Fatal adverse drug events (ADEs) are a significant cause of deaths in hospitalized patients, especially for elderly patients with multiple diseases, according to an article in the Oct. 22, 2001 issue of the Archives of Internal Medicine, published by the American Medical Association.

Just Ebbesen, M.D., of the Central Hospital of Akershus, Nordbyhagen, Norway, and colleagues studied the clinical records, autopsy results and findings from drug analyses performed before and after death for 732 patients who died after admission to the Department of Internal Medicine at the Central Hospital of Akershus in Norway.

The study was conducted from October 1993, through November 1995, to assess the 2-year incidence of drug-related deaths in a major medical department and search for patient characteristics associated with an increased risk of fatal ADEs.

The authors found that in 18.2% of the patients (133 out of 732), death was classified as directly or indirectly associated with 1 or more drugs. This equals 9.5 deaths per 1000 hospitalized patients. The most common drugs associated with fatal ADEs were cardiovascular drugs (used to treat conditions involving the heart, blood vessels or circulation), antithrombotic drugs (used to prevent blood clots) and sympathomimetic agents (a variety of drugs, including some used to treat asthma).

According to background information in the article, ADRs (adverse drug reactions) may be among the six leading causes of in-hospital deaths in the United States.

"In view of an increasing number of drugs in use, an increase in the population age, and an increase in the severity of diseases handled, an increase in the incidence of drug-related deaths might be expected," the authors stated.

On the other hand, the authors note, "Reported frequencies of fatal ADRs or fatal ADEs vary between 0.9 and 6.5 per 1000 hospitalized patients. The perceived magnitude of this problem has caused major concern ..."

The authors reported that men with fatal ADEs were significantly older than those without fatal ADEs; there was no age difference found among women. The number of drugs used on hospital admission was higher in the fatal ADE cases; the percentage of ADEs was higher in those who died of gastrointestinal diseases and lower in those who died of cancer and respiratory diseases. The median time to death was three days.

"... it was concluded that various degrees of inappropriateness were seen in drug choice, route of administration, and/or drug dose," the authors state. "Few fatal ADEs were registered in the patient record, and only 8 were reported to the health authorities according to official regulations."

They concluded that "misinterpretation of symptoms and signs, especially in the emergency department; lack of monitoring drug concentrations; and inadequate adjustment of drug doses according to age, body dimensions, metabolism, and pharmacokinetics have resulted in several fatal ADEs that ought to have been preventable."