ED Visits Abound for Adverse Drug Effects in Older Patients

ATLANTA, Oct. 18 -- Older patients are about as likely to be seen in the emergency room for adverse drug events as they are for automobile accidents, according to a CDC study.

Those 65 and older make up a disproportionate percentage of the more than 700,000 patients seen in emergency departments each year because of adverse drug events, reported Daniel S. Budnitz, M.D., M.P.H., of the CDC, and colleagues, in the Oct. 18 issue of the Journal of the American Medical Association.

While the Medicare-age group makes up just 12% of the U.S. population, it accounted for a quarter of adverse drug events overall (25.3%) and half of the adverse events that required hospitalization (48.9%), they found.

Adverse drug events were a slightly more common cause of ED visits than automobile accidents in this age group (177,504 for adverse drug events annually versus about 175,000 for auto accidents).

Only two of the 18 drugs most commonly causing these events have been in clinical use less than two decades. This confirms previous reports that "a large proportion of the public health burden of [adverse drug events] is attributable to 'older drugs, used poorly.'"

Most conditions caused by adverse drug events were dermatologic, gastrointestinal, or neurological. One third of these were allergic reactions (33.5%, 95% CI 28.6% to 38.4%), and another third were attributed to unintentional overdoses (32.1%, 95% CI 28.6% to 35.7%).

Adverse drug events accounted for 0.6% of all ED visits. The estimated annual population rate of adverse drug events treated in EDs was 2.4 per 1,000 individuals overall (95% CI, 1.7-3.0), but varied by age:

• 4.3 per 1,000 children younger than five years (95% CI 3.1 to 5.4).
• 1.0 per 1,000 children ages five to nine years (95% CI 0.7 to 1.3,
• 2.9 per 1,000 adults ages 60 to 64 (95% CI 1.9 to 3.9).
• 4.9 per 1,000 adults ages 65 or older (95% CI 2.7 to 7.0).

The rate continued to go up among increasingly older age groups and peaked at 6.8 per 1,000 for adults ages 85 or older (95% CI 3.6 to 10.1).

However, newer drugs do not seem to be the main culprits. Insulins and warfarin, which both typically require ongoing monitoring to prevent overdose or toxicity, caused:

• One in every seven estimated adverse drug events treated in EDs (14.1%, 95% confidence interval 9.6% to 18.6%).
• More than a quarter of all estimated hospitalizations (871 cases, 95% CI 17.3% to 35.2%).

In the elderly, insulin, warfarin and digoxin were implicated in:

• One in every three estimated adverse drug events treated in EDs (1592 cases, 33.3%; 95% CI 27.8% to 38.7%), and
• 41.5% of estimated hospitalizations (646 cases, 95% CI 32.4% to 50.6%).

The researchers analyzed data from an adverse drug event surveillance program shared by the CDC, the Consumer Product Safety Commission, and the FDA. The surveillance program included 63 hospitals in a nationally representative, stratified probability sample of all hospitals in the United States.

The investigators defined an adverse drug event as an incident ED visit for a condition that the treating physician explicitly attributed to the use of a drug or a drug-specific effect. Adverse events were included whether the therapeutic agent implicated was prescription only, over-the-counter, vaccine, vitamin, dietary supplement, or herbal product. Intentional self-harm, drug therapeutic failures, drug withdrawal, and drug abuse were excluded as were events that occurred as a result of medical treatment during the visit.

The surveillance system did not include data on deaths from adverse drug events.

The researchers found a total of 21,298 adverse drug event cases during 2004 and 2005, which yielded an estimate of 701,547 cases annually (95% CI 509,642 to 893,452). Of these, 16.7% were hospitalized related to adverse drug events (95% CI 13.1% to 20.3%).

Adverse drug events accounted for 2.5% of ED visits due to unintentional injury and 6.7% of unintentional injury hospitalizations. Most emergency department visits for adverse drug events were among women (annual estimate 60.6%, 95% CI 59.1% to 62.1%).

About one in six adverse drug events required hospitalization. The estimated annual population rate of adverse drug events requiring subsequent hospitalization was:

• 0.4 per 1,000 persons overall (95% CI, 0.2-0.6), but
• 1.6 per 1,000 for persons aged 65 years or older (95% CI 0.7 to 2.5).

"Historically, the public health burden of adverse events from therapeutic drug use among community-dwelling, non-hospitalized patients has been difficult to estimate, but the problem is large and can be expected to increase," the investigators wrote.

According to previous studies, about 82% of the U.S. population uses at least one prescription medication, over-the-counter medication, or dietary supplement and 30% use five or more drugs.

The reason why older individuals are more likely to experience adverse drug events may be greater frequency of use and the number of drugs used by this age group, the researchers noted.

The investigators noted that their study likely underestimates the full burden of adverse events since it did not catch those diagnosed and treated in other settings like primary care offices, non-hospital urgent care centers, or direct admission to hospitals. Also, they said the surveillance system could have been biased toward catching acute, well-known drug effects or effects for which testing is available in the emergency department, such as hypoglycemia or hypocoagulability.

Because efforts to reduce outpatient adverse drug events "have been hampered by sparse data," the findings may help focus prevention efforts, Dr. Budnitz and colleagues wrote.

The study was funded by the CDC, the Consumer Product Safety Commission, and the FDA.