The introduction of a ready-to-use cefuroxime DUPLEX drug delivery system in Denmark promises to save money and avoid the risks of ward-based preparation
Head of Hospital Pharmacy Department, Herning, Denmark
Christine Clark PhD FRPharmS FCPP(Hon)
Freelance Medical Writer, UK
Email: [email protected]
Preparation of intravenous (IV)doses is always a risky procedure and the more steps that are involved, the more opportunities for error there are. Common types of errors include incorrect drug, inaccurate measurement of volumes, incorrect diluent/carrier fluid and poor aseptic technique.1 Studies indicate that the incidence of errors in prescribing, preparing and administering injectable medicines is higher than for other forms of medicines.2,3 Another study showed that errors with antibiotic injections occurred more commonly than with other products.4
A significant amount of nurse time is devoted to preparation of IV doses.5 Ready-to-use (RTU) preparations save nursing time and other resources. One study reported a 32% reduction in nurse time preparing injections when a RTU product was used.6 Another study, involving a two-stage preparation comprising a reconstitution and dilution reported a 53% reduction in nurse time preparing injections when a RTU product was used.7 When there is a shortage of nurses, it becomes all the more critical that their time is available for direct patient care activities. The use of RTU injections reduces the amount of time that nurses have to spend on injection preparation and leaves more time for patient care activities.
The true cost of preparation of injectable doses, taking into account the time, ingredients and overheads involved and also the ‘opportunity cost’, or what else could have been done with the same resource input, is often not fully understood. Studies have shown that the true cost of injectable doses can be considerably higher than the cost of ready-made products from industry.6,7
Seven new ‘super hospitals’ are now being built in Denmark. They will have a strong focus on patient safety and quality of service and will make use of innovative technology and new models of service to ensure that medicines are handled safely and efficiently. An important element of this will be to eliminate the manipulation of medicines on wards and procure medicines that are provided as unit doses or RTU injections where possible. This has been identified as an important step in improving patient safety and the overall quality of patient care.8
Other features that have been identified as important are the use of barcodes on medicines to support ‘closed-loop administration’ processes, PVC-free containers and compliance with the Council of Europe Sharp Injuries Directive.
Preparation of IV cefuroxime doses in Denmark
Cefuroxime (1.5g and 750mg injections) is widely used. In Denmark, a total of 1.6 million doses per annum are used.9 Cefuroxime has to be prepared shortly before use because it is not stable for long periods of time in aqueous solution.10
Currently in Denmark, several large hospital pharmacies prepare doses of cefuroxime in advance using a minibag with integral drug vial adaptor and breakaway seals between the adaptor and the container (for example, Minibag-Plus™, Vial-Mate™, Baxter Healthcare). These are commonly described as ‘break-seal minibags’. They are delivered to the ward for reconstitution immediately before use. Such a system provides RTU products for the wards but requires a significant resource input from the pharmacy.
Another system that is widely used in Denmark involves the aseptic assembly of RTU cefuroxime doses by a robot, using the DivibaX™ (Promens) connector and a semi-rigid polypropylene container of 0.9% sodium chloride injection. The IV container with a docked drug vial is a RTU injection system. The product is over-wrapped in the pharmacy and is stable for up to six months. These injections are delivered to wards for stock. At present, two robots are in operation, at Rigshospitalet in Copenhagen and Odense University Hospital.
On some occasions cefuroxime 1.5g or 750mg is reconstituted and diluted on the ward by a nurse, using the needle and syringe method or an IV bag with an integral vial adaptor.
Reconstitution by nurses consumes considerable resources, including nurse time and disposable items and generates additional costs for wastage and disposal of medical waste.
Many hospital pharmacies do not have sufficient personnel or aseptic unit capacity to prepare all the doses required. In addition, wastage can be significant because of unused doses that are returned to the pharmacy too late to be issued again.
The use of the break-seal minibags enables the pharmacy to provide injections that can be reconstituted on the ward without the use of needles, syringes or separate diluents. However, increasingly, assembly has to be undertaken in a pharmacy aseptic unit, in-line with the current drive to centralise injection preparation in the pharmacy as far as possible. Aseptic assembly also makes it possible to assign a longer shelf life to products. Training of nurses in the reconstitution technique is required to ensure that the whole dose is dissolved and removed from the drug vial. Losses of a proportion of the dose from rubber-stoppered vials have been reported.11 It is possible for unfamiliar users to administer diluent alone, without reconstituting the drug. It is also possible to remove the drug vial and expose the patient to the risk of microbial contamination of the product. Another potential problem is ‘run-back’, where some of the reconstituted solution runs back into the drug vial and is not administered to the patient.
The DivibaX system enables the pharmacy to provide RTU cefuroxime injections to wards for stock. However, assembly is normally undertaken in a pharmacy aseptic unit equipped with the purpose-built robot. It is not possible to remove the drug vial after activation. Two important considerations with the DivibaX system are that the assembly robot can only use the type of IV bag that is made by the Danish Association of Hospital Pharmacies (SAD) and the assembled product is bulky, which puts significant demands on storage space on wards.
B. Braun DUPLEX system
B. Braun cefuroxime 1.5g and 750mg DUPLEX is a point-of-care activated presentation that is stable for a long period of time and is only activated at the point of administration without the need for ancillary equipment. It requires no assembly in the pharmacy and so difficulties with attaching vials are avoided and additional devices (for example, the Minibag Plus Docking Assist Tool or the Promens DivibaX robot) are not required. The DUPLEX presentation comprises 50ml dextrose 5% injection in one compartment and the drug powder in a separate compartment. The product (diluent and drug) contact layer is a mixture of thermoplastic rubber and a polypropylene ethylene copolymer that contains no plasticisers. The seal is broken immediately before administration and the diluent floods into the drug compartment, dissolving the drug powder. It is not necessary to squeeze the solution back into the diluent chamber to ensure that the whole dose is available for administration. It has been designed in such a way that the product has to be activated and the drug dissolved before anything can be administered, therefore, it is not possible to administer the diluent alone. In addition, DUPLEX is PVC-free and complies with Danish guidelines for phthalate reduction in medical devices.11
Table 1 shows the steps involved in preparing cefuroxime injection by each of the current methods and by using the B. Braun DUPLEX bag.
An economic evaluation was performed by adding up the resource costs for each of three methods of preparation of cefuroxime injection (the costs for the DivibaX system were not available).
The costs of nurse time assumed that an experienced nurse was involved and the salary was adjusted for employer’s costs, holidays and efficiency.
The estimate for time taken to prepare an injection by the vial and syringe method was derived from published studies. It is important to note that the time estimate takes into account all of the steps involved because this accurately reflects the time when the nurse is unavailable for other work.
An indicative price (€6.50) for the cefuroxime DUPLEX bag was used. The actual price would be subject to local contract negotiations.
Table 2 shows the comparison of resource costs for the three methods.
The preparation costs were estimated to be €12.88 for the vial and syringe method at ward level, €10.36 for the break-seal minibag prepared in the pharmacy and €6.85 for the cefuroxime DUPLEX bag. The calculation excluded the cost of disposal of waste products but it should be noted that the first 2 methods generate considerably more waste that the DUPLEX bag.
The economic analysis shows that the DUPLEX bag offers a 34% saving compared with resource costs associated with the use of break-seal minibags and a 47% saving compared with resource costs associated with preparation by a nurse using a needle and syringe method. However, this is only reflects the readily identifiable costs and probably underestimates the real savings and benefits. The use of the DUPLEX RTU product could also reduce the risk of administration errors and their associated costs. In this respect, the fact that the product is already barcoded is particularly valuable. In addition, the DUPLEX system generates fewer waste products.
Both the break-seal minibag method and the DivibaX system save nurse time (resource costs at ward level) but require a significant resource input from the pharmacy department. Therefore, the overall resource input is still greater than that required for the DUPLEX method. Moreover, there is an opportunity cost in that the pharmacy aseptic compounding time that is liberated could be used to prepare other products. In fact, there is often insufficient aseptic compounding time and break-seal bags have to be purchased from the UK at greater cost.
The DUPLEX system provides a product that is stable at room temperature with little risk of water vapour loss. It requires no cumbersome preparation, is easy to activate at the point of use and, as it is PVC-free, does not pose a risk of phthalate leaching into the carrier solution. The product is barcoded and this can reduce the risk of administration errors. In addition, the DUPLEX bag generates less pharmaceutical waste (that is, waste materials, including sharps contaminated with drug products that require high-temperature incineration). Finally, it would also help hospitals to comply with EU Directive 2010/32 (sharps injuries),16 the Council of Europe Resolution on hospital preparation of injections17 and Danish guidelines on phthalate reduction in medical devices.11
B. Braun cefuroxime 1.5g DUPLEX offers a high quality product at a significantly lower resource cost than at present. Use of the B. Braun cefuroxime 1.5g DUPLEX would result in immediate savings in ancillary products and would release nurse time for other patient care activities. It would also liberate capacity for the pharmacy compounding robots that could be utilised for other products.
- Preparation of intravenous doses is risky and expensive.
- The use of RTU injections saves time and improves the quality of product provided.
- The DUPLEX system provides a product that is stable at room temperature for long periods.
- The DUPLEX bag can be activated easily at the point of use without any special equipment.
- Use of cefuroxime DUPLEX bags would allow more efficient use of pharmacy and nursing time than alternative systems.
- National Patient Safety Agency. Promoting safer use of injectable medicines. NPSA 2007/20, March 2007. www.nrls.npsa.nhs.uk (accessed 3 February 2013)
- Taxis K, Barber N. Ethnographic study of incidence and severity of intravenous medicine errors. Br Med J 2003;326: 684–7.
- Cousins DH et al. Medication errors in intravenous medicine preparation and administration: a multicentre audit in the UK, Germany and France. Qual Saf Health Care 2005;14:190–5.
- Ross LM. Wallace J, Paton J. Medication errors in a paediatric teaching hospital in the UK: five years operational experience. Arch Dis Child 2000;83:492–7.
- Clark C et al. Parenteral drug delivery – value for money? Pharm J 1986;236:453.
- Van der Linden P et al. Ready-to-use injection preparations versus conventional reconstituted admixtures. Economic evaluation in a real-life setting. Pharmacoeconomics 2002;20:529–36.
- Schmitt E et al. Ready to use injectable paracetamol: easier, safer, lowering workload and costs. EJHP 2003;6:96–102.
- Bräuner H. The need for RTU drugs on children’s wards and neonatal units. 2011. Internal report for Amgros and the Danish Regions.
- Personal communication. Data on file, Amgros
- Trissel LA. Handbook of Injectable Drugs 16th Edition. 2011 Americal Society of Health-System Pharmacists. Bethesda, MD, USA.
- Guideline to the Regions and Municipalities about reduction of phthalates when purchasing medical devices, Danish Health and Medicines Authority. (Vejledning til regioner og kommuner om reduktion af ftalater ved indkøb af medicinsk udstyr).
- Dansk Sygeplejeråd (Danish Nurses Organization) edited 10/12.
- Invest in Denmark. Ministry of Foreign Affairs Denmark. August 2011. http://www.investindk.com/~/media/Files/Sheets/Framework%20conditions/The%20Danish%20Labour%20Market%20-20August%202011.ashx.
- UHY Consulting report Employers now pay average employment costs worth nearly 25% of employees’ salaries. February 2013 http://www.uhy.com/employers-now-pay-average-employment-costs-worth-nearly-25-of-employees-salaries/.
- Armour DJ et al. The economics of a pharmacy-based central intravenous additive service for paediatric patients. Pharmacoeconomics 1996;10:386–94.
- Council Directive 2010/32/EU of 10 May 2010 implementing the Framework Agreement on prevention from sharp injuries in the hospital and healthcare sector concluded by HOSPEEM and EPSU. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:134:0066:0072:EN:PDF.
- Council of Europe. Resolution CM/ResAP(2011)1 on quality and safety assurance requirements for medicinal products prepared in pharmacies for the special needs of patients. https://wcd.coe.int/ViewDoc.jsp?id=1734101&Site=CM