinically significant deficiencies

Question 35

Can medicines be added to a TPN bag?

Answer 35

Due to the complex nature of PN and potential for physicochemical interactions with drug-nutrient combinations, admixture of medications with PN is not advised

Question 36

Discuss potential issues when formulating and preparing TPN

Answer 36

Stability, compatibility and need to consider what method to use when compounding TPN and ensure it’s safe and effective to give to the patient.