Examining Emergency Department Visits for Adverse Drug Events in Older Adults
By R.L. Wynn
Adverse drug events pose a distinct threat to older adult patients. Three recent studies examine the most frequent causes of emergency visits and hospitalizations due to adverse drug events.
Between 2007 and 2009, there were 99,628 emergency hospitalizations annually for adverse drug events in adults 65 years of age or older, according to a report from the Centers for Disease Control (CDC). Four medications or medication classes were implicated alone or in combination in 67% of those hospitalizations. These were warfarin (33.3%), insulins (13.9%), oral antiplatelet agents (13.3%), and oral hypoglycemics (10.7%).
In addition to the emergency hospitalizations report, a different report from the CDC looked at deaths from drug overdoses in the U.S. in 2010. There were 38, 329 deaths: 74% unintentional and 8% suicides, with the remainder undetermined. The most commonly involved drug classes were opioids (75%), benzodiazepines (29%), antidepressants (18%), and antiepileptics and antiparkinsonism drugs (8%).
Another report in the Journal of the American Medical Association in 2014 focused on the increases in emergency department visits involving alprazolam (Xanax). Most of the visits involved patients taking other pharmaceuticals, illegal drugs, or alcohol in combination with alprazolam, with 39% of visits involving 1 other drug, 21% involving 2 other drugs, and 21% involving 3 or more drugs. Opioid painkillers and other benzodiazepines were among the pharmaceuticals frequently taken in combination with alprazolam.
Emergency hospitalizations study
Budnitz, D.S., et al. “Emergency hospitalizations for adverse drug events in older Americans.” New Eng J Med, 2011; 365:2002-12.
The authors used adverse event data from the National Electronic Injury Surveillance System- Cooperative Adverse Drug Event Surveillance project (2007-2009) to estimate the frequency and rates of hospitalization after emergency department visits for adverse drug events in older adults. In addition, the data was used to assess the contribution of specific medications, including those identified as high risk or potentially inappropriate. The primary outcome measure was hospitalization after an emergency department visit for an adverse event due to medications. Each hospitalization was described with respect to the type of event, implicated medications, and the number of concomitant medications. The secondary outcome measure was hospitalization after an emergency department visit for an adverse event due to a medication currently described as “high-risk” in the elderly or “potentially inappropriate” medication use in older adults. Examples of “high-risk” drugs in the elderly are antihistamines, amphetamines, belladonna alkaloids, meperidine, and skeletal muscle relaxants. Examples of “potentially inappropriate” medications are long-term benzodiazepines to treat depression, NSAIDs to treat gastric ulcers, and amphetamines to treat cognitive impairment.
Results of the hospitalization study:
- From 2007 to 2009, 265,802 emergency department visits for adverse drug reactions occurred annually among adults 65 years of age or older.
- An estimated 99,628 (38%) of those visits required hospitalization.
- Nearly half of those hospitalizations (48.1%) involved adults 80 years of age or older.
- Emergency department visits that resulted in hospitalization were more likely to involve unintentional overdoses and five or more medications.
- Thirteen medications and medication classes were implicated alone or in combination in the hospitalizations for adverse events. Out of the 99,628 total hospitalizations, these medications were warfarin (33,171 or 33.3%), insulins (13,854 or13.9%), oral antiplatelet agents (13,263 or 13.3%), oral hypoglycemic agents (10,656 or 10.7%), opioid analgesics (4,778 or 4.8%), antibiotics (4,205 or 4.2%), digoxin (3,465 or 3.5%), antineoplastic agents (3,329 or 3.3%), antiadrenergic agents (2,899 or 2.9%), renin-angiotensin inhibitors (2,870 or2.9%), sedative or hypnotic agents (2,469 or 2.5%), anticonvulsants (1,653 or 1.7%), and diuretics (1,071 or 1.1%).
- Only 1.2% of hospitalizations for adverse drug events were attributed to “high-risk” medications. “Potentially inappropriate” medications were implicated in only 3.2% of hospitalizations.
Most hospitalizations for warfarin and the antiplatelet agents were for acute hemorrhages, including intracranial and gastrointestinal bleeding. Nearly all hospitalizations attributed to insulins and oral hypoglycemic agents were for hypoglycemia, including loss of consciousness and seizures. For the cardiovascular agents (diuretics, antiadrenergic agents, renin-angiotensin inhibitors), hospitalizations were for electrolyte or fluid-volume disturbances.
According to the authors, hospitalizations for adverse drug events are likely to increase as the population lives longer, have larger numbers of chronic conditions, and take more medications. Among adults 65 years of age or older, 40% take 5-9 medications and 18% take 10 or more. Older adults are nearly seven times as likely as younger persons to have adverse events that require hospitalization. Factors associated with older patients are age-related physiological changes, more frailty, a larger number of coexisting conditions, and the taking of multiple medications.
Study on drug overdose deaths
Jones, C.M., et al. “Pharmaceutical overdose deaths, United States, 2010.” JAMA, 2013; 309:657-9.
The data for this study were taken from the National Vital Statistics System multiple cause of death file. The authors extracted the pharmaceutical-related overdose deaths and subdivided those into central nervous system pharmaceuticals, opioid analgesics, and psychotherapeutic pharmaceuticals. Pharmaceutical overdose deaths by definition were those primarily due to prescription drugs.
- In 2010, there were 38,329 drug overdose deaths in the United States.
- Of those drug overdose deaths, 58% (22,134) involved pharmaceuticals.
- Of the pharmaceutical-related deaths, 74.3% were unintentional, 17.1% were suicides, and 8.4% were of undetermined intent.
- Specific drug classes most commonly involved in overdose deaths were opioids (75%), benzodiazepines (29%), antidepressants (18%), and antiepileptic and antiparkinsonism drugs (8%).
- Of the opioid-involved overdose deaths, 29.4% involved the opioid alone.
- Opioids were frequently implicated in overdose deaths involving other pharmaceuticals. They were involved in the majority of deaths involving benzodiazepines (77%); antiepileptic and antiparkinsonism drugs (66%); antipsychotic and neuroleptic drugs (58%); antidepressants (58%); other analgesics, antipyretics, and antirheumatics (57%); and other psychotropic drugs (54%).
This report confirmed the predominant role opioid analgesics play in pharmaceutical overdose deaths, either alone or in combination with other drugs.
Sedative-related emergency visits study
Kuehn, B.M. “ED Visits for Sedatives Increase.” JAMA, 2014; 312:328.
Between 2005 and 2010, the estimated number of ED visits involving non-medical use of alprazolam increased from 57,419 to 124,902, and then plateaued in 2011 at 123,744. According to the author, most of the visits involved patients taking other substances in combination with alprazolam, including other pharmaceuticals, illegal drugs, or alcohol. Thirty-nine percent of visits involved one other drug, 21% involved 2 other drugs, and 21% involved 3 or more drugs. Pharmaceuticals frequently taken in combination with alprazolam were opioid analgesics and other benzodiazepines. These data were taken from a report from the Substance Abuse and Mental Health Services Administration.
According to the author, people abuse alprazolam for its psychoactive effects. Taking too much alprazolam and taking it in combination with other medications may exacerbate the drug’s psychoactive effects, respiratory depression, or lead to withdrawal symptoms such as tremors and seizures.
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