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• To learn about the risks of exposure to systemic anticancer therapy agents
• To read about methods of minimising the risk of exposure to systemic anticancer therapy agents
• To count towards revalidation as part of your 35 hours of CPD, or you may wish to write a reflective account (UK readers)
• To contribute towards your professional development and local registration renewal requirements (non-UK readers)
Many agents used for systemic anticancer therapy (SACT), which include chemotherapy drugs, monoclonal antibodies and other biological therapies, are known to be carcinogenic, teratogenic and mutagenic. Occupational exposure to SACT agents carries a proven risk of short- and long-term adverse health effects such as nausea, headaches, dizziness, hair loss, impaired fertility and cancer. The risk of contamination exists not only for staff who prepare or administer SACT agents, but also for those involved in transport, storage and waste disposal. In the UK, the handling of SACT agents is subject to a series of laws, regulations and guidelines. However, there are still inconsistencies in practice and a lack of awareness of the risks involved and need for training. The necessary preventive measures are not always in place and some staff remain exposed to cytotoxic agents. Furthermore, the risk of occupational exposure to SACT agents has intensified in recent years due to a significant increase in their use. This article prompts nurses to reflect on the health risks associated with handling SACT agents and the preventive and protective measures required.
Cancer Nursing Practice. doi: 10.7748/cnp.2020.e1733
Peer reviewThis article has been subject to external double-blind peer review and has been checked for plagiarism using automated software
Correspondence Conflict of interestNone declared
Simons A, Toland S (2020) Protecting nurses against the risks of occupational exposure to systemic anticancer therapy agents. Cancer Nursing Practice. doi: 10.7748/cnp.2020.e1733
Published online: 30 December 2020
The aim of this article is to prompt nurses to consider the health risks associated with handling agents used for systemic anticancer therapy (SACT), such as chemotherapy drugs, and gain awareness of the preventive measures required to minimise those risks. After reading this article and completing the time out activities you should be able to:
• Detail the risks involved in handling SACT agents.
• Describe the potential routes of exposure to SACT agents.
• Identify the UK legal and policy framework pertaining to the handling of SACT agents.
• Understand how to minimise the risks of exposure in all SACT-related activities.
• Explain the rationale for the management of a spillage of SACT agents.
• The health risks associated with occupational exposure to systemic anticancer therapy (SACT) agents include nausea, headaches, dizziness, hair loss, and impaired fertility
• Exposure to SACT agents can occur through many different methods, such as inhalation of contaminated air or through skin contact with contaminated surfaces, materials and equipment
• Exposure to even minute quantities of some SACT agents – particularly chemotherapy drugs – can increase the risk of experiencing adverse effects
• Many national and international guidelines recommend a hierarchy of control measures to manage risk of exposure to SACT agents
SACT agents comprise chemotherapy drugs – some of which are classed as cytotoxic – monoclonal antibodies and other biological therapies. Many SACT agents, particularly chemotherapy drugs, are known to be carcinogenic (potentially causing cancer), teratogenic (potentially impairing fertility and fetal development) and mutagenic (potentially causing genetic mutation). This has prompted concerns regarding the safety of healthcare professionals who handle SACT agents, particularly the pharmacists who prepare them and nurses who administer them (Suspiro and Prista 2011).
All healthcare professionals handling SACT agents may be subject to significant health risks due to occupational exposure to these agents over time (National Institute for Occupational Safety and Health (NIOSH) 2004, Health and Safety Executive (HSE) 2020, Polovich 2016, Power and Polovich 2018, Sessink 2016).
In recent years, the risk of occupational exposure to SACT agents has intensified due to a significant increase in their use. However, there is still a lack of awareness of the risks involved and of the need for updated and ongoing training of staff (Lucas and Connor 2015, Simons and Toland 2019). Furthermore, the necessary preventive measures are not always put in place. This article provides an overview of the health risks involved in handling SACT agents and the measures that are needed to protect staff.
The mechanism of action of some SACT agents involves some form of DNA damage, affecting the ability of cells to replicate and, in many cases, inducing apoptosis (cell death). That mechanism kills cancer cells but does not target them specifically, so healthy cells are often harmed in the process. This is what causes the side effects of treatment seen in many patients undergoing SACT.
In recent years, there have been substantial increases in the number of SACT agents in use and in the frequency of their use. Improvements in diagnosis mean that there are more people diagnosed with cancer and therefore more patients receiving SACT, including cancer survivors.
Overall, cancer is detected earlier than it used to be, which means patients may receive SACT over a longer period of time (Marsh and Shaunak 2016). The use of SACT has also increased because of a rise in the number of older people, as well as a rise in the available lines of treatment and treatment combinations brought about by pharmaceutical advances (European Biosafety Network 2016). Furthermore, SACT agents are extensively used to treat not only cancer but also non-malignant conditions such as rheumatoid arthritis (Suspiro and Prista 2011). These various factors have led to an increased risk of occupational exposure among healthcare professionals handling SACT agents, particularly those involved in their preparation and administration (European Biosafety Network 2016).
Additionally, there has been a significant increase in the use of newer therapies, such as immunotherapies. Immunotherapy agents are not currently classified as hazardous drugs, but there may be risks associated with occupational exposure to these agents that are not yet known (Lennan 2017). Hazardous drugs are defined as substances that are hazardous to health due to the substance being toxic, harmful, corrosive or irritant (Control of Substances Hazardous to Health (COSHH) Regulations 2002) and include certain SACT agents such as methotrexate and carboplatin. SACT agents include a wide variety of drugs that all have different modes of action and therefore not all are classed as hazardous drugs. Those that are classed as cytotoxic agents, and therefore hazardous drugs, are known to be carcinogenic, teratogenic and mutagenic due to the nature of their mode of action.
In the UK, the COSHH Regulations (2002) require to either eliminate or control hazardous chemicals and substances in the workplace. However, there are no processes in place to monitor their elimination or control, or to ensure that the regulations are adhered to. Furthermore, no documented ‘safe’ level of exposure to cytotoxic drugs has yet been established (Davis et al 2011, Crickman 2017).
Despite existing regulations, guidelines and policies on reducing occupational exposure to hazardous drugs, there is evidence that there still are inconsistencies in practice and that some staff remain exposed to cytotoxic agents. A cross-sectional study in pharmacy and nursing areas found trace levels of the chemotherapy drugs cyclophosphamide and fluorouracil in blood and urine samples of staff (Connor et al 2010). Staff contamination with cytotoxic drugs has been attributed to drug residues on surfaces and materials, such as on the outside of drug vials (Power et al 2014) or syringes and infusion bags (Vyas et al 2016).
The health risks associated with occupational exposure to SACT agents have been identified and documented in a succession of studies, including Falck et al (1979), Anderson et al (1982), Sewell (1995), NIOSH (2004) and Simons and Toland (2015). Both acute and long-term adverse health effects have been reported, including nausea, headaches, dizziness, hair loss, impaired fertility (Sessink 2016, Simons and Toland 2017) and leukaemia and other cancers (NIOSH 2004, Polovich 2004, Connor 2006). Box 1 lists commonly reported adverse effects of cytotoxic drugs on the health of exposed healthcare professionals.
• Vomiting, abdominal pain
• Dizziness
• Headaches, nasal sores, sore throat
• Hair loss
• Acute irritation, hypersensitivity
• Liver damage, alterations to normal blood cell count
• Infertility, spontaneous abortion and congenital malformations
• Abnormal formations of cells, mutagenic activity
• Leukaemia and other cancers
(Adapted from National Institute for Occupational Safety and Health 2004, Polovich 2004, Connor 2006, Sessink 2016, Simons and Toland 2017, Health and Safety Executive 2020)
In response to the studies mentioned in the previous section that demonstrated health risks linked to occupational exposure to SACT agents, various guidelines and policies have been introduced at national and international level, including:
• In the UK, the recommendations of the HSE (2020) on the safe handling of cytotoxic drugs in the workplace.
• In the US, the alerts issued by the NIOSH (2004, 2016) and the guidelines published by the American Society of Health System Pharmacists (2006) and by United States Pharmacopeia (2018).
• Internationally, the standards of practice issued by the International Society of Oncology Pharmacy Practitioners Standards Committee (2007).
• At European Union level, the policy recommendations of the European Biosafety Network (2016).
Furthermore, in the UK, there are major pieces of legislation pertaining to the handling of SACT agents. Table 1 provides an overview of the legal and policy framework that regulates SACT-related activities in the UK.
Health and Safety at Work Act 1974 | The Act stipulates that employers are responsible for providing and maintaining a working environment that is safe, without risks to health, with adequate facilities and arrangements for the welfare of employees. Measures must be in place to ensure safety in relation to the use, handling, storage and transport of dangerous articles and substances, and to provide employees with information, instructions, training and supervision |
The Management of Health and Safety at Work regulations 1999 | The regulations place a duty on employers to assess and manage the risks to their employees and others, with the aim of preventing work accidents and work-related illnesses. Employers are required to conduct risk assessments, have a written health and safety policy, provide employees with advice and training, and consulting employees about risks at work and preventive and protective measures |
The Control of Substances Hazardous to Health (COSHH) Regulations 2002 | The COSHH Regulations require employers to either eliminate or control substances that are hazardous to health, including hazardous chemicals and substances in the workplace. This involves assessing risk, providing information and training, enforcing policies and procedures, and monitoring risk of exposure |
Health and Safety Executive (2020) guidance on the safe handling of cytotoxic drugs in the workplace | The guidance contains recommendations on all aspects of handling cytotoxic drugs, including who is at risk; control of exposure; personal protective equipment (PPE); monitoring exposure in the workplace; occupational health services; managing spillages and contamination; waste disposal; information, instruction and training; and the reporting of incidents |
Guidance on Handling of Injectable Cytotoxic Drugs in Clinical Areas in NHS Hospitals in the UK (Santillo et al 2018) | The guidance – also known as the ‘yellow-cover document’ – is designed to be a reference and source of information for NHS staff who handle injectable cytotoxic drugs. It sets out simple measures to reduce the risks of exposure, advice on the appropriate use of PPE, and training in cytotoxic drug handling |
European Biosafety Network (2016) policy recommendations on preventing occupational exposure to cytotoxic and other hazardous drugs | The recommendations require policy makers to ensure employees receive optimal protection in the workplace. They cover the prevention of occupational diseases; adoption of common minimum standards; use of appropriate PPE; provision of regular information and education; provision of suitable decontamination; cleaning and disinfection guidelines; basic guidelines on the regular monitoring of exposure to cytotoxic drugs; and mechanisms to ensure that the recommendations are implemented effectively |
Exposure to SACT agents can occur through many different methods, such as inhalation of contaminated air or through skin contact with contaminated surfaces, materials and equipment (Sessink 2016). Exposure to even minute quantities of some SACT agents – particularly chemotherapy drugs – can increase the risk of experiencing adverse effects, particularly when there is daily exposure over many years (Sessink 2016). The routes of exposure to SACT agents are:
• Inhalation – for example, in case of spillage or splashing during drug reconstitution, drug administration and waste disposal.
• Absorption – for example, in case of spillage, splashing or needlestick injury during drug reconstitution, drug administration, waste disposal and changing of bed linen.
• Ingestion – for example, in case of suboptimal hand hygiene; eating, drinking or smoking in contaminated areas; and not maintaining the cleanliness of sluices.
There are several activities performed by healthcare professionals that can increase the risk of exposure to SACT agents. The handling of SACT agents can lead to a safety issue for healthcare professionals, particularly pharmacists who prepare them and nurses who administer them (Suspiro and Prista 2011). However, the risk of exposure is not confined to these specific groups, since staff involved in the transport, storage and disposal of SACT agents and/or contaminated materials are also at risk.
The safety of environments where SACT agents are prepared has received a lot of attention ever since the risks of exposure in those environments were first identified in the UK by Sewell (1995). Sewell (1995) raised concerns around safety and quality assurance in the reconstitution of SACT agents. This resulted in rigorous policies and procedures being introduced in pharmacy departments (Beaney 2016). However, exposure can occur during any SACT-related activity, and a lot less attention has been given to the safety of SACT administration and waste disposal.
When a cytotoxic drug leaves the pharmacy department, there is a possibility, despite the best efforts of pharmacy staff, that drug traces will be present on the syringe or infusion bag (Vyas et al 2016). This can potentially cause exposure during subsequent processes, including transport, unpacking, storage and administration.
During administration of SACT agents via infusion, there are two points in the process where the risk of exposure is particularly high. The first is when an infusion bag is ‘spiked’ (when the administration set is inserted into the bag using its sharp end) and the second is when an infusion bag is ‘de-spiked’ (when the administration set is removed from the bag). During spiking and de-spiking, fluid, droplets and/or vapours can leak out of the infusion bag. There is evidence showing a 25% risk of exposure when an infusion bag is spiked and a 100% risk of exposure when an infusion bag is de-spiked (Vandenbroucke and Robays 2001).
In addition, there may be leakage of vapours out of the infusion bag through openings in the administration set such as filters, air inlets or side ports. Administration sets often have an open end that allows connection to a venous access device, which causes a further risk of vapour leakage (Pan American Health Organization 2013, Power 2013).
Some SACT agents – for example, monoclonal antibodies – are reconstituted outside the pharmacy department and there is a risk of drug traces leaking out during reconstitution. Injecting fluid into a vial creates a positive pressure which may result in fluid, droplets and/or aerosols being expelled. Once fluid has been drawn up into the syringe, there is a risk of leakage from the open end of the syringe. A risk of leakage is also present when the syringe is attached to the venous access device and when the drug is administered (Power 2013).
Additionally, a risk of contamination exists when clinical and patient waste are disposed of, as these may contain drug residues that can leak out (NIOSH 2004).
Table 2 summarises SACT-related activities and their specific risks of exposure.
Four of the national and international guidelines (NIOSH 2004, European Biosafety Network 2016, Santillo et al 2018, HSE 2020) recommend a hierarchy of control measures that must be applied in the following order of priority:
1. Use totally enclosed systems where reasonably practicable.
2. Control exposure at its source, for example by using adequate extraction systems and appropriate organisational measures.
3. Issue personal protective equipment (PPE) where adequate control cannot be achieved by previous measures alone.
These three sets of control measures must be used together, not in isolation, as one set of measures will not be sufficient on its own, but they must be applied in the order indicated.
The first control measure within the hierarchy is to use totally enclosed systems for administering drugs, such as closed system transfer devices (CSTDs). CSTDs mechanically prohibit the transfer of environmental contaminants into the system and the leakage of hazardous drug residues or vapours out of the system. They play a central role in minimising the risk of contamination with SACT agents.
The second measure is to control exposure at its source (Gurusamy et al 2018). This involves identifying risks; using biological safety cabinets and adequate ventilation systems; using CSTDs and PPE; monitoring exposure in the workplace; putting health surveillance programmes in place; providing information and training to staff; maintaining equipment appropriately; having appropriate procedures in place for managing spillages and contamination of persons and surfaces; and providing adequate facilities for safe waste disposal.
The third measure is to issue PPE to all staff who handle SACT agents where adequate control cannot be achieved by previous measures alone. All areas where staff handle hazardous drugs must have PPE policies aligned with the UK legislation (that is, The Personal Protective Equipment at Work Regulations 1992). Table 3 shows PPE requirements when handling hazardous drugs according to activity, as outlined by the NIOSH (2016).
(Adapted from National Institute for Occupational Safety and Health 2016)
The ‘yellow-cover document’ (Santillo et al 2018), which serves as the reference within the NHS for the handling of injectable cytotoxic drugs, makes a range of best practice recommendations to staff and employers regarding the administration of SACT. Some of these recommendations are listed in Box 2.
• Do not de-spike empty infusion bags
• Always use a closed system, whether administering SACT as an infusion, bolus dose or directly into the bladder
• Use appropriate personal protective equipment (PPE) when handling SACT agents
• Appropriately dispose of all SACT waste products, including patient waste, using a closed system wherever possible
• Provide annual updated training to all staff who handle SACT agents
• Make cleaning personnel aware of the risks of exposure to SACT agents and request that they wear appropriate PPE when they work in SACT clinical areas
(Adapted from Santillo et al 2018)
The Oncology Nursing Society (2018) has published a toolkit for the safe handling of hazardous drugs by oncology nurses. It details, among others, the procedure for managing a spillage of SACT agents, which features in Box 3. It also advises to keep a spillage kit in areas where SACT agents are handled and lists what a typical spillage kit should contain.
• Cordon off the area, including any contaminated individuals
• Evacuate the area
• Contaminated individuals to remove contaminated clothing and wash skin thoroughly where appropriate
• All staff involved in managing the spillage must wear appropriate personal protective equipment (PPE)
• Absorb the spillage using pads and/or other absorbent equipment
• Form a cuff by folding the top of the bag over onto itself to prevent contamination of the outside of the bag
• Place pads and other equipment in the waste bag
• Check area to ensure all spillage has been absorbed. Spills from chest or waist height may cause droplets to spread several feet from the source
• Use commercially available deactivation products for drugs that have been tested. If none are available, consider a bleach solution and a detergent solution to clean the spill
• Clean area using an inward spiral motion
• Dry area using an inward spiral motion
• Rinse the area with plain water to dilute the hazardous drug residue
• Repeat dilution, cleaning and drying steps described above another two times (so that there are three rounds of dilution, cleaning and drying in total)
• Place all contaminated waste in the waste bag
• Remove contaminated PPE
• Seal the waste bag using the swan-neck technique
• Place waste bag in solid cytotoxic waste bin
• Wash hands
• Document procedure
(Adapted from Oncology Nursing Society 2018)
The ‘yellow-cover document’ and the Oncology Nursing Society toolkit are available online for further information (see Further resources).
There are still inconsistencies in practice that mean some nurses who administer SACT are at risk of occupational exposure to hazardous drugs such as chemotherapy drugs. Over time, contamination with SACT agents can cause short- and long-term adverse health effects including nausea, headaches, dizziness, hair loss, infertility and cancer. Exposure to even minute quantities of some SACT agents can cause a risk, particularly when there is daily exposure over many years. Preventive measures must be implemented in the explicit order of priority described in the existing guidance, so that nurses and other staff who handle SACT agents are adequately protected.
It is imperative to raise nurses’ awareness of the risks associated with handling SACT agents and explain to them the rationale behind the necessary preventive measures. This will empower nurses to take action to protect themselves and others from the risks of occupational exposure to SACT agents and ensure these risks are as reduced as reasonably practicable.
Consider how protecting nurses against the risks of occupational exposure to systemic anticancer therapy agents relates to The Code: Professional Standards of Practice and Behaviour for Nurses, Midwives and Nursing Associates (Nursing and Midwifery Council 2018) or, for non-UK readers, the requirements of your regulatory body
Now that you have completed the article, reflect on your practice in this area and consider writing a reflective account: rcni.com/reflective-account
NHS (2018) Guidance on Handling of Injectable Cytotoxic Drugs in Clinical Areas in NHS Hospitals in the UK
tinyurl.com/NHS-cytotoxic-drugs
Oncology Nursing Society (2018) Toolkit for Safe Handling of Hazardous Drugs for Nurses in Oncology
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