Polypharmacy in Hospitalized Children Raises Safety Concerns

Kate Johnson

January 03, 2012

January 3, 2012 — A large proportion of hospitalized children are exposed to numerous medications on a daily basis in both children's and general hospitals throughout the United States, according to a new study by Chris Feudtner, MD, PhD, from the University of Pennsylvania School of Medicine, Philadelphia, and colleagues.

In addition, children with rare conditions are more likely to be exposed to more substantial polypharmacy, the authors report in an article published in the January issue of the Archives of Pediatric and Adolescent Medicine.

The findings raise patient safety concerns, "given the relationship between polypharmacy and adverse drug events that has been documented for adults in both hospital and nursing home settings," the authors write, and warrants further investigation into drug–drug interactions.

The study used 2006 data from 2 sources: the Pediatric Health Information System, which comprises administrative discharge data from children's hospitals for most US major metropolitan areas, and the Perspective Data Warehouse, which comprises data from academic medical centers, community-based hospitals, and large hospital systems in both rural and urban settings.

In total, the data included 491,451 pediatric hospitalizations in 52 children's hospitals and 260,740 pediatric hospitalizations in 411 general hospitals, representing nearly one fifth of all pediatric hospitalizations across the country for 2006.

"The total number of drug and therapeutic agent exposures over the course of the entire hospitalization equaled a dozen drugs and therapeutic agents for the typical patient admitted to a children's hospital (with a median LOS [length of stay] of 5 days)," they report, "but was only 2 drugs and therapeutic agents for the typical patient admitted to a general hospital (with a median LOS of 2 days).”

This represents exposure of children in children's hospitals to 1.34 times more drugs and therapeutic agents than children admitted to general hospitals, but after adjustment for patient age, sex, LOS, whether surgery was performed, and rarity of medical condition (All Patient Refined Diagnostic Related Groups), the exposure difference between types of hospital is nullified, the authors note.

The study found that for infant patients (younger than 12 months), the typical (median) exposure on the first day of hospitalization in a children's hospital was 4 distinct generic drugs and therapeutic agents; for infants in the 90th percentile of exposure, it was 11.

For children aged 12 months or older, the median and 90th percentile exposures on the first day of hospitalization were 5 and 13 exposures, respectively.

For patients whose LOS reached 30 days, typical and 90th percentile exposures for infants reached 4 and 13, respectively, by 30 days, whereas patients 1 year or older had 9 and 20 exposures, respectively.

The cumulative number of distinct generic drug and therapeutic agent exposures for each successive day of hospitalization was 25 (median) and 51 (90th percentile) for infants, and 42 (median) and 66 (90th percentile) for older children in children's hospitals.

The highest level of cumulative exposure was for patients with less common conditions. Exposure varied considerably between hospitals among patients with the most common conditions of asthma, appendectomy, and seizure, the authors report.

Although the data displayed initial differences between children's hospitals and general hospitals, adjustment for patient case mix showed that this difference was largely explained by differences in patient populations.

"[W]e found that the most common generic drugs and therapeutic agents to which children were exposed included intravenous fluids; analgesics such as the narcotics fentanyl and morphine or the antipyretics/analgesics acetaminophen and ibuprofen; anti-infective agents such as ampicillin, gentamicin, and cephalosporins; anesthetic agents such as lidocaine and propofol; gastrointestinal drugs such as ranitidine, ondansetron, and metoclopramide; and a bundle of drugs often provided to newborns as part of routine care, including vitamin K, erythromycin eye drops, immunization drugs, and application of triple dye anti-infective agents to the umbilicus," the authors write.

“Exposure to certain classes of drugs such as antineoplastic and cardiovascular agents were much more likely to occur in children's hospitals,” they add.

In an editorial accompanying the article, Nancy Morden, MD, and David Goodman, MD, from the Dartmouth Medical School in Lebanon, New Hampshire, write: "We share the authors' unease with the level of polypharmacy in pediatric inpatient settings, but our biggest concern is the lack of information that would tell us if these prescribing patterns are problematic for patients."

Although evidence suggests that complex medication combinations increase the risk for adverse drug events, there is a need to balance this risk with the benefits of symptom relief or disease modification, the editorialists note. "[T]he tragic undertreatment of pain in children has been extensively documented. In addition, the use of anesthetics and sedatives may not be optional when surgery, procedures, or advanced imaging are required."

An important next step is to measure outcomes associated with exposure patterns, they add.

Finally, although pediatric polypharmacy is likely most common in the hospitalized patient, "outpatient polypharmacy is increasingly prevalent in children and also deserves attention."

"Therapy with medications started in childhood for management of chronic conditions often continues for decades — well beyond the duration of any drug approval trials and thus well outside our understanding of potential drug effects," the editorialists conclude.

The study was supported by a Center for Education and Research on Therapeutics grant from the Agency for Healthcare Research and Quality. The study authors and Dr. Morden have disclosed no relevant financial relationships. Dr. Goodman currently receives research funding through grants and contracts from the Robert Wood Johnson Foundation; Health Resources and Services Administration; Department of Health and Human Services, Office of the Assistant Secretary of Planning and Evaluation; National Institute on Aging; National Cancer Institute; and Wellpoint Foundation, and during the last 3 years he has accepted speaker and consulting fees for a number of companies, hospitals, and agencies, a full list of which is available in the article.

Arch Pediatr Adolesc Med. 2012;166:9-16. Article full text, Editorial extract


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