chemotherapy safety in veterinary medicinevetmed.tamu.edu/ce/.../sites/41/...of-chemotherapy.pdf ·...

Chemotherapy Safety in Veterinary MedicineHow do we protect ourselves and our patients

Dr. Emma Warry BVSc (hons) MS DACVIM (oncology)Associate Professor – Clinical

Texas A & M UniversityCollege of Veterinary Medicine - Veterinary Medical Center

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CLASSIFICATION OF HAZADOUS DRUGS

Genotoxicity; Ability to cause a change or mutation in genetic material (mutagen)

Carcinogenicity; Ability to cause cancer in humans, animal models or both (carcinogen)

Teratogenicity; Ability to cause defects in fetal development or fetal malformation (teratogen)

HD listed by NIOSH include more than just chemotherapy drugs;• Antineoplastic or cytotoxic, biological, antiviral, immunosuppressive agents

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CLASSIFICATION OF HAZADOUS DRUGS

Four groups of individuals impacted by the safe handling and administration of chemotherapy;

1. Health care professional• Doctors, Technicians, Pharmacists, Students,

Veterinary Assistants

2. Patient

3. Care Givers/Family members of Patient

4. Ancillary Staff• Hospital cleaning staff, Laundry personnel

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ADVERSE EFFECTS OF EXPOSURE TO HD

Malignancies;LeukemiaLymphomaBladder CancerLiver Cancer

Reproductive;InfertilityProlonged time to conceptionPremature deliveryLow birth rateAbortion/miscarriagesStillbirthLearning disabilities

Integument/Mucosal;Skin irritationMouth and nasal soresHair thinning/alopecia

Neurological;Headaches, dizziness

Gastrointestinal;Nausea, vomiting, abdominal pain

Respiratory;Dyspnea

Most commonly reported complication of HD exposure in the workplace include;• Acute Symptoms• Reproductive abnormalities• Increase in cancer occurrence

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ROUTES OF EXPOSURE

Absorption through mucus membranes most common route of exposure

Surface Contamination;• Floor in chemotherapy handling and administration areas, door

handles, work station benches, outside of drug vials etc• Studies performed in the late 90s/early 00s used wipe samples to

evaluate contamination• Measured levels of cyclophosphamide, ifosfamide, platinum drugs

(carboplatin/cisplatin)• 65 to 75 % of samples from drug preparation and administration areas

had measurable levels of one or more drug

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ROUTES OF EXPOSURE

Inhalation Exposure;• Low levels of HDs have been detected in air samples from areas were

drugs are handled.• Most of these were performed prior to the standard use of BSC

(Biologic Safety Cabnit)• Less likely route of exposure in people when BSC is used

• Risk for exposure is high when drug preparation happens outside BSC• Crushing or breaking tablets

A combination of these routes likely contribute to human exposure

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USP 800

‘Outlines new quality-of-practice standards for handling HDs that promote the safety of patients and health care personnel

who are exposed daily to HDs.’

1. Compounding Supervisor; The compounding supervisor is responsible for the “oversight of monitoring the facility and maintaining reports of testing/sampling performed in facilities”

2. Facility requirements; HDs must be handled at each stage in a way that promotes patient safety, employee safety, and environmental protection a) Receipt, b) Storage c) Compounding d) Containment

• Designation of HD-specific areas for receipt and unpacking, storage, nonsterile compounding, and sterile compounding.

• Requires multiple spaces designated to specific steps in the HD handling process, most of which must have negative pressure from surrounding areas

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USP 800

3. Receipt; Unpacking of HDs and HD active pharmaceutical ingredients (APIs) from the original container be done in a neutral pressure or negative pressure room • Unpacking is not permitted in sterile compounding areas or positive pressure

areas

4. Compounding; Mandates engineering controls to be used in all stages of the compounding process• Controls can be primary, secondary, or supplemental• Containment segregated compounding area (C-SCA); maintain negative

pressure, and have appropriate air exchange

5. Closed System Transfer Devices (CSTD); • When dosage form allows, CSTDs should be used when compounding HDs; they

are required when administering antineoplastic HDs.

6. Environmental Quality Control; • Wipe sampling for HD surface residue should be performed initially and every 6

months thereafter

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USP 800

7. Personal Protective Equipment (PPE); • Development of SOPs• When compounding sterile and nonsterile HDs - gloves, gowns, and head, hair,

and shoe covers should be worn.• All personnel administering chemotherapy must use 2 pairs of gloves and an

HD permeability-resistant gowns when administering any injectable HD

8. Spill Prevention;• Development of SOPs• Training

9. Medical Surveillance Program; UPS states that a medical surveillance program “comprehensive exposure control program” • Proactive approach to minimize adverse health effects • Early detection of exposure, and allows monitoring of trends

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USP 800

Overall Goal of USP 800;“Is intended to provide a standardized guideline because tight control of each step in the HD life cycle is necessary. Overall, properly educating pharmacy workers and physicians—as well as risk management, legal, and drug delivery personnel—is crucial in providing quality protection to patients and their health care team”

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CHEMOTHERAPY SAFTY FOR THEHEALTH CARE PROFESSIONAL

Hierarchy of Controls;1. Elimination of the hazard2. Engineering Controls

• Reducing exposure at the source by eliminating the hazard or isolating the worker from the hazard eg; equipment designed to contain the hazard or provide appropriate ventilation

• Use of a closed system delivery devise3. Administrative Controls

• Reduced exposure by establishing appropriate and mandatory work procedures eg; restricting access to potentially contaminated areas, reducing the number of employees performing tasks that risk exposure

4. Work Place Controls• Minimize the generation of HD contamination and maximize

containment of inadvertent contamination in the event of a breakage or spill

5. Personal Protective Equipment (PPE)• Added when engineering controls are not able to contain the hazard• Provide barrier protection

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2. Engineering Controls

• Standards are established by the United States Pharmacopenia (USP)• Primary Engineering Control (PEC)

• Describe devices that provide a clean environment for compounding/reconstituting/drawing up HD

• Ventilated Cabinet• Hood• Biological Safety Cabinet

Closed System Drug Transfer Devices (CSTD)• Multiple studies have demonstrated a significant reduction in surface

contamination when CSTD are used• Goal of CSTD are to protect personnel, patients, environment during

compounding and administration

Reduced Surface Contamination SHOULD result in reduced exposure for Health Care Professionals

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3. Administrative Controls

• Establish awareness of the issue and provide clear direction for reducing exposure

• Policies, procedures, scheduling practices, staff education and training, validation of competency and medical surveillance

• SAFE storage, transport, administration and disposal• Required use of PPE• Prohibit eating, drinking, smoking, chewing gum (or tabacco),

applying cosmetics, storing food in areas where HDs are used• All employees who handle HD (compounding, administration, spill

control, waste management) must be appropriately trained• Spill policy and procedure• Medical surveillance• Monitoring of compliance

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4. Work Place Controls

• Critical examination of the existing work practices to identify potential opportunities for HD exposure

• Exiting and reentering the BSC without changing gloves• Exiting and reentering preparation area• Failure to wipe off HD vials• Inadequate cleaning of spills and equipment• Priming IV tubing with drug rather than saline• Inadequate hand washing• Contamination of hands and other surfaces while removing

PPE

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Recommended work practices to decrease surface contamination;• Gather all necessary supplies• Double gloving

• Changing gloves every 30 min or if contamination occurs• Wash hands every time gloves are removed• Place waste generated (outer gloves, vials, packaging etc) in a

sealed plastic bag before removing it from the PEC (Primary Engineering Controls)

• Discard the sealed bag into a HD waste bin• Transport drugs in sealed bags

• Avoid reaching into sealed bags used for transportation without PPE• Protect work surfaces with a plastic backed pad• Discontinue and discard infusion bags and bottles with tubing

intact• Keep lid closed on HD disposal containers• Avoid touching equipment when wearing gloves• Clear countertops and other surfaces after completion of HD

handling

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Personal Protective EquipmentSince widespread use of PPE, exposure of HDs has decreased

• Defined as;• Chemotherapy tested gloves (powder free – powder absorbs

contaminants, be dispersed, increase possibility of surface contamination)

• Gowns made of materials tested for use with chemotherapy• Disposable and made a lint free low permeability fabric

• Respirators• Face shields• Goggles

• Double gloving; inner glove should be worn under the gown sleeve, outer glove placed over the gown cuff

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CHEMOTHERAPY SAFTY FOR THEPATIENT

Chemotherapy safety considerations for the PATIENT is mainly focused around reduction/elimination of ERROR

and ensuring safe administration

Potential for Patient Error;• Patient identification• Chemotherapy order• Drug Preparation• Administration

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1. Patient Identification;

• Know your patient• Diagnosis, stage, chemotherapy protocol being used, drug dose,

weight, previous response/toxicity, use of supportive medications, goal of therapy

• Current status of the patient

• Identification band/collar• Placed by the Owner, and checked to ensure that details are

correct

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2. Ordering Chemotherapy; • NO verbal orders

• If changes are made to original orders they must be made in writing

• Standard chemotherapy calculation and order forms• Patient identification• Body weight (m2)• Chemotherapy drug, dose, rate and route of administration• Dose calculation• Supportive care medication

• Double checking• Responsibility of person double checking to review the chart for;

previous dose, tolerability, patient weight, blood work• NOT JUST DOUBLE CHECKING MATH!

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3. Drug Preparation;• Ensure that the drug ordered is the drug prepared, and

that the total dose calculated is the dose that is drawn up.• Only one dose should be drawn up at a time• Check the appearance and integrity of the drug• There should only be ONE chemotherapy drug in the

hood at a time• Labeled appropriately;

• Drug name, concentration (mg/mL), name of the patient• Hazardous drug• If not being administered immediately; date and time of

preparation, expiration date.

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4. Chemotherapy Administration• Verify patient identification

• Double check that the drug that has been prepared is for the patient that is scheduled to be treated

• Extravasation management protocol

• Spill protocol and kit

• Toxicities should be recorded as defined by VCOG

• Administration with a closed system delivery devise• Discussed in detail during the next lecture

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CHEMOTHERAPY SAFTY FOR THECAREGIVER AND FAMILY

Body fluids and waste that should be considered contaminated for 48 to 72 hours;

Urine, stool, vomit, blood, sweat, semen, vaginal fluids

Precautions suggested by Johns Hopkins;• Wear gloves to touch the drug, body wastes or fluid, or

contaminated items• Only use gloves ONCE• Keep medication away from children and pets• Do not store chemotherapy in the kitchen• DO NOT crush tablets• DO NOT throw drug in the bin or flush down the loo• DO NOT eat, drink, chew gum or smoke when administering

chemotherapy• Double bag contaminated items

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• What do I do if I splash myself with a HD or body waste?• Wash well with soap and water• If drug or body waste splashes into eye, rinse with running water

for 10 to 15 minutes, contact health care professional.

• Handling Rubbish or Washing that has come in contact with chemotherapy or body waste within 48 hours after treatment;• Wear gloves• Contaminated rubbish should be double bagged in leak proof

bags• Wash contaminated washing ASAP• Wash separately with regular washing liquid and warm or hot

water• (2 wash cycles)

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• Direct contact with patients receiving chemotherapy;• Hugging and kissing is safe• Patient can visit, sit with, hug and kiss children• Patient can be around pregnant women, but they should not

clean up body fluids following treatment

• Handling waste;• Remove any feces ASAP, double bag and place into the rubbish• Clean litter boxes daily, double bag and place into the rubbish• For cats; 72 hours after chemotherapy administration completely

change the liter box and disinfect by washing in warm soapy water

• Pregnant Women;• Avoid contact with drugs• Avoid contact with waste for at least 72 hours• Talk to physician

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CHEMOTHERAPY SAFTY FOR THEANCILLARY STAFF AND TECHNICIANS

Cleaning of potentially contaminated surfaces; Chemotherapy hood, chemotherapy administration room, runs and cages

• Safety glasses, gown and gloves• As much of the waste as possible should be cleaned up with disposable

paper towels/absorbant agents• Double bag waste and place into HD disposal unit

• Face shields should be used if splashing is possible• Wash hands with warm water and soap after removing gloves

Deactivation of HD should be the goal• Use of alcohol for disinfecting does not deactivate the HD

• May result in spreading contamination further• Sodium Hypochlorite solution is an effective deactivation agent

• 2% sodium hypochlorite solution with detergent• Followed by 1 % sodium thiosulfate (neutralizing solution)• Water• Alcohol

Chemotherapy Safety in Veterinary MedicineManagement of Chemotherapy Accidents

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PREVENTION OF CHEMOTHERAPY SPILLS

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PREVENTION OF CHEMOTHERAPY SPILLS

Spill kit should be located in all areas where chemotherapy is prepared and administered

Contents of spill kit;• Disposable chemotherapy resistant gowns• Chemotherapy resistant shoe covers• Chemotherapy gloves• Chemical splash goggles• Respirator masks• Disposable dustpan and plastic scraper• Puncture proof container for glass• Heavy duty waste sealable disposal bags• Absorbent pads

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MANAGEMENT OF SMALL SPILLS< 500 mLs

• Evacuate patients and personnel not involved with cleanup

• Signs should be placed on the entrances to the area where the spill has occurred. • Only the ‘spill team’ should be present in the area during the

cleanup.

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• All individuals involved with the clean up MUST put on PPE• Double gloves, gown, face shield• Respirator must be worn

• Before starting the clean up – PLAN• The clean up should begin in the least contaminated area and

finish in the most contaminated area

• Contain the spill using absorbent spill control pads or towels

• For liquids; use the absorbent pads to soak up as much as possible• Pads will absorb liquid and turn it to gel

• For powders; dampen the absorbent pad with water first

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• Place pads or towels into the waste disposal bag• Avoid contamination of the mouth of the bag

• Clean the spill area THREE times• Use absorbent pads for each step of the process • Use inward circular motion to clean• Spray the cleaning supplies onto the absorbent pad DO NOT spray

directly onto the spill area• 2% sodium hypochlorite solution with detergent• Followed by 1 % sodium thiosulfate (neutralizing solution)• Water

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• Place all equipment used to clean up the spill into a sealed bag, and then into a second sealed bag before disposing into an appropriate HD container.

• Allow the area to air dry for 15 minutes

• Carefully remove PPE• Dispose of in appropriate container

• Wash hands with soap and water

• Once the spill is initially cleaned by the ‘spill team’, it should be cleaned again by housekeeping.

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MANAGEMENT OF LARGE SPILLS> 500 mLs

• Barricade off the affected area immediately

• Spill team should put on PPE (as described for small spills)

• Contain the spill by placing absorbent pads over the contaminated area

• DO NOT attempt to clean the area

• Contact Facilities Operations Center • Clean up, removal and disposal of contaminated area and items

should be coordinated by Environmental Health and Safety

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EXTRAVASATION

Reported prevalence of chemotherapy extravasation through a peripheral IV catheter 0.1 to 6% and 0.26 to 4.7% when administered through a central venous access device.

Classification of IV administered drugs;Vesicant; Drugs that can result in tissue necrosis

Exfoliates; Drugs that cause inflammation and shedding of skin, but DO NOT cause underlying tissue necrosis

Irritants; Drugs that cause inflammation, pain or irritation at the site of extravasation but without blister formation

Inflammitants; Drugs that cause moderate inflammation, painless erythemia and elevation (flare) at the extravasation site

Neutrals; Drugs that do not cause inflammation or tissue damage when extravasation occurs.

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EXTRAVASATION

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EXTRAVASATIONRISK FACTORS

Chemotherapy agent used;• Vesicant properties of the drug• Concentration• Volume and duration of

extravasation

Patient Factors;• Small +/- fragile veins• Lymphedema• Obesity• Impaired level of consciousness• Previous multiple venipuncture

Iatrogenic Factors;• Lack of training• Poor catheter size choice• Poor location selection• Lack of time• Insecure catheter fixing• Prolonged infusions

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EXTRAVASATIONEXTENT OF TISSUE DAMAGE

• Ph

• Osmolality

• Vasoconstrictivecapability• Vasoconstriction of

capillary smooth muscle -> reduced blood flow

• Duration it can stay in the tissue• Drugs that bind to DNA

are retained in the tissue -> cycle of direct cell injury

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EXTRAVASATIONPREVENTION

Best to be preemptive rather than reactive!

• Medical team training and continuing education

• Appropriate vascular access• Assess location and fragility of vein• Age• Presence of diabetes• Steroid use• History of recent venipuncture• Presence of ecchymosis• Axillary lymph node dissection• Lymphedema• Previous vascular accident

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EXTRAVASATIONPREVENTION

• Appropriate catheter size• Smallest catheter possible in the largest vein available

• Remain patent to blood flow• Remain in place

• Butterfly catheter should NEVER be used for a vesicant

• (Patient Education)• Should be instructed to report any discomfort, pain, swelling

or redness at the infusion site.

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EXTRAVASATIONINITIAL MANAGMENT

• If there is concern that an extravasation event may have occurred STOP the treatment immediately and notify the clinician on the clinic floor.

• DO NOT flush the catheter, try to aspirate the drug; • Syringe attached to the catheter• Percutaneous needle aspiration• Liposuction• Squeeze maneuver• Surgical fenestration and irrigation

• Catheter can now be removed

• Thermal application (hot or cold) should be applied to the area• Should be performed q 4 to 6 hours for 20 min for 48 hours

• Elevation of the affected limb

• Take a photo and outline affected area with skin marker

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EXTRAVASATIONDOXORUBICIN

• COLD compress should be used

Dexrazoxone; FDA approved for treatment of anthrocyclineextravasation• Dose is 10 x the dose of doxorubicin (300 mg/m2) given within 4 to

6 hours of the extravasation event, and then again at 24 and 48 hours • In humans; 1000 mg/m2 IV within 4 to 6 hours, then again at 24 hours,

and 500 mg/m2 IV at 48 hours• Vial contains 500 mg (can not be kept once reconstituted)

• Two large multicenter prospective trials;• Overall efficacy reported to be 98% (no surgical intervention required)

• Reported side effects; transient elevation in liver values, neutropenia

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EXTRAVASATIONVINCA ALKALOIDS

• HOT compress• Vasodilation and absorption of drug from the tissues

• Hyaluronidase; degrades hyaluronic acid in tissues promoting diffusion• Given as multiple subcutaneous injections around the site of the

extravasation• 100-150 IU given as 5 x 0.2mL syringes

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EXTRAVASATIONDMSO

• Doxorubicin, epirubicin, mitoxantrone, ifosphamide, mitomycin C, carboplatin

• Organosulfar solvent with free radical scavenging properties• Applied topically to promote absorption• Should be applied to an area twice the size of the extravasation

area

• General recommendation is for DMSO 99% applied q 12 hours for 14 days

• Mild local burning and breath odor

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QUESTIONS

Margaret River, Western Australia, Australia

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