Articles

Good Idea, Bad Execution: Dosing Errors, A Preventable Harm

We spend a lot time at SBM discussing different elements of the art and science of medicine, and how we believe that practice can be improve. Yet our science-based intentions can be thwarted at the last possible moment – in the form of dosing errors. The workup may have been comprehensive, the diagnosis could be correct, the most clinically and cost-effective intervention chosen, and whammo. An overdose or underdose, possible toxicity, and a failure to achieve the desired outcome. It’s a completely avoidable, but often overlooked aspect of the practice of medicine.

In my last post, I noted how cough and cold products for children have largely been withdrawn from the market due to their lack of efficacy, and the risks related to toxicity. Today’s post is going to dive a little more deeply into factors that can contribute to toxicity in the pediatric population. Let’s start with a vignette that may be familiar to parents:

The new father is wakened from a blissful, deep sleep by a crying child. Once Dad realizes when and where he is, and the source of the crying, he silently curses the short duration of action of the acetaminophen liquid he gave his child at bedtime. It has probably worn off already, and the fever is back.  Stumbling into his child’s room in the dark, he can feel the heat radiating off his body.  He fumbles around for the Tylenol, and something to measure it with. He can’t find the dropper bottle, but finds a bottle of syrup. It’s hard to measure the dose in the dark, and the medicine cup he finds is hard to read. “I think the dose is a teaspoon..that’s 5mL”.  He pours the medicine into his child’s throat, tucks him back into bed, and both are back asleep within minutes.

Did this parent measure the acetaminophen dose correctly? What factors could contribute to a dosing error in this situation?

Dosing errors are the among the most common and most preventable causes of adverse drug events in children. Why children? Drugs for children are often in liquid form for ease of measurement and administration. Typically dosed based on milligrams per kilogram, liquid formulations allow us to (in theory) deliver the exact dose that’s appropriate. But measurement isn’t always easy or intuitive. What’s the best way to measure 2.5mL (half a teaspoon)? How easy is it to confuse teaspoons (5mL) and tablespoons (15mL)? And what instructions should health professionals give parents and caregivers to ensure they can measure and administer a dose accurately? Despite the prevalence of dosing errors, there has been little evidence telling us what health professionals, or parents, can do better. Until now.

In a study by Yin et al in Archives of Pediatric and Adolescent Medicine, the authors set out to determine what works, and what doesn’t, when it comes to measuring liquid medications for children. When measuring a liquid, formulation-specific issues such as viscosity (thickness) and surface tension affect the way a liquid behaves. The delivery instrument of choice should compensate for these factors, so the correct dose is administered. In health care settings, the oral syringe is preferred as many of these factors are minimized. But what about in the hands of consumers?

The Study

The study design was simple but effective. Parents were enrolled from a pediatric clinic. All were instructed to measure 1 teaspoon (5mL) of a medication (acetaminophen) using six different measurement methods (links are sample images):

Each participant measured using all devices, but they were presented in random order. The measured dose was compared (by weight) with a reference dose drawn up with an oral syringe. Literacy of participants was also assessed using the Newest Vital Sign test, to evaluate what influence that might have on measurement practices. Sociodemographic and child health status information were also collected.

The investigators defined an appropriate dose as one that contained no more that 120% of the expected dose. A small error was 120% to 140%, and a large error was anything more than 140% of the target 1 tsp (5 mL) dose.

The Results

302 subjects were recruited; they were mainly female (95%), Hispanic (80%), and non-US born (76%). About half were high school graduates (51%) and the majority were predicted to have a high likelihood (41%) or possible likelihood (38%) of limited literacy.

Underdoses with all devices were virtually nonexistent. Excess doses, on the other hand, were common. The worst product was the printed dosing cup, where only 30% of parents could measure a dose accurately. The etched dosing cup was a bit better, at 50%. The dropper had the most accurate dosing, with 94% measuring correctly. The syringe was 91%, and the dosing spoon was 86%.

When literacy was examined, it was negatively correlated with dose measurement accuracy. That is, caregivers with lower literacy were more likely to make “large errors” with the different dosing instruments. These errors were far more common with the dosing cups, however.

So what can we conclude? Devices matter. Oral syringes are the gold standard for accuracy, and in the case of prescription drugs, should probably accompany all liquids dispensed. Other devices are more or less accurate.  Consider in the context of our sleep-deprived father measuring acetaminophen.  What are the odds that he’ll measure the dose correctly? To answer that, we need to look at how over-the-counter products are labelled, packaged, and used.

Designed for dosing errors?

In late 2009, in response to over-the-counter unintentional overdoses, the FDA released voluntary guidance to industry. Recommendations were as follows:

In a second paper by Yin and associates, just published in the Journal of the American Medical Association, the authors set out to evaluate the dosing directions and measuring devices that accompanied currently marketed pediatric cough and cold products.

The Study

This was a descriptive study that looked at 200 top-selling pediatric over-the-counter oral liquid medications. Samples represented 99% of the U.S. market for analgesics, cough/cold, allergy, and gastrointestinal oral liquids. Products were scored on the following:

  • inclusion of a measuring device (dropper, cup, syringe, etc.)
  • Within-product consistency between labeled directions and markings on the measuring device (e.g., teaspoons, millilitres,  on bottle and label)
  • Across-product variability (e.g., use of non-standard units and abbreviations (not mL, tsp, etc.))
  • Lack of guidance on appropriate use (e.g., caution to only use enclosed measurement device).

This was a baseline study, conducted before the FDA’s guidance could have been implemented. Most of the products (45%)  sampled were cough and cold treatments, with the rest being a mixture of analgesic, allergy, gastrointestinal, and combination products.

The Results

Measuring devices were supplied in 74% of products. Of those devices, significant problems were identified: 98.6% had inconsistencies between the dosing directions on the package, and the markings on the device itself. Deficiences included missing markings (24.3%), superfluous markings (81.1%), atypical units of measure (5.5%).

Evaluation

It seems intuitive that unclear directions can be a contributing factor to dosing errors. Deciphering labels and accurately dosing medications can be challenging to anyone, particularly those with limited health literacy. In the case of over-the-counter medications, there may be few opportunities for consultation before these products are used.

With over-the-counter cough and cold medications for pediatric populations, we had a group of products without good evidence of efficacy and the possible but rare risk of toxicity, particularly in overdose situations. It’s possible that packaging and labelling were factors that contributed to its toxicity and to its ultimately unfavourable risk-benefit evaluation. But the finding in these trials trials provide broader guidance to help us reduce the risk of dosing errors:

  • Measuring devices should be used with all pediatric liquids, over-the-counter or not. Oral syringes are the most accurate devices. Kitchen utensils should be avoided.
  • Consistency between what the label says, and what the measuring device actually measures, is important. Ideally, the device should not be able to measure more than a single dose of the medication.
  • Standardized units of measurement should be used. Even “teaspoon” and “tablespoon” can be misinterpreted into 3-fold errors. Millilitres (mL) is preferable, though it admittedly is not an intuitive measuring unit to everyone.
  • When expressing fractional amounts, always use leading zeros (i.e., 0.5mL)

Conclusion

Arriving at a science-based, individualized treatment for a child isn’t that useful if parents can’t measure the correct dose.  Two recent studies give us data to improve the way we use pediatric liquid medication.  In doing so we can improve patient outcomes and reduce the risks associated with medication use.

References

ResearchBlogging.org
Yin HS, Mendelsohn AL, Wolf MS, Parker RM, Fierman A, van Schaick L, Bazan IS, Kline MD, & Dreyer BP (2010). Parents’ medication administration errors: role of dosing instruments and health literacy. Archives of pediatrics & adolescent medicine, 164 (2), 181-6 PMID: 20124148

Yin HS, Wolf MS, Dreyer BP, Sanders LM, & Parker RM (2010). Evaluation of Consistency in Dosing Directions and Measuring Devices for Pediatric Nonprescription Liquid Medications. JAMA : the journal of the American Medical Association PMID: 21119074

Posted in: Science and Medicine

Leave a Comment (26) ↓

26 thoughts on “Good Idea, Bad Execution: Dosing Errors, A Preventable Harm

  1. Scott says:

    Slightly off the focus of the post, but when I read the hypothetical situation, the first dosing error I thought of had nothing to do with measurement. Specifically, did the (also sleep-deprived) mother do the same half an hour ago the last time the child awoke? Or will she the NEXT time?

    It can be hard to communicate such things effectively in such a situation.

  2. AlexisT says:

    Interesting that the dropper measured slightly better than the oral syringe–I find it slightly easier to measure the exact dose with the syringe. I’ve always used an oral syringe, for two reasons. One, it is more accurate. I love to bake, and I’ve always known that getting an accurate measurement in a liquid measuring cup is difficult. If your eyes are not level with the markings, you’ll be off. (I prefer to use a scale.) Two, a syringe results in less spillage and waste, which is important if you’re dosing a small child who resists being medicated. With a syringe, you can (if absolutely necessary) force the dose in. With those little cups you get with Children’s Tylenol, half the medicine will spill down the child’s chin.

  3. TsuDhoNimh says:

    My dad was a pharmacist in an area with a substantial number of customers who either did not read English or whose eyesight was none too good. (retirement community near a Hispanic migrant worker community)

    He always included a syringe of the appropriate size so they couldn’t easily overdose, with a black marker line at the dose level.

    They even had pictographic labels for dose timing.

    When was this ground-breaking practice developed? About 1964.

  4. Sane Mom says:

    Thank you so much for this post. I’ve been looking into this issue for a couple of weeks since my 18-month-old came down with his first truly nasty cold and I found myself with limited options to help relieve his symptoms.

    I spent much of my twenties working in child care and have administered hundreds of doses of cough and cold meds to very small children. In my (admittedly anecdotal) experience, these meds usually provided some relief from symptoms (or at least helped the children fall asleep, which improved their overall mood for the rest of the day). Of course, I was extremely careful to dose accurately and I never left medicated children unattended.

    So I found it very frustrating not to be able to provide the same relief for my child. I started looking into the logic behind the new AAP guidelines and was a little peeved by what I found. It seemed to me that they simply didn’t trust parents to dose accurately and keep the medication out of reach. But this study gives me some insight into how it’s so easy for well-meaning parents to accidentally overmedicate their kids.

    As for me, I’m keeping the medicines in the cabinet (out of reach, of course) to be used only in extreme cases and only with the permission of my pediatrician. And I’ve always had a preference for the oral syringe.

  5. Ash says:

    Interesting that the droppers scored so well. I find that for baby Tylenol and other relatively viscous liquids the droppers work horribly, often have bubbles in them, and it’s hard to figure out how much you’re giving, so we switched to using an oral syringe. Even then you get some adhering to the outside of the syringe if the liquid is viscous – probably insignificant for larger doses, but if you’re trying to administer a dose around 0.5 mL it might be a factor. A couple of times my son has been prescribed antibiotics that came with a bottle adapter for the syringe – that worked really well, and also reduced the amount of medicine that was wasted at the bottom of the bottle.

  6. Calli Arcale says:

    Ash — I love those syringes and bottles with adapters for easy filling! Those are awesome.

    I agree that those thick syrups are hard to measure with the dropper because of the damn bubbles. I ended up washing and reusing the syringes that came with prescription medicine, because they worked so much better.

    Another problem with the measuring cups — most of them, especially the flimsy ones that come with a lot of generic drugs, is that they bend quite easily. If you’re not holding them very gently, they will be out of calibration at precisely the worst time — while you’re measuring. Alternately, you can place them on a tabletop, but then you must crouch down to bring your eyes level with the cup.

    I think maybe the most important thing to teach in Home Ec (which really should remain a required course) is how to properly measure things. I didn’t learn that lesson until chemistry class.

  7. icewings27 says:

    I totally agree about children’s meds needing to include the appropriate type of measuring device. Ditto what Ash said about Baby Tylenol’s dropper. It’s impossible to measure a correct dose because the liquid is too viscous for the dropper.

    We were prescribed fluoride drops for our infant and the dose was 1 DROP per day. The dropper included with the product has no measurements on it and can hold about a teaspoon of liquid. That’s a heck of a lot more than a drop! And one night my husband gave the dose instead of me, squeezed too hard, and gave our baby a full dropper of the stuff. Fortunately for our son (if not so fortunate for our clothes), he threw it all up in a few minutes. We discontinued fluoride drops, btw.

  8. Interesting article. My son finished his first nasty bug of the season recently. His fever was getting high. We were giving him alternating doses of ibuprofen and Tylenol. The ibuprofen came with an etched cup and a “use measuring device with bottle” warning. I hated that cup. The measuring lines are very hard to see and tiny, so that I would have to search out my reading glasses and stand directly in front of a light to see the correct line.

    For the Tylenol we used a dosing spoon. I too hate the droppers, bubbles. The syringe is great for measuring, but for some reason the children are more resistant to it (maybe because it looks like a shot?) and more often spit out or drool out the medicine. They are good about drinking from the dosing spoon and I find the measurements are very legible, so that is my preferred device.

  9. ConspicuousCarl says:

    I like droppers because I can do a squeeze/release to get it just right all in one quick step. Syringes can be a little stiff and if I accidentally go over I have to rearrange the hands to squeeze it back out. With practice, a dropper is easier (for me) to use as an appendage extension. With a syringe, I always feel like I am operating a device.

    I am disappointed that they did not include an alligator spoon in the study.

  10. @Scott,
    that was my thought as well. I wouldn’t be surprised if unintentionally premature repeat dosing was the second leading cause of adverse drug affects.

    I am thinking of both the situation where one parent was unaware the other had already administered the drug recently or where the parent miscalculated the time elapsed since the last dose. It’s a natural tendency to assume if the symptoms return, it must be time for another dose.

  11. Calli Arcale says:

    Especially in the middle of the night. There have been times when I’ve narrowly avoided repeat dosing *myself* because in the fog of waking up in the middle of the night, I didn’t realize what time it actually was, and I’ve known others who actually did repeat dose themselves only to realize their mistake as the pill went down their throats. (Luckily, a quick call to the clinic revealed they were not in imminent danger, but how often does it happen and people don’t notice, I wonder?)

  12. Scott, “the first dosing error I thought of had nothing to do with measurement. Specifically, did the (also sleep-deprived) mother do the same half an hour ago the last time the child awoke? Or will she the NEXT time?”

    That is a disconcerting thought. I think I will talk to my husband when he gets home and come up with a more formal system to avoid such an error.

    Informally, when one of the kids is sick I check on them before I go to bed (11:00ish) and give them Tylenol if it’s time and they need it. I tell my husband if I gave them something. Usually my husband gets up in the night* if one of the kids needs something. As far as I know, he always wakes me up and asks me when I gave the last dose and what the dose is. I think (in addition to the formal plan) I will be more gracious with my response in the future.

    *If I get up, I generally can’t go back to sleep, so I deal with all calls for the rest of the night.

  13. Geekoid says:

    Based on this data, I think pediatric medications should come with a dropper with the min. dose. If they need twice that, use the dropper twice.

  14. BillyJoe says:

    AlexisT,

    I love to bake, and I’ve always known that getting an accurate measurement…

    My father was a chef and he never made use of any measuring devices ever. It was always a pinch of this and splash of that, a handfull of this and a long pour of that. His meals were in the oven before anyone else could even get the ingredients on the table. It was amazing experience to watch him in action.

  15. BillyJoe – “My father was a chef and he never made use of any measuring devices ever.”

    My mom always used to talk about learning to bake from my great grandma. No recipes, just “oh well, you know a few handfuls of flour, a dash of salt, cut a chunk of butter or maybe shortening, what do you have? some cold water til it holds together, , don’t handle it to much…” Very hard to share a recipe like that on the internet.

  16. Scott says:

    Baking is more sensitive to exact proportions than are other types of cooking. So long as you’re experienced (and tasting!) careful measurement isn’t terribly important if you’re making, say, lasagna. A cake or loaf of bread is MUCH harder to get right without careful measurement.

    @ micheleinmichigan:

    Indeed. My wife and I are planning to start a family next year, and this has definitely gotten me started thinking about ways to address such things. Writing it down every time, and checking the list before giving anything, seems the most robust. But will it be remembered at 3 AM?

  17. Epinephrine says:

    I think maybe the most important thing to teach in Home Ec (which really should remain a required course) is how to properly measure things. I didn’t learn that lesson until chemistry class.

    Or just teach this in science (before chemistry). Measurement and observation are key parts of science and are accessible quite early on. We covered proper measurement of liquids very early, though we weren’t taught to read beyond the markings on an instrument until I was in either late HS or 1st year uni.

    As a comment about dosing; we discovered that we were consistently underdosing our children based on the dosages listed on the label (by age/weight categories). All the measurement accuracy in the world desn’t help if the listed doses are incorrect, and the age/weight tables are not correct for some products, or are valid for the lowest end of the weight range given.

  18. Scott “Writing it down every time, and checking the list before giving anything, seems the most robust. But will it be remembered at 3 AM?”

    We did keep a list when son had his last surgery and we used consistent 4-6 hour doses of Tylenol for about a week for pain relief. It’s easy to lose track of when the last doses was over that period of time.

    But, I have found that for illnesses that come on suddenly (as most small child illnesses do) writing things down gets neglected particularly in the middle of the night. After a discussion, my husband and I agreed that since I am the primary medicine giver, my husband will never give medicine unless he asks me about the last dose first. Which is not to say that is the best method for others…it is an excellent thing to come to some agreement on, though.

  19. We have a dog who needs medicating twice a day. Every morning I get out two pieces of kibble, squirt meds on one (oral syringe with a bottle adapter, THANK YOU) and give it to the dog, leaving the other one out next to the medicine bottle. Seeing the other piece of kibble confirms that the daily medication routine has begun but that the evening meds have not yet been given. Anybody who knows she gets evening meds can give them to her and nobody else will, because they can see that the second kibble has been used.

  20. Alison, that reminds me. I have a 9 lb dog who needs Metacam for back spasms. She needs a very tiny dose. The medicine comes with a oral syringe/bottle adapter and the syringe is marked in pounds for the dosage rather than mm, tsp, etc. It is the best system I’ve used.

  21. micheleinmichigan,

    Love it!

    In theory I bet it could be adapted for humans by having different syringes for different age ranges. Infants get the clear syringe with the appropriate dose/pound markings on it. Preschoolers get the pink syringe, and school-age kids get the blue syringe. Or something. Always marked in pounds.

  22. Maybe the pound dosage syringe could be adapted to human use. Although it just occured to me that you might see a problem with folks thinking the syringe was multi-purpose and using it interchangeably with the infant Tylenol, children’s Tylenol or children’s Ibuprofen and that would be a bad thing.

  23. If all liquid children’s medicines were made to be dispensed per pound, it would work.

  24. They could do that? Then it could work. I think the infant medicine are more concentrated so that you have to give less (because there’s more problem with them drooling, spiting out larger amounts) but you could prevent syringe dosage misuse by having an infant bottle that will not admit a child dosage syringe; like a diesel fuel pump won’t fit into a regular fuel car.

  25. BillyJoe says:

    micheleinmichigan

    “My mom always used to talk about learning to bake from my great grandma. No recipes, just “oh well, you know a few handfuls of flour, a dash of salt, cut a chunk of butter or maybe shortening, what do you have? some cold water til it holds together, , don’t handle it to much…” Very hard to share a recipe like that on the internet.”

    Every christmas, my father used to make the most irresistable chicken croquettes in the world. Really I have never tasted better anywhere. We have all tried to duplicate them, but without success. Perhaps we should have taken a video of him in action. Maybe catch that dash of this and chunk of that and measure it for posterity.

  26. I nearly couldn’t read the vignette. My first thought was also of inadvertently double-dosing–either it’s not time yet or the mom gave a new dose earlier. We’re so totally paranoid about this that we:

    1. double-check the dose in the cup against the label right before we give the medicine–in mL if that info is printed on both

    2. write it down on a chalkboard in the kitchen

    3. double-check the time of last dose before we give a new one

    Even at 3 am.

    I love the oral syringes for dosing, but hate how my 7yr old fills them with water and uses them as “laser-shooters.” Somehow I can never find one when I need it…

Comments are closed.