Any adverse event involving medication in a hospital is commonly considered to be “a pharmacy problem” and yet many events take place outside the pharmacy where pharmacists may have little influence over what happens, said Natasha Nicol (Director of Global Patient Safety Affairs, Cardinal Health, USA). There are about sixteen steps involved in getting medications from the pharmacy to the wards, each of which represents a potential error point, she continued.
Adverse events are rarely due to a single person or an isolated action but time is often wasted looking for a cause when it would be better to get the whole story. Other common mistakes include assuming it is the manager’s duty to fix events, focussing preferentially on “big, bad, ugly” events and remaining reactive – waiting for something to happen and then trying to fix it, rather than pro-actively tackling risks, she said. It is important to understand the roles of human error and system design.
You get the results that the system is designed to deliver. Although safety is almost always a core value in a hospital’s mission, the drive for productivity often conflicts with safety activity and factors such as fatigue, distractions and stressful environments can influence individual behaviour, said Dr Nicol. As a director of pharmacy, she had told her staff that men did not need to wear ties and women did not need to wear skirts because physical comfort at work would help them to perform at their best.
Dr Nicol recommended that pharmacists should focus on prevention strategies. Predictive assessment, instead of reactive approaches, would be really helpful, she said. It is also important to understand people’s motivations and to ensure that policies and procedures are workable in practice. In addition, they should avoid common mistakes, such as trying to investigate everything, viewing any deviation as a violation and failing to ask tough questions to avoid conflict. She suggested that one useful approach would be to use ‘triggers’ such as heavy use of reversal agents including naloxone, vitamin K, protamine and glucagon, to identify problems.
Regarding IT, she said that nurses tend to ‘drift’ from barcode medication administration (BCMA) and devise ‘workarounds’. However, they only do this “because we gave them a poor system. Sometimes the workaround is a better way – so keep an open mind”, she cautioned. Similarly, there should be constant engagement with physicians to monitor electronic prescribing systems and regular reviews of library compliance with smart pumps. As a way of getting started, Dr Nicol recommended visiting one or two departments to find out how they work. “Do not wear a suit or clickety heels and say you are there to learn not to check”, she advised.
Medication use processes
A fatal error in a labour and delivery unit in which a bag of bupivacaine intended for epidural administration was accidentally administered by the intravenous route served to illustrate the impact of shortcomings in the medication use processes, according to Matthew Grissinger (Director, Error Reporting Programs, Institute for Safe Medication Practices, Philadelphia, USA). Although a barcode administration system had recently been introduced the patient was not wearing an identity band, the anaesthetists were intimidating and the nurses were pressured to prepare bupivacaine injections before the orders were written.
In addition, the nurse was tired, having worked two consecutive eight hour shifts followed by a short break, and was distracted by arguments between the 16-year-old patient’s mother and boyfriend. In spite of an exemplary record, she was charged with criminal neglect and faced a possible six-year prison sentence and $25,000 fine. The problems were not directly related to the medication but to the whole system, said Mr Grissinger.
Some 15% of adverse drug events are due to ‘wrong drug’ errors, with other problems accounting for the remaining 85%. One common problem area relates to the documentation of allergies. It is important to find a description of the reaction that led to the diagnosis of an allergy because the label is often applied inappropriately, for example, a digestive upset with a penicillin can be incorrectly documented as a penicillin allergy.
Another common problem is failure to record the patient’s weight accurately with consequent overdosage – and this can be a serious issue, for example, with heparin dosing where the risk of bleeding can be increased. Although no drugs are dosed by body weight in pounds, in the USA (and two other countries) patients are still routinely weighed in pounds. A surprising number of errors have occurred, not because of calculation errors, but because the numerical value of the weight in pounds was used in the milligram per kilogram formula. In addition, nurses sometimes estimate body weights but patients are better at estimating their own weight than either doctors or nurses, said Mr Grissinger.
Turning to drugs in anaesthetic practice, Mr Grissinger pointed out that labels are often limited or absent when physicians prepare injections. This issue appears regularly in the top five problems identified in Joint Commission inspections of office-based surgery settings, he noted. He urged pharmacists to take time to observe how medicines are handled and administered on wards, and also to consider areas such as radiology where they might not yet have visited.
Pain management is an area of IV medication use that can pose significant risks. Confusion between morphine and hydromorphone was so frequent that eventually hydromorphone had to be removed from the electronic prescribing system, said Rita Shane (Chief Pharmacy Officer, Cedars-Sinai Medical Center, Los Angeles, USA). Monitoring patients for sedation is essential during opioid use, especially for patients receiving patient-controlled analgesia. End-tidal carbon dioxide measurement is the ‘gold standard’ but this is difficult to implement as patient acceptance can be problematic.
Pulse oximetry can be very effective if linked to a nursing alert (to warn the nurse of falling oxygen saturation), according to a Cochrane review but it is unhelpful if the patient is receiving oxygen, said Dr Shane. Sharon Steingass (Director, Innovation and Communication, The Ohio State University James Cancer Hospital, Columbus, Ohio) commented that the modified early warning (MEW) score which combines pulse oximetry, vital signs and level of consciousness, provides a good early warning sign and can be built into electronic systems.
Use of a virtual interactive cleanroom improved pharmacy students’ knowledge of aseptic procedures considerably, according to John Hertig (Associate Director, Center for Medication Safety Advancement, Purdue University, Indiana). The web-based Virtually Interactive Cleanroom (VIC) works much like a video game. It allows students to undertake a range of activities including handwashing and gowning, compounding of injectable doses and disposal of waste.
This “makes students feel more comfortable when faced with the real thing”, said Dr Hertig. The software was translated into Mandarin and tested in five Chinese hospitals in Shanghai. The hospitals compounded an average 5000 doses per day and had significant training needs. The results showed that age and gender were important predictors of acceptance with young men liking it best. The technology was a useful adjunct to didactic teaching and had considerable potential for continual competency assessment, he said. It is essential for the simulators to look like the actual working environment. Feedback from the users indicated that they wanted more real-time feedback and a multi-player version.
Implementation science, which provides a systematic method of planning and evaluating practice changes, was used to evaluate the impact of redesign of the discharge medication pathway at Kings College Hospital (KCH) in London. Raliat Onatade (Deputy Director of Pharmacy, Clinical Services, KCH NHS Foundation Trust) described how KCH handles up to 3000 admissions and discharges each month, but junior doctors prioritise sick inpatients over discharges and so preparing the discharge prescription is frequently delayed. The discharge pathway was redesigned such that discharge medication lists were prepared by pharmacists, in consultation with the patients, nurses and doctors.
Doctors then write the clinical summary and check and sign the medication list. The consolidated framework for implementation research was used to ensure that all organisational, professional and cultural elements of the change were fully addressed. One doctor commented, “It’s amazing… when pharmacists do drug lists, they pick up so many medication issues that we have not even thought about and they deal with it…”
On-demand, miniaturised drug production
Methods for small scale, point-of-use manufacture of drugs have now reached an advanced stage according to scientists from the Massachusetts Institute of Technology. The Battlefield Medicines Programme of the Defense Advanced Research Projects Agency (DARPA) set out to develop methods for miniaturised manufacture of drugs – both small molecules and biologics – in response to specific battlefield threats and medical needs.
(DARPA is an agency of the US Department of Defense responsible for the development of emerging technologies for military use). Conventional drug manufacturing and logistics are relatively slow processes and not sufficiently fast or flexible to respond to urgent needs, explained Tyler McQuade (program manager, DARPA). Once developed, the new methods could have other applications such as tackling drug shortages and responding to emergency situations, he added.
As part of this initiative, two linked projects have been developed – the ‘Pharmacy on Demand’ (PoD) programme for small molecules and the ‘Biologically-derived Medicines on Demand’ (Bio-MOD) programme for biologics. The PoD programme aims to develop a small molecule manufacturing device that will be the size of a desk-top printer; so far it has been reduced to the size of a domestic fridge, Klavs Jensen (Warren K. Lewis Professor, Massachusetts Institute of Technology) told the audience.
This has been achieved by developing continuous-flow manufacturing processes rather than the batch processing methods that are used for conventional drug manufacturing. This is advantageous because it uses small amounts of starting materials and avoids accumulation of toxic or reactive intermediates. The challenge was to ensure that all the processes occur simultaneously, in the correct sequence and in a small space, he explained.
Simple drugs that required few steps were tackled first. For example, a continuous process for aliskiren manufacture (developed with Novartis) was able to produce 45g/hour but the equipment was the size of a shipping container. Progressively more complex processes were tackled, including some that required high temperature and pressure at certain points and pumps to drive separators (to remove by-products). The process for fluoxetine involves four reactors, four separations and 11 pumps, said Professor Jensen.
These processes will produce liquid dosage forms that are stable for 14 days. Liquids are easier to pump and mix, noted Professor Jensen.
Ultimately the vision is to design reactors like compact disc boxes that can be fitted together with disposable tubing to provide a fully automated process.
So far this project has demonstrated that end-to-end continuous pharmaceutical manufacture is possible in a reconfigurable system. Professor Jensen said, “this is a true example of the value of multidisciplinary research” drawing on the combined skills of chemical engineers and formulation scientists.
Biologics on demand
The objective of the Bio-MOD programme is to produce multiple protein-based drugs with high purity, efficacy and potency, at the point of care in less than 24 hours. A critical advance in the manufacture of biologics on demand has been the development of cell-free biological systems to synthesise drugs, explained John J Lewin III (Director, critical care and surgery pharmacy division, Johns Hopkins Hospital, Baltimore).
The advantage is that cell lysates can be dried and reconstituted when needed. Lysates of genetically-modified cells have been used to produce streptokinase and EPO; expression of the protein starts within a few hours of reconstitution of the cell lysate, said Dr Lewin. Manufacture and purification of the drug using this approach can be fully automated and the ‘bioreactor’ looks like an IV bag, he added.
Another project involves using a yeast, Pichia pastoris, that can perform humanised glycosylation which is essential for preserving the structural and functional activity of a protein. Using this organism, a prototype benchtop system has been developed that can produce more than 100 doses of interferon a-2b in two days, said Dr Lewin.
The 50th American Society of Heath-System Pharmacists (ASHP) Midyear Clinical Meeting was held in New Orleans, Louisiana, USA in December 2015.