There are many instances in which the cancer patient and its nursing staff may be exposed to toxins and/or require barriers.
Although the beneficial effects of chemotherapy against the cancer generally outweigh the potential side effects in skilled hands, almost all anticancer drugs have side effects. Toxicity is the most significant treatment-limiting factor in cytotoxic drug use.
In addition, multiple studies have shown multiple potential dangers to staff handling cytotoxic drugs, including increased chromosomal alterations, hepatotoxicity and abnormal reproductive outcomes to be associated with exposure to various chemotherapeutic drugs. For these reasons, it is important that written safety protocols be established and followed in the any veterinary clinic administering chemotherapy. There must also be written instructions to pet owners for at-home administration, handling of drugs and for dealing with drug-contaminated excreta. Veterinary nurses have a vital role to play in the care of chemotherapy patients, and in maintaining the health and safety of both patient and staff. Careful administration of cytotoxics and subsequent patient monitoring should avoid many potential complications of using these drugs. If guidelines are followed, the safe use of cyto-toxic drugs should be possible for the majority of veterinary practices, with minimal risk to all staff involved. Practices and personnel should not become complacent with cytotoxic drug use and regular risk assessment, and updates to Control of Substances Hazardous to Health (COSHH) local rules.
Cancer is a major cause of death in older dogs and cats (Withrow, 2007). Despite this, there are a number of treatments available, including chemotherapy, to offer pets a good quality of life. Advances in veterinary oncology have increased owner awareness and the readiness of many veterinary practitioners to treat cancer patients, meaning that greater numbers of pets with cancer are being managed long term.
While the use of chemotherapy is a mainstay of treatment of patients with cancer, due to their cytotoxic nature, they pose a risk for patients, staff members and to pet owners, therefore care is required when handling and administering them, and in the day-to-day care of patients that have received these drugs (Withrow, 2007).
Chemotherapy
Chemotherapy, being a systemic treatment, is most commonly used to treat diffuse cancers, such as lymphoma, leukaemia (Chun et al, 2007). It may be used in a variety of ways, e.g. as an adjunct to surgery and/or radiotherapy and/or other modalities, in the treatment of solid tumours, e.g. sarcomas, carcinomas, to control microscopic/metastatic disease, with curative or palliative intent — the goal of therapy being maintenance of optimum quality of life (Chun et al, 2007). In human cancer therapy, chemotherapy is often aggressive, with severe debilitating side effects, including immune suppression, vomiting and diarrhoea, weight loss and total hair loss. Therefore, in the author's experience, many owners' first reaction to chemotherapy is, ‘I don't want to put my pet through that’. In veterinary oncology, quality of life is paramount and chemotherapy protocols are used that are less aggressive than those used for humans —in general the doses used are one third of those used in human medicine, with lesser intensity (i.e. weekly treatments, rather than daily) (Chun et al, 2007). The caveat for this emphasis on quality of life is often limited longevity. Given all of this, adequate time should be spent with owners to counsel them on what to expect during their pet's chemotherapy, the anticipated chances and duration of remission, potential side effects and estimated cost of treatment, so that an informed decision can be made.
Basic concepts of chemotherapy
The goal of chemotherapy is to inhibit the growth of cancer cells with minimum effect on normal cells. Most chemotherapeutic agents either bind directly to genetic material in the cell nucleus or affect a cell's ability to synthesise protein. This may also damage growth and reproduction of the patient's normal cells, as both healthy cells and cancer cells go through the same cell division cycle (Argyle et al, 2008).
Treatment dose and schedule depends on the type of cancer and chemotherapy method (Chun et al, 2007). In some cases periodic chemotherapy will be necessary to control the cancer for the rest of the pet's life (Argyle et al, 2008). Combining cytotoxic drugs is an effective strategy in chemotherapy, designed to target different parts of the cell cycle to increase the proportion of total tumour cells that are killed at any one treatment time. When drugs are used in combination, they often enhance the activities of each other in both a synergistic and/or additive way. Drugs are also combined to minimise their dose-limiting toxicities and help reduce the development of tumour resistance — cells resistant to one drug may be sensitive to another within that regimen (Argyle et al, 2008).
There are many instances in which the cancer patient and its nursing staff may be exposed to toxins and/or require barriers.
Patient-related toxins
Although in skilled hands, the beneficial effects of chemotherapy against cancer generally outweigh the potential side effects, almost all anti cancer drugs have side effects. Toxicity is the most significant treatment-limiting factor in cytotoxic drug use. These drugs are not selective in their effect on growing or dividing cells; therefore they commonly affect body systems which include those with rapidly dividing cells, e.g. the gastrointestine tract, bone marrow, skin/haircoat (Bexfield, 2006).
Toxicities may manifest at any time during chemotherapy treatment — with some having immediate effect, and others being acute or per-acute. Many are transient and are managed symptomatically; while others are irreversible. Some toxicities are related to the effect of the drug on the patient's physiology; others are due to bacterial toxicity which may result during myelosuppression.
Common adverse effects and their management
Although serious adverse effects can occur following chemotherapy, less than 5% of patients require hospitalisation (Chun et al, 2007). Potential side effects of cytotoxic drugs are listed below (Argyle et al, 2008):
The most common side effect reported by owners is that their pet has an ‘off day’, which usually resolves spontaneously after a short time. Owners should be advised to keep water available at all times and to offer palatable food from time to time. They should contact the clinic if they are concerned about their pet, including: total refusal of food and/or water, and/or repeated vomiting/diarrhoea, for 24 hours or more; if there is blood in the faeces, urine or vomit; noticeably increased thirst/ urination; changes in behaviour, lethargy or manifestation of pain.
Gastrointestinal signs, e.g. anorexia, vomiting and/or diarrhoea — these are usually not severe or prolonged, but patients may experience some form of stomach or intestinal discomfort 2 to 7 days after chemotherapy. Analgesic or antispas-modic medication may be prescribed to prevent or treat this, and for administration at home. In the case of vomiting or nausea anti-emetics may be prescribed. Palatable food may be offered, as long as the patient is otherwise well — small meals should be offered frequently, instead of one large meal, and what is not eaten should be removed after 10 minutes. In the case of anorexia, owners should be provided with clear practical advice on encouraging patients to eat. Appetite stimulants may be tried, but are not usually successful long term and may have adverse effects. If patients experience diarrhoea, but are bright and happy, symptomatic treatment can be given and a normal routine followed. However, if it is persistent, the patient is dull, there is melaena, fresh blood or concurrent pain/nausea, the patient should be re-examined. If side effects are prolonged or severe, hospitalisation may be required.
Alopecia — when human chemotherapy patients lose their hair, it can be devastating. Pets rarely have dramatic hair loss, but many owners worry about it. Some do undergo changes in coat condition, e.g. development of a soft, fluffy ‘puppy-coat’. This is because some of the guard hairs are lost. Certain breeds of dogs, such as Poodles, Old English Sheepdogs and other breeds that have continuously growing hair coats, may have a greater degree of hair loss and cats often lose their whiskers. Re-growth of hair over clipped areas may be slower during treatment, but coat condition normally is restored at the end of chemotherapy treatment.
Myelosuppression — many chemotherapeutic agents impair the bone marrow's ability to produce cells (Argyle et al, 2008). As a result, neutropenia may occur 7 to 10 days after chemotherapy. Neutro-penia, alone, is not dangerous to the patient, but the inability to fight infection is. If thrombocyto-penic, patients may lose normal clotting function and bruising/bleeding may become evident. If significant myelosuppression occurs, chemotherapy may need to be delayed. If the effects are severe, antibiotics may be prescribed to reduce the patient's risk of infection. In this case the owner should be advised to keep the pet in its own environment as far as possible and avoid possible sources of infection. To monitor this possible side effect, a full haematology screen should be performed immediately before, and at the likely nadir (the point at which the cell count is lowest) — usually 7 to 10 days after each dose of chemotherapy.
Tissue damage — many cytotoxic drugs are vesicant (may cause skin irritation) and, if given perivascularly, severe tissue reactions can result, potentially leading to non-healing wounds and potential limb amputations (Chun et al, 2007). Therefore, chemotherapy agents must be administered with the utmost care and only by trained staff. Always ensure adequate restraint of patients during chemotherapy administration. An aseptically prepared ‘clean-stick’ intravenous catheter should be placed specifically for chemotherapy administration (Figure 1). This should be checked for patency and flushed with copious amounts of sterile 0.9% saline immediately before use, ensuring blood is flowing back through the catheter (but without applying excessive suction), the area over the catheter should be palpated and observed for evidence of patient discomfort/resentment or ‘blowing’ of the vein. If there is any doubt the drug should not be given and a new catheter should be placed in a different vein. The veterinary nurse should always be able to visualise the site during chemotherapy administration. If there are signs of leakage/extravasation from the catheter, the animal shows signs of discomfort or if irritation of the injection site develops, administration should be stopped immediately. Apply gentle suction through the catheter to withdraw the drug. When as much of the drug as possible has been aspirated, the catheter should be removed. In the case of vinca-alkaloids, application of hot packs may help; for doxorubicin extravasation, cold packs may be applied. In all cases, the area should be covered with a light sterile dressing and standard wound management protocols instigated. Adequate analgesia is essential as this is a painful condition. Owners should be informed that a problem has occurred, as it will become apparent to them and require careful monitoring. Commonly used vesicant cytotoxic drugs include vincristine, vinblastine and doxorubicin.
Allergic reactions — allergic reaction to chemo-therapeutic agents is uncommon (Chun et al, 2007). These reactions are generally acute and should be treated as any other allergic anaphylaxis. Doxorubicin and L-asparaginase are cited as being the most common drugs to cause anaphylaxis. Signs include vomiting, tachycardia, tachypnoea, red mucous membranes, restlessness and/or urticaria. At risk patients should be closely monitored and ABC-first aid employed if a problem develops. Dexamethasone (corticosteroid) and chlorphen-amine (anti-histamine) may be used in conjunction with standard cerebrocardiopulmonary resuscitation practices.
Cardiotoxicity — some chemotherapeutic agents, specifically doxorubicin, can irreversibly damage the heart muscle. Owners should be warned of this and at-risk patients screened in advance, and the risk versus the benefit should be discussed with the owner.
Sterile haemorrhagic cystitis — this condition may occur with cyclophosphamide use. It is caused by excretion of irritant metabolites in the urine (Lana, 2003). Patients receiving this drug should have frequent urine sampling to monitor for blood. Aforementioned barrier precautions apply when dealing with the excreta of any patient that has had any cytotoxic drug. While administering cyclophospha-mide, hydration should be maintained and diuresis encouraged to prevent this condition.
Tumour lysis syndrome — treating tumours with chemotherapy, radiotherapy or even steroids can cause rapid, massive cell death. This is not common, but may be seen when haemopoietic/lym-phoproliferative tumours are treated, particularly when there is a large tumour burden (Argyle et al, 2008). Breakdown products of dying cancer cells cause release of intracellular contents, such as potassium and phosphate. Metabolic imbalances and toxicities may ensue, e.g. hyperuricaemia, hyper-kalaemia, hyperphosphataemia and (secondary) hypocalcaemia, with resultant acute renal failure (Chun et al, 2007). This is known as acute tumour lysis syndrome and is a potentially fatal complication of treatment. Close monitoring of patients with significant tumour burden is required, especially if the tumour is expected to respond rapidly to treatment, e.g. lymphoma patients receiving their first chemotherapy dose.
In 1979, the British journal, Lancet, first reported evidence that humans handling anti-neoplastic agents may be at risk (Falck et al, 1979). Researchers reported mutagenic activity in the urine of nurses working in a human oncology unit and proposed that the cause was related to exposure to anti-neoplastic agents. Much subsequent research has shown multiple potential dangers to staff handling cytotoxic drugs, including increased chromosomal alterations, hepatotoxicity and abnormal reproductive outcomes to be associated with exposure to various chemotherapeutic drugs. For these reasons, it is important that written safety protocols be established and followed in any veterinary clinic administering chemotherapy. There must also be written instructions to pet owners for at-home administration, handling of drugs and for dealing with drug-contaminated excreta, and laundering of contaminated bedding.
Potential hazards in veterinary practice
While cytotoxic drugs can be life saving for patients with cancer, they not only pose a risk for patients, but also to staff members who handle and administer them, as well as to pet owners. They are cytotoxic and potentially carcinogenic (cancer causing), mutagenic (damaging to DNA) and teratogenic (damaging to unborn foetuses) (Bexfield, 2006). They are irritant to the skin and mucous membranes (Bexfield, 2006). It is important that written safety protocols are established and followed in any veterinary clinic administering chemotherapy and that cytotoxic drug products are handled with extreme caution and awareness of their potential danger. Staff under 16 years of age, those who are pregnant, or trying to become so, or who have compromised immune function should not be involved in chemotherapy — including administration, clearing up, care of patients, laundering contaminated bedding.
Exposure to cytotoxic drugs can occur by:
Skin exposure — direct or indirect contact
Ingestion
Aerosolisation
Accidental inoculation
Exposure to metabolites — present in patients' excreta for 48–72 hours after administration.
Rules and regulations
Guidelines exist on the safe use of cytotoxics in the workplace. These are defined by the Control of Substances Hazardous to Health Regulations 2002 (COSHH) (2002). Drugs considered carcinogenic are subject to Appendix 1 of the COSHH Approved Code of Practice (ACOP). Further information can be found at www.hse.gov.uk/coshh. All staff involved in the use of these drugs should have read and understood these guidelines. Veterinary staff working outside the UK must consult the relevant legislation and codes of practice for the safe handling of cytotoxic drugs in their specific region.
Safe preparation and administration of chemotherapy drugs
Before the administration of chemotherapy, both the nurse and the veterinary surgeon should review the patient's file/chemotherapy protocol. Time should be taken to double check dose calculations of the cytotoxic to be given. It is advisable to use flow sheets to track a patient through:
Each treatment — Blood sample □, Results back? □, OK to proceed? □, Catheter □, Placed by? □ Which vein? □ Drug to be given □ Dose □, Checked twice.
The overall course of chemotherapy — this consolidates the pertinent information from each visit into a single chart for easy reference.
Key points
While cytotoxic drugs can be life saving for patients with cancer, they pose a risk for patients, staff members and pet owners.
Careful administration of cytotoxic drugs and subsequent patient monitoring should avoid many potential complications of using these drugs.
Veterinary nurses have a vital role to play in the care of chemotherapy patients and in maintaining the health and safety of all involved.
If guidelines are followed, the safe use of cytotoxic drugs should be possible, with minimal risk to all those involved.
Hospitalised patients require specialist care and should only be dealt with by trained staff.
Clear instructions to pet owners are vital for at-home administration and handling of drugs and contaminated excreta.
Keep cytotoxic substances locked in a designated cupboard or refrigerator and clearly labelled. No foodstuff should be stored in the vicinity.
There should be no eating and drinking and no through-traffic in the chemotherapy preparation/ administration area.
Keep door closed and display warning sign to ensure no disturbances — it is important that staff or patients are not disturbed.
Protective clothing must be worn when handling, preparing or administering chemotherapy drugs by the person handling the drug and any assistants (Figure 2). This consists of a minimum of two pairs of latex gloves, full-length long-sleeved impermeable gown, mask and goggles. Clients or untrained staff should not assist.
Drugs should ideally be prepared in a fume hood (Figure 3). If not available, use of a vented dispensing pins or closed systems, such as Phaseal® (Figure 4) is recommended.
Drugs should always be prepared on a disposable, plastic-backed absorbent pad.
Use screw-on luer-lock syringes and ‘T’-connectors /giving sets.
When reconstituting powder, tap the vial gently to loosen impactions — this will prevent the need for vigorous shaking of the drug mixture.
Prevention of aerosolisation of drugs is vital. Do not allow pressure to build up in the vials — never push air/drug back into the vial (or into the environment) and wrap a swab around the junction of needle/vial (Figure 5).
Do not re-cap needles — this creates a risk of self inoculation.
Label syringes with drug and patient name — keep in the fume hood/locked cupboard until administration.
Never split tablets/capsules — it poses a safety risk (spills/aerosolisation) and accurate dosing cannot be guaranteed.
If spillage/personal contamination occurs, contain the spill and prevent through-traffic, soak up with paper towel, incontinence pads or dust-free cat litter and wash the area with copious water/disinfectant, clean with paper towels. Do not use sprays/ shower heads as they risk aerosolising the drug.
All contaminated waste should be disposed in a designated sharps bin or clinical waste bin. Protective clothing should be worn to handle waste. Cytotoxic waste should be placed in a solid container, clearly labelled and sealed, ready for collection. Wear protective clothing to handle all waste.
A chemotherapy spill kit should be kept close to hand — this should contain latex gloves, a gown, mask and eye protection; incontinence pads; cat litter and a large zip-lock bag for waste disposal.
If dispensing tablets/capsules to clients, label ‘Cytotoxic — Wear Gloves’ and give written information on safe administration.
Regular and thorough cleaning of all surfaces within the chemotherapy preparation/administration area is essential.
If chemotherapy patients remain in hospital it is important to clearly label the kennels of treated patients and ensure that all ward staff are aware of safety protocols for: dealing with the patient; and handling waste products (Figure 6).
Figure 2. Use of personal protective equipment during chemotherapy administration.Figure 3. Preparation of cytotoxic drugs in a laminar flow fume hood.Figure 4. The use of sealed/closed systems, e.g. Phaseal™, with screw-on syringes and connectors, is recommended.Figure 5. Wrapping a spirit-soaked swab around the drug vial helps prevent aerosolisation.Figure 6. Patient excreta may be hazardous — kennels should be clearly labelled and staff involved in their care aware of the protocols.
There should be clear instructions to pet owners for at-home administration and handling of the drugs and for dealing with drug-contaminated urine and faeces. Owners should be advised to follow similar precautions (to those followed in the hospital) at home, i.e. they should wear gloves to clear up their pets’ excreta, which should be disposed of as cyto-toxic waste themselves. They should keep a plentiful supply of disposable plastic-backed absorbent pads, disposable gloves, large zip-lock bags and disposable towels to hand. Solid matter and/or disposable materials which have absorbed liquid excreta may either be flushed down the toilet (although not in large quantities), or placed into two leak-proof plastic zip-lock bags, each sealed individually, before being placed into their domestic waste, then stored in a solid container, e.g. a wheely bin, to await collection. In the event of ‘accidents’ in the home environment, gross contamination should first be removed, and then the area repeatedly cleaned with a bleach-based disinfectant, according to manufacturers' instructions, taking care not to spread or aerosolise the contaminants. Receptacles that have contained cytotoxic drugs should be sealed into zip-lock bags, labelled as hazardous and returned to the hospital for disposal.
While it is important to point out potential hazards associated with human exposure to metabolites of these drugs, it is equally important not to frighten people. Chemotherapy patients' excretions may be hazardous, but, with the right precautions, it is safe for pets to take part in normal interaction with family members, which is important for both.
Conclusion
Veterinary nurses have a vital role to play in the care of chemotherapy patients and in maintaining the health and safety of both patient, client and staff. Careful administration of cytotoxics drugs and subsequent patient monitoring should avoid many potential complications of using these drugs. If guidelines are followed, the safe use of cytotoxic drugs should be possible for the majority of veterinary practices, with minimal risk to all staff involved. Practices and personnel should always keep the risks of cytotoxic drug use at the forefront of their minds, with regular risk assessments and updates to best working practices being performed.
