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Published on 15 October 2012

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Ready-to-use infusion preparations in critical care


Andrew Parsons MPharm Clin Dip
Department of Pharmacy,
North Bristol NHS Trust, Bristol, UK
Ready-to-use infusion preparations have been highlighted by patient safety organisations as a way of improving the safety of injectables. The article describes factors and issues raised by their introduction into two intensive care units at a UK Trust
Research evidence indicates that the incidence of errors in prescribing, preparing and administering injectable medicines is higher than for other forms of medications.(1) The National Patient Safety Agency (NPSA), which is responsible for patient safety in England and Wales, received around 800 reports a month to its National Reporting and Learning System (NRLS) relating to injectable medicines between January 2005 and June 2006.(1) This represents approximately 24% of the total number of medication incidents, including 25 deaths and 28 cases of serious harm from an injectable medication.(1) Of these errors, 73.1% were the result of preparation and administration, and 28.9% were the result of the wrong dose, strength or frequency.(1) A study looking at variability in concentrations of intravenous drug infusions prepared in a critical care unit found that, in magnesium infusions, six of 30 samples contained four-to-five-times too much magnesium.(2) There can also be wide variations in practice, as described in a paper that found that 53 different strengths of products containing potassium chloride were being prepared in clinical areas across a small sample of English hospitals, rather than a smaller standardised set of preparations.(3)
Patient Safety Alert 20
In response to this, the NPSA published Patient Safety Alert 20: Promoting safer use of injectable medicines in March 2007. The alert made six recommendations to help improve practices in the NHS and independent sector.(1) These are:
  1. Undertake a risk assessment of injectable medicine procedures and products in all clinical areas to identify high risks, and develop an action plan to minimise them
  2. Ensure there are up-to-date protocols and procedures for prescribing, preparing and administering injectable medicines in all clinical areas.
  3. Ensure essential technical information on injectable medicines is available and accessible to healthcare staff in clinical areas at the point of use.
  4. Implement a ‘purchasing for safety’ policy to promote procurement of injectable medicines with inherent safety features
  5. Provide training for, and supervision of, all healthcare staff involved in prescribing, administering and monitoring injectable medicines
  6. As part of the annual medicines management audit programme, healthcare organisations should include an audit of medication practice with injectable medicines.
As part of the recommendation,(1) the alert recommended that high-risk injectable products should be simplified and rationalised by manufacturers to provide the most appropriate vial or ampoule sizes, and that ready-to-administer or ready-to-use injectable products of standard strengths should be available to minimise risks.(1) The alert also recommended that the additional cost of preparing in pharmacy or purchasing ready-to-administer and ready-to-use products should be offset against preparation in the clinical area, which incorporates the cost of the component materials, staff time, wastage and associated risk.(1)
Recommendation 4 advises hospitals to procure licensed ready-to-administer or ready-to-use injectable medicines and suggests that NHS organisations should work together with the pharmaceutical industry to develop these where products are not currently available.(1) High- or moderate-risk preparations should be prepared and/or supplied by pharmacy in ready-to-use or ready-to-administer forms or risk reduction methods should be in place to improve patient safety.(1) Products that are not prepared within the hospital pharmacy department should be procured from specialist manufacturing units and the quality of these products evaluated by a quality assurance pharmacist before use.(1)
The NPSA alert was the first time that ready-to-use or ready-to-administer products had been recommended in national guidance. As critical care areas use a high proportion of ‘high-risk’ injectables, such as vasopressors, inotropes and concentrated potassium chloride, these are the clinical areas that are most likely to benefit from the procurement of ready-to-use products. However, one of the challenges for critical care units and manufacturers was that there was significant variation between critical care areas in different hospitals, potentially leading to an unacceptably large number of different preparations being required by different units. At the same time as the NPSA was published, a multidisciplinary group of pharmacists and anaesthetists published a survey that set out to inform standardisation of intravenous medication concentrations in adult critical care units.(4) The survey identified 372 presentations in use for the 20 most commonly prescribed critical care infusions.(4) This figure did not take diluents into account, which would add an extra level of complexity to the results.(4) A subsequent survey in 2009 by the same team led to a set of standardised concentrations for 18 drugs being generally agreed upon by responders, with adrenaline, potassium chloride and phosphate being the three agents for which no standard concentration could be agreed.(5) Work is currently underway to encourage the adoption of these standards in the UK. The following year, the Intensive Care Society supported the adoption of these standard concentrations and called upon manufacturers to begin preparation of ready-to-use products based upon the list (Table 1).(6)
North Bristol NHS Trust: a case study
North Bristol NHS Trust has three intensive care wards spread over two hospital sites. In 2009, concerns were raised on the wards about the labelling of noradrenaline syringes for infusion. At the time, nurses prepared syringes of 4mg/50ml, 8mg/50ml and 16mg/50ml noradrenaline from ampoules of 1mg/ml noradrenaline. After an incident where a syringe was labelled incorrectly, it was suggested that one solution to reduce the risk of errors in the future would be to procure ready‑to‑administer noradrenaline syringes. As these are labelled as part of the manufacturing process, and only require patient details and time and date of administration to be added, the risk of incorrect labelling should be eliminated. A significant reduction in preparation time was deemed to be an additional benefit by the nursing staff.
The wards had already standardised their infusion concentrations to the Intensive Care Society guidelines and used a pre-printed infusion chart to reduce prescribing errors. The specialist pharmacist for critical care reviewed the available products and performed a financial analysis of the likely impact on expenditure. Although the syringes were more costly than the ampoules, the syringes proved to be more cost effective at higher concentrations. With this in mind, the wards planned to switch to using 8mg/50ml and 16mg/50ml noradrenaline exclusively. An added benefit of having only two strengths was to save storage space and reduce the risk of incorrect strength selection. Funding to cover the additional expenditure was secured from the Trust as a safety initiative.
After receiving approval for the switch to prefilled syringes for noradrenaline, the ready-to-administer syringes were purchased and use commenced in December 2010. The decision was made to only initially procure prefilled noradrenaline syringes, rather than all infusions used on the wards, as several products were unavailable at the time and the cost of switching all infusions at once would be very high. The noradrenaline syringes were to be a pilot and, if successful, other products may be introduced if appropriate.
Storage of ready-to-use and ready-to-administer products can become one of the most complex issues when looking to introduce a product into a critical care area. Space is usually at a premium and products often require refrigeration. Other products might require storage under controlled drug conditions. The prefilled syringes procured by the Trust required refrigeration, with a 60-day shelf life in the fridge. At room temperature, the expiry was reduced to two weeks. Failure of the cold chain because of stock being stored incorrectly or problems with fridges proved to be frustrating. On several occasions, stock was refrigerated quickly enough, despite clear labelling on the external packaging. Stock delivery procedure was then changed to ensure that refrigerated items are handed to staff on delivery. Fridge doors were left open on occasion, and there was a complete failure of one of the ward refrigerators. Pharmacy provided training and education on fridge storage for nursing staff to try and reduce the impact of these problems.
The syringes themselves were quite bulky because they have to be stored with the plunger fully extended. Some products are shipped in protective packaging: usually either a foil pouch or opaque plastic bag. This can lead to problems if the syringes are damaged during transit or storage. The units experienced two instances of syringes leaking under pressure, when a previously unnoticeable crack in the syringe body (hidden behind the drug label) allowed the product to escape. In another instance, a luer-lock broke during connection to the giving set, resulting in a leak under pressure. The number of breakages was small, which did not result in increased costs. Refunds were obtained for any products that arrived damaged from transit. The damaged products did not affect patient care significantly because most problems were spotted before setting up the syringe in the pump.
Initial predictions on usage proved to be overestimates, leading to batches of syringes expiring. The predictions from nursing staff were based on a large number of patients requiring the syringes for a ‘worst case scenario’. Stock accumulated when fewer patients actually required the syringes; the unpredictable nature of critical care meant that demand could fluctuate greatly. The wards soon found that fewer 16mg/50ml syringes were required as stock and levels were adjusted accordingly. Usage was monitored to ensure that stock was rotated appropriately. Supplies were switched between the three units to ensure short-dated stock was used up if possible. The 1mg/ml ampoules remained as stock in reduced amounts to cover for supply shortages. Initially the Trust held larger stock levels of the syringes to avoid shortages, but because of the relatively short shelf life of the product, this proved difficult to maintain. Reduced stockholding proved to be difficult on the occasions where there were delays in receiving supplies from the manufacturer. In these circumstances, regular ampoules were used to make syringes on the ward.
Unit cost also became a factor as the price of the noradrenaline 1mg/ml ampoules fell during the use of the syringes. Cost should not be a barrier to safer practice but it is worth monitoring expenditure to ensure that costs remain within estimates. With several manufacturers now producing ready-to-use and ready-to-administer products, negotiating an effective contract is important to avoid over-paying.
Nursing staff were extremely positive about the syringes and were soon enquiring about the option of obtaining ready-to-administer products for other regularly used infusions. Since introducing the syringes, there have been no recorded cases of the incorrect strength being selected and a previous problem with poorly labelled syringes has been eliminated. The syringes have been introduced into theatres after nursing staff heard about them from their intensive care colleagues. Plans for introducing prefilled alfentanil syringes are currently on hold because of the complicated storage arrangements for this product. Ready-to-use glyceryl trinitrate, potassium chloride and dopamine are all being investigated.
The practice of vial sharing is banned under the Trust’s medicines management policy. However, in reality, the practice can occur without direct supervision. Vial sharing has never been an issue with noradrenaline, but by procuring ready-to-administer or ready-to-use products, it is one way for pharmacy to try and eliminate the practice. Another concern is the risk of de-skilling nursing staff by reducing the number of syringes they prepare. In critical care areas, this should not have a great impact because there are many products that require preparation. However, in other clinical areas, this could be a particular risk and must be considered before the introduction of ready-to-administer products.
The introduction of ready-to-use products into the critical care areas of North Bristol NHS Trust has not always been a straightforward process; however, the benefits in terms of safety by reducing the risk of preparation errors and the satisfaction of the staff have proven its worth. By considering some of the factors discussed in this article, the author hopes that critical care areas in other hospital will be inspired to standardise their practice and switch to ready-to-use products.
Key points
  • Injectable medicines are associated with higher incidences of errors in prescribing, preparing and administration compared with other medication forms. Many injectable medicines used in critical care are classed as having a medium or high risk of patient harm if errors occur.
  • In the UK it has been recommended that ready-to-use or ready-to-administer products of standardised strengths are made available to minimise risks. A set of standardised concentration has been adopted by the Intensive Care Society.
  • Noradrenaline prefilled syringes were introduced to the intensive care wards at North Bristol NHS Trust following an incident where a syringe was incorrectly labelled. Prefilled syringes are supplied as a labelled product, which eliminates the risk of this error occurring again.
  • Benefits of the syringes were: convenience; reduced preparation time; improved labelling; and reduced risk from preparation of syringes on the ward.
  • Issues with the syringes that had to be managed were: increased expenditure; increased storage space requirements;, management of cold change storage; management of damaged syringes; and use of alternative products during periods of supply shortage.
  1. National Patient Safety Agency. NPSA Alert 20. Promoting safer use of injectable medicines. 28 March 2007.
  2. Wheeler D et al. Variability in the concentrations of intravenous drug infusions prepared in a critical care unit. Intensive Care Med 2008;34:1441–7.
  3. Hardy L, Mellor L. Risk assessment of parenteral product preparation across secondary care acute trusts in the north of England. Hosp Pharm 2007;14:58–64.
  4. Borthwick M et al. A Survery to inform standardisation of intravenous medication concentrations in critical care. J Intensive Care Soc 2007;8:92–6.
  5. Borthwick M et al. Towards standardisation of drug infusion concentrations in UK critical care units. J Intensive Care Soc 2009;10:197–200.
  6. Intensive Care Society. Medication concentrations in critical care areas; 2010. (accessed 21 August 2012).

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