Not By the Book -- Dosing Challenges in Pediatric and Neonatal ICUs: An Expert Interview With Cathy M. Haut, MS, CPNP-AC, CCRN

Neil Osterweil

May 26, 2010

May 26, 2010 — Editor's note: Infants and children metabolize drugs differently than adults, but critical care practitioners, lacking evidence to support optimal drug dosing in pediatric patients, must rely on a combination of weight-based standards developed for adults, clinical experience, and guesswork, said Cathy M. Haut, MS, CPNP-AC, CCRN, pediatric nurse practitioner in the pediatric intensive care unit (ICU) at the Children's Hospital at Sinai, and associate faculty member at the University of Maryland School of Nursing in Baltimore.

In an interview with Medscape Nurses, Ms. Haut shared her insights on pediatric dosing in pediatric and neonatal ICUs from a presentation she made at the American Association of Critical-Care Nurses 2010 National Teaching Institute & Critical Care Exposition, held April 30 to May 5 in Washington, DC.

Medscape: How does the lack of good data on drugs, and on dosing in particular, for children manifest in pediatric and neonatal ICUs?

Ms. Haut: The problem is that for many of the medications we have been using for many, many years, we know about common side effects, but we really don't know about dosing, and there's not a lot in the literature about how to determine dosing for kids.

This has come to light recently because of [the increasing prevalence of] obesity and the fact that in children who are ill there a lot of physiologic factors that change and can affect the pharmacokinetics of drugs.

For children who are overweight, there are multiple angles that really haven't been studied, so we really don't know how a child will respond. Antibiotics are probably the easiest to talk about because we know whether or not a child gets better — they have an infection, we treat them, and they get better. But with anything else — beta blockers, anything that affects cardiovascular dynamics — there's a whole lot of uncertainty about how kids are going to respond. We don't have any scientific basis; that's the fact.

Medscape: In the ICU you often have to make quick decisions. Does this increase the risk for errors?

Ms. Haut: You have to make quick decisions and you have to make quick decisions about using some drugs that might be off-label, or that might have insufficient information. There are 2 antibiotics that fall into that category — Unasyn [ampicillin/sulbactam] and Zosyn [piperacillin and tazobactam] — which are expensive, but cover a wide range of organisms, both Gram-negative and Gram-positive. [Ampicillin/sulbactam] in particular is not recommended for children younger than 1 year of age; yet you can choose to use that for overwhelming sepsis because it's the best drug out there. It contains ampicillin, which a common drug that we give to neonates all the time, but sulbactam hasn't been studied [in infants].

Medscape: Are drug-dosing errors common in pediatric and neonatal ICUs?

Ms. Haut: One of the things I asked was how many of the nurses in the audience experienced medication errors — that's one major factor affecting care that is everywhere and has been brought to light by the Institute of Medicine and the Joint Commission in some of the recommendations to help hospitals to minimize calculation errors. Then I asked about reporting adverse effects: Are we as good about reporting adverse effects as we are at reporting errors? The truth is that no, we're not. The opportunity to collect data is there, but it's not always followed up.

Do nurses always recognize when kids have adverse reactions to medications when they're already critically ill? They probably don't.

Medscape: What are the issues regarding drug metabolism in children, as opposed to adults, in the intensive care setting?

Ms. Haut: The pharmacokinetic piece of medication administration is something that nurses really don't get in their education. They're taught what drugs do, but they really don't learn about the processes of absorption, distribution, metabolism, and elimination, which are the 4 ways the body uses a drug to do what it's meant to do. And those — primarily metabolism and elimination — are majorly affected by development.

Neonates certainly metabolize things differently because they have different enzymes present in their livers, and they have different maturation of their liver and kidney function. Elimination is also factored by the illness itself. If you have a child who has cardiorespiratory compromise, the kidney's aren't going to work as well. There are kids who go into renal failure as a result of major sepsis, or trauma, or lots of other causes, so all these things must be taken into account when considering dosing.

The second part of my spiel is that body weight itself isn't the be all and end all. We know that in oncology, for example, dosing is primarily based on body-surface area. There are some studies, primarily by pharmacists, that are looking at dosing by body-surface area, by ideal weight, and by adjusted body weight; those last 2 are kind of foreign.

How do we figure that out [what ideal weight should be]? Thirty-three percent of our children are overweight, so this becomes a real issue. You look at fat content vs lean content vs muscle mass, and it's an eyeball view — you look at a child and say he should be this weight based on his height and on the growth charts we use. Yet in obese kids, the fat and water have a lot to do with how a drug is distributed and how well it is metabolized.

There are so many unknowns that can lead to toxicities and to significant adverse events, and then you have to add the fact that these kids are critically ill and that their bodies function very differently when they're ill than when they're well.

Medscape: How did the current system of pediatric dosing evolve?

Ms. Haut: In pediatrics, we don't have a lot of rationale for why we do some of the things we do. If we go way back and ask when we first started doing this and what the reason was behind this — I've tried to find the history of dosing by weight, and I couldn't find it. We've been doing it forever — I've been a pediatrics nurse for 30 years and we've been doing this all that time — but my question to the audience is why do we do this.

We came across it as a good way to calculate medications and, in some cases, such as antibiotics, it makes no difference since you can give a fairly large dose and generally not cause much more problem than maybe some diarrhea.

But you can't, for example, give a large dose of midazolam [Versed]. A major study of children's responses to midazolam came out with recommendations for using small doses and then gradually increasing that dose, because children respond to midazolam by not breathing.

Medscape: What are the most important points for your colleagues to remember about drug use in the pediatric ICU?

Ms. Haut: Know and think about the medications you're administering. Look at the child, and have an awareness of what the pharmacokinetics of that drug will be in a child of that particular age and size. Every child and every infant needs to be looked at individually.

Ms. Haut has disclosed no relevant financial relationships.

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