Christine Clark PhD FRPharmS FCPP(Hon)
In the United Kingdom just over 133,000 medication incidents were reported to the National Patient Safety Agency (NPSA) in the year 2010–2011 out of an overall total of 1.3 million incidents, Laurence Goldberg (Independent Pharmacy Consultant, UK) told the audience. Among these there were 44 medicines-related deaths and 230 severe incidents. In the same year, the National Health Service paid out £863 million in compensation to patients and their relatives for clinical negligence.
Errors with injectable medicines
The process of preparing and administering intravenous medication involves many steps but the reconstitution and dilution stage is associated with the highest error rate, according to Pascal Bonnabry (Head of Pharmacy, Geneva University Hospitals). “Tackle this and you can eliminate a lot of errors”, he commented.
Errors with parenteral (injectable) products are nearly three times as likely to cause harm or death compared with other medication errors, according to American figures. The reason for the high risk is related to the probability of error, which is high because of the complexity of the process, and the serious nature of the clinical consequences of injecting the wrong preparation.
Human beings perform calculations poorly in real life situations, said Professor Bonnabry. In one study the contents of unused syringes of anaesthetic drugs had been analysed after the surgical sessions had ended. One third of syringes contained drug concentrations with errors of 10% or more, and 4% had errors of 100% or more. The widest variations were seen with fentanyl injection. In addition, studies suggest that microbial contamination of injections prepared in clinical areas varies between 10% and 40%.
The adoption of standardised concentrations and labelling could pave the way for the purchase of ready-to-use products from the pharmaceutical industry. However this was a huge task in one institution and it is something that, ideally, needs to be done nationally or internationally, acknowledged Professor Bonnabry.
A small number of ready-to-use injections are currently available, including bupivacaine for epidural use and morphine for patient-controlled analgesia. One problem is that there are many ‘customers’ in hospital with different interests and needs. The approach adopted at Geneva University Hospitals was first to collect from the clinical areas a list of drugs required in a ready-to-use or ready-to-administer form. These were then risk-assessed by considering the probability of errors and the severity of the consequences, in order to determine a priority order. Finally the feasibility of batch production was evaluated, and at this stage unstable products were rejected. Products that are stable from four months to one year are considered suitable. The aim was to start batch production of stable products and add one or two to the list each year. At present about 30,000 doses are batch-produced each year. The top three products are phenylephrine 1mg in 10ml, insulin 50 units in 50ml and suxamethonium 100mg in 10ml.
Good manufacturing practice
Nurses will always question the claim that it is safer to use ready-to-use injections supplied by the hospital pharmacy and it is important to explain the implications of Good Manufacturing Practice (GMP) and show them the preparation environment. “This is a change of paradigm”, he emphasised. GMP improves safety through two key mechanisms.
First, the opportunities for errors are suppressed through good procedures, computer-assisted production management and the use of aseptic facilities. Second, errors are intercepted before they reach patients through chemical and microbiological quality controls. In Geneva University Hospitals a computer-assisted production process has been developed for drugs that are made from raw materials. It checks and records both operators and ingredients.
This type of approach is known to work well because a recent study in Germany showed that 22% of injections made manually in the intensive care unit deviated from the stated concentration by more than 10% compared with 5% of those made by automated systems in the pharmacy, explained Professor Bonnabry. Aseptic preparation in Geneva University Hospital is undertaken in a Class C
(ISO 7) GMP clean room. Isolators are sterilised with hydrogen peroxide and a Smartfiller® (Added Pharma) pump is used to fill syringes. Simulation studies have shown that injections prepared in a clean room have a 0% microbial contamination rate compared with 6% for operating room and 16% for wards.
Turning to pharmacoeconomics, Professor Bonnabry described how costs could be modelled to take into account the investment costs of a clean room and equipment, development costs, such as stability studies, and costs of preparation. Using phenylephrine as an example and taking a five-year time horizon, he calculated that, for 30,000 syringes per year, the cost per syringe was €5.30, compared with €6.90 for ward-based preparation. This included an estimate of cost avoidance as a result of serious adverse events avoided but did not include the cost-saving that would be made by reducing the numbers of syringes prepared in advance by anaesthetists but discarded unused at the end of an operating session.
The introduction of ready-to-use syringes goes hand-in-hand with other innovations for safety such as electronic prescribing, automated dispensing, the use of smart pumps and the use of barcode scanning on wards to verify drug and patient identification, concluded Professor Bonnabry.
Safer infusion therapy
Errors occurring during the preparation and administration of injectable medication on wards are unlikely to be recognised or intercepted according to Peter Keeling (consultant anaesthetist, Frimley Park Hospital, UK). Errors related to intravenous injections account for up to 60% of serious and life-threatening potential adverse drug events. Errors in prescribing, preparation and administration of injectable medicines are also more common than with other medicines and studies have shown that calculation errors are common.
In one study that examined the variability in concentrations of intravenous infusions prepared by staff in a critical care unit, six out of 30 magnesium infusions contained up to five times too much magnesium – something that could be quite dangerous, noted Dr Keeling.
In the UK, the National Patient Safety Agency (NPSA) had recommended that risk assessments be undertaken for all injectable medicines and that essential technical information, for example, about reconstitution and dilution, be available at the point of use. The NPSA also recommended the use of ready-to-administer or ready-to-use injections of standard strengths. The main barrier to the introduction of standardised injections is variations in clinical practice, explained Dr Keeling. A recent survey of 154 intensive care units in the UK had revealed wide variations in the concentrations and presentations of common injections. For example, no fewer than 23 different concentrations of phosphate injection were in use. A subsequent survey had established that there was about 74% agreement for standardised concentrations of about 20 drugs. As a result, the Intensive Care Society in the UK has now published on its website a list of 16 drugs with recommended standard concentrations.
From the medical viewpoint there are a number of advantages associated with the use of standardised concentrations, said Dr Keeling. They create the opportunity for batch production and this could enable the development of licensed products at realistic prices. Dosage and demonstration charts could be prepared to simplify prescribing and administration and electronic prescribing should be easier to implement. The safety benefits could be considerable, as nurses and doctors would not need to familiarise themselves with new protocols – with the attendant risk of errors – as they move from one ward or unit to another, he added
The full benefits of standardised concentrations for injectable products would be achieved if they were to be adopted throughout Europe, and, possibly also in the USA, said Dr Keeling. In future he hoped that stable injections of standardised concentrations with bar-coded labels would be available from the pharmaceutical industry. These could then be administered using smart pumps with dose-checking software.
In closing the symposium, the chairman, Laurence Goldberg, reiterated the take-home messages from the two speakers:
- Identify high-risk injectable drugs
- Simplify and rationalise the range and presentation of these high-risk injectable drugs
- Provide, where possible, high-risk injectable drugs in a ready-to-use or ready-to-administer form
- Prepare injectable drugs in a GMP‑compliant hospital facility or outsource them from the pharmaceutical industry
- Consider the use of ‘smart’ pumps for the administration of high-risk injectable drugs.
Mr Goldberg concluded that patient safety is affordable but that it is up to pharmacists to ensure that a sound business case is presented to hospital management boards.
The B Braun satellite symposium ‘Is Patient Safety Affordable?’ took place at the European Association of Hospital Pharmacists Congress in Milan, Italy on
21 March 2012.