Elastomeric pumps are frequently used for ambulatory chemotherapy treatments within day-care units and patients’ homes. There is a real risk of chemical contamination on disconnection of the perfusion system. This report describes a study comparing the level of direct cytotoxic contamination on wipes, nurses’ gloves, and tissue ‘models’ of patients’ arms following the disconnection of elastomeric pumps filled with a widely-used cytotoxic agent (5-FU). Results are presented for trials conducted both with and without the use of a closed system transfer device: Qimono© by Vygon.
Many studies have shown that healthcare professionals can be exposed to harmful chemicals during the course of their work. In the case of chemotherapy agents, this exposure runs the risk of significant and serious health effects. These can include cardiac toxicity,1 kidney damage,2 negative reproductive outcomes including infertility,3,4 and cancer.5
The potential risks associated with the administration of cytotoxic drugs have been widely assessed. One report details a study of 170 healthcare personnel in 12 French hospitals. From a total of 1703 urinary samples taken from staff within both day-care units and pharmacy departments, 53% of the healthcare workers sampled were found to have at least one positive urinary sample evidencing contamination by cytotoxic drugs.6 In another study of 103 healthcare professionals in six Canadian hospitals, 55% of 201 urinary samples showed evidence of contamination.7
Studies have also shown higher levels of contamination in day-care nurses as opposed to pharmacy staff. One such report describes a study of 156 surface samplings across 13 hospitals. A total of 78% of samples were positive in day-care units compared to only 66% in pharmacy departments.8 Another study of 250 healthcare professionals in 72 pharmacy departments and 170 day-care units reported that 44% of pharmacy staff were exposed to contamination, compared with 50–58% of day-care staff.6 This differential may be due to greater levels of protection for healthcare workers within pharmacy units, such as isolators, laminar flow hoods, and adapted ventilation. In comparison, health workers in the day-care unit environment are particularly vulnerable to contamination by cytotoxic drugs.
In addition to the direct effects on the health of key workers, such exposure can also impact the efficiency of a healthcare provider, resulting in the potential for time lost through absence and replacement of healthcare workers, cancellation or delay of patient treatments, departmental disorganisation and loss in productivity. Minimising the incidence of contamination is critical to patients, staff, and hospital managers.
Closed system transfer devices are an effective solution
A range of studies have shown the benefits of closed system transfer devices (CSTDs) in reducing the potential for contamination. Comparisons of surface contamination and urinary samples from staff before and after the implemented use of a CSTD have demonstrated reductions in surface contamination and the elimination of contamination within urinary samples.9,10 Another study has reported the elimination of surface contamination above the lower limit of detection following the trial of a CSTD.11
Numerous recommendations and guidelines for cytotoxic drug administration highlight the importance of CSTDs in the prevention of contamination:
- In the US, the National Institute for Occupational Safety and Health’s (NIOSH) advice is to prime intravenous tubing in a ventilated cabinet and to use needleless or closed systems when preparing and administering drugs12
- US Pharmacopeia Convention (USP)-800 states that hazardous drugs must be administered safely using protective medical devices and techniques, including needleless and closed systems. Antineoplastics must be administered with a CSTD when the dosage form allows13
- Within the EU, Groupe d’Evaluation et de Recherche sur la Protection en Atmosphère Contrôlée (GERPAC) asserts that healthcare workers should not be exposed to cytotoxic risk during disconnection of patient parenteral perfusion lines14
- 2016 EU policy recommendations confirm that disconnection prevents an element of risk to healthcare workers and that using a containment device is preferred for the administration of cytotoxic drugs.15 The policy guidance can be summarised as below:
- Level 1 – Replace the product with a less or non-toxic one
- Level 2 – Use closed systems to prevent the occurrence of any form of contamination
- Level 3 – Use local and general ventilation measures
- Level 3b – Organise the work in such a way that the duration and number of employees exposed is reduced
- Level 4 – Use personal protection measures.
Furthermore in January 2019, Directive (EU) 2019/130 of the European Parliament on the protection of workers from the risks related to exposure to carcinogens or mutagens at work was released and mentions that measures to prevent or reduce risk of exposure should include the use of closed systems.16
A new study involving the Qimono© (Vygon) CSTD system
A recent study performed at Saint Louis Hospital, Paris/France by H Levert et al, has evaluated direct and immediate contamination by the cytotoxic drug 5-FU (fluorouracil) during disconnection of elastomeric pump perfusion. 5-FU is an anti-metabolite chemotherapeutic agent used in the treatment of many forms of cancer, including breast, anal, stomach, colon, head and neck, and certain skin cancers.
All handlings were performed by an experienced and confirmed nurse in compliance with ‘standard good practices’.
The drug is used frequently in ambulatory chemotherapy treatments. These can be carried out both in day-care units and in the homes of patients. Chemotherapy nurses and patients may be at greater risk of contamination during treatments outside of the clinical environment. It is vital that disconnection procedures following treatment are optimal in terms of minimising the possibility of contamination during the process.
Three different combinations of perfusion set up were involved in the study:
- Group 1: Standard luer lock male connector (from elastomeric pump tubing) connected to standard luer lock female from vascular access device
- Group 2: Standard luer lock male connector (from elastomeric pump tubing) connected to needleless connector (Q-Syte™ Becton Dickinson) on vascular access device
- Group 3: Qimomale© connected to elastomeric pump tubing, and Qimofemale© connected to vascular access device.
Detection and analysis for 5-FU were performed on samples collected by a standardised protocol from wipes, nurse’s gloves, and tissue modelling the arm of the patient. This allowed a measure to be made of direct contamination by 5-FU during disconnection of the perfusion system (samplings, analysis and controls were performed by Dr Paul Sessink, Exposure Control, Sweden).
High-performance liquid chromatography–mass spectrometry (HPLC-MS) was used to detect the presence of 5-FU (limit of detection: 0.1µg). HPLC-MS is a technique used for the analysis of organic compounds. A mixture in the liquid phase is chromatographically separated into its components. A qualitative analysis of components separated by HPLC is achieved by individually subjecting them to MS as they are transferred via an interface from the chromatography column. Quantitative analysis of the individual components is determined using their peak intensities within the chromatogram. This provides reliable identification with high specificity and sensitivity. As a positive control, drops of 5-FU were placed on the wipes, gloves, and tissue representing the patient’s arm.
Statistical analysis was performed to compare the three groups (Kruskal–Wallis H test) or to compare pairs of groups (Mann–Whitney U test). The confidence level was 95%, with statistical significance defined at p < 0.05. The results for total contamination (wipes + nurse’s gloves + patient’s arm) are shown in Table 1.
A total of ten trials were completed for each type of disconnection. Over the course of the study, detectable total contamination with 5-FU was apparent within every disconnection sample (range: 10–851µg). Median total contamination was highest for Group 1 (158µg) and lowest for Group 3 (95µg). The Kruskal–Wallis H test showed there was a statistically significant difference in overall contamination between the three groups (p = 0.010). Further analysis using the Mann–Whitney U test showed that contamination following disconnection of the Qimomale© and Qimofemale© system (Group 3) was significantly less than for either of the two systems that did not incorporate a CSTD (Group 1 and Group 3, p = 0.018; Group 2 and Group 3, p = 0.036).
Review of recent scientific literature shows that approximately 50% of nurses are contaminated during administration of cytotoxic drugs.
USP800, NIOSH, EU Directive and many countries’ Standards of Good Practices, recommend the use of closed systems to prevent and reduce occupational exposure of healthcare workers.
This new study has reported on contamination by the chemotherapeutic agent 5-FU during modelled chemotherapeutic procedures. Evidence has been provided of the extent of immediate and direct contamination following disconnection of perfusion systems. The lowest levels of post-disconnection contamination were present for the perfusion involving the Qimomale® – Qimofemale® CSTD system.
The study demonstrated:
- No significant contamination difference between Luer Lock Male and Bidirectional valve
- Significantly less contamination with Qimono© (Vygon) vs Luer Lock Male/Luer Lock Female
- Significantly less contamination with Qimono© (Vygon) vs Bidirectional valve.
This provides further evidence of the importance of using a closed system transfer device to minimise the risk of contamination during such procedures.
Both USP 800 (enforceable in the US on 1 December 2019) and the recent update of EU Directive on workers’ protection against the risks of exposure (to be transposed within two years to EU countries) prefigures a strong and sustainable trend to foster global use of CSTDs to reduce HCP contamination.
- Menna P et al. Cardiotoxicity of targeted cancerv drugs: Concerns, “The Cart Before the Horse,” and Lessons from Trastuzumab. Curr Cardiol Rep 2019;21:33.
- Zhang X et al. Evaluation of adverse health risks associated with antineoplastic drug exposure in nurses at two Chinese hospitals: The effects of implementing a pharmacy intravenous admixture service. Am J Ind Med 2016;59(4):264–73.
- Fransman W et al. Nurses with dermal exposure to antineoplastic drugs: Reproductive outcomes. Epidemiology 2007;18:112–19.
- Everaus H. Sterility, infertility, and teratogenicity. In: Olver I (ed) The MASCC Textbook of Cancer Supportive Care and Survivorship. Springer, Cham;2018.
- Skov T et al. Risks for physicians handling antineoplastic drugs. Lancet 1990;336:1446.
- Ndaw S et al. Soignants et médicaments cytotoxiques. Place de la biométrologie dans la maîtrise des risques dans le temps. Bull Epidémiol Hebd 2018;12(13):252–7.
- Hon CY et al. Antineoplastic drug contamination in the urine of Canadian healthcare workers. Int Arch Occup Environ Health 2015;88:933–41.
- Bartel SB et al. Multicenter evaluation of a new closed system drug-transfer device in reducing surface contamination by antineoplastic hazardous drugs. Am J Health Syst Pharm 2018;4:199–211.
- Wick C et al. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health Syst Pharm 2003;60;22:2314–20.
- Nyman HA et al. Workplace contamination with antineoplastic agents in a new cancer hospital using a Closed-System Drug Transfer Device. Hospital Pharmacy 2007;42(3):219– 225.
- Clark BA, Sessink PJ. Use of a closed system drug-transfer device eliminates surface contamination with antineoplastic agents. J Oncol Pharm Pract 2013;19(2):99–104.
- NIOSH. Preventing Occupational Exposures to Antineoplatic and other Harzardous Drugs in Health Care Settings. September 2004.
- US Pharmacopeia Convention-800. Hazardous Drugs Handling in Healthcare Settings. December 2017.
- GERPAC. Preparation and administration of cytotoxic drugs for healthcare professionals and for the environment. July 2007.
- European Policy Regulations. Preventing occupational exposure to cytotoxic and other hazardous drugs. March 2016.
- Directive (EU) 2019/130 of the European Parliament and of the Council of 16 January 2019 amending Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at work. January 2019.