Objective To study reconstitution and preparation dosing errors of liquid oral medications given by caregivers to children.
Methods A prospective observational study was carried out in the departments of general paediatrics and emergency paediatrics at the Robert-Debré Children's University Hospital. An interview with caregivers involved (1) practical reconstitution and preparation of an oral liquid medication from a prescription drawn at random (amoxicillin (Clamoxyl, dosing spoon) or josamycin (Josacine, dose-weight pipette)) and (2) a questionnaire about their use.
Results One hundred caregivers were included. Clamoxyl and Josacine were incorrectly reconstituted in 46% (23/50) and 56% (28/50) of cases, respectively, with a risk of underdosing of Clamoxyl (16/23) and overdosing of Josacine (23/28). Dose preparation with the dosing spoon was incorrect in 56% of cases, and in 10% of cases with the dose-weight pipette. Female sex, native French speaker, and age were significantly associated with correct reconstitution. Male sex and medication were significantly associated with correct preparation.
Conclusions This study highlights the high incidence of errors made by caregivers in reconstituting and preparing doses of these liquid oral medicines, which are associated with considerable risks of over- and underdosing. Factors associated with these errors have been identified which could help health professionals to optimise their strategy for educating families about the use of liquid oral medications and the need to check that they understand these instructions.
- General Paediatrics
- Medical Education
- Paediatric Practice
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What is already known on this topic
Administration devices for oral medications can cause problems which are linked to significant risks of errors.
The US Food and Drug Administration (FDA) has released guidelines on administration devices for self-medicated over-the-counter proprietary products.
The majority of these devices do not meet the FDA guidelines.
What this study adds
Results showed a high incidence of errors made by caregivers in reconstituting and preparing doses of these liquid oral medicines linked to the use of dosing spoons.
Different factors were identified that could help health professionals to educate families about the use of administration devices for oral medications.
Oral liquid medications are the pharmaceutical forms of choice for children and also for adults with dysphagia. In the majority of cases these proprietary products are provided with administration devices with graduation units. The dose-weight pipette is a pipette which directly delivers the dose corresponding to the child’s weight. This is available particularly in the packaging of medicinal products in Europe but is less common in North America. In Europe, an oral syringe is the most used device to administer liquids, followed by a spoon. Spoons are also used more often in France than in other European countries.1
These devices have been found to cause administration problems linked to significant risks of errors.2 The graduations proposed do not always correspond to the dosages described in the summaries of product characteristics. The graduation units vary between proprietary products and occasionally different units are on the same device. Some devices can be associated with variations in volume of over 10% (spoon, beaker, and graduated beaker).3 ,4 A study showed up to 50% variation of the targeted volume with spoons with ¼ and ½ graduation marks.5
According to the report by the American Association of Poison Control Centers (AAPCC) in 2010, 50% of exposures calls to poison centres involved children under 5 years old and approximately 37% involved children under 3 years old.6 The most common errors involving children were a dosing error and confusion between measurement units and errors in the preparation of the dose to be administered. Between 2005 and 2013 in France, 109 cases of administration errors were reported for oral solutions, 102 (94%) of which were in the paediatric population.7 Another study showed 39.4% of caregivers made an error when they prepared the intended dose.8
Faced with these problems and the risks of errors, the Consumer Healthcare Products Association (CHPA) and the Food and Drug Administration (FDA) in the USA produced guidelines on administration systems for companies in order to reduce administration errors for self-medicated over-the-counter proprietary products.9 ,10 Following this publication by the FDA, a US study showed that 98.6% of these devices did not meet the FDA guidelines.11 The European Medicines Agency has also produced more succinct guidelines on graduations and the appropriateness of administration systems.12
Many of the published studies have mostly examined differences in volumes obtained using domestic spoons or oral syringes, either theoretically (by measurement of the volume taken up by the device) or by caregivers.13–15 The analyses of errors in medications given to children were conducted in hospital and primary care settings, although these analyses involved administration errors overall and did not specifically target liquid medications.6 ,16–18
The primary aim of our study was to assess the incidence of reconstitution and preparation errors of liquid oral medications prepared using a dosing spoon or dose-weight pipette by the caregivers of children hospitalised at the Robert-Debré Children's University Hospital.
The secondary aims were to assess caregivers’ knowledge about liquid medications.
Patients and method
A prospective, single centre, observational study was carried out in the Robert-Debré Children's University Hospital (Paris Public Health Service—AP-HP) in the department of general paediatrics and the paediatric emergency department.
The inclusion criteria were caregivers of children hospitalised in the department of general paediatrics or caregivers consulting the emergency department, regardless of age, who understood French. The caregivers were defined as people who prepared a medication for a child and were present at the visit to the emergency department or during the stay in the general paediatrics department. The caregivers were included in chronological order on admission of the child whom they were accompanying. They were given explanations (evaluation of difficulties encountered about reconstitution or dose preparation) about the study and provided with an information letter by the pharmacist who led the study. The exclusion criteria were refusal to take part and caregivers already previously included in the study.
Conduct of the interview
The patients were randomly assigned to one of two antibiotic treatment groups (amoxicillin or josamycin) using different methods of reconstitution and administration: (1) Clamoxyl 500 mg/5 mL (amoxicillin): powder for oral suspension to be reconstituted, presented with a 2.5 and 5 mL graduated dosing spoon; and (2) Josacine 500 mg/5 mL (josamycin): powder for oral suspension to be reconstituted, presented with a dose-weight pipette. Randomisation was stratified by department. The caregivers were given a prescription; these were not prescriptions written specifically for the patient being followed, but a practical exercise using an identical prescription in each study arm. Doses were administered by dosing spoon for Clamoxyl and dose-weight pipette for Josacine.
After the practical stage, the caregiver was asked to answer a questionnaire assessing his/her general knowledge about oral liquid medications (disposal, shelf life, loss of a device, place of storage and whether or not they always read the product leaflet).
The primary end point was the percentage of reconstitution or preparation errors of the liquid medications by the caregivers. The bottle was reconstituted correctly if the final reconstitution volume was correct without agglomerates (clumps). The dose to be administered was prepared appropriately if the device was filled correctly with the dose prescribed on the standard prescription. Overconcentration was determined if the measured liquid height was below the theoretical liquid height. Dosing error was considered if the error exceeded 10%.
The secondary end point was the caregivers’ general knowledge about liquid medications.
The data collected on the patients were their age and hospitalisation department; the data collected on the caregivers were their age, whether they were native French-speaking, the number of children under 6 years old they were responsible for, the family relationship with the patient, socio-occupational category, and whether or not they had previous experience of administering paediatric oral liquid medications. The data were recorded on a case report form produced specifically for this study and then registered in the EpiData software (V.3.1, Denmark).
Results are expressed as numbers and percentages for categorical variables and as mean±SD for continuous variables, according to their distribution. Factors independently related firstly to a reconstitution error and secondly to a preparation error were investigated using multivariate logistic regression models. Variables significant at a 20% threshold in the univariate analysis were included in the multivariate model. In order to select predictive factors for the event being studied a stepwise approach was used, and variables which were significant at a 10% threshold were included in the final model. Lack of co-linearity normality of residuals and lack of homoscedasticity were checked. All of the tests were two-tailed.
Calculation of the number of subjects required
The expected error rate was estimated to be 20%.17 Inclusion of 100 subjects consistent with recruitment feasibility was intended to assess this percentage error rate with a precision of 0.08 at a statistical probability threshold of 5%.
The protocol was submitted to and accepted by the Robert-Debré Hospital Ethics Committee (2013-68). If an error occurred or a question was raised during the interview, the caregivers were provided with an explanation. At the end of the interview with the caregivers, they were given a form summarising the explanations on the reconstitution and preparation of a liquid medication which was explained to them.
One hundred caregivers were questioned. The characteristics of the caregivers are shown in table 1.
In the practical preparation section, 31 (31%) of the caregivers read the leaflet on their own initiative.
Correct reconstitution rates for the two antibiotics are shown in table 2.
The main reconstitution error for Clamoxyl was the change in reconstitution method and ambiguity regarding the bottle type (figure 1A, B). The previous bottle had an encrusted line on the bottle glass which showed the volume to add (figure 1A). The red arrow and black line on the new bottle showing the water volume limit was not clearly visible according to those caregivers who made a reconstitution error (figure 1B).
The results on correct dose preparation by the caregivers are shown in table 2. Twenty-eight preparations (56%) resulted in underdosing for Clamoxyl. These dosing errors were explained by incorrect use of the dosing spoon. Twenty-six of the 28 caregivers who prepared an underdose thought that the line on the spoon represented a dose of 500 mg, whereas in reality this is half the dose (250 mg) (figure 1C). The caregivers said that the 2.5 and 5 mL graduations were not clearly visible.
Reconstitution errors for Josacine were due to difficulties in mixing it to form a homogenous suspension after putting the water in the bottle, as the caregivers had to shake the bottle very vigorously or even tap its sides for a period of time (average mixing time: 43 s (22–60 s)). They forgot to shake the bottle before adding the water in order to detach the powder from the walls of the bottle and it was then difficult to obtain the suspension. In addition, the caregivers did not wait for the foam to settle and/or did not adjust the water level after shaking, leading to overconcentration (median increase in dose: 22% (11–33%)).
The results of univariate and multivariate analysis of factors associated with incorrect reconstitution or preparation are shown in table 3.
The multivariate analysis shows that male caregivers and those of non-native French-speakers were more at risk of incorrectly reconstituting the product. The risk of incorrect reconstitution decreased with caregiver’s age. The risk of incorrect preparation was higher for Clamoxyl and in female caregivers.
The caregivers’ responses to the questionnaire about the use of liquid suspension medications are shown in table 4.
Eighty-two per cent of caregivers said that they had read the leaflet. Caregivers preferred to trust the pharmacist or doctor or did not read the leaflet for two reasons: complexity of the leaflet, and illiteracy. Caregivers mainly read the leaflet for information on the adverse effects of the medication.
This study shows a considerable percentage error in the reconstitution and preparation of oral suspensions by caregivers. Two different methods of reconstitution and dose preparation were assessed. Almost 50% of caregivers did not correctly reconstitute the medication regardless of method, and almost 50% made an error in preparing the dose to be administered with the dosing spoon.
Experience may be a positive factor in correctly reconstituting antibiotics. Women make fewer reconstitution errors than men. This result is consistent with the study which has shown that a greater proportion of women understand medical instructions.19 Women are also more often involved in care provided to children. Age of caregiver is also a predictive factor for correct reconstitution. This may be due to the caregivers’ experience in administrating medications to their children.
Handling practice is a factor found to be responsible for errors about reconstitution or use of administration devices. Caregivers were less attentive and did not read the accompanying leaflet when they had already used Clamoxyl and thought all medications were reconstituted in the same way.20 Another study showed that caregivers made fewer errors with methods of administration of medications which they did not know compared to those which they had already handled (60% compared to 28%).7
Reading the leaflet does not emerge as a factor which reduces the risk of incorrect reconstitution. The leaflets contain too much information in order to be read correctly, while no native French-speaker made significantly more dose reconstitution and dose preparation errors.21 The diagrams showing the dose preparation method were recommended in the CHPA guidelines but have not been included in the FDA guidelines.10 Unlike France, in other countries such as the USA and Canada oral suspensions which are available in powder form are reconstituted by dispensing pharmacies, thereby avoiding reconstitution errors.
The errors in dose preparation particularly involved the presentation of the administration device. Caregivers were at 12 times greater risk of making an error with the dosing spoon than with the dose-weight graduated pipette.
The dosing spoon has a number of disadvantages. Legibility and clarity of the measurement graduation led to an error in 56% of caregivers. The 2.5 and 5 mL markings are not clearly visible on the dosing spoon (figure 1C); the main risk is therefore of underdosing which may be associated with ineffective antibiotic therapy or emergence of resistance, particularly for amoxicillin and reduced penicillin sensitive pneumococci, whereas the current guidelines for doses of amoxicillin in upper respiratory tract infections have been reviewed upwards.22 ,23
The dose-weight administration devices are easier to use, particularly for self-medication, and require fewer explanations, but it is difficult to adjust doses with these devices. The oral syringe which takes up a volume set by the prescription was not examined here but also appears to reduce errors by parents. They allow a more refined adjustment of dosage.24 ,25 Approximately 25% of prescriptions are not consistent with the proprietary product dispensed in pharmacy in terms of volume units.26 Fifty cases of confusion with household spoon and mL have been reported by the Institute for Safe Medication Practice (ISMP) and almost 8500 cases of confusion about units of measure have been reported by the AAPCC in 2010.6 ,27 The oral syringe may therefore be a solution, although it is essential that the device is changed and possibly that measurement units are accompanied by explanations by health professionals to the parents.
If an administration device is lost, a significant number of care workers use domestic spoons (25%) which carry a risk of dose variability, or they use the device for another medication (12%). One study has shown that almost half of caregivers do not know how to recognise a teaspoon compared to other domestic spoons. In addition, they cannot perform accurate conversion calculations such as conversion from weight in pounds to kilograms.28
The French National Agency for the Safety of Health Medicines and Health Products has carried out an awareness campaign for health professionals and parents with a view to reducing this type of error.29
Our results may be influenced by the fact that this study was carried out in a hospital and not in a patient’s home under actual conditions. For ease of analysis reasons we only compared two devices and only two prescription medications. We did not include patients who did not understand French for practical study organisational reasons. It would be interesting to carry out a study of the same type adapting the explanations for this population.30 Our study was focused on antibiotics and it would be interesting to measure the clinical impact of under-dosing and to assess the percentage of reconsultation and/or attendance at the emergency department because of a recurrence of the illness.
The dispensing pharmacist has a role to play in preparing and reconstituting liquid medications. The impact of the pharmacist has been demonstrated in several studies; an interview with a pharmacist combined with giving out a leaflet reminding users about the reconstitution of an oral suspension appears to prevent many errors compared to handing out these forms or the product leaflets alone.31 The pharmacist must also be vigilant in looking for inconsistencies between prescription units and units on the medical device and make the necessary conversions to avoid errors.
This study has identified errors made by caregivers in reconstituting and preparing the dose of commonly used medications. These errors may have mild or severe consequences, depending on the type of medication and the patient’s health. It raises questions as to the use of the dosing spoon. Factors associated with these errors have been identified which could help health professionals to optimise their family education strategy on the use of oral liquid medications. These results are consistent with the findings of an awareness campaign on the use of administration devices for oral medications.
In comparison with the FDA, guidelines for companies about the use of administration devices for self-medication and medications on prescriptions are essential.
We thank Paris Public Health Service—AP-HP for financing the project with the medal internship programme. We thank all the physicians and nurses at the paediatric emergency department of the Robert Debre Teaching Hospital for their contribution to the study. We are indebted to the children and their parents for participating in the study.
Twitter Follow Sonia Prot-Labarthe at @sprotlabarthe
Contributors SP-L, AB-A conceptualised and designed the study, drafted the initial manuscript, and approved the final manuscript as submitted. DG carried out analyses, reviewed and revised the manuscript, and approved the final manuscript as submitted. PBr, PBo reviewed and revised the manuscript, and approved the final manuscript as submitted. ML, XB, PF and PM reviewed and revised the manuscript, and approved the final manuscript as submitted.
Funding All phases of this study were supported by the Internship Medal Program, AP-HP, Paris, France.
Competing interests None declared.
Ethics approval Robert-Debré Hospital Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.