A medication error can be defined as ‘a failure in the treatment process (prescribing, dispensing or administration) that leads to, or has the potential to lead to, harm to the patient.1 A psychological approach of classifying errors has been created and is represented in the flow chart below. So each type of error irrespective of whether it is during prescribing, dispensing or administration should fall into one of the sub categories below.
Figure 1: The classification of medication errors based on a psychological approach.1
In the UK, 216 claims against GPs handled by the medical defence union between 1995 and 2001 were directly related to errors in prescribing, monitoring or administering medicines. When the department of health implemented the plan for improving patient safety one of its main goals where to reduce the number of serious errors in the use of prescribed drugs by 40%.8
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The National Patient Safety Agency (NPSA) is a special health authority that has been established to collect, analyse, and integrate information from NHS organisations, which will aid to produce alerts, guidance or signals to prevent adverse events from occurring. Medication errors can cost human life, livelihood or even careers of medical givers and also pose a huge financial burden on the NHS. It is important that these errors are reported and used as a lesson to prevent reoccurrence.8
There are different types of medication errors and are as follows
Wrong/unclear dose or strength, or wrong frequency
Omitted medicines
Wrong Medicine
Mismatch between patient and medicine
Wrong Formulation
Wrong Route
SCENARIO
A 60 year old man with known multiple myeloma presents to the hospital to receive his sixth cycle of VAD; The physician wrote:
Vincristine 1.6mg continuous infusion over Days 1-4
Doxorubicin 9.0 mg/m2/day continuous infusion Days 1-4
Dexamethasone oral 40mg/day Days 1-4, 9-12 and 17-20
Medication errors
The pharmacist dispensed
Vincristine 1.6 mg/day on days 1, 2, 3 and 4
Doxorubicin 90 mg/m2/day on days 1, 2, 3 and 4
Dexamethasone 40mg/day on days 1-4
Three weeks later
The patient comes back to the hospital complaining of
Shortness of breath and
Severe pain in his extremities. (He described it as shooting, burning pain associated with tingling and numbness).
The physician ordered a 2D echocardiogram for the patient which revealed an ejection fraction (EF) of 25% (last month, patient’s EF was 50%)
REPORT
Based on the scenario above, there were three medication errors made
The patient has been given tenfold more doxorubicin than prescribed.
The patient has been given four times more vincristine than prescribed daily
The patient has not been given a dose of dexamethasone for days 9-12 and 17-20
One of the main causes of the patients’ symptoms is due to the increased dose of doxorubicin. Doxorubicin or Adriamycin (which stands for A in the VAD cycle) belongs to a group of drugs called the anthracyclines. They are known to inhibit DNA replication by intercalating into the β-form of the DNA double stranded helix with guanine-cytosine site specific interactions. This causes a buckle in the conformation and results in a distorted DNA helix hence cell death.2
Anthracyclines are known notoriously for causing dose related cardiomyopathy. The summary of product characteristics of doxorubicin states that dosage is usually calculated on the basis of body surface area. The maximum life time cumulative dose is 550 mg/m2. The risk of developing Congestive Heart Failure increases especially once the patient has exceeded 300mg/m2. 3
The patient has just received 360mg/m2 (90mg/m2 x 4days) for the 6th cycle and has previously received 180mg/m2 (9mg/m2 x 4days x 5cycles) assuming all was correct. Making that a cumulative dose of 540mg/m2 which has almost the lifetime dose of 550mg/m2 and putting the patient at a higher risk for already developed or developing cardiomyopathy. The patient came back reporting of dyspnoea and had an ejection fraction that had dropped by 25%. An ejection fraction less than 40% is indicative of cardiomyopathy or heart failure.
The severe pain, numbness and tingling in the extremities can also be related to another dose limiting side effect called hand – foot syndrome. Mostly experienced with the pegylated liposomal type. The mechanism is unknown but one of the theories is that the high turnover rate of keratinocytes (epidermal cells) makes hands and feet more susceptible to damage and also ability of the drug to accumulate in the skin.4 This symptoms are more related to vincristine
Vincristine belongs to a group of drugs called the vinca alkaloids. They are found in the Madagascar periwinkle. They are inhibitors of mitosis in metaphase hence are M-phase specific. They bind to tubulin and inhibit the mitotic spindles forming. Vinca alkaloids can cause dose related neurotoxicity. It normally presents as peripheral paraesthesia (numbness, tingling, and pain).14, 15
The summary of product characteristics recommends that the maximum weekly dose for vincristine is 2mg. Any more than 2mg could be potentially very serious or even fatal. It could cause extreme bone marrow suppression and peripheral neuropathy. This patient is taking 6.4mg weekly which is the main reason why she is experiencing severe burning in her extremities.15
Dexamethasone is synthetic glucocorticoids which acts by inhibiting the action of inflammatory mediators and suppresses the humoral immune responses. In multiple myeloma dexamethasone inhibits the mRNA expression of interleukin-6 (IL-6) in myeloma cells. Myeloma cells produce IL-6 and express its receptor. Hence IL-6 is considered to be a mediator of plasma cell proliferation. It was found that dexamethasone may induce a plasma cell apoptosis by blocking the IL-6 connections.16 There have been very progressive studies that show that dexamethasone can reduce the cancer’s proliferating ability by up to 25-40%. It has also been show to increase the sensitivity of the cancer to other chemotherapeutic agents. So it is very important to keep taking it during the chemotherapy.16, 17
The errors will be based and classified according to the flow chart in figure 1 above
PRESCRIBING PROCESS
Errors that contributed are
Rule based error: The physician wrote the dose as ‘9.0mg/m2/day’. Prescribing guidance in the BNF states that ‘the unnecessary use of decimal points should be avoided, e.g. 3 mg, not 3.0 mg The dose is not wrong but it has been documented and advised against using decimal points when writing doses because the decimal point could be overlooked or not imprinted properly which could cause a patient to be given 10 fold increments.
An appropriate way would be ‘Doxorubicin 9mg/m2/day continuous infusion on Days 1-4’
Illegible handwriting and Clear instructions: looking at the prescription it seems quite obvious that the Vincristine should be divided into four doses for each day, but if the word ‘over’ was not written clearly or smudged, it could indicate 1.6mg every day. The ISMP guidelines also state that when prescribing for chemotherapy ‘Individual single daily doses in mg/m2 and the final calculated dose in mg should be stated.5
An appropriate way would be to add additional instructions to clarify the request.
‘Vincristine 1.6mg continuous infusion over Days 1-4 (0.4mg/day)’
Same could be said for the Dexamethasone; this would help to clarify instructions
‘Dexamethasone oral 40mg/day on Days 1-4, 9-12 and 17-20 (total of 12 days treatment)’
A patient with heart failure has an ejection fraction of 40% or less. One point for the physician to consider was the patient previous ejection fraction which was 50%. Although the patient’s starting ejection fraction before the chemotherapy was not given, it would be fair to say that it probably was a lot higher than 50%. Coupled with the fact that the patient is 60 years old. It might have been worth considering other treatment options due to cardiotoxicity.
DISPENSING PROCESS
Knowledge based and memory based errors
The pharmacist should have previous knowledge of
Potential cardiac toxicity of doxorubicin, hence should have calculated the dose that the patient had received up till day to ensure that the patient is not in the risk zone.
Dose recommendations of VAD cycle 1.6mg of Vincristine is normally given over 4 days rather than per day and
The Dexamethasone is give every 4days throughout the cycle
Rule-based errors
Good rules not applied or misapplied
It is good practice to check patient previous drug history to be able to highlight drug or dose changes. If the pharmacist had checked that the patient had received it 5 times before, the 90mg overdose would have been spotted.
The prescription was not crosschecked appropriately because it would have also been spotted that 8 days worth of Dexamethasone was not dispensed
Bad rules
The pharmacist did not query the prescription to confirm the dose of doxorubicin or vincristine. It was just ignored and all the precautions to check for safety of a drug were ignored.
Most nurses or another pharmacist know the drugs very well and another way of checking could have been to ask.
Action based errors
Technical errors
The inability of the pharmacist to spot that the doctor has written the Dexamethasone for 8 more days.
The pharmacist missed that the vincristine dose was over 4 days
The decimal point was not spotted in the doxorubicin dose.
Prevention of dispensing error6
Error reporting is important in both detection and prevention: This will help pharmacists, dispensers and technicians to be very careful when dealing with such prescriptions.
Pharmacovigilance is the process of monitoring, evaluating and improving the safety of medicines. It can be carried out from the stage of manufacturing till the administration of the medicine. It also involves detecting, assessing, understanding and preventing the adverse drug
Education: In pharmacy constant education and refresher courses are required to keep up to date with various changes and also to listen to case reports, events or reminders of drugs and their effects.
Computerized systems can contribute to prevention as well as detection: Computer programmes with alerts related to the drug and patient will definitely help with identification and clarification of suspect doses.
Most importantly Standard Operating Procedures should be outlined for every one working in the pharmacy to follow in order to dispense
Examples of medication errors that have been documented and implemented on are
Wrong formulation
A 41-year-old woman with a medical history of proliferative glomerulonephritis from systemic lupus erythematosus was admitted with a diagnosis of cryptococcal meningitis. Her physician prescribed liposomal amphotericin B 5mg/kg/day. She was given amphotericin B deoxycholate 5mg/kg.
The error was notice after she had already had two doses before it was stopped. She developed acute renal failure, anaemia and cardiac arrthymias. The patient was transferred to intensive care despite trying to reverse the toxicity she died six day after admission. 9
Another incident about confusion with amphotericin formulations occurred at Birmingham Heartlands Hospital in July 2007. Two oncology patients died after being treated with the wrong formulation of IV amphotericin. This confusion between the formulations can lead to an overdose resulting in fatality. It said that there had been 53 incidents involving the drug between January 2004 and July 2007.10
Amphotericin B deoxycholate has been reported to produce significant cardiac toxicity (arrhythmias and bradycardia) in adults and children with a history of heart disease and also renal toxicity in overdose.
The NPSA was alerted about these two recent fatal incidents that were reported to the National Reporting & Learning System. Prior to this there have been reports of confusion between the different formulations. In response to this The NPSA issued a Rapid Response Alert to make health care professionals aware of this confusion and to be very careful when prescribing, dispensing or administering this medication.11
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Wrong/unclear dose or strength, or wrong frequency
An overdose of Diamorphine was administered by a by an out of hours GP from Germany to Mr David Gray who unfortunately passed away. The NPSA previously published guidelines on the ‘safer use of injectables’ and ‘Ensuring safer practice with high dose ampoules’ but these was not implemented in a large amount of the NHS trusts. When this case was investigated it was noted that previous incidents that have been reported showed that some healthcare professional did not access the suitability and safety of the opioid doses prescribed.12
The NPSA issued another rapid response report ‘reducing dosing errors with opioid medicines’ which include guidelines to aid prescribers in assessing the needs of their patient and prescribe opioids appropriately.13
Conclusion
Medication errors are very common at every stage from prescribing to administration. It is important to be away of the error prone lists, recorded near misses an adverse evnts in order to prevent recurrence but most importantly to keep the patient safe.
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