Morgan R. Cole, PharmD, BCPS, manager, pharmacy, Helen DeVos Children's Hospital

As if there weren't enough challenges when it comes to pediatric medications, add the taste factor to the list. The reality is that it is difficult, at times impossible, to get a child to swallow foul-tasting medicine. Yet, as a recent FDA Update published in Pediatrics noted, the challenges facing drug companies when it comes to developing pediatric formulations means that kids are often required to swallow drugs designed for adults. (The Best Pharmaceuticals for Children Act web page has more information on pediatric pharmaceutical development efforts). 

Unfortunately, I see a lot of parents address the taste problem by grinding up pills and hiding the powder in ice cream or applesauce, or mixing bad tasting liquids with juice or milk. 

As pediatric clinicians, it is important that we do whatever we can to ensure that our patients take the medication  prescribed as directed-and that we warn parents about the potential dangers of mixing or manipulating those medications.

The first step is to order the medication from a compounding pharmacy or local retail pharmacy that carries commercially available flavoring agents.  For example, FLAVORx^®, a flavoring agent developed to improve the taste of medication without affecting its efficacy. You can read more about it here.

However, discourage parents from mixing liquid medications, pills, or crushed pills with their own food and drink. To often this can have unintended consequences, including erratic absorption. For instance, the drug could bind to the food or drink ingredients and become unavailable for absorption. One such drug is the antibiotic levofloxacin (Levaquin) oral solution. It binds to heavy metals (calcium, iron, and magnesium). That means hiding it in ice cream or milk renders it unavailable because it binds to calcium and/or iron.

In fact, we don't like to see juice, particularly citrus juices, used with medication in any situation, even to wash down the drug. You probably know that grapefruit juice can have multiple interactions with medications, including competing for or inhibiting enzymes required to metabolize medications; but other citrus juices, including orange, also contain compounds that can affect the bioavailability of certain medications.

If a parent has no other way to get a medication into a child (and no flavoring is available),  one possible option could be to mix the drug with chocolate syrup. It masks the bitterness but generally does not bind to the  active ingredients. 

As for crushing pills, counsel your patients that they should only take that step if their pharmacist agrees, as there are many dangerous effects when a medication is crushed when it should be administered whole. We are trained to know which medications can be crushed and which ones cannot be crushed. We even maintain Do Not Crush lists. 

Bottom line: When in doubt, turn to a pharmacist, particularly one with pediatric experience.

Morgan R. Cole, PharmD, BCPS, is the manager of the pharmacy at Helen DeVos Children's Hospital in Grand Rapids, Michigan.

John Huntington, MD, Anesthesiologist

Ever since news articles appeared last spring about an FDA federal panel meeting to evaluate concerns about cognitive problems or learning disabilities from general anesthesia in young children, I, like other anesthesiologists, have been fielding questions from concerned parents about the safety of anesthesia for their children. I'm sure you, as primary care physicians, are receiving similar questions. 

The concern about the possible effects of anesthesia on children's cognitive development began with animal studies published several years ago that demonstrated brain neuron death and long-term cognitive issues in 7-day-old rats given a combination of anesthesia drugs early in life. The FDA held a meeting in 2007 to discuss that research, concluding that anesthesia did not appear to cause similar issues in children but urging continued research. 

Much of the research since then has also been done in animals. However, several retrospective studies do suggest that children who receive repeated exposure to anesthesia before age 4 are more likely to have cognitive problems.^1,2,3,4

The study from Wilder et al, I think, is the one that has raised the current concerns. The authors looked at a cohort of 5,347children, approximately 600 of who had received general anesthesia before age 4 between 1976 and 1982. After 15 years, the authors found a correlation between two or more early anesthesia exposures and learning disabilities (hazard ratio [HR] =1.59, 95% CI 1.06-2.37 for two exposures; and HR 2.60, 95% CI 1.60-4.24, for three or more).⁴

Keep in mind that this is a correlation; we do not know if the anesthesia itself caused the learning deficits. Also consider, as we all know, that children who require two or more surgeries with general anesthesia before age 4 likely have other medical problems that could have contributed to those cognitive deficits. 

Still, if you combine retrospective studies like the one from Wilder et al with the animal studies, you can see how the current firestorm began. Thus, it's not surprising that the FDA felt it had act. 

The bottom line is that, at present, there is no alternative to general anesthesia for young children who require invasive procedures and such treatment is a must; we know even neonates feel pain. However, we always err on the side of caution, such as reserving elective procedures until children are older and limiting the number of anesthetics we give. If a child needs several procedures, we try to combine them into a single surgical session if possible. 

Also, if a child under 4 needs surgery it is likely related to a serious medical condition. So while I'm seeing more questions from parents in the past few months, none have cancelled surgeries. My advice is to take the time to counsel parents about the reality of the studies and our knowledge, and help them, as we do in so many things related to pediatric medicine, weigh the potential risks and benefits of the procedure.  

What are your thoughts about general anesthesia for young children? What are you hearing from parents?

John Huntington, MD, is an anesthesiologist at Helen DeVos Children's Hospital 

References

1. DiMaggio C, Sun LS, Kakavouli A, Byrne MW, Li G. A retrospective cohort study of the association of anesthesia and hernia repair surgery with behavioral and developmental disorders in young children. J Neurosurg Anesthesiol. 2009;21:286-91. 

2. Kalkman CJ, Peelen L, Moons KG, et al. Behavior and development in children and age at the time of first anesthetic exposure. Anesthesiology. 2009;110:805-12.

3. Backman ME, Kopf AW. Iatrogenic effects of general anesthesia in children: considerations in treating large congenital nevocytic nevi. J Dermatol Surg Oncol. 1986;12:363-7. 

4. Wilder RT, Flick RP, Sprung J, et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology. 2009;110:796-804.