Meeting Chairman Mark Foulkes (President Elect, UK Oncology Nursing Society, and Consultant and Lead Cancer Nurse, Royal Berkshire NHS Foundation Trust) said that one of the longest-running debates in cancer nursing and systemic anticancer treatment (SACT) delivery is the use of closed systems and whether they improve staff safety significantly or whether personal protective equipment (PPE) alone could achieve the same result.
Occupational exposure risks for nurses handling SACT
Alison Simons and Samantha Toland (Senior Lecturers at Birmingham City University) have a special interest in SACT safety and the protection of nurses administering chemotherapy.
Reviewing the risks, Ms Simons said that many of the agents used for SACT are hazardous drugs. They are carcinogenic, teratogenic and mutagenic.
‘The drugs cannot distinguish between a patient who is receiving them for treatment and the health professional who is handling them, so there are potential risks for all of us’, said Ms Simons.
There are risks for staff at every point along the drug pathway, from reconstitution and preparation right through to disposal of waste and spillage. The administration step is of particular interest to nurses. Nurses can be exposed to hazardous drugs through inhalation of drug vapours, ingestion from contaminated cups or snacks on wards and by cutaneous absorption from drug splashes.
When considering who is at risk it is helpful to look at the ‘drug pathway’ and it is apparent that a variety of healthcare personnel are involved, including pharmacy technicians, nurses, porters, drivers and waste-disposal personnel.
Ms Simons drew attention to the protective measures used by pharmacists and pharmacy technicians at the reconstitution and manipulation stage compared to those used by nurses at the administration and waste disposal stage. Whereas the pharmacy technician wears full personal protective equipment (PPE) and works in a safety cabinet, the nurse usually wears a plastic apron and thin gloves—both are prone to tearing in use, she said. Furthermore, the nurse's arms are typically bare below the elbow, exposing skin that could easily be splashed with chemotherapy drugs.
Testing of surfaces in wards has shown that contamination with SACT drugs is common, especially in sluice areas and on the floor below drip stands.
Adverse effects of handling cytotoxic drugs
Awareness of the risks prompted nurses in Birmingham to undertake a study to look at the local situation in more depth. Ms Toland described how an informal survey had been carried out first to explore the immediate adverse effects experienced by nurses during the administration of SACT. An anonymous online survey with just four questions prompted 200 responses from 55 healthcare providers, nationwide. Some 46% of the respondents said that they experienced adverse effects on administering SACT and some experienced more than one adverse effect. These included fertility problems (3.6%), dizziness (15.4%), nausea (14.0%) and headache (29.2%). Worryingly, 9.2% said hair loss.
‘We did not expect there to be so many effects and such a wide range’, commented Ms Toland. Many other lower frequency effects were also reported, including an itchy nose, and skin irritation.
In addition to immediate toxic effects, guidelines warn about potential long-term effects such as leukaemias and other cancers. Not knowing what level of exposure is safe makes it difficult to predict what level of long-term exposure is acceptable, commented Ms Toland. It is also difficult to link reactions unequivocally to the administration of the SACT drugs, she acknowledged.
Turning to the question of how to reduce risk, Ms Toland said that several guidance documents are available. These include the National Institute for Occupational Safety and Health (NIOSH) alert (NIOSH, 2004) (from the US), the Control of Substances Hazardous to Health (COSHH) guidance (Health and Safety Executive (HSE), 2002) and HSE guidance (2021). All guidance refers to the hierarchy of controls. This involves first using totally enclosed systems where reasonably practicable. The second level is controlling exposure at source, for example, by using adequate extraction systems and organisational measures. The third level is the use of PPE where adequate control cannot be achieved by other means.
‘What we tend to find is that, for most nurses in the NHS, we rely heavily on PPE rather than other measures that should be in place’, said Ms Toland.
Many different closed systems are available for drug administration. ‘Any closed system is better than no closed system’, she said and when a risk cannot be quantified it is best to reduce it to as low as possible.
After finding the surprising level of adverse events in the initial survey, a second, follow-up, survey was undertaken to find out about nurse training and awareness of SACT risks and the safety precautions practised when handling SACT agents and patient waste. About 60 nurses responded. The results showed that most nurses were aware that there was a risk associated with occupational exposure to SACT, but they were unsure of the reasons for the risks. Only 2% recognised that SACT drugs were carcinogenic and 4% recognised an actual risk to health. Less than 60% of the respondents had received formal or informal education or training in the previous 12 months.
‘The HSE advises that everyone should have an update once every 12 months’, noted Ms Toland. They also found that the precautionary measures were heavily reliant on PPE—usually gloves and aprons. Less than 20% of respondents identified the use of closed systems during administration of SACT.
One of the most important tasks in this area is increasing awareness of the hazards of second-hand exposure to cytotoxic drugs because many nurses are not aware of the risks. In addition, increasing awareness of the guidance that already exists but is often not followed remains important. ‘We would love to see some monitoring of adherence to the guidelines and standardisation of education and training’, said Ms Toland.
Considering the ways in which the current situation could be improved, Ms Toland said that maintenance of a closed system all the way from preparation of SACT to administration and beyond (to waste disposal) is highly desirable. In addition, mandatory guidance or legislation on SACT safety, especially concerning administration and disposal of the drugs, would be helpful. Finally, appropriate use of PPE should be encouraged, perhaps including the adoption of US Pharmacopeia (USP) (2020) 800 standards, which states that there are minimum standards for PPE that every SACT nurse must follow. This calls for full PPE, she noted.
In conclusion, Ms Toland said: ‘A lot of people in this country are burying their heads in the sand where this issue is concerned. We give far more SACT agents now than ever—combined with a multitude of other drugs whose long-term effects are unknown—so raising awareness of the issue is critical.’
Further information is available from the SACT Safety website (www.sactsafety.com).
Using closed system transfer devices: a preliminary study
Tom Marler-Hausen (Matron, Macmillan Cancer Centre, University College London Hospitals NHS Foundation Trust (UCLH)) described a study that examined environmental contamination during IV drug administration following the introduction of a closed system transfer device (CSTD) (Marler-Hausen et al, 2020).
Mr Marler-Hausen suggested that 2020 should be the ‘year of nursing safety’. He said: ‘As a profession we need to do a lot to look after ourselves and that should start with this—when we put nurses in a chemotherapy unit we don't give them the chance of not being unnecessarily exposed to hazardous drugs.’
The purpose of the recent study (Marler-Hausen et al, 2020) was to assess current practice and whether using a closed system in a real-world situation would actually work, bearing in mind that devices are first tested in laboratories and it is important to determine whether the technology is transferable to a busy chemotherapy unit.
A CSTD is defined as a device that mechanically prohibits the transfer of environmental contaminant into a system and the escape of hazardous drug or vapour concentrations outside the system. In addition, CSTDs maintain the sterility of the product and reduce operator exposure to hazardous drugs when they are being prepared or administered.
‘Ultimately it's about reducing operator exposure to these drugs and that's why we want to use them more and more, where appropriate,’ said Mr Marler-Hausen.
The NHS Pharmaceutical Quality Assurance Committee's (PQAC), 2018 guidance stated: ‘to minimise risks it advised that closed system syringe caps are added to each syringe when the original cap is first removed’ (Santillo et al, 2018). However, a Cochrane review (Gurusamy et al, 2018) appears to contradict this because it says that evidence for this is lacking. This situation creates confusion at a time when clarity is required to protect nurses. ‘There is plenty of evidence to say that we should be using closed systems and America has definitely led the way with USP 800 guidance that has the force of law, something that we have lacked in this country’, he said.
The objective of Marler-Hausen et al's (2020) study was to evaluate whether the use of the Tevadaptor CSTD reduced environmental contamination with doxorubicin when administering an intravenous bolus in a large chemotherapy unit. Doxorubicin was chosen because it is frequently administered in the chemotherapy unit. At the time of the study, the chemotherapy unit at UCLH treated more than 60 patients a day.
The nurses in the chemotherapy unit were all trained to the same standard in accordance with the local protocol; all the nurses in the unit were briefed on the study and the processes involved.
Baseline data showed that there was surface contamination on 3/10 outsourced doxorubicin syringes and 5/10 of the syringes prepared in-house. This reinforces the importance of wearing gloves during any handling of cytotoxic syringes and not just at the time of administration, said Mr Marler-Hausen. It also means that syringes could be a source of cross-contamination, he added.
Environmental contamination results showed that doxorubicin was detected on the work surface of one of the pharmacy isolators and in the trays on the chemotherapy unit, indicating that overall contamination was present, but only at low levels.
When a bolus of doxorubicin is administered a gauze pad is held around the connection port when connecting and disconnecting the syringe and during the administration of the drug. A plastic tray is positioned underneath the side port where the connection is made. There is a layer of tissue in the tray to absorb any leakage from the syringe. During the study contamination was measured on the gauze swab, the tissue and the nurse's gloves—first with the current connection device and then with the CSTD.
At the time of the study, it was not possible for the CSTDs to be fitted to the syringes in the pharmacy aseptic unit so nurses in the chemotherapy unit removed the syringe caps and replaced them with CSTDs. This was performed in the intravenous preparation room with nurses working over a plastic tray lined with a tissue. During the study contamination was measured on the tissue and the nurse's gloves.
Looking at current administration practice without a closed system, release of doxorubicin was found during 9 out of 10 administrations. The highest levels of contamination were found on the gauze pad (median 4070 nanograms (ng)). Contamination on the gloves and tissues was found less frequently and at levels approximately 50 times lower (median 73 ng and 82 ng, respectively).
When the closed systems were used, no contamination was detected when connecting the CSTDs and a small amount of doxorubicin was found on the gloves during one administration only. This was attributed to surface contamination of the syringe rather than leakage during connection or administration.
The conclusions from this a small, real-world study were that the current practice for administration of doxorubicin cannot prevent leakage on to the gauze pads; however, the use of a CSTD does prevent leakage.
When environmental contamination does occur, ‘we need to be much better at having regular monitoring of our unit and understanding whether there are additional interventions that can further reduce contamination,’ said Mr Marler-Hausen. Ideally, for risk minimisation, the CSTD would be connected in the pharmacy aseptic unit at the time of syringe preparation; although, in this study, the devices were safely applied by nurses in the chemotherapy unit.
Reflecting on the study, Mr Marler-Hausen said that one of the important questions to consider is what the risks of exposure to cytotoxic drugs are for healthcare workers. The routes for exposure need to be examined carefully and then measures to reduce the risk should be introduced
Denise Davis and Marius Nicola of B. Braun described how the B. Braun ‘Click. Close. Protect.’ system serves to protect nurses from cytotoxic exposure and also protects the product from microbial contamination.
In 2018 the NHS PQAC published guidance to minimise the risks of occupational exposure to cytotoxic agents in clinical areas. This included two key recommendations. First, that the practice of de-spiking empty bags of cytotoxic chemotherapy should be stopped—that is, the chemotherapy bag should remain sealed after emptying/administration and, second, that closed-system caps should be fitted to the syringe before connecting to the patient—that is, a CSTD should be used for chemotherapy administration.
There are several types of connecting device that offer varying levels of protection against leakage. The Luer lock syringes with needle-free (open) systems offer no protection and the closed male connector with a needle-free (leak-proof) connector offers only partial protection. The membrane-to-membrane (dry) connector offers the highest level of protection. When closed male connectors with needle-free ports are used, there is still a risk of residual droplets remaining on the needle-free connector but this does not happen with membrane-to-membrane devices. B. Braun recommends using the Tevadaptor®dry membrane-to-membrane connectors and Cyto-Set®AirStop to ensure minimal risk for health professionals and the environment when hazardous drugs are administered. The B. Braun Click. Close. Protect. system was developed to comply with the PQAC recommendations. It provides a fully closed system from syringe/bag to patient with capacity for up to four chemotherapy infusions without the need to de-spike or disconnect. This system has been described in published reports in the BJN (Marler-Hausen et al, 2014) and Hospital Pharmacy Europe (Brünke, 2015). In addition, there is published evidence of the benefits of Tevadaptor CSTDs in pharmacy compounding (Vyas et al, 2014).
During the discussion that followed at the meeting, a number of points were raised.
Asked if there was scope for a larger study, Mr Marler-Hausen said that the study described could be viewed as a pilot study and a larger study could be undertaken in future. He also suggested that an epidemiological study might be useful to understand the link between exposure to hazardous drugs and adverse effects in nurses.
A study to compare the effect of ‘maximised PPE’ (like a space-suit) with a closed system was also suggested. Paul Sessink, Managing Director, Exposure Control Sweden AB, Sweden, commented that it was generally better to concentrate on reducing contamination in the first place rather than increasing the level of protection by using additional PPE.
Mr Marler-Hausen commented that the precautionary approach appears to be absent from thinking on this topic. Everything is done to make the service run but [outdated] 30-year-old practices for handling cytotoxic drugs continue because of a perceived lack of evidence of problems. A precautionary approach might serve nurses better.
There was general agreement that surface contamination on any surface, including floors, furniture, medical devices and pharmaceutical products, should be eliminated, closed systems should be introduced for preparation and administration, awareness of the risks should be raised and education and training should be implemented and updated for individuals every year.